Internal Medicine Critical Care

Acute Adrenal Insufficiency

- Adrenal crisis is the acute, life-threatening form of adrenal insufficiency
o Can occur in the patient with poor adrenal reserve who is exposed to surgery, infection, injury,
stress, lymphoma, metastatic cancer, amyloidosis, scleroderma, hemochromatosis, or cessation of
corticosteroid medication. These patients may complain of nausea and abdominal pain, and appear
ill.
o Overt Shock
o Clinical features are as described above, but to the extreme and accompanied by shock and
altered mental status
- Adrenal crises may be precipitated by infection, trauma, surgery, stress, lymphoma, metastatic cancer,
amyloidosis, scleroderma, hemochromatosis, or cessation of corticosteroid medication
- Addisonian crisis is heralded by hypotension, acute pain (abdomen, low back), vomiting, diarrhea,
dehydration, hypotension, and altered mental status. If untreated, it can be fatal
- Diagnostic Studies:
o See Addison Disease
- The most common cause of acute adrenal insufficiency is adrenal suppression from prolonged steroid use
with either abrupt steroid withdrawal or exposure to increased physiologic stress such as injury, illness, or
surgery. It may take up to 1 year for the hypothalamic-pituitary-adrenal axis to recover following prolonged
suppression with steroid treatment
- Treatment for acute adrenal insufficiency in adults:
o Begin therapy immediately in any suspected case of adrenal crisis prognosis is related to rapidity
of treatment
DO NOT WAIT FOR PENDING LAB RESULTS BEFORE BEGINNING EMPIRIC TX
Treat HYPOTENSION with volume 2 to 3 L of NS or D5NS
Give IV DEXAMETHASONE 4mg or IV HYDROCORTISONE 100mg
If less ill, can give oral hydrocortisone (20mg/kg)
o Administer IV fluids 5% dextrose in NS is the fluid of choice to correct both hypoglycemia and
hyponatremia
o Steroids hydrocortisone (100 mg bolus) is the drug of choice for cases of adrenal crisis or
insufficiency, as it provides both glucocorticoid and mineralocorticoid effects
o Vasopressors administered after steroid therapy in patients unresponsive to fluid resuscitation
(norepinephrine, dopamine, or phenylephrine preferred)
o Supplementation patients may require lifelong glucocorticoids and/or mineralocorticoids
o Maintenance increased maintenance doses of chronic steroids are required during long periods
of stress (e.g., illness, surgery, trauma, etc.) to satisfy increased physiologic need for cortisol
Thyroid Storm
- Thyroid storm or crisis is a rare but life-threatening condition of extreme hyperthyroidism. Illness, sepsis,
trauma, surgery, RAI administration, and pregnancy may precipitate this condition
- It may not be identified by lab testing but may reveal findings of elevated T3 and free T4 as well as
decreased TSH
- Clinical presentation high fever, tachycardia, agitation, sweating, tremor, instability, delirium, vomiting,
and diarrhea
o Mortality is high, and these patients should be admitted to the ICU

Thyroid storm presents as fever, CNS and cardiovascular dysfunction, in addition to thyrotoxicosis signs and
symptoms
o CNS = agitation, confusion, delirium, coma, seizures
o Cardiovascular = tachycardia, arrhythmia, CHF
o Follows stressful illness, thyroid surgery, or radioactive iodine administration
o Presents with high fever, tachycardia, vomiting, diarrhea, dehydration, marked weakness, and
muscle wasting. Extreme restlessness, confusion, delirium, and emotional lability may also occur
o Although rare, its mortality rate is high
- Thyroid storm is a clinical diagnosis lab tests cannot distinguish from thyrotoxicosis
- Treatment:
o Inhibit thyroid hormone release with thionamides PTU is preferred over methimazole
Monitor for liver dysfunction with PTU
o Inhibit new thyroid hormone production (give at least 1 hour after PTU) Lugol solution or
potassium iodide or iopanoic acid or lithium carbonate
o Block peripheral thyroid hormone effects propranolol
Beta-blockers (primarily propranolol) control symptoms (tachycardia, tremor, diaphoresis,
anxiety, palpitations) in any hyperthyroid episode and are the initial treatment of choice for
thyroid storm and periodic paralysis
o Prevent conversion of T4 to T3 hydrocortisone or dexamethasone
Diabetic Ketoacidosis
- Results from a relative insulin deficiency and counter-regulatory hormone excess causing hyperglycemia
and ketonemia
- Hyperglycemia causes an osmotic diuresis with dehydration, hypotension, and tachycardia
- Ketonemia causes an acidosis with myocardial depression, vasodilation, and compensatory Kussmaul
respiration
o Nausea, vomiting, abdominal pain are common
o The absence of fever does not exclude infection
o Acetone, formed from oxidation of ketone bodies, causes the characteristic fruity odor of the
patients breath
- Causes noncompliance with insulin, infection, pregnancy, hyperthyroidism, substance abuse (cocaine),
medications (steroids, thiazides, antipsychotics, sympathomimetics), heat-related illness, CVA, GI
hemorrhage, MI, PE, pancreatitis, major trauma, surgery
- Diagnosis is based on clinical presentation and laboratory values of a glucose > 250 mg/dL,
bicarbonate < 15 mEq/L, pH < 7.3, and a moderate ketonemia
- An anion gap metabolic acidosis results from formation of ketone bodies
- Osmotic diuresis results in loss of sodium, chloride, calcium, phosphorus, and magnesium, but initial serum
levels may be normal from hemoconcentration
- Serum and urine glucose and ketones are elevated
- Pseudohyponatremia is common for each 100 mg/dL increase in blood glucose, the sodium decreases by
1.6 mEq/L
- Serum potassium may be low from osmotic diuresis and vomiting, normal, or high from acidosis
o In acidosis, potassium is driven extracellularly. Therefore, the acidotic patient with normal or low
potassium has marked depletion of total body potassium
- The goal of treatment is to correct the volume deficit, acid-base imbalance and electrolyte abnormalities,
administer insulin, and treat the underlying cause
- Goal = glucose < 200 mg/dL, bicarbonate > 17, and pH > 7.3
- Cerebral edema is a complication of treatment that occurs predominantly in children.
o Young age and new-onset diabetes are risk factors
o Tends to develop 4-12 hours into treatment, typically manifests as deterioration in neurologic status

o Begin treatment with mannitol 1g/kg before obtaining the diagnostic CT scan
o Gradual correction of sodium, glucose, and hypovolemia may lessen the risk
Acute Hypoglycemia
- Usually a complication of treatment of diabetics with insulin or sulfonylureas (glyburide, glipizide)
o An unusual reaction from treatment with the glitazones, glinides, alpha-glucosidase inhibitors, or
the biguanide metformin
- Fasting hypoglycemia occurs secondary to some endocrine disorders (Addison disease, myxedema), liver
malfunction, acute alcoholism, and ESRD
- Primary hypoglycemia is caused by either hyperinsulinism (e.g., exogenous administration), extrapancreatic
tumors (insulinoma), or -cell tumors
- Postprandial or reactive hypoglycemia is classified as early (2-3 hours after eating) or late (3-5 hours after
eating). It occurs after GI surgery, especially postgastrectomy with dumping syndrome, and Roux-en-Y
gastric bypass surgery. It may also be alcohol related, factitious, immunopathologic, or drug induced
- Symptoms begin at plasma glucose levels of 60 mg/dL
o Cognitive impairment begins at 50 mg/dL
- Fasting hypoglycemia often is subacute or chronic and presents with neuroglycopenia
- Postprandial hypoglycemia usually is acute and presents with sweating, palpitations, anxiety, and
tremulousness
- Other symptoms nausea, dizziness, confusion, slurred speech, blurred vision, headache, lethargy, coma
- Focal neurologic findings may include cranial nerve palsies, hemiplegia, seizures, and decerebrate
posturing
- The Whipple triad history of hypoglycemic symptoms, a fasting blood glucose of 45 mg/dL or less, and
immediate recovery on administration of glucose
- Diagnostic studies depend on the suspected cause
- Treatment is directed at the underlying causes
o If patients have hypoglycemia with an altered mental status, treat with 50% dextrose 50 mL IV. A
continuous infusion of 10% dextrose solution may be required to maintain the blood glucose above
100 mg/dL. Provide a carbohydrate meal if the patient can tolerate PO
o If there is no IV access, administer glucagon 1mg IM or SC
o Refractory hypoglycemia secondary to the sulfonylureas may respond to octreotide 50-100 g SC.
A continuous infusion of 125/hr may be required
o Monitor for rebound hypoglycemia by determining the blood glucose every 30 minutes initially
Acute Angle Closure Glaucoma
- Pathophysiologically, glaucoma is a progressive optic nerve disease often associated with increased
intraocular pressure
o Any impediment to the flow of aqueous humor through the trabecular meshwork and canal of
Schlemm will increase pressure in the anterior chamber
o Can be acute or chronic
Open-angle glaucoma is more common (older than 40 years, African American,
personal/family history of glaucoma or diabetes). It is a chronic, asymptomatic and
potentially blinding disease. Manifests as increased intraocular pressure, defects in the
peripheral visual field, and increased cup-to-disc ratios. The main symptom is loss of
peripheral vision
- ANGLE-CLOSURE GLAUCOMA A symptomatic increase in intraocular pressure. OPHTHALMIC
EMERGENCY that results from complete closure of the angle
o Iris is abnormally positioned
o Impaired outflow from occlusion of the anterior chamber (narrowed)
o Classically presents with eye pain or headache, cloudy vision, colored halos around lights, and the
patient may be vomiting
o Causes pupillary dilation, stress, drugs (anticholinergic or sympathomimetic agents)

Sudden attacks in patients with narrow anterior chamber angles can be precipitated in
movie theaters, while reading, and after ill-advised use of dilatory agents or inhaled
anticholinergics or cocaine
o Painful eye and loss of vision are important clinical features
o Symptoms ~ headache, red eye, mid-dilated pupil, nausea-vomiting, diaphoresis, blurred vision ,
halos increased IOP, hard eye
o Physical Exam ~ circumlimbal injection, steamy cornea (corneal clouding), fixed mid-dilated pupil,
decreased visual acuity, tearing, increased IOP of 40-70 mmHg (normal = 10-20 mmHg)
o The anterior chamber is narrowed. Intraocular pressure is acutely elevated
o Diagnosis unilateral red eye with vomiting is angle-closure until proven otherwise, refer urgently
o Common medications can precipitate an attack:
Topical anticholinergic or sympathomimetic dilating drops
TCAs Amitriptyline
MAOs Hydralazine
Antihistamines Benadryl
Nasal decongestants
SSRIs Citalopram
Antipsychotics Haloperidol, lithium, paroxetine
Migraines Topiramate
Nebulized Bronchodilators
- Treatment:
o Immediate referral!!!
o Start IV carbonic anhydrase inhibitor (i.e., acetazolamide), topical beta-blocker, and osmotic
diuresis (i.e., mannitol)
Mydriatics should NOT be administered to these patients
o Initial treatment is reduction in IOP
Timolol, apraclonidine, and acetazolamide (this last one is contraindicated in sickle cell
patients and those with sulfa allergies)
These all block production of aqueous humor
If IOP > 50 mmHg, vision loss is severe, or patient cannot tolerate PO, then IV
acetazolamide is given
If IOP does not decrease and vision does not improve in 1 hour, then give mannitol
Once the IOP drops below 40 mmHg, can give pilocarpine (facilitates the outflow of
aqueous humor)
Pilocarpine is contraindicated in aphakic and pseudophakic patients, or when
there is a mechanical closure of the angle
o Laser therapy (iridoplasty) or anterior chamber paracentesis given immediately can be first-line
treatment in these patients!!!!!
o Definitive treatment is laser peripheral iridotomy or surgical peripheral iridectomy
Pulmonary Embolism
- Arises from thrombi in the systemic venous circulation or the right side of the heart, from tumors that have
invaded venous circulation, and other sources
o More than 90% originate as clots in the deep veins of the lower extremities
o Others include air emboli from central lines, amniotic fluid from active labor, and fat from long bone
(femur) fracture
- Risk factors = Virchow Triad hypercoagulable state, venous stasis, vascular intimal injury or inflammation
o Specific risks include surgical procedures, cancer, oral contraceptives, pregnancy
- 50-60% of patients with DVT experience PE

o Half are asymptomatic PE is often found on autopsy

o Symptomatic PE is serious and fatal (3rd leading cause of death in hospitalized patients)
- Symptoms sudden onset of pleuritic chest pain, dyspnea, apprehension, cough, hemoptysis, diaphoresis
- Signs tachycardia, tachypnea, crackles, accentuation of pulmonary component of second heart sound,
low-grade fever
o Homans sign lacks sensitivity and specificity
- Diagnostic Studies:
o Spiral CT has replaced V-Q scan as the initial method of identifying PE
o ABG shows acute respiratory alkalosis secondary to hyperventilation
o EKG shows tachycardia and nonspecific ST-T wave changes
The classic S1Q3T3 pattern, indicated cor pulmonale, is seen in less than 20% of patients
with symptomatic PE
o CXR may show nonspecific abnormalities such as basilar atelectasis
Main purpose of obtaining CXR is to rule out other abnormalities and to aid in interpreting
the V-Q scan
o V-Q scan of the lungs shows perfusion defects with normal ventilation
Normal scan rules out a clinically significant thromboembolism
Nondiagnostic scans warrant further imaging
o Measuring plasma D-dimer may be useful to rule out PE if clinical suspicion is low and D-dimer is
negative
o Pulmonary angiography remains the definitive test for diagnosis but is reserved for cases in which
the diagnosis is uncertain after noninvasive testing
- Management:
o Anticoagulation therapy is initiated
Heparin is the anticoagulant of choice
LMWH (enoxaparin) or warfarin is continued after the acute phase
o Duration of therapy depends on the clinical situation
3 months is the minimum
o IVC filter is helpful in those with high risk of recurrence who cannot tolerate anticoagulants
o Prevention is key!
Early ambulation, pneumatic compression stockings, low-dose heparin and LMWH
Acute Respiratory Distress / Failure
- ARDS denotes acute hypoxemic respiratory failure following a systemic or pulmonary insult without
evidence of heart failure.
- Decreased arterial PaO2/FiO2 ratio < 200 mmHg
- Three clinical settings account for 75% of ARDS cases sepsis syndrome (the single most important),
severe multiple trauma, and aspiration of gastric contents. Other causes include shock, toxic inhalation,
near-drowning, and multiple transfusions
- Common risk factors for ARDS:
o Sepsis, aspiration of gastric contents, shock infection, lung contusion, non-thoracic trauma, toxic
inhalation, near-drowning and multiple blood transfusions.
o About 1/3 of ARDS patients have sepsis syndrome.
- The underlying abnormality in ARDS is increased permeability of the alveolar capillary membranes, which
leads to development of protein-rich edema
- Clinical Findings:
o Rapid onset of profound dyspnea that usually occurs 12-48 hours after the initiating event.
o Labored breathing
o Tachypnea

o
o
o
o
o

Frothy pink or red sputum

Intercostal retractions
Diffuse crackles
** A quiet chest, agitation or confusion are ominous signs of impending respiratory failure
Many patients are cyanotic with increasingly severe hypoxemia that is refractory to administered
oxygen

Diagnostic Tests:
o CXR may be normal at first. Usually shows diffuse or patchy bilateral infiltrates (tend to be
peripheral and spare the costophrenic angles) that rapidly become confluent; these
characteristically spare the costophrenic angles.
Air bronchograms occur in about 80% of cases (seen by opacification of surrounding
alveoli)
Upper lung zone venous engorgement is distinctly uncommon.
Heart size is normal and pleural effusions are small or nonexistent.
o Marked hypoxemia occurs that is refractory to treatment with supplemental organ failure,
particularly involving the kidneys, liver, gut, CNS, and cardiovascular system.
Multiple organ failure is common
o Pulmonary capillary wedge pressure is normal
- Prevention:
o Prophylactic use of PEEP in patients at risk for ARDS has not been shown to be effective. IV
methylprednisolone does not prevent ARDS when given early to patients with sepsis syndrome or
sepsis shock.
- Treatment:
o Identify and treat the underlying cause.
o Supportive care is also required to compensate for the severe respiratory dysfunction. Oxygen
should be delivered via endotracheal intubation with positive pressure ventilation and low levels of
positive end-expiratory pressure (PEEP). Hypoxia is often refractory to treatment
The lowest levels of PEEP and supplemental oxygen required to maintain PAO2 above 55
mmHg or the SaO2 above 88% should be use.
o Efforts should be made to decrease FIO2 to less than 60% as soon as possible in order to avoid
oxygen toxicity.
o PEEP can be increased as needed as long as cardiac output and oxygen delivery do not decrease
and airway pressures do not increase excessively.
o Prone position may transiently improve oxygenation in selected patients by helping recruit
atelectatic alveoli; however, great care must be taken during the maneuver to avoid dislodging
catheters and tubes.
- Course and Prognosis:
o Mortality rate is 30-40%
o If ARDS is accompanied by sepsis, the mortality rate may reach 90%.
o of deaths occur within 3 days of onset of symptoms. The remaining occur within 2 weeks of
diagnosis and are caused by infection and multiple organ failure
o The major causes of death are the primary illness and secondary complications such as multiple
organ system failure or sepsis. Median survival is 2 weeks.
o Many patients who succumb to ARDS and its complications die after withdrawal of support.
o Most survivors of ARDS are left with some pulmonary symptoms (cough, dyspnea, sputum
production), which tend to improve over time.
Pneumothorax
- The accumulation of air in the pleural space
- The cause may be spontaneous (primary pneumothorax), traumatic, or iatrogenic
o Ruptured bleb, trauma, injured bronchus or esophagus
o Smoking is the most common risk factor for spontaneous pneumothorax
- Pleural rupture results in entry but not exit of air in the pleural space
o Inspiration results in a greater negative intrapleural pressure, thus further increasing the amount of
air within the pleural space

During expiration, this results in a tension pneumothorax, which causes a shift of the mediastinum,,
which decreases venous return and results in results in a decreased cardiac output, cardiovascular
collapse, hypoxemia, and cyanosis
Tall, thin males between 10-30 years old are at greatest risk
TENSION PNEUMOTHORAX is a deadly variant of pneumothorax in which a pulmonary or chest wall
defect acts as a one-way valve, drawing air into the pleural space during inspiration, but trapping it during
expiration.
o Results from positive pressure in the pleural spaces leading to decreased venous return,
hypotension, and hypoxia
o May be secondary to a sucking chest wound or a pulmonary laceration, infection, CHF, and
positive-pressure mechanical ventilation
o Pathophysiology:
Ipsilateral lung collapse secondary to an increased amount of trapped air on the affect
side
Shift of the mediastinum away from the injured lung
Impaired venous return leading to decreased cardiac output
o Characterized by acute onset of ipsilateral chest pain (pleuritic) and dyspnea
Hallmark of tension PTX = hypotension, tracheal deviation away from the side of the
pneumothorax, and hyperresonance on the affected side
Respiratory distress and falling O2 saturations may be ominous and lead to shock or death
o Physical findings depend on the size of the pneumothorax and may include unilateral chest
expansion, decreased tactile fremitus, hyperresonance, and diminished breath sounds on the
involved side
May be cyanotic
May have a crunching sound (Hammans sign) with mediastinal emphysema
Distended neck veins
o Tension pneumothorax is associated with a mediastinal shift to the contralateral side and impaired
ventilation, leading to cardiovascular compromise
Neck-vein distention, and the trachea and cardiac apex are deviated toward the
uninvolved side
o Most pneumothoraces can be seen on a PA CXR taken on inspiration. Air is seen as a hyperlucent
spaced devoid of pulmonary markings in the periphery of the hemithorax.
If no pneumothorax is seen on inspiratory and patient is still suspicious, get expiratory
(expiration reduces lung volume and increases the radiographic density of the lung,
thereby increasing the contrast between the lung and the air in the pleural space)
o Expiratory CXR reveals the presence of pleural air. A visceral pleural line may be the only
evidence of a small pneumothorax
o ABG analysis, if done, reveals hypoxemia
o Small pneumothorax resolve spontaneously
o For severely symptomatic or large pneumothorax, chest tube placement is performed
o Tension pneumothorax is a medical emergency. If it is suspected, a large-bore needle should be
inserted to allow air to move out of the chest (2nd or 3rd intercostal space at the midclavicular line on
the side of the pneumothorax). Placement of chest tube follows the decompression
o Patients should be followed with serial CXR every 24 hours until resolved
o Administer fluids to increase venous return to the heart
o

SPONTANEOUS PNEUMOTHORAX:
o Primary:
Occurs in patients without known lung disease
Result of a ruptured bleb, most commonly at the apices of the upper lobes
Patients tend to be young adults (85% are < 40 years) that are tall and thin
Higher incidence among smokers
20-50% recurrence rate
o Secondary:
Most common etiology is COPD
Patients tend to be older (45-65 years) and have a higher morbidity and mortality
Other causes malignant neoplasms, tuberculosis, Pneumocystis jiroveci
o Iatrogenic = secondary to invasive procedures
o Unilateral pleuritic chest pain and dyspnea, tachycardia, diminished/absent breath sounds,
hyperresonance to percussion, and decreased tactile fremitus
Chest wall crepitus and tenderness
o CXR shows a visceral pleural line and/or lung retraction from the chest wall (best seen with an endexpiratory film in an upright position)
o Treatment:
Small ones can be observed. Monitor and repeat CXR in 48 hours
May allow to resolve spontaneously with 100% O2 by face mask
o The air in a pneumothorax contains roughly 78% nitrogen. By giving
100% O2, you decrease the partial pressure of nitrogen in the patients
blood, thereby establishing a diffusion gradient
You create an O2 diffusion gradient in the other direction as
well, but the O2 diffuses more slowly and is quickly absorbed
by surrounding tissues
Approximately 1.25% of all intrapleural air is absorbed daily from the pleural
cavity, so it will take weeks for the lungs to fully expand
If the pneumothorax grows or symptoms develop, admit for thoracostomy (chest)
tube
Needle or small-catheter aspiration of risky difficult to reexpand the lung fully, cannot
use with an active leak, unsuccessful in 70% of patients
Most successful therapy thoracostomy tube
4th or 5th intercostal space in the anterior axillary fold or the 2nd or 3rd interspace in
the midclavicular line
It results in complete re-expansion of the lung, resulting in adherence between
the visceral and parietal pleurae
Also results in an inflammatory reaction, which obliterates the pleural space
In healthy and compliant patients, after complete re-expansion of the lung, a
Heimlich valve can be attached to the tube, and then the tube can be removed in
3-4 days
o Patients with severe underlying pulmonary disease, incomplete reexpansion of the lung, and a continuous air leak, cannot be treated with
this technique
Surgical indications persistent air leak for more than 72 hours, a second recurrence,
hemothorax, empyema, a previous contralateral pneumothorax, and bilateral
simultaneous pneumothoraces

Patients with high-risk occupations, such as airline pilots and scuba divers, and
those that live in remote areas, should have surgery after the first episode
Some larger ones may be pleurodesis

Angina Pectoris
- SEE CARDIOLOGY
Myocardial Infarction
- SEE CARDIOLOGY
Cardiac Arrest
- SEE CARDIOLOGY
Cardiac Arrhythmias and Blocks
- SEE CARDIOLOGY
Cardiac Failure
- SEE CARDIOLOGY
Hypertensive Crisis
- Hypertensive Urgency blood pressure that must be reduced within hours.
o Systolic pressure is usually greater than 220, or diastolic is greater than 125
o No e/o acute or progressive (change from baseline) TOD
o Absence of raised intracranial pressure
o Short term Rx with oral meds = labetalol, clonidine, or captopril + OP f/u within 72 hours
- Hypertensive Emergency blood pressure that must be reduced within 1 hour to prevent progression of
end-organ damage or death
o Diastolic pressure is usually greater than 130
o Evidence of rapidly PROGRESSIVE TOD (example MI, pulmonary edema, renal failure)
o Optic disc edema (papilledema) indicates presence of end-organ damage
o Complications hypertensive encephalopathy, nephropathy, intracranial hemorrhage, aortic
dissection, preeclampsia or eclampsia, pulmonary edema, unstable angina, MI in the presence of
strikingly elevated pressure
o Requires immediate, gradual reduction of BP (NOT to normal range)
o Goal of Treatment = controlled, gradual lowering of BP (not too quickly)! Admit and treat with IV
anti-hypertensives (vasodilators or adrenergic inhibitors). 10% decrease in first hour, then 15%
over the next 3-12 hours to BP of no less than 160/110
Rapid correction of BP to normal levels puts patient at high risk for worsening cerebral,
renal, or cardiac ischemia (can precipitate a heart attack)
Watershed infarct = dramatic dropping of infusion of your brain that occurs if you reperfuse the brain too quickly. A type of stroke
- Complications of untreated HTN cardiovascular disease, cerebrovascular disease, dementia, renal
disease, aortic dissection, atherosclerotic complications
- Clinical Features:
o Examine for evidence of papilledema, retinal exudates, neurologic
deficits, seizures, or encephalopathy.
o Assess for carotid bruits, heart murmurs, gallops, asymmetrical
pulses or unequal blood pressures, pulsatile abdominal masses, and
pulmonary rales.
o In the pregnant patient ~ hyperreflexia and peripheral edema
preeclampsia
- Diagnostic Tests:
o Urinalysis look for hematuria, proteinuria, red cell casts or elevations in BUN, Creatinine and K
levels.

EKG ST and T wave changes, consistent with coronary ischemia, electrolyte abnormalities, or
LVH
o CXR congestive heart failure or aortic dissection
o CT if neurological compromise. Can show ischemic changes, edema, or blood.
o Urine or Serum drug screen can identify illicit drug use
o HCG done on all hypertensive women of childbearing potential
- Treatment:
o O2 supplementation
o Cardiac monitoring
o IV access
o Treatment goal is to reduce arterial pressure gradually with attention to therapeutic goal.
If you decrease the BP too rapidly, this may lead to cerebral ischemia
o Preferred agents sodium nitroprusside and, if MI is present, nitroglycerin or a -blocker.
Other acceptable agents = nicardipine, enalaprilat, diazoxide, trimethaphan, and loop
diuretics
Aortic dissection calls for nitroprusside and a blocker, usually labetalol or esmolol, and
urgent surgery
Fenoldopam, a dopamine-1 receptor agonist, appears to be useful in the setting of acute
renal failure
Hydralazine is the preferred agent during pregnancy
Oral agents for less severe emergencies include clonidine, captopril, and nifedipine
- Malignant Hypertension elevated blood pressure associated with papilledema and either encephalopathy
or nephropathy. If untreated, progressive renal failure occurs
o Type of hypertensive EMERGENCY
o Papilledema must be present!!
o Usually accompanied by other end organ damage
o Most common in young adults, prior renal disease, African American males, pregnancy or in
collagen vascular disease
Acute Gastrointestinal Bleed
- Consider life-threatening until proven otherwise
- Upper GI bleed is more common than lower GI bleed
o Upper GI Bleed originating proximal to the ligament of Treitz
PUD, erosive gastritis and esophagitis, esophageal and gastric varices, Mallory-Weiss
syndrome
o Lower GI Bleed originating distal to the ligament of Treitz
Diverticular disease*, colitis, adenomatous polyps, malignancies
Less commonly = vascular ectasia (AV malformation and angiodysplasia), Meckel
diverticulum, IBD, trauma
- Complain of hematemesis, hematochezia, or melena
o Others present with hypotension, tachycardia, angina, syncope, weakness, and confusion
- Hematemesis or coffee-ground emesis suggests an upper GI source
- Melena suggests a source proximal to the right colon
- Hematochezia indicates a more distal colorectal lesion, however, approximately 10% of hematochezia may
be associated with an upper GI bleed
- Weight loss and changes in bowel habits are classic symptoms of malignancy
- Vomiting and retching, followed by hematemesis, is suggestive of a Mallory-Weiss tear
o A history of medication or alcohol use should be sought
This history may suggest PUD, gastritis, or esophageal varices
o

Spider angiomata, palmar erythema, jaundice, and gynecomastia suggest underlying liver disease
Ingestion of iron or bismuth can simulate melena, and certain foods, such as beets, can simulate
hematochezia
o However, stool heme (guaiac) testing will be negative

Diagnosis and Differential:

o A careful ENT exam can exclude swallowed blood as a source
o NG tube placement and aspiration may detect occult upper GI bleeding
A negative NG aspirate does not exclude upper GI source
o A rectal exam is mandatory
o If significant bleed, get type and crossmatch
o Other important tests CBC, electrolytes, BUN, creatinine, glucose, coagulation studies, LFTs
The initial hematocrit may not reflect the actual amount of blood loss
Upper GI bleeding may elevate the BUN level
o Routine abdominal radiographs are of limited value
o Controversy over the initial diagnostic procedure angiography, scintigraphy, colonoscopy, CT
- Emergency Management:
o Stabilization ABCs, oxygen, 2 large-bore IVs
o Replace volume loss immediately with isotonic crystalloids (NS or LR)
o Make transfusion decisions based on clinical factors (continued active bleeding and no
improvement in perfusion after 2 liters of fluid) rather than initial hematocrit values
The threshold for transfusion should be lower in the elderly
o Replace coagulation factors as needed
o NG tube if significant bleeding, regardless of the presumed source
If bright red blood or clots are found, perform gentle gastric lavage
No NG tube if you cannot rule out esophageal varices or Mallory-Weiss tear
o Consider therapeutic endoscopy for upper GI bleed
o Flexible sigmoidoscopy or colonoscopy can aid in diagnosis of some lower GI bleeding sources
Estimated 80% of lower GI bleeds resolve spontaneously
o PPIs (pantoprazole 80 mg bolus followed by 8 mg/hr) reduce rebleeding and the need for
surgery for the treatment of bleeding peptic ulcers and are recommended as adjuncts to
endoscopic therapy.
Usually always initiated with upper GI bleed
H2RAs are NOT beneficial in acute upper GI bleed
o Consider octreotide for patients with uncontrolled bleeding awaiting endoscopy or when endoscopy
is unsuccessful
o Surgery and gastroenterology consults for ALL uncontrolled bleeding
Acute Abdomen
- By definition, acute abdomen implies severe abdominal pain arising rather suddenly and of less than 24
hours duration
o Location is important:
o Foregut structures cause EPIGASTRIC pain stomach, pancreas, duodenum, and biliary tree
o Midgut structures cause PERIUMBILICAL pain small bowel, right and transverse colon
o Hindgut structures cause HYPOGASTRIC pain left colon, sigmoid, rectum
- Nerves to the parietal peritoneum:
o Sensory pathways for visceral pain are present in the lower thoracic and lumbar splanchnic nerves
and in the parasympathetic nerves of the vagus and sacral plexus
- Two types of pain:
o Steady, well-localized pain that usually occurs after ischemia, perforation, inflammation, or
hemorrhage
o Intermittent, colicky, poorly localized pain found with obstruction of the GI tract
- Timing is important:
o Sudden onset of excruciating pain perforation, rupture, or ischemia of a visceral organ

Pain of gradual onset suggests a subacute process PUD, gastritis, cholecystitis, IBD,
diverticulitis

Physical exam is important

o Auscultate:
Absence of bowel sounds means ileus
High-pitched sounds with splashes, tinkles, and rushes, especially in the presence of
distention, indicate SBO
o Percuss to determine the amount of distention
o Rebound tenderness suggests peritoneal irritation
o Rectal and pelvic exams may also be important
Lab tests CBC is the most important
o Increased WBC and left shift indicates an inflammatory process, but the absence of it does not
exclude
o Elevated hematocrit can suggest dehydration
o Anemia can suggest chronic bleeding
o Serum electrolytes may show hypokalemia (during vomiting or diarrhea)
o Serum bicarbonate and anion gap can demonstrate acid-base disturbances
o If suspected biliary disease, check LFTs
o Check amylase and lipase if pancreatic involvement
o Check urinalysis on all patients and pregnancy test on women of child-bearing age
Imaging:
o Standard series of films supine an upright abdominal, standard CXR
Presence of free air can be determined on CXR
Supine and upright abdominal films can reveal intestinal obstruction and the presence of
air-fluid levels
Can also find fecaliths (appendicitis) and kidney stones
o Ultrasound can detect solid organs, free fluid in abdomen, degree of ascites
Duplex ultrasound can also assess vascular structures such as a ruptured or leaking
aortic aneurysm, AV fistula, venous thrombi
o CT can assess all solid organs (intraabdominal and retroperitoneal)
In the diagnosis of hollow organs, such as the small and large intestine, you can evaluate
bowel-wall thickness and the presence of air within the bowel wall as well as the
mesentery
Superior to other radiographic modalities in assessing abnormalities in the kidneys,
pancreas, duodenum, and aorta
Can also detect small amounts of free air in the abdomen, much less than that required in
an upright CXR
o MRI not really used since it is expensive and time consuming. But good for soft-tissue
structures
o Angiography usually used for therapeutic reasons. Can confirm diagnoses
o Barium Studies role has diminished since ultrasound and CT are less invasive
Still useful for colonic carcinoma, volvulus, and determining the extent of mucosal disease
in colitis
o Radionucleotide Scans helpful in localizing the site of a GI bleed
Abdominal scintigraphy with 99mTc (sulfur colloid or labeled RBCs)
Can detect bleeding rates as low as 0.1 mL/min (more sensitive that angiography)
o Endoscopy direct visualization of the GI tract. Diagnostic and therapeutic
Upper endoscopy can visualize bleeding peptic and duodenal ulcers, as well as outlet
obstruction from tumors or strictures

Colonoscopy can reveal inflammation of the colon, neoplasms, intussusception, and

volvulus

Laparoscopy and Laparotomy:

o Laparoscopy is most commonly used for an unclear diagnosis of appendicitis, especially if pelvic
disease is in the DDX
Also for patients with acute cholecystitis as the initial disease approach
o Laparotomy is the final pathway in many with acute abdominal pain
When the patient shows signs of peritonitis or the diagnosis is unclear with a worsening
clinical picture, abdominal exploration via midline laparotomy is the final option
Common Conditions Leading to an Acute Abdomen:
o Peritonitis (GI tract perforation)
Diffuse, severe abdominal tenderness
Guarding and rigidity on physical exam
Absent bowel sounds
Quickly develop systemic sepsis
Upright KUB or CXR will show free intraperitoneal air under the diaphragm
Bring to OR for exploratory laparotomy
o Appendicitis
Mild fever and focal RLQ (McBurneys point) pain with rebound tenderness
Anorexia, nausea, vomiting are common in early disease
Pain may begin periumbilically
Moderate leukocytosis
Mandatory to do pelvic and rectal exams
Fecaliths on plain films
CT has become more widely used instead of ultrasound
o Acute Pancreatitis
Rapid onset of severe epigastric pain, radiates to back
Anorexia, nausea, vomiting
Rebound tenderness not uncommon
Hypoactive or absent bowel sounds
Order CBC (to determine elevated WBC or decreased hematocrit due to hemorrhage),
amylase, lipase
CT with oral and IV contrast to determine presence of pseudocysts, necrosis, or masses
in the gland
Usually supportive medical care. Surgery if there is infection or severe pancreatic
necrosis
o Cholecystitis
Usually in women 40-60 years who are overweight and previous history of pregnancy
Hard to differentiate from biliary colic
RUQ pain accentuated by inspiration (Murphys sign) and accompanied by nausea and
vomiting
Febrile, distended abdomen, guarding
Order CBC, LFTs, amylase, lipase
Ultrasound is test of choice to evaluate gallbladder and biliary tree
Often find gallstones and thickened-wall gallbladder with pericholecystic fluid
Evaluate biliary tree to detect dilated ducts or intraductal stones
HIDA scans (hepatobiliary iminodiacetic acid) can suggest acute cholecystitis if the cystic
duct is occluded and the gallbladder fails to take up the radiolabeled bile
Laparoscopic approach is safe in both acute and chronic settings

Diverticulitis
Usually in the left and sigmoid colon (although diverticulosis can be anywhere)
Sigmoid diverticulitis usually causes LLQ pain with fever and chills
Tenderness to palpation. Occasionally a palpable mass in the case of a phlegmon
CT with oral contrast is diagnostic
Emergency surgery with signs of perforation and significant abscess formation
Small-Bowel Obstruction
Nausea, bilious vomiting, distention
Sharp, colicky abdominal pain
In advanced disease tachycardia, hypotension, fever
Abdominal distention on exam, as well as high-pitched bowel sounds and a tympanitic
abdomen
Labs may show hypochloremic, hypokalemia, metabolic alkalosis
Supine and upright abdominal films useful to show dilated loops of small bowel and airfluid levels
CT or upper GI series can show a lead point for obstruction
Can be initially treated with nonoperative course such as bowel rest and NG suction
Large-Bowel Obstruction
Constipation and abdominal distention
Pain is gradual in onset
Most common causes colon carcinoma, acute diverticulitis, volvulus
Abdominal tenderness and distention on physical exam
Plain films of abdomen and retrograde contrast studies can help localize site of
obstruction
For volvulus, colonoscopy is both diagnostic and therapeutic
Mesenteric Ischemia:
Sudden onset of severe abdominal pain
Nausea, vomiting, diarrhea, GI bleeding
Classic finding pain out of proportion to the amount of tenderness elicited by
abdominal palpation
At risk for sudden development of sepsis (hypotension, tachycardia, hypovolemia)
Plain films are nondiagnostic
CT can reveal thickened loops of affected bowel with air in the bowel wall (pneumatosis)
Once resuscitated, taken to OR for exploratory laparotomy and removal of disease bowel
Ruptured Aortic Abdominal Aneurysm
Abdominal pain accompanied by back or flank pain
Often first seen in shock and are hypovolemic
On exam pulsatile supraumbilical mass is present
Patients with known aneurysm who have abdominal pain, shock, and pulsatile mass are
presumed to have ruptured
Ultrasound, CT, and angiography can confirm diagnosis but too time consuming
Surgery is vital
Gynecologic Causes:
The most life-threatening is ruptured ectopic pregnancy
Another common cause is PID (ages 15-35 years)
Crampy lower-quadrant abdominal pain and high fever
Pelvic exam shows hyperemic, extremely tender cervix with vaginal discharge

 Positive diagnosis can be made with a cervical smear and culture

Ultrasound is used to diagnosis tuboovarian abscess
Other causes ovarian cysts, endometriosis, ovarian torsion, ruptured uterus
Nonsurgical Causes

o
Seizures
- SEE NEUROLOGY
Shock
- Shock is severe cardiovascular failure caused by poor blood flow or inadequate distribution of flow
- Inadequate oxygen delivery to body tissues results in shock, which may lead to organ failure and death
unless a cause can be rapidly identified and treated
- The physical responses to shock are mediated by catecholamines, renin, antidiuretic hormone, glucagon,
cortisol, and growth hormone
- The cardinal signs of shock are simultaneous tachycardia and hypotension
- Shock may result from multiple causes:
o HYPOVOLEMIC SHOCK is caused by hemorrhage, loss of plasma, or loss of fluid and
electrolytes, resulting in decreased intravascular volume. This may be caused by obvious loss or
by third-space sequestration
The 2 major causes are hemorrhage and dehydration
o CARDIOGENIC SHOCK may arise from MI, dysrhythmias, heart failure, defects in the valves or
septum, hypertension, myocarditis, cardiac contusion, rupture of the ventricular septum, or
cardiomyopathies
Due to inability of the heart to adequately pump blood to the body owing either to intrinsic
dysfunction or to extrinsic factors
Intrinsic hear dysfunction is known as cardiogenic shock or CHF
Extrinsic factors = pericardial effusions leading to cardiac tamponade, tension
pneumothorax, and massive PE
o OBSTRUCTIVE SHOCK can be caused by tension pneumothorax, pericardial tamponade,
obstructive valvular disease, and pulmonary problems, including massive pulmonary embolism
o DISTRIBUTIVE SHOCK is shock caused by poorly regulated distribution of blood volume. Think of
misdristribution of blood due to inappropriately low systemic vascular resistance (SVR). The
major causes are septic, neurogenic, and anaphylactic
SEPTIC SHOCK the most common cause
Mortality rate of 30-87%
Most often associated with Gram-negative sepsis in persons at the extremes of
age, persons with diabetes or immunosuppression, or those who have recently
had an invasive procedure
SYSTEMIC INFLAMMATORY RESPONSE SYNDROMES (signs of systemic
inflammation without end organ damage
ANAPHYLAXIS
NEUROGENIC SHOCK causes include spinal cord injury or adverse effects of spinal
or epidural anesthesia
- Signs and symptoms of shock include low blood pressure, orthostatic changes, tachycardia, peripheral
hypoperfusion, altered mental status, oliguria or anuria, insulin resistance, and metabolic acidosis
o The actual BP reading in shock is not as important as the decrease in BP compared to the usual
BP for the individual patient
o The hematocrit in acute blood loss is normal, but patients will have tachycardia (and in severe
cases, hypotension)
- End-organ hypoperfusion usually results in cool or mottled extremities, diminished capillary refill, and weak
(thready) or absent peripheral pulses

Mental status may remain normal, or the patient may be agitated, restless, confused, obtunded, or
comatose
Considering the various etiologies of shock, the evaluation and management of the patient in acute shock
involves assessment of volume status, SVR (afterload), and cardiac output
o PCWP = preload

Diagnostic Studies:
o All patients require CBC, blood type and cross-match, and coagulation parameters
o Electrolytes, glucose, urinalysis, and serum creatinine will aid in determining the cause of shock
o Pulse oximetry or serial arterial blood gases are needed to monitor oxygenation
o EKG and cardiac biomarkers (troponins, BNP, NT-proBNP) may be useful
o Lactate levels can assist in identifying shock as well as monitoring treatment
o Considering the various etiologies of shock, the evaluation and management of the patient in acute
shock involves assessment of volume status, SVR, and cardiac output
- Treatment must address both the specific cause and the manifestations of shock
o The first step in treatment is attention to basic life support (airway, breathing, circulation)
o Specific treatments depend on the cause of shock
o The Trendelenburg or supine position with legs elevated may maximize blood flow to the brain
o Oxygen and IV fluids are essential
Almost all types of shock have a key treatment of fluid resuscitation (except cardiogenic)
o Urine flow should be monitored via indwelling catheter and sustained at 0.5 mL/kg/hr or more
o Continuous cardiac monitoring is preferable to intermittent cardiac monitoring. Central venous
pressure monitoring, pulmonary artery catheters, and capillary wedge pressure monitoring should
be considered for critically ill patients. However, less invasive techniques to monitor cardiac
output, such as TEE, transthoracic bioimpedance, pulse contour techniques, capnography, and
thermodilution techniques, are supplanting cardiac venous monitoring in some patients
o Inotropes (i.e., dobutamine, dopamine, epinephrine) increase cardiac output by increasing heart
rate and contractility
o Pressors (i.e., dopamine, phenylephrine) improve pressure by increasing vascular tone
Hypovolemic Shock
- Due to any process that depletes intravascular volume
o Hemorrhage (abdomen, pelvis/retroperitoneum, thorax)
Identify source FAST abdominal ultrasound, NG tube for upper GI bleed, stool guaiac
to rule out lower GI bleed, pregnancy test, CXR, pelvic x-ray
o Dehydration
Most commonly due to protracted diarrhea, vomiting, overdiuresis, or fluid restriction
o Third spacing
Shifting of intravascular volume into the interstitial space or other compartments
Occurs secondary to burns, trauma, acute pancreatitis, and/or liver disease
- Presentation depends on the degree of volume loss
o Mild (10-20% loss) = patient feels cold, orthostatic hypotension, flat neck veins, pale/cool skin
o Moderate (20-40% loss) = thirsty, tachycardia/hypotensive, oliguric
o Severe (>40% loss) = altered mental status (agitation leading to obtundation), severe hypotension,
tachycardia, tachypnea
- Decreased central venous pressure and increased SVR are also seen
o Decreased cardiac output
- The goal of treatment is restoring intravascular volume
o Oxygen, 2L of IV crystalloids, may need blood products
o Watch lactate levels
o May need to give IV pressors (norepinephrine lowest risk of arrhythmia)
Other options = dopamine, vasopressin, or lastly epinephrine

Cardiogenic Shock
- Etiologics = arrhythmias and MI, vascular disease, myocarditis, cardiomyopathy
- There is a spectrum between CHF and frank cardiogenic shock
- Lactate levels (elevation) allow you to assess tissue hypoxia
- Tachycardia, hypotension, tachypnea, JVD, peripheral edema
o S3 with rales
- Increased central venous pressure, decreased PCWP
- Increased SVR, decreased cardiac output
- EKG abnormalities
- Therapy should be directed at the underlying cause and maintaining adequate BP.
o Inotropes = dopamine is the pressor of choice (increases contractility)
Norepinephrine
Dobutamine (if not hypotensive)
o Vasodilators = nitroglycerin. Decrease preload and afterload, leading to decreased myocardial
work
o Diuretics = decrease preload
o Antiarrhythmics may also be considered
o Surgical intervention = intra-aortic balloon pump (increased cardiac output, decreases afterload,
increases myocardial perfusion)
- Cardiogenic shock is the only form of shock in which fluid resuscitation may actually lead to further failure
Septic Shock
- To meet diagnostic criteria, a patient must fulfill SIRS criteria, have a suspected sources of infection, and
show signs of hemodynamic instability
o SIRS = at least 2 of the following:
Temperature > 38C (> 100.4F) or < 36C (< 96.8F)
Heart rate > 90/min
Respiratory rate >20/min or a PaCO2 < 32 mmHg
WBC count >12,000/mm3, < 4,000/mm3, or the presence of >10% bands
- The patient will have hypotension but will be warm and pink due to vasodilation
- Lactic acidosis supports the diagnosis of septic shock
- Cardiac output is increased, SVR decreased
- Early goal-directed therapy focuses on increasing cardiac output and ensuring tissue oxygenation
- Identify and treat infection with antibiotics (within 1 hour), surgical drainage, and line removal
o Common sources of infection = pneumonia, UTI, soft tissue infections
- Aggressive IV fluids are key, with the use of pressors and blood if needed
Neurogenic Shock
- Due to loss of vascular sympathetic tone, usually secondary to a high cervical spine injury
o Spinal anesthesia can also induce spinal shock
- Hypotension, flat neck veins, normal or slow pulse (no reflex tachycardia), warm/dry skin, decreased rectal
tone, focal neurologic examination
- Increased cardiac output, decreased SVR
- Rule out other etiologies of shock
- IV fluid resuscitation and vasoconstrictors
- High-dose steroids (methylprednisolone)
Coma
- SEE NEUROLOGY

Pericardial Effusion
- Collection of fluid in the sac around the heart which can lead to tamponade.
- Symptoms depend on the rate of accumulation and distensibility of the pericardial sac.
- Patients with symptomatic effusion may present with chest heaviness, dyspnea, cough, and syncope.
- Can progress to life-threatening tamponade
- Physical Exam:
o Tachycardia, narrowed pulse pressure, hypotension, JVD, muffled heart tones, and pulsus
paradoxus.
- Echocardiography is the test of choice demonstrates the size of the effusion and the presence of
tamponade.
- CXR may demonstrate an enlarged cardiac silhouette or pleural effusion.
- ECG:
o Sinus tachycardia, low QRS amplitude, and electrical alternans.
- Emergent ultrasound-guided pericardiocentesis may be required to relieve cardiac tamponade
Cardiac Tamponade
- Defined as fluid accumulation in the pericardium that prevents the heart from adequately filling or
contracting efficiently, thereby decreasing stroke volume
- Tamponade occurs when the pressure in the pericardial sac exceeds the normal filling pressure of the right
ventricle, resulting in restricted filling and decreased cardiac output
- Causes metastatic malignancy, uremia, hemorrhage (excessive anticoagulation), bacterial or tubercular
disorder, chronic pericarditis, and others (e.g., SLE, postradiation, myxedema)
o Can be idiopathic
- Clinical Features:
o The most common complaints are dyspnea and decreased exercise tolerance
o Also nonspecific symptoms weight loss, pedal edema, ascites
o Physical findings tachycardia, low SBP, narrow pulse pressure
Pulsus paradoxus (apparent dropped beats in the peripheral pulse during inspiration)
Neck vein distention
Distant heart sounds
RUQ pain (due to hepatic congestion)
Pulmonary rales are absent
o Becks Triad hypotension, elevated systemic venous pressure (JVP), small/quiet heart
- Diagnosis:
o Low-voltage QRS complexes and ST-segment elevations with PR-segment depression may be
present on the EKG
o Electrical alternans (beat-to-beat variability in the amplitude of the P and R waves unrelated to
inspiratory cycle, QRS complexes in the same lead vary in height) is a classic but uncommon
finding
o CXR may or may not show a large cardiac silhouette
o Echo is the diagnostic study of choice (if time permits)
May use bedside ultrasound for rapid diagnosis
- ED Care and Disposition:
o A true emergency!!!
o Volume expansion with IV bolus of 500-1000 mL normal saline to facilitate right heart filling and to
temporarily improve hemodynamics
o Pericardiocentesis is diagnostic and therapeutic
Pericardial window may be required

Status Epilepticus
- Status epilepticus, either convulsive or nonconvulsive, is diagnosed when seizures fail to cease
spontaneously or recur so frequently that full consciousness is not restored between successive episodes.
The length of time seizure activity must persist to diagnose status epilepticus is general more than 5
minutes.
- Diagnosed when seizures fail to cease spontaneously or recur so frequently that full consciousness is not
restored between successive episodes
- Because of the possibility of permanent brain damage secondary to hyperthermia, circulatory collapse, or
excitotoxic neuronal damage, status epilepticus is a medical emergency
o Immediate management ensure patent airway, including positioning the patient to prevent
aspiration of stomach contents
o Management of hyperthermia, related to increased motor activity and high levels of circulating
catecholamines, may include a cooling blanket or induction of motor paralysis with a
neuromuscular blocking agent
o Diazepam or lorazepam is administered IV until the seizure stops; a loading dose of phenytoin or
fosphenytoin is also given

Internal Medicine Cardiovascular

Congestive Heart Failure
- CHF is a clinical syndrome characterized by abnormal retention of water and sodium. The resulting venous
congestion causes typical symptoms such as dyspnea and edema
- CHF results from pathologic changes in one or more of the following myocardial contractility, structural
integrity of the valves, preload or afterload of the ventricle, and heart rate
- Alterations may result from multiple causes myocardial and pericardial disorders, valvular and congenital
abnormalities
o High-output failure has noncardiac causes (e.g., thyrotoxicosis, severe anemia)
- CHF adversely affects left atrial pressure and cardiac output
- CHF is the final common pathway of essentially every significant pathologic condition affecting the heart
- Most of the time it is left-sided failure (problem with the left ventricle)
- Systolic failure = ejection problem
- Diastolic failure = filling problem
- Clinical Features:
o LEFT-SIDED FAILURE = exertional pulmonary vascular congestion (low cardiac output, elevated
pulmonary venous pressure)
Exertional dyspnea plus cough, fatigue, orthopnea, paroxysmal nocturnal dyspnea, basilar
rales, gallops, exercise intolerance
o RIGHT-SIDED FAILURE = systemic vascular congestion
Distended neck veins, tender or nontender hepatic congestion, decreased
appetite/nausea, dependent pitting edema
Most frequently caused by left-sided failure
Predominant features = peripheral edema and hepatosplenomegaly
o Cardiac signs parasternal lift, enlarged/displaced/hyperdynamic apical impulse, diminished first
heart sound, S3 gallop
S4 gallop in diastolic heart failure
o Sympathetic activity produces pallor and cold, clammy skin
o Nocturia is a common symptom
o Hypotension and a narrow pulse pressure are frequently present
Depending on the etiology of CHF, blood pressure can be normal, elevated, or low
- New York Heart Association Functional Classification of Heart Disease
o Class I no limitation of physical activity. Ordinary physical activity does not cause undue
fatigue, dyspnea, or anginal pain
o Class II slight limitation of physical activity. Ordinary physical activity results in symptoms
o Class III marked limitation of physical activity. Comfortable at rest, but less than ordinary
activity causes symptoms
o Class IV unable to engage in any physical activity without discomfort. Symptoms may be
present even at rest
- Diagnostic Studies:
o Patients may have anemia, renal insufficiency, hyperkalemia, hyponatremia, and elevated liver
enzymes
Those on diuretics may develop hypokalemia
o CXR may show cardiomegaly and bilateral or right-sided pleural effusions, perivascular or
interstitial edema (Kerley B lines), venous dilation and cephalization, and alveolar fluid
o EKG may show nonspecific changes (e.g., low voltage), underlying arrhythmia, intraventricular
conduction defects, LVH, nonspecific repolarization changes, or new or old MI

Echocardiography is the most useful imaging study because it is able to assess size and function
of the chambers, valve abnormalities, pericardial effusion, shunting, and segmental wall
abnormalities.
Also used to determine and monitor the ejection fraction a key diagnostic and prognostic
indicator in CHF
EJECTION FRACTION = a way to quantitate contractility EF% = SV / EDV normal =
~50-75%. If you cannot pump blood forward, it will eventually catch up to you, because
every time you pump blood forward you have the same EDC
o Serum BNP or N-terminal pro-BNP is usually elevated
Secreted from ventricles in response to elevated ventricular filling pressures
Promotes salt and water excretion by kidneys; results in arterial vasodilation
Ineffective against sympathetic and renin-angiotensin effects
Clinically useful in diagnosing CHF may be elevated
Falsely elevated in renal failure
Also test cardiac markers to evaluate for MI
o Stress imaging or radionuclide angiography may be indicated to assess cause or severity of
disease
o Cardiac catheterization is indicated if atherosclerosis is suspected
Catheterization can also visualize the ventricle and determine cardiac output
o Older patients should have thyroid function testing
o Iron studies indicated in suspected cases of CHF due to hemochromatosis
Treatment:
o The key management principle is the recognition and treatment of reversible causes of CHF
o Progressive aerobic exercise, low-sodium diet, tobacco cessation, alcohol cessation, stress
reduction
o Initial therapy in most is ACE inhibitors decrease left ventricular wall stress and slow myocardial
remodeling and fibrosis
If not tolerated, use ARBs
o Beta-blockers may also be useful as they have been shown to improve ejection fraction, reduce left
ventricular dilation, and reduce the incidence of dysrhythmia
o Aldosterone receptor antagonists have also been proven to be useful in combination
o As symptoms progress, right-sided heart failure with fluid retention, sodium retention, and edema
may develop
Thiazide or loop diuretics will need to be added
Alternative = potassium-sparing diuretics, direct inotropic agents (i.e., digitalis), and
arterial and venous vasodilators
Diuretic therapy reduces fluid volume and relieves symptoms
o Calcium channel blockers, preferably amlodipine, are used only to treat associated angina or HTN
o Controlling the ventricular rate and restoring sinus rhythm have been found to improve
hemodynamics in patients with CHF and afib
o Implantable cardioverter-defibrillators (ICDs) are indicated when the ejection fraction falls below 35.
Biventricular pacing is indicated in order to resynchronize the heart when QRS becomes
prolonged
o Coronary revascularization in the presence of reversible ischemia
o In severe cases refractory to therapy, mechanical support with a ventricular device or intra-aortic
balloon pump may be used as a bridge to cardiac transplantation
o

Decompensated CHF:
- ACUTE or ACUTE ON CHRONIC patient is clinically deteriorating or unstable
- Recognize signs and symptoms ASAP
o VITALS tachycardia, tachypneic, use of accessory muscles, BP hypertensive or hypotensive
(ominous sign, can worsen an already poor CO), HR
o SYMPTOMS severe SOB, rales, hypoxic, cyanotic, pale, chest pain, cool or not perfused, poor
pulses, diaphoretic, distressed, poor mental status, pink/frothy sputum
- Aggressive therapy ~ treat early!
o Eliminate or control inciting factors
o Tests to determine causes EKG to r/o ischemia, atrial, or other arrhythmia
o Examine ? new murmur, rales
o Echo to assist diagnosis
o CXR to assess pulmonary edema (the most likely exacerbation of chronic HF)
Can also develop acute pulmonary edema with no prior HF!! CAUSES = MI or severe
ischemia, acute valvular regurgitation (MR, AI), HTN / Renovascular disease, end stage
valvular stenosis (AS, MS), systemic illness (sepsis, anemia, thyrotoxicosis, severe
respiratory illness), NEVER overlook other causes (PE, MI)
TREATMENT diuretics (natriuretics), oxygen (CPAP or BiPAP), morphine if
appropriate, nitrates (vasodilators), inotropes (dobutamine, milrinone), hold / dont initiate
a beta blocker, use ACE / ARB or other afterload reduction, mechanical interventions
(balloon pump), determine and treat underlying cause
- ACUTE PULMONARY EDEMA is one of the most critical presentations of the many clinical effects of heart
failure
o Usually present with symptoms of left ventricular heart failure, severe respiratory distress, frothy
pink or white sputum, moist pulmonary rales, S3, or S4
o Patients are frequently tachycardic and hypertensive
o Afib and PVCs are common
o History of DOE, PND, or orthopnea
o Patients with right ventricular hear failure have dependent edema of the extremities and may have
JVD, hepatic enlargement, and hepatojugular reflex
o The traditional distinction between right and left heart failure does not have great bearing on ED
management, as volume overload and respiratory distress will be approached in the same manner
o Diagnosis of acute pulmonary edema is made with clinical findings and CXR
Also can get EKG, serum electrolytes, serum BUN and creatinine, CBC, ABG, BNP,
cardiac markers
Right-sided failure is a clinical diagnosis
Left-sided failure presents as an enlarged cardiac silhouette on CXR
o ED Care and Disposition:
Oxygen 100% by non-rebreather mask to achieve sats of at least 95%
May need CPAP or BiPAP, or even intubation
Preload reducers nitroglycerin
Diuretics furosemide, bumetanide, or torsemide
Afterload reducers nitroprusside, captopril, enalapril
Inotropic agents dobutamine, dopamine, norepinephrine, milrinone

Hypertension
- Primary (essential) hypertension causes 95% of elevated BP. Pathogenesis is multifactorial
o **HEMODYNAMIC HALLMARK OF ESTABLISHED PRIMARY (or ESSENTIAL)
HYPERTENSION IS ELEVATED PERIPHERAL VASCULAR RESISTANCE (PVR)
o Genetic predisposition
o More prevalent with increased age and in blacks
o Second most common cause of chronic kidney disease (>25% of cases) ~ diabetes is #1 cause
o Other hypothesized factors sympathetic nervous system hyperactivity, abnormal cardiovascular
or renal development, imbalance in RAAS system, defects in sodium excretion (natriuresis),
abnormalities in sodium and potassium exchange at the cellular level
o Exacerbating factors excessive alcohol, cigarettes, lack of exercise, polycythemia, use of
NSAIDs, low potassium intake
Exacerbated in males, blacks, sedentary individuals, smokers
o Metabolic syndrome (truncal obesity, hyperinsulinemia and insulin resistance, hypertriglyceridemia,
hypertension) is associated with development of diabetes and increased risk of cardiovascular
complications
3 or more of the following abdominal obesity, triglycerides > 150 mg/dL, HDL < 40
mg/dL for men and < 50 mg/dL for women, fasting glucose > 110 mg/dL, HTN
**CLINICAL IDENTIFICATION OF METABOLIC SYNDROME = 3 or more of the following
5 factors
RISK FACTOR
DEFINING LEVEL
Abdominal Obesity
Waist Circumference
Men
>102 cm (>40 in)
Women
>88 cm (>35 in)
Triglycerides
150 mg/dL
HDL Cholesterol
Men
<40 mg/dL
Women
<50 mg/dL
Blood Pressure
130 / 85 mm Hg
Fasting Glucose
110 mg/dL
- Secondary hypertension causes 5% of cases sleep apnea, estrogen use, pheochromocytoma,
coarctation of the aorta, pseudotumor cerebri, parenchymal renal disease, renal artery stenosis, chronic
steroid therapy, Cushings syndrome, thyroid and parathyroid disease, primary hyperaldosteronism,
pregnancy
o Chronic kidney disease most common cause of secondary HTN.
85% of patients with CKD have HTN
Expanded plasma volume and peripheral vasoconstriction caused by activation of
vasoconstrictor pathways (RAAS and sympathetic) and by inhibition of vasodilator
pathways (nitric oxide)
o Renal artery stenosis <2% of patients with HTN. Results in 30% of medically refractory HTN
Excessive renin release in response to decrease in renal blood flow and perfusion
pressure
If you start them on an ACE inhibitor, you may see a worsening of their renal insufficiency.
Creatinine levels may creep up, and this is a clue that they have blockages
2 pathologic processes:
Atherosclerosis of proximal renal arteries. + CHD
Fibromuscular dysplasia (FMD) ~ a fibrous thickening of intima, media, or
adventitia of renal artery. Women 15-50 and a genetic predisposition. Unusual
in males

 Typical of atherosclerosis disease!!!

o Coarctation of the aorta congenital abnormality.
Narrowing of aorta, usually ascending region.
Stenosis increases PVR.
Rare (1:10,000).
Associated with bicuspid aortic valve or Turners syndrome
o Hyperaldosteronism most common etiologies:
Unilateral aldosterone producing adenoma
Bilateral adrenal hyperplasia
Mechanism = excessive sodium-potassium exchange; results in hypokalemia; associated
with hypertension
o Cushings syndrome aldosterone-like effect precipitates persistent HTN
HTN is reversible if cause is eliminated!! (pituitary adenoma, corticosteroid Rx, etc)
o Pheochromocytoma catecholamine producing adrenal tumors
Risk if undiagnosed = outpouring of catecholamines during unrelated surgical or radiologic
procedure leading to severe, abrupt hypertensive crisis; mortality rate >80%
Could be from contrast dyes
You will remember these patients!
o Obstructive sleep apnea airway collapses or blocked during sleep
Hypertension response to chronic, intermittent hypoxia during nocturnal apneic episodes
- Most patients with mild to moderate HTN are asymptomatic. The most commonly voiced symptom is
nonspecific headache
- Detection of target organ damage renal damage, CHF/MI (atherosclerosis), ophthalmic injury (retinal
hemorrhage), stroke, aortic dissection, dementia
o TOD = 5 organ systems affected neurologic, ophthalmologic, cardiovascular, renal, vascular
JNC 7 Hypertension Staging:
CATEGORY
SBP
DBP
Normal
<120
<80
Pre-HTN
120-139
80-89
HTN, Stage 1
140-159
90-99
HTN, Stage 2
>160
>100
- Diagnosed when patient has elevated BP readings during at least 2 visits
Diagnostic Studies
- EKG may reveal LVH or heart failure. A strain pattern is associated with advanced disease and a poorer
prognosis
- Chest radiography may show ventricular hypertrophy. However, this is not necessary in evaluation of
uncomplicated HTN!
- Decreased hemoglobin or hematocrit or elevations in BUN, creatinine, glucose may indicated related renal
disease or diabetes
- Other parameters to measure serum uric acid, plasma aldosterone concentration, plasma renin activity,
calculation of plasm aldosterone to renin ration, serum electrolytes
- Lipid profile is important for ascertaining risk of atherosclerosis
- Urinalysis for proteinuria
- In hypertensive urgencies and emergencies diagnostic testing targets end-organ function

Management and Non-Pharmacologic Treatment:

- The goal is to achieve BP < 1140/90 mmHg
o In patients with diabetes or CKD, treatment goal is < 130/80 mmHg
- Lifestyle Modifications:
o Weight Reduction maintain normal body weight (BMI 18.5-24.9) systolic BP reduction of 520 mm Hg per 10-kg weight loss
o Adopt DASH diet (Dietary Approach to Stop Hypertension) SBP reduction of 8-14 mm Hg
Low saturated fat, cholesterol, and total fat
Increased fruits and veggies
Fat-free or low-fat dairy
Increased fiber
o Dietary Sodium Reduction <2.4 grams sodium or 6 grams NaCl SBP reduction of 2-8 mm
Hg
o Aerobic Physical Activity brisk walking (>30 min/day, most days) SBP reduction of 4-9 mm
Hg
o Moderation of alcohol consumption males max 2/day, females and low weight people max 1/day
SBP reduction of 2-4 mm Hg
o Smoking cessation
- Medications ~ for uncomplicated HTN, thiazide diuretic should be used in the drug treatment for most, either
alone or combined with drugs from other classes (JNC 7)
o Large clinical trials show most single meds lower BP 20/10 mm Hg. Most patients require 2 or
more meds to achieve goal BP
- Compelling Indications ~ high risk groups require tighter BP control to reduce complications
o CHF diuretic, beta-blocker, ACE-inhibitor, ARB, aldosterone antagonist
o High Coronary Disease Risk beta-blocker, ACE-inhibitor, CCB, diuretic
o Chronic Kidney Disease ACE-inhibitor, ARB
o Diabetes Mellitus beta-blocker, ACE-inhibitor, diuretic, ARB, CCB
o Post-MI beta-blocker, ACE-inhibitor, aldosterone antagonist
o Recurrent Stroke Prevention ACE-inhibitor, diuretic
JNC 7:
BLOOD PRESSURE
WITHOUT COMPELLING
WITH COMPELLING INDICATION
INDICATION
Normal (<120/80)
Lifestyle
Lifestyle
Prehypertension (120-139/80-89)
Lifestyle
Lifestyle + Drug for Indication
Stage 1 Hypertension (140-159/90Lifestyle + Thiazide
Lifestyle + Drug for Indication
99)
Stage 2 Hypertension (>160/>100)
Lifestyle + 2 drug regimen (1 is
Lifestyle + 2 drug regimen (1 for
thiazide)
indication)
Pharmacological Treatment
- DIURETICS initially reduce plasma volume and chronically reduce peripheral vascular resistance
o Recommended as initial therapy for essential hypertension
o Can cause hypokalemia may need potassium supplements
o Thiazide diuretics are most effective hydrochlorothiazide, chlorthalidone
o Only use loop diuretics in those with renal dysfunction and when close electrolyte monitoring is
assured
o Potassium sparing diuretics / aldosterone receptor antagonists spironolactone
Increasingly used in refractory hypertension as additions to other drugs

ACE INHIBITORS inhibit bradykinin degradation and stimulate synthesis of vasodilating prostaglandins
o Initial drug of choice for patients with comorbid diabetes and chronic kidney disease (help preserve
kidney function)
o Have been shown to reduce mortality after an MI and in patients with heart failure and should be
initiated in these patients unless contraindicated
o Major side effect is cough
- ARBs (angiotensin II receptor blockers) block the interaction of angiotensin II on receptors.
o Like ACE inhibitors, beneficial in diabetes and CKD (help preserve kidney function)
o Do not increase bradykinins, so thus do not cause cough
- BETA BLOCKERS are used to decrease heart rate and cardiac output
o More effective in younger white patients
o Have been shown to reduce mortality after MI and in patients with heart failure and are
recommended in these patients unless contraindicated
o Use with caution in patients with pulmonary disease or diabetes
- CALCIUM CHANNEL BLOCKERS are for peripheral vasodilation
o May be preferable for blacks and elderly
- ALPHA BLOCKERS lower peripheral vascular resistance
o Helpful for refractory HTN
o May be the initial drug of choice in men with symptomatic BPH
- ALDOSTERONE RECEPTOR ANTAGONISTS (spironolactone), are increasingly used in refractory HTN as
an addition to other antihypertensives
o Proven useful in combination with beta-blockers and ARBs after an MI and in patients with heart
failure
- Central sympatholytics, arteriolar dilators, and peripheral sympathetic inhibitors also play a role in treatment
of refractory HTN
- Aliskiren, a renin inhibitor, is approved for mono- or combination therapy
**Treatment of secondary HTN targets the underlying cause
Heart Murmurs
- Congenital heart anomalies are the most common congenital structural malformations. They are classified
as either cyanotic or noncyanotic
- Cyanotic anomalies involve right-to-left shunts
o TETRALOGY OF FALLOT ventricular septal defect, aortic origination over the defect, right
ventricular outflow obstruction, and RVH
6-10% of significant congenital heart defects
Crescendo-decrescendo holosystolic murmur at LSB, radiating to back
Cyanosis, clubbing, increased RV impulse at LLSB, loud S2
Polycythemia usually present
Tet (hypercyanotic) spells include extreme cyanosis, hyperpnea, and agitation ~ a medical
emergency!!!!!
o PULMONARY ATRESIA most soften occurs with an intact ventricular septum. The pulmonary
valve is closed; an atrial septal opening and patent ductus arteriosus are present
1-3% of congenital heart disease
Murmur depends on presence or tricuspid regurgitation
Cyanosis with tachypnea at birth, tachypnea without dyspnea, hyperdynamic apical
impulse, single S1 and S2
Sudden onset of severe cyanosis and acidosis requires emergency treatment

HYPOPLASTIC LEFT HEART SYNDROME a group of defects with a small left ventricle and
normally placed great vessels
7-9% of significant congenital heart defects
Murmur is variable and not diagnostic
Shock, early heart failure, respiratory distress, single S2
Presentation varies with specific syndrome
Occurs more often in males
Accounts for 25% of cardiac deaths before age 7 days
o TRANSPOSITION OF THE GREAT VESSELS most commonly is a complete transposition of
the aorta and pulmonary artery
5-7% of all congenital heart defects
Systolic murmur if associated with VSD
Systolic ejection murmur if with pulmonary stenosis
Cyanosis in newborn is the most common sign
Tachypnea without respiratory distress
If large VSD, symptoms of CHF and poor feeding
Single loud S2, absent lower extremity pulses if with aortic arch obstruction
Noncyanotic types
o ATRIAL SEPTAL DEFECT an opening between the right and left atria. Of the four main types,
ostium secundum is the most common
7% of congenital heart disease, 2nd most common
Systolic ejection murmur at 2nd left intercostal space
Early to middle systolic rumble
Failure to thrive, fatigability, RV heave, wide fixed split S2
o VENTRICULAR SEPTAL DEFECT may be perimembranous (most common), muscular, or
outlet openings between the ventricles
Most common of all congenital heart defects
Systolic murmur at LLSB
Others depend on severity of defect
Physical findings depend on the size of defect from asymptomatic to signs of CHF
Outlet VSDs more common in Japanese and Chinese
o AV SEPTAL DEFECT (AV canal) due to incomplete fusion of the endocardial cushions.
Common in Down syndrome (15-20% of Down syndrome patients)
5% of all defects
Murmur depends on the degree of the defect
Cyanosis may be present
Infants present with CHF
If defect is large enough, first diagnosis may occur in adulthood with partial defects
Because this refers to a constellation of defects, presentation is variable depending on
whether the defect is complete, partial, or transitional
o PATENT DUCTUS ARTERIOSUS a failure or delayed closure of the channel bypassing the
lungs, which allows placental gas exchange during the fetal state. Unlike other congenital
anomalies, surgical treatment is usually not indicated as many patients respond to IV indomethacin
12-15% of significant congenital heart disease; higher in premature infants
Continuous (machinery) murmur in patients with isolated PDA
Wide pulse pressure, hyperdynamic apical impulse
o

COARCTATION OF THE AORTA involves narrowing in the proximal thoracic aorta

Systolic murmur LUSB and left interscapular area; may be continuous
Infants may present with CHF
Older children may have systolic HTN or murmur or underdeveloped lower extremities
Differences between arterial pulses and blood pressure in the upper extremities and lower
extremities pathognomonic
- Diagnostic Studies:
o EKG, echo, Doppler ultrasonography, MRI, CXR, radionuclide flow studies, cardiac catheterization,
and angiography
- Treatment:
o Most are treated with early surgical repair
o Interventions such as extracorporeal membrane oxygenation and alprostadil (prostaglandin E1) to
maintain a patent ductus can be helpful in stabilizing infants with cyanotic disease prior to surgery
o Many anomalies require staged procedures conducted as the patient grows
Valvular Heart Disease
STENOSIS:
- Narrowing or obstruction to forward flow while valve is open
- During systolic with aortic and pulmonic involvement
- Diastole with tricuspid or mitral involvement
- Chamber behind stenosis must hypertrophy to generate pressure / increased velocity
- Chronic slow progression of disease
REGURGITATION / INSUFFICIENCY:
- Backward leakage during time when valve is closed
- Aortic and pulmonic regurgitation DIASTOLE
- Mitral and tricuspid regurgitation SYSTOLE
- Chamber with and behind regurgitant jet must dilate to accommodate increased volume
- Acute vs. Chronic
TIMING OF MURMURS IN CYCLE:
- Systole
o Aortic and pulmonic stenosis
o Mitral and tricuspid regurgitation
- Diastole
o Mitral and tricuspid stenosis
o Aortic and pulmonic regurgitation
- Congenital malformation murmurs (depends)
o Septal defects (atrial and ventricular), Tetralogy of Fallot & Coarctation
o Taught in pediatrics! Just know they exist
TIMING OF SYMPTOMS IN VALVULAR HEART DISEASE:
- Stenosis
o Symptoms precede LV dysfunction
o Typically, intervene for symptoms
- Regurgitation
o LV dysfunction may precede symptoms
o Monitor LV function
o Intervene for symptoms AND to preserve cardiac function
o

PATHOPHYSIOLOGY OF VALVULAR DISEASE:

- Excess load on myocardium
o Increased pressure, increase volume
- Compensatory mechanisms
o Hypertrophy (from increased pressure) in stenotic disease
Normal LV wall thickness is < 12 mm
o Dilation (from increased volume) in regurgitant disease)
- Understand the pathophysiology is a critical step!!
- All valvular disease imparts a hemodynamic overload on either the RV, LV, or both
o Increase volume is the problem in regurgitant disease
o Increased pressure is the problem in stenotic disease
- Volume and pressure alterations lead to symptoms and compensatory mechanisms
Aortic Stenosis
- Narrows the valve opening, impeding the ejection function of the left side of the heart
o Causes LVH
- The most common valvular disease in the United States and the second most frequent cause for cardiac
surgery
- Occurs most often in older/calcific or younger/bicuspid
- Symptoms = angina, syncope, CHF
- Thready pulses
o Pulsus parvus (weak) et tardus (late). Aka slow-rising pulse
- Hyperdynamic, displaced impulse
- Harsh, medium pitch, midsystolic ejection murmur heard best at the RUSB and 2nd RICS, radiates to neck,
subclavian artery, and LSB
o Often with a loud thrill
o Accentuated leaning forward
o Decreased with standing and Valsalva
- CXR shows LAE and LVH
- Cardiac cath shows valve gradient/area
- TEE
- Avoid venodilators (nitrates) and negative inotropes (BB and CCBs) in severe AS
- Aortic valve replacement for all symptomatic patients and those with severe AS (area < 1.0 cm2, mean
pressure gradient > 40 mmHg
- Balloon valvotomy
Aortic Regurgitation
- Results in volume overloading due to the retrograde blood flow into the left ventricle
o Causes increased LVEDP and pulmonary congestion
- No classic patient, think bicuspid or Marfan syndrome
- CHF symptoms
- High-pitched, blowing, early diastolic decrescendo murmur at the 2nd-4th LICS/LUSB and radiating to the
apex and RSB
o Accentuated with leading forward, expiration, hand grip
- Wide pulse pressure due to increased stroke volume
- Bounding pulses
o Corrigans pulse = water hammer = rapid rise/fall or distention/collapse
- Austin Flint murmur = mid-to-late diastolic rumble at apex
- Hills sign = popliteal SBP brachial SBP > 60mmHg

Duroziez sign = systolic murmur heard over femoral artery when compressed
Pistol shot sounds = heard over femoral artery
Traubes sound = double sound heard over femoral artery when compressed distally
Mussets sign = head bobbing with each heartbeat
Mullers sign = systolic pulsations of the uvula
Quinckes pulses = subungual capillary pulsations
CXR shows LAE and LVH
Echo
If severe AI, use vasodilators (nifedipine, ACE, hydralazine)
Surgery for acute AI or severe/symptomatic AI aortic valve replacement
Mitral Stenosis
- Impedes blood flow between the left atrium and ventricle
- Think rheumatic disease first. Usually in females
- Dyspnea, orthopnea, PND, fatigue
- Atrial fibrillation
- Low-pitched, mid-diastolic rumple near the apex
o Heard best in LLD position
o Accentuated with exercise, LLD, expiration
- Accentuated S1, opening snap following S2
- CXR shows atrial enlargement alone
- Echo
- Intervene for symptoms diuretics and salt restriction, manage afib, anticoagulate, nitrates and beta
blockers
- For symptomatic patients after trial of medical therapy or if there are episodes of pulmonary edema, a
decline in exercise capacity or any evidence of pulmonary HTN (peak systolic pulmonary pressure
>50mmHg); softer criteria in presence of AFib.
o Percutaneous mitral valvotomy or mitral valve replacement
Mitral Regurgitation
- Allows retrograde blood flow and volume overload of the left atrium
- Myxomatous valve (MVP) or post-MI (dilated cardiomyopathy)
- Pulmonary edema / CHF symptoms, atrial fibrillation
- High-pitched, blowing holosystolic murmur heard best at the apex, with radiation to the axilla (left)
o thrill (visible, palpable heave at apex)
o Increased with handgrip
o Decreased with Valsalva
- Laterally displaced and hyperdynamic apical impulse
- S1 obscured/soft, S2 often decreased and widely split
- Brisk carotid upstroke
- Echo or cardiac cath
- CXR shows atrial enlargement alone
- Medical management is not very effective in asymptomatic patients
o If symptomatic, decrease preload (diuretics, nitrates) and use afterload reducing agents (ACE)
- Surgery if symptomatic or decrease in LV function
o Repair favored over placement

Mitral Valve Prolapse

- Usually is asymptomatic, but may be associated with mitral regurgitation
- Most patients are thin females with minor chest wall deformities, midsystolic clicks, and late systolic murmur
- Association with collagen vascular disease (Marfans, Ehlers Danlos)
- Atypical chest pain, palpitations
- Usually with mitral regurgitation (from leaflet prolapse or ruptured chordae)
o Also could have infective endocarditis, embolic events
- High-pitched, midsystolic click mid-to-late systolic murmur (mitral regurgitation)
o Exaggerated by Valsalva
o Reduced by squatting
- Echo
- Reassurance
- Endocarditis prophylaxis no longer recommended
- Beta-blockers for palpitations
- Aspirin or anticoagulation for afib or TIA/CVA risk
Tricuspid Stenosis
- Uncommon in adults. Usually congenital and rheumatic
- Rarely in isolation usually accompanies mitral valve disease (MS > MR)
- In all cases, right-sided pressure overload leads to right-sided cardiomegaly, systemic venous congestion,
and right-sided heart failure
- Patients usually present with exercise intolerance and symptoms of right-sided heart failure (JVD, peripheral
edema, hepatosplenomegaly). JVD with giant venous A waves
- Soft, high-pitched diastolic murmur at LSB
o Increases with inspiration
- Balloon valvuloplasty or surgical valve replacement if symptoms and mean valve gradient > 5mmHg
Tricuspid Regurgitation
- May be intrinsic or functional (related to RV dilation or increases in pulmonary artery pressure)
- In all cases, right-sided pressure overload leads to right-sided cardiomegaly, systemic venous congestion,
and right-sided heart failure
- Patients usually present with exercise intolerance and symptoms of right-sided heart failure (JVD, peripheral
edema, hepatosplenomegaly)
- C-V waves of the jugular veins with venous congestions (elevated JVP)
- Holosystolic (pansystolic), blowing murmur at LLSB, radiates to sternum and xiphoid area
o Increases with inspiration
- Only treat if severe diuretics (decrease fluid volume and RA filling pressure), dioxin
o Repair > replacement
- Underlying pulmonary hypertension is treated with arterial vasodilators or positive inotrope
Pulmonary Stenosis
- Most commonly congenital usually presents in late adolescence to adulthood
- In all cases, right-sided pressure overload leads to right-sided cardiomegaly, systemic venous congestion,
and right-sided heart failure
- Patients usually present with exercise intolerance and symptoms of right-sided heart failure (JVD, peripheral
edema, hepatosplenomegaly)
- Soft to loud, harsh mid-systolic crescendo-decrescendo murmur heard best at the 2nd-3rd LICS, radiating to
the left should and neck. Possibly associated with a thrill
- Early pulmonic ejection sound common
- Wide splitting of S2, soft P2. S4 is common. JVD with prominent A wave

Echo = RVH

Pulmonary Regurgitation
- Usually due to pulmonary HTN or connective tissue disease (Marfans)
o 2nd most common causes = infective endocarditis
- Usually asymptomatic for years
- In all cases, right-sided pressure overload leads to right-sided cardiomegaly, systemic venous congestion,
and right-sided heart failure
- Patients usually present with exercise intolerance and symptoms of right-sided heart failure (JVD, peripheral
edema, hepatosplenomegaly)
- Hyperdynamic RV with palpable heave
- Low-pitched, diastolic murmur in 3rd-4th intercostal spaces adjacent to sternum
o Increases with inspiration
Coronary Heart Disease
Acute MI NSTEMI / STEMI
- Almost all MIs result from coronary atherosclerosis and superimposed coronary thrombosis. Usually
caused by acute disruption of 25-70% atherosclerotic lipid rich lesions and subsequent inflammatory
response (causes thrombi formation)
- STEMI = ST segment elevation MI
o Caused by thrombotic obstruction of epicardial coronary arteries
o Fatality in 1/3 of patients; over of deaths occur within 1 hour of event from ventricular fibrillation
o 20% go unrecognized
o Sudden onset CP associated with SOB, nausea, diaphoresis
o CP persists > 30 min, may not respond to NTG
o Physical:
HTN or hypotension
Tachycardia or bradycardia
S3, S4, or both
Signs of CHF
Systolic murmurs (mitral regurgitation, ventricular septal defect)
Friction rub (usually day 2 or 3)
o Diagnostic Findings:
EKG helps to identify site of infarct vessel
ST segment elevation
Early peaked T-waves
Q-waves
Extent of ST deviation and QRS duration correlate with risk of adverse outcomes
o Cardiac Biomarkers:
Myoglobin = peaks around 6-7 hours, duration is 24 hours
CK = peaks around 12 hours, duration is 36 hours
CK-MB = peaks around 24 hours, duration is 48-72 hours
LDH = peaks around 24-48 hours, duration is 10-14 days
TnT = peaks around 12-48 hours, duration is 5-14 days ***

Treatment:
Emergent PCI preferred if early presentation (< 3 hours from symptom onset) and skilled
team available (door to balloon time < 90 minutes)
Lytics within 12 hours of onset and no PCI options
ABSOLUTE lytic contraindications = any prior intra-cranial hemorrhage, cerebral
AVM, malignant neoplasm, active bleeding, suspected aortic dissection, ischemic
CVA in past 3 months or closed head trauma, severe uncontrollable HTN
tPA, rPA, TNK, SK
The most significant complication of thrombolytics is hemorrhage, particularly
ICH
o May need cryoprecipitate or FFP
Maintenance anticoagulation and antiplatelet therapy
Aspirin / clopidogrel = antiplatelet
Heparin, enoxaparin (LMWH) = anticoagulant
Place ALL patients on cardiac monitor, receive IV line, give supplemental oxygen
ASA should be administered in a dose of 160-325 mg (chewed) in patients with suspected
ACS, unless contraindicated or already taken
Beta blockers for all patients within the first 24 hours unless contraindications (heart
failure, bradycardia, heart block)
Oxygen
NTG + / - morphine
ACE inhibitors initiated within the first 24 hours, especially in the presence of heart failure
Heparin / LMWH
GP IIb/IIIa inhibitors
Statins
Aldosterone inhibitors
Complications:
Arrhythmias (VT, VF, or heart block)
CHF / cardiogenic shock
RV infarction
Ventricular Free Wall Rupture
Ventricular Septal Rupture
Mural thrombus / embolus
CVA
Pericarditis
Post-Infarction angina

Unstable Angina
- Unstable Angina / NSTEMI = non ST segment elevation MI
o New, sudden onset CP / pressure with associated SOB, nausea, diaphoresis
o Chest pain at greater frequency, severity, or with less activity
o Chest pain at rest or nocturnally
o Chest pain previously controlled with nitrates, now refractory
o Physical and diagnostic findings are similar to angina ~ EKG more likely to show acute ischemic
changes (ST depression and T-wave inversion)
o Cardiac enzymes negative for USA, but ELEVATED in NSTEMI
o Diagnosis and treatment = admit and monitor, best rest and oxygen
Serial EKG and cardiac enzymes

ASA, beta blocker, NTG, ACE, and anticoagulation (heparin/LMWH vs platelet GP IIb/IIIa
inhibitors)
Cardiac risk stratification with cardiac catheterization preferred
Plavix (clopidogrel) following cath

Angina Pectoris
- Represents cardiac ischemia, a form of ACS
- Myocardial ischemia (process that interrupts blood flow to the coronary arteries) results from imbalance of
myocardial oxygen supply and demand
- Usually caused by chronic coronary atherosclerosis (>75% stenosis) of major coronary arteries (slower,
more progressive process) with collaterals
- Provides diagnosis in most cases!!
o Deep pressure-like pain in substernal region, may radiate to jaw, neck, or arm
o Frequently associated with SOB
o Transient lasting 2-30 minutes
o Precipitated by physical exertion of emotional stress
o Responsive to rest or SL NTG (sublingual nitroglycerin)
- Physical is often normal
- Findings secondary to risk factors:
o Elevated BP + S4, arterial bruits
o Retinal changes (AV nicking, papilledema, cotton wool spots), corneal arcus
Corneal Arcus = very common bilateral gray, white, or yellowish circumferential deposits in
the peripheral cornea. May be age-related (arcus senilis) or in association with
hyperlipoproteinemia types 2 and 3 in younger people.
o Xanthelasma, xanthomas
Tuberous Achilles Xanthomas = thickening of tendons due to accumulation of cholesterol
Xanthelasma = sharply demarcated yellowish collection of cholesterol underneath the skin
around the eyelids
o CHF (transient LV dysfunction)
o Murmurs (transient papillary muscle dysfunction)
- Diagnostic Findings: EKG
o Between episodes = 1/3 have normal resting EKG. Nonspecific ST-T wave changes, evidence of
prior MI (pathological Qs), conduction abnormalities (*LBBB*, RBBB, fascicular blocks)
o During angina = ST depression/possibly elevation, T-wave inversion
- Laboratory Data
o Cardiac Enzymes should be negative (CK, CKMB, troponin)
o Elevated cholesterol
o Elevated glucose
o CXR = often normal. Evidence of CHF, arterial calcifications
- Diagnosis = stress testing!! Predictors of CAD in ETT:
o Development of typical angina
o ST segment changes without angina = >70% chance of significant CAD
o ST segment changes and typical angina = >90% predictive
o >ST changes, > chance of CAD
o Systolic BP drop > 10 mm Hg = BAD!!!
- Treatment:
o Risk Factor Modifications
o Medications
81-325 mg ASA daily

Beta blocker
ACE inhibitor
Nitrates, PRN or long acting
Statins / Lipid Agents
Consider revascularization (PCI / Stent vs CABG)

Prinzmetal / Variant Angina

- Chest pain 2 to myocardial ischemia
- Occurs at rest, typically early morning and may wake patient up from sleep
- No correlation with exertion or emotional stress
- Associated with ST elevations on EKG ~ RCA most often involved
o Complications include acute MI, VT, VFib, and sudden cardiac death
- Mechanism = coronary artery spasm
o Occurs in diseased or normal arteries
o Sites of spasm often adjacent to atheromatous plaques
o Often affects women < 50 years old
o May be associated with other vasospastic disease (migraines, Raynauds)
- Rx = nitrates, CCB, +/- beta blockers
Cardiac Arrhythmias / Conduction Disorders
Atrial Fibrillation / Flutter
- ATRIAL FIBRILLATION:
o Occurs when there are multiple, small areas of atrial myocardium continuously discharging in a
disorganized fashion
Results in the loss of effective atrial contraction and decreases LVEDV, which may
precipitate CHF in patients with impaired cardiac function
o EKG characteristics:
Fibrillatory waves of atrial activity, best seen in leads V1, V2, V3, and aVF
Irregular ventricular response, usually 170-180 bpm in patients with a healthy node
o May be paroxysmal (lasting < 7 days), persistent (lasting > 7 days), or chronic (continuous)
o May be idiopathic or found in association with longstanding HTN, ischemic heart disease,
rheumatic heart disease, alcohol use (holiday heart), COPD, and thyrotoxicosis
o Rates of > 300 bpm with a wide QRS complex are concerning for a preexcitation syndrome such
as Wolff-Parkinson-White syndrome
o If not anticoagulated, increased risk of embolic event
Conversion from chronic Afib to sinus rhythm carries a risk of arterial embolism, therefore,
anticoagulation for 3 weeks is required before cardioversion in patients with Afib for longer
than 48 hours duration and in those with an uncertain time of onset who are not on
anticoagulants
o ED Care and Disposition:
If unstable synchronized cardioversion (50-100 J)
If stable with Afib for longer than 48 hours anticoagulate with heparin before
cardioversion
Consider TEE to rule out atrial thrombus before cardioversion
Control rate with diltiazem
Alternative agents = verapamil, metoprolol, digoxin
If preexcitation syndromes (e.g., WPW) = procainamide
o Avoid BB and CCB due to the risk of causing degeneration to Vfib
In patients with impaired cardiac function (EF < 40%) amiodarone or digoxin
Contraindicated if shellfish or iodine allergy
Increased risk of rhabdomyolysis if given with simvastatin
Patients with Afib shorter than 48 hours may be chemically or electrically converted in the
ED this is the rhythm arm of treatment
If normal cardiac function = amiodarone, ibutilide, procainamide, flecainide, or
propafenone

Long-term anticoagulation based on CHADS score with warfarin or aspirin (other options
are now dabigatran, rivaroxaban)
- ATRIAL FLUTTER:
o A rhythm that originates from a small area within the atria
o Most commonly seen in patients with ischemic heart disease as well as CHF, acute MI, pulmonary
embolus, myocarditis, blunt chest trauma, and digoxin toxicity
o Atrial fluter may be a transitional arrhythmia between sinus rhythm and atrial fibrillation
o EKG characteristics:
A regular atrial rate between 250-350 bpm
Saw tooth flutter waves directed superiorly and most visible in leads II, III, and aVF
AV block, usually 2:1, but occasionally greater or irregular
o Carotid sinus massage or Valsalva maneuver are useful techniques to slow the ventricular
response by increasing the degree of AV block, which can unmask flutter waves in uncertain cases
o Consider anticoagulation in patients with an unclear time of onset or duration longer than 48 hours
before conversion to sinus rhythm due to increased risk of atrial thrombus and embolization
o ED Care and Disposition same as atrial fibrillation
Sick Sinus Syndrome
- Physiologically inappropriate sinus bradycardia, sinus pause, sinus arrest, or episodes of alternating sinus
tachycardia and bradycardia
- Most often in elderly
- Often cause by scarring of the hearts conduction system
- May occur in infants who have had heart surgery
- May be caused or exacerbated by digitalis, CCBs, BBs, sympatholytic agents, antiarrhythmic drugs, and
aerosol propellant abuse
o Reversible if caused by drugs
- May also result from underlying collagen vascular or metastatic disease, surgical injury, or, rarely, coronary
disease
- Most patients are asymptomatic
o May have syncope, dizziness, confusion, heart failure, palpitations, or decreased exercise
tolerance
- Most symptomatic patients require permanent pacing
Supraventricular Tachycardia
- SINUS TACHYCARDIA = normal sinus P waves and PR intervals, atrial rate between 100-160 bpm
o Occurs in response to physiologic stimuli (pain or exertion), pharmacologics (sympathomimetics,
caffeine, bronchodilators), or pathologic stimuli (fever, hypoxia, anemia, hypovolemia, pulmonary
embolism, hyperthyroidism)
o Diagnose and treat the underlying condition
- SVT is a regular, rapid rhythm that arises from impulse reentry or an ectopic pacemaker above the
bifurcation of the His bundle
o The reentrant variant is the most common
o Patients often present with acute, symptomatic episodes termed paroxysmal SVT
- Atrioventricular nodal reentrant tachycardia can occur in a normal heart or in association with rheumatic
heart disease, acute pericarditis, MI, MVP, or preexcitation syndromes. In patients with atrioventricular
bypass tracts, reentry can occur in either direction, usually (80-90%) in a direction that goes down the AV
node and up the bypass tract producing a narrow QRS complex.
o A regular, narrow-complex tachycardia usually represents an AV nodal reentry tachycardia such as
PSVT
- In the remaining 10-20% of patients, reentry occurs in the reverse direction (antidromic conduction)

Ectopic SVT usually originates in the atria, with an atrial rate of 100-250 bpm and may be seen in patients
with acute MI, chronic lung disease, pneumonia, alcohol intoxication, or digoxin toxicity

There is a high incidence of tachyarrhythmias in patients with preexcitation syndromes including PSVT, atrial
fibrillation, and atrial flutter. All forms of preexcitation are caused by accessory tracts that bypass part of all
of the normal conducting system, the most common form being WPW syndrome. The ventricles are
activated by an impulse from the atria soon that would be expected if the impulse were transmitted down the
normal conducting the pathway
- ED Care and Disposition:
o In unstable patients synchronized cardioversion
o In stable patients first, perform Valsalva maneuvers
Valsalva (strain in supine position)
Diving reflex (face in cold water)
Carotid sinus massage (only if no bruits)
o Administer adenosine, 6 mg IV rapid bolus, followed by 20 mL normal saline flush
If no effect within 2 minutes, give a second dose of 12 mg IV
Most patients experience distressing chest pain, flushing, or anxiety lasting less than 1
minutes
May even get transient atrial fibrillation/flutter after conversion
This is the first-line treatment for WPW-associated SVT with a narrow complex
o If narrow-complex SVT and normal cardiac function, cardioversion can also be achieved with
second-line agents:
CCBS = diltiazem, verapamil
Beta-blockers = esmolol, metoprolol, propranolol
Digoxin
o If wide-complex SVT, approach as presumed ventricular tachycardia unless there is a known
history of WPW
These patients are at risk for degeneration into Vfib, so avoid agents that preferentially
block the AV node (beta-blockers, CCBs, digoxin)
Treat stable patients with procainamide (contraindicated in those with myasthenia gravis)
Bundle Branch Block
- Fascicular blocks
- Right Bundle Branch Block (RBBB):
o Prolongs the QRS duration (>0.12 sec) and cause a RSR in the early precordial leads (V1-2)
- Left Bundle Branch Block (LBBB):
o A bifascicular block
AV Block
- Characterized by refractory conduction of impulses from the atria to the ventricles through the AV node
and/or bundles of HIS
- May produce weakness, fatigue, light-headedness, syncope
- 1st Degree
o Not truly a block just slowed conduction down normal pathway (delay in AV conduction)
o PR interval 200 ms (0.2 seconds)
o Typically related to aging of conduction system
o Other transient causes
High vagal tone
Ischemia
Electrolyte abnormalities
Meds: BB or CCB
o No therapy required
o Prognosis = very good

2nd Degree
o Characterized by intermittent AV nodal conduction some impulses reach the ventricles, whereas
others are blocked, thereby causing grouped beating
o Type 1 = Wenckebach
Progressive prolongation of PR interval (with gradually falling RR) until AV node fails to
conduct and a ventricular beat is dropped
Regularly irregular
PR then resets
Type 1 conduction delay usually located in AV node
Usually asymptomatic
Occurs in:
Athletes (high vagal tone)
Elderly (slowed conduction)
Ischemia
Drugs BB / CCB / anti-arrhythmics
Good prognosis
Treatment if symptomatic and signs of hypoperfusion, use atropine, elective
pacemaker, or immediate transcutaneous pacing
o Type 2 = Mobitz
Constant PR interval with randomly dropped ventricular beats
Complete interruption in AV conduction with resulting AV dissociation
Blocks usually located below AV node in Bundle of His
Can be symptomatic and often progresses to complete heart block
Rx = stop all nodal blockers
Atropine is first-line in symptomatic patients
Place transcutaneous pacer pads in case of further deterioration to 3rd degree block
Initiate transcutaneous cardiac pacing in those unresponsive to atropine
Typically requires pacemaker, especially if:
Symptomatic
Exercise-induced
HR < 40 or pause > 3 seconds
- 3rd Degree = Complete Heart Block
o No conduction between atria and ventricles
o Usually see ventricular (wide, slow) escape rhythm
o Usually symptomatic
o Causes aging, ischemia (acute MI), post-surgical (especially valve), congenital, electrolytes,
digoxin toxicity, high vagal tone
o Almost always requires pacer
Ventricular Tachycardia / Fibrillation
- VENTRICULAR TACHYCARDIA:
o Defined as 3 or more consecutive PVCs at a rate faster than 100 bpm. Rate is 150-250
o EKG characteristics:
Wide QRS complex
Rate faster than 100 bpm (most commonly 150-250 bpm)
A regular rhythm
Constant QRS complex
o May be sustained or unsustained
-

A frequent complication of acute MI and dilated cardiomyopathy

Most common causes = acute MI and ischemic heart disease
So, consider all patients for urgent revascularization
o Extreme RAD or LAD suggests v-tach
o ALL wide QRS tachycardias are v-tach until proven otherwise
o Atypical Vtach (torsade de pointes) occur when the QRS axis swings from positive to negative in a
single lead at a rate of 200-240 bpm
o May be asymptomatic or experience dizziness and syncope
o If there is severe hypotension or loss of consciousness, cardioversion may be necessary
o Preferred pharmacologic interventions for acute v-tach lidocaine, procainamide, and
amiodarone. Empiric magnesium may help
o For chronic, recurrent sustained v-tach without a reversible cause implantable defibrillatory
o Hemodynamically unstable (pulse / no pulse)
ACLS shock now, think later
Without a pulse = unsynchronized cardioversion, starting at 100 J
With a pulse = synchronized cardioversion
If recurs, load with anti-arrhythmic
Treat underlying cause
o Stable:
Amiodarone
Call cardiologist
Treat underlying cause
Ischemia
Low K or Mag or Calcium (get K+ 4.0, Mag 2.0)
Hyperthyroid
Digoxin toxicity
Consider anti-arrhythmic
o Long-term Management
Address underlying cause
ICD (especially if EF 35% or + EPS)
Anti-arrhythmic therapy if recurrent
Catheter ablation
o Torsades de pointes is treated with IV magnesium, correction of electrolyte abnormalities
(hypokalemia or hypomagnesemia) and withdrawal of drugs that may have precipitated the event
If recurrent, permanent pacemaker
VENTRICULAR FIBRILLATION:
o The totally disorganized depolarization and contraction of small areas of ventricular myocardium
during which there is no effective ventricular pumping activity
o EKG characteristics:
Fine-to-coarse zigzag pattern without discernible P waves or QRS complex
o Most commonly seen in patients with severe ischemic heart disease, with or without acute MI
o Can also be caused by digoxin or quinidine toxicity, hypothermia, chest trauma, hypokalemia,
hyperkalemia, or mechanical stimulation
o Perform immediate electrical defibrillation (unsynchronized) at 200 J (biphasic) and 360 J
(monophasic)
If Vfib persists, do 5 cycles of CPR, check pulse, and defibrillate again if no pulse
o

If the initial 2 cycles of CPR and defibrillation are unsuccessful, administer antiarrhythmic
treatment using amiodarone
Lidocaine is second-line
If still no pulse after third CPR-defibrillation cycle, give epinephrine or vasopressin
In refractory Vfib, administer magnesium sulfate

Premature Beats
- PREMATURE ATRIAL CONTRACTIONS:
o EKG Characteristics:
The ectopic P wave appears sooner (premature) than the next expected sinus beat.
The ectopic P wave has a different shape and direction
The ectopic P wave may or may not be conducted through the AV node
o Most PACs are conducted with typical QRS complexes, but some may be conducted aberrantly
through the infranodal system, typically with a right bundle branch block pattern.
o When the PAC occurs during the absolute refractory period, it is not conducted. Since the sinus
node is often depolarized and reset, the pause is less than fully compensatory. PACs are
associated with stress, fatigue, alcohol use, tobacco, coffee, COPD, dig toxicity, CAD, and may
occur after adenosine-converted paroxysmal SVT. PACs are common in all ages, often in the
absence of significant heart disease. Patients may complain of palpitations or an intermittent
sinking or fluttering feeling in the chest
o Management:
Discontinue precipitating drugs (alcohol, tobacco, or coffee) or toxins.
Treat underlying disorders (stress or fatigue)
PACs that produce significant symptoms or initiate sustained tachycardia can be
suppressed with agents such as Beta-adrenergic antagonists (eg, metoprolol 25-50 mg
PO TID), usually in consultation with followup physician.
- PREMATURE VENTRICULAR CONTRACTIONS:
o Due to impulses originating from single or multiple areas in the ventricles.
o EKG characteristics:
Premature and wide QRS complex
No preceding p wave
The ST segment and T wave of the PVC are directed opposite the preceding major QRS
deflection
Most PVCs do not affect the sinus nose, so there is usually a fully compensatory postectopic pause the PVC may be interpolated between 2 sinus beats
Many PVCs have a fixed coupling interval from the preceding sinus beat
Many PVCs are conducted into the atria, thus producing a retrograde P wave.
o If 3 or more PVCs occur in a row, patients are considered to have non-sustained ventricular
tachycardia.
o PVCs are very common, occurring in most patients with ischemic heart disease and acute MI.
Other common causes: CHF, dig tox, hypokalemia, alkalosis, hypoxia, and sympathomimetic
drugs.
o Ventricular parasystole occurs when the ectopic ventricular focus fires frequently enough to
compete with the SA node and is associated with cardiac ischemia, electrolyte imbalance, and
hypertensive or ischemic heart disease.
o Management:
Stable patients require no treatment
Patients with 3 or more PVCs occur in a row should be managed as VT.
For hemodynamically unstable patients with PVCs, consider lidocaine unless the patient is
allergic to amide anesthetics.

Myocarditis
- Often follows an upper respiratory infection (viral)
- May present several days to a few weeks after the onset of an acute febrile illness or a respiratory infection
or with heart failure without antecedent symptoms\may present with chest pain (pleuritic or nonspecific) or
signs of heart failure
- Exam reveals tachycardia, gallop rhythm, evidence of heart failure or arrhythmias (such as sustained vtach)
- May have elevated markers
- Echocardiogram documents cardiomegaly and contractile dysfunction
- Myocardial biopsy, though not sensitive, may reveal a characteristic inflammatory pattern
- MRI may now have a role in diagnosis
- Treatment:
o If LV EF is <40%, treat with ACE inhibitors and beta-blockers
o NSAIDs for myocarditis-related chest pain
o If there is a specific infecting agent, use antibiotics
o Corticosteroids and/or immunosuppressants may help
Endocarditis
- Most cases of native valve infective endocarditis are caused by viridans streptococci, S. aureus,
enterococci, and HACEK organisms
o HACEK = Haemophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis,
Eikenella corrodens, Kingella species
o In IV drug users, S. aureus is the most common cause, and tricuspid valve is frequently involved
Usually right sided valved involvement (TV > PV)
Frequent pulmonic and systemic emboli
o Prosthetic valve endocarditis most often is caused by S. aureus, gram negatives, or fungi during
the first 2 months after implantation. Later, disease is usually due to strep or staph
Occurs in 2% of valve replacements with 1/3 cases < 2 months
Staph epidermidis most common agent
High need for redo surgery and high mortality 25-30%
o Organism usually determines acute vs. subacute presentation
- Microbial invasion of the endocardium ~ typically involves cardiac valve
o Most patients with endocarditis usually have an underlying regurgitant cardiac defect that provides
a nest for development of vegetation
o Occurs at areas of endocardial injury caused by turbulence, trauma, or inflammation
- Associated with transient, bacteremias such as IVDA, intravascular devices, or post-surgical inoculations
o Other bacteremias dental, upper respiratory, urologic, and lower GI procedures
o Infection can also result from direct intravascular contamination
- Clinical Features
o Most patients present with fever several days to weeks (may be absent in elderly)
o Also have nonspecific complaints (HA, myalgias, cough, dyspnea, arthralgias, back or flank pain,
GI complaints)
o Approximately 90% will have a stable murmur
May be absent in right-sided infections
A changing murmur is rare but diagnostically significant
o Classic Features occur in 25% of patients:
Palatal, conjunctival, or subungual petechiae
Splinter hemorrhages
Osler nodes (painful, violaceous, raised lesions of the fingers, toes, or feet)
Janeway lesions (painless red lesions of the palms or soles)

 Roth spots (exudative lesions in the retina)

o Pallor and splenomegaly are common
o Strokes and emboli may occur
- Laboratory Studies:
o 3 sets of blood cultures at least 1 hour apart (before starting abx)
o Echocardiography useful to identify valves involved
TEE is particularly useful
The presence of vegetation is diagnostic
o Chest radiography may demonstrate underlying cardiac abnormality or reveal pulmonary
infiltrates if the right side of the heart is involved
o EKG has no specific diagnostic features
o Anemia / leukocytosis, elevated ESR, hematuria / proteinuria, positive rheumatoid factor antibody
o Duke Criteria are used to establish diagnosis :
MAJOR Criteria:
2 positive blood cultures of a typically causative microorganism
Evidence of endocardial involvement on echocardiography
Development of a new regurgitant murmur
MINOR Criteria:
Predisposing factor
Fever higher than 100.48F (38.8C)
Vascular phenomena (embolic disease or pulmonary infarction)
Immunologic phenomena (glomerulonephritis, Osler nodes, Roth spots)
Positive blood culture not meeting major criteria
**Patients must have 2 major, 1 major + 3 minor, or 5 minor criteria
(IE is considered possible with 1 major + 1 minor, or 3 minor)
- Treatment
o Empiric antibiotics should cover staphylococci, streptococci, and enterococci
Gentamicin with ceftriaxone or vancomycin is the appropriate initial therapy for patients
with suspected IE
Gentamicin, vancomycin, plus cefepime (4th generation cephalosporin) is appropriate for
acutely ill patients with heart failure pending blood cultures
Typically 4-6 weeks
o Antibiotic prophylaxis to prevent endocarditis is recommended before invasive dental work or
surgical procedures in those with prosthetic valves, previous IE, some congenital or acquired heart
disease, HCM, and cardiac transplant recipients
Amoxicillin (if pcn allergic clindamycin, azithromycin, cephalos)
These guidelines have recently changed! No longer recommended for most
Recommendations for antibiotics ONLY for the highest risk groups
Prosthetic cardiac valves (mechanical and tissue), previous endocarditis, cardiac
transplant with valvular heart disease, congenital heart disease (unrepaired
disease or repaired with prosthetic device with a residual deficit or within 6
months), hypertrophic cardiomyopathy
NOT for these groups:
Prior CABG, pacemaker / ICD, MVP or mitral regurgitation, ASD, prior rheumatic
fever
o Valve replacement, especially of the aortic valve, may be necessary if the condition does not
resolve with antibiotics, if an abscess develops, or if a fungal infection is the caused

Anticoagulation contraindicated!!!

Pericarditis
- Most commonly idiopathic (90%) or due to viral infection
o Can also be the result of bacterial infection, autoimmune or connective tissue disease, neoplasms,
radiation therapy, chemotherapy, or other drug toxicity, cardiac surgery, or myxedema
o Tuberculous pericarditis is common outside of developed nations
- More common in men and those younger than 50 years old
- The primary presenting symptom of acute pericarditis is sharp, pleuritic substernal radiating chest pain often
relieved by sitting upright and leaning forward
o A cardiac friction rub is characteristic
- Constrictive pericarditis presents with slowly progressive dyspnea, fatigue, and weakness, accompanied by
edema, hepatomegaly, and ascites
- In infectious conditions, patients may be febrile
- Diagnostic Studies:
o Elevated WBC count indicates infection, necessitating blood and pericardial fluid cultures
o CXR or echo is useful to determine the extent of cardiac effusion or pericardial calcification
Normal or water bottle-shaped enlarged cardiac silhouette
o EKG change most commonly associated with acute pericarditis is diffuse ST-segment elevation
PR depressions
o Echo, Doppler ultrasound, CT, or MRI may be helpful for more accurate diagnosis or before
invasive procedures
o Pericardiocentesis / biopsy if tuberculous pericarditis is suspected
- Treatment:
o In the presence of hemodynamic compromise (especially with symptomatic effusion or
tamponade), pericardiocentesis is necessary to relieve fluid accumulation. Recurrent effusions
may be treated surgically with a pericardial window
o Strictly inflammatory conditions may be treated with steroids or NSAIDs
Give with PPI to protect against ulcer formations, since using a high dose of NSAIDs
o Infectious conditions may require antibiotic therapy only if bacterial infection is suspected
o Pericardiectomy may be performed to relieve constrictive pericarditis
o For recurrent pericarditis, consider colchicine with NSAIDs
Cardiomyopathy
Dilated Cardiomyopathy
- The most common type (95%)
- Associated with reduced strength of ventricular contraction, resulting in dilation of the left ventricle
- Causes genetic abnormalities (25-30%), excessive alcohol consumption, postpartum state,
chemotherapy toxicity, endocrinopathies, and myocarditis
o May be idiopathic
- Takotsubo Cardiomyopathy (aka stress-induced cardiomyopathy) occurs after a major catecholamine
discharge and results from hypocontractility of the left ventricular apex. The clinical presentation can be
indistinguishable from acute MI
o Presents with retrosternal chest pain indistinguishable from acute MI
- Dilated cardiomyopathies result in signs and symptoms of left or biventricular congestive failure
o The most common presentation is dyspnea
o Patients may have an S3 gallop, pulmonary crackles (rales), and increased jugular venous pressure

Diagnostic Studies:
o EKG may show nonspecific ST- and T-wave changes, conduction abnormalities, and ventricular
ectopy
o CXR in long-standing disease shows cardiomegaly and pulmonary congestion
o Echocardiography demonstrates LV dilation and dysfunction, with high diastolic pressures and low
cardiac output
o Nuclear studies and cardiac catheterization also provide useful information
o Takotsubo Cardiomyopathy can demonstrate EKG changes and mild cardiac enzymes
suggestive of MI. Cardiac catheterization reveals hypocontractility of the left ventricular apex and
patent coronary arteries
- Treatment:
o Abstinence from alcohol is essential
o Treat underlying disease
o CHF requires supportive treatment
o Takotsubo cardiomyopathy is usually treated with supportive care. Inotropes should generally be
avoided. Most patients return to baseline within 2 months
Hypertrophic Cardiomyopathy
- Demonstrates massive hypertrophy (particularly of the septum), small left ventricle, systolic anterior mitral
motion, and diastolic dysfunction. Microscopic myocardial abnormalities promote the development of
arrhythmia
- It is transmitted genetically.
o The apical variety is more common in persons of Asian descent
o Hypertrophic cardiomyopathy in the elderly is a distinct form
- Sudden cardiac death occurs in patients younger than 30 years at a rate of 2-3% yearly
- Patients most commonly present with dyspnea and angina. Syncope and arrhythmias are common.
o It may be asymptomatic.
o Sudden death may be initial presentation
- Physical exam may show sustained PMI or triple apical impulse, loud S4 gallop, variable systolic murmur, a
bisferiens carotid pulse, and jugular venous pulsations with a prominent a wave
- Diagnostic Studies:
o CXR is often not remarkable
o EKG abnormalities include nonspecific ST- and T-wave changes, exaggerated septal Q waves, and
LVH
o Echocardiography is the key to diagnosis. It demonstrates LVH, asymmetric septal hypertrophy,
small left ventricle, and diastolic dysfunction
o Myocardial perfusion studies, cardiac MRI, and cardiac catheterization can also be helpful
- Treatment:
o Initial treatment employs beta blockers or calcium channel blockers; disopyramide is used for its
negative inotropic effects
o Surgical or nonsurgical ablation of the hypertrophic septum may be required
o Dual-chamber pacing, implantable defibrillators, or mitral valve replacement may be indicated

Restrictive Cardiomyopathy
- Results from fibrosis or infiltration of the ventricular wall because of collagen-defect diseases, most
commonly amyloidosis, radiation, postoperative changes, diabetes, and endomyocardial fibrosis
- The left ventricle is small or normal, with mildly reduced function
- Patients present with decreased exercise tolerance
o In advanced disease, patients develop right-sided congestive failure
- Pulmonary hypertension is usually present
- Diagnostic Studies:
o CXR may show a mildly to moderately enlarged cardiac silhouette
o Echocardiography is the key to diagnosis; other low-voltage changes on EKG are typical. Cardiac
MRI is distinctive, and cardiac cath may demonstrate normal or mildly reduced LV function
o Endomyocardial biopsy may be necessary to differentiate restrictive disease from other forms of
cardiomyopathy or pericarditis
- Treatment diuretics may help patients with restrictive cardiomyopathies
Hyperlipidemia
- Elevated LDL levels increase the risk of CAD
- Higher HDL levels are thought to be protective
- Elevated triglycerides are also a risk factor for atherosclerosis. Severe elevations can cause pancreatitis
- Causes may be genetic (primary hyperlipidemia, familial hypercholesterolemia), or, more commonly,
secondary to DM, alcohol use, hypothyroidism, obesity, sedentary lifestyle, renal or liver disease, or drugs
(estrogen, thiazides, beta-blockers)
- Most patients have no signs or symptoms
- Eruptive and tendinous xanthomas are common with hyperlipidemia and usually indicate a genetic cause
o Nearly of people with xanthelasmas (the most common form of xanthomas, affecting the
eyelids) have normal lipid profiles
- Patients with severe hypercholesterolemia may develop premature arcus senilis
o Lipemia retinalis (cream-colored retinal vessels) is seen with triglyceride levels of > 2,000 mg/dL
- Diagnostic Studies:
o Patients with any evidence of CVD or who have a CHD risk equivalent should be screened with a
fasting complete lipid profile. Those without cardiac risk factors should be screened with at least a
measurement of total cholesterol
Established CHD Risk (past history of MI or known obstructive CAD) = risk of >20% per
10 yrs (>20 of 100 patients will develop CHD or have recurrent CHD event within 10 yrs)
CHD Risk Equivalents carry risk for major coronary events = risk of established CHD.
Risk equivalent factors = 10 year risk of CHD >20%
Peripheral arterial disease
Abdominal aortic aneurysm
Symptomatic carotid artery disease
Diabetes
Risk factors family history, HTN, cigarette smoking, DM (risk equivalent), low HDL,
older age (men 45; women 55), males
If no evidence of CVD and no other risk factors, males at 35 and females at 45 (USPSTF)
NCEP recommends screening all adults at age 20 regardless of risk factors
LDL (mg/dL)
TOTAL CHOLESTEROL (mg/dL)
HDL (mg/dL)
Optimal < 100
Desirable < 200
Protective > 60
Near optimal 100-129
Borderline high 130-159
Borderline high 200-239
Borderline 41-59
High 160-189
High > 239
At risk < 40

Very high > 190

Treatment:
o Lifestyle changes are first line
Reduce total fat intake to 25-30% of diet, saturated fat to 7% or less, and dietary
cholesterol to < 200 mg/day
The Mediterranean diet reduces LDL cholesterol without reducing HDLs
Soluble fiber, garlic, soy, pecans, plant sterols, and vitamin C may help reduce
LDL
Encourage 30 minutes of aerobic exercise daily may help increase HDL
Increase antioxidants from fruits and vegetables. Soluble fiber may reduce LDL levels
CAD prophylaxis with aspirin 81 mg unless otherwise contraindicated
Smoking cessation
Modest alcohol use may improve the lipid profile
o Pharmacologic treatment
Statins (HMG-CoA inhibitors) reduce cholesterol production in the liver and increase the
ability of the liver to remove LDL cholesterol from the blood
Inhibits the rate-limiting enzyme in formation of cholesterol
Can lowe LDL by 20-60% and triglycerides by 15-30%
Side effects myalgias and mild GI complaints
o More severe cases of myositis (especially if taken with niacin or a
fibrate), liver toxicity, and rhabdomyolysis have been reported
Monitor liver enzymes
Measure CPK if myalgias develop
Monitor lipid levels every 6 weeks until goals are met
Niacin has an optimal effect on lipids and reduces long-term risk of CAD by reducing
production of VLDL and LDL, and increasing HDL. May also reduce triglycerides
Side effect = flushing
Prostaglandin-induced niacin flushing can be reduced by taking aspirin 30
minutes prior or a daily NSAID
Extended-release niacin is often better tolerated
Bile acid sequestrants (cholestyramine, colesevelam, and colestipol) bind bile acids in the
intestine
These resins reduce the incidence of coronary evens in middle-aged men, but
have no effect on total mortality
Associated with constipation and gas
May interfere with absorption of fat-soluble vitamins, potentially effecting warfarin
management
Fibric acid derivatives (gemfibrozil, fenofibrate, clofibrate) are peroxisome proliferatoractivated receptor alpha (PPAR-alpha) agonists and are the most potent medications for
lowering triglyceride levels and raising HDL.
Reduce synthesis and increase breakdown of VLDL
Side effects gallstones, hepatitis, myositis
Ezetimibe blocks intestinal absorption of dietary and biliary cholesterol by blocking a
cholesterol transporter at the brush border
May be used as monotherapy or in combo with a statin
o Guidelines have changed, but for boards, use the following treatment guidelines:
Goal LDL < 160

< 130 for moderate risk

< 100 for high risk or CHD risk equivalent

Rheumatic Heart Disease / Rheumatic Fever

- Rheumatic fever is a systemic immune response occurring usually 2-3 weeks following a -hemolytic
streptococcal pharyngitis
o Most commonly affects the heart, joints, skin, and CNS
- Most common in recent immigrants, but new U.S. outbreaks have occurred. Children from ages 5-15 years
are most often affected
- Rheumatic valve disease may be self-limited or lead to progressive deformity of the valve
o The typical lesion is a perivascular granuloma with vasculitis
- The mitral valve is most often involved (75-80%), followed by aortic valve (30%)
o Aortic or tricuspid involvement rarely occurs in isolation
- Jones Criteria 2 major or 1 major + 2 minor are required to establish the diagnosis of rheumatic fever
o Major carditis, erythema marginatum, subcutaneous nodules, chorea, polyarthritis
o Minor fever, polyarthralgias, reversible prolongation of the PR interval, elevated ESR/CRP
- Supportive evidence is needed = positive throat culture or rapid strep test and elevated or rising
streptococcal antibody titer (antistreptolysin O [ASO] titer)
- Treatment:
o Strict bed rest
o IM penicillin for documented streptococcal infection
Erythromycin if penicillin-allergic
o Salicylates reduce fever and relieve joint problems
o Corticosteroids relieve joint symptoms but do not prevent cardiac disease
o Prevent = early treatment of streptococcal pharyngitis
Prevention of recurrence is essential to prevent heart damage
Benzathine penicillin every 4 weeks is a common prophylactic regimen
o The American Heart Association no longer recommends antibiotics before invasive procedures to
prevent endocarditis in patients with a history of rheumatic heart disease
Prophylaxis is recommended if a patient has a prosthetic cardiac valve, previous
endocarditis, or specific forms of congenital heart disease)
- Complications of acute rheumatic fever CHF, rheumatic pneumonitis, rheumatic heart disease (most
commonly valvular defects, but also arrhythmias, pericarditis, or effusions)
Vascular Disease
Aortic Aneurysm / Dissection
- An ANEURYSM is an abnormal dilation of an artery
o Saccular aneurysms occur when a portion of the artery forms an outpouching, or mushroom
o Fusiform aneurysm occur when the entire arterial diameter grows
- True aneurysms involve all layers of the arterial wall intima, media, adventitia
- An artery is considered aneurysmal if the diameter is >1.5 times its normal size (otherwise an enlarged
artery is considered ectatic)
- A DISSECTION occurs when a defect in the intima allows blood to enter between the layers of the wall.
Blood pressure then causes the layers of the wall to separate from one another.
- AORTIC DISSECTION is a disease process in which the intima of the aorta tears and allows blood entry
into the media of the aorta
o Associated with hypertension, Marfan syndrome, connective tissue disorders, bicuspid aortic valve,
trauma, aortic manipulation, or catheter injury
o More common than thoracic or abdominal aneurysms
o Can cause aortic rupture, peripheral or organ ischemia due to flow occlusion, stroke, aortic valve
insufficiency, and cardiac tamponade

Dissection is usually initially seen with chest pain or back pain between the shoulder blades
May have aortic regurgitation murmur, widened mediastinum on CXR, ischemia of EKG,
or changes in pulse on exam
The best modalities for imaging are TEE, spiral CT, and MRI/MRA
o Typically presents with acute onset of pain that is most severe at onset located in the chest and
radiating to the back
o Most patients are male, older than 50 years, and have a history of HTN
Or younger patients with connective tissue disorders, congenital heart disease, and
pregnancy
o Two groups of aortic dissection:
Stanford Type A tear is in the ascending aorta distal to the aortic valve
Stanford Type B patients whose tear is distal to the left subclavian artery in the
descending aorta
o Also the DeBakey classification:
Type 1 ascending and descending aorta
Type 2 only ascending aorta
Type 3 only descending aorta
o CXR is abnormal in 80% of patients
Abnormal aortic contour
Widening of the mediastinum
Deviation of the trachea, mainstem bronchi, or esophagus
Apical capping
Pleural effusion
Calcium sign
o CT is the most sensitive
o TEE is test of choice
o Type A is treated surgically with excision of the tear and a portion of the ascending aorta,
replacement with aortic graft, and repair or replacement of the aortic valve
Treated surgically due to the risk of rupture into the pericardium with resulting tamponade,
risk of acute AR with onset of severe CHF, and risk of ischemia
o Type B (uncomplicated) is treated medically with tight control of blood pressure with beta-blockers
and afterload reducers (sodium nitroprusside)
Beta-blockers are primary because they decrease the stress on the aortic wall
Complicated type B may need surgery either by aortic excision and graft replacement
with necessary revascularizations or by refenestration of the false lumen to allow passage
of blood back into the true lumen
Vasodilators (nitroprusside) should only be used after adequate inotropic blockage has
been made with beta-blockers or CCBs
ABDOMINAL AORTIC ANEURYSM:
o The classic presentation is an older (>60 years) male smoke with atherosclerosis who presents
with sudden onset severe back or abdominal pain, hypotension, and a pulsatile abdominal mass
o Localized irreversible arterial dilatation that increases the area of the abdominal aorta by at least
50%. Normal diameter is about 2 cm, so AAA has diameter of 3 cm or more
o More common in whites than blacks
o Branches of the AA include the celiac trunk, SMA, IMA, renal arteries, gonadal arteries
Most AAA (95%) begin distal to the takeoff of the renal arteries
o Most are associated with atherosclerosis.
o

o
o

o
o

Abdominal/flank pain and hypotension are the most common symptoms of rupturing or expanding
(symptomatic) AAA
Most aneurysms (75%) are discovered when still asymptomatic, either as a pulsatile mass
on exam or incidentally on other work-up
When palpable, usually located to the left of the midline, above the umbilicus, in the
epigastric area
The primary physical finding is a laterally expansile pulsating abdominal mass in the
epigastrium. The width, not the intensity, of the pulsation suggests the presence of AAA
Ripping or tearing pain that is severe and abrupt in onset
Commonly with nausea and vomiting
May have Cullen (periumbilical ecchymosis) or Grey-Turner sign (flank ecchymosis)
Ultrasound is an accurate and noninvasive method to assess the size of the aneurysm and
presence of clot
CT or MRI/MRA provides anatomic detail and precise localization of the aneurysm
CT is the best way to monitor growth of AAA
Only in a stable patient
Plain films are not helpful
Treatment:
If asymptomatic, treatment depends on size of the lesion (proportional to its risk of leak or
rupture)
< 4 cm in diameter are unlikely to rupture. Medically manage with beta-blockers
o Re-scan ever 6th months
4-5 cm in diameter can have two options early operation or close follow-up
> 5 cm in diameter has a rupture incidence of >25% at 5 years, and repair is
recommended
Any patient with symptoms should have immediate workup. If diagnosed with rupture or
leak, immediate fluid resuscitation and operative intervention
Repair of the AAA:
Gold standard surgical placement of a vascular prosthesis within the lumen of the
aneurysm via a midline or left retroperitoneal incision below the 12th rib
Basic principles proximal aortic control above the aneurysm as well as distal control
below the aneurysm.
The proximal anastomosis is done to the neck of the aorta, which is the nonaneurysmal
aorta just above the aneurysm. The graft is then sewn to healthy aorta just below the AAA
If the AAA disease extends to the distal aorta, a bifurcated graft is sewn to both
iliac arteries
Endovascular repair is now widely used endovascular stented graft via open femoral
access. The distal limbs of the grafts are placed in both iliac arteries
Always have blood available!!!

Peripheral Arterial Disease

- PAD usually is a result of atherosclerosis and is a significant independent risk factor for cardiovascular
morbidity and mortality
- Lower extremity disease results in ischemia and pain, causing significant limitation of activity or disability
- Acute arterial occlusion may be caused by thrombosis or embolism
- Thrombotic disease also may be a result of trauma, hypovolemia, inflammatory arteritis, polycythemia,
dehydration, repeated arterial punctures, and hypercoagulable states
- Three patterns of disease:
o Type 1 15-20% of patients, limited to the aorta and common iliac artery, most commonly found
in those 40-55 years old who smoke heavily or have hyperlipidemia
o Type 2 25% of patients, involves the aorta, common iliac artery, and external iliac artery
o Type 3 most common (60-70% of patients), multilevel disease affecting the aorta and the iliac,
femoral, popliteal, and tibial arteries
- Patients with type 2 and 3 PAD have typical risk factors for atherosclerotic disease and usually a high
incidence of cerebrovascular and coronary artery disease
- Modifiable risk factors = smoking, diabetes, HTN, lipids, sedentary lifestyle / obesity
o Atherosclerosis is the most common cause of chronic lower limb occlusive disease
- Clinical Findings:
o Intermittent Claudication muscular pain in lower leg induced by exercise and relieved by rest
Usually the first symptom of peripheral disease
Later, pain at rest occurs (frequently nocturnal)
o Femoral and distal pulses will be weak or absent
o An aortic, iliac, or femoral bruit may be present
o Erectile dysfunction occurs with iliac artery disease (Leriches syndrome)
o Severe, chronic disease results in numbness, tingling, and ischemic ulcerations (may lead to tissue
necrosis or gangrene)
o Symptoms of occlusion depend on the artery, the area it supplies, and the collateral circulation
Buttock / Hip = aortoiliac disease
Thigh = common femoral artery
Upper calf = superficial femoral artery
Lower calf = popliteal artery
Foot = tibial / peroneal artery
o Extremity occlusion usually results in pain, pallor, pulselessness, paresthesias, poikilothermia, and
paralysis. The SIX Ps!!!!!!!!!
Cool skin temperature or abnormal skin color, poor hair growth
- Laboratory Studies:
o Doppler flow studies are used to determine systolic pressures in the posterior tibial and dorsalis
pedis arteries
o Ankle / Brachial Index (ABI)
ABI is a non-invasive test performed to assess asymptomatic PAD or mild-moderate
claudication
They are helpful to predict critical limb ischemia and amputation, propensity for wound
healing, and patient survival
Can be used as a screening tool or to monitor the efficacy of therapeutic interventions
ABI = ratio of SBP ankle / SBP arm
Normal ABIs (inpatients without PAD) ankle systolic pressure is 10-15 mmHg higher
than brachial systolic pressure

An ABI of < 0.9 indicates significant disease

Normal = 1.0+
< 0.9 = diagnosis of peripheral vascular disease
< 0.7 = intermittent claudication
< 0.4 = rest pain
< 0.1 = impending tissue necrosis
o CT or magnetic resonance angiography is used for locating stenotic sites and for accurate
diagnosis of thrombosis or embolism
- Treatment:
o Smoking cessation, progressive exercise, lipid-lowering medications (reduce the risk for new-onset
or worsening claudication)
o Acute arterial occlusion should be treated with initiation of anticoagulation unfractionated heparin
Also give aspirin
Thrombolytics are controversial
Definitive treatment with vascular surgeon catheter-directed embolectomy is the
preferred approach
Reperfusion injury after revascularization of the injury can result in
myoglobinemia, renal failure, hyperkalemia, and metabolic acidosis
o For chronic PAD with no immediate limb threat, discharge on aspirin
Cilostazol (Pletal) is the main drug treatment
Antiplatelet therapy (aspirin, clopidogrel) should be used routinely in all patients without a
contraindication
o Erectile dysfunction may require revascularization or treatment with a phosphodiesterase, such as
sildenafil
o Indications for operation for carotid artery disease 75% stenosis, 70% stenosis and symptoms,
bilateral disease and symptoms, or >50% stenosis and recurring TIAs despite aspirin therapy
Phlebitis / DVT / PE
- General Characteristics:
o Involves partial or complete occlusion of a vein and inflammatory changes. Virchows triad of
stasis, vascular injury, and hypercoagulability predispose a vein to development of
thrombophlebitis.
o Superficial thrombophlebitis may occur spontaneously or following trauma and occurs frequently at
the site of IV or PICC.
o DVT most often occurs in the LE and the pelvis.
o DVT is associated with major surgical procedures (especially total hip replacement), prolonged bed
rest, use of oral contraceptives and hormone replacement therapy, and inherited (e.g. factor V
leiden) and cancer-associated hypercoagulable states. Increasingly, air travel is being recognized
as a cause.
Other risk factors include advanced age, type A blood, obesity, multiparity, IBD, and lupus
erythematous.
o PE occurs when a portion of a clot breaks off and travels to a pulmonary artery
- Clinical Features:
o Superficial thrombophlebitis may present with dull pain, erythema, tenderness, and induration of
the involved vein or with no symptoms. It is most common in the long saphenous vein. A cord may
be palpable following resolution of acute symptoms.
o Half of patients with DVT have no early signs and symptoms. Classic findings of DVT include
swelling of the involved area with heat and redness over the site; Homans sign is unreliable (pain
in the calf with forced dorsiflexion)

Consider the diagnosis of PE in those with acute dyspnea, chest pain, unexplained tachycardia,
hypoxemia, syncope, or shock
The most common symptoms include dyspnea, pleuritis or nonpleuritic chest pain,
anxiety, cough, and syncope
Common signs = hypoxemia, tachypnea, tachycardia, hemoptysis, diaphoresis, and lowgrade fever
Differential:
o Consider the probability of PE prior to decision to initiate testing reserve testing for those whose
probability is higher. Use the PERC rule
Age < 50 years
Pulse oximetry > 94% on room air
Heart rate < 100 bpm
No prior VTE
No recent surgery or trauma (requiring hospitalization, intubation, or epidural anesthesia
within 4 weeks prior)
No hemoptysis
No estrogen use
No unilateral leg swelling
o When PE cannot be excluded with the PERC rule, use Wells Criteria high risk >6, moderate risk
2-6, low risk <2
Heart rate > 100 bpm = 1.5 points
Hemoptysis = 1 point
History of VTE = 1.5 points
Malignancy (active) = 1 point
Leg swelling, pain with palpation of deep veins (clinical signs of DVT) = 3 points
Immobilization within prior 4 weeks = 1.5 points
Alternative diagnoses less likely than PE = 3 points
Diagnostic Studies:
o Duplex ultrasound is the preferred study for DVT. Negative results in a patient with a high suspicion
for DVT indicate the need for further study.
o Venography is the most accurate method for definitive diagnosis of DVT, but it is associated with
increased risk and rarely is needed.
o D-dimer is a fibrin degradation product that is elevated in the presence of thrombus. An elevated ddimer does not sufficiently diagnose thrombophlebitis; most hospitalized patients will have an
elevated level. A negative d-dimer test (<500), however, suggests that US may be omitted.
Recommended if pretest probability is low or intermediate
o CT of the chest (chest CTA) is the test of choice to rule out PE
V/Q scan for those who cannot undergo CT (e.g., contrast allergy)
Treatment:
o Superficial disease is usually treated with bed rest, local heat, elevation of the extremity, and
NSAIDs. More serious disease may require surgical intervention.
o Prevention of DVT in bedridden patients is accomplished by elevation of the foot of the bed, leg
exercises, and compression hose; in high-risk patients, anticoagulation may be appropriate.
o Prevention of perioperative and travel-associated DVT includes early or frequent ambulation, leg
exercises and compression hose.
o Preferred treatment is anticoagulation with LMWH; heparin followed by warfarin (INR 2.0-2.5) may
be used.
Thrombolytic therapy usually not needed unless massive PE
o

IVC filter if contraindications to anticoagulation or if anticoagulation failed

Continue outpatient anticoagulation for 3, 6, or 12 months

Varicose Veins
- Usually in women who have been pregnant
o Other risk factors = obesity, family history, prolonged sitting or standing, history of phlebitis
- Main mechanisms = superficial venous insufficiency and valvular incompetence
o Also inherited defects in vein walls or valves
- Dilated, tortuous veins develop superficially in the lower extremities, particularly in the distribution of the
great saphenous vein
o Also, smaller blue-green, flat reticular veins; telangiectasias; spider veins all are evidence of
venous dysfunction
- Chronic distal edema, abnormal pigmentation, fibrosis, atrophy, and skin ulceration may develop in severe
or prolonged disease
- The Brodie-Trendelenburg test differentiates saphenofemoral valve incompetence from perforator vein
incompetence
- Diagnostic studies are not necessary
o But, Doppler sonography locates incompetent valves before surgery and identifies those due to
congenital malformation
- Treatment:
o Graduate elastic stockings
o Leg elevation and regular exercise provide symptomatic relief
o Small venous ulcers heal with leg elevation and compression bandages
Larger ulcers require compression boot dressing (Unna boot) or skin grafts
o Interventional techniques = endovenous radiofrequency or laser ablation, sclerotherapy, surgical
stripping of saphenous tree
Chronic Venous Insufficiency
- Characterized by loss of wall tension in veins, which results in stasis of venous blood and often is
associated with a history of DVT, leg injury, or varicose veins
- Prevention is accomplished by early aggressive treatment of venous reflux states, such as acute
thrombophlebitis or varicose veins, use of compression hose, and weight reduction
- Progressive edema starting at the ankle is followed by skin and subcutaneous changes
- Itching, dull pain with standing, and pain with ulceration is common
- Skin is shiny, thin, and atrophic with dark pigmentary changes and subcutaneous induration
- Ulcers most commonly occur just above the ankle (stasis ulcer)
- Treatment = elevation of legs, avoid prolonged sitting or standing, compression hose
- Stasis dermatitis should be treated with wet compresses and hydrocortisone cream
o Chronic dermatitis may require addition of zinc oxide with ichthammol and an antifungal cream
- Ulcerations may be treated with wet compresses, compression boots or stockings, and, occasionally, skin
grafting

Internal Medicine Pulmonary

Acute / Chronic Bronchitis
- More than 90% of cases are caused by viruses including rhinovirus, coronavirus, and RSV
o Also influenza A or B, parainfluenza
- Defined as inflammation of the airways (trachea, bronchi, bronchioles) characterized by cough
- In patients with chronic lung disease, causes also include H. flu, S. pneumo, M. cat
- Signs and symptoms cough (with or without sputum), dyspnea, fever, sore throat, headache, myalgias,
substernal discomfort, and expiratory rhonchi or wheezes
o Sputum color is not predictive of bacterial involvement!!!
- Can be difficult to distinguish from pneumonia, so the examination should be conducted to identify comorbid
conditions that may influence treatment
o Bronchitis lacks the suggestive symptoms and signs of pneumonia, specifically fever > 38C
(100.4F), adult heart rate > 100 bpm, and/or adult respiratory rate > 24 breaths/min
- Diagnosis of acute bronchitis is clinical:
o Acute onset cough (< 3 weeks duration)
o Absence of chronic lung disease history
o Normal vital signs
o No ausculatory abnormalities that suggest pneumonia
- Generally no laboratory evidence is required unless there is a strong need to differentiate bronchitis from
pneumonia. The CXR will be negative in acute bronchitis
- Treatment:
o Supportive measures hydration, expectorants, analgesics, 2-agonists, and cough suppressants
o For acute exacerbations of chronic bronchitis, in which bacterial causes are more likely, empiric
first-line treatment is a second-generation cephalosporin, second-line treatment is a secondgeneration macrolide or TMP/SMX
?? azithromycin first-line ??
o Antibiotics are indicated for the following elderly patients, those with underlying
cardiopulmonary diseases and a cough for more than 7-10 days, and any patient who is
immunocompromised
o For acute exacerbations in otherwise healthy adults, no empiric treatment is needed
Asthma
- Obstructive pulmonary disease
- Characterized by three components obstruction of airflow, bronchial hyperreactivity, and inflammation of
the airway. It is a disease of chronic inflammation leading to airway narrowing and increased mucus
production
- Many asthma syndromes extrinsic allergic, allergic bronchopulmonary aspergillosis, intrinsic asthma,
extrinsic nonallergic, aspirin sensitivity, exercise induced, and asthma associated with COPD
- The strongest predisposing factor to asthma is atopy. The atopic triad consists of wheeze, eczema, and
seasonal rhinitis
- Exacerbations often are correlated with common precipitants allergens (especially dust, dust mites,
dander, cockroaches, pollen), exercise, URI, postnasal drip, GERD, drugs (beta-blockers, ACE, aspirin,
NSAIDs), stress, cold air or change in weather, environmental irritants
- Patients have an intermittent occurrence of cough, chest tightness, breathlessness, and wheezing. of
children have no wheeze
- Patients undergo asymptomatic periods between attacks
- Asthma is classified according to frequency of symptoms and PFTs. In children, especially those under 5,
the classification of asthma severity is more aggressive.

Laboratory Findings:
o Airflow obstruction is indicated by decreased ratio of FEV1 to FVC (FEV1/FVC < 75%). A greater
than 10% increase in FEV1 after bronchodilatory therapy is supportive of the diagnosis
o ABG measurements may be normal in mild cases, but in severe cases, they can reveal hypoxemia
and hypercapnia, with a PaO2 of less than 60 mmHg and a PaCO2 of more than 40 mmHg. ABGs
are rarely indicated or obtained unless the patient is severely ill or nonresponsive to treatment
o CXR may show hyperinflation. Radiography is only indicated if pneumonia is suspected, the
asthma is complicated, or another disorder is suspected
o Handheld peak expiratory flow meters estimate variability and quantify severity of attacks. Use of
this objective device should be encouraged in patients with chronic disease
o A histamine or methacholine challenge test (bronchial provocation test) may help to establish the
diagnosis of asthma when spirometry is nondiagnostic. An FEV1 decrease of more than 20% is
diagnostic
Treatment:
o The goals of treatment are to minimize chronic symptoms, prevent recurrent exacerbations and
thus minimize the need for urgent care visits, and maintain near-normal pulmonary function
o Asthma medications can be divided into long-term control (corticosteroids, cromolyn, nedocromil,
long-acting bronchodilators, leukotriene modifiers, and theophylline) and quick-relief medications
(short-acting inhaled beta-agonists, ipratropium bromide, and systemic corticosteroids)
o Treatment algorithms are based on both the severity of the patients baseline asthma and the
severity of asthma exacerbations.
o -adrenergic agonists should be available to induce bronchodilation during acute symptoms
(rescue medication)
o Inhaled corticosteroids are the most effective anti-inflammatory medications for management of
chronic asthma
o Educated patients about disease and peak flow monitoring.
Green Zone (> 80%)
Yellow Zone (50-80%)
Red Zone (< 50%)

Bronchodilators:
Methylxanthine derivatives Theophylline (Slobid, Theodur, Uniphyl)
Beta-2 agonists Albuterol (Ventolin, Proventil, Proair), Levalbuterol (Xopenex),
Salmeterol (Serevent)
Anti-cholinergics Atropine, Ipratropium (Atrovent)
Anti-Inflammatory Agents:
Mast cell stabilizers Cromolyn (Intal), Nedocromil (Tilade)
Steroids Beclomethasone (Qvar), Fluticasone (Flovent), Budesonide (Pulmicort),
Mometasone (Asmanex), Ciclesonide (Alvesco), Triamcinolone (Azmacort), Flunisolide
(Aerobid),
Combination Therapy Advair (fluticasone + salmeterol), Symbicort
(budesonide + formoterol), Dulera (mometasone + formoterol)
Systemic Steroids useful for acute attacks
Leukotriene inhibitors Zileuton (Zyflo), Zafirlukast (Accolate), Montelukast (Singulair)
Anti-IgE antibodies
Inhaled Steroid Side Effects
Topical side effects oral thrush, change in phonation
Systemic side effects dose dependent (uncommon if total daily dose is < 1200 mcg of
beclomethasone / day)
Systemic Steroid Side Effects
Short term side effects increased appetite, weight gain, fluid retention, irritability
Long term side effects growth suppression, adrenal suppression, immunosuppression,
decreased bone density, hypertension, diabetes, glaucoma, cataracts
Mainstays of Treatment ICS, SABA / LABA, LTRA
Beta-adrenergic agonists reduce smooth muscle constriction. Administered via nebulizer
or metered-dose inhaler
LABA are used in combo with ICS if ICS fails alone. Not appropriate for
monotherapy
SABA for exercise-induced. Use 5-20 minutes before activity
Careful of abuse and/or tolerance
ICS is most effective treatment for chronic asthma
LTRA are oral meds that are also recommended for the initial treatment of mild persistent
asthma. May also be used as adjunct to an ICS. Most effective in younger patients and
those with a shorter duration of asthma. Also may help with exercise-induced

Chronic Obstructive Pulmonary Disease (COPD)

- COPD is a clinical and pathophysiologic syndrome that includes emphysema and chronic bronchitis. These
disorders have overlapping features, and because patients often have characteristics of more than one
disorder, both are classified together as COPD
o EMPHYSEMA is a condition in which the air spaces are enlarged as a consequence of destruction
of alveolar septae
o CHRONIC BRONCHITIS is a disease characterized by a chronic cough that is productive of
phlegm occurring on most days for 3 months of the year for 2 or more consecutive years without an
otherwise-defined acute cause
- Smoking is the most important cause of COPD. Other causes include environmental pollutants, recurrent
URI, eosinophilia, bronchial hyperresponsiveness, and 1-antitrypsin deficiency
- Patients present with a history of progressive SOB, excessive cough, and sputum production. Patients with
predominantly emphysematous COPD may have dry cough and weight loss
- Physical exam in a patient with advanced COPD may reveal asthenia, dyspnea, pursed-lip breathing, and
grunting expirations
- Chest examination:
o Signs of hyperinflation with increase in the AP dimension are noted
Barrel chest = increased AP diameter. Suggests hyperinflation and air trapping secondary
to incomplete expiration
o Percussion yields increased resonance ~ caused by hyperinflation and air trapping secondary to
incomplete expiration
o Auscultation reveals decreased breath sounds and early inspiratory crackles
Distant breath sounds are caused by barrel chest, hyperinflation, and air trapping
Coarse crackles are a common finding in exacerbations. A discontinuous sound referring
to mucus or sputum in airways. Indicative of airway inflammation and mucus
oversecretion
o Wheezing may not be present at rest but can be evoked with forced expiration or exertion
A common finding in exacerbations
Described as a continuous musical lung
Indicative of airway inflammation and resistance
o The duration of expiration is prolonged
o Poor air movement is secondary to loss of lung elasticity and tissue breakdown

In patients with chronic bronchitis, rhonchi reflect secretions in the airways, and breathing typically is raspy
and loud
Laboratory Findings:
o CXR:
May show hyperinflation of the lungs and flat diaphragms, however, a CXR is not sensitive
or specific enough to serve as a diagnostic or screening tool
If emphysema is the main clinical feature, parenchymal bullae or subpleural blebs are
pathognomonic
In chronic bronchitis, nonspecific peribronchial and perivascular markings may be present
o PFTs:
Airflow obstruction demonstrated on forced expiratory spirometry is suggestive
The FEV1/FVC ratio is decreased (< 0.70 or less than the lower limit of normal)
To diagnose, need FEV1/FVC < 0.70 or less than the lower limit of normal, PLUS FEV1 <
80% predicted. Must be incompletely reversible with inhaled bronchodilator (hallmark)
When evaluating a patient for possible COPD, spirometry is performed pre and post
bronchodilator administration (e.g., inhalation of albuterol) to determine whether airflow
limitation is present and whether it is partially or fully reversible
Airflow limitation that is irreversible or only partially reversible with bronchodilator
is suggestive of COPD rather than asthma
o CBC may show polycythemia (increased hematocrit aka increased RBC) caused by chronic
hypoxemia
Hypoxia is caused by impaired gas exchange in lung parenchyma, worsens with exercise
o Pulse oximetry does not provide information about alveolar ventilation or hypercapnia (PaCO2 > 45
mmHG)
In patients with chronic disease, 88-90% may be acceptable
o ABG in mild to moderate COPD, usually reveal mild to moderate hypoxemia without
hypercapnia. As the disease progresses, hypoxemia worsens and hypercapnia may develop
PaCO2 > 50 mmHg or PaO2 < 60 mmHg suggests respiratory insufficiency
Check in patients who are acutely ill, especially if they have an abnormal pulse ox reading
Also perform in stable patients with FEV1 < 50% predicted or with clinical signs suggestive
of disease progression
Hypercapnia, hypoxia, and respiratory acidosis are signs of impending respiratory failure
and possible need for intubation
Treatment:
o In symptomatic patients, the goal of treatment is to improve functional state and relieve symptoms
o Smoking cessation is the single most important intervention
o Anticholinergic inhalers (ipratropium or tiotropium) are superior to -adrenergic agonists in
achieving bronchodilation
o Short-acting bronchodilators should be prescribed for acute exacerbations of dyspnea
o These patients are at high risk for acute infections, therefore oral antibiotics frequently are
necessary
o Supplemental oxygen is the only therapy that may alter the course of COPD in patients with resting
hypoxemia (PaO23 < 55 mmHg or SaO2 < 88%)
o Graded aerobic physical exercise should be encouraged
o Steroids are effective but should be used with caution
o Human 1-antitrypsin replacement may be recommended for patients who are deficient
o Patients should receive the pneumococcal vaccine and yearly influenza vaccine

o
o

Mainstay of treatment is inhaled bronchodilators beta agonists (albuterol) and anticholinergics

(ipratropium). Theophylline is also one, but is rarely used unless people are refractory (more side
effects and toxicity)
All COPD patients should be prescribed a short-acting bronchodilator for an as-needed basis
(inhaled method is preferred)
Combination of beta-agonist and anticholinergic is optimal, but both are effective as
monotherapy
Seem to be equally effective
Beta-agonist has a more rapid onset of action
Add a regularly scheduled long-acting bronchodilator if symptoms are not controlled with a shortacting usually GOLD category B and higher
Long-acting beta-agonist (salmeterol, formoterol) or long-acting anticholinergic (tiotropium,
aclidium, glycopyrronium) is acceptable
Until recently, anticholinergic was preferred because most of the effects of the
once daily anticholinergic seemed to be superior to the twice daily beta agonists.
Now, there are once daily LABAs and twice daily LAMAs
In patients with GOLD stage II-IV COPD whose symptoms are not well-controlled with a
single long-acting bronchodilator, the addition of a second class may provide additional
benefit (can also add inhaled glucocorticoids)

o
o
o
o

Inhaled corticosteroids (inhaled glucocorticoids) can help reduce systemic inflammation that
characterizes COPD
They decrease exacerbations and modestly slow progression of respiratory symptoms,
but appear to have little impact on lung function and mortality
Should NOT be used as monotherapy (never without a long-acting bronchodilator)
Usually added to the regimen in GOLD stages III-IV for patients who have significant
symptoms or repeated exacerbations
Refractory Disease
Some patients continue to have symptoms or repeated exacerbations of COPD despite
therapy with an optimal long-acting inhaled bronchodilator plus an inhaled glucocorticoid
Ensure proper inhaler technique and smoking cessation
Assess for exercise-related oxygen desaturation using pulse-ox. If desaturation occurs
and is associated with symptoms, use of supplemental oxygen may reduce symptoms
Can try triple inhaler therapy long-acting beta-agonist + long-acting anticholinergic +
inhaled glucocorticoid
Can also try a low dose of oral theophylline can help with bronchodilation
Can be toxic!! Metabolized in the liver. Many interactions
Phosphodiesterase-4 (PDE-4) inhibitors can decrease inflammation and may promote
airway smooth muscle relaxation
Roflumilast an oral PDE-4 that is FDA approved for patients with chronic
bronchitis, severe or very severe airflow limitation, and a history of exacerbations
Systemic glucocorticoids are rarely used because chronic use can have adverse effects
Mucoactive agents are not accepted as routine care for COPD patients
Oral expectorants (guaifenesin, etc.) offer little benefit to COPD patients
May need antibiotics (macrolides in particular)
May have antiinflammatory effects in addition to antibiotic effects
For patients who continue to have frequent exacerbations despite optimal therapy for
COPD with bronchodilators and antiinflammatory agents prophylaxis with azithromycin

STAGING OF COPD (GOLD System)

- STAGE 1 mild. FEV1/FVC < 70% and FEV1 80%, with or without symptoms
o Often minimal SOB with or without cough and/or sputum. Usually goes unrecognized that lung
function is abnormal
- STAGE 2 moderate. FEV1/FVC < 70% and FEV1 = 50-80% predicted value, with or without symptoms
o Often moderate or severe SOB on exertion, with or without cough, sputum or dyspnea. Often the
first stage at which medical attention is sought due to chronic respiratory symptoms or an
exacerbation
- STAGE 3 severe. FEV1/FVC < 70% and FEV1 = 30-50% predicted value, with or without symptoms
o More severe SOB, with or without cough, sputum or dyspnea often with repeated exacerbations
which usually impact quality of life, reduced exercise capacity, fatigue
- STAGE 4 very severe. FEV1/FVC < 70%, FEV1 < 30% predicted value or FEV1 < 50% with chronic
respiratory failure
o Appreciably impaired quality of life due to SOB possible exacerbations which may even be life
threatening at times
GROUPS OF COPD & TREATMENT
- GROUP A patients have few symptoms and low risk of exacerbations
o Short-acting bronchodilator PRN
- GROUP B patients have more symptoms and low risk of exacerbations
o Short-acting bronchodilator PRN
o Long-acting bronchodilator
- GROUP C patients have few symptoms but higher risk of exacerbations
o Short-acting bronchodilator PRN
o Long-acting bronchodilator
o May need to add inhaled corticosteroid if patients have frequent exacerbations
o May need refractory meds
- GROUP D patients have more symptoms and high risk of exacerbations
o Short-acting bronchodilator PRN
o Long-acting bronchodilator
o May need to add inhaled corticosteroid if patients have frequent exacerbations
o May need refractory meds
o May need long-term supplemental oxygen (PaO2 < 55 mmHg or SaO2 < 88%)
Pneumonia (Viral, Bacterial, Fungal, HIV-related)
- Denotes inflammation in the alveoli or interstitium of the lung caused by microorganisms
- Ranks as the primary cause of mortality from infectious diseases
Classic Community-Acquired Pneumonia (CAP)
- Acquired in the home or nonhospital environment
- In most cases, the causative agent is not identified. However, in those cases where an agent is identified,
bacteria are more commonly found
o S. pneumo**, H. flu, M. cat, S. aureus, Klebsiella, and other gram-negative bacilli
o Viral causes influenza, RSV, adenovirus, parainfluenza

Typical presentation is a 1-10 day history of

increasing cough, purulent sputum, SOB,
tachycardia, pleuritic chest pain, fever or
hypothermia, sweats, and rigors
- Physical exam may reveal altered breath sounds
and crackles, dullness to percussion if an effusion is
present, and bronchial breath sounds over an area
of consolidation
o Chest exam alone is NOT sufficient to
confirm or exclude the diagnosis
- Laboratory Findings:
o Organisms may be detected with
conventional stain or sputum culture,
although typically this is not done before
starting treatment. The most common
bacterial pathogen identified is S. pneumo
o CXR shows lobar or segmental infiltrates,
air bronchograms, and pleural effusion.
There is no pathognomonic radiographic
presentation
o Procalcitonin levels rise in response to
proinflammatory stimulus, especially
bacterial infection. Elevated levels support
a bacterial versus viral origin
- Treatment:
o Patient who is otherwise healthy and free of
respiratory distress or complications may
be treated as outpatient with oral antibiotics
and appropriate supportive care
o A macrolide (clarithromycin, azithromycin)
or doxycycline is the appropriate choice for outpatient treatment
A fluoroquinolone or a macrolide + beta-lactam is top choice for patients with underlying
chronic disease/significant comorbidities
Beta-lactam = Augmentin
o Neutropenia, involvement of more than 1 lobe, or poor host resistance indicates a need for
hospitalization. Also, consider hospitalization in patients older than 50 years with comorbidities,
altered mental status, or hemodynamic instability
o If inpatient treatment is necessary, consider coverage of S. pneumo and Legionella with a
fluoroquinolone or a combination beta-lactam (i.e., ceftriaxone or cefotaxime) + a macrolide (i.e.,
azithromycin)
Levofloxacin or ceftriaxone + azithromycin
If ICU admission levofloxacin + ceftriaxone + vancomycin (if MRSA suspected)
o PCV recommended as a series of 4 doses for children 6 weeks 15 months. PPSV for children 25 years old who have not been immunized, those 65 years old or any person with a chronic
illness that increases the risk of CAP (cardiopulmonary disease, SCD, tobacco abuse,
splenectomy, liver disease)
Atypical CAP
- Clinical presentation different from classic CAP
- Mycoplasma pneumoniae is the most common cause of atypical pneumonia. Other causes are viruses
(influenza A or B, adenoviruses), Chlamydia pneumoniae, Legionella, Moraxella

Typical presentation of atypical pneumonia is a low-grade fever with relatively mild pulmonary symptoms,
which are self-limited, occurring in young, otherwise healthy adults. A nonproductive cough, myalgia, and
fatigue are common
Mycoplasma may cause reddened tympanic membranes or bullous myringitis a rare but unique feature
Legionella infection is associated with exposure to contaminated water droplets from cooling and ventilation
systems. Acute development of high fever, dry cough, dyspnea, and systemic symptoms is common
Viral pneumonias are variable in presentation but often are associated with epidemics and upper respiratory
symptoms
Laboratory Findings:
o Organisms usually are not detected with conventional stain or culture of sputum
o WBC count is normal or only slightly elevated
o Radiography shows segmental unilateral lower lung zone infiltrates or diffuse infiltrates

Treatment:
o Antibiotic treatment is started empirically based on clinical features. Erythromycin or doxycycline
(for suspected M. pneumoniae and Legionella infection) and tetracycline (for suspected Chlamydia
infection)
o Viral pneumonias are treated with supportive measures (analgesics, fluid, cough suppressants)
unless influenza is suspected. If antiviral treatment is indicated, use neuraminidase inhibitors
(zanamivir or oseltamivir)
Hospital-Acquired (Nosocomial) Pneumonia
- Caused by organisms that colonize ill patients, staff, and equipment produce clinical infection more than
48 hours after admission to the hospital Those at the highest risk are patients in the ICU and on mechanical
ventilation
- The second most common cause of hospital-acquired infection (after UTI)
- Causative organisms are unique. Mortality rate is 20-50%
o Usual organisms are S. aureus and gram-negative bacilli, which are easy to recover from
respiratory secretions
o Pseudomonas aeruginosa is the most likely pathogen in ICUs and carries the worst prognosis.
Others are S. aureus, Klebsiella, E. coli, Enterobacter
- Clinical features are similar to CAP
- Laboratory Findings diagnosis is clinical and supported with gram stain and culture of sputum and blood.
CXR can help support diagnosis
- Treatment empiric antibiotics to cover Pseudomonas (cefepime, ceftriaxone, respiratory fluoroquinolone,
ticarcillin/clavulanic acid, piperacillin/tazobactam, imipenem, meropenem).
o Double coverage against Pseudomonas with levofloxacin + cefepime or piperacillin/tazobactam
o Also, initiate coverage against MRSA with vancomycin or linezolid
Fungal Pneumonia
- Etiology:
o Zygomycetes, hyaline hyphomycete, dematiaceous hyphomycete, endemic mycoses** (dimorphic
fungi), yeasts (Pneumocystis pneumonia)
o Endemic mycoses are the only fungal that can occur in immunocompetent people:
Most likely to present as CAP are Histoplasma, Blastomyces, and coccidioides
Exception: allergic, non-invasive pulmonary aspergillosis
- Epidemiology:
o History of travel found in nature, soil or bird droppings
- Pathophysiology:
o Infections are acquired by inhalation
- Signs/Symptoms:
o Most go unrecognized; only a small fraction of patients become symptomatic
o Fever, cough symptoms of pneumonia
- Treatment:
o Natural course is spontaneous resolution unless inoculum is very large, host is
immunocompromised.
o Antifungals
HIV-Related Pneumonia
- Streptococcus is the most common cause of bacterial pneumonia in patients with HIV infection
- Pneumocystis jiroveci is the most common opportunistic infection in patients with HIV disease, typically with
CD4 counts of less than 200 cells/L
- Pneumocystis infection also occurs in patients with cancer, malnourish states, and immunosuppression
- Other pathogens common in patients with HIV and pneumonia are Streptococcus, Haemophilus,
Pseudomonas, Mycobacterium

Pneumocystis pneumonia typically presents with fever, tachypnea, dyspnea, and nonproductive cough
Nonpneumocystis pneumonia typically follows a more fulminant course than in non-HIV-infected persons
Laboratory Findings:
o CXR is the cornerstone of diagnosis. The radiograph typically shows diffuse or perihilar infiltrates.
No effusions are seen
o Lymphopenia and a low CD4 count are typical
o Sputum staining, via either induced sputum or bronchoalveolar lavage, will establish the diagnosis
in more than 90% of patients
- Treatment:
o TMP/SMX (Bactrim) is the treatment of choice
o Extremely high mortality rate (near 100%) if not treated
- Prophylaxis is recommended in patients with a CD4 count of less than 200 cells/L or with a history of
Pneumocystis infection. TMP/SMX is the antibiotic of choice
Pulmonary Neoplasm
- The leading cause of cancer deaths in men and women
- Smoking is the number 1 risk factor
- Two major categories based on staging and treatment options:
o SMALL CELL LUNG CANCER:
Aka oat cell
25-35% of cases
Always associated with smoking
More likely to spread early
Rarely amenable to surgery (mean survival is 6-18 weeks if untreated)
Tends to originate in the central bronchi
Metastasizes to regional lymph nodes
Prone to early metastasis and an aggressive clinical course assume micrometastases at
presentation
The most chemo sensitive type
Paraneoplastic syndromes Cushing syndrome, SIADH, peripheral neuropathy,
Myasthenia (Eaton-Lambert), cerebellar degeneration
o NON SMALL CELL LUNG CANCER:
Grows more slowly and is more amenable to surgery
Types:
Squamous Cell Carcinoma
o 25-35% of cases
o Most common type in males
o 95% of patients are smokers
o Bronchial in origin
o Centrally located mass
o More likely to present with hemoptysis and therefore more likely to be
diagnosed via sputum cytology
o Radiosensitive, chemo resistant
o Paraneoplastic syndromes hypercalcemia

Adenocarcinoma
o The most common type of lung cancer 35-40%
Most common type in females
o Weakest associated with tobacco
o Arises from mucous glands
o Usually appears in the periphery of the lung
Typically metastatic to distant organs
o Not amenable to early detection through sputum examination
o Bronchoalveolar cell carcinoma is a subtype low-grade carcinoma
May not be associated with tobacco at all
May resemble pneumonia
o Paraneoplastic syndromes thrombophlebitis
Large Cell Carcinoma
o A heterogenous group of undifferentiated types that do not fit elsewhere
o Cytology typically shows large cells
o Doubling time is rapid
o Central or peripheral masses
o Metastasis is early
o Paraneoplastic syndromes gynecomastia
Symptoms of lung cancer new or changing cough, hemoptysis, pain, anorexia, weight loss, asthenia
May have lymphadenopathy, hepatomegaly, clubbing of fingers
Paraneoplastic syndromes occur in 10-20% of patients with lung cancer
o Syndromes present in all anemia, DIC, eosinophilia, thrombocytosis, acanthosis nigricans
Diagnostic Studies:
o CXR and CT scans usually demonstrate abnormalities
o Cytologic examination of sputum, if adequate cells are obtained, permits definitive diagnosis of a
specific cell type in many cases
o Bronchoscopy, examination of pleural fluid, and biopsy are used to establish a diagnosis by looking
at specific cell types through direct visualization
o PET scans may also aid in diagnosis and prevent unnecessary surgery
Workup:
o Step 1 CXR
o Step 2 CT
o Step 3 bronchoscopy
With bronchial washings, brushings, and/or biopsy
o Trans-thoracic needle aspiration (TTNA)
Good for peripheral masses
Can cause pneumothorax
o Surgery is rarely indicated
Management:
o For SCLC, combination chemotherapy is the treatment of choice, and results in improved median
survival
Although, patients rarely live for more than 5 years after the diagnosis is established
o For NSCLC, surgery remains the treatment of choice
The 5-year survival rate after resection is 35-40%

Complications (SPHERE): common to all types of lung cancer

o SVC syndrome compression of the SVC leads to plethora, headache, mental status changes
o Pancoast tumor tumor of the lung apex
Causes Horner syndrome and shoulder pain
Affects brachial plexus and cervical sympathetic nerve
o Horner syndrome unilateral facial anhidrosis, ptosis, miosis
o Endocrine carcinoid syndrome (flushing, diarrhea, telangiectasias)
o Recurrent laryngeal nerve hoarseness
o Effusions exudative
Carcinoid Tumor
- Also known as carcinoid adenomas or bronchial gland tumors
- Well-differentiated neuroendocrine tumors that affect men and women equally. Patients are usually younger
than 60 years old
- Low-grade malignant neoplasms. Grow slowly, rarely metastasize
o More commonly found in the GI tract
- Usually asymptomatic, but hemoptysis, cough, focal wheezing, and recurrent pneumonia can occur
- Carcinoid syndrome flushing, diarrhea, wheezing, hypotension
o Rare, occurs in 10% of patients
- Diagnostic Studies:
o Bronchoscopy reveals a pink or purple central lesion that is well vascularized. The lesion can be
pedunculated or sessile
o CT and octreotide scintigraphy localize the disease
CT will localize the lesion as well as monitor for growth
- Treatment surgical excision carries a good prognosis
o Lesions are resistant to radiation therapy and chemotherapy
o Octreotide can be used to treat symptoms
Bronchiectasis
- Bronchiectasis is defined as an abnormal, permanent dilation of the bronchi and destruction of bronchial
walls. It can be congenital (cystic fibrosis) or acquired from recurrent infections (TB, fungal infection, lung
abscess) or obstruction (tumor)
- Results from bronchial injury subsequent to severe infection and/or inflammation
- Half of all cases occur in patients with cystic fibrosis
- Symptoms chronic purulent sputum (often foul smelling), hemoptysis, chronic cough, and recurrent
pneumonia
- Physical Exam localized chest crackles and clubbing of the fingers
- Diagnostic Studies:
o High-resolution chest CT is the imaging modality of choice. It reveals dilated, tortuous airways
o CXR in patients with clinically significant bronchiectasis is abnormal. The degree of abnormality
depends on the extent and severity of the disease. Crowded bronchial markings and basal cystic
spaces are characteristic. CXR may reveal tram-track lung markings, honeycombing, and
atelectasis
o Bronchoscopy is warranted to evaluate hemoptysis, remove secretions, and rule out obstructing
lesions
- Management:
o A productive cough should be managed with appropriate abx, bronchodilators, chest physiotherapy
o Antibiotics for 10-14 days for acute symptoms
Suppressive therapy may be helpful in severe disease or in patients with rapid recurrence
Amoxicillin, Augmentin, TMP/SMX, or ciprofloxacin
o Bronchodilators are helpful for maintenance and for treating acute exacerbations

Patients with disabling symptoms or progressive bronchiectasis can be considered for lung
transplant, however, surgical interventions have little long-term benefit
Solitary Pulmonary Nodule
- Pulmonary nodules are known as coin lesions. If the lesion measures > 3 cm, it is referred to as a mass
- Solitary nodules are more often infectious granulomas from old or active TB, fungal infection, or foreign
body reaction
o Approximately 40% are malignant and represent carcinoma, hamartoma, or metastasis (but these
are usually multiple) as well as bronchial adenoma (95% are carcinoid tumors)
- Malignancy is rare in patients younger than 30 years
o Smokers have increased rate of malignancy risk increased with number of pack-years smoked
- Most pulmonary nodules are found unexpectedly at radiography and are asymptomatic
- Diagnostic Studies:
o CT provides accurate assessment of physical features
o Definitive diagnosis requires biopsy, but this is not always required
o A pulmonary nodule (coin lesion) is a round or oval, sharply circumscribed pulmonary lesion/mass
(up to 3 cm in diameter) surrounded by normal lung tissue
o Central cavitation, calcification, or surrounding (satellite) lesions may occur
o A lesion that has not enlarged in more than 2 years suggests a benign cause. Most are infectious
granulomas
o Malignant lesions occasionally are symptomatic, tend to occur in patients older than 45 years,
usually are greater than 2 cm in diameter, often have indistinct margins, exhibit rapid progression in
size, and rarely are calcified
- Management:
o Lesions with a low probability of malignancy can be watched
CT every 3 months for a year. If stable, reduce CT frequency to every 6 months for the
next 2 years
o Lesions with a high probability of malignancy should be resected as soon as possible. An interim
biopsy of a solitary nodule is not recommended
o Lesions with intermediate probability of malignancy should be biopsied
Transthoracic needle biopsy or bronchoscopy if the lesion is peripheral
False-positive rates can be as high as 25%
High-resolution CT or PET may aid in establishing the diagnosis
High-resolution CT is best to delineate the mass and detect adenopathy or the
presence of multiple nodules
Sarcoidosis
- A multiorgan disease of idiopathic cause
- Characterized by non-caseating granulomatous inflammation in affected organs (e.g., lungs, lymph nodes,
eyes, skin, liver, spleen, salivary glands, heart, nervous system)
- Approximately 90% of patients have lung involvement
- The incidence is highest in North American blacks (especially women) and Northern European whites
- Common respiratory symptoms cough, dyspnea of insidious onset, and chest discomfort
- Patients may present with malaise, fever, and symptoms consistent with the involvement of various organs
- Extrapulmonary findings are common and include erythema nodosum or enlargement of parotid glands,
lymph nodes, liver, or spleen
- Diagnostic Studies:
o Serum blood test may show leukopenia, eosinophilia, elevated ESR, hypercalcemia, hypercalciuria
o Angiotensin-converting enzyme levels are elevated in 40-80% of patients
o Radiographic findings symmetric bilateral hilar and right paratracheal adenopathy and bilateral
diffuse reticular infiltrates
o

Transbronchial biopsy of the lung or fine-needle node biopsy confirms the diagnosis. Biopsy
shows non-caseating granulomas
- Management approximately 90% of cases are responsive to corticosteroids and can be controlled with
modest maintenance doses
Hypoventilation Syndrome
- PRIMARY ALVEOLAR HYPOVENTILATION (Ondine curse) is a rare syndrome of unknown cause
characterized by inadequate alveolar ventilation despite normal neurologic function and normal airways,
lungs, chest wall, and ventilatory muscles
o Hypoventilation is more marked during sleep
o Usually nonobese males from 20-30 years old, with lethargy, headache, somnolence
Dyspnea is absent
o Physical exam shows cyanosis and evidence of pulmonary hypertension or cor pulmonale
o Hypoxemia and hypercapnia are present improve with voluntary hyperventilation
o Erythrocytosis is common
o Give supplemental oxygen
o This resembles central alveolar hypoventilation, which is impaired ventilatory drive with chronic
respiratory acidemia and hypoxemia following brainstem insult
- OBESITY-HYPOVENTILATION SYNDROME (Pickwickian syndrome) is when alveolar hypoventilation
appears to result from combination of blunted ventilatory drive and increased mechanical load imposed
upon the chest by obesity
o Voluntary hyperventilation returns the PO2 and PCO2 to normal values, a correction NOT seen in lung
diseases causing chronic respiratory failure such as COPD
o Most also have obstructive sleep apnea
o Therapy = weight loss, NPPV, and respiratory stimulants (theophylline, acetazolamide,
medroxyprogesterone)
Pulmonary Hypertension
- Present when the pulmonary arterial pressure rises to a level inappropriate for a given cardiac output. Once
present, it is self-perpetuating
- Primary (idiopathic) pulmonary hypertension is rare and has a fatal outcome
- Secondary pulmonary hypertension has many causes that develop as a result of obliteration and obstruction
of the pulmonary arterial tree
- Hypoxia is the most important and potent stimulus of pulmonary arterial vasoconstriction. Other causes
include acidosis and veno-occlusive conditions
- Clinical manifestations dyspnea, angina-like retrosternal chest pain, weakness, fatigue, edema, ascites,
cyanosis, and effort syncope
- Signs narrow splitting and accentuation of the second heart sound and a systolic ejection click
- Diagnostic Studies:
o CXR = enlarged pulmonary arteries
o EKG = RVH, atrial hypertrophy, RV strain
o Echo = useful in estimating pulmonary arterial pressure
Right heart catheterization offers more precise hemodynamic monitoring
- Management:
o Treatment of primary pulmonary hypertension may include chronic oral anticoagulants, calcium
channel blockers to lower systemic arterial pressure, and prostacyclin (a potent pulmonary
vasodilator). Despite these measures, heart-lung transplantation usually is needed
o Treatment of secondary pulmonary hypertension consists of treating the underlying disorder in
addition to those treatments mentioned earlier
Idiopathic Pulmonary Fibrosis
- The most common diagnosis in patients with interstitial lung disease
o

Three histopathologic patterns with different natural histories and treatments

o Usual interstitial pneumonia
o Respiratory bronchiolitis-associated interstitial lung disease
o Acute interstitial pneumonitis
- Symptoms insidious dry cough, exertional dyspnea, and constitutional symptoms (fatigue, malaise, etc.)
- Examination clubbing of the fingers, inspiratory crackles
- Diagnostic Studies:
o CXR = evidence of progressive fibrosis over several years
o CT = diffuse, patchy fibrosis with pleural-based honeycombing
o PFTs = restrictive pattern (decreased lung volume with a normal to increased FEV1/FVC ratio)
o Bronchoalveolar lavage, transbronchial biopsy, and surgical lung biopsy may also help to secure
the diagnosis
- Management is controversial, because none has been shown to improve survival or quality of life compared
to no treatment
Pneumoconiosis
- Pneumoconioses are chronic fibrotic lung disease caused by the inhalation of coal dust or varius inert,
inorganic, or silicate dusts
- Clinically important pneumoconioses include coal workers pneumoconiosis, silicosis, and asbestosis
Disease
Occupation
Diagnosis
Complications
ASBESTOSIS
Insulation, demolition,
Biopsy = asbestos bodies
Increased risk of lung cancer
construction
CXR = linear opacities at bases and mesothelioma, especially if
and pleural plaques
a smoker
COAL WORKERS
PNEUMOCONIOSIS
SILICOSIS

Coal mining

BERYLLIOSIS

High-technology fields
(aerospace, nuclear power,
ceramics, foundries, tool and die
manufacturing)

Mining, sand blasting, quarry

work, stone work

CXR = nodular opacities at

upper lung fields
CXR = nodular opacities at
upper lung fields

Progressive massive fibrosis

CXR = diffuse infiltrates and

hilar adenopathy

Requires chronic steroids

Increased risk of tuberculosis,

progressive massive fibrosis

In simple cases, pneumoconioses are usually asymptomatic

In complicated cases, patients have dyspnea, inspiratory crackles, clubbing of the fingers, and cyanosis
Diagnostic Studies:
o PFTs = restrictive dysfunction and reduced diffusing capacity
o CXR:
Coal Workers Pneumoconiosis = small opacities are prominent in the upper lung fields
Silicosis = small rounded opacities are seen throughout the lung, and hilar lymph nodes
may be calcified
Asbestosis = interstitial fibrosis, thickened pleura, and calcified plaques appear on the
diaphragms or lateral chest wall
Management:
o Primarily supportive no effective treatment is available
Oxygen, vaccinations (pneumococcal, influenza vaccine), and rehabilitation
o Corticosteroids may relieve the chronic alveolitis in silicosis

Smoking cessation is especially important with asbestosis, because smoking interferes with short
asbestos fiber clearance from the lung. Smoking and asbestos are synergistically linked to lung
cancer, especially mesothelioma

Cor Pulmonale
- Pulmonary heart disease
- Denotes RV systolic and diastolic failure, resulting from pulmonary disease and the attendant hypoxia or
from pulmonary vascular disease (pulmonary HTN)
- Most commonly caused by pulmonary HTN, COPD, or idiopathic pulmonary fibrosis
o Less frequently, pneumoconiosis and kyphoscoliosis
- Predominant symptoms are related to the pulmonary disorder chronic productive cough, exertional
dyspnea, wheezing, easy fatigability, and weakness
o When the disease causes RV failure, symptoms are more pronounced
o Dependent edema, RUQ pain may also occur
- Signs cyanosis, clubbing, JVD, RV heave or gallop, prominent lower sternal or epigastric pulsations
(parasternal lift), an enlarged and tender liver (hepatosplenomegaly), dependent edema, and ascites
- Severe lung disease can be a cause of low cardiac output by reducing LV filling and subsequently LV
preload and stroke volume
- Polycythemia is often present secondary to chronic hypoxemia
- EKG shows tall, peaked P waves (P pulmonale), RAD, and RVH
- CXR shows enlarged RV and PA
- Echocardiogram or radionuclide angiography excludes primary LV dysfunction
- PFTs confirm the underlying lung disease
- Therapy is directed at the pulmonary process responsible for right heart failure
- Oxygen, salt and fluid restriction, and diuretics are the mainstays of treatment
o Combination diuretics (loop, thiazides, and spironolactone) are often helpful
Pleural Effusion
- The accumulation of significant volumes of pleural fluid
- Can result from inflammation of structures adjacent to the pleural space or lesions within the chest
- Small effusions may not cause symptoms and may be first discovered on routine radiography
- About 25% of effusions are associated with malignancy
- Four Types:
o EXUDATES = associated with leaky capillaries
Examples infection, malignancy, trauma
o TRANSUDATES = intact capillaries, associated with increased hydrostatic or decreased oncotic
pressure
Examples CHF, atelectasis, renal or liver disease (cirrhosis)
o EMPYEMA = infection within the pleural space
o HEMOTHORAX = bleeding into the pleural space, commonly as a result of trauma or malignancy
- With a small inflammatory effusion, patients are often asymptomatic
- Large or bilateral pleural effusions may lead to dyspnea, but orthopnea is uncommon in the absence of CHF
- A dull to flat percussion note over the area of fluid may be heard as well as reduced or absent breath
sounds
- The mediastinum usually is shifted away from the side of the large effusion

Diagnostic Studies:
o Radiographic findings blunting of the costophrenic angle, loss of sharp demarcation of the
diaphragm and heart, mediastinal shift to the uninvolved side
o Lateral decubitus radiography can help to identify small effusions and differentiate free-flowing
versus loculated fluid
o CT may be useful if plain-film radiography cannot separate parenchymal and pleural densities
o Thoracentesis is the gold standard the fluid is sent for protein, lactate dehydrogenase (LDH), pH,
total WBC and differential cell counts, glucose, cytology, and Gram stain with culture and sensitivity
o Transudate vs. Exudate ~ Lights Criteria. Fluid is considered to be an exudate if it meets any one
of the following:
Pleural fluid protein to serum protein ratio > 0.5
Pleural fluid LDH to serum LDH ratio > 0.6
Pleural fluid LDH > the upper limit of normal for serum LDH
Management:
o Unless the cause has been clearly established, the presence of fluid is an indication for
thoracentesis. Removal of fluid via thoracentesis allows fluid examination, radiographic
visualization of the lung parenchyma, and relief of symptoms
o Transudate pleural effusions resolve when underlying causes are treated
o Malignant effusions may require drainage and pleurodesis. The most commonly used irritants are
doxycycline and talc
o Empyema requires drainage and antibiotics therapy

Internal Medicine Gastrointestinal

Ulcerative Colitis
- Differentiate from inflammatory infectious conditions and Crohn disease
- The disease generally starts distally, at the rectum, and progresses proximally. Disease is continuous, and
skip areas are NOT seen as in Crohn disease
- Disease is confined to the colorectal mucosa
- Onset generally is gradual but also can be abrupt
- Characterized by intermittent episodes of crampy abdominal pain and bloody diarrhea, with complete
remission between bouts
- Tenesmus and bloody, pus-filled diarrhea are the most common symptoms
o Bloody diarrhea is a clinical hallmark
- Pain is less common but may occur, typically in the LLQ
- Weight loss, malaise, and fever may occur in more severe disease
- GI hemorrhage is the most common complication
- Toxic megacolon and malignancy are more likely in UC than in Crohns disease
o Toxic megacolon is the most feared complication and presents with fever, tachycardia, dehydration,
and a tender, distended abdomen
- Other complications scleritis and episcleritis, arthritides, sclerosing cholangitis, and skin manifestations
(erythema nodosum and pyoderma gangrenosum)
- As opposed to Crohns disease, where smoking increases disease, ironically smoking seems protective in
UC. Smokers who have recently quit will often have a disease flare
- Diagnostic Studies:
o Anemia, increased sedimentation rate, and decreased serum albumin are common
o Abdominal plain-film radiography may show colonic dilatation.
o Sigmoidoscopy or colonoscopy is the best method of establishing the diagnosis
Endoscopy demonstrates thickened, friable mucosa
o Colonoscopy and barium enema should be avoided in acute disease because of the risks of
perforation and toxic megacolon
- Treatment:
o Patients with severe disease should be admitted for IV fluids, parenteral analgesia, bowel rest,
correction of electrolytes abnormalities, and NG suction if obstruction/ileus/toxic megacolon
If significant GI hemorrhage, toxic megacolon, or bowel perforation, consult
gastroenterology and surgery. Also, consider:
IV antibiotics ciprofloxacin and metronidazole
Parenteral steroids with either hydrocortisone, methylprednisone, or prednisone
o The majority of patients with mild and moderate disease can be treated outpatient and then followup with gastroenterology
Topical or oral aminosalicylates and corticosteroids are the mainstays of medical
treatment
Mesalamine is the treatment of choice
Sulfasalazine, 5-ASA
Immunomodulators are indicated for refractory disease
6-mercaptopurine or azathioprine for maintenance of refractory disease
Cyclosporine, infliximab for severe disease (more controversial)
o Supportive measures nutritious diet, iron replacement, dietary elimination of lactose, addition of
bulking agents (psyllium)

Avoid antidiarrheals!!! They can precipitate toxic megacolon

Surgery can be curative in UC. Segmental resection is possible, but total proctocolectomy is the
most common surgical cure
Subtotal colectomy with ileostomy is the procedure of choice in the emergency setting or if
you cannot differentiate between UC and Crohns
Indications for surgery colonic obstruction, massive blood loss, failure of medical
therapy, toxic megacolon, cancer

Crohns Disease
- An IBD for which there is some genetic predisposition, although the cause is unknown
- Males and females are equally affected. Peak incidence between 15-35 years old
- A chronic, idiopathic granulomatous inflammatory disease, characterized by segmental ulceration of the GI
tract anywhere from the mouth to the anus
- May involve both the small and large bowels as well as the mouth, esophagus, and stomach. Most
commonly the terminal ileum and right colon are involved, but the rectum frequently is spared. Skip areas
are characteristic
- Unlike UC where the disease is confined to the mucosa, CD has segmental transmural inflammation
- Complications include fistulas, abscesses, aphthous ulcers, renal stones, and predisposition to colonic
cancer
o Perianal fistulas, palpable abdominal mass, rectal prolapse, strictures and obstruction, and
perforations are more common than in UC
o Toxic megacolon can also occur associated with massive GI bleed
- The success or failure of treatment is variable. The disease usually waxes and wanes throughout life
- Abdominal cramps and diarrhea in a patient younger than 40 years are the most common presenting
complaints
o Patients commonly report a history of recurring fever, abdominal pain, and diarrhea over several
years before a definitive diagnosis is made
- Low-grade fever, polyarthralgia, anemia, and fatigue frequently are encountered
- Blood is often present in stool
- Extraintestinal manifestations arthritis, uveitis, nephrolithiasis, and kin disease (erythema nodosum,
pyoderma gangrenosum)
- Diagnostic Studies:
o Colonoscopy is the most valuable tool for establishing the diagnosis, determining the extent and
severity of disease, and guiding the treatment
o Contrast studies and endoscopic procedures should be avoided in patients with fulminant disease
because of the possibility of inducing toxic megacolon or perforation
o Biopsy will reveal involvement of the entire bowel wall in Crohns disease. Granulomas are
frequent (non-caseating granulomas)
o Blood tests may include increased sedimentation rate, anemia, and nutritional and electrolyte
imbalances during exacerbations

Treatment:
o For acute attacks oral corticosteroids (prednisone) are used with or without aminosalicylates.
Metronidazole or ciprofloxacin is added in perianal disease, fissures, or fistulae.
Infliximab may be used in refractory cases
o Elemental diet is nearly as effective as corticosteroids, but relapse is more likely
o Mesalamine is generally the best option for maintenance therapy
o For patients with malabsorption, supplementation may be needed especially for vitamin B12, folic
acid, and vitamin D
o Smoking cessation is critical for reducing the frequency and severity of attacks
o Surgery is not curative in Crohns disease and is reserved for treatment of complications.
Segmental resection is the approach of choice
The primary indication for surgery of the small intestine is obstruction due to fibrosis and
stricture (or other complications)
Subtotal colectomy with ileostomy and Hartmann closure of the rectum is the operation of
choice in an emergency
Diverticular Disease
- DIVERTICULOSIS can be described as large outpouchings of the mucosa in the colon
- DIVERTICULITIS is defined as inflammation of the diverticula caused by obstructing matter
- In patients with diverticulosis, diverticulitis and its complications can be prevented with a high-fiber diet and
avoidance of obstructing or constipating foods
- Diverticulitis
o Generally presents with sudden-onset abdominal pain, usually in the LLQ or suprapubic region,
with or without fever
o Symptoms may range from mild disease to severe infection with peritonitis
o Altered bowel movement as well as nausea and vomiting are common
- Diverticular bleeding generally presents as sudden-onset, large-volume hematochezia. It resolves
spontaneously, although continuous or recurrent bleeding are indications for surgery
- Diagnostic Studies:
o Occult blood in the stool and mild to moderate leukocytosis may occur with diverticulitis
o Plain-film radiography should be done to rule out free air
o CT is warranted if patients do not respond to therapy
o Barium enema should be avoided during an acute episode, because it may lead to perforation and
peritonitis
- Treatment:
o Low-residue diet and broad-spectrum antibiotics are appropriate for patients with mild diverticulitis
Metronidazole + ciprofloxacin
o Hospitalization for IV administration of antibiotics, bowel rest, and analgesics often is required. A
nasogastric tube is inserted if ileus develops
o Surgical management may be necessary in severe cases including peritonitis, large abscesses,
fistulae, or obstruction
o Patients with diverticulosis should maintain a high-fiber diet to prevent diverticulitis. Recent studies
have negated the need to recommend avoidance of nuts, seeds, and popcorn

Acute / Chronic Pancreatitis

- ACUTE:
o The most common causes are cholelithiasis or alcohol abuse, but hyperlipidemia, trauma, drugs,
hypercalcemia, and penetrating PUD also may cause pancreatitis
Also associated with medications, especially many of the antiretroviral medications used
to treat HIV
o The range of presentation is wide ranges from mild episodes of deep epigastric pain with nausea
and vomiting to the sudden onset of severe pain with shock
o The classic presentation is epigastric pain radiating to the back. The pain typically lessens when
the patient leans forward or lies in a fetal position
o Nausea and vomiting are common
o Fever, leukocytosis, and sterile peritonitis may occur
o Severe hypovolemia, adult respiratory distress syndrome, and tachycardia of greater than 130 bpm
indicated a grave prognosis
o Hemorrhagic pancreatitis may cause bleeding into the flanks (Grey Turner sign) or umbilical area
(Cullen sign)
o Diagnostic Studies:
Elevation of serum amylase occurs but may be transient and can return to normal about
48-72 hours
Serum lipase is more sensitive and specific than amylase for acute pancreatitis, but only
with elevated of threefold or greater
WBC count generally is elevated, and hemoconcentration may occur with third spacing of
fluid
Liver enzymes may increase as a result
of biliary obstruction
Mild hyperbilirubinemia and bilirubinuria,
hyperglycemia, and hypocalcemia may
occur
Ultrasound may be helpful to look for
gallstones. Plain films may reveal a
sentinel loop
Poor prognosis is indicated by Ransons criteria, and risk of mortality rises with each
additional factor
On admission age > 55 years, WBC > 16,000, glucose > 200, LDH > 350,
AST > 250
Requires 48 hours of hospitalization for determination. If hematocrit drops
>10%, serum calcium < 8, base deficit > 4, BUN increase > 5, arterial pO2
<
60mmHg, or fluid sequestration >6L
o Treatment:
Oral intake must be stopped to prevent continued secretion of pancreatic juices
Fluid volume must be restored and maintained. Parenteral hyperalimentation should be
started early to prevent nutritional depletion
Pain is managed with an opioid (meperidine). Antibiotics should be considered
The patient must be monitored closely for complications, including pancreatic pseudocyst,
renal failure, pleural effusion, hypocalcemia, and pancreatic abscess

CHRONIC:
o Almost 90% of cases are caused by alcohol abuse. Other causes cholelithiasis, PUD,
hyperparathyroidism, and hyperlipidemia
o Some chronic cases can resolve if alcohol consumption is decreased
o The classic triad of pancreatic calcification, steatorrhea, and diabetes mellitus occurs in only 20%
of patients
o Clinical features are the same as acute
Also fat malabsorption and steatorrhea late in the disease. Fecal fat will be elevated if
malabsorption is present
o Diagnostic Studies:
The amylase level may be elevated early but will decrease with each episode of
pancreatitis and cease to be a useful marker
Abdominal plain-film radiography reveals calcification in 20-30% of patients. Gallstones
may also be seen
o Treatment:
Same as acute. Recommend a low-fat diet at discharge
Surgical removal of part of the pancreas can control pain
The only definitive treatment for chronic pancreatitis is to address the underlying cause,
which most commonly is alcohol
Hiatal Hernia
- A hernia is a protrusion of an organ or structure though the wall that normally contains it
- Hernias of various types can entrap the intestines and cause intestinal blockage
- Diaphragmatic or hiatal hernia involves protrusion of the stomach through the diaphragm via the esophageal
hiatus
- Can be sliding (95%) or paraesophageal
- Can cause symptoms of GERD
- Acid reduction may suffice, although surgical repair can be used for more serious cases
o Losing weight nearly always cures it
o Eat smaller meals
o Avoid smoking
o Antacids
o Avoid spicy foods and hot drinks
Gastroesophageal Reflux Disease
- Reflux esophagitis is the recurrent reflux of gastric contents into the distal esophagus because of
mechanical or functional abnormality of the lower esophageal sphincter
- GERD is present in an estimated 10% of the population; up to 60% of the population experiences heartburn
at some point in their lives.
- Factors that protect the esophagus include gravity, lower esophageal sphincter tone, esophageal motility,
salivary flow, gastric emptying, and tissue resistance
- In a minority of patients, reflux causes erosion of the esophagus that leads to Barretts esophagus
(replacement of normal squamous epithelium with metaplastic columnar epithelium), which can predispose
to malignancy
- Heartburn is the most common presenting feature it generally is worse after meals and when lying down,
and often is relieved with antacids. Regurgitation or dysphagia may occur
- Hoarseness, halitosis, cough, hiccupping, and atypical chest pain are less common symptoms of reflux
- More severe disease, generally caused by a severe impairment of lower esophageal sphincter tone, occurs
spontaneously when supine, while less severe disease is associated with a pattern of heartburn following
meals but not associated with nighttime symptoms

Diagnostic Studies:
o Most often a clinical diagnosis is made based on a history of heartburn and regurgitation of gastric
contents, especially if relieved by antacids. More severe disease warrants endoscopy to confirm
the diagnosis and to asses for epithelial damage
o Endoscopy is also warranted in patients older than 45 years with a new onset of symptoms, longstanding or frequently recurring symptoms, and failure to respond to therapy or symptoms,
indicating more severe conditions such as anemia, dysphagia, or recurrent vomiting
o Be sure to consider the possibility that symptoms are caused by myocardial ischemia do EKG
and cardiac workup
o Barium swallow, esophageal manometry, and ambulatory 24-hour pH monitoring may be indicated
in more severe or refractory cases
o CBC to evaluate for anemia if there is suspicion or evidence of esophageal bleed
- Treatment:
o Lifestyle modifications should be implemented, with further workup if symptoms persist
Cessation of smoking, avoidance of eating at bedtime, avoidance of large meals,
avoidance of alcohol and foods that cause irritation, and raising the head of the bed
o Antacids or alginic acid may be used for mild symptoms
o H2-blockers may be used, but generally in larger doses than for PUD. H2-blockers are the first-line
treatment for mild GERD. They may be used for symptomatic relief
Cimetidine, ranitidine, famotidine, nizatidine
o An acid-suppressant PPI is the most powerful anti-GERD medication. PPIs are first-line for
moderate to severe disease or in patients who are unresponsive to H2-blockers or have evidence of
erosive gastritis they bring symptomatic relief and promote healing of eroded tissue
Omeprazole, rabeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole
o A combination of H2-blocker at bedtime and a PPI in the daytime may be helpful in patients with
significant nighttime symptoms
o -agonists, -adrenergic antagonists, nitrates, calcium channel blockers, anticholinergics,
theophylline, morphine, meperidine, diazepam, and barbiturate agents decrease lower esophageal
sphincter pressure and, therefore, should be avoided
o Surgical and endoscopic techniques are available for refractory cases but have not been shown to
prevent complications of the disease
Peptic Ulcer Disease
- Any ulcer of the upper digestive system (e.g., gastric ulcer, duodenal ulcer)
- Caused by any discreet break in mucosa injury, NSAIDs, stress, alcohol, or other irritants
o H. pylori is the most common cause of PUD. When this is the cause, the ulcer disease can be
eradicated with treatment
- Lifetime risk 5-10%. M=F
- Both gastric ulcers and HP are highly associated with gastric malignancy. Although most patients with HP or
a gastric ulcer will not get gastric cancer, almost all patients with gastric cancer have had HP or a gastric
ulcer
- Abdominal pain or discomfort is the primary clinical feature
o The pain may be described as burning or gnawing and often radiates to the back
o The pain of a duodenal ulcer often improves with food, whereas the pain of a gastric ulcer typically
worsens, which leads to anorexia and associated weight loss
It is often difficult to localize the site until endoscopy is performed
- Dyspepsia (belching, bloating, distention, heartburn) or nausea is also reported
- Complications bleeding, perforation, penetration
o Bleeding manifests as melena

PUD is the most common cause of nonhemorrhagic GI bleeds

Diagnostic Studies:
o Endoscopy is best for detecting small or healing ulcers. It differentiates gastritis from ulcer
disease, provides samples for culture or urease testing, and allows immediate biopsy of gastric or
suspicious ulcers to rule out malignancy
o Barium radiography was once widely used and cheaper, but it is less sensitive, with a 30% falsenegative rate. Endoscopy is more sensitive and definitive
o Urea breath test may be helpful for detecting HP, as will stool or blood antibody tests
Serum antibody tests are highly sensitive and moderately specific but cannot be used to
confirm cure
Stool antigen testing is comparably sensitive, more specific, and can also be used to
evaluate for cure
Urea breath test can also be used to test for cure
Neither test for cure is accurate until 4 weeks after completion of treatment
- Treatment:
o Avoid irritating factors (smoking, NSAIDs, alcohol)
o Combination therapy for HP regimen should be taken for 14 days. Options:
PPI + clarithromycin + amoxicillin (sometimes add metronidazole)
Bismuth salicylate + tetracycline + metronidazole + PPI
o Prophylactic treatment with misoprostol or a PPI should be considered in patients with a history of
ulcer who require daily NSAID use, a history of complications such as bleed, a need for chronic
steroids or anticoagulants, or significant other comorbidities
- Zollinger-Ellison Syndrome is a disease in which a gastrin-secreting tumor (gastrinoma) causes
hypergastrinemia, which results in refractory PUD
Gastritis / Duodenitis
- Inflammation of the stomach or duodenum
- Protective factors mucus, bicarbonate, mucosal blood flow, prostaglandins, alkaline state, hydrophobic
layer, and epithelial renewal
o Any imbalance in protective factors can lead to inflammation
- Causes
o Autoimmune disorders (e.g., pernicious anemia) and other noninfectious factors cause type A
gastritis, which involves the body of the stomach
o Helicobacter pylori is a gram-negative, spiral-shaped bacillus. It is implicated in almost all nonNSAID-induced GI mucosal inflammation
H. pylori causes type B gastritis, which involves the antrum and body of the stomach
H. pylori tolerates well the acidity of a normal stomach and also is associated with peptic
ulcer, gastric adenocarcinoma, and gastric lymphoma
o NSAIDs can cause gastric injury by diminishing local prostaglandin production in the stomach or
duodenum
o Stress from CNS injury, burns, sepsis, or surgery can lead to erosion of the stomach or duodenum
o Alcohol use is another leading cause of gastritis
- The clinical features of gastritis generally reflect the underlying syndrome rather than the gastric injury itself
- Dyspepsia and abdominal pain are common indicators of gastritis
- Diagnostic Studies:
o Endoscopy with biopsy reveals the location and extent of gastritis as well as the presence of H.
pylori
o A urea breath test can be used to detect H. pylori; urea is a product of the bacterial metabolism.
Fecal antigen testing or serology for H. pylori is also helpful
o Specific tests for underlying conditions (e.g., vitamin B12 level, CBC for pernicious anemia) should
be assessed as indicated by history

Treatment:
o Remove the causative factor (e.g., NSAIDs, alcohol). Treat the underlying cause
Gastroenteritis / Infectious Diarrhea
- Diarrhea is defined as three or more watery stools per day
- There are four basic mechanisms:
o Increased intestinal secretion (e.g., cholera)
o Decreased intestinal absorption (e.g., enterotoxins, inflammation, or ischemia)
o Increased osmotic load (e.g., laxatives, lactose intolerance)
o Abnormal intestinal motility (e.g., irritable bowel syndrome)
- 85% of causes are infectious
- Determine if diarrhea is acute (< 3 weeks duration) or chronic (> 3 weeks)
o Acute diarrhea more likely represents a serious problem, such as infection, ischemia, intoxication,
or inflammation
- Secretory diarrhea (large volume without inflammation) indicates pancreatic insufficiency, ingestion of
preformed bacterial toxins, or laxative use
- Inflammatory diarrhea (bloody diarrhea with fever, dysentery) indicates invasive organisms or inflammatory
bowel disease
- Antibiotic-associated diarrhea is almost always caused by C. diff colitis, which in the most severe cases
causes the classic pseudomembranous colitis
o Most commonly cause by clindamycin
- The most common cause in HIV/AIDS patients is Cryptosporidium
- Features such as fever, pain, presence of blood, or type of food ingested may help in the diagnosis of
infectious gastroenteritis, food poisoning, diverticulitis, or IBD
- Neurological symptoms can be seen in certain diarrheal illnesses, such as seizure with shigellosis or
hyponatremia, or paresthesia and reverse temperature sensation with ciguatoxin
- Other information about the host:
o Lakes or streams Giardia
o Oysters Vibrio
o Rice Bacillus cereus
o Eggs Salmonella
o Meat Campylobacter, Staphylococcus, Yersinia, E. coli, Clostridium
- Medications can contributes (antibiotics, colchicine, lithium, laxatives)
- Travel can predispose to enterotoxigenic E. coli or Giardia
- Social history, such as sexual preference, drug use, and occupation, may suggest diagnoses such as HIVrelated illness or organophosphate poisoning
- Begin exam with assessment of hydration status!!!
- The most specific tests for diarrheal illness involve examination of the stool
o Stool culture testing for severely dehydrated or toxic patients, those with blood or pus in the
stool, immunocompromised, those with diarrhea > 3 days
o WBCs in stool denote an inflammatory process
o Consider testing for Salmonella, Shigella, Campylobacter, Shiga toxin-producing E. coli, or
amoebic infection
o If diarrhea > 7 days, those who have travelled abroad, or consumed untreated water, do a stool
O&P to rule out Giardia or Cryptosporidium
o C. difficile toxin for ill patients with anti-biotic associated diarrhea or recent hospitalization
o Not always indicated, since most viral diarrheal illnesses are self-limited
o In extremely dehydrated or toxic patients, electrolyte determinations and renal function tests may
be useful (hemolytic-uremic syndrome, characterized by acute renal failure, thrombocytopenia, and
hemolytic anemia, may complicate E. coli O157:H7 infections in children and elderly

o
o

If toxicity is suspected, test for theophylline, lithium, or heavy metals

Only radiograph to rule out obstruction or pneumonia, particularly Legionella
CT or angiography for acute mesenteric ischemia

Treatment of diarrhea consists of correcting fluid and electrolyte problems

o Fluid replacement can be IV (500 mL bolus in adults, 20 mL/kg in children) with normal saline
In mildly dehydrated patients who are not vomiting, they may tolerate oral rehydrating
solution containing sodium (e.g., Pedialyte) as well as glucose to enhance fluid absorption
(glucose transport unaffected by enterotoxins)
Goal is 50-100 mL/kg over the first 4 hours
o BRAT diet (bananas, rice, apples, toast)
Avoid raw fruit, caffeine, and lactose and sorbitol-containing products
o Antibiotics for adults with severe or prolonged diarrhea. AVOID antibiotics in infectious diarrhea
due to E.coli O157:H7
May use for Shigella sp., Campylobacter sp., severe causes of C. diff infection
o Antidiarrheal agents, especially in combination with antibiotics, have been shown to shorten the
course of diarrhea
- Antibiotic-associated diarrhea often responds to withdrawal of the offending agent
o Metronidazole or vancomycin in certain situations
o Or fidaxomicin
- Almost all diarrheal emergencies (e.g., GI bleed, adrenal insufficiency, thyroid storm, toxicologic exposures,
acute radiation syndrome, and mesenteric ischemia) are of noninfectious origin
o Patients with these conditions require intensive treatment and hospitalization
Gastroenteritis
- Most common etiologies rotavirus, caliciviruses (includes noroviruses), astroviruses, adenoviruses
o Rotavirus is the major cause of nonbacterial gastroenteritis, peaks in cooler months. Profuse
diarrhea, vomiting, low-grade fever
o Noroviruses cause similar episodic outbreaks of vomiting and watery diarrhea
- Bacterial Gastroenteritis non-typhoidal Salmonella, Shigella, Campylobacter, E. coli (EPEC, 0157-H7),
Vibrio (developing nations eating undercooked shellfish)
o Fever, abdominal cramping, malaise, tenesmus (vomiting is less common)
o Stool contains mucus and may be guaiac positive or streaked with blood
o Shigellosis can cause neurologic manifestations
o Salmonella can invade bloodstream and cause extraintestinal disease (meningitis, osteomyelitis)
especially in children with sickle cell anemia
o Shigella and E. coli can cause HUS
o Yersinia can develop erythema nodosum, and can also get RUQ pain that mimics appendicitis
o Cholera (vibrio) stools become colorless and mucus flecked rice-water stools
o C. difficile can cause antibiotic-associated diarrhea and pseudomembranous colitis
- Giardiasis
o The most common intestinal parasitic disease in the United States, many water-related outbreaks
o Giardia lamblia beaver fever
o Transmission person to person (cyst ingestion), contaminated food / water
o Frequent, foul-smelling, watery stools (rarely have blood or mucus), abdominal pain, nausea,
vomiting, anorexia, and flatulence
o Diagnosis Giardia antigen, stool O&P
o May resolve spontaneously without treatment (5-7 days)
o Rx Tinidazole, Nitazoxanide, Metronidazole (increased GI side effects)
o Prevention Boil, filter, iodinate drinking water. Dont trust any open source
o Pearl can cause vulvovaginitis in prepubescent girls

Viral Gastroenteritis

Treatment Gastroenteritis
o Most cases, viral and bacterial, are self-limiting
o Supportive; correcting dehydration (oral rehydration) and maintaining hydration in setting of
ongoing losses
o Antibiotic therapy is recommended for Shigella infections and E. coli EPEC infections in children <
3 months of age. TMP-SMX or erythromycin
o Antibiotic therapy is not indicated for Salmonella or E. coli 0157:H7
o Children with Campylobacter infection usually recover without treatment but antibiotics hasten
recovery and reduce length of carrier status (erythromycin or azithromycin)
o C. difficile and giardiasis = metronidazole

Acute Infectious and Travelers Diarrhea

- Norovirus causes 50-80% of all infectious diarrhea in the United States, followed much less frequently by
non-Shiga toxin-producing E. coli, C. difficile, invasive bacteria (Campylobacter, Shigella, Salmonella), Shiga
toxin-producing E. coli, and protozoa
- Patients with severe abdominal pain, fever, and bloody stool should undergo stool studies for specific
pathogens, including culture for Salmonella, Shigella, Campylobacter, and E. col O157:H7
o Also assay for Shiga toxin, and microscopy or antigen assay for Entamoeba histolytica
- Exposure of a traveler or hiker to untreated water, and illness that persists for more than 7 days, should
prompt an evaluation for a protozoal pathogen
o Stool should be tested by enzyme immunoassay for E. histolytica antigen, Giardia intestinalis
antigen, and Cryptosporidium parvum antigen
- Treatment of moderately severe infectious diarrhea (including viral causes) includes antibiotics, antimotility
agents, fluid resuscitation (oral or parenteral), and dietary modification
o Ciprofloxacin BID x 3 days will shorten the course of illness by ~24 hours
Similar dosing for culture proven Shigella or enterotoxigenic, enteropathogenic,
enteroinvasive E. coli
However, both antibiotics and antimotility agents should be avoided in cases of Shiga
toxin-producing E. coli O157:H7
TMP/SMX for children or nursing mothers (BID x 3 days)
o Metronidazole TID x 5-10 days for Giardia or Entamoeba infection
For Entamoeba, add iodoquinol TID x 20 days or paromomycin TID x 5-10 days
o Antimotility agents, such as loperamide, will shorten the course of symptoms when combined with
an antibiotic
Other options include bismuth subsalicylate or diphenoxylate and atropine
Avoid antimotility agents in those with bloody or suspected inflammatory diarrhea because
of the potential for prolonged fever, toxic megacolon in C. difficile patients, and hemolyticuremic syndrome in children infected with Shiga-toxin producing E. coli
Clostridium Difficile-Associated Infection, Diarrhea, and Colitis
- C. difficile is an anaerobic bacillus which secretes two toxins that interact in a complex manner to cause
illness ranging from diarrhea to pseudomembranous colitis
- Pseudomembranous colitis is an inflammatory bowel disorder in which membrane-like yellowish plaques of
exudate overlay and replace necrotic intestinal mucosa
- Broad-spectrum antibiotics, most notably clindamycin, cephalosporins, ampicillin, amoxicillin, and
fluoroquinolones, alter gut flora in such a way that C. difficile can flourish within the colon, causing
enteropathy
- Transmission of the organism can occur from contact with humans and fomites
- C. difficile is the most common cause of infectious diarrhea in hospitalized patients
- Onset is typically 7-10 days after initiating antibiotic treatment, but may occur up to several weeks following
treatment
- Clinical manifestations can range from frequent, watery, mucoid stools to a toxic picture, including profuse
diarrhea, crampy abdominal pain, fever, leukocytosis, and dehydration
- Confirm the diagnosis by demonstration of C. difficile toxin in stool. No need for colonoscopy
- Mild C. difficile infection in an otherwise healthy patient can be treated with discontinuing the offended
antibiotic, confirmation of infection, and clinical monitoring
- Oral metronidazole QID x 10-14 days is the treatment of choice otherwise
- Patients with severe diarrhea, those with a systemic response (fever, leukocytosis, or severe abdominal
pain), and those whose symptoms persist despite appropriate outpatient management, must be hospitalized
and should receive vancomycin QID x 10-14 days. Symptoms usually resolve within a few days
- Patients with pseudomembranous colitis complicated by toxic megacolon or intestinal perforation require
immediate surgical consultation. Rarely, emergency colectomy may be required for fulminant colitis

- Use of antidiarrheal agents is controversial

Esophagitis
- Infectious Esophagitis:
o Often Immunosuppressed patients:
Candida should be considered, especially if oral thrush is present. Common in patients
with uncontrolled diabetes and those being treated with systemic steroids, radiation
therapy, or systemic antibiotic therapy.
CMV and Herpes Simplex Virus are common viral causes
HIV idiopathic ulceration, Mycobacterium tuberculosis, EBV, and Mycobacterium avium
intracellulare are uncommon
o Signs and Symptoms:
Odynophagia, dysphagia are most common
Substernal chest pain in some patients
Oral thrush in 75% of patients with candida esophagitis and only 25% with viral
esophagitis (poor predictor of disease)
Colon or retina infections (CMV)
Physical exam may reveal signs of an underlying immune deficiency such as fever,
lymphadenopathy, or rashes
o Diagnostics:
EGD with biopsies for diagnostic uncertainties
Candidal esophagitis diffuse, linear, yellow-white plaques adherent to the mucosa.
CMV and HIV esophagitis endoscopy reveals one to several large, shallow, superficial
or deep ulcerations.
Herpes esophagitis results in multiple small, shallow ulcerations.
Cytology or culture from endoscopic brushings is needed for definitive diagnosis
Evaluate for underlying immunodeficiency
o Treatment:
Candidiasis systemic therapy. Empiric trial of antifungal therapy (fluconazole, 400 mg
on day 1, then 200-400 mg/d for 14-21 days). Patients not responding to therapy within 35 days should get the EGD.
Or ketoconazole
CMV immune restoration with highly active antiretroviral therapy (HAART). Initial
therapy is with ganciclovir, 5 mg/kg IV q12 hours for 3-6 weeks. Neutropenia is a frequent
dose-limiting side effect. Once resolution of symptoms occurs, it may be possible to
complete the course of therapy with oral valganciclovir, 900 mg once daily.
Foscarnet is indicated in cases of poor tolerability or poor response
Herpetic immunocompetent patients may be treated symptomatically and generally do
not require specific antiviral therapy. Immunosuppressed patients can be treated with oral
acyclovir 400mg orally 5x daily or 250mg/m2 IV q8-12 hours, usually for 14-21 days. Nonresponders require therapy with foscarnet IV.
o Prognosis long term suppressive therapy is sometimes required.
- Pill-Induced Esophagitis:
o Due to direct, prolonged mucosal contact
o Most commonly due to NSAIDs, potassium chloride, quinidine, zalcitabine, zidovudine,
alendronate and risedronate, emepronium bromide, iron, vitamin C, and antibiotics (doxycycline,
tetracycline, clindamycin, TMP-SMX)
Dont give known agents to patients with esophageal dysmotility, dysphagia, or strictures
o Most likely to occur if pills are swallowed without water or when supine

To prevent damage, take pills with 4 oz of water and remain upright for 30 minutes after
ingestion
o Retrosternal chest pain, odynophagia, dysphagia usually begin several hours after taking a pill
Occur suddenly and may persist for days
- Eosinophilic Esophagitis:
o Previously recognized in children but is increasingly identified in young or middle-aged adults,
predominately men (75%).
o Associated with asthma, allergic rhinitis, urticaria, hay fever, atopic dermatitis, food allergy, or
medicine allergy (>50% of patients)
o Pathophysiology:
Eosinophilic infiltration of the esophagus from allergic or idiopathic etiology
Dysphagia, food impaction, reflux
Strictures, mucosal rings (including multiple rings), linear furrowing, ulceration, "feline"
esophagus, eosinophilic abscesses, and esophageal polyps
Higher concern for perforation with dilation
o Clinical:
Primary symptom in adults: long history of dysphagia or an episode of food impaction
Heartburn may be present.
More varied presentation in kids
Abdominal pain
Vomiting
Chest pain
Failure to thrive
o Diagnosis:
Few have eosinophilia or elevated IgE
Abnormal barium swallow:
Small-caliber esophagus
Focal or long, tapered strictures
Multiple concentric rings
Endoscopy with esophageal biopsy and histologic evaluation is required to establish the
diagnosis.
White exudates or papules
Red furrows
Corrugated concentric rings and strictures
However, esophagus is grossly normal in one-third of patients.
Multiple biopsies (at least 5) from the proximal and distal esophagus should be
obtained to demonstrate multiple (>15/hpf) eosinophils in the mucosa.
Skin testing for food allergies in children.
o Treatment:
PPIs BID for two months, up to 75% improve
Corticosteroids Swallowed fluticasone, 70% improve
Leukotriene Inhibitors
Mast Cell Inhibitors / Antihistamines
Endoscopic Dilation
Mallory-Weiss Tear
- UPPER GI BLEED

Linear mucosal tear (nonpenetrating) in the esophagus, generally at the gastroesophageal junction, that
occurs with forceful vomiting or retching, causing hematemesis
o Hypothesized to occur from events that suddenly raise transabdominal pressure, such as lifting,
retching, or vomiting
- Often associated with alcohol use and alcoholism, but should be considered in all upper GI bleeds
- Patients with portal hypertension are at higher risk of continued or recurrent bleeding
- Patients usually present with hematemesis with or without melena
o Usually have a history of retching, vomiting, or straining
- Diagnosed by upper endoscopy
o 0.5-4 cm linear mucosal tear located either at the GE junction or, more commonly, below the
junction in the gastric mucosa
- Initially, treat as needed with fluid resuscitation and blood transfusions
o Most stop bleeding spontaneously and resolve without treatment
o A PPI may be useful if the active bleed is resolved
o May need endoscopic injection of epinephrine or thermal coagulation
Can also mechanically compress the artery with an Endoclip or band
o If endoscopic therapy still fails, do angiographic arterial embolization or operative intervention
Esophageal Dysmotility
- Disorders of esophageal motility include neurogenic dysphagia, Zenker diverticulum, esophageal stenosis,
achalasia, diffuse esophageal spasm, and scleroderma
- Dysmotility can be caused by neurologic factors, intrinsic or extrinsic blockage, or malfunction of
esophageal peristalsis
- Dysphagia is the most common presenting symptom for all motility disorders. Its presentation can help to
determine the underlying cause
- Neurogenic dysphagia causes difficulty with both liquids and solids and is caused by injury or disease of
the brain stem or the cranial nerves involved in swallowing (IX, X)
- Zenker diverticulum is an outpouching of the posterior hypopharynx that can cause regurgitation of
undigested food and liquid into the pharynx for several hours after eating
- Esophageal stenosis causes dysphagia for solid foods. Slow progression of solid food dysphagia indicates
a more benign process (e.g., webs or rings), and rapid progression indicates malignancy
- Achalasia is a global esophageal motor disorder in which peristalsis is decreased and lower esophageal
sphincter tone is increased, causing slowly progressive dysphagia with episodic regurgitation and chest
pain
- Diffuse esophageal spasm is characterized by dysphagia or intermittent chest pain that may or may not be
associated with eating
- Scleroderma eventually progresses to involve the esophagus in most patients with the disease, causing
decreased esophageal sphincter tone and peristalsis, predisposing the patient to the symptoms and
complications of reflux esophagitis
- Diagnostic Studies:
o Barium swallow can reveal both structural and motor abnormalities of the esophagus that may
cause dysphagia. Achalasia typically has a parrot beak appearance (i.e., a dilated esophagus
tapering to the distal obstruction) on barium swallow
o Endoscopy (esophagogastroduodenoscopy) allows for direct observation and biopsy of
abnormalities
o Esophageal manometry can be used to assess the strength and coordination of peristalsis
- Treatment:
o Neurogenic dysphagia must be managed by treating the underlying disease
o Strictures:
Most benign strictures can be managed by dilation
Malignant strictures must be resected

Diverticula, achalasia, and stenosis may be managed surgically (endoscopic dilation, resection) if
the condition is severe enough to warrant intervention. Medical therapies such as CCBs, nitrates,
and botulinum have not been proven effective

Esophageal Varices
- Dilations of the veins of the esophagus, generally at the distal end
- The underlying cause in adults is portal hypertension, most commonly caused by cirrhosis either from
alcohol abuse or from chronic viral hepatitis. Use of NSAIDs can exacerbate bleeding (hepatic vein
obstruction)
- Budd-Chiari syndrome may cause thrombosis of the portal vein leading to esophageal varices
- Patients generally present with painless upper GI bleed that can be bright red frank bleeding or coffee
ground in appearance. Large bleeds may cause hypovolemic shock
- Diagnosis:
o Generally is established clinically when a patient with signs of cirrhosis presents with hematemesis.
Endoscopy will localize the bleeding
o Varices generally are asymptomatic until they bleed, at which point they frequently are lifethreatening
- Treatment:
o Prevention of variceal bleeding in cirrhotic patients may be done with -blockers with or without
isosorbide mononitrate, along with discontinuation of hepatotoxic agents. Endoscopic band ligation
may be used if medical therapy is insufficient
o Hemodynamic support with high-volume fluid replacement and vasopressors and immediate
control of bleeding are necessary because bleeding varices have high mortality (~30% with first
bleed and 50% within 6 weeks)
o Endoscopic band ligation is the preferred therapy for acute bleed. Endoscopic pharmacologic
vasoconstriction (e.g., octreotide) in conjunction is highly effective as well
Esophageal Neoplasms
- Squamous cell carcinomas and adenocarcinomas are the most common type
- Barrett esophagitis is associated with adenocarcinomas in the distal of the esophagus, where
squamous cell lesions tend to occur in the proximal
- Local spread to the mediastinum is common because the esophagus has no serosa
- Esophageal cancers are frequently related to cigarette smoking and chronic alcohol use. Contributing
factors include exposure to other caustic agents (e.g., nitrosamine, fungal toxins, and other carcinogens),
hot foods, mucosal abnormalities, poor oral hygiene, and HPV
- The main clinical feature of esophageal cancer is progressive dysphagia for solid food associated with
marked weight loss. Heartburn, vomiting, and hoarseness may occur
- Diagnostic Studies:
o Biphasic barium esophagram is the best initial test to visualize the lesion
o Endoscopy with brushings is used for diagnosis
o Endoscopic sonography and CT may be used for staging
- Treatment:
o Treatment of esophageal cancer is general surgical. Radiotherapy and adjunctive chemotherapy
have been used in various combinations with or without surgery
o Prognosis depends on stage of disease at diagnosis ranging from 4-60% 5-year survival
Cancer of the Stomach
- ZOLLINGER-ELLISON SYNDROME
o In ZES, a gastrin-secreting tumor (gastrinoma) causes hypergastrinemia, which results in refractory
PUD
o Only 1% of cases of PUD are caused by ZES
o Most gastrinomas are found in the pancreas or duodenum, but they may be found anywhere or
may metastasize
o About of gastrinomas are part of the MEN type 1 syndrome, an autosomal dominant condition
o Most commonly, the clinical presentation is indistinguishable from that of PUD, although ZES
usually is more advanced or refractory to treatment

Abdominal pain may be accompanied by a secretory diarrhea that improves with H2blockers
(ranitidine, cimetidine) or PPIs (omeprazole, lansoprazole)
o Occult or frank bleeding, causing anemia, may be present
o Diagnostic Studies:
A fasting gastrin level > 150 pg/mL indicates hypergastrinemia
A secretin test is needed to confirm the presence of ZES
Patients are given secretin 2 U/kg IV
In most patients with ZES, the gastrin levels will increase by > 200 pg/mL
Endoscopy, CT, or MRI may help to localize the tumor
o Treatment:
Use of PPIs controls gastrin secretion
Surgical resection of the gastrinoma should be attempted when possible
GASTRIC ADENOCARCINOMA
o Among the most common types of cancer worldwide, but is less common in the United States
o Twice as common in men. Almost never occurs younger than 40 years old
o With early diagnosis, 80% cure rate
If the muscularis propria is involved, the cure rate is 50%
If there is lymphatic spread, the cure rate is 10%
o A strong association of gastric adenocarcinoma with H. pylori, although genetic factors are involved
in some types
Cigarette smoking also increases risk
o Dyspepsia and weight loss associated with anemia and occult GT bleeding in a patient older than
40 years of age are the typical presenting complaints
o Progressive dysphagia may be caused by a neoplasm impinging on the esophagus
o Postprandial vomiting may be caused by a neoplasm near the pylorus
o Signs of metastatic spread left supraclavicular adenopathy (Virchow node) and an umbilical
nodule (Sister Mary Joseph nodule)
o Diagnostic Studies:
Iron deficiency anemia is the most common lab finding
Liver enzymes may be elevated with hepatic metastases
Endoscopy with cytology should be done on any patient older than 40 years of age with
dyspepsia who is unresponsive to therapy
After the diagnosis has been established, abdominal CT is used to determine the extent of
disease
o Treatment:
Treatment is either curative or palliative resection of the tumor
Chemotherapy or radiation may provide some palliative benefit
CARCINOID TUMORS
o Carcinoid tumors of the stomach rarely occur in response to hypergastrinemia and generally are
benign and self-limited
GASTRIC LYMPHOMA
o Gastric lymphomas account for less than 2% of gastric malignancies, but the stomach is the most
common extranodal site for non-Hodgkin lymphoma
o The risk of gastric lymphoma is greater by sixfold if H. pylori infection is present
o Clinical features are the same as those for gastric adenocarcinoma
o Diagnostic Studies:
Findings differ from those of gastric adenocarcinoma only in the pathology of the lesion
o Treatment:
o

Treatment is resection with or without radiation or chemotherapy

Colorectal Cancer
- The third leading cause of cancer death in the United States after lung cancer and skin cancers. ~90%
occur in those older than 50 years old
- Hereditary Nonpolyposis Colorectal Cancer also leads to an extremely high risk of colon cancer, and those
with familial polyposis have a virtually 100% risk of developing the disease
o An autosomal dominant condition accounting for 3% of colorectal cancers
- Prognosis is good in early disease
- When the cancer involves only the mucosa (Dukes A or Stage 1), the 5-year survival rate is greater than
90%. Penetration through the wall or involvement of regional lymph nodes (Dukes B or Stage 2) has a 5year survival rate of 70-80%. When there is metastasis (Dukes C or Stage 3 = lymph node positive, Dukes
D or Stage 4 = distant metastases), the 5-year survival rate drops to 5%
- Colorectal cancer is slow growing, and symptoms often appear late in the disease
o Abdominal pain, change in bowel habits, occult bleeding, and intestinal obstruction are common
presentations
o Fatigue and weakness may occur if chronic blood loss has led to anemia
o Changes in stool size and shape may be noted, as may frank blood in the stool
- Diagnostic Studies:
o Occult blood in the stool can be an early marker and is used for screening adults older than 40
years. Flexible colonoscopy is recommended in those older than 40-50 years. Overall screening
recommendation is after age 50 (every 5-10 years, depending on the method)
Or 10 years before the earliest diagnosis of colon cancer in a first-degree relative
o Carcinoembryonic antigen (CEA) may be used to monitor, but not to detect, colorectal cancer
o Sigmoidoscopy, colonoscopy, or barium enema may all be used to visualize suspected colonic
masses, whereas chest radiography and CT are used to detect metastases
- Treatment:
o Surgical resection
o Add chemo in patients stage III (Dukes C) or higher. Sometimes in stage II (Dukes B)
o Radiation may be used for rectal tumors
Acute / Chronic Hepatitis
- Chronic = < 6 weeks
o Most often results from viral infection (hepatitis B, C, D) or inherited disorders (Wilsons disease,
1-antitrypsin deficiency), autoimmune disease of liver, or hepatic effects of systemic disease
- The most common cause of acute hepatitis is viral; toxins (e.g., alcohol) are the second most common
cause
- Consider in patients with RUQ or epigastric abdominal pain, nausea, vomiting, diarrhea, jaundice, or pruritus
o The presence of altered mental status, abnormal bruising, or bleeding suggest fulminant hepatic
failure or a chronic process
o Patients with cholestasis may notice pale stools or dark urine
- Historical clues and risk factors ingestion of wild mushrooms, raw seafood, herbal remedies, acute and
chronic use of medications (acetaminophen, phenytoin, statins, INH, OCPs, anabolic steroids, nitrofurantoin,
minocycline, valproic acid, amiodarone), alcohol abuse, IV drug use, unprotected sexual activity, positive
HIV status, and travel to endemic countries
o Acetaminophen and toxic mushroom ingestion are important causes of acute hepatitis and liver
failure
- All individuals born between 1945 and 1965 should be screened for hepatitis C

Types and Transmission:

o Hepatitis A and E are self-limited and mild, without long-term sequelae
Hepatitis A and E are transmitted fecal-oral, most commonly from improper food handling
or from asymptomatic children to adults
Can be prevented by maintaining a sanitary water supply and hand washing
o Hepatitis B and C can have a highly variable presentation, ranging from asymptomatic to fulminant.
Chronic hepatitis B or C causing liver damage may require treatment
Hepatitis B is transmitted sexually, by transfusion, or by IV drug use
Hepatitis C is transmitted via exposure to contaminated blood or blood products
o Hepatitis D is only seen in conjunction with hepatitis B and is associated with a more severe course
o Hepatitis C and HIV are frequent co-infections, as are hepatitis B and HIV, necessitating specialist
care if treatment of the hepatitis is indicated
o Hepatitis B, C, and D are transmitted parenterally or by mucous membrane contact
o Of those with chronic hepatitis C, only 20-30% will progress to serious liver disease, which occurs
most often when alcohol is involved or the patient is co-infected with hepatitis B or HIV
A prodrome of nausea, vomiting, malaise, and fever followed by liver enlargement, abdominal pain, and
jaundice suggests acute viral hepatitis
o Can range in severity from asymptomatic infection to fulminant hepatic failure to chronic cirrhosis
o A few days of generalized pruritus and dark urine may precede the onset of GI symptoms and
jaundice
Fulminant Hepatic Failure defined as acute hepatocellular necrosis with rapid development of
encephalopathy and liver failure in <8 weeks
o Rare
o Present with encephalopathy (asterixis), coagulopathy, and rapidly worsening jaundice
Diagnostic Studies:
o Serum transaminase levels are elevated (ALT, AST, GGT)
Values in the hundreds of units are suggestive of viral inflammation, but elevations in the
thousands suggest hepatocellular necrosis, extensive liver injury, and more fulminant
disease
In acute and chronic viral hepatitis, the ratio of AST:ALT is usually <1, whereas a ratio >2
is more suggestive of alcoholic hepatitis
o Serum alkaline phosphatase elevations
If >3x normal, suspect cholestasis
Supported by elevated GGT
o Total serum bilirubin level and direct (conjugated) bilirubin
Direct bilirubin of 30% or higher is consistent with viral hepatitis
Bilirubin of greater than 3.0 mg/dL will be associated with scleral icterus, if not frank
jaundice
o IgM antibody to hepatitis A virus (anti-HAV) can be detected with the onset of clinical disease (after
a 15- to 40-day incubation period), but it disappears after several months. HAV IgG indicates
resolved hepatitis A
o Hepatitis B surface antigen (HBsAg) indicated ongoing infection of any duration; antibody against
hepatitis B surface antigen (anti-HBs) indicates immunity by past infection or vaccination
o Hepatitis B core antibody (anti-HBc) is present between the disappearance of HBsAg and the
appearance of anti-HBs, indicating acute hepatitis
o Hepatitis B envelope antigen (HBeAg) indicates active infection that is highly contagious, whereas
anti-HBe indicates a lower viral titer

Hepatitis C or D generally is detected by its antibody, which for hepatitis C generally indicates
ongoing infection, as it does for hepatitis D if hepatitis B infection is ongoing

Hepatitis B may exist in a carrier state or a chronic infection. Both exhibit positive HBsAg, but in
chronic infection, liver damage is demonstrated by elevated AST and ALT and by hepatocellular
damage on biopsy. In chronic infection, the viral DNA load will be greater than 105 copies. HBeAg
seroconversion (to negative) tends to occur with a reduction in viral DNA
o Hepatitis C antibody-positive patients should be evaluated for genotype and viral load. Types 2
and 3 have a better treatment prognosis than type 1, as does a lower HCV viral load. Liver biopsy
is currently the preferred method for evaluating the level of fibrosis and the need for treatment
- Treatment:
o Supportive (with the exception of treatment for acetaminophen toxicity)
Rest, adequate oral intake, strict personal hygiene, avoidance of hepatotoxins (alcohol
and rest)
o Return for worsening symptoms, especially vomiting, fever, jaundice, abdominal pain
o For alcohol-induced hepatitis, can manage outpatient nutritional supplementation including
thiamine, folate, magnesium, and potassium supplements
o All HIV-positive patients with chronic hepatitis B should be treated for HIV with therapies that cover
both infections. Tenofovir with either emtricitabine or lamivudine will cover the hepatitis B and the
additional antiretroviral medication will cover the HIV infection
o Patients with hepatitis C should be vaccinated against A and B
o The standard of care for the treatment of HCV is rapidly advancing. The availability of HCV
specific protease inhibitors now allows for interferon sparing regimens for some patients,
depending on the genotype of the virus. These agents have also dramatically boosted the efficacy
of interferon-alpha/ribavirin regimens previously used. The goal of therapy is reduction of viral RNA
to undetectable at 6 months posttherapy
o Admit if encephalopathy, PT prolonged by more than a few seconds, elevated INR, intractable
vomiting, hypoglycemia, bilirubin level > 20 mg/dL, age > 45 years, pregnancy,
immunosuppression, or suspected toxin-induced hepatitis
Correct volume depletion and electrolyte imbalances with IV crystalloid
Treat hypoglycemia initially with 1 ampule of 50% dextrose in water IV followed by the
addition of dextrose to IV fluids and careful monitoring
o Admit patients with fulminant hepatic failure to the ICU, with aggressive support of circulation and
respiration, monitoring and treatment of increased intracranial pressure if present, correction of
hypoglycemia and coagulopathy, administration of oral lactulose or neomycin, and a proteinrestricted diet
Consult hepatologist and liver transplant service
Cirrhosis
- Irreversible fibrosis and nodular regeneration throughout the liver
- More than 45% of cases are alcohol related, with the remainder associated with hepatitis B or C or with
congenital disorders
- Often report a gradual deterioration in their health, with anorexia, muscle loss (often masked by edema or
ascites), fatigue, nausea, emesis, diarrhea, and increasing abdominal girth (ascites)
- Weakness, fatigue, and weight loss are common
- Nausea, vomiting, and anorexia usually are present
- Menstrual changes (generally amenorrhea), impotence, loss of libido, and gynecomastia occur
- Abdominal pain and hepatomegaly generally are present
- On physical jaundice, ascites, a small and firm liver, splenomegaly, pedal edema, and spider angiomata
- Late-stage disease includes ascites, pleural effusions, peripheral edema, ecchymoses, esophageal varices,
and signs of hepatic encephalopathy (e.g., asterixis, tremor, dysarthria, delirium, and eventually coma)
o Hepatic encephalopathy characterized by a fluctuating level of consciousness and confusion
and, possibly, hyperreflexia, spasticity, generalized seizures, and coma. Also asterixis (liver flap)
o

 A diagnosis of exclusion
- Spontaneous bacterial peritonitis presents with fever, chills, worsening ascites, and abdominal pain. It may
lead to diarrhea and renal failure
o Spontaneous Bacterial Peritonitis (SBP) is the most common complication of cirrhotic ascites
o Suspect in any cirrhotic patient with fever, abdominal pain or tenderness, worsening ascites,
subacute functional decline, or encephalopathy
o Other subtle clues include deteriorating renal function, hypothermia, and diarrhea
- Diagnostic Findings:
o Laboratory values often are minimally abnormal until late in the disease
o Anemia is common, as are mild elevations of AST and alkaline phosphatase, increased -globulin,
decreased albumin, and abnormal coagulation studies
o Ultrasonography, CT, or MRI can confirm the size and number of nodules and is helpful in guiding
biopsy
o Patients with ascites for the first time or those with ascites who develop fever, abdominal pain, GI
bleeding, or encephalopathy should undergo ultrasound guided paracentesis to check for SBP
Test ascitic fluid level for total protein and glucose level, LDH, gram stain, WBC count with
differential
Total WBC > 1000/mm3 or neutrophil count > 250/mm3 is diagnostic for SBP
Cultures are often negative, but gram-negative Enterobacteriaceae (E. coli,
Klebsiella) usually account for SBP cases
- Treatment:
o Abstinence from alcohol is the key feature of treatment
Adopt a protein-restricted diet (prevents encephalopathy)
o Salt restriction and bed rest may be sufficient treatment for ascites, although spironolactone (100
mg daily), may be added as a diuretic
o Liver transplant is indicated in selected patients
o Paracentesis for symptomatic relief of ascites or to diagnose SBP
Administer albumin before paracentesis to guard against complications related to fluid
shifts (removal of >1 liter of ascitic fluid can lead to hypotension)
o Spontaneous bacterial peritonitis is treated with antibiotics
Cefotaxime, piperacillin/tazobactam, ampicillin/sulbactam, ticarcillin/clavulanate, or
ceftriaxone
o The mainstay of therapy for hepatic encephalopathy is lactulose
Also, place on a protein-restricted diet
Hepatic Cancer
- Liver neoplasms may be malignant or benign, and malignant neoplasms may be primary or metastatic
- Benign liver neoplasm include cavernous hemangioma, hepatocellular adenoma, and infantile
hemangioendothelioma
- The liver is a common site of metastasis for other primary cancers, especially lung and breast cancers.
o If the primary tumor is silent, liver manifestations may be the presenting complaints
- Primary hepatocellular carcinoma is associated with hepatitis B, hepatitis C, aflatoxin B1 exposure
(produced by Aspergillus spp. and found in contaminated vegetation and contaminated food), and cirrhosis
- Presenting complaints malaise, weight loss, abdominal swelling, weakness, jaundice, and upper
abdominal pain
- Clinical manifestations typically occur late in disease
- Hepatomegaly, splenomegaly, hepatic bruit, ascites, jaundice, wasting, and fever may be detected on
examination
- Diagnostic Studies:

-Fetoprotein may be elevated in hepatic carcinoma. It is also elevated in chronic hepatitis C and
cirrhosis
o Imaging with sonography, CT, MRI, or hepatic angiography can show the lesion
o Needle biopsy generally should not be performed if the tumor is resectable for fear of seeding
- Treatment:
o Benign neoplasms should be treated if the tumor size indicates a danger of rupturing the hepatic
capsule
o Treatment of metastatic disease involves treatment of the primary lesion
o Surgical resection of hepatic carcinoma may be attempted if the cancer is confined to one lobe and
there is no concurrent cirrhosis. Liver transplant also can be considered. The overall prognosis is
poor
Cholelithiasis
- By age 75, 35% of women and 25% of men have gallstones
- Only 30% of people with gallstones develop symptomatic disease
- Generally, the only complications of choledocholithiasis should be treated, because most people with
gallstones will never develop the disease
- Complications include cholecystitis, pancreatitis, and acute cholangitis
Cholecystitis
- In the vast majority of cases (>90%), obstruction of the cystic (bile) duct by a stone (causing inflammation) is
the initiating event
- After obstruction of the cystic duct, the gallbladder distends, causing subserosal edema, venous and
lymphatic obstruction, cellular infiltration, and localized areas of ischemia
- Associated with a variety of bacterial pathogens in 50-75% of cases
o E. coli, Klebsiella, Streptococcus fecalis, Clostridium spp., Enterobacter spp., Proteus spp.
o Tailor antibiotic regimens to cover these pathogens
- If left untreated, severe, gangrenous cholecystitis (usually seen in diabetics) may develop, leading to
increased morbidity and mortality from perforation of the gallbladder or overwhelming sepsis
o Another potential complication of untreated cholecystitis is perforation of the gallbladder into the
wall of adjacent hollow viscera (duodenum, jejunum, or colon), causing a cholecystenteric fistula
o If a stone subsequently passes into the hollow viscera, bowel obstruction may result. This is called
GALLSTONE ILEUS
- Risk Factors advanced age (>40), female sex and parity, obesity, rapid weight loss or prolonged fasting,
familial tendency, use of some medications, Asians, chronic liver disease, and hemolytic disorders (e.g.,
sickle cell disease)
- Typically it is distinguished from an attack of biliary colic by persistent (as opposed to intermittent) RUQ
pain, fever, elevated WBCs, and alteration of liver chemistries
o Colicky epigastric or RUQ pain becomes steady and increases in intensity. It often occurs after a
high-fat meal
o Persistent RUQ pain with peritoneal irritation (rebound tenderness or Murphys sign) is the most
characteristic symptom and sign
o Pain can be in RUQ and/or midepigastrium and can radiate to the left upper back and/or right
shoulder / subscapular
o Nausea, vomiting, and anorexia are common. Constipation and mild paralytic ileus may occur
o Physical exam reveals an ill-appearing patient with a fever
Can frequently palpate inflamed gallbladder in the RUQ as a tender, distended mass (but
not always present)
Diabetics in particular may have severe cholecystitis with minimal exam findings
o

Murphys sign sudden pain from deep palpation in the RUQ during inspiration, as the
inflamed gallbladder descends to meet the examining hand. Patients often stop their
inspiratory effort during mid-breath
The most sensitive physical exam finding!!!

Diagnostic Studies:
o Lab findings elevated WBC with associated bandemia (leukocytosis with left shift)
Elevated LFTs (particularly AST, ALT, alkaline phosphatase)
After 24 hours, bilirubin levels increase in blood and urine
Total bilirubin is usually moderately elevated (1-2), although significant elevation
(>2) should raise suspicion of concomitant common bile duct obstruction
o Gallstones are found in 95% of patients with cholecystitis. Although only 20% are radiopaque, the
remainder generally are visible by sonography
o Two most common radiologic studies used are abdominal ultrasound and HIDA scan
Plain radiographs are of limited utility because only 15% of gallstones are radio-opaque
**On ultrasound gallstones present? Gallbladder distended? Thickening of
gallbladder wall and/or pericholecystic fluid found? Is dilatation of the intrahepatic or
extrahepatic bile ducts present?
Gallbladder-wall thickening is often used as a criterion for diagnosis (>3-5 mm)
The most reliable ultrasound signs are documentation of stones, a distended gallbladder
(>4 cm), and presence or absence of ultrasonic Murphys sign
Must always evaluate the diameter of the extrahepatic bile ducts to exclude the possibility
of choledocholithiasis
Suggested when the common bile duct diameter is >5-7 mm
If the diagnosis is questionable, use a HIDA scan
If there is obstruction of the cystic duct, the gallbladder will not be visualized
Test is not very useful for NPO
o ERCP can identify cause, location, and extent of biliary obstruction
Treatment:
o Admit, NPO (for pancreatic rest), start IV fluids (crystalloid IV fluids)
Pressors are indicated for hypotension not responsive to fluid resuscitation
o For vomiting antiemetics (ondansetron or prochlorperazine)
If intractable vomiting, NG tube
o IV morphine for discomfort
o If the diagnosis of cholecystitis or cholangitis is confirmed, start IV antibiotics
Use third-generation cephalosporins (cefotaxime or ceftriaxone) + metronidazole
For sepsis, obvious peritonitis, or cholangitis, use triple therapy ampicillin, gentamicin,
clindamycin
o Consult Surgery!!!!!
o Unless contraindications exist (MI, pancreatitis, cholangitis), cholecystectomy should be performed
in the first 24-36 hours of admission
If patients do not present until day 4 or 5 of the illness, may want to manage with
antibiotics and defer surgery, because the inflammatory process is the most severe
between 72 hours and 1 week
o Patients with uncomplicated biliary colic whose symptoms abate with supportive therapy within 4-6
hours of onset can be discharged home if they can maintain oral hydration
May prescribe oral opioid analgesics for 24-48 hours
Follow-up with PCP in a timely manner

Cholangitis
- An infection of the common bile duct. Results from complete biliary obstruction (often a common bile duct
stone, less often a tumor) with a bacterial superinfection (most commonly gram negative organisms E.
coli, Enterococcus, Klebsiella, Enterobacter)
o Usually caused by choledocholithiasis
Although neoplasms, postoperative strictures, or other causes of obstruction may be
involved
- A life-threatening condition with high mortality
- Classically marked by fever, RUQ pain, jaundice Charcot Triad
- Progression of cholangitis to sepsis defines Reynolds Pentad Charcot + hypotension + mental status
changes
o Indicates sepsis. If present, the disease may become rapidly fatal
- Elderly patients may present with confusion, falls, and incontinence
- Diagnostic Studies:
o RUQ ultrasonography will generally show biliary dilation or stones and is a good initial test
o Causes elevated serum bilirubin and transaminase levels, as well as leukocytosis with left shift
o ERCP is the optimal procedure for both diagnosis and treatment but, unless urgent decompression
is necessary, should not be done until the patient is stable
- Treatment:
o Antibiotics (generally a fluoroquinolone, a cephalosporin, ampicillin, or gentamicin with
metronidazole), fluid and electrolyte replacement, and analgesia are the initial treatment
Ampicillin + gentamicin + clindamycin
Or equivalents (metronidazole instead of clindamycin, third-generation cephalosporins or
piperacillin/tazobactam, or a fluoroquinolone for ampicillin)
o ERCP for drainage, sphincterotomy, and stone removal and stent placement can be done when the
patient is stable.
Percutaneous transhepatic biliary drainage or surgical biliary drainage may be required
Primary Sclerosing Cholangitis
- PSC is a chronic thickening of the bile duct walls of unknown etiology, although 80% of cases are
associated with IBD (generally ulcerative colitis, although only 10% of people with UC will develop PSC)
- Male to female ratio is 7:3, and the age at diagnosis is between 21-67 years (mean 39 years)
- Jaundice and pruritus are the most common presenting features, with fatigue, malaise, and weight loss seen
in many patients
- Hepatomegaly and/or splenomegaly may be found on examination
- Labs are the same as for acute cholangitis
- Treatment:
o Localized strictures may be relieved with balloon dilation and stent placement. Long-term stenting
increases risk of cholangitis
o Liver transplant is the only treatment with a known survival benefit
Celiac Disease
- Amongst the most common genetic conditions in Europe and the United States (multifactorial inheritance)
- Characterized by inflammation of the small bowel, with the ingestion of gluten-containing foods such as
wheat, rye, and barley leading to malabsorption
- Clinical presentation is highly variable, often leading to a delay in diagnosis in milder cases
- Diarrhea, steatorrhea, flatulence, weight loss, weakness, and abdominal distension are common
- Infants and children may present with failure to thrive
- Older patients may present with iron deficiency, coagulopathy, and hypocalcemia
- IgA antiendomysial and antitissue transglutaminase (anti-tTG) antibodies are the serologic screening tests
- Small bowel biopsy is needed to confirm the diagnosis

Treatment involves a gluten-free diet. Refer to nutritionist. A lactose-free diet may also be needed initially
until the intestinal inflammation resolves
- Supplementation may be needed to correct nutritional deficiencies in iron, B12 and folic acid, calcium and
vitamin D
- Prednisone may be required in refractory cases
Irritable Bowel Syndrome
- A functional disorder without a known pathology. It is thought to be a combination of altered motility,
hypersensitivity to intestinal distention, and psychological distress
- The most common cause of chronic or recurrent abdominal pain
- Generally remains an intermittent, lifelong problem. Symptoms typically begin during early to mid-adulthood
- W>M. Exacerbations may be associated with menses or stress
- A diagnosis of exclusion.
o DDX lactose intolerance, cholecystitis, chronic pancreatitis, intestinal obstruction, chronic
peritonitis, and carcinoma of the pancreas or stomach
- Abdominal pain may occur anywhere or may be localized to the hypogastrium or LLQ
o Pain may be worsened by food intake and typically is relieved with defecation
o Pain may be associated with bowel distention from accumulation of gas and associated spasm of
the smooth muscle, postprandial urgency is common
- Physical examination generally is normal but may include a tender, palpable sigmoid colon and
hyperresonance on percussion over the abdomen
- IBS is strongly identified with changes in stool frequency and character. Constipation, diarrhea, or
alternating constipation and diarrhea may occur
- Dyspepsia is common
- Urinary frequency and urgency are common in women
- The stool should be tested for blood, bacteria, parasites, and lactose intolerance
- Colonoscopy, barium enema, ultrasonography, or CT should be performed to rule out other pathology
- Endoscopic studies are indicated in patients with persistent symptoms, weight loss or anorexia, bleeding, or
history of other GI pathology
- Reassurance and a strong provider-patient relationship are key. Avoid any known triggers
- A high-fiber diet and bulking agents, such as psyllium hydrophilic mucilloid, are the mainstays of treatment
- Antispasmodics, antidiarrheals, prokinetics, or antidepressants can be used if indicated by the patients
symptoms or course of illness
Anal Fissure
- Small tears in the anoderm typically in the posterior midline, although sometimes seen anteriorly
- Any fissure off the midline should raise suspicion for Crohns disease
- Most commonly caused by the passage of a large or hard stool, however diarrhea can sometimes cause it
- Often heal on their own but sometimes require medical or surgical management
o Failure to heal has been ascribed to persistent trauma from hard stools, poor blood supply, spasm
of the internal sphincter, or a combination
- Chronic fissures (>3 weeks) often have a sentinel skin tag at the distal aspect caused by inflammation
- Pain initiated with each bowel movement that can last several hours
- The expectant pain with defecation can compound the problem by causing increasing constipation and
harder stools
- Blood is usually on the toilet paper, but bleeding should not be profuse
- Differential patients with anal pain usually have a fissure, an abscess, or a thrombosed external
hemorrhoid
- Commonly, the onset of symptoms can be pinpointed to a day, and often to the passage of a hard stool
- Pain often subsides between bowel movements

Examination generally shows a small, radial tear in the anoderm, with or without a sentinel skin tag, and
internal sphincter muscle fibers can sometimes be identified at the base of the tear
- Treatment is aimed at relieving sphincter spasm and pain, and preventing stricture formation
- The best form of initial treatment is correcting the constipation with a high-fiber diet (bran), increased liquid
intake, and the addition of a bulking agent and a stool softener
- Sitz baths and lidocaine jelly
- Chronic fissures (>3 weeks) and recurrent fissures do not respond well
- Can also try topical nitroglycerin (side effect is severe headache) or topical diltiazem
- Fissures that fail conservative management are best treated with surgery lateral internal sphincterotomy.
This is extremely effective
o The biggest risk of sphincterotomy is incontinence to gas or liquid. Usually is temporary and
resolves within a few weeks. Occurs in up to 30%
o Also bleeding and infection, but these are rare
Fistula-In-Ano
- An anal fistula is an abnormal inflammatory tract, originating from an infected anal gland
- Commonly result from perianal or ischiorectal abscesses
o Drainage of the abscess creates a fistulous connection between the anal canal and the skin
- Crohn disease, ulcerative colitis, tuberculosis, gonococcal proctitis, and carcinomas should also be
considered in the etiology
- Persistent bloody, malodorous discharge occurs as long as the fistula remains open
- Blockage of the tract causes recurrent bouts of inflammation and abscess formation
- Ultrasonography with endoprobe and enhanced with hydrogen peroxide may aid in the diagnosis
- Non-ill appearing patients may be treated with analgesics, antipyretics, and oral antibiotics such as
ciprofloxacin BID and metronidazole QID x 7 days
- Surgical excision is the definitive treatment and should not be delayed in ill appearing patients
o Sitz baths and local cleaning with temporize the condition before surgery
- This fistula will spontaneously obliterate in 50-70% of patients. When it does not, it must be opened
surgically to prevent recurrent infections
o Fistula tracks follow Goodsalls rule, if they are not caused by Crohns disease. This rule states
that the external opening of the fistula situated behind the transverse anal line will open into the
anal canal in the midline posteriorly
Hemorrhoids
- Varices of the hemorrhoidal plexus
- Pregnancy predisposes
- External hemorrhoids are visible perianally. Usually are painful. Found below the dentate line and are
covered with anoderm
- Internal hemorrhoids are found above the dentate line where little to no sensation is present, and are
covered with mucosa. Most often present in the left lateral, right posterior, and right anterior portions of the
anal canal. The blood inside the hemorrhoids is arterial
o Stage I internal hemorrhoids are confined to the anal canal and may bleed with defecation.
Bleeding without prolapse
o Stage II internal hemorrhoids protrude from the anal opening but reduce spontaneously. Bleeding
and mucoid discharge may occur. Prolapse outside the anal canal with spontaneous reduction
o Stage III internal hemorrhoids require manual reduction after bowel movement. Patients may
develop pain and discomfort.
o Stage IV internal hemorrhoids are chronically protruding and risk strangulation. Prolapse that will
not reduce (incarcerated) outside the anal canal
- Internal hemorrhoids usually enlarge from constipation and straining. They are NOT painful unless a
thrombosed external hemorrhoid component is present. Bleeding is common

Thrombosed hemorrhoids are usually painful and may appear as a bluish-purple mass protruding
from the rectum
External hemorrhoids are very painful the worst in the first 48-72 hours. Bleeding is uncommon unless the
clot has eroded through the skin from pressure necrosis
Other causes of rectal bleeding diverticulosis, AVM, IBD, ischemia, anal fissures
Always consider carcinoma until proven otherwise! Suspect if recent weight loss, change is stools, or family
history of colon cancer
External hemorrhoids can be seen on physical exam no need for digital exam
Internal hemorrhoids, if not prolapsed, are best diagnosed by anoscopy
o They are not readily palpable
o Found at 2, 5, and 9-oclock positions when the patients are prone
Treatment:
o Unless a complication is present, management is usually nonsurgical
Hot sitz baths for at least 15 minutes, 3x/day, and after each bowel movement
After each bath, thoroughly dry the anus
Topical steroids and analgesics
Bulk laxatives (psyllium) or stool softeners should be used after the acute phase has
subsided
Laxatives causing liquid stool contraindicated may result in cryptitis and sepsis
o External hemorrhoids will almost always resolve on their own if one can ignore the pain
o Internal hemorrhoids usually only resolve completely after pregnancy. Otherwise they wax and
wane and get worse
o Thrombosed external hemorrhoids should be treated with warm soaks, stool softeners, and pain
medicine.
Acute and recently thrombosed painful hemorrhoids (< 48 hours) can be treated with clot
excision
If patients are seen later than 4 days, Sitz baths and reassurance are treatment of choice
o Internal hemorrhoids can often improve by avoiding constipation and straining a high-fiber diet,
increased liquid intake, bulking agents, and stool softeners are very effective
o Painful thrombosed external hemorrhoids that are not improving or worsening should be excised
o Stage I and II disease can be managed with a high-fiber diet and increased fluids. Bulk laxatives
are helpful
o Higher-stage hemorrhoidal disease may benefit from suppositories with anesthetic and astringent
properties
o Surgical treatment is indicated for those unresponsive to conservative treatment and all stage IV
hemorrhoids. Choices include injection, rubber band ligation, or sclerotherapy
Stage I banding or surgical excision if banding fails
Surgical excision is best for large or prolapsed hemorrhoids or those that fail banding.
Complications are uncommon bleeding, infection, recurrence
o

Hernias
- A protrusion of an organ or structure though the wall that normally contains it.
- Hernias of various types can entrap the intestines and cause intestinal blockage.
- Inguinal hernia:
o Indirect most common. passage of intestine through the internal inguinal ring down the inguinal
canal, may pass into the scrotum
o Direct passage of intestine through external inguinal ring at Hesselbachs triangle, rarely enters
the scrotum
o Femoral least common; passage through femoral ring.
- Umbilical hernia generally is congenital and appears at birth. Many resolve on their own. May need surgery

Incisional hernias are associated more commonly with vertical incisions, especially in patients with
concurrent obesity or wound infection
Ventral hernia occurs when there is a weakening in the abdominal wall. May either be incisional or umbilical
Treatment is surgical.

Internal Medicine Genitourinary

Benign Prostatic Hypertrophy
- Proliferation of the fibrostromal tissue of the prostate can lead to compression of the prostatic urethra,
creating an obstruction of the urinary outlet
- A disease of older men, mean age of onset 60-65 years
- Symptom complex is referred to as prostatism and includes obstruction and irritation symptoms
o Obstructive decreased force of urinary stream, hesitancy and straining, postvoid dribbling, and
sensation of incomplete emptying
o Irritative frequency, nocturia, urgency
- Recurrent UTIs and urinary retention can also occur
- DRE typically reveals an enlarged prostate
- PSA typically is slightly elevated
- Other tests are done to evaluate for renal damage, infection, and prostate or bladder cancer, as suspected
- Men with mild to moderate symptoms may choose watchful waiting and frequent monitoring
- Medical therapy options -adrenergic agonists (prazosin, etc.), 5-reductase inhibitors (finasteride,
dutasteride), and phosphodiesterase-5 inhibitors (tadalafil, vardenafil)
o Anticholinergic agents may be appropriate and effective treatment alternatives for management of
lower urinary tract symptoms secondary to BPH in men without an elevated postvoid residual and
when symptoms are predominantly irritative
o Tamsulosin + tolterodine extended release reduces symptoms in men with lower urinary tract
symptoms and overactive bladder
o Intramuscular cetrorelix improves symptom score in men with symptomatic BPH
- Behavioral strategies limit fluids prior to bedtime
- Procedures that may be used to relieve obstruction include use of balloon dilation, microwave irradiation,
and stent placements
- Surgical treatment is transurethral resection of prostate (TURP) or transurethral incision of prostate
Prostate Cancer
- Common, slow-growing, malignant neoplasm of the adenomatous cells (>95% adenocarcinoma, <5% other
types) of the prostate gland that can lead to urinary obstruction and metastatic disease
- The majority of prostate cancers (75%) originate in the peripheral zone (outer portion of the prostate
palpable on rectal exam)
o Transitional zone (20%) is the portion of the prostate surround the majority of the urethra (BPH
symptoms)
o Central zone (5%) is the portion of prostatic urethra with ejaculatory ducts
- Rarely in men younger than 40 years
- Cause unknown
o Risk Factors genetics, hormonal influence, dietary and environmental factors, infectious agents
- Many cases are not clinically apparent
- Symptoms of urinary obstruction or irritative voiding symptoms can occur if the tumor has invaded into the
urethra, bladder neck, or trigone of the bladder
o In advanced disease, patients may present with bone pain from metastases, possible spinal cord
impingement if the vertebral bodies are involved
- Prostate may be enlarged, nodular, and asymmetric

Diagnostic Studies:
o PSA is usually elevated
o Pathologic examination of tissue removed for treatment of obstructive prostatic hyperplasia reveals
that 10% have malignancy
o Transrectal ultrasonography reveals hypoechoic lesions in the prostate (peripheral zone)
o Biopsy confirms the diagnosis of adenocarcinoma and allows histologic grading (Gleason grading
system, based on architectural pattern), which can provide prognostic information
The Gleason grading system adds together the primary and secondary grades of the
tumor, resulting in a final score of 2-10
The total score can be used for prognostic purposes, with a higher score indicating a
worse prognosis than a lower score
- Treatment depends on the staging, which is done by abdominal and pelvic CT or MRI, pelvic
lymphadenectomy, and bone scan
o Low-grade tumors that are well differentiated may not require any treatment, whereas higher grade
tumors more typically are aggressive and, therefore, should be managed more aggressively
o Stages A and B disease (tumor confined to the prostate) may be treated with radical retropubic
prostatectomy, brachytherapy, or external beam radiation therapy
o Stage C disease (tumor with local invasion) is treated similar to stages A and B disease but with
reduced effectiveness
o Stage D disease (distant metastases) is treated with hormonal manipulation using orchiectomy,
antiandrogens, luteinizing hormone-releasing agonists, or estrogens
Chemotherapy has limited usefulness, and palliative treatment is given for advanced
disease
Prostatitis
- Acute bacterial prostatitis is caused by ascending infection of gram-negative rods into the prostatic ducts
- Chronic bacterial prostatitis may be associated with evolution or recurrence of an acute bacterial infection.
Its route of infection is the same as for acute prostatitis. The same gram-negative organisms are most
commonly responsible. Usually E. coli, Enterococcus may be identified less often
- Chronic nonbacterial prostatitis is the most common of the prostatitis syndromes, and its cause is unknown.
It may represent a noninfectious inflammatory disorder, perhaps with an autoimmune origin, and is a
diagnosis of exclusion. It is often associated with the term chronic pelvic pain syndrome
- Prostatic abscess is an uncommon complication of acute bacterial prostatitis
- Acute infection is characterized by sudden onset of high fever, chills, and low back and perineal pain
- Chronic infection has more variable symptoms, ranging from asymptomatic to acute symptomatology
- All forms present with irritative bladder symptoms (frequency, urgency, dysuria) and some obstruction
- The prostate is swollen and tender. Vigorous prostate exam should be avoided in suspected acute
prostatitis as it may cause septicemia
- Laboratory Findings:
o Urinalysis reveals pyuria. Hematuria and bacteriuria may also be found
o Prostatic fluid culture typically is positive for E. coli in acute infections. Chronic infection is
characterized by recurrence of the same organism or enterococcus. In nonbacterial prostatitis,
cultures are negative
o The four-glass localization test is the classic means of distinguishing a chronic prostate infection
from another UTI. Urine samples are taken at initial void, midstream, and after prostatic massage.
Prostatic secretions account for the fourth sample. Assessment of the samples helps to localize the
nidus of infection. This test should be avoided in a patient suspected to have acute prostatitis

Treatment:
o Antibiotics are the most effective for bacterial infections. Hospitalization may be indicated in acute
prostatitis. Treatment with parenteral antibiotics (fluoroquinolones or gentamycin and ampicillin)
may be needed until culture results are available and the patient is afebrile for 24-48 hours
Uncomplicated cases ciprofloxacin 500 mg BID or levofloxacin 500 mg QD x 2-6
weeks, or TMP/SMX 160/800 mg BID x 6 weeks
Culture urine 1 week after conclusion of therapy
If fever is not resolved after 36 hours, suspect a prostatic abscess and consult a urologist
for management
In chronic prostatitis, a fluoroquinolone for 1-3 weeks is more effective than TMP/SMX for
1-3 months
o NSAIDs for analgesia, 1-blockers may be helpful if lower urinary tract symptoms are present
o Chronic, recurrent, or resistant prostatitis with or without prostatic calculi may require TURP for
ultimate resolution
Acid Base Disturbances
- Disturbances in the acid-base equilibrium are common, especially in patients who are critically ill
- They may be respiratory (characterized by alterations in CO2) or metabolic (characterized by changes in
HCO3- Hydrogen ion concentration (pH) is normally 7.38-7.42 (7.40 is absolute normal)
o Less = acidemia
o Greater = alkalemia
- Compensation for changes in the pH will always occur in the buffering system, the lungs or kidneys. The
degree of compensation depends on the duration of the disturbance and the functioning of the organ
DISORDER
pH PCO2 HCO3Respiratory Acidosis

Respiratory Alkalosis

Metabolic Acidosis

*
Metabolic Alkalosis

*
* = primary disturbance
- METABOLIC ACIDOSIS
o pH < 7.35
o Plasma bicarbonate < 22 mEq/L
o Increase in hydrogen ion concentration or loss of bicarbonate
In spontaneously breathing patients, the increase in hydrogen ion should stimulate a
compensatory increase in ventilatory rate and thus decrease PCO2
o Presence or absence of an anion gap helps to categorize
Anion gap is calculated as the difference between the concentration of the major
extracellular cation sodium and the major anions chloride plus bicarbonate
Normal anion gap = 8-12 mEq/L and corresponds to unmeasured anions, primarily
plasma protein and a small amount of fixed acids
When calculating anion gap, it must be remembered that the negative charge of albumin
can have an impact on the overall anion gap. If hypoalbuminemia is present, for each 1.0
g/dL decrease in serum albumin, the anion gap should be increased by 2.5 mEq/L

Anion Gap Metabolic Acidosis

Causes (Dr. Maples) diabetic ketoacidosis, renal failure, methanol, alcohol,
paraldehyde, lactic acidosis, ethylene glycol, salicylates
In surgical patients, the most important causes are lactic acidosis (occurs secondary to
hypoperfusion and blood loss), diabetic ketoacidosis, renal failure, and ethanol ingestion
In trauma patients, assume it is due to blood loss (hypoperfusion, and tissue hypoxia) until
proven otherwise
o Non-Anion Gap Metabolic Acidosis
Characterized by loss of buffer base
Causes GI tract losses (especially biliary and pancreatic losses), renal tubular
acidosis, Addisons disease, TPN, and use of carbonic anhydrase inhibitors
o Regardless of the etiology, acidosis can cause nausea and vomiting, abdominal pain, changes in
sensorium, and tachypnea, sometimes a Kussmaul respiratory pattern
o Metabolic acidosis has detrimental effects on body homeostasis hypoxia, myocardial
depression, hypotension, arrhythmias, hyperkalemia, hyperventilation, insulin resistance,
obtundation, coma
o Hyperventilation is the earliest and most recognized sign, resulting from stimulation of the
respiratory drive to blow off CO2
o Treatment depends on etiology
In trauma patients, restore blood and fluid
In DKA, manage insulin and restore volume
If acidosis is severe (pH <7.2), or patients have life-threatening ventricular arrhythmias,
hemodynamic instability, inadequate compensatory response, treat with sodium
bicarbonate
Risks of sodium bicarbonate therapy include hypernatremia, hyperosmolarity,
volume overload
METABOLIC ALKALOSIS
o Inability of the kidneys to excrete excess bicarbonate or retain hydrogen ion
Rise in serum bicarbonate
Usually no change in PCO2
o Usually accompanied by respiratory compensation (increase/retaining of PCO2)
o Causes are divided by response to chloride
Chloride Responsive/Sensitive nasogastric losses, vomiting, past use of diuretics,
volume contraction, posthypercapnic
Usually have a contracted ECV and chloride deficit (urinary chloride <10 mEq/L)
Hypovolemic hypochloremic
Chloride Resistant/Insensitive mineralocorticoid excess, aldosteronism, renal artery
stenosis, renin-secreting tumor, Cushings syndrome, Bartters syndrome
Normovolemic or hypervolemia and urinary chloride >10
Volume-expanded patients
o Severe metabolic alkalosis (pH > 7.60 and HCO3- > 35 mEq/L is associated with cerebral
hypoperfusion, a leftward shift of the oxyhemoglobin dissociation curve, and hypokalemia
Respiratory symptoms hypoventilation and hypoxemia
o Neurologic manifestations are common, especially signs of hypocalcemia
o Treatment directed at underlying deficit
Contraction alkalosis (chloride responsive) is treated with normal saline (sodium chloride)
Chloride-unresponsive may require carbonic anhydrase inhibitors (acetazolamide)
May need to remove an adrenal adenoma
o

 Or by using an aldosterone antagonist (spironolactone)

Interventions to increase renal excretion of bicarbonate are the most effective therapy
- RESPIRATORY ACIDOSIS
o pH is low and PCO2 is elevated
o Can be acute or chronic
o Due to ineffective alveolar ventilation
o May be secondary to hypoventilation life-threatening!!!!!
o The normal compensatory response is a gradual slow increase in plasma bicarbonate by the
kidneys
o Causes decompensation of preexisting respiratory disease, asthma, neuromuscular disorders,
CNS depression, airway obstruction
o Symptoms metabolic encephalopathy (hypercapnic encephalopathy) with headache and
drowsiness is the most characteristic change
With an ensuing hypercapnia, a resultant hypoxemia also ensues
o Plasma bicarbonate concentrations do not increase much in acute. In chronic, renal adaptation is
substantial
o Treatment directed at improving alveolar ventilation
May require intubation and mechanical ventilation (especially if PCO2 > 60 mmHg)
- RESPIRATORY ALKALOSIS
o pH is high and PCO2 is low (hypocapnia)
o May be acute or chronic
o Caused by alveolar hyperventilation
Anxiety is the most common cause
In surgical patients, may be due to hypoxia, CNS lesions, pain, hepatic encephalopathy,
mechanical ventilation
o In acute, renal compensation is minimal. However, in chronic, the kidney responds by decreasing
the excretion of hydrogen ion. Serum bicarbonate also decreases
Serum chloride levels elevate to maintain electroneutrality
o Most patients are asymptomatic
Severe may cause dizziness, chest pain (tightness), tetany-like syndrome (may be
indistinguishable from acute hypocalcemia), carpopedal spasm, circumoral numbness,
cramps, and confusion
o Hyperventilation is particularly dangerous is those with subarachnoid hemorrhage because it
exacerbates vasospasm
o Treat the underlying cause
Acute Renal Failure
- Deterioration in renal function (GFR) leads to excessive accumulation of nitrogenous waste products in the
serum (urea, creatinine) referred to as azotemia
- Patients usually have signs and symptoms of their underlying causative disorder but eventually develop
stigmata of renal failure
o Volume overload, hypertension, pulmonary edema, mental status changes or neurologic
symptoms, nausea and vomiting, bone and joint problems, anemia, and increased susceptibility to
infection (a leading cause of death) can occur as patients develop more chronic uremia
- RIFLE classification of acute renal failure is based on GFR and urine output
o Risk of renal dysfunction vs. injury to kidney vs. failure of kidney function vs. loss of kidney function
vs. ESRD
- History and physical provide clues to etiology
- Majority of causes are due to reduced renal perfusion and acute tubular necrosis

Analysis of diagnostic tests allows patients to be categorized as prerenal, renal, or postrenal.

o Fractional excretion of sodium can be calculated to help in this categorization
Prerenal = < 1
Renal = > 1
May be < 1 in patients with intrinsic renal failure plus glomerulonephritis,
hepatorenal syndrome, radiocontrast acute tubular necrosis, renal allograft
rejection, and certain drugs (ACE, NSAIDs)
Postrenal = > 1
o Normal urinary sediment may be seen in prerenal and postrenal failure, hemolytic-uremic
syndrome, and TTP
With the exception of only a few hyaline casts
o The presence of albumin may indicate glomerulonephritis or malignant hypertension
o Granular casts are seen in acute tubular necrosis
o Albumin and red blood cell casts are found in glomerulonephritis, malignant hypertension, and
autoimmune disease
o White blood cell casts are seen in interstitial nephritis and pyelonephritis
o Crystals can be present with renal calculi and certain drugs (sulfa, ethylene glycol, radiocontrast
agents)
GFR is the key parameter to measure renal function
o Serum creatinine or BUN is less reliable, although more easily measured
o BUN provides an estimate of renal function but is much more sensitive to dehydration, catabolism,
diet, renal perfusion, and liver disease
Urea is reabsorbed in the nephron during stasis, which causes false elevations of BUN,
therefore, this is not a reliable indicator of renal function
Renal ultrasound is the radiologic procedure of choice in most patients with renal failure when upper tract
obstruction and hydronephrosis is suspected. Can also be used to differentiate an acute vs. chronic
problem
o Color flow Doppler can assess renal perfusion and diagnose large vessel causes of renal failure
o A kidney smaller than 10 cm indicates a chronic problem
PRERENAL FAILURE is produced by conditions that decrease renal perfusion and is the most common
cause of community-acquired acute renal failure (70% of cases)
o It also is a common precursor to ischemic and nephrotoxic causes of intrinsic renal failure
o Common causes of prerenal failure hypovolemic states (vomiting/diarrhea, diuretics and other
antihypertensives, reduced intake), hypotension, fluid sequestration (cirrhosis, nephrotic syndrome,
pancreatitis, burns, septic shock, others), blood loss, aortic aneurysm, renal artery stenosis or
embolic disease, or decreased cardiac output from cardiac dysfunction
o Effective intravascular volume should be restored with isotonic fluids (NS or LR) at a rapid rate.
Volume resuscitation is the first priority
o If cardiac failure is causing prerenal azotemia, cardiac output should be optimized to improve renal
perfusion, and reduction in intravascular volume (i.e., with diuretics) may be appropriate
o Urine sodium < 20 mEq/L, FENA < 1%, urine osmolality > 500 mOsm/kg, elevated BUN:Cr (20:1),
urine specific gravity > 1.020
INTRINSIC RENAL FAILURE has vascular and ischemic etiologies. Glomerular and tubulointerstitial
diseases are also causative
o Ischemic renal failure, traditionally known as acute tubular necrosis, now called acute kidney injury.
ATN causes most cases of intrinsic renal failure, and is also the most common cause of
hospital-acquired renal failure
It is caused by severe and prolonged prerenal etiologies

Nephrotoxins (prescribed and environmental) are the second most common

cause of ATN
o NSAIDs, aminoglycosides, radiologic contrast
o Other causes of intrinsic interstitial disease (acute interstitial nephritis, SLE, infection),
glomerulonephritis, vascular diseases (polyarteritis nodosa, vasculitis)
o Adequate circulating volume must be restored first, as hypovolemia potentiates and exacerbates all
forms of renal failure
o Low dose dopamine may improve renal blood flow and urine output, but it does not lower mortality
rates or improve recovery
o Use caution with renally excreted drugs (digoxin, magnesium, sedatives, narcotics)
o Fluid restriction may be required
o Increased urine sodium > 40 mEq/L, FENA > 1-2%, urine osmolality 300-500 mOsm/kg, decreased
BUN:Cr (< 15:1), urine specific gravity 1.010-1.020
- POSTRENAL AZOTEMIA occurs primarily in elderly men with high-grade prostatic obstruction
o Lesions of the external genitalia (i.e., strictures) are also common causes
o Significant permanent loss of renal function occurs over 10-14 days with complete obstruction and
worsens with associated UTI
o Appropriate urinary drainage should be established - procedure depends on level of obstruction
Foley catheter to relieve obstruction caused by prostatic hypertrophy
o For the acutely anuric patient, obstruction is the major consideration. May need emergency
urology consultation if no urine is obtained on initial bladder catheterization
o With chronic urinary retention, postobstructive diuresis may occur due to osmotic diuresis or
tubular dysfunction. Patients may become suddenly hypovolemic and hypotensive. Urine output
must be closely monitored, with appropriate fluid replacement
o Urine sodium, FENA, osmolality, and BUN:Cr can vary depending on how long obstruction has been
present
- If treatment of the underlying cause fails to improve renal function, hemodialysis or peritoneal dialysis
should be considered
o Often initiated when BUN > 100 mg/dL or serum creatinine is > 10 mg/dL
Chronic Renal Failure
- CKD is progression of ongoing loss of kidney function (GFR). Defined as GFR < 60 mL/min/1.73m2 or
presence of kidney damage (proteinuria, glomerulonephritis, or structural damage from polycystic kidney
disease) for 3 months
- CKD is classified into 5 stages based on the estimated GFR
o Stage 1 kidney damage with normal GFR >90 mL/min/1.73m2 body surface area (BSA) and
persistent albuminuria
o Stage 2 kidney damage with mild decrease in GFR to 60-89 mL/min/1.73m2 BSA
o Stage 3 moderate decrease in GFR 30-59 mL/min/1.73m2 BSA
o Stage 4 severe decrease in GFR 15-29 mL/min/1.73m2 BSA
o Stage 5 kidney failure with GFR less than 15 mL/min/1.73m2 BSA
- In stages 1 and 2, the patient is generally asymptomatic without an increase in BUN or serum creatinine.
Acid-base maintenance is adaptive through an increase in remaining nephron function
- When the patient is in stage 3, he or she may still remain asymptomatic, however serum creatinine and
BUN increase
o In addition, other hormone (PTH, erythropoietin, calcitriol) become abnormal
- In stage 4, the patient may become symptomatic with anemia, acidosis, hyperkalemia, hypocalcemia, and
hyperphosphatemia
- In stage 5, the patient is a candidate for renal replacement therapy
- The most common causes diabetes mellitus, hypertension, glomerulonephritis, polycystic kidney disease

Others primary glomerular diseases (membranous nephropathy, minimal change disease, IgA
nephropathy), secondary glomerular diseases (sickle cell anemia, SLE), tubulointerstitial renal
diseases (nephrotoxins, infection, multiple myeloma, HIV), chronic pyelonephritis (tuberculosis),
vascular diseases (renal artery stenosis or obstruction), obstructive nephropathies (nephrolithiasis,
prostate disease, neurogenic bladder)
Patients with CKD generally progress to chronic renal failure
o The rate of development depends on the underlying cause, the effectiveness of treatments, and
the individual patient
o The 5-year survival rate for chronic renal failure is 5%
Uremic symptoms may develop (stages 3-5) insidiously and include fatigue, malaise, anorexia, nausea,
vomiting, metallic taste, hiccups, dyspnea, orthopnea, impaired mentation, insomnia, irritability, muscle
cramps, restless legs, weakness, pruritus, easy bruising, and altered consciousness
Signs include cachexia, weight loss, muscle wasting, pallor, hypertension, ecchymosis, sensory deficits,
asterixis, and Kussmaul respirations
Anemia (due to decreased production of erythropoietin by the kidneys) and iron deficiency (anemia of
chronic disease)
Hyperkalemia, metabolic acidosis, increased phosphate, hypocalcemia (due to vitamin D3 deficiency and
binding with excess phosphate), secondary hyperparathyroidism leading to osteoporosis
Diagnostic Studies:
o Measurement of GFR is the gold standard
The Cockroft-Gault formula = patient age, body weight, serum creatinine
Gender
Modification of Diet in Renal Disease (MDRD) equation = serum albumin, BUN, patient
age, body weight, serum creatinine
More accurate
Takes into account gender and ethnicity
For children, use a pediatric GFR calculator
o Proteinuria is a marker for kidney damage. Microalbuminuria appears early in the disease
o BUN and creatinine are elevated
o Hemoglobin and hematocrit, serum electrolytes, and urinalysis are abnormal
o Serum biomarker cystatin C is elevated with GFR is <88 mL/min/1.73m2 BSA
Clinical role has not been identified
Treatment:
o Aimed at slowing the progression of CKD and treating reversible causes of acute deterioration
o Avoid nephrotoxic drugs (NSAIDs, aminoglycosides, contrast)
o Avoid blood draws on 1 arm and avoid subclavian lines to preserve vasculature for future access
(e.g., AV fistula)
o ACE inhibitors and ARBs slow the progression of renal dysfunction, particularly in proteinuric
patients
o Sodium restriction and/or loop diuretics to prevent volume overload
o Manage comorbid conditions
Tight HTN control (BP < 130/80 mmHg)
Tight glycemic control in diabetic patients (HgbA1c 6.5-7.5%)
Cholesterol-lowering therapy (LDL < 100 mg/dL, HDL > 50 mg/dL, triglycerides < 150
mg/dL)
Tobacco cessation
Weight control
o

Erythropoietin, iron supplements, and antiplatelet therapy should be considered to maintain

hemoglobin (11-12 g/dL, < 13.5 in males) and bleeding time as needed
Increased hemoglobin shows an increased risk of stroke
Medical therapy requires careful drug dosing to adjust for decreased renal function

Dietary management restriction of protein intake, adequate caloric intake, calcium and vitamin
D supplements, limitation of water/sodium/potassium/phosphorus/magnesium
Kayexalate as needed for hyperkalemia
Bicarbonate or citrate if HCO3- is < 22
Oral phosphate binders (calcium carbonate taken with meals) and calcitriol (1,25-OH
vitamin D) for renal osteodystrophy)
o Need for hemodialysis, peritoneal dialysis, or kidney transplantation should be coordinated with
nephrology
Preparation starts in stage 4
Peritoneal dialysis affords patients the opportunity to receive dialysis at home rather than
having to go to a center, and it is also considered more physiologic than hemodialysis.
However, infection is a concern, and medical personnel are not present to observe
whether other interventions are needed
If renal transplantation, need lifelong immunosuppression
Indications for dialysis (AEIOU):
Acidosis unresponsive to medical therapy
Electrolyte abnormalities (K > 6.5 mEq/L)
Ingestions (methylene, ethylene glycol)
Overload (fluid)
Uremic symptoms (e.g., pericarditis, encephalopathy)
**Creatinine level is NOT an indication for dialysis
o Pneumococcal vaccination is recommended
Nephritic Syndrome
- One of the 2 categories of glomerular disease
- Presents with tea-colored urine, decreased urine output, HTN, and edema in dependent ares (including
periorbital and scrotal)
o Edema is not as significant as nephrotic syndrome
- Signs and symptoms (PHAROH)
o Proteinuria (minimal compared to nephrotic syndrome)
o Hematuria
o Azotemia (increased BUN)
o RBC casts
o Oliguria
o Hypertension
- Diagnostic Studies:
o Urinalysis reveals hematuria and some degree of proteinuria
o Serum studies show decreased GFR with elevated BUN and creatinine
o Complement, ANA, ANCA, and anti-GBM antibodies should be measure
o A positive antistreptolysin O (ASO) titer indicates postinfectious glomerulonephritis
- Treatment:
o Etiology dependent
o Hypertension, fluid congestion, and uremia should generally be treated with salt and water
restriction
o Diuretics, dialysis, steroids, and stronger immunosuppressants may be administered as necessary
o

Nephrotic Syndrome
- One of the 2 categories of glomerular disease
- Defined as excretion of > 3.5 g protein per 1.73 m2 of body surface in 24 hours
- Manifests with hypoalbuminemia, lipiduria, hypercholesterolemia, and edema
- Can predispose to thrombosis secondary to loss of protein S and C and antithrombin III
o Hypercoagulability due to an imbalance of clotting factors in the coagulation cascade due to an
overall decrease in anticoagulation proteins, especially antithrombin III (lost in urine), and to
increased hepatic synthesis of procoagulant proteins such as fibrinogen
- Affects children and adults
- Prognosis depends on cause and degree of renal damage
- Symptoms malaise, abdominal distention, anorexia, facial edema / puffy eyelids, oliguria, scrotal
swelling, SOB, weight gain, foamy urine
- Signs ascites, edema, HTN, orthostatic hypotension, retinal sheen, skin striae
o Generalized edema = puffy eyes in the morning, pitting edema in the legs, pleural effusions,
ascites
- Associated with an increased risk of infection (especially from encapsulated organisms) due to loss of
immunoglobulins
- Diagnostic Studies:
o Urinalysis reveals proteinuria, lipiduria, glycosuria, hematuria, foamy urine
o 24-hour urine collection is preferred
Can also use the protein-to-creatinine ratio)
o Microscopic exam of the urine shows RBC casts, granular casts, hyaline casts, and fatty casts
Key finding is the oval fat body, which is a renal tubular cell that has reabsorbed some of
the excess lipids in the urine
o Blood chemistry shows hypoalbuminemia, azotemia, and hyperlipidemia
Hyperlipidemia is secondary to the liver producing increased lipoproteins due to
hypovolemia from the loss of intravascular volume (edema)
Albumin < 3 g/dL
o C3 levels can be low or normal, depending on the cause
o Renal biopsy may be useful
- Treatment:
o Medical therapy = ACE inhibitors early in disease, careful use of diuretics to reduce fluid
accumulations
o Sodium and fluid restriction to manage edema
o Dietary protein and potassium intake can be normal but not excessive
o Treat infections aggressively
o Use anticoagulants if thromboses are present
o Antihyperlipidemic (statins)
o Nephrotoxic drugs (e.g., NSAIDs, aminoglycoside antibiotics) should be avoided
o Children respond better to steroids than adults
o May need steroids for severe disease
o Frequent relapses or steroid non-responders may be treated with cyclophosphamide, cyclosporine,
tacrolimus, or mycophenolate mofetil
Urinary Tract Infection (Cystitis)
- Infection of the normal bladder. Most commonly caused by E. coli, sometimes gram-positive (enterococci)
o Also Saprophyticus, Enterobacter, Klebsiella, Serratia, Proteus, Pseudomonas
- Route of infection is typically ascending from the urethra. More common in women
- Irritative voiding symptoms are common frequency, urgency, dysuria
- Suprapubic discomfort

Gross hematuria may occur. Symptoms in women often may appear following sexual intercourse or use of
a diaphragm with spermicide
- Physical exam may elicit suprapubic tenderness, but exam is often unremarkable, especially in elderly
patients
- Urinalysis shows pyuria (>2-5 WBCs in women, >1-2 WBCs in men), bacteriuria, and varying degrees of
hematuria
o Leukocyte esterase and nitrates
o Increased urine pH (proteus)
- Urine culture is positive (>103 cfu/mL of clean-catch urine) for the offending organism
- Imaging is warranted only if pyelonephritis, recurrent infections, or anatomic abnormalities are suspected
- Uncomplicated cystitis in women can be treated with short-term antimicrobials
o Suggested regimen is TMP/SMX x 3-5 days or fluoroquinolone x 3-5 days
o Nitrofurantoin during pregnancy (treat asymptomatic bacteriuria in pregnancy!!!)
- Uncomplicated cystitis is rare in men
- Criteria for complicated UTI prior history of UTI (reoccurrence in <1 month or more than 3 infections per
year, which defines recurrent), atypical organism (non-E. coli) or known antibiotic resistance, functionally
abnormal urinary tract, comorbidities, advanced neurologic disease, nursing home residency, indwelling
catheter or recent urinary tract instrumentation, pregnancy, male sex
o Use fluoroquinolones (ciprofloxacin or levofloxacin), cefpodoxime, or fosfomycin for 10-14 days
- Encourage fluids. Preventive measures including proper hygiene, urine acidification, voiding after sex
- Hot sitz baths or urinary analgesics (phenazopyridine) may provide symptomatic relief. Phenazopyridine will
discolor the urine (dark orange or reddish)
Pyelonephritis
- Acute pyelonephritis is an infectious inflammatory process involving the kidney parenchyma and renal
pelvis. Bacteremia may occur in up to 10% of cases, however this is more common in diabetics and women
- Gram-negative bacteria are the most common E. coli (85%), Proteus, Klebsiella, Enterobacter,
Pseudomonas. The infection usually ascends from the lower urinary tract
- Chronic pyelonephritis is the result of progressive inflammation of the renal interstitium caused by bacterial
infection, and occurs in patients with anatomic urinary tract abnormalities such as vesicoureteral reflux
- Symptoms fever, flank pain, shaking chills, irritative voiding symptoms. Nausea, vomiting, and diarrhea
are not uncommon
- Young children may have fever and abdominal discomfort
- Signs fever, tachycardia, pronounced costovertebral angle tenderness
- CBC shows leukocytosis and left shift
- Urinalysis shows pyuria, bacteriuria, and varying degrees of hematuria. WBC casts may be seen
- Urine culture (obtain before starting antibiotics) will demonstrate heavy growth of the offending agent
- In complicated pyelonephritis, renal ultrasonography may show hydronephrosis secondary to obstruction
- In the outpatient setting, treatment with fluoroquinolones or TMP/SMX for 1-2 weeks. Longer for
immunocompromised
- Hospital admission for those with severe infections or complicating factors (older age, comorbid conditions,
signs of obstruction, inability to tolerate oral antibiotics)
- IV fluoroquinolones or ampicillin and gentamicin. Continue for 24-28 hours after the patient becomes
afebrile. Then given oral antibiotics for 2 weeks minimum
- Failure to respond warrants ultrasound imaging to exclude complicating factors such as stones or possible
abscess formation
- Follow-up urine cultures are mandatory 1-2 weeks following treatment
o Not mandatory for uncomplicated cases

Renal Calculi
- Nephrolithiasis. Occur throughout the urinary tract and are common causes of pain, infection, and
obstruction
- Stones are caused by increased saturation (supersaturation) of urine with stone-forming salts (calcium,
oxalate and other solutes) or a possible lack of inhibitors (citrate) in the urine to prevent crystal formation. If
either situation happens, then precipitation occurs and crystalluria develops
o Typically formed in the proximal tract and pass distally. Lodge at the ureteropelvic junction (kidney
stones), the ureterovesicular junction (bladder stones), or the ureter at the level of the iliac vessels
- Nephrolithiasis commonly occurs during the 3rd-4th decade of life. The disease is 2-3x more common in
males than females
- Four major types of stones:
o Calcium 75-85% of stones are formations of calcium crystals. Radiopaque
o Uric Acid 5-8% of stones are formed by precipitation of uric acid. Radiolucent. Form in
individuals with persistently acid urine with or without hyperuricemia
o Cystine less than 1% of stones are caused by an impairment of cystine transport. These stones
are radiolucent. They occur only in autosomal recessive cystinuria
o Struvite 10-15% of stones are formed by the combination of calcium, ammonium, and
magnesium. They are radiopaque. Formation is increased by urinary tract infections with ureaseproducing bacterium; therefore, this type is common in patients with abnormal urinary tract
anatomy and urinary diversions and in those who require frequent catheterization
- Patients usually have complete return to health, but recurrence can occur. Frequency of recurrence has
been up to 30-50% in 5 years
- Clinical Features:
o Nephrolithiasis generally is asymptomatic until inflammation or complete or partial ureteral
obstruction develops
o Clinical features of nephrolithiasis include unilateral back pain and renal colic that waxes and
wanes
o Symptoms include hematuria, dysuria, urinary frequency, fever, chills, nausea, and vomiting
o Location can determine direction of pain and its radiation
A stone in the upper ureter the pain tends to radiate to the anterior abdomen
A stone in the lower part of the ureter the pain tends to radiate to the ipsilateral groin,
testicle in men, or labia in women
A stone lodged in the UVJ urinary frequency and urgency are noted as well as lower
pelvic pain
As the stone passes through the ureter it may mimic other acute conditions, for example,
acute cholecystitis, acute appendicitis, acute cystitis, and diverticulitis
- Laboratory Findings:
o Serum chemistries are usually normal, however there may be a leukocytosis from infection or
stress
Urinalysis usually reveals microscopic or gross hematuria and may show leukocytes
and/or crystals
Urine culture should be performed to rule out infection
o Imaging modality of choice is the helical (spiral) CT. this does not require the use of radiocontrast
and can detect stones as small as 1 mm
o Plain-film radiography of the abdomen can identify radiopaque stones; unfortunately it may miss a
small stone even if radiopaque
o Renal ultrasonography can only identify stones in the kidney, proximal ureter, or the UVJ

An intravenous pyelogram (IVP) is a rarely indicated in the treatment and evaluation of a patient
with nephrolithiasis. If an IVP is considered, remember to make sure that the patient has normal
renal function
- Treatment all stones should undergo chemical analysis, as the type of stone may dictate additional
treatment
o Stones measuring less than 5 mm
Many are likely to pass spontaneously and, in an otherwise healthy individual, may be
managed on an outpatient basis
Drink lots of fluids, use analgesics
Strain urine to catch the stone and save it for analysis
An alpha blocker or calcium channel blocker may facilitate passage
Follow-up weekly or biweekly to monitor progress. Most stones that pass do so within 2-4
weeks of onset of symptoms
o Stones measuring 5-10 mm
Less likely to pass spontaneously. Consider early elective intervention if no other
complicating factors (e.g., infection, high-grade obstruction, solitary kidney, anatomic
abnormality preventing passage, intractable pain)
Increased fluids and analgesics
Elective lithotripsy or ureteroscopy with stone basket extraction may be used
o Stones measuring greater than 10 mm
Not likely to pass spontaneously. Patients are more likely to have complications
The patient should be treated on an inpatient basis if he or she is unable to maintain
adequate oral intake
Vigorous hydration
Ureteral stent or percutaneous nephrostomy (gold standard) should be used if renal
function is jeopardized
Urgent treatment with extracorporeal shock wave lithotripsy can be used for renal stones
of less than 2 cm or for ureteral stones of less than 1 cm. Ureteroscopic fragmentation
also may be used. Percutaneous nephrolithotomy can be used for stones of greater than
2 cm
Ureteroscopy is more effective than lithotripsy for ureteral calculi
o Analgesics should be administered, including morphine, meperidine, or ketorolac. Depending on
stone makeup antibiotics if signs of infection are present. HCTZ to decrease urine calcium
excretion. Allopurinol to decrease urine uric acid excretion. Alkali to increase urine citrate
excretion
Glomerulonephritis
- Generally refers to damage of the renal glomeruli by deposition of inflammatory proteins in the glomerular
membranes as the result of an immunologic response. The severity of disease is dictated by the degree of
glomerular injury
o Normal function of the glomerulus primary filtration for the urinary stems
- About 60% of cases are in children 2-12 years old
- Prognosis is excellent in children, worse in adults (especially those with preexisting renal disease)
- A major causes of CKD
- Causes are divided into focal GN (characterized by involvement of less than half of the glomeruli, less
severe proteinuria) and diffuse GN (affects most glomeruli, severe proteinuria)
o

Hematuria is present; urine often is tea or cola colored

Oliguria or anuria is present
Edema of the face and eyes is present in the morning, and edema of the feet and ankles occurs in the
afternoon and evening
Hypertension also is a common, but not essential, clinical finding
Laboratory Findings:
o Antistreptolysin O titer is increased in 60-80% of cases and should be considered if there is a
possibility of a recent streptococcal infection. A common cause of GN is poststreptococcal
infection (PSGN)
o Urinalysis reveals hematuria (> 3 RBCs/HPF). RBCs will also often be misshaped (acanthocytes)
due to their passage though the glomerulus as opposed to a normal-shaped RBC that could
represent bleeding from the bladder or urethra. Also RBC casts and proteinuria (1-2 g/24hr)
o Serum complement (C3) levels are often decreased
o Renal biopsy may be done to determine exact diagnosis or severity of disease
Treatment:
o Steroids and immunosuppressive drugs may be used to control the inflammatory response which is
responsible for the damage. These are usually not needed in PSGN
o Dietary management salt and fluid intake should be decreased
o Dialysis should be performed if symptomatic azotemia is present
o Medical therapy:
ACE inhibitors are renoprotective (reduce urinary protein loss) in chronic GN
Use medications as appropriate for hyperkalemia, pulmonary edema, peripheral edema,
acidosis, and hypertension
IgA nephropathy:
o Most commonly found glomerulonephritis pathology
o Caused by deposition of IgA immunoglobulins with resultant inflammation and mesangial cell
proliferation.
Poststreptococcal glomerulonephritis:
o Deposits of antigen are found humped in the subepithelial region.
o Pathology may develop 2-3 weeks following a bout of pharyngitis or cellulitis
o Labs:
Elevated ASO titer (pharyngitis)
Elevated serum creatinine
Urine red blood cells, RBC cast, WBC cast, sterile pyuria
Low C3, normal to slightly decreased C4( usually normal in MRSA)
Cryoglobulinemia may be present
Elevated IgA levels in MRSA infection
Rapidly progressive glomerulonephritis (RPGN):
o Extensive formation of extracapillary crescents in more than half of glomeruli giving rise to
synonym crescentic glomerulonephritis.

o Rapid progression into acute renal failure if untreated.

o Maximal inflammation and renal failure within days.
Conditions that may present with mild focal nephritis or diffuse nephritis:
o Antiglomerular basement membrane disease:
Goodpasture disease
Caused by direct glomerular damage occurring as a result of inflammation triggered by
antibodies directed against components of the glomerular basement membrane.
Immunofluorescence Microscopy linear deposits of immunoglobulin
Circulating antibodies may also lead to pulmonary hemorrhage, causing a constellation of
pathology called Goodpasture Syndrome.

Immune complex disease:

Glomerular deposition of immune complexes that result in an inflammatory response.
IF reveals granular immunoglobulin deposits
o Pauci-immune disease:
Group of disorders characterized by the presence of ANCA that are associated with
multisystemic disease. Minimal or no immunoglobulin is seen by IF, hence pauci-immune.
Glomerular injury is still believed to be immunologic
Considered part of the Wegener granulomatosis spectrum of disease. Patients should be
watched carefully for evidence of systemic vasculitis.
Clinical presentation:
o Can present with symptoms related to underlying etiology or manifest as other clinical syndromes:
Acute nephritis, RPGN:
Abrupt onset of hematuria, hypertension, edema, oliguria, and azotemia
May be preceded by insidious and nonspecific symptoms of fatigue and edema.
RPGN acute glomerulonephritis that advances to ESRD in days to weeks.
Nephrotic Syndrome:
Proteinuria >3 grams/day
Hypoalbuminemia, edema, hyperlipidemia, coagulation abnormalities with
increased risk for DVT and renal vein thrombosis
CKD:
Advanced disease can lead to volume overload, hyperkalemia, metabolic
acidosis, hypertension, anemia, and bone disease.
Hemoptysis:
Most commonly caused by anti-GBM (Goodpasture) disease due to pulmonary
alveolar hemorrhage.
ANCA-associated vasculitis with glomerulonephritis and pulmonary capillaritis
(Wegeners disease)
Renal-dermal syndromes:
SLE, Henoch Schnlein Purpura (HSP), cryoglobulinemia, and ANCA-associated
vasculitis
Palpable purpura (HSP), necrotic dermal inflammation, ulcers, or nodules
Workup:
o Electrolytes, creatinine
o Urinalysis proteinuria, hematuria
o Microscopic examination of urine sediment dysmorphic RBCs or RBC casts and lipiduria
o RPGN, serology
o Anti-GBM antibodies
o ANCA
o Serum complement levels
o Renal biopsy with exam by light microscopy, immunofluorescence and electron microscopy is
useful for establishing a diagnosis in the setting of acute nephritis, RPGN, and nephrotic syndrome.
Treatment:
o Supportive care with fluid and electrolyte management
o Poststreptococcal antibiotics
o Nephrosis control proteinuria with ACE-I and ARBs
o Diabetics control blood pressure and glycemic disease
o Severe edema sodium and water restriction and careful use of loop diuretics
o

Immunosuppressive agents Goodpasture syndrome, Wegener granulomatosis, and

polyarteritis. Can limit disease in idiopathic nephrotic syndrome, lupus nephritis, and idiopathic
RPGN. Can be considered in IgA-nephropathy and amyloidosis.
Acute Interstitial Nephritis
- Accounts for 10-15% of cases of intrinsic renal failure
- An interstitial inflammatory response with edema and possible tubular cell damage is the typical pathologic
findings
- Drugs cause over 70% of cases
o Also occurs in infectious diseases, immunologic disorders, or as an idiopathic condition
o Most common drugs are penicillins and cephalosporins, sulfonamides and sulfa-containing
diuretics, NSAIDs, rifampin, phenytoin, and allopurinol
Also, PPIs
o Infectious causes = streptococcal infection, leptospirosis, CMV, histoplasmosis, FMSF
o Immunologic entities = more common with glomerulonephritis
SLE, Sjgren, sarcoidosis, cryoglobulinemia
- Clinical features:
o Fever
o Transient maculopapular rash
o Arthralgias
o Peripheral blood eosinophilia
o Classic triad = fever, rash, arthralgia (only 10-15% of cases)
- Acute or chronic kidney injury
- Diagnostic Studies:
o Urine often contains red cells (95%), white cells, and white cell casts
o Proteinuria may occur (especially if NSAID-induced), but is modest (< 2g/24 h)
o Pyuria (including eosinophiluria), WBC casts, hematuria
- Treatment:
o Carries a good prognosis
o Recovery over weeks to months, but may need urgent dialysis in up to of cases
o Rarely progress to ESRD
o Supportive measures and removal of inciting agent
o May give a short course of corticosteroids
Polycystic Kidney Disease
- Characterized by growth of numerous cysts in the kidneys. The cysts are made of epithelial cells from the
renal tubules and collecting system. The cysts replace the mass of the kidneys, resulting in reduced
function and leading to kidney failure
- Autosomal dominant polycystic kidney disease (ADPKD) is the most common form and almost always is
bilateral. Symptoms typically develop during the fourth decade of life
o 2 genes identified PKD 1 and PKD 2
- Autosomal recessive polycystic kidney disease (ARPKD) is less common and begins in utero. It can lead to
fetal and neonatal death. Surviving infants have significantly reduced life expectancy usually due to renal
and hepatic failure
- An acquired form of cystic kidney disease (ACKD) occurs in individuals with long-term renal disease or
ESRD. It is more common in African American men than in other ethnicities
- The most common symptoms of ADPKD are back and flank pain (secondary to the massive enlargement of
the kidneys and/or liver) and headaches (greater risk of intracranial aneurysms). Nocturia is an early sign of
abnormal renal function; it reflects the early impairment in urinary concentration
- Hematuria, hypertension, recurrent UTI, weight loss, and renal colic, as well as nausea and vomiting, also
may be present
o

One or both kidneys may be palpable and feel nodular or tender. Cysts also may be present on the liver,
pancreas, and other locations

Diagnostic Studies:
o Anemia may be noted on CBC
o Urinalysis shows proteinuria, hematuria, and, commonly, pyuria and bacteruria
o Imaging Studies:
The diagnostic method of choice is ultrasonography, which shows fluid-filled cysts
Plain-film radiography of the abdomen shows enlarged kidneys
Excretory infusion urography reveals multiple lucencies
Angiography shows bending of small vessels around cysts
CT shows large renal size and multiple thin-walled cysts
o Genetic studies for PKD 1 and PKD 2 can detect the presence of the mutation before symptoms
develop. Early detection may allow affected individuals to forestall loss of kidney function through
diet and BP control
- Treatment:
o There is no cure for ADPKD. Treatment is supportive to ease symptoms and prolong life
o General measures should include management of pain (secondary to cyst hemorrhage), control of
hypertension (goal of <130/80 mmHg through use of an ACE inhibitor or ARB), high intake of fluids,
and a low-protein diet
o Infections should be treated vigorously with antibiotics (TMP-SMX, fluoroquinolones,
chloramphenicol, or vancomycin) that can penetrate the cyst wall
o Dialysis or transplantation should be considered when renal insufficiency becomes life-threatening.
Transplantation has been successful, and non-PKD kidneys do not develop cysts
Hydronephrosis
- Water inside the kidney
- Distention and dilation of the renal pelvis and calyces, usually caused from obstruction of the free flow of
urine from the kidney (distal to the renal pelvis)
o Hydroureter = dilation of the ureter
- Can also be present without obstruction
- Obstructive nephropathy (e.g., hydronephrosis) is the most common cause of tubulointerstitial disease
- In young adults, renal calculi is the most common cause
o Prostatic hypertrophy, carcinoma, or calculi are the primary causes in older patients
- Can be a normal finding in pregnant women
- Renal ultrasonography is the test of choice
- If untreated, it leads to progressive atrophy of the kidney
- Medical treatment is limited mostly pain control
- Treat the underlying condition
Erectile Dysfunction
- Defined as the consistent inability to maintain an erect penis with sufficient rigidity to allow sexual
intercourse
- Normal erections require intact parasympathetic and somatic nerve supply, unobstructed arterial inflow,
adequate venous constriction, adequate venous constriction, hormonal stimulation, and psychological
desire. Disorders of any of these systems may result in impotence
- Most cases of male erectile disorders have a primary organic rather than a psychogenic cause. Nearly all
cases have a secondary psychogenic component
- Major predictors = HTN, DM, hyperlipidemia, cardiovascular disease
- Evaluate medical history (HTN, DM, endocrine disease, medications, pelvic surgery, trauma)
- Medications such as some antihypertensive (beta-blockers) may be the cause might have to switch
agents
- Take a sexual history timing and frequency of sexual relations, partners, presence of morning erections,
ejaculation, ability to masturbate

o The International Index of Erectile Function (IIEF) is a validated questionnaire

Physical exam to look for penile deformities (e.g., Peyronie disease [fibrous plaque causing penile
curvature], testicular atrophy, HTN, peripheral neuropathy, other signs of endocrine, vascular, or neurologic
abnormalities)
- Diagnostic Studies:
o CBC, urinalysis, lipid profile, thyroid function tests, serum testosterone, glucose, prolactin
screening
o Measurement of FSH and LH if patients have abnormalities of testosterone or prolactin
o Nocturnal penile tumescence testing will differentiate organic from psychogenic impotence.
Patients with psychogenic impotence have normal nocturnal erections of adequate
frequency and rigidity
o Direct injection of vasoactive substances into the penis induces erections in men with intact
vascular systems
Patients who do not achieve erections with injections may undergo studies to evaluate the
arterial and venous vasculature, such as ultrasonography of the cavernous arteries, pelvic
arteriography, and cavernosonography
- Treatment:
o True psychogenic causes can be treated with behaviorally oriented sex therapy
May also help those with organic causes of impotence
o Hypogonadism may benefit from testosterone replacement therapy, but evidence is limited
o Weight loss for BMI > 30 kg/m2 may help
o Phosphodiesterase-5 (PDE-5) inhibitor therapy is the mainstay of treatment
Sildenafil, vardenafil, tadalafil are the drugs currently indicated
Side effects = headache, flushing, dyspepsia, rhinitis, visual disturbances, possible
priapism
Avoid PDE-5 therapy in those taking nitrates (combination can cause a significant drop in
blood pressure)
o For men in whom PDE-5 therapy is ineffective or inappropriate, there are other treatments
Vacuum constriction devices, injected or inserted vasoactive substance, penile prostheses
Patients with disorders of the arterial system are candidates for arterial reconstruction
Spermatocele
- A painless cystic mass containing sperm, usually less than 1 cm in size
- They lie superior and posterior and are distinct from the testes
- Some may simulate a solid tumor
- Palpable, round, firm cystic mass with distinct borders, free floating above the testicle, which
transilluminates. The mass may be tender
- Needle aspiration should not be performed
- Scrotal ultrasonography provides a very accurate diagnosis
- No medical treatment required
- Large spermatoceles can be surgically removed or sclerosed
Hydrocele
- A mass of the fluid-filled congenital remains of the tunica vaginalis, usually resulting from a patent processus
vaginalis
- A soft, nontender fullness of the hemiscrotum that transilluminates
- The mass may wax and wane in size
o An indirect hernia may be concurrently present
- Few studies are warranted
o Urinalysis with microscopic analysis is negative
-

Ultrasonography rarely is indicated but can distinguish between hydrocele, spermatocele, and
testicular tumors
- Elective repair as clinically indicated
Variocele
- The formation of a venous varicosity within the spermatic vein (pampiniform plexus)
- The left spermatic vein has an increased incidence of varicosity because the vein is longer than the right
and joints the left renal vein at right angles
- A chronic, nontender mass that does not transilluminate is seen, usually on the left side
- The lesion has the consistency of a bag of worms, increases in size with Valsalva, and decreases in size
with elevation of the scrotum or supine position
- No lab studies are required
- If the diagnosis is inconclusive, Doppler sonography is the diagnostic method of choice
- Treatment is surgical repair (left spermatic vein ligation) this can be performed if the variocele is painful or
if it appears to be the cause of infertility
Testicular Torsion
- SURGICAL EMERGENCY!!!!! Requires prompt recognition and correction to prevent loss of the testicle
- Rotation of the testicle around the spermatic cord. Usually these patients lack the posterior attachment to
the tunica vaginalis that keeps the testis from rotating around the spermatic cord. Causes the bell-clapper
deformity (ability of the untethered testis to twist on its stalk)
o Compromises arterial supply and venous drainage of the testis, leading to testicular ischemia
- Young men (rare over 30) usually 12-18 years old
o Especially common in those with a history of cryptorchidism (late descent of the testes)
- Pain hallmark presentation of acute onset unilateral scrotal pain (enough to wake from sleep)
o Nausea and vomiting are common
o Scrotum appears swollen and erythematous, testis is very tender
o Elevated testis (high-riding testis on affected side)
o Phrens sign is NOT reliable (pain relief with lifting affected testicle, points to epididymitis, but
Doppler U/S is superior)
Negative Prehn sign
- Absence of cremasteric reflex (MOST SENSITIVE FINDING)
o Unilateral
o Blue dot sign (on upper aspect of scrotum) suggests torsion of appendix testes rather than entire
testicle
Torsion of the appendages is more common but it is not dangerous, because the
appendix testes and appendix epididymis have no known function
- Doppler ultrasound may helpful for differential, but this is a clinical diagnosis
- Radioisotope scan demonstrates decreased uptake in affected testes
- Urologic Emergency immediate referral
4-6 hours for salvage
- Attempt Detorsion twisting the testes outward and laterally
o Opening a book (medial to lateral direction)
Right counter Clockwise
Left clockwise
Usually torsion occurs medially
- Emergent surgical intervention on the affected testis must be followed by elective surgery (orchiopexy) on
the contralateral testis, which also is at risk of torsion
o

Epididymitis
- Infection of the epididymis acquired by retrograde spread of organisms through the vas deferens
- In men younger than 35, chlamydia and gonococci are the most common organisms
- In men older than 35, E. coli is the most common organism
- Presents with heaviness and dull, aching discomfort in the affected hemiscrotum, which can radiate up the
ipsilateral flank. History of the patient may reveal heavy lifting, trauma, or sexual activity
- The epididymis is markedly swollen and exquisitely tender to touch, eventually becoming a warm,
erythematous, enlarged scrotal mass. As the disease progresses, it may become difficult to distinguish the
testes from the epididymis
- The patient may have fever and chills
- The Prehns sign (relief of pain with scrotal elevation) is a classic sign, but it is not very reliable
- Urinalysis reveals pyuria and bacteruria
- Cultures show positive results for suspected organisms
- In men younger than 35 years ceftriaxone 250 mg IM + doxycycline 100 mg bid x 10 days (or
azithromycin 1 g x 7 days)
o Administer for gonococci or Chlamydia
o Test for cure 1 week after conclusion of therapy
- In men older than 35 years ciprofloxacin 500 mg bid x 10-14 days
- Supportive care includes bed rest, scrotal elevation, and analgesics
Bladder Cancer
- Causal factors include exposure to tobacco; occupational carcinogens from rubber, dye, printing, and
chemical industries; schistosomiasis; exposure to cyclophosphamide; and chronic infections
- Uroepithelial tumors (98% are transitional cell carcinomas) account for 3% of cancer deaths in the United
States. Bladder carcinoma is 3x more common in men than in women, and it usually occurs in patients 4070 years of age
- Painless hematuria is the most common presenting symptoms
o Bladder irritability and infection are other presenting symptoms
- Diagnostic Studies:
o CBC and blood chemistry should be done to evaluate for infection and renal function
o Cystoscopy, which has an accuracy rate of nearly 100%, is the definitive diagnostic procedure.
Biopsy confirms the pathologic diagnosis
o Radiologic procedures include IV urogram, pelvic and abdominal CT, chest radiography, bone
scan, and retrograde pyelography for renal pelvic or ureteral tumors and staging
- Treatment depends on the stage
o Superficial lesions are treated with endoscopic resection and fulguration, followed by cystoscopy
every 3 months.
o Recurrent or multiple lesions can be treated with intravesical instillation of thiotepa, mitomycin-C, or
bacillus Calmette-Gurin (BCG)
o Radical cystectomy is used for recurrent cancer, diffuse transitional cell carcinoma in situ, and for
tumors that have invaded the muscle
o Combination chemotherapy has been used in bladder-sparing trials with or without radiation
therapy. External beam irradiation therapy is typically reserved for those individuals who are no
surgical candidates due to significant comorbid medical conditions

Renal Cell Carcinoma

- Also known as hypernephroma or renal adenocarcinoma
- The most common type of renal malignancy
- More common in men, those >55 years, American Indian/Alaskan Native men
- Cause unknown cigarette smoking is linked
- Forms of hereditary RCC von Hippel-Lindau disease, hereditary papillary renal carcinoma
- A wide range of presenting signs and symptoms often called the internists tumor because it is commonly
discovered as an incidental finding on abdominal imaging
- Most common symptom = gross or microscopic hematuria, followed by pain or an abdominal mass
o The classic triad of gross hematuria, flank pain, and a palpable mass only occurs in a small
percentage of patients
- Associated with paraneoplastic syndromes erythrocytosis, hypercalcemia, hypertension and hepatic
dysfunction in the absence of hepatic metastases
- Diagnostic Studies:
o Patients presenting with hematuria should undergo ultrasonography to rule out a stone
o CT scanning with and without contrast is the primary technique for diagnosing RCC. Other
confirming studies include MRI with contrast and angiography
- Treatment depends on the Fuhrman grade (1-4) and stage (TNM) of the tumor a thorough evaluation is
needed
o Radical nephrectomy is the primary treatment for localized disease (stage T1-T3a lesions).
Neoadjuvant or adjuvant radiation therapy has not been shown to prolong survival for early stage
lesions
o Radiation therapy is an important method of palliation in patients with disseminated disease to the
brain, bone, and lungs. Radical nephrectomy has little role in advanced disease
o Hormonal therapy and chemotherapy have shown little effect
o Medications, such as interferon- and interleukin, have been successful in reducing the growth of
some RCCs, including some with metastasis.
Renal Vascular Disease
- Renal Artery Stenosis (RAS)
- Produced by atherosclerosis occlusive disease (80-90%) or fibromuscular dysplasia (10-15%, primarily in
women)
- Approximately 5% of patients with hypertension suffer from RAS
- Most commonly in those over 45 years of age with a history of other atherosclerotic disease
o Other risk factors CKD, DM, tobacco use, HTN
- May have refractory HTN, new-onset HTN, pulmonary edema with poorly controlled BP, and acute kidney
injury upon starting an ACE inhibitor
- Physical exam may reveal an audible abdominal bruit on the affected side
- Lab values may show elevated BUN and creatinine in the setting of significant renal ischemia
- Abdominal ultrasound may reveal asymmetric kidney size when one renal artery is affected out of proportion
to the other
- Best screening methods = Doppler ultrasonography, CT angiography, and MRA
- Renal angiography is the gold standard for diagnosis
o Lesions most commonly in the proximal third or ostial region of the renal artery
o Fibromuscular dysplasia has a characteristic beads-on-a-string appearance on angiography
- Treatment is controversial
o Medical management vs. angioplasty with or without stenting vs. surgical bypass
o Treatment of fibromuscular dysplasia with percutaneous transluminal angiography is often curative

Hypovolemia / Hypervolemia
- When altered, fluid and electrolytes should be corrected in the following order:
o Volume pH potassium, calcium, and magnesium sodium and chloride
- Because the osmolarity of normal saline matches that of serum, it is an excellent fluid for volume
replacement
- Hypotonic fluids such as 5% dextrose in water (D5W) should never be used to replace volume
- Lactated Ringer solution is commonly used for surgical or trauma patients, however only normal saline can
be given in the same line with blood components
- D5 NS, with or without potassium, is given as maintenance fluid
- The more concentrated dextrose solutions, D10W or D20W, are used for patients with compromised ability
to mobilize glucose stores, such as patients with hepatic failure, or as part of total parenteral nutrition
solutions
- Tachycardia and hypotension are late signs of dehydration
- Plasma and urine osmolarity are perhaps the most reliable measures of dehydration. Other lab values are
not very helpful
- Volume overload is a clinical diagnosis
- Blood pressure does not necessarily correlate with volume status alone patients with volume overload can
have hypotension or hypertension
- Hyper- and hyponatremia reflect disturbances in water hemostasis. Serum sodium accurately reflects
changes in serum osmolality and, therefore, changes in free water balance
o SEE HYPERNATREMIA/HYPONATREMIA
- Volume Depletion:
o Occurs when body fluids are lost from the extracellular compartment at a rate that exceeds intake
o Fluids can be lost from the GI tract, kidneys, or skin
Also from third spacing in the abdomen (i.e., ascites) or from injured tissues (i.e., burns)
o Volume-depleted patients become thirsty, and urinary output decreases
o Mild volume depletion can cause increased heart rate, fatigue, and muscle cramps
o Moderate fluid loss causes dizziness and hypotension when standing
o Severe hypovolemia results in general hypotension, signs of ischemia and shock, and lethargy and
confusion
o Decreased skin turgor and dry mucous membranes are unreliable signs of hypovolemia in older
adults
o Diagnostic Studies:
Hematocrit and serum albumin may be increased
Urinary sodium decreases
Urea increases (secondary to urine stasis in the nephron), but there is little change in
serum creatinine
o Treatment:
Mild hypovolemia can be treated by increasing salt and water intake
Severe volume depletion can be treated with oral fluids containing electrolytes, glucose,
and amino acids
IV fluids should be used when patients cannot tolerate oral solutions. Isotonic fluids
should be given until tissue perfusion has improved

Internal Medicine Rheumatology

Fibromyalgia
- A central pain disorder whose cause and pathogenesis are poorly understood
- Can occur with RA, SLE, Sjgrens syndrome
- Nonarticular musculoskeletal aches, pains, fatigue, sleep disturbance, multiple tender trigger points on
examination
- Fibromyalgia is characterized by pain above and below the waist that is bilateral and axial for a duration of
at least 3 months
- Anxiety, depression, headaches, IBS, dysmenorrhea, paresthesias are associated
- Recognized by the typical pattern of pain and other symptoms also a diagnosis of exclusion. Rule out
hypothyroidism, hepatitis C, vitamin D deficiency
- No routine laboratory markers
- Abnormality of the T-cell subsets
- SSRIs, SNRIs, TCAs can be helpful
- NSAIDs are not effective
- Pregabalin (Lyrica) is the only FDA-approved drug, reporting reduced pain and improved sleep
o Side effects fatigue, trouble concentrating, sleepiness, edema
- Aerobic exercise improves conditioning and functioning
- Patient education, stress reduction, sleep assistance, treatment of psychological problems
Gout / Pseudogout
- A systemic disease of altered purine metabolism and subsequent sodium urate crystal precipitation in the
synovial fluid
- M > F (9:1). After menopause, rate is more equivalent
- Most common presenting feature is initial attack of the metatarsal phalangeal joint of the great toe
(podagra). This is presenting symptom 70% of the time
o Other joints are also affected foot joints, ankles, knees
- Pain, swelling, redness, tenderness develop suddenly at and surrounding the joint
- In chronic gout, tophi (chalky deposits of urate crystals) can form adjacent to joint considered diagnostic
- Joint fluid analysis is diagnostic if rod-shaped, negatively birefringent urate crystals are see
- Serum uric acid levels of greater than 8 mg/dL is suspicious, but not diagnostic
- Best to take uric acid levels NOT during acute attack
- Diagnosis can also be made by clinical examination
- Characteristic erosions (small, punched out lesions and interosseous tophi) present on plain radiographs
also make the diagnosis
- Elevation and rest can alleviate symptoms
- Dietary modifications decreased ingestion of purines and alcohol can reduce elevated urate levels
- Pharmacotherapy:
o NSAIDs are the initial drug of choice indomethacin 25-50 mg tid until symptoms resolve
o Colchicine is also very effective. Use is limited due to the pervasive GI side effects
o Corticosteroid injections
o Oral prednisone can be used if other medications are not tolerate and septic arthritis has been
ruled out
o BETWEEN acute attacks colchicine, probenecid, allopurinol, febuxostat, sulfapyrazine
Do not start allopurinol during an acute attack, but do not need to discontinue in a patient
already on maintenance

Pseudogout
- Calcium pyrophosphate dehydrate (CPPD) disease
- Affects peripheral joints usually lower extremity
- Results from intra-articular deposition of calcium pyrophosphate
- Acute presentations can mimic gout it tends to be recurrent and abrupt
- Most commonly involved joints are knee, wrist, elbow
- Rhomboid-shaped calcium pyrophosphate crystals that are negatively birefringent are found in joint
aspiration
- Radiographs show fine, linear calcifications in cartilage (chondrocalcinosis)
- Treatment NSAIDs, colchicine, intra-articular steroid injections
Rheumatoid Arthritis
- A chronic disease with synovitis affecting multiple joints as well as other systemic extra-articular
manifestations
- Females > males (3:1)
- Onset typically between 40-60 years old
o The juvenile form occurs in patients younger than 16 years old
- A cascade of events leads to joint destruction. Hyperplastic synovial tissue (pannus) may erode cartilage,
subchondral bone, articular capsule, tendons, and ligaments
- MCP most commonly involved, then PIP, then MTP, shoulder, ankle, cervical spine, hip, elbow, TMJ
o The DIP joints are usually spared
- Affected joints have swelling, tenderness, warmth, decreased ROM
- Atrophy of interosseous muscles of the hands is an early finding
- Deformities:
o Ulnar deviation
With volar subluxation
o Boutonniere deformity (flexed PIP, hyperextended DIP)
o Swan-neck deformity (hyperextended PIP, flexed DIP)
- Diagnostic Criteria need a score of 6/10 to make the diagnosis:
o Joint involvement (0-5 points)
1 medium or large joint = 0 points
2-10 medium or large joints = 1 point
1-3 small joints = 2 points
4-10 small joints = 3 points
Greater than 10 joints (at least 1 small) = 5 points
o Serology (0-3 points)
RF and ACPA negative = 0 points
RF or ACPA low positive = 2 points
RF or ACPA high positive = 3 points
o Duration of symptoms (0-1 point)
< 6 weeks = 0 points
> 6 weeks = 1 point
o Acute phase reactants (0-1 point)
CRP and ESR not elevated = 0 points
Increase CRP or ESR = 1 point
- Extraarticular manifestations changes in the skin, lungs, kidneys, eyes, liver, blood system, and heart
o Osteoporosis is frequently diagnosed

Diagnostic Studies:
o Aspiration and joint fluid analysis are useful laboratory tests to quantify inflammation and exclude
the presence of gout or septic arthritis
Yellow to opalescent in color
3,000-50,000 WBC/L
25-50% PMNs
Negative culture
o ESR and CRP are elevated
o Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, although
nonspecific, are positive in 80% and 95% of patients, respectively
Levels may be low in early disease
o Soft-tissue swelling and juxta-articular demineralization are seen on radiography
- Treatment:
o Consult rheumatologist
o PT/OT
o Early and aggressive pharmacologic management to reduce pain, preserve function, and present
deformity
NSAIDs in conjunction with DMARDs
DMARDs as soon as diagnosis is made
Methotrexate is the most common initial choice
Other synthetic DMARDs = corticosteroids, sulfasalazine, antimalarials,
leflunomide
Newer biologic DMARDs = etanercept, abatacept, rituximab, infliximab,
adalimumab
Combination therapy may be required, but take into account safety and cost
o Methotrexate + biologic DMARD is common
o Reconstructive surgery for severe cases
Juvenile Idiopathic Arthritis (JIA) / Juvenile Rheumatoid Arthritis (JRA)
- Characterized by chronic synovitis and a number of extra-articular manifestations (fever, rash, weight loss,
other organ involvement)
- Females > males (2:1)
o Females also have earlier age of onset (1-3 years old, vs. males around 8-12 years old)
- Forms of arthritis:
o Systemic (15%)
o Pauciarticular (50%) = 4 joints
o Polyarticular (35) = 5 joints
- The American College of Rheumatology defines JIA by age (younger than 16 years old) and duration of
disease (> 6 weeks) and divides JIA into three subtypes:
o Systemic
Spiking fevers (39-40C; 102.2-104F), myalgias, poly-arthralgias, and a typical
salmon-pink maculopapular rash appearing in the evening and with fever
The rash may be elicited by scratching the skin in susceptible areas (Koebner
phenomenon)
Minimal articular findings, but hepatosplenomegaly, LAD, leukocytosis, pericarditis, or
myocarditis may occur
o Pauciarticular
Characterized by the involvement of four or fewer medium to large joints

Patients are also at risk for development of asymptomatic uveitis that may lead to
blindness if they have a positive ANA test

Polyarticular
This type resembles adult RA with its symmetric involvement and involves five or more of
the small and large joints
Systemic symptoms include low-grade fever, fatigue, rheumatoid nodules, and anemia
- Diagnostic Studies:
o No specific diagnostic tests for JIA, but 10-15% of patients have a positive RF
Anti-CCP antibody may be positive as well
ESR and CRP are increased or normal with the systemic type
The ANA test may be increased in the pauciarticular type and indicates a tendency for
uveitis
o Imaging studies are similar to those for adults with soft-tissue swelling and periarticular
osteoporosis findings. Joint destruction is less frequent
- Treatment:
o NSAIDs, PT/OT are the most beneficial
o Methotrexate or leflunomide may be used as second-line agents, early on, if no improvement with
NSAIDs
o Monitor children with JIA for any growth abnormalities, nutritional deficiencies, and school/social
impairment
o 75-80% remit without serious disability
Patients who are RF positive are at greatest risk of progressing to disabling arthritis into
adulthood
Polyarteritis Nodosa
- Small and medium artery inflammation involving the skin, kidney, peripheral nerves, muscle, and gut occurs
- M:F = 3:1
- Onset generally between 40-60 years old, but can occur in all age groups
- Cause is unknown
o Associated with hepatitis B is seen in up to 30% of patients
- Clinical features fever, anorexia, weight loss, abdominal pain, peripheral neuropathy, arthralgias, arthritis
o Skin lesions, including palpable purpura and livedo reticularis, occur in some patients
o HTN, edema, oliguria, and uremia may be present in patients with renal involvement
- Diagnostic Studies:
o Diagnosis is usually established by vessel biopsy or angiography
o Elevated ESP and CRP and proteinuria may be present as well as a positive HBsAg
o Present of antineutrophil cytoplasmic antibody (ANCA) is suggestive but not diagnostic of
polyarteritis nodosa
- Treatment:
o Initial management is with high doses of corticosteroids
o Cytotoxic drugs and immunotherapy may be used. Concomitant tx of hep B may be required
o HTN should be treated if present
Polymyositis
- An inflammatory disease of striated muscle affecting the proximal limbs, neck, and pharynx. The skin can
also be affected (dermatomyositis)
- Other organ systems affected = joints, lungs, heart, GI tract
- Cause is unknown, but there is a strong association with an occult malignancy
- Women > men (3:1)
- Clinical features insidious, painless, proximal muscle weakness; dysphagia; skin rash (malar or
heliotrope); poly-arthralgias; muscle atrophy
- Diagnostic Studies:
o Muscle enzymes creatine phosphokinase (CPK) and aldolase will be elevated
o

o Muscle biopsy should be performed and will show myopathic inflammatory changes
- Treatment high-dose steroids, methotrexate, or azathioprine until symptoms resolve
Polymyalgia Rheumatica
- Characterized by pain and stiffness in the neck, shoulder, and pelvic girdles and is accompanied by
constitutional symptoms (e.g., fever, fatigue, weight loss, depression)
- Affects women twice as often as men, usually in patients older than 50 years
- Cause unknown
o Associated with giant cell (temporal) arteritis in up to 30% of cases
- Stiffness usually is the predominant feature, being most severe after rest and in the morning
- Musculoskeletal symptoms usually are bilateral, proximal, and symmetrical
- Giant cell (temporal) arteritis must be ruled out. It characteristically presents with scalp tenderness, jaw
claudication, headache, and temporal artery tenderness. It may lead to vision loss
- Diagnostic Studies:
o ESR markedly elevated (>50 mm/hr)
o Temporal arteritis is confirmed by biopsy (minimum length 2.5 cm)
- Treatment:
o Patients respond quickly to low-dose corticosteroid therapy may be required for up to 2 years and
slowly tapered
Higher doses are required if giant cell arteritis is present treatment should NOT be
delayed while awaiting biopsy
Reactive Arthritis (Reiter Syndrome)
- A seronegative arthritis that presents with a tetrad of urethritis, conjunctivitis, oligoarthritis, and mucosal
ulcers
- Often seen as a sequelae to STIs (chlamydial urethritis or Ureaplasma) or gastroenteritis (Shigella,
Salmonella, Yersinia, Campylobacter)
- Patients may have asymmetric arthritis that involves large joints usually below the waist (i.e., knee and
ankle), mucocutaneous lesions (balanitis, stomatitis), urethritis, and conjunctivitis are common
- Gender ratio is 1:1 after enteric infections and 9:1 after STIs (male predominance)
- The leading cause of nontraumatic monoarthritis
- 50-80% of patients are HLA-B27 positive
- Synovial fluid is usually culture negative
- Evidence of permanent and progressive joint disease may be present on radiography
- NSAIDs and PT are the mainstays of treatment
- Antibiotics given at the time of infection will reduce the chance of developing the disorder but do not
alleviate the symptoms of the reactive arthritis
Systemic Lupus Erythematosus
- An autoimmune disorder characterized by inflammation and positive ANAs and involvement of multiple
organs
- Commonly affects women of childbearing age usually African Americans
- Diagnosis based on certain criteria ~ requires at least 4 be met, including a significantly high-titer ANA
o Malar rash
o Discoid rash
o Photosensitivity
o Oral ulcers
o Arthritis
o Serositis (heart, lungs, or peritoneal)
o Renal disease (proteinuria, cellular casts)
o ANA
o Hematologic disorders (hemolytic anemia, leukopenia, leukocytosis, thrombocytopenia)

o
o

Immunologic disorders (LE cell, anti-DNA, anti-Sm, false-positive serologic test for syphilis)
Neurologic disorders (seizures or psychosis in absence of any other cause)

Drug-induced lupus must be rule out. There are many drugs that cause a lupus-like syndrome
o Procainamide, hydralazine, isoniazid, methyldopa, quinidine, chlorpromazine
o If the offending agent is stopped, the symptoms typically resolve
o These patients have positive antihistone antibodies
- Routine lab studies CBC, BUN, creatinine, urinalysis, ESR, serum complement (C3 or C4)
o Antibodies to Smith antigen, double-stranded DNA, or depressed levels of serum complement may
be used as markers for disease progression
o ANA is present (99%), but low titers have low predictive value
- Treatment:
o Regular exercise and sun protection are important for all patients
o NSAIDs for musculoskeletal complaints
o Antimalarials (quinacrine, hydroxychloroquine) can be used for musculoskeletal complaints or
cutaneous manifestations
o Corticosteroids (topical or intralesional) for cutaneous manifestations
Low or high dose oral corticosteroids used for disease flares and tapered as symptoms
resolve
o Methotrexate is used at low doses for arthritis, rashes, serositis, constitutional symptoms
Systemic Sclerosis (Scleroderma)
- Scleroderma is of unknown cause and is characterized by deposition of collagen in the skin and, less
commonly, in the kidney, heart, lungs, and stomach
- F>M (4:1)
- Peak age of onset is between 30-50 years old
- Two types of scleroderma:
o Diffuse affects the skin as well as the heart, lungs, GI tact, and kidneys
o Limited mostly affects the skin of the face, neck, and distal elbows and knees and late in the
disease causes isolated pulmonary hypertension
- Skin involvement occurs in 95% of patients. Changes most often begin with swelling in the fingers and
hands and may spread to involve the trunk and the face
- Raynaud phenomenon, vasospasm of the digital arteries, is seen in more than 75% of patients
- Calcinosis cutis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia (CREST)
syndrome is associated with limited scleroderma
- Patients usually present with skin changes, poly-arthralgias, and esophageal dysfunction
- Diagnostic Studies:
o ANA is present in 90% of patients with diffuse scleroderma
o Anticentromere antibody is associated with CREST syndrome and anti-SCL-70 antibody is
associated with diffuse disease and portends a poor prognosis
o Patients should be monitored for development of HTN, heralding kidney involvement
- Treatment:
o There is no cure for scleroderma
o Treatment is aimed at organ-specific disease processes (i.e., PPIs for refluex, ACE inhibitors fo
renal disease, avoidance of triggers and treatment with CCBs for Raynaud, and
immunosuppressive drugs for pulmonary hypertension)
Sjgren Syndrome
- An autoimmune disorder that destroys the salivary and lacrimal glands (exocrine glands)
- It may also be a secondary complication to a preexisting connective tissue disorder such as RA, SLE,
polymyositis, or scleroderma
- It is most often diagnosed in middle-aged females

Mucous membranes are most affected. Dry mouth (xerostomia) and dry eyes (xerophthalmia or
keratoconjunctivitis sicca) are characteristic features of primary Sjgren syndrome
The parotid glands also may be enlarged
Diagnostic Studies:
o RF is present in 70% of cases, ANA in 60%, anti-Ro antibodies in60%, and anti-La antibodies in
40% of cases
o A Schirmer test evaluates tear secretions by the lacrimal glands. Wetting of less than 5 mm of filter
paper placed in the lower eyelid for 5 minutes is positive for decreased secretions
o Biopsy of the lower lip mucosa confirms lymphocytic infiltrate and gland fibrosis
Treatment:
o Management is mainly symptomatic, with the goal of keeping mucosal surfaces moist. This can be
achieved by using artificial tears and saliva, increased oral fluid intake, and ocular and vaginal
lubricants
o Pilocarpine may increase saliva flow
o Cyclosporine may improve ocular symptoms

Internal Medicine Neurology

Seizure Disorder
- Seizures are characterized as either generalized or partial depending on whether the disturbance affects the
entire brain or only a portion
o They can be further categorized as idiopathic or secondary seizures
Idiopathic seizures usually begin between 5-20 years old and have no specific cause
Secondary seizures may result from congenital abnormalities or perinatal injury, metabolic
disorders, trauma, tumors, vascular disease, infectious disease, or degenerative disease
such as Alzheimer disease. Seizures in the elderly are frequently due to strokes and/or
tumors
- Seizures are transient disturbances of cerebral function caused by abnormal paroxysmal neuronal
discharges in the brain
- Status epilepticus, either convulsive or nonconvulsive, is diagnosed when seizures fail to cease
spontaneously or recur so frequently that full consciousness is not restored between successive episodes.
The length of time seizure activity must persist to diagnose status epilepticus is general more than 5
minutes.
- GENERALIZED SEIZURES
o Characterized by a sudden loss of consciousness and are either convulsive (grand mal or tonicclonic) or nonconvulsive (absence)
Generalized convulsive seizures are associated with a postictal obtundation and
confusion lasting for minutes to hours
Generalized nonconvulsive seizures (absence) are associated with only minor motor
activity, such as blinking or facial twitching
Absence (petit mal):
o Begin in childhood, are often familial, and typically subside before
adulthood.
o Brief, often unnoticeable, episodes of impaired consciousness lasting
only seconds and occurring up to hundreds of times per day. Present as
staring spells.
o Differential diagnosis = syncope, cardiac dysrhythmias, brain stem ischemia, pseudoseizure
- PARTIAL SEIZURES
o Simple partial seizures are no accompanied by an impairment of consciousness. There may be
isolated tonic or clonic activity of a limb or transient altered sensory perception, which may spread
to include the entire side of the body in a jacksonian march
o Complex partial (temporal lobe) seizures often are characterized by an aura (transient
abnormalities in sensation, perception, emotion, or memory), followed by impaired consciousness
lasting for seconds to minutes. Nausea or vomiting, focal sensory perceptions, and focal tonic or
clonic activity may accompany a complex seizure
o Differential diagnosis = TIA, rage attack, panic attack
- Postictal Todds paralysis may be seen weakness or paralysis that is often unilateral and resolves
over 24 hours
- Diagnostic Studies:
o In generalized nonconvulsive seizures (absence), EEG typically shows generalized bilaterally
synchronous and symmetric 3-Hz spike-and-wave activity
o EEG and imaging studies in generalized convulsive seizures are often normal
o In simple partial seizures, EEG may show a focal rhythmic discharge at the onset of seizure, but,
occasionally, no ictal activity will be seen

Lab studies, such as CBC, blood glucose, electrolytes, calcium, magnesium, liver and renal
functions, and serologic test for syphilis, are indicated to evaluate potential metabolic or toxic
causes
o Distinguish pseudoseizures (psychogenic) from true seizures (electrical)
Serum prolactin levels are usually increased after true tonic-clonic seizures but are
unaffected by pseudoseizures (sometimes partial seizures)
Prolactin level remains elevated only in the first half-hour following a seizure.
o Brain MRI should be completed to rule out a structural abnormality in a patient presenting with the
first seizure
o Lumbar puncture may be warranted (if infection is suspected) after neuroimaging excludes a tumor
or other space-occupying lesion
- Treatment:
o Correction of hyponatremia, hypoglycemia, or drug intoxication may be all that is necessary
o Anticonvulsant therapy typically is not indicated in the setting of a single unprovoked seizure in a
patient with a normal neurologic examination and normal brain imaging and EEG.
The risk of seizure recurrence is < 50% even if no treatment is initiated in this setting
o The goal of medical therapy is to prevent seizures by using a single agent in progressive doses
until seizures are controlled or toxicity occurs
Generalized convulsive, simple partial, and complex partial seizures typically are treated
with carbamazepine, phenytoin, and valproic acid. Phenobarbital and primidone are less
effective. Newer anticonvulsants, such as gabapentin, topiramate, lamotrigine,
oxcarbazepine, levetiracetam, and zonisamide, also are effective
Felbamate typically is reserved for patients who are unresponsive to other medications or
combinations because of serious potential side effects, including aplastic anemia and
hepatic failure
Valproic acid or ethosuximide is used for generalized nonconvulsive (absence) seizures
Syncope
- A transient LOC accompanied by loss of postural tone, followed by complete resolution without intervention
- Typically a benign vasovagal event, but may represent a life-threatening dysrhythmia/condition, especially in
elderly
- 50% of causes presenting to the ED have no definite etiology
- Most commonly reflex mediated a sympathetic response to stress is suddenly withdrawn, leading to
pronounced vagal tone with hypotension or bradycardia
- Hallmark of vasovagal syncope = occurrence in a standing patient with a prodrome of dizziness, nausea,
pallor, diaphoresis, and diminished vision
o Search for a stimuli
- Carotid sinus hypersensitivity is more common in the elderly, and is suggested by a history of presyncopal
shaving, head-turning, or wearing of a constricting collar
- In situational syncope, the autonomic reflexive response may result from a specific physical stimulus such
as micturition, defecation, or extreme coughing
- Orthostatic syncope occurs when a sudden change in posture after prolonged recumbence is associated
with inadequate compensatory increases in heart rate and peripheral vascular resistance
o Any disorder causing volume depletion may cause orthostatic syncope
- Cardiac syncope is due to a dysrhythmia or structural cardiopulmonary lesions
o Tachydysrhythmias (e.g., Vtach, torsades des pointes, SVT) are common, but the most common is
incidental bradycardia
o Syncope from dysrhythmias is typically sudden and without prodrome
o Also structural abnormalities
In the elderly, may be due to aortic stenosis
o

 In younger patients, usually HCM

- Cerebrovascular disorders are rare causes of syncope
- Work-Up:
o History, physical, EKG
o Sudden events that occur without warning suggest dysrhythmias
Exertion may imply a structural cardiopulmonary lesion
o May need lab testing
Hematocrit may explain orthostatic syncope (bleeding)
Pregnancy test in women
Electrolytes
o A significant (> 20 mmHg) blood differential between upper extremities suggests subclavian steal
syndrome
o Carotid sinus massage (only if patients have no bruits) if carotid sinus hypersensitivity is suspected
Positive test requires reproduction of symptoms as well as bradycardic or hypotensive
response
o Orthostatic hypotension = autonomic instability from drugs or disease
A SBP drop of at least 20 mmHg upon standing
o Differentiate from seizure
Hallmarks of seizure = tongue biting, incontinence
Seizure also has postictal confusion and slow return to normal consciousness
- ED Care and Disposition:
o Syncope, by definition, results in spontaneous recovery of consciousness. So, the main ED goal is
to identify patients at risk for further medical problems. Categorize into 1 of 3 classes after taking
history, physical, and EKG
Established Diagnosis direct attention at underlying cause
Unclear Diagnosis, High-Risk those who have a concern for sudden cardiac death or
ventricular arrhythmia
High-risk = abnormal EKG, complaint of SOB, SBP < 90 mmHg on arrival,
hematocrit < 30%, age > 45 years, history of ventricular dysrhythmia or CHF
Admit!
Unclear Diagnosis, Low-Risk unlikely to have a cardiac etiology for syncope
Have none of the high-risk criteria listed above
Usually vasovagal and no further work-up is required if the incident is isolated
If cases are recurrent or worrisome, can try a Holter or loop-event monitor as an
outpatient
Migraine Headaches
- More typically present unilaterally, with throbbing or pulsating discomfort. Patients often identify triggers
chocolate, red wine, hard cheese, MSG, hormonal changes, exertion, fatigue, stress
- Often relate a family history. Women more than men. Often following menstrual cycle patterns
- Pathophysiology was classically attributed to intracranial vasospasm followed by extracranial vasodilation.
More current theories related to dysfunction of the trigeminovascular system, resulting in perivascular
release of substance P
- Often associated with other diseases, such as seizure disorders, essential tremor, Tourettes syndrome,
depression, anxiety, stroke
- Migraine with aura (classic migraine) presents with an aura commonly involving visual changes, field cuts,
or flashing lights affecting ones visual hemifield
o The throbbing pain often is contralateral to the aura and associated with the other symptoms that
are seen in migraine without aura

o Migraine with aura can also be associated with transient neurologic deficits and hemisensory loss
Migraine without aura (common migraine) frequently is accompanied by N/V, photophobia, phonophobia,
and anorexia
- Patients also exhibit irritability and fatigue. Often retreat to quiet, dark rooms. Prefer to lie quietly.
- Route laboratory tests are done only to rule out other disorders
- Imaging studies or LP only done in select clinical settings and only to rule out causes of acute secondary
headache
- Treatment:
o Mild to moderate migraine:
Abortive therapy aspirin, acetaminophen, NSAIDs, isometheptene. A variety of
products may be combined with caffeine, which has an adjunctive effect
Subsequent measures serotonin-receptor agonists (triptans sumatriptan,
zolmitriptan, rizatriptan, naratriptan, almotriptan, frovatriptan, eletriptan). Various forms of
ergotamines are also useful
o Frequent migraines may need prophylactic measures
Beta-blockers, TCAs, CCBs, NSAIDs, valproic acid, topiramate
Biofeedback therapy often is employed in the hope of reducing headaches by dealing
better with stress
Botox injections for severe, intractable migraine
o Avoid triggers
o Psychotherapy and stress reduction
Tension Headaches
- Once thought to be caused by muscle contraction. Current theory relates tension headaches to abnormal
neuronal sensitivity
- May be associated history of significant stress or minor trauma to the head or neck
- The most frequent type of headache
- Typified by a band-like pain around the head or generalized head pain. Discomfort is usually reported as
steady or aching (nonpulsatile) and is not associated with focal neurologic symptoms. Typically bilateral and
without photophobia, phonophobia, N/V
- Pain may be episodic or chronic. Stress, sleep deprivation, hunger, and eyestrain are typical precipitants
- May be a tenderness of the posterior cervical and occipital muscles or the scalp, but the physical exam is
general normal
o Tenderness of the temporalis, masseter, posterior cervical, trapezius, sternocleidomastoid, and
occipital muscles
- Routine lab tests are only helpful to rule out concurrent illness or underlying rheumatologic cause
- Imaging studies, LP, or EEG only done if there is a high index of suspicion for a structural lesion
- Medical treatment is usually with simple analgesics (aspirin, acetaminophen, NSAIDs). If not effective, a
trial of antimigraine agents can be tried
- Ketorolac intramuscular can be used in the outpatient or hospital setting for more severe tension-type
headaches
- When appropriate, local heat and muscle relaxants may be employed for muscle-tension discomfort.
Physical therapy and stress reduction techniques also help
- In the setting of depression or significant stress or chronic recalcitrant tension headaches, antidepressants
or psychotherapy may be indicated
Cluster Headaches
- Migrainous neuralgia
- Severe, unilateral, periorbital headaches that last for 30-90 minutes and occur several times a day over a
periods of weeks to months
- The typical patient middle-aged man, often without a family history of headache or migraine
- May have a vascular etiology, and evidence suggests a disturbance of serotonergic mechanisms
-

The unilateral pain of cluster headache is often accompanied by ipsilateral lacrimation, conjunctival
injection, nasal congestion, and myosis and ptosis
Often pace incessantly around the room, because the pain is severe and not relieved by rest
Lab studies only to find other causes.
Imaging or LP to rule out other causes of acute cephalgia

Treatment:
o Abortive and symptomatic therapy includes administration of 100% oxygen and/or injection of
subcutaneous sumatriptan
o Other possible treatments are injectable forms of ergotamines, intranasal triptans, and analgesics
(e.g., intranasal butorphanol)
o Prophylactic therapy of choice for cluster headaches is verapamil. Other options include valproate,
cyproheptadine, lithium, oral corticosteroids
Transient Ischemic Attacks
- TIAs are defined as a transient ischemic neurological deficit that resolves within 24 hours
- 80% resolve within 60 minutes
- TIAs precede 30% of acute ischemic stroke (AIS)
- Left untreated, 30% of TIAs progress to AIS (20% within the first month and 50% within the first year)
Increased risk especially within 48 hours of the TIA.
- If the TIA is related to disturbance in carotid circulation, patients may demonstrate contralateral hand-arm
weakness with sensory loss, ipsilateral visual symptoms or aphasia, or amaurosis fugax. Carotid bruit may
be present, but with a high-grade stenosis (95%) it may be absent
- Those experiencing vertebrovascular TIA may demonstrate diplopia, ataxia, vertigo, dysarthria, cranial nerve
palsies, lower extremity weakness, dimness or blurring of vision, perioral numbness, or drop attacks
- Arteriography is the definitive study, by MRA also is used and is less invasive
- CT or MRI will exclude a possible small cerebral hemorrhage
- Treatment:
o Because TIA may indicated an impending stroke, prophylactic antiplatelet therapy is initiated when
the TIA is not cardiogenic. This may include aspirin, ticlopidine, clopidogrel, dipyridamole,
sulfinpyrazone
Antiplatelet therapy is contraindicated for hemorrhagic stroke
o Cardiogenic TIA requires anticoagulants, initially with IV heparin for those who are admitted to the
hospital and with warfarin for long-term therapy
o Carotid endarterectomy may be indicated in patients with anterior circulation TIAs and moderate to
high-grade carotid stenosis on the side appropriate to account for the symptoms
o Vital adjunctive therapies control of BP, serum cholesterol, blood glucose, and atrial fibrillation.
Discontinue cigarette smoking, avoid excessive alcohol use, lose weight if appropriate
Cerebral Vascular Accident
- Stroke is defined as any disease process that interrupts blood flow to the brain
o Ischemic strokes (87%) are more common than hemorrhagic strokes (10%)
Ischemic strokes account for 80% of all strokes. of ischemic strokes are thrombotic
and embolic. Emboli commonly arise from the heart, aortic arch, or large cerebral
arteries
Hemorrhagic strokes, which usually are secondary to hypertension, account for 20% of
strokes
- Specific findings in stroke patients depend on the regions of the brain that are compromised and the severity
of the insult
o Anterior Cerebral Artery contralateral leg weakness and sensory changes
o Middle Cerebral Artery hemiparesis (arm > leg), facial plegia, and sensory loss
Weakness in the lower half of the face (variable) and ipsilateral gaze preference may
occur
Aphasia (receptive and/or expressive) is often present if the dominant hemisphere
(usually left) is affected
Expressive aphasia = Brocas area
Receptive aphasia = Wernickes area

Contralateral hemineglect suggests nondominant hemisphere involvement

o Posterior Circulation unilateral headache, visual field defects, dizziness, vertigo, diplopia,
dysphagia, ataxia, cranial nerve deficits, or bilateral limb weakness
o Basilar Artery severe quadriplegia, coma, locked-in syndrome
o Cerebellar present similarly to other posterior stroke syndromes
An emergent noncontrast CT is essential to determine whether hemorrhage or a stroke mimic is present.
Most acute ischemic strokes will not be visualized in the early hours of a stroke
ED Care and Disposition:
o ABCs. Keep oxygen 92%
o IV access, NPO, cardiac monitor, rapid glucose
o Once stabilized, immediately send for noncontrast CT
o Blood Pressure:
If not a candidate for thrombolysis, no intervention unless >220/120
Labetalol
If a candidate for thrombolysis, target is 185/110
Labetalol or nitroglycerin paste
If target BP cannot be reached, then patient is no longer a tPA candidate
o Institute tPA for acute ischemic stroke if 3 hours of symptom onset
Indicated for those 18 years
Absolute Contraindications:
Current intracranial or subarachnoid hemorrhage
Previous head trauma or stroke within preceding 3 months
Prior intracranial hemorrhage, AVM, or aneurysm
Use of heparin within preceding 48 hours and a prolonged aPTT
Platelet count < 100,000/mm3
Pretreatment BP >185/110
Relative Contraindications
Major surgery within preceding 2 weeks
Previous GI or urinary tract hemorrhage within preceding 3 weeks
Seizure present at onset of stroke
Previous MI within preceding 3 months
Evidence of bleeding or acute major fracture
Blood glucose level <50 mg/dL
INR > 1.7
Some say can still give if < 4.5 hours since symptom onset, but there are additional
contraindications:
Age > 80 years
Severe stroke as assessed clinically (NIHSS score > 25)
Combination of previous stroke and diabetes mellitus
Blood glucose <50 mg/dL or >400 mg/dL
Oral anticoagulant treatment
No aspirin or heparin should be administered in the initial 24 hours after treatment.
Intracerebral bleeding should be suspected as the cause of any neurologic worsening
o No role for heparin or warfarin in the acute treatment of TIA or stroke in the ED, even in the
presence of atrial fibrillation
o If an ischemic stroke presents outside tPA therapeutic timeline, supportive care in the ED

Aspiration prevention, normalization of glucose level, falls precaution, treatment for

comorbidities)

Intracranial Tumors / Spinal Tumors (Primary CNS Neoplasms)

- Approximately half of all primary intracranial neoplasms are gliomas. The remainder are meningiomas,
pituitary adenomas, neurofibromas, and others
- Approximately 10% of spinal tumors are intramedullary, ependymoma is the most common
- Certain tumors, especially neurofibromas, hemangioblastomas, and retinoblastomas,, may have a familial
basis
- The most common sources of intracranial metastasis are carcinoma of the lung, breast, kidney, and GI tract
- Spinal tumors may lead to spinal cord dysfunction by direct compression, by ischemia secondary to arterial
or venous obstruction, or by invasive infiltration
- Intracranial tumors may produce a generalized disturbance of cerebral function and lead to evidence if
increased intracranial pressure (i.e., personality changes, intellectual decline, emotional lability, seizures,
headaches, nausea, vomiting, and malaise)
- Intracranial tumors may also produce focal deficits, depending on their location
o Frontal lobe lesions progressive intellectual decline, slowing of metal activity, personality
changes, contralateral grasp reflexes, and, possibly, expressive aphasia
o Temporal lobe lesions seizures, olfactory or gustatory hallucinations, licking or smacking of the
lips, depersonalization, emotional and behavioral changes, visual field deficits, and auditory
illusions
o Parietal lobe lesions contralateral disturbance of sensation, may cause sensory seizures, a
cortical sensory loss (impaired stereognosis) or inattention
o Occipital lob lesions crossed homonymous hemianopia or a partial field defect, visual agnosia
for objects and colors, or unformed visual hallucinations
o Brain stem and cerebellar lesions cranial nerve palsies, ataxia, incoordination, nystagmus, and
pyramidal and sensory deficits in the limbs on one or both sides
- Symptoms of spinal tumors usually develop insidiously, with pain characteristically aggravated by coughing
or straining and either localized to the back or felt diffusely in an extremity as motor defects, paresthesias, or
numbness, especially in the legs
o Physical exam of patients with spinal tumors may reveal localized spinal tenderness
- Diagnostic Studies:
o Head CT or MRI with contrast may detect the lesion, define location and size, evaluate extent to
which normal anatomy is distorted, and the degree of any associated cerebral edema or mass
effect
o Arteriography may demonstrate stretching or displacement of normal cerebral vessels as well as
the presence of tumor vascularity
o EEG may demonstrate a focal disturbance resulting from the neoplasm or a more diffuse change
reflecting altered mental status
o CT myelography or MRI of the spine may be needed to identify and localize the site of spinal cord
compression
o CSF removed at myelography is xanthochromic and contains greatly increased protein
concentration, normal cell content, and normal glucose concentration
- Treatment:
o Complete surgical removal of the tumor may be possible if it is extra-axial or not in a critical or
inaccessible region of the brain
o Surgical shunting of an obstructive hydrocephalus may dramatically reduce clinical deficits
o Radiation, chemotherapy, or both increase median survival rates in malignant neoplasms,
regardless or any preceding surgery
o Corticosteroids help to reduce cerebral edema and usually are started before surgery
o Anticonvulsants commonly are administered in standard doses
o Intramedullary cord lesions are treated by decompression and surgical excision and irradiation

Treatment of epidural spinal metastases consists of irradiation, irrespective of cell type

Essential Tremor
- Benign essential (familial) tremor
- The cause is unknown. It often is inherited in an autosomal dominant manner and may thus be called
familial tremor
- May begin at any age
- Enhanced by emotional stress
o Small quantities of alcohol common provide dramatic, temporary relief from the tremor
- Although tremor may interfere with manual skills, it causes only minimal disability
- Patients with benign essential tremor display a rhythmic, 6-8 Hz to-and-fro movement, usually of the upper
extremities by sometimes of the head (titubation)
- Speech may also be affected if the laryngeal muscles are involved
- No laboratory testing is needed or warranted
- Treatment:
o Low doses of a beta-blocker, usually propranolol, may be useful in controlling tremor but only when
tremor is associated with certain circumstances and intermittent dosing is adequate. Otherwise, it
will have to be used indefinitely
o Primidone may be useful in controlling tremor if propranolol fails
o The combination of primidone and propranolol is effective in some patients who are refractory to
treatment with one agent
Parkinson Disease
- Idiopathic Parkinsons occurs in all ethnic groups, with an approximately equal sex distribution, and most
often begins between 45-65 years of age. Life expectancy is 9 years from diagnosis
- Characterized by degeneration of cells in the substantia nigra, causing a deficiency of the neurotransmitter
dopamine and an imbalance of dopamine and acetylcholine
- Hypokinetic syndrome caused by the idiopathic depletion of dopamine in the substantia nigra and
nigrostriatal tract
- Other insults that can cause parkinsonian syndrome euroleptic (antipsychotic) and metoclopramide use,
postencephalitis, toxic exposures (manganese, MPTP, carbon disulfide), bihemispheric ischemia, and
trauma.
- Patients generally complain of problems related to their slowed movements, difficulty arising from a seated
position, difficulty ascending and descending stairs, trouble with getting dressed, and difficulty with
handwriting (micrographia)
- The essential features that establish a diagnosis of Parkinsons disease are resting tremor, bradykinesia,
rigidity, and postural instability
- The tremor is one of the earliest signs (presenting complaint in of patients). It typically has an
asymmetric onset, is most noticeable at rest, at 4-6 cycles/sec, and may be only very slight with voluntary
effort. It typically is described as pill-rolling. Improves or resolves with action (movement)
o Initially, the tremor is confined to one limb or the limbs on one side, but eventually it may be present
in all the limbs and at the lips and mouth. Usually does not affect the head
- Bradykinesia, or a generalized slowness of voluntary movements, is evident in the slow, shuffling gait,
reduced arm swing, slowed rapid alternating movements, infrequent blinking, and masklike faces
o A festinating gait without arm swing wide leg stance with short accelerating steps
- Rigidity is found as resistance to passive ROM testing, and cogwheel rigidity may be noted
- Postural instability is seen, including difficulty in standing from a seated position, unsteadiness on turning,
difficulty in stopping, and a tendency to fall
- Depression and cognitive impairment develop in more than 50% of patients over time
- Generally, no lab testing is needed or warranted. Blood tests and imaging to rule out other causes

Treatment:
o Designed to best restore the balance between dopamine and acetylcholine by blocking the effect of
acetylcholine with anticholinergic drugs, administering levodopa (the precursor of dopamine) or a
combination of both
o Amantadine, a mild anticholinergic, is often helpful for patients with mild symptoms but no disability
o Benztropine, trihexyphenidyl, and other anticholinergic drugs are particularly helpful in treating the
tremor (and rigidity) of Parkinsons disease and are less helpful for bradykinesia
o Levodopa is converted to dopamine in the body and improves all symptoms of Parkinson disease.
Carbidopa, when added to levodopa in various concentrations, allows lower doses of levodopa and
reduced side effects
o LEVODOPA AND CARBIDOPA = MAINSTAYS OF TREATMENT
A marked response is an important supportive feature in making the diagnosis of
Parkinsons
o Dopamine agonists, such as bromocriptine, act directly on dopamine receptors and often are
reserved for patients who become refractory to levodopa/carbidopa therapy
Also pramipexole
o Selegiline, a monoamine oxidase B inhibitor, inhibits breakdown of dopamine, and studies indicate
it may arrest progression of the disease
o Catecholamine-O-methyl-transferase (COMT) inhibitors reduce the metabolism of levodopa to 3-Omethyldopa and result in more stable plasma levels and more constant dopaminergic stimulation of
the brain. Two COMT agents, tolcapone and entacapone, are available as adjuncts to
levodopa/carbidopa therapy, and may permit a lowering of the total levodopa/carbidopa dose.
Increase the availability of levodopa to the brain and may decrease motor fluctuation
o Surgical pallidotomy or chronic DBS may be tried for refractory cases
o Physical therapy may help some patients, and quality of life may be improved with household
modifications or the availability of special utensils
o Psychological support for patient and family
Multiple Sclerosis
- Characterized by inflammation associated with multiple foci of demyelination in the CNS white matter
- Patients with MS usually follow either a relapsing-remitting pattern of episodes or a primary progressive
course
o A secondary progressive form also is seen, in which the relapsing-remitting pattern changes to one
of progressive degeneration
- MS is thought to be an immunologic disorder associated with CNS immunoglobulin production and alteration
of the T lymphocytes. A viral infection may act as a precipitant
- Based on numerous studies of twins, familial cases, and the association with specific human leukocyte
antigen (HLA) (HLA-DR2), a genetic relationship is considered to be likely
- MS typically begins between 18-45 years. Women > Men. Average age of onset is about 5 years younger
in women than in men
- Presenting signs and symptoms focal weakness, numbness or tingling, optic neuritis, blindness, blurry
vision, diplopia, focal neuralgias, balance problems, fatigue, or urinary symptoms
o The most common presenting symptoms are sensory complaints in the limbs (seen in about of
patients) followed by vision loss
- Symptoms last for days to weeks and affect different areas over different episodes or exacerbations
- Patients often develop cognitive and psychological deficits
- The diagnosis must be questioned if signs and symptoms are not related to multiple areas of the CNS over
time

Diagnostic Studies:
o The diagnosis cannot be based exclusively on laboratory findings
o MRI with gadolinium is very effective for visualizing white matter lesions in the CNS
o CSF can reveal a sterile inflammation with a mild lymphocytosis or slight protein elevation,
elevated immunoglobulin G index, oligoclonal bands, and increased myelin basic protein
o Visual-, auditory-, and somatosensory-evoked potentials are helpful for assessing nerve
transmission
- Treatment:
o Corticosteroids may hasten maximal recovery from acute exacerbations. High-dose IV
corticosteroids often are used in the setting of optic neuritis
o Plasma exchange can give benefit to patients with acute exacerbations who do not respond to
high-dose IV corticosteroids
o Interferon- decreases the frequency of relapses, especially moderate and severe attacks
o Daily subcutaneous injections of glatiramer acetate also decrease the frequency of relapses,
especially in mild disease
o Several studies suggest that immunosuppressive agents such as cyclophosphamide or
azathioprine may arrest the course of the secondary progressive form
o Otherwise, therapy is symptomatic:
Amantadine and pemoline can improve fatigue
Baclofen and diazepam improve spasticity
Several agents may relieve urologic dysfunction. Anticholinergics (oxybutynin) may be
effective
Meningitis
Bacterial Meningitis
- Typical symptoms are based on 3 processes inflammation, increased intracranial pressure, or tissue
necrosis
- Causes of bacterial meningitis:
o Primary causes S. pneumo, Neisseria meningitis, group B streptococci (especially in infants)
o Rate of H. flu type b (Hib) meningitis has dramatically increased since the widespread use of the
Hib vaccine
o < 1 month group B strep
o 1-2 months E. coli
o 2 months 6 years S. pneumo, N. meningitidis
o School age / adolescent S. pneumo, N. meningitidis
- Altered mental status, fever, headache, vomiting, and a stiff neck are the typical signs of meningitis,
although all may not be present.
o A petechial rash is characteristic of Neisseria meningitis
- Symptoms typically are acute, with patients presenting within hours or 1-2 days of infection
- Careful initial examination may reveal evidence of soft-tissue abscess, otitis, or other parameningeal
infection
- Meningeal signs may be absent or very subtle at the age extremes or be difficult to assess with impaired
consciousness
o Kernigs sign patient supine and thigh flexed to 90, attempts to straighten or extend the leg are
met with resistance
o Brudzinskis sing flexion of the neck causes involuntary flexion of knees and hips
Alternative sign is passive flexion of the leg on one side causing contralateral flexion of
the opposite leg

Laboratory Studies:
o Prompt lumbar puncture and CSF analysis are essential. CT is performed before lumbar puncture
to rule out evidence of a space-occupying lesion (especially if focal neurologic deficit, new-onset
seizures, papilledema, altered mental status)
The CSF may be slightly turbid to grossly purulent
CSF pressure is elevated in more than 90% of cases
CSF WBC count is elevated, ranging from 1,000 to as high as 10,000 L with increased
neutrophils
CSF protein concentration of 100-500 mg/dL are most common
CSF glucose levels often are decreased and may be less than 40 mg/dL
o Gram stain and culture of CSF is diagnostic in more than 80% of cases
- Treatment:
o Antibiotic treatment is begun immediately if the CSF is not clear and colorless. Do NOT delay if LP
cannot be accomplished or if imaging is necessary. The initial choice of antibiotic is based
empirically on the patients age and the most likely pathogen
Neonates receive ampicillin and cefotaxime
In some cases, ampicillin, gentamicin, and cefotaxime
Infants up to 3 months of age receive the same combination, with higher doses of
cefotaxime or ceftriaxone
Immunocompetent children older than 3 months and adults younger than 55 years receive
cefotaxime or ceftriaxone PLUS vancomycin
Adults older than 55 years and those of any age with alcoholism or debilitating illness
receive ampicillin PLUS cefotaxime or ceftriaxone PLUS vancomycin
If it is a hospital-acquired, posttraumatic or post-neurosurgery meningitis, or if the patient
is immune compromised, the combination give is ampicillin PLUS ceftazidime PLUS
vancomycin
Dexamethasone is recommended in adults with meningitis secondary to S. pneumo and
in children older than 1 month of age with meningitis secondary to Hib. If given promptly,
it will greatly reduce morbidity and mortality
o Repeat lumbar puncture and CSF analysis are crucial to assess response to treatment
The CSF should be sterile after 24 hours
A decrease in pleocytosis and the proportion of neutrophils should be seen within 3 days
Viral (Aseptic) Meningitis and Encephalitis
- Viral meningitis most frequently is associated with enteroviruses (coxsackievirus A or B, echoviruses),
herpes simplex virus 2, and arthropod-borne viruses
- Aseptic meningitis also may reflect an inflammatory process in the parameningeal area (i.e., sinusitis, otitis,
abscess)
- Viral encephalitis may not have and identifiable cause in many cases but frequently is associated with
childhood exanthems, arthropod-borne agents, and HSV-1
- Viral meningitis is preceded by nonspecific prodrome of fever, malaise, sore throat, myalgias. Usually
resolves in 2-4 days and may improve after LP
o This is absent in bacterial meningitis and the fever is very high. Also mental status changes, focal
neuro signs, ataxia, seizures, shock
- Viral meningitis and encephalitis often present as an acute confusional state, especially in children and
young adults
- Signs and symptoms generally are not as acute as in bacterial meningitis and may have persisted for
several days
- Examination may reveal a number of systemic manifestations, suggesting a particular causal agent (e.g.,
rash, pharyngitis, adenopathy, pleuritis, carditis, jaundice, organomegaly, diarrhea)

In encephalitis, because it involves the brain directly, there may be markedly altered consciousness,
seizures, personality changes, or other focal neurologic signs
- Laboratory Studies:
o As with bacterial meningitis, prompt LP and CSF analysis are crucial after assessing for evidence
of increased intracranial pressure
o The CSF opening pressure generally in normal
o Cell present in the CSF are more likely to be lymphocytes or monocytes, and the WBC count
generally is less than 1,000/L
o The CSF protein, glucose, and serum blood counts are more likely to be normal
- Treatment:
o With the exception of infection with HSV, the course of aseptic meningitis generally is benign and
self-limited, and no specific therapy is required. Suspected herpes virus infection is treated with
acyclovir
o Mild headaches can be treated with acetaminophen
o Seizures can be suppressed with anticonvulsants
o Breathing should be supported, if necessary
Granulomatous Meningitis
- Pathogens include Mycobacterium tuberculosis, fungi (Cryptococcus, Coccidioides sp., Histoplasma), and
spirochetes (Treponema pallidum, Borrelia burgdorferi)
- Incidence is highest in immunocompromised individuals
- Noninfectious causes include sarcoidosis and other granulomatous conditions
- Presentation is less acute. Patients typically have symptoms for weeks to months
- Subtle mental status changes are common
- Laboratory Studies:
o Culture is key but results may take weeks depending on etiology
o CSF shows high protein, low glucose, and a lymphocytosis
o CT or MRI will show marked enhancement of the meninges and, occasionally, hydrocephalus
o Serologic studies may help confirm suspected etiologies
- Treatment is dependent on cause
Encephalitis
- Viral encephalitis may not have an identifiable cause in many cases but frequently is associated with
childhood exanthems, arthropod-borne agents, and HSV type 1
- Often presents as an acute confusional state, especially in children and young adults (similarly to viral
meningitis)
o Signs and symptoms generally are not as acute as in bacterial meningitis and may have persisted
for several days
o Examination may reveal a number of systemic manifestations, suggesting a particular causal agent
(e.g., rash, pharyngitis, adenopathy, pleuritis, carditis, jaundice, organomegaly, diarrhea)
o Because encephalitis involves the brain directly, there may be markedly altered consciousness,
seizures, personality changes, or other focal neurologic signs
- In North America, viruses that cause encephalitis are the arboviruses (including the West Nile Virus), HSV,
HZV, EBV, CMV, and rabies
o Encephalitides may show special regional trophism
o HSV involve limbic structures of the temporal and frontal lobes, with prominent psychiatric features,
memory disturbance, and aphasia
o Some arboviruses predominantly affect the basal ganglia, causing chorea-athetosis and
Parkinsonism
o Involvement of the brainstem nuclei leads to hydrophobic choking characteristic of rabies
encephalitis

Symptoms of West Nile Virus include fever, headache, muscle weakness, and lymphadenopathy
Most infections are mild and last only a few days
More severe symptoms and signs consist of high fever, neck stiffness, AMS, tremors, and
seizures
- Consider in patients presenting with any or all of the following features:
o New psychiatric symptoms
o Cognitive deficits (aphasia, amnestic syndrome, acute confusional state)
o Seizures
o Movement disorders
- Headache, photophobia, fever, and meningeal irritation may be present
- Motor and sensory deficits are not typical
- Diagnostic Studies:
o Prompt lumbar puncture and CSF analysis are crucial after assessing for evidence of increased
intracranial pressure
o The CSF opening pressure generally is normal
o Cells present in the CSF are more likely to be lymphocytes or monocytes, and the WBC count
generally is < 1,000/L
o Findings on CT or MRI and LP aid in the ED diagnosis of encephalitis
Neuroimaging, particularly MRI, not only excludes other potential lesions, such as brain
abscess, but may display findings highly suggestive of HSV encephalitis if the medial
temporal and inferior frontal gray matter is involved
Findings of aseptic meningitis are typically found on CSF examination
o For West Nile Virus, the most widely used screening test is the IgM ELISA assay for detecting
acute antibody
- Treatment:
o With the exception of infection with HSV/HZV, the course of aseptic meningitis generally is benign
and self-limited, and no specific therapy is required. Suspected herpes virus infection is treated
with acyclovir
If suspected CMV encephalitis, treat with IV ganciclovir
o Mild headaches can be treated with acetaminophen
o Seizures can be suppressed with anticonvulsants
o Breathing should be supported, if necessary
o There is no specific treatment for West Nile Virus infection
Prevention = DEET insect repellant
Brain Abscess
- Brain abscesses typically result from direct spread of infection from sinus, ear, or soft tissue and results in a
single abscess
o Hematogenous spread to the brain is less common, but it is characterized by multiple abscesses
- Abscesses may be localized to the extradural (epidural) space, subdural spaces, or the brain parenchyma
- Brain abscesses present as space-occupying lesions vomiting, fever, altered mental status, focal
neurologic signs
o These signs and symptoms may have been preceded by previous evidence of dental infection,
otitis, sinusitis, or pharyngitis
- Diagnostic Studies:
o Lumbar puncture is contraindicated in patients with focal neurologic symptoms or focal neurologic
signs
Brain stem herniation may be precipitated by LP in this setting
If meningitis is suspected, empiric treatment can be initiated and imaging accomplished
If negative for a space-occupying lesion, LP can be performed
o

o
o

CT or MRI is helpful in establishing the diagnosis, especially with contrast

The bacteriology of brain abscess usually is polymicrobial and may include both gram-positive and
gram-negative organisms

Coma
-

Treatment:
o Acutely = respiratory and circulatory support, airway management, monitoring of vital functions
o Treat brain abscesses with appropriate antibiotics that penetrate brain tissues well
IV penicillin G or ceftriaxone PLUS metronidazole
Vancomycin is added if S. aureus is suspected
o Surgical excision or decompression may be required in cases of very large lesions or delayed
response to therapy
LOC without spontaneous recovery
Coma Unarousable unresponsiveness in which the subjects lie with eyes closed
Severity can be classified using the Glasgow Coma Scale.
Pupillary findings, other cranial nerve evaluation, hemiparesis, and response to stimulation can assign the
cause in a probably general category diffuse (toxic-metabolic coma) or focal (structural coma) CNS
dysfunction.
o Toxic-metabolic coma is characterized by lack of focal physical examination findings. The pupils
are typically small and reactive, but may be large in severe sedative poisoning as from
barbiturates.
o Structural Coma is divided into hemispheric (supratentorial) or posterior fossa (infratentorial) coma.
Coma from supratentorial lesions or masses may present with progressive hemiparesis or
asymmetric muscle tone and reflexes.
Coma without lateralizing signs may result from decreased cerebral perfusion from
increased ICP. Reflex changes in blood pressure and heart rate may be observed from
increased ICP.
Coma from posterior fossa or infratentorial lesions may cause abrupt coma, abnormal
extensor posturing, and loss of pupillary reflexes and extraocular movements. Brainstem
compression with loss of brainstem flexes may develop rapidly.
Pontine hemorrhage, another infratentorial cause of coma, may present with pinpoint
pupils.
Glasgow Coma Scale severe brain injury (coma) < 9 points
o Eye Opening
Spontaneous = 4 points
To verbal command = 3 points
To pain = 2 points
None = 1 point
o Verbal Response
Alert and oriented = 5 points
Confused, yet coherent speech = 4 points
Inappropriate words and jumbled phrases = 3 points
Incomprehensible sounds = 2 points
No sounds = 1 point
o Motor Response
Obeys commands = 6 points
Localizes to a noxious stimulus = 5 points
Withdraws from a noxious stimulus = 4 points
Abnormal flexion (decorticate posturing) = 3 points
Abnormal extensor response (decerebrate posturing) = 2 points
No response = 1 point
Neurologic Exam:

o Cornerstone of assessment
o Descriptive, systematic
o Reference point for serial assessment
- Breathing:
o Abnormalities of respiration can help localize but almost always in the context of other signs
Central-reflex Hyperpnea (midbrain-hypothalamus)
Apneustic, cluster, Ataxic (Lower pons)
Loss of automatic breathing (medulla)
- Cranial Nerve Exam:
o Systematic assessment of brainstem function via reflexes
o Cranial Nerve Exam
Pupillary light response (CN 2-3)
Oculocephalic/ calorics (CN 3,4,6,8)
Corneal reflex (CN 5,7)
Gag reflex (CN 9,10)
Afferent: Glossopharyngeal
Efferent: Vagus
Taken in context of other findings
- Goals in emergency:
o Stabilize the airway, ventilation and circulation
o Identify and treat reversible causes, such as hypoglycemia and opioid toxicity.
o Consider empiric naloxone. Administer thiamine before glucose in hypoglycemic patients with a
history of alcohol abuse or malnutrition.
o If elevated ICP is suspected, elevate the head to 30 degrees and keep at midline. Mannitol will help
reduce ICP.
- Catatonia:
o Symptom complex associated with severe psychiatric disease with:
Stupor, excitement, mutism, posturing
Can also be seen in organic brain disease: encephalitis, toxic and drug-induced psychosis
- Conversion Reactions:
o Fairly rare not!
o Oculocephalics may or may not be present
o The presence of nystagmus with cold water calorics indicates the patient is physiologically awake
o EEG used to confirm normal activity
Myasthenia Gravis
- Involves muscle weakness and fatigability, which improve with rest
- The onset usually is insidious, but the disorder sometimes is made evident by a coincidental infection that
exacerbates symptoms
- The disorder may occur at any age but is more common in young women and older men
- Antibodies directed against the acetylcholine receptor on the muscle surface cause an increased rate of
receptor destruction, leading to weakness
- Typical presenting problems include ptosis, diplopia, difficulty in chewing or swallowing, respiratory
difficulties, limb weakness, or a combination of any of these
o Approximately 60% present with ptosis and/or diplopia
- Symptoms may fluctuate in intensity during the day, and there is a tendency to have longer term
spontaneous relapses and remissions that may last for weeks
- Clinical examination confirms the weakness and fatigability of affected muscles, which improve after a short
rest

Sensation is normal, and there usually are no reflex changes

The diagnosis may be confirmed if marked clinical improvement is achieved by administering a short-acting
anticholinesterase (edrophonium)

Diagnostic Studies:
o Chest CT or MRI should be obtained to rule out a coexisting thymoma
o Electrophysiologic studies may show a decrementing muscle response; these studies are helpful in
making the diagnosis of myasthenia gravis. Repetitive nerve stimulation and single-fiber EMG are
the two studies frequently used
o Serum assay for elevated levels of circulating acetylcholine receptor antibodies is another way of
establishing the diagnosis; this assay is positive in 80-90% of patients
If negative, antibodies to muscle-specific tyrosine kinase (MuSK) should be checked.
MuSK antibodies are positive in nearly half of those with myasthenia gravis and negative
acetylcholine receptor antibodies
- Treatment:
o The mainstay of therapy is administration of a cholinesterase inhibitor, such as pyridostigmine,
which produces a transient improvement in strength
o Thymectomy often leads to improvement of symptoms
o Corticosteroids, immunosuppressive agents, IVIG, and plasmapheresis are effective in patients
with refractory disease
Giant Cell Arteritis
- A systemic inflammatory condition of medium and large vessels
- Primarily affects those older than 50 years of age and frequently coexists with polymyalgia rheumatica
- It most frequently involves the temporal artery and other extracranial branches of the carotid artery
- If not treated aggressively, it can cause blindness
- Large-vessel problems (e.g., thoracic aortic aneurysm) occur in 15% pf patients within 7 years
- Patients are typically elderly and complain of unilateral temporal headache
o Addition signs and symptoms scalp tenderness, jaw claudication, throat pain, diplopia, and
elevated markers
- Symptoms of polymyalgia rheumatica (pain and stiffness mainly of shoulder and pelvic girdle) are present in
50% of patients
- Nonclassic symptoms include respiratory tract problems, mononeuritis multiplex, fever of unknown origin, or
unexplained neck and head pain
- The temporal artery examination is usually normal but may be nodular, enlarged, tender, or pulseless
- Diagnostic Studies:
o ESR and CRP are markedly elevated
o Most patients have a normochromic normocytic anemia and thrombocytosis; some have elevated
alkaline phosphatase
o Temporal artery biopsy should be performed promptly for definitive diagnosis. Temporal artery
ultrasonography may show thickening (halo sign), stenosis, or occlusion
- Treatment:
o High-dose prednisone (1-2 months before tapering) and low-dose aspirin
o Treatment should be initiated immediately and not delayed for biopsy results
Bells Palsy
- Unilateral facial muscle weakness is noted without evidence of other neurologic disease and without
apparent cause. more than 60% occur on the right side
- Bell palsy is thought to primarily be caused by HSV activation, although other viruses (e.g., herpes zoster),
trauma, neoplasia, or toxins can also be causative. End result is damage to the myelin layer facial nerve
- More frequently seen in pregnant women and people with diabetes
- Often associated with trauma, infection, neoplasia, or toxins
- There can be a paralysis of all muscles supplied by cranial nerve VII (complete palsy) or variable weakness
in different muscles (incomplete palsy)

Facial muscle weakness typically begins abruptly but may progress over a matter of hours to 2 days.
Paralysis involves the forehead and lower face. Patients cannot close the eye, raise the brow, or smile on
the affected side
- Pain about the ipsilateral ear often precedes the facial weakness or is noted concurrently with the weakness
- Depending on the site of the nerve lesion, patients may demonstrate impairment of taste, lacrimation, or
hyperacusis
- Clinical evaluation reveals no abnormality beyond the motor function of cranial nerve VII
- The weakness peaks in about 21 days or less, and recovery (partial or complete) occurs within 6 months
- A clinical diagnosis. Specific diagnostic confirmation with nerve conduction studies or EMG is only done in
patients with atypical or prolonged Bells palsy
- Appropriate diagnostic procedures may be done to identify other conditions that may produce facial palsy,
including stroke, tumors, Lyme disease, AIDS, and sarcoidosis
- Approximately 60% of cases resolve spontaneously and require no treatment. Course is varied can span
from a few days to a few months
o Supportive care = lubricating eye drops to prevent corneal drying
- A poorer prognosis, with possible incomplete recovery, is associated with patients presenting with severe
pain and complete palsy, hyperacusis, or advanced age
- A course of oral prednisone, with or without acyclovir, if begun soon after the onset of symptoms, has been
shown to increase the percentage of patients who completely recover and should be considered in those at
risk of a poor prognosis
Guillain-Barr Syndrome
- An idiopathic polyneuropathy often following minor infections, immunizations, or surgical procedures, but in
many cases, no cause is identified
- Clinical and epidemiologic evidence seems to indicate a relationship with a preceding infection of the lungs
or GI tract
- Infection with Campylobacter jejuni is the most common precipitant. Other viral precipitants are EpsteinBarr virus, cytomegalovirus, and HIV. In about half of the cases, no preceding infection is confirmed
- Patients generally present with symmetrical extremity weakness that begins distally and ascends; proximal
muscles tend to be affected more than distal muscles.
o Deep tendon reflexes may be decreased or absent
o Cranial nerves are affected in 45-75% of patients
- Sensory abnormalities are common but generally less marked than the motor symptoms
- Pain is present in more than 85% of cases and can be severe in a subset of patients
- Significant autonomic dysfunction may be noted, including tachycardia, cardiac irregularities, labile blood
pressure, disturbed sweating, impaired pulmonary function, sphincter disturbances, or paralytic ileus
- Guillain-Barr syndrome can be life threatening if the muscles of respiration or swallowing are involved;
approximately 30% of patients will require ventilatory assistance
- Diagnostic Studies:
o Electrophysiologic studies may reveal marked slowing of nerve conduction velocities, both motor
and sensory. These studies also may document denervation or axonal loss
o CSF evaluation typically yields an elevated protein, but the cell counts are normal
- Treatment:
o Patients should hospitalized with close monitoring of respiratory status because autonomic
involvement may rapidly result in complications and death from orthostatic hypotension or
arrhythmias
o Plasmapheresis, instituted as early as possible, is very effective in reducing the time required for
recovery and may reduce the likelihood of residual neurologic deficits. In patients who are severely
affected, plasmapheresis also may shorten the time on a respirator as well as the length of time it
may take to resume walking independently

IVIG also is very effective and is used in preference to plasmapheresis in adults with
cardiovascular instability and in children
o Patients will benefit from physical, occupational, and speech therapy during rehabilitation
o Recovery is slow, but approximately 60% make a full recovery within 1 year. The mortality rate in 1
year is approximately 5%
Huntington Disease
- An inherited, autosomal dominant disorder that occurs throughout the world in all ethnic groups, with a
prevalence of < 5 per 100,000
- The gene responsible for Huntington disease is on the short arm of chromosome 4
- Symptoms of the disease usually do not develop until after 30 years of age. By this time, those who are
affected have already had children who may be similarly affected
- The disease is characterized by progressive chorea and dementia; it is usually fatal within 15-20 years
- The earliest mental changes often are behavioral, with irritability, moodiness, and antisocial behavior that
generally progress to an obvious dementia
- The earliest physical signs may be a mere restlessness or fidgetiness, but, eventually, severe choreiform
movements and dystonic posturing occur
- Diagnostic Studies:
o CT demonstrates cerebral atrophy as well as atrophy of the caudate nucleus
o MRI and PET scans have shown decreased glucose metabolism in an anatomically normal
caudate nucleus
- Treatment:
o Huntington disease has no cure, and progression of the disease cannot be halted
o Symptomatic treatment for the disease may include phenothiazines to control dyskinesia and
haloperidol or clozapine to control any behavioral disturbances
o Children of Huntington patients should receive genetic counseling. Genetic testing is very sensitive
and specific and can make a definitive diagnosis even in the presymptomatic state
Cerebral Aneurysm / Subarachnoid Hemorrhage
- A ruptured cerebral aneurysm, or, less commonly, an arteriovenous malformation (AVM) causes bleeding
into the subarachnoid space
o Intracranial AVM accounts for less than 10% of SAHs. Most AVMs are congenital. More often in
men
- Develop when intracranial aneurysms rupture and bleed
o Intracranial aneurysms are saccular, berry-shaped aneurysms found at the arterial branch points
within the circle of Willis
Ruptured saccular (berry) aneurysm counts for ~75% of nontraumatic cases of
subarachnoid hemorrhage
o Can occur at any time, but especially during periods of strenuous activity
- Risk factors for developing aneurysms smoking, hypertension, hypercholesterolemia, and heavy alcohol
use
o Also associated with polycystic kidney disease and coarctation of the aorta
- Vigorous physical activity and cocaine use are associated with triggering SAH, presumably causing
elevation of the blood pressure
- Sudden onset of severe headache worst headache of my life
o Vomiting, photophobia, nuchal irritation, low-grade fever, AMS, seizures
- Frequently, blood pressure rises precipitously as a result of the hemorrhage
- Patients with SAH may develop fever up to 102F (38.9C) and frequently display confusion, stupor, coma,
and nuchal rigidity or other signs of meningeal irritation
- A herald bleed, or aneurysmal leak, occurs in up to 40% of patients, producing a less severe but atypical
headache and is accompanied by focal neurologic signs resulting from pressure on the brain or cranial
o

nerves. The herald bleed and corresponding sentinel headache usually occur 1-3 weeks prior to the severe
SAH
ICP transiently increases with each cardiac contraction, causing a pulsatile headache
Progressive neurologic deficits may develop as a result of blood clot mass effects, vasospasm with
infarction, or hydrocephalus
o Coma and death may occur

Use the five-point Hunt-Hess system to gram severity

o Grade 1 mild headache and slight nuchal rigidity
o Grade 2 CN palsy, severe headache, nuchal rigidity
o Grade 3 mild focal deficit, lethargy, or confusion
o Grade 4 stupor, hemiparesis, early decerebrate rigidity
o Grade 5 deep coma, decerebrate rigidity, moribund appearance
- CT without contrast is the initial modality for suspected SAH
o Very sensitive to detect SAH within 12 hours of symptom onset
o If negative but SAH still suspected, do a lumbar puncture to look for RBC or xanthochromia
Xanthochromia does not develop until 12 hours after symptom onset
Will have markedly elevated opening pressures and grossly bloody fluid
o If SAH is present, four-vessel cerebral angiography is performed to define the aneurysm neck and
relationship with surrounding vessels
o EEG may indicate the side or site of hemorrhage or may show only diffuse, non-specific changes
- Supportive medical treatment involves prevention of elevated arterial or intracranial pressures that might
lead to rerupture of the affected vessel.
- Initial medical treatment control hypertension with IV medications (labetalol)
o Important, but prevent hypotension and inadequate cerebral perfusion
o Phenytoin for prophylactic treatment of seizures
o Mannitol to control edema if evidence of increase ICP
o Nimodipine to reduce risk of developing delayed neurologic deficits from vasospasm
- Hyponatremia is a common problem with SAH, so monitor serum sodium
- Emergency external ventricular drainage may be indicated to decrease ICP
- In rare cases with progressive neurologic deterioration, emergency craniotomy and evacuation of a blood
clot are required to prevent herniation
- Definitive treatment is obliteration by microsurgical clipping or endovascular coiling of the aneurysm
Concussion
- No universal definition
- Difficult to recognize
- A complex pathophysiological process affecting the brain, induced by traumatic biochemical forces.
- Common defining features:
o Due to a direct or indirect impact that transmits an impulsive force transmitted to the head
o Results in rapid onset of short-lived neurologic impairment that resolves spontaneously
o Can result in neuropathologic structural changes
o Acute clinical symptoms are functional disturbances
o May or may not include LOC
o Clinical and cognitive symptoms typically resolve sequentially
o Neuroimaging is usually negative
- Pathophysiology:
o Diffuse axonal injury, mechanical tissue damage, ischemia, synaptic loss, neuronal dysfunction
o Neuron activity is suppressed by potassium moving into the extracellular space due to neural
membrane disruption from transmitted shear forces
o To restore balance, sodium-potassium pumps work overtime, requiring more energy at the same
time cerebral blood flow is decreased due to altered autonomic regulation = at risk for further injury

Symptoms:
SOMATIC
COGNITIVE
AFFECTIVE
Blurry vision
Amnesia
Anxiety
Convulsions/seizure
Confusion
Depression
Dizziness
Delayed responses
Emotional lability
Poor balance
Difficulty concentrating
Irritability
Fatigue
Poor memory recall
Personality
Headache
Disorientation
changes
Light-headedness
Fogginess
Phonophobia
Inattention
Nausea
Slurred speech
Vomiting
Paresthesias
Tinnitus
Progression to Resolution:
o Symptoms may begin at the time of injury or can be delayed
o In many cases, symptoms will resolve within 72 hours
o 80-90% of these injuries will completely resolve within 7-10 days
o Resolution is generally defined as no symptoms at rest or with exertion
o Patients at risk for prolonged recovery:
> 3 symptoms at presentation
Specific symptoms (Fogginess)
Headache >60 hr
LOC >60 sec
Amnesia
History of concussion
<18 years old
Co-morbid conditions
Medication use
Dangerous style of athletic play
High risk sport (contact)
Diagnosis/Evaluation:
o Challenging diagnosis to determine due to multiple factors:
Subjective reports from patients and observers
Subtle symptoms are easily dismissed
Objective data is not readily available or validated
Imaging is usually normal
Treatment:
o Cognitive rest
o Physical rest
o Pharmacotherapy
o Transition back to school
o Graded return to play
Post-concussion syndrome:
o A complex disorder in which a variable combination of post-concussion symptoms such as
headaches and dizziness lasts for weeks and sometimes months after the injury that caused the
concussion.
o Not necessarily associated with severity of initial injury.

o Variable presentation and duration

o Lasts few weeks months, in some instances can persist greater than a year
o Management options symptomatic (rx for HA, t/c biofeedback, neuropsych testing-intervention)
- Second Impact Syndrome:
o Usually thought to involve a patient with post concussive symptoms who sustains a 2nd impact
leading to diffuse cerebral swelling, brain herniation, and death
o Controversial:
No agreement on definition
Limited epidemiologic data
Incidence unknown
Literature shows documented cases predominantly occur in patients <20 yr old
Brain herniation and death can occur within minutes
o Following a concussion
Potassium concentration increased
Hypermetabolism may persist up to and maybe greater than 10 days
Therefore
Brain is vulnerable
Decreased ability to autoregulate intracranial and cerebral perfusion pressures
Literature shows documented cases predominantly occur in patients <20 years old
Delirium
- Characterized by alteration of consciousness, waxing and waning of symptoms, psychomotor retardation or
agitation, and decreased attention span
- A medical emergency evaluate promptly.
- Most common with surgical admissions, especially orthopedic and urologic procedures
- Maintain a high index of suspicion
- Perform a complete physical exam including neuro and rectal exam
- Identify and treat reversible factors (unnecessary medications, infection, anemia, dehydration, CHF,
electrolyte imbalance, CNS oxygenation, sensory deprivation, fecal impaction, urinary retention)
- Encourage family visitation, remove/avoid restraints when possible, mobilize the patient, assist with feeding,
reduce noise, provide with familiar surroundings
- Recommend lorazepam or haloperidol in small doses if medication is necessary
- Defined as an acute change in mental status and symptoms that fluctuate over minutes and hours and
inattention combined with either altered level of consciousness or disorganized thinking.
- Causes of delirium: MOVE, STUPID
o Metabolic hepatic encephalopathy, thiamine deficiency, hypoglycemia
o Oxygen hypoxia , hypercarbia
o Vascular anemia, MI
o Endocrine/electrolytes hyponatremia, hypercalcemia, fluid imbalance, hyper/hypothyroidism
o Seizures ictal/postictal
o Trauma/tumor/temperature
o Uremia acute renal failure, dehydration
o Psychogenic
o Infection/intoxication UTI, pneumonia, meningitis, sepsis; alcohol, benzos, CO, barbiturates,
etc.
o Drugs/degeneration
- Signs and Symptoms:
o Waxing and waning consciousness and perceptual disturbances hallucinations, delusions,
agitation, persecutory thoughts are common.

o
o

Anxiety, paranoia, or combativeness may be present. Symptoms often worsen at night, a

phenomenon known as sundowning. However some patients may have responsiveness known
as quiet delirium, which may go unnoticed if the team is monitoring only for agitated patients.
attention span, short-term memory, and reversed sleep-wake cycles

Workup:
o Thorough H/P, vitals, neuro exam
o Consider chronic medical conditions that may make the patient more susceptible to delirium
o Electrolytes, Calcium, CBC with diff, UA, urine toxicology screen.
o ABG, LFTs, TFTs, RPR or VDRL, LP, serum B12 and folate
o Imaging:
CXR to r/o pneumonia, TB, and CHF
CT and MRI if:
Head trauma or CNS pathology is suspected after lab work is done and is found
to be noncontributory to a medical diagnosis
There is a high index of suspicion of anatomic CNS pathology
EEG to r/o seizures
ECG to r/o MI
LP especially if the patient is febrile with or without meningismus
- Treatment:
o Treat underlying cause
o Normalize fluid and electrolyte status and provide an appropriate sensory environment (windows
and light)
o Use nonsedating antipsychotics (haloperidol) for agitation
o Avoid benzodiazepines for sedation as they will worsen most patients symptoms
Dementia
- Dementia is characterized by progressive impairment of intellectual functioning, with compromise in at least
two of the following spheres of mental activity language, memory, visuospatial skills, emotional behavior,
personality, and cognition
- Unlike delirium, dementia is usually reversible
- Forms Alzheimers Disease, vascular dementias, dementia due to other degenerative disorders
(Parkinsons, Huntingtons, other), frontotemporal dementia, and dementia due to infection (HIV, CreutzfeldtJakob), toxins, depression, or hydrocephalus
- ALZHEIMERS DISEASE:
o The most common form of dementia. 60-80% of patients
o Risk factors old age, family history, lower education levels, and female gender
o Characterized by steadily progressive memory loss and other cognitive deficits and typically begins
during the 6th or 7th decade of life
o Prevalence doubles every 5 years in the older population, reaching 30-50% at age 85
o Genetic factors and familial cases have been mapped to chromosomes 1, 14, 19, 21
o Characteristic pathology consisting of intracellular neurofibrillary tangles and extracellular neuritic
plaques with amyloid deposition. Also neuronal loss
o The diagnosis can be established when an otherwise alert patient exhibits progressive memory
loss and other cognitive deficits, such as disorientation, language difficulties, inability to perform
complex motor activities, inattention, visual misperception, poor problem-solving abilities,
inappropriate social behavior, or hallucinations
Anterograde amnesia is the first sign
Subsequent cognitive defects aphasia, acalculia, depression, agitation, apraxia
o Intellectual decline should be present in two or more areas of cognition and documented by a
mental status examination or similar scale
o Formal neuropsychological testing can help to confirm the suspected diagnosis and document the
progression of disease

Diagnostic Studies:
A clinical diagnosis of exclusion. Can only be definitively diagnosed on autopsy
CBC, heavy metal screens, serum electrolytes, calcium, glucose, TSH, vitamin b12, renal
and liver function tests, and drug and alcohol levels. These labs are done to rule out
treatable causes
MRI or CT is helpful only in ruling out other treatable causes of dementia
PET scan for biparietal hypometabolism
o Treatment:
Standard medical therapy, initially in low doses, is useful in treating insomnia, agitation,
and depression
A trial of acetylcholinesterase inhibitors such as tacrine, donepezil, galantamine, or
rivastigmine, may improve memory function.
Memantine is a N-methyl-D-aspartic acid (NMDA) receptor antagonist that can be added
to the acetylcholinesterase inhibitor (preferred), or it can be used alone. It is thought to
regulate glutamate and has been approved for use in severe Alzheimers Disease
Vitamin E (alpha-tocopherol) and selegiline are antioxidants may slow cognitive decline
The patient requires vigilant family supervision. Day care centers, respite care are
adjuncts to family supervision
VASCULAR DEMENTIA:
o 15-20% of patients with chronic dementia
o Usually referred to as multi-infarct dementia, which includes lacunar and multiple cortical infarcts
Multi-infarct dementia is more common in men than women
It is associated with hypertension, with or without a history of TIA or stroke
o 15-20% of people with dementia have evidence of both vascular and Alzheimers-type
o Usually manifests as forgetfulness in the absence of depression and inattentiveness. Symptoms
typically occur in a stepwise fashion and are related to the area of the CNS affected.
o Two distinct syndromes:
Cortical symptoms speech difficulty, trouble performing routine tasks, sensory
interpretation difficulty, confusion, amnesia, and executive dysfunction
Subcortical symptoms gait problems, urinary difficulties, motor deficits, and personality
changes
o Social graces may be well maintained, so mental status testing is important to establish diagnosis
o Progression of the disease leads to loss of computational ability, problems with word finding and
concentration, difficulty with routine daily activities, and, ultimately, complete disorientation and
social withdrawal
o Laboratory testing and images are useful only in establishing other treatable causes of dementia
o Treatment:
Control HTN and metabolic disorders to help slow the progression of symptoms
As in Alzheimer disease, standard medical regimens can be used to treat insomnia,
agitation, or depression
Treat insomnia, agitation, or depression
FRONTOTEMPORAL DEMENTIA:
o Secondary to degeneration of the frontal lobe of the brain and may include the temporal lobe
o Etiologies Picks disease, dementia associated with ALS, and others
o Frontal lobe symptoms behavioral (euphoria, apathy, disinhibition) and compulsive disorders
o Several primitive reflexes (frontal release signs) are often elicited, including the palmomental,
palmar grasp, and rooting reflexes
o

Laboratory Studies:
MRI reveals frontal lobe and/or anterior temporal lobe atrophy but in early cases may
appear normal
PET scans classically show frontal and/or anterior temporal hypometabolism, which helps
to differentiate from Alzheimers associated with biparietal hypometabolism
o Treatment:
Supportive care NO curative treatment
Behavioral symptoms may require treatment (SSRIs, etc.)
- PSEUDODEMENTIA:
o A term that describes patients with psychiatric illness who appear to be demented
o Often seen as part of a major depression episode
o Patients typically complain of memory problems, by attention span and concentration appear intact
while appearing upset or distressed
o In true dementia, the patient will often give wrong answers, have poor attention and concentration,
and appear indifferent or unconcerned
- Treatment:
o Antidepressant therapy with an SSRI (e.g., citalopram) is first line
o Acetylcholinesterase inhibitors are not indicated for pseudodementia
Peripheral Neuropathies
- Focal neuropathies:
o Carpal Tunnel:
Results from compression of the median nerve at the wrist where it passes through the
carpal tunnel.
Most commonly seen in women 30-55 yo
Risk factors repetitive use injury, pregnancy, diabetes, hypothyroidism, acromegaly,
RA, obesity
Signs and symptoms:
Wrist pain
o Numbness and tingling of the thumb, index finger, middle finger, and
medial half of the ring finger on the palmar aspects.
o Weak grip
o Decreased thumb opposition.
Pain and symptoms are exacerbated by activities that require wrist flexion, such
as typing, holding a cup of coffee or opening a jar.
Symptoms may awaken patients at night and are relieved by shaking out the
wrists. Patients often complain of nocturnal pain and paresthesias.
Thenar atrophy may occur in severe cases.
Workup:
Tinels sign:
o Taping on the palmaris longus tendon at the wrist over the median
nerve to elicit a tingling sensation in the thumb and affected fingers.
Phalens sign:
o Requires that the patient oppose the dorsal aspects of the hands with
the wrists flexed at 90 degrees for at least 30 seconds. The onset of
paresthesias confirms the diagnosis.
EMG and nerve conduction studies
Treatment:
Avoid aggravating factors and splint the wrist in neutral position.
o

Cubital Tunnel:
Results from compression of the ulnar nerve at the elbow.
Causes tingling in the 5th and lateral 4th fingers that may progress to paralysis and wasting
of the intrinsic hand muscles.
Treatment:
Anti-inflammatory medications and splinting with a long arm posterior splint or a
sling.
o Deep Peroneal Entrapment:
Causing foot drop and numbness between the first and second toes
o Meralgia Paresthetica:
Entrapment of the lateral femoral cutaneous nerve causing numbness and pain of the
anterior lateral thigh
o Mononeuritis Multiplex:
Dysfunction of multiple peripheral nerves separated temporally and anatomically.
Plexopathies:
o Brachial Plexopathy:
Causes weakness in the arm or shoulder girdle followed by pain and paresthesias.
Patients have weakness in various distributions of the brachial plexus.
ED eval find acute reversible cause (direct trauma, shoulder reduction) and refer for
other causes (neoplasm, radiation).
o Lumbosacral Plexopathy:
Due to radiation or diabetic amyotrophy, or compression from AA, retroperitoneal
hemorrhage, or AVM, will cause weakness, decreased sensation, and possibly decreased
reflexes in the areas innervated by the affected portions of the plexus.
Plain radiographs, MRI, and abdominal CT may be useful to determine etiology.
HIV-Associated Peripheral Neurologic Disease:
o Antiretroviral drug-induced and HIV neuropathy are chronic and do not cause acute symptoms.
Patients with HIV have a high rate of mononeuritis multiplex and a myopathy resembling
pyomyositis.
o In early infection, they are more prone to GBS.
o In the later stages of AIDs, patients develop CMV radiculitis, with acute weakness and decreased
sensation in the lower extremities, hyporeflexia, and varying bowel and bladder dysfunction.
o MRI: Shows swelling and clumping of the cauda equina.
o Treatment for CMV radiculitis: IV ganciclovir 5mg/kg q12 for 3-6 weeks
Chronic Neurologic Disorders:
o Amyotrophic Lateral Sclerosis:
Clinical features:
Causes progressive muscle atrophy and weakness
Upper motor neuron dysfunction causes limb spasticity, hyperreflexia, and
emotional lability.
Lower motor neuron dysfunction causes limb weakness, atrophy, fasciculations,
dysarthria, dysphagia, and difficulty in mastication.
Symptoms are asymmetric.
Patients may appear to have an acute compressive radiculopathy.
Respiratory muscle weakness causes progressive respiratory depression.
Management:
Respiratory failure, pneumonia, choking, trauma are common ED presentations.
o

Optimize pulmonary function with nebulizer treatments, steroids, antibiotics, and

intubation as indicated.
Admit patients with pneumonia or inability to handle secretions.
o Poliomyelitis and Postpolio Syndrome:
Poliomyelitis caused by enterovirus that induces paralysis by motor neuron destruction
and muscle denervation and atrophy. Most patients have a mild viral syndrome and no
paralysis. Major illness most commonly involves the spinal cord, resulting in asymmetric
proximal limb weakness and flaccidity, absent tendon reflexes, and fasciculations.
Maximal paralysis occurs within 5 days and is followed by muscle wasting. Autonomic
dysfunction is common. Paralysis will resolve within the first year in nearly all patients.
Postpolio syndrome recurrence of motor symptoms after a latent period of several
decades. Symptoms may include muscle fatigue, joint pain, or weakness of new and
previously affected muscle groups.
Acute care is supportive. Lamotrigine may improve quality of life. Consult neuro.
- Diabetic Peripheral Neuropathy
o The most common type of neuropathy in the western hemisphere
o Common. Present as a mixed polyneuropathy (motor, sensory, autonomic) in 70% of cases. the
remainder of cases involve largely sensory neuropathies
Less commonly, patients develop mononeuropathies involving specific peripheral or
cranial nerves
o Neuropathy generally is related to the duration and severity of hyperglycemia, but it may be the
presenting symptom in occult diabetes. Neuropathy is the result of vascular insufficiency or nerve
infarction
o Symptoms are more common in the lower extremities than the upper extremities and consist of
numbness, pain, dysesthesias (burning) or paresthesias
o A distal symmetric polyneuropathy also can be diagnosed before the development of any
symptoms in the form of reduced DTRs (e.g., ankle jerk) or impaired vibratory sensation
o Autonomic complications related to diabetes include postural hypotension, cardiac arrhythmias,
thermoregulatory sweating, and disturbances of bowel/bladder/gastric/sexual function
o Diagnostic Studies:
Serial nerve conduction studies can be completed to document the presence, severity,
and course of the neuropathy
Additional diagnostic workup to rule out other causes of polyneuropathy uremia,
alcohol abuse or nutritional deficiencies, connective tissue disease, vasculitis, vitamin B12
deficiency, hypothyroidism, or amyloidosis
o Treatment:
Tight control of hyperglycemia is vital to prevent or slow progression of the disease
No specific treatments for diabetic peripheral nerve complications, with the exception of
an entrapment neuropathy that may respond to a decompression procedure
Amitriptyline, nortriptyline, desipramine, gabapentin, or pregabalin may be used for
controlling deep, constant, aching pain
Duloxetine, a SNRI, has been approved for painful diabetic neuropathy
Postural hypotension may respond to salt supplementation, lower extremity pressure
stockings, or medications such as fludrocortisone or midodrine
Complex Regional Pain Syndrome
- Aka Reflex Sympathetic Dystrophy
- CRPS usually begins after an operation, an injury (such as fracture), or following a vascular event such as
stroke or myocardial infarction

The disorder is characterized by regional pain in the affected limb, restricted mobility, edema, color changes
of the skin, and spotty bone thinning
Most patients do not have an identifiable neurologic lesion responsible for the pain
The cause of CRPS is not well understood, but it is thought to be partially secondary to abnormal sensitivity
to inflammatory mediators of pain
Most cases of CRPS occur following a soft-tissue injury; however no inciting event is identified in about
of cases
The hallmark feature of CRPS is severe burning or throbbing pain with associated allodynia in the affected
region/extremity. Cyanosis, abnormal sensitivity to cold and warm exposure, abnormal skin temperature,
and atrophy may also be present
Other causes of these symptoms, depending on the presentation, include vasculitis, claudication, nerve root
impingement, atrophy from disuse, and progressive systemic sclerosis
Diagnostic Studies:
o Bone scintigraphy, plain x-rays, and MRI can be helpful in making the diagnosis of CRPS, although
the diagnosis is primarily clinical
o Regional nerve block may be used diagnostically; complete relief of pain is consistent with CRPS
Treatment:
o Early mobilization following an injury may reduce the chance of developing CRPS
o Amitriptyline, nortriptyline, gabapentin, pregabalin, or lamotrigine are effective choices for pain
relief
o NSAIDs may be beneficial in select patients
o Calcitonin is effective at reducing pain and can be used as an adjunctive therapy; this medication
also prevents bone resorption
o Bisphosphonates, IVIG, regional nerve blocks, or dorsal column stimulation may be effective if
other treatments fail

Internal Medicine Hematology

Iron Deficiency Anemia
- Iron deficiency is the most common cause of anemia worldwide
- In adults, GI blood loss secondary to PUD, NSAID use, or cancer is the likely cause; heavy menstrual blood
loss may be a cause; however, GI bleeding must be ruled out
- Low dietary intake of iron may occur in children, impoverished persons, and pregnant women
- Other causes decreased absorption of iron, increased requirements, hemoglobinuria, blood donation,
iron sequestration, trauma, and intravascular hemolysis
- Lack of iron causes few specific complaints. General complaints in moderate to severe iron deficiency
include pallor, easy fatigability, irritability, anorexia, tachycardia, tachypnea on exertion, and poor weight gain
in infants
- Pica is a hallmark of iron deficiency
- Severe deficiency (Hct < 25%) may cause brittle nails, cheilosis, smooth tongue, and formation of
esophageal webs (Plummer-Vinson syndrome)
- Diagnostic Studies:
o Hemoglobin and hematocrit are decreased
o Peripheral smear
Initially, no changes in red cell size
Later, the peripheral smear shows hypochromic microcytic red cells, anisocytosis, and
poikilocytosis
o A plasma ferritin level of less than 20g/L reliably indicates iron deficiency anemia
o Serum iron is decreased to less than 30g/dL, and TIBC is elevated. Transferrin saturation
decreases to less than 15%
- Treatment:
o Ferrous sulfate, 325 mg three times per day orally, should be given in a slowly escalating dose. It
is best absorbed on an empty stomach but is frequently given with meals due to intolerability.
Supplemental vitamin C may enhance absorption
o Although Hgb/Hct will be within the normal range in 2 months, therapy should be continued for up
to 6 months or longer to replenish tissue stores measured by ferritin
o Iron supplementation during pregnancy and lactation is essential
o Parenteral iron is appropriate for patients with intolerance to oral iron, GI disease, and continuing
blood loss. Sodium ferric gluconate is less likely than iron dextran to cause anaphylaxis
o Workup for occult blood loss is imperative
o Treatment failures may be caused by noncompliance, poor absorption, incorrect diagnosis, or
ongoing blood loss
Sickle Cell Anemia
- Hemolytic anemia
- Sickle cell disease is a family of autosomal recessive inherited hemoglobinopathies (SS, SC, SD, SO Arab,
S beta + thalassemia, and S beta 0 thalassemia)
- RBCs containing primarily Hgb S sickle under hypoxia, dehydration, acidosis, and extreme temperature
conditions
- In the United States, this disease most often is seen in blacks (1 in 400 births), 8% carry the Hgb S gene as
the sickle cell trait
- Problems begin about 6 months after birth when protective Hgb F levels fall to adult levels

Sickle cell patients present with a spectrum of mild to severe complaints:

o Vascular occlusions
o Painful crises
o Strokes
o Chest syndrome
o Bone infarctions
o Avascular necrosis (AVN)
o Splenic sequestration
o Delayed growth/puberty
Sickle complications can be precipitated by red cell dehydration, acidosis, or hypoxemia as well as stress,
menses, and temperature changes. Patients should avoid high altitudes (above 7,000 feet) and deep-sea
diving
Patients with sickle cell anemia are at increased risk for cholelithiasis, splenomegaly, leg ulcers, infection
with encapsulated organisms (e.g., S. pneumo), strokes, AVN, priapism, retinopathies leading to blindness,
and osteomyelitis
Hemolytic or aplastic crises may be life threatening
AVN of the femoral and humeral head is more common in type SC
Life expectancy for type SS is 40-50 years of age and has been increasing over the past few decades due
to advancement in monitoring and treatment
Sickle cell trait may result in difficulty concentrating urine
Diagnostic Studies:
o Electrophoresis demonstrates the level of different hemoglobins in the red cell. Hgb S is 50% or
greater in sickle cell anemia
o Peripheral smear may reveal sickled cells (5%-50%O and target cells, nucleated RBCs, and
Howell-Jolly bodies
o Reticulocyte count, indirect bilirubin, and LDH are elevated when hemolyzing
o WBC count is elevated; thrombocytosis may be present
Treatment:
o Symptomatic treatment of pain episodes includes administration of analgesics, hypotonic fluids,
and rest
o Stroke, sequestration, acute chest syndrome, and multiorgan failure may require transfusion or
exchange transfusion
o Patients should receive low-dose penicillin from birth until age 6 years, pneumococcal vaccine
(booster vaccine every 10 years), transcranial Doppler (TCD) screening for stroke prevention,
pulmonary function testing (PFT) for restrictive disease screening, and chronic folate
supplementation
o Daily lifelong hydroxyurea therapy should be considered for all SS and S beta 0 thalassemia
patients as young as 1 year old to increase Hgb F production, prevent complications, and increase
lifespan
o Genetic counseling for patients with either the disease or trait is recommended. Prenatal testing is
available

Anemia of Chronic Disease

- Normocytic anemia (70%, may be microcytic)
- Often associated with chronic inflammatory diseases
- Normal or increased ferritin and normal or reduced transferrin
- These anemias are caused by organ failure or impaired marrow function resulting from systemic disease.
Upregulation of hepcidin in response to inflammatory mediators is an important cause
- LOW reticulocyte response
- Anemia of inflammation (results from chronic inflammatory disease, such as RA, IBD, malignancy, chronic
infections, SLE)
o These things all increase hepcidin levels, which block the iron absorption from the gut and the
release of iron from the bone marrow
o Elevated CRP or Westergren ESR is characteristic
o A normal or elevated ferritin level with a high percent saturation is typical
o Treat the underlying cause this will reduce inflammation and the anemia will improve
o May need transfusion if symptomatic
o Patients do not respond to epo or iron supplements
- Anemia of chronic disease usually is mild and remits with treatment of the disease
o Usually normochromic, normocytic (or mildly hypochromic, microcytic)
o Normal or increased bone marrow iron stores and serum ferritin and normal or low TIBC
o Serum iron is low in anemia of inflammation
Thalassemia
- Thalassemia is a genetic underproduction of - or -globin chains resulting in deficient hemoglobin
synthesis and RBC hemolysis
- -Thalassemia is more common in people of Southeast Asian or Chinese origin; -thalassemia is more
common in African and Mediterranean populations
- Thalassemia should be suspected in a person with a positive family history or a personal history of lifelong
microcytic anemia with normal iron stores
- Deficits range from silent carrier status to profound anemia
- -Thalassemia
o Patients may have mild symptoms or none (thalassemia trait; carriers). Patients often are
diagnosed after a nonresponse to a treatment for a suspected iron deficiency
o Patients with one -globin chain have Hgb H disease, which is variably symptomatic; when all four
chains are deleted, stillbirth occurs from hydrops fetalis
- -Thalassemia major (Cooley anemia)
o Symptoms begin by 4-6 months of age, when the switch from fetal hemoglobin (Hgb F) to adult
hemoglobin (Hgb A) occurs. These problems include severe anemia, growth retardation, abnormal
facial structure, pathologic fractures, osteopenia, bone deformities, hepatosplenomegaly, and
jaundice
o Before effective iron chelation and allogeneic stem cell transplantation, patients usually died from
cardiac failure by age 30 years

Diagnostic Studies:
o Thalassemias are differentiated per typical hematocrit, hemoglobin electrophoresis, reticulocyte
count, and peripheral smear
TYPE
HEMATOCRIT
HEMOGLOBIN
PERIPHERAL SMEAR
RETICULOCYTE
ELECTROPHORESIS
COUNT
-Thalassemia minor 28-40%
Normal
Target cells, acanthocytes
Normal
(trait)
-Thalassemia H
22-32%
Hemoglobin H
Target cells, poikilocytes
Increased
-Thalassemia minor

28-40%

Hemoglobin A2, Hemoglobin F

Target cells, basophilic stippling

Normal or increased

-Thalassemia major

As low as 10%

Hemoglobin F, Hemoglobin A2

Target cells, poikilocytes,

basophilic stippling, nucleated
RBCs

Increased

Serum iron and ferritin levels characteristically are normal or elevated

Hemoglobin level usually is between 3-6 g/dL
Thalassemia produces more marked microcytosis for degree of anemia than iron deficiency does;
red cell morphologic changes occur earlier
o Diagnosis is confirmed by hemoglobin electrophoresis
- Treatment:
o Patients with mild disease should not receive iron if ferritin is normal because of the risk of iron
overload
o Persons with Hgb H disease need folic acid supplements and should avoid iron supplements and
oxidative drugs (e.g., dapsone, primaquine, quinidine, sulfonamides, nitrofurantoin)
o Treatment for -Thalassemia major consists of transfusions to keep hemoglobin concentrations at
least 12 g/dL; however, iron overload may result in hemosiderosis, heart failure, cirrhosis, and
endocrinopathies. Parenteral deferoxamine or oral deferasirox is administered to treat or postpone
hemosiderosis
o Allogeneic bone marrow transplantation also is used with increasing success. Splenectomy may
also be required
o Genetic counseling, testing, and prenatal diagnosis for severe forms are essential
Vitamin B12 Anemia
- Aka cobalamin deficiency
- Macrocytic anemia
- Pernicious anemia is the most common cause due to lack of intrinsic factor, which is necessary for vitamin
B12 absorption
- Other causes strict vegan diet, gastric surgery, blind loop syndrome, pancreatic insufficiency, metformin
use, and Crohn disease
- Irreversible neurologic damage can be caused by uncorrected deficiency. Folate administration can mask
the deficiency but does not correct it
- Foods of animal origin supply vitamin B12
- Absorption occurs in the terminal ileum and storage is in the liver
- Examination of the mouth may reveal smooth tongue, glossitis, or cheilosis
- Neurologic findings stocking-glove paresthesias; loss of position, fine touch, and vibratory sensation;
balance problems and ataxia; or dementia
- Abdominal surgical scars may indicate gastrectomy or bariatric surgery, which may lead to impaired vitamin
B12 absorption as a contributing factor
o
o
o

Diagnostic Studies:
o Hypersegmented neutrophils (more than six lobes) are seen on the peripheral smear.
Anisocytosis, poikilocytosis, and macro-ovalocytosis may be seen as well
o Serum LDH and indirect bilirubin can be elevated if hemolysis is present
o Serum vitamin B12 is abnormally low
o Schilling test (a 24-hour urine collection of radioactive vitamin B12) is rarely used today
o Anti-intrinsic factor antibodies can be present
o Both serum MMA and homocysteine levels are increased in anemia due to vitamin B12 deficiency
- Treatment:
o Lifelong supplemental vitamin B12 (1,000 g monthly) usually is given intramuscularly (IM) for
pernicious anemia
o Daily (1,000 g) oral cobalamin may be used. A nasal spray or gel is also available
o Reversible causes of malabsorption should be treated
o Strict vegans; patients with gastric bypass, gastrectomy, or resection of the ileum; and those with
blind loop syndrome require vitamin B12 supplementation
o Neurologic signs and symptoms are reversible if treated within 6 months
Folic Acid Deficiency Anemia
- Macrocytic anemia
- Folic acid deficiency most often is caused by poor dietary intake. Other causes include defective
absorption, pregnancy, chronic hemolytic anemias, alcohol abuse, and folic acid antagonists (e.g.,
phenytoin, TMP/SMX, sulfasalazine)
- Inadequate intake is common in alcoholics, persons with anorexia, and those whose diet is low in fruits and
vegetables
- Malabsorption is a rare cause as folic acid is absorbed throughout the GI tract
- The daily requirement of folic acid is 50-100 mg/dL and is usually met by a balanced diet
- Pregnancy, chronic hemolytic anemias, and exfoliative skin disease increase daily requirements and may
necessitate supplementation
- Clinical features sore tongue (glossitis), vague GI symptoms, but NO neurologic symptoms
- Laboratory Findings:
o Macro-ovalocytes and hypersegmented polymorphonuclear cells are pathognomonic
o Howell-Jolly bodies (nuclear DNA remnants) are typical
o RBC folate level of less than 150 ng/mL is diagnostic
o Serum vitamin B12 level is normal
o Serum homocysteine levels are elevated. MMA is not elevated
- Treatment:
o Oral replacement (1 mg/day) with folic acid is first-line treatment
o Avoid alcohol and colic acid metabolism antagonists (e.g., TMP/SMX, seizure medications, etc.)
TEST
VITAMIN B12 DEFICIENCY
FOLATE DEFICIENCY
Serum Vitamin B12
Low
Normal or low
Serum Folate
Normal
Low
RBC Folate
Normal
Low
Methylmalonic Acid (MMA) High
Normal
Homocysteine
High
High

G6PD Deficiency Anemia

- Hemolytic anemia
- An X-linked recessive disorder commonly seen in American black males (10-15%) and some Mediterranean
populations
- Oxidative drugs (e.g., aspirin, dapsone, primaquine, quinidine, sulfonamides, nitrofurantoin), fava bean
ingestion, and infection cause episode hemolysis
- Severe deficiency may cause chronic hemolysis
- Patients with episodic hemolysis usually are healthy and have no splenomegaly
- Female carriers are rarely affected
- Laboratory Findings:
o During hemolytic episodes, reticulocytes and serum indirect bilirubin increase
o Peripheral smear reveals bite cells and Heinz bodies (denatured hemoglobin)
o G6PD levels will be low between hemolytic episodes; in severe cases, G6PD levels will always be
low
- Treatment:
o In most cases, hemolytic episodes are self-limited as red cells are replaced as soon as the
offending agent is stopped
o Oxidative drugs and fava beans should be avoided
Acute / Chronic Leukemia
- Leukemias are characterized by increased production of abnormal leukocytes and leukocyte precursors in
circulation and bone marrow
- Leukemias are classified according to cell type, either myelocytic (ML) or lymphocytic (LL) and whether
acute (AML, ALL) or chronic (CML, CLL)
- Risk factors genetics and exposures to ionizing radiation, benzene, and certain alkylating agents
Acute Leukemias (ALL and AML)
- Incidence increases with age. In children 3-7 years old, ALL (80%) is more common than AML
- AML primarily is a disease of adulthood (median age at onset is 60 years)
- Most clinical findings are related to replacement of normal bone marrow with abnormal WBCs
- Gingival bleeding, epistaxis, and menorrhagia may be the presenting complaint in patients with
thrombocytosis
- Neutropenia predisposes to infections, most commonly those caused by Gram-negative bacteria or fungi
- Children and young adult present with fatigue, abrupt onset of fever, lethargy, headache, and bone and/or
joint pain, especially in the sternum, tibia, and femur
- Older adults have a slow, progressive onset, with lethargy, anorexia, and dyspnea
- Symptoms of anemia, thrombocytopenia, gingival hyperplasia, rashes, or cranial nerve palsies may occur
- Lymphadenopathy and hepatosplenomegaly are more common with ALL than in AML
- Diagnostic Studies:
o CBC reveals pancytopenia with circulating blasts; bone marrow biopsy demonstrates over 20%
blasts
o Hyperuricemia may be present
o Auer rods (rod-shaped structures in cell cytoplasm) can be seen in AML
o Terminal deoxynucleotidyl transferase is diagnostic for ALL
o Cytogenetic studies are the most powerful prognostic factors; presence of the Philadelphia
chromosome (15% of ALL, 90% of CML) is unfavorable

Treatment:
o Induction (remission-inducing) chemotherapy is targeted toward eradication of most of the
leukemic cells
o Consolidation therapy destroys the remainder of the leukemic cells
o Increased serum urate levels may be caused by the treatment. Allopurinol and diuretics may be
needed to prevent uric acid stones
o Allogeneic bone marrow transplantation is used in patients with adverse cytogenetics or poor
response to treatment
o Greater than 50% of children with ALL can be cured with chemotherapy (induction plus
consolidation therapy). Prognosis is related to age and WBC count at diagnosis
o Greater than 70% of adults younger than 60 years of age achieve complete remission with
treatment for AML; further chemotherapy leads to cure in 30-40% of patients
Chronic Leukemias (CML and CLL)
- CLL is a clonal malignancy of B lymphocytes
- CML is a myeloproliferative disorder
- CLL is the most prevalent of all leukemias. It is twice as common in men as in women. Incidence increases
with advancing age; median age at presentation is 65 years
- The B cell form accounts for 95% of CLL cases
- CML:
o Presents in young to middle-aged adults (median age at presentation is 55 years). Greater than
80% are alive 6 years later
o Occurs in 3 phases
Chronic
Accelerated
Acute (blast crisis, defined as >30% blast cells in the blood or bone marrow)
o The symptoms of CML develop gradually. CML generally runs a mild course until the blast-crisis
phase, which indicates accelerated disease and short survival.
Fatigue, anorexia, weight loss, low-grade fever, and excessive sweating are common
Most patients also have abdominal fullness caused by splenomegaly
Rare presentations include blurred vision, respiratory distress, and priapism
- CLL:
o CLL usually has an indolent course, with a median survival time of 6 years. Patients with stage 0-I
have a median survival of 10-15 years. It often is harmless but is resistant to cure. A variant,
polymorphocytic leukemia, is more aggressive
o Clinical manifestations peripheral lymphocytosis and lymphocytic invasion of bone marrow, liver,
spleen, and lymph nodes
o Patients may have recurrent infections, splenomegaly, and lymphadenopathy
- Diagnostic Studies:
o The hallmark of CLL is isolated lymphocytosis, with a leukocytosis of >20,000/L
o The hallmark of CML is leukocytosis, with a median WBC count of 150,000/L. The Philadelphia
chromosome is identified in 95% of cases
o Identification of the BCR-ABL gene by polymerase chain reaction has replaced the search for the
Philadelphia chromosome to establish the diagnosis
o Peripheral smear:
CML may show anemia and thrombocytosis
CLL shows increased mature small lymphocytes; smudge cells are pathognomonic
o Bone marrow is hypercellular with a left shift

Treatment:
o CML

Imatinib mesylate (Gleevac) is standard therapy. It is very effective during the chronic
phase
Allogeneic bone marrow transplantation may be the initial treatment and is the only
therapy proven to be curative. A cure rate of 80% is achieved in those younger than 40
years old with transplantation from HLA-matched siblings. Bone marrow transplantation is
reserved for patients with severe disease, which progresses after initial treatment

CLL

Treatment of CLL usually is palliative once the disease is advanced

Lymphoma
Hodgkin Disease
- Hodgkin disease refers to a group of cancers characterized by enlargement of lymphoid tissue, spleen, and
liver and the presence of Reed-Sternberg cells in lymph node biopsy tissue
- The Epstein-Barr virus also appears to be an important factor; it can be found in 40-50% of cases
- It is most common between the ages of 15-45 years, peaking in the 20s, and again after age 50 years. it is
rare in children younger than age 5 years
- Patients usually present with painless cervical, supraclavicular, and mediastinal lymphadenopathy. Pain in
the affected node after ingestion of alcohol may occur
- Stage A designation indicates a lack of constitutional symptoms.
o of patients present with constitutional (stage B) symptoms (fever, night sweats, weight loss,
pruritus, and fatigue), which are associated with a poorer prognosis
- Diagnostic Studies:
o Other causes of lymphadenopathy should be excluded, such as syphilis, HIV, and mononucleosis
o Refer for lymph node biopsy if suspected for lymphoma
o Reed-Sternberg cells confirm the diagnosis
o Basic staging includes CT of neck, chest, abdomen, and pelvis as well as biopsy of the bone
marrow; laparotomy is no longer routine
- Treatment:
o Combination chemotherapy cures more patients, even those with advanced-stage disease
o Radiation therapy is the initial treatment of choice for patients with low-risk stage IA and IIA
disease; the 10-year survival rate exceeds 80%
o Most other patients receive Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD)
chemotherapy; shorter, intensive treatments are under study
Non-Hodgkin Lymphoma
- About 90% of cases are derived from B lymphocytes
- The incidence of B-cell lymphomas is higher in patients with HIV disease and other immunodeficiencies
- Peak incidence occurs between 20-40 years of age
- These lymphomas are divided into clinically indolent and aggressive groups
o Indolent lymphomas tend to convert to aggressive disease
o of aggressive lymphomas are curable with chemotherapy
- Diffuse or isolated, painless, persistent lymphadenopathy is the most common presentation; bone marrow
involvement is frequent
- Common extralymphatic sites are the GI tract, skin, bone, and bone marrow. Burkitt lymphoma is likely to
present with abdominal fullness
- Fever, night sweats, weight loss, pruritus, and fatigue are less likely than with Hodgkin disease but do occur
in intermediate- and high-grade disease
- Diagnostic Studies:
o Rule out other causes of lymphadenopathy

Persistent, unexplained, enlarged nodes should be biopsies

Staging is accomplished by chest radiography, CT of the abdomen and pelvis, bone marrow
biopsy, and possibly lumbar puncture
- Treatment is based on the stage of disease and the patients clinical status
o Patients with indolent lymphoma with one or two involved nodes may be treated with radiation
alone
o Intermediate- or high-grade lymphomas are treated with chemotherapy, immunotherapy, and
autologous stem cell transplantation
Multiple Myeloma
- Multiple myeloma is a malignancy of plasma cells, producing an abundance of monoclonal paraprotein (M
protein)
- Replacement of bone marrow leads to pancytopenia, osteolysis with bone pain, osteoporosis,
hypercalcemia, and pathologic fractures. Plasmacytomas may cause spinal cord compression
- Patients are prone to recurrent infections, particularly with encapsulated organisms, because of neutropenia
and failure of antibody production
- Paraprotein levels are increased (IgG or IgA may cause hyperviscosity; light-chain components may lead to
renal failure)
- Median age at diagnosis is 65 years
- The most common presenting complaints include anemia, bone pain (particularly in the low back or ribs),
and infection. Less common presenting complaints include renal failure, spinal cord compression, and
hyperviscosity syndrome
- Diagnostic Studies:
o Patients will be anemic, with normal cell morphology; rouleaux formation is common (RBCs stack
like coins)
o The hallmark of myeloma is a monoclonal spike on serum protein electrophoresis. Also with
positive Bence Jones protein in urine
o Lytic lesions are present on radiography of the axial skeleton; generalized osteoporosis may be
present
o BMP hypercalcemia and increased serum protein; elevated BUN/creatinine if with renal
involvement. Hypercalcemia is a late finding
o Bone scans are not helpful because multiple myeloma does not have an osteoblastic component
- Treatment involves referral for specialist care with combination chemotherapy and transplant options.
Bisphosphonates are important adjunctive therapy
Clotting Factor Disorders
- Acquired platelet dysfunction is more common than congenital
o The most common causes of acquired are aspirin / other NSAIDs. Also seen with other drugs,
uremia, alcoholism, myeloproliferative disease, hypothermia, various vitamin deficiencies, etc.
- PVC Pipes differential diagnosis
o Platelets (not enough, or not working secondary to aspirin/NSAIDs/uremia/genetic causes
o vWD
o Clotting factors, vitamin K deficiency, liver disease, presence of factor inhibitors
o Pipes (vasculitis, scurvy, Ehlers-Danlos syndrome, palpable purpura, steroids
Clotting Factor Disorders
- von Willebrand disease
- Hemophilia A
- Hemophilia B
o
o

von Willebrand Disease

- Autosomal dominant inherited congenital disorder. Most common inherited bleeding disorder
- vWF is necessary to anchor platelets to the injured vessel wall.
- Caused by deficiency (type 1), dysfunction (type 2) or complete absence (type 3) of von Willebrand factor
- Characterized by reduced levels of factor VIII antigen or ristocetin cofactor
o vWF stabilizes factor VIII and low levels can cause pseudohemophilia A with a prolonged aPTT
- Clinical Manifestations: (similar to thrombocytopenia)
o Epistaxis
o Menorrhagia
o Bleeding after tooth extraction, or during shedding a tooth
o Ecchymoses, petechiae
o Gingival bleeding, traumatic oral and lip bleeding
o Postoperative bleeding
o Gastrointestinal bleeding
o Hematuria
o Joint bleeding (type 3 and 2N) spontaneous hemarthrosis and soft-tissue bleeds are less
common than in hemophilia A
o Intramuscular, deep subcutaneous, or submucous bleeding (type 3 and 2N)
- Detecting and Treating vWD:
o Screening:
von Willebrand factor antigen
von Willebrand factor activity / ristocetin cofactor (functional evaluation)
PTT (increased/prolonged, low factor VIII) a normal value does not exclude vWD
PT is generally normal
Normal platelet count
o Treatment:
DDAVP aka desmopressin (stimulates release of vWF from cells) treatment of choice
Aminocaproic Acid
vWF containing concentrate (Humate P) may be used in severe episodes (type 3)
Factor VIII concentrates are preferred if factor replacement is necessary
Avoid aspirin and other medications that alter platelet function
Vitamin K Deficiency
- The most common acquired coagulopathies
- May things depend on vitamin K for their activity (coagulation factors II, VII, IX, X and antithrombotic factors
proteins C & S)
- When vitamin K is deficient, coagulation is impaired
- Often occurs because of malabsorption, especially with cystic fibrosis
- Overdose of warfarin (interferes with vitamin K metabolism) can cause severe vitamin K deficiency
- The most common disorder resulting from vitamin K deficiency is hemorrhagic disease of the newborns (so
neonates should receive IM vitamin K at birth)
- Deficiencies may be secondary to poor diet, liver failure, malabsorption, malnutrition, and use of some drugs
(especially broad-spectrum antibiotics)
- The typical patient is postoperative, not eating well, and receiving broad-spectrum antibiotics that suppress
colonic bacteria
- May get soft-tissue bleeding
- PT is prolonged and PTT may be prolonged. Fibrinogen, thrombin time, and platelet count are normal.
- Liver enzymes may be elevated
- Levels are vitamin K, and factors II, VII, IX, and X are decreased

Hemophilia A
- Factor 8 deficiency
- Occurs in 1 in 5,000 males
- X-linked recessive disease characterized by excessively prolonged coagulation time
- The most severe bleeding disorder
- Clinical Findings:
o Symptoms are consistent with degree of clotting factor deficiency
o Mild case may go unnoticed until severe trauma
o Moderate cases bleed with trauma
o Severe cases bleed spontaneously often noticeable by toddler stage
o Hemarthroses, epistaxis, intracranial bleeds, etc.
- Laboratory Evaluation:
o Prolonged aPTT should correct to normal when mixed 1:1 with normal plasma
o PT is normal
o Fibrinogen and platelet count are normal
o Thrombin time is normal
- Diagnosis:
o Based on aPTT
o Specific factor assays and presence of inhibitor necessary
- Treatment:
o Prevent trauma whenever possible
o Early, appropriate replacement therapy with recombinant Factor 8
o Manage bleeding episodes at home with trained parental oversight
o Avoid circumcision in boys with family history of hemophilia
o Avoid aspirin. Celecoxib or opioids may be used to control pain
Hemophilia B
- Factor 9 deficiency
- 15-20% of hemophilia. X-linked recessive
- Christmas disease
- Clinical Findings indistinguishable from Hemophilia A
- Laboratory Evaluation prolonged aPTT, normal PT
o The same as hemophilia A
- Diagnosis specific factor assays and presence of inhibitor
- Treatment:
o Appropriate replacement therapy (recombinant factor 9)
o Prevent trauma whenever possible
o Manage bleeding episodes at home with trained parental oversight
o Avoid circumcision in boys with family history of hemophilia
Hypercoagulable State
- The differential diagnosis can be remembered with the mnemonic PVCs:
o P = Platelets, too many (usually more than 1 million/L) or overactive (TTP, HIT, HUD, and HELLP)
o V = Vascular injury from plaques, trauma, or burns
o C = Clotting factors, anticlotting factors protein C, protein S, or antithrombin III deficient or not
working
o S = Stasis and Surgery
- Virchow Triad blood stasis, hypercoagulable state, and vascular injury

Acquired hypercoagulable states are associated with malignancy (Trousseau syndrome), pregnancy,
nephrotic syndrome, ingestion of certain medications (especially estrogen), immobilization,
myeloproliferative disease, ulcerative colitis and Crohn disease, Behet syndrome, polycythemia vera,
intravascular devices, DIC, hyperlipidemia (particularly familial type II hyperbetalipoproteinemia), PNH, TTPHUS, hyperviscosity syndrome, anticardiolipin antibodies, HIT, and antiphospholipid syndrome
- Heparin therapy (unfractionated heparin or LMWH) can cause HIT, causing a decrease in platelets (usually
in half), followed by platelet activation causing clotting and infarction
- Genetic causes include antithrombin III deficiency, factor V Leiden (activated protein C resistance), protein C
deficiency, protein S deficiency, dysfibrinogenemia, and abnormal plasminogen
- Lupus anticoagulant. An IgM or IgG immunoglobulin is seen in 5-10% of patients with SLE but is more
common in persons without lupus or in those taking phenothiazines
- Diagnostic Studies:
o Hypercoagulation panel includes protein S, protein C, antithrombin III assay, factor V Leiden assay,
fasting homocysteine level, anticardiolipin antibodies, prothrombin 20210 mutation test, fibrinogen
level, and HIT assay
o Russells viper venom time is specific to detect lupus anticoagulant
o CBC reveals increased hematocrit and RBCs in polycythemia vera. Thrombocytopenia occurs with
HIT, TTP, DIC, HUS, and HELLP
o D-dimer is elevated in active thrombosis
o Metabolic panel will uncover hepatic or renal dysfunction or hyperglycemia in diabetes
o Lipid panel to assess for hyperlipidemia
o ANA and CRP in SLE
o HIT assay if exposed to heparin
- Treatment:
o To prevent or treat thrombotic stoke or MI, use antiplatelet therapy aspirin, clopidogrel,
prasugrel, or dipyridamole/aspirin combination
o To prevent or treat DVT, PE, or arterial thrombosis, use parenteral unfractionated heparin or LMWH
as first choice followed by the non-heparinoids fondaparinux or danaparoid
o Oral anticoagulant is preferred for chronic use; choices include vitamin K antagonist, warfarin,
direct thrombin inhibitor dabigatran, or factor Xa blocker rivaroxaban
o Parenteral tPA is used to lyse clots in attempt to re-perfuse tissue
o Prednisone is used for lupus anticoagulant autoimmune causes
o At-risk persons with previous thrombotic events should be anticoagulated for prolonged periods
until the D-dimer values return to baseline
Factor V Leiden:
- The Leiden variant of factor V cannot be inactivated by Protein C (resistance to the protein).
- Caused by a mutation. Most common hereditary hypercoagulable state.
- Mainly limited to those of European extraction.
- Pathophysiology:
o Heterozygous state increase risk of thrombosis up to 8-fold. Homozygous state increases risk 100fold.
- Labs genotyping
- Treatment no role for family testing, no indication for primary prophylaxis
Protein C & S Deficiency:
- Also known as prothrombic state or thrombophilia, it is the propensity to venous thrombosis due to an
abnormality in the coagulation. Reduced level of inhibitors of the coagulation cascade.
- Etiology:
o Predisposition to recurrent venous thromboses. Like antithrombin deficiency but rather uncommon
as a cause for venous thromboses.

o Protein S: commonly acquired in acute illness

Hereditary Homozygous form = death; Heterozygous = asymptomatic
Pathophysiology:
o C & S are natural anticoagulants. Both are Vitamin K dependent (liver). Important in the
physiological prevention of thrombosis.
- Signs and symptoms:
o Liver disease
o Use of warfarin: warfarin induced skin necrosis (Protein C deficiency)
o Vitamin K deficiency
o Acute thrombosis
o Homozygous Protein C: presents in the neonates: purpura fulminans
- Lab findings:
o Function or antigenic assays
- Treatment:
o Long term warfarin treatment: with heterozygous C and S
Antithrombin III Deficiency:
- As the name suggests, it inactivates thrombin. Reduced levels of inhibitors of the coagulation cascade.
- Activity is markedly stimulated by Heparin. Its deficiency is manifested by recurrent venous thromboses and
pulmonary embolism.
- Hereditary disorder; Homozygous = Death; Heterozygous = Asymp
- Pathophysiology deficiency allows unopposed conversion of fibrinogen to fibrin.
- Clinical findings depleted in pregnancy, liver disease, nephrotic syndrome, DIC
- Treatment anticoagulants
Malignancy:
- Malignant diseases in general are associated with an increased risk for venous thrombotic embolism and
pulmonary embolism that is not related to DIC (disseminated intravascular coagulation). S
- UFH therapy in malignancy associated VTE or PE appears to achieve outcomes superior to those provided
by treatment with LMWH, direct thrombin inhibitors, or warfarin, possible because of multiple beneficial
anticoagulant effects mediated by longer glycosaminoglycan sequences in UFH.
Hormonal Hypercoagulable States
- Pregnancya hypercoagulable state; a number of physiologic mechanisms increase the risk of thrombosis,
particularly in the 3rd trimester and up to 6-weeks post-partum. Risk of thrombosis is also increased by
mechanical compression of gravid uterus upon pelvic veins.
- Oral Contraceptiveslike pregnancy, a number of physiological mechanisms increase the risk of
thrombosis. Cigarette use in women using oral contraceptives also significantly increased thrombosis risk,
and this increase is thought to result from increased platelet reactivity, mediated in part by increased
thromboxane synthesis.
- Etiology:
o Principal associated risk factors for fetal loss or stillbirth are FVL, the G20210A prothrombin
mutation (hereditary), AT deficiency, and protein C and S deficiency.
- Lab findings:
o Pregnancy increase in procoagulant proteins
vWF:
FVII:
Protein S:
Fibrinogen:
o Oral contraceptives increased clotting factors, decreased anticoagulants
FII, FVII, FVIII, FX, Fibrinogen:
Protein C:
-

Protein S:

Antiphospholipid Syndrome
- Disorder that manifests clinically as recurrent venous or arterial thrombosis and/or fetal loss. Used to be
called lupus anticoagulant which is a misnomer. Antiphospholipid (aPL) is more accepted terminology now.
- Etiology:
o Often occurs in association with SLE or other rheumatic or autoimmune disorder. Or may present
as a primary disorder.
- Pathophysiology:
o Antibody that interferes with the natural anticoagulant system.
- Signs and symptoms:
o Recurrent arterial or venous thromboses: DVTs or PEs
o Autoimmune diseases
o Thromboses after surgical procedures
o 2nd trimester miscarriages/Pre-eclampsia
o Migraines
o Thrombocytopenia
o Valvular heart disease heart murmurs
o Limb asymmetry
o Livedo reticularis vascular condition characterized by purplish discoloration of the skin
- Lab findings:
o Iatrogenic aPTT: prolonged, due to in vitro effect of the antibody on the aPTT
o Thrombocytopenia
o Mixing study: fails to normalize/correct
o Antibody levels: high IgG or IgM (anticardiolipin, anti-b2 glycoprotein I, lupus anti-coagulant)
o Confirmatory tests required to make diagnosis: radiology, pathology
- Treatment:
o Once a thrombotic event occurs, treatment with Warfarin is usually continued indefinitely.
Idiopathic Thrombocytopenic Purpura
- An acquired autoimmune (IgG) hemorrhagic disorder that results from excessive destruction of platelets
- Autoimmune :
o Caused by an antibody that binds to the platelet membrane
o The most common thrombocytopenia in childhood and often follows a viral infection (varicella,
rubella, mumps, infectious mononucleosis)
o Chronic ITP peaks from ages 20-50 years and is more common in women
Often coexists with other autoimmune diseases, HIV, and hepatitis C
- Clinical Findings:
o A diagnosis of exclusion
o 1-4 weeks after an acute viral illness
o Abrupt onset of petechiae, bruising, epistaxis. May also have hemorrhagic bullae on the skin and
mucous membranes
o No splenomegaly
o Heparin is the drug that most commonly causes an ITP-like reaction is hospitalized patients (HIT=
heparin-induced thrombocytopenia). Others include sulfonamides, quinine, thiazides, cimetidine,
gold.
o Other causes of secondary thrombocytopenia SLE, CLL
- Laboratory Evaluation:
o Severe thrombocytopenia
o Smear can show megathrombocytes.
o Coagulation studies are normal

o Bleeding time is prolonged

Diagnosis:
o Bone marrow biopsy not usually indicated
- Treatment:
o Benign, self-limited disease that does not cause severe bleeding
o Does not affect outcome; only to increase platelets acutely
o Rarely indicated for platelet counts over 30, 000
o If indicated corticosteroids, IVIG, anti-D immunoglobulin
Usually for chronic ITP
o Avoid antiplatelet medications (NSAIDs, etc). Acetaminophen is safe
o 80% have spontaneous resolution within 6 months
o Splenectomy for those children > 4 years old or those with severe or chronic ITP (>1 year)
Thrombotic Thrombocytopenic Purpura
- Platelet Consumption:
o Congenital or acquired deficiency of enzyme necessary to cleave von Willebrand factor
o Congenital TTP is very rare and often fatal
o Usually found in previously healthy people ages 20-50 years
o More common in women and those with HIV
o Can be precipitated by estrogen use, pregnancy, drugs (quinidine, clopidogrel, and ticlopidine)
- Clinical Findings:
o May be jaundiced or pale
o Purpura, petechiae, pallor, abdominal pain, microangiopathic hemolytic anemia, fever
o CNS symptoms wax and wane over minutes
o May have significant renal disease
o Possibly pancreatitis
o Recurrent episodes are common
- Laboratory Evaluation:
o Severe thrombocytopenia
o Typically have schistocytes in circulation (red cell fragmentation)
o RBC destruction
o Negative Coombs test
o Markedly elevated LDH. Increased indirect bilirubin
o Coagulation tests are normal
- Treatment plasma exchange (emergency large-volume plasmapheresis)
o Prednisone and antiplatelet agents have also been used
Hemolytic Uremia Syndrome (HUS)
- Similar to TTP but found primarily in children (younger than 10 years), particularly after infection with E. Coli
0157:H7, Shigella sp., Salmonella sp., and various viruses
- Pregnancy and estrogen use may precipitate HUS in adults
- Similar to TTP but no neurologic findings
- More renal problems than TTP
- Same laboratory evaluation as TTP, but thrombocytopenia is less severe
- Treatment:
o In children, conservative management is usually all that is required. Fluids and electrolyte balance
o Treatment of adults is plasmapheresis
-

Internal Medicine Endocrinology

Hyperthyroidism
- Hyperthyroidism is defined as excess circulating thyroid hormone due to thyroid gland hyperactivity
- Thyrotoxicosis is a general term for excess circulating thyroid hormone (T3 or T4) from any cause. serum
TSH is suppressed in primary hyperthyroidism
- The condition is more common in women than men (8:1) and occurs in 2% of the U.S. society. Typical age
of onset is between 20-40 years old
- Graves disease is the most common cause of hyperthyroidism (80% of cases)
o Other causes toxic multinodular goiter (2nd most common cause), Hashimoto thyroiditis, pituitary
tumor, pregnancy, exogenous thyroid hormone, excessive dietary iodine intake, radiographic
contrast, and amiodarone use
- Graves disease is an autoimmune disease affecting TSH receptors. Some antibodies act like TSH to cause
secretion of thyroid hormone, whereas others stimulate glandular growth only. Diffuse, symmetric
enlargement and goiter may be seen
o Graves disease is associated with HLA markers and other autoimmune diseases
o Thyroid cancer can coincide with Graves disease
o Thyroid storm is an acute, life-threatening state of thyrotoxicosis that is most common in patients
with antecedent Graves disease
- The clinical features of thyrotoxicosis are manifestations of enhanced adrenergic activity
o Weight loss despite good intake may be seen
o Anxiety, warm and moist skin, onycholysis, and insomnia are common, as are fine tremor, fatigue,
muscle cramps, and weakness
o Women report menstrual irregularity
o 3% of patients with hyperthyroidism experience pretibial myxedema
- Cardiac presentations tachycardia, palpitations, forceful heartbeat, and PVCs
o Atrial fibrillation occurs in 8% of patients, with greater frequency in elderly men with ischemic or
valvular heart disease
- There may be a change in bowel pattern, menorrhagia, brittle hair, or heat intolerance.
- Diffuse, symmetrical thyroid enlargement and goiter may be seen
- A brisk hyperreflexia may be seen on examination of DTRs
- Graves disease is the only type of hyperthyroidism that is associated with inflammation of the eyes, upper
eyelid retraction, lid lag with downward gaze, swelling of the tissue around the eyes, and protrusion or
bulging of the eyes
o Infiltrative ophthalmopathy is seen in 20-40% of patients, but true exophthalmos is seen in only 5%.
The risk is higher with smokers
o Ophthalmopathy also occurs in persons with type I amiodarone-induced thyrotoxicosis
- Complications afib, hypercalcemia, osteoporosis, impotence, nephrocalcinosis, decreased libido,
gynecomastia, and decreased sperm count
o Chronic thyrotoxicosis may cause osteoporosis, clubbing, and finger swelling
o About 15% of Asian or Native American men with thyrotoxicosis may develop hypokalemic periodic
paralysis lasting 7-72 hours, often after IV dextrose, oral carbohydrate, or vigorous exercise
Hypokalemic periodic paralysis responds to propranolol, which normalizes the serum
potassium and phosphate levels and reverses the paralysis within 3 hours. Avoid IV
dextrose or oral carbohydrates. Therapy is continued with propranolol along with PTU or
MMI

Diagnostic Studies:
o Elevated triiodothyronine (T3) and free thyroxine (T4) levels
Elevations of T3 are more pronounced than T4
T4can be normal, which indicate T3 toxicosis which has a more favorable treatment
prognosis to antithyroid medication. T3 toxicosis is seen in early disease or relapse
o TSH levels are extremely low or undetectable in primary hyperthyroidism
o Peroxidase antibodies and thyroglobulin antibodies are positive in Graves disease but not toxic
multinodular goiter
o Radioactive iodine uptake study (which should NEVER be done in pregnant women or those with
laboratory-confirmed disease) shows increased uptake in Graves disease and toxic multinodular
goiter
Uptake is more diffuse and symmetric in Graves disease
o MRI and CT scanning of the orbits is performed for severe or unilateral ocular signs or when
causation may be other than Graves
Treatment:
o Beta-blockers (primarily propranolol) control symptoms (tachycardia, tremor, diaphoresis, anxiety,
palpitations)
The initial treatment of choice for thyroid storm and periodic paralysis
o The thiourea class of drugs (PTU, MMI)
PTU during pregnancy or breast-feeding
Both PTU and MMI cross placenta and affect fetal thyroid function, but PTU to a
lesser effect
PTU is associated with arthritis, lupus, aplastic anemia, thrombocytopenia, and hepatic
necrosis
MMI is generally preferred over PTU due to dosing convenience and less risk of fulminant
hepatic necrosis
MMI is associated with serum sickness, cholestatic jaundice, alopecia, nephrotic
syndrome, and hypoglycemia
Fetal anomalies = aplasia cutis and esophageal or choanal atresia
TSH levels should be checked 4-6 weeks after treatment is started
o Radioactive iodine ablation is used in older patients, those with PTU/MMI reaction or failure, or
poor compliance
Stop antithyroid medications 3-5 days prior to procedure
RAIU used to determine dosing
Improvement may be seen after 4-6 weeks
Almost 80% cured with 1 dose
At least 50% become hypothyroid within a year
Ablation is contraindicated in pregnancy/nursing as iodine is concentrated in fetal thyroid
tissue. It can also induce thyroiditis and swelling (life-threatening)
o Iodinated contrast agents provide temporary treatment and may be helpful in highly symptomatic
patients. T3 levels may drop by more than 50% in 24 hours
o Ophthalmopathy responds best to IV methylprednisolone but may respond to high-dose, tapered
prednisone treatment, particularly in nonsmokers
Retrobulbar radiation treatment or optic nerve decompression surgery may be indicated
o Atrial fibrillation is not likely to convert electrically while patient is hyperthyroid and should be
promptly treated
Digoxin may be used in large doses and beta-blockers with caution (especially in the
presence of cardiomyopathy or heart failure)

Anticoagulation with warfarin to prevent thromboembolism

Thyroiditis
- Hashimotos (chronic lymphocytic) thyroiditis is the most common thyroid disorder in the United States, and
may be associated with other autoimmune or polyglandular syndromes.
o Also the most common cause of sporadic goiter in children
o Affects 1% of population and 5% of those over age 65 years. Tends to be familial. More common
in women (6:1) and patients with hepatitis C
o Frequency is increased with excess dietary iodine supplementation and exposure to head and
neck radiation during childhood
o Certain drugs, such as amiodarone, interleukins, and interferon, are also associated with thyroiditis
o The thyroid is diffusely enlarged with firm, small nodules. Changes may be asymmetric
o It often progresses to hypothyroidism with detectable thyrotropin receptor-blocking antibodies and
antithyroid peroxidase
o Signs and symptoms are usually of hypothyroidism (more likely in smokers), but transient
thyrotoxicosis may occur
Usually not painful, although neck tightness occurs
Depression and chronic fatigue are common and may persist after treatment
Autoimmune xerostomia and keratoconjunctivitis may occur, as may mild myasthenia
gravis. It is also associated with IBD and celiac disease
o In elderly women (10% of cases), the gland is atrophic and fibrotic
o Testing involves screening for serum antithyroid peroxidase and antithyroglobulin antibodies, which
will confirm autoimmune disease. The increase in T4 is greater than that of T3. TSH levels are
suppressed
o Treatment requires lifelong replacement with thyroid hormone for hypothyroidism or large goiter,
with watchful waiting in others
- Subacute painful (granulomatous, de Quervains, giant cell) thyroiditis may present either with acute
symptoms or silently and accounts for about 5% of clinical disease
o Most common in young or middle-aged women
o A viral cause is suspected (coxsackie, EBV, mumps, measles, adenovirus, echovirus, influenza).
Incidence peaks in summer
o The thyroid gland is often tender. Fever, fatigue, dysphagia, and otalgia may be present and
persist for months
o Presents as an acute, painful glandular enlargement with dysphagia, low-grade fever, fatigue, and
malaise. Radiation of pain to the ears is common. Most common in young and middle-aged
women
o Thyrotoxicosis initially presents, follow by a period of hypothyroidism with resumption of euthyroid
within 12 months
Manifestations last from weeks to months and usually resolve within 12 months
o ESR is markedly elevated. Antithyroid antibody titers are low
o Treatment aspirin. Other treatment directed at symptoms (BB, iodinated contrast products)
Antithyroid medications and steroids have no proven benefit
- Postpartum thyroiditis occurs soon after parturition and usually resolves completely
o Manifests with hyperthyroidism 1-6 months after delivery and lasts for 1-2 months
o Treatment may not require therapy. Propranolol for cardiac symptoms
- Suppurative (infectious) thyroiditis is rare
o Fever, pain, redness, and a fluctuant neck mass are common in suppurative thyroiditis associated
with bacterial, fungal, or parasitic causes
Usually caused by gram-positive bacteria (S. aureus)
o Tender thyroid gland, fever, pharyngitis, and overlying erythema along with leukocytosis and
elevated ESR

o FNA with gram stain and culture is required

o Treatment antibiotic therapy and surgical drainage
- Riedels (invasive fibrous, woody, ligneous) is the rarest form
o Development of dense fibrous tissue in the thyroid gland
o There may be extraglandular fibrous involvement such as sclerosing cholangitis, retroperitoneal
fibrosis, and orbital pseudotumor
o Over 80% of cases are in females
o An asymmetric, hard, woody thyroid may be palpated
o RAIU is decreased in the involved areas of the thyroid gland, and thyroid antibodies may be
present in 45% of patients
o Diagnosis by biopsy (hard to differentiate from carcinoma)
o May respond to long-term tamoxifen treatment
- Drug-Induced (amiodarone)
o Contains iodine
o May cause a serum increase of T4 by 20-40% during the first month of therapy but causes cellular
resistance to T4
o A resultant hypothyroid picture ensues with elevated TSH and symptoms typical of hypothyroidism
- Ultrasonography helps distinguish thyroiditis from goiter or nodules and helps guide fine-needle biopsies of
suspicious nodules. Color-flow Doppler ultrasonography is used to distinguish thyroiditis from Graves
disease. Radioactive iodine uptake may also be helpful
o If TSH is low, assess patient for hyperthyroidism and undergo radionuclide thyroid scan
Cold nodules (no uptake) are hypofunctioning and require surgery
Hot nodules (increased uptake) are functional and thus carry a lower risk of malignancy
Hypothyroidism
- Common. Incidence is increased in iodine-deficient countries
- Second only to diabetes as the most common endocrine disorder in the United States
- Pathology most commonly starts in adulthood. It is usually autoimmune in nature, which causes antibodies
against TSH receptors, antiperoxidase, and thyroglobulin
o Associated with other autoimmune disorders (pernicious anemia, rheumatoid arthritis, SLE,
Sjgren, myasthenia gravis)
o The antiperoxidase and antithyroglobulin antibodies serve as disease markers, by the anti-TSH
antibodies actually cause disease
- Causes:
o Primary hypothyroidism accounts for 95% of cases
Autoimmune thyroid destruction (e.g., Hashimoto thyroiditis and end-stage Graves)
Hashimoto is the most common cause
Other causes of primary = iodine therapy causing gland shrinkage, surgical thyroidectomy,
iodine-deficient diet, amyloidosis, lymphoma, scleroderma, lithium, amiodarone,
interferon, and birth enzyme/hormone defects (rare)
o Secondary causes dont involve the gland itself pituitary or hypothalamic neoplasms, congenital
hypopituitarism, pituitary necrosis such as Sheehan syndrome, TSH or TRH deficiency (rare)
- Clinical Features:
o Weakness, dry or coarse skin, lethargy, slow speech, cold intolerance, eyelid edema, forgetfulness,
facial edema, constipation, coarse hair, weight gain, facial dullness, depression, anemia,
bradycardia, hyporeflexia
o A palpable, diffusely enlarged thyroid with fine nodules is often present
o Myxedema is a nonpitting fluid retention state due to mucopolysaccharide buildup. It most
commonly occurs in the pretibial area
o Hyponatremia may occur secondary to alteration in renal tubular sodium reabsorption

Increased risk of hypercholesterolemia and CAD

Anemia can result from iron deficiency or from chronic disease
There is decreased absorption of iron and folate as well as decreased GI motility
o Up to 30% of Down patients will have hypothyroidism
- Diagnostic Studies:
o The single best screening test is TSH (elevated)
o Normal or low-normal free T4 and TSH indicates a euthyroid state
o Low free T4 and elevated TSH indicates primary hypothyroidism
o Low free T4 and low or normal TSH indicates secondary hypothyroidism
o Normal free T4 and elevated TSH without symptoms indicate subclinical hypothyroidism
18% will develop overt hypothyroidism
o Presence of antithyroid peroxidase and antithyroglobulin antibodies in the serum confirms
autoimmune disease
o Imaging is not routinely required unless there is a concern for malignancy (i.e., nodularity)
- Treatment:
o Levothyroxine is a replacement T4. The T4 is converted into T3
Adjust dose every 4-6 weeks based on TSH value
o Asses patients for adrenal insufficiency and angina prior to initiating treatment
Start lower in elderly or coronary disease
o T4 needs increase in the third trimester of pregnancy and with some medications
o Once stable, check levels twice yearly
- Myxedema Crisis:
o Myxedema coma is life-threatening, severe hypothyroidism characterized by obtundation, CO2
retention, and coma
Coma does not need to be present
Altered mental status is the hallmark
High mortality, even with optimal treatment. Transfer to ICU
o Patients may exhibit severe hypothermia, hypoventilation, hyponatremia, hypoglycemia,
hypotension, rhabdomyolysis, and acute kidney injury
o Can be precipitated by sepsis, cardiac disease, respiratory distress, CNS disease, cold exposure,
drug use, or noncompliance with treatment
o Treatment thyroxine IV bolus
Consider hydrocortisone if adrenal insufficiency is suspected
o Patients are overly sensitive to morphine, which can lead to death
Diabetes Mellitus (Type I & Type II)
- A group of disorders characterized by disordered metabolism and inappropriate hyperglycemia. This may
be due to deficiencies in insulin secretion, inadequate response to insulin, or both
- Most patients with diabetes have type 1 (<10%) or type 2 (>90%)
o Rare types maturity-onset diabetes of the young (MODY), diabetes caused by mutant insulins
or insulin receptors, diseases of the exocrine pancreas, endocrinopathies, drug and chemical
induced diabetes, and other genetic syndromes.
- Insulin resistance syndrome (metabolic syndrome, syndrome X) is a constellation of hyperglycemia,
hyperinsulinemia, dyslipidemia (including elevated triglycerides and decreased high-density lipoprotein
[HDL]), and hypertension; it predisposes patients to coronary artery disease (CAD) and stroke. Patients also
may have hyperuricemia and abdominal obesity, as well as prothrombotic and proinflammatory states.
- Diabetic retinopathy is the leading cause of blindness among people in the U.S. who are older than 60 years
o Other ocular problems include premature cataracts and glaucoma
o
o

Diabetic nephropathy causes approximately of end-stage renal disease in the U.S. Patients with type 1
DM have a 30-40% change, whereas those with type 2 DM have a 15-20% chance of serious renal disease
Patients with diabetes have accelerated large vessel atherosclerosis, putting them at increased risk for
stroke and CAD. Large vessel atherosclerosis in diabetic patients also is the cause of at least half of the
nontraumatic lower extremity amputations in the U.S.
Also associated with cardiomyopathy
Diabetic peripheral vascular disease is caused by poor perfusion and inadequate delivery of nutrients.

Neuropathy is the most common complication of DM

o Commonly causes a characteristic peripheral symmetric polyneuropathy but may cause a
peripheral mononeuropathy or mononeuropathy multiplex
o Painful foot neuropathy may be physically and emotionally disabling
o Nerve damage also causes autonomic dysfunction, leading to erectile dysfunction, atonic bladder,
and delayed gastric emptying
- Skin changes associated with DM include candidal infections, slow wound healing, necrobiosis lipoidica
diabeticorum, and acanthosis nigricans
- Periodontal disease is more common in diabetic patients and is more severe with poor glucose control and
tobacco use
Type 1 Diabetes Mellitus
- Occurs most often in young people (before school age or near puberty) of normal or low weight, particularly
those of Scandinavian ancestry. Nonautoimmune type 1 disease occurs primarily in those of Asian or
African origin
- Little or no endogenous insulin secretion
o Plasma glucagon is elevated
o Pancreatic B cells fail to respond to stimuli and undergo autoimmune destruction. If untreated, this
is a catabolic state with ketosis
- Most type 1 DM is an autoimmune disease (90%) with 95% of patients having HLA-DR3 or HLA-DR4
antigens. HLA-DQ genes are even more specific, and 85% of patients have islet cell antibodies. 16 other
genetic regions related to risk have also been identified. It is estimated that genetic factors account for of
the susceptibility to DM and environment factors for
- Extrinsic factors hypothesized to affect pancreatic B-cell function include mumps and Coxsackie B4 virus
infection, toxic chemicals and destructive cytokines and antibodies
- The most common findings polydipsia, polyuria, nocturia, and rapid weight loss despite normal or
increased appetite, associated with a random plasm glucose of 200 mg/dL or greater
- Blurred vision is common. Pruritus, weakness, postural hypotension, paresthesias, and vulvovaginitis may
occur
- Untreated type 1 DM results in diabetic ketoacidosis, leading to anorexia, nausea, vomiting, dehydrations,
stupor, and ultimately coma. Fruity breath suggests ketoacidosis
- Laboratory Studies:
o Random plasma glucose of > 200 mg/dL with classic symptoms or fasting levels of 126 mg/dL on
more than 1 occasion is diagnostic
o Most patients with new-onset type 1 DM will have a severely elevated glucose, warranting no
further diagnostic study. Suspected cases can be confirmed by glucose tolerance testing
o Patients are likely to have glucosuria. They also may have ketonemia and/or ketonuria
o Hemoglobin A1 (glycosylated hemoglobin, HbA1) reflects glycemic control over the preceding 8-12
weeks. This test should not be used for diagnosing diabetes
HbA1c levels are highly specific and are used to follow treatment
Serum fructosamine reflects control over the preceding 1-2 weeks, resulting in more rapid
change than HbA1c. This test should be complementary to glycosylated hemoglobin and
not substitutive
o Patients should use portable glucometer to monitor control
o Well-controlled type 1 DM results in normal lipid values
o Patients with DM should also be closely monitored for risk of cardiovascular disease

Treatment:
o Diet is central to management
Manage according to activity level, food preferences, and need to attain/maintain ideal
weight
Patients with type 1 DM should follow a well-balanced diet and may apply the principles of
carb counting, often administering 1 U of short or rapidly acting insulin for each 10-15
grams ingested in addition to basal insulin needs
Carbs should comprise 45-65% of the diet, protein 10-35% of total daily calories,
and fat 25-35% with less than 7% saturated
Cholesterol should be limited to fewer than 33 mg/day or less
A diet high in soluble fiber improves glucose through slowed absorption and improves
cholesterol levels. Insoluble fiber improves colonic transit
Patients should coordinate meals and snacks with exercise and insulin administration
Artificial sweeteners appropriate for patients with diabetes include aspartame, saccharin,
sucralose, and acesulfame potassium
o Insulin may be delivered by subcutaneous injection, injector pens, or insulin pump
Glycemic response depends on depth of injection, injection site, proximity of site to
muscles being exercised, and ambient temperature
Regular insulin is absorbed most rapidly from the abdomen, but any site with loose skin
may be used. Analog insulins are less affected by site of injection
Human insulin causes markedly less antibody response than animal insulin and is
available in regular or neutral protamine hagedorn (NPH) formulations
Analog insulins rapid-acting (lispro, aspart, glulisine) and long-acting (glargine,
detemir)
Rapid-acting have a more rapid onset and a shorter duration of action than
regular insulin
Rapid-acting reach peak serum values in 60-90 minutes and have a 4-5 hour duration of
action. They may be taken 20 minutes before a meal
Regular insulin is short acting and is used an hour before meals. The effect appears in 30
minutes, peaks in 2-4 hours, and lasts for 5-8 hours. IV administration is useful in diabetic
ketoacidosis and in perioperative management of patients with diabetes
NPH insulin in a longer-acting form with onset of action in 1-3 hours, peak effect in 5-8
hours, and duration of action of less than 24 hours (ranges 12-24 hours), often requiring
two injections per day. NPH is often used in combination with regular or lispro (analog)
insulin for improved control
Basal insulins include glargine and detemir. Basal coverage is the background insulin
required for housekeeping functions and suppression of glucago
Glargine is given once a day for basal coverage, but cannot be mixed with other
human insulins due to its acidity. It lasts for about 24 hours without peaks
Detemir lasts for 12-24 hours and is relatively peakless. May be given daily or
twice daily for basal coverage
o Daily aspirin (81-325 mg) reduces the risk of diabetic atherothrombosis
o Careful foot care, moderate exercise, meticulous personal hygiene, and prompt treatment of
infections are imperative
o Pancreas transplant is becoming more common but is not considered standard therapy

Type 2 Diabetes Mellitus

- A heterogenous group of diseases. Occurs most often in middle-aged or older people, however it is
increasingly found in younger persons
- Overweight and obesity are the strongest contributing factors. Distribution of fat to the upper body is
associated with the highest risk, and exercise and weight loss decrease the risk
- Type 2 DM has a strong genetic component, but a specific gene has not yet been identified
- Accounts of more than 90% of diabetes cases in the U.S. and is found more often in African Americans,
Hispanics, Pima Indicans, and Pacific Islanders
- In type 2 DM, insulin levels are high enough to prevent ketoacidosis, but tissues are resistant. Impaired
pancreatic B-cell response to glucose also often is present. Resistance is increased with aging, sedentary
lifestyle, and abdominovisceral obesity
- Untreated type 2 DM can lead to hyperosmolar nonketotic states
- Many patients have polyuria and polydipsia. Ketonuria and weight loss are rare
- Also may present with fatigue, pruritus, recurrent candidal vaginitis, chronic skin infections, blurred vision, or
poor wound healing
- Many patients, particularly those who are obese, have few symptoms. DM is discovered during routing
laboratory testing. Distribution of the fat to the upper body is associated with increased risk measuring
waist-to-hip ratio is useful in monitoring treatment
- Women who have delivered LGA babies or had polyhydramnios, preeclampsia, or unexplained fetal loss are
at increased risk
- Laboratory Studies:
o The diagnostic criteria for type 2 DM are the same as those for type 1 DM
Random glucose > 200 mg/dL or fasting glucose 126 mg/dL on more than 1 occasion
Prediabetes = random glucose 140-199, or fasting glucose 100-125
o An oral glucose tolerance test may be needed in symptomatic patients, with fasting glucose levels
between 100-125 mg/dL
o HbA1c and fructosamine are used to monitor chronic control
o Diabetic dyslipidemia includes high triglycerides, low HDL, and alteration of LDL to smaller, denser
particles. It is very common in type 2 DM
o Impaired fasting glucose (glucose of 100-125 mg/dL in fasting state) and impaired glucose
tolerance (glucose of 140-199 mg/dL 2 hours after 75g oral glucose) are considered strong risk
factors for the development of type 2 DM. These individuals benefit most from primary prevention
efforts (diet, weight loss, exercise)
- Treatment:
o Individualize diet. In obese patients, goal should be weight loss may restore insulin
responsiveness
o Cholesterol, protein, fat, fiber, and artificial sweetener recommendations are the same as type 1
o Regular exercise is correlated with better glucose control
o Oral hypoglycemic agents potentiate insulin secretion
Most commonly used are sulfonylureas, which stimulate pancreatic B-cell insulin release
(glyburide, glipizide, glimepiride are second-generation agents with few drug interactions).
They are associated with weight gain and increased risk of hypoglycemia
Other, newer insulin-stimulating drugs are repaglinide and nateglinide, which are
associated with lower rates of hypoglycemia

o
o
o

o
o

Metformin reduces hepatic glucose production. First line (especially in obese with mild
disease). Decreases glucose levels by suppressing hepatic glucose production without the risk of
hypoglycemia, assists with weight loss, and decreases triglycerides
Contraindicated in patients at risk for lactic acidosis, those with serum creatinine > 1.5
mg/dL (males) or > 1.4 mg/dL (females), or abnormal creatinine clearance. Associated
with GI side effects (abate with time and are limited with medication titration)
A vitamin B12 deficiency may occur with longer term use this may be confused with
diabetic neuropathy
Thiazolidinediones (pioglitazone preferred) sensitize peripheral tissues to insulin. Can be used
alone or in combo. Reduce glucose without increasing the risk for hypoglycemia
Contraindicated in patients with CHF (especially stages 3 or 4) or liver disease
Rosiglitazone can cause cardiac disease
Pioglitazone is associated with bladder cancer
Both increase fracture risk
-glucosidase inhibitors (acarbose, miglitol) delay absorption of carbohydrate by blocking
intestinal -glucosidase enzyme, thereby decreasing postprandial glucose in the blood stream
Major side effects are GI symptoms
Duration of action is 4 hours
GLP-1 agonist, incretin mimetic (exenatide, liraglutide) lowers blood glucose via slowing of
gastric emptying, stimulating the pancreatic insulin response to glucose, and reducing glucagon
release after meals. Must be injected. Associated with weight loss.
Adverse effects include nausea and pancreatitis. Contraindicated in patients with
gastroparesis.
Liraglutide is associated with C-cell tumors in animals and may not be used in patients
with a history of thyroid cancer
Bydureon (exenatide) is contraindicated in patients with medullary thyroid carcinoma or
family history of MEN2
DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin) inhibits DPP-4, prolonging the
endogenous action of GLP-1 (aka slowing incretin metabolism), stimulating insulin
synthesis/release, and suppressing glucagon. It has a low risk of hypoglycemia and does not
cause nausea and vomiting. They are weight neutral
Serious allergic reactions (anaphylaxis, SJS) have occurred
Limited cases of pancreatitis and reports of urticaria/angioedema
Pramlintide is a synthetic analog of cell-produced amylin delays gastric emptying, suppresses
glucagon secretion, and decreases appetite
Injectable. Only approved for patients on insulin therapy
Approximately of patients with type 2 DM require insulin, either alone or in combo with other
agents. Basal insulin is recommended in patients who cannot be adequately controlled on other
medications or if the HgbA1c is higher than desirable despite treatment
Acceptable glucose levels are 70-130 mg/dL before meals and after an overnight fast, and 180
mg/dL at 1 hour and < 150 mg/dL at 2 hours postprandially
Daily aspirin (81-325 mg) reduces the risk of diabetic atherothrombosis. Careful monitoring and
treatment of BP to a goal of < 130/80 mmHg is essential. Hyperlipidemia should be treated with a
goal of less than 100 mg/dL LDL (or < 70 with cardiovascular risk factors) and greater than 50
mg/dL HDL
Careful foot care, moderate exercise, meticulous personal hygiene, and prompt treatment of
infections are imperative
Annual ophthalmologic exam to monitor for retinopathy

Annual urine albumin and serum creatinine is also recommended. Early identification and
treatment will reduce risk or slow progression of diabetic nephropathy
o Aggressive insulin management of a patient with not-so-tightly controlled type 2 diabetes while the
patient is hospitalized has been associated with increased morbidity. More research is needed in
this area
o Guidelines for hospitalized patients treated with insulin varies with degree of critical illness. Insulin
should be initiated in critically ill patients at the threshold of persistent hyperglycemia of less than
180 mg/dL with a glucose goal of 140-180 mg/dL. Non-critically ill patients should have insulin
titrated to limit premeal glucose levels to less than 140 mg/dL and random glucose levels to less
than 180 mg/dL. Hypoglycemia is to be avoided. Desirable glucose levels for all patients require
individualization
Diabetes Insipidus
- A disorder of water
- Insipid means tasteless, as opposed to sweet (mellitus)
- DI is caused by deficiency of or resistance to vasopressin (antidiuretic hormone, ADH)
- Serum osmolality is 285-295 mOsm/kg. At 295 mOsm/kg, maximum antidiuresis occurs; at 290 mOsm/kg,
thirst kicks in. Normal specific gravity is between 1.010 and 1.030. Insipidus may be closer to 1.00
- Primary DI may be familial (genetic) or sporadic
- Secondary DI is due to hypothalamic or pituitary pathology caused by tumor, anoxic encephalopathy,
surgery, accidental head trauma, infection, sarcoidosis, multifocal Langerhans cell granulomatosis, or
metastatic disease
- There are 4 types of DI. All manifest with polydipsia, polyuria, and a dilute urine. Hypothalamic (central)
and nephrogenic are more common.
o Neurogenic / Hypothalamic (or central) DI inability to produce and secrete vasopressin from the
posterior pituitary (levels will be low)
Commonly occurs after head trauma or brain surgery
May be inherited
May lack osmostat
Responds to desmopressin
o Nephrogenic DI kidneys that are unresponsive to normal vasopressin levels (levels will be high)
May be an inherited X-linked trait or acquired as a result of lithium therapy, hypokalemia,
hypercalcemia, or renal disease (chronic renal failure)
May be inherited
Abnormal receptors in the kidneys
No response to desmopressin
o Transient DI of pregnancy and the puerperium rapid destruction/breakdown of vasopressin
o Primary polydipsia disorder of thirst mechanism (ADH levels low)
- Physical findings are associated with the primary cause
- Polyuria (50-60 mL/kg/day), nocturia, and polydipsia are the main symptoms. Seizures may develop related
to the level of hypernatremia
- Intense thirst with fluid intake of 2-20 L/day, craving for ice water, and large-volume polyuria are most
common
o Other possible presentations = hypernatremia and dehydration
- Unremitting enuresis may be present in partial disease
- Diagnostic Studies:
o There is no single diagnostic test, and clinical judgement is needed
o Serum osmolality is high; urine osmolality is low
o BUN may be low. Uric acid may be elevated. Serum sodium can be normal or high depending on
compensatory fluid intake
o

Neurogenic (central) and nephrogenic DI can be distinguished by water deprivation and

desmopressin (1-deamino-8-D-arginine vasopressin) testing
If the test results in reduced urine output and resultant increase in urine osmolality, central
DI is diagnosed
If little or no change in urine osmolality results, it is most likely nephrogenic DI
o Urine osmolality < 250 mOsm/kg, despite hypernatremia, indicates DI
o MRI of the pituitary, hypothalamus, and the skull may reveal mass lesions
- Treatment:
o Neurogenic or central DI is best treated with parenteral or intranasal desmopressin acetate
Also the treatment of choice for DI associated with pregnancy and the puerperium
o Diuretics, chlorpropamide, or carbamazepine can be used in patients with mild disease
Some mild cases may require no treatment except adequate hydration
o Central and nephrogenic DI respond partially to HCTZ with potassium or amiloride
supplementation
o Nephrogenic DI may respond to indomethacin, either alone or in combination with HCTZ,
desmopressin, or amiloride
o Dietary measure, such as limiting salt and protein intake, can be helpful in nephrogenic DI
o With treatment, prognosis is good with no reduction in life expectancy
Addisons Disease (aka Adrenal Insufficiency)
- Adrenal insufficiency results when the physiologic demand for glucocorticoids and mineralocorticoids
exceeds the supply from the adrenal cortex. The pituitary secretes ACTH and associated melanocyte
stimulating hormone (MSH). ACTH stimulates the adrenal cortex to secrete cortisol. Cortisol has a negative
feedback on the pituitary to inhibit secretion of ACTH and MSH
- Primary adrenal insufficiency is due to adrenal gland failure, resulting in cortisol and aldosterone deficiency.
The most common cause of primary Addison is autoimmune destruction of the adrenal cortex (80% of
cases).
o Aka Addisons Disease
o Deficiencies of all 3 zones of adrenal cortex cortisol, aldosterone and adrenal androgens
o The most common cause is autoimmune destruction of the adrenal cortex (80% of cases)
o Can occur alone or as part of a polyglandular autoimmune (PGA) syndrome or genetic disorders
such as adrenoleukodystrophy
o Tuberculosis can be a leading cause in areas of prevalence. Calcification of adrenal glands in a
setting of symptoms is diagnostic
o Manifestations include weakness, dehydration, hypotension, anorexia, nausea, vomiting, weight
loss, and abdominal pain
o Hyperpigmentation of the skin and mucous membranes occurs as a result of uninhibited MSH
secretion in conjunction with ACTH
- Secondary adrenal insufficiency results from inadequate secretion of ACTH with resultant cortisol deficiency.
Secondary causes are pituitary based
o Deficiencies only in cortisol
Exogenous glucocorticoids = most common (discontinuation of long term therapy)
o Commonly see in patients on therapeutic doses of glucocorticoids.
o Usually caused by pituitary failure
o Aldosterone levels are not significantly affected because of regulation through the reninangiotensin system. Therefore, hyperpigmentation and hyperkalemia are not seen
- Congenital adrenal hyperplasia (CAH) results from enzyme deficiency in cortisol production
o Patients typically present in the first month of life with nonspecific symptoms of lethargy, vomiting,
poor feeding, and poor weight gain
o Examination reveals dehydration, hyperpigmentation, and, in females, clitoromegaly
o

Clinical Manifestations aldosterone AND cortisol problem

o Addisons disease begins insidiously with nonspecific problems fatigue, weakness, weight loss,
nausea, anorexia, abdominal pain, irritability/anxiety
It may coexist with other autoimmune disorders such as vitiligo
o Most patients have myalgias and arthralgias, emotional changes
o Many have GI symptoms
o Amenorrhea is common in females
o Many patients develop hypersensitivities
o Hyperpigmentation** (due to elevated ACTH, ONLY in primary disease) often seen in the skin folds,
pressure areas, and nipple areas
May produce diffuse tanning over non-sun-exposed skin; multiple freckles; and
hyperpigmentation of knuckles, elbows, knees, palmar creases, pressure areas such as
bra or belt lines, and nipple areas
o Vitiligo and pallor (white patches)
o Orthostatic hypotension**. Common. Systolic BP less than 110 mmHg found in 90% of patients
o Delayed DTRs
o Salt craving
o Small heart, hyperplasia of lymphoid tissues, scant axillary and pubic hair, hypogonadism
o Addisonian crisis hypotension, acute pain (abdomen, low back), vomiting, diarrhea,
dehydration, altered mental status. If untreated, can be fatal
Diagnostic Studies:
o Hyponatremia primary and secondary
o Hyperkalemia primary only
o Hypoglycemia
o Mild hypercalcemia
o Low BUN
o Neutropenia, mild anemia (normochromic, normocytic), relative lymphocytosis, and eosinophilia
may occur
o Mild acidosis
o AM Cortisol (8:00 am):
Normal reference 6-24 ug/dL
18 is a normal result rules out AI
3 g/dL is a positive result rules in AI
Accompanied by elevated of plasma ACTH (> 200 pg/mL)
Low levels of ACTH indicate secondary disease
o To distinguish between primary adrenal insufficiency from secondary, measure 8am Cortisol and
ACTH level. ACTH >100 = primary (adrenal gland failure)
Low levels of ACTH indicate secondary disease
o Cosyntropin Stimulation Test (ACTH) is also diagnostic
Diagnosis is confirmed with a suboptimal one hour cortisol response to cosyntropin. A
serum cortisol rise of < 20 g/dL after administration of cosyntropin is suspicious
o Antiadrenal antibodies will be present in 50% of patients. Antithyroid antibodies are found in 45%
of patients
o Serum dehydroepiandrosterone (DHEA) levels are < 1,000 ng/mL. A level higher than this
excludes Addisons disease
o Order adrenal CT or pituitary MRI
o CXR and abdominal CT scanning may be indicated for suspected secondary disease

The diagnosis of adrenal insufficiency can be difficult because the clinical features are nonspecific
o The diagnosis of primary adrenal insufficiency and CAH is based on the presence of the clinical
features and lab findings of hyponatremia, hyperkalemia, hypoglycemia, anemia, metabolic
acidosis, and prerenal azotemia
o All patients with adrenal insufficiency have low cortisol levels
o Secondary adrenal insufficiency will not have findings of hyperkalemia as there is not a deficiency
of aldosterone
- Treatment:
o Primary disease is treated with a combination of corticosteroids and mineralocorticoids. These
include oral hydrocortisone or prednisone and fludrocortisone acetate for its sodium-retaining effect
o DHEA may be given. Studies show improved well-being, increased muscle mass, and reversal of
femoral neck bone loss. Monitoring is needed for androgenic effects
o Patients must be fully informed about their condition as infections must be treated immediately and
aggressively along with treatment of the underlying disease with increased hydrocortisone dosing.
A medical alert bracelet or medal may be lifesaving
o Neonates with CAH are treated with NS 20 mL/kg for hypovolemia, hydrocortisone for
glucocorticoid/mineralocorticoid deficiency, and D10 for hypoglycemia
Cushings Disease
- CUSHINGS SYNDROME (hypercortisolism, cortisol excess) is the effects of excess cortisol on the body.
May be exogenous or endogenous.
o The exogenous form is caused by chronic excess glucocorticoid, most commonly from
corticosteroid drugs used to treated other diseases
o Overproduction of cortisol can be either ACTH-dependent or ACTH-independent
of cases arise from excessive autonomous adrenal cortical secretion and are ACTH
independent.
o Adrenocortical tumors and nonpituitary ACTH-producing tumors (most often small cell lung
carcinoma) may also cause Cushings syndrome
- CUSHINGS DISEASE (ACTH excess) is caused by excess secretion of ACTH by the pituitary, often
resulting from a small (<5 mm), benign pituitary adenoma (most often located in the anterior pituitary)
o The major cause of endogenous Cushings Syndrome. Most common in premenopausal women
o Normal regulation of cortisol is controlled by corticotropin-releasing hormone (CRH), which is
produced by the hypothalamus
o CRH stimulates ACTH, which stimulates cortisol secretion from zona fasciculata of adrenal cortex.
o Cortisol induces catabolism of fats and proteins and also has antiinflammatory effects.
- Hypercortisolism may present as obesity, HTN, and thirst and polyuria with or without glycosuria
o Obesity is centripetal, and extremities appear wasted
o Fat deposition also causes the characteristic buffalo hump, moon facies, and supraclavicular pads
(dorsocervical fat pads)
- The most specific signs are proximal muscle weakness and pigmented striae more than 1 cm wide.
o Striae are purple. Located on lateral abdomen, axillae, internal thighs
Patients may present with backache and headache
- Oligomenorrhea or amenorrhea and erectile dysfunction are common
- Disorders of calcium metabolism may cause osteoporosis, vertebral fractures, hypercalciuria, and kidney
stones. Avascular necrosis may occur
- Impaired wound healing, acne, easy bruisability, and superficial skin infections occur. Patients are
susceptible to opportunistic infections
o If ACTH dependent hyperpigmentation
- Psychiatric symptoms range from emotional lability to psychosis

Diagnostic Studies:
o First, determine cortisol excess using overnight dexamethasone suppression test (suppression to
< 5 g/dL excludes Cushing with some certainty)
In Cushings disease, the overnight dexamethasone suppression test will result in a
plasma cortisol of greater than 10 g/dL (< 5g/dL is normal)
o Additional testing includes a 24-hour urine collection for free cortisol and creatinine
Excretion of free cortisol in the urine of greater than 125 mg/dL in 24 hours is diagnostic,
as is greater than 95 mcg of cortisol per gram of creatinine
o Late night salivary cortisol assays may also be useful
o The cortisol excretion test and plasma cortisol test should be confirmed with a low-dose
dexamethasone suppression test. False positives are caused by rifampin, phenytoin, primidone,
phenobarbital, carbamazepine, fenofibrate, estrogens, and pregnancy
o Plasma ACTH of less than 20 pg/mL suggests adrenal tumor. Higher levels suggest pituitary or
ectopic production (making ACTH)
o MRI is preferred to identify pituitary tumors (especially in Cushings disease). CT may show
adrenocortical or other tumors. Somatostatin receptor scintigraphy is useful to detect occult tumors
o Hyperglycemia, impaired glucose tolerance, and hypokalemia (without hypernatremia) are not
unusual
o Consider workup for ectopic ACTH producers
SCLC, thymomas, and thyroid or pancreatic islet cell tumors
- Treatment:
o Treatment of Cushings disease is transsphenoidal resection of the pituitary adenoma and
hydrocortisol replacement.
An alternative is gamma knife radiosurgery. This is helpful if the tumor is well seen on
MRI and not near the optic pathway
Irradiation gives remission in 50-60% of nonresectable tumors
o In patients who fail surgery, bilateral adrenalectomy will eliminate Cushings. However, then
patients need lifelong glucocorticoid and mineralocorticoid replacement
Nelsons Syndrome continued enlargement of the adenoma due to lack of feedback
o Medical therapy before surgery can inhibit glucocorticoid synthesis. Mitotane, metyrapone, or
ketoconazole may suppress hypercortisolism. Parenteral octreotide suppresses ACTH in of
cases
o Adrenal inhibitors also can be used
Metyrapone and/or ketoconazole may suppress hypercortisolism
Parenteral octreotide suppresses ACTH in of cases
Pheochromocytoma
- A tumor of the adrenal medulla that produces excess catecholamines
- Follows the rule of 10s 10% malignant, 10% extra-renal, 10% bilateral, 10% familial
- Risk factors family history, MEN II syndrome, von Recklinghausens disease, von Hippel-Lindau disease
- Presents with uncontrolled HTN, palpitations, headache, episodic diaphoresis, flushing, anxiety
- Diagnostic Studies:
o Urine vanillylmandelic acid (VMA) and metanephrines
o Urine and serum epinephrine and norepinephrine levels
o Imaging CT, MRI, and MIBG scan to highlight norepinephrine analog
- Treatment:
o Surgical resection with perioperative alpha-blockade (i.e., phenoxybenzamine or prazosin) to
decrease catecholamine-induced vasoconstriction
Beta-blockers AFTER alpha-blockage, as unopposed stimulation of alpha-receptors can
lead to vasoconstriction and thus a possible hypertensive crisis

Main role of beta-blockers is to prevent tachycardia and arrhythmias

Hypoparathyroidism
- Acquired hypoparathyroidism is most commonly encountered following parathyroidectomy or thyroidectomy
o It may also be due to autoimmune disease, heavy metal toxicity (e.g., Wilson disease,
hemochromatosis), thyroiditis, or hypomagnesemia (chronic alcoholism)
o DiGeorge syndrome is a congenital cause of hypocalcemia arising from parathyroid hypoplasia,
thymic hypoplasia, and outflow tract defects of the heart
o Congenital pseudohypoparathyroidism results from a group of disorders characterized by
alterations in serum calcium related to resistance to PTH
- The hypocalcemia may cause tetany, carpopedal spasms, muscle or abdominal cramps, and paresthesias
as well as teeth, nail, and hair defects and hyperreflexia
o Chvostek sign is contraction of eye, mouth, or nose muscles, elicited by tapping along the course
of the facial nerve anterior to the ear
o Trousseau sign produces spasm in the hand and wrist with compression to the forearm
- Findings in patients with chronic disease include lethargy, anxiety, parkinsonism, mental retardation,
personality changes, and blurred vision caused by cataracts
- Diagnostic Studies:
o The hallmark is decreased PTH and adjusted serum calcium and increased phosphate levels.
Serum magnesium may be low
Hypomagnesemia may worsen symptoms
Alkaline phosphate will be normal
o EKG changes may include prolonged QT intervals and T-wave abnormalities
o Radiography may demonstrate chronic increased bone mineral density, especially in the lumbar
spine and skull
- Treatment:
o PTH is available for use in the treatment of osteoporosis but has not been approved for use in
patients with hypoparathyroidism
o Treatment should be directed at correcting the hypocalcemia with calcium and vitamin D.
Maintenance therapy includes oral calcium (1-2 g/day) and vitamin D preparations to keep
serum calcium at 8-8.6 mg/dL. Calcitriol is also used
Magnesium supplementation may be required
o Monitoring of treatment includes measurement of adjusted serum and urine calcium levels
o Phenothiazines and furosemide should be avoided because of the risk of further calcium loss
o Emergency treatment for tetany includes airway maintenance and slow administration of IV calcium
gluconate
o A subsequently administered formulation of recombinant human PTH (teriparatide) is effective,
extremely expensive, and only FDA-approved for severe cases that do not respond to other
measures due to the risk of osteosarcoma
Hyperparathyroidism
- There are 4 pea-sized parathyroid glands on the posterior aspect of the thyroid gland. These glands
secrete parathyroid hormone (PTH) and cause serum calcium levels to rise. The parathyroid gland
responds to low or falling calcium levels and thus mobilizes calcium from bones by osteoclast stimulation. It
also stimulated the kidneys to resorb calcium and increases GI absorption of calcium
- Benign parathyroid adenomas cause 85% of primary hyperparathyroidism. Parathyroid gland hyperplasia is
the cause in 15%. Carcinoma is rare and accounts for less than 3%
- Hyperparathyroidism is more common in women than men at a 2:1 ratio, and the incidence increases after
age 50 years
- Primary hyperparathyroidism is the most common cause of hypercalcemia in ambulatory patients, whereas
malignancy is the most common cause in hospitalized patients. Hypercalcemia is also common with renal
failure, milk-alkali syndrome, multiple myeloma, head-neck-lung cancers, sarcoidosis, tuberculosis,

medications (thiazides, calcium or vitamin D, lithium), Hodgkin lymphoma, adrenal insufficiency, prolonged
bed rest, and hyperthyroidism (secondary hyperparathyroidism)
In patients with chronic kidney disease, secondary hyperparathyroidism occurs due to hyperphosphatemia,
causing increased ionized calcium levels and decreased renal production of active vitamin D
Patients with MEN 1 (parathyroid, pituitary, pancreas) and MEN 2A (HPT, pheo, medullary cancer of thyroid)
have HPT involving multigland hyperplasia of the parathyroids
Mild hypercalcemia is likely to be asymptomatic
More severe hypercalcemia causes thirst, anorexia, nausea, vomiting, abdominal pain, constipation, fatigue,
anemia, weight loss, peptic ulcer disease, pancreatitis, HTN, and depressed deep tendon reflexes.
Stones, bones, groans, moans
o Renal loss of calcium and phosphate = kidney stones
o Bone loss from PTH = pain in bones
Cortical bone or diffuse bone demineralization; trabecular bone increase
Pathologic fractures, cystic bone lesions (jaw is most common)
o Increase GI absorption and abdominal cramps = groans
o Irritability, psychosis, and depression = moans
Patients may develop polydipsia and polyuria caused by hypercalcemia-induced nephrogenic diabetes
insipidus
Other findings include renal failure, pancreatitis, gastric ulcers, weakness, fatigue, anorexia, polydipsia, and
polyuria
Diagnostic Studies:
o Hypercalcemia of hyperparathyroidism is often identified on routine chemistry panels in
asymptomatic patients; abnormal screening studies should be repeated
o Adjusted serum calcium level >10.5 mg/dL and phosphate < 2.5 mg/dL with PTH >55 pg/mL
indicates a primary disorder
Adjusted total calcium = measured serum calcium (mg/dL) + [0.8 x (4.0 serum albumin
[g/dL])]
o Urine calcium excretion is usually low for the degree of hypercalcemia
o Elevated serum levels of intact PTH confirm hyperparathyroidism
o Elevated calcium with low PTH indicates secondary disorder such as malignancy
o Extreme elevations of both calcium and PTH indicate parathyroid cancer
o Imaging studies, including ultrasonography, CT, MRI, and sestamibi scan, are less useful in the
diagnosis of HPT but more helpful if surgery for parathyroid adenoma is anticipated
o All patients should be screened for familial benign hypocalciuric hypercalcemia with a 24-hour
urine for calcium and creatinine before treating for HPT
o Patients with low bone mineral density, normal serum calcium, and elevated PTh level should be
assessed for secondary HPT from vitamin D or calcium deficiency, hyperphosphatemia, or renal
failure
o EKG findings may include prolonged PR interval, shortened QT interval, bradyarrhythmias, heart
block, and asystole
Treatment:
o Patients with mild asymptomatic primary HPT may only need to keep active, avoid immobilization,
and drink adequate fluids
o Patients should avoid thiazide diuretics, large doses of vitamins A and D, and calcium-containing
antacids and supplements
o Monitoring includes a schedule of serum calcium and albumin levels, kidney function and urinary
calcium excretion, and bone density studies. Bisphosphonates may be a temporizing measure to
decrease serum calcium levels. Cautious administration of vitamin D may be indicated

IV hydration and bisphosphonates are recommended for acute hypercalcemic crisis. Furosemide
may promote urinary calcium excretion

Parathyroidectomy is indicated for symptomatic primary disorder. Hypocalcemia and transient

hyperthyroidism may occur postoperatively. Surgery is indicated in the presence of the following:
Symptomatic hypercalcemia (proximal muscle weakness, gait disturbance, atrophy,
hyperreflexia)
History of episode of life-threatening hypercalcemia
Adjusted calcium level more than 1 mg/dL above upper limit
Urinary calcium excretion greater than 400 mg in 24 hours (differentiate familial benign
hypocalciuric hypercalcemia)
Creatinine clearance < 60 mL/min
Bone density consistent with osteoporosis ( 2.5 SD below normal) or previous fragility
bone fracture
Age younger than 60 years
Osteitis fibrosa cystica
Nephrolithiasis
Pregnancy
Parathyroid carcinoma
Growth Hormone Excess / Acromegaly
- Etiology
o A generally benign pituitary adenoma, often >1 cm in diameter, stimulates GH release. The excess
GH stimulates release of insulinlike growth factor 1 (IGF-1) from the liver. Somatotroph-producing
tumors account for 10-15% of pituitary tumors
o Usually mixed cell tumors, they are often associated with PRL secretion (40%)
o Ectopic tumors (islet cell type) and MEN type I are uncommon causes of excess growth-hormone
releasing hormone (GHRH)
- Presentation:
o Gigantism occurs in children prior to closure of the epiphyses and causes excess growth of long
bones. It is extremely rare with only 100 cases to date
o Acromegaly causes enlargement and elongation of the hands, feet, and jaw as well as internal
organ involvement in adults. Onset is in the 30s so it does not affect the long bones
Affected individuals have an increased risk of DM (30%), HTN, and CAD
Other features doughy, moist handshake, macroglossia; carpal tunnel syndrome;
deep, coarse voice; obstructive sleep apnea; goiter; HTN and cardiomegaly; weight gain
and insulin resistance; arthralgias and arthritis; colon polyps; hyperhidrosis; cystic acne;
acanthosis nigricans; headaches; spinal stenosis; temporal hemianopsia; decreased
libido; erectile dysfunction; and menstrual abnormalities
At diagnosis, 10% have overt heart failure with dilated left ventricle and reduced ejection
fraction
- Diagnostic Studies:
o Screening with random serum IGF-1 may be done and, if normal for age, rules out acromegaly. If
elevated fivefold, it is highly suggestive of an adenoma. PRL levels are also measured because
GH-secreting tumors often cosecrete PRL
o A 75-g loading dose 1-hour glucose tolerance test will show failure of GH to decrease to less than
2 g.L
o Random measurement of GH is nor accurate as levels may fluctuate
o MRI is the imaging modality of choice; a negative scan virtually rules out a GH pituitary adenoma.
MRI will reveal a pituitary tumor in 90% of patients. Skull radiography often shows enlarged sell
and thickened skull. Radiography of hands or feet may reveal tufting of the terminal phalanges
o

Treatment:
o Somatostatin analogs (octreotide/lanreotide) are inhibitory and may decrease tumor size
o Dopamine agonists like cabergoline or bromocriptine suppress GH levels in some patients with
acromegaly who fail surgery
o Transsphenoidal microsurgery is most successful in patients with preoperative blood GH levels
below 50 ng/mL and with pituitary tumors no larger than 2 cm in diameter. The best measure of
surgical success is normalization of GH and IGF-1 levels
o Pegvisomant, a GH receptor antagonist, blocks hepatic IGF-1 production, thereby providing
symptomatic relief and normalization of IGF-1 in about 90%% of patients
o Acromegalic patients have increased morbidity and mortality from cardiovascular disorders and
progression of acromegalic symptoms
Hypocalcemia
- More common than hypercalcemia
- Can be found in a significant number of critically ill patients
- Commonly results from a chronic disease (most common cause is CKD) or hypoparathyroidism
o In the surgical patient, may occur after parathyroid or thyroid surgery
o Also seen in associated with severe pancreatitis, magnesium deficiency, and after massive blood
transfusion
- Although it typically presents in a mild, asymptomatic form, severe hypocalcemia can result in complete
cardiovascular collapse
- Symptoms dry skin, brittle nails, pruritus, muscle cramping, SOB, numbness and tingling of extremities
o Severe cardiovascular manifestations include syncope and angina
- Signs psoriasis, dry skin, and perioral numbness
o Cardiovascular signs wheezing, bradycardia, crackles, and a third heart sound
- Classic neurologic findings:
o Trousseau sign carpal tunnel spasm after BP cuff applied for 3 minutes to occlude the brachial
artery. This causes spasm of the muscles in the hand and forearm. The MCP joints flex, the DIP
and PIP joints extend, and the fingers adduct. A sign of latent tetany
o Chvostek sign spasm of facial muscle after tapping the facial nerve in front of ear/angle of the
jaw (masseter muscle). The facial muscles on the same side of the face will contract momentarily
(nose or lips twitch). A sign of nerve excitability (tetany)
o Others irritability, confusion, dementia, seizures
- Diagnostic Studies:
o Defined as a correct serum calcium level < 8.5 mEq/L\
Need to correct for low albumin
o Ionized calcium should also be measured. Magnesium, phosphate, albumin, LFTs, and other
electrolytes should be obtained
o Measure BUN and creatinine to assess kidney function
- Treatment:
o Treat emergent cardiovascular states
o Severe hypocalcemia should be replaced IV calcium gluconate or chloride
Once corrected, enteral therapy with elemental calcium is begun at 1-4 g/day
o Mild hypocalcemia can be treated on an outpatient basis with oral calcium and vitamin D
supplements
o May also need to replace magnesium in conjunction with calcium

Hypercalcemia
- Hypercalcemia is a significant elevation in serum calcium after adjustment for albumin level
- This is one of the most common disorders of calcium and phosphorus, especially in hospitalized patients
with malignancy (e.g., lung cancer, squamous cell carcinoma of the head, neck and esophagus, female
genital tract carcinoma, multiple myeloma, lymphoma, renal cell carcinoma)
o Other causes include vitamin D intoxication, hyperparathyroidism, and sarcoidosis
Increased PTH levels result in increased serum calcium and decreased phosphorus
o Other causes of enhanced bone resorption Pagets disease, pheochromocytoma,
hyperthyroidism, use of thiazide diuretics
- Severity of symptoms depends on the calcium level. Most are asymptomatic until serum calcium is greater
than 12 mg/dL. Symptoms also differ by the rapidity of onset of hypercalcemia, state of hydration, and
presence of any underlying malignancies
o Anorexia, nausea, constipation, polyuria, polydipsia, dehydration, change in level of consciousness
(lethargy, stupor, and coma)
o Signs of intravascular volume depletion (e.g., orthostatic hypotension and tachycardia) are frequent
- Diagnostic Studies:
o Serum calcium is high
The calcium level must be corrected for albumin levels
Corrected calcium = measure total calcium + [0.8 x (4 albumin)]
o CXR may reveal an underlying pulmonary mass
o Perform urinalysis for hematuria, an early sign of renal cell carcinoma
o ESR may be elevated in monoclonal gammopathy. Protein electrophoresis of serum or urine may
be needed to confirm the diagnosis
o A 24-hour urine collection must be done for calcium determination
An elevated urine calcium suggests malignant neoplastic or paraneoplastic process or
hyperparathyroidism
A decreased urine calcium suggests primary hyperparathyroidism
o Elevations of serum vitamin D levels are consistent with vitamin D toxicity
- Treatment:
o Isotonic saline should be used for volume repletion
Loop diuretics should be used if the patient is hypervolemic after volume repletion
o Bisphosphonates can also be considered in severe hypercalcemia
o Calcitonin reduces bone resorption and has an immediate effect. Lasts 48 hours. Can be
prolonged with concomitant corticosteroids
o Manage the underlying cause
Hyponatremia
- Hyponatremia is defined as a plasma sodium concentration of < 135 mEq/L
o Signs and symptoms may not occur until the concentration falls below 125 mEq/L
- Hyponatremia is the most common electrolyte disorder seen in the general hospital population secondary to
the use of hypotonic fluid administration
- Type is determined by the serum osmolality and volume status
o Hyponatremia with hypervolemia occurs in the setting of CHF, nephrotic syndrome, renal failure,
and hepatic cirrhosis
o Hyponatremia with euvolemia occurs with hypothyroidism, glucocorticoid excess, and SIADH
SIADH is defined as hypotonic hyponatremia, urine osmolality of > 100 mOsm/kg, normal
cardiac/hepatic/thyroid/adrenal/renal function, and the absence of extracellular fluid
volume deficit
Urine sodium is usually > 40 mEq/L
o Hyponatremia with hypovolemia occurs with renal or nonrenal sodium loss

Differential Diagnosis:
o Is the plasma osmolality between 280-295 mOsm/kg?
YES isotonic hyponatremia (paraproteinemia, hypertriglyceridemia)
o Is the plasma osmolality > 295 mOsm/kg?
YES hypertonic hyponatremia (hyperglycemia(
o Is the plasma osmolality < 280 mOsm/kg?
YES hypotonic hyponatremia and measure the urine osmolality
o Is the urine osmolality < 100 mOsm/kg?
YES excessive water intake (primary polydipsia)
o Is the urine osmolality > 100 mOsm/kg?
YES renal diluting ability and assess the ECFV
o Does the ECFV appear normal?
YES think endocrinopathies (hypothyroidism, glucocorticoid insufficiency), SIADH
(drugs, tumors, CNS disorders, nausea, pain, stress), a reset osmostat, potassium
depletion, or thiazide diuretics
o Is the ECFV decreased and the urine sodium increased (> 20 mEq/L)?
YES renal solute loss (diuretics, osmotic diuresis, Addison disease)
o Is the ECFV decreased and the urine sodium decreased (< 10 mEq/L)
YES think extrarenal sodium loss
o Is the ECFV increased and the urine sodium increased?
YES renal failure
o Is the ECFV increased and the urine sodium decreased?
YES edematous disorders (CHF, cirrhosis, nephrotic syndrome)
Symptoms correlate to the sodium concentration and may include lethargy, disorientation, muscle cramps,
anorexia, hiccups, nausea, vomiting, and seizures
Signs include weakness, agitation, hyporeflexia, orthostatic hypotension, Cheyne-Stokes respirations,
delirium, coma, or stupor
Diagnostic Studies:
o Serum sodium of < 135 mEq/L
o Plasma osmolality usually is decreased, except in cases of fluid redistribution due to
hyperglycemia or proteinemia
o Urine sodium is either increased or decreased depending on the cause
o If SIADH is suspected,, CT may be done to rule out a CNS disorder, and CXR may be done to rule
out lung pathology
Treatment:
o Treat hypovolemia on an inpatient basis, especially if symptomatic or if serum sodium is
<125mEq/L
Consider consulting a nephrologist and/or endocrinologist
o Treat underlying cause usually requires fluid restriction except in hypovolemic hyponatremia
where isotonic saline is the treatment
o Monitor volume status
o In severe symptomatic hyponatremia with a sodium < 120 mEq/L, hypertonic saline may be used
very cautiously
Overly rapid correction can cause cerebral pontine myelinolysis, resulting in neurologic
damage
Serum sodium levels should be checked hourly and neurologic status closely monitored

o
o

In chronic hyponatremia unresponsive to fluid restriction, demeclocycline may be used to induce

nephrogenic DI but may cause nephrotoxicity in patients with cirrhosis. Vasopressin antagonists
(conivaptan) may be considered in euvolemic or hypervolemic hyponatremia
Fluid restriction, a loop diuretic, and treatment of the underlying condition will suffice in those with
normovolemic or hypervolemic states

Hypernatremia
- In hypernatremia, the water content of body fluid is deficient in relation to sodium content (serum sodium >
145 mEq/L)
o There is either too much salt or not enough water
- Always accompanied by hyperosmolarity
- Hypernatremia generally results from either inadequate fluid intake or excess water loss
o Causes deficit of thirst, hypotonic fluid loss, urinary loss, GI loss, insensible loss, burns, diuretic
therapy, osmotic diuresis (hyperglycemia, mannitol administration), sodium excess, and diabetes
insipidus
- It occurs commonly in the elderly and may occur in infants with diarrhea
- Neurologic manifestations results from alterations in the brain water content and include thirst, restlessness,
irritability, disorientation, lethargy, delirium, convulsions, and coma
o Brain cell shrinkage may be substantial and can causes damage to the supporting vasculature
- Other findings dry mouth and dry mucous membranes, lack of tears and decreased salivation, flushed
skin, tachycardia, hypotension, fever, oliguria of anuria, hyperventilation, lethargy, and hyperreflexia
o In children, use of the clinical dehydration scale may further distinguish degree of dehydration
- Diagnostic Studies:
o Plasma sodium > 145 mEq/L
o Urine sodium is decreased if due to extrarenal losses and is elevated if due to renal losses or
sodium excess
Urine is concentrated with extrarenal losses and diluted with diabetes insipidus
o Diabetes Insipidus
Low urine sodium and polyuria usually indicate DI
Antidiuretic stimulation does not increase urine osmolality in nephrogenic DI
o Hyperosmolar coma may be indicated by elevated serum glucose, decreased urine output, and
increased urine osmolality
- Treatment:
o Hypernatremia should be treated on an inpatient basis
o Treat underlying cause
o Free water may be administered orally, which is the preferred roue, or IV or Sq, as a 5% dextrose
solution in water or saline
o Hypovolemia should be treated first (with isotonic saline or LR) and the hypernatremia second
o Dialysis should be implemented if sodium is greater than 200 mEq/L
o Use caution during treatment because rapid correction of hypernatremia can cause pulmonary or
cerebral edema, especially in patients with diabetes mellitus
Correction should not progress at a rate >0.5 mEq/L/hr, unless neurologic symptoms are
present
Pagets Disease of the Bone
- Osteitis Deformans
- A common condition manifested by one or more bony lesions having high bone turnover and disorganized
osteoid formation
o Involved bones become vascular, weak, and deformed
- Most common in the United Kingdom
- Usually in those >40 years and discovered incidentally

Cause is unknown, but may be genetic

Often asymptomatic
o Bone pain may be the first symptom
- Can involve just one bone (monostotic) or multiple bones (polyostotic) particularly the skull, femur, tibia,
pelvis, humerus
- The bones become soft, leading to bowed tibias, kyphosis, and frequent chalkstick fractures with slight
trauma
- If the skull is involved, patients may report headaches and large head (increased hat size)
- Deafness may occur
- Increased vascularity over the bones causes increased warmth and can cause vascular steal syndromes
- Diagnostic Studies:
o Serum alkaline phosphatase is markedly elevated (unless monostotic)
o Serum calcium and phosphate are normal
o Urinary hydroxyproline is elevated
o Screen for vitamin D deficiency
o On radiograph dense, expanded bones
Initial lesions are osteolytic with focal radiolucencies (osteoporosis circumscripta) in the
skull or advancing flame-shaped lytic lesions in long bones
- Complications:
o If immobilization occurs, hypercalcemia and renal calculi may develop
o Vertebral collapse may lead to spinal cord compression
o Increased vascularity may cause high-output cardiac failure
o Arthritis
o Cranial nerve palsies from impingement of neural foramina
o Deafness, tinnitus, vertigo
o Jaw involvement can cause tooth misalignment
o Osteosarcoma (rare)
- Treatment:
o Only treat if symptomatic, unless there is extensive involvement of the skull, long bones, or
vertebrae
o Bisphosphonates are the treatment of choice
Alendronate, risedronate, tiludronate, zoledronic acid
Treat until alkaline phosphatase normalizes, then give a 3 month break, and resume if alk
phos rises again
May get a first dose effect pain immediately after starting bisphosphonates
Flu-like symptoms are common
May also get osteonecrosis of jaw (rare)
Take with 8 oz glass of water (relatively contraindicated if esophagitis, strictures,
achalasia, hiatal hernia)
Do not lay down for 30 minutes after taking (risk of esophagitis)
Solitary Thyroid Nodule
- Common in the general population and affects women more than men
- Nodules must generally be over 1 cm in diameter to be palpated
- Most are asymptomatic and are discovered incidentally
- The presence of one palpable nodule increases the risk of additional nodules
- Only 5% of palpable nodules are malignant
- Thyroid adenoma is the most common benign nodule
o The nodule of adenoma is encapsulated, but the nodules of multinodular goiter are not
encapsulated

Bleeding into the nodule causes pain and enlargement

Types:
o Follicular adenoma is the most common type
o Papillary adenomas are very rare
o Hurtle cell has eosinophilic staining and has malignant potential

Workup difficult to differentiate between adenoma and thyroid cancer (true adenomas are NOT cancer
precursors)
o If the TSH is low, the patient should be assessed for hyperthyroidism and undergo radionuclide
thyroid scan
Cold nodules (no uptake) are hypofunctioning and require surgery
Hot nodules (increased uptake) are functional and, therefore, carry a lower risk of
malignancy
o High-resolution ultrasonography is the most sensitive test to detect thyroid lesions, determine size
and structure, and assess diffuse changes in the gland.
Ultrasonography is preferred over CT scan due to higher accuracy, lower cost, and lack of
radiation
o Malignancy is suspected in the presence of irregular or indistinct margins, heterogenous
echogenicity, intranodular vascular margins, microcalcifications, complex cyst patterns, or size
greater than 1 cm
Lesions suspicious for malignancy should undergo ultrasound-guided FNA.
Approximately 75% of FNA of solitary nodules show benign lesions
o All thyroid nodules need periodic monitoring. In benign lesions, T4 replacement is shown to
decrease nodule size by 20%. If no response to T4 therapy and the patient is euthyroid, the T4
therapy can be discontinued
Thyroid Cancer
- Thyroid cancer is more common in women (3:1), but prognosis is worse in men
- About 9% of thyroid cancers are fatal. most remain microscopic and indolent
- Prognosis depends on staging, with a 99% 5-year survival with locally confined, < 1.0 cm diameter papillary
carcinoma
- Types:
o Papillary type is the most common (76%) but least aggressive and spreads by local extension.
They are caused by genetic mutation or translocation
o Follicular type (16%) often metastasizes to lung, bone, brain, and liver
o Anaplastic type (1%) is seen in the elderly and is the most aggressive, often causing dysphagia or
vocal cord paralysis
o Medullary type (4%_) is distributed as sporadic, familial, and associated with MEN
syndrome
These tumors may cause symptoms from their possible secretion of calcitonin,
prostaglandins, serotonin, ACTH, and other peptides
o Thyroid lymphoma and other malignancies represent 3%
- Risk factors childhood irradiation to the head and neck (25x increase in thyroid cancer, may emerge 1040 years postexposure), family history, Gardner syndrome, MEN type II syndrome
- Presentation and Treatment:
o Painless neck swelling and a palpable, single firm nodule is the most common presentation
o Ultrasonography is routinely performed. RAIU may be helpful to assess risk of malignancy and
help plan the surgical approach
o PET scanning is particularly useful in detecting thyroid cancer metastases with limited iodine
uptake
o Surgical resection is indicated
RAI ablation may be useful for residual disease
Patients require T4 replacement for life
-

Pituitary Adenoma
- Can cause several endocrine disorders
- Hypopituitarism
o Pituitary adenomas are usually sporadic, but are sometimes part of MEN 1. This type usually
secrete prolactin, GH, or both, and are more aggressive than sporadic adenomas
- Pituitary tumors rarely cause diabetes insipidus
- Acromegaly is nearly always caused by a pituitary adenoma (stimulates GH release, and thus GH excess)
o These tumors may be locally invasive, particularly into the cavernous sinus
o Less than 1% are malignant
o Most are macroadenomas (> 1cm in diameter)
- Hyperprolactinemia that are non-gestational can be caused by PRL-secreting adenomas (more common in
women)
o Most are microadenomas (< 1cm in diameter)
- Cushing Disease = hypercortisolism due to ACTH hypersecretion by the pituitary, is usually caused by a
benign pituitary adenoma that is typically very small (< 5mm) and usually located in the anterior pituitary
(98%) or posterior pituitary (2%)
- TSH hypersecretion by the pituitary may be caused by a tumor, and is a rare cause of hyperthyroidism

Internal Medicine Infectious Disease

HIV Infection
- A human retrovirus that requires reverse transcriptase for replication
- The highest prevalence is in Central and East sub-Saharan Africa
- HIV infects all cells containing the T4 antigen, primarily the CD4 helper inducer lymphocytes
o The result is a disordered function of the immune system
o HIV attaches to the T4 antigen, replicates, and causes cell fusion or cell death
o Macrophages serve as a reservoir of virus and promote its dissemination to other organs
- HIV is transmitted through bodily fluids. Risks include sexual contact, parenteral exposure (blood or blood
products, including injection drug use and occupational exposure), and perinatal exposure
- Clinical Features:
o The acute HIV syndrome is infrequently identified. It is a cluster of nonspecific findings similar to
EBV infection. Some patients may develop persistent generalized lymphadenopathy without
symptomatic HIV disease
o A syndrome of nonspecific and specific diagnoses. Can be progressive and insidious or rapidly
fatal. The time from infection to symptomatic disease averages 10 years but is quite variable
o Systemic manifestations = fever, night sweats, weight loss. The wasting syndrome is a result of
increased metabolic rate and decreased protein synthesis. Disproportionate loss of muscle mass
o Immunodeficiency causes infectious and malignant disease at any site. Common sites include the
lungs, upper respiratory system, lymph system, CNS, PNS, mouth, GI tract, eyes, and skin
o AIDS is defined as a CD4 count below 200 cells/L or the development of an AIDS indicator
disease. A diagnosis of AIDS can be made without laboratory evidence of HIV infection
o Opportunistic infections and malignances develop as the CD4 count drops. Few patients in the
United States develop opportunistic infections or malignancies because of the success of highly
active antiretroviral therapy
o The current WHO classification system is based on symptoms:
Stage 1 asymptomatic disease
Stage 2 minor symptoms
Stage 3 moderate symptoms
Stage 4 AIDS
o In general, as the CD4 count decreases, the viral load increase, and symptoms of infections and
malignancies become more frequent and severe
- Laboratory Studies:
o Screening for HIV infection detects antibodies
o Two ELISA tests followed by a confirmatory Western blot analysis confirm HIV infection with a
sensitivity of greater than 95%
o Most patients develop antibodies within 6 months of exposure
o Persons at high risk for infection, patients in all health care settings, and all pregnant women
should be tested for HIV
Testing is recommended after notifying patient that it will be done unless patient opts out
Written separate consent is no longer recommended by the CDC
o Other laboratory findings anemia, leukopenia, thrombocytopenia, polyclonal
hypergammaglobulinemia, hypercholesterolemia, cutaneous anergy
o CD4 count decreases as the illness progresses. For the best accuracy, measure it at the same
time of day and by the same laboratory
o If CD4 > 350, can have levels measure every 6 months. Otherwise, measure every 3 months or
with any change in patient status
o Risk of disease progression increased with a CD4 count < 200 or CD4 lymphocyte % of < 20%

The viral load is a measure of actively replicating virus, which correlates with disease progression
Changing viral loads may also support treatment response
- Treatment
o Primary prevention is essential safe sex (latex only barrier methods), drug rehab, screening of
blood products, universal precautions in health care delivery
o Secondary prevention antiretrovirals and chemoprophylaxis. Screen patients for diseases such
as TB and other infections. Counsel on ways to maintain health and prevent spread of the virus
o Postexposure prophylaxis can be offered to those with a high probability of exposure, including
healthcare workers who sustain occupational injuries. PEP should be started within 72 of exposure
The chance of contracting HIV from a needlestick injury involving a patient with known
HIV disease is 0.3%
Counsel healthcare workers who sustain an injury. Testing should be done on the
healthcare worker and the patient
Retesting is recommended in 6 weeks, 3 months, and 6 months
Antiretroviral therapy is an option. The decision to begin therapy should be made by the
patient. Combination therapy with drugs from different classes should be continued for at
least 4 weeks. Full-course PEP reduces the change of HIV transmission by up to 70%
o Treat pregnant women with antiretrovirals during pregnancy, labor, and deliver. HIV can also be
transmitted through breast milk
o Drug treatment of HIV includes antiretroviral therapy and treatment of or prophylaxis against
opportunistic infections and malignancies
Combination antiretroviral treatment is based on CD4 count, viral load, and overall patient
status (nutrition, compliance, access, and acceptance of therapy)
Goal is suppression of the viral load. A rising or persistently high viral load, clinical
progression, or continued immunologic deterioration signals treatment failure
Prophylaxis against opportunistic infections and malignancies is based on the likelihood of
developing disease as judged by the CD4 count and viral load. Discontinuation of
prophylaxis after a sustained response to HAART must be considered
Candidiasis
- Candida albicans is the most common form of pathogenic Candida sp. It is part of the normal flora of
human hosts and is an opportunistic pathogen
- Risk factors neutropenia, recent surgery, chronic illness (especially diabetes mellitus), broad-spectrum
antibiotic therapy, IV catheterization (especially TPN), chemotherapy or corticosteroids, injection drug use,
and cellular immunodeficiency (such as in HIV disease)
- Cutaneous disease:
o Diaper dermatitis. This does not indicate immune deficiency in newborns. The diaper area is red,
with defined margins. Pustules, vesicles, papules, or scales may be seen, and satellite lesions are
characteristic
o Children and adults (particularly adults with diabetes) may develop candidal dermatitis in dark,
moist ares (axillae, under breasts or large panniculus), especially if the immune system is stressed.
Lesions have distinct borders, and satellite lesions are common
o Treat with topical antifungal cream
- Mucosal disease of the mouth and esophagus:
o Oral mucosal candidiasis (thrush) causes white plaques that can be scraped off, revealing
reddened mucosa. In denture wearers, infection may manifest as a painful red palate
o Esophagitis is heralded by odynophagia and pain on swallowing. Symptoms resemble GERD
o Treatment is with oral fluconazole, itraconazole, or amphotericin B if recurrent or recalcitrant
- Vulvovaginal disease occurs in 75% of females at least once during their lifetime
o Risk factors age extremes, pregnancy, uncontrolled diabetes mellitus, corticosteroids, HIV
o

o
o
o

Symptoms pruritus, burning, dyspareunia, and a white, cottage cheese or curd-like discharge
Physical exam reveals white plaques on vaginal walls
Treatment is with topical azoles or oral fluconazole

Candidal fungemia can be life-threatening

o It occurs in very ill patients with indwelling instrumentation. Any suspect catheters should be
removed
o IV amphotericin B is recommended. The mortality rate is > 40%
o If disseminated disease develops (positive blood cultures; retinal lesions; or infection of the dermis,
brain, meninges, or myocardium), flucytosine should be added. Alternatively, fluconazole can be
tried
- Hepatosplenic candidiasis occurs in patients with very low WBC counts, such as those with leukemia
o With aggressive chemotherapy, the WBC count begins to rise, and the patient develops fever, RUQ
pain and tenderness, and nausea
o An increase in alkaline phosphatase and multiple low-density defects in the liver, spleen, and
kidneys develop. The diagnosis is confirmed with biopsy
o Treatment is amphotericin B.
Once the patient is responding, he or she can be switched to fluconazole
- Endocarditis occurs through direct inoculation at surgery, in injection drug users, or in late-stage HIV
disease
o Approximately 50% of cases involve nonalbicans Candida sp. and are resistant to treatment.
These organisms cause large vegetations
o Splenomegaly, petechiae, murmur, and large vessel embolization are common
o Treatment is amphotericin B, but infected valves must be surgically replaced. Once the patient has
recovered, he or she typically will receive lifelong fluconazole
Cryptococcus
- Cryptococcus neoformans is an encapsulated, budding yeast found in soil contaminated with dried pigeon
dung
- Transmitted through inhalation and causes illness in patients with cellular immune deficiency, such as HIV,
cancer, or long-term corticosteroid therapy
- Pulmonary disease may develop in patients with COPD, chronic steroid use, or posttransplant. Fever,
cough, and dyspnea occur
o CXR reveals nodules or pneumonitis
- Cryptococcal CNS disease causes headache and meningeal signs. It occurs with a CD4 count of less than
50 cells/L. Patients exhibit mental status changes and cranial nerve or visual abnormalities
- Cryptococcoma is a rare, intracerebral mass lesion that causes obstructive hydrocephalus
- Disseminated disease, although rare, may affect the skin, prostate, osteoarticular surfaces, eye, lymph
tissue, or other sites
- Diagnostic Studies:
o CSF shows variable pleocytosis (predominantly lymphocytes), increased opening pressure,
increased protein, and decreased glucose
o Budding, encapsulated fungus may be isolated on culture
o Cryptococcal antigen can be detected in CSF and serum. India ink stain or serology with latex
agglutination assay or cryptococcal antigen assay (CRAG) is helpful
o CT or MRI is indicated if cryptococcoma is suspected
- Treatment:
o In patients with HIV, oral fluconazole is continued for 10 weeks. In severe infections, amphotericin
B can be given for the first 2 weeks, followed by oral fluconazole. Flucytosine may be added in
severe disease. Lifelong fluconazole therapy is recommended
o In non-HIV immunocompromised patients, the mortality rate is much higher. Treatment is
amphotericin B

Histoplasmosis
- Histoplasma capsulatum is a dimorphic fungus found in soil infested with bird or bat droppings
- It is endemic to many areas and is transmitted by inhalation
- Most infections are asymptomatic or mild and unrecognized. Patients with cellular immunodeficiency are at
risk for symptomatic infections
- Acute histoplasmosis occurs in epidemics when soil is disturbed. Patients are prostrate and febrile, with few
pulmonary complaints
- Progressive disseminated histoplasmosis may be fatal within 6 weeks. Patients complain of fever, dyspnea,
cough, weight loss, and prostration. Ulcers may develop in the mouth, pharynx, liver, spleen, adrenals, and
elsewhere
- Chronic progressive pulmonary histoplasmosis occurs in older patients, especially those with COPD. It
manifests as chronic progressive pulmonary changes with calcified nodes and pericarditis
- Disseminated disease occurs in immunocompromised patients, especially in those with late-stage HIV
disease. It more likely represents reactivation rather than a new acute infection
o Highest risk is with CD4 count of less than 100 cells/L. Patients develop fever and multiorgan
failure. Fulminant disease, septic shock, and death are common
o CXR shows miliary infiltrates
- Diagnostic Studies:
o Anemia of chronic disease and increased alkaline phosphatase, LDH, and ferritin are seen in the
severely ill. A pancytopenia may also develop
o A urine antigen assay can confirm the presence of disseminated disease
o Bronchoalveolar lavage may be helpful in patients with chronic pulmonary disease
- Treatment:
o Itraconazole orally for weeks to months is recommended
o Amphotericin B is recommended for patients who cannot tolerate or fail itraconazole therapy or in
patients with meningitis or severe disease
o Lifelong suppressive therapy with itraconazole is recommended for the immunocompromised
Pneumocystis
- Pneumocystis jirovi pneumonia (PJP, formerly known as Pneumocystis carinii pneumonia [PCP])
- Caused by a fungus found in the lungs of humans and many animals
- Evidence of infection can be found in almost all persons by a young age. It is probably transmitted through
the air and lies latent in the alveoli
- Premature or debilitated infants in underdeveloped areas are infected during epidemics
- Sporadic cases are found in patients with abnormal cellular immunity, which is caused by factors such as
cancer, severe malnutrition, immunosuppressive drugs, irradiation, or in those with HIV/AIDS and a CD4
count < 200
- PJP is the most common opportunistic infection in HIV disease
- Typically, PJP disease presents with fever, SOB, and a nonproductive cough
- Physical exam findings are disproportionate to imaging results, which show diffuse interstitial infiltrates that
may be heterogenous, miliary, or patchy
o Between 5-10% of patients have a normal CXR
- Less commonly, patients may present with a spontaneous pneumothorax. Recurrent pneumothorax is
related to previous pentamidine use
- Patients also may develop fatigue, weakness, and weight loss. Infection is likely to recur without treatment
of the underlying disease or chemoprophylaxis
- Diagnostic Studies:
o Blood gas reveals hypoxia, hypocapnia, and reduced carbon dioxide diffusion
o LDH typically is increased
o WBC count is usually low

The organism can be demonstrated with specific stains of induced sputum or via bronchoalveolar
lavage
- Treatment:
o Empiric treatment is recommended for immunocompromised patients presenting with cough or
dyspnea. The drug of choice is TMP-SMX
Patients often get worse at the start of treatment. Steroids are added if the partial
pressure of oxygen in arterial blood (PaO2) is < 70 mmHg to prevent the deterioration and
promote oxygenation
Hypersensitivity reactions to TMP-SMX (likely because of the sulfa component) manifest
with fever, rash, malaise, neutropenia, hepatitis, nephritis, thrombocytopenia, and
hyperbilirubinemia. Systematic desensitization often is successful
o Dapsone is an alternative treatment and is as effective as TMP-SMX. It is more expensive than
TMP-SMX, but it is a good choice for patients who are sensitive to sulfa.
Side effects anemia, rash, fever
Do not taken with didanosine
o Alternatively, pentamidine can be used with IV or IM. Nebulized pentamidine can be used to
prevent PJP
Side effects rash, neutropenia, abnormal liver function, serum folate deficiency,
calcium imbalance, hypoglycemia or hyperglycemia, hyponatremia, and nephrotoxicity
Rarely, fatal pancreatitis occurs
o Atovaquone is reserved for patients who cannot tolerate TMP-SMX or pentamidine. It must be
taken with a fatty meal and causes mild to minimal side effects
o Once a patient is successfully treated for PJP, prophylaxis is continued. All patients with a CD4
count < 200 should receive prophylactic treatment
TMP-SMX is the drug of choice
Botulism
- Clostridium botulinum, a strictly anaerobic, spore-forming bacillus found in the soil, may inadvertently be
packed in food (home canned, smoked, or commercial), where toxin is produced and stored until ingested.
- Botulinum toxin inhibits the release of acetylcholine a the neuromuscular junction
- Infant and wound botulism result from exposure to the bacteria or spores and elaboration of the toxin in vivo
- Injection drug users are at increased risk of wound botulism
- Infants should not be fed honey because of the increased risk of botulism
- The initial clinical symptom is visual changes, including diplopia and loss of accommodation. Manifestations
typically appear 12-36 hours after ingestion
- Additional manifestations ptosis; impaired extraocular muscle movements; fixed, dilated pupils; cranial
nerve palsies; dysphonia; dry mouth; dysphagia; nausea; and vomiting
- Mental status changes or sensory deficits do NOT occur
- Respiratory paralysis ensues and, unless mechanical assistance is provided, death results
- Diagnostic Studies:
o The toxin can be identified using specific antiserum after mouse inoculation with the patients
serum
- Treatment;
o Botulinum antitoxin is available through the CDC
The CDC will also assist with obtaining assays of serum, stool, or suspect food
o Respiratory failure necessitates intubation and mechanical ventilation. If dysphagia persists, IV
nutritional support and hyperalimentation are required
o

Chlamydia
- Chlamydiae are a large group of obligate intracellular parasites, including Chlamydia psittaci (psittacosis),
Chlamydia pneumoniae (respiratory infections), and Chlamydia trachomatis (trachoma, inclusion
conjunctivitis, pneumonia, and genital infections)
- Clinical Findings:
o Lymphogranuloma venereum starts with a vesicular or ulcerative lesion, which may go unnoticed
The infection spreads to the lymph nodes, causing inguinal buboes. These may fuse and
break down, resulting in multiple draining sinuses and scarring
Anorectal disease causes tenesmus, discharge, and fistulae
o Urethritis and Cervicitis
In males, infection with Chlamydia is the most common cause of nongonococcal urethritis.
Discharge is less painful than with gonococcal urethritis and usually is watery
Females typically are asymptomatic or may develop cervicitis, salpingitis, or PID.
Infection with Chlamydia is a leading cause of infertility
- Laboratory Studies:
o Diagnosis is typically established clinically and is presumptive. Gram stain is negative
o Complement fixation test or immunofluorescence, ELISA, or DNA probes (nucleic acid
amplification) may help to confirm the present of the disease
- Treatment azithromycin, doxycycline, and erythromycin are effective. Erythromycin is the drug of choice
in pregnant women. All partners should be treated
Cholera
- Vibrio cholerae produces a toxin that activates adenylyl cyclase intestinal epithelial cells of the small
intestine. This results in hypersecretion of water and chloride ion and a massive diarrhea. Death results
from hypovolemia
- Epidemics of cholera occur in times of war, overcrowding, and famine, and where sanitation is inadequate.
- Infection results from ingestion of contaminated food or water
- A sudden onset of severe, frequent, rice water diarrhea (gray, turbid, and without odor, blood, or pus);
dehydration, hypotension, and electrolyte imbalance develop rapidly
- Diagnostic Studies:
o Stool cultures are positive for V. cholerae
o Serum agglutination tests are available
- Treatment:
o Replacement of fluids and electrolytes is essential. Oral rehydration with water containing salt and
sugar is adequate for mild or moderate cases (1 tsp salt, 4 tsp sugar, 1 cup water). Severe cases
require IV replacement
o Antibiotics will shorten duration and reduce severity of symptoms, but rehydration is vital to
survival. Antibiotics should be reserved for the severely ill or those with serious comorbidities
o Tetracycline, ampicillin, chloramphenicol, TMP-SMX, and fluoroquinolones are effective.
Resistance exists, so susceptibility testing is encouraged
o The key to prevention is clean water and food sources as well as proper waste disposal. A vaccine
is available, but protection is temporary, with boosters needed every 6 months
Diphtheria
- Corynebacterium diphtheriae is transmitted via respiratory secretions. The organism has a propensity for
mucous membranes, especially the respiratory tract
- It produces an exotoxin that causes myocarditis and neuropathy
- Nasal infection produces few symptoms other than nasal discharge
- Laryngeal infection causes upper airway and bronchial obstruction
- Pharyngeal infection is the most common form. A tenacious gray membrane covers the tonsils and pharynx,
and patients complain of mild sore throat, fever, and malaise
- Myocarditis and neuropathy involving the cranial nerves may develop

o Untreated cases exhibit toxemia and prostration

Diagnosis is clinical.
o Culture will confirm
- Treatment:
o A horse serum antitoxin must be given in all cases of diphtheria. It is obtained from the CDC
o Airway obstruction may necessitate removal of the membrane via laryngoscopy
o Penicillin or erythromycin is effective. Azithromycin or clarithromycin is an effective alternative
o Patients should be isolated until three negative pharyngeal cultures are documented
o Contacts should be treated with erythromycin to eradicate carrier states
- Diphtheria toxoid is available as a vaccine (DTaP, Td). Unimmunized persons who are exposed to
diphtheria should receive active immunization and antibiotic therapy
Gonococcal Infections
- Neisseria gonorrhoeae is a gram-negative intracellular diplococcus that is transmitted during sexual activity.
The highest incidence is found in 15-29 year olds
- The incubation period is 2-8 days after exposure
- Men:
o Men complain of burning on urination and a serous or milky discharge. 1-3 later, urethral pain is
more pronounced, and discharge becomes yellow, creamy, profuse, and can be tinged with blood
o Without treatment, the infection may regress and become chronic or progress to involve the
prostate, epididymis, and periurethral glands with acute, painful inflammation. This may progress
to chronic infection, resulting in prostatitis and urethral strictures
- Women:
o Women often remain asymptomatic or may develop dysuria, urinary frequency and urgency, and a
purulent urethral discharge. Vaginitis and cervicitis are common
o Asymptomatic gonorrhea is a cause of PID and infertility as well as perpetual transmission of the
pathogen
- Gonococcal bacteremia is associated with peripheral skin lesions or septic arthritis of the knee, ankle, wrist
- Conjunctivitis is caused by direct inoculation. Patients present with copious purulent discharge, which
usually is unilateral. Global rupture is a risk if the patient is not treated adequately
- Laboratory Studies:
o Gram stain of urethral discharge typically shows gram-negative intracellular diplococci. Smears
are less often positive in women
o Cultures are essential in all cases
- Treatment:
o Resistance to penicillin, tetracycline, and fluoroquinolones is widespread
o Currently, the treatment of choice is IM ceftriaxone or oral cefixime. Typically given in combo with
oral doxycycline or azithromycin
o All partners must be treated. Concurrent treatment against Chlamydia is recommended
o Infection is reportable in most states
-

Salmonellosis
- There are more than 2,000 serotypes of salmonellae, all of which are members of the species Salmonella
enterica and are transmitted by ingestion of contaminated food or water
- Three patterns are recognized:
o ENTERIC FEVERS (typhoid fever)
Incubation period is 5-14 days. Organisms enter mucosal epithelium of intestines and
invade/replicate within macrophages in the Peyers patches, mesenteric lymph nodes,
and the spleen. Bacteremia accompanies infection
Onset is insidious. Prodrome of malaise, headache, cough, sore throat. As the fever
increases, abdominal pain, distention, and constipation and/or diarrhea (pea soup)
develops. Fever peaks on days 7-10 and patient appears toxic, then improves over the
next 7-10 days. Children often have abrupt onset. Relapses are common (15% of cases)
Physical findings splenomegaly, abdominal distention and tenderness, and
bradycardia. A rash develops during the second week (pink papules, primarily on the
trunk, that fade on pressure)
Organisms can be isolated from blood during the first week of the illness. Later, the blood
cultures will likely be negative. Stool culture is not reliable
Complications can occur (30% of untreated cases). Intestinal hemorrhage can be fatal.
Others include urinary retention, pneumonia, thrombophlebitis, myocarditis, psychosis,
cholecystitis, nephritis, osteomyelitis, and meningitis
Treatment increasing resistance to ampicillin, chloramphenicol, and TMP-SMX.
Resistant strains may be susceptible to ceftriaxone or fluoroquinolones (but
contraindicated in children and pregnancy). Treatment should be done for 2 weeks
Prevention treatment of carriers often is not effective. Immunization may be provided
for household contacts of carriers, travelers to endemic areas, or during epidemics, but it
is not very effective. Protection of the food and water supplies as wells as proper waste
disposal are key to control of the disease
o GASTROENTERITIS
The most common form of Salmonella infection. Incubation period is 8-48 hours after
ingestion of contaminated food or drink
Fever, nausea, vomiting, crampy abdominal pain, and bloody diarrhea lasts 3-5 days
Diagnosis made through stool culture
Illness is self-limited, and treatment is symptomatic
If patients are severely ill or malnourished, sickle cell disease, or develop bacteremia
TMP/SMX, ampicillin, or ciprofloxacin
o BACTEREMIA
Characterized by prolonged or recurrent fevers, with bacteremia and local infection in the
bone, joints, pleura, pericardium, lungs, or other sites
Most common in immunocompromised persons
Treatment is the same as typhoid fever
Drain any abscess
Immunosuppressed patients may benefit from therapy with ciprofloxacin

Shigellosis
- Shigella somnei, Shigella flexneri, Shigella dysenteriae are the most common species that cause dysentery
- Illness starts abruptly with diarrhea, lower abdominal cramps, and tenesmus accompanied by fever, chills,
anorexia, headache, and malaise
- Stools are loose and mixed with blood and mucus. Abdomen is tender
- Dehydration is common
- HLA-B27 individuals may mount a reactive arthritis because of temporary disaccharidase deficiency
- Diagnostic Studies:
o Stool is positive for leukocytes and RBC
o Culture yields Shigella spp.
o Sigmoidoscopy will reveal inflamed engorged mucosa, punctate lesions, or ulcers
- Treatment:
o Replacement of fluid volume is essential
o TMP/SMX is antibiotic of choice, although ciprofloxacin or a fluoroquinolone may be substituted.
Amoxicillin is not effective
Tetanus
- Clostridium tetani spores are ubiquitous in soil. The spores germinate in wounds where the bacteria
produce a neurotoxin (tetanospasmin), which interferes with neurotransmission at spinal synapses of
inhibitory neurons. The result is uncontrolled spasm and exaggerated reflexes
- Puncture wounds are most susceptible. The elderly, migrant workers, newborns, and injection drug users
are at particular risk.
- The incubation period is from 5 days to 15 weeks
- Pain and tingling at the site of inoculation is followed by spasticity of the muscles nearby
- Jaw and neck stiffness, dysphagia, and irritability are common. Hyperreflexia and muscle spasms develop,
especially in the jaw (trismus) and face
- Painful tonic convulsions, spasm of the glottis and respiratory muscles, and asphyxia develop if the patient
is untreated
- The patient typically is alert throughout the course
- Treatment:
o Tetanus immune globulin should be given intramuscularly. A full course of tetanus toxoid should be
administered once the patient recovers.
o Bed rest, sedation, and mechanical ventilation often are necessary to control tetanic spasms
o Penicillin is given to all patients to eradicate toxin-producing organisms
o Mortality is high
o Active immunization is recommended starting in childhood.
3-4 initial doses are followed by boosters every 10 years.
An additional booster is recommended if a major injury occurs and if it has been more
than 5 years since the last booster
Passive immunization with tetanus toxoid in addition to vaccine is recommended for
patients with major wounds and uncertain tetanus status
Pertussis
- Whooping Cough
- Strictly human disease; etiologic agent is Bordetella pertussis a gram-negative pleomorphic bacillus
- Infection is highest in premature infants and in those with cardiac, pulmonary, or neuromuscular disorders
o Older children and adults tend to have milder disease
- Incubation period is 6 days
- Patients are almost invariably afebrile

Clinical disease has 3 stages that last ~8 weeks:

o Catarrhal Stage insidious onset of low grade fever, cough (hacking, most prominent at night),
coryza, loss of appetite, malaise
Follows a 7-10 day incubation period and lasts 1-2 weeks
This is the most infectious stage
o Paroxysmal Stage cough with inspirational whoop. Posttussive emesis is common. Facial
petechiae and scleral hemorrhages can develop due to forceful cough. Infants are at risk for
apnea
Lasts 2-6 weeks
o Convalescent Stage gradual symptom resolution
This stage usually begins 4 weeks after onset of the cough and may last for an additional
several weeks (2-8 weeks)
- The peak incidence of pertussis in infants in the US occurs in those less than 4 months of age
o Immunization not completed
o At risk for most severe complications
- Infants are most likely to have atypical symptoms. Apneic spells are most common
- Diagnosis culture, PCR, fluorescent antibody staining
- Laboratory increased WBC with lymphocytosis; CXR = segmental atelectasis, perihilar infiltrates
- Treatment:
o Erythromycin is the treatment of choice
o Treatment is aimed at stopping transmission, although it may also aid in reducing severity of
paroxysms
o Alternative therapies azithromycin, clarithromycin, ,TMP-SMX
o Supportive therapy is essential
o Also treat close contacts with antibiotics (erythromycin)
- Prevention:
o Acellular pertussis vaccine is recommended, beginning in infancy. It is given in combination with
diphtheria and tetanus toxoids
o Vaccination of adults is now recommended. Tdap is the vaccine of choice
Tuberculosis
- Mycobacterium tuberculosis infection is acquired by inhaling organisms within aerosol droplets expelled
during coughing by people with active disease
- Most exposed people mount an immune response sufficient to prevent progression from primary infection to
clinical illness. Overall, 10% of persons infected with TB will develop the disease. This is called primary TB
- Approximately 5% of exposed people fail to contain the primary infection and progress to active TB within 2
years. This is known as progressive primary TB
- Approximately 95% of infected persons will contain the bacterium without becoming symptomatic. This is
known as latent TB infection (LTBI). These patients are not considered to be infectious, nor can they spread
the disease. They are asymptomatic but have inactive TB in their body, most commonly in the apices of the
lungs. Reactivation TB develops from LTBI in the setting of immune compromise
- Cough is the most common symptom. It begins as a dry cough and progresses to a productive cough, with
or without hemoptysis, typically over 3 weeks or longer
- The classic symptom complex includes fever, drenching night sweats, anorexia, and weight loss
o Other common pulmonary symptoms are cough, pleuritic chest pain, dyspnea, and hemoptysis.
Posttussive rales are classic
- On exam, patient may appear chronically ill and malnourished

Laboratory Findings:
o Radiography:
Primary TB homogenous infiltrates, hilar/paratracheal lymph node enlargement,
segmental atelectasis, cavitations with progressive disease
Reactivation TB fibrocavitary apical disease, nodules, infiltrates, posterior and apical
segments of the right upper lobe, apical-posterior segments of the left upper lobe, superior
segments of the lower lobes
Ghon complexes (calcified primary focus) and Ranke complexes (calcified primary focus
and calcified hilar lymph node) represent healed primary infection
o The tuberculin skin test (TST) identifies those that have been infected, but does not differentiate
between active and latent infection. TST (such as the PPD) is reported according to diameter of
induration, NOT erythema

Definitive diagnosis requires the identification of Mycobacterium tuberculosis from cultures (6-8
weeks to grow) or by DNA or RNA amplification techniques (1-2 days). Demonstration of acid-fast
bacilli on sputum supports, but does not confirm, a diagnosis of TB
o Biopsy revealing caseating granulomas (aka necrotizing granulomas) is the histologic hallmark
Treatment:
o Any confirmed or suspected cases should be reported to public health agencies who will
investigate contacts. Patients with active disease should be isolated until a minimum of 2 weeks of
treatment is completed
o Directly observed therapy may be recommended to improve compliance
o Antituberculous drugs, including isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and
ethambutol (EMB) are the cornerstone of therapy. Multiple drug regimens:
LTBI INH x 9 months or RIF x 4 months or RIF + PZA x 2 months (only if in contact
with TB-resistant persons)
Treat for LBTI only after active TB is ruled out as active TB is treated with a
multidrug regiment
Active TB INH + RIF + PZA + EMB x 2 months, followed by 4 months of additional
multidrug treatment based on culture and sensitivity results
INH + RIF usually, but is only recommended if the isolate is INH sensitive
Drug-resistant TB seek expert advice
o Antituberculous class-specific side effects:
INH hepatitis, peripheral neuropathy
Coadminister vitamin B6 (pyridoxine) to reduce the risk
RIF hepatitis, flu syndrome, orange body fluid (e.g., orange urine)
EMB optic neuritis (red-green vision loss)
o Patients with active disease require combination chemotherapy for 6-9 months
o

 Patients infected with HIV require therapy for at least 1 year

o INH for 6-12 months is indicated for prophylaxis in patients who have tested negative in the past
but are now positive with known or unknown exposure (converters)
o Persons exposed to active TB should be screened with TST. Indurations greater than 5 mm should
be treated aggressively
o The bacille Calmette-Gurin (BCG) vaccine can be administered to a tuberculin-negative person in
cases with a high risk for intense, prolonged exposure to untreated or ineffectively treated cases of
infectious TB. This is not recommended in the U.S., but is common in areas with endemia TB
o Children, adolescents, and the immunocompromised who have been in close contact with a person
with active TB should be offered treatment until a TST is negative 12 weeks after exposure.
Treatment of other cases should be dictated by TST status
Parasitic Infections
Amebiasis
- Cysts of Entamoeba histolytica are visible in the soil and water for weeks to months. Transmission to
humans, the only host, occurs through fecally contaminated food or water, fly droppings, or human-tohuman contact
- Once ingested, cysts pass through to the intestines where they hatch. Trophozoites invade the mucosa and
induce necrosis. Amebic ulcers typically are flask shaped and occur anywhere in the large bowel or terminal
ileum. They usually are limited to the muscularis, but if they penetrate the serosa, they may cause
perforation, abscess, or peritonitis
- Infection rare in US; in developing world is second leading cause of deaths due to protozoal disease.
o Suspect in immigrants, travelers back and forth from endemic areas,
- Intestinal disease often is asymptomatic
- Colitis can be mild to moderate (few semiformed stools without blood) or severe dysentery (greater number
of liquid stools streaked with blood or bits of necrotic tissue)
o Patients may have cramps, fatigue, weight loss, and increased flatulence. Cycles of remission and
recurrence are typical
o Physical exam may reveal distention, hyperperistalsis, and generalized abdominal tenderness
during recurrences
o Patients with severe disease become prostrate and toxic with fever, colic, tenesmus, and vomiting
o Complications appendicitis, bowel perforation, fulminant colitis, massive mucosal sloughing,
hemorrhage
o Localized ulcerative lesions of the colon and localized granulomatous lesions of the colon
(ameboma) result in pain, intestinal obstruction, and hemorrhage
o Amebomas may be single or multiple and must be differentiated from colon cancer, tuberculosis, or
lymphogranuloma venereum. Biopsy reveals granulation tissue
- Extraintestinal disease
o Hepatic amebiasis and amebic liver abscess can be asymptomatic or result in symptoms either
suddenly or gradually, over days to months
o Findings fever, pain, tender hepatomegaly, malaise, prostration, sweating, chills, anorexia, and
weight loss
o Pulmonary symptoms (coughing, right lower lung findings) may occur if the abscess is in the
superior liver
o Abscesses may rupture and spill into the pleural, peritoneal, or pericardial space this can be fatal
o Less commonly, amebiasis may metastasize to the lungs, brain, or genitalia

Diagnostic Studies:
o Stool specimens reveal cysts or trophozoites
o Sigmoidoscopy, colonoscopy, or rectal biopsy shows ulcers
Collection of exudates should be examined for trophozoites
o Serology can detect antibodies up to 10 years after infection and, therefore, cannot be used to
differentiate past from present infection. Serology will be positive, but stool examination frequently
is negative
o WBC count is moderately elevated but without eosinophilia.
o Minimal changes, if any, to liver enzymes
o Ultrasonography, CT, MRI, or radioisotope scanning reveals the size and location of hepatic
abscesses
- Treatment:
o Asymptomatic infection should be treated with a luminal amebicide (diloxanide furoate, iodoquinol,
or paromomycin)
o Mild to moderate infections should be treated with tinidazole or metronidazole plus a luminal
amebicide.
Alternatives include tetracycline and a luminal amebicide followed by chloroquine
o Severe infection also should be supported with fluids, electrolyte replacement, and opioids to
control bowel motility and decrease the risk of toxic megacolon
o Hepatic abscess is treated with tinidazole or metronidazole plus a luminal amebicide, followed by
chloroquine. If there is no response within 3 days of initial treatment, the abscess should be
drained.
Complications include bacterial infection, bleeding, and peritoneal spilling
o Follow up with at least 3 stool examination at 2-3 day intervals starting 2-4 weeks after the end of
treatment
Colonoscopy also may be used to confirm treatment success
Postdysenteric colitis after severe infections usually is self-limited but may be a trigger for
ulcerative colitis
o Prognosis with treatment is very good. Without treatment, mortality can be high
o Prevention is through adequate control of the food and water supply, proper sanitation, and
personal hygiene
Hookworms
- Endemic to moist tropics and subtropics
o Sporadic cases occur in the southeastern United States
25% of the worlds population is infection
o Humans are the only host
- Eggs are passed in the stool and hatch in moist soil
o The larvae last for hours to weeks. They penetrate the skin and migrate in the bloodstream to the
pulmonary capillaries, where they destroy alveoli and are carried by cilia to the mouth. Once
swallowed, the larvae attach to the small bowel mucosa and suck blood. Once mature, they
release eggs to continue the cycle
o A light infection is defined as 1,000 eggs/g feces and moderate infection as 2,000-8,000 eggs/g
feces
- The site of penetration is pruritic. An erythematous dermatitis with maculopapular or vesicular eruption
follows
o Scratching can cause secondary bacterial infections
- The pulmonary stage may cause cough, wheeze, blood-tinged sputum, and low-grade fever
- With a light infection and adequate iron intake, the patient may remain asymptomatic during the intestinal
stage

Heavy infection leads to anorexia, diarrhea, vague pain, and ulcer-like epigastric symptoms.
Severe infection causes anemia, protein loss, and malabsorption
- Diagnostic Studies:
o The eggs can be demonstrated in feces
o Stool is positive for occult blood.
o Hypochromic, microcytic anemia and eosinophilia may be found
- Treatment:
o Mebendazole (BID x 3 days) or either pyrantel or albendazole (QD x 2-3 days) is effective
Pyrantel cannot be used in children younger than 5 years
None of the treatments are recommended in pregnancy
o Supportive treatment includes a high-protein diet, vitamins, and ferrous sulfate
Pinworms (Enterobiasis)
- Humans are the only host for Enterobius vermicularis
- There is a worldwide distribution, and children are infected more than adults
- Adult worms are loosely attached to the mucosa, primarily in the cecum. Gravid females pass through the
anus to lay eggs on the perianal skin. Each female is capable of producing a large number of eggs. The
eggs are viable for 2-3 weeks outside the host and are infective within a few hours
- Infection is easily passed through hands, food, drink, and fomites. The eggs are swallowed and hatch in the
duodenum; larvae pass to the cecum and mature in 3-4 weeks. The lifespan is 30-45 days
- Many patients are asymptomatic
- Characteristic symptoms perianal pruritus (crawling sensation that is worse at night), insomnia, weight
loss, enuresis, and irritability.
o Examination at night may reveal worms in the anus or in the stool
o Scratching causes excoriations and secondary skin infections (i.e., impetigo)
- Migration can cause vulvovaginitis, diverticulitis, appendicitis, cystitis, and granulomatous reactions
- Diagnostic Studies:
o Eggs can be captured on a piece of cellophane tape over the perianal skin
3 tries over 3 consecutive nights yields 90% success rate
- Treatment:
o All members of the household should be treatment concurrently
o Albendazole, mebendazole, or pyrantel is given in a single dose and then repeated 2-4 weeks later
o Hand washing after defecation and before meals must be stressed. Linens should be washed
thoroughly
Malaria
- Malaria is the most important parasitic disease of humans, causing hundreds of millions of illnesses and
nearly a million deaths each year.
- Etiology:
o Plasmodium, 4 species and each has a different geographic distribution and treatment regimen.
Plasmodium falciparum is the one we really worry about.
Others = Plasmodium vivax, Plasmodium malariae, Plasmodium ovale
- Epidemiology/Prevalence: More than 40% of the worlds population is at risk.
o 300-500 million cases/year
o >3 million deaths/year, endemic in most of the tropics including much of South and Central
America, Africa, the Middle East, the Indian subcontinent, Southeast Asia, and Oceania.
o Transmission, morbidity, and mortality are greatest in sub Saharan Africa, where most deaths of
malaria are in young children. 90% of the deaths occur in this region
o Malaria is also common in travelers from nonendemic areas of the tropics.
o Risk depends on where you go, time of year and species prevalence
- Pathophysiology:
o

Organism initially develops in the liver then parasitizes RBCs. Complex life cycle involving two
hosts: 1) infected female Anopheles mosquito and 2) humans.
o During feeding, mosquitoes inject sporozoites, which circulate to the liver, and rapidly infect
hepatocytes, causing asymptomatic liver infection. Merozoites are subsequently released from the
liver and they rapidly infect erythrocytes to begin the asexual erythrocytic stage of infection that is
responsible for human disease. These schizonts have escaped the liver and invaded the RBCs,
where they multiply and cause rupture of the cell within 48 hours
o Efficient transmission, favorable conditions for mosquito survival, repellant resistance, poverty
o Incubation period = 8-60 days
Signs and symptoms:
o Onset of symptoms may be as early as 5 days after exposure or cessation of prophylaxis or as
long as 2 months.
o The typical malarial attack starts with shaking chills (the cold stage), followed by fever(the hot
stage), and finally, diaphoresis (the sweating stage)
o Release of tissue necrosis factors and cytokines contribute to fatigue, headache, dizziness,
myalgia/arthralgia, back pain, vomiting, splenomegaly; anemia, thrombocytopenia, dry cough
o There may be liver and spleen enlargement if symptoms continue for more than 4 days
o Severe malaria defined as presence of signs of severe illness or organ dysfunction or a high
parasite load.
o Complications hypotension, CNS malaria, organ failure, pulmonary edema, metabolic
derangement.
Infection with P. falciparum can be much more severe and can manifest as cerebral malaria, hyperpyrexia,
hemolytic anemia, noncardiogenic pulmonary edema, acute tubular necrosis, adrenal insufficiency, cardiac
dysrhythmias, and other complications
Diagnostic Studies:
o Blood films (thick and thin) are stained with Giemsa or Wright stain and examined at 8-hour
intervals for 3 days during and between attacks. The percentage of infected RBCs ranges from 520%
o During attacks, leukocytosis or leukopenia may develop
o Severe infections cause hepatic changes, hemolytic jaundice, thrombocytopenia, marked anemia,
and reticulocytosis
o Antibodies appear 8-10 days later, which is too late for diagnostic benefit in most cases. antibodies
also persist for 10 years, making the distinction between old and new infection difficult
Treatment:
o Prevention is key!
Careful evaluation of risk to exposure
Mosquito protection (nets and screens, repellant, clothing)
o Chemoprophylaxis is recommended for patients traveling to areas of endemicity. Resistance is
increasing travelers should check with local health authorities
Chloroquine is the drug of choice for both prophylaxis and treatment. It is generally welltolerated and safe in pregnancy
Transient GI symptoms, headache, pruritus, dizziness, blurred vision, malaise,
and urticaria can be reduced if taken with meals or given in divided doses twice
per week rather than daily
If chloroquine resistant, use mefloquine
No regimen provides 100% protection
o Severely ill patients can be treated with parenteral quinine, quinidine, or chloroquine plus either
doxycycline, clindamycin, or a tetracycline
o

o
o

Alternative drugs atovaquone and proguanil (Malarone), mefloquine, hydroxychloroquine,

atovaquone/doxycycline, or other combinations (especially if suspect resistance to chloroquine)
Prognosis is good if treated except in cases involving P. falciparum, which has a mortality rate of
14-17% despite treatment

Toxoplasmosis
- Toxoplasma gondii is an obligate intracellular protozoan
- The definitive hosts are cats
- Humans are infected after ingestion of cysts in raw or undercooked meat, ingestion of oocysts in food or
water contaminated by cats, transplacental transmission of trophozoites, or, rarely, direct inoculation of
trophozoites via blood transfusion
- Infection is confirmed by isolated of T. gondii or identification of tachyzoites in tissue or body fluids
- Clinical manifestations may be grouped into 4 syndromes:
o Primary infection in the immunocompetent person:
Fever, malaise, headache, sore throat, lymphadenopathy mimics mononucleosis
Positive IgG and IgM serologic tests
o Congenital infection:
Follows acute infection of seronegative mothers and leads to CNS abnormalities and
retinochoroiditis
Highest risk during 3rd trimester
o Retinochoroiditis:
Presents weeks to years after congenital infection, commonly in teenagers or young
adults
Uveitis is also seen
Pain, photophobia, and visual changes (usually without systemic symptoms)
o Infection in immunocompromised persons:
Reactivation occurs in patients with AIDs, cancer, or those given immunosuppressive
drugs
Reactivation leads to encephalitis, retinochoroiditis, pneumonitis, myocarditis
Positive IgG, but negative IgM serologic tests
- Diagnostic Studies:
o Lots of serologic methods are used Sabin-Feldman dye test, ELISA, indirect fluorescent antibody
test, agglutination tests
IgG seen within 1-2 weeks of infection and persist for life
IgM peak earlier and decline more rapidly (but still may persist for years)
- Treatment:
o Self-limited in immunocompetent people
However, for severe, persistent, or visceral disease, may consider treating for 2-4 weeks
o Treatment is appropriate for primary infection during pregnancy in order to reduce the risk of fetal
transmission
o For retinochoroiditis, most episodes are self-limited
Treat if very symptomatic or immunocompromised
o Treat all immunocompromised patients with active infection
o Drugs for toxoplasmosis are only active against tachyzoites, so they do not eradicate infection
Combination of pyrimethamine + sulfadiazine
Add folinic acid to prevent bone marrow suppression check WBC count weekly
Screen for sulfonamide sensitivity (rashes, GI symptoms, hepatotoxicity)
To prevent crystal-induced nephrotoxicity, good urinary output should be
maintained
Pyrimethamine side effects headache, GI symptoms
o Toxic during first trimester
For pregnancy, use spiramycin

Lyme Disease
- Borrelia burgdorferi
- Transmitted to humans by Ixodides a small tick that often goes unnoticed
o Must feed for more than 24-36 hours to transmit the spirochete
o 75% do not recall being bit by a tick
- The most common vector-borne disease in the United States
- Clinical Findings:
o Stage 1 early localized infection 7-10 days after bite
Erythema migrans a flat or slightly raised red lesion that expands over several days,
typically with central clearing (bulls eye). Most common areas are the groin, thigh, or
axilla. Typically resolves in 3-4 weeks without treatment
About 25% of patients do not have EM. 20% have multiple lesions
Flu-like illness occurs in 50% of patients
o Stage 2 early disseminated infection days to weeks later
Manifestations typically involve the skin, CNS, and musculoskeletal system
Headache, stiff neck, fatigue, malaise, intermittent musculoskeletal symptoms
Cardiac (pericarditis, arrhythmias, heart block) or neurologic (aseptic meningitis, Bells
palsy, encephalitis) manifestations occur in up to 20%
o Stage 3 late persistent infection months to years later
Musculoskeletal disease includes joint pain without objective findings, frank arthritis
(typically large joints), and chronic synovitis. This most likely is immunologic rather than
an infectious phenomenon
CNS and PNS manifestations include subacute encephalopathy (memory loss, mood
changes), axonal polyneuropathy (paresthesia, encephalopathy), and leukoencephalitis
(cognitive change, paraparesis, ataxia, bladder dysfunction)
Acrodermatitis chronicum atrophicans, a bluish-red discoloration of distal extremities with
atrophy, is seen in Europe by not the U.S.
- Laboratory Studies:
o Antibodies can be detected by immunofluorescent assay or ELISA techniques
o A Western blot assay is used as a confirmatory test
o IgM wanes after 6-8 weeks. IgG may persist indefinitely
o Up to 50% with early disease can be antibody negative during the first few weeks.
Acute and convalescent titers can be compared for support of the suspected diagnosis
o Tests lack sensitivity high probability of false-positive (especially with rheumatoid arthritis, SLE,
mono, endocarditis, and other infections)
o Early disease diagnosis should be based on clinical findings. Late disease is diagnosed by
objective evidence of clinical manifestations and laboratory evidence of disease
- Treatment:
o Doxycycline is the drug of choice in patients with erythema migrans or a suspicion of Lyme disease
based on clinical findings (neurologic, cardiac, and musculoskeletal) and a history of a tick bite
Alternatives amoxicillin, cefuroxime, ceftriaxone, cefotaxime
o Symptomatic treatment with analgesics, such as NSAIDs, may help in those with musculoskeletal
complaints
o Prevention is important proper clothing, tick repellant, etc.
o Prophylactic antibiotics are NOT recommended

Rocky Mountain Spotted Fever

- Rickettsia rickettsii is transmitted by the wood tick. Transmission is highest during the late spring and
summer
- Most commonly occurs in the eastern United States
- Fever, chills, headache, nausea, vomiting, myalgias, restlessness, insomnia, and irritability develop 2-14
days after exposure.
o Less common manifestations cough, pneumonitis, delirium, seizures, stupor, coma
- The face typically is flushed and the conjunctiva infected. Faint macules to maculopapules to petechiae
develop first on the wrists and ankles and then spread to the extremities and trunk. About 10% of patients
do not exhibit a rash
- Less common findings splenomegaly, hepatomegaly, jaundice, myocarditis, uremia, ARDS, and
necrotizing vasculitis
- Diagnostic Studies:
o Leukocytosis, thrombocytopenia, hyponatremia, proteinuria, and hematuria are common. A
transient rise in aminotransferases or bilirubin is possible
o CSF analysis reveals pleocytosis and hypoglycorrhachia
o A rise in antibody titers appears during the second week of illness
- Treatment:
o Mild, untreated cases wane during the second week
o Prompt treatment with doxycycline or chloramphenicol hastens recovery
o Poor outcomes occur in advanced age and in patients with atypical features. Death is caused by
pneumonitis or respiratory or cardiac failure
o Sequelae of disease may include seizures, encephalopathy, peripheral neuropathy, paraparesis,
bowel or bladder incontinence, cerebellar dysfunction, vestibular dysfunction, heating loss, or
motor deficits
o Prevention is key! Protective clothing, tick repellant, and prompt tick removal reduce the incidence
of the disease
Syphilis
- The spirochete Treponema pallidum causes the chronic systemic infection of syphilis
- Transmission occurs most frequently during sexual contact
- Congenital syphilis is transmitted via the placenta from the mother to the fetus and can result in severe
defects
- Most likely enters the body through minute abrasions in the skin or mucosal surface and replicates locally
- Early infectious (primary and secondary) and late (tertiary) syphilis are separated by a symptom-free latent
phase, during which the infectious stage may recur
- Initial lesions commonly occur on the vulva, vagina, cervix, anus, nipples, or lips
- Initial lesion that characterized primary stage painless, red, round, firm ulcer with a clean base and
indurated margins approximately 1cm in size with raised edges known as a chancre
o Develops at the site of inoculation after about 3 days and is usually associated with concomitant
regional adenopathy (rubbery, discrete, nontender)
o Material expressed from the chancre usually reveals motile spirochetes under dark-field
microscopy
- Secondary stage occurs as T. pallidum disseminates. Between 1-3 months after primary stage resolves, the
secondary stage appears as a maculopapular rash and/or moist papules on the skin or mucous membranes
o Classically, the rash appears on the palms of the hands or soles of the feet
o The dermatologic manifestations of secondary syphilis are why syphilis is known as the great
imitator
Lesions may involve skin, mucous membrane, eye, bone, kidney, CNS, or liver
o All lesions resolve spontaneously, and this stage can be entirely asymptomatic

o After resolution of this stage, the infection enters a latent phase that can last for years
Tertiary syphilis is uncommon characterized by granulomas (gummas) of the skin, bones, and viscera,
cardiovascular syphilis with aortitis, and neurosyphilis with meningovascular disease, paresis, and tabes
dorsalis, also ophthalmic lesions
o Neurosyphilis can result in asymptomatic disease, meningovascular syphilis (chronic meningitis),
generalized paresis, or tabes dorsalis (chronic progressive degeneration of parenchyma)
o Tabes dorsalis manifests with impaired proprioception, loss of vibratory sense, Argyll Robertson
pupil (reacts to light but does not accommodate), or tabes dorsalis crisis (severe pain and
neurological decompensation)
Congenital syphilis leads to abnormalities in the skin or mucous membranes, nasal discharge (snuffles),
hepatosplenomegaly, anemia, and osteochondritis. If infants are not treated, they may develop interstitial
keratitis, Hutchinson teeth, saddle nose, deafness, and CNS abnormalities
Diagnostic Studies:
o T. pallidum may be identified on dark-field microscopy, but the technique is difficult.
Immunofluorescent staining techniques are somewhat more reliable. The organism cannot be
cultured. Serologic testing is the recommended method for diagnosis
Screening can be performed with nontreponemal anticardiolipin antibodies. Two types of nontreponemal
serologic tests for syphilis are available and they detect nonspecific antibodies to lipoidal antigens
o The VDRL and RPR tests become positive 4-6 weeks after infection. These tests are positive in
99% of cases during primary and secondary syphilis, but may be negative during late forms of
syphilis. False-positive results occur, especially in those with autoimmune disorders
RPR test not available as a point-of-care assay
Positive result must be confirmed with specific treponemal antibody studies, such
as the fluorescent treponemal antibody absorption test (FTA-ABS) and the
Treponema pallidum particle agglutination assay (TPPA)
These two tests remain positive for 6-12 months after treatment of primary syphilis,
usually with progressively decreasing titers
They may be negative during early infection
Will become positive several weeks after the initial visit, and should be repeated
1-3 months after appearance of the ulcer in the compliant patient in whom the
diagnosis cannot be made at first presentation
Patients who are asymptomatic with a positive titer are considered to be in early latent
(acquired < 1 year) or late latent (acquired > 1 year) syphilis
o Treponemal antibody tests use live or killed T. pallidum as antigen to detect specific antibodies
The fluorescent treponemal antibody absorption (FTA-ABS) test is the most widely used.
It is useful in determining whether a positive nontreponemal antigen test is a true positive
The test is accurate in most patients with primary syphilis and in virtually all patients with
secondary syphilis, but it may be falsely positive in patients with Lyme disease, SLE,
malaria, or leprosy
o Specific testing for tertiary syphilis includes lumbar puncture, joint fluid analysis, and biopsy as
indicated
Treatment:
o Penicillin is the drug of choice
Primary, secondary, or early latent benzathine penicillin G, 2.4 million units IM one time
Late latent or latent of unknown duration penicillin G 2.4 million units IM weekly x 3
weeks
o If penicillin allergic tetracycline 500mg orally QID or doxycycline 100mg orally BID x 2 weeks, or
ceftriaxone 1g IM or IV daily x 8-10 days, or even azithromycin 2g single oral dose
o Penicillin is the only treatment in pregnancy

Neurosyphilis is a more serious infection and requires aqueous crystalline penicillin G, 3-4 million
units IV q4h x 10-14 days. This may be followed with 3 weekly doses of benzathine penicillin G
o Treatment success can be verified by following RPR or VDRL titers at 6, 12, and 24 months
Titers should decrease fourfold by 6 months and become nonreactive by 12-24 months
after completion of treatment
o The Jarisch-Herxheimer reaction is an acute febrile reaction frequently accompanied by fever,
chills, headache, myalgia, malaise, pharyngitis, rash, and other symptoms that usually occur within
the first 24 hours (generally within the first 8 hours) after any therapy for syphilis. It occurs when
there is a sudden massive destruction of spirochetes
Most common with early syphilis
Antipyretics may be used to prevent this reaction during the first 24 hours of treatment
May induce preterm contractions or cause fetal distress in pregnancy
o All cases are reportable!!!!!
Cytomegalovirus
- Most infections with CMV are asymptomatic
- Illness occurs in the immunocompromised, especially in patients with HIV disease or posttransplant
- Perinatal infection and CMV inclusion disease occur in 10% of babies born to mothers with primary CMV
infection during pregnancy
o The infant may be asymptomatic until later in life
o Clinical findings include jaundice, hepatosplenomegaly, thrombocytopenia, periventricular CNS
calcifications, mental retardation, motor disability, and purpura
- Acute acquired CMV can be transmitted through sexual contact, breast milk, blood transfusion, or
respiratory droplets
o Patients develop fever, malaise, myalgias, arthralgias, splenomegaly, abnormal liver enzymes,
leukopenia, and atypical lymphocytes
o It is similar to EBV infection but without pharyngitis, respiratory symptoms, or heterophile
antibodies
- Posttransplant patients and those who are otherwise immunocompromised are at risk for myriad clinical
manifestations
o Retinitis occurs with a CD4 count of < 50 cells/L. Examination reveals neovascularization and
proliferative lesions, commonly referred to as pizza pie. With aggressive treatment of HIV
disease, the frequency of retinitis can be reduced
o GI manifestations include esophagitis and odynophagia, small bowel inflammatory ulcers, diarrhea,
hematochezia, abdominal pain, weight loss, and cholangiopathy. Diagnosis may require biopsy
o Pulmonary manifestations occur in 15% of bone marrow transplant patients; 80-90% of these are
fatal
o Neurologic manifestations include polyradiculopathy, transverse myelitis, and encephalitis
o CMV infection is theorized to play a role in the pathogenesis of inflammatory bowel disease,
atherosclerosis, and breast cancer
- Diagnostic Studies:
o Patients may exhibit lymphocytosis or leukopenia
o Culture is very difficult. Antigens can be detected in blood, urine, or CSF via PCR
o Tissue biopsy looks for intracytoplasmic inclusions (owls eyes)
- Treatment:
o Measures to prevent CMV infection include limiting blood transfusions, filtering to remove
leukocytes, and restricting the organ donor pool to seronegative donors. CMV immunoglobulin and
IV ganciclovir reduce the risk of pneumonia in bone marrow transplant recipients
o Ganciclovir, valganciclovir, foscarnet, and cidofovir are effective against CMV
Initial IV loading therapy is followed by maintenance therapy
o

Sustained-release ganciclovir implants for suppression of retinal infections are effective

Epstein-Barr Infection
- EBV is human herpes virus 4, a universal virus transmitted via saliva
- The most characteristic disease is mononucleosis (the kissing disease)
o EBV has also been implicated in Burkitt lymphoma, nasopharyngeal carcinoma, pediatric
leiomyomas, collagen vascular diseases, and other disorders
- After an incubation period of several weeks, patients develop fever and sore throat
o Oral lesions include exudative pharyngitis, tonsillitis, gingivitis, and soft palate petechiae
o Severe infections also exhibit malaise, anorexia, and myalgia
- Lymph nodes, typically in the posterior cervical nodes, are enlarged, discrete, and nonsuppurative, with
minimal pain
- Splenomegaly is present in 50% of cases
- A maculopapular and, occasionally, petechial rash develops in 15% of cases
o Administration of amoxicillin rases the incidence of rash to 90%
- Less common manifestations hepatitis, mononeuropathy, aseptic meningitis, myositis, gallbladder
disease, renal failure because of interstitial nephritis, and dyspnea and cough (pseudocroup)
- Complications are many
o The most common include secondary bacterial pharyngitis (most commonly strep), splenic rupture,
pericarditis, myocarditis, aseptic meningitis, transverse myelitis, and encephalitis
- Diagnostic Studies:
o An early granulocytopenia is followed by a lymphocytic leukocytosis. Atypical lymphocytes appear
as larger cells that stain darker and are frequently vacuolated
o Hemolytic anemia and thrombocytopenia may develop
o Heterophile antibodies and screening mononucleosis tests are usually positive within 4 weeks
A false-positive syphilis test (VDRL or RPR) occurs in 10% of infected patients
o Increased hepatic aminotransferases, increased bilirubin, and decreased cryoglobulins also may
be found
- Treatment:
o Symptomatic nonaspirin antipyretics and anti-inflammatories
o Antivirals will decrease viral shedding but do not affect the course of the illness
o Patients with splenomegaly should avoid contact sports
o Steroids are indicated for thrombocytopenia, hemolytic anemia, or airway obstruction secondary to
enlarged lymph nodes
o Prognosis is good. although full recovery may take months, 95% recover without specific
treatment
Herpes Simplex Infection
- Humans are the only reservoir of HSV. Transmission is via close contact and inoculation of virus into the
mucosal surface or through cracks in the skin. The virus is inactivated at room temperature or by drying
- HSV type 1:
o More than 85% of the U.S. population has evidence of infection with HSV-1. Transmission is via
infected saliva
o Primary infection can be asymptomatic or produce severe disease
o Recurrent, self-limited attacks are common. Precipitating factors include sun exposure, surgery,
stress, fever, and viral infection
- HSV type 2:
o About 25% of the U.S. population is infected with HSV-2. Transmission is via sexual contact or
from the mothers genital tract during delivery
o The virus typically causes genital lesions (vulva, vagina, cervix, glans, prepuce, and penile shaft)
o Asymptomatic shedding and painful eruptions can be frequent

HSV remains latent within the dorsal root ganglia (HSV-1 has a predilection for the trigeminal nerve and
HSV-2 for the sacral root ganglia). Reactivation may be precipitated by fever, stress, menses, trauma,
ultraviolet light, weight gain or loss, immunosuppression, or other factors. Reactivation is more frequent and
more severe in those who are immunocompromised
Clinical Findings:
o Initial infection has a higher rate of systemic signs, longer duration of herpetic symptoms, and a
higher rate of complications
Acute Herpetic Gingivostomatitis (HSV-1)
Typically occurs in those from 6 months to 5 years of age
Incubation period is 3-6 days. Acute symptoms last 5-7 days. Lesions heal in
about 2 weeks, although shedding may continue
Patients present with abrupt onset, fever, anorexia, listlessness, and gingivitis.
Mucosa is red, swollen, and friable. Vesicles appear on the oral mucosa, tongue,
and lips. These vesicles may rupture and coalesce to form ulcers and plaques.
Regional lymphadenopathy is common
Acute Herpetic Pharyngotonsillitis
This is common in adults manifesting initial HSV-1 disease and less common in
those manifesting HSV-2 disease
Patients present with fever, malaise, headache, sore throat. Vesicles form on the
posterior pharynx and tonsils. These vesicles rupture and form shallow ulcers. A
grayish exudate may be present over the posterior mucosa
Primary Genital Herpes (invariably HSV-2)
The initial episodes may be asymptomatic or severe, with a prodrome of
systemic and local symptoms
Preexisting antibodies to HSV-1 may have an ameliorating effect on the severity
of primary HSV-2 infection
Fever, headache, malaise, and myalgias are common. Vesicles develop on the
external genitalia, labia, vaginal mucosa, glans, penis, prepuce, shaft, or perianal
area. Nearby cutaneous lesions also may occur
Vesicles rupture and form tender ulcers, which crust over. Mucosa may be red
and edematous
Females tend to have more severe disease and higher rates of complications.
The cervix is involved in more than 70% of female patients, manifesting as
ulcerative or necrotic mucosa
o Recurrence of HSV lesions is heralded by burning or stinging. Neuralgia also may occur, but
constitutional symptoms are unlikely
Lesions begin as erythematous papules that rapidly develop into tiny, thin-walled, grouped
vesicles, which continue to erupt over 1-2 weeks.
Typical locations are the vermillion border (type 1) and the genital area, including the
penile shaft, labia, perianal area, and buttocks (type 2)
On average, HSV-1 infections tend to recur twice per year. Maximum shedding is during
the first 24 hours of each outbreak. The number of episodes tends to decrease with time
In 90% of cases, HSV-2 can reactivate within 12 months. More than 30% of patients have
6 episodes per year, and about 20% have more than 10 episodes per year. Reactivation
can be subclinical, however viral shedding without visible lesions leads to further
transmission of the virus

Complications of HSV infection

Pyoderma, eczema herpeticum, herpetic whitlow (grouped vesicles on the fingers,
common in healthcare workers), herpes gladiatorum (disseminated cutaneous infections,
common in wrestlers), esophagitis, keratoconjunctivitis (dendritic corneal ulcers, may
cause blindness), and disseminated neonatal infection. Viremia may result in visceral
infection with multiple organ involvement, leukopenia, thrombocytopenia, and DIC
Herpes simplex infection of the CNS may cause septic meningitis, ganglionitis, myelitis, or
encephalitis. HSV accounts for 10-20% of all encephalitides in the United States.
Patients develop headache, meningeal irritation, change in mental status, seizures, and
focal necrosis syndromes (temporal cortex, limbic system). CSF shows a moderate
pleocytosis of mixed cells, mildly elevated protein, and normal glucose. HSV DNA by
PCR or MRI will confirm infection. The mortality rate is greater than 70% without
treatment neurologic sequelae are typical even with treatment
Genital herpes in pregnancy is dangerous to both the mother and the infant. First
infection during pregnancy has a high risk of disseminated infection and maternal
mortality. Infants exposed to herpes in utero or during delivery have a high rate of visceral
and CNS infection. Mortality and sequelae rates are high. Cesarean section is
recommended for women with active infections
- Diagnostic Studies:
o The diagnosis usually is established clinically
o Vesicular fluid may be cultured or stained (Tzanck smear), revealing multinucleated giant cells
o Antibodies can be identified in the serum by PCR techniques
- Treatment:
o Local wound care and supportive therapy are recommended
o Treatment is with antivirals (e.g., acyclovir, valacyclovir)
o Patients with frequent outbreaks may benefit from suppressive therapy. Foscarnet is beneficial in
immunocompromised patients with resistant infections
o Keratitis is treated with trifluridine
Influenza
- Caused by an orthomyxovirus. Readily transmitted through droplet nuclei and occurs in epidemics and
pandemics during the fall or winter
o Peaks between late December and early March
- Three strains exist (A, B, and C) and are typed based on the surface antigens hemagglutinin (H) and
neuraminidase (N). Influenza A is more pathogenic. Major mutations cause antigenic shifts. Minor
mutations cause antigenic drifts. Public health authorities follow changes in strains to predict new virus
- An avian influenza A subtype (H5N1) has caused epidemic infection in birds and has been transmitted from
birds to humans. If a mutation occurs to allow human-to-human transmission, this highly virulent and lethal
subtype could become responsible for widespread disease
- In 2009, a new highly transmissible H1N1 variant emerged with potential to become a severe pandemic
- Incubation period about 2 days (18-72 hours)
- Classic flu symptoms are abrupt in onset and include fever of 38.6C-39.8C (101F-103F) with chills or
rigor, headache, myalgia, and generalized malaise
o Respiratory symptoms = dry cough, rhinorrhea, sore throat, with bilateral tender and enlarged
cervical lymph nodes
o Fever lasts for 1-7 days
- Primary influenza pneumonia may develop in the elderly or those with chronic cardiovascular disease.
Patients exhibit progressive cough, dyspnea, and cyanosis as well as confusion
- Children usually have GI symptoms
o

Complications are common in the elderly and chronically ill. Necrosis of respiratory epithelium results in
secondary bacterial infection (Staphylococcus, Streptococcus, or Haemophilus sp.), acute sinusitis, otitis
media, and purulent bronchitis
Reyes Syndrome:
o Fatty liver with encephalopathy
o Rapidly progressive, has a 30% fatality rate, and may develop 2-3 weeks after onset of influenza A
or varicella infection, especially if aspirin is ingested. Peak age is 5-14 years rare in patients over
18 years
o Vomiting, lethargy, jaundice, seizures, hypoglycemia, increased liver enzymes and ammonia levels,
prolonged prothrombin time, and changes in mental status
o Treatment is supportive
Laboratory Studies:
o Leukopenia and proteinuria may be found
o The virus can be isolated from the throat or nasal mucosa. Viral cultures take 3-7 days to return.
Direct immunofluorescent tests are labor intensive and less sensitive, but recently developed rapid
serology tests are proving to be helpful. Sensitivities range from 50-70%, but specificities 90-95%.
Results are most accurate during the first few days (72 hours) of illness
o CXR in primary influenza pneumonia will show bilateral diffuse infiltrates
Treatment:
o Supportive care rest, analgesics, cough suppressants prn
o Amantadine and rimantadine are no longer recommended as single therapy due to resistance
o Neuraminidase inhibitors = zanamivir inhalation (Relenza) or oral oseltamivir (Tamiflu). Will
significantly reduce severity if given within 48 hours of onset of symptoms. They are effective
against both influenza A and B and have fewer side effects than amantadine and rimantadine.
Recommended for patients with influenza requiring hospitalization or in those with high risk of
morbidity and mortality
The prevalence of resistance to oseltamivir is on the rise. Recommend zanamivir or a
combo of oseltamivir and rimantadine if influenza A is suspected or confirmed.
Neuraminidase inhibitors are contraindicated in patients younger than 12 years.
emergency use with half strength dosing also may be effective in preventing influenza
during time of high transmission
o Prognosis in uncomplicated cases is very good recovery in 1-7 days. Morbidity and mortality is
highest in the very young and very old. Pneumonia is the cause of most influenza fatalities
Prevention trivalent influenza virus vaccine
o Configuration is based on the strains isolated during the preceding year. Vaccine should be given
to all patients yearly in October or November and is especially recommended for all people older
than 65 years, children or adolescents on chronic aspirin therapy, nursing home residents, patients
with chronic lung or heart disease, and all health care workers
o Contraindicated in patients with hypersensitivity to eggs or other components of the vaccine, during
acute febrile illness, or in cases of thrombocytopenia
o Tenderness, redness, and induration at the site of injection may occur. Myalgias and fever are
rare. It is also available as a nasal spray (FluMist) for those from 5-49 years old
o Immunity is set within 2 weeks of vaccination. Antibodies wane quickly in the elderly and the sick,
but the vaccine has been proven to decrease mortality and morbidity from the flu
o Flu season = October March. Peaks in January (or later). Differs per geographic region

Rabies
- Rhabdovirus is transmitted via infected saliva from an animal bite or an open wound
- Vectors dogs, bats, skinks, foxes, raccoons, and coyotes
o Rodents and lagomorphs do not transmit rabies
- Incubation period between the bite and the onset of symptoms is from 10 days to years (typically 3-7 weeks)
o A correlation exists between the length of incubation and the distance of the wound from the brain
- A history of an animal bite may not be apparent
- There is typically pain and paresthesias at the site. The skin is sensitive to changes in temperature and the
wind
- Patients are restless, with muscle spasms and extreme excitability. They exhibit bizarre behavior,
convulsions, and paralysis. Thick, tenacious saliva is produced
- Hydrophobia is defined as painful spasms caused by drinking water
- Less commonly, patients may exhibit an ascending paralysis
- Diagnostic Studies:
o Suspect animals should be sacrificed so that their brains can be tested for the virus using
fluorescent antibody markers
o Domestic animals may be quarantined and observed for bizarre behavior
o PCR tests and genetic probes for use in humans are expensive and often negative early in the
disease
o CSF may show rabies reverse transcriptase by PCR
o MRI may reveal nonenhancing, ill-defined changes in the brain stem, hypothalamus, or subcortical
matter
- Treatment:
o No specific treatment against rabies disease is available. Mechanical ventilation and oxygen
therapy should be started
o Rabies vaccine immunoglobulin is given along with monoclonal antibodies, ribavirin, interferon-,
and ketamine
o It is almost universally fatal within 7 days, most likely from respiratory failure
- Prevention is key
o Control of bat populations
o Immunize all household pets
o Persons who are exposed regularly (veterinarians, park rangers) should also receive active
immunization
- After an animal bite, local care with cleansing, debridement, and flushing is recommended. Wounds should
NOT be sutured
- Postexposure immunization includes rabies immunoglobulin (in the wound and IM at a distant site) and
human diploid cell vaccine (HDCV)
o 5 injections of 1 mL IM are given on days 0, 3, 7, 14, and 28
o The vaccine may cause pruritus, erythema, and tenderness in 25% of cases, and 20% also
develop myalgias, headache, and nausea
- If the patient has received active immunization in the past, immunoglobulin is not given.
o HDCV is given on days 0 and 3 only
- Preexposure vaccination of persons at high risk (veterinarians, animal handlers, Peace Corps volunteers,
travelers) is accomplished with IM HDCV doses on days 0, 7, and either 21 or 28
o HDCV can also be administered intradermally on days 0, 7, and 28
o Rabies antibody titers should be checked every 2 years boosters are given to persons who
become seronegative

Varicella Zoster
- Varicella virus is a member of the herpesvirus family. It is highly contagious, especially the day before the
rash appears
- Results from activation of latent varicella zoster virus that has been dormant in ganglionic satellite cells
- Incubation period is 10-20 days. A single attack confers lifelong immunity
- Most cases occur in late winter or spring
- It typically is a benign illness in childhood, but it can be life-threatening, especially in adults or the
immunocompromised
- Outbreaks may be precipitated by illness, stress, or advancing age
- Clinical features:
o Varicella is characterized by a generalized eruption that follows a centripetal pattern
o Pain or dysesthesia in the involved dermatome begins several days before lesions emerge.
o Erythematous papules develop first, progress to vesicular clusters, which crust after about a week.
Dewdrops on rose petal
o Lesions appear in crops, so at any given time, several morphologies can be identified
o The mucous membranes may also be involved
o Lesions of the ophthalmic branch of the trigeminal nerve, especially if accompanied by lesions on
the nose, are concerning for ophthalmic involvement (keratitis, ulceration).
o A thorough eye exam slit lamp
o Generalized eruptions may occur in immunocompromised patients.
- Systemic symptoms are highly variable and include low-grade fever, malaise, muscle aches, arthralgias,
and headache
o Severe, progressive infections manifest with deeper lesions of the lung, liver, pancreas, or brain
The mortality rate approaches 10%
- Complications are varied secondary bacterial infection of excoriated lesions, varicella embryopathy, and
Reye syndrome
- Zoster is characterized by a painful eruption, usually following a dermatomal pattern. The thoracic and
lumbar areas are the most common sites.
o Trigeminal eruptions that include the tip of the nose (Hutchinson sign) risk corneal involvement
- Diagnostic Studies:
o Clinical diagnosis
o Confirmatory laboratory studies are rarely done, but, if necessary, serology and fluorescent
microscopy will confirm the diagnosis (PCR)
- Treatment:
o Treatment is generally supportive
o Antivirals started in the first 72 hours of presentation shortens healing time, decreased formation of
new lesions, and helps prevent postherpetic neuralgia.
Acyclovir or valacyclovir
Patients with HIV should take acyclovir
o Aluminum acetate compressions TID and analgesics provide symptomatic relief.
o Advise patients that herpes zoster is contagious to anyone who has not had chicken pox of the
varicella vaccine.
o Consult ophthalmology if eye involvement is suspected
o Treatment of postherpetic neuralgia is difficult tricyclic antidepressants, capsaicin cream,
narcotic analgesics, or corticosteroids

Prevention:
o Prevention of bacterial superinfection involves good hygiene and trimming of fingernails
o Immunocompromised patients exposed to varicella should receive acyclovir and varicella-zoster
immunoglobulin
o Prevention of varicella is through live attenuated vaccine given at 1-2 years of age. Older patients
without evidence of immunity should receive two doses, given 2 months apart. Avoid giving the
vaccine during pregnancy
o Steroids may prevent postherpetic neuralgia in some patients
Rates of postherpetic neuralgia are higher in the elderly and in patients with trigeminal
lesions
o Zostavax was licensed in 2006. A single dose is indicated in patients 60 years or older
Contraindications allergic to gelatin or neomycin, immunocompromised patients,
untreated tuberculosis, pregnancy