 Cardiovascular

o Stroke
 Ischemic Stroke
 Management
o Maintain sufficient cerebral perfusion
 Permissive Hypertension – perfusion of penumbra
depends on the mean arterial pressure.
 Treat severe hypertension if BP >220/120 mmHg
o CHF
 Vasodilators Hydralazine and Isosorbide Dinitrate added if ineffective
with diuretics, beta blockers, and ACE inhibitor (or ARB)
 Treathypertension with ACE Inhibitors and Beta Blockers
 Treatment
 Digoxin

o Sinus Bradycardia
 Treatment = Atropine
o Diastolic Dysfunction
 Due to LVH as a response to chronic systolic hypertension. Ventricle
becomes stiff and unable to relax or fill adequately, thus limiting its
forward output
o SVT
 Treatment: Radiofrequency ablation
o Hypertension
 ACE + Arb will lead to higher creatinine levels causing an increased
likelihood that dialysis will become necessary
o Aortic Stenosis
 Hemolytic Anemia + Schistocytes
 Low haptoglobin and elevated bilirubin
o Kawasaki Disease
o Acyantonic Congenital Heart Defects
o Heart Sounds
 Mitral Valve Prolase
o Cyanotic Congenital Heart Defects
 HEENT
o Chronic Otitis Media **
 Chronic Suppurative Otitis Media
 Otitis Media with Effusion (Glue ear)
o Inflammation of the Eyelids
 Hordeolum (Stye)
 Definition: common acute inflammation of the TEAR GLAND or
EYELASH FOLLICE
 Blepharitis
  Definition: Chronic and/or recurrent scally inflammation of the
eyelid margins
 Chalazion
 Definition: Focal granulomatous swelling of the SEBACEOUS
GLANDS
 Diagnostics: everting the eyelid may allow for better visualization
of the lesion
 Biopsy: for persistent or recurrent chalazion
 Treatment:
o Conservative: wait and watch; warm compresses
o Persistent chalazia: Incision and curettage
 Persisnte or recurrent chalazion may be a sign of
sebaceous carcinoma (of Meibomian gland!)
o Traumatic Eye Injuries
 Closed Globe Contusion (Bruising)
 Open Globe Injuries
 Ortbial Floor Fracture
 Ocular Chemical Burns
o Keratitis
 Inflammation of the cornea, a clear and transparent covering over the iris
and pupil
 Bacterial Keratitis
 Mainly: Staph, Strep, Pseudomonas
 Syphilis; Klebsiella
 Risk Factors: Contact Len Use
 Clinical Features:
o Progressive Pain
o Foreign Body Sensation
o Purulent Discharge
o Photophobia
o Excessive Tearing
o Conjunctival Injection
 Diagnostics
o Slit Lamp: Hypopyon (collection of leukocytes at the
bottom of the anterior chamber); Fluorscein staining:
round corneal infiltrate
 Treatment
o Topical broad spectrum antibiotics
 Cefazolin
 Oflaxacin
 Ciprofloxacin
 Complications
o Irreversible vision loss
 o Corneal destruction
 Viral Keratitis
 Herpes Simplex Keratitis
o Infection due to HSV Type 1 from trigeminal ganglion
o Clinical
 Unilateral
 Eye Redness
 +/- Eye Pain
 Foreign Body Sensation
 Photophobia
 Blurry Vision
o Diagnostics
 Fluorescein staining: superficial corneal ulcers
(dendritic ulcers) that resemble the branches of a
tree
o Treatment
 Topical trifluridine or ganciclovir
 Oral antiviral
 Herpes Zoster Keratitis
o Reactive herpes zoster virus (ophthalmic nerve)
o Clinical Features: Prodrome of headache fever
 Impaired vision, eye irritation; photophobia; eye
pain
o Diagnosis:
 Slit Lamp
 1-2 punctate lesions
 4-6 days: dendritic lesions on the corneal
surface
 Treatment
 Oral Acyclovir, Valacyclovir
 Acanthamoeba keratitis
 Acanthamoeba infection
o Inflammation of the Eyelids
 Blepharitis
 Treatment: Warm compresses
o Otosclerosis
o Idiopathic Intracranial Hypertension
 Etiology – Vitamin A analogs, tetracyclines
 Treatment
 Adopt a low sodium weight loss diet
 Begin acetazolamide (believed to reduce the rate of CSf
production, thereby decreasing intracranial hypertension)
o Laryngitis
  Viral infection causing inflammation of the vocal cords lasting less than 3
weeks
 Symptoms – loss/muffling of the voice
 Treatment – Reassurance
 Do not treat children under the age of 2 years of age with OTC
cough and cold medications
o Central Retinal Vein Occlusion (CRVO)
 Diagnostics
 Fundoscopic Exam - Tortuous an dilated retinal veins
o Esotropia
 Light Reflex over the lateral portion of the iris
o Exotropia
 Light reflex over the medial iris
o Hypertropia
 Light reflex over the inferior iris
 Involvement of the superior oblique muscle innervated by CN IV
o Hypotropia
 Light reflex over the superior iris
o Conjunctivitis
 Viral
 Etiology
o Adenovirus
o Herpes Simplex
o Varicella Zoster Virus
 Bacterial
o Herpangina
 Caused by the Coxsackie A Virus
 Multiple 1-mm vesicles on the posterior oropharynx and tonsils
o Meniere’s Disease
 Multiple episodes of vertigo lasting for 20-120 minutes accompanied by a
fluctuating hearing loss, tinnitus, and a sense of aural fullness;
 Treatment
 Lifestyle: Avoid caffeine, alcohol, stress; Low sodium diet
 Bed Rest
 Medical Therapy
o Vestibular Suppressants (Dimenhydrinate); Antiemetics
o Prophylaxis: Histamine Analog (Betahistine)
o Glaucoma
 Acute or chronic destruction of the optic nerve with or without
concomitant increased intraocular pressure
 Open Angle Glaucoma
 Slowly progressive and asymptomatic but leads to bilateral
peripheral vision loss
  Treatment = Non-selective beta blockers (can cause
bradarrhythmias by blocking B1 and orthostatic hypotension by
blocking B2)
 Etiology
o Increased IOP; Age >40
 Pathophysiology
o Secondary clogging of the trabecular meshwork or
reduced drainage  gradual increase in IOP  vascular
compression  Ischemia to the optic nerve
 Clogging Due to inflammatory cells (uveitis); red
blood cells (hemorrhage); retinal detachment
 Reduced drainage due to: increased episcleral
venous pressure; damaged trabecular meshwork
after a chemical injury
 Diagnostics
o Tonometry: Measures IOP
o Gonioscopy: Eye examination that allows direct
visualization of the anterior chamber and the chamber
angle
o Fundoscopy: Cupping and pallor of optic disc
 Therapy
o Conservative: Topical prostaglandins
o Improve drainage: Topical prostaglandins (latanoprost)
o Reduce aqueous humor production: topical beta blockers
(timolol) alpha 2 agonists (apraclonidine)
o Avoid epinephrine in angle closure glaucoma
 Acute Angle Closure Glaucoma
 Sudden and sharp increase in intraocular pressure caused by an
obstruction of aqueous outflow (most commonly occlusion of the
chamber angle)
 Unilateral red, hard, and severely painful eye
 Steamy cornea and blurred vision
 Etiology: Advanced age; Female gender; Inuit and Asian ethnicity;
Rubeosis iridis; Mydriasis (blocked by the iris) due to drugs
(anticholinergics e.g. atropine; sympathomimetics;
decongestants; darkness stress/fear response
 Pathophysiology
 Flow of aqueous humor against resistance generates an average
intraocular pressure between 10-21 mmHg
 Blocked trabecular meshwork  decreased drainage of aqueous
humor from the eye  sudden IOP
 Primary: chamber angle narrowed due to the peripheral iris
obstructing the trabecular meshwork
  Secondary: scarring, lens luxation, or rubeosis iridis
 Clinical Features
 Unilaterally inflamed, reddened, severely painful eye (hard on
palpation)
 Diagnostics:
 Rock hard globe on palpation
 Gonioscopy (gold standard)
 Tonometry: increased IOP
 Treatment
 First Line:
o Eye drops: Beta blockers (timolol); Alpha 2 agonist
o Systemic: Carbonic anhydrase inhibitor oral or IV
(acetazolamide)
 Topical Cholinergics (pilocarpine) added once IOP is <40 mmHg
 Analgesics and antiemetics
 Definitive surgical treatment
o Once acute attack controlled
o Shunt from posterior to anterior chamber through the
peripheral iris
 Neodymium YAG laser iridotomy
o Otitis Malignant Externa
 Commonly caused by an infection with pseudomonas aeruginosa;
Connection between diabetes and MOE may be related to increased pH
in diabetic cerumen
 Diagnostic: Blood Cultures
 Treatment: High Dose IV Ciprofloxacin
 Pharmacology
o Renin-Angiotensin-Aldosterone System Inhibitors
 Drops in blood pressure reduce renal perfusion.
 If the pressure in the renal artery falls by more than 10–15 mm Hg →
proteolytic renin is released from the juxtaglomerular
apparatus → renin converts angiotensinogen to angiotensin I → ACE cleaves C-
terminal peptides on angiotensin I, converting it to angiotensin II → increases the
blood pressure in two ways: (1) vasoconstriction and (2) stimulation of the
release of aldosterone, which increases the retention of water and sodium
 Types of RAAS Inhibitors
 ACE Inhibitors = Enalapril, Lisinopril, Ramipril, Captopril,
Benazepril
 ARBs = Valsartan, Candesartan, Losartan, Irbesartan
 Indications:
o Arterial Hypertension
o Diabetes Mellitus
 Nephroprotective
 Arterial Hypertension
 Microalbuminuria (>300 mg/g)
  Coronary Heart Disease
o Heart Failure with reduced EF
o History of Myocardial Infarction
o Nondiabetic Associated CKD with Proteinuria
o Scleroderma associated hypertensive crisis
 Effects
 Side Effects
o ACE Inhibitors = Dry cough due to increase in bradykinin
concentration; angioedema; hyperkalemia; pemphigus
vulgaris
 Contraindications
o Absolute
 Hypersensitivity
 C1 esterase inhibitor deficiency
 Pregnancy
 Breastfeeding
o Relative
 Aortic Stenosis
 Renal Dysfunction
 Bilateral Renal Artery Stenosis (reduced GFR too
low)
o Chemotherapeutic Agents
 Overview - Indications
 Alkylating Agents
o Oxazaphosphorines
o Nitrogen Mustards
o Hydrazine
o Plantinum Based Agents
 Topoisomerase Inhibitors
o Topoisomerase I Inhibitor
o Topoisomerase II Inhibitor
 Mitotic Inhibitors
o Vinca Alkaloids
o Taxanes
 Antimetabolies
o Antifolates
o Pyrimidine Antagonists
o Purine Analogs
o Purine Antagonists
o Ribonucleotide Reductase Inhibitors
 Other
o Antibiotics
o Enzymes
 o Proteasome Inhibitors
o Tyrosine Kinase Inhibitors
 Mode of Action
 Side Effects
 Alkylating Agents
o Oxazaphosphorines
 Hemorrhagic Cystitis  Mesna (neutralizes
acrolein, a metabolite product)
o Nitrogen Mustards
o Hydrazine
o Platinum Based Agents
 Nephrotoxic (prevent with amifostine, free radical
scavenger)
 Topoisomerase Inhibitors
o Anthracyclines = Dilated Cardiomyopathy
o Topoisomerase I Inhiitors
o Topoisomerase II Inhibitors
 Mitotic Inhibitors
o Vinca Alkaloids
 Neurotoxic (Vincristine)
o Taxanes = Pulmonary Fibrosis
 Antimetabolies
o Antifolates  Folinic acid (Leucovorin) Resuce
o Pyrimidine antagonists = Leucovorin increases effect
o Purine analogs
 Toxicity increases with allopurinol and febuxostat
(metabolized by xanthine oxidase)
o Purine Antagonist
o Ribonucleotide Reductase Inhibitor
 Antibiotics
o Bleomycin = Pulmonary Fibrosis
o Malignant Hyperthermia
o Diuretics
 Thiazide Diuretics
 1st line drug for black patients with isolated systolic hypertension
 Inhibition of Na/Cl cotransport in the DCT
o Increased reabsorption of calcium
o Increased excretion of sodium, chloride, and potassium
 Side Effects
o Hypokalemia and Metabolic Alkalosis
o Hypercalcemia – beneficial in osteoporosis
o Hyperglycemia – Avoid in diabetics
 o Hyperlipidemia – Avoid in metabolic
syndrome/hypercholesterolemia
o Hyperuricemia
 Potassium Sparing Diuretics
 Indications
o Hypertension
o Ascites/Edema due to CHF
o Hyperaldosteronism
o Chloroquine and Hydroxychloroquine
 Effects
 Anti-malarial: the drugs stabilize the lysosomes of the schizonts
and reach a high concentration in the vacuoles → their alkaline
nature raises the internal pH → bind to heme to form the heme-
chloroquine complex, which is highly toxic to the schizont → the
parasite perishes
 Anti-Rheumatoid: these drugs interfere with "antigen processing"
in macrophages and other antigen-presenting cells → decrease
the formation of peptide-MHC protein complexes → down-
regulate the immune response against autoantigenic peptides
 Side Effects
 Visual Disturbances
o Irreversible retinopathy “Bull’s Eye Maculopathy”
o Blurred Vision
 Indicatios
 P. malaria, P. ovale, P. falciparum (NOT P VIVAX)
o Pain Management
 Types of Pain
 Referred Pain
 Phantom Limb Pain
 Evaluation of Pain
 Treatment of Pain
 Additional Methods of Pain Management
o Antibiotics
 Beta Lactam Antibiotics
 Penicillins
 Carbapenems
 Monobactams
 Cephalosporins
o Cefazolin = Recommended prophylactic antibiotic for most
patients undergoing orthopedic procedures
o Third Generation – Ceftriaxone
 Glycopeptides (Vancomycin)
 Epoxides (Fosfomycin)
 Lipopeptides (Daptomycin)
 Sulfonamides and Trimethoprim (Cotrimoxazole (TMP/SMX) =
(Trimethoprim + Sulamethoxazole)
 Fluoroquinolones
 Nitroimidazoles (Metronidazole)
 Aminoglycosides (Gentamicin, Amikacin, Tobramycin, Streptomycin,
Neomycin)
 Tetracycline
 Glycylcyclines (Tigecycline)
 Lincosamides (Clindamycin)
 Amphenicols (Chloramphenicol)
 Oxazolidinones (Linezolid)
 Macrolides (Erythromycin, Azithromycin, Clarithromycin)
 Adverse Effects
o Increased intestinal motility  GI Discomfort
o QT Interval Prolongation  Torsades de Pointe
 Contraindications
o Pregnancy
 Nitrofurans (Nitrofurantoin)
 Polymyxins
 Antimycobacterial Drugs
 Rifamycins
 Isoniazid
 Pyrazinamide
 Ethambutol
 Dapsone
 Contraindications
 Infants = Chloramphenicol
 < 8 years = Tetracyclines
 < 18 years = Fluoroquinolones
 Pregnant Women
o All Trimesters
 Tetracyclines
 Fluoroquinolones
 Erythromycin
 Clarithromycin
 Streptomcyin
 Breastfeeding Women
o Sulfonamides
o Tetracyclines
o Metronidazole
o Fluoroquinolones
o Nitrofurantoin
  Renal Failure
o Absolutely Contraindicated: Tetracyclines
o Relatively Contraindicated: Aminoglycosides,
Cephalosporins, Fluoroquinolones
o Opioids
 Tramadol
 Lowers seizure threshold
 Complications
 Long term = Hypogonadism
 Causes constriction of the sphincter of Oddi
 Prevention of constipation: Polyethylene glycol (MiraLax)
o Non-Opioid Analgesics
 NSAIDs
 Side Effects
o Increased risk of heart attack and stroke WITH THE
EXCEPTION OF ASPIRIN AND NAPROXEN
o Beta Antagonists
 Contraindications
 Absolute Contraindications
o Symptomatic Bradycardia
o Sick Sinus Syndrome
o Cardiogenic Shock/Hypotension
o Decompensated Heart Failure
o Asthma
o Combination with Calcium Channel Blockers
 Relative Contraindications
o Psoriasis
o Raynaud’s Phenomenon
o Pregnancy (Atenolol is ABSOLUTELY CONTRAINDICATED)
o Pharmacokinetics
 3A4 Inhibitor
 Clarithromycin is a strong 3A4 inhibitor
 Other Inhibitors: Antifungals (azoles), Macrolides (Erythromycin,
Clarithromycin), anti-HIV medications, Grapefruit Juice,
Cimetidine
 Inducers: Carbamazepine, Rifampicin, St. John’s Wort,
Barbiturates, Several, anti-HIV medications, Griseofulvin
 Substrates
o Amlodipine is metabolized by 3A4
o Others: Statins (Except pravastatin), Steroid hormones
(estrogen, glucocorticoids, testosterone),
Immunosuppressives, Macrolides, Carbamazepine,
 Haloperidol, Benzodiazepine, Oral Anticoagulants, Calcium
Channel Blockers (Amlodipine)
o Glucocorticoids
 Inhibit apoptosis in neutrophils; Promote apoptosis in monocytes,
lymphocytes, and eosinophils
o Statins
 Names
 Atorvastatin
 Simvastatin
 Pravastsatin
 Lovastatin
 Fluvastatin
 Pitavastatin
 Rosuvastatin
 Effects
 Competitive inhibition of HMG-CoA Reductase  Reduced
intrahepatic cholesterol biosynthesis  upregulation of
expression of LDL receptor gene via sterol regulatory element
binding protein (SREBP)
o Decreases LDL; Increased HDL; Decreased Triglycerides
 Side Effects
 Hepatic: Increased LFTs (CYP3A4 & CYP2C9)
 Muscular: Decrease the synthesis of coenzyme Q10 and impair
energy production within muscle which can result in myalgia,
muscle weakness, and increased serum creatine kinase
concentrations due to myositis and/or rhabdomyolysis
o Myalgia – continue as long as CK remains normal
o Statin associated myopathy
 Muscle pain and weakness
 Increased CK
 Progress to rhabdomyolysis: may lead to
myoglobinuria  AKI (Increased BUN & Creatinine)
 Indications
 LDL > 190 mg/dL
 Atherosclerotic CVD, stroke, PAD
 40-75 with diabetes and LDL levels of 70-18 mg/dL
 40-75 with an estimated 10 year ASCVD risk >7.5% and LDL levels
70-189 mg/dL
 Contraindications
 Hypersensitivity
 Active Liver Disease
 Muscle Disorder
 Pregnancy, Breastfeeding
  Interactions
 Lipid Lowering Agents
o Fibrates
o Nicotinic Acid
o Both together may cause myopathy
 CYP3A4 Inhibitors
o HIV/HCV protease inhibitors
o Macrolides (especially erythromycin and clarithromycin)
o Azole antifungals
o Cyclosporine
 Warfarin
o CHF
 Digoxin
 Cardiac Glycoside Poisoning
o Etiology
 Digoxin overdose
 Hypokalemia (potassium depleting diuretics)
 Renal Failure
 Treatment with verapamil, diltiazem, amiodarone,
and/or quinidine (can cause overdose)
 Volume depletion
o Clinical Features
 Nausea/Vomiting; Diarrhea; Gastrointestinal Pain;
and Anorexia
 Blurry vision with a yellow tint and halos;
disorientation; weakness
o Diagnostics:
 ECG; PVCs, T wave inversion/flattening; Decreased
QT interval; Increased PR interval
o Laboratory Studies: Serum digoxin concentration;
Hyperkalemia; Creatinine and BUN
o Treatment:
 Digoxin specific antibody fragments
 Atropine for symptomatic bradycardia; Slowly
normalize serum K+; Magnesium; Class IB
antiarrhythmics;
o Digoxin contraindicated in ventricular fibrillation; must use
coaution in pregnant women
o Oral Anticoagulants
 Direct inhibition of thrombin (dabigatran)
 Warfarin = reduced activation of the vitamin K dependent clotting factors
2, 7, 9 and 10
 Direct Inhibition of Factor Xa (Apixaban and rivaroxaban)
 GPIIb/IIIa complex inhibition (Abciximab, Epitifibatide, tirofiban)
  Thrombocyte Phosphodiesterase III Inhibitor (Cilostazol and
dipyridamole)
 Recombinant tissue plasminogen activator (alteplase, reteplase,
tenecteplase) and streptokinase – increase conversion of plasminogen to
plasmin
 Heparin = Induction of conformational change in antithrombin III
o Signal Transduction
 Receptors
 Intracellular Receptors
 Cell Surface Receptors
 G Protein Coupled Receptors
o Receptor Type & Connected G proteins
 Alpha 1 = Gq; alpha 2 = Gi
 Beta1, 2, 3 = Gs
 M1, M3 = Gq; M2 = Gi
 Histamine H1 = Gq; Gs = H2
 Dopamine D1 = Gs; D2 = Gi
 Vasopressin V1 = Gq; V2 = Gs
o Gs = Adenylyl Cyclase; Gi = Inhibit adenylyl cyclase; Gq =
phospholipase C
 Receptor Tyrosine Kinase
 Non-Receptor Tyrosine Kinases
o Nitrates
 Agents
 Nitroglycerin
 Isosorbide Dinitrate
 Isosorbide Mononitrate
 Sodium Nitroprusside
 Effects
 Exogenous supply of nitric oxide through nitrate  activation of
guanylyl cyclase  increased cyclic guanosine monophosphate
(cGMP)  Activation of Protein Kinase G
o Peripheral Vasodilation
o Coronary Dilation
 Anginal Pain Relief
 Side Effects
 Circulatory Dysregulation: Hypotension
 Nitrate Induced Headache (Vasodilation of the cerebral arteries)
 Gastroesophageal Reflux
 Development of Tolerance
 Cyanide Toxicity
 Indications
 Angina Pectoris
  Hypertensive Crisis
 Hypertensive Pulmonary Edema
 Chronic Heart Failure
 Contraindications
 Hypotension
 Endocrinology
o Lipid Disorders
o Cushing Syndrome
o Disorders of Sex Development
 Congenital Adrenal Hyperplasia
 Androgen Insensitivity Syndrome
 5-alpha reductase deficiency
 Klinefelter Syndrome
 Turner Syndrome
 Swyer Syndrome
 Pure Gonadal Dysgenesis
 Aromatase Deficiency
 Ovotesticular Disorder of Sex Development
o Hyperprolactinemia
 Causes hypogonadotrophic hypogonadism
o Transplantation**
o Primary Hyperaldosteronism
o Acromegaly
o Inborn Errors of Metabolism
o Carcinoid Tumor
 VIPoma
 Increases relaxation of gastric and intestinal smooth muscles
causing unregulated fluid and electrolyte secretion leading to
secretory tea colored diarrhea along with the resulting
dehydration and hypokalemia
 Inhibits gastric acid secretion, increases bone resorption, and
stimulates gluconeogenesis leading to
achlorhydria/hypochlorhydria
o Acute Pancreatitis
 Diagnostics
 Most useful initial test – Ultrasound
o PCOS
 Pathophysiology
 Reduced insulin sensitivity
 Hyperinsulinemia results in: obesity, epidermal
hyperplasia/hyperpigmentation (acanthosis nigricans); increased
androgen production in ovarian theca cells (increased LH;
Increased androgens; Inhibit production of SHBG in liver)
  Clinical Features
 Menstrual irregularities; Difficulties conceiving or infertility;
Obesity; Hirsutism; Androgenic alopecia; Acne vulgaris; Acanthosis
nigricans; Premature adrenarche;
 Diagnostics
 Hyperandrogenism; Oligo- and/or anovulation; Polycystic ovaries
on ultrasound (transvaginal ultrasound)
 Increased testosterone; Increased LH (LH:FSH >2:1)
 Differential
 Pregnancy; Congenital Adrenal Hyperplasia; Cushing’s Disease;
Pituitary Adenoma; Hyperprolactinemia
 Treatment –
 If treatment for infertility not sought:
o If BMI >25 kg/m^2
 First Line = Weight Loss
 Second Line = Combined Oral Contraceptive
o If not overweight: combined oral contraceptive therapy
 If seeking treatment for infertility
o First Line: Ovulation induction with clomiphene citrate
(inhibits hypothalamic estrogen receptors thereby
blocking the normal negative feedback effect of estrogen
 increased pulsatile secretion of GnRH  increased FSH
and LH which stimulates ovulation
o Second Line: Ovulation induction with oxogenous
gonadotropins or laparoscopic ovarian drilling
 Complications
 Cardiovascular Events
 Type II Diabetes Mellitus
 Endometrial Cancer
 Increased miscarriage rate
o Pituitary Adenoma
 Can cause hypothyroidism with decreased TSH levels (central
hypothyroidism)
 Diagnostics:
 Elevated prolactin levels
 MRI of the Pitutiary
o Diabetes Mellitus **
 Epidemiology
 Type 1
o Childhood onset
 Type 2
o Adult onset
 Etiology
 Type 1: Autoimmune beta cell destruction
o Associated with hashimoto thyroiditis, Type A gastritis,
Celiac Disease, Primary Adrenal Insufficiency
 Type 2: Hereditary and environmental factors
o Associated with metabolic syndrome
o Risk Factors: Obesity, High calorie diet; High waist to hip
ratio; Physical inactivity; First degree relative with
diabetes; Ethnicity
 Classification
 Pathophysiology
 Clinical Fatures
 Diagnostics
 Differential Diagnosis
 Treatment
 Algorithm
 Insulin Therapy
 Complications
 HHS
o Marked hyperglycemia (>600 mg/dL) increases serum
osmolality (>320 mOsm/kg)
o Sodium levels low due to extracellular water shifts from
the hyperosmolarity (hypertonic hyponatremia)
 DKA
o Cerebral edema is a risk
 Diabetic Nephropathy
 Diabetic Retinopathy
 Diabetic Neuropathy
 Diabetic Foot
 Prognosis
 Special Patient Groups
o Metabolic Syndrome
 Definition
 Presence of >3 of the following:
o Insulin Resistance: Fasting Glucose >100 mg/dL
o Elevated BP: >130/85 mmHg
o Elevated Triglycerides: >150 mg/dL
o Low HDL-C
 In Men: < 40 mg/dL
 In Women: <50 mg/dL
o Abdominal Obesity
 > 102 cm (>40 in) in men
 > 88 cm (>35 in) in women
 Treatment
 o First Line: Lifestyle Modifications
 Dietary Changes: Calorie Restriction
 Physical Activity: minimum of 30 minutes moderate
exercise per day (2.5 hours per week) which
increases insulin sensitivity, lowers blood pressure,
and promotes weight loss
o Medical Therapy:
 Treat Hypertension (Ace Inhibitors, Diabetes
Mellitus, and Dyslipidemia (Statin)
o Bariatric Surgery
 If BMI >40 with no success with dietary and
lifestyle changes
 Complications
o Cardiovascular Disease
o Type II Diabetes
o Non-Alcoholic Steatohepatitis  increased risk of
developing liver cirrhosis and hepatocellular carcinoma
o Anti-diabetic Drugs
 Biguanides
 Mechanism of Action: Enhances effect of insulin
o Reduction in insulin resistance via modification of glucose
metabolic pathways
 Inhibits mitochondrial glycerophosphate
dehydrogenase
 Decreases hepatic gluconeogenesis and
intestinal glucose absorption
 Increases peripheral insulin sensitivity
o Lowers postprandial and fasting blood glucose levels
o Reduces LDL, increases HDL
 Indications: Type 2
 Clinical Characteristics
o Glycemic efficacy
o Weight Loss of Weight Stabilization
o No risk of hypoglycemia
 Important Side Effects
o Metformin Associated Lactic Acidosis
 GI Prodromal Syndromes: Nausea, vomiting,
diarrhea, abdominal pain
 Severe symptoms: muscle cramps,
hyperventilation, apathy, disorientation, coma
 High risk groups: Elderly; Cardiac or Renal
Insufficiency
 Diagnostics
  ABG: Metabolic Acidosis and Anion Gap
 Increased Serum Lactate
o GI Complaints
o Vitamin B12 Deficiency
o Metallic Taste in the Mouth
 Contraindications
o Renal Failure (GFR <30 mL/min)
o Severe Liver Failure
o IV Iodinated Contrast Medium
o Pause prior to surgery
o Ketoacidosis
o Heart Failure, Respiratory Failure, Shock, Sepsis
o Alcoholism
 Thiazolidinediones (Pioglitazone, Rosiglitazone)
 Clinical profile
o Mechanism of Action: Activation of the transcription factor
PPAR (peroxisome proliferator activated receptor of
gamma type)  increase transcription of genes involved in
glucose and lipid metabolism  increased levels of
adipokines such as adiponectin  increased storage of
triglycerides and subsequent reduction of products of lipid
metabolism  glucose utilization is increased and hepatic
glucose production reduced
o Clinical Characteristics: Lowers a1c by 1% in 3 months
 No risk of hypoglycemia
o Important Side Effects
 Fluid Retention and Edema
 Weight Gain
 Increased risk of heart failure
 Increased risk of bone fractures (osteoporosis)
o Contraindications
 CHF
 Liver Failure
 Sulfonylureas (Glyburide, Glipizide)
 Clinical Profile
o Mechanism of Action: Block ATP Sensitive potassium
channels of the pancreatic beta cells  depolarization of
the cell membrane  calcium influx  insulin secretion
o Clinical Characteristics: lowers a1c by 1.2% over 3 months
 Important Side Effects
o Life Threatening Hypoglycemia
 Increased risk in patients with renal failure
 Weight Gain
  Hematological: Granulocytopenia, Hemolytic
Anemia
 Allergic Skin Reactions
 Alcohol Intolerance
 Contraindications
o Severe Cardiovascular Comorbidity
o Obesity
o Sulfonamide Allergy
o (Beta blockers may mask the warning signs of
hypoglycemia and decrease serum glucose levels even
further
 Meglitinides (sulfonylurea analogue – repaglinide, nateglinide)
 Mechanism of Action: Enhances insulin secretion similar to
sulfonylureas
 Important side effects:
o Life threatening hypoglycemia
o Weight Gain
 Contraindications
o Severe Liver Failure
o Severe Renal Failure
 Incretin Mimetics (Exenatide, Liraglutide)
 Mechanism of Action: Food Intake  activation of
enteroendocrine cells in GI tract  release GLP-1  GLP-1
degradation via DPP-4  end of GLP-1
o Incretin mimetic drugs bind to GLP-1 receptors and are
resistant to degradation by DPP-4 enzyme  insulin
secretion increase, decrease glucagon secretion, slow
gastric emptying (increased feeling of satiety, decreased
weight)
 Clinical Characteristics
o Weight Loss
 Side Effects
o GI Complaints
o Increased risk of pancreatitis and potentially pancreatic
cancer
 Contraindications
o Symptomatic GI motility disorders
o Chronic pancreatitis or family history of pancreatic tumors
 Dipeptidyl peptidase 4 inhibitors (Sitagliptin, Saxagliptin)
 Mechanism of action: indirectly increase the endogenous incretin
effect by inhibiting the DPP-4 enzyme that breaks down GLP-1 
increased insulin secretion, decreased glucagon secretion,
delayed gastric emptying
  Important Side Effects
o GI Complaints: Diarrhea, Constipation
o Arthrlagia
o Increased risk of pancreatitis
o Acute Renal Failure
 Contraindications
o Liver Failure
 SGLT-2 Inhibitors (Dapaglifozin, Empagliflozin, Canagliflozin)
 Mechanism of Action: Reversible inhibition of the sodium
dependent glucose co-transporter SGLT-2 in the proximal tubule
of the kidney  reduced glucose reabsorption in the kidney 
glycosuria and polyuria
 Clinical Characteristics: Promotes weight loss, reduces blood
pressure
 Important Side Effects:
o Urinary Tract Infections, Genital Infections
o Dehyhdration
o Severe Diabetic Ketoacidosis
 Contraindications
o CKD
o Recurrent UTIs
 Alpha Glucosidase Inhibitors (Acarbose, Miglitol)
 Mechanism of Action: Inhibits alpha glucosidase  decrased
intestinal glucose absorption
 Clinical Characteristics: No risk of hypoglycemia
 Important Side Effects: GI Complaints (Flatulence, Abdominal
Discomfort, Diarrhea)
 Contraindications
o IBS
o Malabsorption Conditions
o Sever Renal Failure

o Glucagonoma
 Increased fasting glucagon levels
 Increases gluconeogenesis and inhibits glycolysis causing hyperglycemia
 Necrolytic Migratory Erythema
 Paraneoplastic cutaneous reaction
 The direct action of glucagon on skin, protein deficiency, and/or a
deficiency of zinc and fatty acids due to chronic diarrhea

o Acute Adrenal Insufficiency
  Symptoms: Fatigue and lack of energy, weight loss, hypotension, loss of
appetite, nausea, and vomiting. Dry skin, hyperpigmentation, and
abdominal pain
 Diagnostics
 Laboratory Findings: Electrolyte disturbances, hyponatremia,
hyperkalemia, hypercalcemia, azotemia, anemia, and eosinophilia
o Diabetes Insipidus
 Etiology
 Central Diabetes Insipidus
o Primary: Idiopathic
o Secondary: Brain tumors, neurosurgery, TBI, Ppituitary
ischemia
 Nephrogenic Diabetes Insipidus
o Medications (lithium, demeclocycline)
o Hypokalemia, Hypercalcemia
o Renal Disease (ADPKD)
o Pregnancy
 Clinical Features
 Polyuria; Nocturia; Polydipsia; Dehydration
 Treatment
 Central: Desmopressin
o Alternative: Chlorpropamide (increases ADH release)
 Nephrogenic: Thiazide Diuretics; NSAIDs; Amiloride
o Thyroid
 Hypothyroid
 Can cause an elevated LDL because T4 is required for upregulation
of the LDL receptor on cell surfaces
 Antithyroid Drugs
 Methimazole – thioamide that interferes with the production of
T3 and T4. Inhibits thyroid peroxidase and the oxidation of iodide.
 Graves Disease
 Etiology
o B and T lymphocyte mediated autoimmune disorder
o 50% have family history
 Pathophysiology
o TSH receptor stimulating IgG immunoglobulin 
hyperthyroid
o TRAb stimulate:
 Orbital fibroblast  hyaluronic acid synthesis and
differentiation of fibroblasts to adipocytes
(opthalmopathy with exophthalmos)
  Dermal fibroblasts and deposition of
glycosaminoglycans in connective tissue (pretibial
myxedema)
o Thyroid Cancer
o General Endocrinology
 Hypothalamic Neuropeptide Y decreased due to an increase in leptin
serum concentration = decreased appetite
 Leptin insensitivity = unopposed appetite  Obesity
o Subacute Thyroiditis
 Summary
 Transient patchy inflammation of the thyroid gland associated
with granuloma formation or lymphocytic infiltration
 Subacute granulomatous thyroiditis = Usually occurs after a viral
upper respiratory tract infection
 Subacute lymphocytic thyroiditis = postpartum period,
autoimmune diseases, or side effect of drugs
 Etiology
 DeQuervain Thyroidits
o Viral Infection: Mumps, Coxsackie, Influenza, Echovirus,
Adenovirus, Mycobacterial Infection
 Subacute Lymphocytic Thyroiditis
o Drugs: alpha interferon, lithium, amiodarone, interleukin-
2, tyrosine kinase inhibitors
o Autoimmune disease
o Postpartum thyroiditis
 Pathophysiology
 Inflammation of the thyroid gland associated with a triphasic
response
o Thyrotoxic phase (lasts 4-6 weeks): damage to follicular
cells and release of pre-formed colloid (stored thyroid
hormones)
o Hypothyroid phase (4-6 months): depletion of pre-formed
colloid and impaired synthesis of new thyroid hormones as
a result of damage to follicular cells
o Euthyroid phase: Thyroid function recovers and
pathological changes are no longer visible in the thyroid
gland
 Clinical Features
 Subacute Granulomatous Thyroiditis
o Possible history of URTI
o Painful, diffuse, firm goiter
o Fever and/or malaise
 o Features of hyperthyroidism followed by features of
hypothyroidism
 Subacute Lymphocytic Thyroiditis
o Painless, diffuse, firm goiter
o Features of hyperthyroidism followed by features of
hypothyroidism
 Diagnostics
o Thyroid Function Test
 Thyrotoxic phase: Increased T3 and T4; Increased
thyroglobulin; Decreased TSH
o Confirmatory Test
 Increased ESR
 Decreased iodine uptake
o Ultrasound: Thyroid with poorly defined hypoechoic
regions and decreased vascularity; cobblestone
appearance
o Histology:
 Subacute granulomatous thyroiditis:
Granulomatous inflammation, multinucleated giant
cells
 Subacute lymphocytic thyroiditis: Absence of
germinal follicles, lymphocytic infiltration
 Treatment
o Thyrotoxic phase:
 Beta Blockers
 NSAIDs (Granulomatous)
 Corticosteroids
 Antithyroid drugs should not be administered
o Gastrointestinal
 Meckel Diverticulum
 Pathophysiology
o Omphalomesenteric duct = connecting yolk sac to the
alimentary tract in the embryo
o Incomplete obliteration of the omphalomesenteric duct
 Anatomy
o Meckel diverticulum = true diverticulum
o 2 types of mucosal lining = native ileal mucosa +
heterotopic mucosa
o Blood supply: vitelline artery
 Clinical Features
o Asymptomatic
o Symptomatic
 Painless lower GI bleeding
  Hematochezia
 Tarry Stools
 Currant Jelly Stools
 Diagnostics
o Imagiang
 Meckel Scintigraphy Scan (99mTc)
 CT Angiography
 Alcoholic Liver Disease
 Differential Diagnosis
o Non-Alcoholic Steatohepatitis
 Colorectal Cancer
 Prevention
o Asymptomatic men and women >50 years of age
o Low risk individuals:
 Complete colonoscopy = every 10 years if no polyps
or carcinomas detected
 Annual fecal occult blood tet (poor sensitivity)
 Sigmoidoscopy = every 5 years and FOBT every 3
years
 Annual Fecal Imunochemical Testing
 CT Colonography every 5 years
o High Risk Individuals
 Complete colonscopy 10 YEARS EARLIER thant he
index patient’s age at diagnosis or NO LATER than
40 years of age
o If poly removed:
 Hyperplastic polyp < 10 mm in size = 10 years
 Low risk adenoma: 1-2 tubular polyps < 10 mm in
size and without intraepithelial neoplasia = 5-10
years
 High risk adenoma (3-10 tubular polyps; 1 polyp >
10 mm; 1 villous or tubulovillous polyp; 1 tubular
polyp = 3 years
 More than 10 adenomas = <3 years
 Lynch Syndrome
 Prevention
o Cancer Screening
 Annual Colonscopy 2-5 years before earliest case of
tumor in the family
 Annual pelvic exam with transvaginal sonography
and endometrial biopsy at 30-35 years of age or 3-
5 years before earliest case of tumor in family
 Annual physical exam and urinalysis
 o Total Colectomy
 Colonic Polyps
 Classification
o Low Malignant Potential
 Hamartomatous
 Juvenile Polyposis Syndrome
 Peutz jeghers Syndrome
 Cowden Syndrome
 Cronkhite Canada Syndrome
 Inflammatory Polyps
 Ulcerative Colitis
 Mucosal Polyps
 Submucosal Polyps
o Moderate Malignant Potential
 Serrated Polyps
 Hyperplasti Polyps
 Sessile Serated Polyps
 Traditional Serrated Adenoma
o High Malignant Potential
 Adenomatous Polyps
 Tubular Adenoma
 Tubulovillous Adenoma
 Villous Adenoma
 Subtypes and Variants
o Hereditary Polyposis Syndrome
o Adenomatous Polyposis Syndromes
 Familial Adenomatous Polyposis
 Prevention:
o Screening begins at 10 years of age =
Rectosigmoidoscopy
o Upper endoscopy begins at 25 years
of age
 Primary Biliary Cholangitis
 Pathophysiology
o Inflammation and progressive destruction of the small and
medium sized intrahepatic bile ducts (progressive
ductopenia)  defective bile duct regeneration  chronic
cholestasis  secondary hepatocyte damage
 Clinical Features
o Fatigue
o Marked generalized pruritis
o Hyperpigmentation
o Hepatomegaly, Dull Lower Margin, RUQ Discomfort
 o Splenomegaly
o Maldigestion
o Xanthomas and Xanthelasma
 Diagnostics
o Laboratory Tests
 Increased Cholestasis (ALP, GGT, Conjugated
Bilirubin)
 Transaminases within normal limits
 Increased AMA
 Increased ANA
 Increased IgM
o Liver Biopsy
 Pathology
 Treatment
o 1st Line = Ursodeoxycholic Acid
o Inguinal Hernia
 Indirect Inguinal Hernia
 Failure of the processus vaginalis to close
o Pernicious Anemia
 Increased risk of developing gastric adenocarcinoma
 90% have chronic atrophic gastritis
o Anal Fissures
 90% occur at the posterior midline, distal to the pectinate line (dentate
line)
o Inflammatory Bowel Disease
 Ulcerative Colitis
 Management
o Begin screening colonoscopy 10 years after the initial
diagnosis and continue every 2-5 years
 Crohn’s Disease
o PPIs
 The use of PPIs + H2 Receptor Antagonist  Vitamin B12 Deficiency
o Intestinal Ischemia
 Acute Mesenteric Ischemia
 Clinical Features
o Periumbilical Pain disproportionate to physical findings
o Diarrhea
o Nausea + Vomiting
o Diverticulitis
 Indications for surgery: Generalized peritonitis; Unconfined perforation;
Uncontrolled sepsis; Undrainable abscess; Failure of conservative
management
o Irritable Bowel Syndrome
  Treatment: Citalopram
o Nonalcoholic Fatty Liver Disease
 Accumulation of fat in hepatocytes
 Associated with insulin resistance, central adiposity, increased BMI, HTN,
Dyslipidemia
o Acute Rectal Fissure
 Treatment: Internal Sphincterotomy; Botulinum toxin injection
o Zenker Diverticulum
 Increased intrapharyngeal pressure on a physiologically weakened area of
the hypopharynx (Killian triangle) causes the local mucosa and submucosa to
bulge through the muscularis propria
 Pressure increase is usually due to esophageal dysmotility (e.g., inadequate
relaxation of the upper esophageal sphincter). Pulsion diverticula (due to
increased intraluminal pressure), such as Zenker diverticulum or colonic
diverticula in diverticulosis, are typically false diverticula, whereas traction
diverticula (due to inflammatory processes) are true diverticula.
o Inborn errors of carbohydrate metabolism
 Glycogen Storage Disorders
 Type I (Von Gierke)
 Type II (Pompe)
 Type III (Cori)
 Type IV (Anderson)
 Type V (McArdle)
o Myophosphorylase Deficiency (McArdle’s Disease)
glycogen storage disease that presents with myalgias,
rhabdomyolysis, myoglobinuria, and early fatigue from
exercise due to inability to break down glycogen for use as
energy in muscle tissues
o Second wind phenomenon
 Type VI (Hers)
 Galactosemia
 Most common form is galactose-1-phosphate uridylyltransferase
deficiency which leads to the accumulation of galactose-1-
phospahte and galactitol
 Accumulation of galactitol causes infantile cataracts
 Symptoms become apparent when the newborn starts feeding
breast milk and/or routine formula
 Must avoid food containing lactose (cow and breast milk)
 Disorder of Fructose Metabolism
o Rare Neurological Diseases
 Adrenoleukodystrophy
 X linked neurological disease caused by an impaired peroxisomal
ATP binding cassette transporter protein that leads to an
accumulation of very long chain fatty acids in the adrenal glands,
testes, and white matter, and subsequent neuron demyelination
 o Celiac Disease
 Associated with Turner Syndrome
 MSK
o Collection of Orthopedic Conditions
 Popliteal Baker Cyst
 Bursitis
 Meniscal Cyst
 Stress Fracture
 Genu Valgum
 Genu Varum
 Greater Trochanteric Pain Syndrome
 Forearm Fractures
o Insertional Tendinopathies
o Dupuytren’s Contracture (Palmar Fibromatosis)
 Fibromatosis of the palmar fascia leading to overproliferation of
fibroblasts and formation of collagen nodules/cords
o Reactive Arthritis
o Spinal Stenosis
o Subacromial Bursitis
 Subacromial Impingement Syndrome
o Orthopedic Shoulder Examination ***
o Soft Tissue Lesions of the Shoulder
o Patellofemoral Pain Syndrome
 Peripatellar pain
 Malalignment of the patella and femoral grove with resultant patellar
chondromalacia
o Friedreich Ataxia
 8-15 years old
 Etiology
 Trinucleotide repeat expansion (GAA) in the FXN gene on
chromosome 9  intramitochondrial accumulation of iron and
dysregulation of cellular antioxidant defense  oxidative damage
to CNS and CVS cells  CNS and CVS degeneration
 Clinical Features
 Neurological
o Progressive Ataxia
 Bilateral lower limbs equally affected
 Wide based steppage gait with dysmetria
and frequent falling
 Torso and Arms
 Action and intention tremors
 Choreiform movements
  Associated impaired proprioception, vibration
sense, and loss of deep tendon reflexes
o Dysarthria and dysphagia
 Skeletal Deformities
o Secondary Scoliosis
o Foot deformity: foot inversion (pes cavus) with hammer
toes
 Concentric hypertrophic cardiomyopathy
 Diabetes Mellitus
 Personality Changes
 Diagnostics
 Trinucleotide repeat expansion assay
 ECG: T wave inversion and ventricular hypertrophy
 Echocardiography: symmetric, concentric ventricular hypertrophy
 Nerve conduction studies
o Sensory: absent or reduced sensory nerve action
potentials
o Motor: normal until advanced
 MRI brain/spinal cord: cervical spine atrophy
 Treatment
 None
o Paget Disease of Bone
o Septic Arthritis
 Etiology
 Mechanism of Infection
o Hematogenous Spread
 Distant site
 Disseminated Infection
o Direct Contamination
 Risk Factors
o Prosthetics; Interventions; Immunosuppression; Diabetes
Mellitus; Age; Chronic Skin Infections; IV Drug Use
 Causative Organisms
o Most common in adults and children >2 years =
staphylococcus aureus
o Streptococci
o S. epidermidis
o H. influenzae
o N. gonorrhea
o Gram negative rods (E. coli and P. aeruginosa)
o M. tuberculosis; Mycobacteria
o B. burgdorferi
  X-Ray of the Femur/Hip then CBC and ESR then ultrasonography (highly
sensitive for effusion)
 Treatment
 Initial Management
o
o Transient Synovitis
o Polymyositis
 Proximal muscle involvement
 Elevation of muscle enzymes CK and Aldolase
 Treatment = Corticosteroids
o Ankle Injury
 Ottawa Ankle Rules
o Necrotizing Fascitis
 Group A Streptococcus
 Treatment
 Mild Infection = Oral Antibiotics (Pencillin V or Cephalosporin or
Dicloxacillin or Clindamycin)
 Moderate Infection = IV Antibiotics (Penicillin or Ceftriaxone or
Cefazolin or Clindamycin
 Severe Infection = Surgical Debridement + Empiric Antibiotic
Treatment (Vancomycin + Piperacillin/Tazobactam)
o Adehsive Capsulitis
 Anterosuperior and Anteroinferior Capsular Ligaments
o Achilles Tendinopathy
o Physical Examination
 Muscle Strength
 0 = Inability to contract muscle
 1 = Contraction without movement
 2 = Gravity neutralized
 3 = Movement against gravity only
 4 = Movement against gravity plus some additional resistance
 5 = Movement against substantial resistance
o Lateral Epicondylitis
 Degeneration of the extensor carpi radialis muscle tendon
 Treatment: Conservative Management
o Patellofemoral Pain Syndrome
 Anterior knee pain that is worse with running downhill.
 Apprehension when knee extended with pressure over the patella and
patella will sometimes track laterally
 Treated with exercises to strengthen the quadriceps and hips and by
using a knee sleeve with a doughnut type cushion that the patella fits into
o Osgood Schlatter
  Avascular necrosis from overuse of the quadriceps muscle during periods
of growth
 Causes a traction apophysitis at the tibial insetion of the quadriceps
tendon
 Inflammation of the patellar ligament at the tibial tuberosity
 Clinical: Anterior knee pain that worsens with exercise; Tibial bump may
be felt and can often be seen on X-Ray
o Progressive Muscular Dystrophies
 Epidemiology – Only males affected
 Age of onset:
o DMD: 2-5 years
o BMD: usually not earlier than 15 years of age
 Etiology
 DMD and BMD: X Linked Recessive
 LGMD: Autosomal Dominant or Autosomal Recessive
 Chromosomal defects affect the dystrophin gene on the short arm
of the X chromosome (Xp21)
o Frameshift mutation in DMD
o Point mutation in BMD
 Pathophysiology
 Dystrophin protein anchors the cytoskeleton of a muscular cell to
the extracellular matrix by connecting cytoskeletal actin filaments
to membrane bound dystroglycan that is in turn connected to the
extracellular laminin
 Dystrophin gene mutation and subsequent alterations of the
protein  partial or almost complete impairment of the protein
 disturbance of numerous cellular signaling pathways 
necrosis of affected muscle cells and subsequent replacement
with connective and fat tissue  muscle appears larger
(pseudohypertrophy)
 Clinical Features
 Duchenne Muscular Dystrophy
o Paresis and atrophy starting in the proximal lower limbs
o Weak reflexes
o Waddling gait (bilateral Trendelenburg Sign)
o Gower Maneuver
o Calf Pseudohypertrophy
o Inability to walk by 12 years of age
o Cardiac and respiratory muscle involvement
 Dilated cardiomyopathy
 Cardiac arrhythmias
 Respiratory insufficiency
 Becker Muscular Dystrophy
 o Slower progression
 Diagnostics
 Blood tests: Increased creatine kinase
 Genetic analysis: detect dystrophin gene mutation
 Muscle biopsy
o DMD: Absent dystrophin
o BMD: Reduced dystrophin
 Treatment
 Medical Therapy
o DMD: Glucocorticoids
o BMD: Glucocorticoids (efficacy is low)
 Supportive Therapy
o Physiotherapy; Orthopedic assistive devices; Psychological
Support; Ventilation Support
 Prognosis
 DMD: 30 years (cardiac or pulmonary death)
 BMD: 40-50 years
o Common Peroneal Nerve Injury
 High stepping gait, weakness of foot eversion and dorsiflexion, and
decreased sensation in the anterolateral aspect of the leg and dorsum of
the foot
 Most common peripheral nerve lesion of the lower extremity
 Susceptible to injury during obstetric procedures
 Microbiology
o Rabies
 Rhabdoviridae
 Transmission: Saliva of rabid animal after bite injury
 Pathophysiology: migrates from bite wound retrograde along
microtubules using dynein
o Amebiasis
 Entamoeba histolytica
o Helminth Infections
 Toxocariasis
 Enterobiasis
 Ascariasis
 Trichinellosis
 Taeniasis
 Hookworm Infections
 Strongyloidiasis
 Diphyllobothriasis
o Malaria
 Epidemiology
 Tropical Africa
  Tropical and Subtropical regions such as Asia and Latin America
 Etiology
 Pathogen: Plasmodia
 Vector: female Anopheles mosquito
 Partial Resistance against Malaria:
o Sickle Cell Trait
o Thalassemia, Hb C
 Species
o Plasmodium vivax and Plasmodium ovale (every 2 days
fever)
o Plasmodium malaria (every 3 days)
o Plasmodium falciparum
 Pathophysiology
 Developmental Stages of Plasmodium in RBCs
o Immature trophozoite: thick, dark purple ring-shaped
inclusions (similar to signet ring cell carcinoma)
 With Plasmodium falciparum: fine rings
o Mature trophozoite: ameboid rings
 With Plasmodium falciparum: finer rings in comparison
to immature trophozoites
o Immature schizont: irregular round, ameboid, almost filling the
entire erythrocyte
 With Plasmodium falciparum: hardly detectable in the
blood
o Mature schizont: conglomerate of 6–24 merozoites (round with
central darkening), which develops from an immature schizont
 With Plasmodium falciparum: hardly detectable in the
blood
o Gametocytes
 Macrogamete: mature female (sexual) form, visible as a
round structure filling almost the entire erythrocyte
 Microgamete: mature male (sexual) form, visible as a
round structure within the erythrocyte. In comparison to
macrogametes, it is smaller and has a brighter nucleus.
 Clinical Features
o Incubation: 7-42 days
 Relapse in P. ovale or P. vivax
 Hypnozoites persist within the liver and cause
reinfection after lying dormant for months or even
years
o Flu Like Symptoms
o High Fever
 Tertian Malaria: every 48 hours
 Quartan malaria: every 72 hours
 Falciparum malaria: irregular fever spikes with no
noticeable rhythm
o Weakness, Paleness, Dizziness
o Increased bleeding risk
 o GI; Diarrhea, Abdominal Pain, Nausea, Vomiting
o Liver: Hepatosplenomegaly
o Severe Malaria:
 Most commonly from falciparum malaria
 Kidneys: hemoglobinuria
 Cerebral: hallucinations
 Cardiopulmonary: Heart Failure
 Diagnostics
o History
o CBC
o Blood Smear
 Treatment
o Tertian malaria
 P. vivax & ovale = Chloroquine or
hydroxychloroquine + Primaquine
 P. vivax = artemether lumefantrine + primaquine
o Quartan Malaria = Chloroquine or Hydroxychloroquine
o Sepsis
 Staph Aureus

o Entamoeba histolytica
 Cysts or trophozoites ingest phagocytosed erythrocytes
 Treatment = paramomycin or diloxanide
o Campylobacter
 Treatment – Macrolides (Azithromycin)
o Neisseria gonorrhea
 Treatment – Ceftriaxone + Azithromycin
o Community Acquired Pneumonia
 Diagnostics:
 CURB-65 Score and SaO2
 Treatment –
 Amoxicillin in children 60 days to 5 years of age for activity against
Streptococcus pneumoniae
 Azithromycin for children 5-16 years old because of its activity
against Mycoplasma pneumoniae and Chlamydia pneumoniae
o Sepsis
 Management
 Respiratory stabilization with oxygen
 Fluid resuscitation
 Vasopressors (Dopamine and Norepinephrine)
o Croup
 Clinical:
  Inspiratory stridor, Chest wall retraction, diminished air
movement
 Diagnostics:
 Steeple Sign
 Treatment
 Mild croup: Cool mist inhalation, infant in upright position,
Dexamethasone
 moderate to severe croup: Nebulized epinephrine
o Tuberculosis
 Diagnostics
 Interferon gamma release assay –
o Amount of interferon gamma expressed by T cells
o Not influenced by prior BCG vaccination
 Management:
 Asymptomatic patient with a positive IFN-gamma release assay or
TB skin test, treat if high risk factors for TB using Isoniazid for 9
months

o Asbestosis
 Diagnosis:
 Elongated, yellow asbestos body
 Bilateral infiltrates, Pleural Thickening
o Calcified pleural plaques
o Bilateral ground glass opacities
 Increased Alveolar Arterial Gradient
o Ventilation-Perfusion mismatch due to impaired diffusion
of oxygen across the capillary membrane within the alveoli
from inflammation and fibrosis of pleural parenchyma
o Pertussis
 Treatment
 Macrolides
 Post-Exposure Prophylaxis to all close contacts
o Influenza
 Complications
 Highest risk groups: Children under 2 years old, pregnant women,
adults over 65, morbidly obese (BMI > 40 kg/m^2), and Native or
Alaskan Americans
o Streptococcus
 Group A
 Treatment: Penicillin
o Rocky Mountain Spotted Fever
 Transmission through ticks
  Clinical Diagnosis: Fever, hypotension, rash, myalgia, vomiting, and
headache (sometimes severe)
o Sepsis
 >38.3 C; WBC >12,000/mm3; Respiratory Rate >20 min;
o Clostridium dificile colitis
 Severe = Vancomycin oral 500 mg TID
o Dengue
 Clinical Presentation: Retro-orbital pain, fever, malaise, myalgia
 Treatment
o Varicella Zoster Virus
 Multinucleated giant cells and Cowdry A inclusions via Tzanck test of
shingles lesions
 Immunosuppression is a risk factor for reactivation of VZV after a period
of latency in dorsal root ganglia
o Shingles
 Complications
 Post-herpetic neuralgia
o Treatment
 1st line: TCAs
 Relative Contraindictions (heart disease,
epilepsy, glaucoma): Glaucoma, Pregabalin
 2 Line: Topical capsaicin, opioids, intrathecal
nd

glucocorticoid injections
o Cytomegalovirus (CMV)
 Immunocompetent patients >90% asymptomatic; <10% CMV
mononucleosis
 Immunocompromised patients: CMV Mononucleosis; CMV Pneumonia;
CMV Retinitis; CMV Esophagitis; Adrenal Insufficiency; CMV Encephalitis
 Psychiatry
o Substance-Related and Addictive Disorders
 Nicotine Use Disorder
 Varenicline
 Alcohol Disorder
 Minor alcohol withdrawal = tremor, anxiety, nausea, vomiting,
and/or insomnia
 Major withdrawal = visual and auditory hallucinations,
diaphoresis, tachycardia, and elevated BP
 Delirium Tremens = Delirim
o Anxiety
 Anxiety, shortness of breath, paresthesia, and carpopedal spasm =
hyperventilation
o Medications
 Anti-depressants
  SSRIs
o Duloxetine
 Indicated for both depression and chronic pain
 Unlikely to cause weight gain
o Parvovirus B19
 Associated with Fifth Disease (nonspecific fever, arthropathy, chronic
anemia, and transient aplastic crisis)
 Parvovirus Arthritis
 Mild febrile illness, maculopapular rash beginning on the perioral
areas of the face several days later and spreading to the
extremities from there. Adopts a lacy and reticular pattern.
Symmetric polyarthritis in the fingers, hands, knees, and ankles
while the rash can be absent
 Treatment with analgesics and NSAIDs.
o Prednisone can also be prescribed
 OBGYN
o Pregnancy Loss
 Etiology
 Spontaneous Abortion
o Maternal
o Fetoplacental
o Miscellaneous
 Stillbirth
o Maternal
o Fetoplacental
o Miscellaneous
o Pregnancy***
o Childbirth
 40 weeks pregnanncy
o Ectopic Pregnancy
o Lichen Planus
o Lichen Sclerosus
o Atrophic Vaginitis
o Chorioamnionitis
 Infection of amniotic fluid, fetal membranes, and placenta
 Common bacteria: Ureaplasma urealyticum, Mycoplasma hominis,
Gardnerella vaginalis, Bacteroides, Group B Streptococcus, E. Coli
 Risk Factors:
 Prolonged labor or premature rupture of membranes
 Pathological bacterial colonization of vaginal tract
 Multiple digital vaginal exams, invasive procedures
 Symptoms
 Maternal
 o Fever (>100 F)
o Tachycardia (>120 /min)
o Uterine tenderness, pelvic pain
o Malodorous and purulent amniotic fluid, vaginal discharge
o Premature Contractions, PROM
 Fetal Tachycardia > 160 /min
 Diagnostics: Clinical Diagnosis
 Maternal Blood Tests
o Leukocytosis >15,000 cells/uL; Elevated CRP
 Bacterial Cultures
o Urogenital secretions
o Amniotic fluid
 Group B Streptococcus screening: cervicovaginal and rectal swabs
 Management
 Maternal Antibiotic Therapy
o Vaginal Birth: IV Ampicillin + Gentamicin
o Cesarean Birth: IV Ampicillin and Gentamicin +
Clindamycin
 Delivery
o Swift delivery generally indicated to minimize both
maternal and fetal complications
 Complications
 Maternal
o Uterine atony, postpartum hemorrhage, endometritis
o Septic shock, DIC, venous thrombosis, pulmonary
embolism, death
 Fetal/Neonatal
o Fetal death, premature birth
o Asphyxia, Intraventricular hemorrhage, Cerebral palsy
o Neonatal Infection
o Neonatal Infection and Sepsis
o Omphalitis
o Preterm Labor and Birth
 Definition:
 Preterm Labor: Regular uterine contractions with cervical
effacement, dilation, or both before 37 weeks gestation
 Preterm Birth: Live birth between 20 0/7 weeks and 36 6/7 weeks
of gestation
 WHO Subcategories
o Extremely Preterm (<28 weeks)
o Very Preterm (28 to < 32 weeks)
o Moderate to Late Preterm (32 to < 37 weeks)
 Epidemiology
  Complications of preterm birth are leading cause of death in
children < 5 years of age worldwide
 Approximately half of patients who deliver prematurely are
diagnosed with preterm labor
 Clinical Features
 Regular uterine contractions and associated symptoms of labor
 Cervical dilation >3 cm, effacement, or both
 Premature Rupture of Membranes
 Diagnostics
 Clinical Diagnosis
 Supportive Tests
o Transvaginal Cervical Ultrasound for diagnosis of short
cervix
o Cervicovaginal fetal fibronectin detection test: a positive
test supports diagnosis of preterm labor
 Treatment
 Single course of antenatal steroids
o Indication: 24-34 weeks gestation with risk of delivery
within next 7 days
o Improves fetal lung maturity and surfactant production
 Tocolysis: Administartion of tocolytics to inhibit uterine
contractions and prolong pregnancy
o Recommended for up to 48 hours to enable administration
of antenatal corticosteroids in preterm labor
o First Line: Beta adrenergic agonists, NSAIDs, or Calcium
Channel Blockers
o Second Line: Magnesium Sulfate
o Contraindications
 Maternal drug contraindications
 Nonreassuring fetal CTG
 Intrauterine fetal CTG
 Intrauterine fetal demise
 Chorioamnionitis
 Preterm premature rupture of membranes
 Antepartum hemorrhage with hemodynamic
instability
 Severe pre-eclampsia or eclampsia
 Lethal fetal anomaly
 Fetal Neuroprotection: Magnesium sulfate
o Indication: If birth < 32 weeks anticipated
o Decreases risk and severity of neurological diseases
(cerebral palsy)
 Antibiotics for Group B Streptococcus prophylaxis is
recommended in preterm labor, preterm premature rupture of
membranes and when GBS infection is evident
 Complications
o Neonatal respiratory distress syndrome (RDS)
o Bronchopulmonary dysplasia (BPD)
o Patent ductus arteriosus (PDA)
o Retinopathy of prematurity (ROP)
o Necrotizing enterocolitis (NEC)
o Periventricular leukomalacia (PVL)
o Neurological disorders (e.g.,cerebral palsy, learning
disabilities, developmental delays, ADHD)
o Problems
of homeostasis: apnea, bradycardia, hypothermia
o Infection and sepsis (e.g., pneumonia)
o Anemia of prematurity: impaired ability to produce
adequateerythropoietin (EPO); should be suspected
in premature infants with low hemoglobin
o Intraventricular hemorrhage (IVH)
 Risk factors
 Birth weight < 1500 g and delivery
before 32 weeks'gestation
 Maternal chorioamnionitis
 Hypoxia during or after birth
 Clinical features
 Usually occurs within 5 days ofbirth
 Most infants are asymptomatic, but
saltatory (over several days) or, more
rarely, catastrophic (over minutes to hours)
courses are also possible
 Lethargy, hypotonia, irregular
respirations, seizures, bulginganterior
fontanelle
 Cranial nerve abnormalities (e.g., pupils
react sluggishly to light) and changes
in eyemovement (e.g., roving eye
movements)
 Diagnosis
 Cranial ultrasound
 Since most patients are asymptomatic,
screening ultrasounds are routinely
performed in infants with a birthweight <
 1500 g and delivery before 30
weeks gestation.
 Prevention
o Avoid modifiable risk factors
o Manage cervical insufficiency
o Vaginal progesterone supplementation
 Singleton pregnancy at 16-24 weeks gestation with
a prior singleton preterm birth, regardless of
cervical length and/or cervical cerclage
 Women < 24 weeks gestation with a short cervical
length (< 25 mm)
o Benign Breast Conditions
 Fibrocystic Changes
 Mastitis
 Fat Necrosis of the Breast
 Benign Breast Neoplasms
 Fibroadenoma
 Phyllodes Tumor
 INtraductal Papilloma
 Gynecomastia
o Breast cancer
 Overview
 Noninvasive (in situ) carcinoma
o Ductal Carcinoma in Situ
o Lobular Carcinoma in Situ
 Invasive Carcinomas
o Invasive Ductal Carcinoma
o Invasive Lobular Carcinoma
 Inflammatory Breast Cancer
 Clinical Features
 Subtypes
 Paget Disease of the Breast
 Inflammatory Breast Cancer
o Congenital TORCH Infections
 Toxoplasmosis, Other (Varicella-Zoster, Parvovirus, Listeriosis); Rubella;
Cytomegalovirus; Herpes Simplex Virus
 Transplacental transmission occurs following primary infection of a
seronegative mother during pregnancy → maternal IgM
antibodies (which are unable to cross the placenta) form first, and
protective IgG antibodies (which are able to cross the placenta) have not
yet been formed → the infant is not protected from infection via
the placenta!
 Congenital Toxoplasmosis
  Toxoplasma gondii
 Transmission
o Pregnant women
o Fetus
 Clinical Features
o First Trimester
 Chorioretinitis (form of posterior uveitis)
 Diffuse intracranial calcifications
 Signs of hydrocephalus
o Second Trimester
 Subclinical or Mild Toxoplasmosis
o Sequelae
 Epilepsy
 Diagnosis
o Fetus: PCR for T. gondii DNA in amniotic fluid
o Newborn:
 CT/MRI
 T. gondii specific IgM antibodies; PCR for T. gondii
DNA
 Ophthalmological Evaluation for Chorioretinitis
 Treatment:
o Pregnant Woman: Spiramycin
o Fetal Infection: Pyrimethaminel, Sulfadiazine, and Folinic
Acid
o Newborn Infection: Pyrimethamine, Sulfadiazine, Folinic
Acid
 Congenital Syphilis
 Pathogen: Treponema pallidum
 Transmission:
 Clinical Features
o Early Congenital Syphilis (onset prior to 2 years)
 Hepatomegaly and Jaundice
 Rhinorrhea
 Maculopapular Rash on Palms + Soles
 Skeletal Abnormalities
o Late Congenital Syphilis (onset after 2 years age)
 Facial features: saddle nose, frontal bossing, short
maxilla
 Dental findings: Hutchinson teeth and mulberry
molars
 Eyes and ears: interstitial keratitis, sensorineural
hearing loss
 Skin: Rhagades, Gummas
  Skeletal: Saber Shins (Anterior bowing of the tibia);
Painless arthritis in knees and other joints
 Neurological: Cranial Nerve Deficits, ID,
Hydrocephalus
 Diagnosis
o Newborn
 Initial: RPR or VDRL
 Confirmatory: Darkfield Microscopy or PCR
o Fetus: Repeated Ultrasound Examinations showing
placentomegaly, hepatomegaly, ascites, and hydrops
fetalis
 Treatment: IV Penicillin G for both pregnant and newborns
 Prevention: Maternal screening
 Congenital and Newborn Listeriosis
 Pathogen: Listeria monocytogenes
 Transmission
 Clinical Features
o Intrauterine transmission to the fetus
 Granulomatosis infatiseptica
 Severe systemic infection characterized by
disseminated abscesses
 Most common findings: respiratory distress
syndrome and skin lesions
 Signs of meningitis
o Transmission during birth
 Late onset syndrome: Listeria
meningitis/encephalitis
 Diagnosis: Culture from blood or CSF samples (pleocytosis)
 Treatment: IV Ampicillin and Gentamicin
 Prevention: Avoid soft cheese
 Congenital and Perinatal Varicella Infection
 Pathogen: VZV
 Transmission
o Pregnant Women
o Fetus: Vertical transmission during pregnancy or delivery
 Clinical Features
o Congenital Varicella Syndrome (1st and 2nd trimester
 Hypertrophic scars (cicatricial skin lesions)
 Limb Defects (hypoplasia
 Ocular Defects (chorioretinitis, cataracts,
microphthalmus)
 CNS Defects (Cortical atrophy, seizures, intellectual
disability)
 o Neonatal Varicella
 Mild Infection (maternal exanthema > 5 days
before birth)
 Sever Infection (maternal exanthema < 5 days
before birth); hemorrhagic exanthema,
encephalitis, pneumonia, or congenital varicella
syndrome
 Diagnosis
o Newborns: Usually clinical diagnosis based on appearance
of skin lesions
 DFA or PCR of fluid collected from bilsters or CSF
 Serology
o Fetus: PCR for VZV DNA (fetal blood, amniotic fluid) and
ultrasound to detect fetal abnormalities
 Treatment
o Acyclovir
o Postexposure prophylaxis in newborn infants if the mother
displays symptoms of varicella <5 days before delivery 
IgG antibodies (varicella zoster immune glbulin or VZIG)
o Hormonal Contraceptives
 Effects
 Estrogen
o Hypothalamus: Decreased GnRH
o Pituitary: Decreased LH  inhibit ovulation, decrease FSH
 prevents ovarian folliculogenesis
 Progestin
o Inhibits GnRH and LH secretion  suppresses ovulation;
inhibits endometrial proliferation; changes cervical mucus
and impairs fallopian tube peristalsis  inhibition of
sperm ascension and egg implantation
o Inhibits follicular maturation
 Antiprogestin: inhibits or delays ovulation by inhibiting the
progesterone receptor
o The menstrual cycle and menstrual abnormalities
o Cervical Cancer ***
 LSIL = repeat pap smear twice at 12 month intervals in patients 21-24
years of age; negative twice patient may return to routine screening
 If pap smear shows ASC-H, HSIL, AGC  colposcopy should be performed
o Pregnancy Loss
 Mifepristone = approved for induction of medical abortion
o Menopause
 Definitions
 Perimenopause –
  Premonapause – 45-55 years of age
 Menopause – confirmed after 12 months of amenorrhea; 49-52
years
 Post menopause – time period beginning 12 months after last
menstrual period
 Pathophysiology
 Decreased ovarian function  Decreased estrogen and
progesterone levels  loss of negative feedback to gonadotropic
hormones  increased GnRH levels  increased levels of FSH
and LH in blood  anovulatory cyclesbecome more and more
frequent  progressive follicular depletion
 Onset of menopause might be delayed and symptoms might be
milder in obese women
 Clinical Features
 Irregular Menses
 Autonomic Symptoms
o Increased sweating, hot flashes, heat intolerance
o Vertigo; Headache
 Mental Symptoms
o Impaired sleep; Depressed mood or mood swings
o Anxiety/Irritability
o Loss of Libido
 Atrophic Features
o Breast tenderness and reduced breast size
o Vuvlovaginal atrophy
 Atrophy of the vulva, cervix, vagina
 Weight Gain and Bloating
 Subtypes/Variants
 Surgical Menopause
 Diagnostics
 Decreased estrogen/progesterone
 FSH levels can fluctuate widely in perimenopause
 Lipid Profile: Increased total cholesterol; Decreased HDL
 Treatment
 Lifestyle Modifications
o Hot Flashes: Avoid triggers; environmental temperature
regulation
o Atrophic vaginal symptoms: vaginal estrogen creams,
rings, or tablets
o Impaired sleep and/or hot flashes: exercise, acupuncture,
relaxation techniques
o Prevent osteoporosis: Smoking cessation, Adequate
Vitamin D Intake
  Hormone Replacement Therapy
o Types
 Estrogen Therapy: If hysterectomy
 Estrogen + Progestin Therapy: If have uterus
o Risks
 Cancer
 Unopposed estrogen = endometrial
hyperplasia  increased risk of endometrial
cancer
 Estrogen plus progestin therapy 
increased risk of breast cancer
 Cardiovascular Disease: CHD, DVT, PE, Stroke
 Gallbladder Disease
 Stress Urinary Incontinence
o Contraindications
 Vaginal Bleeding
 Pregnancy
 Breast Cancer/Endometrial Cancer
 Chronic Liver Disease
 Hyperlipidemia
 Recent DVT/Stroke
 Coronary Artery Disease
 Premature Menopause = before the age of 40
 Ovarian Insufficiency
 Primary ovarian Insufficiency
 Secondary Ovarian Insufficiency
o Function Disorder (ovarian endometriosis, PCOS, cancer of
reproductive organs)
o Genetic syndromes (Turner Syndrome, Swyer Syndrome,
Androgen Insensitivity Syndrome
o Autoimmune Diseases (Autoimmune lymphocytic
oophoritis, Hashimoto’s Thyroiditis)
o Infection: Measles, mumps, TB of genital tract
o Smoking
o Post-oophorectomy
o Radiation/Chemotherapy
o Prolonged GnRH
o Induction of multiple ovulation in infertility
o Secondary amenorrhea
 Most common causes = PCOS, Primary Ovarian Failure, Hypothalamic
Amenorrhea, Hyperprolactinemia
o Postpartum Hemorrhage
 Definition: Blood loss > 500 mL after vaginal birth; Blood loss > 1000 mL
for cesarean section occurring at any time
  Primary PPH: Blood loss within 24 hours
 Secondary PPH: Blood loss from 24 hours to 12 weeks postpartum
 Etiology
 Uterine Atony (most common)
 Abnormal placental separation
 Maternal injury during birth
 Bleeding diathesis
 Clinical Features: Anemia; Hypovolemic Shock
 Complications: Thromboembolism; Sheehan Syndrome;
 Uterine Atony
 Definition: Failure of the uterus to effectively contract and retract
after complete or incomplete delivery of the placenta, which can
lead to severe postpartum bleeding from the myometrial vessels
 Epi: responsible for ~80% of PPH
 Risk Factors: Multiparity, Multiple Pregnancy, Post Term
Pregnancy, Instrumental Delivery, Anatomical Abnormalities,
Large for gestational age newborn (> 4000 g); Poor myometrial
contractions following prolonged or rapid and forceful birth
 Clinical Findings: Abnormal vaginal bleeding; Soft, enlarged
(increased fundal height), boggy ascending uterus
 Diagnosis: Clinical
 Treatment:
o General measures: Monotirong, adequate large bore IV
access (>16 gauge) and an ice pack
 Fluid therapy (IV crystalloid solutions)
 Oxygenation
o Uterine massage and external compression
 Bimanual uterine massage: clenched fist inserted
into the anterior vaginal fornix and exerts pressure
on the anterior wall of the uterus. The other hand
is positioned externally and presses against the
inner fist, located in the uterine body
 Tranexamic acid: ASAP to stop fibrinolysis and to
reduce mortality
 Uterotonic agents
 IV oxytocin
 IM Carboprost tromethamine (If no asthma,
prostaglandin analog)
 IM Methylergonovine (if no HTN or arterial
disease)
 Prostaglandins such as misoprostol
 Speculum examination of the vagina and ervix to
evaluate possible sources of extrauterine bleeding
  Intracavitary application of prostaglandin
 Exclude coagulation
 Uterotonics are first line treatment with decreased uterine tone
 Methylergonavine should be avoided if hypertensive
o Pre-Eclampsia
 Elevated blood pressure and proteinuria after 20 weeks gestation
 Management
 24 hour urine for quantitative measurement of protein or a spot
urine protein to creatinine ratio, blood pressure monitoring, and
laboratory evaluation (H&H, Platelets, Serum Transaminase,
Creatinine, Albumin, LDH, and Uric Acid)
o Vaccinations
 Tdap
 Between 27 and 36 weeks gestation to maximize the maternal
antibody response and passive antibody transfer to the infant
o Pre-Eclampsia
 Place on magnesium sulfate to prevent seizures and labor should be
induced immediately
o Postmenopausal estrogen plus progesterone
 Increases the risk for coronary heart disease, stroke, breast cancer,
gallbladder disease, dementia, and venous thrombosis
 Dereased risk of fracture and reduced risk of endometrial cancer
o Painless Postmenopausal Bleeding
 Best initial test = transvaginal ultrasonography
o Endometriosis
 Diagnosis
 Definitive = Laparoscopy
 Treatment
 Medical Therapy
o Mild to moderate: NSAIDs and Hormonal Contraceptives
o Severe: GnRH Agonists and Estrogen-Progestin OCPs
 Surgical Therapy
o First Line: Laparoscopic excision and ablation of
endometrial implants
o Second Line = Hysterectomy w/ or w/o bilateral salpingo-
oophorectomy
o Precocious Puberty
 Central vs. Peripheral
 Differentiate with GnRH stimulation test
o Increase in LH levels >5 mIU/mL following GnRH
stimulation indicates central precocious puberty
o LH levels <5 mIU/mL indicate peripheral precocious
puberty
o Nausea and Vomiting in Pregnancy
 Vitamin B6
 Doxylamine
o Antepartum Hemorrhage
 Abruptio Placentae
 Partial or complete separation of the placenta from the uterus
prior to delivery
 Epidemiology: most often in the third trimester
 Etiology:
o Vascular: HTN; Pre-eclampsia/eclampsia
o Abdominal Trauma
o Sudden decrease in intrauterine pressure
o Previous abruption
o Maternal Age
o Alcohol and Cigarette Consumption
 Clinical Features
o Continuous, dark, vaginal bleeding of sudden onset
o Abdominal pain or back pain; uterine tenderness
o Hypertonic contractions; Premature labor
o Fetal Distress
 Decelerations on fetal heart monitor
o Vaginal exam contraindicated!
 Diagnostics: Clinical Diagnosis
 Treatment:
o General Approach: hemodynamic control; correct
coagulopathy; RhD Prophylaxis in RhD negative mothers
o Specific approach according to severity
 Normal fetal findings and hemodynamically stable
 Up to 34th week of pregnancy
o Fetal lung maturity induction with
corticosteroids
o If necessary, tocolysis (slows
progression of cervical dilation) with
nifedipine or beta 2 adrenergic
agonist
o Aim for normal delivery
 34th to 36th week
o Active Uterine contractions present:
Vaginal Delivery
o No contractions + no signs of fetal
distress + bleeding stopped:
expectant management
 After 36th week = deliver!!
  Acute symptoms and live fetus = emergency
cesarean section
 Acute symptoms + intrauterine fetal death =
vaginal delivery through pharmacological uterine
contraction inducers and opening of the amniotic
sac
 Emergency C-section must be performed if
maternal risk due to severe bleeding or
slow progression of birthing process even in
the case of intrauterine fetal death
 Complications
o Intrauterine Fetal Death (severe hypoxia)
o Maternal DIC and hypovolemic shock
o Couvelaire uterus
 Retroplacental hemorrhage may extend through
the uterus into the peritoneum
 Myometreum weakened with possible subsequent
uterine rupture during contractions
 Placenta Previa
 Definition: presence of the placenta in the lower uterine segment.
May lead to partial or full obstruction of the neck of the uterus
with high risk of hemorrhage (rupture of placental vessels) and
birth complications
 Etiology
o Maternal age >35; Multiparity; Short intervals between
pregnancy
o Previous curettage or C-section
o Previous placenta previa
 Classification
o Low lying Placenta = lower edge of placenta lies less than 2
cm from the internal cervical os
o Marginal previa = placenta reaches internal cervical os
o Partial previa = placenta partially covers internal cervical
os
o Complete previa = placenta completely covers the internal
cervical os
 Clinical Features
o Sudden painless bright red vaginal bleeding
o Usually occurs during the 3rd trimester (before rupture of
the membranes) and stops spontaneously after 1-2 hours
and recurs during birth
 Diagnostics
o Transvaginal ultrasound
  Treatment
o Approach
 <37 weeks gestational age
 No active bleeding and no evidence of fetal
distress: expectant
 Active bleeding or evidence of fetal distress:
immediate delivery
 >37 weeks gestational age: immediate delivery
o Expectant Management
 Hospitalization and observation for 48 hours
 If gestational age <34 weeks: fetal lung maturity
induction with corticosteroids (betamethasone)
 If mild uterine contractions present: tocolysis with
magnesium sulfate
o Route of Delivery
 Lower segment cesarean section almost always
preferred
 Ideally scheduled at 36-37 weeks gestation
 Vaginal birth could cause severe hemorrhage due
to rupture of placental vessels
 Vasa Previa
 Definition: fetal vessels are located in the membranes near the
internal os of the cervix
 Risk Factors: Placental anomalies; placenta previa; multiparity
 Clinical Features
o Painless vaginal bleeding after rupture of membranes
o Fetal distress
 Diagnostics
o Transabdominal or Transvaginal ultrasound with color
Doppler
 Treatment = Emergency Cesarean if signs of fetal distress
o Chancroid = Haemophilus ducreyi
o Chancre = primary syphilis
o Granuloma inguinale
 Painless nodules
 Klebsiella granulomatis
o Vulvar and Vaginal Cancer
o Screening
 High Blood Pressure = >40 years old
 Flexible Sigmoidoscopy = every 5 years
 Pap smear = every 3 years in women 21-29 years of age
 Fecal occult blood test = older than 50 years of age
 DEXA = all women > 65 year of age to screen for osteoporosis
  Colonoscopy = every 10 years starting at 50 years old
 Lipid profile = 45-75 years old with an ASCVD 10 year risk >10%
 Blood Glucose Screening = 40-70 years old
 HIV = 13-64 years
 Mammography = routine mammograms every 2 years in women 50-74
years of age.
o Endometriosis – diarrhea, dyschezia, and hematochezia
o Cervical trauma
 Postcoital bleeding
o Childbirth
o Genital Herpes
 Painful ulcers on an erythematous base
 Bilateral tender inguinal lymphadenopathy
o Ovarian Tumors ***
 Epithelial Tumors
 Cystadenoma/Cystadenomcarcinoma
o Serous
o Mucinous
 Endometrioid Carcinoma
 Germ Cell Tumors
 Teratoma
o Mature
 Dermoid Cyst
 Struma Ovarii
o Immature
 Dysgerminoma
 Yolk Sac Tumor of the Ovary
 Non-Gestational Choriocarcinoma
 Sex Cord Stromal Tumors of the Ovary
 Estrogen Producing
o Granulosa Cell Tumor
o Theca Cell Tumor
 Androgen Producing
o Sertoli-Leydig Cell Tumors
 Ovarian Fibroma (Meig’s Syndrome)
 Metastasis
 Krukenberg Tumor
o Fetal Death
 Stillbirth = after 20 weeks gestation
 Placental abnormalities and obstetric complications were the largest
category
o Breast Conditions
 Benign
  Fibroadenoma
o Thyroid and Pregnancy
 Pregnant woman with Graves Disease, Propylthiouracil is the therapy of
choice during the first trimester.
 Propylthiouracil crosses the placenta less readily and is associated
with a lower risk of birth defects when compared with
methimazole. T3 and T4 levels should be checked every 3 weeks
and the dose of the PTU should be decreased once the mother is
euthyroid or only mildy hyperthyroid
 Methimazole during first trimester associated with congenital
defects such as aplasia cutis, choanal atresia, esophageal atresia,
and omphalocele
 During second and third trimester, methimazole is the preferred
antithyroid drug because PTU associated with a higher risk of
hepatocellular damage and agranulocytosis
o Beta Blockers in Pregnancy
 Propranolol and Metoprolol safe during pregnancy
 Atenolol associated with an increased risk of fetal growth restriction.
o Child Development and Milestones
 the FDA currently recommends that all exclusively breastfed infants receive 400
international units of vitamin Dsupplementation per day. This supplementation
protects against hypocalcemia and rickets, a disease of bone deformities in
children due to a deficiency of vitamin D. Rickets is characterized by impaired
calcification of the bones, delayed closure of the fontanelles, frontal bossing,
prominence of costochondral junctions (“rachitic rosary”), and genu
valgum or genu varum. Children with rickets present with varying degrees
of pain, poor growth, motor delays, and an increased risk of infections.
o Hypertensive Pregnancy Disorders
 Before 20 weeks gestation or prior to pregnancy or persisting beyond the
42 postpartum day is known as chronic or pre-existing hypertension
 Gestational Hypertension – induced after 20 weeks gestation
 Pre-eclampsia
 Gestational hypertension with proteinuria, renal insufficiency,
thrombocytopenia, evidence of liver damage, and/or cerebral
edema
 HELLP Syndrome = Hemolysis; Elevated Liver Enzymes; Low
Platelets
o Hemolysis (low hemoglobin; elevated LDH)
o Abdominal pain due to stretching of Glisson capsule from
hepatic swelling
o Schistocytes
 Eclampsia – severe form of pre-eclampsia with convulsive seizures and/or
coma
 Treatment
o Anticonvulsive Therapy
  Magnesium Sulfate IV
 Antidote: Calcium Gluconate IV
o HPV
 16 and 18 responsible for the majority of cervical cancers; Facilitate the
transcription of proteins that alter tumor suppression upon successful
infection of cervical cells.
 E2F transcription factors that promote G1 to the S phase transition are normally
inhibited by the retinoblastoma protein (Rb). High-risk types of HPV induce
production of the oncoprotein E7, which binds and inactivates Rb protein, thereby
increasing G1to S phase transition and cell proliferation. High-risk HPV also
induces the production of the oncoprotein E6, which binds and inactivates
the tumor suppressor protein p53.
 Oncogenic HPV DNA induces the expression of the E6 protein, which
binds and INACTIVATES p53
o Retinopathy of Prematurity
 Supplemental oxygen at birth
 Higher arterial oxygen tension in a premature infant inhibits
vascularization of the peripheral retina leading to ischemia and
production of VEGF leading to neovascularization and formation of new
blood vessels that can cause hemorrhages, form fibrovascular
membranes, and ultimately lead to retinal detachment or blindness
o Prenatal Care
 Frequency of checkups
 Until 28th week of pregnancy = monthly
 28th to 36th week = every two weeks
 From 36th week to birth = every week
 Initial examination (~10 weeks gestation)
 Personal and family history
 Gynecological examination
 Blood pressure
 Weight
 Laboratory analysis
o CBC
o Hemoglobin (anemia)
o Blood typing (ABO and rhesus)
 Rhesus negative mothers receive prophylactic anti-
D immunoglobulins at 28 weeks to prevent
alloimunization
o Urine dipstick protein testing = proteinuria
o Urine culture (asymptomatic bacteriuria)
o Screen for STDs
 HIV
 Syphillis
 Hepatitis B surface antigen
 Chlamydia
  All patients <25 years of age
 >25 years of age with high risk of infection
 Rubella and varicella antibody testing
o PAP smear
o Ultrasound assessment of the estimated gestational age
through CROWN RUMP LENGTH
 General advice
o Vaccination against seasonal influenza
o Nutritional recommendations
o Tdap vaccine during the 3rd trimester
 Subsequent examinations
 Weight monitoring
 Blood pressure monitoring
 First Trimester screening
o Screening of chromosomopathies
 Physical examination
o Fundal height and position of the fetus (identified through
the first Leopold’s maneuver)
o Fetal heart monitoring
 Laboratory
o Group B Streptococcus screening during 35-37 week
gestation (vaginal and rectal swab for culture and gram
staining)
o Repeat Hb from 24th week of pregnancy
o 50 g one hour oral glucose challenge test at 24-28 weeks
gestation
 Positive Screening = 100 g three hour oral glucose
tolerance test (oGTT) to confirm diagnosis
 Glucose would increase transport into adpiocytes
via GLUT-4
o Repeat rhesus screening = unsensitized Rh(D) negative
women should receive anti(d) immune globulin
 Prenatal Diagnostics
 All pregnant women should be offered noninvasive aneuploidy
screening tests (before 20 weeks gestation)
o Testing maternal serum (specific biomarkers and
ultrasound markers )
o Cell free fetal DNA testing
 All pregnant women should be given the alternative option to
undergo invasive genetic testing (amniocentesis or CVS)
 Non-invasive Screening Test
o First Trimester Combined Screening (11-13 weeks
gestation)
  Sonographic nuchal translucency
 Subcutaneous area between the skin
and cervical spine of the fetus in the sagittal
section. Nuchal translucency increases when
fluid accumulates in the area.
 B-hCG in maternal serum
 PAPP-A (pregnancy associated protein A
 Conditions Identified
 Down Syndrome/Trisomy 21: Increased
hCG, decreased PAPP-A; thickened NT
 Trisomy 18: decreased hCG; Decreased
PAPP-A; thickened NT
 Trisomy 13: Decreased PAPP-A; Increased
NT
 Molar pregnancy: increased hCG
 Ectopic Pregnancy: decreased hCG
 Neural Tube Defects: Increased hCG
o Quad Screen Test (15-20 weeks gestation)
 hCG; AFP; Estriol; Inhibin A
o Triple Screen (15-20 weks gestation)
 hCG; AFP; Estriol
 Conditions identified
 Trisomy 21: elevated B-hCG; decreased AFP
and free estriol; Increased Inhibin A
 Trisomy 18: decreased b-hCG; decreased
AFP and decreased free estriol;
 Neural Tube Defects: normal B-hCG;
Increased AFP; normal free estriol; normal
Inhibin A
 Abdominal Wall Defects
o Normal B-hCG; elevated AFP
o Sequential Integrated Test (10-13 weeks gestation
followed by 15-20 weeks gestation)
 First trimester combined test plus quad screen test
o Cell Free fetal DNA testing (cff-DNA)
 From 10 weeks gestation onward
 Fetal DNA isolated from maternal blood specimen
for genetic testing
 Invasive Diagnostic Tests
o Chorionic Villus Sampling (10-13 weeks)
 Transcervical or transabdominal
o Amniocentesis (15th week of pregnancy onwards)
o Indications
 Early pregnancy
  Sonographic appearance of fetal nuchal
edem in 12th to 14th week of pregnancy
 Maternal age >35 years
 Suspected toxoplasmosis
 Late Pregnancy
 Determination of bilirubin levels in cases of
rhesus incompatibility
 Monitoring of electrolytes in suspected
renal failure
 Estimation of lung maturity in imminent
preterm delivery via lecithin-sphingomyelin
ratio
 Determination of insulin levels in
gestational diabetes
 Drainage of excess amniotic fluid in
polyhydramnios or amniotic fluid
o Neonatal Jaundice
 Physiological Jaundice
 Always unconjugated hyperbilirubinemia
 Pathological Neonatal Jaundice (conjugated or unconjugated jaundice)
 Conjugated
o Decreased bilirubin excretion
 Intrahepatic cholestasis
 Sepsis
 Hepatitis A
 Hepatitis B
 TORCH Infection
 Cystic Fibrosis
 Extrahepatic Cholestasis
 Biliary Atresia
 Choledochal Cyst
o Intrahepatic pathology
 Infectious Hepatitis
 Metabolic Diseases
 Dubin-Johnson Syndrome
 Rotor Syndrome
 Galactosemia
 Alpha-1-Antitrypsin
 Unconjugated
o Hemolytic
 Infection or Sepsis
 Hematomas
 Hemolytic Disease of Newborn
  RBC Structural Defects
 Ineffective Erythropoiesis
 Glucose-6-Phosphate Dehydrogenase Deficiency
o Nonhemolytic
 Hyperbilirubinemia Syndromes
 Crigler Najjar Syndrome
 Gilbert Syndrome
 Glucuronyl Transferase Deficiency
 Increased Enterohepatic Circulation
 Subtypes and Variants
 Breastfeeding Jaundice
o Insufficient breast milk intake  lack of calories and
inadequate quantities of bowel movements to remove
bilirubin from body  increased enterohepatic circulation
 increased reabsorption of bilirubin from the intestines
o Clinical Features – within 1 week of birth
o Treatment: Increase breastfeeding sessions
 Breast Milk Jaundice
o Pathophysiology: increased concentrations of b-
glucuronidase in breast milk  increased deconjugation
and reabsorption of bilirubin  persistence of physiologic
jaundice
o Clinical Features: Onset within 2 weeks after birth
o Treatment: Continued breastfeeding and supplementation
with formula feeds
 Phototherapy
 Indicated in total serum bilirubin
 >15 mg/dL in a 48 hour old term infant; >20 mg/dL in a 96 hour
old infant
 Contraindicated in increased direct (conjugated) bilirubin
 Geriatic Medicine
o Cachexia = inflammatory response with elevated cytokines + normal appetite in
early stages of starvation
o Starvation = refeeding causes a reversal of changes
 Pulmonology
o COPD
 Chronic airway inflammation
 C: Dyspnea, Productive Cough, Expiratory Wheezing
 Diagnostics
 <70% FEV1/FVC Ratio
 DLCO normal in patients with chronic bronchitis
 Chronic low blood oxygen levels may lead to hypoxic pulmonary
vasoconstriction causing an increase in pulmonary arterial
 pressure and increased pulmonary vascular resistance and RVH
eventually Right Heart Failure
 Management
 Continuous oxygen therapy in patients with severe hypoxemia
(oxygen saturation <90% or a PaO2 <60 mmHg)
 Exacerbation: Prednisone + Albuterol; Macrolide antibiotic can
also reduce the duration and severity of the exacerbation
o Atelectasis
 Etiology
 Obsttuctive Atelectasis: airway obstruction (foreign body, mucus
plug, malignancy)  nonventilated alveoli  reabsorption of gas
in the poststenotic space  lung collapse
 Non-obstructive Atelectasis
o Compression Atelectasis = external space occupying lesion
that compresses the lung  forcefully pushes air out of
the alveoli
o Adhesive atelectasis: surfactant deficiency or dysfunction
 increases surface tension of alveoli  Instability and
collapse (ARDs or RDS in premature infants)
o Cicatrization atelectasis: parenchymal scarring that leads
to contraction of the lung (Chronic Destructive Lung
Processes such as TB and fibrosis)
o Relaxation atelectasis: loss of contact between parietal
and visceral tissue (pneumothorax, pleural effusion)
o Replacement atelectasis: all alveoli in entire lobe replaced
by tumor (bronchioalveolar cell carcinoma)
 Post-Operative Atelectasis – most common post operative
complications (after chest or abdominal surgery) often occurs
within 72 hours of surgery
 Rounded atelectasis: folding of the atelectacic lung tissue (with
fibrous bands and adhesions ) to the pleural (asbestosis)
 Clinical Features
 Small number of affected alveoli  Asymptomatic
 Large number of affected alveoli  acute dyspnea, chest pain,
tachypnea, tachycardia, and cyanosis
 Dull percussion note, diminished breath sounds, and decreased
fremitus over the affected lung
 Diagnostics
 ABG: hypoxemia, potential low PaCO2 and respiratory alkalosis
o Non ventilated alveoli  increased physiologic dead space
 Chest XR and CT: evidence of lobar collapse
o Direc Signs: displacement of fissures and homogenous
opacification of collapsed lobe
 o Indirect Signs:
 Elevation of ipsilateral diaphragm
 Displacement of the hilum and mediastinal
structures toward the affected side
 Loss of volume in the affected side of the chest
 Increased lucency and overinflation of the
unaffected lung; silhouetting of the diaphragm or
the heart border
 Bronchoscopy (diagnostic and therapeutic)
o May be performed if the etiology is uncertain despite
imaging and mucus plugs can be removed
 Treatment
 Analgesia
 Early mobilization
 Deep breathing exercises, directed coughing, and incentive
spirometry
o Pneumonia
 Pneumocystis pneumonia
 Etiology
o Pathogen: Pneumocystis jirovecii
o Risk Factors:
 HIV Infection CD4 < 200 /uL
 Primary Immunodeficiency Disorders (SCID)
 Malignancy (Leukemia, non-Hogdkin Lymphoma)
 Immunosuppressive Treatment
 Malnutrition
 Diagnostics
o Laboratory Tests:
 CD4 count <200 /uL
 Elevated Beta-D-glucan
 Confirmatory Test: Microscopic identification of P
jirovecii via bronchoalveolar lavage or induced
sputum with methenamine silver staining and
immunofluorescence
 Treatment
o High Dose
o Hospitalization based on CURB-65 score (Confusion, Urea
>7, Respiratory Rate >30 min, BP Systolic <90 or Diastolic
<60, Age >65;
 <1 = outpatient; >2 Hospitalization; >3 ICU Care
o Pleural Effusion
 Diagnostics:
 Blunting of the costophrenic angle
o Bronchiolitis
 Lower Respiratory Tract Infection in which the bronchioles become
inflamed because of a viral infection (RSV).
 Common during winter months in children <2 y/o
 Clinical Features
 URTI symptoms
 Respiratory distress (in infants)
o Tachypnea, prolonged expiration
o Nasal flaring, intercostal retractions
o Cyanosis
 Poor feeding in breastfed infants
 Auscultatory findings: wheezing, crackles
 Clinical Diagnosis
 Treatment = Supportive (Hydration, Relief of congestion/obstruction
monitoring)
 Hospitalize if:
o Toxic appearance, poor feeding, dehydration, or lethargy
o Marked respiratory distress, oxygen saturation <92%
o Age <12 and/or history of prematurity
o Heart, Lung, or Neurological Condition
o Immunodeficiency
 Increased risk of developing asthma
o ARDS
o Chronic Cough
 Patients with chronic cough (>3 months) are treated empirically for UACS,
GERD, and asthma.
 PFT is the first step in management
 Upper Airway Cough Syndrome
 Abnormally increased nasal mucus secretion that drips down the back of
the throat and can lead to coughing, a feeling of obstruction in the throat,
and throat clearing. Causes include allergies, cold temperatures, viral or
bacterial infections, dry air, and certain medications.
 First-line treatment includes first-generation antihistamines (e.g.,
diphenhydramine).
 UACS was previously referred to as post-nasal drip syndrome.
o Obstructive Sleep Apnea
o Obesity Hypoventilation Syndrome
 Diurnal alveolar hypoventilation
 Resulting daytime hypercapnia and respiratory acidosis with metabolic
compensation (elevated bicarbonate)
o Chronic Pulmonary Aspergillosis
 Clinical Presentation: Hemoptysis, Weight Loss, Productive Cough
 Diagnostics:
  XRay – Monad Sign (Fungus bal in pre-existing lung cavity).
Upper lobe mostly affected because of an increased concentration
of oxygen
o Moving from supine to prone or lateral recumbent
demonstrates mobility of the fungus ball
 Laboratory Positive Sputum Culture or Positive Aspergillus IgG
Serology
o Bronchiectasis
 Clinical Presentation: chronic cough, dyspnea, hemoptysis, copius
amounts of sputum, crackles
 Exacerbated by acute respiratory tract infections
 Diagnostics:
 XRay: Fibrosis of the bronchial walls = tram track lines and
increased translucency
 Confirmed by CT scan
o Acute Tonsillitis
 Diagnostics
 Gold standard = throat culture for antibiotic sensitivity
o Asthma ***

 Can be triggered by viral respiratory infections and is exacerbated by
exercise
 Treatment
 Beta-2 agonists
 Inhaled corticosteroids
 Leukotriene pathway modifiers
 Omalizumab
o Anti-IgE antibody that binds to serum IgE
o Reduces serum levels of IgE to prevent binding of IgE to
high affinity IgE Receptors (FCERI) on mast cells and
basophils
 Methylxanthines
 Mast-Cell Stabilizers
o Cancer
 Nodules on CXR
 CT Scan
o <4 mm Follow up in 12 months
o 4-6 mm 6-12 months
o 6-8 mm 3-6 months
o >8 mm PET scan
 Biopsy
o CT guided transthoracic biopsy
o Bronchoscopy with transbronchial biopsy
 Squamous Cell Carcinoma of the Lung
 Most common type of lung cancer in smokers
 Central located cavitary lesions
  Associated with paraneoplastic syndromes (Hypercalcemia)
 Fatigue, Weight Loss, Hemoptysis
o Cystic Fibrosis
 Etiology
 Defective CFTR protein (most common is DeltaF508 on
chromosome 7)
 Pathophysiology
 Mutated CTFR  misfolded protein  retained protein in RER
unable to reach cell membrane  defective chloride channel 
inability to transport intracellular chloride ions across the
membrane  exocrine glands produce hyperviscous secretions 
accumulation of secretions and blockage of exocrine glands 
chronic inflammation  organ damage
 Clinical Features
 Gastrointestinal
o Meconium ileus
o FTT
o Pancreatic Disease
 Pancreatitis
 Exocrine Pancreatic Insufficiency
 Foul smelling steatorrhea
 Malabsorption
 Abdominal Distenion
 Diarrhea
 ADEK Deficiency
o Liver and Bile Duct Abnormalities
 Cholecytolithiasis, Cholestasis
 Fatty metamorphosis of the liver eventually
progressing to liver cirrhosis
 Biliary cirrhosis with portal hypertension
o Intestinal Obstruction
 Abdominal distention
 Respiratory
o Obstructive Lung Disease
o Chronic Sinusitis – nasal polps may eventually develop
o Recurrent or chronic productive cough and pulmonary
infections with characteristic microorganisms
 Dangerous bacteria (Pseudomonas aeruginosa)
 Expiratory wheezing (obstruction), barrel chest,
moist rales (pneumonia), hyperresonance to
percussion
 Signs of chronic respiratory insufficiency: digital
clubbing
o Airway hyperreactivity
 Sweat Glands
o Salty Tasting Sweat
  Musculoskeletal
o Kyphoscoliosis
 Urogenital
o Urinary
 Nephrolithiasis, Nephrocalcinosis
 Frequent UTIs
o Genital
 Males
 Obstructive azoospermia
 Vas deferens may also be absent
 Female
 Viscous cervical mucus may obstruct
fertilization in females
 Diagnostics
 General
o Best initial test is the sweat chloride test
 Diagnostic Criteria
 Neonatal Screening
o Elevated Immunoreactive Trypsinogen (IRT)
 Detects elevated levels of IRT in heel-prick blood
o DNA Assay
 Laboratory Tests
o Quantitatve Pilocarpine Iontophoresis
 Chloride Levels > 60 mmol/L on two or more
occasions are consistent with CF
o DNA Analysis
 Prenatal – Via chorionic villus sampling or
amniocentesis
 Postnatal/adult analysis
o Nasal Potential Difference Test
 Supportive Tests
o Stool: Decreased chymotrypsin and pancreatic elastase
o Chest XR/CT: Hyperinflation
o PFTs: Decreased FEV1:FVC ratio and Increased RV and
TLC
 Treatment
 Symptomatic Management
o Respiratory
 Hypertonic saline nebulization or dornase alpha
(mucolytic agent)
 Bronchodilator
 Chest Physiotherapy
 Chronic Rhinosinusitis = Intranasal glucocorticoids
 Mucolytics (N-acetylcysteine)
 Chronic Respiratory Insufficiency
 Long Term Oxygen Inhalation Therapy
 o Diet
 Additional Sodium Chloride Intake
 High energy diet
 Pancreatic enzyme supplements
 Oral supplementation of lipophilic vitamins A, D,
E, K
 Pulmonary Infections
o Infants
 Staphylococcus aureus = IV Vancomycin
o Adults
 Pseudomonas aeruginosa = Inhaled tobramycin
 Preventative Measures
o Annual influenza vaccine for all CF patients > 6 months
with inactivated influenza vaccine
o Pneumococcal vaccine
o Palivizumab: antibody for RSV for infants < 24 months
 Provides passive immunization to RSV infection
 Indication: infants at risk for severe bronchiolitis
 Complications
 Gastrointestinal
o Meconium ileus
 Failure to pass the first stool in neonates
 CF (90%)
 Clinical Findings:
 Distal small bowel obstructions
 Bilious vomiting
 Abdominal Distention
 No passing of meconium or stool
 Diagnostic
 Abdominal X-Ray
o Dilated small bowel loops,
microcolon, Neuhauser Sign
 Treatment
 Enema with a contrast agent
 Respiratory
o Hemoptysis
o Allergic Bronchopulmonary Aspergillosis
o Pulmonary Emphysema
 Pneumothorax
 Cor Pulmonale
o Interstitial Lung Disease
 Excess collagen deposition in the extracellular matrix of the lung
 Diffuse thickening of the alveolar walls result in progressive fibrosis of
the lung parenchyma, which in turn causes reduced vital capacity, and the
dyspnea, chronic dry cough, and fatigue
o Pleural Scarring
 Pediatrics
o Neonatal Thyrotoxicosis
 Usually resolves within 12 weeks when maternal TRAbs disappear
 Treatment includes methimazole and beta blocker
 Transplacental passage of TSH receptor antibodies
o Vaccinations
o Tetralogy of Fallot
o Puberty
 Idiopathic Central Precocious Puberty
 Elevated GnRH levels
 Treatment = Leuprolide or Buserelin
o Growing Pains
o Legg-Calve-Perthes Disease
o Fever
 Most common in any child younger than 29 days should undergo a
complete sepsis workup and be admitted for observation
 Most common bacterial organism = Group B Streptococcus and
Escherichia coli
 Broad empiric coverage with ampicillin and cefotaxmine
recommended
o RSV Bronchiolitis
 Upper respiratory tract infection followed by cough and signs of
respiratory distress (nasal flaring, intercostal retractions, Rhinorrhea,
Cough, Wheezing, Mild Tachypnea, Expiratory wheezes)
 Treatment = Hydration and Supplemental Oxygenation
 Nebulized hypertonic saline
o Acute Otitis Media
 Treatment = Amoxicillin/Clavulanate
 Prophylactic antibiotics not recommended
o Atopic Dermatitis
 Clinical Features
 Infantile AD
o Eczema: over the cheeks, face, head, and extensor
surfaces of the extremities that usually spares the diaper
area (begin as cradle cap)
o Dennie-Morgan Fold : increased folds below the eye
 Childhood AD
o Eczema: Flexural creases (antecubital and popliteal
fossae), skin folds, extensor surfaces of hands
o Lichenified lesions (thickening of the skin with accentuated
skin markings
 Adult AD
 o Lichenified lesions and pruritis of flexor surfaces of the
extremities
o Also:
 Nummular eczema (coin shaped lesion)
 st
Treatment = 1 line is topical corticosteroids
o Croup
 Swelling of the larynx causing a barking cough
 Treatment = Epinephrine then Oral dexamethasone
o Whooping Cough
 Catarrhal stage = Viral URI
 Paroxysmal stage = severe coughing spells that occur in paroxysms
followed by the inspiratory whoop
 Post-tussive emesis
 Nasopharyngeal culture and PCR
 Dermatology
o Impetigo
 Etiology:
 Staphylococcus aureus: Bullous and nonbullous impetigo
 Strep pyogenes (GAS)
 Clinical Features
 Nonbullous impetigo
o Lesions: Papules  Small vesicles surrounded by erythema
 pustules that rupture  oozing secretion that dries 
honey colored crusts  heal without scarring
 Negative nikolsky sign
o Localization: Face, especially around the nose and mouth
 Bullous impetigo
 Ecthyma
 Systemic Signs
o Staphylococcal Scalded Skin Syndrome
 Etiology
 Staphylococcus aureus strains that produce exfoliative toxins
o Toxins A and B cleave desmoglein 1 in the granular layer of
the epidermis, thereby disrupting keratinocyte
attachments
o Vitiligo
 Autoimmune destruction of melanocytes
o Psoriasis
 Epidemiology: Age of onset 20-40 years old
 Etiology: Polygenetic
 Infectious (B-hemolytic streptococci, staph, HIV); Mechanical
Irritation; Drugs (Beta Blockers, Chloroquine, Lithium, Interferon)
 Pathophysiology
  Increased proliferation of keratinocytes
o Acanthosis: thickening of epidermis
o Parakeratosis: retention of nucleated keratinocytes in
stratum corneum
 T Cells
 Clinical Features
 Course: Relapsing with symptom free intervals
 Well-demarcated, erythematous lesions and silvery white scaling
plaques
o Mainly on scalp, back, elbows, and knees (Extensor
surfaces)
o Pruritis
 Involvement of nails
o Nail pitting
o Oil drop sign
o Brittle nails
o Onycholysis
 Subtypes
o Psoriatic Arthritis
 Definition: Inflammation of joints
 Clinical Features
 Oligoarthritis
 Enthesitis (where tendons attach to bone)
 Tenosynovitis
 Dactylitis (sausage digit)
 Diagnostics
 Evidence of psoriasis
 Psoriatic nail dystrophy
 Negative rheumatoid factor
 Dactylitis
 Radiologic Signs
o Pencil in Cup Deformity
o Asymmetric Paravertebral
Ossification
 Treatment
 NSAIDs
 Moderate to Severe: DMARDs
 Physical Therapy
o Cutaneous Variants
 Plaque Psoriasis: symmetrically distributed, thick,
scaly, erythematous lesions
  Guttate psoriasis: size of drops of water; mainly in
children and adolescents after streptococcal
infection (URTI)
 Erythrodermic psoriasis: generalized erythematous
lesion with diffuse scaling; lead to fever and
dehydration
 Ivnerse psoriasis: may affect skin folds and flexural
creases of large joints

Diagnostics
o Koebner Phenomenon – skin injury lead to skin lesions
typical of underlying condition
o Auspitz Sign = small pinpoint bleeding when scales scraped
off
o Skin Biopsy
 Parakeratosis
 Munro microabscesses
 Acanthosis
 Spongiotic Dermatitis
o Laboratory Tests
 Elevated ESR & CRP
 Treatment
o Mild to Moderate:
 First Line: Moisturizers & Topical Medications
 Steroids; Vitamin D Derivatives
(Calcipotriene); Tar Preparations; Retinoids;
Vitamin A Derivatives
o Moderate to Severe
 Topical Medications
 Systemic Agents (Methotrexate, Retinoid,
Cyclosporine), Phototherapy
o Severe Psoriasis
 Topical + Systemic Treatment
 Phototherapy
 Antiproliferative effects and anti-
inflammatory effects
 UVB
 PUVA (Psoralen + UVA)
o Photodermatoses
 Zinc Oxide
o Scabies
 Treatment: Permethrin
  Binds to voltage gated sodium channels to delay repolarization of
neuron cell membranes which causes paralysis and death of the
mite
o Contact Dermatitis
 Type IV Hypersensitivity Reaction
 Diagnosis = Patch Test
 Treatment
 Mild to Moderate = Topical corticosteroid, oatmeal bath, soothing
lotion, wet ressing, topical antihistamine
 Severe = Systemic corticosteroids, Systemic Antihistamines
o Pityriasis Rosea
 Differential Diagnosis = Drug Eruptions, Secondary Syphilis, Guttate
Psoriasis, Erythema MIgrans
o Lichen Simplex Chronicus
 Treatment
 Moisturizers and/or calamine lotion
 Topical glucocorticoids, calcineurin inhibitors, capsaicin,
antihistamines
 Systemic H1 Antihistamines
o Benign Skin Lesions
 Vascular Skin Tumors
 Cherry Hemangioma
o Epidemiology: Increases with Age
o Pathophysiology: Proliferation of dilated mature capillaries
o Clinical Features: Bright cherry red, dome shaped papules
or macules
 Strawberry Angioma = benign vascular tumor of
infancy/childhood
 Pyogenic Granuloma
o Definition: Benign vascular tumor
o Etiology: Associated with trauma and pregnancy
o Clinical Features: soft, round, bright red tumor that bleeds
easily
o Diagnostics: Clinical
o Treatment: Surgical Excision
 Hypertrophic Scars
 Definition: High fibroblast proliferation and collagen production as
excessive skin tissue response to penetrating trauma; Does not
grow beyond the boundaries of the original lesion
 Etiology: Imbalance in wound healing processes
 Clinical Features: Raised scar tissue; Pruritis
 Diagnosis: Clinical
 Treatment
 o Medical Therapy
 1st Line: Intralesional Steroid Injection
o Surgery: Cryotherapy; Laser; Surgical Excision; Light
Therapy
 Keloid Scars
 Caused by high fibroblast proliferation collagen production as
excessive skin tissue response to typically small skin injuries
 GROWS BEYOND THE BOUNDARIES OF THE ORIGINAL LESION
 Does not regress spontaneously
 Recurs after resection
 Etiology: Imbalance in wound healing
 Clinical Features: Scar tissues of varying consistency that may be
brownish-red in color; Pruritis; Localization: earlobes, face, neck
 Diagnostics: Clinical appearance of lesion
 Treatment: Same as for hypertrophic scars
 Warts
 Definition: Hyperkeratosis and hyperplasia of epidermis
commonly caused by human papillomavirus
 Epidemiology: children and young adults
 Clinical Features
o Common Warts (Verruca vulgaris)
 Localized to elbows, knees, fingers, palsm
 Appearance: skin colored or whitish, rough, scaly
papules or plaques (cauliflower like appearance)
o Flat Warts (Verruca Plana)
 Localized to face, back of hands, legs
 Appearance: Flesh colored, smooth papules, flat
surface
o Plantar Wart (verruca Plantaris)
 Localized to soles of the feet
 Appearance: Flesh colored, hyperkeratotic surface
o Treatment: Salicylic Acid; 5-FU; Topical Retinoic Acid;
Cryotherapy or Surgical Excision
 Seborrheic Keratosis
 Histology: Immature keratinocytes with small keratin filled cysts
(horn cysts)
 Clinical Features: Multiple darkly pigmented papules/plaques,
sharply demarcated and soft
o Greasy, wax like stuck on appearance
o May be irritated by external trauma or spontaneously
o Localization: Trunk, back of hands, face, and neck
 Diagnosis:
 Treatment: Not necessary
  Dermatofibroma
 Definition: Fibroblast proliferation resulting in small, fibrous
benign dermal growth
 Clinical Features: Asymptomatic; Slowly growing skin colored or
brownish nodules of ~3-10 mm diameter
 Localization: lower extremities
 Diagnostics: Dimple Sign
 Nevus
 Lipoma
 Melasma
 Acanthosis Nigricans
 Solar Lentigo
o Cancerous Lesions
 Basal Cell Carcinoma
o Acne Rosacea
 Treatment = Doxycycline
o Tinea Capitis
 Treatment = Oral griseofulvin
o Intertrigo
 Skin inflammation caused by skin on skin friction. Facilitated by moisture
trapped in deep skinfolds where air circulation is limited
 Treatment: keep skin clean and dry, evaluate for infection
o Tinea versicolor
 Commonly caused by increased growth of Malssezia globose
 Abnormal pigmentation involving the trunk, back, and/or abdomen
following a history of travel to a humid and warm place such as the
Caribbean
 Lesions become more apparent after UV exposure or tanning because the
surrounding skin gets darker, which provides greater contrast to the
lesions
 KOH Preparation
o Epidermoid Cyst
 Firm, mobile, slow-growing nodule arising from the epidermis
o Autoimmune Blistering Diseases
 Pemphigus Vulgaris
 Autoimmune blistering caused by autoantibodies against
desmosomal adhesion proteins including desmoglein 3 and
desmoglein 1
 Medicatinos such as captopril, glyburide, thiol containing drugs
(penicillamine) and phenol containing drugs (cephalosporins,
rifampicin, phenobarbital, aspirin) can induce the formation of
these autoantibodies
  Desmosomal adhesion proteins enable keratinocyte adherence,
damage to these proteins causes intraepidermal bullae formation
and positive Nikolsky sign
 Occur first on mucous membranes and an become confluent or
erode to form painful ulcers
o Collection of Dermatological Disorders
 Sebaceous and Epidermoid Cysts
 Cat Scratch Disease
 Millaria
 Nummular Eczema
 Livedo reticularis
 Xeroderma pigmentosum
 Pseudofolliculitis barbae
 Most common in black males
 Pathophysiology
o Extrafollicular penetration: hair enters interfollicular
epidermis after it exits the follicular orifice
o Transfollicular penetration: hair penetrates the dermis
before exiting the follicular orifice
 Clinical Findings
o Firm, hyperpigmented, tender, pruritic papules and
pustules on hair growing areas
 Treatment
o Cessation of shaving; alternative hair removal techniques
o Adjunctive: Topica (retinoids, corticosteroids,
antimicrobials)
 Albinism
 Rheumatology
o Rheumatoid Arthritis ***
 Presentation
 Affects wrists and other extremity joints that have a high ratio of
synovium to articular cartilage
 Diagnostics
 Anti-CCP antibody (highly specific marker)
 IgM Autoantibodies targeting Fc region of IgG
 Imaging
o Early: Soft Tissue swelling
o Late: Joint Space Narrowing, Erosions of Cartilage and
Bone;
 Treatment
 Acute Inflammatory Therapy
o Indication: Acute Attack
o Glucocorticoids
 o NSAIDs and COX-2 Inhibitors
 Long Term
o Methotrexate
 Folic Acid given 24-48 hours after to minimize side
effects
o Biologic Therapy
 TNF-alpha inhibitors (adalimumab, infliximab,
etanercept)
 Complications
 Atlanto-axial Subluxation
o Pain/Stiffness of the Neck
o Cervical Radiculopathy
o Diagnostic: Extension/Flexion X-rays of the Cervical Spine
o Ankylosing Spondylitis
 Etiology
 90-95% HLA-B27
 Clinical Features
 Articular symptoms
o Back and Neck Pain
 Morning stiffness that improves with activity
o Limited mobility of the spine (especially forward lumbar
flexion)
o Inflammatory enthesitis
 Extra-Articular Manifestations
o Most common: Unilateral anterior uveitis
o GI Symptoms
o Prostatitis
o Fatigue
o Restrictive Pulmonary Disease
 Diagnostics
 Differential Diagnosis
 Treatment
 NSAIDs
 TNF-Alpha Inhibitors (Etanercept)
 Complications
 Uveitis
o Presentation = Painful red eye with conjunctival injection,
photophobia, and sluggishly reacting pupil
o Treatment = Topical corticosteroids
o Sarcoidosis
 Epidemiology: Bimodal Distribution
  Pathophysiology: T Cell Dysfunction and increased B Cell Activity;
Formation of non-caseating granulomas commonly within the lungs and
lymphatic system
 Clinical Features
 Acute Sarcoidosis
o High fever, malaise, lack of appetite, weight loss
o Pulmonary dyspnea, cough, chest pain
o Extrapulmonary: Arthritis, anterior uveitis, erythema
nodosum
 Chronic Sarcoidosis
o Pulmonary (Most Common)
 Dry cough, exertional dyspnea
o Extrapulmonary
 Common
 Peripheral Lymph Nodes
 Iridocyclitis
 Skin:
o Lupus pernio
o Scar Sarcoidosis
o Other Manifestations: MSK, Bone Lesion, Nervous, Heart,
Liver, Kidney, Spleen (GRUELING – granulomas, arthritis,
uveitis, erythema nodosum, lymphadenopathy, interstitial
fibrosis, engative TB, gammaglobulinemia
o Granulomatosis with Polyangitis
 c-ANCA
o Drug Induced Lupus
 SHIPP Hydralazine; Procainamide
o Gout
 Etiology
 Deposition of urate crystals in the joints
 Hyperuricemia predisposes to gout (end product of purine
metabolism that is renally excreted)
o Insufficient excretion or increased production leads to
hyperuricemia
 Primary Hyperuricemia
 Idiopathic extracellular supersaturation of uric acid
 Secondary Hyperuricemia
 Decreased uric acid excretion
o Medications (pyrazinamide, aspirin, loop diuretics,
thiazides, niacin)
o Chronic Renal Insufficiency; Lead nephropathy
o Ketoacidosis (starvation, Diabetes mellitus, lactic acidosis)
 Increased uric acid production
 o High cell turnover (Tumor Lysis Syndrome, Hemolytic
Anemia, Psoriasis, Myeloproliferative Neoplasms)
o Enzyme defects (Lesch Nyhan, PRPP Synthetase
overactivity, von Gierke Disease
o High Protein Diet
o Obesity
 Combined decreased excretion and overproduction (high alcohol
consumption)
 Pathophysiology
 Uric acid has poor water solubility
 Clinical Features
 Asymptomatic Stage
 Acute Gouty Arthritis
o Usually monoarticular
 Acute severe pain with overlying erythemia,
decreased ROM, swelling, and warmth
 More likely to occur at night, typically waking the
patient
 Joint may present with desquamation of the
overlying skin
o Location: Peripheral small joints in the lower extremities
 Podagra (MTP inflammation)
 Gonagra (knee)
 Chiragra (finger joints, especially the thumb)
 Intercritical Stage
 Chronic Gouty Arthritis
o Progressive joint destruction
o Tophi formation
 Multiple painless hard nodules with possible joint
deformities
 Bone tophi – urate crystal deposition in bones
 Soft tissue tophi – urate crystal deposition in the
pinna of the external ear, subcutis, tendon sheaths,
or synovial bursas
 Diagnostics
 Arthrocentesis
o Needle shaped negatively birefringent monosodium urate
crystals
o WBC >2000 /uL with >50% neutrophils
 Laboratory Tests
o Elevated serum uric acid
o Typical in acute attacks: Increased WBC and ESR
 Imaging
 o Ultrasound – Double contour sign (hyperechoic
monosodium urate crystals)
o MRI – Excellent to detect tophi formation
o CT – bone erosions
o XRay – Chronic gout only – punched out lytic bone lesions
 Treatment
 Acute Gout Attack
o NSAIDs (Indomethacin, Naproxen, Ibuprofen)
 Aspirin contraindicated because it inhibits uric acid
excretion, thereby delaying the cessation of
symptoms
o Colchicine
 Inhibition of microtubule polymerization – inhibits
phagocytosis of urate crystals, leukocyte activation
and micragion, and cell chemotaxis
 Use in patients who cannot tolerate NSAIDs (CKS or
GI Ulcers) or glucocorticoids
 Side effects: Diarrhea, Nephrotoxicity, and
Myelosuppression
o Oral Glucocorticoids
 Indications: No response or contraindication to
NSAIDs and Colchicine
o Proton Pump Inhibits should be given to patients being
treated with both NSAIDs and Glucocorticoids to avoid
gastrointestinal ulcers
o Intra-articular corticosteroid
 Indications: single joint involvement
 Chronic Gout
o General Measures: Weight Loss, Purine Restricted Diet,
Reduce Alcohol Consumption; High fluid intake; Consume
dairy products, Vitamin C, and Coffee
o Medical Therapy
 Indications
 Recurrent Gout (more than 2 gout attacks
per year)
 Uric Acid Nephropathy
 Tophi Development
 Serum Uric Acid >9 mg/dL
 General Approach
 Delay initiation of urate lowering
medications until ~2 weeks after an acute
attack has resolved
  Urate lowering medications may trigger or
prolong an acute gout attack
 st
1 Line Treatment: Xanthine Oxidase Inhibitors
(Allopurinol)
 Mechanism of Action: Reversible inhibitor
of xanthine oxidase  hypoxanthine and
xanthine will not be degraded into uric acid
 Side Effects: Skin Reaction; TEN; SJS
 Indications: Chronic Gout and/or
hyperuricemia >9 mg/dL; Hyperuricemia
Prophylaxis (TLS)
 Contraindications: Acute Gout Attack
Previous hypersensitivity; Kidney Disease
(Dose adjustment)
 Interactions: Increased bone marrow
toxicity with purine analog (6-
mercaptopurine and azathioprine)
 nd
2 Line Treatment (Benzbromarone, Probenecid,
Lesinurad)
 Mechanism of Action: Inhibition of Uric Acid
Reabsorption along renal tubules --.
Increased renal elimination
 Notable side effects: Urolithiasis; GI
symptoms; Rash
 Indication: In combination with allopurinol
 Contraindications: Acute Gout Attack;
Kidney Disease
 Recombinant Uricase (Rasburicase)
 Mechanism of Action: Catalyzes the
breakdown of uric acid to allantoin (water
soluble)
 Side Effects: Infusion Reactions
(premedications administered as
prophylaxis e.g. hydrocortisone and
antihistamine)
 Indications: Rapid relief desired; No benefit
from 1st and 2nd line
 Contraindications: Acute Gout Attack; G6PD
Deficiency (causes hemolytic crisis due to
production of hydrogen peroxide)
 Allopurinol + Azathioprine leads to INCREASED
BONE MARROW TOXICITY
  During first 2 weeks of an acute gout attack,
treatment with allopurinol should not be initiated
or altered  can lead to urate crystal mobilization
which worsens the symptoms!
 Complications
o Nephrolithiasis: Uric Acid Stones
o Uric Acid Neprhopathy
 Chronic Tubulointerstitial Nephropathy with
Monosodium urate crystal deposition in the stroma
of the kidney  Inflammatory process
 Clinical Presentation: Hypertension; Renal Failure
(rare)
Acute Uric Acid Nephropathy: Possible in TLS
o Pseudogout
 Paroxysmal joint inflammation due to calcium pyrophosphate crystal
deposition (calcium pyrophosphate dehydrate)
 Epidemiology (Adults >50 y/o)
 Etiology: mostly idiopathic
 Secondary form: joint trauma, familial chondrocalcinosis,
hyperparathyroidism, hemochromatosis, gout,
hypophosphatemia
 Clinical presentation
 Often asymptomatic
 Acute (pseudogout attack): monoarthritis (rarely oligoarthritis),
mostly affecting the knees and other large joints (hips, wrists, and
ankles)
 Diagnostics
 Arthrocentesis:
o Polarized light microscopy: detection of rhomboid shaped,
positively birefringent CPPD crystals
o Synovial fluid: 10,000 – 50,000 WBCs/ uL with >90%
neutrophils
 X-Ray Findings: Cartilage calcification of the affected joint
(chondrocalcinosis)
o Fibrocartilage (meniscus, annulus fibrosus of IV disc) and
hyaline cartilage (joint cartilage)
 Test for hypercalcemia
 Treatment
 Asymptomatic: No treatment
 Symptomatic Treatment
o Best initial treatment: NSAIDs
o Alternative: Colchicine or Intra-articular Corticosteroids
 Arthroscopic Lavage
  Possible Joint Replacement
o Inflammatory Myopathies
 Etiology
 Polymyositis: cell mediated cytotoxicity against unidentified
skeletal muscle antigens, chiefly affecting the endomysium
 Dermatomyositis: idiopathic or paraneoplastic antibody-mediated
vasculopathy associated with malignancy (NHL; Lung, Stomach,
Colorectal, Ovarian)
 Clinical Features
 Proximal Muscle Weakness
o Pelvic and Shoulder Girlde muscles most common
o Difficulty combing hair, standing up, climbing stairs
o Dysphagia
 Muscle Tenderness
 Cutaneous Manifestations of Dermatomyositis
o Gottron Papules
 Extensor surface of the hands
o Heliotrope rash: erythematous rash on the upper eyelids
o Midfacial erythema
o Photosensitive poikiloderma
 Shawl sign
 V Sign
 Cutaneous Manifestations of Inclusion Body Myositis
o Asymmetric muscle involvement of both proximal and
distal muscle groups
 Diagnostics
 PM Diagnostic Criteria
o Proximal Muscle Involvement
o Positive laboratory findings
o EMG suggestive of inflammatory myopathy
 Laboratory Test
o Increased muscle enzymes
 Increased CK and Aldolase
 Elevated Enzymes: Myoglobin, LDH, AST, ALT
o Inflammatory Markers: Increased ESR, CRP, Leukocytosis
o Antibodies
 ANA
 MSA: Anti-Mi-2; Anti-Jo-1
 Other
o EMG
o Imaging
o Muscle Biopsy
  PM: Cell Mediated Inflammation, Intrafascicular
Infiltration of Cytotoxic CD8+ T cells
 DM: Antibody Mediated Inflammation involving
parafascicular and perivascular infiltration with
plasmacytoid dendritic cells and B lymphocytes
 Inclusion Body Myositis: Endomysial Inflammation
+ Intramuscular Vacuoles
 Infectious Disease
o HIV ***
 Prophylaxis
 CD4 <200 = Trimethoprim Sulfamethoxazole for Pneumocystis
pneumonia
 CD4 <100 = Toxoplasma gondii
 CD4 <50 = Mycobacterium avium intracellulare complex
 Neurosurgery
o CSF Rhinorrhea
 Leakage of CSF from the anterior nares
o Meningioma
 Neurology
o Neurocutaneous Syndromes (Phakomatosis – neuro-oculo-cutaneous syndromes
= derived from ectoderm)
 Autosomal Dominant or Spontaneous
 Neurofibromatosis Type I
o Melanocyte Dysfunction
 Café au lait spots
 Lisch Nodules
 Axillary and inguinal Freckling (Hyperpigmentation)
o Multiple Neurofibromas
 Soft Painless Nodules
 Seizure when CNS involved
o Scoliosis
o Bone Involvement
o Optic Gliomas
o Associated with Pheochromocytoma and Wilms Tumor
 Neurofibromatosis Type II
o Bilateral Vestibular Schwannomas (acoustic neuromas) 
ipsilateral tinnitus, hearing loss, vertigo
o Multiple cerebral and spinal tumors
o Meningioma
 Pheochromocytoma
o Contraindications
 Selective beta blockers, Metoprolol
 Tuberous Sclerosis
 o Intellectual Disability
o Infantile Spasms or Seizures
o Skin Manifestations
 Adenoma sebaceum
 Ash leaf spots
 Shagreen patch
o Small Benign Tumor
 Brain tumors
 Hamartoma
 Giant Cell Astrocytoma
 Cardiac rhabdomyoma
 Renal cysts of renal angiomyolipoma
 Ungual fibroma
 Von Hippel-Lindau Disease
o Hemangioblastomas
o Bilateral Renal Cell Carcinoma
o Pheochromocytoma
 Autosomal Recessive: Ataxia Telangiectasia
 Progressive cerebellar ataxia
 Telangiectasias on the face and conjunctivae
 Decreased immunocompetence
 Febrile Seizures
 Definition: Seizures associated with fever (>100.4 F) in absence of
CNS infection, metabolic abnormalities, or history of afebrile
seizures
 Epidemiology: Peak incidence common between 6 months and 5
years of age
 Clinical Features
o Simple Febrile Seizure
 Generalized, usually tonic-clonic seizures
 Symmetrical
 Duration: <15 minutes; Maximum of one seizure
within 24 hours
 Age: 6 months to 5 years
 Post-Ictal Phase
 Quick return to normal
 Confusion and drowsiness may be present
for a short period of time
 Prolonged drowsiness or deviated eyes may
be a sign of other etiology
o Complex Febrile Seizure
 Focal onset
 Pronounced on one side of the body
  Transient hemiparesis and speech impairment
 Duration: > 15 minutes; > 1 seizure within 24 hours
 Diagnostics
o Simple febrile seizures do not require specific diagnostic
workup
o Focus on identifying the cause of fever
o Complex febrile seizures always require specific
investigative tests (EEG and imaging)
o Determine cause of fever
 Physical Exam
 UA and Urine Cultures
 Blood Tests (CBC w/ diff, CRP, Electrolytes, Blood
Glucose)
 Imaging to locate source of infection (U/S, X-Ray)
 Toxicology if suspected
o Additional diagnostic steps: for complex febrile seizures
and/or abnormal neurological exam
 Lumbar puncture  Exclude meningitis and/or
herpes encephalitis
 EEG
 Imaging
 Treatment
o Uncomplicated seizures resolve after a few minutes
spontaneously
o Abortive Therapy
 Treatment of Choice: IV Lorazepam
 Repeat medication after 5 minutes
o Reassure caregivers and provide information
o After a febrile seizure, initiate antipyretic therapy (NSAIDs
and acetaminophen) at an early stage (temperatures from
100.4 F) as they restore the central thermoregulatory
setpoint back to normal by reducing the synthesis of
prostaglandin E2
 Non-inherited: Sturge Weber Syndrome
 Port wine stain
 Vascular malformation of chroic and CNS
o Early onset glaucoma
o Epilepsy or epileptic spasms in infancy
o Intellectual Disability
o Myotonic Syndromes
 Epidemiology: Myotonic Dystrophy Type I: Congenital, Juvenile, or Adult;
Myotonic Dystrophy Type II: Usually Adult Onset
 Clinical Features
 Myotonic Dystrophy
o Meningitis
o Leukocoria “Cat’s eye pupil”
 All patients with leukocoria should undergo prompt fundoscopic
examination to rule out retinoblastoma
 White mass in the retina on fundoscopy
o Retinoblastoma
 Clinical Features
 Leukocoria (white fundal reflex
 Strabismus
 Painful, red eye
 Loss of vision
 Retinal Detachment (later stage)
 Diagnostics
 Fundus examination: grayish white, vascularized retinal tumor
 Molecular genetic testing of leukocytes for mutations in the RB1
gene recommended for all patients with retinoblastomas
 Differential Diagnosis
 Leukocoria is considered a retinoblastoma until proven otherwise;
a fundus examination of an infant presenting with leukocoria
should be conducted as quickly as possible
 Treatment
 Low Risk Retinoblastoma:
o Cryotherapy; Photocoagulation; Brachytherapy
 High Risk Retinoblastoma: Chemotherapy
 If eye not salvageable
o Enucleation
o Adjuvant systemic chemotherapy
 Increased risk for osteosarcoma
o Parkinson’s Disease
 Treatment
 First Line = Pramipexole or Ropinirole
o Trigeminal Neuralgia
 Treatment
 Conservative Therapy
o Drug of Choice: Carbamazepine
 Surgical Treatment: Microvascular Decompression or Ablative
Therapy
o Cerebellar Syndromes
 Etiology
 Acute
o Infarction, TIA
o Head Trauma, Edema, Hemorrhage
o Infections
  Adult: VZV, EBV, Lyme, Tertiary Syphilis, Malaria
 Children: VZV, Coxsackievirus, Parvo B19, HHV-6,
HAV, Enterovirus, Measles, Mumps, Lyme Disease
o Medications, toxins, poisons: Barbiturates,
benzodiazepines, heavy metals, chemotherapy
 Subacute/Chronic
o Alcoholism
o Intracranial tumors
o Vitamin Deficiency: Vitamin B12, Vitamin B1 (Wernicke)
o Paraneoplastic Cerebellar Degeneration
o Genetic: Spinocerebellar Ataxia, Friedrich Ataxia, Ataxia
Telangiectasia
o Multiple Sclerosis
o Wilson Disease
 Clinical Features
 Cerebellar Ataxia
o Gait Ataxia: Abnormal wide based, and unsteady gait;
irregular, uncoorindated movements of the limbs
 Romberg Test: Unable
 Unterberger: Positive
o Truncal Ataxia: Inability to sit upright and/or stand without
support
 Dysmetria and tremor (postural, action, intention tremor)
o Finger to Nose Test: Patient unable to touch tip of nose
with index finger
o Heel Knee Shin: inability to slide heel of one foot down the
shin of the opposite leg; heel will deviate to alternate sides
 Dysdiadochokinesia
o Inability to perform rapidly alternating agonistic-
antagonistic movements
o Rapid alternating movement test: unable to rapidly screw
in an imaginary light bulb simultaneously with both hands
 Rebound phenomenon
o Patient bends arm at elbow resisting examiner’s pull on
the forearm. Sudden release of arm by examiner results in
overshooting movement
o Indicates impaired coordination between muscular
agonists and antagonists
 Pronator Drift: Stretch supinated arms out in front of them at
shoulder level; arm ipsilateral to the lesion will pronate and drift
upwards
 Dysarthria (Scanning speech): Words are broken down into
separate syllables
  Oculomotor dysfunction, including nystagmus
 Acute cerebellar hemorrhage: occipital headache, neck stiffness,
vomiting, nystagmus, gait ataxia
 Muscular hypotonia
 Vertigo
 Diagnostics
 Neuroimaging (CT/MRI)
 Laboratory Testing: CBC, Electrolytes, B12, B1
 Genetic Testing
 ∂P
o Headache
 Cluster Headache
 Prevention = Verapamil
 Vasoconstriction of cranial blood vessels in response to high
oxygen concentration and hypocapnea
 Abortive Therapy
o Oxygen
o Sumatriptan
 Migraine
 Epidemiology
o Peak incidence 30-40 years old
 Etiology
o Potential triggers = emotional stress; weather changes;
food and beverages; poor sleeping habits
 Pathophysiology
o Not fully understood
o Vascular dysregulation (vasodilation and vasospasms);
Dysregulation of pain sensitization in trigeminal system
o Cortical spreading depression
 Clinical Features
o Recurrent attacks and may occur with aurua
o Prodrome (24-48 hours before)
 Excessive yawning; Difficulties writing or reading
o Aura
 Visual disturbances
 PHotopsia, Central Scotoma, Flashing Lights,
Fortification spectra (star like zig zags)
 Paresis
 Impaired sensibility, paresthesia
 Dizziness
 Aphasia
o Headache
 Typically unilateral
  4-24 hours, rarely lating over 72 hours
 Progression of pulsating, throbbing, or pounding
pain
 Accompanied by photophobia, phonophobia, and
nausea/vomiting
o Prodrome
 Exhaustion/Euphoria
 Muscle weakness
 Anorexia or Food Cravings
 Diagnostics
o With aura >2 attacks; without aura >5 attacks
o Physical exam to exclude red flag symptoms
o Neuroimaging should be used in unusual clinical
presentation
 Treatment
o Abortive Therapy
 Limit stimuli
 Mild to moderate = NSAIDs
 Severe = Triptans (sumatriptan) or ergotamine
 Sumatriptan
o 5-HT1 receptor agonist
(vasoconstriction of dilated cranial
and basilar arteries)
o Indicated in migraine and cluster
headaches
o Contraindicated in coronary artery
disease, peripheral artery disease,
HTN, and pregnancy/breastfeeding
 Initial therapy if nausea/vomiting = antiemetics
(prochlorperazine, chlorpromazine)
o Prophylactic Therapy
 Non-pharmacological = lifestyle (exercise, avoid
triggers)
 Pharmacological
 Indications = frequent attacks >3/month;
Long lasting (>12-24 hours); Abortive theray
fails
 Agents =
o Beta blockers (metoprolol,
propranolol, bisoprolol)
o Tricyclic antidepressants
(amitriptyline)
o Anticonvulsants (topiramate or
valproate)
 o Calcium channel blockers
(conflicting study results)
o Syncope
 Aortic Stenosis
 Vasovagal
 Orthostatic
o Stroke ***
 May be ischemic or hemorrhagic
 Transient Ischemic Attack – Temporary, focal cerebral ischemia result in
brief neurologic deficits lasting <24 hours
 Stroke = acute neurologic condition caused by an acute cerebrovascular
event
 Ischemic = cerebral infarction due to insufficient cerebral blood flow
(more common)
 Etiology
o Large artery atherosclerosis (secondary to HTN0
o Embolic stroke
 Cardiac emboli (A Fib)
 Infectious emboli
 Ahteroemboli
 Paradoxical embolism (R->L cardiac shunt)
o Small Vessel Occlusion
 Lipohyalinotic thickening of the small vessels –
occlusion of small, penetrating arteries that
originate directly from large vessels
o Other causes
 Watershed
 Coagulopathies
 Hemorrhagic = Due to hemorrhage (Intracerebral or subarachnoid)
 Intracerebral = within the brain parenchyma
o Hypertension
o Cerebral Amyloid Angiopathy – deposition of beta amyloid
in vessel walls result in focal damage with formation of
microaneurysms and elevated risk of rupture
o Ruptured AVM
 Subarachnoid = into the subarachnoid space
o Ruptured aneurysm (usually in circle of Willis)
 Round saccular aneurysm at major branches in
large arteries
 Clinical Features
 Sudden onset of focal neurologic deficits and nonspecific
symptoms
 SAH = worst headache of my life, neck stiffness, pupils not
reactive to light
 By vessel
o MCA
 Contralateral sensory loss and paralysis in the
arms, lower half of the face, and lower limbs
 Gaze deviates TOWARD the side of infarction
 Contralateral homonymous hemianopia without
macular sparing
 Aphasia
o ACA
 Contralateral paralysis in lower limbs >> upper
limbs
o PCA
 Visual field defects (Contralateral homonymous
hemianopia with macular sparing)
 Contralateral hemisensory loss (thalamic
involvement)
 Memory deficits
o Penetrating Arteries (Lacunar syndromes)
o Vertebrobasilar
 Vertebrobasilar Insufficiency
 Ipsilateral cranial nerve deficits
 Vertigo, drop attacks, tinnitus, Gait ataxia
 Brainstem
 Wallenberg (Lateral medullary syndrome)
 Medial medullary syndrome
 Weber Syndrome
 Millard Gubler Syndrome
 Foville Syndrome
o Extracranial Arteries
 Internal Carotid Artery
 Ipsilateral amaurosis fugax
 Common carotid artery
 Horner’s Syndrome
 Vertebral Artery
 Wallenberg Syndrome
 By affected region
o Pure motor stroke
 Most common type of lacunar stroke (Posterior
limb or the angle of the internal capsule)
 Contralateral hemiparesis
o Pure sensory stroke
 Thalamus
  Contralateral numbness and paresthesia of the
face, arm, leg
o Sensoriomotor stroke
 THalamocapsular area
 Hemiparesis and ipsilateral sensory impairment
o Ataxic hemiparesis
 Corona radiate or the posterior limb of the internal
capsule
o Dysarthria clumsy hand syndrome
 Base of the pons
 Dysarthria, dysphagia, contralateral facial and hand
weakness
o Hemiballismus
 Subthalamic nucleus
 Contralateral involuntary large and fierce flinging
of the arm or leg
 Others
o Putamenal Stroke
 Contralateral hemiplegia, hemisensory loss and
gaze palsy, ipsilateral deviation of the eyes, stupor,
and coma
o Cerebellar Stroke
 Cerebellar signs (ataxia, nystagmus, slurred speech)
 NO hemiparesis
o Thalamic Stroke
 Contralateral hemiparesis and hemisensory loss
 Miotic and unreactive pupils, upgaze palsy with
gaze deviation away from the side of the lesion
(wrong way eyes)
o Pontine stroke
 Decreased level of consciousness or coma,
quadriplegia, ocular bobbing, facial palsy,
dysarthria
 Lateral pontine Syndrome
 Infarction of the lateral pons
 Descending tracts –
 corticospinal tract (contralateral
hemiparesis)
 Lateral spinothalamic tract – contralateral
loss of pain and temperature sensations
 Cerebellar tracts – ipsilateral limb and gait
ataxia
 Cranial nerve nuclei
  Facial nerve nuclei
 Descending sympathetic tract
o Ipsilateral Horner’s Syndrome
 Initial Evaluation
o Clinical assessment and history
 Identify risk factors
 Signs of the affect vessel or region
 Onset of symptoms
o Rule out other causes of neurologic deficits
o Rule out atrial fibrillation via ECG
o Laboratory studies (CBC, Coagulation studies, Electrolytes,
Serum troponin)
 Neuroimaging
o Noncontrast cranial CT detects acute hemorrhage
 Cannot reliably identify early ischemia
 Ischemia
 Acute Ischemia (6-12 hours after)
o Hyperdense occluded vessels
o Parenchymal hypodensity
o Effacement of the sulci and loss of
corticomedullary differentiation
 12-24 hours after = hypodense
 Days after = hyperdense
 Hemorrhage
 Hyperacute = Hypodense lesion
 Acute
o Hyperdense lesion
o Hpodense perifocal edema
o Possible midline shift
o MRI
 Diffusion weighted imaging identifies ischemia
earlier than CT (3-30 minutes after onset)
 Ischemia
 T1 = Hypointense
 T2 = Hyperintense
 Hemorrhage
 Hyperacute
o T1 = Hypointense
o T2 = Hyperintense
 Acute = Hypointense
o Other studies
o CT, MRA
o Digital Subtraction Angiography
 o Transcranial Doppler Sonography
 Lumbar Puncture
o Definitive diagnostic test for SAH
o Yellowish (Xanthochromia) or red discoloration
o Increased RBCs, Increased WBCs, Increased protein
 Histologic changes in infarcted region
o 12-24 hours = red neurons (eosinophilic cytoplasm +
pyknotic nucleus)
o 1-3 days after = neutrophils = liquefactive necrosis
o 3-5 days = macrophages (microglia)
o 5-15 days = reactive gliosis (astrocytes) + vascular
proliferation
o >15 days = Glial scarring
 Treatment
o Acute stabilization/resuscitation and intensive care
moitoring
 Maintain sufficient oxygen supply
 Maintain blood glucose levels within 140-180
mg/dL
o Control elevated ICP and/or cerebral edema; monitor for
signs of brain herniation
 Head elevation to 30 degrees
 Hyperventilation
 Administer IV mannitol
 NO GLUCOCORTICOIDs
o Maintain cerebral perfusion
 Antihypertensive treatment
 Ischemic Stroke = PERMISSIVE HYPERTENSION;
Treat severe hypertension when >220/120 mmHg
 Hemorrhagic stroke = Maintain blood pressure
<160 mmHg
 NITRATES SHOULD BE AVOIDED MAY INCREASE
INTRACRANIAL PRESSURE
o Cardiac monitoring for at least 24 hours
o Ischemic Stroke Treatment
 Intravenous rTPA
 Inclusion criteria = within 3 hours of
symptom onset; >18 years old
 Exclusion criteria
o Pre-existing conditions
 Previous intracranial
hemorrhage
 Head trauma or stroke within
the past 3 months
  Recent intracranial or
intraspinal surgery
 Intracranial neoplasm
o Current Conditions
 Intracranial bleeding
 Active internal bleeding
 Hypertension >185/110
mmHg
 Anticoagulation (prolonged
PTT or INR >1.7)
 Low platelet count
 Intra-arterial thrombolysis
 Intra-arterial administration of tPA close to
the vessel occlusion within 6 hours of
symptom onset
 Mechanical thrombectomy
 Indicated in patients with proximal large
artery occlusion in the anterior cerebral
circulation
 Antiplatelet therapy
 ALL ischemic stroke patients
 Contraindicated for 24 hours after
thrombolytic therapy
 Drug of Choice = Aspirin
o Hemorrhagic Stroke Treatment
 Intracerebral Hemorrhage
 Reverse anticoagulation
 Cranitomy and Clot evacuation
o Indications
 Signs of brain herniation
 Brainstem compression
 Obstructive hydrocephalus
 Hemorrhage extension >3 cm
 (patients with hemorrhage in
basal ganglia or internal
capsule should generally not
undergo surgical clot
removal)
 Subarachnoid Hemorrhage
 Reverse Anticoagulation
 Prevent vasospasm (ischemic stroke) with
IV calcium channel blocker (nimodipine)
  Neurosurgery = surgical clipping or
endovascular coiling
 Epilepsy
 Childhood Absence Epilepsy
o Characteristics
 5-10 seconds up to 100x per day
 Brief unresponsiveness without convulsions
 Amnestic during seizures; Appear to be staring or
daydreaming with lip smacking, eye fluttering, or
head nodding
 No postictal phase
o EEG = 3 hz spikes and waves in all regions of the brain
o Treatment:
 1st line: Ethosuximide
 Inhibition of the low threshold T-type Ca2+
channels in the thalamus that are thought
to be responsible for the rhythmic 3 Hz
discharge seen
 2 line: Sodium valproate
nd

 3rd line: Lamotrigine

 Resting Tremor
 Etiology
o Parkinson’s Disease
o Drug Induced Parkinsonism
o Progressive Supranuclear Palsy
 Clinical Features
o Asymmetric resting tremor (4-6 hz)
o Pill rolling of hands that subsides with voluntary
movements
o Worsens with emotional stress
o Reduced with target directed movement
 Diagnosis: Clinical
 Treatment: Dopaminergic agents
 Postural Tremor
 Essential Tremor
o Bimodal distribution (teens and 6th decade of life)
o Etiology: Positive family history (AD)
o Clinical Features
 Localization (hands, head)
 Bilateral postural tremor with 5-10 hz
 Slowly progressive
 Worse with voluntary movement
 Resolves at rest
  Improves with alcohol consumption
o Diagnosis: Clinical
o Treatment
 1st Line = Propranolol
 2nd Line = AnticonvulsantsPrimidone
(anticonvulsant barbituate)
 Physiologic Tremor
o Etiology:
 Stress, exercise, fatigue
 Drug Induced (Valproate, Lithium, SSRI, TCAs, Beta-
2 agonists, Levothyroxine, Immunosuppressants
daclizumab, basiliximab; Withdrawal from alcohol
benzos, barbituates, marijuana; medical conditions
hyperthyroidism pheochromocytoma or Lewy Body
Dementia;
 Magnesium deficiency, hypoglycemia, Wilson’s
Disease
o Clinical Features
 Fine bilateral postural tremor in the hands and
fingers
 Occurs while holding a position against gravity
o Diagnosis: Underlying disease
o Treatment: Reversible once underlying cause is treated
 Orthostatic Tremor
o Etiology
o Clinical Features
 Long periods of standing leading to trembling
feeling
o Diagnostics: Synchronized shaking; EMG detection of 13-
18 hz tremor
o Treatment: Symptom based; Clonazepam, Gabapentin
 Intention Tremor
 Etiology
o Cerebellar stroke, tumor or trauma
o Multiple Sclerosis
o Drug Induced Alcohol/Lithium
o Wilson’s Disease
 Clinical Features
o Coarse hand tremor frequency < 5 Hz
o Worse with goal directed movemented
o Other cerebellar signs dysmetria (abnormal heel to shin
and finger to nose testing); Dysdiadochokinesia (inability
to perform rapid alternating hand movements);
Dysarthria; Nystagmus; Abnormal Gait
  Diagnostics
o CT/MRI: Cerebellar Lesion
o IgG in CSF if Multiple Sclerosis
o Screen for alcohol abuse or toxic lithium blood levels
 Additional Types of Tremors
 Flapping Tremor (asterixis)
o Etiology
 Metabolic Encephalopathy (alcohol or hepatic)
 Wilson’s Disease
o Clinical Features
 Irregular, high oscillations when arms and hands
are extended
o Diagnostics:
 Determine cause of encephalopathy
o Treatment
 Psychogenic Tremor
o Etiology
 Conversion Disorder
o Cilnical Features
 Mostly postural tremor with sudden onset
 Worsens under direct observation and diminishes
with distraction
o Diagnostics: Of exclusion
o Treatment: Cognitive Behavioral Therapy
o Amyotrophic Lateral Sclerosis
 Destruction of UMN and LMN in multiple body segments
 Neurological deficits in cranial nerves progressing to other body
segments (weakness, fasciculations, hyperreflexia)
o Neurological Examination
 Upper Motor Neuron Lesion
 Pronator Drift
o Multiple Sclerosis
 Treatment
 Interferon Beta
o Prevents exacerbations by downregulating expression of
MHC molecules on antigen presenting cells, inhibiting T
cell proliferation and decreasing the level of
proinflammatory cytokines while increasing the level of
regulatory cytokines
 Natalizumab
o Increased risk of developing progressive multifocal
leukoencephalopathy caused by the JC virus
 o Decreases migration of lymphocytes to the CNS and
increases the risk of PML
o Brain Tumors
 Primary Brain Tumors
 Pediatric Primary Brain Tumors:
o Most common benign: pilocytic astrocytoma
o Most common malignant: medulloblastoma
o Pilocytic Astrocytoma
o Medulloblastoma
o Ependymoma
 Develop from lining of the ventricular system and if
grow large enough, will cause obstruction of CSF
flow and consequent dilation of the ventricles
proximal to the obstruction (obstructive
hydrocephalus)
 Most common location for ependymoma in
children and last ventricle along the CSF pathway
and all ventricles become dilated with trapped CSF
o Craniopharyngioma
o Pinealoma
 Adult Primary Brain Tumors
o Most common benign: meningioma
o Most common malignant: glioblastoma multiforme
o Glioblastoma multiforme
o Meningioma
o Hemangioblastoma
o Schwannoma
o Oligodendroglioma
o Pituitary Adenoma
 Brain f
 Etiology
o Most common: Lung Cancer
o Breast Cancer
o Malignant melanoma
o Renal Cell Carcinoma
o Colorectal Carcinoma
 Clinical Features
o Acute or subacute onset of symptoms due to rapid tumor
growth
 Headaches
 Cognitive Deficits
 Focal Neurological Deficits
 Diagnostics:
o Neuroimaging
  Well circumscribed tumors at the junction of gray
and white matter and/or watershed areas of the
arterial system
 Treatment
o Limited Brian Metastases: Surgical resection or
stereotactic radiosurgery
o Extensive brain metastases: stereotactic radiosurgery,
whole brain radiotherapy, or chemotherapy
 Urology
o Cystoscopy
 Indications
 Hematuria
o Microhematuria (not grossly visible)
o Macrohematuria (grossly visible)
o Urinalysis = >3 erythrocytes/HPF or >5 erythrocytes/ uL
 Recurrent UTIs
 Suspected Interstitial Cystitis
o Infertility
 Defect in Sertoli cell tight-junction proteins (claudins and occludins) can
result in infertility due to impairment of the blood-testis barrier.
Spermatozoa enter the bloodstream which are recognized by serum
immune cells foreign and thus anti-sperm antibodies are created.
o Incontinence
 Stress Incontinence
 Etiology
o Urethral Hypermobility
o Intrinsic Sphincter Deficiency
 Clinical Features
o Loss of urine during physical activity that leads to
increased intra-abdominal pressure (laughing, sneezing,
coughing, exercising)
o No urge to urinate prior to the leakageDe
 Urge Incontinence
 Mixed Incontinence
 Total Incontinence
 Overflow Incontinence
o Nephrolithiasis
 Calcium Oxalate Stones = Dumbbell Shaped Stones
 Prevent by adequate hydration
o Scrotal Abnormalities
 Communicating Hydrocele
 Patent processus vaginalis
 Increases with crying or Valsalva
  Often reducible
o Urinary Tract Infections
 Urinary Tract Infections
 Nephrology
o AKI
 Acute Interstitial Nephritis
 Allergic reaction to medications (penicillin, sulfa antibiotics,
diuretics, NSAIDs, PPIs)
 Rash, eosinophilia, and other symptoms
o Rhabdoymyolysis
 Elevated levels of CK or myoglobuin with Dipstick positive for blood but
negative for RBCs
o End Stage Renal Disease
 Morphine should be avoided (toxic metabolites morphine-3-glucuronide
and morphine-6-glucuronide) causing neuroexcitatory effects (confusion,
sedation, respiratory depression, and myclonus)
o Renal Artery Stenosis
 Hyperplasia of juxtaglomerular cells
 Increased renin from the juxtaglomerular apparatus
o Pyelonephritis
o Tubulointerstitial Diseases
 Acute Tubulointerstitial Nephritis
 Allergic Interstitial Nephritis
 Crystal Induced Acute Kidney Injury
 Chronic Tubulointerstitial Nephritis
 Analgesic Nephropathy
 Myeloma Kidney
 Renal Papillary Necrosis
o Nephrotic Syndrome
 Massive Renal Loss of Protein (>3.5 g/day)
 Hypoalbuminemia
 Edema
 Hyperlipidemia
 Resulting in: Edema, Hypercoaguability (Antithrombin III Deficiency), and
an increased risk of infection (loss of immunoglobulin)
 Laboratory Findings: Hyperlipidemia and Fatty Casts on Urinalysis
 Most common = Focal Segmental Glomerulosclerosis and Membranous
Nephropathy
 Etiology
 Minimal Change Disease
o Most common cause of nephrotic syndrome in children
o Associated with tumors (Hodgkin Lymphoma)
o LM: No Change; EM: Effacement of Foot Processes
 o Treatment: Responds well to corticosteroids
 Focal Segmental Glomerulosclerosis
o Most common in black people
o Associated with heroin, HIV, obesity, and Sickle Cell
Disease
o LM: Segmental Sclerosis; IM: IgM and C3 inside sclerotic
regions; EM: Effacement of foot processes
o Treatment: ESRD if untreated; Immunosuppressive
treatment
 Membranous Nephropathy
o Most common in white populations
o Antibodies to phospholipase A2 receptor
o Associated with infections (Hepatitis B and C, SLE, Tumors,
and Medications)
o LM: Glomerular Capillary Loops and Basement Membrane
appear thickened
o Treatment: Corticosteroids
 Membranoproliferative Glomerulonephritis
o Immunoglobulin mediated
 Associated with SLE, Hepatitis C, Monoclonal
Gammopathy
o Complement Medicated
 Dense Deposit Disease and C3 Glomerulonephritis
o Findings
 Immunoglobulin Mediated
 Low serum complement
 IM: IgG deposits on basement membrane
 Complement Mediated
 Low serum C3 levels: patients with dense
deposit disease often have IgG antibodies
(nephritic factor against C3 convertase,
leading to persistent complement activation
 IM: C3 deposits on basement membrane
 Both: EM Basement membrane thickening, GBM
splitting (tram track appearance)
o No single treatment
 Diabetic Nephropathy
o LM: Thickening of the Glomerular Basement Mebrane;
Nodules within glomeruli (Kimmelstiel Wilson Nodules)
o Treatment is of underlying disease
 Amyloidosis
o Can be associated with multiple myeloma
 o LM: Congo red stain shows apple green birefringence
under polarized light
o Treatment: Melphalan; Corticosteroids
 Lupus Nephritis
o ANA; Anti-DNA Antibodies
 Pathophysiology
 Structural damage of glomerular filtration barrier → massive renal
loss of protein → reactively increased hepatic protein synthesis
o Loss of negative charge of GBM → loss of selectivity of barrier
(especially for negatively charged albumin)
o Podocyte damage and fusion (sign of nephrotic
syndrome) → non-selective proteinuria
 If protein loss exceeds hepatic synthesis (usually with a loss of protein >
3.5 g/24hours) → hypoproteinemia/hypoalbuminemia, initially both
normal GFR and creatinine
o Decreased serum albumin → ↓ colloid osmotic
pressure→ edema (especially if albumin levels < 2.5 g/dl)
o Elevated lipoproteins to compensate the loss of
albumin→ ↑ cholesterol and triglycerides → lipiduria (fatty casts)
o Decreased levels of antithrombin III (AT III) and loss of fluid into
the extravascular space (“thickening” of the blood)
→ hypercoagulability
o Loss of IGs → increased risk of infection
o Loss of "transport proteins" → vitamin D deficiency,
possible thyroxine deficiency, altered pharmacodynamicsof
drugs
 Clinical Features
 Marked edema: typically starting with periorbital edemaand
later pitting edema
 Weight gain
 Possibly frothy urine
 Hypertension
 Hypercoagulable state with increased risk of thrombosisand embolic
events (e.g., pulmonary embolism, renal vein thrombosis)
 Increased susceptibility to infection
 Symptoms of hypocalcemia
 Diagnostics
 Urinalysis
o Dipstick (commonly used for screening) : usually shows ≥ 3+
protein
o 24-hour urine collection or spot urine (confirmatory
tests): Heavy proteinuria (> 3.5 g/24h)
 While 24-hour urine collection is more precise, a spot
urine is usually more practical in a clinical setting.
o Urine sediment: Nephrotic sediment
 Proteinuria
 Lipiduria, fatty casts (hyaline casts with fat globule
inclusions and proteins) appear as “Maltese cross” sign
under polarized light
 Renal tubular epithelial cell casts
 Blood
o ↓ Total serum protein, albumin, IGs, AT III
o ↑ Cholesterol, triglycerides
 o Protein electrophoresis: ↓ albumin and γ-zone, ↑ α2- and β-zone
o Possibly ↑ creatinine and/or BUN
 Pathology
 Renal Biopsy
o Indication: To confirm diagnosis or in patients with nonspecific
disease pattern
o Minimal change disease
 Because minimal change disease has a very good
prognosis, a renal biopsy is generally not performed
unless treatment fails.
 Structural defect of the podocytes
 Light microscopy: no changes (→ "minimal
change")
 Electron microscopy: effacement of the foot
processes
o Focal segmental glomerulosclerosis (FSGS): damage to
the podocytes
 Electron microscopy: effacement of the foot processes
 Immunofluorescent
microscopy: IgM and C3 insidesclerotic lesions
 Light microscopy: segmental sclerosis and loss
ofpodocytes
o Membranous nephropathy (MN): deposition
of antibodiesbetween podocytes and the basal membrane
 Electron microscopy: subepithelial dense deposits,
also known as "spike and dome" appearance
 Immunofluorescent microscopy: subepithelial
deposits of immune complexes and complement
 Light microscopy: thickening of
glomerular capillary loops and basal membrane
o Membranoproliferative glomerulonephritis:immune-
mediated proliferation of the mesangium
 Electron microscopy: thickening and splitting of the
glomerular basement membrane ("train-
track"appearance)
 Immunofluorescent microscopy: IgG deposits on
basement membrane
 Treatment
 General =
o Low sodium low protein diet
o Start with ACE Inhibitor or Angiotensin II Blockers/Sartans
o Diuretics to reduce edema
o Treat hypercholesterolemia with statins
o Substitute Vitamin D if deficient
o Consider thrombosis prophylaxis
o AT III Deficiency = Heparin is ineffective
 Disease Specific
o Minimal Change Disease = Glucocorticoids for 12 weeks
o Focal Segmental Glomerulosclerosis
 Glucocorticoids; Cyclosporine or Tacrolimus
o Membranous Nephropathy
  Glucocortioids + Cyclosporine/Tacrolimus or
Cyclophosphamide
o Mebranoproliferative Glomerulonephritis
 No clear recommendation
 Complications
 Thrombotic Complications
o Deep Vein Thrombosis
o Renal Vein Thrombosis
 Atherosclerotic Complications
o Abnormal lipid metabolism in combination with a
hypercoagulable state leads to an increased risk of
atherosclerotic complications
o Presentation: Myocardial Infarction; Stroke
 End Stage Renal Disease
 Prognosis
o Nephritic Syndrome **
 Terminology
 Diffuse: All glomeruli affected
 Focal: Only a number of glomeruli affected
 Global: Entire glomerulus
 Segmental: only part of the glomerulus affected
 Proliferative: increased number of cells in the glomerulus
 Sclerosing: scarring of the glomerulus
 Necrotizing: cell death within the glomerulus
 Crescent: Accumulation of cells (macrophages, fibroblasts,
epithelial cells) in bowman’s space
 Presentation
 Hematuria with acanthocytes
 RBC casts
 Proteinuria (<3.5 g/day)
 Mild to moderate edema
 Oliguria (500 ml/24 hours)
 Azotemia (nitrogenous waste)
 Hypertension
 Sterile Pyuria (WBCs in urine)
 Pathophysiology
 Glomerular filtration barrier
o Initial segment – fenestrated glomerular capillary
endothelium prevents large proteins from passing through
o Second segment – glomerular basement membrane
contains a negative charge produced by heparan sulfate
 o Final segment – visceral epithelial cells produce/maintain
the GBM and contain intercellular junctions created by
podocytes that prevent further protein loss
 Damage to the glomeruli  disruption of glomerular filtration
barrier  nephritic or nephrotic syndrome
 Causes
 Poststreptococcal glomerulonephritis
 IgA Nephropathy
 Granulomatosis with polyangiitis (Wegener’s)
 Microscopic polyangiitis
 Churg-Strauus Syndrome
 Goodpasture Syndrome (Anti-GBM)
o Autoantibodies gainst noncallagenous domain of the
alpha-3 subunits present only in certain tissues (lungs,
kidney)
 Alport Syndrome (Hereditary nephritis)
 Thin Basement Membrane Disease
 Rapidly Progressive Glomerulonephritis
 Lupus Nephritis
 Hematology
o Hypersensitivity Reactions
 Type I
 Anaphylaxis
 Type II
 Type III
 Type IV
o Congenital Immunodeficiency Disorders
 Hyper IgM Syndrome
 Defect in the CD40 ligand
 At risk for pneumocystisi
o Henoch Schonlein Purpura
 Tetrad: Palpable Purpura, Arthrlagia, GI Symptoms, Renal Disease
 Deposition of IgA immune complexes in vascular walls activates
complement system, leading to vascular inflammation and damage
 Involvement of renal capillaries and mesangium often leads to hematuria,
often with RBC casts
o Chemotherapeutic Agents
 Vincristine
 Side Effects: neurotoxicity within 4-5 weeks of therapy
o Decreased intestinal motility (constipation) and mixed
sensory and motor neuropathy (numbness and tingling
then decreased deep tendon reflexes)
o Thrombocytopenia
  Purpura
 Vasculitis causes
o Meningococcal Infection
o DIC
o Henoch Schonlein Purpura (IgA Nephropathy)
 ITP
o IgG antibodies against GpIIb/IIIa receptors on platelets
o Anemia
 Microcytic Anemia
 Iron Deficiency Anemia
o Causes:
 Premenopausal women = Menstrual blood loss
o Serum iron and transferrin saturation decreased; TIBC
increased;
o Clinical Findings: Koilonychia
 Anemia of Chronic Disease
o Serum iron decreased; TIBC and transferrin saturation
decreased or normal; Low reticulocytes; Low iron
o Normal MCV
o Treatment: Oral Prednisone therapy
o DVT
 OCPs decrease protein S levels
o MGUS
 Serum M protein < 1.5 g/dL
 Lower back pain, anemia, and M-spike = osteolytic lesion workup
o ADAMTS13
 Treatment = Plasma exchange therapy + Glucocorticoid
o Thalassemia
 Alpha thalassemia
 Determined by the number of missing alleles
 Cis deletion common in Asian populations
 Deletion of 3 alleles = causes fetal gamma globin chains to
tetramerize and form Bart’s hemoglobin (gamma4) instead of
Hemoglobin alpha2, gamma2
 Beta Thalassemia Major
 Frequent blood transfusions = prone to developing secondary iron
overload due to high iron content of red blood cells; Decreased
transferrin/TIBC levels; elevated transferrin saturation
o Folate Deficiency
 Pathophysiology
 → ↓ DNA synthesis → megaloblasticerythropoiesis → megaloblastic
anemia (+ ↓ inother cell lines)
 → ↓ methionine + ↑ homocysteine → endothelial damage (→ ↑ risk of
cardiovascular disease +thromboembolic events)
  During fetal development: → nucleotide synthesis impairment → neural
tube defects
 → Aberrant DNA methylation → increased risk of cancer

o Hereditary Spherocytosis
 Defective RBC proteins in the RBC cytoskeleton membrane
spectrin/Ankyrin
 Continuous loss of the outer lipid bilayer and a decrease in erythrocyte
surface area, which creates sphere shaped erythrocytes with decreased
membrane stability
 RBCs susceptible to phagocytosis by splenic macrophages, which leads to
anemia
 Bone marrow compensates for RBC loss with increased RBC production
which can result in folate deficiency as folate is used up during DNA
synthesis
 Elevated MCHC
 Jaundice, Splenomegaly
 Extravascular hemolysis
 Patients with hemolytic anemia should receive daily folic acid
supplementation to prevent megaloblastic anemia
 Detection with Eosin-5-maleimide binding test specific for hereditary
spherocytosis
 Increased risk of cholecystitis
o Lymphoma (Leukopenia WBC <4,500/uL)
 Non-Hodgkin Lymphoma
 Types
o B Cell Lymphoma
 Low Grade (CLL)
 Small Lymphocytic Lymphoma
 Hairy Cell Leukemia
 Waldenstrom’s Macroglobulinemia
 Follicular Lymphoma
 MALT Lymphoma
 High Grade
 Burkitt Lymphoma
 Diffuse Large B-Cell Lymphoma
 Precursor B Cell Lymphoblastic Lymphoma
 Mantle Cell Lymphoma
o T Cell Lymphoma
 Indolent: Mycosis Fungoides
 Aggressive:
 Adult T Cell Lymphoma
 Cutaneous T Cell Lymphoma
 Precursor T Cell Lymphoblastic Lymphoma
 Clinical Features
o Painless LAD
o Splenomegaly, Hepatomegaly
o Extranodal Disease
o B Symptoms (Weight Loss, Fever, Night Sweats)
o Fatigue; Bone Marrow Involvement (Anemia, Bleeding,
Increased susceptibility to infections)
 Stages
o Ann Arbor Staging System
o Classification
 Limited Disease: lymph node involvement limited
to one side of the diaphragm
 Advanced Disease: lymph node involvement on
both sides of diaphragm
 Diagnostics
o Blood Tests
 CBC (WBC, Anemia, Thrombocytopenia)
 Serum Chemistry (Elevated LDH, Hypercalcemia)
 Virus Serology
o Histology
 Excisional Lymph Node Biopsy
o Imaging
 X-Ray and CT required for staging
o Further Tests
 IHC:
 B Cell Lymphomas: CD20 Positive
 T Cell Lymphomas: CD3 positive
 Lumbar Puncture with CSF Examination in case of
 Primary CNS Lymphoma
 Neurologic Signs/Symptoms
 HIV-Positive Patients
 Treatment
o Low Grade NHL =
 Limited Stage  Radiation Therapy
 Advanced Stage  Palliative (Polychemotherapy to
slow progression)
o High Grade NHL
 Curative  Polychemotherapy
o CHOP Regimen (Cyclophosphamide, Hydroxydaunorubicin,
Oncovin- Vincristine, Prednisolone)
 If B Cell add Rituximab
o Primary CNS Lymphoma = Intrathecal Methotrexate +
Chemotherapy
 o Hairy Cell Leukemia: Chemotherapy with Cladribine or
Pentostatin
o Burkitt Lymphoma: Similar to ALL
o CLL
 Hodgkin Lymphoma
 Categories:
o Classical HL (CHL)
 Nodular Sclerosis
 Mixed Cellularity
 Lymphocyte Depleted
 Lymphocyte Rich
o Nodular Lymphocyte Predominant HL (NLPHL)
 Epidemiology: Bimodal Distribution
 Etiology
o Strong association with EBV
o Immunodeficiency
o Autoimmune Diseases (RA, Sarcoidosis)
 Clinical Features
o Painless Lymphadenopathy
 Cervical Lymph Nodes > Axillary Lymph Nodes >
Inguinal Lymph Nodes
 Mediastinal Mass
 Splenomegaly or Hepatomegaly
o B Symptoms
 Night Sweats, Weight Loss, Fever > 100.4 F
o Pel-Ebstein Fever (Intermittent Fever)
o Alcohol Induced Pain (highly specific for HL)
o Pruritis
 Stages
o Stage 1: 1 lymph node
o Stage 2: One side of diaphragm
o Stage 3: both sides of diaphragm
o Stage 4: Disseminated spread
 Diagnostics
 Blood Tests
o Elevated or decreased WBCs
o Anemia
o Eosinophilia
 Serum Chemistry
o Increased LDH
o Hypercalcemia
 Histology
o Required diagnostic step
 o Lymph Node Excision
 Reed Sternberg Cells (Pathognomic for HL)
 Polynuclear Giant Cells (originating from B Cells
CD15/CD30 positive)
 Inflammatory background
 Granuloma Formation
 Imaging
o Chest XRay or CT Scan
o Bone Scintigraphy or PET-CT
 Pathology
 Classical Hodgkin Lymphoma (CHL)
o Nodular Sclerosing Subtype (Most common; Good
Prognosis)
o Mixed Cellularity (30% of cases)
o Lymphocyte Rich Classical HL (Rare; Good Prognosis)
o Lymphocyte Depleted (Very Rare; Bad Prognosis)
 Nodular Lymphocyte Predominant HL (Rare; Very Good Prognosis)
 Treatment
 Early Stage (I and II): Combination of chemotherapy and radiation
therapy
o Most widely used is ABVD (Adriamycin-Doxorubicin,
Bleomycin, Vinblastine, Dacarbazine)
 Advanced Stage
o Threee possible treatments:
 ABVD
 Stanford V
 BEACOPP
o Leukemia (increase in premature leukocytes that are subsequently released into
the bloodstream)
 Acute Leukemia (no maturity)
 Epidemiology
o ALL = Peak incidence 2-5 years
 Most common malignant disease in children
 80% are lymphocytic
o AML = Peak incidence 65 years
 80% during adulthood are myelogenous
 Etiology
o ALL
 Linked to infection with HTL virus
 Genetic
 Down Syndrome
 Philadelphia Translocation (9;22)
 NF1
  Ataxia Telangiectasia
o AML
 Environmental
 Benzene
 Ionizing Radiation
 Tobacco; Chemotherapy Drugs
 Genetic/Chromosomal
 Down Syndrome
 T(15;17) Translocation APML M3
 Fanconi Anemia
 Philadelphia Translocation
 Myeloproliferative
 Myelodysplastic Diseases
 Osteomyelofibrosis
 Chronic Myelogenous Leukemia
 Classification
o AML = FAB Classification
 Based on appearance of cells
 M3 = APL
 Auer Rods
o ALL (cytogenetic criteria)
 B Cell ALL
 Early Pre-B
 Common
 Pre-B
 Mature B
 T Cell ALL
 Pre-T
 Intermediate-T
 Mature T
 Pathophysiology
o Two hit hypothesis
 1st clonal proliferation of a lymphoid or myeloid
stem cell
 2nd impairs normal hematopoietic differentiation
 Clinical Features
o Fatigue, pallor, weakness (anemia)
o Bleeding (petechiae, epistaxis, hematoma –
thrombocytopenia)
o Hepatomegaly and/or splenomegaly (leukemic infiltration)
o Headache, visual field changes, CNS symptoms
o Fever
o AML Symptoms
  Leukemia Cutis (nodular skin lesions with purple or
gray-blue color)
 Gingival Hyperplasia (AML M4 and M5)
o ALL Symptoms
 Painless LAD
 Fever, Night Sweats, Unexplained Weight Loss
 Bone Pain
 Diagnostics
o Lab Tests
 CBC
 Peripheral Blood Smear
 Increased Uric Acid and LDH
 Bone Marrow Aspirate/Biopsy
 Immunophenotype
 CSF Analysis
o Imaging
 CXR = Mediastinal Widening
 Abdominal Ultrasound = Organ Enlargmenet
 Treatment
o Chemotherapy
 Induction Therapy (reduction of tumor cell count)
 Re-Induction Therapy (similar to induction)
 Consolidation Therapy (destruction of remaining
tumor cells)
 Maintenance Therapy (maintaining remission)
o Chemotherapeutic Drugs
 ALL
 Induction Therapy: Vincristine,
Glucocorticoids, Asparaginase
 In philadelphia chromosome mutation
t(9;22) BCR-ABL Tyrosine Kinase Inhibitor
(imatinib)
 AML
 Induction Therapy: Cytarabine and
Anthracyclines (Danorubicin)
o AML M3 = All Trans Retinoic Acid
t(15;17)
o Preventative CNS Treatment
o Supportive Therapy
o Allogenic Stem Cell Transplant
 Complications
o Tumor Lysis Syndrome
 Prognosis
 Chronic Leukemia (Partial maturity)
 CML
o Definition: Granulocytes = neutrophil, basophil, eosinophil
 Cells divide too quickly
o Epidemiology: 50-60 years
o Etiology: Idiopathic; IR; Aromatic Hydrocarbons
o Pathophysiology:
 Philadelphia Chromosome
 Reciprocal translocation between
chromosome 9 and 22  fusion of ABL
gene with the BCR gene on chromosome 22
 encodes a BCR-ABL non receptor
tyrosine kinase
 Inhibits physiologic apoptosis and increases
mitotic rate
 Genetic Changes
o Clinical Features
 Chronic Phase
 Persist for up to 10 years
 Weight Loss, Fever, Night Sweats, Fatigue
 Splenomegaly
 No swollen lymph nodes
 Accelerated Phase
 Erythrocytopenia: Anemia
 Thrombocytopenia: Petechial Bleeding
 Neutropenia: Infection and Fever
 Extreme Pleocytosis
o Infarctions: Splenic and Myocardial
Infarctions, Retinal Vessel Occlusion
o Leukemic Priapism
o Terminal Phase: Myelofibrosis
 Extreme Splenomegaly
 Blast Crisis (Terminal Stage of CML)
 Symptoms resemble acute leukemia
 Rapid progression to pancytopenia
o Diagnostics
 Peripheral Blood Analysis
 CBC/Blood Smear
o Extreme Leukocytosis (>500,000 /uL)
with midstage progenitor cells
 Basophilia and Eosinophilia
 Blasts can indicate transition in accelerated
phase
  Thrombocytosis
 Cytochemistry: Decreased LAP
 Cytogenitcs: BCR-ABL fusion gene
 Bone Marrow
 Hyperplastic Myelopoiesis
 Elevated granulocytic precursor cells
o Treatment
 Tyrosine Kinase Inhibitors: Imatinib
 Binds to active site for ATP on abnormal
BCR-ABL tyrosine Kinase  inhibits
proliferation and induces apoptosis of cells
 Allogeneic Stem Cell Transplant
 Cell Count Normalization = Hydroxyurea
 Blast Phase: Acute Leukemia Treatment
 CLL
o Definition (lymphocytes B & T Cells)
 Cells don’t die when they should
 Chronic Lymphocytic Leukemia: Low Grade B Cell
Lymphoma with Lymphocytic Leukocytosis
 Chronic Lymphocytic T-Cell Leukemia
o Epidemiology
 Median age: 70-72 years
o Etiology
 Advanced Age
 Environmental Factors: Organic Solvents
o Classification
 Rai Staging System
o Pathophysiology
 Acquired mutations in hematopoietic stem cells 
Increased proliferation of leukemic B cells with
impaired maturation and differentiation in the
bone marrow resulting in:
 Suppression of the proliferation of normal
blood cells
o Immunosuppression
 Hypogammaglobulinemia
 Granulocytopenia
o Thrombocytopenia
o Anemia
 Infiltration of the Lymph Nodes, Liver, and
Spleen
 Bruton’s Tyrosine Kinase
o Clinical Features
  Asymptomatic for long period of time
 Weight Loss, Fever, Night Sweats, Fatigue
 Painless LAD
 Hepatomegaly and/or splenomegaly
 Repeated infections: Severe bacterial infections;
Mycosis; Viral Infections
 Symptoms of Anemia and Thrombocytopenia
 Dermatologic: Leukemia Cutis; Chronic Pruritis;
Chronic Urticaria
o Diagnostic
 Laboratory
 CBC
o Persisting Lymphocytosis with high
percentage of small mature
lymphocytes
 Blood Smear: Smudge Cells
 Flow Cytometry: Detection of B CLL (CD19,
CD20, CD23); Light Chain restriction (kappa
or lambda)
 Serum Antibody Electrophoresis
 Bone Marrow Aspiration
 Not necessary to confirm diagnosis
 Additional
 Genetics
 Ultrasound
 Liver Histology
 Lymph Node Biopsy
o Treatment
 Principles of Treatment
 Asymptomatic CLL: Observe and Monitor
 Symptomatic CLL or Advanced Stage
o Chemotherapy
o CD20+ = Rituximab
o Targeted therapy with ibrutinib
 Refractory CLL or early recurrence in fit
young patients: allogeneic stem cell
transplant
 Treatment Regimens
 <65-70
o FCR (Fludarabine,
Cyclophosphamide, Rituximab)
 >65-70
o Chlorambucil + monoclonal antibody
 o Complications
 Immunosuppression with subsequent infections
 Secondary malignancies
 Hyperviscosity Syndrome
 Autoimmune Hemolytic Anemia
 Richter’s Transformation (transformation into a
high grade NHL)

o AIHA
 Circulating antibodies (positive direct Coombs test) consistent with
autoimmune hemolytic anemia
 Diagnostics = nucleated RBCs and polychromasia (indicates release of
immature RBCs into the circulation as a result of elevated erythropoietic
activity
o Paroxysmal Nocturnal Hemoglobinuria
 Clinical Presentation: Fatigue, abdominal pain, jaundice, and dark urine in
the morning
 Pancytopenia, evidence of intravascular hemolysis (unconjugated
hyperbilirubinemia, elevated LDH, low haptoglobin) and red urine
without RBCs in the sediment (consistent with hemoglobinuria)
 Decreased CD55 and CD59 in the RBC membrane
 At risk for venous thrombosis
 Treatment with oral prednisone
o Factor V Leiden (mutation of coagulation factor V)
 Does not allow activated Protein C (potent anticoagulant) to inhibit the
coagulation cascade leading to a procoagulant state by activation of
prothrombin into thrombin.
o Waldenstrom macroglobulinemia
 Indolent type of non-Hodgkin lymphoma caused by an abnormal
production of IgM antibodies by monoclonal plasma cells.
 Presents in old age with impaired platelet function (nosebleeds), anemia
(Hb < 13.5 g/dL), and mild thrombocytopenia, progressive neuropathy
(pain and numbness in feet), and hyperviscosity syndrome (vision and
hearing loss)
 Increased ESR, LDH, and ALP can be seen
o Hemolysis
 Extravascular hemolysis
 Elevated LDH; Haptoglobin level normal; No hemoglobinuria
 Intravascular hemolysis
 Exertional hemoglobinuria
o Mechanical destruction of RBCs in the feet during
strenuous exercise;
o Reticulocytosis; Elevated LDH; Decreased haptoglobin;
Hemoglobinuria
o G6PD Deficiency
 Impaired production of NADPH
 Impaired regeneration of reduced glutathione (antioxidant that protects
the erythrocyte membrane from oxidative damage)
 Vulnerable to oxidative stress caused by primaquine or antibiotics such as
sulfamethoxazole and dapsone
 Offers resistance against Plasmodium infection
o Polycythemia Vera
 Mutation in JAK2 gene leads to uncontrolled EPO Independent
proliferation of the myeloid cell lines, resulting in increased blood cell
mass
 Increased red blood cell mass suppresses secretion of EPO by the kidneys,
resulting in low EPO levels
 Individuals with PV usually have normal arterial O2 saturation and a
slightly increased or normal plasma volume
o Von Willebrand Disease
 Deficiency in von Willebrand Factor
 Hinders the ability of platelets to adhere to subendothelial collagen and
inhibits platelet activation which leads to a prolonged bleeding time
o Myeloproliferative Neoplasms
 Overview = All show varying degrees of JAK2 mutations (valine 
phenylalanine)
 Primary Myelofibrosis
 Bone marrow fibrosis, extramedullary hematopoiesis, and
splenomegaly
 Peak incidence between 60-70 years
 Clinical Features
o Weakness, fatigue, weight loss
o Splenomegaly: LUQ pain
o Thrombocytosis and Leukocytosis
o Pancytopenic Phase (Late Phase)
 Erythrocytopenia  anemia
 Thromboytopenia  petechial bleeding
 Leukopenia  increased susceptibility to infections
 Diagnosis
o Elevated LAP, LDH, and Uric Acid
o Peripheral Blood Smear: Dacrocytes
o Bone Marrow Aspiration: Punctio Sicca
 Treatment
o Curative: Allogenic Stem Cell Transplant
o Supportive
 Hyperproliferative Phase:
  Prevent thromboembolisms: antiplatelet
drug
 Control cell count: hydroxyurea, interferon
alpha, cladribine
 Pancytopenic Phase
 JAK2 Inhibitior: Ruxolitinib
 Periodic Transfusions
 Low Dose Thaldiomide + Glucocorticoids
 Essential Thrombocytopenia
 Clinical Features
o Thromboembolic events
o Increased risk of fetal loss
o Vasomotor symptoms (headache, visual disturbances,
acral paresthesias)
o Acute gouty arthritis
o Petechial Bleeding
 Diagnostics
o Thrombocytosis (>600,000 /uL)
o Increased LDH and Uric Acid
o Bone Marrow Aspiration: Hyperplasia of Megakaryocytes
 Differential Diagnosis
o Reactive Thrombocytosis
 Etiology: Inflammation, Infection; Malignancy; Iron
Deficiency
 Treatment: Prevent thromboembolisms: Low dose
aspirin; Reduce thrombocyte count: hydroxyurea
or interferon alpha
 Chronic Eosinophilic Leukemia
 Description: Leukemia with monoclonal proliferation of
eosinophilic granulocytes that causes peripheral eosinophilia and
tissue damage
 Clinical Features
o Hepatosplenomegaly
o Anemia and/or coagulation disorders
 Diagnosis
o CBC: Elevated eosinophilic granulocytes
o Peripheral blood smear and bone marrow aspiration:
monoclonal blast cells or cytogenetically abnormal
eosinophils
o Migratory thrombophlebitis
 Secondary to an occult malignancy, classically pancreatic cancer
 Trousseau Syndrome (months to years before a malignant process
detected)
  Diarrhea (steatorrhea secondary to exocrine pancreatic insufficiency) and
poor appetite and a long smoking history
 Abdominal CT is the most specific and sensitive diagnostic test for
detecting underlying visceral cancer
o Hemophilia
 Hemophilic arthropathy
 Iron deposition causes increased synovial inflammation and
recurrent synovitis eventually leading to erosion and loss of
cartilage, joint space narrowing, and permanent joint destruction
o Malabsorption Syndrome
 Inadequate breakdown and absorption of fats and fat soluble vitamins
ADEK, leading to deficiency of II, VII, IX, and X.
o Inherited hyperbilirbinemia
 Indirect
 Gilbert’s Syndrome
o Common, inherited hyperbilirubinemia that causes mild
excess (<3 mg/dL) of indirect bilirubin (unconjugated
hyperbilirubinemia), scleral icterus, and fatigue
o Commonly after a period of stress and/or fasting
 G6PD deficiency
o Recent primaquine usage
o Blood smear with Heinz bodies
 Crigler Najjar Syndrome
o Type I – affected neonates demonstrate exceptionally high
levels of indirect bilirubin and often require liver
transplantation
o Type II – more mild, intermittent periods of jaundice
o Phenobarbital is prescribed to induce the production of
the underlying, partially deficienct UDP
glucuronosyltransferase enzyme
 Direct
 Rotor Syndrome
o Increased urinary coproporphyrin and normal liver
histology
o Aplastic Anemia
 Hyperplasia of adipocytes in bone marrow
 Causees
 Medications (carbamazepine, NSAIDs)
 Radiation
 Viruses (Parvovirus B19)
 Inherited (Fanconi anemia)
 Preleukemia
o Sickle Cell Anemia **
  Transient Aplastic Crisis = reticulocytopenia
 Treatment
 Hydroxyurea
 Family Medicine
o Screening
 Low Dose CT in adults 55-80 y/o with a 30 pack year smoking history and
currently smoke or have quit within the past 15 years
 Genetics
o Fragile X Syndrome
 Mitral Valve Prolapse (Mitral Regurgitation) in ½ of Fragile X patients
 Toxicology
o Metal Toxicity
 Lead Toxicity
 Cognitive Deficits
 Behavioral Problems
 Fatigue
 Constipation
 Abdominal Pain
 Gingival Hyperpigmentation
 Microcytic, Hypochromic Anemia
o Poisoning