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MKSAP 5

I. Cardiovascular Medicine

Clinical follow-up in 1 year for


asymptomatic bicuspid aortic valve with
preserved LV function.
-------------------------------------------------Bicuspid valves eventually develop aortic
stenosis, regurgitation, or aortic root dilatation
or dissection that require surgery.
Because worsening of aortic regurgitation can
be insidious, routine follow-up is indicated in
at least yearly intervals, with repeat TTE
(transthoracic echocardiography) to monitor
progression.
Bicuspid aortic valve is a/w ascending aorta
dilatation.
o TTE monitors for aortic enlargement.
-------------------------------------------------Asymptomatic chronic aortic regurgitation
with normal LV size & function have an
excellent prognosis; do not require
prophylactic surgery.
AVR surgery is for severe aortic regurgitation
& cardiopulmonary symptoms.
Asymptomatic patients with severe
regurgitation, surgery is recommended once
there are signs of LV enlargement or adverse
hemodynamic effects on the LV, or EF falls
below 50 to 55%.
-------------------------------------------------Endocarditis prophylaxis is only for
prosthetic cardiac valves, known history of
prior infective endocarditis, cardiac transplant
recipients with valve abnormalities,
unrepaired cyanotic congenital heart disease,
& complex congenital heart disease with
residual abnormalities.
--------------------------------------------------blocker (metoprolol) is indicated for all
stages of systolic heart failure, even
asymptomatic patients with LV EF > 50%.

-------------------------------------------------Hypertrophic cardiomyopathy
o harsh systolic murmur at the lower left
sternal border between sternum & apex.
o Valsalva & squat-to-stand maneuvers
increase murmur intensity.
o Handgrip exercise decreases murmur
intensity due to increased afterload &
decreases the relative pressure gradient
across the LV outflow tract.
o TEE can confirm diagnosis of
hypertrophic cardiomyopathy.
Aortic stenosis
o early systolic murmur heard best at the
right second IC space, but can be heard
anywhere from the cardiac base to apex.
o radiates toward the carotid arteries.
o murmur decreases with Valsalva
maneuver
Mitral valve prolapse is the most common
cause of mitral regurgitation.
o midsystolic click followed by a late
apical systolic murmur.
o squat-to-stand maneuver transiently
decreases preload on the heart, which
decreases LV chamber size & increases
systolic buckling of the redundant mitral
valve into the left atrium, moving the
midsystolic click earlier in systole &
increasing the intensity.
Tricuspid regurgitation murmur
o loudest at the lower left sternal border
o louder with inspiration
-------------------------------------------------A small patent ductus arteriosus in an adult
produces a continuous murmur that envelopes
the S2 & heard beneath the left clavicle.
A moderate-sized PDA may present with
symptoms of heart failure, a continuous
"machinery-type" murmur best heard at the
left infraclavicular area, & bounding pulses
with a wide pulse pressure.
--------------------------------------------------

Chronic aortic regurgitation findings include


cardiomegaly, tachycardia, widened pulse
pressure, thrill at the base of the heart, soft S1,
sometimes absent aortic closure sound, & S3.
A high-pitched diastolic murmur begins
immediately after S2, heard best at the second
right or third left IC space with the patient
leaning forward, in end-expiration.
Manifestations of a widened pulse pressure
may include
o Traube sign (pistol-shot sounds over
peripheral arteries)
o de Musset sign (head bobs with each
heartbeat)
o Duroziez sign (systolic & diastolic
murmur heard over the femoral artery)
o Quincke sign (systolic plethora &
diastolic blanching in the nail bed with
compression)
-------------------------------------------------Valsalva maneuver & squat-to-stand maneuver
increases the murmurs of hypertrophic
cardiomyopathy & mitral valve proplapse.
-------------------------------------------------VSD presents with a harsh systolic murmur
parasternally that radiates to the right sternal
edge & palpable thrill but no change in the
carotid artery pulsation.
Maneuvers that increase afterload, such as
handgrip exercise, increases the left-sided
murmurs of mitral regurgitation & VSD
-------------------------------------------------Congenital bicuspid aortic valve is a
common cause of calcific aortic stenosis.
Presence of a bicuspid aortic valve accelerates
the process of aortic calcification; patients
develop stenosis in their thirties or forties.
-------------------------------------------------Hypertrophic cardiomyopathy is a/w rapid
upstrokes of the carotid arteries, distinguishing
it from aortic stenosis, which is a/w a carotid

artery pulsation that has a slow up-rise &


diminished in volume.
-------------------------------------------------Aortic stenosis is an early systolic murmur
that radiates toward carotid arteries.
o decreases with the Valsalva maneuver.
-------------------------------------------------Aortic coarctation in an adult is characterized
by HTN & continuous or late systolic murmur
that may be heard over the back
-------------------------------------------------Hypertrophic cardiomyopathy is caused by
LV outflow tract obstruction from a thickened
interventricular septum.
In severe cases, systolic anterior motion of
the mitral valve apparatus into the LV
outflow tract contributes to the murmur.
If mitral valve leaflet coaptation is affected,
there may be concurrent mitral regurgitation.
Stand-to-squat & passive leg lift transiently
increase venous return (preload), which
increases LV chamber size & volume.
Consequently, there is less relative obstruction
& turbulence in the LV outflow tract,
decreasing murmur intensity.
Handgrip exercise diminishes murmur intensity
by increasing afterload, decreasing the pressure
gradient across the LV outflow tract.
Valsalva & squat-to-stand transiently
decrease venous return, the septum &
anterior mitral leaflet brought closer together.
o Turbulent flow & murmur are increased.
-------------------------------------------------Tricuspid regurgitation is best heard at the
lower left sternal border & intensity increases
with inspiration.
o usually a secondary consequence of
pulmonary HTN, RV enlargement with
annular dilatation, or endocarditis.
-------------------------------------------------Acute aortic regurgitation is a/w rapid onset
dyspnea, exercise intolerance, or chest pain
(aortic dissection).

Findings include tachycardia, hypotension,


soft S1 (premature mitral valve closure), S3
&/or S4 gallop, accentuated pulmonic closure
sound, & pulmonary crackles.
-------------------------------------------------Mitral stenosis is usually caused by rheumatic
valve disease.
Clinical presentation tends to be 20 to 30 years
after the initial episode of rheumatic fever, &
most cases in women.
Patients with may be asymptomatic, but
become symptomatic with additional
hemodynamic stress, such as the increased
volume load of pregnancy.
This hemodynamic stress may precipitate an
arrhythmia (atrial fibrillation) that can
exacerbate heart failure symptoms.
Findings include an accentuation of P2
(evidence of elevated pulmonary arterial
pressure), opening snap followed by a lowpitched, diastolic rumble heard with the bell at
the apex in the left lateral decubitus position.
-------------------------------------------------Transthoracic echocardiography (TTE) is
indicated when a grade 3/6 or greater
systolic murmur is heard.
-------------------------------------------------Midsystolic murmurs grade 2/6 or less are
innocent murmurs, when short in duration,
a/w a physiologically split S2, without other
abnormal cardiac sounds or murmurs.
A hyperdynamic circulation (severe anemia,
thyrotoxicosis, or pregnancy) also may
produce an innocent midsystolic pulmonary
or aortic flow murmur.
The most common etiology in persons older
than 65 years is minor valvular abnormalities
due to aortic sclerosis.
Aortic sclerosis is characterized by focal areas
of valve thickening leading to mild valvular
turbulence, producing the auscultated murmur.
--------------------------------------------------

New-onset VSD occurs 5 to 7 days following


an MI, characterized by cardiogenic shock &
new systolic murmur; thrill along the left
sternal border.
-------------------------------------------------Rheumatic mitral stenosis findings include
an opening snap & low-pitched mid-diastolic
murmur that accentuates presystole.
S1 may be intensified.
-------------------------------------------------An ejection click & systolic murmur suggest
the presence of a bicuspid aortic valve.
S4 is common.
-------------------------------------------------Aortic coarctation is diagnosed in childhood
by association of a systolic murmur with
systemic HTN & reduced femoral pulse.
> 50% with aortic coarctation also have a
bicuspid aortic valve.
-------------------------------------------------Physical findings in atrial septal defect are
fixed splitting of S2 & RV heave.
A pulmonary mid-systolic flow murmur &
tricuspid diastolic flow rumble caused by
increased flow through the right-sided valves
from a large left-to-right shunt may be heard.
-------------------------------------------------Chronic aortic regurgitation shows a
widened pulse pressure with bounding
peripheral & carotid pulses.
Findings include an early holodiastolic murmur
along the left upper sternal border, high-pitched
& heard at end-expiration, leaning forward.
-------------------------------------------------Bioprosthetic valves are less durable than
mechanical valves because of the progressive
degenerative calcification of biologic material.
-------------------------------------------------Aortic stenosis, atrial fibrillation can be a/w
rapid & severe clinical deterioration due to the
more rapid rate & loss of atrial contribution to
left ventricular filling.
-------------------------------------------------

Endocarditis should be suspected if an


abnormal murmur is heard, particularly with
a compelling history or concurrent fever.
Incidence is higher in patients with underlying
valve abnormalities & prosthetic valves.
------------------------------------------------Aortic valve sclerosis, or valve thickening
without outflow obstruction, present in >25%
older than 65 years, diagnosed when an
asymptomatic murmur is auscultated or an
incidental echocardiograph.
Progression to stenosis is slow; < 20% develop
valve obstruction over the next 10 years.
In early stages, aortic stenosis presents subtly
with dyspnea or decreased exercise tolerance
Classic manifestations of aortic stenosis are
angina, syncope, & heart failure.
Atrial fibrillation can be a/w rapid & severe
clinical deterioration due to the rapid rate &
loss of atrial contribution to LV filling.
Angina occurs in > 50% with severe stenosis,
due to maldistribution of coronary flow in
the hypertrophied myocardium.
Aortic stenosis patients have increased
sensitivity to ischemic injury, &
subsequently higher mortality.
-------------------------------------------------Amlodipine & felodipine are the only
calcium channel blockers with demonstrated
neutral effects on mortality in heart failure.
o used in heart failure for management of
HTN or angina not adequately controlled
with ACE inhibitors or -blockers.
First-generation calcium channel blockers
(nifedipine) increase the risk of heart failure
decompensation & hospitalization.
-------------------------------------------------Spironolactone is indicated only for treatment
of NYHA class III or IV heart failure; a/w
30% reduction in mortality.
-------------------------------------------------Spironolactone is indicated for treatment of
severe (NYHA functional class III or IV)

systolic heart failure in addition to ACE


inhibitor, -blocker, & diuretic as needed.
Spironolactone blocks aldosterone, which is
not completely suppressed by chronic ACE
inhibitor therapy; aldosterone has adverse
effects of sodium retention, potassium
wasting, & myocardial fibrosis.
Addition of spironolactone is a/w a 30%
relative reduction in mortality.
-------------------------------------------------Serum creatinine & potassium levels should
be monitored when taking spironolactone.
Contraindications to therapy include a serum
creatinine level > 2.5 mg/dL in men ,
creatinine > 2.0 mg/dL in women or
potassium level > 5 meq/L.
---------------------------------------------ACE inhibitors (Lisinopril) are indicated for
treatment of all NYHA functional classes of
systolic heart failure, including NYHA class I.
ACE inhibitors reduce mortality & morbidity
& delay the onset of clinical heart failure in
patients with asymptomatic LV dysfunction.
-------------------------------------------------Patients intolerant of ACE inhibitors owing
to hyperkalemia or renal insufficiency, the
combination of hydralazine & a nitrate is a
suitable alternative, with hemodynamic effects
of vasodilation & afterload reduction.
This is a/w a reduction in mortality, although
to a lesser degree than with ACE inhibitors.
-------------------------------------------------ARBs are only for patients who are intolerant
of ACE inhibitors, owing to ACE inhibitorinduced cough.
-------------------------------------------------Eplerenone is an alternative to spironolactone
in severe heart failure (NYHA class III or IV)
if gynecomastia develops as a side effect of
spironolactone.
--------------------------------------------------

Amlodipine is the only calcium channel blocker


with a neutral (rather than detrimental) effect
on morbidity & mortality in heart failure.
Thus, it is acceptable for angina or HTN not
controlled with ACE inhibitors or -blockers.
-------------------------------------------------Digoxin is indicated for moderately to severely
symptomatic heart failure (NYHA class III-IV)
or rate control in atrial fibrillation.
-------------------------------------------------Digoxin has not been shown to affect mortality
but does reduce hospitalizations.
--------------------------------------------------Blockers should not be initiated or increased
during decompensated states (volume overload
or hypotension) because the transient decline
in cardiac output may worsen a
decompensated state.
------------------------------------------------ACE inhibitor (Lisinopril) & -blocker
(Carvedilol) are indicated for all patients with
systolic heart failure regardless of symptoms or
functional status, including asymptomatic or
very functional patients.
These have additive benefits with regard to
morbidity & mortality in systolic heart failure.
-------------------------------------------------Treat NYHA class I or II systolic heart failure
with a -blocker & ACE-I.
-------------------------------------------------An exercise stress test is contraindicated in a
patient with decompensated heart failure.
-------------------------------------------------B-type natriuretic peptide (BNP) is
synthesized by cardiac ventricles in response
to increased wall stress due to pressure or
volume overload.
BNP assays are useful in differentiating acute
heart failure from noncardiac dyspnea.
BNP concentration higher than 500 pg/mL has
a high likelihood of acute heart failure.
--------------------------------------------------

Echocardiogram should be obtained in all


newly diagnosed or suspected heart failure
to determine whether the heart failure is
systolic or diastolic, & detect structural or
functional abnormalities (regional wall
abnormalities, pericardial disease, or valvular
abnormality).
------------------------------------------------New-onset heart failure & angina should be
evaluated with cardiac catheterization &
angiography if they are possible candidates
for revascularization.
-------------------------------------------------Stress testing is preferred when assessing for
CAD patients with an intermediate risk with
no features of unstable angina.
Exercise stress test is recommended in a
patient with an intermediate probability of
CAD & normal resting ECG.
Nuclear medicine stress test is helpful if
resting ECG is abnormal.
-------------------------------------------------Typical angina (substernal chest pain on
exertion, relieved by rest) & new-onset heart
failure (exertional dyspnea & orthopnea),
findings (elevated JVP, pulmonary crackles,
S3 & S4), & echocardiogram with a
subnormal EF.
Definitive testing for coronary artery disease
(CAD) by cardiac catheterization is warranted
Primary aim is to identify possible targets for
revascularization (percutaneous or surgical)
with the goals of reducing angina, improving
systolic function, reducing the risk of heart
failure progression, & improve survival.
-------------------------------------------------Presence of elevated CVP, pulmonary crackles,
ventricular gallops (S3 or S4), any cardiac
murmur, & lower extremity edema all increase
the likelihood of heart failure.
--------------------------------------------------

Coarctation of the aorta may rarely present


initially as HTN during pregnancy.
------------------------------------------------Peripartum cardiomyopathy is defined as
heart failure with a LV ejection fraction < 45%
diagnosed between 3 months before & 6
months after delivery in absence of an
identifiable cause; usually diagnosed during
the first month postpartum.
Clinical features consistent with heart failure
(progressive dyspnea), evidence of LV
dysfunction (tachycardia, elevated CVP, S3 &
S4, displaced & diffuse apical impulse, mitral
regurgitant murmur, pulmonary crackles), &
CXR (pleural effusions, interstitial infiltrates).
-------------------------------------------------Concurrent therapy with ACE inhibitor & ARB
is a/w risk of worsening renal function,
symptomatic hypotension, & non-compliance.
-------------------------------------------------Digoxin use in treating heart failure patients in
sinus rhythm is primarily for symptom control
rather than improving survival.
Digoxin has not been shown to affect mortality
but shown to reduce hospitalizations.
Digoxin can be added to other therapy in
patients with NYHA class III or IV heart
failure for symptom control.
Maintaining lower serum concentrations of
digoxin is as effective as higher concentrations
& potential toxicities are avoided.
Higher digoxin levels is a/w higher mortality
in patients with systolic heart failure.
-------------------------------------------------Treat NYHA class IV heart failure with digoxin
-------------------------------------------------Left bundle branch block (LBBB) & RBBB
increase in frequency with age.
LBBB often occurs with underlying heart
disease. In older patients, LBBB is a/w
increased mortality. In younger patients,
LBBB is not a/w syncope or sudden death &
prognosis is generally excellent.

RBBB is similarly a/w increased mortality in


older patients with underlying heart disease.
When RBBB is not a/w underlying cardiac
disease, outcomes are generally excellent
-------------------------------------------------Other cardiac causes of syncope & sudden
death in young patients include hypertrophic
cardiomyopathy & arrhythmogenic right
ventricular dysplasia.
-------------------------------------------------Risk factors for acquired long QT syndrome
(LQTS) include females, hypokalemia,
hypomagnesemia, structural heart disease,
previous QT-interval prolongation, & history
of drug-induced arrhythmia.
-------------------------------------------------Cardiac events in LQTS include syncope &
cardiac arrest due to torsade de pointes
ventricular tachycardia.
LQTS may be congenital or acquired.
Congenital LQTS is suggested by recurrent
syncope triggered by activity & family history
of early sudden death (cousin drowning).
-----------------------------------------------Indications for a pacemaker include
symptomatic SA node dysfunction (sinus
bradycardia, intra-atrial block, exit block) &
symptomatic bradycardia due to advanced
second- or third-degree heart block.
-------------------------------------------------Implantable cardioverter-defibrillator
(ICD) placement is not indicated for
ventricular arrhythmias (Vfib) < 48 hours after
an acute STEMI.
-------------------------------------------------All patients, even those who have not suffered
arrhythmia during myocardial infarction,
should be reevaluated after an MI by
transthoracic echocardiogram (TTE) to
further stratify risk. If ejection fraction is
reduced (<35%), the patient may be a
candidate for defibrillator placement.
-------------------------------------------------

Unlike sudden cardiac death occurring in other


settings, cardiac arrest occurring within the
first 48 hours of transmural acute MI does
not require defibrillator placement.
-------------------------------------------------Primary criterion for ICD implantation for
primary prevention of sudden cardiac death in
the setting of heart failure is LV EF < 35%.
-------------------------------------------------Medical therapy (amiodarone, procainamide,
flecainide) does not improve survival in
patients with VT & structural heart disease.
ICD therapy improves survival rates in
hemodynamically unstable VT after cardiac
arrest who have ischemic or non-ischemic
cardiomyopathy & EF < 35%.
In patients with LV dysfunction in the
absence of VT, ICD implantation has also
been shown to improve survival.
-------------------------------------------------In the population of cardiac arrest survivors,
amiodarone does not improve mortality.
-------------------------------------------------Sustained ventricular tachycardia (VT)
occurs commonly with previous MI, & it is the
scar formed by the infarction that provides the
anatomic substrate for reentry.
Areas of fibrosis interspersed with viable
myocardial tissue are present in the border zone
of dense scar tissue & impart the conduction
delay critical to establishing reentry circuits.
-------------------------------------------------PVCs often are not a/w symptoms, although
they can cause palpitations or a sensation that
the heart has stopped, owing to the post-PVC
compensatory pause.
PVCs at rest in the setting of a structurally
normal heart appear to be a/w little to no
increased risk of cardiovascular events,
particularly patients younger than 30 years.
If symptoms can be clearly correlated with
PVCs, treatment may be appropriate, although
many patients respond to reassurance.

First-line is a -blocker (metoprolol) or


calcium channel blocker (verapamil).
-------------------------------------------------Most patients with atrial fibrillation are
treated with a combination of rate control &
long-term anticoagulation.
In patients with nonvalvular atrial fibrillation,
warfarin with a target INR of 2.0 to 3.0
decreases stroke risk by 62%, compared with a
19% decrease with aspirin.
CHADS2 score is used to determine if the risk
of stroke a/w atrial fibrillation warrants
chronic anticoagulation.
Points are scored for the presence of specific
risk factors for stroke:
o CHF,
o HTN,
o Age >75 years,
o Diabetes,
o Stroke or TIA (2 points)
2 points for a history of stroke or TIA
(strongest risk factor) & 1 point for all others.
risk of stroke is lowest for score = 0 (1.2%).
risk is 18% for a CHADS2 score of 6 (max).
CHADS2 score of 3 or greater & patients
with a history of TIA or stroke are high risk
& should be considered for chronic
anticoagulation with warfarin.
-------------------------------------------------Two strategies for persistent or paroxysmal
atrial fibrillation: controlling ventricular
response (rate control) & antiarrhythmics to
maintain sinus rhythm (rhythm control).
There is no survival advantage a/w either of
these strategies, but older patients (age >70),
rate control is a/w improved quality-of-life
scores.
More hospitalizations & adverse drug reactions
occur in patients receiving rhythm control
compared with rate control.
Patients should receive medication to control
the ventricular rate (metoprolol) & not an

antiarrhythmic agent (amiodarone).


-------------------------------------------------Treat atrial fibrillation with metoprolol &
warfarin.
-------------------------------------------------Most patients with inappropriate sinus
tachycardia respond to -blockers or
nondihydropyridine calcium channel blockers,
but some refractory cases are treated with
sinoatrial node ablation.
------------------------------------------------Sinoatrial ablation is indicated for patients
with atrial tachycardia that uses part of the
sinoatrial node as a reentry circuit.
-------------------------------------------------In patients with hyperthyroidism, -blocker
may provide symptomatic relief until the
underlying thyroid disease is treated.
-------------------------------------------------Measuring TSH level is an appropriate first
step to determine the underlying cause of the
sinus tachycardia.
-------------------------------------------------Electrical cardioversion is indicated for an
unstable patient with any arrhythmia (other
than sinus tachycardia) including atrial
fibrillation with a rapid ventricular rate.
-------------------------------------------------High dose Vitamin E can cause loose stools
& may inhibit vitamin K carboxylase, but is
not a/w cardiac side effects.
-------------------------------------------------Trazodone (antidepressant) does not cause
slowing of cardiac conduction, although it may
be a/w palpitations & ventricular ectopy.
-------------------------------------------------Memantine inhibits the glutamatergic Nmethyl-D-aspartate (NMDA) receptor on
central neurons.
Side effects: hallucinations, confusion,
restlessness, anxiety, dizziness, headache,
fatigue, & constipation.
--------------------------------------------------

In patients with preexisting heart block, use


cholinesterase inhibitors with caution.
-------------------------------------------------Donepezil inhibits acetylcholinesterase. Its
activity occurs preferentially in the CNS, but
mild peripheral cholinergic side effects are
common including increased vagal tone,
bradycardia, & atrioventricular block.
-------------------------------------------------Sinoatrial node dysfunction comprises a
collection of pathologic findings (sinus arrest,
sinus exit block, & sinus bradycardia) that
result in bradycardia.
-------------------------------------------------Mobitz type I block (Wenckebach block)
manifests as progressive PR interval
prolongation until there is a dropped beat.
Mobitz type II block manifests as a dropped
beat without progressive PR
prolongation.
-------------------------------------------------50% with SA node dysfunction also have
associated supraventricular tachycardia,
most often atrial fibrillation or atrial flutter.
Tachycardia-bradycardia syndrome is
characterized by rapid ventricular conduction
during episodes of atrial fibrillation, but
resting bradycardia between episodes.
Symptomatic sinus node dysfunction is an
indication for pacemaker placement, even if
the bradycardia occurs as a consequence of
drug therapy, if there is no other alternative.
-------------------------------------------------Pericardial tamponade from rupture of the
LV free wall leads to sudden hypotension &
death.
Ventricular free wall rupture typically
occurs 1 to 4 days after acute MI. Patients
present with cardiovascular collapse,
tamponade, or pulseless electrical activity.
-------------------------------------------------Aortic dissection presents with severe, sharp,
tearing chest pain.

Pain may radiate widely & a/w syncope,


systemic ischemia (impaired blood flow to an
organ or limb), or heart failure (aortic valve
disruption, tamponade).
Ascending aortic dissection is often a/w
acute aortic regurgitation (diastolic murmur at
the base of the heart), myocardial ischemia,
cardiac tamponade or hemopericardium, &
hemothorax or exsanguination.
-------------------------------------------------Mechanical complications occur 2 to 7 days
after a STEMI.
Late complications following STEMI include
cardiogenic shock, VSD, mitral regurgitation,
free wall rupture, & LV thrombus.
Progressive hypotension, respiratory distress,
new systolic murmur & thrill suggest either
ischemic mitral regurgitation or VSD.
Following echocardiography to confirm the
diagnosis, this patient should undergo
emergent surgery to repair the defect or valve.
-------------------------------------------------VSD manifests as a new systolic murmur,
hypotension, & respiratory distress 1 to 3 days
following an MI.
-------------------------------------------------Ventricular free wall rupture typically
occurs 1 to 4 days after acute MI.
It is unlikely for pericardial tamponade to be
present upon initial presentation unless the
patient had chest pain for several days prior to
the hospitalization.
-------------------------------------------------Right ventricular infarction occurs in 20%
of inferior wall STEMI & should be
considered with a clinical triad of JVD,
hypotension, & clear lung fields.
Diagnosis is made with a right-sided EKG, with
ST-segment elevation in leads V3R & V4R..
Treatment consists of restoration of blood flow
to the RV with thrombolytics or primary
percutaneous coronary intervention, aggressive
volume loading with IV normal saline to

increase RV filling, & dopamine or


dobutamine if hypotension persists.
-------------------------------------------------First-degree AV block is diagnosed when the
PR interval is > 0.20 sec; & no drop beats.
It is a/w a soft S1. Presence of first-degree
heart block suggests AV nodal disease but
rarely requires therapy.
First-degree AV block is a/w acute reversible
conditions, including inferior MI, rheumatic
fever, & digitalis intoxication. Additionally,
any medication that slows conduction through
the AV node (diltiazem)
-------------------------------------------------Thrombolytics are an alternative to primary
PCI in suitable candidates with STEMI.
By lysing the clot that is limiting blood flow to
the myocardium, thrombolytics restore
perfusion to the ischemic area, reduce infarct
size, & improve survival.
Thrombolytics should be administered within
12 hours after the onset of chest pain.
-------------------------------------------------Treatment for acute STEMI is
revascularization or thrombolytic therapy.
The patient has no contraindications for
thrombolytic therapy; hemodynamically stable
without cardiogenic shock.
Treatment of choice is percutaneous coronary
intervention (PCI) provided that it can be done
immediately or in less than 60 minutes if
transfer to another hospital is necessary.
-------------------------------------------------Ventricular free wall rupture typically leads to
pericardial tamponade manifesting as
sudden hypotension & death.
Free wall rupture typically occurs 1 to 4 days
after acute MI. Patients usually present with
cardiovascular collapse, tamponade, or
pulseless electrical activity.
-------------------------------------------------Pulmonary embolism can complicate acute MI
& should be suspected with new-onset pleuritic

chest pain, dyspnea, & hypotension.


-------------------------------------------------History of chest pain, dyspnea a week ago &
EKG findings of Q waves in leads II, III, &
aVF suggest an acute inferior wall MI.
Presence of a new systolic murmur &
respiratory distress several days after an acute
MI indicates the possibility of either a
ventricular septal rupture or mitral regurgitation
Papillary muscle rupture generally presents
several days after the infarct event.
Severe mitral regurgitation complicating an
acute MI is common with inferior infarcts
versus anterior infarcts & should be suspected
in patients with pulmonary edema &
respiratory distress.
--------------------------------------------------blockers are first-line therapy for unstable
angina & NSTEMI unless contraindicated.
Ongoing ischemia despite -blocker therapy,
a calcium channel blocker can be added.
-------------------------------------------------An intra-aortic balloon pump is indicated for
an acute coronary syndrome with cardiogenic
shock that is unresponsive to medical therapy,
acute mitral regurgitation secondary to
papillary muscle dysfunction, ventricular
septal rupture, or refractory angina.
The intra-aortic balloon pump reduces
afterload during ventricular systole &
increases coronary perfusion during diastole.
Patients with refractory cardiogenic shock
who are treated with an intra-aortic balloon
pump have a lower in-hospital mortality rate
than patients who are not treated.
------------------------------------------------Treat NSTEMI with a -blocker.
-------------------------------------------------Elevated troponin I, ST-segment depression &
T-wave inversions are indicative of a NSTEMI.
Early IV -blocker reduces infarct size,
decreases frequency of recurrent myocardial

ischemia, & improves short- & long-term


survival.
-Blockers diminish myocardial oxygen
demand by reducing HR, systemic arterial
pressure, & myocardial contractility;
prolongation of diastole augments perfusion to
the injured myocardium.
-Blockers can be used in LV dysfunction if
heart failure status is stable.
-------------------------------------------------Wide QRS tachycardia in the presence of
known structural heart disease, especially a
prior MI, is likely ventricular tachycardia.
Any wide QRS tachycardia should be
considered to be ventricular tachycardia
until proven otherwise.
o The most important differentiating point
is the history of ischemic heart disease.
-------------------------------------------------Supraventricular tachycardia with a wide
QRS complex, usually due to coexisting
bundle branch block or pre-excitation (WolffParkinson-White syndrome), can mimic
ventricular tachycardia.
Differentiating ventricular tachycardia from
supraventricular tachycardia with aberrant
conduction is important because the treatment
differs markedly.
-------------------------------------------------Ventricular tachyarrhythmias are characterized
by wide QRS complexes (QRS >0.12 sec) &
ventricular rates > 100/min.
o In ventricular tachycardia, ventricular
rate ranges from 140 to 250/min
o In torsades de pointes, ventricular rate
ranges from 200 to 300/min
o In ventricular fibrillation, the rate is
typically > 300/min.
-------------------------------------------------Revascularization, either a percutaneous
coronary intervention or coronary artery
bypass grafting surgery, has been shown to
reduce angina, increase longevity, &

improve LV performance.
-------------------------------------------------Coronary revascularization is beneficial in
chronic stable angina & the following
conditions: angina pectoris refractory to
medical therapy; large area of ischemic
myocardium & high-risk criteria on stress
testing; high-risk coronary anatomy, including
left main coronary artery stenosis or threevessel disease; & significant coronary artery
disease with reduced LV systolic function.
------------------------------------------------Multifocal atrial tachycardia (MAT)
characteristically occurs in the setting of
chronic lung disease & is manifested by
three or more P-wave configurations on
EKG with associated tachycardia.
-------------------------------------------------History of tachycardia, recent syncope, &
EKG showing a short PR interval & presence
of a delta wave signifies preexcitation.
Wolff-Parkinson-White syndrome, a type of
AV reentrant tachycardia, is most likely.
-------------------------------------------------Because CT angiography provides no
functional information (the extent of ischemia),
a markedly abnormal study is followed by
referral to coronary angiography or stress
testing to determine the ischemic burden.
Benefits of CT angiography are greatest in
symptomatic patients with an intermediate
pretest probability of CAD.
-------------------------------------------------Coronary calcium testing may be considered
in asymptomatic persons with a 10 to 20%
Framingham 10-year risk category
(intermediate risk) & young persons with a
strong family history of premature
cardiovascular disease.
-------------------------------------------------Coronary angiography should be reserved
for patients with chronic CAD who have
lifestyle-limiting angina despite medical

therapy, markedly positive results on


noninvasive stress testing, successful
resuscitation from sudden cardiac death, or
documented ventricular tachycardia.
Coronary angiography can also be considered
in patients with nonspecific chest pain to
exclude CAD as a cause for current symptoms
if they have had recurrent hospitalizations.
-------------------------------------------------Screening for CAD in adults who are
asymptomatic is not recommended because
the probability of a false-positive is greater
than the probability of a true positive.
For an intermediate probability of CAD,
noninvasive exercise stress test provides the
most useful information.
-------------------------------------------------Ventricular tachycardia is characterized by
wide QRS complex (QRS >0.12 sec) &
ventricular rate ranging from 140-250/min.
-------------------------------------------------Atrial fibrillation shows a rapid, irregularly
irregular rhythm with no discernible P waves
& atrial fibrillatory waves at a rate between
350 & 600 beats/min.
Fibrillatory waves vary in amplitude,
morphology, & intervals, creating a rough,
irregular baseline between QRS complexes.
The patient's evaluation should include a
transthoracic echocardiogram to exclude
occult valve or other structural heart disease &
assess the size of the left atrial appendage.
Thyroid studies should be performed to
exclude hyperthyroidism.
-------------------------------------------------Patients with chronic stable angina are
treated with (1) aspirin, (2) -blocker, (3) ACE
inhibitor, (4) nitroglycerin, & (5) statin.
-------------------------------------------------Although clopidogrel is beneficial in patients
with acute coronary syndromes, it has small
clinical benefit in chronic stable angina & is

a/w increased risk of bleeding.


-----------------------------------------------Vascular-protective medications include
clopidogrel, aspirin, ACE inhibitors, & statins.
------------------------------------------------Ranolazine should only be considered in
patients with chronic stable angina who
remain symptomatic despite optimal doses of
-blockers, calcium channel blockers, nitrates.
-------------------------------------------------Chronic stable angina can be treated with
calcium channel blockers if unable to tolerate
-blockers, or added to -blocker therapy for
difficult-to-control symptoms.
-------------------------------------------------Sick Sinus Syndrome (SA node dysfunction) is
a frequent cause of pacemaker implantation
consists of symptomatic sinus bradycardia &
tachycardia-bradycardia syndrome
(alternating atrial tachyarrhythmias &
bradycardia).
In "tachy-brady" syndrome, bradycardia
usually occurs after termination of tachycardia
o atrial fibrillation is the most common
tachyarrhythmia observed.
-------------------------------------------------Atrial fibrillation is characterized by an
absence of discernible P waves, replaced by
fibrillatory waves that vary in amplitude,
shape, & timing.
-------------------------------------------------Atrial flutter is characterized by presence of
multiple P waves on EKG in a "sawtooth"
pattern, with 2:1 ventricular conduction.
-------------------------------------------------Exercise stress test is recommended in patients
with intermediate probability of CAD &
normal EKG who are able to exercise because
it provides information about exercise tolerance
& hemodynamic response to exercise.
-------------------------------------------------Dobutamine stress echocardiography is
appropriate for patients who are unable to

exercise & not hypertensive at rest.


-------------------------------------------------Coronary angiography would only be
appropriate if the patient were presenting with
an acute coronary syndrome or after an
abnormal stress test to determine if there is
an indication for revascularization.
-------------------------------------------------An adenosine nuclear perfusion stress test is
contraindicated in patients with significant
bronchospastic disease & hence is not the
choice for a patient with asthma.
-------------------------------------------------Normal wall motion on echocardiography
during chest pain excludes coronary ischemia
or infarction.
-------------------------------------------------Descending thoracic aortic aneurysm is a/w
splanchnic ischemia, renal insufficiency, lower
extremity ischemia, or focal neurologic deficit
due to spinal cord ischemia.
-------------------------------------------------Transesophageal echocardiography is not
sensitive for detection of pulmonary emboli
but for acute chest pain if aortic dissection is
suspected.
Ascending aortic dissection is a/w acute
aortic regurgitation, myocardial ischemia,
cardiac tamponade or hemopericardium, &
hemothorax or exsanguination.
o > 20 mm Hg variation in systolic BP in
the arms may be present.
-------------------------------------------------A resting radionuclide perfusion study can
be helpful in diagnosis of coronary ischemia
when the EKG is nondiagnostic but does not
provide additive information to that already
obtained by echocardiography.
-------------------------------------------------Normal echocardiogram between episodes of
chest pain does not rule out unstable angina
because wall motion returns to normal
between ischemic episodes

-------------------------------------------------Symptoms of chest pain & dyspnea, findings


of asymmetric leg edema, elevated CVP,
tachypnea, & tachycardia suggest the
possibility of pulmonary embolism.
CT pulmonary angiography is the most
appropriate diagnostic test to perform.
-------------------------------------------------In the treatment of chronic stable angina, the
-blocker dose should be titrated to achieve a
resting HR of 55 to 60/min & 75% of the HR
that produces angina with exertion.
-------------------------------------------------Ranolazine is a novel anti-anginal agent
approved for chronic stable angina; should
only be used in addition to baseline therapy
with a -blocker, CCB, & long-acting nitrate.
-------------------------------------------------Medical therapy for chronic stable coronary
artery disease (CAD) includes both antianginal
& vascular-protective agents.
o Anti-anginal therapy: -blockers,
calcium channel blockers, & nitrates.
o Vascular-protective therapy includes
Aspirin, ACE inhibitors, & stAtins.
-------------------------------------------------First-degree block requires no specific
treatment.
-------------------------------------------------Mobitz type I second-degree heart block is
characterized by progressive prolongation of
the PR interval until a dropped beat occurs.
Mobitz type I block can occur in absence of
heart disease, including athletes & older
adults; patients with underlying heart disease,
including acute ischemia; patients who take
drugs that block the AV node, such as blockers (metoprolol), CCB, & digoxin.
Mobitz type I is characteristically transient &
usually requires no specific treatment,
however, some patients may develop
excessively slow heart rates & experience

symptoms related to decreased cerebral or


coronary perfusion.
If treatment is necessary, it begins by
identifying & correcting reversible causes of
slowed conduction, such as myocardial
ischemia, increased vagal tone (from pain or
vomiting), & discontinuation of drugs that
depress AV conduction.
------------------------------------------------Mobitz type II second-degree AV block is
characterized by a regularly dropped beat
without progressive PR prolongation.
It is a/w additional disease in the conduction
system, such as bundle branch block or
bifascicular or trifascicular block.
Mobitz type II may suddenly & unpredictably
progresses to complete heart block & usually
treated with a pacemaker.
-------------------------------------------------Classic triad of sudden severe headache,
diaphoresis, & palpitations is suggestive of
pheochromocytoma.
Other manifestations include hyperglycemia,
weight loss, arrhythmias (atrial & ventricular
fibrillation), & catecholamine-induced
cardiomyopathy.
-------------------------------------------------Panic disorder is characterized by recurrent,
unexpected attacks that feature abrupt onset
of numerous somatic symptoms (palpitations,
sweating, tremulousness, dyspnea, chest pain,
nausea, dizziness).
Symptoms peak within 10 minutes of onset, &
usually last from 15 to 60 minutes.
Treatment is cognitive-behavioral therapy
(CBT) & SSRI (paroxetine).
-------------------------------------------------First-degree block is characterized by
prolongation of the PR interval to > 0.2 sec &
not a/w alterations in heart rate.
--------------------------------------------------

Two types of second-degree block, both


recognized by presence of a P wave that is not
followed by a ventricular complex.
Mobitz type I block (Wenckebach block)
manifests as progressive PR interval
prolongation until there is a dropped beat.
Mobitz type II block manifests as a dropped
beat without PR-interval prolongation.
-------------------------------------------------Mobitz type I block usually does not progress
to complete heart block.
Mobitz type II block, which is usually a/w a
bundle branch block, typically progresses to
third-degree block.
-------------------------------------------------Third-degree block is complete absence of
conduction of atrial impulses to the ventricle &
most common cause of marked bradycardia;
ventricular rates are 30-50 bpm.
Patients with atrioventricular block may be
asymptomatic or have severe bradycardiarelated symptoms (weakness, presyncope,
syncope) & ventricular arrhythmias.
-------------------------------------------------This patient has third-degree AV heart block
due to Lyme carditis. Presence of the a skin
rash (erythema migrans) with or without a
history of tick bite in an endemic region by
Borrelia burgdorferi infection.
Lyme carditis is manifested by acute-onset,
high-grade AV conduction defects that may be
a/w myocarditis.
-------------------------------------------------Complete response to empiric PPI therapy is
diagnostic of GERD.
-------------------------------------------------Ambulatory esophageal pH monitoring can
be used if the patient does not respond to
empiric therapy for GERD or if the patient has
atypical symptoms.
-------------------------------------------------Esophagogastroduodenoscopy (EGD) is
indicated in patients with long-standing reflux

disease to screen for Barrett esophagus &


patients with alarm symptoms: anemia,
weight loss, or dysphagia, but not for the
initial screening test for GERD.
-------------------------------------------------The approach for suspected esophageal chest
pain is to rule out cardiac ischemia & then
treat empirically with a PPI.
-------------------------------------------------Classic triad of right ventricular MI:
hypotension, clear lung fields, & elevated CVP.
ST-segment elevation on right-sided EKG
lead V4R is the most predictive finding.
-------------------------------------------------Volume expansion is the primary supportive
treatment for the hemodynamic abnormalities
of a right ventricular MI.
In right ventricular MI, right ventricular
contractility is reduced, resulting in higher RV
diastolic pressure, lower RV systolic pressure,
& reduced preload or filling of the LV.
Volume expansion improves hemodynamic
abnormalities of right ventricular MI because
the gradient of pressure from the right atrium
to the left atrium maintains filling of the LV.
Inotropic support, using IV dobutamine, is
appropriate in right ventricular MI whose
hypotension is not corrected after 1 L of saline
infusion.
-------------------------------------------------Inotropic agents increase cardiac contractility,
thus increasing myocardial oxygen demand &
potentially extend the infarction.
-------------------------------------------------All patients with an inferior STEMI should
have a right-sided EKG at presentation.
-------------------------------------------------Patients with peptic ulcer disease do not have
pain at diagnosis; ulcers are usually detected
during an evaluation for potential ulcer-related
complications such as overt or obscure bleeding

Symptoms present as dyspepsia or a


nonspecific, gnawing epigastric pain.
-------------------------------------------------Classic presentation of aortic dissection
consists of sudden-onset severe chest pain
radiating to the back. Other findings include a
BP differential between the right & left arms,
murmur of aortic regurgitation, & widened
mediastinum on CXR.
-------------------------------------------------Pain of acute pericarditis is pleuritic, may
radiate to the top of the shoulder, & often
worse when the patient is supine. Fever &
pericardial friction rub are usually evident.
Hallmark EKG changes include diffuse ST
elevations & PR depression.
-------------------------------------------------A normal EKG at rest does not exclude
ischemic heart disease nor does a normal
troponin level.
-------------------------------------------------Ischemic cardiac pain has a predictable
relation to exercise & relief with rest or
nitroglycerin.
Sharp pain, well-localized pain, & back pain
are infrequently a/w ischemic heart disease.
-------------------------------------------------Ascending aortic dissection characteristics:
back pain, unequal BPs or pulses, or a
widened mediastinum on CXR
-------------------------------------------------PCI is effective if completed within 6 hours
of the onset of chest pain; the earlier the
intervention, the better the outcome.
-------------------------------------------------Percutaneous angioplasty & stent placement
is the preferred therapy for STEMI because it
is a/w a lower 30-day mortality rate compared
to thrombolytics..
Contraindications to thrombolytic therapy
include prior intracerebral hemorrhage,
ischemic stroke within 3 months, suspected
aortic dissection, or active bleeding.

------------------------------------------------Chest pain from acute pericarditis is sharp &


pleuritic, worsened by a supine position.
Acute pericarditis is diagnosed by presence
of at least two of the three classic features:
o pleuritic chest pain
o friction rub
o diffuse ST-segment elevation, often with
PR segment depression
-------------------------------------------------Pulmonary embolism may present with the
classic symptoms of dyspnea, chest pain,
hemoptysis, or syncope.
-------------------------------------------------In NSTEMI, ischemia is severe & results in a
release of biomarkers of myocardial injury
hours after the onset of ischemic chest pain:
troponin I, troponin T, & CK-MB.
In unstable angina, there is no detectable
increase in these enzymes.
-------------------------------------------------Although most patients with STEMI
ultimately develop Q waves, some exhibit
diagnostic ST-segment elevation & cardiac
enzyme elevations without Q waves.
-------------------------------------------------Chest pain at rest, elevated serum troponin I
level, & ST-segment depression prominent in
leads V2 through V6. are features that indicate
NSTEMI.
-------------------------------------------------Chronic stable angina refers to a coronary
artery syndrome characterized by chest
discomfort that occurs predictably &
reproducibly at a certain level of exertion &
relieved with rest or nitroglycerin.
-------------------------------------------------Coronary angiography is indicated in
patients with chronic stable angina who
experience lifestyle-limiting angina despite
optimal medical therapy.
--------------------------------------------------

II. Endocrine & Metabolism

Bone density scans are reported as T-scores


(standard deviation from the mean BMD of a
young healthy population) & Z-scores
(standard deviation from BMD of age- & sexmatched group).
Osteoporosis is diagnosed by the presence of
fragility fractures (secondary to minor
trauma, falling from a standing position), or
bone mineral density (BMD) T-score < -2.5 in
patients without fragility fractures.
At the spine, a T-score of -1 = 10% bone loss.
-------------------------------------------------Osteopenia is defined as a BMD T-score
between -1 & -2.5.
-------------------------------------------------Bisphosphonates are first-line drugs for
postmenopausal women with osteoporosis.
Alendronate & risedronate reduce the risk of
both vertebral & nonvertebral fractures.
Some patients with osteoporosis may be
intolerant of oral bisphosphonates because of
aggravation of underlying GERD. For these
patients, once yearly IV zoledronate infusion
is a potent & effective alternative.
Injectable bisphosphonate (zoledronate)
should also be considered when oral
bisphosphonates are unsuccessful,
contraindicated (esophageal stricture or
achalasia), or likely to be poorly absorbed
(uncontrolled celiac disease & inflammatory
bowel disease) & or unable to remain upright
for 30 - 60 minutes after dosing.
IV ibandronate every 3 months is an
alternative to annual IV alendronate.
-------------------------------------------------Treat postmenopausal osteoporosis of the hip
& spine with annual IV zoledronate infusion
-------------------------------------------------Teriparatide is the only anabolic agent listed,
all other medications are anti-resorptive
agents.

Teriparatide is reserved for patients at high


risk of fracture, including those with very low
BMD (T-score below -3.0) with a previous
vertebral fracture & contraindications to
bisphosphonates.
Teriparatide should be considered in patients
intolerant of other medications & greatest
fracture risk (T-score <-3.5 or <-3.0 with a
fragility fracture).
Teriparatide improves bone mineral density,
stimulates osteoblastic bone formation, &
reduces risk of new vertebral & nonvertebral
fractures.
Given as a subcutaneous injection, teriparatide
should not be used for more than 2 years.
Animal studies have shown an increased risk
of osteosarcoma; should be avoided in
patients with Paget disease of bone,
unexplained elevation of alkaline phosphatase,
previous radiation involving the skeleton, &
history of skeletal cancer.
-------------------------------------------------Raloxifene is a selective estrogen receptor
modulator (SERM) that has estrogen-like
effects on bone but inhibits the effects of
estrogen in the breast & uterus.
Raloxifene increases bone mass & decreases
the risk of vertebral fractures in
postmenopausal women but does not affect
the incidence of hip fractures.
Raloxifene is not a/w adverse cardiovascular
events & decreases the risk of breast cancer in
high-risk women.
Side effects: hot flushes &
thromboembolism.
It is a second-line drug to bisphosphonates.
-------------------------------------------------Use of conjugated estrogens &
medroxyprogesterone in postmenopausal
women increased bone mass but also increased
the risk of cardiovascular disease, stroke,
breast cancer, DVT, & pulmonary embolism.
-------------------------------------------------

Calcitonin nasal spray increases bone mass


in the spine & decreases vertebral fractures but
does not affect the incidence of hip fractures.
This drug is indicated for women who are
more than 5 years postmenopausal.
It is second-line to the bisphosphonates.
------------------------------------------------Bisphosphonates (alendronate) are
pyrophosphate derivatives that bind to the
bone surface & inhibit osteoclastic bone
resorption.
They lower fracture risk in osteoporosis.
They are poorly absorbed & must be taken in
the fasting state to optimize absorption.
-------------------------------------------------Zoledronate is a bisphosphonates that can be
administered intravenously; a/w a long
duration of action & reduces fracture risk.
A single dose suppresses bone turnover
markers for a full year & induces significant
gains in bone mineral density.
-------------------------------------------------Pneumococcal vaccine is indicated for
persons age 65 years & older or those
younger than 65 years who live in long-term
care facilities, who have chronic illnesses, or
who are Alaskan natives or American Indians.
-------------------------------------------------After three consecutive negative annual
cytology smears, the risk of cervical cancer is
reduced to ~ 1/100,000 person-years.
Three consecutive normal Pap smears in a
monogamous patient whose last Pap smear
was 14 months ago, it is reasonable to increase
screening interval to every 2 to 3 years, with
consideration of stopping screening at age 65
if Pap smears continue to be normal.
-------------------------------------------------Osteoporosis screening is recommended for
women age 65 years & older; women 60 to 64
years old at increased risk for osteoporosis.
Screen for osteoporosis with dual-energy x-ray
absorptiometry (DEXA) scan.

The most predictive risk factor for


osteoporosis is weight below 70 kg (154 lb).
-------------------------------------------------In patients with hyperparathyroidism,
localization of abnormal parathyroid glands
preoperatively by means of ultrasonography,
technetium Tc 99m sestamibi scintigraphy,
or MRI offers the possibility of a less invasive
surgical approach.
-------------------------------------------------USPSTF advises against using estrogen or
estrogen plus progestin for prevention of
chronic diseases, including osteoporosis, after
menopause; data showed an increased risk of
breast cancer, coronary heart disease, stroke,
VTE, dementia & cognitive decline, &
urinary incontinence.
-------------------------------------------------Vitamin D deficiency contributes to bone loss
from decreased intestinal calcium absorption
& secondary hyperparathyroidism.
Vitamin D supplements can improve muscle
strength, leading to fewer falls.
-------------------------------------------------Vitamin D supplementation is an important
part of treatment for osteoporosis.
Vitamin D levels are best measured by looking
at 25-Hydroxy vitamin D. A wide range of
"optimal" levels are reported.
Levels < 30 ng/mL are defined as insufficient,
& < 20 ng/mL are deficient.
-------------------------------------------------A common vitamin D supplementation
strategy includes a loading dose of 50,000 IU
orally once a week for 10 weeks & followed
by a daily maintenance dose of 2000 IU.
-------------------------------------------------Treat osteoporosis with bisphosphonates,
vitamin D & calcium.
-------------------------------------------------Stress-level dosages of corticosteroids are
administered to adrenal insufficiency during
times of increased physiological stress.

-------------------------------------------------Patients with adrenal insufficiency should


increase their corticosteroid dosage during
stressful events (infection, surgery).
Patients who develop nausea & vomiting that
limit the use of orally corticosteroids; should
be administered parenteral corticosteroids.
-------------------------------------------------Cortisol replacement with corticosteroids &
normal saline to restore intravascular volume
are vital to treating acute adrenal insufficiency
Stress-level dosages of corticosteroids are
10-times the normal daily replacement dosage;
equivalent to 100 mg of IV hydrocortisone
daily, in divided dosages 3-4 times per day.
Once hydrocortisone dosage is over 60 mg
per day, fludrocortisone is unnecessary
because that dose of hydrocortisone has
adequate mineralocorticoid activity.
------------------------------------------------Fludrocortisone is a mineralocorticoid that is
required in primary adrenal insufficiency.
Hyponatremia is a common feature of
adrenal insufficiency, easily corrected with
normal saline & hydrocortisone to restore
plasma volume.
Fludrocortisone is usually not necessary in a
hospitalized patient receiving normal saline &
high dose hydrocortisone, which has
mineralocorticoid activity.
o This therapy will maintain vascular
volume & suppress vasopressin, which is
responsible for the hyponatremia.
-------------------------------------------------Treat adrenal insufficiency during stress with
IV stress doses of hydrocortisone.
-------------------------------------------------Addison disease (primary adrenal insufficiency)
is a/w low cortisol & elevated ACTH levels.
-------------------------------------------------Secondary adrenal insufficiency due to
exogenous corticosteroids may be a/w

suppression of both ACTH & cortisol &


clinical findings of excess glucocorticoids.
-------------------------------------------------Systemic corticosteroids are the most common
cause of central adrenal insufficiency, with
supraphysiologic dosages of exogenous
corticosteroids causing disruption of
hypothalamic/pituitary ACTH production.
Consequently, the adrenal cortex atrophies.
When subsequently challenged by stress, the
hypothalamus & pituitary are unable to
stimulate adequate adrenal cortisol production.
This central effect of exogenous corticosteroids
can occur after 3 weeks of suppressive therapy.
The patient develops Cushing syndrome as a
result of chronic systemic exposure to
intraarticular corticosteroids injections.
Despite her cushingoid features, however, she
has clinical & biochemical evidence of adrenal
insufficiency. Low-normal serum ACTH level
& partial response to cosyntropin stimulation
(synthetic ACTH) indicates central
(secondary) adrenal insufficiency.
Patients with adrenal insufficiency often
decompensate during concurrent illnesses.
-------------------------------------------------Classic symptoms of pheochromocytoma:
palpitations, sweating, headaches, & HTN.
Additionally, biochemical testing reveals
increased plasma levels of catecholamines.
Most pheochromocytomas are located in the
adrenal medulla, some are extra-adrenal.
Abdominal CT has high sensitivity in detecting
adrenal pheochromocytoma & extra-adrenal
catecholamine-secreting paragangliomas.
MRI is as sensitive as CT in detecting adrenal
pheochromocytomas & superior in detecting
extra-adrenal catecholamine-secreting
paragangliomas.
If abdominal CT shows no masses, the next
best localizing study would be a
metaiodobenzylguanidine (MIBG) scan.

MIBG scintigraphy is highly specific (99%)


but less sensitive (80%) than CT techniques.
MIBG scintigraphy is for patients with
equivocal CT results, extra-adrenal tumors, or
suspected malignancy.
-------------------------------------------------Screen for pheochromocytoma with plasma
metanephrine & normetanephrine.
Diagnose pheochromocytoma with
abdominal CT scan.
-------------------------------------------------Cosyntropin stimulation test is used to
determine the adrenal reserve by measuring
the response to a standard dose of synthetic
ACTH. The test does not detect Cushing
syndrome but, rather, adrenal insufficiency.
------------------------------------------------Adrenal imaging is indicated if the
hypercortisolism is ACTH independent
(normal or low ACTH level). In patients with
hypercortisolism a/w suppressed ACTH
secretion, a CT scan of the adrenal glands
often shows a tumor (adenoma or carcinoma).
-------------------------------------------------The cause of ACTH hypersecretion is either a
pituitary adenoma or an ectopic source, such
as a carcinoid tumor.
Partial ACTH suppression with high-dose
dexamethasone suggests an ACTH-secreting
pituitary microadenoma.
High-dose dexamethasone is usually not
successful in suppressing ACTH production
from an ectopic source.
-------------------------------------------------Evaluate a patient with suspected Cushing
disease with pituitary MRI.
------------------------------------------------Renovascular hypertension due to
fibromuscular disease of the renal arteries
presents in patients younger than 35 years, &
azotemia is rarely present.
Atherosclerotic renovascular hypertension
is common in patients older than 55 years &

a/w vascular disease in other vessels;


azotemia is often present.
-------------------------------------------------Screen for primary hyperaldosteronism with
serum aldosterone to plasma renin ratio.
A ratio greater than 20, particularly when
serum aldosterone level is > 15 ng/dL, is
diagnostic.
After biochemical confirmation, localization
procedures are appropriate to differentiate
aldosterone-producing adenomas, which are
amenable to surgical resection, from bilateral
hyperplasia, which is medically treated.
Given the high incidence of incidental adrenal
lesions, however, imaging studies, such as CT
of the adrenal glands, should not be
performed before biochemical testing that
confirms the presence & diagnosis of
hyperaldosteronism.
-------------------------------------------------A patient with drug-resistant hypertension
(uncontrolled HTN on three drugs, including a
diuretic), unprovoked hypokalemia, &
probable metabolic alkalosis; also an
inappropriately high urine potassium level.
Primary hyperaldosteronism is a likely
cause of his HTN & hypokalemia.
-------------------------------------------------Hypersecretion of glucocorticoids &
catecholamines should be evaluated in all
patients, including asymptomatics, with
incidentally discovered adrenal adenoma.
-------------------------------------------------Because overt clinical manifestations are scant,
screening tests are necessary to identify
potentially functional adrenal incidentalomas
secreting cortisol, aldosterone, or
catecholamines.
Subclinical Cushing syndrome is the most
common abnormality a/w adrenal
incidentalomas.
Because patients have no symptoms or
physical findings of Cushing syndrome, the

possibility of autonomous hypersecretion of


glucocorticoids should be evaluated with an
overnight dexamethasone suppression test.
Additionally, plasma catecholamine
measurements are reasonable screening tests
to rule out pheochromocytoma.
-------------------------------------------------Patients with metastatic cancer of the
adrenal glands have clinical evidence of
disease elsewhere. Imaging of the mass
(vascularity, size, CT attenuation) can provide
important clues.
Risk of primary or metastatic cancer is 2% for
tumors less than 4 cm in diameter but
increases to 25% for tumors 6 cm or larger.
Metastatic lesions to the adrenal glands
have high CT attenuation (>20 Hounsfield
units) & often bilateral.
Primary adrenocortical carcinoma tends to be
large with irregular borders & areas of necrosis.
Pheochromocytoma, adrenal carcinoma, &
metastatic disease to the adrenal glands are
often vascular, whereas benign adrenal
adenomas are not highly vascular.
-------------------------------------------------Overnight dexamethasone suppression test &
plasma-free metanephrines should be done to
evaluate an incidental adrenal adenoma.
-------------------------------------------------Severe illness can cause euthyroid sick
syndrome, a/w abnormal results on thyroid
function tests that normalize after recovery.
-------------------------------------------------With a history of a recent severe illness,
results of thyroid function tests (low TSH &
free T3 levels & low-normal free T4 level) are
consistent with changes from a nonthyroidal
illness (euthyroid sick syndrome)
The best next step is to allow the patient to
recover for 4 to 8 weeks & repeat the thyroid
function tests.
--------------------------------------------------

Ultrasound of the thyroid gland can be used


to distinguish the high vascular flow of
Graves disease from the low-flow pattern of
autoimmune thyroiditis.
-------------------------------------------------Postpartum thyroiditis can cause postpartum
thyrotoxicosis, hypothyroidism, or both.
With postpartum thyroiditis, thyroid scans &
radioactive iodine uptake tests will be low
during the thyrotoxic phase & become
elevated during the hypothyroid phase as the
thyroid gland recovers & becomes very avid for
iodine as stores are repleted.
-------------------------------------------------Postpartum thyroiditis occurs in within a
few months of delivery, is a variant of
painless thyroiditis.
Patients may have transient thyrotoxicosis
alone, hypothyroidism alone, or thyrotoxicosis
followed by hypothyroidism, then recovery.
-------------------------------------------------Radioactive iodine therapy preceded or
followed by adjunctive therapy with an
antithyroidal is used to treat Graves disease.
Antithyroidals attempt to decrease the risk of a
transient worsening of thyrotoxicosis after
thyroid ablation.
Because antithyroidals render the thyroid
radioresistant, they must be stopped for several
days before & after giving radioactive iodine.
The expected outcome is hypothyroidism,
occurs within 2 to 3 months, at which time
thyroid hormone replacement is begun.
-------------------------------------------------Graves disease can present with subclinical or
overt thyrotoxicosis. Physical exam may
reveal tachycardia; elevated systolic BP with a
widened pulse pressure; palpable goiter,
which is classically smooth; thyrotoxic stare
due to lid retraction; proptosis; &, rarely, an
infiltrative dermopathy.
Use a -blocker (atenolol) to control
tachycardia.

-------------------------------------------------Methimazole has fewer side effects & results


in quicker achievement of the euthyroid state
than propylthiouracil.
Because of a presumed immunomodulatory
effect, antithyroidals result in drug-free
remission rates in patients with Graves
disease treated for 1 year.
-------------------------------------------------Treat Graves disease with atenolol &
methimazole.
-------------------------------------------------Thyroid-binding globulin (TBG) levels
increase during pregnancy due to estrogen
elevation. However, without an increase in
dosage of levothyroxine, free T4 levels may
decrease as T4 becomes bound by TBG.
After delivery, TBG levels decrease, as do
thyroid hormone requirements.
-------------------------------------------------Undertreatment of maternal hypothyroidism
can have a potentially negative effect on fetal
neurocognitive development.
-------------------------------------------------Guidelines recommend TSH & total T4 levels
be monitored throughout pregnancy because
standard free T4 levels are not as accurate.
Total T4 should be kept at 1.5 times the
normal range, & TSH should be kept in the
lower range of normal during pregnancy.
This may require an increase in levothyroxine
of 35 to 50% as early as the first trimester.
-------------------------------------------------Because a fetus depends on maternal thyroid
hormone for the first 10 to 12 weeks of
gestation, thyroid levels of pregnant women
with hypothyroidism should be monitored.
-------------------------------------------------Manage hypothyroidism during pregnancy by
monitoring TSH & total T4.
-------------------------------------------------Limited laboratory testing is required in the
evaluation of a thyroid nodule.

Beyond a routine CBC & serum chemistry


panel, serum TSH level should be measured to
guide evaluation (autonomously functioning
nodules & multinodular goiters that suppress
TSH levels are rarely malignant).
Measurement of serum free T4 level is also
reasonable if patients have thyroid-related
symptoms but unnecessary in asymptomatic
patients with a normal TSH.
-------------------------------------------------Thyroid scan & radioactive iodine uptake
(RIU) test are appropriate in the context of a
suppressed serum TSH level because a toxic
nodule or multinodular goiter may be present.
Because such hyperfunctional nodules rarely
harbor cancer (<1%), their evaluation &
management are far different.
-------------------------------------------------FNA biopsy for any nodule > 1 cm diameter,
& biopsy of smaller nodules should be
considered in patients with cancer risk factors.
-------------------------------------------------Factors a/w cancer risk for a thyroid nodule
include extremes of age (<20 or >60), males,
history of head or neck irradiation, family history
of thyroid cancer (medullary thyroid cancer),
nodule size > 1 cm, rapid nodule growth, &
hoarseness.
Fine-needle aspiration is a simple method of
determining the presence of malignancy.
-------------------------------------------------Thyroglobulin, a glycoprotein integral in
follicular storage of thyroid hormone, detected
in serum, can be elevated in hyperthyroidism
& destructive thyroiditis.
-------------------------------------------------Thyroglobulin is an effective tumor marker
in patients with papillary or follicular thyroid
cancer after thyroidectomy & radioactive
iodine ablation, because normal thyroid
release of thyroglobulin should no longer be
present.
--------------------------------------------------

Intake of exogenous thyroid hormone


suppresses thyroglobulin levels, which
makes its measurement useful in patients with
thyrotoxicosis due to surreptitious use of
thyroid hormone.
-------------------------------------------------Radioactive iodine uptake (RAIU) test
measures thyroid gland iodine uptake over a
timed period, 24 hours.
Patients with thyrotoxicosis have an above- or
high-normal RAIU, which is inappropriate in
the context of a suppressed TSH level.
Patients with thyroiditis or exposure to
exogenous thyroid hormone, RAIU will be
below normal (<5% at 24 hours).
-------------------------------------------------Hashimoto disease is the most common cause
of hypothyroidism; confirming diagnosis with
TPO antibody measurement is not necessary.
Measurement of TPO antibody levels may be
helpful in subclinical hypothyroidism
(elevated TSH level but normal free T4).
In these patients, increased TPO antibody
titers confer an increased risk of
hypothyroidism, which escalates as TSH
levels rise above the reference range.
-------------------------------------------------Treat hyperlipidemia in a patient with a
history of stroke or TIA with a statin.
History of stroke or TIA is considered to be a
coronary artery-equivalent disease.
LDL-cholesterol goal is < 100 mg/dL to
reduce the risk for future coronary events.
Reduction of BP & treatment with a statin
may prevent recurrent stroke in patients with
no evidence of HTN or hyperlipidemia based
upon current thresholds for treatment.
-------------------------------------------------Niacin modestly lowers LDL-cholesterol
levels & increase HDLs but often not
tolerated because of its adverse effects
(nausea & flushing), particularly at the

dosage needed to achieve adequate reduction


of the LDL-cholesterol level.
Niacin would be a poor choice for diabetics
because it can cause glucose intolerance,
potentially worsening glucose control.
------------------------------------------------Ezetimibe reduces LDL-cholesterol levels by
reducing cholesterol absorption from the
intestine; there are no clinical trials showing
that this medication reduces cardiovascular
disease events.
Ezetimibe should be reserved as an adjunct to
other cholesterol-lowering medications if goal
level is not achieved or patients intolerant or
allergic to other proven medications.
-------------------------------------------------Colestipol interrupts bile acid reabsorption &
reduces LDL-cholesterol levels.
Used as second-line with statins because it
acts synergistically to induce LDL receptors.
However, colestipol can interfere with the
absorption of other medications; for this
reason, is not the best initial management.
-------------------------------------------------Diabetes is a CAD equivalent risk factor, &
diabetics have the same LDL-cholesterol goal
as patients who had an MI; below 100 mg/dL.
-------------------------------------------------Statin is first-line for cholesterol reduction
A 40-mg daily dose of simvastatin would
likely reduce LDL-cholesterol level by 30%.
-------------------------------------------------Statin therapy is appropriate for a patient
with no risk factors if LDL-cholesterol level
is above 190 mg/dL & optional if LDL level
is between 160 - 190 mg/dL.
-------------------------------------------------Fibrate therapy is indicated for
hypertriglyceridemia (>200 mg/dL) in the
setting of elevated non-HDL-cholesterol levels
-------------------------------------------------Hyperlipidemia is defined as total cholesterol
level above 200 mg/dL.

1.
2.
3.
4.
5.

LDL-cholesterol goal depends on the


presence/absence of major cardiovascular risk
factors:
cigarette smoking,
HTN,
older age (men 45 years; women 55 years),
low HDL-cholesterol level (<40 mg/dL),
family history of CAD (first degree male
relative <55 years; female relative <65 years).
-------------------------------------------------In patients with zero or one risk factor, the
LDL-cholesterol goal is below 160 mg/dL.
-------------------------------------------------The non-HDL cholesterol goal is calculated
as 30 mg/dL above the LDL cholesterol goal.
-------------------------------------------------Fibrate therapy would be indicated if the
patient had a coronary heart disease equivalent
such as diabetes or PVD, because fibrates in
this setting results in reduced mortality.
-------------------------------------------------In evaluating & managing low HDL cholesterol,
the primary target of therapy is LDL cholesterol
After LDL cholesterol has been managed,
non-HDL cholesterol is a secondary target
in patients with elevated triglycerides.
-------------------------------------------------Patients in whom the HDL cholesterol remains
low despite use of statins or fibrates to treat
high LDL or non-HDL cholesterol, or patients
with isolated low HDL cholesterol, the first
management step is lifestyle interventions
(exercise, tobacco cessation, weight
management).
-------------------------------------------------Manage isolated low HDL cholesterol with
therapeutic lifestyle changes.
-------------------------------------------------Hypothyroidism is a/w elevated lipid levels
& can cause secondary hyperlipidemias.
Hypothyroidism is not directly a/w formation
of xanthomas & usually does not result in

lipid levels high enough to cause xanthomas.


-------------------------------------------------Xanthomas are skin conditions a/w primary
(genetic defects) or secondary hyperlipidemias
Xanthomas are yellow, orange, reddish, or
yellow-brown papules, plaques, or nodules. If
infiltration is deep, the xanthoma may be
nodular with normal-appearing overlying skin.
Xanthelasma is a type of eyelid xanthoma
characterized by soft, nontender, nonpruritic
plaques; can occur without hyperlipidemia, but
is often a/w familial dyslipidemias.
-------------------------------------------------The type of xanthoma correlates with the type
of lipoprotein that is elevated.
Eruptive xanthomas present as clusters of
erythematous papules on extensor surfaces;
a/w extremely high (> 3000 mg/dL) serum
triglyceride levels; regresses with treatment.
Plane xanthomas are yellow-to-red plaques
found in skin folds of the neck & trunk. They
can be a/w familial dyslipidemias &
hematologic malignancies.
Tendon xanthomas are subcutaneous nodules
occurring on the extensor tendons; a/w
familial hypercholesterolemia.
-------------------------------------------------Ketoacidosis can develop in insulin-deficient
diabetes mellitus patients with only moderate
plasma glucose elevations.
Insulin drip is the most effective treatment of
DKA.
-------------------------------------------------IV insulin infusion is the method of insulin in
an emergency because dehydration may be
severe (which decreases subcutaneous
absorption) & for rapid titration of insulin.
Plasma glucose level should be measured
every 1 to 2 hours & adjustments made to the
insulin infusion, as required, to gradually
normalize glucose levels & reverse the
ketoacidosis.

After the metabolic abnormalities have been


corrected & transfer to subcutaneous insulin
(when the patient starts eating).
IV & subcutaneous insulin need to be
overlapped to avoid rebound ketoacidosis.
Short-acting or rapid-acting insulins should be
given for 1 to 2 hours, or intermediate or longacting insulins for 2 to 3 hours before
terminating the insulin infusion to ensure
adequate overlap.
-------------------------------------------------Treat hyperglycemic hyperosmolar syndrome
with intravenous fluids.
-------------------------------------------------Hyperglycemic hyperosmolar syndrome
diagnostic criteria: plasma glucose > 600 mg/dL,
arterial pH >7.30, serum bicarbonate >15 mg/dL,
serum osmolality > 320 mosm/kg H2O, &
absent urine or serum ketones.
Patients usually have a precipitating factor
(severe infection, MI, new kidney insufficiency)
Management involves identifying the
precipitating illness & restoring a markedly
contracted plasma volume.
Normal saline, which is comparatively
hypotonic in such patients, is chosen first to
replenish the extracellular space.
If the patient is hypotensive, fluids should be
administered as rapidly as tolerated to restore
plasma (intravascular) volume.
When BP is restored & urine output is
established, administration rates should be
slowed & hypotonic solutions should be given.
Total body water deficit can be calculated;
with the goal of replacing one-half the deficit
during the first 24 hours & the remainder
during the next 2 to 3 days.
-------------------------------------------------Potassium should be monitored because
potassium level may fall as urine output is
restored & kidney function improves.
Potassium is shifted intracellularly by
insulin therapy.

Potassium should not be administered until


urine output is verified, because these
patients are prone to acute kidney injury.
-------------------------------------------------Insulin reduces glucose levels but should be
administered only after expansion of the
intravascular space has begun.
If given earlier, movement of glucose into cells
can further reduce circulating volume, which
threatens cerebral, kidney, & coronary perfusion.
-------------------------------------------------Patients with DKA will report a several-day
history of polyuria, polydipsia, & blurred vision,
culminating in nausea, vomiting, abdominal
pain, dyspnea, & altered mental status.
Physical exam reveals deep, labored breathing
(Kussmaul respirations), fruity odor to the
breath (acetone), poor skin turgor, tachycardia,
& hypotension.
This complication can occur as a result of
precipitating acute stresses such as infections
(influenza, pneumonia, or gastroenteritis) or
acute MI; patients with insulin pumps, when a
technical interruption of insulin infusion occurs;
& nonadherence to their medication regimen.
-------------------------------------------------Diagnosis of DKA is based on a blood glucose
> 250 mg/dL, anion gap metabolic acidosis
(arterial pH <7.30), serum carbon dioxide
level < 15 meq/L, & positive serum or urine
ketone concentrations.
-------------------------------------------------Tests to establish the diagnosis of DKA are
serum glucose, electrolytes, ketones & ABG.
-------------------------------------------------Current choices of long- or intermediateacting basal insulins include insulin glargine,
insulin detemir, & neutral protamine
Hagedorn (NPH) insulin.
Optimal basal insulin should be peakless &
24-hour duration of action.
Both insulin glargine &, to a lesser extent,
insulin detemir meet these requirements.

NPH insulin usually administered twice daily


because its duration of action typically extends
only 12 to 18 hours with a peak of activity at
4 to 8 hours, which can precipitate
hypoglycemic episodes.
-------------------------------------------------Regular insulin has a 6 to 8 hours duration of
action; not an optimal preprandial product.
-------------------------------------------------Rapid-acting insulin analogues lispro, aspart,
& glulisine.
An ideal prandial insulin has a brisk peak &
a short overall duration of action to properly
cover postprandial glucose excursions.
-------------------------------------------------Diabetic retinopathy is a microvascular
complication of type 1 diabetes mellitus &
leading cause of visual loss in adults.
Diabetic retinopathy is classified as
o nonproliferative (hard exudates,
microaneurysms, & minor hemorrhages),
& not a/w visual decline
o proliferative ("cotton-wool spots" &
neovascularization), a/w vision loss.
Changes in retinal blood flow occur after
several years, causing retinal ischemia, which
in turn promotes growth factors that stimulate
proliferation of new blood vessels. This
process leads to scarring & fibrosis.
Fibrous tissue puts traction on the retina,
causing retinal detachment & vision loss.
New vessels can also become more permeable
& leak serum, which causes macular edema.
Tight glycemic control has been shown to
decrease incidence & progression of retinopathy
BP reduction appears to exert as great a
benefit on retinopathy as glycemic control.
-------------------------------------------------Laser photocoagulation of the retina can help
preserve vision in patients with proliferative
diabetic retinopathy &/or macular edema.
--------------------------------------------------

Recent guidelines recommend attempting to


improve glycemic control in all hospitalized
patients (140 to 200 mg/dL).
-------------------------------------------------Basal-bolus insulin regimen consisting of a
long-acting insulin & rapid-acting insulin
analogue before meals is recommended for
hospitalized patients with uncontrolled diabetes.
This allows for an easily titratable regimen &
conveniently held during diagnostic testing or
procedures when nutritional intake is interrupted.
Sliding scale regular insulin is a/w increased
hyperglycemic & hypoglycemic excursions &
results in inferior glycemic control compared
with a basal-bolus correction regimen in
hospitalized patients.
-------------------------------------------------Metformin is the first-line for type 2 diabetes
mellitus because of its low cost, effectiveness,
good tolerability, safety, favorable effects on
body weight, & absence of hypoglycemia.
Metformin is contraindicated in patients with
renal insufficiency (creatinine level >1.5 mg/dL
for men, >1.4 mg/dL for women).
-------------------------------------------------Pioglitazone is available for monotherapy, but
side effects of weight gain, edema, increased
peripheral bone fracture rates in women, &
high cost make it less attractive than
metformin as a first-line therapy.
-------------------------------------------------Glimepiride (sulfonylurea) is a/w weight gain
& risk of hypoglycemia.
-------------------------------------------------Exenatide (GLP-1 agonist, incretin mimetic)
is an injectable agent.
Only approved in combination regimens with
oral agents & inappropriate as monotherapy.
-------------------------------------------------Diabetes mellitus is categorized as type 1,
type 2, gestational, or secondary.
--------------------------------------------------

Type 1 diabetes, usually has an acute or


subacute onset, is characterized by polyuria,
polydipsia, polyphagia/hyperhagia, ketonemia
or ketonuria, & weight loss.
-------------------------------------------------Secondary diabetes mellitus consists of a
group of unrelated conditions a/w
hyperglycemia through effects on either
insulin availability or insulin sensitivity.
Includes various endocrine disorders, such as
Cushing syndrome & acromegaly; pancreatic
conditions, acute & chronic pancreatitis &
pancreatic cancer; drug-induced hyperglycemia;
& several genetic syndromes.
This patient has a history of alcohol abuse,
history of recurrent pancreatitis, & pancreatic
calcifications on abdominal CT, which
collectively confirm chronic pancreatitis.
-------------------------------------------------Some older patients previously diagnosed with
type 2 diabetes mellitus have autoimmune
beta-cell destruction, a more gradually
progressive nature (latent autoimmune
diabetes of adulthood).
-------------------------------------------------Impaired fasting glucose, impaired glucose
tolerance, or both mark the transition from
normal glucose tolerance to type 2 diabetes.
Impaired fasting glucose is diagnosed when
fasting plasma glucose is 100 to 125 mg/dL.
Impaired glucose tolerance (analogous
prediabetic state) is diagnosed when the
plasma glucose at the 2-hour mark of an
OGTT is 140 to 199 mg/dL
-------------------------------------------------Diet & exercise is the recommended approach
for either impaired fasting glucose or impaired
glucose tolerance; the prediabetic states.
Relative risk reduction (RRR) in incidence
of diabetes with IGT a/w intensive lifestyle
change is 58%.
-------------------------------------------------

Metformin is a/w an RRR of 31%, which is


inferior to the 58% RRR with diet & exercise.
Metformin may be considered in patients with
both IFG & IGT, who constitute a higher risk
Acarbose therapy resulted in only a 25% RRR.
.-------------------------------------------------Rosiglitazone & pioglitazone have been a/w
62% & 81% RRRs, respectively, in the
incidence of diabetes.
These agents are not endorsed for routine use
in patients with prediabetes because of their
costs & adverse effects, including edema,
increased fracture risk in women, & possible
increased cardiovascular morbidity.
-------------------------------------------------Type 2 diabetes mellitus criteria
o fasting plasma glucose > 126 mg/dL
o random plasma glucose > 200 mg/dL
o plasma glucose level > 200 mg/dL after a
2-hour oral GTT
o OR venous hemoglobin A1c > 6.5%
-------------------------------------------------Metabolic syndrome criteria
o BP 130/85 mm Hg
o lipid levels
triglyceride level 150 mg/dL
HDL-cholesterol <40 mg/dL in men
o fasting plasma glucose level 110 mg/dL
o waist circumference (>40 in [>102 cm] in
men)
--------------------------------------------------

III. Gastroenterology & Hepatology

Disease involving the small intestine often


cause non-bloody diarrhea; hematochezia is
more likely when the colon is involved.
-------------------------------------------------Crohn disease presents with abdominal pain,
diarrhea, & weight loss.
Endoscopic exam may show aphthous ulcers
or large ulcers that can coalesce & cause a
"cobblestone" appearance.
-------------------------------------------------Ulcerative colitis is often characterized by
bloody diarrhea a/w rectal discomfort.
Fever, weight loss, tachycardia, dehydration,
& significant abdominal tenderness or rebound
indicates severe disease.
Endoscopic findings can be subtle, showing
mucosal edema & erythema; inflammation
causes friability, ulceration, & bleeding.
-------------------------------------------------Two types of microscopic colitis.
Average age of onset for collagenous colitis is
in the sixth decade & tends to affect women.
Average age of onset for lymphocytic colitis
is the seventh decade, & affects women more.
-------------------------------------------------Microscopic colitis is characterized by
chronic watery diarrhea without bleeding.
Colonoscopy shows normal mucosa
macroscopically; histology shows either
increased intraepithelial lymphocytes
(lymphocytic colitis) or increased submucosal
collagen layer (collagenous colitis).
Loperamide, diphenoxylate, & bismuth
subsalicylate, alone or combination, are
effective as initial therapy.
-------------------------------------------------First-line therapy for induction & maintenance
of remission in moderate ulcerative colitis is
mesalamine or another 5-aminosalicylates.
--------------------------------------------------

Oral prednisone is used when UC symptoms


do not respond to 5-aminosalicylates.
-------------------------------------------------Topical therapy is appropriate for distal
ulcerative colitis; includes cortisone foam &
mesalamine or corticosteroid suppositories
for proctitis & hydrocortisone or mesalamine
enemas for left-sided colitis.
Oral 5-aminosalicylates, including
sulfasalazine, mesalamine, balsalazide, &
olsalazine, are appropriate for distal disease
that does not respond to topical therapy or for
mild to moderate pancolitis.
-------------------------------------------------Azathioprine (AZA) or 6-mercaptopurine
(6-MP) may be used for incomplete disease
remission while on corticosteroids.
Both agents have delayed onset of action,
concomitant use with a 3- to 4-month course
of prednisone is often necessary.
-------------------------------------------------Infliximab is a TNF inhibitor; patients with
severe ulcerative colitis or do not respond to
corticosteroid therapy for remission.
Not appropriate as first-line.
-------------------------------------------------Ischemic colitis has a more acute course &
spares the rectum because of dual blood
supply & a/w other evidence of
atherosclerotic vascular disease.
-------------------------------------------------Bleeding is less common with Crohn colitis;
endoscopic inflammatory changes are patchy
& spares the rectum but can extend through
the entire GI tract.
-------------------------------------------------Mild to moderate left-sided ulcerative colitis
His ex-smoking status, microcytic anemia, &
presence of arthritis, which is the most
common extraintestinal manifestation of
inflammatory bowel disease.
Ulcerative colitis typically involves the
rectum & extends proximally with contiguous

inflammation that is limited to the mucosa


of the colon & rectum.
Patients present with bloody diarrhea a/w
rectal discomfort, fecal urgency, & cramps.
Those with proctitis can present with
constipation.
-------------------------------------------------Rheumatoid nodules are found in the
subcutaneous tissue just distal to the elbow
on the extensor surface of the forearm.
Nodules also may be found on the extensor
surface of the hand & Achilles tendons.
-------------------------------------------------Pyoderma gangrenosum occurs in 10% of
ulcerative colitis.
Pyoderma gangrenosum is an uncommon,
neutrophilic, ulcerative skin disease.
Lesions tend to be multiple & appear on the
lower extremities.
They begin as tender papules, pustules, or
vesicles that spontaneously ulcerate &
progress to painful ulcers with a purulent base
& undermined, ragged, violaceous borders.
-------------------------------------------------Dermatitis herpetiformis is characterized by
grouped, pruritic, erythematous papulovesicles
on the extensor surfaces of the arms, legs,
central back, buttocks, & scalp.
A genetic predisposition is linked to the same
genes a/w celiac disease.
-------------------------------------------------Extraintestinal manifestations occur in 10 to
20% with inflammatory bowel disease.
Erythema nodosum occurs commonly in
Crohn disease, manifests as small, exquisitely
tender nodules on the anterior tibial surface,
is the most common cutaneous manifestation.
Erythema nodosum presents as sudden onset
of one or more tender, erythematous nodules
on the anterior legs that are easily palpated
than visualized. A residual ecchymotic
appearance is common as the lesions age.

The eruption is preceded by a prodrome of


fever, malaise, & arthralgia.
Treating the underlying bowel disease usually
results in remission of erythema nodosum.
-------------------------------------------------Hepatorenal syndrome = development of
kidney failure in patients with portal HTN &
normal renal tubular function.
Intense renal vasoconstriction leads to an
acute kidney dysfunction characterized by
increased renal sodium avidity, relatively
normal urine sediment, & oliguria.
Spontaneous bacterial peritonitis, vigorous
diuretic therapy, paracentesis without volume
expansion, & GI bleeding may precipitate
hepatorenal syndrome.
Diagnosis is based on exclusion of other causes
of acute kidney injury such as prerenal azotemia,
renal parenchymal disease, or obstruction.
The most effective treatment for hepatorenal
syndrome is liver transplantation.
-------------------------------------------------First-line therapy for hepatic encephalopathy
is lactulose.
-------------------------------------------------Management for hepatic encephalopathy is
to treat the infection, discontinue diuretics &
increase the lactulose therapy.
Lactulose dose should be titrated to achieve
2-3 soft stools per day with a pH below 6.0.
-------------------------------------------------Severe encephalopathy manifests as
worsening somnolence; progressing from subtle
findings, such as mild mental status changes or
reversal of the sleep-wake cycle, to irritability,
confusion, slurred speech, & ultimately coma.
There can be multiple inciting causes of
encephalopathy in patients with cirrhosis,
including dehydration, diet indiscretions,
infection (spontaneous bacterial peritonitis),
GI bleeding, & medications. This patient
likely worsened with development of the UTI.
--------------------------------------------------

Ascites is the most common complication of


portal HTN secondary to cirrhosis.
Any patient with new-onset ascites should
undergo diagnostic paracentesis.
Initial evaluation of ascitic fluid should
include measurement of albumin & cell count
with differential, Gram stain, & culture.
The serum-to-ascites albumin gradient
(SAAG) is calculated by subtracting the ascitic
fluid albumin level from serum albumin level.
SAAG gradient greater than 1.1 g/dL
indicates portal hypertension.
-------------------------------------------------A gradient of < 1.1 g/dL is not a/w portal HTN
but ascites can be caused by other mechanisms,
including infection, inflammation, or low serum
oncotic pressure, such as nephrotic syndrome,
malignancy, or tuberculosis.
Ascites, elevated aminotransferase & bilirubin
suggest portal HTN caused by cirrhosis.
-------------------------------------------------Other causes of portal HTN, include
constrictive pericarditis, right-sided heart
failure, & Budd-Chiari syndrome.
-------------------------------------------------Primary biliary cirrhosis is a slowly
progressive autoimmune disease that affects
women older than 25 years.
Pruritus predates the development of jaundice,
& often a/w other immune disorders
(hypothyroidism, Sjogrenor sicca syndrome, &
scleroderma)
Antimitochondrial antibodies in 95% of cases
-------------------------------------------------Primary sclerosing cholangitis is strongly a/w
ulcerative colitis & marked elevations of
alkaline phosphatase.
-------------------------------------------------Cholestatic liver disease is characterized by
elevations of alkaline phosphatase & modest
aminotransferase elevations. The most likely
diagnosis is primary sclerosing cholangitis.

The most common symptoms of primary


sclerosing cholangitis are pruritus & fatigue;
as the disease progresses, patients develop
jaundice.
-------------------------------------------------Primary sclerosing cholangitis is a chronic
condition that presents in the fourth or fifth
decade of life; more common in men &
characterized by progressive bile duct
inflammation, destruction &, ultimately,
fibrosis of intrahepatic & extrahepatic bile
ducts, leading to cirrhosis.
Strong association with ulcerative colitis.
Severity of ulcerative colitis does not correlate
with severity of primary sclerosing cholangitis
Treatment of ulcerative colitis does not affect
the prognosis of cholangitis.
-------------------------------------------------Alcohol consumption in sufficient quantity to
cause cirrhosis (> 6 drinks per day for men &
> 3 per day for women for 10 years)
-------------------------------------------------Nonalcoholic steatohepatitis (NASH) is a/w
obesity, type 2 diabetes, & hyperlipidemia &
potential cause of cirrhosis.
-------------------------------------------------Nonalcoholic fatty liver disease (NAFLD)
consists of fat accumulation, inflammation, &
fibrosis in absence of significant alcohol intake.
Fatty liver disease in absence of inflammation
is common in women & 60% of obese patients
Nonalcoholic steatohepatitis (NASH) is a
subcategory of NAFLD defined as presence of
inflammation occurring in 20% of obese
patients of which 2 - 3% develop cirrhosis.
NASH is commonly seen in patients with
underlying consequences of obesity,
including insulin resistance, HTN, &
hyperlipidemia (metabolic syndrome).
NAFLD is diagnosed when patients with
characteristic clinical risk factors are found to
have mildly to moderately elevated serum
aminotransferase concentrations.

Imaging with ultrasonography, CT, or MRI


can confirm the presence of steatosis.
Liver biopsy is sometimes necessary to
establish the diagnosis of NASH.
-------------------------------------------------Hepatitis C virus (HCV) is the most common
bloodborne infection in the US. Although
screening of blood products & reduced
transmission among injection drug users have
resulted in a decreasing number of new cases;
the # of deaths is increasing because of the
"backlog" of chronic infections & long duration
of chronic infection before cirrhosis develops.
Acute hepatitis C is usually asymptomatic &
rarely present clinically; 60 - 85% develop
chronic infection.
-------------------------------------------------Anti-HCV antibody test is the screening test
for at-risk persons; a positive test in a person
with one of the risk factors confirms exposure
HCV RNA test is required to determine active
infection rather than just exposure.
------------------------------------------------The diagnostic "gold standard" for hepatitis C
(HCV) is presence of HCV RNA in serum.
-------------------------------------------------Acute hepatitis A is diagnosed by presence of
IgM antibody to HAV (IgM anti-HAV),
appears at the onset of the acute phase &
undetectable in 3 to 6 months.
IgG anti-HAV becomes positive during the
acute phase but persists for decades, a marker
of immunity to further infection.
Positive IgG anti-HAV titer, but negative titer
for IgM anti-HAV has had hepatitis A in the
remote past or received a hepatitis A vaccine.
-------------------------------------------------Chronic hepatitis B patients have positive
HBV surface antigen & positive IgG antibody
to hepatitis B core antigen; IgM to hepatitis B
core antigen is negative.
--------------------------------------------------

Markedly elevated aminotransferase levels,


positive hepatitis B surface antigen, & IgM
to HBV core antigen establishes the diagnosis
of acute hepatitis B infection.
Greatest risk for exposure to hepatitis B virus
are a history of multiple sexual partners &
injection drug users.
Most patients clear their infection after a few
months. 5% develop acute progressive
hepatitis B with hepatic decompensation &
need urgent liver transplantation.
Patients may have an elevated INR & rising
bilirubin level & encephalopathy, a marker
of fulminant hepatic failure.
-------------------------------------------------Primary biliary cirrhosis is a chronic
progressive cholestatic liver disease of
unknown cause. An autoimmune disorder in
women age 40 60 years.
-------------------------------------------------Primary biliary cirrhosis diagnostic triad
includes a cholestatic liver profile, positive
anti-mitochondrial antibody titers, &
compatible histology on liver biopsy.
Serum alkaline phosphatase level is elevated
10 times or more above normal.
-------------------------------------------------Autoimmune hepatitis commonly occurs in
girls & young women.
Most have other autoimmune disorders &
family history of autoimmunity.
Fatigue is the most common symptom, also
jaundice, anorexia, myalgias, & diarrhea.
Most have hepatomegaly & aminotransferase
concentrations in the thousands (<500 IU at
presentation), elevated bilirubin, near-normal
alkaline phosphatase, &
hypergammaglobulinemia.
Autoimmune serologic tests, anti-smooth
muscle antibodies, ANA, & antibody to
liver/kidney microsome type 1 (anti-LKM1),
may be positive.
--------------------------------------------------

Characteristic findings of alcoholic hepatitis


in chronic alcohol abuse: history of recent
heavy alcohol use, elevated serum AST & ALT
values (usually < 500 U/L & frequently < 300
U/L), AST to ALT ratio > 2 to 1, elevated
alkaline phosphatase, jaundice, coagulopathy,
& encephalopathy.
-------------------------------------------------Patients infected with hepatitis B, HDV
infection may present as an acute hepatitis
(coinfection) or exacerbation of preexisting
chronic hepatitis (superinfection).
A history of injection drug use are at greatest
risk for acquiring HDV infection.
-------------------------------------------------Hepatitis A is almost always self-limited,
although acute hepatitis A may rarely present as
fulminant hepatitis requiring liver transplant.
Clinical course may include a prolonged
cholestatic phase characterized by persistence
of jaundice for up to 6 months.
Treatment of acute hepatitis A is supportive.
Serum immune globulin should be
administered to all household & intimate
contacts within 2 weeks of exposure.
-------------------------------------------------Hepatitis A vaccine should be offered to
travelers who go to underdeveloped countries,
men who have sex with men, injection drug
users, & patients with chronic liver disease.
-------------------------------------------------Acute hepatitis A infection may have clinical
symptoms & findings of acute hepatitis
(fatigue, nausea, vomiting, jaundice,
aminotransferase levels >1000 U/L).
Major routes of transmission are ingestion of
contaminated food or water & contact with an
infected person.
High risk groups include living in or traveling
to underdeveloped countries, children in day
care centers, men who have sex with men, &
people who ingest raw shellfish.

Hepatitis A is the most likely infection in a


traveler to an undeveloped country without
other risk factors.
-------------------------------------------------Chronic hepatitis B in absence of cirrhosis
may develop hepatocellular carcinoma;
should undergo periodic screening.
-------------------------------------------------Hepatocellular carcinoma is the most
common primary intrahepatic tumor & fastest
growing cause of cancer-related death in men.
Common causes of cirrhosis leading to HCC
are chronic hepatitis B & C infections &
alcoholic liver disease.
--------------------------------------------------Fetoprotein is not specific for HCC &
should not be used alone as a screening test.
Combined use of -fetoprotein measurement
& ultrasonography increases the sensitivity
of detection, but risk increased false-positives.
-------------------------------------------------Patients with a compatible ultrasound &
serum -fetoprotein level > 500 ng/mL can
be diagnosed with hepatocellular carcinoma
without a biopsy.
-------------------------------------------------Anal fissure is a tear in the lining of the anal
canal causing painful hematochezia; rectal
outlet bleeding & pain with defecation is
probably due to recent constipation.
-------------------------------------------------Chronic fissures are often accompanied by
external skin tags. Recurrent or nonhealing
fissures should raise concern for underlying
diseases, particularly Crohn disease.
-------------------------------------------------Common causes of acute, severe lower GI
bleeding are colonic diverticula, angiectasia
(angiodysplasia), colitis (inflammatory bowel
disease, infection, ischemia, or radiation), &
colonic neoplasia.
Bleeding from a colonic diverticulum &
vascular ectasia is typically acute & painless.

Ischemic colitis occurs in older individuals


with significant cardiac & peripheral vascular
disease, presents with severe abdominal pain
& occult bleeding.
-------------------------------------------------Blood or coffee-ground-like material on
gastric lavage indicates ongoing or recent
upper GI bleeding; needs upper endoscopy.
Negative nasogastric tube lavage is reliable
in ruling out upper GI bleeding only if the
aspirate contains bile (yellow or green fluid
that tests positive with a urine dipstick),
indicating passage of the tube beyond the
pylorus into the duodenum.
-------------------------------------------------Most likely sources of painless lower GI
bleeding are diverticulosis & vascular ectasia.
-------------------------------------------------Nonselective -blocker is useful in primary &
secondary prevention of variceal bleeding
but not as acute therapy.
-------------------------------------------------Arteriography is not first-line therapy for a
variceal bleed from venous portal HTN; no
intervention should take precedence over
restoration of intravascular volume.
Arteriography is reserved for a presumed
arterial source of bleeding as can be seen in
peptic ulcer disease or tumors along the GI
tract. Arteriography can be used to identify &
embolize the specific vessel involved. This is
reserved for cases of active bleeding & either
endoscopic therapy has failed to stop the
bleeding or presence of active bleeding
interferes with identification of the bleeding
site & the patient is unstable.
-------------------------------------------------Volume restoration is a priority management
intervention for GI bleeding in
hemodynamically unstable patients.
-------------------------------------------------Initial management of acute variceal
hemorrhage is intravascular volume

restoration using a large bore peripheral IV


line or central line.
Packed erythrocytes are used to replace blood
loss & clotting factors are replaced as needed.
Following restoration of intravascular volume,
the patient should undergo urgent
esophagogastroduodenoscopy & band
ligation of esophageal varices.
Band ligation has been shown to be as
effective as sclerotherapy for preventing early
rebleeding. Therapy should also be started to
control bleeding with intravenous octreotide,
which reduces portal venous blood inflow by
inhibiting release of vasodilatory hormones.
-------------------------------------------------Upper endoscopy should be performed at the
time of an upper GI bleed after appropriate
volume resuscitation to diagnose the cause of
bleeding, provide a prognosis, & perform
endoscopic guided therapy if required.
An ulcer with a visible vessel has a 50% risk
of rebleeding if not treated endoscopically.
-------------------------------------------------Intravenous omeprazole has been shown to
reduce the risk of recurrent upper GI bleeding
in peptic ulcers after endoscopic hemostasis.
------------------------------------------------Diverticulosis is a major cause of massive
painless lower GI bleeding in older patients.
-------------------------------------------------Diverticulitis results from obstruction at the
diverticulum neck by fecal matter, leading to
mucus & bacterial overgrowth.
85% of diverticulitis occurs in the sigmoid or
left colon, LLQ pain is the most common
manifestation; also fever & leukocytosis
Overt rectal bleeding is typically not seen.
-------------------------------------------------Most patients with acute mesenteric ischemia
are older than 50. Severe abdominal pain is
invariably present, but early exam findings are
minimal ("pain out of proportion to exam").

Although occult blood-positive stool is


common, overt bleeding is rare. Late signs &
symptoms include nausea, vomiting, fever,
hematemesis, obstruction, back pain, & shock.
-------------------------------------------------Most patients with colonic ischemia are older
than 60 years & present with LLQ pain,
urgent defecation, & red or maroon rectal
bleeding that does not require transfusion.
May have mild tenderness over the involved
segment of colon.
Hypovolemia & peritonitis are rare.
Colonoscopic findings are generally segmental
& include hemorrhagic nodules, linear &
circumferential ulceration, & gangrene.
-------------------------------------------------Colonic ischemia can occur in association
with colonic hypoperfusion in the setting of
aortic or cardiac bypass surgery, prolonged
physical exertion (long-distance running), &
any cardiovascular event accompanied by
hypotension. Medications such as OCPs,
drugs such as cocaine, vasculitides, &
hypercoagulable states are risk factors.
-------------------------------------------------In GI bleeding of obscure origin, repeat
upper endoscopy will identify a bleeding
source in a significant proportion of patients.
-------------------------------------------------Initial endoscopy may miss lesions that are
difficult to see or bleed intermittently.
1/3 - 2/3 of GI bleeding of obscure etiology
are found within reach of upper endoscopy,
which is the next procedure following
nondiagnostic upper & lower endoscopy.
Repeat upper endoscopy is particularly
appealing in a patient with a hiatal hernia
because of the possibility of Cameron lesions.
Cameron lesions are linear gastric ulcers or
erosions in the hiatal hernia sac. Cameron
lesions are an incidental finding, seen in 5% of
hiatal hernias.
--------------------------------------------------

If repeat upper endoscopy is negative, repeat


colonoscopy or capsule endoscopy.
In wireless capsule endoscopy, a patient
swallows a video capsule that, by intestinal
motility, passes through the stomach & into
the small intestine. This procedure has been
shown to detect sources of bleeding in 70% of
patients & considered the test of choice
following upper & lower endoscopy studies.
-------------------------------------------------Double balloon endoscopy may be performed
through an oral or a transanal route.
The role for double balloon endoscopy is to
evaluate or treat findings seen on capsule
endoscopy, for evaluation of ongoing bleeding
when bleeding is brisk enough that the need
for endoscopic hemostasis is expected, & as a
complementary test when a small-bowel
source of bleeding remains a concern despite
a nondiagnostic capsule endoscopy.
-------------------------------------------------Esophageal pH monitoring, consists of
inserting a pH monitor in the distal esophagus
& record results over 24 hours, is the most
accurate means to confirm GERD.
-------------------------------------------------Functional dyspepsia is defined as chronic or
recurrent discomfort in the epigastrium with
no organic cause determined.
A patient with dyspepsia who is taking
NSAIDs & no concerning alarm features,
stopping the NSAID is appropriate.
NSAIDs are most frequently a/w dyspepsia. If
stopping or changing the NSAID is not a
viable option, initiation of a PPI is warranted.
-------------------------------------------------Upper endoscopy is necessary to rule out
organic causes, & only after this is performed
can the diagnosis of functional dyspepsia be
distinguished from organic dyspepsia (peptic
ulcer disease, reflux esophagitis, malignancy).

An empiric trial of a PPI is indicated for ulcerlike functional dyspepsia.


-------------------------------------------------Alarm features such as unexplained iron
deficiency anemia, unintentional weight loss,
dysphagia, odynophagia, palpable abdominal
masses, or jaundice would necessitate an
urgent upper endoscopy.
Because the incidence of malignancy is
significantly greater in patients older than 55,
upper endoscopy is indicated in any patient
older than 55 years with new-onset dyspepsia
even without alarm features.
-------------------------------------------------Malignancy always needs to be considered in
a patient with a gastric ulcer; therefore,
biopsies of the ulcer & follow-up endoscopy
to ensure ulcer healing.
However, a duodenal ulcer is less likely to
represent a malignancy, & biopsy of the ulcer
or follow-up endoscopy is not needed.
-------------------------------------------------Measure serum gastrin for suspicion of an
acid hypersecretion state, such as gastrinoma
(Zollinger-Ellison syndrome); features include
multiple peptic ulcers, ulcers in unusual
locations, severe esophagitis, or fat
malabsorption.
-------------------------------------------------Common causes of peptic ulcer disease are
NSAIDs & H. pylori infection; > 90% of cases.
-------------------------------------------------Testing for H. pylori is indicated in patients
with active peptic ulcer disease (duodenal or
gastric) or history of PUD who have not been
previously treated for H. pylori.
Biopsy with histologic assessment & rapid
urease test are commonly used endoscopic tests.
Sensitivity of the rapid urease test can be
reduced by 25% in patients who have taken a
PPI (omeprazole) within 2 weeks, or bismuth
or antibiotics within 4 weeks of endoscopy;
therefore, biopsy with histologic evaluation for

evidence of H. pylori infection is the


endoscopic test of choice for this patient.
Sensitivity of urea breath testing, like that of
the rapid urease test, is reduced by drugs that
affect urease production such as a PPI.
-------------------------------------------------Peptic ulcer disease treatment is guided by
biopsy & presence of H. pylori infection.
Presence of documented H. pylori infection,
triple therapy consist of a PPI, amoxicillin,
& clarithromycin as the initial treatment.
Triple therapy is not indicated in the absence
of documented infection.
-------------------------------------------------Biopsies of all gastric ulcers should be
performed; even small, benign-appearing
gastric ulcers may harbor malignancy.
In benign ulcers, biopsies can also provide
evidence for the presence of H. pylori
infection & guide appropriate therapy.
-------------------------------------------------Management of GERD, including patients
with erosive esophagitis, is PPI therapy.
-------------------------------------------------Sucralfate (aluminum sucrose sulfate) is a
topical therapy for PUD & GERD.
Sucralfate adheres to the mucosal surface &
promotes healing by an unknown mechanism.
Sucralfate is as effective as a H2 receptor
antagonist for the treatment of GERD &
nonerosive esophagitis but less effective than
a PPI & no role in treating erosive esophatitis.
-------------------------------------------------A promotility agent such as metoclopramide
can theoretically be beneficial in the treatment
of GERD by increasing LES pressure,
enhancing gastric emptying, or improving
peristalsis. However, promotility agents have
significant EPS side effects & FDA has
imposed a black box warning.
-------------------------------------------------Treat erosive esophagitis with a PPI.
--------------------------------------------------

Ambulatory esophageal pH monitoring is


the gold standard for diagnosing GERD &
used in patients in whom the diagnosis is
uncertain or unresponsive to empiric therapy.
-------------------------------------------------Response to empiric treatment with a PPI such
as omeprazole is sufficiently sensitive &
specific to diagnose GERD; however, this
patient also has alarm symptom of dysphagia.
Upper endoscopy should be performed to
evaluate for acid-induced esophageal stricture
& esophageal carcinoma.
-------------------------------------------------In patients with GERD & alarm symptoms,
upper endoscopy is indicated.
-------------------------------------------------Imipenem is only helpful in acute pancreatitis
with evidence of pancreatic necrosis.
Diagnosis with contrast-enhanced CT scan
shows non-enhancing pancreatic tissue.
Patients with non-infected pancreatic necrosis,
antibiotics may decrease the incidence of
sepsis, systemic complications (respiratory
failure), & local complications (infected
pancreatic necrosis or pancreatic abscess).
There is no benefit from antibiotic use in acute
pancreatitis without pancreatic necrosis, &
such treatment may lead to nosocomial
infections with resistant pathogens.
-------------------------------------------------Two routes for nutrition in patients with
severe acute pancreatitis: enteral nutrition &
parenteral nutrition.
o Enteral nutrition is provided through a
feeding tube, past the ligament of Treitz
so as not to stimulate the pancreas.
o Parenteral nutrition is provided through
a large peripheral or central IV line.
Enteral nutrition is preferred over parenteral
nutrition because of lower complication rates;
lower incidence of infections, reduced surgical
interventions to control complications of

pancreatitis, & reduced length of hospital stay.


-------------------------------------------------Autoimmune pancreatitis is a type of chronic
pancreatitis. Findings include
hypergammaglobulinemia, diffuse pancreatic
enlargement, mass lesion in the pancreas,
irregular main pancreatic duct, & presence of
autoantibodies such as ANA.
-------------------------------------------------Serum triglyceride level exceeding 1000 mg/dL
may develop hypertriglyceridemic
pancreatitis.
-------------------------------------------------Classic presentation of acute pancreatitis is
acute onset epigastric abdominal pain, nausea,
& vomiting a/w markedly elevated pancreatic
enzymes.
80% of acute pancreatitis cases are due to
gallstones & alcohol abuse.
Presence of stones in the gallbladder, a dilated
bile duct, & elevated aminotransferase suggest
gallstones as the cause of pancreatitis.
Scleral icterus, jaundice, & elevated bilirubin
level suggest continuing bile duct obstruction.
Abdominal ultrasound has a sensitivity of only
50% to 75% for choledocholithiasis
A common duct stone should be suspected in
the correct clinical situation even when
ultrasonography does not show a stone.
-------------------------------------------------ERCP with sphincterotomy & stone extraction
is the treatment of choice for gallstone
pancreatitis.
-------------------------------------------------Acute pancreatitis presents with sudden onset
epigastric pain, often radiates to the back,
accompanied by nausea, vomiting, fever, &
tachycardia. Physical exam shows epigastric
tenderness, abdominal distension, hypoactive
bowel sounds, & occasional guarding.
The diagnosis is confirmed by lab results
showing serum amylase & lipase levels at
least three times the upper limit of normal.

Abdominal ultrasonography should be used


to detect cholelithiasis in patients with
suspected gallstone pancreatitis.
ERCP is recommended in patients with
evidence of gallstone pancreatitis & suspected
biliary obstruction.
Biliary obstruction is suspected if
cholelithiasis or choledocholithiasis is present,
bile ducts are dilated, & liver enzymes elevated.
Aminotransferase concentrations rise initially
in gallstone pancreatitis, with subsequent rise
of alkaline phosphatase & bilirubin if
obstruction persists.
ERCP with sphincterotomy has been shown
to lower morbidity & mortality, significantly
reducing rates of cholangitis & biliary sepsis.
-------------------------------------------------MRCP is used to evaluate biliary obstruction
if ultrasonography is nondiagnostic.
In a patient with choledocholithiasis
identified by ultrasonography, MRCP is
unlikely to provide additional diagnostic
information & cannot be used therapeutically
to remove the obstructing stone.
-------------------------------------------------Acute cholecystitis presents with RUQ pain &
gallstones, but bilirubin level is usually not
greater than 2 mg/dL, & normal
aminotransferase levels.
-------------------------------------------------Classic acute cholangitis diagnosis is based
upon the presence of Charcot triad (fever,
jaundice, & RUQ abdominal pain).
Bile duct dilation, with stones in the
gallbladder, suggests acute cholangitis due to
choledocholithiasis.
Broad-spectrum antibiotics to cover aerobic
& anaerobic gram-negative bacilli &
enterococci should be started immediately.
Endoscopic retrograde
cholangiopancreatography (ERCP) with
sphincterotomy should be performed to

remove impacted stones.


-------------------------------------------------Acute cholangitis is a/w biliary obstruction &
the subsequent suppurative infection within
the biliary tree.
Obstruction is most often due to gallstones.
-------------------------------------------------Acute cholecystitis presents with biliary colic,
including pain radiating to the right shoulder,
Murphy sign, fever, leukocytosis, mild
bilirubin & aminotransferase elevation,
gallstones & pericholecystic fluid, &
thickening of the gallbladder wall (>3mm).
When ultrasoound reveals gallstones &
positive ultrasonographic Murphy sign,
positive predictive value for acute
cholecystitis is 92%.
-------------------------------------------------Patients with acute hepatitis have a marked
elevation of aminotransferases, whereas
patients with primary sclerosing cholangitis
have a cholestatic pattern (primary elevation
of bilirubin & alkaline phosphatase).
-------------------------------------------------Acute hepatitis presents with fatigue, nausea,
mild upper abdominal pain, & jaundice. Serum
AST & ALT values are greater than 500 U/L.
-------------------------------------------------Gilbert syndrome is a common disorder a/w
indirect hyperbilirubinemia. Patients have a
serum total bilirubin < 3.0 mg/dL & serum
direct bilirubin level < or equal to 0.3 mg/dL.
A presumptive diagnosis can be made in an
otherwise healthy patient who has indirect
hyperbilirubinemia, normal liver enzymes, &
normal hemoglobin concentration (which
excludes hemolysis).
-------------------------------------------------Primary sclerosing cholangitis is a chronic
cholestatic liver disease a/w inflammatory
bowel disease (common in ulcerative colitis),
characterized by fibrosis, inflammation, &
stricturing of the biliary tree.

Cholestatic liver diseases primarily cause


elevation of serum alkaline phosphatase values
& minor elevations of aminotransferase levels.
Most are asymptomatic with abnormal liver
biochemistry tests, but jaundice & pruritus can
occur with advanced disease.
Diagnosis is made by ERCP, which is useful in
advanced disease to rule out cholangiocarcinoma
& stents can be placed if there is a dominant
stricture.
-------------------------------------------------Cholecystectomy provides definitive therapy
for symptomatic gallstone disease.
Although ursodeoxycholic acid may decrease
the risk for future stone formation, it is less
effective than cholecystectomy in patients with
existing stones, & its use is limited to patients
who are unable to undergo surgery.
-------------------------------------------------ERCP with sphincterotomy is indicated for
patients with biliary obstruction due to
choledocholithiasis.
-------------------------------------------------Incidental finding of indirect (unconjugated)
hyperbilirubinemia in an asymptomatic patient
with a normal hemoglobin level & normal
liver tests is indicative of Gilbert syndrome.
No additional diagnostics or therapy is required.
-------------------------------------------------Patients with hemolysis significant enough to
cause unconjugated hyperbilirubinemia
generally have a low hemoglobin level &
abnormal MCV (low) & RDW (high).
-------------------------------------------------Cholestasis due to oral contraceptives will
cause conjugated (direct) hyperbilirubinemia
& elevated serum alkaline phosphatase.
-------------------------------------------------Predominance of unconjugated bilirubin
indicates either overproduction of bilirubin
(hemolysis) or impaired conjugation.
Gilbert syndrome is a benign syndrome, also
known as constitutional hepatic dysfunction

& familial nonhemolytic jaundice, is


characterized by total bilirubin concentrations
up to 3.0 mg/dL from a reduced expression of
the enzyme that conjugates bilirubin.
-------------------------------------------------A nonhepatic injury pattern (muscle injury)
would be a/w striking elevations of AST,
lesser elevations of ALT, & would not be a/w
elevations of conjugated bilirubin.
-------------------------------------------------Cholestatic injury (cholestasis) consists of a lack
of or abnormality in the flow of bile, indicated
by elevated serum alkaline phosphatase &
minimal AST & ALT elevations.
Cholestasis can occur without jaundice
because of the capacity of the liver to continue
to secrete bile sufficiently until the injury to
the bile ducts is significant. Profound
disruption of the bile secretory mechanisms
results in conjugated hyperbilirubinemia.
The first evaluative step in a patient with a
cholestatic pattern of injury is to obtain an
ultrasound to determine if intrahepatic or
extrahepatic biliary obstruction is present.
-------------------------------------------------This patient has acute hepatocellular damage
a/w mild hyperbilirubinemia that could be
caused by acute hepatitis.
Hepatocellular injury often results in an
elevation of serum ALT & AST levels, which
reflect release of intracellular enzymes from
injured hepatocytes.
AST is also released from other tissues, such
as the heart & skeletal muscle. Therefore,
elevations of ALT, which is minimally
produced in nonhepatic tissues, are more
specific for diagnosing liver disease.
Hepatocyte dysfunction is often a/w
conjugated hyperbilirubinemia, in which the
direct bilirubin fraction is > 50%.
--------------------------------------------------

Because Salmonella gastroenteritis is usually


self-limited, antibiotic treatment is generally
not required for most healthy persons.
Treating salmonellosis with ciprofloxacin
would be reasonably likely to be effective in
vitro, although resistance to fluoroquinolones
is increasing in many parts of the world.
-------------------------------------------------Although evidence that antibacterial treatment
of Shigella or travelers' diarrhea (caused by
certain toxin-producing strains of E. coli)
might hasten recovery, benefits of early
treatment are modest & diminish with time.
Treatment of presumed or documented
Salmonella diarrhea is problematic. For most
patients with salmonellosis, recovery occurs
equally fast with or without antibiotics.
There may be a delay in clearing the
salmonellae from the stool of antibiotic-treated
patients, & effects of the antibiotics can
independently contribute to toxicity, including
C. difficile toxin-mediated diarrhea.
Treatment is recommended only for (1)
immunocompetent patients younger than 2 years
or older than 50 years to avoid the incidence of
complications; (2) immunocompetent patients
with severe illness requiring hospitalization; (3)
immunocompetent patients with known or
suspected atherosclerotic plaques or
endovascular or bone prostheses because of
seeding of salmonellae to these areas during a
bloodstream infection; & (4)
immunocompromised patients, such as patients
with uncontrolled HIV infection or those
requiring corticosteroids & other
immunosuppressive agents.
-------------------------------------------------Ischemic colitis symptoms include LLQ
abdominal pain & bloody diarrhea, which are
often self-limited.
Supportive treatment with IV fluids & bowel
rest. Most symptoms resolve within 48 hours.
--------------------------------------------------

Uncomplicated diverticulitis present with


abdominal pain & fever. Physical exam
discloses LLQ abdominal tenderness.
Leukocytosis is present, & urinalysis may
show sterile pyuria due to inflammation close
to the bladder.
-------------------------------------------------Typical presentation of Crohn disease is
abdominal pain, diarrhea, & weight loss that
occurs over a period of months, if not years.
-------------------------------------------------Clostridium difficile infection (CDI) presents
with watery diarrhea, although the range of
symptoms span an asymptomatic carrier state
to severe fulminant colitis with toxic
megacolon.
-------------------------------------------------CDI with associated colitis typically have
diarrhea up to 10 or 15 times daily, lower
abdominal pain, cramping, fever, &
leukocytosis that exceeds 15,000/L.
CDI with colitis is most commonly a/w prior
antibiotic use.
The colitis is produced by two toxins, A & B
with different mechanisms of action, but both
are highly potent & cause cytotoxicity at
extremely low concentrations.
Presence of either toxin confirms diagnosis.
Treatment of severe CDI with colitis consists
of oral vancomycin & IV metronidazole.
-------------------------------------------------Irritable bowel syndrome (IBS) is the most
common GI condition with symptoms that
meet Rome III criteria.
Rome III Criteria for IBS are symptoms of
recurrent abdominal pain or discomfort &
change in bowel habit for at least 6 months,
with symptoms on at least 3 days a month for
at least 3 months.
Two or more of the following must also apply:
(1) pain is relieved by a bowel movement; (2)
onset of pain is related to a change in

frequency of stool; (3) onset of pain is related


to a change in the appearance of stool.
Supportive treatment with reassurance that she
has a chronic but not life-threatening disease
with recommendation of a high-fiber diet.
-------------------------------------------------Irritable bowel syndrome is a clinical
diagnosis of exclusion & in absence of alarm
symptoms, invasive workup is not necessary.
-------------------------------------------------Anti-endomysial antibodies are a marker for
celiac disease.
An empiric gluten-free diet is never appropriate
without establishing the histological diagnosis
of celiac disease with a small-bowel biopsy.
-------------------------------------------------Three classic findings in chronic pancreatitis
are (1) mid-epigastric abdominal pain, (2)
postprandial diarrhea, & (3) diabetes mellitus
secondary to pancreatic insufficiency.
Plain films of the abdomen will show
pancreatic calcifications in 30% of patients.
Abdominal CT scan is able to detect
pancreatic calcification in up to 90%.
-------------------------------------------------Malabsorption occurs in chronic pancreatitis
when 80% of the pancreas is destroyed.
Malabsorption presents with diarrhea &
steatorrhea, weight loss, & fat-soluble vitamin
deficiencies because the damaged pancreatic
gland is no longer producing the pancreatic
exocrine enzymes to absorb food.
Additional clues to the diagnosis include
elevated pancreatic enzymes & LFTs.
-------------------------------------------------Diagnose chronic pancreatitis with
abdominal CT scan.
-------------------------------------------------Acute radiation proctitis usually manifests
within 6 weeks of therapy with symptoms of
diarrhea & tenesmus.
The proctitis is due to direct radiation injury to
the rectal mucosal, which occurs commonly in

patients receiving pelvic radiation. & usually


resolves soon after radiation is discontinued.
Flexible sigmoidoscopy is the most
appropriate diagnostic test.
Diagnosis is established by endoscopic findings
of mucosal telangiectasia, with biopsy showing
submucosal fibrosis & arteriole endarteritis.
Chronic proctitis can occur months to years
after treatment & a/w a worse prognosis.
-------------------------------------------------Routine stool cultures only test for salmonella,
shigella, & campylobacter. Therefore, patients
with bloody diarrhea, stool should be sent
specifically for E. coli O157:H7 testing.
-------------------------------------------------Hemolytic uremic syndrome (HUS) is
characterized by thrombocytopenia &
thrombotic microangiopathy.
Thrombotic microangiopathy is a clinical
syndrome characterized by thrombocytopenia
& microangiopathic hemolytic anemia
(schistocytes on the peripheral blood smear,
elevated reticulocyte count, & elevated lactate
dehydrogenase level).
Thrombotic microangiopathy may manifest as
thrombotic thrombocytopenic purpura or HUS
HUS is usually caused by infection with Shiga
toxin-producing E. coli (O157:H7), related to
ingestion of contaminated, undercooked beef,
or complement dysregulation caused by
genetic mutations.
Additional manifestations of HUS include
acute kidney injury & neurologic findings
(headache, confusion) but the only diagnostic
criteria are thrombocytopenia &
microangiopathic hemolytic anemia in the
absence of any other potential cause.
-------------------------------------------------Acute cholangitis is a/w biliary obstruction &
is characterized by pain, fever, & jaundice.
-------------------------------------------------The diagnosis of chronic pancreatitis should
be strongly considered in patients with a

history of alcoholism presenting with chronic


upper abdominal pain radiating to the back,
diabetes, steatorrhea, & pancreatic
calcifications on abdominal CT.
-------------------------------------------------The best imaging modality to confirm suspected
diverticulitis & evaluate for extraluminal
complications is contrast-enhanced CT scan.
-------------------------------------------------Colonoscopy is generally avoided during an
episode of acute diverticulitis for concern of
increased risk of perforation with air
insufflation & would miss extraluminal
complications such as abscess formation.
Before the availability of CT scans, barium
enema was used to diagnose diverticulitis but
also presents a risk for perforation & not
sensitive to the presence of extraluminal
complications.
-------------------------------------------------LLQ pain, fever, & elevated leukocyte count
are classic symptoms & signs of diverticulitis.
The most sensitive imaging modality to
confirm this diagnosis & evaluate for
complications such as perforation, abscess,
obstruction, & fistula is a contrast-enhanced
CT scan of the abdomen & pelvis.
-------------------------------------------------Ischemic colitis presents commonly in elderly
patients with atherosclerotic vascular disease
with crampy abdominal pain & bloody stool;
most cases are self-limited, transient &
resolves with conservative management.
Acute colonic ischemia usually present with
rapid onset abdominal pain & tenderness over
the affected bowel. Rectal bleeding or bloody
diarrhea develops within 24 hours of the onset
of abdominal pain.
The typical finding on CT scan is thickening
of the bowel wall in a segmental pattern,
which is not specific for ischemia & can be
seen in infectious colitis & Crohn disease.

Findings of patchy segmental ulcerations on


colonoscopy with a compatible history
establishes the diagnosis.
Colonic strictures are a rare complication.
-------------------------------------------------Patients with Crohn disease commonly
present with a chronic history of abdominal
pain, diarrhea, & weight loss. The patient's
acute onset of symptoms with bloody diarrhea
is not consistent with Crohn disease.
-------------------------------------------------Irritable bowel syndrome is a clinical
diagnosis. In the absence of alarm symptoms
& there are no laboratory, radiographic, or
endoscopic findings that aid in diagnosis.
Additional evaluation is not only unnecessary
& expensive but potentially harmful when
invasive procedures are ordered.
Because fiber supplementation has not been
helpful, a non-absorbed osmotic laxative such
as polyethylene glycol will likely provide
significant relief.
-------------------------------------------------This patient has irritable bowel syndrome.
As a young woman, she fits the demographic
profile, & meets the Rome III criteria, with
abdominal pain relieved by defecation &
change in bowel habits.
Diagnostic criteria require the presence of at
least two of three symptoms occurring for 3
months (not necessarily consecutive) during a
12-month period, including pain relieved with
defecation, onset a/w change in stool
frequency, or change in stool consistency.
In clinical practice, these criteria have a
positive predictive value of 98%.
She has no alarm symptoms, including older
age, male sex, nocturnal awakening, rectal
bleeding, weight loss, or family history of
colon cancer. In absence of alarm symptoms,
additional tests have diagnostic yield of <2%.
--------------------------------------------------

Diverticulitis presents with fever & crampy


abdominal pain, commonly in the LLQ & a/w
a change in bowel habits.
Leukocytosis may be present.
-------------------------------------------------Abdominal pain, back pain, & syncope often
herald an AAA rupture.
-------------------------------------------------Contained rupture of AAA is often mistaken
for renal colic, acute MI, or diverticulitis.
Renal colic may produce severe pain in the
lower back, flank, or groin. Typically, the pain
waxes & wanes.
-------------------------------------------------Clinical presentationsevere abdominal or
back pain with syncope followed by
abdominal discomfortis typical for a
ruptured abdominal aortic aneurysm
(AAA) that has been locally contained.
The sentinel event of severe sudden abdominal
& back pain a/w loss of consciousness marks
the occurrence of AAA rupture.
Leukocytosis & anemia are common.
A CT scan should be performed for diagnosis;
the aneurysm should be repaired emergently.
-------------------------------------------------Although an abdominal CT scan is usually
necessary for a definitive diagnosis of acute
abdominal pain, initial screening with
supine & upright abdominal radiographs
should be done first to look for air-fluid levels,
suggestive of a bowel obstruction, & free
peritoneal air, suggestive of perforated viscus.
Colonoscopy is not indicated in a patient with
acute peritoneal signs & has the potential to
worsen the situation by causing a perforation
of inflamed bowel wall.
-------------------------------------------------CXR & supine & upright abdominal
radiographs should be obtained in every
patient with significant acute abdominal
pain to exclude bowel obstruction or
perforation or intrathoracic processes

(pneumonia, pneumothorax, or aortic


dissection) that can present as abdominal pain.
-------------------------------------------------All patients with abdominal pain should have
measurements of serum amylase & lipase to
evaluate for acute pancreatitis.
-------------------------------------------------Acute abdomen refers to sudden & severe
abdominal pain for less than 24 hours.
Rebound tenderness & severe diffuse
abdominal pain are suggestive of an acute
abdomen with peritonitis.
Acute in onset of pain generally points to acute
inflammatory, infectious, or ischemic causes.
Upper abdominal pain is usually of gastric,
hepatobiliary, or pancreatic origin, whereas
pain in the lower abdomen originates from the
hindgut & genitourinary organs.
-------------------------------------------------Evaluate acute abdominal pain with supine &
upright abdominal radiographs.
-------------------------------------------------Non-contrast helical abdominal CT scan is
the imaging modality of choice for the
diagnosis of nephrolithiasis.
-------------------------------------------------Acute renal colic is characterized by sudden
onset of unilateral flank pain; may also cause
nausea & vomiting
Patients with stones located in the ureters or
urethra may have irritative symptoms such as
urinary urgency & frequency.
90% of patients with nephrolithiasis have
either gross or microscopic hematuria.
Non-contrast helical abdominal CT has
replaced intravenous pyelography as the gold
standard for diagnosing kidney stones.
This test reveals urinary tract obstruction with
hydronephrosis, detects stones as small as 1
mm in diameter, & evaluates other potential
causes of abdominal pain & hematuria.
However, noncontrast helical abdominal CT is

expensive & has a higher radiation exposure


than other imaging studies.
Most kidney stones are radiopaque & easily
visualized on plain radiographs of the
abdomen, which are inexpensive, noninvasive,
& widely available.
However, false-negative results may occur in
patients with small stones or radiolucent
stones composed of uric acid or related to use
of indinavir, & with interference of the
overlying bowel. Similarly, vascular
calcification & phleboliths may cause falsepositive results for kidney stones.
-------------------------------------------------Intravenous pyelography has a high
sensitivity & specificity in the diagnosis of
kidney stones. However, this study requires
bowel preparation & use of IV iodinated
contrast agents, which are contraindicated in
patients with acute kidney injury & chronic
kidney disease.
--------------------------------------------------

IV. General Internal Medicine

Ambulatory BP monitoring is primarily


indicated for patients with white coat HTN.
White coat HTN is defined as at least three
separate office BP >140/90 mm Hg with at
least two sets below 140/90 mm Hg obtained
in non-office settings.
-------------------------------------------------Treat prehypertension with lifestyle
modification: maintaining normal body weight,
regular aerobic exercise, DASH diet, reducing
sodium intake, & moderating alcohol intake.
-------------------------------------------------Stage 2 HTN (systolic BP 160 mm Hg or
diastolic BP 100 mm Hg).
Both lifestyle modifications &
antihypertensives are indicated.
-------------------------------------------------Treat stage 2 HTN with two-drug therapy.
-------------------------------------------------Initiate treatment with two medications in
patients with stage 2 HTN or those whose BP
is > 20 mm Hg systolic or > 10 mm Hg
diastolic above target.
Low-dose hydrochlorothiazide & ACE
inhibitor (lisinopril) would be reasonable to
ensure adequate BP control.
Thiazide diuretics are superior to -blockers,
ACE inhibitors, & calcium channel blockers
as initial therapy for reducing cardiovascular
& kidney risk in patients with HTN.
-------------------------------------------------Renovascular HTN due to fibromuscular
disease of the renal arteries usually presents in
patients younger than 35 years of age.
Atherosclerotic renovascular disease is
common in older patients & a/w vascular
disease in other vessels (carotid or coronary
arteries & peripheral vessels).
o Azotemia is often observed with
atherosclerotic renovascular HTN.
--------------------------------------------------

Classic triad of sudden severe headaches,


diaphoresis, & palpitations carries a high
degree of specificity (94%) & sensitivity
(91%) for pheochromocytoma in
hypertensive patients.
Absence of all three symptoms reliably
excludes the condition.
-------------------------------------------------Classic features of aortic coarctation include
a pulse delay between the upper & lower
extremities (radial to femoral artery delay).
An ejection click & early systolic murmur
consistent with a bicuspid aortic valve, present
in > 50% of patients with aortic coarctation.
The systolic & diastolic murmurs noted over
the back are related to collateral vessels, which
also cause the sign of rib notching, seen on
CXR on the inferior surface of the posterior
upper thoracic ribs bilaterally.
Also, indentation of the aortic wall at the site
of coarctation combined with pre- & postcoarctation dilatation produces the "3" sign.
-------------------------------------------------Normal BP is < 120/80 mm Hg.
Cardiovascular risk correlates directly with BP
stage, beginning at 115/75 mm Hg & doubling
with each 20/10 mm Hg increment.
The goal of antihypertensive treatment in
essential HTN is BP < 140/90 mm Hg.
A target BP is < 130/80 mm Hg for patients
with type 2 diabetes mellitus & nondiabetic
chronic kidney disease in absence of
proteinuria, which is a/w a lower rate of
cardiovascular outcomes.
Target BP of < 125/75 mm Hg is for patients
with kidney disease accompanied by a urine
protein-creatinine ratio > 1 mg/mg.
-------------------------------------------------Low-dose diuretic therapy is appropriate in
older patients with HTN because these patients
are more likely to be salt sensitive.
Antihypertensive therapy has been shown to
benefit patients age 60 to 80 years.

Antihypertensive therapy in patients older than


80 years is a/w a decrease in stroke &
cardiovascular mortality.
-------------------------------------------------Because older patients with HTN are more
likely to be salt sensitive & responsive to a
diuretic, low-dose chlorthalidone (thiazide) is
appropriate with 1 week follow-up to assess
for electrolyte abnormalities or azotemia.
------------------------------------------------Thiazides should be used as initial therapy for
most patients with HTN, either alone or in
combination with another class of
antihypertensive agents.
Diuretics enhance the antihypertensive
efficacy of multidrug regimens & inexpensive.
-------------------------------------------------Treat HTN in an elderly patient with the
addition of hydrochlorothiazide.
-------------------------------------------------Patients with stage 1 HTN who do not have
evidence of cardiovascular disease or target
organ damage, therapeutic lifestyle changes
can be tried for 6 to 12 months before
initiating drug therapy.
------------------------------------------------Lifestyle modifications is recommended for all
patients with HTN, including prehypertension.
8 weeks of a diet of fruits, vegetables, low-fat
dairy products, whole grains, poultry, fish, &
nuts, along with a reduction in intake of fats,
red meat, & sweets, caused an 11.4-mm Hg
decrease in systolic BP & 5.5-mm Hg decrease
in diastolic BP.
Alcohol consumption should be limited to
two drinks daily for men & one for women
because excess amounts of alcohol may
contribute to HTN & resistance to
antihypertensive medications.
-------------------------------------------------Disequilibrium in the elderly is described as a
vague sense of unsteadiness, often occurring

while standing or walking.


-------------------------------------------------Disequilibrium in the elderly is multifactorial,
including peripheral neuropathy, visual loss,
decline in bilateral vestibular function,
deconditioning, autonomic neuropathy, & drug
side effects.
Treatment involves reducing polypharmacy,
installing safety features in patients' homes,
providing assistive devices such as walkers &
canes, correcting eyesight & hearing, &
instituting physical therapy to improve
muscle strength.
-------------------------------------------------USPSTF recommends one-time ultrasound
screening for abdominal aortic aneurysm in
men 65 to 75 years of age who are current or
former smokers; it does not extend this to
never-smokers because of the lower risk of
large aneurysms in this population.
-------------------------------------------------A two-item screening instrument has a
sensitivity of 96% & specificity of 57% for
diagnosing depression.
A "yes" response to either of the following
questions constitutes a positive screen:
1. "Over the past 2 weeks have you felt
down, depressed, or hopeless?"
2. "Over the past 2 weeks have you felt little
interest or pleasure in doing things?"
A positive screening result should be followed
by a full diagnostic interview to determine
the presence of a depressive disorder.
-------------------------------------------------USPSTF recommends screening be restricted
to primary care settings in which an accurate
diagnosis of depression can be made,
effective treatment can be provided, & followup care is available.
-------------------------------------------------Tolterodine & oxybutynin are anticholinergic
agents for treating urge urinary incontinence.
------------------------------------------------

Doxazosin (-adrenergic blockers) is effective


for the urinary symptoms a/w BPH, such as
slow urinary stream, hesitancy, & nocturia.
-------------------------------------------------Urge urinary incontinence (overactive
bladder) is manifested by involuntary leakage
of large amounts of urine. The incontinence is
frequently preceded by a sense of urgency but
an inability to get to the bathroom in time.
This patient's memory loss & findings on the
MMSE could indicate early dementia, which
is a risk factor for urge incontinence.
-------------------------------------------------Evaluate a fall in an elderly patient with the
"get up & go" test.
-------------------------------------------------Risk factors for falling include lower
extremity weakness, gait deficit, arthritis,
impaired activities of daily living, female sex,
& age over 80 years. Other risk factors include
balance deficits, impaired vision, depression,
psychotropic drug use, cognitive impairment, &
use of an assistive device.
"Get up & go" test is appropriate for
screening because it is a quantitative
evaluation of general functional mobility.
A strong association exists between
performance on this test & functional
independence in activities of daily living.
Persons are timed in their ability to rise from a
chair, walk 10 feet, turn, & return to the chair.
Most adults complete this task in 10 seconds,
& most frail elderly persons, 11 to 20 seconds.
Those requiring more than 20 seconds should
undergo a fall evaluation.
-------------------------------------------------Elderly persons should be screened for hearing
impairment with the whispered-voice test or
the handheld audioscopy, even if they deny
having a hearing problem.
-------------------------------------------------Referring patients for formal audiometry,
although the gold standard for evaluating

hearing loss, is expensive & time consuming.


-------------------------------------------------Whispered-voice test is a quick & easy
assessment tool that has the best test
characteristics among the office maneuvers.
This test assesses the ability to hear a
whispered voice with the examiner standing
behind the patient 2 feet from the patient's ear
while occluding & simultaneously rubbing the
opposite external auditory canal & whispering
three numbers or letters.
-------------------------------------------------Screening for hearing loss is important in
elderly persons because hearing impairment is
prevalent but frequently underdiagnosed.
-------------------------------------------------Oral hypoglycemics do not typically cause
incontinence, & discontinuing these agents in
a patient with diabetes could precipitate
hyperglycemia & increased incontinence.
-------------------------------------------------UTI is a common cause of transient
incontinence in the elderly, particularly if
other contributing factors such as cognitive
impairment or impaired mobility are present.
Presence of significant pyuria in this setting
generally justifies empiric antibiotic therapy
pending urine culture results.
-------------------------------------------------New-onset urinary incontinence should be
evaluated for transient, reversible causes,
using the mnemonic DIAPERS: Drugs,
Infection, Atrophic vaginitis, Psychological
(depression, delirium, dementia), Endocrine
(hyperglycemia, hypercalcemia), Restricted
mobility, & Stool impaction.
-------------------------------------------------Diagnose & treat cystitis as the cause of
urinary incontinence with ciprofloxacin.
------------------------------------------------Enlarging, firm axillary lymphadenopathy in
a woman older than 40 years suggests the
possibility of metastatic breast cancer.

The most appropriate initial evaluation is


lymph node biopsy.
-------------------------------------------------Early antigen antibody test for EBV may not
become positive until a month after the illness.
The capsid (anti-VCA) IgM antibody becomes
positive earlier, as does the heterophile
agglutination test (monospot), & these are the
usual early tests ordered for EBV infection.
-------------------------------------------------Signs or symptoms that suggest a pathological
cause of lymphadenopathy (systemic
symptoms, progressive enlargement, persistence
beyond 2 weeks), CBC with differentials &
CXR would be reasonable tests.
-------------------------------------------------A patient younger than 40 years of age,
lymphadenopathy less than 2 cm, mobile &
rubbery in consistency, located in regions
typical for benign lymphadenopathy, & no
features that suggest a serious cause of
generalized lymphadenopathy.
Her recent viral-like illness suggests that it is
reactive lymphadenopathy. Therefore,
watchful waiting is the correct course of action.
-------------------------------------------------Individual lesions of acute urticaria last less
than 24 hours. Lesions can be observed by
drawing circles & observing their duration.
Acute urticaria is generally related to
environmental allergens, including drugs,
foods, & occasionally inhalants.
Penicillin, aspirin, NSAIDs, contrast dyes, &
sulfonamides are common drug-related causes
of acute urticaria.
-------------------------------------------------Hallmark of urticaria is the rapid appearance
of the wheal, a superficial, itchy, sometimes
painful, discrete swelling of the skin. Wheals
can be multiple or isolated & usually involve
the trunk & extremities, sparing palms & soles
--------------------------------------------------

Urticaria, aka hives, is a common skin finding


that arises from a recurrent, but transient,
cutaneous swelling with sudden erythema
caused by vascular extravasation.
A severe, life-threatening form of urticaria is
called angioedema.
-------------------------------------------------Hallmark of angioedema is self-limited,
localized swelling of the skin or mucosa,
usually the lips, face, hands, feet, penis, or
scrotum. Skin is normal or red in color;
itching is absent unless a/w urticarial lesions.
-------------------------------------------------For chronic urticaria, patient diaries are
often helpful in determining the cause.
An individual wheal in chronic urticaria lasts
more than 24 hours & may occur several times
per week for up to six weeks.
-------------------------------------------------Acne is classified by severity & type as
noninflammatory & inflammatory acne.
Non-inflammatory acne consists of open
comedos ("blackheads") or closed comedones
("whiteheads"). Subsequent inflammatory
papules, pustules, or nodules may develop.
Acne lesions develop in areas that have a high
concentration of sebaceous glands, including
face, neck, chest, upper arms, & back.
Exacerbating factors are mechanical
obstructions (clothing) & medications (anabolic
steroids such as danazol & testosterone,
corticosteroids, INH, lithium, & phenytoin).
-------------------------------------------------Non-inflammatory acne can be treated with
topical comedolytic agents such as retinoids,
benzoyl peroxide, salicylic acid, azelaic acid.
Mild inflammatory acne consist of comedones
& few papules & pustules can be treated with
topical comedolytic agents combined with a
topical antibiotic.
If topical therapy is ineffective, oral antibiotics
is indicated.

Oral antibiotics may be first-line therapy in


cases where the cystic & pustular acne lesions
are extensive & topical application would be
impractical or a high likelihood of failure with
topical treatment alone.
-------------------------------------------------Treat cystic & pustular inflammatory acne
with oral antibiotics.
-------------------------------------------------Isotretinoin is the only medication that alters
the natural history of acne, & indicated for
cystic & pustular acne that is unresponsive to
antibiotics.
Isotretinoin is highly teratogenic &
potentially severe side effects, including
hypertriglyceridemia, pseudotumor cerebri,
decreased bone mineral density, & possibly
depression & psychosis; strict attention to
informed consent & careful monitoring are
mandatory if this medication is used.
-------------------------------------------------Squamous cell carcinoma presents as a scaly,
hyperkeratotic, red or pink papule, patch, or
plaque.
It is not brown, tan, or black & does not have a
warty appearance like seborrheic keratoses.
-------------------------------------------------Basal cell carcinoma is a pearly or translucent
papule or nodule with associated telangiectasias.
-------------------------------------------------Seborrheic keratosis is a benign skin condition
common in adults; increases in number with age.
They are characterized by sharply demarcated,
tan to dark brown, warty papules, plaques, &
nodules that have a waxy texture & appear to be
"stuck on" the skin.
They are frequently located in the scalp, on
the back & chest.
-------------------------------------------------Seborrheic dermatitis causes white, scaling
macules & papules on yellowish-red skin &
may be greasy or dry.

Sticky crusts & fissures often develop behind


the ears, & significant dandruff or scaling of
the scalp frequently occurs.
Seborrheic dermatitis may involve the
nasolabial folds, eyebrows, & forehead.
This condition usually improves during the
summer & worsens in the fall & winter.
-------------------------------------------------Malar rash a/w systemic lupus
erythematosus is usually photosensitive &
often spares the nasolabial folds & areas
below the nares & lower lip (areas relatively
protected from the sun).
-------------------------------------------------Psoriasis includes an erythematous plaque
with an adherent, variably thick, silvery scale.
-------------------------------------------------Dermatomyositis is a/w periungual erythema &
malar erythema, consisting of a light purple
(heliotrope) edematous discoloration of the
upper eyelids & periorbital tissues.
Dermatomyositis also may cause an
erythematous, papular eruption that develops
in a V-shaped pattern along the neck & upper
torso; in a shawl-shaped pattern along the
upper arms; the elbows, knees, ankles, & other
sun-exposed areas.
Involvement of the hands may include scaly,
slightly raised, purplish papules & plaques in
periarticular areas of the metacarpal &
interphalangeal joints & bony prominences
(Gottron sign or Gottron papules) & scaly,
rough, dry, darkened, cracked, horizontal lines
on the palmar & lateral aspects of the fingers
(mechanic's hands).
-------------------------------------------------Rosacea is an inflammatory dermatitis
characterized by erythema, telangiectasias,
papules, pustules, & sebaceous hyperplasia on
the central face, including nasolabial folds.
Rhinophyma, or the presence of a bulbous,
red nose, is a variant of this condition.

Recurrent flushing in response to stimuli


such as spicy food or alcohol is common.
-------------------------------------------------In patients with herpes zoster, administration
of oral acyclovir, valacyclovir, or famciclovir
within 72 hours of the development of rash
decreases acute pain severity & duration,
promotes rapid healing of lesions, & decreases
postherpetic neuralgia incidence & severity.
-------------------------------------------------Therapy with IV acyclovir for patients with
severe herpes zoster ophthalmicus or for
those who develop CNS complications of
herpes zoster.
-------------------------------------------------Oral valacyclovir & famciclovir are
preferred because of improved bioavailability.
Acyclovir is poorly absorbed & requires more
pills daily.
Adding corticosteroids may accelerate
healing of lesions, decrease the time to acute
pain resolution, decrease insomnia incidence,
help patients return to normal daily activities
sooner, & decrease analgesic medication needs
However, corticosteroids do not appear to
decrease postherpetic neuralgia incidence.
Therefore, corticosteroids should be used only
as an adjunct to antiviral agents.
-------------------------------------------------Rocky Mountain spotted fever (RMSF) is a
tick-borne disease caused by R. rickettsii.
RMSF present with subtle, fine, pink, blanching
macules & papules on the wrists & ankles that
then spread centripetally & to palms & soles.
As the rash spreads, the characteristic
petechial & purpuric "spots" appear. Most
patients have fever, severe headache, myalgia.
-------------------------------------------------Erythema migrans is distinguished from
erythema multiforme by the lesion size, its
location, & lack of associated mucosal
involvement.
--------------------------------------------------

Erythema migrans (aka erythema chronicum


migrans) is the hallmark cutaneous lesion of
early Lyme disease.
A centrifugally spreading ring of erythema that
resembles a bull's eye develops at the site of
infection 3 to 30 days after a tick bite.
Typically found near the axilla, inguinal region,
popliteal fossa, or belt line; palmar involvement
is rare.
-------------------------------------------------Erythema multiforme is a mucocutaneous
reaction characterized by targetoid lesions &
both skin & mucosal involvement. 90% of
recurrent cases are a/w infections, commonly
herpes simplex virus (HSV-1 & HSV-2).
No virus is routinely recovered with culture, &
treatment with antivirals do not affect the
outcome of an acute outbreak.
Suppressive antivirals may minimize the
number of erythema multiforme recurrences.
Recurrences of erythema multiforme can
occur in the absence of apparent clinical
reactivation of HSV; patients may not be
aware that they are infected with HSV.
-------------------------------------------------"Red man syndrome" is the most common
adverse reaction to vancomycin. This reaction
does not appear to be antibody related
Characterized by flushing, erythema, & pruritus
involving the upper body, neck, & face.
-------------------------------------------------Allergic contact dermatitis is a delayed-type
hypersensitivity reaction. The first reaction to
an antigen may occur several weeks after
exposure, but subsequent reactions usually
develop within 24 to 48 hours of reexposure.
Allergic contact dermatitis is intensely itchy.
In acute reactions, the skin is red, edematous,
weepy, & crusted; may be vesicles or bullae.
-------------------------------------------------Stevens-Johnson syndrome is characterized
by fever followed by erythematous macules &

plaques that progress to epidermal necrosis &


sloughing; < 10% of the body surface area.
Mucous membranes are affected; ocular,
oral, & genital surfaces may be involved.
Toxic epidermal necrolysis is a more severe
variant of this condition, & defined as
epidermal necrosis & sloughing involving
more than 30% of the body surface area.
Sulfonamide is the most likely causative drug,
but SJS can be caused by other antibiotics,
antiepileptics, allopurinol, & systemic diseases.
-------------------------------------------------Seborrheic dermatitis lesions are ill-defined
(lack a distinct border), yellowish-red, vary in
size, & a/w a greasy or dandruff-like scale;
absence of pustules.
Commonly occurs on the scalp, central face,
upper mid-chest, & oily areas of the body.
-------------------------------------------------Psoriasis can present on the trunk with red to
salmon-colored papules & plaques covered
with a heavy silver-white scale.
------------------------------------------------Cutaneous candidiasis is a superficial
infection that occurs in warm, moist skin areas.
Patients with this infection have altered local
immunity, such as increased moisture at the
site of infection, diabetes, or altered systemic
immunity.
The infection begins with pustules on a red
base that become eroded & confluent. The
rash evolves into a sharply demarcated, bright
red patch or patches, with small, pustular
lesions at the periphery (satellite lesions).
------------------------------------------------Superficial fungal infections, tinea, are
classified by body part.
Tinea cruris is a subacute, chronic
dermatophyte infection of the skin, involving
the groin, pubic region, & inner thighs; in
contrast to candidiasis, scrotum is rarely
involved.

Recognized as light pink to red papules & thin


plaques with scaling borders. The lesions may
have an arciform or polycyclic pattern.
The lesion has an "active border," the border
has more redness & scaling than the inner
portion, which may have central clearing.
The presence of fungi can be confirmed with a
potassium hydroxide (KOH) preparation.
-------------------------------------------------Dermatomyositis has characteristic cutaneous
manifestations combined with proximal
inflammatory muscle weakness; cutaneous
disease may be the only manifestation.
Distinctive cutaneous features are the
heliotrope rash characterized by a violaceous
to dusky erythematous periorbital rash &
Gottron papules which are slightly elevated,
scaly, violaceous papules & plaques over bony
prominences & small joints of the hands.
-------------------------------------------------Patients with SLE almost exclusively develop
acute cutaneous lupus erythematosus (LE),
precipitated by sunlight.
Acute cutaneous LE can present as the classic
"butterfly rash," characterized by confluent
malar erythema, or as generalized, red, papular
or urticarial lesions on the sun-exposed skin.
-------------------------------------------------Rosacea is a chronic inflammatory skin
disorder of unknown etiology affecting the
face, typically cheeks & nose, & usually after
the age of 30 years.
Erythema with telangiectasias, pustules, &
papules without comedones are found.
Rosacea can be differentiated from seborrheic
dermatitis by the presence of pustules.
In early stages, rosacea can present with only
facial erythema & resemble the butterfly rash
of SLE; however, acute cutaneous LE
typically spares the nasal labial folds & areas
under the nose & lower lip.
--------------------------------------------------

Seborrheic dermatitis affects areas of the


scalp (dandruff) & face that are rich in
sebaceous glands & distinguished from other
dermatoses primarily by its distribution.
Lesions are erythematous, with dry or greasy
scales & crusts, & may be pruritic.
Common areas of involvement include the
nasolabial folds, cheeks, eyebrows, eyelids, &
the external auditory canals. Frequent
remissions & exacerbations are common.
Treatment consists of low-potency
corticosteroids (face), ketoconazole cream
(face), & medicated shampoos that contain tar,
ketoconazole, or selenium sulfide (scalp).
-------------------------------------------------Venous stasis dermatitis affect the lower legs,
around the medial malleoli, results from
venous HTN, edema, chronic inflammation, &
microangiopathy.
Bilateral involvement, absence of fever or
leukocytosis, hyperpigmentation due to
hemosiderin deposition, & minimal pain help
distinguish venous stasis from cellulitis.
-------------------------------------------------Atopic dermatitis, when acute, results in
poorly demarcated, eczematous, crusted,
erythematous papulovesicular plaques &
excoriations that characteristically are pruritic
& involve the antecubital, popliteal fossae, &
flexural wrists.
-------------------------------------------------Contact dermatitis can be differentiated from
cellulitis by the presence of pruritus &
absence of fever.
-------------------------------------------------Cellulitis is a rapidly spreading, deep (dermis),
subcutaneous infection caused by S. aureus or
group A streptococci.
Characterized by a well-demarcated area of
warmth, swelling, tenderness, & erythema
accompanied by lymphatic streaking &/or
fever & chills.

Risk factors for lower-extremity cellulitis


include inflammation (eczema), tinea pedis,
onychomycosis, skin trauma, chronic leg
ulcerations, type 2 diabetes, & edema.
Cellulitis is a clinical diagnosis; cultures are
not necessary & seldom positive.
Treatment is based on the risk of MRSA
infection & severity of illness & consists of
oral antibiotics & analgesics; intravenous
antibiotics may be necessary for unsuccessful
outpatient treatment, patients with diabetes, or
signs of systemic toxicity.
-------------------------------------------------Diagnose abnormal uterine bleeding with an
endometrial biopsy.
-------------------------------------------------Abnormal uterine bleeding can including
infrequent menses, excessive flow, prolonged
duration of menses, intermenstrual bleeding,
& postmenopausal bleeding.
In all patients with abnormal bleeding,
physical exam should include a pelvic exam
& Pap smear.
-------------------------------------------------After performing appropriate lab studies, an
assessment of the endometrial lining with an
endometrial biopsy is appropriate to rule out
endometrial cancer or hyperplasia in
patients older than 35 years of age with
abnormal uterine bleeding.
-------------------------------------------------In patients with anovulatory bleeding,
initiation of oral contraceptives or cyclic
progestins can help maintain regular cycles.
However, this intervention would be
inappropriate without first eliminating the
possibility of endometrial cancer as the cause
of the abnormal uterine bleeding.
-------------------------------------------------Estrogen is the most effective treatment for
the relief of hot flushes, with a 50% to 90%
response rate, & evidence shows that even low
doses provide effective symptom relief.

Relief of hot flushes is now considered the


primary reason for initiating estrogen
replacement therapy.
-------------------------------------------------Secondary amenorrhea is defined by absence
of menses for 3 or more consecutive months in
a woman who has menstruated previously.
Menstrual failure can be complete
amenorrhea or varying degrees of
oligomenorrhea, the latter is more common.
Pregnancy should be excluded in all patients
prior to other evaluations.
-------------------------------------------------After pregnancy is excluded, initial evaluation
of secondary amenorrhea includes
measurement of FSH, TSH, & prolactin.
-------------------------------------------------Polycystic ovary syndrome is the most
common cause of secondary amenorrhea.
Hypogonadotropic hypogonadism (low FSH
& low estrogen) is most commonly caused by
hyperprolactinemia.
In young women, secondary amenorrhea may
be a/w hypergonatrophic hypogonadism.
This group includes primary ovarian failure
(often due to Turner syndrome mosaicism &
autoimmune disorders) & exposure to
chemotherapy or radiation treatments.
------------------------------------------------Evaluation of secondary amenorrhea is first
directed toward ovarian failure,
hyperprolactinemia, & thyroid disease.
o FSH, prolactin, TSH, & free T4 levels
are measured.
o FSH > 20 mU/mL (20 U/L) suggests
ovarian failure.
If serum FSH & prolactin levels are normal,
next step is progestin withdrawal challenge.
If the progestin challenge does not result in
withdrawal bleeding, then assessment of the
pelvic anatomy with ultrasonography or
MRI would be appropriate.
--------------------------------------------------

This patient has an unremarkable personal &


family medical history & no evidence of
androgen excess. Results of screening lab
studies are negative for thyroid disorders,
ovarian dysfunction, & hyperprolactinemia.
Differential diagnoses of secondary
amenorrhea includes anatomic defects &
chronic anovulation, with or without estrogen.
Differential diagnosis can be narrowed with a
progestin withdrawal challenge.
-------------------------------------------------Positive withdrawal bleeding after the
progestin withdrawal challenge suggests an
estradiol level of > 40 pg/mL & thus obviates
the need for serum estradiol measurement.
Menstrual flow on progestin withdrawal
indicates relatively normal estrogen
production & patent outflow tract, which
limits the differential diagnosis of secondary
amenorrhea to chronic anovulation with
estrogen present; excludes anatomic defects
& chronic anovulation without estrogen.
------------------------------------------------Evaluate secondary amenorrhea with a
progestin withdrawal challenge after
stopping OCPs.
-------------------------------------------------Raloxifene is a selective estrogen receptor
modulator (SERM) that is approved for
prevention of postmenopausal bone mass loss,
but does not help with hot flushes or other
postmenopausal symptoms.
-------------------------------------------------Treatments for which there is evidence of
benefit for hot flushes include selective
serotonin & norepinephrine reuptake inhibitors
venlafaxine & SSRIs such as citalopram,
paroxetine, fluvoxamine, & fluoxetine.
These are considered second-line agents,
especially in women who also have symptoms
of mood or anxiety disorders.
--------------------------------------------------

Contraindications to estrogen use include


undiagnosed vaginal bleeding, breast cancer,
other estrogen-sensitive cancers, current or
previous history of venous or arterial
thrombosis, & liver dysfunction or disease.
-------------------------------------------------Estrogen replacement therapy (ERT)
provides relief for hot flushes a/w menopause.
Relief of hot flushes is the primary indication
for ERT, although it also reduces the rate of
postmenopausal bone density loss.
Benefits of ERT must be weighed against the
risks, including potential increased rates of
breast cancer, thromboembolic events, &
cardiac events.
-------------------------------------------------Estrogen replacement therapy provides
effective relief of hot flushes.
-------------------------------------------------PCOS affects women of child-bearing age,
presents with oligomenorrhea & signs of
androgen excess (hirsutism, acne, alopecia).
Insulin resistance is a major feature, as are
overweight & obesity.
There is a mild elevation in testosterone &
DHEAS & LH to FSH ratio of > 2:1.
Diagnosis requires two of the three following:
(1) ovulatory dysfunction, (2) lab or clinical
evidence of hyperandrogenism, & (3)
ultrasound evidence of polycystic ovaries.
-------------------------------------------------Patients who present with menorrhagia
(heavy menstrual bleeding) with a known
etiology, several therapeutic agents can
decrease bleeding.
For moderate bleeding that can be managed
on an outpatient, a progestational agent such
as medroxyprogesterone acetate can be
given for 10 to 21 days. The progesterone will
typically act to stabilize the endometrium &
stop uterine blood flow.
Alternatively, a monophasic oral contraceptive
may be dosed four times a day for 5 to 7 days,

& subsequently reduced to daily dosing for 3


weeks, followed by withdrawal bleeding.
-------------------------------------------------NSAIDs inhibit prostaglandin synthesis &
may decrease mild bleeding by 30%.
Once daily oral contraceptives are effective in
decreasing menstrual blood loss by 50%;
however, with heavy menstrual bleeding,
neither of these medications would be as
effective as medroxyprogesterone.
-------------------------------------------------If the patient were orthostatic or dizzy from
blood loss, intravenous estrogen would be
appropriate.
Parenteral conjugated estrogens are 70%
effective in stopping the bleeding entirely.
Pulmonary embolism & venous thrombosis
are complications of IV estrogen therapy.
------------------------------------------------Treat heavy menstrual bleeding with oral
medroxyprogesterone for 10 21 days.
-------------------------------------------------Unexplained weight loss occurs in half of the
patients with severe COPD, because of the
loss of skeletal muscle mass.
Unexplained weight loss carries a poor
prognosis in COPD, independent of other
indicators, such as FEV1 or PCO2.
-------------------------------------------------Severe COPD can cause systemic effects,
including unexplained weight loss, skeletal
muscle dysfunction, increased cardiovascular
morbidity & mortality, risk for type 2 diabetes
mellitus, osteoporosis, fractures, & depression.
-------------------------------------------------Many drugs can cause involuntary weight loss
by inducing anorexia, dysgeusia, GI symptoms,
dry mouth, confusion or inattention, or
movement disorder.
Medication list should be reviewed with
attention to anticholinergic agents, digoxin,
anti-parkinsonian agents, iron & potassium
supplements, aspirin & NSAIDs, opiates,

antidepressants (bupropion, fluoxetine), thyroid


hormone supplementation, & hypoglycemic
agents (metformin, exenatide).
-------------------------------------------------Psychiatric disorders are common causes of
involuntary weight loss among patients who
do not have a physical cause for weight loss.
-------------------------------------------------Among patients with involuntary weight loss,
lack of focal symptoms & negative baseline
evaluation predict the absence of malignancy.
The most appropriate management step is to
re-evaluate the patient in 6 months.
-------------------------------------------------Stomal stenosis (stricture at the anastomosis
of the gastric pouch & jejunum) presents with
nausea, vomiting, & inability to eat.
Barium swallow or upper endoscopy can
establish the diagnosis.
-------------------------------------------------Stomal stenosis is a cause of persistent nausea
& vomiting occurring within the first few
months after gastric bypass surgery.
Undergo upper endoscopy to rule out a
complication, especially stomal stenosis or
marginal ulcerations or erosions.
If a stricture is diagnosed at the time of
endoscopy, endoscopic dilation of the
stricture results in relief of symptoms without
the need for repeat surgery.
-------------------------------------------------A RUQ ultrasound would be useful for the
diagnosis of biliary colic.
Gallstones are very common after gastric
bypass surgery with rapid weight loss.
-------------------------------------------------Sulfonylureas (glipizide) is a/w weight gain.
Insulin is also a/w weight gain.
------------------------------------------------Pharmacologic treatment may be considered
when obese patients fail to lose weight after
an adequate trial of diet & exercise &
treatment of contributing comorbidities.

The best management is to add a weight loss


medication such as orlistat with meals, with
continued encouragement of diet & exercise.
-------------------------------------------------A sleep study may be indicated to confirm
sleep apnea in patients with daytime fatigue,
somnolence, HTN, or history of snoring.
-------------------------------------------------All patients with a BMI > 25, obtain a blood
glucose level, serum creatinine, & fasting lipid
profile (HDL, triglycerides, LDL) to assess for
obesity-associated conditions.
-------------------------------------------------Abnormal waist circumference (>40 in [102
cm] for males or >35 in [88 cm] for females)
is a measure for central obesity, a surrogate
estimate for visceral fat.
Visceral fat is a more metabolically active fat
that releases free fatty acids into the portal
system, which contributes to hyperlipidemia,
hyperinsulinemia, & atherogenesis.
BMI has a good correlation with risks a/w
obesity & body fat, such as diabetes mellitus,
heart disease, osteoarthritis, gallbladder
disease, GERD, & certain types of cancer.
-------------------------------------------------Bariatric surgery should be considered for
patients with BMI of 35 or greater & serious
obesity-related medical comorbidities (HTN,
diabetes, dyslipidemia, CAD, or sleep apnea)
or BMI of 40 or greater without
comorbidities in whom weight loss attempts,
including drug therapy, were unsuccessful.
-------------------------------------------------Surgery may be recommended to persons with
progressive obesity, such as continuing weight
increases of more than 5 kg/yr before age 30.
-------------------------------------------------For smoking cessation, bupropion &
nortriptyline appear to be equally effective &
of similar efficacy to nicotine replacement
therapy but less effective than varenicline.
--------------------------------------------------

Adverse effects of bupropion include


insomnia, dry mouth, nausea & serious
psychiatric symptoms, including risk of
seizures.
-------------------------------------------------Nicotine replacement therapy should not be
combined with varenicline; the combination
may increase the risk of nausea, vomiting,
headache, dizziness, & other adverse effects.
-------------------------------------------------Varenicline would be the best alternative to
nicotine replacement therapy.
Varenicline for 12 weeks increased the odds of
long-term smoking cessation threefold
compared with placebo. The main side effect
was nausea, which subsides over time.
-------------------------------------------------Risk of a cardiovascular event is reduced
within 5 years of smoking cessation in women.
-------------------------------------------------Women who are current smokers have a
threefold higher risk of cardiovascular disease
compared with women who have stopped
smoking or have never smoked.
Duration of smoking does not correlate with
risk of future cardiovascular disease.
-------------------------------------------------Smoking cessation is a/w a decreased rate of
decline in lung function.
-------------------------------------------------COPD findings include pulmonary function
results FEV1 <80% & FEV1/FCV <0.7.
-------------------------------------------------Smoking cessation is the single most effective
intervention to reduce the risk of developing
COPD & stop its progression.
-------------------------------------------------Short-term tobacco dependence treatment is
effective; every tobacco user should be offered
counseling & nicotine replacement (patch,
gum, inhaler, & nasal spray) at every visit.

Counseling should focus on establishing a quit


date, emphasizing abstinence, using family
members, & avoiding alcohol & other drugs.
-------------------------------------------------A CXR is not indicated in acute bronchitis
without signs or symptoms of pneumonia,
such as fever, dyspnea, & pleuritic chest pain.
-------------------------------------------------Antibiotics are appropriate for patients with
pertussis to decrease disease transmission,
although these agents have a limited effect on
symptoms.
Pertussis should be suspected when a
community outbreak has been reported.
Symptoms include coughing paroxysms &
post-tussive vomiting but are not reliable
indicators of infection.
-------------------------------------------------In patients with an acute COPD exacerbation,
antibiotic therapy is most likely to be helpful
in those with at least two of the following:
increased sputum purulence (change in color),
increased sputum volume, or increased
dyspnea.
-------------------------------------------------50% of patients with acute bronchitis have
purulent sputum, but this is not a reliable
predictor of bacterial infection.
Most studies fail to show that antibiotics, such
as azithromycin, significantly improves
outcomes, including symptom resolution &
early return to work.
-------------------------------------------------Treatment of acute bronchitis is symptomatic.
Albuterol may decrease cough severity &
duration in adults with acute bronchitis when
there is evidence of wheezing.
There is no evidence to support the use of
most OTC & prescription antitussives.
NSAIDs, with or without an antihistamine,
may decrease cough severity. A trial of
ibuprofen may be reasonable.
--------------------------------------------------

All patients with hemoptysis should have a


CXR; patients at high risk for lung cancer
should be referred for chest CT & fiberoptic
bronchoscopy even if CXR is normal.
-------------------------------------------------Sputum cytology exam alone is not effective
in early diagnosis of lung cancer because of
low sensitivity.
-------------------------------------------------Patients with hemoptysis should have a CXR.
The most common causes of hemoptysis in
ambulatory patients are infection (bronchitis,
pneumonia) & malignancy.
Risk factors that increase the risk of
malignancy include male sex, age older than
40 years, smoking history of > 40 pack-years,
& symptoms lasting for more than 1 week.
These patients should be referred for chest CT
& fiberoptic bronchoscopy even if CXR is
normal.
-------------------------------------------------Use chest CT to evaluate a patient with
hemoptysis for lung cancer.
Patients with chronic cough & normal CXR,
chest CT is only indicated for those at high
risk for lung cancer.
-------------------------------------------------Asthma & nonallergic eosinophilic bronchitis
may present without any symptoms other than
cough.
-------------------------------------------------Spirometry would be indicated in the
evaluation of chronic cough that has not
resolved after the initial management
measures (history, physical exam, CXR,
cessation of ACE inhibitor, treatment for upper
airway cough syndrome).
-------------------------------------------------Upper airway cough syndrome (UACS) is a
common cause of chronic cough.
A trial of 1st -generation
antihistamine/decongestant combination for
several weeks is appropriate.

In a nonsmoking patient who is taking an ACE


inhibitor, the ACE inhibitor should be
discontinued for several weeks before treating
for UACS; median time to resolution is 26
days from withdrawal of the ACE inhibitor.
-------------------------------------------------A cough of longer than 8 weeks meets the
definition for chronic cough.
Initial evaluation includes a history & physical
exam to determine likely etiologies, followed
by a CXR to identify obvious abnormalities.
If CXR is normal, discontinue ACE inhibitors
& smoking, if these factors are identified,
pursue empiric management of chronic cough
for nonsmoker & not taking an ACE inhibitor.
-------------------------------------------------Patients with chronic cough, normal CXR
findings, normal spirometry, & negative
methacholine challenge test, the diagnosis of
non-asthmatic eosinophilic bronchitis
(NAEB) should be considered.
This diagnosis is considered after patients fail
to respond to treatments directed at UACS,
GERD, & asthma.
Although confirmation of NAEB requires a
bronchial biopsy, response to empirically
administered inhaled corticosteroids is often
used to establish the diagnosis.
-------------------------------------------------Empiric management for chronic cough with
first-generation antihistamine/decongestant
combination to treat UACS; even in the
absence of evidence of a postnasal drip.
Diagnosis of chronic cough is often based
upon the patient's response to empiric therapy,
& may take weeks or even months for the
cough to resolve with appropriate therapy.
-------------------------------------------------Patients who do not smoke, not taking an ACE
inhibitor, with a normal CXR, upper airway
cough syndrome (UACS) (previously termed
postnasal drip), asthma, & GERD are

responsible for 99% cases of chronic cough.


-------------------------------------------------Initiate empiric management for chronic
cough with antihistamine/decongestant
combination.
-------------------------------------------------Diagnosis of cough-variant asthma is
suggested by the presence of airway
hyperresponsiveness & confirmed when cough
resolves with a trial of inhaled albuterol.
If the patient does not respond to albuterol,
eosinophilic bronchitis should be considered
as the cause of chronic cough, &
bronchoscopy with biopsy should be
performed to confirm the diagnosis.
-------------------------------------------------The most common causes of chronic cough
are asthma, postnasal drip syndrome (chronic
sinusitis-rhinitis), & GERD.
Bronchoscopy & chest CT play no role in
diagnosing cough due to these three causes.
------------------------------------------------Diagnose cough-variant asthma with a trial
of inhaled albuterol.
-------------------------------------------------The triad of back pain, muscle weakness, &
loss of bowel or bladder control suggests
spinal cord compression.
The three most common malignancies
responsible for spinal cord compression are
prostate, breast, & lung cancer.
This patient most likely has spinal cord
compression due to bone metastases from
recurrent prostate cancer.
-------------------------------------------------Clinicians should have a low threshold of
suspicion for spinal cord compression in a
patient with known cancer or a risk for
recurrent cancer. The absence of neurologic
findings should not alter that strategy.
Patients whose cord compression is discovered
after developing neurologic deficits are more
likely to remain functionally impaired after

intervention.
-------------------------------------------------Spinal cord compression is an oncologic
emergency, & thoracolumbar spine MRI is
needed to confirm the diagnosis & assist in
treatment planning.
-------------------------------------------------Initial symptom in patients with epidural
spinal cord compression due to tumor usually
has spinal or radicular pain that may precede
the onset of neurologic symptoms, including
weakness, numbness, or sphincter disturbances
-------------------------------------------------This patient has acute low back pain resulting
from a recent injury. He has no signs of
neurologic compromise or potentially serious
underlying conditions.
Acetaminophen or NSAIDs are first-line
treatment of acute nonspecific low back pain.
An opioid analgesic or tramadol is an option
when used judiciously in patients with severe,
disabling acute low back pain that is not
controlled (or unlikely to be controlled) with
acetaminophen or NSAIDs.
Prognosis for acute low back pain is generally
good & most patients improve within 1 month.
-------------------------------------------------Lumbar plain radiographs are generally not
recommended in evaluation of nonspecific low
back pain because there is no evidence that
routine plain radiography is a/w greater
outcome improvement than selective imaging.
-------------------------------------------------Acetaminophen or NSAIDs are first-line
therapy for acute nonspecific low back pain.
-------------------------------------------------Vertebral osteomyelitis is most often
disseminated hematogenously.
Segmental arteries supply blood to the
vertebrae, with bifurcating arteries supplying
blood to the inferior margin of one end plate &
the superior margin of the adjacent end plate.

When infection occurs, it generally follows


this vascular pattern, involving bone in two
adjacent vertebral bodies with invasion into
the intervertebral disk (diskitis).
Potential sources of hematogenous
osteomyelitis include skin (injection drug
users), UTI, or RTI; endocarditis; or
intravascular catheter-related infection.
Patients with infectious diskitis are at risk for
spinal epidural abscess.
-------------------------------------------------MRI is the preferred imaging modality for
suspected vertebral osteomyelitis, diskitis, or
spinal epidural abscess.
MRI can show changes of acute osteomyelitis
within days of infection, & superior to plain
films & CT scans; can detect soft tissue
abscesses & epidural, paravertebral, or psoas
abscesses possibly requiring surgical drainage;
& delineate anatomy before surgery.
-------------------------------------------------Blood cultures are positive in up to 75% of
patients with vertebral osteomyelitis, should
be obtained for suspected cases.
-------------------------------------------------"Red flags" suggesting a systemic illness as
the cause of back pain include localized pain,
history of IV drug use, fever, & elevated ESR.
These findings strongly suggest the possibility
of vertebral osteomyelitis, infectious diskitis,
or spinal epidural abscess.
Most patients with vertebral osteomyelitis
have back or neck pain that gradually worsens
over weeks or months; fever is present in only
50% & leukocytosis is typically absent, but the
ESR is often greater than 100 mm/h.
TTP over the involved spine is common.
-------------------------------------------------Back pain & neurologic impairment from
spinal stenosis may be treated with surgery.
In considering surgical treatment for patients
with back pain from radiculopathy or spinal
stenosis, guidelines recommend referring

patients after a minimum of 3 months to 2


years of failed nonsurgical interventions.
Failure is defined as progressive neurologic
deficits & severe pain that is not responsive to
conservative treatment.
-------------------------------------------------With a cutoff of two positive answers, the
CAGE questionnaire is 94% sensitive & 97%
specific for detecting alcohol abuse or
dependence in primary care settings &
indicates that further assessment is warranted.
-------------------------------------------------Traditional therapy for cyanide poisoning
includes inhalation of amyl nitrite followed
by the administration of IV sodium nitrite or
sodium thiosulfate.
Cyanide poisoning results from inhalation of
gaseous hydrogen cyanide or the ingestion of
potassium or sodium cyanide.
Hydrogen cyanide poisoning is also common
as a result of smoke inhalation from fires.
Ingestion of cyanide is most often a/w suicides
& homicides.
Inhalation results in seizures, coma, &
cardiopulmonary arrest. Chronic exposure to
low levels results in weakness & paralysis.
-------------------------------------------------Intravenous fomepizole is an effective
treatment for ethylene glycol & methyl alcohol
poisoning. These alcohols cause an anion gap
metabolic acidosis & osmolar gap.
-------------------------------------------------Benzodiazepines, such as diazepam, can be
used to treat cocaine toxicity, characterized by
HTN, tachycardia, hyperthermia, mydriasis, &
agitation.
-------------------------------------------------The patient's acute ventilatory failure is most
consistent with hypoventilation resulting from
opioid intoxication. In pure hypoventilation,
the alveolar-arterial difference is normal.
Improved alertness after administration of
naloxone confirms opioid intoxication.

Naloxone has a short half-life & given as a


continuous intravenous infusion. If the
response to naloxone is inadequate,
intubation would be appropriate.
--------------------------------------------------

Manage hypoventilation caused by opioid


overdose with naloxone.
-------------------------------------------------Disulfiram leads to an accumulation of
aldehyde if alcohol is consumed, resulting in
vomiting, headache, & anxiety. Studies are
inconclusive on its efficacy in abstinence.
-------------------------------------------------Naltrexone, an opioid receptor antagonist, has
been shown to be effective in short-term
treatment of alcohol dependence & decreasing
frequency of relapse.
Benzodiazepines, diazepam, would be used in
acute alcohol detoxification.
-------------------------------------------------Manage alcohol dependence with naltrexone.
-------------------------------------------------This patient's sympathomimetic syndrome is
consistent with cocaine intoxication. Clinical
findings include tachycardia, HTN, mydriasis,
hyperthermia, agitation, & psychosis.
------------------------------------------------Initial treatment of acute cocaine intoxication
is sedation with a benzodiazepine, lorazepam,
administered intravenously or intramuscularly.
Control of agitation usually brings about a
decrease in HR, BP, & temperature.
Intravenous fluids should be administered to
establish adequate urine output for possible
rhabdomyolysis, & EKG should be obtained
to assess for myocardial ischemia. Lab studies
should include electrolytes & serum creatine
kinase & liver function.
CT scan of the brain may be indicated to rule
out intracranial injury.
-------------------------------------------------

Haloperidol is not initially indicated for


control of agitation in cocaine abuses.
Haloperidol has the potential to lower the
seizure threshold & would not be an initial
treatment in a patient who has had a seizure.
After agitation is controlled, haloperidol can
be considered if the patient manifests
psychotic features.
-------------------------------------------------Benzodiazepines are the drug of choice for
prophylaxis of alcohol withdrawal seizures.
-------------------------------------------------Patients with alcohol withdrawal syndrome
who are treated with benzodiazepines have
fewer complications, including delirium
tremens & alcohol-withdrawal seizures.
Longer acting agents (chlordiazepoxide or
diazepam) may be more effective in
preventing seizures but risk of excess sedation
in older adults & patients with liver disease.
Patients with a history of seizures should
receive a prophylactic benzodiazepine on a
fixed schedule, even if asymptomatic during
the acute alcohol withdrawal period.
-------------------------------------------------Clinicians should identify the severity of
alcohol withdrawal & factors that may
predict the onset of serious complications.
The 10-item Clinical Institute Withdrawal
Assessment Scale for Alcohol, Revised, can be
used to measure symptom severity & help
provide guidance in the course of treatment.
Patients scoring > 10 points usually need
additional medication for withdrawal, &
patients scoring > 15 points are typically
hospitalized to manage alcohol withdrawal.
Benzodiazepines are first-line therapy for
patients who require prophylaxis or treatment
for alcohol withdrawal.
-------------------------------------------------Bipolar disorder presents with episodes of
mania or hypomania.

Criteria for mania include a distinct period of


abnormally & persistently elevated, expansive,
or irritable mood lasting at least 1 week.
Symptoms include inflated self-esteem or
grandiosity, decreased need for sleep,
distractibility, increased goal-directed
behavior, & excessive involvement in
pleasurable activities that have a high potential
for consequences (buying sprees, sexual
indiscretions).
Ask depressed patients about a personal &
family history of manic symptoms in order to
select an appropriate therapy.
-------------------------------------------------A history of self-harm, dysfunctional
relationships, or intense anger suggests
borderline personality disorder.
-------------------------------------------------20% & 30% of spouses experience depression
or complicated grief after loss of a loved one.
Most negative symptoms of bereavement
peak before 6 months, & most are able to
resume social activities & other activities of
daily living by 6 months.
------------------------------------------------Major depression in the setting of
bereavement cannot be diagnosed unless the
symptoms persist for more than 2 months or
include substantive functional impairment,
morbid preoccupation with worthlessness,
suicidal ideation, psychotic symptoms, or
psychomotor retardation.
-------------------------------------------------Patients who meet symptoms of major
depression for at least 2 consecutive weeks,
8 or more weeks after their loved one's death
are candidates for pharmacologic therapy.
Mirtazapine would be an appropriate initial
choice because it is an effective antidepressant
& side effects of sedation & weight gain
Weight gain may be advantageous in a
depressed patient with weight loss.
-------------------------------------------------

Major depression is characterized by the


presence of at least five of the nine criteria for
this disorder, including at least one of the two
hallmark features of depressed mood &
anhedonia.
The nine depressive symptoms are as follows:
sleep disturbance, psychomotor agitation or
retardation, appetite disturbance, concentration
impairment, low energy level, depressed
mood, lost interest in activities, guilt or
worthlessness, & suicidal ideation.
-------------------------------------------------Patients with suicidal ideation & a plan
should be urgently referred to a psychiatrist or
hospitalized for psychiatric assessment.
Patients with good social support can likely be
safely referred to a psychiatrist for
management.
-------------------------------------------------Manage a patient with depression with suicidal
features with an urgent mental health referral.
-------------------------------------------------The goal of depression therapy should not be
simply improvement of symptoms but rather
remission of depressive symptoms.
Patients with no response to full-dose therapy
within 6 weeks should receive another
medication or referral for psychotherapy.
STAR*D trial found that 25% of patients with
major depression who did not respond to an
initial antidepressant achieved remission when
another agent was substituted.
-------------------------------------------------Both citalopram & sertraline are SSRIs; the
STAR*D trial reported identical responses
when one SSRI was substituted for another or
when an SSRI was changed to an
antidepressant from a different class.
-------------------------------------------------Electroconvulsive therapy is reserved for
situations warranting immediate change &
should be considered if profound suicidal
ideation or psychotic features are present or

if the patient fails to respond to multiple


antidepressants.
------------------------------------------------Causes of syncope include neurocardiogenic
(vasovagal) syncope, bradyarrhythmia,
tachyarrhythmia, outflow tract obstruction, &
seizures.
The next step is monitoring for an arrhythmia.
The gold standard for diagnosis of an
arrhythmic cause of syncope is documentation
of a rhythm disturbance at the time of
symptom occurrence.
The choice of monitoring test should be
related to the frequency of the symptoms.
This patient has recurrent, infrequent events;
therefore, an implantable loop recorder
would be most likely obtain useful findings.
Implanted loop recorders record patientactivated events & automatically records
bradycardic & tachycardic events; it is less
prone to acquisition errors.
-------------------------------------------------Evaluate recurrent syncope with an
implantable loop recorder.
Event monitors are complex enough in their
use that patient acquisition errors can occur,
rendering the results less reliable.
-------------------------------------------------Sudden loss of consciousness irrespective of
body position & lack of preceding symptoms
suggest the possibility of cardiac arrhythmia.
-------------------------------------------------Neurocardiogenic (vasovagal) syncope is one
of the most common types of syncope where
triggers lead to increased parasympathetic
tone, causing a drop in heart rate & BP
(cardioinhibitory response); decreased
sympathetic tone, causing vasodilation &
hypotension (vasodepressor response); or a
combination of the two.
The increased vagal tone seen in
neurocardiogenic syncope typically causes a

prodrome of nausea, diaphoresis, & pallor.


-------------------------------------------------Syncope a/w aortic stenosis is usually a/w
exertion.
-------------------------------------------------Three major groups of disorders cause
syncope of cardiac origincardiac outflow
obstruction, arrhythmias, & cardiac ischemia.
Causes of obstructed cardiac output leading to
syncope include severe aortic stenosis,
hypertrophic obstructive cardiomyopathy, &
pulmonary embolism.
-------------------------------------------------In patients with trifascicular block,
permanent pacer implantation is recommended
for intermittent third-degree AV block, type II
second-degree AV block, & alternating bundle
branch block.
A pacer is not indicated for asymptomatic
trifascicular block.
-------------------------------------------------The first principle of diagnosis of a suspected
cardiac arrhythmia is to record the abnormal
rhythm. The best approach in this patient is an
implantable loop recorder that continuously
records the EKG & allows the patient to save
the previous 30 seconds to 2 minutes
(adjustable) after regaining consciousness.
-------------------------------------------------This 57-year-old man has had three episodes
of syncope in the past 6 months. His forehead
bruise is a classic sign of syncope due to
heart block, with the sudden loss of
consciousness & lack of preceding symptoms
resulting in falling & injury.
-------------------------------------------------Diagnose intermittent complete heart block
as the cause of recurrent syncope.
-------------------------------------------------The patient's history is consistent with
vasovagal (neurocardiogenic) syncope on
the basis of the history of prolonged standing

& prodromal symptoms of nausea, diaphoresis


& lightheadedness.
These presyncopal warning symptoms are
highly sensitive for the diagnosis of vasovagal
syncope if lasting more than 10 seconds.
Brief myoclonic jerking after losing
consciousness is not unusual with syncope,
especially vasovagal syncope.
In addition, normal physical exam findings,
normal EKG, & lack of orthostasis all point
toward vasovagal syncope.
The best management option for this patient is
no further testing.
-------------------------------------------------If the cause of syncope is unexplained from
the initial evaluation, continuous telemetry is
used to screen for paroxysmal arrhythmias.
If symptoms are infrequent, an event monitor
or loop recorder should be used.
If symptoms are frequent, 24-hour ambulatory
monitoring may be useful to exclude
arrhythmia as a cause of symptoms.
-------------------------------------------------Orthostatic hypotension is a frequent cause
of syncope & presyncope defined as a systolic
BP decrease of at least 20 mm Hg or a
diastolic BP decrease of at least 10 mm Hg
within 3 minutes of standing.
Patients with orthostatic hypotension should
be educated to avoid rising to standing
positions quickly, wear elastic support hose, &
avoid volume depletion & large meals.
-------------------------------------------------Orthostatic hypotension is classified into
medication-induced, neurogenic, &
nonneurogenic categories.
Diseases causing neurogenic orthostatic
hypotension are diabetic or alcoholic
polyneuropathy, multiple sclerosis, & multiple
systems atrophy.
Common medications a/w orthostatic
hypotension include -adrenergic blockers,

nitrates, diuretics, phosphodiesterase


inhibitors, & antidepressants.
Nonneurogenic orthostatic hypotension may
be caused by disorders such as adrenal
insufficiency, venous pooling, or volume
depletion from an acute medical illness.
-------------------------------------------------Patients with diabetic autonomic neuropathy
experience symptoms of dizziness due to
standing-induced hypotension.
-------------------------------------------------Situational syncope is a neurocardiogenic
reflex mediated in response to a stimulus,
typically coughing, micturition, or defecation.
-------------------------------------------------The patient's cardiac history, lack of
presyncopal prodrome, & head laceration
suggest cardiac arrhythmia as the cause of
syncope.
Ventricular tachycardia (VT) is the most
feared cause of syncope because its tendency
to recur, & cause of sudden cardiac death.
VT is most commonly seen in patients with
advanced systolic heart failure & underlying
ischemic heart disease.
Myocardial scarring from a previous MI can
serve as the reentrant focus for ventricular
arrhythmias.
-------------------------------------------------Screening for colorectal cancer is cost
effective & well tolerated; it also saves lives
because the 10 to 15 years needed for a polyp
to develop into cancer are sufficient time to
detect & remove an adenoma.
-------------------------------------------------Average risk for colorectal cancer includes
persons with no personal or family history of
colon adenoma or cancer & who do not have a
condition that predisposes them to cancer,
such as inflammatory bowel disease.
--------------------------------------------------

Screen a patient at average risk for colon


cancer with colonoscopy every 10 years.
-------------------------------------------------Starting at the age of 50 years, average-risk
patients should be offered several methods of
screening, because personal preference &
insurance coverage variations may render
some methods more appropriate than others.
Sensitivity & specificity may vary among the
different screening methods, but it is more
important to choose & follow a screening
program than concern about which method.
Screening methods include structural tests
(colonoscopy & sigmoidoscopy) that can
accomplish both detection & prevention
(identification & removal of precursor lesions)
& stool-based tests (FOBT), which detect
existing cancers &, to a lesser degree, polyps.
Annual home high-sensitivity FOBT,
sampling two to three consecutive specimens,
is a screening method if the patient is willing
to undergo colonoscopy if results are positive.
Other screening programs include
o colonoscopy every 10 years
o flexible sigmoidoscopy every 5 years
combined with annual high-sensitivity
FOBT every 3 years.
Annual rectal exam with office FOBT is not
considered adequate screening for colorectal
cancer because of poor sensitivity.
-------------------------------------------------Screen for colorectal cancer with annual
home high-sensitivity FOBT; colonoscopy if
results are positive.
-------------------------------------------------HPV vaccine for cervical cancer prevention
for all females between ages 9 & 26 years
regardless of sexual activity.
The vaccine has high success in preventing
infections with HPV strains which cause most
cases of genital warts & cervical cancer.
The vaccine does not protect against all types
of HPV, so women should continue to get

regular Pap smears.


-------------------------------------------------Tetanus booster vaccination (Tdap) can be
omitted in patients who received a tetanus
booster within the past 5 years & patients
with clean minor wounds who have received
vaccination within the past 10 years.
-------------------------------------------------Tetanus immune globulin is indicated for
patients who have not completed the primary
series of tetanus immunizations or in patients
who have an unclear immunization history.
-------------------------------------------------All patients evaluated for wounds should have
their tetanus vaccination status reviewed.
Most patients who develop tetanus are not
completely vaccinated. If there is any doubt
about a patient's vaccination history, the
complete series should be administered.
The first & second dose should be separated
by 4 weeks, & third dose should be given 6 to
12 months later.
Because susceptibility to tetanus & diphtheria
often co-exist, both tetanus & diphtheria
toxoid (Td) should be administered, not just
tetanus toxoid alone.
Tetanus-diphtheria toxoid & acellular pertussis
(Tdap) vaccine should be used in place of one
of the Td vaccinations in adults age 19 to 64
years who have not received their single
booster dose of this vaccine.
-------------------------------------------------Zoster vaccine can be given concomitantly
with all other live & inactivated vaccines,
including influenza & pneumococcal vaccine.
Zoster vaccine is given as a single
subcutaneous dose.
A booster is not recommended.
-------------------------------------------------Zoster vaccine is a live attenuated vaccine &
contraindicated with active, untreated TB,
immunocompromised, & patients receiving

chemotherapy, radiotherapy, or large doses of


corticosteroids.
Immunization should be avoided if an
immunocompromised person is in the
household.
-------------------------------------------------Zoster vaccine is indicated in
immunocompetent patients older than 60 years
for prevention of herpes zoster (shingles).
Live attenuated zoster vaccine in adults 60
years or older reduces the incidence of herpes
zoster & postherpetic neuralgia.
Zoster vaccine is more efficacious in
preventing herpes zoster among adults 60 to
69 years of age than those 70 years or older.
Zoster vaccine prevents postherpetic neuralgia
to a greater extent among adults aged 70 years
or more.
-------------------------------------------------Immunize a patient with a previous history of
herpes zoster with the zoster vaccine.
-------------------------------------------------Cancer-specific mortality is the best end
point for measuring the effect of cancer
screening on patient outcomes.
-------------------------------------------------A single revaccination with pneumococcal
vaccine is recommended in adults older than
65 years if they were vaccinated more than 5
years previously at a time when they were less
then 65 years of age & immunosuppressed
patients 5 years or more after the first dose.
Patients with COPD who received their first
pneumococcal vaccination after age 65 years
do not need revaccination.
Pneumococcal vaccination is recommended
for younger patients who are active smokers or
have COPD, asthma, & disorders that increase
the risk for invasive pneumococcal disease.
-------------------------------------------------Immunize a patient with COPD against
influenza with trivalent killed vaccine.
--------------------------------------------------

The main influenza vaccine used is a trivalent


inactivated virus, but an intranasally
administered vaccine from a trivalent live
attenuated virus is also available for patients
age 5 to 49 years who are not pregnant,
immunosuppressed, or living with an
immunosuppressed person.
-------------------------------------------------Influenza vaccination is recommended for
pregnant women whose last two trimesters
coincide with the influenza season (late
December through mid-March)
-------------------------------------------------Annual influenza vaccination is recommended
in patients with COPD, regardless of age.
-------------------------------------------------Screening EKGs are not recommended
because abnormalities of the resting EKG are
rare, not specific for coronary artery disease,
& do not predict subsequent mortality from
coronary disease.
-------------------------------------------------Pneumococcal vaccine is a/w substantial
reductions in morbidity & mortality among the
elderly & high-risk adults & is, therefore,
recommended for all adults aged 65 years &
older or with other risk factors (diabetes,
cirrhosis, asplenia).
Patients who receive their initial vaccine at
younger than 65 years of age should receive a
second dose after 5 years.
One-time revaccination is also recommended
in 5 years for patients with chronic kidney
disease, asplenia, cancer or immunosuppressed
------------------------------------------------Women aged 65 years & older should be
screened routinely for osteoporosis &
beginning at age 60 years for women at
increased risk for osteoporotic fractures.
-------------------------------------------------One-time screening for AAA with
ultrasonography is recommended for all men
aged 65 to 75 years who have ever smoked.

Ultrasound identification & repair of AAA


larger than 5 cm in diameter reduces AAArelated mortality in older men.
Death from AAA rupture is rare after a single
normal screening test & repeat screening in
these persons is not recommended.
-------------------------------------------------The receiver operating characteristic (ROC)
curve is a visual representation of the true
positive rate (sensitivity) plotted as a function
of the false positive rate (1.0-specificity) for
different cut points.
A test with the best sensitivity & specificity
for each of its cut points will have a curve that
"crowds" the upper left margins of the curve.
This concept is particularly valuable when
comparing two or more tests. The test with the
greatest overall accuracy will have the
largest area under the ROC curve.
-------------------------------------------------Positive likelihood ratios of 2, 5, & 10
increase the probability of disease by 15%,
30%, & 45%, respectively.
-------------------------------------------------The likelihood ratio (LR) of a test is the
proportion of patients with the disease who
test positive divided by the proportion without
the disease who also test positive.
The numerator is the test's sensitivity; the
denominator is the false-positive rate.
LRs can be used to approximate the
probability of disease after a test is performed
Three associations must be remembered:
positive LRs of 2, 5, & 10 increase the
probability of disease by 15%, 30%, & 45%,
respectively.
An appendiceal CT scan has a positive LR for
appendicitis of 13.3; therefore, if the pretest
probability of appendicitis was 50%, a positive
scan result increases the probability for disease
by roughly 45%, resulting in a posttest
probability of 95% (45% added to the 50%

pretest probability of disease).


-------------------------------------------------Predictive values address the chance of disease
given a positive or negative test result & are
based on the prevalence of disease in the
population being tested; therefore, predictive
values change as the populations vary.
As the prevalence of disease decreases
(prevalence in the community compared with
that in an experiment), the positive predictive
value decreases & negative predictive value
increases. The opposite is true if the disease
prevalence increases.
------------------------------------------------Sensitivity & specificity are test characteristics
that do not change as populations vary.
Likelihood ratios are based on sensitivity &
specificity; do not change as populations vary.
-------------------------------------------------A highly sensitive test reduces the probability
of missing the diagnosis.
Because a highly sensitive screening
identifies most patients with the condition, a
negative screening test helps "rule out" the
diagnosis.
Highly sensitive tests often have a high falsepositive rate (positive test results in patients
without the disease). Therefore, a positive
screening test is usually followed by a highly
specific (& sometimes more invasive) test,
which often is the gold standard for the
diagnosis.
Because a highly specific test is negative in
patients without the disease, a positive test
helps "rule in" the diagnosis.
The concepts of sensitivity & specificity can
be remembered by "SpIN" & "SnOUT,"
indicating that a very specific test, when
positive, rules in a disease & highly sensitive
test, when negative, rules out disease.
-------------------------------------------------Sensitivity quantifies the percentage of
patients with disease (in this case, patients

with a positive prostate cancer biopsy) who


have a positive screening test.
Sensitivity is equal to a/(a + c).
Specificity quantifies the percentage of
normal patients (a negative biopsy for
prostate cancer) with a negative screening test.
Specificity is equal to d/(b + d).
-------------------------------------------------Positive predictive value (PPV) is calculated
as the true positive rate divided by all
positive test results.
--------------------------------------------------

V. Hematology

Presence of Auer rods confirms the myeloid


nature of acute myeloid leukemia (AML).
-------------------------------------------------Acute myeloid leukemia (AML) should be
considered when circulating blasts are present
in the peripheral blood smear.
Diagnosis of AML is confirmed by a bone
marrow aspirate showing hypercellular
marrow containing > 20 to 30% myeloblasts.
Auer rods are clumps of azurophilic, needleshaped crystals made from primary
cytoplasmic granules.
-------------------------------------------------Acute lymphoblastic leukemia (ALL)
typically has lymphocytosis, neutropenia,
anemia, thrombocytopenia, lymphadenopathy,
& hepatosplenomegaly at presentation.
An increased number of lymphoblasts found
on bone marrow exam are suspicious for the
diagnosis.
-------------------------------------------------The prototype of the myeloproliferative
syndromes, CML results from a balanced
translocation between chromosomes 9 & 22
[t(9;22), Philadelphia chromosome], which
creates the oncogene BCR-ABL which codes
a protein that functions as tyrosine kinase.
t(9;22) is diagnostic of CML & also the
causative genetic event & therapeutic target.
-------------------------------------------------Diagnosis of chronic myeloid leukemia
(CML) is based on the presence of the
BCR/ABL oncogene, peripheral blood smear
showing increased granulocytes with a marked
left shift, & hypercellular bone marrow with
marked myeloid proliferation.
A routine blood count shows leukocytosis
with circulating myeloid precursors in all
stages of development.
--------------------------------------------------

Acute promyelocytic leukemia (APL) is a


subtype of AML that accounts for 10% of
patients with AML.
The disorder is exquisitely sensitive to
anthracycline cytotoxic therapy.
The addition of all-trans-retinoic-acid
(ATRA) & arsenic trioxide to the therapy has
resulted in high cure & salvage rates.
Patients with APL may have circulating blasts,
but the predominant cell is a large immature
granulocyte with multiple granules overlying
the cytoplasm & nucleus.
-------------------------------------------------Myelodysplastic syndromes are clonal
disorders of hematopoietic stem cells in
patients older than 50 years, characterized by
ineffective hematopoiesis & peripheral
cytopenia.
The natural history of distinct subtypes of
myelodysplasia ranges from indolent chronic
anemia to rapid death from progression to
acute leukemia, most patients eventually
progress to leukemic syndromes or die from
complications of bone marrow failure.
Patients with myelodysplastic syndrome
treated with azacitidine have significantly
delayed transformation to leukemia &
improved quality of life.
-------------------------------------------------Chronic myeloid leukemia (CML) is
recognized by an elevated leukocyte count &
increased numbers of granulocytic cells in all
phases of development on peripheral blood
smear.
Very immature cells or blasts represent 1% to
5% of the granulocytes, with increasing
numbers of promyelocytes, myelocytes, &
metamyelocytes.
CML is usually discovered incidentally.
-------------------------------------------------Acute myeloid leukemia (AML) typically
presents with severe pancytopenia &
circulating myeloid blasts.

Infection & bleeding are common presenting


problems of patients with AML.
Fever in patients with AML is almost always
related to infection; the patient must be
evaluated for a source of infection & treated
empirically with broad-spectrum antibiotics.
-------------------------------------------------Acute lymphoblastic leukemia (ALL) is an
extremely aggressive disease of precursor T
or B cells that is usually of explosive onset.
Rapidly rising levels blast cells in the blood &
bone marrow, bulky lymphadenopathy (in the
mediastinum), younger age at onset, &
cytopenia secondary to bone marrow
involvement are the usual presenting features.
-------------------------------------------------Chronic lymphocytic leukemia (CLL) is
characterized by abnormal accumulation of
morphologically mature-appearing
lymphocytes with immunophenotypes
(CD5+, CD20+, & CD23+ B cells) in the
blood, bone marrow, or lymphatic tissues.
Diagnosis is by flow cytometry to avoid the
need for bone marrow aspiration or biopsy.
CLL occurs after age 40 years, with
increasing frequency in successive decades.
CLL is often found incidentally on routine
blood workup as a lymphocytosis without
other evident disease.
-------------------------------------------------Major criteria for multiple myeloma include:
plasmacytoma on tissue biopsy; >30% clonal
plasma cells in bone marrow; high M-protein
levels (IgG >3.5 g/dL & IgA >2.0 g/dL; &
Bence Jones proteinuria (urine protein
excretion >1.0 g/24h).
Minor criteria include 10 to 30% plasma cells
in the bone marrow; M-protein level less than
3.5 g/dL; lytic bone lesions; & diminished
levels of non-monoclonal proteins.
Diagnosis is established with one major &
one minor criterion or three minor criteria.
--------------------------------------------------

AL (light-chain) amyloidosis is a monoclonal


plasma cell dyscrasia in which secreted
immunoglobulin is deposited as fibrils in
kidneys, heart, & peripheral nerves, thereby
producing progressive organ dysfunction.
Symptoms include fatigue, weight loss, &
easy bruising.
Kidney involvement produces nephrotic
syndrome with large amounts of non-lightchain proteinuria; azotemia develops late.
Cardiac involvement can be detected as
thickening of the septum & leads to heart
failure & arrhythmias.
Peripheral nerve involvement causes
sensorimotor neuropathy.
Detection of monoclonal immunoglobulin in
serum, blood, or tissues differentiates AL
amyloidosis from other forms of amyloidosis.
-------------------------------------------------Monoclonal gammopathy of undetermined
significance (MGUS) is characterized by the
presence of a low serum monoclonal protein
(M-protein) level (<3.0 g/dL), < 10% plasma
cells in the bone marrow, & absence of lytic
bone lesions, anemia, hypercalcemia, or renal
insufficiency a/w plasma cell proliferative
process or B-cell lymphoproliferative disorder.
Incidence of MGUS increases with age, &
persons older than 80 years may be affected.
No specific treatment is required, except for
close follow-up to identify progression to
myeloma & periodic of serum M-protein
measurement.
The risk of progression correlates best with the
M protein level: higher level = greater risk.
-------------------------------------------------Hypercalcemia, osteopenia, anemia,
leukopenia, renal insufficiency, & history of
encapsulated organism-related pneumonia
is characteristic of multiple myeloma.
Diagnosis is supported by the bone marrow
aspirate, showing clusters of plasma cells.

These cells can easily be distinguished from


megaloblastoid erythrocytes by their dispersed
chromatin pattern & perinuclear halo (Golgi).
-------------------------------------------------Decreased anion gap in the presence of
anemia, proteinuria, hypercalcemia, & renal
failure suggests multiple myeloma.
Acute kidney injury is the initial presentation
in many patients with multiple myeloma.
Except in multiple myeloma, hypercalcemia
in the presence of acute kidney injury is
relatively unusual because hyperphosphatemia
& decrease in renal 1- hydroxylation of 25hydroxycholecalciferol both act to predispose
to hypocalcemia.
-------------------------------------------------Factor V Leiden mutation results in
resistance to activated protein C.
Neither the factor V Leiden mutation nor the
prothrombin G20210A mutation is a/w
increased fetal loss.
------------------------------------------------Hyperhomocysteinemia is not a/w recurrent
fetal loss.
Hyperhomocysteinemia is a/w an increased
risk of venous & arterial thrombosis.
-------------------------------------------------Positive results for anticardiolipin antibody
or lupus inhibitor assay should be confirmed
over time to ensure that they are not transient,
which can occur after viral infections.
Two positive lab test at least 12 weeks apart
should be documented to confirm the presence
of an antiphospholipid antibody syndrome
before a patient is committed to lifelong
anticoagulation.
-------------------------------------------------Diagnosis of antiphospholipid antibody
syndrome requires a history of a thrombotic
event (including recurrent fetal loss) in a/w
persistent lupus anticoagulant or persistently
elevated levels of IgG anticardiolipin or 2glycoprotein I antibodies.

There is a strong correlation between these


antibodies & pregnancy loss, presumably due
to placental insufficiency secondary to
thrombosis.
-------------------------------------------------Treat a patient with antiphospholipid
antibodies after a first DVT with
anticoagulation indefinitely.
------------------------------------------------Absolute risk of new venous
thromboembolism (VTE) in patients with
antiphospholipid antibodies is low, < 1%/yr.
This risk may be increased to up to 10% per
year in women with antiphospholipid
antibodies or antiphospholipid antibody
syndrome & recurrent fetal loss & to > 10%
per year in patients with antiphospholipid
antibodies & previous VTE who have
discontinued anticoagulants within 6 months.
-------------------------------------------------Thrombophilic screening should be
performed a few weeks after completion of
therapy; not at the onset of a thrombotic event
nor during anticoagulant therapy.
-------------------------------------------------A patient with an idiopathic pulmonary
embolism & strong family history of VTE has
a high likelihood of having an underlying
thrombophilic condition.
Thus, test for activated protein C resistance,
prothrombin gene mutation, antiphospholipid
antibodies, factor V Leiden, antithrombin
deficiency, protein C deficiency, protein S
deficiency, & lupus inhibitor.
Screening for thrombophilia should not be
performed during anticoagulant therapy
because both heparin & warfarin will
influence the results. Neither should it be done
during the acute presenting episode before
anticoagulants are initiated because the
thrombosis may influence the results

Thrombophilia testing is best done a few


weeks after a course of therapy is completed.
-------------------------------------------------A healthy patient has petechiae caused by a
very low platelet count. Peripheral blood
smear showing few, but large platelets
supporting the presence of a young platelet
population, consistent with increased turnover.
These findings suggest immune
thrombocytopenic purpura (ITP)
Bone marrow exam is not essential.
A presumptive diagnosis of ITP should be
established; initiate high-dose corticosteroids.
-------------------------------------------------Corticosteroids are generally indicated in
patients with ITP who have symptomatic
bleeding & platelet counts < 50,000/L or
those with severe thrombocytopenia & platelet
counts < 15,000/L.
-----------------------------------------------Splenectomy is not indicated as first-line
therapy for ITP but may be considered when
other less-invasive therapies have failed.
-------------------------------------------------Initiate corticosteroids to manage ITP.
-------------------------------------------------Microangiopathic hemolytic anemia is
suggested by the presence of schistocytes
(erythrocyte fragments) on peripheral blood
smear, reticulocytosis, & elevated LDH.
-------------------------------------------------Immune thrombocytopenic purpura is a
disorder of platelet destruction caused by
antibodies reactive with platelet glycoproteins
(glycoprotein IIb-IIIa), platelet fibrinogen
receptor, & glycoprotein Ib.
Patients have isolated thrombocytopenia,
generally without splenomegaly or adenopathy
Peripheral blood smear shows only decreased
numbers but large (immature) platelets with
normal erythrocyte & leukocyte morphology.
--------------------------------------------------

Pseudothrombocytopenia is a condition in
which platelets agglutinate & clumped
platelets are not recognized as such by
automated blood counters.
Diagnosis is suspected by finding large
platelet clumps on a stained blood film.
If platelet clumping is observed, the platelet
count is repeated using an alternative
anticoagulant to EDTA, such as heparin or
sodium citrate.
-------------------------------------------------Thrombotic thrombocytopenic purpura
(TTP) has the principal triad:
microangiopathic hemolytic anemia
(schistocytes on the peripheral blood smear);
thrombocytopenia with normal coagulation;
& CNS symptoms.
The presence of renal failure & fever
compose the pentad of TTP findings.
------------------------------------------------Classic TTP occurs mainly in adults, &
pathogenesis is related to deficient von
Willebrand factor (vWF) cleavage.
Patients with TTP often have increased levels
of ultralarge vWF multimers (ULvWF),
which are active in binding to platelets &
inducing platelet agglutination.
ULvWFs are usually not present in the
circulation because cleavage of vWF
monomers by ADAMTS13.
A severe deficiency of ADAMTS13 has been
shown in most patients with TTP.
-------------------------------------------------Plasma exchange is the principal treatment
modality for TTP & should be initiated as
soon as possible to decrease patient morbidity.
-------------------------------------------------Heparin-induced thrombocytopenia (HIT)
should be considered in any patient with an
otherwise unexplained decrease in the platelet
count of at least 50% &/or new thrombotic
event 5 to 10 days after initiation of heparin.
--------------------------------------------------

Lepirudin & argatroban are direct thrombin


inhibitors that are the agents of choice for
treatment of HIT or HIT/T.
-------------------------------------------------Up to 2% of patients treated with heparin
(either unfractionated or low MW heparin)
develop heparin-induced thrombocytopenia
(HIT), & 30% of patients with HIT also
develop thrombosis (HIT/T).
-------------------------------------------------Diagnosis of HIT/T relies on platelet
activation or measures binding of antibodies
to PF4/heparin complexes.
14
C-serotonin release assay (SRA) is
considered the "gold standard" for diagnosis,
with a positive predictive value approaching
100% & NPV of 20%; therefore, negative
SRA does not exclude HIT/T.
-------------------------------------------------Patients with HIT/T have circulating antibodies
to platelet factor 4 (PF4)/heparin complexes.
-------------------------------------------------Gestational thrombocytopenia is the most
common cause of pregnancy-associated
thrombocytopenia.
These women have a mild thrombocytopenia
with platelet counts between 70,000/L 150,000/L & appears in late gestation.
-------------------------------------------------Strokes due to occlusion of a large vessel are
not uncommon in sickle cell disease & are an
indication for chronic blood transfusion
therapy to maintain peripheral blood
hemoglobin S level below 50%.
It is highly likely that this adolescent has
homozygous sickle cell disease & had
occlusion of a major vessel in the distribution
of the left middle cerebral artery causing right
hemiparesis & aphasia.
-------------------------------------------------Sickle cell disease commonly has target cells
with a "bull's-eye" appearance.
--------------------------------------------------

Iron deficiency anemia is a/w erythrocytes


that have increased central pallor & variation
in size (anisocytosis) & shape
(poikilocytosis).
-------------------------------------------------Radionuclide bone scan is typically reserved
for patients who have a contraindication for
MRI (metal implants).
-------------------------------------------------Localized osteoporosis may occur in patients
with injuries & is a prominent feature of
complex regional pain syndrome (reflex
sympathetic dystrophy), which is
characterized by pain in the extremities a/w
swelling, limited ROM, vasomotor instability,
& skin changes.
-------------------------------------------------Osteonecrosis (previously called avascular
necrosis) of the femoral head in adults is often
a/w trauma, sickle cell disease, alcohol abuse,
gout, corticosteroid use, & hypercoagulable
states; or idiopathic.
Pain is the most common symptom, usually
located in the groin, thigh, or buttock.
Plain radiography is often the initial diagnostic
test, & early findings may include increased
density, reflecting marrow infarction &
calcification. However, changes on plain
radiography may take weeks to months, &
insensitive in diagnosis of early osteonecrosis.
MRI is > 90% sensitive in the diagnosis of
osteonecrosis & the preferred imaging
procedure when plain radiographs are normal.
-------------------------------------------------Diagnose osteonecrosis of the hip with MRI.
-------------------------------------------------Patients with sickle cell disease, acute chest
syndrome should be managed by exchange
transfusion.
-------------------------------------------------Pulmonary crises usually start with
infarctions that may become secondarily
infected. With time, multiple infarctions

predominate, & pulmonary congestion &


intrapulmonary shunting develop & lead to
more hypoxia & sickling.
------------------------------------------------Acute chest syndrome in sickle cell anemia
should be managed by exchange transfusion.
RBC exchange transfusions are performed to
increase the Hgb A level to at least 50% &
thereby decrease the percentage of abnormal
sickle cells & prevent hemoglobin S
polymerization & sickling.
-------------------------------------------------Since the increased blood volume resulting
from red blood cell transfusions, it is not
possible to increase the hemoglobin A to more
than 50% without inducing volume overload;
therefore, exchange transfusions is required.
-------------------------------------------------Hydroxyurea may reduce the frequency of
painful crises & acute chest syndrome but is
not used in the acute treatment.
The drug works by increasing hemoglobin F,
which helps prevent hemoglobin S
polymerization & sickling.
-------------------------------------------------Patients with hypertrophic cardiomyopathy
are relatively asymptomatic; however, some
may develop symptoms of pulmonary
congestion (exertional dyspnea, orthopnea, &
paroxysmal nocturnal dyspnea), chest pain,
fatigue, palpitations, dizziness, & syncope.
Physical exam in the presence of left
ventricular outflow obstruction shows a
variable & dynamic systolic murmur that is
increased by the Valsalva maneuver.
-------------------------------------------------Cardinal symptoms of aortic stenosis are
angina, syncope, & dyspnea.
A midsystolic crescendo-decrescendo murmur
is heard at the second right intercostal space;
the murmur radiates to the carotid arteries.
--------------------------------------------------

Pulmonary hypertension is characterized by


right-sided heart failure with peripheral
edema, abnormal venous waveforms, fixed
splitting of S2, loud or palpable pulmonic
valve closure, tricuspid regurgitation, right
ventricular heave, & clear lungs.
-------------------------------------------------Pulmonary hypertension is a common cause
of morbidity & mortality in homozygous
sickle cell disease.
-------------------------------------------------Transient aplastic crisis in a patient with
chronic hemolytic anemia is usually due to
acute infection with parvovirus B19, a
ssDNA virus.
The propensity of this virus to infect bone
marrow erythroid progenitor cells can cause
profound anemia in someone who is
dependent on rapid erythrocyte production.
Acute infection is diagnosed by finding serum
IgM antibodies against parvovirus B19.
Recovery occurs spontaneously in days to
weeks.
-------------------------------------------------Parvovirus B19 infection also causes
erythema infectiosum (fifth disease), a
common childhood illness characterized by a
"slapped-cheek" appearance of the face
followed by a lacy red rash on the trunk &
limbs.
This virus can also cause polyarthritis in
adults (after exposure to a child with erythema
infectiosum), hydrops fetalis if infection
occurs early during pregnancy, & chronic
infection in immunocompromised persons,
including patients with HIV.
-------------------------------------------------Diagnose parvovirus B19 infection as the
cause of aplastic crisis in sickle cell disease.
-------------------------------------------------Coagulation-related bleeding may be
delayed in onset, is manifested more by deep
tissue bruises (ecchymoses), & may produce

hemarthroses in patients with congenital


deficiencies.
Platelet-related bleeding tends to occur
immediately after injury & often affects the
mucous membranes or the skin in the form of
petechiae.
-------------------------------------------------In the absence of a personal or family history
of abnormal bleeding, liver disease, significant
alcohol use, malabsorption, or anticoagulation
therapy, the likelihood of a bleeding disorder
is low, & no further testing is required.
Patients with any of these risk factors should
be screened further by obtaining a
prothrombin time (PT/INR), aPTT, &
platelet count.
Plasma fibrinogen & von Willebrand factor
testing should be considered in patients with a
history of bleeding problems.
-------------------------------------------------Screen for bleeding disorders with a clinical
history.
The clinical history should focus on presence
of any systemic illnesses & previous bleeding.
If bleeding is reported, severity should be
determined, whether it is spontaneous or an
excessive response to normal bleeding after
injury, surgery, or dental procedures; whether
the bleeding pattern is lifelong or recently
acquired; & whether the bleeding suggests a
platelet or coagulation defect.
-------------------------------------------------von Willebrand disease is an autosomal
dominant disorder characterized by a personal
& family history of bleeding tendency,
prolonged bleeding time, borderline-elevated
aPTT, & low factor VIII level.
von Willebrand disease is one of the few
hemostatic disorders characterized by both a
platelet & coagulation defect.
-------------------------------------------------Vitamin K deficiency can occur in patients
receiving TPN or long-term antibiotics &

those who are malnourished, particularly in


the setting of warfarin administration.
This condition is characterized by a
progressively prolonged PT & aPTT (with
PT much more prolonged than aPTT) &
normal thrombin time.
-------------------------------------------------Hemophilia A (factor VIII deficiency) is not
a/w a prolonged bleeding time, nor is it
transmitted from father to son (X-linked).
-------------------------------------------------von Willebrand factor (vWF) supports
platelet adhesion & acts as a carrier protein for
factor VIII.
Diagnosis is confirmed by measuring the vWF
antigen level & activity.
-------------------------------------------------Immune thrombocytopenic purpura (ITP) may
be autoimmune mediated or drug-induced.
-------------------------------------------------The only lab finding a/w ITP is
thrombocytopenia.
-------------------------------------------------Neither TTP nor HUS is a/w elevations of the
PT or PTT or D-dimer or depression of the
fibrinogen level.
-------------------------------------------------Two thrombotic microangiopathies in the
differential diagnosis of DIC are thrombotic
thrombocytopenic purpura (TTP) & hemolytic
uremic syndrome (HUS).
The two syndromes overlap, & often difficult
to distinguish between them.
Pentad of TTP includes: thrombocytopenia,
microangiopathic hemolytic anemia,
neurologic deficits, renal impairment, & fever.
HUS is a condition primarily of children &
mainly affects the kidneys as a result of
intrarenal platelet-fibrin thrombi.
-------------------------------------------------DIC most commonly occurs with infections,
cancer, & obstetrical complications.

Gram-negative sepsis is the most common


infection a/w DIC.
-------------------------------------------------DIC is the result of widespread activation of
coagulation that leads to formation of fibrin
clots.
Some patients have a thrombotic disorder, but
in most patients, secondary fibrinolysis
dissolves the fibrin clot & consumption of
platelets & coagulation factors causes
thrombocytopenia, clotting factor
deficiencies, bleeding, & vascular injuries.
Erythrocyte consumption is manifested by a
microangiopathic hemolytic anemia with
schistocytes on a peripheral blood smear.
------------------------------------------------Diagnosis of DIC is based on a prolonged PT,
aPTT, & thrombin time; high D-dimer titer;
reduced serum fibrinogen & platelet count;
& microangiopathic hemolytic anemia.
-------------------------------------------------Acquired qualitative platelet disorders are
most commonly caused by drugs, especially
aspirin & NSAIDs.
Antiplatelet agents to treat cardiovascular
disease may also cause platelet disorders
(abciximab, eptifibatide, clopidogrel).
Uremia is another common cause of a
qualitative platelet disorder; attributed to
impaired platelet-vessel wall adhesion.
-------------------------------------------------All coagulation factors are synthesized in the
liver, & severe hepatic impairment leads to
various factor deficiencies.
Vitamin K deficiency may further increase
the risk for deficient coagulation factors.
Patients with cirrhosis have an enlarged
spleen & reduction in the platelet count
(50,000 to 100,000/L) caused by splenic
sequestration (hypersplenism), which may
increase the risk for bleeding.

Coagulation usually does not become impaired


until the cirrhosis is advanced, & PT, aPTT, &
thrombin time are all prolonged.
If diagnosis remains in doubt, an inhibitor
mixing study should be done, which involves
repeating the abnormal assay with a 1:1
mixture of the patient's plasma & normal
plasma to detect either a factor deficiency or
the presence of an inhibitor.
Results of the mixing study will normalize in
a patient with a factor deficiency but will
remain abnormal if an inhibitor is present.
-------------------------------------------------Warm antibody-mediated hemolytic
anemia, a common complication of lymphoid
malignancies, is characterized by spherocytes.
-------------------------------------------------Microangiopathic hemolytic anemia is a
nonimmune hemolytic anemia characterized
by schistocytes on peripheral blood smear,
reticulocytosis, elevated levels of
unconjugated bilirubin, lactate dehydrogenase,
& depressed levels of haptoglobin.
Microangiopathic hemolysis may be a/w
thrombocytopenia.
-------------------------------------------------Autoimmune hemolytic anemia (AIHA) is
characterized by increased destruction of
erythrocytes a/w reticulocytosis. Elevated
unconjugated bilirubin, lactate dehydrogenase,
uric acid & depressed levels of haptoglobin.
AIHA may be idiopathic or result from drugs,
lymphoproliferative disorders, collagen
vascular diseases, or malignancies.
-------------------------------------------------Warm antibody-mediated hemolytic
anemia, the most common type of AIHA, is
diagnosed by the direct Coombs test, which
detects IgG or complement on the cell
surface, & spherocytes.
IgG antibodies bind to Rh-type antigens on the
erythrocyte surface at 37.0C (98.6F).
--------------------------------------------------

If a confirmatory test (serum ferritin levels)


supports the diagnosis of iron deficiency
anemia, a source of GI blood loss should be
sought, regardless of whether the stool is
positive or negative for occult blood.
A GI lesion, such as colon cancer or gastritis,
is far more likely than dietary inadequacies or
malabsorption in an otherwise healthy adult.
-------------------------------------------------Findings on peripheral blood smear suggestive
of iron deficiency anemia show changes in
size (anisocytosis), & shape (poikilocytosis)
hypochromia, & also likely to be microcytic.
-------------------------------------------------Symptomatic hemolytic anemia can usually
be treated with oral iron & folate, although
more severe cases may warrant blood
transfusion or recombinant human
erythropoietin.
-------------------------------------------------Schistocytes (fragmented RBCs) are found in
patients with microangiopathic hemolytic
anemias (TTP, HUS, & DIC) & mechanical
destruction due to prosthetic heart valves.
Mild hemolytic anemia is common in patients
with prosthetic heart valves.
-------------------------------------------------All patients with hemolytic anemia have
common findings including an increased
serum lactate dehydrogenase, decreased
serum haptoglobin level, & reticulocytosis.
-------------------------------------------------Subclinical vitamin B12 deficiency with
subtle signs & symptoms can be detected by
elevated methylmalonic acid.
Levels of methylmalonic acid & homocysteine
become elevated in vitamin B12 deficiency
before serum B12 levels decrease below the
normal range.
Only homocysteine is elevated in folate
deficiency.
--------------------------------------------------

Findings of macrocytic anemia,


thrombocytopenia, elevated LDH level, &
neurologic findings are very suggestive of
vitamin B12 deficiency.
-------------------------------------------------Diagnose cobalamin deficiency in a patient
with a low-normal vitamin B12 level with
methylmalonic acid & homocysteine.
-------------------------------------------------The degree of poikilocytosis & anisocytosis is
only modest but the hypochromia is striking
& helps differentiate thalassemia from iron
deficiency anemia.
-------------------------------------------------Thalassemia presents with a low MCV &
target cells on peripheral smear; erythrocyte
count is usually normal, or slightly elevated
Target cells are characterized by a central
dense deposit of hemoglobin surrounded by a
halo of pallor, giving a "bull's-eye" appearance
-------------------------------------------------Direct antiglobulin test is positive in patients
with warm antibody-mediated hemolysis &
negative in hereditary spherocytosis.
-------------------------------------------------Because reticulocytes can have normal G6PD
levels, measuring G6PD levels during an acute
episode may produce a false-negative result.
-------------------------------------------------G6PD deficiency is the most common
disorder of erythrocyte metabolism.
G6PD is necessary for generating adequate
NADPH to prevent oxidant stress.
G6PD is found on the X-chromosome, &,
therefore, deficiency rarely occurs in women.
The acute onset of symptoms can be
precipitated by drugs, infection, or DKA.
Hemolysis can be precipitated by
trimethoprim-sulfamethoxazole.
-------------------------------------------------2 to 4 days after introduction of the oxidative
stress in patients with G6PD deficiency, onset

of jaundice & dark urine occurs, with or


without abdominal & back pain.
Hemoglobin level decreases by 3 to 4 g/dL, &
an appropriate increase in reticulocytes.
Hemolysis spontaneously resolves in 1 week
as older enzyme-depleted cells are replaced by
new cells with sufficient G6PD to prevent
further hemolysis.
Additional lab findings with G6PD deficiency
include a negative direct & indirect
antiglobulin (Coombs) test & presence of
"bite" or "blister" cells, produced when
accumulated oxidized hemoglobin remains
adherent to the erythrocyte membrane with an
adjacent membrane-bound clear zone.
-------------------------------------------------Treat iron deficiency anemia with oral iron.
-------------------------------------------------Iron deficiency anemia is confirmed by the
low MCV, low serum iron level, elevated
TIBC, & low transferrin saturation
(iron/TIBC).
-------------------------------------------------Iron deficiency is treated with oral iron salts;
ferrous sulfate, 325 mg TID, is the least
expensive preparation.
Patients who are unable to absorb iron orally
(Crohn disease, celiac disease, or small bowel
resection) may receive parenteral iron.
-------------------------------------------------Patients with aplastic anemia have
pancytopenia, low reticulocyte count, &
hypoplastic bone marrow (<20% cellularity)
with normal maturation of all cell lines.
------------------------------------------------Aplastic anemia is a fatal disorder in which
myeloid progenitor cells & stem cells are
severely diminished or absent in the bone
marrow because of an intrinsic defect of the
stem cells or immune-mediated stem cell
destruction, which leads to transfusiondependent anemia, thrombocytopenia, &
severe neutropenia.

Interferon-activated T lymphocytes are


involved in autoimmune destruction of stem
cells in a significant proportion of patients
with the idiopathic or the acquired form of
aplastic anemia; this explains why
immunosuppressive therapy is effective in
some patients.
Initial management involves withdrawal of
any potentially causative agents & CT scan of
the chest to rule out an associated thymoma.
-------------------------------------------------Immune thrombocytopenic purpura (ITP)
have petechiae & ecchymoses but do not have
a decreased leukocyte count nor anemia, but
some may have an associated autoimmune
hemolytic anemia or iron deficiency anemia
due to bleeding.
-------------------------------------------------This patient has iron deficiency in the setting
of inflammatory anemia due to rheumatoid
arthritis, a cause of inflammatory anemia.
Inflammatory cytokines block iron utilization,
decrease transferrin (& TIBC), & increase
ferritin levels.
In contrast, the physiologic response to iron
deficiency is to increase transferrin (& TIBC)
levels & decrease ferritin levels.
When inflammation accompanies iron
deficiency, inflammatory cytokines always
confound the expected pattern of serum iron
chemistries for iron deficiency alone.
-------------------------------------------------Because this patient also has rheumatoid
arthritis, serum ferritin levels are expected
to rise (as much as threefold) owing to the
effects of inflammatory cytokines.
Therefore, this patient's serum ferritin level of
36 ng/mL suggests iron deficiency.
As a rule of thumb, serum ferritin levels
lower than 100 to 120 ng/mL (100-120 g/L)
may reflect iron deficiency in patients with
inflammatory states.
-------------------------------------------------

Methotrexate is an antimetabolite that inhibits


dihydrofolate reductase & causes
megaloblastic maturation
Low-dose methotrexate is unlikely to cause
significant megaloblastic anemia, whereas
higher doses may do so with a significant rise
in MCV.
--------------------------------------------------

VI. Infectious Disease

Vertebral osteomyelitis is an infection of the


spine that must be considered in any patient
with new-onset back pain & fever.
Acute hematogenous osteomyelitis is more
likely to present with acute pain & fever than
with chronic contiguous osteomyelitis (foot
ulcer-associated osteomyelitis).
Hematogenous osteomyelitis most often
involves the intervertebral disk space & two
adjacent vertebrae.
Potential sources of hematogenous infection
include the genitourinary tract (particularly
following instrumentation), skin (injection
drug use), infected intravascular devices
(central venous catheter), & endocarditis, but
often, the infection source cannot be identified
Patients with hematogenous osteomyelitis,
leukocyte count is typically normal, but the
ESR is elevated in 80% to 90% of patients &
often greater than 100 mm/h.
-------------------------------------------------Diagnose the cause of vertebral osteomyelitis
with blood cultures.
-------------------------------------------------For suspected vertebral osteomyelitis, a
microbiologic diagnosis must be established to
guide antibiotic therapy.
Because the infection is often hematogenous,
obtain initial blood cultures in all patients.
Cultures are positive in up to 75% of patients.
Staphylococcus aureus is the most frequent
cause of vertebral osteomyelitis.
Antibiotics should be withheld until a
microbiologic diagnosis is made.
However, if imaging studies suggest vertebral
osteomyelitis but blood cultures are negative,
CT-guided percutaneous needle biopsy
should be performed.
--------------------------------------------------

Evaluate vertebral osteomyelitis with a


lumbar spine MRI.
-------------------------------------------------MRI is the most appropriate imaging study for
suspected vertebral osteomyelitis & a more
sensitive study than CT scans or plain
radiographs.
In addition, MRI can detect an epidural
abscess or a paravertebral or psoas abscess
that may require surgical drainage.
If MRI cannot be performed (pacemakers or
metal prosthetic devices) or results are
inconclusive, a gallium nuclear study is very
sensitive & specific.
-------------------------------------------------Foot infections are a significant cause of
morbidity in patients with diabetes mellitus
&, if untreated, can progress to osteomyelitis
that may require amputation for cure.
Appropriate assessment of diabetic foot
infections is essential. Unless bone is visible,
physical exam findings are often inconclusive
for diagnosing osteomyelitis.
Plain radiographs are insensitive & may show
soft tissue swelling but no bony abnormalities
for 2 or more weeks after the infection.
MRI is the most sensitive & specific study for
diagnosing foot infection-associated
osteomyelitis.
CT scan is neither as sensitive nor specific as
MRI & indicated only when MRI cannot be
performed.
-------------------------------------------------Diagnose osteomyelitis of the foot in a patient
with diabetes with a bone biopsy.
-------------------------------------------------The most appropriate management of
osteomyelitis of a diabetic foot is to perform
a bone biopsy to obtain deep pathogens,
which is the only way to establish a definitive
diagnosis & guide therapy.
Contact with bone (using a sterile, blunt,
stainless steel probe) in the depth of an

infected pedal ulcer in patients with diabetes


mellitus is strongly correlated with the
presence of underlying osteomyelitis, with a
positive predictive value of 90%.
-------------------------------------------------Failure to identify the causative deep-bone
pathogens may lead to spread of infection to
adjacent bones or soft tissues & need for
extensive debridement or amputation.
The one exception is Staphylococcus aureus,
which, if found in superficial cultures,
correlates well with findings on deep cultures.
------------------------------------------------Empiric therapy should include activity
against streptococci, MRSA, aerobic gramnegative bacilli, & anaerobes.
Imipenem alone will not adequately cover
MRSA, vancomycin & ceftazidime will not
adequately cover anaerobes.
Vancomycin & metronidazole will not
adequately cover gram-negative organisms.
-------------------------------------------------Synthetic penicillins, oxacillin & nafcillin, are
appropriate for treating patients with MSSA
bacteremia & endocarditis.
-------------------------------------------------A patient has bacteremia most likely resulting
from right-sided endocarditis. Treatment
requires using the most effective drug with the
fewest side effects, oxacillin.
Penicillins have never been shown to be less
effective than other antibiotics for treating
susceptible strains of S. aureus..
In the rare setting an isolate of S. aureus is
susceptible to penicillin G, this would be the
drug of choice.
-------------------------------------------------Both vancomycin & daptomycin have been
used to treat S. aureus bacteremia &
endocarditis. Although both are effective for
treating MRSA strains, they show no clinical
superiority for treating MSSA.

1.
2.
3.

Patients with MSSA infections appear to have


a slower response to vancomycin than to the
semisynthetic penicillins oxacillin or to
cephalosporins, & this accounts for the
preference of -lactam versus vancomycin
therapy.
-------------------------------------------------Treat MSSA right-sided endocarditis with
oxacillin.
-------------------------------------------------Three major clinical criteria for endocarditis:
typical microorganism grown on two blood
cultures
echocardiographic evidence of endocardial
involvement (oscillating intracardiac mass)
new valvular regurgitation murmur
Endocarditis is also suggested by: several
months of fever, fatigue & muscle aches.
Also supporting the diagnosis are the presence
of a bicuspid aortic valve, fever, &
conjunctival hemorrhage, which fulfill three
of the minor clinical criteria for endocarditis.
-------------------------------------------------In a patient with uncomplicated endocarditis,
addition of gentamicin decreases the total
treatment course from 4 weeks to 2 weeks.
Endocarditis due to sensitive viridans
streptococci on native valves can be treated for
4 weeks with penicillin or ceftriaxone, or for
2 weeks when either agent is combined with
synergistic low-dose gentamicin.
-------------------------------------------------Treatment for septic pulmonary emboli from
an infected tricuspid valve in an injection
drug user should include empiric therapy for
MRSA, such as vancomycin plus cefepime.
-------------------------------------------------A tricuspid valve endocarditis is suggested
by a right sternal border systolic murmur that
increases with inspiration, which developed
septic pulmonary emboli to both lung fields
leading to multilobar pneumonia.

Septic pulmonary emboli are common in


tricuspid endocarditis. In this instance, the
most likely infecting organism is
Staphylococcus aureus, & treatment of a
possible methicillin-resistant strain must be
initiated pending culture & susceptibility
results.
Vancomycin plus cefepime provides
appropriate coverage for endocarditis caused
by S. aureus, gram-negative bacilli
(Pseudomonas aeruginosa), & other likely
infectious causes of pneumonia, especially
Streptococcus pneumoniae.
-------------------------------------------------In HIV-infected patients, Pneumocystis
pneumonia typically has a subacute onset of
cough, fever, & dyspnea.
The most common radiographic abnormalities
are diffuse, bilateral, interstitial infiltrates.
Trimethoprim-sulfamethoxazole plus
prednisone would treat P. jirovecii pneumonia
-------------------------------------------------The organisms a/w the development of
infective endocarditis after dental procedures
are viridans streptococci.
For non-penicillin-allergic, oral amoxicillin is
the recommended prophylactic regimen given
30 to 60 minutes before a procedure.
Patients unable to take oral medications, IM
or IV ampicillin, cefazolin, or ceftriaxone is
recommended.
Oral clindamycin, azithromycin, or
clarithromycin is recommended for infective
endocarditis prophylaxis in penicillin-allergic.
-------------------------------------------------Withhold infective endocarditis prophylaxis
in a patient with a heart murmur a/w a native
valve abnormality.
-------------------------------------------------Evidence is clear that bacteremia resulting
from normal, daily activities is much more
likely to cause infective endocarditis than
bacteremia a/w dental procedures, & that only

an extremely small number of cases of


infective endocarditis are prevented by
prophylaxis.
Antibiotic prophylaxis is now recommended
only for patients with underlying conditions
a/w the highest risk of adverse outcome from
infective endocarditis; this does not include
heart murmurs a/w native valve abnormalities.
-------------------------------------------------A history of alcohol abuse & alcoholwithdrawal seizures, puts a patient at risk for
aspiration pneumonia
A lung abscess is characterized radiologically
by a cavity with an air-fluid level, which
probably occurred as a complication of
aspiration pneumonia.
Lung abscesses are polymicrobial infections
caused by anaerobes that are normally present
in the mouth; micro-aerophilic streptococci,
viridans streptococci, & gram-negative enteric
pathogens have also been implicated.
-------------------------------------------------Possible anaerobes in patients with lung
abscess as a complication of aspiration
pneumonia include: Peptostreptococcus
species, Fusobacterium nucleatum, Prevotella
melaninogenica, & Bacteroides species
(including B. fragilis).
------------------------------------------------Patients with lung abscess as a complication
of aspiration pneumonia require treatment
with an antimicrobial agent effective against
-lactamase-producing strains of oral
anaerobes, such as ampicillin-sulbactam
(Unasyn).
-------------------------------------------------The most common pathogens identified from
recent studies of patients with mild
community-acquired pneumonia (CAP)
were Streptococcus pneumoniae, Mycoplasma
pneumoniae, & Chlamydophila pneumoniae.
Macrolides have been commonly prescribed
for treatment of outpatients with CAP, &

numerous randomized clinical trials have


demonstrated the efficacy of clarithromycin
or azithromycin as monotherapy.
Erythromycin is a less expensive macrolide
but not generally recommended owing to the
need for more frequent dosing, more GI upset,
& lack of coverage for H. influenzae.
-------------------------------------------------Treat community-acquired pneumonia in a
patient with no comorbidities with
clarithromycin or azithromycin.
-------------------------------------------------Legionella pneumonia symptoms may
include chest pain, cough with nonproductive,
mildly productive, or blood-streaked sputum.
GI symptoms are prominent & include
diarrhea, abdominal pain, nausea, & vomiting.
Most patients are lethargic, have headache, &
some may be obtunded.
High fever is common, & oral temperature
greater than 40.0C (104.0F) is suggestive of
legionnaires disease.
Risk factors for legionnaires disease include
smoking, diabetes mellitus, hematologic
malignancy, other types of cancer, chronic
kidney disease, & HIV infection.
-------------------------------------------------Urinary antigen tests for detection of
Legionella pneumophila serogroup 1 have
high sensitivity & specificity, but these tests
do not detect other Legionella species;
therefore, a negative test cannot be used to
exclude diagnosis of Legionella pneumonia.
-------------------------------------------------Legionella species would not be isolated from
blood cultures or thoracentesis fluid.
-------------------------------------------------Hyponatremia is found more often in patients
with legionnaires disease than in patients with
pneumonia from other causes.
-------------------------------------------------MRSA should be suspected in persons with
severe, rapidly progressive pneumonia,

especially during influenza season; those with


cavitary infiltrates on CXR; or those with a
history of MRSA infection.
Cefotaxime & levofloxacin for patients
admitted to the ICU with pneumonia & no risk
factors for Pseudomonas aeruginosa infection
(bronchiectasis, corticosteroid or broadspectrum antibiotic use in the previous month,
malnutrition) is appropriate.
However, if MRSA pneumonia is suspected,
vancomycin or linezolid should be added to
this empiric antibiotic regimen.
-------------------------------------------------Adults who receive pneumococcal vaccine at
or after age 65 should receive a single dose.
One-time pneumococcal revaccination 5 years
after the first dose for adults age 65 years &
older who received their first dose for any
indication younger than age 65 years.
-------------------------------------------------CDC recommends one-time pneumococcal
revaccination for adults at risk for serious
pneumococcal infection or likely to have a
rapid decline in antibody levels.
Persons at highest risk include adults with
anatomic or functional asplenia (including
sickle cell disease), HIV infection, leukemia,
lymphoma, Hodgkin disease, multiple
myeloma, generalized malignancy, chronic
kidney disease, nephrotic syndrome, or other
conditions a/w immunosuppression (organ or
bone marrow transplantation), & those
receiving immunosuppressive chemotherapy,
including long-term corticosteroids.
-------------------------------------------------Treat latent TB with isoniazid prior to the
administration of a TNF- inhibitor.
-------------------------------------------------Screening for latent TB is indicated prior to
solid organ transplant, initiation of
chemotherapy or TNF- inhibitors, or other
major immunocompromising conditions.
--------------------------------------------------

Infliximab, adalimumab, & etanercept are a/w


an increased incidence of reactivation TB,
particularly extrapulmonary tuberculosis.
All patients should undergo screening for
latent TB infection. If screening is positive
(PPD result of 5 mm or more of induration or
positive interferon- release assay),
appropriate treatment for latent TB is indicated
with at least 2 months of isoniazid before
initiating a TNF- inhibitor.
-------------------------------------------------Prophylactic isoniazid therapy is beneficial
in patients on prednisone (15 mg/d) or any
other immunosuppressive agent & have 5 mm
or more of induration on TB skin testing.
-------------------------------------------------Treat latent TB in an immunosuppressed
patient with isoniazid for 9 months &
pyridoxine (Vit B6) is added to prevent
isoniazid-induced peripheral neuropathy.
-------------------------------------------------Malnutrition, immunosuppressed states, &
stress are risk factors for primary progression
or reactivation of latent/quiescent TB.
-------------------------------------------------Three cut-points have been defined for a
positive tuberculin reaction: 5 mm, 10 mm,
& 15 mm of induration.
Induration of 5 mm or more is considered
positive in persons at highest risk of
developing active TB (HIV,
immunosuppressed, persons with close contact
with anyone with active TB, or those with a
CXR consistent with prior TB).
Induration of 10 mm or more is considered
positive in persons who have immigrated to
the US from high-risk countries within the past
5 years; injection drug users; prisoners; health
care workers; & patients with silicosis,
diabetes mellitus, chronic renal failure,
leukemia or lymphoma, carcinoma of the head,
neck or lung, recent significant weight loss, or
history of gastrectomy or jejunoileal bypass.

Healthy adolescents who are exposed to adults


in high-risk categories should also be screened
using this 10-mm cut-off.
PPD cut-off point of 15 mm induration is used
for all low-risk persons.
-------------------------------------------------Suspected or confirmed TB are treated with
four-drug therapy: isoniazid, rifampin,
pyrazinamide, & ethambutol for 2 months,
followed by de-escalation of antimicrobial
therapy once drug susceptibility of isoniazid &
rifampin is established. These agents are
continued for 7 months, totaling a 9-month
treatment course.
-------------------------------------------------Tuberculin reactivity caused by BCG
vaccination wanes with the passage of time &
is unlikely to persist more than 10 years after
vaccination in the absence of Mycobacterium
tuberculosis infection.
Tuberculin skin testing reactions in persons
vaccinated with BCG should be interpreted
using the same criteria as used in those who
have not received the vaccine.
-------------------------------------------------Exposure to TB in the distant past may have
an initial negative skin test; performing a
second test 7 to 21 days after the first may be
helpful in reducing the false-negative response
Two-step testing often "boosts" a negative
test result to positive as the immune system
recalls its previous exposure, thus divulging a
true-positive result.
Two-step testing may be helpful in
distinguishing new from old exposures in
annual employee-testing programs.
-------------------------------------------------Vitamin B6 (pyridoxine) should also be
considered as 2% treated with isoniazid
develop peripheral neuropathy that is
preventable.
Supplemental pyridoxine is important in
patients at high risk for neuropathy (diabetes,

uremia, alcoholism, malnutrition, HIV


infection, pregnancy, or seizure disorders).
-------------------------------------------------Standard therapy for active TB includes at
least 6 months of four-drug therapy (isoniazid,
rifampin, pyrazinamide, & ethambutol).
-------------------------------------------------Positive tuberculin skin test is defined as an
induration > 10 mm for patients who are
recent arrivals from high-prevalence countries.
-------------------------------------------------Tuberculin skin test with induration > 10 mm
is also considered positive in the following
high-risk groups: injection drug users,
residents or employees of high-risk congregate
settings (prisons & jails, nursing & homeless
shelters), mycobacteriology lab personnel,
persons with clinical conditions that put them
at high risk for active disease, children
younger than 4 years or children exposed to
adults in high-risk categories.
-------------------------------------------------If radiographic results are negative, treatment
for latent TB consists of isoniazid therapy
with vitamin B6 (pyridoxine) supplementation
-------------------------------------------------Manage latent tuberculosis with a CXR.
-------------------------------------------------TB is a communicable disease & inhaled into
the respiratory system via airborne droplets.
Diagnosis of pulmonary TB should be
considered in any patient with cough for
longer than 3 weeks, loss of appetite,
unexplained weight loss, night sweats,
hoarseness, fever, fatigue, or chest pain.
Index of suspicion should be substantially high
for patients who have spent time in developing
countries, geographic areas of the US such as
Miami or NYC, or a correctional facility.
-------------------------------------------------Institute immediate airborne precautions in
the setting of suspected TB.

Airborne infection precautions are


appropriate for illnesses transmitted by
airborne droplet (TB, measles, varicella).
This includes: patient placement into a
negative-pressure room & respiratory
protection by health care workers. Acceptable
protection includes a "respirator," which refers
to an N95 mask (filtering capacity of 95% of
particulates) or higher filtering face-piece
respirator or powered air-purifying respirator.
-------------------------------------------------Human nasopharynx is the only known
reservoir for meningococcal meningitis.
Meningococci are spread from person to
person by respiratory droplets of infected
nasopharyngeal secretions.
Persons with significant exposure to the index
patient (same household, day-care center, or
direct contact with a patient's oral secretions)
should receive chemoprophylaxis antibiotics.
-------------------------------------------------Droplet precautions are recommended for
patients with known or suspected illnesses
transmitted by large-particle droplets, such as
Neisseria meningitidis & influenza.
Patients are isolated in private rooms, &
hospital personnel wear face masks when
within 3 feet of the patient.
-------------------------------------------------Droplet precautions should be initiated when
Neisseria meningitidis is suspected & require
health care workers within 6 to 10 feet of the
index patient wear a face mask.
-------------------------------------------------Environmental contamination with vegetative
C. difficile & C. difficile spores frequently
occurs. C. difficile is transmitted to other
patients through the hands & clothes of health
care workers & common equipment that is
used on patients without cleaning.
A C. difficile bundle consisting of barrier
precautions, enhanced cleaning with bleach, &

soap-&-water hand hygiene is useful in


preventing the spread of C. difficile.
Alcohol-based hand hygiene products do not
kill C. difficile spores & ineffective at
removing them from hands.
-------------------------------------------------Semi-erect position reduces the risk of
ventilator-associated pneumonia (VAP).
Semi-erect positioning at 45 is useful because
it reduces the risk of excursion of bacteria
from the stomach into the upper airways.
-------------------------------------------------Prevent catheter-associated UTIs with
decreased catheter use.
Catheters should be used for specific
indications, not for convenience & should be
removed as soon as possible.
------------------------------------------------Toxoplasmosis encephalitis typically occurs
in HIV-infected patients when CD4 cell count
is < 100/L & a/w ring-enhancing lesions on
brain MRI, often with mass effect.
-----------------------------------------------Progressive multifocal leukoencephalopathy
is a demyelinating disease of the CNS caused
by the polyomavirus JC virus.
Occurs almost exclusively in the severely
immunocompromised, including those with
advanced HIV-1 infection.
Clinical findings include dementia,
hemiparesis or paralysis of one extremity,
ataxia, hemianopia, & diplopia.
MRI appearance of these lesions is
hyperintense (white) areas on T2-weighted
images & fluid-attenuated inversion recovery
(FLAIR) sequences & hypointense (dark)
areas on T1-weighted images.
-------------------------------------------------Disseminated Mycobacterium avium
complex (MAC) infection is common in
patients with advanced-stage HIV infection
& CD4 cell count of < 50/L.

Symptoms include fever, weight loss,


hepatosplenomegaly, lymphadenopathy,
malaise, & abdominal pain.
Diagnosis is confirmed by recovering the
pathogen from sterile tissue (usually blood).
-------------------------------------------------Cryptococcal meningitis is the most common
form of meningitis in patients with AIDS, who
typically present with headache, irritability, &
nausea that can mimic other disorders.
Most patients have a CD4 cell count of less
than 100/L.
Diagnosis is based on detection of
cryptococcal antigen in the CSF or culture of
Cryptococcus neoformans in the CSF.
-------------------------------------------------Toxoplasmosis almost always presents as
reactivation disease in patients with HIV
infection & typically occurs when CD4 cell
count is less than 100/L.
findings are fever & neurologic deficits.
MRI shows ring-enhancing lesions, often with
associated edema.
Sulfadiazine plus pyrimethamine & folinic
acid are given initially.
Follow-up MRI is critical to assess treatment
response. If there is no therapeutic response
after 14 days, stereotactic brain biopsy is
recommended to rule out other causes,
especially a primary CNS lymphoma.
-------------------------------------------------HIV RNA viral load is the most sensitive test
for infection during the acute stage.
-------------------------------------------------Antibodies to HIV do not commonly occur
until about 6 weeks after infection & may be
negative during the acute symptomatic phase.
Patients diagnosed with acute HIV infection
on the basis of an HIV viral load measurement
should have confirmatory serologic antibody
testing at a subsequent point in time.
--------------------------------------------------

This patient's prolonged febrile syndrome in


the setting of HIV risk factors should raise
concerns for recent infection with HIV.
Detection of HIV RNA is the most sensitive
test for detecting HIV infection during the
acute symptomatic phase.
In addition to the acute retroviral syndrome,
this patient must be evaluated for secondary
syphilis using the rapid plasma reagin test.
Secondary syphilis & acute retroviral
syndrome should always be considered in
sexually active patients with rash, fever, &
generalized lymphadenopathy.
-------------------------------------------------Recurrent herpes zoster infection should
trigger testing for possible HIV infection.
-------------------------------------------------------------------------------------------------Herpes zoster infection is the reactivation of
the varicella virus in a single cutaneous nerve.
Recurrence in the immunocompetent host is
uncommon but does occur.
When recurrent disease is present, underlying
cause is overwhelmingly HIV infection.
-------------------------------------------------Herpes zoster presents as a band of crusts &
blisters on an erythematous base along a
dermatomal distribution on the hemi-thorax.
Evidence of scarring in a dermatome several
centimeters above the current site, represents a
previous herpes zoster infection.
Almost half of all herpes zoster episodes
diagnosed in HIV patients are recurrences.
-------------------------------------------------All patients with HIV & herpes zoster
infection are treated with antiviral therapy
regardless of the age of the zoster lesions.
Most patients with HIV infection can be
treated with an oral antiviral with good
bioavailability, valacyclovir or famciclovir,
Patients with severe disease, evidence of
dissemination, or ophthalmologic involvement

may have better outcomes if treated with


intravenous acyclovir.
-------------------------------------------------The advent of highly active antiretroviral
therapy has not lessened the incidence of
recurrent herpes zoster infection in patients
with HIV infection.
-------------------------------------------------Fluconazole is not recommended for the
primary prophylaxis of Candida infections
despite its effectiveness in this role.
The potential for drug resistance, numerous
potential drug-drug interactions, the ease &
effectiveness of treating infection when it does
occur, & lack of survival benefit argue against
prophylactic use.
-------------------------------------------------No proven survival benefit is a/w CMV
prophylaxis.
-------------------------------------------------Azithromycin is used for prophylaxis against
Mycobacterium avium complex (MAC) when
CD4 cell count < 50/L.
-------------------------------------------------Effective prophylaxis against opportunistic
infections a/w HIV infection may prolong
life in some patients.
CD4 cell count is an indicator of immune
competence. Prophylaxis recommendations
are based on CD4 cell count.
Threshold for Pneumocystis & toxoplasmosis
prophylaxis is 200/L & 100/L, respectively.
Trimethoprim-sulfamethoxazole is the firstline agent for both.
------------------------------------------------Pneumocystis jirovecii pneumonia remains
the most common AIDS-defining illness &
cause of death in patients with AIDS.
Diagnosis should be considered in any patient
with a CD4 cell count < 200/L who presents
with fever, dry cough, & dyspnea developing
over several days or weeks.

CXR typically shows bilateral interstitial


infiltrates, but findings can vary from normal
to consolidation or pneumothorax.
Diagnosis is established by silver stain of
induced sputum or a bronchoscopic sample
showing characteristic cysts.
3-week course of TMP-SMX is the standard
treatment.
Corticosteroids are required for patients with
evidence of hypoxia (arterial PO2 <70 mm Hg
or alveolar-arterial gradient >35 mm Hg) &
continued for the entire course of treatment.
-------------------------------------------------Dapsone can be an adjunctive treatment to
trimethoprim in acute P. jirovecii or can be
used alone as a prophylactic agent for
patients with a CD4 count less than 200/L in
patients who are intolerant of TMP-SMX.
But Dapsone is not recommended as single
drug therapy for P. jirovecii pneumonia.
-------------------------------------------------Treat Pneumocystis jirovecii pneumonia with
TMP-SMX plus corticosteroids.
-------------------------------------------------Ambulatory patients with Pelvic inflammatory
disease (PID) should receive IM ceftriaxone
also oral doxycycline; with or without
metronidazole.
Duration of treatment is 14 days.
-------------------------------------------------PID is a polymicrobial infection of the
endometrium, fallopian tubes, & ovaries
Diagnosis is based on the presence of
abdominal discomfort, uterine or adnexal
tenderness, or cervical motion tenderness.
Other diagnostic criteria include temperature
higher than 101.0F (38.3C), cervical or
vaginal mucopurulent discharge, leukocytes in
vaginal secretions, & documentation of
gonorrheal or chlamydial infection.
--------------------------------------------------

PID is most likely to occur within 7 days of


the onset of menses.
-------------------------------------------------All women with suspected PID should be
tested for gonorrhea, chlamydia, & HIV
infection, & undergo pregnancy testing.
-------------------------------------------------Patients with PID should be hospitalized if (1)
no clinical improvement after 48 to 72 hours
of antibiotics; (2) inability to tolerate oral
antibiotics; (3) severe illness with nausea,
vomiting, or high fever; (4) suspected intraabdominal abscess; (5) pregnancy; or (6)
noncompliance with outpatient therapy.
-------------------------------------------------Primary genital HSV infection is
characterized by fever, headache, & painful,
ulcerated, vesicular lesions.
-------------------------------------------------Vulvovaginal candidiasis symptoms include
pruritus, external & internal erythema, &
nonodorous, white, curd-like discharge.
-------------------------------------------------The primary ulcerative lesion (chancre) in
syphilis develops 3 weeks after infection, has
a clean appearance with heaped-up borders,
painless & often unrecognized, particularly
women.
-------------------------------------------------Chancroid is an uncommon STD caused by
Haemophilus ducreyi characterized by the
presences of ragged, purulent, painful ulcers
a/w tender lymph nodes that may suppurate.
-------------------------------------------------Diagnosis of genital herpes is suspected on
clinical grounds but may be confirmed by viral
culture or serology if diagnosis is in doubt.
-------------------------------------------------Primary genital herpes simplex virus (HSV)
infection is a/w HSV-1 or HSV-2, but HSV-2 is
the more common pathogen.
Genital herpes lesions begin as vesicles that
ulcerate & quite painful.

Initial infection is often the most severe & can


be accompanied by local lymphadenopathy &
systemic symptoms.
Recurrences vary in frequency & typically less
severe than the initial episode. Many
recurrences are subclinical but contagious.
-------------------------------------------------Disseminated gonococcal infection may cause
arthritis & tenosynovitis, & often a/w sparse
peripheral necrotic pustules (dermatitis).
-------------------------------------------------For disseminated gonococcal infection (DGI)
initial treatment should include parenteral
therapy with IV ceftriaxone or a comparable
third-generation cephalosporin.
-------------------------------------------------DGI causes septic or sterile immune-mediated
arthritis & tenosynovitis & frequently involves
knees, hips, & wrists but not the spine.
Dermatitis a/w sparse peripheral necrotic
pustules also is common.
A prodrome of migratory arthralgia &
tenosynovitis may precede the settling of the
synovitis in one or several joints.
-------------------------------------------------On diagnosis of DGI, prompt evaluation for
additional STDs, syphilis & HIV, is indicated.
Empiric treatment for Chlamydia trachomatis
infection with doxycycline also should be
considered, because co-infection with N.
gonorrhoeae & C. trachomatis is common.
-------------------------------------------------Genitourinary symptoms a/w DGI usually are
absent in women, & genital infection in women
may have occurred long before systemic
dissemination.
Patients with rectal & pharyngeal colonization
of Neisseria gonorrhoeae in the setting of DGI
are commonly asymptomatic.
Patients in whom DGI is clinically suspected,
routine culture of the rectum & pharynx, as
well as the blood & joints, is indicated.
--------------------------------------------------

Cervicitis is caused by chlamydial &/or


gonococcal infection.
Defined by either (1) mucopurulent cervical
discharge or (2) endocervical bleeding; easily
induced by gentle passage of a swab through
the cervical os.
Although gonorrhea infection is often
symptomatic, either may be asymptomatic or
only mildly symptomatic.
-------------------------------------------------A woman with a high pretest probability for
cervicitis who may easily be lost to follow-up,
treat empirically for gonorrhea & chlamydia
rather than wait for specific testing.
Ceftriaxone with either doxycycline or
azithromycin is an appropriate regimen.
-------------------------------------------------Absence of gram-negative diplococci on Gram
stain does not rule out gonorrhea, because it is
observed in only 50% of women.
In the presence of a documented gonorrhea
infection by nucleic acid or culture, chlamydia
is always treated even in the absence of positive
test results for chlamydia infection.
-------------------------------------------------This patient has cervicitis & should be treated
empirically for gonorrhea & chlamydia.
-------------------------------------------------Routinely screen sexually active women under
age of 25 years for chlamydia, gonorrhea, HIV.
-------------------------------------------------Screen for syphilis in persons at risk & all
pregnant women.
Pregnant women are screened during the first
prenatal visit & third trimester &, for women
at high risk, at the time of delivery.
Other high-risk persons include commercial sex
workers, prisoners, persons diagnosed with
another STD, men who have sex with men, &
those who engage in other high-risk behaviors.
Screening is not recommended in the general
population because a positive test result will

most likely be a false-positive test result.


-------------------------------------------------HIV screening for patients in all health care
settings with "opt-out screening," in which the
patient is notified that testing will be performed
unless the patient declines.
Pregnant women at increased risk or in areas of
high prevalence should have an additional HIV
test during their third trimester.
-------------------------------------------------Trimethoprim-sulfamethoxazole, 160 mg/800
mg BID for 3 days, is effective for self-treated
uncomplicated cystitis.
-------------------------------------------------Recurrent UTIs are common in women & are
believed to represent new infection rather than
a relapse of a previous episode.
Recurrent urinary tract infection (UTI), can be
self-treated with TMP-SMX on development of
symptoms.
-------------------------------------------------Most women are able to diagnose a UTI
accurately & begin antimicrobial treatment.
Self-treatment is highly effective in compliant
women.
-------------------------------------------------Sexual intercourse is a risk factor for acute &
recurrent UTIs, as is the use of spermicides or
spermicides plus a diaphragm.
-------------------------------------------------Manage recurrent cystitis with patient-initiated
trimethoprim-sulfamethoxazole.
-------------------------------------------------Pyelonephritis is a/w abrupt onset of fever,
chills, sweats, nausea, vomiting, diarrhea, &
flank or abdominal pain; hypotension & septic
shock may occur in severe cases.
Presence of bacteriuria & pyuria is the gold
standard for diagnosing pyelonephritis if a/w
suggestive history & physical exam findings.
Leukocyte casts in the urine are suggestive of
pyelonephritis but are uncommonly detected.

Blood cultures should be obtained in patients


who appear ill.
Hypotensive patients should receive IV fluids.
-------------------------------------------------Treatment of pyelonephritis consists of
antibiotics for 7 to 14 days.
Patients who are acutely ill, nauseated, or
vomiting should receive parenteral therapy
initially & can begin receiving oral therapy
once oral intake is tolerated.
Standard therapy in nonpregnant women is
ciprofloxacin or levofloxacin. Alternatives to
fluoroquinolones include extended-spectrum
cephalosporins or penicillins,
------------------------------------------------Pyelonephritis should be treated with
ciprofloxacin or levofloxacin.
-------------------------------------------------Eradication of bacteriuria in patients treated for
pyelonephritis can be confirmed through
repeat urinalysis & urine culture.
-------------------------------------------------Screening for asymptomatic bacteriuria is
recommended only for pregnant women &
before transurethral resection of the prostate,
urinary tract instrumentation involving biopsy,
or other tissue trauma resulting in mucosal
bleeding.
-------------------------------------------------For asymptomatic women, bacteriuria is
defined as 2 consecutive voided urine
specimens with isolation of the same bacterial
strain in quantitative counts of at least 105
cfu/mL.
Escherichia coli remains the single most
common organism isolated, but Proteus
mirabilis is more common in men.
Treatment of asymptomatic bacteriuria in
women with diabetes is not indicated.
-------------------------------------------------Screening or treatment of asymptomatic
bacteriuria is not recommended for most

nonpregnant women.
-------------------------------------------------Adding or starting an aminoglycoside should
be avoided in a patient with reduced kidney
function.
-------------------------------------------------A patient presenting with acute prostatitis
should initiate intravenous ciprofloxacin.
Failure of clinical improvement after 36 to 72
hours is most likely due to a complication such
as prostatic abscess.
Further evaluate with a transrectal ultrasound
(TRUS) or abdominal/pelvic CT is indicated.
TRUS might be the preferred diagnostic
modality in patients with chronic kidney disease
Contrast-enhanced CT should be avoided in
patients with reduced kidney function.
Transurethral catheterization should be
avoided in acute prostatitis.
If bladder drainage is necessary, it should be
suprapubic to reduce the risk of prostatic
abscess & septicemia.
-------------------------------------------------Pregnant women are screened for
asymptomatic bacteriuria, which is a/w low
birth weight, prematurity, & increased risk for
pyelonephritis.
An appropriate antibiotic for this patient is
ampicillin, amoxicillin, or nitrofurantoin.
These antibiotics are FDA pregnancy risk
category B drugs.
Ciprofloxacin & trimethoprim are category
C drugs, therefore not indicated in pregnancy.
-------------------------------------------------Urine cultures should be obtained after
treatment in pregnant women with
asymptomatic bacteriuria to confirm
eradication of bacteria.
-------------------------------------------------Treat asymptomatic bacteriuria in a pregnant
patient with ampicillin.
--------------------------------------------------

Antibiotics are unlikely to be effective for most


patients with suspected acute sinusitis.
Signs & symptoms are not reliable for
diagnostic purposes.
Symptoms may last up to 2 weeks & resolve
without additional studies or antibiotics.
Treat acute sinusitis with symptomatic
measures.
-------------------------------------------------Most patients with suspected acute sinusitis
receive antibiotics, but there is little evidence to
support the effectiveness of this practice.
Patients with more severe symptoms had a
longer period of illness, but antibiotics did not
decrease symptom severity or infection
duration.
Administration of antibiotics, if used, should be
limited to patients with at least two of the
following findings: symptoms lasting > 7 days,
facial pain, & purulent nasal discharge.
Amoxicillin or doxycycline are first-line agents
TMP-SMX is acceptable if -lactam-allergic.
-------------------------------------------------Managing pharyngitis includes estimating the
probability of the presence of group A hemolytic streptococcal (GABHS) infection.
The four-point Centor criteria (fever, absence
of cough, tonsillar exudates, & tender anterior
cervical lymphadenopathy) are used as a
prediction rule in suspected GABHS infection.
Patients with 0 or 1 criterion have a low (<3%)
probability of GABHS, & neither testing nor
antibiotic treatment is recommended.
Patients with two Centor criteria have an
intermediate probability for GABHS infection,
& rapid streptococcal antigen testing is a
reasonable strategy.
Patients with Centor scores of 3 or 4 who have
negative rapid antigen testing should then
undergo throat cultures to guide treatment.
Empiric antibiotic therapy is recommended for
patients meeting all four Centor criteria because

probability of GABHS is 40% or greater.


-------------------------------------------------If treatment is indicated, antibiotic of choice is
penicillin for acute pharyngitis.
Macrolides & first- & second-generation
cephalosporins are alternative choices for
penicillin-allergic patients.
-------------------------------------------------Otitis media is the most frequent bacterial
infection in children & less common in adults.
In cases of acute otitis media, a viral URI
precedes the ear infection.
Eustachian tube obstruction occurs secondary
to inflammation. Bacteria subsequently enter
the middle ear by means of a compliant
eustachian tube, aided by other factors,
including nose blowing, sniffing, & negative
middle ear pressure.
------------------------------------------------Microbiology of otitis media in adults is similar
to that of children: Streptococcus pneumonia,
Haemophilus influenzae, Staphylococcus
aureus& Moraxella catarrhalis.
-------------------------------------------------Antibiotics should be reserved for patients
with evidence of purulent otitis.
-------------------------------------------------Amoxicillin is the initial antibiotic for acute
otitis media because of its proven efficacy,
safety, relatively low cost, & narrow spectrum
of activity.
If symptoms do not improve after 48 to 72
hours with amoxicillin, initiation of
amoxicillin-clavulanate, cefuroxime, or
ceftriaxone is recommended.
Alternative agents for patients with penicillin
allergy are oral macrolides (azithromycin,
clarithromycin).
Follow-up is not necessary unless symptoms
persist or progress.
-------------------------------------------------Treat otitis media with amoxicillin.
--------------------------------------------------

Prevent URIs with hand washing.


-------------------------------------------------A serious complication of untreated group A
-hemolytic streptococcal (GABHS)
infection is peritonsillar abscess.
-------------------------------------------------Complications of untreated group A hemolytic streptococcal (GABHS) infection
include peritonsillar abscess ("quinsy"),
poststreptococcal glomerulonephritis, &
rheumatic fever.
The patient is not responding to antibiotics. He
most likely has a peritonsillar abscess.
-------------------------------------------------Patients with peritonsillar abscess who present
first with sore throat are distinguished by
worsening sore throat despite antibiotic
therapy, fever dysphagia, pooling of saliva,
possible drooling, & muffled voice.
On physical exam, the patient is ill-appearing &
often has enlarged tonsils with deviation of the
uvula to the unaffected side.
Complications include airway obstruction,
dissection of the infection to the parapharyngeal
space, spontaneous abscess drainage &
aspiration of pus (while sleeping) & sepsis.
Treatment consists of needle drainage or
surgical incision & drainage of the abscess.
The most appropriate management for this
patient is emergent ENT consultation.
-------------------------------------------------Diagnostic criteria for sepsis include either a
culture-proven infection or visual identification
of an infection (wound with purulent drainage)
& at least two criteria fulfilling the definition
of a systemic response to infection (fever,
tachycardia, tachypnea, & elevated leukocyte
count with immature band forms).
Organ dysfunction or perfusion abnormalities
(hypotension & lactic acidosis) occur in patients
with severe sepsis or septic shock.
-------------------------------------------------Septic shock: subset of severe sepsis, defined

1.
2.
3.
4.

as sepsis-induced hypotension despite


adequate fluid resuscitation plus presence of
perfusion abnormalities.
Patients receiving inotropic or vasopressor
agents may no longer be hypotensive by the
time they develop hypoperfusion abnormalities
or organ dysfunction; however, they would still
be considered to have septic shock.
-------------------------------------------------Severe sepsis: sepsis a/w organ dysfunction,
hypoperfusion, or hypotension.
-------------------------------------------------Systemic inflammatory response syndrome
(SIRS): systemic inflammatory response to a
wide variety of severe clinical insults,
manifested by at least two of the following:
Temp > 38.0C (100.4F) or < 36.0C (96.8F)
HR > 90/min
RR > 20/min or arterial PCO2 < 32 mm Hg
leukocyte count > 12,000/L (12 109/L) or <
4000/L (4 109/L) or greater than 10%
immature band forms.
-------------------------------------------------Most patients with sepsis need at least 4 to 6 L
of intravascular volume replacement within the
first 6 hours.
-------------------------------------------------Sepsis can result in tissue hypoperfusion.
Management of sepsis includes placement of a
central venous line & aggressive fluid
resuscitation will have the greatest impact on
improving a patient's chances of survival.
Most patients need intravascular volume
replacement of at least 4 to 6 L of within the
first 6 hours, & one of the biggest pitfalls of
management is underestimating the
intravascular volume deficit.
------------------------------------------------Vasopressors are part of early goal-directed
therapy if mean arterial pressure is < 65 mm Hg
after initial adequate fluid resuscitation.
Vasopressor therapy with norepinephrine,
vasopressin, or dopamine is used when

appropriate fluid challenge fails to restore


adequate tissue perfusion or life-threatening
hypotension.
------------------------------------------------Norepinephrine is the most commonly used
vasopressor for septic shock, a potent
peripheral vasoconstrictor that reverses the
endotoxin-induced vasodilation that is the
hallmark of septic shock.
Dopamine is also acceptable but is a/w more
tachycardia & arrhythmia. Low-dose dopamine,
however, is not indicated.
------------------------------------------------Drotrecogin alfa (activated protein C) is
approved for patients with severe sepsis who
are at high risk for death.
It is indicated in patients that meet the high-risk
mortality threshold determined by a severity-ofillness scoring system such as APACHE (Acute
Physiology & Chronic Health Evaluation) II
with a score of greater than 25 or presence of
septic shock requiring vasopressors, sepsisinduced ARDS requiring mechanical
ventilation, or two or more sepsis-induced
organ dysfunctions.
It is a/w increased bleeding risk at rates similar
to those of heparin.
Drotrecogin alfa is contraindicated in the
presence of active bleeding, concurrent therapy
with other anticoagulants, & platelet counts less
than 30,000/L, & patients with risks of
uncontrollable or CNS bleeding.
-------------------------------------------------Activated protein C (Drotrecogin alfa)
improves survival for severe sepsis in patients
with APACHE score of 25 or greater.
-------------------------------------------------Activated protein C (drotrecogin alfa) is a
time-sensitive intervention that can improve
survival in severe sepsis at high risk of death,
who have APACHE score of 25 or greater.
Patients with either a single failing organ
system or APACHE score less than 25 do not

appear to benefit & risk bleeding complications.


-------------------------------------------------Activated protein C is an anticoagulant; when
administered to patients with a platelet count
between 30,000/L & 50,000/, there is a
relative risk reduction in mortality of > 30%.
Platelet counts below 30,000/L are considered
a relative contraindication.
-------------------------------------------------Goals of fluid resuscitation in severe sepsis are
a central venous pressure of 8 - 12 mm Hg,
mean arterial pressure greater than 65 mm Hg,
urine output greater than 0.5 mL/kg/h, & central
venous oxygen saturation greater than 70%.
There is no benefit to the use of colloid
compared with crystalloid fluids.
-------------------------------------------------For severe sepsis, aggressive fluid resuscitation
with resolution of lactic acidosis within 6 hours
will have a beneficial effect on patient survival.
Fluid resuscitation should target central
venous oxygen saturation (SCVO2) or mixed
venous oxygen saturation (SVO2) at least 70%.
Other reasonable goals include CVP of 8 to 12
mm Hg, MAP at least 65 mm Hg, & urine
output at least 0.5 mL/kg/h.
This translates into administration of 5 to 6 L of
fluid over 6 hours.
Early goal-directed therapy that includes
interventions within the first 6 hours to
maintain a SCVO2 of greater than 70% &
resolve lactic acidosis results in higher survival.
-------------------------------------------------Treat severe sepsis with aggressive fluid
resuscitation.
-------------------------------------------------In sepsis, vasopressors can be added as part of
early goal-directed therapy if a fluid challenge
fails to achieve a mean arterial pressure
greater than 65 mm Hg despite adequate fluid
resuscitation.
--------------------------------------------------

In septic patients with identifiable or potential


sources of infection, source control, including
indwelling catheters, drainage of abscesses, &
surgical debridement of wounds should be
done promptly.
Patient with evidence of tissue destruction &
infection with gas-forming organisms, early
surgical debridement is an urgent necessity.
-------------------------------------------------Serotonin syndrome presents with high fever,
muscle rigidity, & cognitive changes.
Unique findings are shivering, hyperreflexia,
myoclonus, & ataxia.
-------------------------------------------------Neuroleptic malignant syndrome is a lifethreatening disorder caused by an idiosyncratic
reaction to neuroleptic tranquilizers
(dopamine D2-receptor antagonists) &
antipsychotics.
The most common offending neuroleptic agents
are haloperidol & fluphenazine.
The syndrome occurs with all drugs that cause
central dopamine receptor blockade, usually
soon after starting a new drug or with dose
escalation.
It has been reported with Parkinson disease
patients who abruptly discontinue levodopa
or anticholinergics.
Most patients develop muscle rigidity,
hyperthermia, cognitive changes, autonomic
instability, diaphoresis, sialorrhea, seizures,
arrhythmias, & rhabdomyolysis within 2 weeks
after initiating the drug.
-------------------------------------------------Malignant hyperthermia is an inherited
skeletal muscle disorder characterized by a
hypermetabolic state precipitated by exposure
to volatile inhalational anesthetics (halothane,
isoflurane, enflurane, desflurane, sevoflurane)
& depolarizing muscle relaxants
succinylcholine & decamethonium.

It usually occurs on exposure to the drug but


can occur several hours after the initial
exposure & can develop in patients who were
previously exposed to the drug without effect.
Increased intracellular calcium leads to
sustained muscle contractions, with skeletal
muscle rigidity & masseter muscle spasm,
tachycardia, hypercarbia, HTN, hyperthermia,
tachypnea, & cardiac arrhythmias.
Rhabdomyolysis (elevated creatine kinase) &
acute renal failure can develop.
It should be suspected in patients with a family
history of problems during anesthesia.
-------------------------------------------------Patients with systemic lupus erythematosus
(SLE) can have cutaneous involvement at some
point in their disease course.
Most rashes a/w SLE occur in sun exposed areas
>90% with SLE develop joint involvement that
can manifest as arthralgia or true arthritis.
Joint pain is often migratory, & can be
oligoarticular/polyarticular,
asymmetric/symmetric.
-------------------------------------------------Familial Mediterranean fever is an autosomal
recessive disorder prevalent in people of
Jewish, Turkish, Arabic, & Armenian heritage.
Most patients have onset of illness before age
10 years, 95% before age 20 years.
The key feature is short periods of fever (1-3
days) a/w serositis; abdominal pain, & pleuritis
& synovitis are also common.
Episodes of fever are accompanied by elevated
markers of inflammation such as leukocytosis
& ESR elevation.
-------------------------------------------------Factitious fever usually is diagnosed in young
women with unusual fever patterns such as
very high or brief spikes & rapid defervescence
without chills, & diaphoresis.
A fever diary will typically demonstrate a lack
of normal diurnal temperature variation.

Physical & lab findings of infection or


inflammation are lacking during febrile illness.
-------------------------------------------------Most early localized Lyme disease occurs in
the summer & fall & is characterized by the
erythema migrans rash, expanding
erythematous patch appears 5 to 14 days after
inoculation by an infected tick.
-------------------------------------------------Babesiosis is caused by Babesia microti, an
intracellular protozoan parasite.
It is transmitted to humans by ticks & occurs
primarily in northeastern US with an epicenter
in Cape Cod, Massachusetts, & associated
islands.
Most infections are subclinical, but a
nonspecific febrile illness can occur.
Babesiosis should be considered in patients who
have traveled to endemic areas & now have a
nonfocal febrile illness with chills, sweats,
myalgia, arthralgia, nausea, vomiting, fatigue.
Physical exam: fever, splenomegaly,
hepatomegaly, & jaundice.
-------------------------------------------------Rocky Mountain spotted fever (RMSF)
presents with a flu-like illness during the
summer months.
Because of the nonspecific nature of symptoms,
RMSF should be considered in patients with a
nonspecific febrile illness within 3 weeks of
potential tick exposure.
Immediate treatment with doxycycline should
be given pending results of diagnostic studies.
Many people with tick-borne infection do not
recall a specific tick bite.
Characteristic blanching erythematous
macules located around the wrists & ankles
that spread centripetally.
The most commonly available diagnostic test
for RMSF is a convalescent serology.
--------------------------------------------------

VII. Nephrology

Hyponatremia early signs include nausea,


vomiting, & headaches.
Progressive manifestations include impaired
mental status & seizures.
-------------------------------------------------Hypokalemia can cause diffuse muscle
weakness, GI tract atony, respiratory failure, &
cardiac arrhythmias.
-------------------------------------------------Hypercalcemia may manifest as decreased
neuromuscular excitability that causes
decreased muscular tone.
-------------------------------------------------Severe hypophosphatemia most often
develops in patients with chronic alcoholism
who have poor oral intake, decreased intestinal
absorption due to frequent vomiting & diarrhea,
& increased kidney excretion due to the direct
effect of ethanol on the tubule.
Despite total body phosphorus depletion,
patients may have normal serum phosphorus
levels on admission.
Severe hypophosphatemia often develops over
the first 12 to 24 hours after admission,
usually because of IV glucose administration,
which stimulates insulin release & causes
phosphate to shift into cells.
Sudden development of hypophosphatemia may
cause confusion, rhabdomyolysis, hemolytic
anemia, & severe muscle weakness that can
lead to respiratory failure.
Oral phosphate is the preferred treatment in
this setting, but IV may be needed if oral
therapy cannot be tolerated.
-------------------------------------------------The most common cause of hypercalcemia in
the outpatient setting is hyperparathyroidism.
-------------------------------------------------Diagnosis of humoral hypercalcemia of
malignancy can be made in the absence of

PTHrP measurements if compatible with


malignancy, hypercalcemia, & suppressed PTH.
-------------------------------------------------Humoral hypercalcemia of malignancy
results from the systemic effect of parathyroid
hormone-related protein (PTHrP) produced by
neoplastic cells.
This peptide's N-terminal shares homologic
features with PTH & most, if not all, of the
metabolic effects of PTH.
Tumors that elaborate PTHrP are most
commonly squamous cell carcinomas, such as
those of the lung, esophagus, & head & neck.
-------------------------------------------------PTH increases the serum calcium level is by
up-regulation of the 1-hydroxylase, which
stimulates conversion of vitamin D to its active
form, 1,25-dihydroxy vitamin D. This form of
vitamin D increases the percentage of dietary
calcium absorbed by the intestine.
Body stores of vitamin D are assessed by
measuring the 25-hydroxy vitamin D level,
which has a long half-life.
-------------------------------------------------Calcitonin is secreted by thyroid parafollicular
C cells; serum level is elevated in patients with
medullary thyroid cancer or C-cell
hyperplasia.
Calcitonin lowers the calcium level by
enhancing cellular uptake, renal excretion, &
bone formation.
-------------------------------------------------Primary hyperparathyroidism is the most
common cause of hypercalcemia in the
outpatient setting.
The first step in the diagnosis of hypercalcemia
is determination of the PTH level with an assay
for intact PTH.
Diagnosis is confirmed if the PTH level is high
or "inappropriately" normal.
-------------------------------------------------Sarcoidosis causes hypercalcemia through
increased production of 1-hydroxylase & is

treated with prednisone.


-------------------------------------------------A patient presents with severe constipation due
to hypercalcemia in the setting of sarcoidosis.
Sarcoidosis is a multisystem, granulomatous,
inflammatory condition of unknown cause that
occurs in young adults of both sexes.
The temporal pattern of disease progression
ranges from asymptomatic to acute systemic
presentations with fever, erythema nodosum,
polyarthralgia, & hilar lymphadenopathy
(Lofgren syndrome).
90% of patients have pulmonary involvement
at presentation.
-------------------------------------------------Hypercalcemia & hypercalciuria in
sarcoidosis are caused by unregulated
production of 1-hydroxylase by activated
macrophages in the granuloma tissue.
Increased 1-hydroxylase activity increases the
production of 1,25 [OH]2 vitamin D.
Increased amounts of vitamin D3 result in
increased GI absorption of calcium, resulting in
hypercalcemia.
Corticosteroids decrease vitamin D3 production
by decreasing activated macrophages.
-------------------------------------------------Measures taken to treat acute symptomatic
hypercalcemia include increasing urinary
excretion of calcium.
Urine calcium excretion can be attained by
inhibition of proximal tubular & loop sodium
resorption, achieved by volume expansion using
IV normal saline infusion (1-2 L for 1 hour).
This is reserved for symptomatic patients with
moderate calcium elevation (>12 mg/dL).
-------------------------------------------------Cinacalcet binds to the parathyroid calciumsensing receptor, leading to decreased release of
parathyroid hormone.
This therapy is indicated only in refractory
secondary hyperparathyroidism of chronic
kidney disease (low serum calcium & elevated

PTH levels) or tertiary hyperparathyroidism


(elevated serum calcium & elevated serum PTH
levels).
------------------------------------------------Hydrochlorothiazide indirectly inhibits
calcium excretion by the kidney, leading to
calcium retention, causing hypercalcemia.
-------------------------------------------------1,25-hydroxy vitamin D deficiency is
commonly seen in chronic kidney disease, due
to decreased activity of 1-hydroxylase
responsible for converting 25-OH vitamin D to
the active form.
-------------------------------------------------Acute pancreatitis can generate free fatty acids
that avidly chelate insoluble calcium salts in the
pancreatic bed, resulting in hypocalcemia.
-------------------------------------------------The most likely cause of the patient's
hypocalcemia is calcium chelation with free
fatty acids liberated by pancreatic enzymes in
an episode of acute gallstone pancreatitis.
When the pancreas is injured, secretion of
pancreatic enzymes is blocked, which leads to
autodigestion of the pancreas.
Pancreatic enzymes are then released within the
peritoneum & digest fat; the generated free fatty
acids avidly chelate insoluble calcium salts,
resulting in hypocalcemia & deposition of
calcium salts in the pancreatic bed known as
saponification, which can lead to symptomatic
hypocalcemia & calcium deposits.
Pancreatic calcification identified by imaging
studies is diagnostic of chronic pancreatitis.
-------------------------------------------------Distinguishing between central & nephrogenic
diabetes insipidus in a patient who is already
hyperosmolar can be done by measuring
plasma arginine vasopressin (AVP).
o central diabetes insipidus have an
inappropriately low AVP levels
o nephrogenic diabetes insipidus has a
normal to elevated AVP levels

Or by evaluating the response to administered


AVP or, preferably, the selective AVP V2
receptor agonist desmopressin.
-------------------------------------------------Hyperosmolar patients without glucosuria who
have submaximally concentrated urine have
diabetes insipidus by definition.
-------------------------------------------------Hyperosmolar state is estimated by serum
sodium level x2 (normal, 275-295 mosm/kg).
The appropriate renal response to
hyperosmolality is to maximally concentrate the
urine (generally to > 800 mosm/kg).
If this response is not seen, the patient has
either diabetes insipidus or a solute diuresis.
Solute diuresis is most often caused by
hyperglycemia. The renal threshold for glucose
reabsorption is 200 to 225 mg/d.
Solute diuresis is characterized by isotonicity
of the urine, whereas hyperosmolar state has a
markedly hypotonic urine.
-------------------------------------------------Diagnose laxative abuse in a patient with
hypokalemia.
-------------------------------------------------GI disorders are the most common clinical
cause of extrarenal potassium losses.
Diarrhea leads to fecal potassium wastage &
a/w normal anion gap acidosis due to GI loss
of bicarbonate.
Villous adenoma & laxative abuse are two
conditions that can cause GI potassium losses.
-------------------------------------------------Urine potassium concentration of < 20 meq/L
is suggestive of extrarenal losses (laxative
abuse), whereas a higher concentrations than
this is suggestive of kidney losses.
-------------------------------------------------A patient abusing laxatives is supported by the
serum electrolyte pattern suggesting
hypokalemia & metabolic acidosis.
--------------------------------------------------

The first step in treating urgent hyperkalemia


is to administer IV calcium gluconate to
antagonize hyperkalemic cardiac toxicity, an
effect that begins within 2 to 3 minutes.
-------------------------------------------------Urgent therapy of hyperkalemia consists of
antagonism of the membrane effects of
hyperkalemia & induction of intracellular
potassium shift.
Removing potassium from the body (by sodium
polystyrene sulfonate, hemodialysis, peritoneal
dialysis) is important, but the effects cannot be
accomplished with the necessary urgency.
-------------------------------------------------Sodium bicarbonate & -antagonists such as
albuterol & glucose (with or without insulin)
would facilitate intracellular potassium shift.
However, their effect is slow (10 minutes for
sodium bicarbonate, 15 - 30 minutes for
albuterol, & 30 minutes for glucose & insulin).
-------------------------------------------------EKG showing spiking of the T waves &
widening of QRS complexes indicate
hyperkalemic cardiotoxicity in this patient
with chronic kidney disease.
-------------------------------------------------Treat urgent hyperkalemia with intravenous
calcium gluconate.
-------------------------------------------------A patient with long-standing diabetes mellitus,
HTN, proteinuria, & elevated serum creatinine
are consistent with diabetic nephropathy.
Aggressive BP control, particularly with
modulators of the renin-angiotensin-aldosterone
system, would help slow the progression of the
disease but will likely worsen hyperkalemia.
-------------------------------------------------Discontinue medications that interfere with the
renin-angiotensin-aldosterone system,
including NSAIDs &, if needed, ACE inhibitors
& ARBs, to correct significant hyperkalemia
in the setting of chronic kidney disease.

However, discontinuing ibuprofen alone would


most likely not help to lower blood pressure,
control volume overload, or fully correct
hyperkalemia; a loop diuretic is warranted.
Additional interventions to help decrease the
risk of hyperkalemia include low-potassium
diet & use of sodium bicarbonate.
-------------------------------------------------Discontinuation of ibuprofen & initiation of
furosemide are appropriate next steps in the
initial management of chronic kidney disease.
-------------------------------------------------Until GFR decreases to < 15 mL/min/1.73 m2,
chronic kidney disease usually does not cause
hyperkalemia without other mitigating factors.
These factors include use of medications that
interfere with the renin-angiotensinaldosterone system & NSAIDs.
Use of NSAID ibuprofen is most likely
contributing to this patient's hyperkalemia &
reduced GFR, thus should be discontinued.
-------------------------------------------------Hydrochlorothiazide can cause severe
hyponatremia.
-------------------------------------------------Hydrochlorothiazide is a common cause of
hyponatremia in the outpatient setting;
especially in the elderly.
Early signs of symptomatic hyposmolality may
be very nonspecific, such as nausea, vomiting,
& headaches (hyponatremic encephalopathy).
Worsening of brain swelling then causes
decreased mental status & seizures.
Diuretic-induced hyponatremia most commonly
occurs in patients taking thiazide diuretics.
Elderly women with low body mass indices
who tend to increase fluid intake after initiation
of therapy with thiazides are often affected.
Thiazide diuretics work at the level of the
convoluted tubule & collecting segment.
These agents maintain urinary concentrating
capacity but not diluting capacity, which makes
them prone to hyponatremic encephalopathy.

By inducing relative volume depletion, ADH


secretion is stimulated, which leads to urine
concentration & water retention.
Treatment includes stopping the diuretic &
infusing normal saline (mildly symptomatic)
or 3% saline (significantly symptomatic).
-------------------------------------------------Acetazolamide acts in the proximal tubule as a
carbonic anhydrase IV inhibitor.
Blocking this enzyme impairs bicarbonate
reabsorption but not diluting capacity & most
often a/w hypokalemia & metabolic acidosis.
-------------------------------------------------Plasma osmolality can be directly measured by
an osmometer or calculated using the equation:
Plasma osmolality (mosm/kg = 2 serum [Na+]
(meq/L) + BUN (mg/dL)/2.8 + plasma glucose
(mg/dL)/18
normal: 275-295 mosm/kg
-------------------------------------------------Hyponatremia can be caused by a decrease in
effective arterial blood volume, which results in
baroreceptor stimulation of ADH secretion,
which impairs water excretion.
Consequently, distal delivery of filtrate to the
tip of the loop of Henle decreases. A decrease in
effective arterial blood volume may be a/w low
extracellular fluid volume (hypovolemic
hyponatremia) or high extracellular fluid
volume in edematous patients (hypervolemic
hyponatremia), including heart failure,
cirrhosis, & nephrotic syndrome.
-------------------------------------------------True hyponatremia may be a/w an elevation in
plasma concentration of an effective osmole,
such as glucose. This elevation results in an
increase in plasma osmolality (hyperosmolar
hyponatremia), causing water to leave the cells
& results in a diluted serum sodium
concentration.
--------------------------------------------------

A mixed metabolic & respiratory alkalosis


is suggested by an elevated pH & serum
bicarbonate concentration & PCO2 is lower
than expected for the degree of alkalosis.
-------------------------------------------------For each 1 meq/ increase in serum bicarbonate,
PCO2 can be expected to increase by 0.7 mm
Hg (0.09 kPa).
-------------------------------------------------Ethylene glycol poisoning presents with an
anion gap metabolic acidosis, kidney injury,
increased osmolal gap, & calcium oxalate
crystals in the urine.
-------------------------------------------------A patient with ethylene glycol poisoning may
manifest as acute kidney injury a/w an
increased anion gap metabolic acidosis &
increased osmolal gap.
Osmolal gap is the difference between the
calculated plasma osmolality & measured
plasma osmolality.
The normal osmolal gap is 10 mosm/kg.
-------------------------------------------------Osmolality formula:
2 [Sodium] + [Glucose]/18 + [BUN]/2.8 =
296 mosm/kg
sodium is meq/L; glucose & BUN are mg/dL.
-------------------------------------------------An elevated osmolal gap suggests the presence
of an unmeasured osmole that is commonly
ethanol but can be ethylene glycol or methanol
However, only ethylene glycol is a/w kidney
injury & calcium oxalate crystals in the urine.
-------------------------------------------------In acute respiratory alkalosis, for each 10 mm
Hg decline in PCO2, the expected decline in
serum bicarbonate is 2 meq/L.
-------------------------------------------------Anion gap is is calculated as [Na+] - ([Cl-] +
[HCO3-]).
Normal anion gap is 12 2.
--------------------------------------------------

Common causes of respiratory alkalosis


include psychogenic (hyperventilation a/w
anxiety), normal pregnancy, pulmonary
vascular disease (pulmonary HTN or
pulmonary embolism), pulmonary parenchymal
disease (pneumonia & pulmonary fibrosis),
heart failure, sepsis, cirrhosis.
-------------------------------------------------Renal compensatory response occurs in
respiratory acidosis.
Persistent hypercapnia stimulates the secretion
of protons in the distal nephron. The urinary pH
decreases, & excretion of urinary ammonium,
titratable acid, & chloride is enhanced.
Consequently, reabsorption of bicarbonate
throughout the nephron is enhanced.
The predicted increase in serum bicarbonate is
calculated as 1 meq/L for each 10 mm Hg
increase in PCO2 (acute)
o or 4 meq/L for each 10 mm Hg increase in
PCO2 (chronic; such as COPD).
Because this patient with COPD probably has
chronic retention of CO2, an increase in serum
bicarbonate by at least 8 meq/L is expected.
-------------------------------------------------Normal anion-gap metabolic acidosis can be
of kidney or extrarenal origin.
Metabolic acidosis of kidney origin, such as
renal tubular acidosis (RTA), is caused by
abnormalities in tubular hydrogen transport.
o kidney causes are a/w low net acid
excretion & decreased urine ammonium.
Metabolic acidosis of extrarenal origin is
commonly caused by GI losses of carbon
dioxide; other extrarenal causes include
external loss of biliary & pancreatic secretions
& ureteral diversion procedures.
o Extrarenal causes are a/w an appropriate
increase in net acid excretion primarily
reflected by high levels of urine
ammonium excretion
--------------------------------------------------

Urine ammonium measurement is not a


commonly available study, but can be indirectly
assessed by calculating the urine anion gap
(UAG) using the formula:
Urine anion gap = ([urine sodium] + [urine
potassium]) - [urine chloride]
UAG is normally between 30 & 50 meq/L.
-------------------------------------------------Metabolic acidosis of extrarenal origin is
suggested by a large, negative UAG caused by
significantly increased urine ammonium
excretion.
Metabolic acidosis of kidney origin is
suggested by a positive UAG related to
minimal urine ammonium excretion.
This patient's UAG is 20 meq/L; although it is
within the normal range, it is inappropriately
low for the degree of acidosis. This is
compatible with renal tubular acidosis.
o It is not compatible with gastroenteritis or
laxative abuse, both causes of extrarenal
normal anion-gap acidosis.
-------------------------------------------------Bone disease due to secondary
hyperparathyroidism commonly occurs in
patients with end-stage kidney disease & is
a/w elevated serum PTH & alkaline
phosphatase, hyperphosphatemia, &
hypocalcemia.
-------------------------------------------------Osteoporosis is defined by low bone mass,
which is a/w reduced bone strength & increased
risk of fractures.
Osteoporosis is commonly in postmenopausal
women but may develop secondary to drugs
such as corticosteroids & anticonvulsants.
Osteoporosis does not affect serum calcium,
phosphorus, PTH, or alkaline phosphatase
concentrations.
-------------------------------------------------Chronic kidney disease (CKD) is a/w
progressive alterations in mineral & bone
metabolism that can cause bone disease.

Patients with end-stage kidney disease (ESKD),


the inability to excrete phosphorus leads to
hyperphosphatemia. Loss of kidney function
is a/w 1,25-dihydroxy vitamin D deficiency.
Hyperphosphatemia along with decreased 1,25
dihydroxyvitamin D levels result in
hypocalcemia, which leads to direct
stimulation of PTH secretion.
Decreased 1,25 dihydroxyvitamin D levels also
causes increased production of PTH.
Therefore, bone disease due to secondary
hyperparathyroidism is the most common bone
pathologic finding seen in patients with ESKD.
Hyperphosphatemia, hypocalcemia, & elevated
serum PTH & alkaline phosphatase is consistent
with secondary hyperparathyroidism.
-------------------------------------------------Diabetic nephropathy is characterized by
proteinuria, HTN, & decline in GFR in patients
with a long-standing history of type 1 diabetes
or a 5- to 10-year history of type 2 diabetes.
This progresses over years from
microalbuminuria to macroalbuminuria to
an elevated serum creatinine.
-------------------------------------------------Although this patient's long-standing history of
diabetes & proteinuria is suggestive of diabetic
nephropathy, the presence of glomerular
hematuria (dysmorphic erythrocytes &
erythrocyte casts) & rapid onset of
symptomatic nephrotic syndrome are not
consistent with diabetic nephropathy, but raise
suspicion for primary glomerular disease.
-------------------------------------------------Kidney biopsy would be appropriate for a
patient with nondiabetic kidney disease to
establish a diagnosis & determine treatment.
-------------------------------------------------Delay kidney replacement for patients with
stage 5 chronic kidney disease who are not
hypervolemic, hyperkalemic, acidotic, uremic.
The best course of action would be to follow
the patient closely to ensure he does not

develop uremic signs or symptoms or other


indications for dialysis & strive for
transplantation rather than dialysis.
-------------------------------------------------Kidney transplantation is the treatment of
choice for uremia.
Transplantation in patients who have not yet
been treated with hemodialysis is a/w better
patient & allograft outcomes.
-------------------------------------------------Patients with stage 5 chronic kidney disease
(GRF <15 mL/min/1.73 m2 or receiving
dialysis often develop signs of uremia & require
kidney replacement therapy.
Absolute indications include uncontrollable
hyperkalemia, uncontrollable hypervolemia,
altered mental status or excess somnolence,
pericarditis, or bleeding-diathesis secondary to
uremic platelet dysfunction.
Relative indications include nausea, vomiting,
& poor nutrition caused by decreased appetite;
severe metabolic acidosis; mild changes in
mental status such as lethargy & malaise;
asterixis; & worsening of kidney function with
GFR < 15 mL/min/1.73 m2.
-------------------------------------------------Uncontrolled HTN & proteinuria are important
modifiable risk factors for progressive kidney
disease.
Patients with chronic kidney disease,
guidelines recommend BP targets
o less than 130/80 mm Hg
o < 125/75 mm Hg when significant
proteinuria is present.
ACE inhibitors & ARBs are preferred agents in
chronic kidney disease & slow progression of
kidney disease in patients with diabetes.
These agents reduce efferent arteriolar
resistance & lower intraglomerular pressure &,
therefore, a/w increases in serum creatinine in
patients with a reduced GFR.
An increase in creatinine of up to 30% is
acceptable.

In a patient whose BP remains elevated &


significant proteinuria, the next step would be
to increase losartan. It is not necessary to
discontinue losartan, because the increase in
creatinine is not unexpected.
-------------------------------------------------Prerenal disease is a/w relative low BP,
oliguria, & normal urinalysis.
-------------------------------------------------Renal vein thrombosis is a.w hematuria &
nephrotic-range proteinuria; often a/w
membranous nephropathy, malignancy, trauma,
or hypercoagulable states.
-------------------------------------------------Nausea, vomiting, & anorexia accompanied by
relatively low BP in the absence of edema or
urine sediment abnormalities strongly suggest
prerenal azotemia.
-------------------------------------------------Prerenal azotemia develops when
autoregulation of kidney blood flow can no
longer maintain GFR.
This condition generally occurs in patients with
a MAP below 60 mmHg or at higher pressures
in individuals with chronic kidney disease
(CKD) or those taking medications that alter
local glomerular hemodynamics (NSAIDs).
Patients with prerenal azotemia may have a
history of fluid losses & decreased fluid intake
accompanied by physical exam findings
consistent with extracellular fluid volume
depletion, such as postural hypotension.
-------------------------------------------------Tumor lysis syndrome may manifest as
hyperkalemia, hyperphosphatemia, &
hyperuricemia.
Tumor lysis syndrome occurs in patients with
extremely rapidly progressive lymphoid
neoplasms & those who have bulky lymphoid
neoplasms that respond rapidly to treatment.
Rasburicase can be used to treat malignancyrelated hyperuricemia & prevent tumor lysis
syndrome in high-risk patients or as therapy for

established tumor lysis syndrome & associated


hyperuricemia.
-------------------------------------------------Acute kidney injury in patients with
malignancy is often due to prerenal disease,
obstruction, or use of nephrotoxic agents.
Presence of hypotension, hyponatremia, &
decreased urine sodium excretion accompanied
by a bland urine sediment raises suspicion for
prerenal azotemia.
Dialysis would be indicated if the azotemia
persisted or worsened after correction of the
hypovolemia, particularly for other uremic
complications such as encephalopathy or
refractory hyperkalemia.
-------------------------------------------------Manage prerenal azotemia with isotonic
saline volume replacement.
-------------------------------------------------Acute interstitial nephritis (AIN) commonly
develops after exposure to certain medications,
including trimethoprim & NSAIDs.
Manifestations include rash, pruritus, fever, &
eosinophilia.
Urine sediment findings: leukocyte casts,
pyuria, microscopic hematuria, & proteinuria.
-------------------------------------------------Acute tubular necrosis (ATN) develops after a
sustained period of ischemia or exposure to
nephrotoxic agents such as IV aminoglycosides,
cisplatin, or radiocontrast.
Elevated serum creatinine, minimal proteinuria,
& muddy brown casts on urinalysis are seen.
-------------------------------------------------Rhabdomyolysis develops when muscle injury
leads to the release of myoglobin & other
intracellular muscle contents into circulation.
Myoglobin is known to cause nephrotoxicity
by inducing kidney ischemia & tubular
obstruction.
Rhabdomyolysis develops after exposure to
myotoxic drugs, infection, excessive exertion,
or prolonged immobilization.

Diagnosis should be considered in patients with


a serum creatine kinase (CK) > 5000 U/L
who demonstrate heme positivity on urine
dipstick in the absence of hematuria.
-------------------------------------------------Acute interstitial nephritis (AIN) is caused by
a hypersensitivity reaction to a medication or
by certain infections or autoimmune conditions.
Urinalysis findings in patients may include
leukocyte casts & eosinophils.
-------------------------------------------------Hemolytic uremic syndrome (HUS) manifests
as acute kidney injury (AKI) accompanied by
thrombocytopenia & microangiopathic
hemolytic anemia (schistocytes on peripheral
blood smear).
Two most common causes of HUS are
1. infection by Shiga toxin-producing
Escherichia coli (E. coli O157:H7)
2. familial deficiency of factor H
The toxin causes bloody diarrhea & enters the
circulation & binds to platelets, glomerular
capillary endothelial cells, mesangial cells, &
glomerular & tubular epithelial cells.
Shiga toxin binds to platelets by means of
globotriaosylceramide receptors, which leads to
platelet aggregation.
Shiga toxin also stimulate endothelial cells to
release large von Willebrand factor
multimers, to further enhance platelet
aggregation.
Factor H, a protein in the complement
pathway, normally protects cells from damage
by the alternative complement pathway.
A deficiency of factor H allows C3 to potentiate
autoantibody-mediated or immune complexmediated injury to glomerular cells, leading to
exposure of subendothelium & activation of
both platelets & coagulation.
-------------------------------------------------Kidney ultrasound is indicated for all patients
with acute kidney injury to define kidney

anatomy & exclude hydronephrosis.


-------------------------------------------------The patient with lower urinary tract symptoms
with difficulty voiding & suprapubic fullness is
consistent with bladder outlet obstruction
from prostatic hypertrophy.
Obstruction can cause ischemic tubular injury,
intrarenal vasoconstriction, & interstitial
fibrosis that may lead to end-stage kidney
disease if uncorrected.
Complete obstruction is a/w significantly
decreased urine output, but partial obstruction
may have polyuria caused by loss of tubular
function or excretion of excess retained solute.
Acute kidney injury (AKI) caused by urinary
tract obstruction have a favorable prognosis
when obstruction is relieved within 1 week of
onset.
Kidney ultrasound would reveal a distended
bladder & possible hydronephrosis.
Insertion of a Foley catheter is initial treatment
-------------------------------------------------Kidney biopsy should be considered when the
diagnosis of AKI remains unclear after
excluding prerenal & postrenal disease.
Biopsy is warranted to help guide therapy or
provide prognostic information.
-------------------------------------------------Rhabdomyolysis is a/w muscle pain, weakness,
& dark urine; lab findings include elevated
serum creatine kinase & positive urine dipstick
for blood in the absence of erythrocytes.
-------------------------------------------------Rhabdomyolysis is caused by skeletal muscle
damage that leads to release of intracellular
components into the circulation.
Nontraumatic causes include alcohol (due to
hypophosphatemia), drug use, infections, &
metabolic disorders.
Classic triad: muscle pain, weakness, dark urine
Diagnosis is based on clinical findings &
history of predisposing factors (prolonged
immobilization or drug toxicity) & confirmed

by presence of myoglobinuria, increased serum


creatine kinase, & some cases, hyperkalemia.
A positive urine dipstick for blood in the
absence of erythrocytes.
The disorder resolves within days to weeks.
Treatment is aggressive fluid resuscitation;
adjusted to maintain hourly urine output at least
300 mL until urine is negative for myoglobin.
-------------------------------------------------Diagnose rhabdomyolysis secondary to
narcotic overdose.
-------------------------------------------------In patients with nonglomerular hematuria,
kidney ultrasound & cystoscopy are indicated
to exclude a genitourinary tract malignancy
in individuals with risk factors.
-------------------------------------------------Persistent hematuria is defined as the
presence of three or more erythrocytes/hpf in
the urine detected on two or more samples.
Bleeding with persistent hematuria may
originate anywhere along the genitourinary tract
Differentiating between glomerular &
nonglomerular hematuria guides management.
This patient's normal-appearing erythrocytes
revealed on urine microscopy & absence of
erythrocyte casts & protein in the urine are
consistent with nonglomerular hematuria.
-------------------------------------------------One possible cause of persistent nonglomerular
hematuria is genitourinary tract malignancy.
Risk factors include males, age greater than 50
years, tobacco use, & exposure to drugs such as
cyclophosphamide & benzene, & radiation.
A patient with several risk factors, cystoscopy
is indicated to exclude a malignancy.
-------------------------------------------------A slightly increased serum creatinine level is
suggestive of glomerular disease, which often
manifests as a decrease in kidney function.
Glomerular hematuria is commonly a/w
dysmorphic erythrocytes & erythrocyte casts.

Glomerular disease also is unlikely in the


absence of proteinuria.
Kidney biopsy is often used to evaluate
patients with glomerular disease.
-------------------------------------------------Evaluate persistent hematuria with cystoscopy.
-------------------------------------------------Acute interstitial nephritis is a/w acute kidney
injury, sterile pyuria, & leukocyte casts.
-------------------------------------------------Acute kidney injury (AKI) is evidenced by the
sudden onset of oliguria & increased BUN &
serum creatinine.
Urine (normal upon admission) is positive for
leukocytes & leukocyte casts, but negative
culture (sterile pyuria), this is consistent with
acute interstitial nephritis.
Patients may have fever, rash, & eosinophilia.
--------------------------------------------------lactam antibiotics, are the most common
etiology of acute interstitial nephritis.
-------------------------------------------------Acute tubular necrosis (ATN) is the most
common form of intrarenal disease that causes
acute kidney injury in hospitalized patients.
Onset occurs after a sustained period of
ischemia or exposure to nephrotoxic agents.
Urinalysis reveals muddy brown casts; &
absence of leukocytes & leukocyte casts.
-------------------------------------------------Cholesterol crystal embolization may cause
AKI in those with aortic atherosclerotic plaques
This condition may occur spontaneously but
often develops after coronary or kidney
angiography or aortic surgery.
-------------------------------------------------Evaluate for suspected orthostatic proteinuria
by obtaining separate upright (daytime) &
supine (overnight) urine collections for protein
quantitation.
Orthostatic proteinuria is defined by an
increase in urinary protein excretion only in the

upright position; when supine, urinary protein


excretion rate is normal (<50 mg/8 h).
Most common in children or young adults.
The total urine protein excretion rate is usually
< 1 g/24 h, & urinalysis is otherwise normal.
The condition is benign; often resolves
spontaneously, renal function remains normal.
Kidney biopsy is not the appropriate next step.
-------------------------------------------------If the patient prove to have persistent
proteinuria, urine protein electrophoresis &
immunofixation studies may be useful in
determining whether the proteinuria reflects
glomerular or tubular disease.
--------------------------------------------------

VIII. Neurology

Loss of sensation in a "stocking-glove"


distribution a/w paresthesias or painful
dysesthesias is the most common presentation
of diabetic neuropathy.
-------------------------------------------------No direct treatment for diabetic neuropathy
exists, other than to improve glycemic control.
Pharmacologic therapy may help symptoms.
Partial serotonin & norepinephrine reuptake
inhibitors (duloxetine), tricyclic antidepressants
(amitriptyline), & antiseizure medications
(gabapentin, phenytoin, carbamazepine) are
frequently used to treat associated pain.
-------------------------------------------------Multiple sclerosis is the most common
demyelinating disorder characterized by
discrete subacute episodes of neurologic
dysfunction that progress over days to weeks,
plateau; then improves partially or completely
over subsequent days to months.
Lumbar puncture & CSF exam should be
considered in patients with acute, severe, or
rapidly progressive neuropathy & those with
a demyelinating neuropathy (MS).
Lumbar puncture may confirm the presence of
an inflammatory process in the CSF but would
not result in a specific diagnosis.
-------------------------------------------------Carpal tunnel syndrome refers to median
nerve compression at the wrist in the carpal
tunnel. Symptoms include aching wrist pain
with sparing of the palm, numbness & tingling
in the median nerve sensory distribution of the
fingers, & weakness of thenar muscles.
Paresthesias are often worse at night.
-------------------------------------------------Ulnar nerve compression at the wrist is also
called Guyon tunnel syndrome, because
entrapment occurs where the ulnar nerve
transverses the Guyon tunnel between the

pisiform & hamate bones on the anterolateral


side of the wrist, & also cyclist's palsy.
-------------------------------------------------de Quervain tenosynovitis is an exerciserelated injury a/w knitting & sports involving
extensive wrist action.
Tenderness may be elicited in the anatomic
snuffbox (extensor pollicis brevis & abductor
pollicis longus tendons).
Pain elicited by flexing the thumb into the
palm, closing the fingers over the thumb, &
then bending the wrist in the ulnar direction
(Finkelstein test) is confirmatory.
-------------------------------------------------Ganglion cysts are synovia-filled cysts arising
from joints or tendon sheaths that typically
appear on the dorsal hand or ventral wrist. They
can cause pain & compress other structures.
-------------------------------------------------Guillain-Barre syndrome is a disorder
affecting the peripheral nervous system a/w
rapidly progressive extremity weakness,
paresthesias, & areflexia.
Patients typically develop paresthesias distally
in the lower extremities that are followed by
limb weakness & gait unsteadiness.
Symptoms peak within 4 weeks of onset.
In addition to sensory loss & limb weakness,
deep tendon reflexes are absent or reduced.
Diagnosis is confirmed by electromyography,
which usually shows a demyelinating
polyradiculoneuropathy.
IV immune globulin & plasma exchange are
equally efficacious for treatment.
-------------------------------------------------Diabetes mellitus most commonly causes a
slowly progressive, distal, symmetric
sensorimotor polyneuropathy.
Autonomic dysfunction frequently is a/w
diabetic neuropathy & characterized by
symptoms of impotence, gastroparesis, &
orthostatic hypotension.
--------------------------------------------------

Amyotrophic lateral sclerosis (ALS) is a


degenerative disease of the anterior horn cells
of the spinal cord
ALS presents with both upper & lower motor
neuron signs
o hyperreflexia, spasticity, & Babinski
positive (UMN signs)
o weakness, muscle atrophy, &
fasciculations (LMN signs).
-----------------------------------------------The seventh cranial nerve innervates all
muscles of facial expression (mimetic muscles).
Any cause of a complete facial neuropathy
will therefore impair the entire hemiface,
including the forehead corrugators typically
spared by cerebral lesions.
-------------------------------------------------The precise cause of Bell palsy is not known, &
still considered an idiopathic disorder.
-------------------------------------------------Bell phenomenon describes the reflexive
rolling upwards of the globe during eye closure.
When a normal patient is asked to close the
eyes, forced eyelid opening will reveal this
phenomenon, as will the selective paralysis of
the orbicularis oculi due to a facial neuropathy.
Facial neuropathies will otherwise spare the
extraocular muscles that govern globe
movement.
-------------------------------------------------Bell palsy is a diagnosis of exclusion.
Exclude other identifiable causes of facial
paralysis: Lyme disease, HIV, acute & chronic
otitis media, cholesteatoma, multiple sclerosis.
-------------------------------------------------Cerebral infarction, brain hemorrhage, or any
structural brain lesion can cause weakness of
the lower face but not the forehead because
the bilateral cortical representation of the
midline forehead.
-------------------------------------------------Treatment with sumatriptan is indicated for
migraine headache.

All triptans promote vasoconstriction & block


pain pathways in the brainstem.
Triptans are contraindicated with stroke &
uncontrolled hypertension.
-------------------------------------------------Initial subarachnoid hemorrhage is a/w a
high risk of rebleeding.
Rebleeding is a/w high mortality.
Treatment involves localizing the aneurysm
with cerebral angiography & securing it to
prevent subsequent bleeding.
-------------------------------------------------A lumbar puncture with subsequent CSF
analysis is necessary in any patient with
thunderclap headache & normal findings on a
CT scan to fully evaluate a possible
subarachnoid hemorrhage.
-------------------------------------------------Thunderclap headache is a severe & explosive
headache that is maximal in intensity at or
within 60 seconds of onset.
CT scan is the initial test in a patient with
thunderclap headache in whom a subarachnoid
hemorrhage is suspected; a ruptured
intracranial aneurysm is the most serious cause.
On the day of the hemorrhage, extravasated
blood will be present in more than 95% of
patients, but in the following days, this
proportion falls sharply.
If an initial CT scan of the head reveals nothing,
a lumbar puncture should be performed next.
Xanthochromia or gross hemorrhage is
diagnostic for subarachnoid hemorrhage.
Subsequent angiography (CT or MRI) can
confirm the presence of a ruptured aneurysm in
patients with a positive lumbar puncture.
-------------------------------------------------Evaluate a subarachnoid hemorrhage with a
lumbar puncture & cerebrospinal fluid analysis.
-------------------------------------------------For uncomplicated ischemic strokes in
patients without concurrent acute coronary
artery disease or heart failure, consensus exists

that antihypertensive medications, such as


intravenous labetalol or nicardipine, should
be withheld if the systolic BP is < 220 mm Hg
or the diastolic BP is < 120 mm Hg, unless
there are manifestations of end-organ damage.
-------------------------------------------------There is no urgent need to treat hypertension in
an uncomplicated ischemic stroke.
Many patients have spontaneous declines in BP
during the first 24 hours after stroke onset.
-------------------------------------------------A patient is not eligible for recombinant TPA
therapy if the time interval between now &
previous symptom-free state is > 3 hours.
Aspirin given within 48 hours of stroke onset
results in a small but significant reduction in the
risk for recurrent stroke during the first 2 weeks
after a stroke & improves outcome at 6 months.
Therefore, aspirin is recommended as initial
therapy for most patients with acute stroke.
-------------------------------------------------The preferred treatment of ischemic stroke is
IV recombinant tissue plasminogen
activator if it can be given within 3 hours
from stroke onset.
-------------------------------------------------Aspirin is indicated for acute ischemic stroke
in patients who are not eligible for rtPA.
For patients with acute stroke who are eligible
for thrombolysis, aspirin should be withheld in
the ER & 24 hours after rtPA administration.
------------------------------------------------Elevated BP is common at the time of initial
stroke presentation, even among patients
without chronic hypertension.
Rapid lowering of BP may further impair
cerebral blood flow & worsen ischemic injury.
Elevated BP often will resolve spontaneously or
improve during the first few days after a stroke.
The threshold for acute BP lowering in patients
with acute stroke who are eligible for
thrombolysis is 185/110 mm Hg. In such a
setting, preferred agents include intravenous

infusions of labetalol or nicardipine.


-------------------------------------------------Treat an acute hemispheric stroke with
thrombolytic therapy (IV recombinant tissue
plasminogen activator).
-------------------------------------------------On admission to a hospital ward, a patient with
stroke should be given nothing by mouth until
a swallowing assessment is conducted.
A patient with significant language disturbance,
there is concern for the possibility of
aspiration; the patient should not be prescribed
a diet until a swallowing assessment has been
conducted to determine safety in swallowing.
A water swallow test performed at the bedside
by a trained observer is the best bedside
predictor of aspiration.
-------------------------------------------------Early mobilization & graded exercise promotes
more complete recovery from stroke & prevents
complications such as decubitus ulcers,
deconditioning, & loss of function.
Early mobilization with physical &
occupational therapy is recommended.
-------------------------------------------------Treat acute stroke with early mobilization.
-------------------------------------------------Bacterial meningitis in adults is characterized
by fever, headache, nuchal rigidity, & signs of
cerebral dysfunction.
In elderly patients insidious onset with lethargy
or obtundation & variable signs of meningeal
irritation may be present, particularly in the
setting of diabetes mellitus.
-------------------------------------------------Etiologic agents of bacterial meningitis are
Streptococcus pneumoniae, Listeria
monocytogenes, Neisseria meningitidis, &
aerobic gram-negative bacilli.
-------------------------------------------------Empirically treat penicillin-resistant S.
pneumonia with vancomycin & ceftriaxone.

Treat meningitis caused by L. monocytogenes,


with the addition of ampicillin.
-------------------------------------------------Adjunctive dexamethasone should be
considered in patients with acute bacterial
meningitis because the benefit on adverse
outcomes & death in adults with suspected or
proven S. pneumoniae meningitis.
-------------------------------------------------Treat bacterial meningitis empirically with
vancomycin, ampicillin, & ceftriaxone.
-------------------------------------------------Meningococcal infection should be considered
in the differential diagnosis of any previously
healthy patient who presents with acute-onset
fever, headache, rash, & myalgia.
-------------------------------------------------Viral meningitis can present with fever,
headache, stiff neck, & photophobia & may be
a/w a maculopapular eruption.
-------------------------------------------------Neisseria meningitidis (meningococcal)
infection is characterized by the sudden onset of
fever, myalgia, headache, & rash in a previously
healthy patient.
Early in its course, meningococcal disease may
be indistinguishable from other common viral
illnesses; the rapidity with which the disease
worsens (often over hours) & progresses to
septic shock differentiates it from other illnesses
A petechial rash is most common & may
coalesce to form purpuric lesions.
Diagnosis is established by clinical presentation
& confirmed with blood & CSF cultures.
-------------------------------------------------Vibrio vulnificus is a gram-negative bacillus
that can cause septicemia, wound infection, &,
rarely, gastroenteritis.
Wound infection occurs by skin inoculation.
Septicemia & gastroenteritis occur after
ingestion of raw or undercooked shellfish.
--------------------------------------------------

Meningitis caused by Listeria monocytogenes is


a/w extremes of age (neonates & age >50 years).
Presentation of Listeria meningoencephalitis
ranges from a mild illness with fever & mental
status changes to a fulminant course with coma.
It is not a/w a rash.
-------------------------------------------------Rocky Mountain spotted fever is transmitted
by American dog ticks in spring & early summer
-------------------------------------------------Classic presentation of Rocky Mountain
spotted fever is a severe headache, fever,
myalgia, & arthralgia. Thrombocytopenia &
acute kidney injury can occur.
-------------------------------------------------Rocky Mountain spotted fever (RMSF) can
manifest as headache, fever, myalgia, rash,
&abdominal pain.
Purpuric rash typically develops 3 to 4 days
after the onset of constitutional symptoms &
begins on the wrists & ankles before spreading
centripetally.
Thrombocytopenia, relative leukopenia, &
elevated transaminases may be present,
particularly if the patient resides or has traveled
to areas where RMSF-associated American dog
ticks are present.
-------------------------------------------------Neisseria meningitidis meningitis commonly
occurs in children & young adults.
Immunization with the meningococcal vaccine
protects against serogroups A, C, Y, & W-135,
but not serogroup B.
-------------------------------------------------CSF protein concentration > 220 mg/dL, CSF
glucose < 34 mg/dL, CSF blood-glucose ratio
less than 0.2, CSF leukocytes > 2000/L, or
CSF neutrophils > 1180/L are individual
predictors of bacterial meningitiswith a 99%
or greater certainty.
-------------------------------------------------Viral meningitis can present with a syndrome
similar to bacterial meningitis.

CSF findings typically reveal a lymphocytic


pleocytosis, glucose level > 45 mg/dL, protein
level < 200 mg/dL, & negative Gram stain.
-------------------------------------------------Streptococcus pneumoniae is the most
common cause of bacterial meningitis in adults.
Clinical presentation of pneumococcal
meningitis is not specific, but CSF & blood
cultures will grow gram-positive diplococci.
-------------------------------------------------Neisseria meningitidis meningitis occurs
primarily in children & young adults.
Characterized by abrupt onset of flu-like illness
including fever, headache, neck stiffness,
altered mental status, intense myalgias, & rash.
Rash is petechial, purpuric, or maculopapular.
Evolution of this infection can be rapid &
fulminant, potentially resulting in septic shock
& death.
Invasive infections can be established by the
growth of these gram-negative diplococci
from CSF & blood cultures.
-------------------------------------------------Listeria monocytogenes is a gram-positive
bacillus that can cause invasive disease in
immunocompromised states, including
extremes of age (neonates & >50 years of age),
alcoholism, malignancy, immunosuppression,
diabetes mellitus, pregnancy, hepatic failure,
CKD, iron overload, collagen vascular
disorders, use of antitumor necrosis factor-
agents, & HIV infection.
GI tract is the usual portal of entry with
consumption of contaminated cole slaw, raw
vegetables, milk, cheese, processed meats,
smoked seafood, & hot dogs, potentially
resulting in a febrile gastroenteritis syndrome
including diarrhea.
-------------------------------------------------Ropinirole & pramipexole are dopamine
agonists used to treat Parkinson disease.
--------------------------------------------------

First-line medications to treat essential tremor


include propranolol, primidone, gabapentin,
& topiramate.
-------------------------------------------------Essential tremor progression is typically slow,
with intermittent lengthy periods of stability.
Features that may be predictive of a more
severe essential tremor include a positive
family history of tremor, longer tremor
duration, voice tremor, & unilateral tremor.
Alcohol consumption suppresses symptoms in
most patients with essential tremor.
-------------------------------------------------Propranolol is a first-line drug of choice for
essential tremor.
-------------------------------------------------Essential tremor is characterized by an upper
extremity high-frequency tremor, present with
both limb movement & sustained posture of the
involved extremities & absent at rest.
The tremor is characteristically bilateral, but
there can be mild to moderate asymmetry.
Essential tremors typically improve with
alcohol & worsen with stress.
Tremor amplitude over time generally increases
& can be so severe as to interfere with writing,
drinking, & other activities requiring smooth,
coordinated upper limb movements.
-------------------------------------------------Essential tremor primarily occurs when a
patient maintains a posture, such as when the
hands are outstretched.
It may also be present during movement,
particularly postural adjustments.
Autosomal dominant transmission.
-------------------------------------------------Sustained levodopa responsiveness is
expected in Parkinson disease & confirms the
clinical diagnosis.
-------------------------------------------------Parkinson disease remains a clinical diagnosis
based on a cardinal set of clinical features:
resting tremor, bradykinesia, rigidity, & postural

instability; tremor, bradykinesia, & rigidity are


asymmetric.
-------------------------------------------------Neuroleptic malignant syndrome is a lifethreatening disorder caused by an idiosyncratic
reaction to neuroleptic tranquilizers (dopamine
D2-receptor antagonists) & antipsychotic
drugs, haloperidol is the most common.
Most patients develop muscle rigidity,
hyperthermia, cognitive changes, autonomic
instability, diaphoresis, sialorrhea, seizures,
arrhythmias, & rhabdomyolysis within 2 weeks
of initiating the drug.
-------------------------------------------------Huntington disease is a hereditary, progressive,
neurodegenerative disorder characterized by
increasingly severe motor impairment,
cognitive decline, & psychiatric symptoms.
Symptoms begin in the fourth & fifth decade.
Chorea refers to brief, irregular, nonrhythmic,
nonstereotypical movements & can involve the
extremities, head, trunk, & face.
Other motor symptoms include ataxia, dystonia,
slurred speech, swallowing impairment, &
myoclonus.
Dysphoria, agitation, irritability, anxiety,
apathy, disinhibition, delusions, &
hallucinations commonly seen.
-------------------------------------------------Cervical dystonia, formerly torticollis, is a
focal dystonia that causes abnormal postures of
the head, neck, & shoulders.
Quick, nonrhythmic, repetitive movements can
occur & mistaken for tremor.
-------------------------------------------------Medications that block D2 dopamine receptors
can cause acute dystonic reactions.
Dystonic movements are due to sustained
contraction of agonist & antagonist muscles,
resulting in twisting & repetitive movements or
sustained abnormal postures.

These movements frequently affect the ocular


muscles (oculogyric crisis), face, jaw, tongue,
neck, & trunk. The limbs are rarely affected.
Neuroleptic, antiemetic, & serotoninergic
agents have been implicated in acute dystonic
reactions, usually occur within 5 days of
initiating the offending drug.
Treatment consists of IV diphenhydramine,
benztropine mesylate, or biperiden.
-------------------------------------------------Memantine is a first-line agent for treatment of
moderate to advanced Alzheimer dementia.
-------------------------------------------------Memantine has been shown to improve
cognition & global assessment of dementia.
-------------------------------------------------This patient has Alzheimer dementia that is
moderately advanced & now has difficulties
with basic activities of daily living.
N-methyl-D-aspartate receptor antagonist
memantine is the only first-line treatment of
moderate to advanced Alzheimer dementia.
-------------------------------------------------Treat functional decline in advanced
Alzheimer dementia with memantine.
-------------------------------------------------For mild, moderate, or severe Alzheimer
dementia the use of acetylcholinesterase
inhibitors are a/w a small but statistically
significant improvement in performance of
instrumental & functional activities of daily
living & caregiver stress; may be a/w improved
cognitive function.
Cholinesterase inhibitors are generally safe but
have side effects: diarrhea, nausea, vomiting, &
symptomatic bradycardia; GI side effects are
usually transient and mild.
-------------------------------------------------The Folstein Mini-Mental State Exam
(MMSE) discriminates well between the major
stages of dementia used for prognosis &
management purposes. The MMSE score range:
o 21 to 25 corresponds to mild dementia

o 11 to 20 to moderate dementia
o 0 to 10 to severe dementia.
-------------------------------------------------Treat mild Alzheimer dementia with an
acetylcholinesterase inhibitor (donepezil,
rivastigmine, & galantamine).
-------------------------------------------------Frontotemporal dementia is a progressive
neuropsychiatric condition.
Behavioral & personality changes ranging from
apathy to social disinhibition.
They fail to change clothes, brush their teeth,
pursue former interests, or initiate any previous
activities that constituted a normal day.
They may fixate, in a idiosyncratic fashion, on a
particular activity, such as sorting through a
wallet, hoarding magazines, or watching TV.
-------------------------------------------------Dementia with Lewy bodies is accompanied
by parkinsonism, visual hallucinations, &
fluctuating symptoms.
The characteristic cognitive profile includes
impaired learning & attention, psychomotor
slowing, constructional apraxia, & more
profound visuospatial impairment
-------------------------------------------------The main features of Creutzfeldt-Jakob
disease are dementia that progresses over
months (not years) & startle myoclonus.
Other features include visual or cerebellar
disturbance, pyramidal/extrapyramidal
dysfunction, & akinetic mutism.
-------------------------------------------------Alzheimer dementia is characterized by
prominent memory loss, constructional apraxia,
anomia, anosognosia (impaired recognition of
illness), & personality change.
-------------------------------------------------Dementia is a clinical syndrome in which
multiple cognitive domainsmemory,
language, spatial skills, judgment, & problem
solvingare impaired to a disabling degree.
--------------------------------------------------

Delirium is an altered level of alertness, in


connection with globally impaired cognition.
It is characterized by abrupt onset a/w rapid
fluctuations of alertness, attention, memory, &
psychomotor activity (lethargy or agitation).
Dementia is an acquired & persistent
impairment of intellectual ability that
compromises at least three areas of mental
functioning: language, memory, visuospatial
skills, emotion or personality, or cognition.
Dementia typically has an insidious onset & is
usually stable from day to day.
Over the protracted course of dementia,
patients may experience an acute delirium,
with confused & slurred speech, somnolence,
agitation, tremulousness, unsteadiness, falls, &
worsened incontinence.
Often, the delirium is from a superimposed
illness (commonly UTI or pneumonia), injury,
or medication error.
-------------------------------------------------Prophylactic treatment for migraine should be
considered in patients with 2 or more days of
headache per week.
-------------------------------------------------Preventative migraine treatments: topiramate,
valproic acid, amitriptyline, metoprolol,
propranolol, timolol, & extract of the plant
Butterbur root Petasites hybridus
-------------------------------------------------Treat a patient prophylactically for migraine
with propranolol.
-------------------------------------------------No consistent, statistically significant benefits
for botulinum toxin injection in the treatment
of episodic migraine headache.
-------------------------------------------------Thunderclap headache is a severe & explosive
headache that is maximal in intensity at or
within 60 seconds of onset.
Every thunderclap headache must be evaluated
immediately with non-contrast CT of the head

to detect potentially catastrophic conditions,


especially subarachnoid hemorrhage.
A negative head CT scan should be followed by
a lumbar puncture to assess for blood in the
CSF not detected on the CT scan.
-------------------------------------------------If both the CT scan & lumbar puncture are
negative, other causes of thunderclap headache,
such as an unruptured cerebral aneurysm,
carotid or vertebral artery dissection, cerebral
venous sinus thrombosis, & reversible cerebral
vasoconstriction syndrome, can be excluded by
noninvasive CT angiography.
Angiography of the head & neck can detect
unruptured aneurysms as small as 3 mm in
diameter.
Magnetic resonance angiography (MRA)
would also be appropriate.
-------------------------------------------------Due to the risk of intracerebral bleeding with
mass effect, the performance of a lumbar
puncture could result in brainstem herniation.
Thus, lumbar puncture is performed only after a
CT scan is performed.
-------------------------------------------------Vasoconstrictive drugs (sumatriptan), would
not be appropriate until the other causes of
thunderclap headache have been excluded.
Drugs with the potential to constrict
extracranial & intracranial cerebral vessels can
precipitate or exacerbate the cerebral ischemia
that may be a/w arterial dissection & reversible
cerebral vasoconstriction syndromes.
-------------------------------------------------Migraine headache is a recurrent disorder that
manifests in attacks lasting 4 to 72 hours.
Typical characteristics are unilateral location,
pulsating quality, moderate or severe intensity,
aggravation by routine physical activity, &
a/w nausea &/or photophobia & phonophobia.
-------------------------------------------------Tension-type headache is a dull, bilateral, or
diffuse headache, often described as a pressure

or squeezing sensation of mild to moderate


intensity.
There are no accompanying migraine features
(nausea, emesis, photophobia, phonophobia), &
the pain neither worsens with movement nor
prohibits activity.
The key feature that establishes a diagnosis is
the lack of disabling pain
-------------------------------------------------Cluster headache is a painful, disabling
headache that is a/w autonomic symptoms
such as tearing or rhinorrhea.
Typically unilateral & periorbital/temporal &
a/w at least one of the following features on the
same side as the headache: conjunctival
irritation/lacrimation, rhinorrhea/nasal
congestion, eyelid edema, facial/forehead
sweating, & miosis/ptosis.
Cluster episodes usually last 6 to 8 weeks &
remission periods usually last 2 to 6 months.
-------------------------------------------------Chronic daily headache is a nonspecific term
that refers to both primary (includes migraine)
& secondary headache disorders in which
headache is present on more than 15 days per
month for at least 3 months.
Risk factors include obesity, history of frequent
headache (> 1 per week), caffeine consumption,
& overuse (>10 days per month) of acute
headache medications, including analgesics,
ergots, triptans, & opioids.
More than half of all patients with chronic daily
headache have sleep disturbance & mood
disorders, such as depression & anxiety.
-------------------------------------------------Trigeminal neuralgia is a/w pain occurring in
paroxysms that involves one or more divisions
of the trigeminal nerve.
Each episode may persist between a few
seconds & 2 minutes, & pain may be intensely
sharp or stabbing.

Behavior such as face washing or touching,


tooth brushing, or chewing may be a trigger.
-------------------------------------------------Patients with migraine may experience aura
within 1 hour of or during headache.
Aura constitutes neurologic abnormalities,
including visual loss, hallucinations, numbness,
tingling, weakness, or confusion.
Aura is caused by spreading cortical depression
a wave of abnormal electrical discharges that
travel slowly across the brain's surface &
essentially short-circuit the brain.
Auras lasts a few minutes or up to 1 hour per
symptom.
-------------------------------------------------Partial seizures in which the patient maintains
full awareness are classified as simple partial,
whereas those involving an alteration of
consciousness are classified as partial complex
Partial seizures that originate in the temporal
lobe often begin with an aura, which may
consist of a feeling of deja vu, rising epigastric
sensation, or autonomic disturbances.
Automatisms, such as lip smacking, are also
suggestive of partial complex seizures.
-------------------------------------------------Cognitive impairment accompanied by
fluctuating lethargy & inattention,
hallucinations, & asterixis most likely results
from a toxic encephalopathy.
-------------------------------------------------Delirium is an acute state of confusion that
manifests as a reduced level of consciousness,
cognitive abnormalities, perceptual
disturbances, or emotional disturbances.
The presence of asterixis suggests a
toxic/metabolic cause. A prime suspect is
nortriptyline; which has anticholinergic
properties & likely to cause impairment in
patients with latent cholinergic deficiency
(elderly or patients with mild cognitive
impairment, early dementia, or Parkinson).
--------------------------------------------------

Wernicke encephalopathy is caused by


thiamine deficiency & may result in mental
status changes, ophthalmoplegia, nystagmus,
& unsteady gait; best treated with thiamine.
When there is additional loss of memory with a
confabulatory psychosis, the condition is
described as Wernicke-Korsakoff syndrome.
-------------------------------------------------Electroencephalography can exclude a seizure
disorder (nonconvulsive status epilepticus).
Infections (encephalitis & meningitis) for which
IV administration of broad-spectrum antibiotic
drugs (vancomycin, ampicillin, & ceftriaxone)
may be appropriate also should be part of the
differential diagnosis & can be excluded with
CSF analysis.
-------------------------------------------------No drug is approved for the treatment of
delirium, but clinical practice guidelines
recommend antipsychotic agents, haloperidol.
-------------------------------------------------There is no evidence of superiority for secondgeneration antipsychotics compared with
haloperidol for delirium.
Haloperidol does not cause respiratory
suppression, which is one reason that it is often
used in patients with hypoventilatory
respiratory failure who require sedation.
All antipsychotics, especially "typical" agents
such as haloperidol, pose a risk of torsades de
pointes, extrapyramidal side effects, &
neuroleptic malignant syndrome.
-------------------------------------------------Treat delirium in the ICU with an antipsychotic
agent (haloperidol).
-------------------------------------------------Patients with chronic dementia are at greater
risk for post-operative delirium after surgery
with general anesthesia.
Such delirium is highly predictable & often
easily managed by identification & correction
of any underlying disorders & removal or

reduction of contributing factors.


-------------------------------------------------Surgery does not exacerbate Alzheimer
dementia (or dementia of any other cause) but
rather produces a superimposed delirium.
-------------------------------------------------Patients with delirium have acute, fluctuating
mental status changes, with difficulty in
focusing or maintaining attention &
disorganized thinking.
Four types of delirium, based on psychomotor
activity,: 1) hypoactive, 2) hyperactive, 3)
mixed delirium with hypo- & hyperactivity, &
4) delirium without changes in psychomotor
activity.
-------------------------------------------------Low-dose haloperidol may lessen the severity
& duration of patients with severe delirium, but
it is not indicated for the prevention of delirium.
Use of antipsychotics in elderly patients with
dementia is a/w an increased risk of death,
mainly due to infection, (pneumonia).
-------------------------------------------------Benzodiazepines & diphenhydramine can
cause delirium in the elderly.
-------------------------------------------------Urinary catheters are a/w increased risk of
delirium.
In the absence of a medical indication for a
catheter it should be removed.
-------------------------------------------------Elderly patients with a history of dementia are
at very high risk for developing delirium
during a hospitalization.
Delirium is an acute state of confusion that
manifests as a reduced level of consciousness,
cognitive abnormalities, perceptual
disturbances, or emotional disturbances.
--------------------------------------------------

IX. Oncology

Morphine is effective in treating cancer-related


dyspnea as well as dyspnea related to end-stage
cardiopulmonary disorders or malignancy.
-------------------------------------------------In terminally ill patients with malignancy or
cardiopulmonary disease, narcotics such as
immediate-release morphine can be an
effective treatment for dyspnea.
-------------------------------------------------Treat dyspnea in a palliative care setting with
an opioid.
-------------------------------------------------Because of the severity of this patient's pain,
long-acting morphine sulfate (or other strong
opioids such as hydromorphone or fentanyl)
& immediate-acting morphine sulfate for
breakthrough pain is the therapy of choice.
The transition from parenteral to oral morphine:
10 mg IV morphine = 30 mg of oral morphine.
-------------------------------------------------Because long-acting morphine is dosed every
12 hours, half of the calculated oral dose is
given twice daily.
10% of the total oral dose is made available as
immediate-acting morphine for breakthrough
pain ("rescue dose").
If the immediate-acting opioid is needed more
than 3x per day, the dose of long-acting opioid
can be increased.
-------------------------------------------------It is appropriate to use the same drug for both
breakthrough & basal dosing to simplify dose
titrations & minimize drug-related side effects.
-------------------------------------------------Treat cancer pain with long-acting &
immediate-release morphine sulfate.
-------------------------------------------------Pain control is a common management issue in
terminally ill patients.

Use of as-needed doses of opioid analgesics


combined with non-opioid adjunctive therapy
is effective for mild to moderate cancer pain.
This patient has discomfort from pain that
returns before he is scheduled to take his next
dose of analgesic therapy, & he is taking the
medication on a continual basis.
An appropriate solution would be to give him
sustained-release morphine TID.
When adding a long-acting opioid, avoid
overmedication by giving a starting dose of
30 - 50% of the average 24-hour dosage of
narcotic.
A breakthrough pain strategy should be
continued if the longer-acting pain medication
does not provide complete relief.
Opioid dosage for breakthrough pain is
calculated as 10% of the total daily opioid dose
given as an immediate-release opioid.
-------------------------------------------------Use sustained-release morphine to treat
moderate to severe cancer-related pain.
-------------------------------------------------Use short-acting opioid for mild to moderate
cancer-associated pain when non-opioid drugs
fail to adequately control pain.
-------------------------------------------------Patients with mild to moderate cancer pain,
prescribe an intermittent low-dose narcotic in
addition to adjuvant, non-narcotic pain
medicine.
Choices include immediate-release
oxycodone, morphine, or oxymorphone.
------------------------------------------------Initiating a long-acting narcotic such as a
fentanyl transdermal patch or extendedrelease oxycodone should not be indicated until
the patient's pain is adequately controlled with
short-acting narcotics, which can be rapidly
titrated to achieve adequate pain control.
Once pain control is established, the cumulative
dose of the short-acting opioid can be used to
calculate an effective dose of long-acting

opioid, with the dose reduced by 30% to 50%


& access to a short-acting opioid maintained for
break-through pain.
-------------------------------------------------Keratoacanthomas are rapidly growing,
nontender, firm nodules with depressed
keratotic centers.
-------------------------------------------------Keratoacanthoma is an epithelial neoplasm,
characterized by rapid growth over 2 - 6 weeks
& by a crater-like configuration. Early lesions
are misdiagnosed as skin infections.
Typical early lesion is a hard, erythematous
nodule with a keratotic (horny) center.
Typically occur on heavily sun-damaged skin,
in older persons, with a peak age of 60 years.
As the lesion enlarges, the center of the crater
becomes more prominent.
-------------------------------------------------Keratoacanthomas may cause significant local
tissue destruction, thus simple observation is
not recommended despite the tendency for
spontaneous involution.
Prompt surgical excision is recommended for
solitary lesions on the trunk or extremities.
Intralesional 5-fluorouracil or methotrexate,
topical imiquimod, & radiation therapy have
also been used to treat large lesions or in areas
where surgical excision is anatomically difficult
-------------------------------------------------Keratoacanthomas are capable of spontaneous
resolution by terminal differentiation, in which
the tumor "keratinizes itself to death."
-------------------------------------------------Seborrheic keratosis is a painless,
nonmalignant growth appearing as a waxy
brownish patch or plaque that lacks a pearly
appearance & typically exhibit horn cysts
(epidermal cysts filled with keratin) on the
surface with a stuck-on warty appearance.
-------------------------------------------------Squamous cell carcinomas are rapidly
growing, hyperkeratotic, flesh-colored, pink or

red ulcerated macules, papules, or nodules that


commonly appear on the scalp, neck, & pinnae.
A shave or punch biopsy is used to confirm the
diagnosis of suspicious lesions.
-------------------------------------------------Basal cell carcinoma is often found on the face
& characterized by slow growth & presence of
a skin-toned to pink, pearly, translucent
papule with rolled borders, telangiectasia, &
central depression with ulceration.
Flecks of melanin pigment are common.
A biopsy is necessary, as amelanotic
melanoma may have a similar appearance.
-------------------------------------------------Most nodular BCCs are treated with excision,
whereas ill-defined lesions, high-risk histologic
types, & tumors on the face & hands are treated
with Mohs micrographic surgery.
-------------------------------------------------Actinic keratoses are precancerous lesions that
can develop into invasive squamous cell
carcinoma & typically appear as erythematous
lesions with overlying hyperkeratosis.
-------------------------------------------------Actinic keratosis occur on sun-exposed skin of
older white-skinned persons.
Common findings are 1- to 3-mm, elevated,
flesh-colored or red papules, surrounded by a
whitish scale.
Most patients will have 6 to 8 lesions.
Most remain stable & some regress, but others
enlarge to become invasive squamous cell
carcinomas.
-------------------------------------------------Nodular melanomas present as uniformly dark
blue or black "berry-like" lesions that are
symmetric, elevated, & one color.
-------------------------------------------------Spitz nevus is a clinically benign mole found in
children or young adults.
Presents as a dome-shaped uniformly pink, red,
or pigmented nodule.

Its surface can be smooth or verrucous,


commonly on the face & lower extremities.
histopathologic features may overlap with those
of melanoma.
-------------------------------------------------Keratocanthoma is a rapidly growing lesion
thought to be a form of squamous cell cancer.
As the lesions mature, a central keratotic plug
becomes visible & becomes crater-like.
It rarely progresses to invasive or metastatic
cancer & involutes within months.
-------------------------------------------------Nodular melanoma presents as uniformly dark
blue or black "berry-like" lesions that most
commonly originate from normal skin.
Mostly symmetric, elevated, & one color.
Often found in people aged 60 years or older.
Often do not fulfill the ABCDE (asymmetry,
irregular borders, color variegation, diameter
expanding, & evolution over time) criteria for
melanoma & tend to expand vertically.
-------------------------------------------------Bowen disease is recognized as a gradually
enlarging, well-demarcated, erythematous scaly
plaque that can resemble superficial basal cell
carcinoma, psoriasis, or eczema.
-------------------------------------------------Squamous cell carcinoma in situ (Bowen
disease) is a form of intraepidermal carcinoma,
a malignant tumor of keratinocytes.
It presents as a single lesion, found on the head,
neck, & extremities most commonly in men.
Cheeks & lower extremities are the most
commonly affected sites in women.
Lesions vary from a few millimeters to several
centimeters in diameter. Lesions can arise de
novo or from a preexisting actinic keratosis.
------------------------------------------------Psoriasis is a chronic skin condition that
presents in young adults.
Lesions are characterized as 1 - 10 cm in
diameter erythematous papules & plaques with

silver scales, having sharply defined margins


raised above the normal surrounding skin.
These plaques are symmetrically distributed &
usually involve the scalp, extensor elbows,
knees, & back.
-------------------------------------------------Discontinue screening for cervical cancer in
patients who have had a vaginal hysterectomy
for benign disease.
-------------------------------------------------Women older than 30 years with three previous
normal annual Pap smears, screening interval
can be lengthened to every 3 years.
Annual Pap tests do not identify more invasive
cancer than tests performed every 2 or 3 years
in low-risk women who have had several
normal tests.
-------------------------------------------------Screen for cervical cancer every 3 years in
low-risk women.
-------------------------------------------------HPV vaccine for cervical cancer prevention for
all females between the ages of 9 - 26 years
regardless of sexual activity.
The vaccine has a high success rate in
preventing HPV strains 6, 11, 16, & 18, which
cause cases of genital warts & cervical cancer
30% of cervical cancers will not be prevented;
therefore, women should continue to receive
regular Pap smears even after the vaccination.
-------------------------------------------------Colposcopy with biopsy is indicated for
patients with atypical squamous cells (ASC)
on cervical cytologic screening & who test
positive for high-risk HPV subtypes.
-------------------------------------------------Atypical squamous cells (ASC) is the most
common abnormal finding following cervical
cancer screening.
Most ASC abnormalities resolve spontaneously,
but 15% harbor a precancerous lesion on biopsy
ASC should be tested for HPV infection.

Colposcopy with biopsy is performed on


patients with ASC testing positive for high-risk
HPV subtypes (Types 16 or 18).
Colposcopy provides an illuminated, magnified
view of the cervix, vagina, & vulva & enhances
detection of premalignant & malignant lesions
that can biopsied.
-------------------------------------------------There is no effective treatment for cervical
HPV infection, including interferon.
-------------------------------------------------Prostate cancer is a hormone-responsive
tumor, & will most likely respond to hormone
deprivation therapy with surgical castration or
gonadotropin hormone-releasing hormone
(GnRH) agonists such as leuprolide.
------------------------------------------------GnRH therapy causes impotence, hot flushes,
gynecomastia, & loss of libido, as does
orchiectomy.
Patients may experience tumor-flare reactions
with GnRH agonists, which initially cause an
increase in LH & FSH, leading to a transient
increase in testosterone, which can exacerbate
prostate cancer symptoms.
This reaction can be prevented by a brief course
of concomitant antiandrogen therapy with
agents: bicalutamide, nilutamide, or flutamide.
-------------------------------------------------Treat asymptomatic metastatic prostate cancer
with androgen deprivation therapy.
-------------------------------------------------In men age 75 years or older there is little to no
benefit a/w prostate cancer screening.
If screening were to be performed, men ages 50
to 70 years would benefit most.
-------------------------------------------------Evidence is insufficient to recommend for or
against prostate cancer screening using PSA
testing or DRE & recommended that
physicians discuss potential, but uncertain,
benefits & possible harms before ordering PSA
testing.

Moderate to substantial harms, including


erectile dysfunction, urinary incontinence,
bowel dysfunction, & death, in addition to
small harms, including prostate biopsy-induced
pain & discomfort & psychological effects of
false-positive test results, are a/w prostate
cancer screening.
-------------------------------------------------Manage prostate cancer screening by
discussing risks & benefits.
-------------------------------------------------Any PSA level rise > 0.75 ng/mL/year is
considered abnormal & should be evaluated.
-------------------------------------------------PSA level greater than 4.0 ng/dL should have
further evaluation for prostate cancer.
-------------------------------------------------Patients with an elevated or rising serum PSA
level during routine screening should undergo
prostate biopsy, even if they are asymptomatic.
These patients need ultrasound-guided biopsies
of their prostate (typically in 6 random areas) to
assess for the presence of prostate cancer.
After prostate cancer is diagnosed, studies such
as a bone scan or CT scan of the abdomen &
pelvis should be considered in patients with
signs or symptoms suggestive of metastasis.
-------------------------------------------------A patient with limited-stage small-cell lung
cancer (SCLC) should receive chemotherapy &
radiation therapy.
SCLC is a systemic disease; patients who
present with seemingly localized disease almost
always have concurrent micrometastases &
the complicated staging system of non-small
cell lung cancer does not apply.
Patients with visibly localized disease that can
be encompassed within a radiation therapy port
are designated as having limited-stage disease.
Patients with tumor beyond the confines of a
radiation port have extensive-stage disease.
--------------------------------------------------

Chemotherapy plus radiation therapy is firstline treatment for limited-stage SCLC.


Typical regimens consist of a combination of a
platinum agent (carboplatin or cisplatin) &
etoposide or irinotecan.
-------------------------------------------------In the evaluation of suspected lung cancer,
obtaining a tissue diagnosis is critical for
treatment planning & determining prognosis.
Biopsy of the mass or hilar lymph nodes by CT
guidance or bronchoscopy would establish the
diagnosis but not the stage & would not
determine resectability.
-------------------------------------------------Diagnose & stage advanced lung cancer with
a peripheral lymph node biopsy.
-------------------------------------------------No follow-up for low-risk patients with
pulmonary nodules 4 mm or smaller.
Follow-up CT at 12 months for patients with
such nodules who are at risk for lung cancer.
-------------------------------------------------Chest CT screenings have shown that 25 to
50% have one or more pulmonary nodules
detected on the initial CT scan. Even in patients
at relatively high risk for lung cancer, the
likelihood that a small nodule is malignant is low
-------------------------------------------------Screening for early-stage lung cancer is not
recommended with the use of any methodology.
-------------------------------------------------A randomized, controlled trial is generally
accepted as the definitive means of establishing
efficacy for a screening test.
-------------------------------------------------The colon cancer risk in patients with
ulcerative colitis or Crohn disease reaches a
significant level after 8 years of inflammation.
Patients with inflammatory bowel disease
should initiate screening for colorectal
cancer after 8 years' disease duration.
--------------------------------------------------

The recommendation is to initiate a surveillance


program with colonoscopy 8 years after onset
of disease, with follow-up colonoscopy every 1
to 2 years thereafter.
Random biopsies are performed in fourquadrant fashion throughout the entire colon.
Colectomy is recommended for patients with
dysplastic findings on biopsy.
-------------------------------------------------Fecal occult blood testing (FOBT) is a/w a
reduction in mortality rates from colorectal
cancer when annual or biennial testing is done.
Six-window FOBT is performed by taking two
separate samples from each of three
spontaneously passed stools (six samples).
An asymptomatic patient with a single positive
FOBT on routine screening requires follow-up
with colonoscopy.
-------------------------------------------------Options for colorectal cancer screening
include colonoscopy, FOBT, flexible
sigmoidoscopy, or barium enema used alone or
in combination for screening.
These screening modalities are reserved for
asymptomatic patients.
-------------------------------------------------Symptomatic patients with suspected colon
cancer should be evaluated with colonoscopy.
-------------------------------------------------Common signs & symptoms of colorectal
cancer are influenced by the site of the primary
tumor & may include a change in bowel habits,
diarrhea, constipation, feeling that the bowel
does not empty completely, bright red blood in
the stool or melanotic stools, & stools that are
narrower in caliber than usual.
Other signs include abdominal discomfort
(frequent gas pains, bloating, fullness, cramps),
weight loss, fatigue, & vomiting.
-------------------------------------------------Findings that should prompt investigation for
colon cancer include a rectal or abdominal

mass, hepatomegaly, abdominal tenderness, or


iron deficiency anemia.
If one or more such findings are present, a full
colorectal exam with colonoscopy should be
done. However, the exam may be limited to
sigmoidoscopy for rectal bleeding in most
persons younger than 40 years of age because
colorectal cancer is uncommon in such patients
(except those with hereditary colorectal cancer
syndromes), & in most young patients with
hematochezia, a rectosigmoid lesion, usually
hemorrhoids, is the cause of rectal bleeding.
-------------------------------------------------Patients with inflammatory bowel disease
have an increased risk for colorectal cancer.
-------------------------------------------------Familial adenomatous polyposis & attenuated
familial adenomatous polyposis are most
commonly diagnosed after polyposis is
detected on endoscopy.
Test for mutations in the APC gene.
-------------------------------------------------For a family history of colorectal cancer in a
first-degree relative, screening is initiated at
age 40 years or beginning 10 years earlier
than the youngest affected family member.
If normal, repeat colonoscopy every 3 to 5 year.
-------------------------------------------------A family history of colorectal cancer or
adenomatous polyps significantly increases a
person's risk for colorectal cancer.
Presence of colorectal cancer in a first-degree
relative carries a 2x to 3x increased lifetime risk;
the risk is doubled again if the affected relative
was diagnosed before age 45 years.
-------------------------------------------------Treat a small, focal breast cancer with
lumpectomy, sentinel node dissection,
followed by breast irradiation.
-------------------------------------------------Breast lumpectomy plus radiation therapy is
known as "breast-conserving therapy."

Breast-conserving therapy consists of excision


of the primary tumor followed by radiation to
the remaining ipsilateral breast tissue & is
generally indicated for patients with focal
disease & small tumors.
Patient preferences must be considered in the
surgical decision-making process.
Survival rate is equivalent to that of those who
undergo mastectomy, with breast-conserving
therapy resulting in improved cosmetic
outcomes & less morbidity than mastectomy.
Patients treated with lumpectomy without
radiation therapy have a high risk for local
recurrence.
Sentinel lymph node biopsy is a safe &
accurate method for screening the axillary
lymph nodes for metastases in women with
small breast tumors.
Sentinel lymph node biopsy has replaced full
axillary lymph node dissection for the staging
of disease in women with early-stage,
clinically lymph node-negative breast cancer.
The first draining (or sentinel) lymph node is
identified by injecting blue dye & radioactive
colloid into the tumor site.
If the sentinel lymph node does not contain
metastases, it is unlikely that distal axillary
lymph nodes will contain metastases; no
further surgery is indicated, & toxicity from a
full axillary lymph node dissection is avoided.
If the sentinel lymph node shows metastatic
involvement, then axillary lymph node
dissection is performed to determine the
number of involved lymph nodes.
-------------------------------------------------Early-stage breast cancer (stage I) is based on
the tumor size (<2 cm); absent lymph node
involvement; & no apparent metastases based
on symptoms, history, physical exam findings,
mammography, CXR, & routine blood tests.
Helpful in directing the approach to
management of this patient is to perform an
assay for expression of ER & PR to determine

the optimal systemic treatment; this should be


performed in all cases of primary breast cancer.
-------------------------------------------------Endocrine therapy (tamoxifen, aromatase
inhibitors, fulvestrant, & megestrol acetate) is
beneficial only in patients with ER-positive or
PR-positive tumors.
Tumors that are hormone receptor-negative are
refractory to endocrine treatment & should
receive chemotherapy instead.
-------------------------------------------------Evaluate early-stage breast cancer for tumor
estrogen- & progesterone-receptor status.
-------------------------------------------------A breast mass requires triple assessment:
palpation, mammography with or without
ultrasound, & surgical evaluation for biopsy.
-------------------------------------------------A breast mass requires aspiration or biopsy
regardless of mammography results.
-------------------------------------------------After a bilateral diagnostic mammography,
initial workup of a dominant breast mass is to
distinguish a simple cyst from a solid mass by
FNA or ultrasonography.
If the cystic fluid from FNA is bloody, the fluid
should undergo cytologic evaluation.
Women with simple cysts should undergo a
breast exam 4 to 6 weeks after cyst aspiration to
evaluate for cyst recurrence or a residual lump.
A solid mass requires a tissue diagnosis by
FNA biopsy (FNAB), core-needle biopsy, or
excisional biopsy.
Benign FNAB or core-needle biopsy results &
negative mammogram require close clinical
follow-up.
-------------------------------------------------Paget disease of the breast is a ductal
carcinoma defined as a persistent, scaling,
eczematous, or ulcerated lesion involving the
nipple/areolar complex.
Histological hallmark is the presence of
malignant, intraepithelial adenocarcinoma cells

(Paget cells) within the epidermis of the nipple


a/w underlying invasive or intraductal cancer.
It is often misdiagnosed as eczema or psoriasis,
but with a lack of response to appropriate
therapy, biopsy should be performed.
-------------------------------------------------Characteristic lesions of chronic cutaneous
lupus erythematosus are discoid lesions
appearing as erythematous, infiltrated plaques
covered with scale & a/w follicular plugging.
These lesions are on the face, neck, & scalp.
As they expand, they develop depressed
central scars.
-------------------------------------------------Testing for BRCA-1 & BRCA-2 genes should
be performed only in women who appear to
have a genetic risk (multiple relatives with
breast or ovarian cancer, especially early-onset
of disease).
-------------------------------------------------A breast mass that has persisted through
several menstrual cycles needs further
evaluation despite a normal mammogram.
Because she is older than 30 years & the
mammogram is classified as BI-RADS 2,
ultrasound is the next appropriate test.
This is true for BI-RADS 1-3.
Ultrasound distinguishes cystic from solid
masses.
A cystic mass should be aspirated & fluid sent
for cytologic evaluation if bloody or recurrent.
A solid mass requires biopsy by FNA, core
needle, or excision.
If the mammogram is BI-RADS 4 or 5,
malignancy is much more likely & tissue
diagnosis with FNA or biopsy is the most
appropriate management.
-------------------------------------------------The Breast Imaging Reporting & Data System
(BI-RADS) is a standardized reporting system
for mammography findings & source of
recommendations for further management.

Category assignments are either incomplete


(category 0) or final assessment (categories 1
through 6).
Category 2 correspond to findings compatible
with benign nodules or cysts or benign
calcifications.
--------------------------------------------------

X. Pulmonary Medicine

Appropriate treatment for a patient with DVT


that is either idiopathic or a/w a transient risk
factor is an initial short course of an
immediate-acting anticoagulant such as
unfractionated heparin, low-molecular-weight
heparin, or fondaparinux for at least 5 days.
Warfarin should be started at approximately
the same time that heparin is administered, &
the two drugs should be overlapped until the
INR reaches a therapeutic range (>2) measured
on two occasions 24 hours apart.
This timing allows for further reduction of
prothrombin, the vitamin K-dependent factor
with the longest half-life (~ 60 h), which is
responsible for the antithrombotic effect of
warfarin.
5 to 7 days of therapy are required to achieve
this therapeutic level.
-------------------------------------------------Lower doses of warfarin are recommended in
the elderly, especially with liver disease,
malnourishment, or recent major surgery.
-------------------------------------------------Negative D-dimer assay results & low Wells
criteria probability score reliably exclude a
diagnosis of DVT.
-------------------------------------------------In the Wells criteria, the following clinical
variables each earn 1 point: active cancer;
recent immobilization or major surgery;
paralysis or recent plaster cast; tenderness along
the deep veins; swelling of the entire leg;
greater than a 3-cm difference in calf
circumference compared with the other leg;
pitting edema; & collateral superficial veins.
Clinical suspicion that an alternative diagnosis
is likely earns -2 points.
The pretest probability of DVT is considered
high with scores of greater than or equal to 3,
moderate with scores of 1 to 2, & low with

scores less than or equal to 0.


-------------------------------------------------A D-dimer assay has been shown to have a
high negative predictive value, especially if the
suspicion for DVT is low.
The Wells criteria have been established to
assess the likelihood of DVT
With a negative D-dimer assay & low clinical
suspicion, the presence of DVT can be reliably
excluded without the need for more invasive or
complex imaging.
-------------------------------------------------Ventilation/perfusion scanning is an
appropriate noninvasive test to diagnose acute
pulmonary embolism, especially in the
presence of chronic kidney disease.
-------------------------------------------------This patient is at high risk for pulmonary
embolism because of his recent hospitalization,
cancer, & nephrotic syndrome.
A negative D-dimer test would not be sufficient
to rule out a PE under these circumstances.
A positive ventilation/perfusion scan would
confirm the diagnosis of PE in patients with a
high pretest probability, especially in the
absence of parenchymal lung defects on CXR.
-------------------------------------------------CT angiography is an acceptable modality to
diagnose acute PE but requires a significant
amount of contrast infusion, which would be
contraindicated in a patient with an elevated
serum creatinine level.
------------------------------------------------Three direct thrombin inhibitors are in
clinical use: lepirudin, a recombinant form of
the leech enzyme hirudin; bivalirudin, an
engineered form of hirudin that alters its
thrombin-binding capacity & half-life; &
argatroban, a small molecule that binds
irreversibly to the active site of thrombin.
Each of these is a parenterally administered
drug with limited indications, & all require
therapeutic monitoring.

Lepirudin should be considered when a patient


has heparin-induced thrombocytopenia.
-------------------------------------------------Unfractionated heparin, low-molecular-weight
heparin (LMWH), & fondaparinux can be used
for prevention of venous thromboembolism in
hospitalized, medically ill patients.
-------------------------------------------------Patients with renal impairment (GFR <30
mL/min/1.73 m2), dosing of LMWH must be
adjusted & fondaparinux is contraindicated.
-------------------------------------------------Drug-induced lung toxicity typically presents
as a hypersensitivity-type reaction, with
symptoms of fatigue, low-grade fever, cough, &
peripheral blood eosinophilia.
-------------------------------------------------Definitive diagnosis of drug-induced lung
disease requires exclusion of other known
causes & symptom improvement with drug
withdrawal.
A high index of suspicion is essential, because
early identification & drug withdrawal can
prevent morbidity & mortality.
Amiodarone for a-fib is a well-known cause of
drug-induced lung toxicity.
-------------------------------------------------Asbestosis refers to bilateral interstitial
fibrosis of the lung parenchyma caused by
inhalation of asbestos fibers.
An exposure history of appropriate duration,
latency (typically 20-30 years), & intensity &
radiographic evidence of interstitial fibrosis on
CXR or chest CT are sufficient for diagnosis.
Symptoms include breathlessness, bibasilar
inspiratory crackles, & digital clubbing &
restrictive pattern on pulmonary function test.
-------------------------------------------------Acute eosinophilic pneumonitis is a rapidly
progressive illness, occur over days to 3 weeks
a/w fever, sputum production, eosinophilia, &
peripherally distributed infiltrate.
--------------------------------------------------

Connective tissue diseases, such as


scleroderma, are most commonly a/w diffuse
parenchymal lung disease (DPLD).
DPLD is most likely a/w systemic sclerosis in
patients with antitopoisomerase I (anti-Scl-70)
antibody positivity.
DPLD a/w systemic sclerosis usually manifests
as dyspnea, dry cough, & decreased exercise
tolerance. Fine bibasilar crackles that extend
into late inspiration are heard on physical exam.
On pulmonary function testing, these patients
have a restrictive pattern with a decreased FVC
& DLCO normal FEV1/FVC ratio).
High-resolution CT (HRCT) is more sensitive
than CXR for DPLD & reveals ground-glass &
reticular linear opacities, subpleural cysts, &
honeycombing in cases of advanced disease.
If the clinical context, temporal pattern of
disease, & HRCT findings do not yield a
diagnosis, it may be reasonable to obtain a
bronchoscopic or surgical lung biopsy. The
diagnostic yield of surgical lung biopsy is 90%.
-------------------------------------------------In patients with systemic sclerosis, pulmonary
vascular disease may manifest as isolated
pulmonary arterial hypertension (PAH) or as
a complication of vascular obliteration in
patients with DPLD.
Patients may present with fatigue, decreased
exercise tolerance, dyspnea, or syncope.
Findings include an increased P2 &
persistently split S2; CXR are usually normal.
A decrease in DLCO in the setting of normal
lung volumes is consistent with PAH.
-------------------------------------------------Bronchoalveolar lavage is safe & simple to
perform & helpful to diagnose infections &
carcinoma, as well as eosinophilic pneumonia.
-------------------------------------------------Sleep apnea with nocturnal hypoxemia may be
a/w secondary polycythemia.

The secondary polycythemia will most likely


resolve once the sleep apnea is corrected.
-------------------------------------------------Excessive daytime sleepiness is the hallmark of
sleep apnea.
Other clinical manifestations of sleep apnea
include morning headaches, nocturia, &
alterations in mood.
------------------------------------------------Hypoxia is the main inducer of erythropoietin
production by the proximal nephrons.
An elevated erythropoietin level strongly
supports diagnosis of secondary polycythemia.
-------------------------------------------------Polycythemia vera is characterized by a low
serum erythropoietin level & increased
erythrocyte mass & mild elevation in leukocyte
& platelet counts.
Hematocrit > 60% for men & 56% for women
in the absence of secondary causes of
erythrocytosis & presence of splenomegaly
establish the diagnosis.
A JAK2 mutation is detected in 95% of cases,
& a polymerase chain reaction assay for this
mutation can aid in establishing the differential
from secondary causes of erythrocytosis.
-------------------------------------------------Idiopathic pulmonary fibrosis presents with
slowly progressive dyspnea & chronic,
nonproductive cough.
CXR is almost always abnormal at presentation,
with decreased lung volumes & basal reticular
opacities.
Patients have a physiologic restrictive process
(decreased FVC, total lung capacity, functional
residual capacity) & impaired gas exchange
with a decreased DLCO.
-------------------------------------------------Diagnosis of asbestosis is based on a history of
asbestos exposure with an appropriately long
latent period (10 to 15 years) & evidence of
interstitial fibrosis without other likely causes.

The most specific finding on CXR is bilateral


partially calcified pleural plaques.
Pleural plaques are focal, often partially
calcified, fibrous tissue collections on the
parietal pleura & a marker of asbestos exposure.
-------------------------------------------------Sarcoidosis occurs in young & middle-aged
adults, with peak incidence in the third decade.
> 90% have lung involvement.
CXR may show hilar lymphadenopathy alone,
hilar lymphadenopathy & reticular opacities
in the upper lung zone, or reticular opacities
without hilar lymphadenopathy.
-------------------------------------------------Cryptogenic organizing pneumonia often
presents with subacute disease progression &
bilateral alveolar-filling opacities on CXR.
-------------------------------------------------Cryptogenic organizing pneumonia (COP) in
a nonsmoker without any exposure history has
acute to subacute development of nonspecific
systemic & respiratory symptoms with a
dominant alveolar opacification on CXR..
-------------------------------------------------COP is often acute or subacute, with symptom
onset occurring within 2 months of
presentation in the majority of patients.
Presentation is very suggestive of an acute or
subacute lower respiratory tract infection
that patients have almost always been treated
with & failed to respond to one or more courses
of antibiotics before diagnosis.
One of the key radiographic features of COP is
the tendency for COP opacities to "migrate"
or involve different lung areas on serial exams.
A dominant alveolar opacification process is
present & opacities are almost always bilateral
with varied distribution.
-------------------------------------------------Polysomnography is required to determine the
presence & severity of OSA.
--------------------------------------------------

Risk factors for obstructive sleep apnea (OSA)


include excessive body weight, abnormalities of
craniofacial anatomy, male sex, underlying
medical or neurologic disorders (myxedema,
acromegaly, & stroke), alcohol use, medications
(muscle relaxants, sedatives, opioids, &
anesthetics), & aging.
Patients with untreated OSA have a greater
likelihood of developing systemic & pulmonary
arterial hypertension, coronary artery disease,
acute MI during sleep, heart failure, stroke,
recurrent atrial fibrillation, insulin resistance,
mood disorders, & parasomnias.
-------------------------------------------------Treatment of OSA modestly reduces BP in
many, but not all, patients with HTN.
------------------------------------------------Untreated obstructive sleep apnea has a
greater likelihood of developing systemic HTN
-------------------------------------------------A 24-hour urine free cortisol measurement is a
screening test for Cushing syndrome.
Although patients with hypercortisolism may
develop obesity & HTN, this patient has few
other compatible findings such as ecchymosis,
muscle weakness, hypokalemia, unexplained
osteoporosis, & diabetes mellitus.
-------------------------------------------------The plasma aldosterone to plasma renin ratio
is the screening test for hyperaldosteronism.
Hyperaldosteronism causes hypertension,
hypokalemia, & metabolic alkalosis.
-------------------------------------------------Diagnose obstructive sleep apnea as a
secondary cause of hypertension.
-------------------------------------------------Pulmonary embolism should be considered in
all patients with obstructive sleep apnea &
compatible symptoms, because it is a frequent
cause of death.
--------------------------------------------------

A CT pulmonary angiogram is a reasonable


diagnostic test if PE is a consideration.
-------------------------------------------------Factors other than ventricular wall stress that
increase BNP levels include renal failure, older
age, & female sex.
Obesity reduces BNP.
-------------------------------------------------Polysomnography is required to determine the
presence & severity of OSA.
Although snoring, morning headaches, &
daytime sleepiness are common symptoms of
OSA, clinical & physical exam features are
neither sensitive nor specific for the diagnosis.
-------------------------------------------------This patient also has low oxygen saturation
while awake, suggesting the presence of
obesity-hypoventilation syndrome.
Symptoms of obesity-hypoventilation syndrome
are the same as OSA, & most patients also have
OSA.
Diagnosis is established by documenting
alveolar hypoventilation (PCO2 >45 mm Hg)
in the absence of other known causes.
Additional studies include CXR & pulmonary
function testing.
-------------------------------------------------Evaluate a patient with probable OSA with
polysomnography & ABG.
-------------------------------------------------Patients with severe 1-antitryspin deficiency
are predisposed to early-onset COPD,
especially panacinar emphysema, which
involves the lung bases.
1-antitrypsin (AAT) deficiency is a clinically
underdiagnosed disorder that primarily affects
the lungs but also the liver &, rarely, the skin.
AAT protects against proteolytic degradation of
elastin, a protein that promotes elasticity of
connective tissue.
In patients younger than 45 years & bilateral
basilar emphysema; ruled out AAT deficiency.
--------------------------------------------------

Sweat chloride test is a screening test for


cystic fibrosis
10% with cystic fibrosis are older than 18 years
Of these patients, GI symptoms & infertility
are the most common presenting problems.
In cystic fibrosis lung disease, CXR typically
shows hyperinflation & accentuated
bronchovascular markings, appearing first in
the upper lobes, followed by bronchiectasis &
cyst formation.
-------------------------------------------------Prescribe pulmonary rehabilitation for a
patient with severe COPD.
-------------------------------------------------A patient on maximum medical treatment for
COPD & still symptomatic, would benefit from
comprehensive pulmonary rehabilitation,
which includes patient education, exercise
training, psychosocial support, & nutritional
intervention as well as the evaluation for
oxygen supplementation.
Referral should be considered for any patient
with chronic respiratory disease who remains
symptomatic or decreased functional status
despite otherwise optimal medical therapy.
-------------------------------------------------Lung transplantation should be considered in
patients who are hospitalized with COPD
exacerbation complicated by hypercapnia
(PCO2 > 50 mm Hg), FEV1 not exceeding 20%
of predicted & either homogeneous disease on
high-resolution CT scan or DLCO < 20% of
predicted who are at high risk of death after
lung volume reduction surgery.
-------------------------------------------------The effect of lung volume reduction surgery
is larger in patients with predominantly upperlobe disease & limited exercise performance
after rehabilitation.
The ideal candidate should have an FEV1
between 20% & 35% of predicted, DLCO no
lower than 20% of predicted, hyperinflation, &

limited comorbidities.
-------------------------------------------------Noninvasive positive-pressure ventilation
(NPPV) should be initiated early in the course
of moderate to severe exacerbations of COPD.
-------------------------------------------------Suitable candidates for NPPV include patients
with moderate to severe dyspnea, use of
accessory respiratory muscles, RR > 25/min, &
pH < 7.35 with PCO2 > 45 mm Hg (6.0 kPa).
If the patient's condition deteriorates or does not
improve after 1 to 2 hours of NPPV, intubation
should be considered.
-------------------------------------------------Excessive oxygen supplementation can worsen
CO2 retention during a COPD exacerbation.
Therefore, oxygen should be titrated to
maintain a saturation of ~ 90%.
-------------------------------------------------Regular use of inhaled corticosteroids in
patients with COPD is a/w a reduction in the
rate of exacerbations; patients who have
frequent exacerbations benefit most.
-------------------------------------------------When inhaled corticosteroids are combined
with a long-acting 2-agonist, the rate of
decline in quality of life & health status is
significantly reduced; lung function is improved
& dyspnea is alleviated.
-------------------------------------------------Anticholinergic agents in COPD are especially
useful when combined with short-acting or
long-acting 2-agonists.
Tiotropium is effective in patients with stable
COPD for up to 24 hours & should not be
combined with short-acting anticholinergic
agents, such as ipratropium.
-------------------------------------------------Treat severe COPD by adding an inhaled
corticosteroid.
-------------------------------------------------Use of long-term oxygen therapy in patients
with chronic respiratory failure improves

survival & beneficial effect on hemodynamics,


exercise capacity, & mental status.
Oxygen is usually prescribed for patients who
have arterial PO2 < 55 mm Hg or oxygen
saturation < 88% with or without hypercapnia
or who exhibit arterial PO2 of 56 to 59 mm Hg
or oxygen saturation < 89% with one or more of
the following: pulmonary HTN, evidence of
edema or cor pulmonale as a result of right
heart failure, or hematocrit > 56%.
Treatment duration should be at least 15 hours
a day.
-------------------------------------------------Inhaled corticosteroids & long-acting -agonist
(salmeterol), may be indicated to reduce the
frequency of COPD exacerbations, reduce
hospitalizations, & improve lung function, but
these medications do not increase survival.
-------------------------------------------------Methylxanthines (theophylline), are used only
after other long-acting bronchodilators have
been tried.
They have a narrow therapeutic window.
Toxicity is dose-related, & common side effects
include headache, insomnia, nausea, &
heartburn, & potential for development of
arrhythmias & tremor.
Methylxanthines are metabolized by
cytochrome P450, & drug interactions are
common.
Methylxanthines decrease dyspnea & improve
lung function, but do not impact survival.
-------------------------------------------------Treat hypoxic COPD with long-term oxygen.
-------------------------------------------------Antibiotics for moderate to severe exacerbations
of COPD include a third-generation
cephalosporin plus a macrolide or monotherapy
with a fluoroquinolone.
-------------------------------------------------Oral or IV corticosteroids, short-acting
bronchodilators (albuterol or ipratropium), &

supplemental oxygen are the principle


treatments for acute exacerbations of COPD.
However, many patients will also benefit from
the addition of antibiotics.
Antibiotics can improved several clinical
outcomes, including resolution of symptoms,
shorter hospital stay, & mortality.
Antibiotics are recommended for patients with
severe COPD exacerbations & those on
mechanical ventilation. Patients with moderate
to severe exacerbations characterized by
increased dyspnea, increased sputum volume,
increased sputum purulence, or need for
hospitalization also benefit from antibiotics.
------------------------------------------------Optimal antibiotic regimen for the treatment of
exacerbations is based on the most commonly
isolated bacterial pathogens, including
Haemophilus influenzae, Streptococcus
pneumoniae, & Moraxella catarrhalis.
Antibiotic regimens for community-acquired
infection include coverage with a thirdgeneration cephalosporin in combination with
a macrolide or monotherapy with a
fluoroquinolone.
Because of the high incidence of H. influenzae
& M. catarrhalis resistance, amoxicillin is no
longer considered a first-line agent for patients
with moderate to severe COPD exacerbations.
-------------------------------------------------Treat an exacerbation of COPD with antibiotics
-------------------------------------------------Persistent asthma not adequately controlled
with daily low- or moderate-dose inhaled
corticosteroids, adding a long-acting -agonist
improves asthma control & quality of life.
-------------------------------------------------Persistent asthma is defined as asthma
symptoms occurring 2 or more days per week
or 2 or more nights per month.
Initially treat with daily inhaled corticosteroid
If asthma is not controlled on low- or moderatedose inhaled corticosteroids, adding a long-

acting -agonist (salmeterol or formoterol) has


been shown to be superior to doubling the dose
of corticosteroid for improving asthma control
& quality of life.
-------------------------------------------------Advise against using a long-acting -agonist
as a single controller therapy due to concern
of asthma-related deaths.
-------------------------------------------------Theophylline & leukotriene-modifying drugs
are third-line agents that should be considered
in patients who remain symptomatic despite the
addition of a long-acting -agonist to
corticosteroid therapy.
-------------------------------------------------Treat inadequately controlled persistent asthma
by adding a long-acting -agonist.
-------------------------------------------------Asthma during pregnancy follows the rule of
thirds: the condition improves in 1/3 of patients,
worsens in 1/3, & remains unchanged in 1/3.
Uncontrolled asthma has a significantly worse
impact on pregnancy outcome than the potential
risk of medications during pregnancy.
Short-acting -agonists, Budesonide, are
regarded as safe during pregnancy.
Aewer data on other inhaled corticosteroids,
such as fluticasone, is a category C drug.
------------------------------------------------Theophylline & aminophylline are pregnancy
risk category C drugs also, but extensive
clinical experience suggests that they are safe
during pregnancy. However, the metabolism
of these agents may be altered in pregnancy,
requiring increased drug level monitoring.
-------------------------------------------------Manage persistent asthma during pregnancy
with inhaled corticosteroids.
-------------------------------------------------A patient with previously well-controlled
asthma has "loss of control" after a respiratory
tract infection.

A short course of an oral corticosteroid


(prednisone, 0.5 mg/kg daily, 5 to 7 days) can
resolve the asthma symptoms & regain control.
It is unclear whether doubling (or quadrupling)
the dose of inhaled corticosteroids is an
effective strategy in place of oral corticosteroids
-------------------------------------------------Adding a long-acting -agonist would be
reasonable if symptoms persist after the oral
corticosteroid therapy, but the persistence &
severity of the patient's current symptoms
suggest an ongoing airway inflammation &
systemic corticosteroid is warranted.
-------------------------------------------------Begin step-up therapy for asthma with oral
systemic corticosteroids.
-------------------------------------------------A short course of oral corticosteroids may
restore control in previously well-controlled
asthma patients who have developed unstable
disease as a result of respiratory tract infection.
-------------------------------------------------Nebulized therapy at home is reserved for
patients who cannot use a metered-dose inhaler
appropriately.
Although nebulized bronchodilator therapy can
be effective in reversing bronchoconstriction
than metered-dose inhaled bronchodilators,
nebulized therapy should not be used as a
substitute for oral corticosteroid therapy in
patients with asthma exacerbations.
-------------------------------------------------Respiratory acidosis, hypoxemia, & fatigue
are indications for intubation & mechanical
ventilation in an acute exacerbation of asthma.
-------------------------------------------------Cause of acute ventilatory failure in patients
with exacerbations of asthma is increased
airway resistance & dynamic hyperinflation that
reduces chest-wall compliance. Both contribute
to excessive work of breathing.
Bronchospasm, airway edema, & secretions, as
well as excessive expiratory airway collapse,

can severely reduce airway diameter, resulting


in markedly prolonged expiration.
Increased respiratory drive & high metabolic
demands increase minute ventilation, &
expiration between breaths is incomplete.
Progressive stacking of breaths leads to an
equilibration at a higher lung volume with
higher positive end-expiratory alveolar pressure
(auto-PEEP or intrinsic PEEP), a/w dynamic
air trapping & hyperinflation.
The associated flattening of the diaphragm
decreases its function & forces greater reliance
on accessory muscles, further increasing carbon
dioxide production & oxygen consumption as a
result of the inefficiency of these muscles
compared with a functioning diaphragm.
Severe air trapping can cause alveolar rupture
& marked reductions in venous return to the
right heart, results in pneumothorax &
hypotension, respectively.
Typically, asthma exacerbation initially
present with respiratory alkalosis.
Slightly elevated or even normal PaCO2 levels
often indicate impending respiratory failure
rather than recovery, & clinical correlation is
critical for interpreting ABG findings.
Additional features that suggest respiratory
failure include pulse oximetry less than 95%,
PO2 < 75 mm Hg, RR > 30/min, HR > 120/min
-------------------------------------------------Chylothorax is drainage of lymphatic fluid into
the pleural space secondary to disruption or
blockage of the thoracic duct or one of its
lymphatic tributaries.
Malignancy is the most common cause of
chylothorax, trauma is the #2 most common.
Chylothorax can also occur in association with
pulmonary tuberculosis & chronic mediastinal
infections, sarcoidosis, & radiation fibrosis,
lymphangioleiomyomatosis.
--------------------------------------------------

Chylothorax pleural fluid is milky-appearing


but may also be serous or serosanguineous in
malnourished patients with little fat intake.
Pleural fluid triglyceride concentration in a
chylothorax is typically >110 mg/dL &
cholesterol concentration is low.
-------------------------------------------------Parapneumonic effusion is usually a/w a
neutrophilic pleocytosis.
-------------------------------------------------Tuberculosis is the most common cause of
lymphocyte-predominant exudate, as high as
90 to 95% lymphocytes.
The effusion is usually pale yellow in color.
Patients with tuberculous pleural effusion
usually present with a nonproductive cough,
chest pain, & fever.
-------------------------------------------------TB pleural effusion typically presents with a
lymphocyte-predominant exudative effusion.
-------------------------------------------------Evaluate a tuberculous pleural effusion with a
pleural biopsy & culture.
------------------------------------------------TB pleural effusion is suspected based on the
subacute (3-week) duration of symptoms &
turbid yellow character of the pleural effusion.
Because of the patient's young age &
presentation with an isolated pleural effusion,
primary tuberculosis is most likely.
-------------------------------------------------The cellular response in the TB pleural fluid is
classically lymphocytic (> 80% mature
lymphocytes). However, it can be neutrophilic
within the first 2 weeks, then evolve into the
classic lymphocyte-predominant exudate.
Whereas pleural fluid cultures for
Mycobacterium are positive in < 1/3 of cases,
the combination of pleural biopsy for
histologic evaluation & culture is positive in
more than 2/3 of cases.
------------------------------------------------Parapneumonic pleural effusion.

Fluid in the pleural space blocks transmission


of sound between the lung & chest wall
Percussion over an effusion is dull.
Tactile vocal fremitus is diminished or absent.
Breath sounds are decreased to absent.
Fever & pleural effusion suggests an underlying
infection, malignancy, or associated collagen
vascular disease.
-------------------------------------------------Patients with lobar pneumonia typically have
tachypnea, fever, crackles, bronchial breath
sounds, & dullness to percussion with reduced
breath sounds.
Consolidated lung tissue is an excellent
transmitter of sound & vibration, tactile vocal
fremitus is increased, not decreased as in
pleural effusion.
--------------------------------------------------

In pleural effusions a/w pneumonia, presence


of loculated pleural fluid, pleural fluid with a
pH < 7.20, glucose level less than 60 mg/dL,
lactate dehydrogenase level > 1000 U/L,
positive pleural fluid Gram stain or culture, or
presence of gross pus in the pleural space
predicts a poor response to antibiotics alone;
such effusions are treated with drainage of the
fluid through a catheter or chest tube.
-------------------------------------------------This patient's history is compatible with
community-acquired pneumonia (cough,
sputum, fever, chills), & radiography is
consistent with free-flowing pleural effusion.
Because this patient's pleural fluid findings
predict a poor response to antibiotics alone, his
effusion is called a complicated
parapneumonic effusion.
-------------------------------------------------Most pleural effusions resolve with treatment of
the underlying disease.
The only effusions that usually require invasive
treatment are complicated parapneumonic
effusions, empyema, & malignancy.

In patients with pneumonia, thoracic empyema


develops when antibiotics are not given (or
delayed) & pleural space is not drained in a
timely manner. In this case, video-assisted
thorascopic surgery (VATS) is indicated to
break down loculations & drain pus from the
pleural cavity.
-------------------------------------------------Treat a complicated pleural effusion with
chest tube drainage.
-------------------------------------------------Pulmonary arterial hypertension (PAH) is
a/w collagen vascular disease related to
systemic sclerosis.
Pulmonary disease is the primary cause of
morbidity in patients with systemic sclerosis.
PAH is the most common manifestations of
lung involvement, particularly in those with
limited cutaneous disease.
Worsening fatigue & dyspnea on exertion in the
presence of clear lung fields are consistent with
PAH.
-------------------------------------------------Physical signs of elevated pulmonary artery
pressure include a loud P2, fixed split S2,
pulmonic flow murmur, tricuspid regurgitation.
CXR are usually normal in early disease but
may show enlargement of the pulmonary
arteries, right atrium, & right ventricle.
EKG may show RV strain or hypertrophy.
Pulmonary function studies in PAH reveal an
isolated decreased DLCO in the setting of
normal airflow & lung volumes (excluding
restrictive lung disease).
-------------------------------------------------Clinical diagnosis of COPD should be
considered in any patient who has dyspnea,
chronic cough or sputum production, &/or a
history of COPD risk factors.
Diagnosis is confirmed & staged by spirometry:
FEV1/FVC <70%.
Physical exam findings: barrel chest, decreased
breath sounds, & wheezing.

-------------------------------------------------Interstitial lung disease (ILD) is a common


pulmonary manifestation in patients with
systemic sclerosis who also have dyspnea &
fatigue, & dry cough.
Lung volumes are < 80% of predicted.
-------------------------------------------------Pulmonary arterial hypertension is a/w
systemic sclerosis.
-------------------------------------------------Vocal cord dysfunction (VCD) can have throat
or neck discomfort, wheezing, stridor, anxiety.
The disorder can be difficult to differentiate
from asthma; affected patients do not respond
to the usual asthma therapy.
CXR shows decreased lung volumes, in
contrast to hyperinflation in acute asthma.
Oxygen saturation is normal in patients with
VCD.
Laryngoscopy, especially when done while the
patient is symptomatic, can reveal characteristic
adduction of the vocal cords during
inspiration.
Another test that helps make the diagnosis is
flow volume loops.
In patients with VCD, the inspiratory limb of
the flow volume loop is "flattened" owing to
narrowing of the extrathoracic airway (at the
level of the vocal cords) during inspiration.
-------------------------------------------------Initiate therapies targeted at VCD including
speech therapy, relaxation techniques, &
treating underlying causes such as anxiety.
-------------------------------------------------Diagnose vocal cord dysfunction with
laryngoscopy.
-------------------------------------------------Radiographic findings of heart failure include
cardiomegaly, pulmonary vascular congestion,
Kerley B-lines, & pleural effusions; pulmonary
edema may be recognized as perihilar
interstitial infiltrates.
--------------------------------------------------

Spontaneous pneumothorax is a relatively


common event in healthy young persons.
The radiographic abnormality is characterized
by loss of normal lung markings in the
periphery of the hemithorax & presence of a
well-defined, visceral pleural line at some point
between the chest wall & hilum.
Spontaneous pneumothorax occurs when a
subpleural bleb ruptures into the pleural
space, that commonly occurs during exertion.
The presence of air within the pleural space
allows the lung to collapse toward the hilum.
A small amount of bleeding may accompany
rupture of the bleb producing the appearance of
a flat-line junction between the air & fluid that
collects at the base of the hemithorax; known as
a hydropneumothorax.
--------------------------------------------------

-------------------------------------------------Heart failure due to aortic stenosis is the most


likely cause of dyspnea on exertion & orthopnea
Classic manifestations of severe aortic stenosis
are angina, syncope, & heart failure.
Early stages may present subtly, with dyspnea
or decrease in exercise tolerance.
Half of patients with aortic stenosis are
diagnosed when heart failure develops.
Characteristic findings of severe aortic stenosis,
include narrow pulse pressure; delayed,
diminished carotid upstroke; sustained apical
impulse; late-peaking systolic ejection murmur
radiating to the carotids; & S4.
-------------------------------------------------Adults with unrepaired atrial septal defects
may be asymptomatic or may present with
symptoms related to excess pulmonary blood
flow, including fatigue, dyspnea, palpitations, or
right-sided heart failure.
Characteristic findings in atrial septal defect:
fixed splitting of S2 & right ventricular heave.

A pulmonary mid-systolic flow murmur &


tricuspid diastolic flow rumble caused by
increased flow through the right-sided valves
from a large left-to-right shunt may be heard.
-------------------------------------------------In severe pulmonary stenosis, the JVP
demonstrates a prominent a wave.
A right ventricular lift is common.
An ejection click is common, & systolic
murmur is present, with the pulmonic
component of S2 delayed.
-------------------------------------------------Findings of constrictive pericarditis include
elevated JVP, pulsus paradoxus, or pericardial
knock.
-------------------------------------------------Features of hepatopulmonary syndrome
include signs of portal hypertension, dyspnea,
platypnea (SOB relieved with laying down),
hypoxemia with orthodeoxia, cyanosis, &
clubbing.
-------------------------------------------------Emphysema can cause dyspnea, hypoxemia, &
diminished breath sounds.
Presents with cough, or physical exam findings,
such as hyperresonance to percussion,
wheezes, or prolonged expiration.
-------------------------------------------------Hepatopulmonary syndrome manifests as
dyspnea at rest or on exertion, platypnea, &
hypoxemia: common in chronic liver disease.
In the context of chronic liver disease, cyanosis,
clubbing, & hypoxemia are characteristic.
Hypoxemia results from pulmonary vascular
dilatation with intrapulmonary shunt &
ventilation-perfusion mismatch, which may
worsen when the individual is sitting upright.
These can cause orthodeoxia (fall in partial
pressure of oxygen with upright posture) &
platypnea (dyspnea worse when upright)
CXR is typically normal.
--------------------------------------------------

Patients with neuromuscular respiratory


failure, featuresinclude increased residual
volume/total lung capacity ratio, normal
FEV1/FVC ratio, low maximum respiratory
pressures, & normal DLCO are typical.
-------------------------------------------------Severe muscle weakness due to a subacute or
chronic neuromuscular disorder such as ALS or
myasthenia gravis can present with
respiratory failure.
An increased residual volume/total lung
capacity (RV/TLC) ratio is commonly seen in
obstructive disorders, but may also be caused
by a neuromuscular restrictive disorder.
The normal FEV1/FVC ratio & low maximum
respiratory pressures indicate neuromuscular
weakness rather than obstructive lung disease.
------------------------------------------------Pulmonary hypertension presents with
hypoxia & hypocapnia.
The pulmonary arterial hypertension may be
a/w a mild decrease FEV1 or FVC but the
RV/TLC & maxmal inspiratory pressure are
normal. The DLCO is usually decreased.
-------------------------------------------------Cough-variant asthma.
Asthma is an episodic disease, with normal
exam findings & spirometry between episodes.
A methacholine challenge test can induce
bronchoconstriction even when the patient is
asymptomatic & spirometry is normal.
False-positive results can occur with allergic
rhinitis, COPD, heart failure, cystic fibrosis, or
bronchitis.
-------------------------------------------------Methacholine challenge testing is done by
giving increasing concentrations of
methacholine by nebulization & performing
spirometry after each dose.
The methacholine dose that leads to a > 20%
decrease in the FEV1 from baselone is known
as the provocative concentration 20 (PC20) &
calculated from a dose-response curve.

o
o
o

PC20 above 16 mg/mL is normal.


PC20 < 4 mg/mL is consistent with asthma.
PC20 between 4 & 16 mg/mL suggests some
bronchial hyperreactivity, less asthma specific.
-------------------------------------------------Methacholine challenge testing is useful in
evaluating patients with suspected asthma who
have episodic symptoms & normal baseline
spirometry.
-------------------------------------------------Rheumatoid arthritis-interstitial lung disease
Diagnosis of rheumatoid arthritis is suggested
by the symmetrical synovitis of the wrists &
MCP joints.
CXR is often normal in rheumatoid arthritisinterstitial lung disease, particularly in the early
course of the disease.
However, pulmonary function tests show
proportionate reduction in FEV1 & FVC
resulting in a normal FEV1/FVC ratio. This is
consistent with a restrictive pattern, which is
supported by the finding of reduced TLC.
Additionally, the decreased DLCO is
compatible with interstitial lung disease.
-------------------------------------------------COPD & asthma shows an obstructive pattern
with reduced FEV1/FVC ratio; TLC may be
normal or increased.
In COPD, the DLCO is often low.
DLCO is normal in asthma.
-------------------------------------------------COPD should be considered in any patient
with dyspnea, chronic cough or sputum
production, or history of COPD risk factors.
Diagnosis is confirmed & staged by spirometry
Spirometry should be performed after the
administration of an adequate dose of an
inhaled bronchodilator (salbutamol 400 g) to
minimize variability.
-------------------------------------------------Measurements of postbronchodilator
FEV1/FVC ratio & FEV1 are recommended

for diagnosis & assessment of severity of


COPD, respectively
Postbronchodilator FEV1 < 80% of predicted &
FEV1/FVC ratio < 0.70 confirm the presence of
airflow limitation that is not fully reversible,
establishes the diagnosis of COPD, & excludes
the diagnosis of asthma.
-------------------------------------------------DLCO measures the ability of the lungs to
transfer gas from alveoli to the RBCs in
pulmonary capillaries.
DLCO is low in conditions characterized by
barriers to diffusion (interstitial edema,
interstitial infiltrates, tissue fibrosis) or loss of
lung tissue (emphysema).
-------------------------------------------------Patients with heart failure typically have
normal pulmonary function testing, except for
the possibility of decreased DLCO due to
interstitial edema.
-------------------------------------------------Interstitial lung disease patients may have
dry crackles on exam.
Pulmonary function testing typically shows a
proportionate decrease in FEV1 & FVC
resulting in a normal FEV1/FVC ratio, a
decreased TLC, & decreased DLCO.
--------------------------------------------------

XI. Rheumatology

For a strong suspicion of giant cell arteritis,


temporal artery biopsy should be performed
after corticosteroid therapy is begun.
-------------------------------------------------Headache, temporal artery tenderness, fever,
acute visual loss, & mild anemia are suggestive
of giant cell arteritis (GCA).
Immediate high-dose IV methylprednisolone.
Pain in the shoulder & hip girdle accompanied
by a significant elevation in ESR is consistent
with polymyalgia rheumatica, present in 33%
of patients with GCA.
------------------------------------------------Anterior ischemic optic neuropathy causes
acute & complete visual loss in patients with
GCA; funduscopic exam reveals a pale,
swollen optic nerve.
Patients with GCA may rarely regain vision if
treated with high-dose IV methylprednisolone
followed by oral prednisone.
This prevents blindness in the contralateral eye.
Although temporal artery biopsy is the gold
standard for diagnosing GCA, diagnostic testing
should not precede corticosteroid treatment.
-------------------------------------------------GCA is a medical emergency even in the
absence of visual loss.
In a patient suspicious for GCA but who does
not have visual loss, immediate initiation of
high-dose oral prednisone before performing
diagnostic testing.
-------------------------------------------------Low-dose oral prednisone is an adequate for
isolated polymyalgia rheumatic.
-------------------------------------------------Wegener granulomatosis should be considered
in patients with upper- & lower-airway
manifestations, renal involvement, &
inflammatory arthritis.
--------------------------------------------------

Wegener granulomatosis is a necrotizing


vasculitis that affects the upper- & lowerrespiratory tract & kidneys.
Purpura is consistent with vasculitis.
Diffuse pulmonary infiltrates (a/w alveolar
hemorrhage), history of refractory otitis media,
renal failure, & glomerulonephritis.
-------------------------------------------------Wegener granulomatosis may be a/w
inflammatory arthritis involving small &
large joints & joint effusions.
c-ANCA & antiproteinase-3 antibodies is
90% specific.
-------------------------------------------------Patients with long-standing rheumatoid
arthritis may develop interstitial pneumonitis,
likely in men.
Radiograph show bibasilar interstitial markings.
Interstitial lung disease a/w rheumatoid arthritis
has an insidious onset & a/w seropositive,
erosive joint disease.
-------------------------------------------------Pneumocystis pneumonia may manifest as
fever, dyspnea, tachypnea, & crackles
Dyspnea is progressive, not acute, & would not
result in rapid pulmonary failure.
CXR may show diffuse infiltrates.
-------------------------------------------------Methotrexate-induced pneumonitis can occur
at any time in the course of therapy, regardless
of the dosage or duration of treatment.
-------------------------------------------------Polyarteritis nodosa commonly affects the
kidneys & cause significant hypertension,
renal insufficiency, & renal vasculitis with
classic angiographic diagnostic findings.
-------------------------------------------------Polyarteritis nodosa is characterized by a
necrotizing inflammation of medium-sized or
small arteries without glomerulonephritis or
vasculitis of arterioles, capillaries, or venules.
Manifestations include fever; musculoskeletal
symptoms; & vasculitis involving the nervous

system, GI tract, heart, & non-glomerular renal


vessels that is a/w significant hypertension,
renal insufficiency, proteinuria, & hematuria.
-------------------------------------------------Polyarteritis nodosa commonly affects the
kidneys & cause significant HTN, kidney
insufficiency, & renal vasculitis a/w
proteinuria & hematuria.
Prompt immunosuppressive therapy with
corticosteroids or cyclophosphamide is
critical to reduce the risk of irreversible kidney
failure, but a definitive diagnosis by
angiography of the renal arteries must be
established before beginning this treatment.
-------------------------------------------------Sural nerve biopsy may establish the
diagnosis, & kidney angiography can support
the diagnosis of polyarteritis nodosa.
After exclusion of other causes of medium- or
small-vessel vasculitis, angiography of the
renal arteries is performed when there is no
appropriate tissue to biopsy.
Specific angiographic findings include
microaneurysms or beaded pattern with areas
of arterial narrowing & dilation.
-------------------------------------------------Abdominal fat pad aspiration may help to
diagnose AL amyloidosis.
-------------------------------------------------Primary Sjogren's syndrome is diagnosed in
patients between 40 - 60 years of age, & with a
9:1 female predominance.
Manifests as symptomatic oral & ocular dryness
Lymphocytic inflammation of the lacrimal
glands causes an aqueous tear deficiency with
resultant keratoconjunctivitis sicca, whereas
lymphocytic inflammation of the major &
minor salivary glands is a/w salivary gland
enlargement & xerostomia.
Autoantibodies to Ro/SSA & La/SSB are not
specific for Sjogren's syndrome.
--------------------------------------------------

Sjogren's syndrome is an autoimmune disease


characterized by keratoconjunctivitis sicca,
xerostomia, & presence of autoantibodies.
-------------------------------------------------Fibromyalgia is characterized by diffuse pain
on both sides of the body, above & below the
waist as well as axial skeletal pain.
The presence of pain in at least 11 of 18
specified potential tender points.
Most have fatigue & sleep disturbance; may
be a/w dry eyes & mouth.
Comorbidity with other symptom-defined
syndromes include chronic fatigue syndrome,
migraine, irritable bowel syndrome, pelvic pain,
& temporomandibular joint (TMJ) pain..
-------------------------------------------------Polymyositis manifests as significant proximal
muscle weakness & elevated creatine kinase.
-------------------------------------------------Raynaud phenomenon is present in > 95% of
patients with systemic sclerosis & more likely
in patients with limited cutaneous disease.
-------------------------------------------------Systemic sclerosis is classified according to the
degree of skin involvement.
Systemic sclerosis with limited cutaneous
involvement, or CREST syndrome
(calcinosis, Raynaud phenomenon, esophageal
dysmotility, sclerodactyly, & telangiectasia), is
a/w skin thickening distal to elbows & knees.
Systemic sclerosis with diffuse cutaneous
involvement is a/w skin thickening proximal to
the elbows & knees.
Both types may affect the face.
-------------------------------------------------Raynaud phenomenon is caused by
microvascular involvement in patients with
systemic sclerosis & characterized by intimal
proliferation & progressive luminal obliteration,
as well as digital spasm.
Does not respond to anti-inflammatory agents;
therefore, prednisone is not indicated.
--------------------------------------------------

Episodes of Raynaud phenomenon are often


precipitated by cold exposure or stress &
usually involve the extremities.
Cigarette smoking is contraindicated &
avoidance of cold is recommended.
Dihydropyridine calcium channel blockers
such as amlodipine reduce the frequency &
severity of attacks in both primary & secondary
Raynaud phenomenon, used as first-line
treatment in those whom cold avoidance does
not provide sufficient relief.
Other agents include peripherally acting -1
blockers, phosphodiesterase inhibitors, &
endothelin receptor antagonists.
-------------------------------------------------Topical nitrates applied to the finger webs are
second-line therapy of Raynaud phenomenon.
------------------------------------------------Interstitial lung disease (ILD) with
progressive pulmonary fibrosis & secondary
pulmonary arterial hypertension is one of the
leading causes of death in patients with
polymyositis & dermatomyositis.
anti-Jo-1 antibodies increase risk for ILD.
Patients have progressive dyspnea, basilar
crackles, bibasilar infiltrates on CXR, &
restrictive changes on pulmonary function
studies, including decreased FVC, TLC, &
diffusing capacity of the lungs for CO.
CXR demonstrate an interstitial pattern, &
high-resolution CT scans of the chest
commonly suggest a diagnosis of nonspecific
interstitial pneumonia.
-------------------------------------------------Patients with SLE have sun sensitivity,
triggered or exacerbated by UVA & UV B light
Facial rash is a classic presentation, involving
the bridge of the nose, malar areas, & forehead,
with erythematosus plaques & a fine scale.
Nasolabial folds are spared, which distinguishes
it from other common rashes of the face,
including rosacea & seborrheic dermatitis.

Rash may last for hours or days & tends to recur


-------------------------------------------------Rosacea is a chronic inflammatory skin
disorder that begins in early to middle age adult
Characterized by central telangiectasis,
flushing, & acneiform papules & pustules.
-------------------------------------------------Dermatomyositis has pronounced proximal
muscle weakness & elevated creatine kinase.
Patients with dermatomyositis may have a
facial rash that extends up to the eyelids,
giving them a purplish (heliotrope) hue.
Another characteristic finding is red to purplish
plaques on the dorsal hands, more prominent
over the joints (Gottron papules).
-------------------------------------------------HTN, ankle edema, hematuria, proteinuria,
hypoalbuminemia, & erythrocyte casts on
urinalysis are suggestive of lupus nephritis
despite the absence of renal insufficiency.
To prevent irreversible renal damage, early
treatment with a high-dose corticosteroid such
as prednisone is indicated.
Subsequent management of HTN with an
ACE inhibitors to control proteinuria.
Ibuprofen may help to control arthralgia.
However, NSAIDs can worsen renal function
in lupus nephritis & therefore contraindicated.
-------------------------------------------------Treatment with high-dose corticosteroids is
indicated in patients with strong suspicion for
lupus nephritis.
-------------------------------------------------Drug-induced lupus caused by the TNF
inhibitor infliximab.
The most appropriate next step is to
discontinue infliximab & begin prednisone.
Prednisone also should be added to control
pleuritis & synovitis
-------------------------------------------------Many patients who use TNF inhibitors
develop autoantibodies, including antinuclear,
anti-double-stranded DNA, & anti-Smith

antibodies.
-------------------------------------------------If her rheumatoid arthritis flares were
related to active rheumatoid arthritis,
symptoms would be alleviated by initiation of
sulfasalazine or increase in infliximab dosage.
However, her musculoskeletal features, fever,
malar rash, photosensitivity, purpura,
symptoms of pleuritis, ANA & anti-ds DNA
antibody positivity, & findings on CXR raise
suspicion for drug-induced lupus.
-------------------------------------------------Antibodies a/w systemic sclerosis:
o anti-topoisomerase I (anti-Scl-70)
o anticentromere
anti-Scl-70 antibody is seen in patients with
diffuse systemic sclerosis & a/w development
of interstitial lung disease.
anticentromere antibody is a/w limited
cutaneous systemic sclerosis.
-------------------------------------------------Pleuritic chest pain, symmetric synovitis of
the hand & wrist joints, leukopenia,
proteinuria, & positive ANA likely has SLE.
-------------------------------------------------Patients with a high pretest probability of SLE
& ANAs (titer 1:160) should undergo
confirmatory testing, such as measurement of
compliment levels C3, C4, & total hemolytic
compliment (CH50) & specific autoantibody
testing, such as anti-ds DNA antibody
anti-dsDNA antibody is very specific for SLE
-------------------------------------------------Anti-SS-A (anti-Ro) & anti-SS-B (anti-La)
antibodies are neither sensitive nor specific for
SLE; often seen in Sjogren syndrome.
-------------------------------------------------Anti-cyclic citrullinated peptide antibodies
are highly specific for rheumatoid arthritis.
-------------------------------------------------MRI, with gadolinium enhancement, is
sensitive for detecting early erosive
inflammatory changes in sacroiliac joints &

spine, a/w ankylosing spondylitis.


-------------------------------------------------

Radiographic evidence of sacroiliitis is


required for definitive diagnosis & the most
consistent finding a/w ankylosing spondylitis.
However, normal radiographs of the pelvis do
not exclude sacroiliitis.
Onset usually occurs in teenage years or 20s &
manifests as persistent pain & morning
stiffness involving the low back that are
alleviated with activity.
HLA-B27 positivity is a strong risk factor.
-------------------------------------------------Diagnose ankylosing spondylitis with an
MRI of the sacroiliac joints.
-------------------------------------------------Patients with uveitis a/w systemic disease
usually have a history or physical exam that
suggest an underlying disorder.
The most common systemic illnesses in
patients with anterior uveitis are sarcoidosis,
reactive arthritis, & ankylosing spondylitis.
-------------------------------------------------A patient has anterior uveitis with a
hypopyon, & the associated systemic disease
is most likely ankylosing spondylitis.
Classic triad for acute anterior uveitis is pain,
sensitivity to light, & blurred vision; headache,
tenderness, & tearing may also occur
Photophobia during penlight exam has a
positive predictive value of 60% for severe eye
disease & negative predictive value of 90%.
-------------------------------------------------Acute anterior uveitis, particularly unilateral
presentations that fluctuate between both eyes,
is a/w HLA-B27-related arthropathies,
including ankylosing spondylitis.
Chronic back stiffness is highly suggestive of
ankylosing spondylitis.
-------------------------------------------------Sicca syndrome manifests as dry mouth, eyes,
& vagina, with parotid glands enlargement in

a/w concomitant redness & gritty irritation of


the eyes.
Suggests primary or secondary Sjogren
syndrome.
-------------------------------------------------Enteropathic arthritis presents with a history
of crampy abdominal pain & recent onset of
bloody diarrhea & rectal urgency; & weight
loss. This presentation raises suspicion for
inflammatory bowel disease.
For the past 3 weeks, this patient has had acute
arthritis of the knee & ankle accompanied by
inflammatory features such as tenderness &
swelling; synovial fluid findings confirm the
presence of an inflammatory process.
Presence of acute oligoarticular arthritis
involving the lower extremities in a patient
with inflammatory bowel disease is suggestive
of enteropathic arthritis; enteropathic
arthritis also may manifest as axial arthritis,
such as a spondyloarthropathy.
-------------------------------------------------Gonococcal arthritis may be a/w
oligoarticular arthritis, & may be migratory.
However, gonococcal arthritis commonly have
tenosynovitis & cutaneous involvement.
-------------------------------------------------Whipple disease is an extremely rare
infectious syndrome caused by Tropheryma
whippelii. T
The most common symptom is arthritis; other
symptoms include diarrhea, malabsorption, &
CNS & constitutional symptoms.
Joint involvement is migratory & follows a
chronic course.
-------------------------------------------------No confirmatory laboratory tests for psoriatic
arthritis are available.
-------------------------------------------------HIV patients with a CD4 cell count < 200/L
who are not taking antiretrovirals commonly
have psoriasis or other skin conditions

Psoriasis in patients with low CD4 cell count


can be severe, affect > 50% of body surface
area, & present in an atypical fashion
(explosive onset).
-------------------------------------------------Diagnosis of HIV-related psoriatic arthritis
should be suspected in patients with explosive
onset, widespread psoriasis & occurrence of
dactylitis; marked DIP joint involvement;
asymmetric joint involvement; symptoms of
enthesitis; or joint ankylosis.
-------------------------------------------------Prominent morning stiffness that lasting more
than 1 hour & fatigue are consistent with early
presentations of rheumatoid arthritis.
Most often involves the small joints of the
hands & feet in a symmetric pattern.
Presence of rheumatoid factor & anti-cyclic
citrullinated antibodies is highly specific for
rheumatoid arthritis, & radiographic
manifestations include periarticular
osteopenia & articular erosions.
-------------------------------------------------In patients with rheumatoid arthritis, early,
aggressive disease control is critical & should
be instituted as soon as diagnosis is established.
Begin disease-modifying antirheumatic
drug (DMARD) therapy within 3 months of
the onset & diagnosis of RA.
-------------------------------------------------Hydroxychloroquine is warranted in a patient
with early, mild, & nonerosive rheumatoid
arthritis & well tolerated.
-------------------------------------------------Etanercept, a biologic DMARD, would be an
appropriate adjunct in whom an oral DMARD
has not provided adequate disease control.
Etanercept & other TNF inhibitors have
greater efficacy when used in combination
with methotrexate.
-------------------------------------------------Methotrexate is used as an initial DMARD in
the treatment of rheumatoid arthritis.

However, this agent is a/w hepatotoxicity, &


risk is increased in patients who regularly
consume alcohol; therefore, methotrexate is
not indicated for those who consume alcohol.
-------------------------------------------------Combination therapy with an NSAID &
DMARD has been shown to reduce joint pain
& swelling in rheumatoid arthritis.
-------------------------------------------------Rheumatoid arthritis is the most common
cause of chronic, inflammatory polyarthritis in
premenopausal women.
-------------------------------------------------Rheumatoid arthritis commonly affects the
MCP, PIP, & wrist joints.
-------------------------------------------------Parvovirus B19 infection in adults may
induce an acute rheumatoid factor-positive
oligo- or polyarthritis.
The arthritis does not cause joint destruction,
& supportive analgesic therapy with NSAIDs
is appropriate as tolerated.
Diagnosis may be established by detecting
IgM antibodies against parvovirus B19.
-------------------------------------------------Screen for latent tuberculosis prior to
initiating TNF- inhibitor therapy.
-------------------------------------------------When rheumatoid arthritis control is not
achieved with oral DMARDs (methotrexate),
biologic therapy should be initiated.
Initial biologic therapy should be a TNF-
inhibitor added to the baseline methotrexate
therapy, because the rate of progression has
been shown to decrease with this combination.
Reactivation TB is the most common
infectious complication of TNF- inhibitors.
Tuberculin skin testing is indicated before
beginning treatment with these agents, &
positive results warrant treatment for latent TB
Periodic tuberculin skin testing is
recommended during treatment with a TNF-

inhibitor.
-------------------------------------------------In a patient with symmetrical synovitis of the
small joints of the hand & prolonged morning
stiffness, x-rays showing joint erosions is most
supportive of rheumatoid arthritis.
-------------------------------------------------Marginal joint erosions on radiograph most
likely suggest rheumatoid arthritis (RA).
Plain radiographs of the hands & feet should
be performed at the time of diagnosis to detect
erosions & joint-space narrowing.
-------------------------------------------------Patients with osteoarthritis not adequately
controlled with acetaminophen, the next
intervention is usually an NSAID.
-------------------------------------------------Acute osteoarthritis of the knee.
Classic findings of osteoarthritis include pain
with activity that is relieved with rest.
Radiographic findings of joint space
narrowing, subchondral sclerosis & osteophyte
formation are consistent with osteoarthritis
A valgus deformity predisposes to medial
compartment osteoarthritis due to uneven
loading forces when ambulating.
Failed treatment with acetaminophen,
therefore an oral NSAID is the next step.
-------------------------------------------------Intra-articular corticosteroid or hyaluronan
injections may be considered in patients with
mono- or pauciarticular osteoarthritis in whom
NSAIDs are either contraindicated or do not
provide adequate pain relief.
-------------------------------------------------de Quervain tenosynovitis is an inflammation
of abductor pollicis longus & extensor pollicis
brevis tendons. Pain is present on palpation of
the distal aspect of the radial styloid.
-------------------------------------------------Rheumatoid arthritis is an inflammatory
arthritis most often affecting the small joints of

the hands (wrist, mcp & pip joints) & feet


(metatarsophalangeal joints) symmetrically.
Stiffness usually lasts > 1 hour, & synovial
swelling, tenderness, & warmth are apparent.
-------------------------------------------------Chronic pain at the base of the thumb is
suggestive of osteoarthritis.
-------------------------------------------------Osteoarthritis in the first carpometacarpal joint
presents with well localized TTP.
Movement of the thumb in a circular motion
("grind test") will often elicit the pain.
Predisposing factors include repetitive use of
the wrist or thumb.
Patients may present with pain, swelling, or
enlargement of the carpometacarpal joint
recognized as squaring or boxing at the base
of the thumb.
Associated findings include enlargement of the
DIP joints (Heberden nodes) or PIP joints
(Bouchard nodes).
-------------------------------------------------Physical therapy is an appropriate first-line
management option osteoarthritis of the knee,
& quadriceps muscle training in particular has
been shown to reduce pain in this setting.
Use of OTC acetaminophen or NSAID on a
PRN basis also may benefit.
-------------------------------------------------Arthroscopy & MRI of an osteoarthritic knee
would likely reveal abnormalities of the
articular cartilage but are not needed to
establish the diagnosis of osteoarthritis.
-------------------------------------------------Osteoarthritis of the knee can be diagnosed if
knee pain is accompanied by at least three of
the following features: age > 50 years,
morning stiffness lasting < 30 minutes,
crepitus, bony tenderness, bony enlargement,
& absence of palpable warmth.
Radiographic findings of osteophytes, jointspace narrowing, sclerosis, & cyst formation.
--------------------------------------------------

Osteoarthritis affects weight-bearing joints


such as the knees & characterized by pain on
activity that is relieved with rest.
Swelling is minimal, & ROM is limited.
-------------------------------------------------Rheumatoid arthritis usually have symmetric
arthritis that affects at least three joints as well
as an elevated ESR & a/w morning stiffness
that persists for > 30 minutes.
-------------------------------------------------Avascular necrosis of the knee typically
experience pain on weight bearing & painful,
limited range of motion a/w pain at rest
Commonly occurs with corticosteroid use,
SLE, or consume excessive alcohol.
Radiographs reveal density changes;
subchondral radiolucency; cysts; sclerosis; &,
eventually, joint-space narrowing.
-------------------------------------------------Gout is caused by the deposition of
monosodium urate crystals in the tissues of
& around the joints.
Early attacks are monoarticular & commonly
involve the first metatarsophalangeal joint,
Chronic gout may manifest as symmetric
involvement of small joints of the hands & feet
accompanied by tophi & subcortical erosions
-------------------------------------------------This patient has calcium pyrophosphate
dihydrate (CPPD) deposition disease
presenting as pseudogout.
Pseudogout manifests as acute or subacute
attacks of warmth & swelling in one to two
joints that resemble acute gouty arthropathy.
Pseudogout is a/w inflammatory synovial fluid
& presence of CPPD crystals that are weakly
positively birefringent & rhomboid in shape
seen on polarized light microscopy.
Treatment of an acute pseudogout attack
involves NSAIDs, but a corticosteroid or
colchicine would be appropriate alternatives.
--------------------------------------------------

Osteoarthritis that manifests in patients with


CPPD deposition or presence of
chondrocalcinosis on radiography is known
as pseudo-osteoarthritis.
This degenerative condition mimics
osteoarthritis except that it may affect joints
not typically involved in osteoarthritis, such as
wrists, MCP joints, shoulders, & ankles.
The synovial fluid is noninflammatory.
-------------------------------------------------Treatment of pseudo-osteoarthritis is no
different than the treatment of osteoarthritis &
includes adequate analgesia, PT & OT.
Arthroplasty for symptomatic disease
unresponsive to conservative therapy.
-------------------------------------------------Prophylactic colchicine, low-dose
corticosteroids (10 mg/d or less), or NSAIDs
initiated at least 1 week before beginning or
adjusting the dose of uric acid-lowering
therapy help to prevent disease flares a/w
changes in uric acid levels & may need to be
continued until therapeutic serum uric acid
levels have been achieved.
-------------------------------------------------Criteria to initiate treatment of hyperuricemia
in symptomatic gout include presence of tophi
or renal stones, multiple acute gout attacks, or
history of a decreasing period between attacks.
Uric acid-lowering therapy typically is not
initiated until a patient experiences two
documented acute attacks.
Dietary purine restriction, weight loss, &
discontinuation of alcohol may help decrease
uric acid levels in patients with mild
hyperuricemia & symptomatic gout.
Medications that raise serum uric acid levels,
such as thiazides & low-dose salicylates,
should be discontinued if alternative therapy is
available.
Most patients with recurrent gouty attacks,
particularly those with tophaceous deposits,

require medications to lower serum uric acid.


-------------------------------------------------The goal in uric acid-lowering therapy is to
achieve a serum uric acid level < 6.0 mg/dL,
not just levels within the normal range.
When uric acid levels are below 6.0 mg/dL,
monosodium urate crystals from within the
joint & from soft-tissue tophaceous deposits
are reabsorbed.
--------------------------------------------------

Allopurinol & febuxostat are xanthine


oxidase inhibitors useful in reducing uric acid
levels in patients with recurrent attacks of
acute gout & uric acid tophi or renal stones.
Rapid control of serum uric acid is not
necessary during an acute attack
Acute increases & decreases in uric acid level
alter the steady state & may prolong the
current attack or precipitate new attacks.
-------------------------------------------------Definitive diagnosis of gout requires the
identification of monosodium urate crystals
on arthrocentesis or aspiration of a tophus.
During an attack of gout, needle-shaped
monosodium urate crystals that typically
appear engulfed by neutrophils are visible on
compensated polarized light microscopy.
-------------------------------------------------NSAIDs, corticosteroids, & colchicine are
options in treatment of an acute attack of gout.
-------------------------------------------------Colchicine is most effective in patients with
monoarticular involvement &, when used
within the first 24 hours of symptoms, can
abort a severe attack.
At the first sign of an attack in patients with
normal renal function, colchicine is
administered two or three times daily until the
patient experiences symptomatic relief,
develops GI toxicity, or reaches a maximum
dose of 6 mg per attack.
--------------------------------------------------

Oral, intra-articular, or IV corticosteroid


therapy is also effective in acute gouty attacks.
However, oral & intravenous therapy may be
problematic in patients with diabetes mellitus.
-------------------------------------------------NSAIDs are highly effective when
administered during an acute attack, but they
should be used with caution in patients at risk
for renal impairment, bleeding, or ulcer
disorders, especially in the elderly.
-------------------------------------------------Prosthetic joint infection may occur at any
time in the postoperative period.
Infections after the first postoperative year are
frequently caused by hematogenous spread of
organisms to the prosthetic joint.
The source includes skin or genitourinary tract
infection or an abscessed tooth.
Pain is the predominant or only symptom.
ESR is usually elevated.
-------------------------------------------------In patients with prosthetic joint infection,
pain is the predominant or only symptom;
fever & leukocytosis are frequently absent.
Gold standard for diagnosis is arthrocentesis
or intraoperative tissue sampling with culture
before antibiotic therapy is initiated.
-------------------------------------------------All patients with acute monoarthritis should
be presumed to have septic arthritis until
synovial fluid analysis via arthrocentesis
excludes this condition.
-------------------------------------------------Septic arthritis should be suspected in
patients with underlying rheumatologic
disorders such as rheumatoid arthritis with a
sudden single joint flare not accompanied by
other features of the pre-existing disorder.
-------------------------------------------------Septic arthritis presents as acute monoarthritis
& characterized by pain on passive ROM in the
absence of known trauma.

Arthrocentesis of the wrist will most likely


help establish a diagnosis.
Synovial fluid analysis is the only definitive
way to diagnose septic arthritis & critical to
guide antibiotic treatment.
Patients with suspicion for this condition
should begin empiric systemic antibiotics until
culture results are available.
-------------------------------------------------Hematogenous spread is the most common
mechanism of joint infection; because the
synovium has no basement membrane it is
vulnerable to infection.
Staphylococcus is the most common grampositive organism affecting native & prosthetic
joints, & infection with methicillin-resistant
strains is increasingly common.
Joints that have been previously damaged are
more likely to become infected than structurally
normal joints.
Patients with rheumatoid arthritis have
usually used intra-articular corticosteroids or
immunosuppressive agents at some point &
therefore, particularly susceptible to infection.
Septic arthritis also is more likely to have a
polyarticular presentation in patients with
pre-existing rheumatoid arthritis.
Vancomycin is the empiric therapy of choice
for community-acquired septic arthritis &
synovial fluid positive for gram-positive cocci
or patients at low risk for gram-negative
infection & negative synovial fluid Gram stain.
Because of increasing concern about MRSA
infection in the community, vancomycin is the
initial treatment pending culture results.
-------------------------------------------------Treat presumed MRSA septic arthritis with
vancomycin.
-------------------------------------------------Ceftriaxone is the initial choice in patients at
risk for gonococcal infection.
Gonococcal arthritis is the most common form
of bacterial arthritis in young & sexually active

persons; should be considered in patients with


migratory tenosynovitis & arthralgia.
-------------------------------------------------Patients with polymyalgia rheumatica
typically achieve resolution of symptoms with
low-dose prednisone (10 - 20 mg/d); once
symptoms are controlled, prednisone dosage
can be tapered.
Polymyalgia rheumatica commonly recurs
when the prednisone dosage is being tapered.
During flares, prednisone dosage should be
increased to the minimum amount needed to
provide symptomatic relief; once symptoms
subside, tapering of the dosage is warranted.
Because two previous attempts to taper this
patient's prednisone dosage below 7.5 mg/d
have been unsuccessful, the addition of a
steroid-sparing agent as well as an increase in
her prednisone dosage is warranted.
The most appropriate management in this
patient is to increase the prednisone dosage to
7.5 mg/d & add methotrexate.
Methotrexate in particular has been shown to
be an effective steroid-sparing agent in
patients with polymyalgia rheumatica.
-------------------------------------------------Infliximab has not been shown to be an
effective steroid-sparing agent in patients with
polymyalgia rheumatic..
-------------------------------------------------Referred shoulder pain is always a/w a
normal shoulder exam that does not alter the
severity or character of the pain.
-------------------------------------------------Referred shoulder pain is often the result of an
underlying intrathoracic process.
CXR may identify an underlying intrathoracic
process, such as an apical lung tumor, effusion,
or pneumothorax.
-------------------------------------------------Rotator cuff tendinitis, inflammation of the
supraspinatus &/or infraspinatus tendon that

can also involve the subacromial bursa, is a


common overuse injury.
Characterized by subacromial tenderness &
impingementpainful compression of the
rotator cuff tendons & subacromial bursa
between the humeral head & acromion with
arm elevation.
Pain occurs with reaching overhead & when
lying on the shoulder.
Passive painful-arc maneuver assesses the
degree of impingement.
Subacromial pain at 60 to 70 degrees of
abduction suggests moderate impingement,
while pain at 45 degrees or less suggests severe
impingement.
Pain with resisted mid-arc abduction is a
specific finding for rotator cuff tendinitis.
Treatments include NSAIDs, ice, & exercises.
-------------------------------------------------A torn rotator cuff usually results in arm
weakness, particularly with abduction &/or
external rotation.
Positive drop-arm test (inability to smoothly
lower the affected arm from full abduction) is a
very specific but insensitive method for
diagnosing rotator cuff tear.
-------------------------------------------------Anserine bursitis diagnosis rests on the finding
of focal tenderness on the upper, inner tibia, 5cm
distal to the medial articular line of the knee.
The maneuver with the knee semiflexed helps
confirm the diagnosis.
Patients are usually middle-aged or older &
often have knee osteoarthritis.
There is no redness, swelling, or increased
warmth at the painful site.
The underlying problem is strain of the pes
anserinus tendon rather than true bursitis.
Corticosteroid injection at the bursal site
almost always provides relief of pain.
Often, knee pain attributed to even severe
osteoarthritis disappears after treatment of the
anserine bursitis.

Because the corticosteroid is injected into soft


tissue, the risk of tendon rupture is minimal.
-------------------------------------------------Suspicion for a meniscal tear typically describe
a twisting injury with the foot in a weightbearing position; a popping or tearing sensation
is felt, followed by severe pain.
Swelling occurs over several hours, in contrast
to ligamentous injuries, swelling is immediate.
Meniscal tears may report a clicking or locking
secondary to loose cartilage in the knee but
often have pain only on walking, particularly
going up or down stairs.
Pain along the joint line is 76% sensitive for a
meniscal tear, & audible pop or snap on the
McMurray test is 97% specific.
-------------------------------------------------Patellofemoral pain syndrome is the most
common cause of chronic knee pain in active
adults, women, younger than 45 years.
Exacerbation of the pain by going down steps &
development of knee stiffness & pain at rest
when the knee is flexed for an extended period
of time are clues to the diagnosis.
Reproducing the pain by firmly moving the
patella along the femur confirms the diagnosis.
-------------------------------------------------Patients with pain over the greater trochanter
describe it as hip pain.
Patients with trochanteric bursitis can point
with one finger to the source of the pain on the
lateral hip & actively resisted abduction of the
hip worsens the pain.
Treatment of choice is corticosteroid injection.
-------------------------------------------------Nail pitting suggests psoriatic arthritis, even
in the absence of psoriatic skin lesions.
-------------------------------------------------Oosteoarthritis does not usually occur in the
metacarpophalangeal, wrist, elbow, shoulder, &
ankle joints; except in pseudo-osteoarthritis
--------------------------------------------------

Rheumatoid arthritis & osteoarthritis can both


involve the PIP joints, but MCP joint
involvement occurs in rheumatoid arthritis
DIP joint involvement is characteristic of
osteoarthritis.
-------------------------------------------------A history of joint pain, joint swelling, & fever
are the only findings a/w septic arthritis.
Most have involvement of only one joint.
Hallmark of a septic joint is pain on passive
range of motion in the absence of trauma, &
an infected joint typically appears swollen &
warm with overlying erythema.
-------------------------------------------------Lateral epicondylitis is a clinical diagnosis
based upon localized pain made worse by wrist
extension, point tenderness, & absence of
limited ROM or inflammation of elbow joint.
--------------------------------------------------

Olecranon bursitis, or carpet-layers elbow,


occurs when the olecranon bursa develops an
effusion, either from trauma, inflammatory
process, or infection.
On exam, an inflamed bursa does not cause
restriction or pain with range of motion of the
elbow, evidence that the joint is not involved.
The bursa can be extremely TTP.
-------------------------------------------------Cubital tunnel syndrome, or ulnar nerve
entrapment, is a common cause of pain &
sensory & motor loss in the ulnar region &
paresthesias in the ulnar aspect of the arm &
hand.
Systemic diseases such as end-stage renal
disease may be involved; extrinsic causes such
as ganglion cysts or external pressure are
common as well.
--------------------------------------------------

Lateral epicondylitis, "tennis elbow"


Epicondylitis is caused by microtearing of the
tendons resulting from repetitive motions.
Lateral epicondylitis is the most common cause
of elbow pain.
Tenderness of the lateral epicondyle & pain on
resisted wrist extension & hand gripping.
Treatment consists of ice, NSAIDs, local
steroid injection, & forearm brace or isometric
exercises to strengthen the forearm.
-------------------------------------------------Medial epicondylitis, or golfer's elbow, is less
common.
There is tenderness in the medial epicondyle &
pain with wrist flexion.
--------------------------------------------------