ED'S PATHOLOGY MELTDOWN

Part II -- Systemic Pathology

[This is the second half of my "high-yield facts" for pathology exam
takers. On-line, they are available at
http://www.pathguy.com/meltdown.txt
http://www.pathguy.com/boildown.txt
Since they do not explain the "why"'s, and are unreadable if you are
not familiar with the material, they are worthless to anyone who has
not had classroom or on-the-job pathology experience. As before, you
would be stupid to use these while you are actually trying to learn.
YOU WOULD BE EVEN STUPIDER TO USE THEM AS A SUBSTITUTE FOR YOUR OWN
DOCTOR'S ADVICE. Brackets [] mark stray thoughts added for your
enjoyment, rather than for testability.
If you've used these notes, then drop me an E-mail message
(erf@uhs.edu) and tell me what you think. I claim copyright,
which as far as I'm concerned means you can share these notes freely in
any medium so long as they're never altered, and never sold for a
profit.
THESE NOTES ARE DEDICATED TO MY STUDENTS. EVERYTING THAT I NOW DO
RIGHT AS A TECHER, I'VE LEARNED HOW TO DO FROM THEM. HEALTH AND
FRIENSHIP.
* * *
"Where there is love of medicine, there is love
of humankind."
-- Hippocrates]
I do not teach tumors staging, to emphasize that it's the clinician's
job. If this will be on your exam, grab a good medicine or surgery
book.
"Arteriosclerosis" is a word to avoid. It includes (1)
atherosclerosis; (2) Monckeberg's medial calcific sclerosis; (3)
hyaline arteriolar sclerosis; (4) hyperplastic arteriolar sclerosis;
(5) intimal fibrosis.
Intimal fibrosis: Dense, more-or-less uniform fibrosis of the intima,
narrows the lumens, severity correlates with age and long-term high-
blood pressure; worst in the kidney.
Hyperplastic arteriolar sclerosis: Onion-skinning of the intima,
concentric layers of cells. Typical of scleroderma, hemolytic-uremic
syndrome, malignant hypertension, severe pulmonary hypertension.
Hyaline arteriolar sclerosis: Increased basement membrane in the media.
Typical of prolonged hypertension, prolonged hyperglycemia, old
radiation injury.
Monckeberg's medial calcific sclerosis: Non-disease, with dystrophic
calcification of the media of arteries without compromise of the
lumens. If widespread, loss of arterial compliance raises widens pulse
pressure.
Atherosclerosis is the great epidemic disease; the peak was the late
1960's, and all atherosclerosis-related problems are probably becoming
less common. A stereotyped response of arterial intima to a variety of
injuries. Accumulation of LDL-derived cholesterol-rich debris in
intimal cells, and the resulting tissue reactions. Calcium, if present
at all, is not the problem.
Atherosclerosis causes harm by (1) occluding arteries slowly over time
(angina, ischemic scarring of the myocardium, atherosclerotic dementia,
leg claudication, intestinal angina, watershed infarct of splenic
flexure); (2) occluding arteries suddenly by rupture of plaques
(thrombosis, atheroembolization) or hemorrhages into plaques
(myocardial infarct, atherosclerotic stroke, gangrene of the bowel);
(3) weakening the walls of arteries (atherosclerotic aneurysms).
The causes are mixed. Abnormal LDL's (oxidized-LDL as in smokers and
maybe in iron-overloaded people, glycosylated-LDL as in diabetes, some
variants of lipoprotein A, certain mutations of apolipoprotein E, and
so forth) and LDL processed down the "bad" (non-apoprotein B receptor-
mediated; remember that common familial hypercholesterolemia is a
relative lack of apo-B-receptors) pathway aren't broken down fully in
myointimal cells. Endothelial damage (turbulence, bifurcations, high
pressure, smokers?) is an additional risk. Clotting (good platelet
function, good or hyper-coagulability) places a person at risk. Women
are protected during reproductive life. Eskimos are protected by
dietary omega-three fatty acids, maybe.
You can't do anything about your gender or heredity, but modifiable
risks include, from most to least important (1) high LDL / low HDL-C
(reflect heredity, lack of exercise, nephrotic syndrome,
hypothyroidism, others); (2) cigarette smoking; (3) hypertension; (4)
diabetes; (5) lack of exercise (exercise increases apo-B receptors).
Expect, soon, to see (6) increased blood homocysteine from heredity or
lack of folic acid / B12. I say obesity and stress are not independent
risk factors.
Fatty streaks: Lipid accumulated in myointimal cells. Ubiquitous and
banal.
Fibrous plaques: Cells proliferate, some scar tissue has formed around
the fat deposits, which might have become necrotic by now. As the
surrounding tissue continues to crack and heal, the lesions get
Complicated plaques: (1) plaque ulcerates, and a clot forms; (2) plaque
ulcerates, and debris embolizes; (3) a little vessel hemorrhage into
the plaque, expanding it; (4) plaque blocks flow of nutrients to media,
weakening it.
Leukocytoclastic vasculitis: Type III immune injury of the venules.
Common, often from drugs (haptens), lupus, other immune-complexes.
Palpable purpura.
Polyarteritis and Wegener's: Already covered; don't miss these.
Remember that both feature lesions in various states of development and
healing. Henoch-Schonlein is an IgA-based vasculitis.
Cryoglobulinemia is usually either hepatitis B-antigen and antibody
complexes, or rheumatoid factors; these precipitate in the cold as
immune complex vasculitis.
Temporal arteritis: Granulomatous attack on elastic of branches of
external carotid system. Older folks. Headache worst over temples.
Sudden blindness. Jaw claudication. Most have pain syndrome
"polymyalgia rheumatica". All physical exam and lab findings normal
except for high sedimentation rate. Treat with glucocorticoids.
Takayasu's aortic arch syndrome: thickening of the wall of the arch and
its main branches; most common in young Asian women.
Raynaud's: Most are functional / idiopathic; in CREST-Scleroderma, the
problem is intimal proliferation; rule out ergotism, Takayasu's,
cryoglobulin, Buerger's.
Kawasaki's: Mysterious process affecting kids, often of Japanese
ancestry, following viral illness, ? carpet cleaning. Rash (includes
mucosae, palms and soles), big lymph nodes, coronary vasculitis with
aneurysms the most worrisome feature. Histology looks like
polyarteritis nodosa, with three-layer vasculitis.
Buerger's thromboangiitis obliterans: Young male heavy smokers;
inflamed neurovascular bundles with thrombosis and gangrene.
Mycotic aneurysm: Site where septic arterial embolus has lodged, caused
a secondary infection, and inflamed the wall.
Atherosclerotic aortic aneurysm: Usually distal abdominal aorta.
Tension on wall becomes greater as the aneurysm gets bigger, hence the
accelerated expansion. Embolization, occlusion by thrombus, and/or
rupture.
Syphilitic aortitis: Thoracic aneurysms; stretch-marks are "tree
barking"; compromise of the coronary ostia leads to myocardial
infarction; rupture into airways produces dramatic last moment to life.
Dissecting hematoma ("dissecting aneurysms"): Marfanoids, some Ehlers-
Danlos, copper deficiency, lathyrism folks, or anybody else may have a
rip into a weak layer of the media ("cystic medial necrosis", a
misnomer). Rupture back into the pericardial sac with tamponade.
Successive occlusion of arteries. Widened mediastinum on x-ray.
Venous insufficiency in leg veins: Varicosities (blow out one valve,
the pressure on the next is greater making it likely to blow out, too).
Stasis pigmentation is hemosiderin; stasis ulcers are venous infarcts.
Thrombophlebitis: Blood clot, most common in leg veins. Budd-chiari:
Thrombosis of hepatic veins; think polycythemia vera. Trousseau's
migratory thrombophlebitis: Unexplained venous clots suggest cancer of
the pancreas. Superior vena cava syndrome, from clot or cancer: Dusky
face and upper body, headache. Inferior vena cava syndrome, from clot
or cancer: Dusky lower body, curious collaterals.
Coarctation of the aorta: Common, especially in Turner's. Rib-notching
by collaterals.
Lymphangitis: red streaks, typically strep infection. Lymphedema:
After surgery, or carcinomatosis, lymphogranuloma venereum (wicked
chlamydia in the perineum), or filariasis; Milroy's and Turner's
feature lymphedema as a birth defect. Risk of lymphangiosarcoma. With
epidermal hyperplasia and thickening of the connective tissue:
elephantiasis. In breast cancer, "orange-peel" (peau d'orange) change.
Port-wine stain follows a branch of the trigeminal nerve. Think of
underlying hemangioma of the meninges (Sturge-Weber). Gorbachev's
birthmark.
Pyogenic granuloma: Neither pyogenic nor a granuloma, but a mass of
granulation-tissue. Gums in pregnancy, anyplace else on anybody
("rotten cherry").
Thrombocytopenia from consumption in a large hemangioma: Kasabach-
Merritt syndrome.
Von Hippel-Lindau: Hemangiomas, notably of the retina; renal cell
carcinoma, cerebellar hemangioblastoma. Deletion of a bit of 3p.
Glomangiomas: Painful blue bumps at sites of glomi (coccyx,
fingertips).
Osler-Weber-Rendu: Multiple telangiectasias of the entire GI tract,
with ability to bleed; autosomal dominant.
Kaposi's "sarcoma": Misnamed proliferative response to infection by
herpes 8 / KSHV. Little or no anaplasia; little sprouting vessels;
epidemic in sub-Saharan Africa whether or not HIV is on-board; long a
problem for the immunosuppressed (old men, renal transplant patients,
others).
Cirsoid (racemose) aneurysm: Huge tangle of blood vessels.
Angiosarcoma of the liver: vinyl chloride workers.
"What's a 'double-blind study'? Two pathologists
trying to read an EKG!"
-- Anonymous & baseless
"Once I had brains, and a heart also; so having
tried them both, I should much rather have a
heart."
-- The Tin Woodsman of Oz

Words likely to cause trouble: (1) angina: chest-pain due to cardiac

ischemia, in the absence of infarction; (2) stable angina: from narrow
coronaries, i.e., when I climb stairs or walk against the wind, it
hurts like this (fist sign); (3) Prinzmetal's angina: from spasm of the
coronary arteries; (4) unstable angina: as when a thrombus on top of a
plaque is forming, then lysing, then forming, then lysing; (5) forward
failure: congestive heart failure considered as a vicious cycle
involving salt retention, volume overload, and the inability to perfuse
the kidneys; (6) backwards failure: congestive heart failure considered
as a vicious cycle involving increased venous hydrostatic pressure and
total-body salt and water overload; (7) contraction band:
hypereosinophilic stripe crossing a freshly-dead myocardial cell, where
the calcium got and clamped the sarcomeres; (8) sudden cardiac death:
dropping over dead all-of-a-sudden from some heart-cause, most often
ischemia without infarction, and with or without a fresh lesion in the
coronaries; (9) syndrome X: an angina syndrome caused by failure of the
small vessels to dilate appropriately, most typical in ill-controlled
diabetics.
Aerobic athletes get hypertrophy of the myocardium, which is good.
Also increased mitochondria, increased vascular collaterals (little
vessels develop). Good for helping you survive an infarct and/or avoid
ischemia if something happens to your vessels. Plus, sports are fun.
Unless you have septal hypertrophy / hypertrophic cardiomyopathy, or
your coronary arteries are ruined by atherosclerosis already, or
something else really unusual, aerobic exercise is good for you.
Heart failure: Cannot pump enough blood. Tends to be a vicious cycle,
with ischemic damage to the ventricle and/or alteration in its shape
(i.e., stretched) so as to make pumping inefficient.
Except in pure mitral stenosis or amyloidosis, the failing left
ventricle will be hypertrophic.
THE COMMON CUASES OF LEFT-SIDED FAILURE
Ischemia (myocardial infarct, ischemic muscle disease)
Aortic or mitral valve disease
Systemic hypertension
Myocardial disease
THE COMMON EFFECTS OF LEFT-SIDED FAILURE
-- Dyspnea (from pulmonary edema and total-body hypoxia)
First, on exertion
Later, PAROXYAMSL NOCTURNAL DYSPNEA ("cardiac dyspnea"); on
lying down for a while, fluid redistributes itself in the
body, resulting in pulmonary edema; patients may throw the
windows open at night, or learn to sleep on various numbers
of pillows; you the physician will hear rales; the
pathologist may see "brown induration" and hemosiderin-laden
"heart failure" macrophages; remember these?)
-- Cough ("from the left atrium pushing on the bronchus"; this is
common in mitral valve disease even in the absence of failure;
why?)
-- Prerenal azotemia
-- Hypoxic encephalopathy
-- Sodium overload and systemic dependent edema (from hypoperfused
kidneys)
HIGH-OUTPUT FAILURE is a special situation, glossed-over by "Big
Robbins", in which the heart fails because it must pump an excessive
among of blood. The causes
Anemia
Hyperthyroidism
High fever
Shunts between an artery and a vein
Beriberi (arterioles open)
Paget's disease of bone (abnormal bone vasculature)
Iatrogenic (i.e., shunts in dialysis)
THE COMMON CAUSES OF RIGHT-SIDED FAILURE
Pulmonary emboli (acute or chronic)
Any disease interfering with lung ventilation
Emphysema
Cystic fibrosis
Most other bad, diffuse lung diseases
NOTE: The mechanism, of course, is increased pulmonary
vascular resistance due to fibrosis and/or the hypoxic
vascular response
Left-sided heart failure!
Cardiac defects with left-to-right shunts (why?)
Tamponade (some definitions)
THE EFFECTS OF RIGHT-SIDED FAILURE
 Splanchnic congestion (you'll feel big livers & spleens; check for
"hepatojugular reflux")
Jugular venous distention (look carefully)
Total-body dependent edema (from increased venous hydrostatic
pressure, etc.)
Effusions (transudates, of course; notably pleural, notably more
on the right side than on the left; why?)
NOTE: You'll never see "cardiac cirrhosis" except in prolonged
severe tricuspid insufficiency.
Atherosclerosis in the coronaries can produce (1) sudden death
(ischemia makes ectopic foci arise); (2) infarct leading to sudden
death, rupture, mural thrombus, pericarditis, cardiogenic shock (>40%
of the muscle); (3) angina (stable, unstable). Infarcts can be due to
rupture of a plaque with thrombosis, embolization to a coronary, or
rupture of a small vessel into a plaque. Pathologists will diagnose
sudden cardiac death in somebody who drops over dead and turns out to
have bad coronary atherosclerosis. Tobacco and cocaine render the
heart much more prone to die.
Subendocardial infarcts arise in a setting of coronary ischemia,
generally in systemic hypotension / shock /congestive heart failure.
The subendocardium is farthest from the oxygen, so it dies first. This
in turn hurts cardiac function.
Remember cocaine, Prinzmetal's, lupus, rheumatoid vasculitis,
polyarteritis nodosa, embolization (i.e., endocarditis), dissecting
hematoma, and syphilis as the other causes of myocardial infarction.
For some reason that I cannot explain, exam-writers often want you to
be able to date myocardial infarcts.
0-30 minutes Wavy fibers at the edges, loss of glycogen from
cytoplasm.
1- 2 hours Mitochondrial calcium, maybe contraction bands,
maybe hydropic changes, maybe even a little fatty
change.
4-12 hours Earliest nuclear changes, polys appear
8-24 hours First gross changes, i.e., pallor; good coagulation
necrosis; often good contraction bands
24-72 hours Road-kill, lots of polys, fibers very dead; infarct
feels soft and looks pale and yellowish (why?)
3- 7 days Macrophages, granulation tissue starts at rim;
grossly you see the red granulation tissue around
the infarct; wall is at its weakest, and this is
time for rupture.
10 days Nice granulation tissue; cleanup team may be
removing the dead fibers, or they may persist for
weeks
7 weeks Nice scar.

More words that can cause trouble: (1) atresia: the hole never opened;
(2) clubbing: curious change of the tips of the digits, from cyanosis
from any cause, and from other causes; (3) concentric hypertrophy:
common hypertrophy of the left ventricle, as in an athlete,
hypertensive, or aortic-valve disease patient; (4) congenital heart
disease: malformations at or around birth; (5) cor triloculare
biatriatum: no ventricular septum; (6) cyanotic congenital heart
disease ("blue baby"): right-to-left shunt present at birth; (7)
dilatation: the ventricle just can't empty fast enough, and ends up
getting badly stretched; (8) Eisenmenger's syndrome: shunt reversal
(left-to-right becomes right-to-left from increased resistance in
damaged pulmonary arterial system; (9) endocarditis: non-ischemic
damage to the endocardium sufficient to allow a fibrin mass to form;
(10) pressure overload: the effect of vascular fluid overload and/or
excess systemic vasoconstriction and/or an over-dynamic left ventricle,
detrimental to the heart's function; (11) jet lesion: hyperplastic
endocardium, i.e., little white ridges, where a jet of blood (flowing
abnormally) strikes against it; (12) late cyanosis: Eisenmenger's; (13)
paradoxical embolus: passes through the foramen ovale from the right
atrium to the left atrium, or by some other route from the systemic
venous to the systemic arterial circulation; (14): polycythemia: too-
high hematocrit, enough to make the blood overly viscous; (15)
hypertensive heart disease: the effects of pressure overload and maybe-
more, in severe or longstanding high blood pressure; (16) reperfusion
injury: calcium and oxygen damage ischemic myocardium when blood flow
is restored.
Jugular venous pulse: "A"-wave is atrial contraction; "C" wave is from
the ventricle contracting and pushing blood back up out of the atria;
"V" wave is the atrium filling before the tricuspid valve opens. "X"
wave is the dip during early systole (i.e., tricuspid valve is sinking
down), "Y" wave is the dip during diastole (i.e., the ventricle is
filling).
A couch potato's heart should not weight more than 350 gm, less for
little folks. Left ventricle should not be more than 1.5 cm thick,
right ventricle not more than 0.5 cm thick.
Hypertensive's heart exhibits big, thick fibers with large boxcar
nuclei (heart muscle cells are ordinarily tetraploid; they may increase
to 8-ploid or more). In congestive failure secondary to hypertensive
disease, the blood pressure will return to normal, confusing the
clinicians.
Cor pulmonale: Right ventricular hypertrophy/dilatation/failure from
lung disease (i.e., narrowed vessels and/or congenital malformations
and/or pulmonary emboli). The strained right ventricle is very prone
to develop rhythm disturbances, and I have no problem signing out a
sudden death in such a person as due to cor pulmonale.
6-8 kids per 1000 have congenital heart disease. Down's: endocardial
cushion defects (i.e., low-atrial and/or high-ventricular septal
defect). Cyanosis: 5 gm/dL or more of unoxygenated hemoglobin in the
arteries. Remember right-to-left shunts (i.e., cyanotic shunts) tend
to produce polycythemia, with extra viscosity that doesn't help
matters; bacteria can go straight to the brain without being filtered
through the lungs, and paradoxical embolization is commonplace.
Tetralogy: Overriding aorta, stenotic pulmonary artery and/or valve,
hypertrophic right ventricle, ventricular septal defect. Shoe-shaped
heart on x-ray. Infected pulmonic valves. The common right-to-left
shunt at birth.
Uncorrected transposition, the blood flow is:
right atrium --> right ventricle --> aorta
left atrium --> left ventricle --> pulmonary artery
To survive the first minute of life, there must be an atrial and/or
ventricular septal defect. Right-to-left shunt.
CORRECTED TRANSPOSITION, the atria are rearranged, so that the blood
flow is:
right atrium --> left ventricle --> pulmonary artery
left atrium --> right ventricle --> aorta
The problem is that the mitral and tricuspid valves are malformed.
The other causes of congenital right-to-left shunt are truncus
arteriosus (i.e., aorta and pulmonary artery are the same vessel; this
will eventually cause bad pulmonary hypertensive damage), total-
anomalous pulmonary venous return (i.e., all to the right atrium), and
tricuspid atresia.
Half of VSD's ("Roger's disease") close by themselves. Otherwise, it's
surgery time.
Atrial septal defects: Most are ostium secundum (i.e., patent foramen
ovale); some are sinus venosus defects near the superior vena cava;
some are ostium primum defects at the crux of the heart (think of
Down's). Lutembacher's: atrial septal defect plus mitral stenosis,
i.e., left-to-right shunt is especially bad. Atrial septal defects are
often trivial, and even the bad ones may not make much noise during
childhood; beware fixed-splitting of the second heart sound.
Patent ductus arteriosus: Fails to close (try using a prostaglandin
antagonist). Machinery murmur, easy surgery.
The three principal left-to-right shunts: (1) ventricular septal
defect; (2) atrial septal defect, and (3) patent ductus arteriosus.
Congenital bicuspid aortic valve is a common (maybe 1%) of folks. It
tends to calcify in old age, producing stenosis. Congenital aortic
stenosis: Valve is a fibrous ring, or there's a fibrous ring below the
valve (subvalvular) or above it (supravalvular).
Aortic stenosis from any cause, including septal hypertrophy
(hypertrophic cardiomyopathy) is bad; one reason is the propensity to
cause sudden death by coronary insufficiency (Bernoulli's principle
sucks blood out of the coronaries; shortening of diastole limits time
for coronary filling).
Problem terms: (1) Anitschkow cell: cell of unknown nature, looks like
a muscle cell, stains like a macrophage, bears a caterpillar pattern of
heterochromatin in its long nucleus, typical of rheumatic fever;
(2) Aschoff body: an inflamed area in rheumatic fever, rich in
Anitschkow cells and fibrinoid; (3) antihyaluronidase: antibody against
strep, marker for recent strep infection; (4) antistreptolysin O
("ASO"): antibody against strep, marker for recent strep infection;
(5) Barlow's syndrome: extremely common sub-disease of the mitral
valve, "floppy valve", "prolapsing valve"; (6) caterpillar cell:
anitschkow cell of rheumatic fever; (7) dextrocardia with situs
inversus: backwards organs, including a usually well-formed heart; (8)
dextrocardia, isolated: heart positioned backwards, often with other
malformations; (9) erythema marginatum: snake-like red wandering
lesions of acute rheumatic fever; (10): friable: crumbly; (11):
Kartagener's syndrome: immotile cilia producing sinusitis,
bronchiectasis, and situs inversus; (12) lines of closure: where the
valve leaflets bump up against each others, the site where rheumatic
fever lesions begin; (13): McCallum's patches: white geographic patches
on the left atrium; (14): mid-systolic click: the sound of the Barlow
floppy-valve snapping tight like a sail; (15) regurgitation: same as
insufficiency, backflow through a valve that did not close; (16) Roth
spots: on the retina, where septic emboli have been caught in the
branches of arteries; (17) situs inversus totalis: all organs
backwards; (18): splinter hemorrhages: the familiar lines under the
fingernails, seen in keyboard users, patients with endocarditis, or
anybody else; (19); Sydenham's chorea / St. Vitus's dance: movement
disorder when rheumatic fever involves basal ganglia; (20) tamponade:
increased pressure in the pericardial sac prevents venous return; (21)
valvular stenosis: the valve failed to open when it should; (22)
vegetations: masses of fibrin plus perhaps something else, on the
endocardium, usually of the heart; (23) opening snap: as in mitral or
tricuspid insufficiency, with thickened valves making the snap.
MITRAL STENOSIS
Old rheumatic fever
(All other causes are uncommon)
MITRAL REGURGITATION
Old rheumatic fever
Bacterial endocarditis
Barlow's syndrome
Other birth defects at the crux
Ruptured papillary muscle (MI)
Ruptured chorda (bacterial endocarditis, Barlow's)
Dilated annulus (left CHF)
Calcified mitral annulus (maybe)
AORTIC STENOSIS
Old rheumatic fever
Congenital bicuspid valve that calcified
Normal valve that calcified
Birth defects (valvular, sub-valvular)
NOTE: Some of the biggest hearts in clinical medicine result from
aortic stenosis. Obviously, the pulse pressure is narrowed, and
systole is prolonged. This can have very bad consequences for
myocardial perfusion.
NOTE: As I trust you've figured out, "aortic stenosis" (by custom)
refers to stenosis of the valve, not the aorta. If a portion of
the aorta is stenotic, it's called "coarctation". If the entire
aorta is stenotic, you didn't get born.
AORTIC REGURGITATION
Old rheumatic fever
Bacterial endocarditis
Syphilis
Dissecting hematoma / steering wheel injury
Marfan's
The ring dilates
Rheumatoid arthritis
Ankylosing spondylitis / HLA-B27 family
Syphilis
NOTE: You'll learn about increased pulse pressure, "Corrigan's
 jumping pulse", pistol-shot sign, etc., etc. on rotations.
TRICUSPID STENOSIS
Old rheumatic fever
Carcinoid heart disease
TRICUSPID REGURGITATION
Old rheumatic fever
Carcinoid heart disease
Bacterial endocarditis (ask about IV drug use!)
Loeffler's
Dilated annulus (right CHF)
NOTE: Look for those jumping neck veins!
PULMONIC STENOSIS
Tetralogy of Fallot
Carcinoid heart disease
Congenital ("funnel")
PULMONIC INSUFFICIENCY
Dilated annulus (right CHF). Rare.
Vegetations......
ACUTE RHEUMATIC FEVEER
Small, warty, sterile, on the lines of closure
Seldom embolize
BACTERIAL ENDOCARDITIS
Often large, loaded with bacteria
Find them on any deformed intracardiac surface
Very prone to embolize
NON-BACTERIAL THROMBOTIDC ("MARANTIC") ENDOCARDITIS
Small, sterile, on the lines of closure
May embolize
LIBMAN-SACKS ENDOCARDITIS OF LUPUS
Any size, sterile, on either surface of the leaflet
May embolize
As with any intracardiac lesion involving turbulence, deformed valves
are prone to develop bacterial endocarditis.
Calcific aortic stenosis: While bicuspid valves are notorious for
calcifying later in life, sometimes a normal, tricuspid valve
accumulates calcium-rich excrescences in its cusps. These can
interfere with the valve opening, and can block the coronary ostia.
The latter is very serious.
{ 3560} calcified tricuspid aortic valve
{ 6461} calcified tricuspid aortic valve

The four complications of "Barlow's" elongated posterior mitral valve

leaflet sub-disease: (1) bacterial endocarditis; (2) mitral
insufficiency (notably if that chorda ruptures); (3) rhythm
disturbances (notably paroxysmal atrial tachycardia, nobody knows why);
(4) cardiac neurosis. Marfans and marfanoids (Sticklers, xyy's, some Ehlers-
Danlos, just-tall-and-slim, others) tend to have Barlow's.
Rheumatic fever follows strep throat particularly in poor kids; note no
bugs in the lesions. Molecular mimicry: the antibody against M-protein
cross-reacts with tissue; of course this is not the whole story, but
the rest is unknown. Rheumatic fever is an important disease, and a test-
writer's favorite. Look for:
Evidence of carditis (i.e., pericardial pain, enlarged heart,
murmurs, failure); rheumatic fever features a pancarditis (all 3
layers).
Polyarthritis
Sydenham's chorea (St. Vitus's dance), from involvement of the
basal ganglia. This is a big deal right now. Mediated by
antibodies that cross-react with neurons (type II immune injury)
Erythema marginatum, a snake-like red skin eruption
Subcutaneous nodules, little masses of fibrinoid with granulomas
around them, over the bony bumps on arms and legs.
Fever
Lab evidence of recent strep infection (i.e., a high anti-
streptolysin O and/or anti-hyaluronidase and/or anti-DNAse titer,
a culture result, or whatever)
Here are the Jones criteria for making the diagnosis. You need one
major and two minor, or two majors).
Major: Polyarthritis; carditis; chorea; subcutaneous nodules;
erythema marginatum.
Minor: Arthralgia; fever; preceding group A strep infection;
preceding bout of rheumatic fever; elevated sed rate; prolonged PR
interval on EKG.
When the verrucae spread and organize, they may cause regurgitation
(i.e., the valve leaflets scar up, and scar contracts) and/or stenosis
(i.e., the verrucae stick together, joining leaflets before they scar
up.) Valves involved: mitral most often, aortic next, tricuspid next;
pulmonic seldom.
Bacterial endocarditis arises in several typical settings: (1) low-
virulence (green viridans after the dentist, enterococcus after a trip
to the urologist or proctologist) strep infecting a rheumatic valve or
some other site of bad turbulence; (2) virulent strep involving a
normal valve (bad luck, "acute bacterial endocarditis"); (3) something
horrid on the right side of a drug-infecter's heart; (4) low-virulence
staph or fungi on a prosthetic valve. Neutrophils aren't much use in
cleaning up infected fibrin bits on the endocardium, since it's
avascular and the blood is flowing too fast to allow margination. Once
the infection is set up, the foul breakdown products of these bacteria
are going to make a person systemically sick. Fever, arthritis, the
acute phase reaction, anemic of chronic disease, diffuse proliferative
glomerulonephritis, evidence of B-cell hyper-activation (rheumatoid
factor, cryoglobulins, false-positive syphilis test), clubbing, etc.,
etc., are prone to supervene. Embolization / immune complex injury
produces Osler's nodes (sore finger pulp), Janeway's flat red lesions
on palms (painless), Roth spots, splinter hemorrhages (the latter at
least in books; do you believe it?), as well as abscesses wherever they
land.
Nonbacterial thrombotic endocarditis ("marantic endocarditis") is
little fibrin things on the valve leaflets of those with
hypercoagulable blood and profound disability. Nobody understands it;
it's almost the norm in fatal cancer of the pancreas.
Carcinoid tumors release their foul products into the bloodstream,
causing the familiar syndrome, and endocardial fibrosis of the right
side of the heart only. (Neuropeptide K and substance P are the
fibrogenic ones; serotonin and bradykinin get blamed for the wheezing,
flushing, and diarrhea.)
More words to remember: (1) adriamycin / daunorubicin / the
anthracyclines: "the red death", a red-colored cancer chemotherapeutic
agent that is a notable heart muscle poison; (2) cardiomyopathy: non-
ischemic disease of the heart muscle itself; daunorubicin; (3)
myocarditis: autoimmune (rheumatic fever, post-coxsackie) or infectious
(i.e., Chagas, toxoplasmosis, coxsackie A & B, diphtheria toxin).
Cardiomyopathies: (1) restrictive (stiff heart, i.e. amyloidosis); (2)
muscle-bound heart (i.e., hypertrophic cardiomyopathy); (3) flabby
heart (i.e., all the others; this includes really bad hemochromatosis
and Pompe's glycogenesis in which the heart might also be sort of
stiff).
Dilated cardiomyopathy features a big, baggy, weak heart, typically
with mural thrombi.
Alcoholic cardiomyopathy: some effect from alcohol (i.e., in the
alcoholic with other wasted muscles); beriberi and cobalt (only in
Quebec, and only in the past, from cobalt added to make a better head).
Reggie Lewis's disease: Hypertrophic cardiomyopathy features disarray
of the myocardial fiber arrangement, irregular bulges of muscle in
these areas, typically occluding the outflow tract, and some vascular
intimal fibrosis. "Asymmetric septal hypertrophy" / "idiopathic
hypertrophic subaortic stenosis" / "obstructive hypertrophic
cardiomyopathy": the classic hypertrophic cardiomyopathy in which the
septum is primarily involved. Don't build your heart up with aerobics
if you've got this. The murmur becomes less upon maneuvers to increase
left ventricular volume ("knee bends"), louder if decreased
("valsalva"), in contrast to other causes of aortic stenosis. Genes
include the beta-myosin chain.
Endomyocardial fibroelastosis: fibrosis of the endocardium, with
stiffening. Common in kids in sub-Saharan Africa. Loeffler's
endocarditis features fibrosis and eosinophils.
Cocaine heart: (1) coronary vasospasm; (2) muscle fiber necrosis; (3)
super-sensitized to the effects of catecholamines, thus prone to rhythm
disturbances.
Hemopericardium: ruptured MI, penetrating injury, and backwards rupture
of an aortic dissection
To get tamponade, you need about 150 mL of fluid accumulating almost
instantaneously, or more if it's prolonged. Look for Kussmaul's sign
(neck veins pop out when inspiration causes additional tightening of
the pericardium), exaggerated inspiratory drop in blood pressure
(ditto).
Fibrinous pericarditis: myocardial infarction, uremia, radiation,
lupus, rheumatic fever and trauma as the causes of fibrinous
pericarditis. Autoimmune pericarditis after MI: Dressler's. Coxsackie
B. Friction rub, bread-and-butter look (actually, a pulled-apart
ketchup sandwich).
Atrial myxomas ("wrecking balls"), the only common primary tumors of
the heart. Left atrium, attached to septum. Cardiac rhabdomyoma: a
hamartoma in tuberous sclerosis.
Say "REE-nin", not "RENN-in", when talking about that important hormone
from human physiology. Rennin is from a calf's stomach and you use it
to make cheese.
"It's not the cough
That carries you off,
It's the coffin
They carry you off in."
-- Ogden Nash
Chest wall problems
structural THE CHEST DEFORMITIES
neuromuscular THE PARALYSIS & WEAKNESS SYNDROMES
Obstructed upper airway
structural QUINSY ("PERITONSILLAR ABSCESS")
CROUP ("LTB"")
functional THE SLEEP APNEAS
Obstructed large bronchi
all, subtotal CHRONIC BRONCHITIS
one, total OBSTRUCTIVE ATELECTASIS
ENDOGENOUS LIPID PNEUMONIA
Constricted small bronchi
mast-cell mediated THE ASTHMAS
platelet-mediated PULMONARY EMBOLUS
apudoma products CARCINOID SYNDROME
Fibrotic respiratory bronchioles SILICOSIS
Collapsed respiratory bronchioles EMPHYSEMA/"CHRONIC BRONCHITIS"
Fluid-filled alveolar spaces
transudate ALVEOLAR PULMONARY EDEMA
exudate & pus THE PNEUMONIAS
exudate, fibrin, debris THE RESPIRATORY DISTRESS SYNDROMES
surfactant ALVEOLAR LIPOPROTEINOSIS
ENDOGENOUS LIPID PNEUMONIAS
other lipid EXOGENOUS LIPID PNEUMONIAS
blood GOODPASTURE'S DISEASE
WEGENER'S GRANULOMATOSIS
OTHER PULMONARY BLEED SYNDROMES
organisms alone PNEUMOCYSTOSIS, CRYPTOCOCCOSIS
Fluid-filled alveolar septa
transudate INTERSTITIAL PULMONARY EDEMA
exudate THE PNEUMONITIS FAMILY
(VIRUSES, MYCOPLASMA)
Fibrosis around ulcerated bronchi BRONCHIECTASIS
Fibrosis of alveolar septa
slow THE INTERSTITIAL RESTRICTIVE LUNG
DISEASES
(Hamman-Rich, rheumatoid lung,
sarcoid, asbestosis, many
others)
fast THE RESPIRATORY DISTRESS SYNDROMES
Collapsed alveoli
extrapulmonary disease COMPRESSIVE ATELECTASIS
large-airway disease OBSTRUCTIVE ATELECTASIS
alveolar disease THE RESPIRATORY DISTRESS SYNDROMES
ischemia PULMONARY EMBOLUS, SEVERE SHOCK
Necrotic lung ("cavities", etc.)
infarction PULMONARY EMBOLUS (COMPLICATED)
suppurative NECROTIZING PNEUMONIAS
LUNG ABSCESS
caseous TUBERCULOSIS, HISTOPLASMOSIS,
BLASTOMYCOSIS, COCCIDIOIDOMYCOSIS
weird immune WEGENER'S GRANULOMATOSIS
malignant LUNG CANCER
Pulmonary hypertension
2ø to low alveolar oxygen see above; also MOUNTAIN DWELLERS
2ø to alveolar fibrosis see above
primary PULMONARY EMBOLUS
VASCULITIS
IDIOPATHIC
High pCO2 all whole-lung ventilation problems
Low PO2 all whole-lung ventilation problems
perfusing non-ventilated lung
fluid/fibrosis in alveolar septa
MOUNTAIN DWELLERS
Blood pCO2 is almost entirely a function of adequacy of ventilation.
Blood pO2 is a function of adequacy of ventilation, ventilation-
perfusion matching, inspired oxygen content, right-to-left shunting,
nad the thickness of the alveolar wall (extra collagen, fibrin, edema,
hyperplastic cells).
Pulmonary edema is due to (1) increased pulmonary venous hydrostatic
pressure, i.e., left CHF; (2) plugged lymphatics (i.e., cancer); (3)
excess water on board (kidney failure, iatrogenic); (4) low serum
albumin (i.e., nephrotic syndrome, cirrhosis, kwashiorkor); (5)
inflamed alveolar septa (i.e., pneumonitis). Less well understood: (6)
opiate overdose; (7) altitude sickness; (8) acute brain injury.
Edema may be confined in the septa (interstitial edema, creating an
alveolar-capillary oxygen block) or eventually spill out into the
alveoli (alveolar edema, when you'll hear the rales).
Pulmonary congestion results from increased venous hydrostatic
pressure, i.e., left CHF. The little capillaries are prone to break
from time to time, creating little accumulations of hemosiderin-laden
macrophages, and perhaps eventually some fibrosis.
Pulmonary thromboemboli need no description here; most come from leg
veins and hence bear valve markings. They cause problems by
(1) limiting the amount of effective lung tissue available for gas
exchange; (2) sudden increases in pulmonary vascular resistance make
the right ventricle unhappy; (3) platelets release serotonin, a
bronchoconstrictor which makes folks wheezy; (4) if bronchial
circulation is inadequate, i.e., you are in shock or heart failure, you
may infarct some of your lung, get a pleural friction rub, and
generally be miserable. Saddle embolus: Instant death.
Any cause of increased resting blood flow through the lungs (i.e.,
left-to-right shunts), any cause of generalized alveolar hypoxia (i.e.,
via the hypoxic vascular response), and any cause of pulmonary alveolar
fibrosis will eventually lead to the vicious cycle of damaged vessels,
narrowed vessels (i.e., increased vascular resistance), and increased
pulmonary blood pressure. Pulmonary vascular resistance is the factor
that tends to be most limiting on quality of life.
Adult respiratory distress syndrome (ARDS, diffuse alveolar damage,
many other synonyms) means the small lung vessels have leaked fibrin.
The fibrin coats the alveolar spaces ("hyaline membranes"), debris and
dead junk accumulate, the dead type I pneumocytes are replaced by big
type II pneumocytes which aren't very permeable to oxygen and which,
while healing, aren't going to make surfactant, causing widespread
atelectasis. The fibrin membranes are likely to turn into scar, and
that's the end of the lung. Causes include sepsis (most common),
aspiration, severe wounds elsewhere, radiation, burns, viruses, drug
toxicity, and many others, including oxygen therapy itself. Silo-
filler's disease: nitric oxide.
Neonatal respiratory distress results mostly from damage caused by
breathing, to immature lungs. Replacing the surfactant helps, but is
not curative, and if the primary problem was lack of surfactant, then
the problem would be most severe right after birth; in reality it takes
several hours. Again, the hyaline membranes are made of fibrin.
Surviving kids may have fibrosis ("bronchopulmonary dysplasia") and it
may not be possible to get them off the ventilator.
Atelectasis means collapsed alveoli, from airway obstruction (i.e.,
something in the big airway), compression (i.e., something filling the
pleura, or you not taking a deep breath), and/or lack of surfactant
(ischemia from pulmonary embolus, diffuse alveolar damage, hyaline
membrane disease, etc.)

"Sudden infant death syndrome", a mysterious process by which a child,

age 1 month to 1 year, simply dies, probably exists. It's now clear
that many of these result from the baby falling asleep face-down on the
mattress and smothering. It's also painfully clear that many, if not
most, of the rest are the result of negligence or worse by caregivers.
Supporting this politically-incorrect conclusion are these facts:
(1) SIDS is largely an underclass problem; (2) SIDS incidence increases
tremendously if a parent is under the purview of the criminal justice
system; (3) SIDS incidence increases dramatically between 5 PM on
Friday and 8 AM on Monday; (4) when one identical twin dies of SIDS,
it's almost the rule that the other one dies at the same time;
(5) crime-scene examinations, if properly performed, eliminate the
"mystery" in many cases; (6) Waneta E. Hoyte, the mother whose "tragic
story" spawned the whole apnea monitor racket, confessed in 1994 that
she smothered her five children because their crying made her feel
helpless. To cover your butt, you still have to prescribe an apnea
monitor even though evidence that they've ever saved any lives is very
dubious.
Before you sign out a "SIDS" death, be sure you've ruled out ectodermal
dysplasia (i.e., no sweat glands), botulism (i.e., ate raw honey),
seizures (got Arnold-Chiari by any chance?), and lots else.
Emphysema and chronic bronchitis are only artificially separated. The
fundamental problem in each is loss of elasticity of the alveoli,
causing the respiratory bronchioles to collapse on expiration. Smoking
inhibits alpha-1-antitrypsin, enhances elastase function, and draws
neutrophils to the area to do damage. Emphysema from smoking tends to
be centrilobular, since smoke accumulates where the wind slows down.
If you are alpha-1-antitrypsin deficient, the emphysema tends to be
panacinar.
The pink puffer has a strong hypercarbic respiratory drive, and works
hard to breathe; since he's also going to be keeping his airway clear,
his "chronic bronchitis" will be less noticeable. Puffers have an
attitude, stay slim from the work of breathing, and get diagnosed with
"emphysema".
The blue bloater has lost his hypercarbic respiratory drive, and is now
mercifully on hypoxic drive. He coughs, but not effectively enough to
clear his secretions, so the doctor hears his airway crud gurgling and
diagnoses "chronic bronchitis". Since these folks aren't working hard
to breathe, and can't do much physical, they get fat. Hypercarbia-
acidosis makes them mellow.
The classic definition of emphysema as "an abnormal, permanent
dilatation of part of all of the acinus, with destruction of alveolar
walls" reflects the rather advanced disease; eventually, anything
that's going to kill off the elastic tissue kills the whole of the
septa. They are hyperinflated because puffers and bloaters learn to
keep their chest expanded to keep their respiratory bronchioles open.
Other tricks include breathing against pursed lips. "Bullous
emphysema" / "blebs" result from the lung collapsing under its own
weight, leaving huge empty sacks which the surgeon can remove; blebs
can rupture, causing pneumothorax.
"Chronic bronchitis" is pretty much a synonym for smokers' cough or the
equivalent from other processes. Reid Index is the percent of the
thickness of the lamina propria occupied by glands. The process is
often superinfected, especially by pneumococcus and H. flu.
Bronchial asthma results from chronically inflamed small bronchi, which
are rendered twitchy and prone to episodes of constriction. Extrinsic
(allergic) asthma is typical in kids, who tend to outgrow it, and in
workers exposed to allergens. There's likely to be lots of
eosinophils. Intrinsic asthma is havoc played by leukotrienes,
especially after taking aspirin; this is poorly understood, and
patients tend to have nasal polyps. Curschmann's spirals in the
sputum; mucus plugging as the principal autopsy finding. Charcot-
Leyden crystals are eosinophil protein debris, long red lozenge-shapes.
"All that wheezes is not asthma." Wheezing may also result from:
-- foreign body or tumor in the upper airway
-- pulmonary edema (especially left-sided congestive heart
failure)
-- pulmonary embolus
-- chronic bronchitis
-- carcinoid syndrome

Bronchiectasis: non-healing ulcers of the bronchi; massive sputum

production, bad breath, continuing expansion due to scar contraction;
increased dead space. Think of cystic fibrosis, Kartagener's,
neglected TB, or after whooping cough.
Bronchopneumonia: inflammatory exudate in the alveolar spaces,
distributed in patches usually in several loves. Think of relatively
low-virulence bacteria.
Why sick people get bronchopneumonia:
-- Many of them don't cough and clear their lungs like they should
because of medications, old age, physical weakness, pulmonary
fibrosis, other disease, or whatever;
-- Many of them have poor mucociliary elevator function from smoking,
infection, other disease, or whatever;
-- Many of them have poor alveolar macrophage function from smoking,
oxygen therapy, alcoholism, or whatever;
-- Pulmonary edema from whatever cause is a great culture medium;
-- Glop in the lungs (cystic fibrosis, airway obstruction, "chronic
bronchitis", etc., etc.) helps get the lungs infected.
Special bronchopneumonias:
-- Staphylococcus: Complicating influenza, may get toxic shock
-- Streptococcus B: newborns
-- Gram negative rods: nosocomial, or after GI tract surgery
(remember that the meanest bugs are the ones that live in the
hospital)
-- Anaerobic pneumonia: alcoholics with bad (but still present) teeth
Lobar pneumonia: Inflammatory exudate filling a single lobe, i.e., the
germs are aggressive and will stop only at the interlobar fissues.
Think pneumococcus, Friedlander's Klebsiella, others. Stages: (1)
"Congestion" (i.e., edema); (2) red hepatization (i.e., bloody and
fibrinous; (3) gray hepatization (i.e., the red cells have lysed but
the fibrin is still there; (4) resolution (you hope).
Pneumonitis: Inflammatory exudate confined to the interstitium. Think
of a virus or mycoplasma.
The pneumonias (bronchopneumonia, lobar pneumonia) kill by (1) taking
up alveolar space, and (2) more importantly, diverting blood through
unventilated areas.
Lung abscess: Aspiration of bugs from a dirty mouth, necrotizing
pneumonia (staph, klebsiella, pseudomonas, legionella), obstructed
airway behind a cancer, infected cancer, septic embolus (infection, dope-
shooter), infarcting a pneumonia. Lung abscess can seed systemically.
Pulmonary fibrosis: A family of diseases with collagen laid down in the
alveolar walls, leading to obliteration. Idiopathic form is "Hamman-
Rich". Others worth remembering: Rheumatoid arthritis, scleroderma,
asbestosis, berylliosis, bad farmer's lung, histiocytosis X, bleomycin,
cyclophosphamide, amiodarone, busulfan, paraquat, sarcoidosis,
"Restrictive lung disease": It's hard to get the air in, range is from
the fibrosis family to pleural effusions to boa constrictors.
"Obstructive lung disease": It's hard to get the air out, i.e.,
emphysema, asthma, maybe bronchiectasis.
Sarcoidosis: Mysterious proliferation of non-caseating granulomas.
Pulmonary alveolar obliteration, lupus pernio on the skin, anergy,
increased angiotensin-converting enzyme, hypercalcemia from vitamin D
overactivation. T4 cells leave blood and go to tissue, making for a
peripheral blood picture like AIDS. Don't ask for a Kveim test.
Goodpasture's: Autoantibody against basement membrane of lung and
kidney, with hemoptysis and rapidly-progressive glomerulonephritis.
Treat with plasmapheresis, removing the harmful antibody.
Eosinophilic pneumonia may be idiopathic (Loeffler's), parasite larvae
migrans.
Aspergillus lung infections: Fungus balls, superinfecting asthma,
others.
Endogenous lipid pneumonia: Obstruction of an airway gives surfactant
accumulation, typically in macrophages; common behind tumors.
Exogenous lipid pneumonia: Oil down the airway, mineral oil can kill
you, vegetable oil is worse, animal (cod-liver-oil) killed children in
bygone eras; lipid-laden macrophages. Alveolar lipoproteinosis:
idiopathic, or acute silicosis; the lung fills with surfactant-rich
junk, patients cough up jello.
Lung (i.e., bronchogenic) cancer is finally decreasing in incidence
among men, still increasing among women, as smoking becomes a teenaged
girl's vice. Other risk factors are asbestos exposure, nickel,
chromates, coal tar; the radon-in-your-home story (thousands of dollars
"to protect your family") doesn't square with the extremely low
incidence of lung cancer in non-smokers.
Oat cell carcinoma: Kulchitsky (APUD) cell of origin, tiny white
fishflesh primaries near hilum with early and widespread metastases; 15
micron almost-no-cytoplasm cells, paraneoplastic syndromes include
Eaton-Lambert, inappropriate ADH, Cushingism from ACTH, more; not
hypercalcemia. Bombesin's the autocrine growth factor.
Squamous cell carcinoma: Pearls, bridges (prickles, desmosomes),
single-cell apoptosis (single-cell keratinization), tonofilaments;
large central lesions with a tendency to cavitate; parathyroid-hormone-
like activity raises serum calcium; men smoking non-filtered
cigarettes.
Adenocarcinoma: Glands, papillae, mucin, surfactant protein, lumens,
microvilli; peripheral lesions; women smoking filtered cigarettes and
so inhaling more deeply than men. Bronchioloalveolar carcinoma is
cancer cells growing along the septa, causing fatal mucus accumulation.
Large cell undifferentiated carcinoma: Massive lesions, horribly
anaplastic large cells. Hundred-day tumor.
Pancoast-tumor: any lung cancer which has invaded the brachial plexus
and cervical sympathetic chain, i.e., arm pain, Horner's.
Bronchial carcinoid: John Wayne's cancer, a low-grade APUDoma with
little ability to kill.
Choanal atresia: Can't breathe through nose, i.e., baby turns blue on
feeding, pink when he/she stops and cries. Acute epiglottitis: Croup,
inspiratory stridor, think H. flu. Laryngeal masses: HPV, overuse
("teacher's nodule"). The trachea almost never gets sick except in
diphtheria. Common cancer is squamous cell, from smoking-drinking.
Chinese nasopharyngeal cancer: Epstein-Barr.
Mesothelioma: Cancer of mesothelium, usually pleura. Usually asbestos-
exposed. Long spaghetti microvilli, biphasic pattern (adenocarcinoma
plus spindle cell sarcoma).
Chylothorax: Damaged thoracic duct; chylomicrons separate out on
refrigeration. Pseudochylous (i.e., cholesterol and neutrophil debris)
is more common.
Anemias For Understanders....
TOO MANY RED CELLS BEING DESTROYED IN THE BODY (hemolysis)------------
Membrane defects  BILIRUBIN \ ³
SPHEROCYTES \  LDH 1 \<--
 MCHC \<------ Hereditary spherocytosis  RETICULOCYTES\
(HYPERCHROMIA)\ Spur cell anemias
cirrhosis
abetalipoproteinemia
+ HAM TEST <--------- Paroxysmal nocturnal hemoglobinuria
(ACID HEMOLYSIS) Enzyme deficiencies
/ G-6-PD deficiency
HEINZ BODIES <-----/ Other deficiencies of HMP shunt enzymes
Pyruvate kinase deficiency
Other glycolytic pathway enzyme deficiencies
Abnormal hemoglobin
TARGET CELLS<-/ Unstable hemoglobin
SICKLED CELLS <-------- Sickle cell disease
HEMOGLOBIN C CRYSTALS<--Hemoglobin C disease
HEMOGLOBIN SC CRYSTALS<-Hemoglobin SC disease
/---- Immune hemolysis (antibodies against red cell antigens)
 ³ Hemolytic disease of newborn (Rh, etc.)
SPHEROCYTES ³ Autoimmune hemolytic anemias
³ Systemic lupus
+ DIRECT  Methyldopa ("Aldomet")
COOMBS TEST Malignant lymphoma and other cancers
"Idiopathic" warm antibody type
Paroxysmal cold hemoglobinuria
Drug haptens (high-dose penicillin)
Mechanical injury
"March hemoglobinuria" (pavement pounding)
/Clostridial sepsis
--------/ Burns
 \ Prosthetic heart valves
SCHISTOCYTES \Microangiopathic hemolysis (fibrin slices RBC's)
AND OTHER \ Disseminated intravascular coagulation (DIC)
FRAGMENTS \ Thrombotic thrombocytopenic purpura (TTP)
\ Hemolytic-uremic syndrome
Malaria
"Hypersplenism" (big spleen from various causes)
Cirrhosis
Rheumatoid arthritis
Gaucher's disease, etc.
Normoblasts being destroyed (not principal mechanism)
Megaloblastic anemia 
Idiopathic myelofibrosis (no  reticulocytes)
Thalassemias
TOO MANY RED CELLS BEING LOST FROM THE BODY (acute hemorrhage)
Trauma 
GI tract bleeding  RETICULOCYTES
Uterine bleeding, etc.

ENOUGH HEMOGLOBIN NOT BEING MADE

 MCV \ Not enough usable iron  SERUM IRON
(MICROCYTES)³<--/ Actual iron deficiency (none stored)
 MCHC / / \
(HYPOCHROMIA) / Diet (junk food, poverty) \
PENCIL CELLS\<---/ Pregnancy 
TARGET CELLS/ ³  SERUM FERRITIN
\ ZERO MARROW IRON STORES
\ Chronic blood loss
\ Heavy menstruation
\ Frequent blood bank deposits
\ Lots of blood tests (preemies, others)
\Slow GI bleeding, etc.
³--"Anemia of chronic disease" (never severe)
 (RE cells fail to get iron into normoblasts)
 SERUM FERRITIN Rheumatoid arthritis, systemic lupus
 Chronic infections (TB, osteomyelitis, etc.)
³ Advanced cancer
DIMORPHIC <--------"Sideroblastic anemias"
RBC POPULATIONS (iron stays in normoblast organelles)
Alcoholism
Drugs (isoniazid, etc)
Lead poisoning (inhibits ferrochelatase)
*Pyridoxine responsive anemia
Preleukemia ("myelodysplasia"), etc.
Not enough heme rings
Erythropoietic porphyria
---------- Lead poisoning (inhibits porphyrin synthesis)
BASOPHILIC Not enough globin chains
STIPPLING <-------- Thalassemias -----------------------> PANCAKE CELLS
ENOUGH NORMOBLASTS NOT BEING MADE --------------->  RETICULOCYTES
Renal disease (not enough erythropoietin)
Hypothyroidism
 MCV <------- Not enough nucleic acid (megaloblastic anemias)
(MACROCYTES)  Cancer chemotherapy
HYPERSEGMENTED PMN's B12 deficiency
 SERUM B12 <-----------/ Pernicious anemia
³ Weird diets ("vegans", all vegetables)
SCHILLING TESTS <-------³ Malabsorption (gut diseases)
WITH AND WITHOUT \ Fish tapeworm infestation
INTRINSIC FACTOR Folic acid deficiency ---------->  RBC FOLATE
Weird diets (junk food, alcoholics)
Pregnancy
Chronic severe hemolysis
Phenytoin (blocks absorption by gut)
Folic acid antagonists (methotrexate)
Zidovudine and other AIDS drugs
/Infiltrative disease of bone marrow
³ "Myelophthisic anemia"
 Cancer
TEARDROP RBC'S Tuberculosis
Fibrosis ("myelofibrosis")
"Myeloid metaplasia"
Polycythemia vera rubra (end-stage)
"Idiopathic"
"Primary" failure of normoblast production
"Pure" red cell aplasia/hypoplasia
Hereditary (Blackfan-Diamond)
Thymoma / thymic hyperplasia
Chloramphenicol
"Aplastic anemia" ( granulocytes, plts also)
Radiation
Benzene
Drugs (phenylbutazone, gold, many others)
Aplastic crises (Hgb SS, other hemolyzers)
Do you remember all those hemoglobins?
Hemoglobin is four globin chains plus four heme units (porphyrin
plus iron):
2à + 2á = Hgb A (à2 á2A) 96% in normal adults
2à + 2ë = Hgb A2 (à2 ë2) 3% in normal adults
2à + 2 gamma = Hgb F (à2 gamma2) 1% in nl. adults
Hgb F is the main hemoglobin in the fetus, and remains abundant until
the child is two years old.
Do you remember the hemoglobins seen only in disease?
Wrong ways of combining normal chains:
4á = Hgb H (á4)
4 gamma = Hgb Bart's (gamma4)
Mutations:
2à + 2áS = Hgb S (à2ásS2)
2à + 2áC = Hgb C (à2ácC2)
2à + 2 á-ë Lepore = Hgb Lepore (à2 á-ë2)
And about 300 other, less common, variants. (Some cause problems,
some don't.
Anemia: any reduction below normal limits of the total circulating red
cell mass. All anemias except the anemia of acute blood loss are
detected by your discovery of decreased hematocrit and/or decreased
hemoglobin. Acute anemia (i.e., blood loss) produces shock.
(Hemoglobin and hematocrit stay normal or near-normal until plasma
volume is restored.) Chronic anemia requires increased cardiac output
and eventually may produce hypoxia, weakness, malaise, easy
fatiguability, koilonychia, fatty change in myocardium.

Chronic blood loss: Anemia usually develops only when iron stores run
out, i.e., iron deficiency anemia results. The bone marrow can
increase erythropoiesis to eight times normal in the face of chronic
bleeding or hemolysis. Hemorrhage is much commoner than hemolysis!

Intravascular hemolysis: as in DIC, or when RBC's are sensitized to

complement or mechanically injured)
Extravascular hemolysis: Lysed in the RE system, as when RBC's are too
stiff or fragile or are altered immunologically.
Ongoing hemolysis will result in several pathophysiologic changes:
Increased total body iron (gut overabsorbs), high reticulocyte count,
zero haptoglobin, jaundice, bilirubin gallstones, expanded marrow space
("crewcut skull films" in kids)
Hereditary spherocytosis: deficient spectrin, ankyrin, and/or protein
4.1; red cells are fragile and spherical. Increased osmotic fragility.
Treatment is splenectomy.
Hereditary deficiency of HMP shunt or glutathione systems cause
oxidative damage to red cells. Masses of denatured hemoglobin are
"Heinz bodies". Best-known is G6PD deficiency, common in Afro-
Americans; must avoid fava beans, some antimalarials, some other drugs.
Sickle hemoglobin features substitution of valine for glutamine at the
sixth position of the beta chain (áS). Deoxygenation results in
tactoid formation ("crystallization", "gelation") of HgbS. This forms
sickle-shaped cells, and results in stasis (sludging), vaso-occlusive
phenomena, and hemolysis. Made worse by high ionic strength and
dehydration, better by hemoglobin F. Autosplenectomy and
susceptibility to pneumococcal sepsis. Sickle cell disease is
preventable by screening for carriers; sicklers have a pain problem
commensurate with cancer patients.
Hemoglobin C is another black hemoglobin, almost as common as Hgb S.
Heterozygotes have mild hemolysis; homozygotes have moderate hemolysis.
SC patients have a mild sickling problem.
Hemoglobin E: Southeast asian, mild hemolysis in heterozygotes.
Alpha-thal. Four alpha-chain genes in health. Africa, anywhere else.
Lack one: Thal minima, no health problems, 3% hemoglobin Bart's at
birth.
Lack two: Alpha thal minor, smallish (82 fL or so) red cells, 5-
10% hemoglobin Bart's at birth, trace hemoglobin H as adult,
 anemia is rare.
Lack three: Hemoglobin H disease; H has high affinity for oxygen,
and tends to form Heinz bodies.
Lack four: Hemoglobin Bart's disease, hydrops fetalis, i.e.,
congestive heart failure in the unborn child.
Beta-thal. Two beta-chain genes in health. Mostly Mediterranean.
(Alleles: á0 -- no chains produced; á+ -- some chains produced,
but not enough)
Lack one: Thal minor, basophilic stippling, small red cells (67 fL
or so), pancake-shaped (leptocytes), mild intramedullary hemolysis
(i.e., slight unconjugated hyperbilirubinemia).
Lack two: Thal major, horrible anemia with intramedullary
hemolysis, weird-shaped cells, need for transfusions, death from
iron overload.
Paroxysmal nocturnal hemoglobinuria: Abnormal sensitivity of RBC's to
complement-mediated lysis, especially at low pH (i.e., while you're
asleep). The cells have lost the gene (PIG-A) to make an inositol-
based anchor for a group of surface proteins, including those that
confer resistance to lysis by the body's own complement. Ham test.
Coombs test (direct): Checks for antibody coating red cells in you.
(Indirect is a laboratorian's test for the presence of antibodies, but
not on your red cells).
IgG (warm) autoimmune hemolytic anemia: lymphoma, lupus, methyldopa.
IgG (cold) autoimmune hemolytic anemia: mycoplasma, infectious mono,
lymphoma.
Mechanical hemolysis: prosthetic valves, DIC, TTP, HUS, burns,
malignant hypertension, scleroderma, lupus vasculitis. Look for helmet
cells, burr cells, triangle cells, target cells, schistocytes.
Infections of red cells: babesia, malaria, bartonella.
In all megaloblastic anemias (i.e., the nuclei cannot keep up with the
cytoplasm while developing), expect to see:
-- anemia (and maybe neutropenia and maybe thrombocytopenia)
-- increased mean corpuscular volume (why?) with normochromia
and considerable anisocytosis (ask a pathologist to show you
a "macro-ovalocyte")
-- hyper-segmentation of the neutrophil and eosinophil nuclei
(why?)
-- shortened red cell survival time (often, much of the
hemolysis takes place in the marrow; the marrow may appear
hypercellular and serum LDH-1 levels, suggestive of
hemolysis, can be extremely high)
Pernicious anemia ("true pernicious anemia", "addisonian pernicious
anemia", etc.): Lack of B12 due to lack of intrinsic factor. Dread
neurologic syndrome of subacute combined degeneration of the cord.
Diagnosis with Schilling test. This is a boards favorite. Understand
why the physical findings:
 -- findings of anemia (pallor of all organs, big heart)
-- slight icterus (why? ever hear of the "lemon yellow" pernicious
anemia patient?)
-- peripheral smear (from life) with macro-ovalocytes
-- neutrophils on peripheral smear with 6-10 segments
-- hypercellular, megaloblastic marrow;
-- glossitis (can't replace those stratified squamous cells fast
enough)
-- autoimmune-style chronic gastritis ("fundic"; "type A";
achlorhydric) with some intestinal metaplasia
-- immature, large nuclei in the remaining stomach epithelial cells
-- loss of myelin in the posterior columns; NOTE: Often the lateral
columns are affected, too. This is called "subacute combined
degeneration of the cord", typical of B12 deficiency.
Other causes of B12 deficiency: extreme vegetarians, whole stomach cut
out by the surgeon, bad malabsorption, diphyllobothrium fish tapeworm,
bad terminal ileum (B12 absorption site) from Crohn's.
Folic acid deficiency (ever know someone who called it "vitamin P"?
"folic" means "from (green) leaves"). Another megaloblastic anemia.
Junk food, pregnancy, dilantin, birth control pills.
A person may become iron-deficient by:
-- heavy menstrual loss
-- abnormal blood loss (GI bleeding -- remember hookworm --, GU
bleeding, uterine bleeding)
-- lousy diet (there's not much iron in twinkies, fries, or diet
pepsi; heme iron is much better absorbed than iron from beans;
poor diet is seldom the sole cause in U.S. adults, however U.S.
kids can and do become iron deficient, despite "Big Robbins")
-- malabsorption (sprue, those others)
-- no HCl and/or no access of food to the duodenum (as after ulcer
surgery)
Doc: If you find iron deficiency, you MUST find the cause.
The iron-deficient patient develops a hypochromic, microcytic (why?)
anemia, which can be very severe. Tiny red cells with wide central
pallor. Pencil cells. High total iron binding capacity, low serum
iron, zero serum ferritin.
Anemia of chronic disease: From prolonged interleukin 1 production.
Osteomyelitis, rheumatoid arthritis, tuberculosis, leprosy, and
generally the same diseases that cause amyloidosis A. Normoblasts have
difficulty taking up iron. Iron stays in the marrow macrophages.
Hemoglobin 8-10 g/dL, small red cells..
Sideroblastic anemia: Ferrochelatase cannot place iron into the heme
ring. Alcoholics, preleukemia, isoniazid.
Red cells stop being made: Aplastic crisis in sicklers and
spherocytosis is likely mediated by parvovirus 19. Chloramphenicol
suppresses erythropoiesis, and sometimes extremely well and
permanently. Thymomas. Blackfan-Diamond (apoptosis unless loaded with
erythropoietin). Renal failure benefit from erythropoietin injections.
White cells: A tough chapter.
Epstein-Barr virus: Burkitt's lymphoma in Africa; other B-cell
lymphomas in the immunosuppressed
HTLV-I: Adult T-cell leukemia-lymphoma; Caribbean spastic
paralysis / leukemia
HTLV-II: Hairy cell leukemia
HIV: Immunosuppression allows Epstein-Barr lymphomas of
brain; EBV and non-EBV lymphomas elsewhere
Herpes 8 /KSHV newly-implicated in some, if not many, lymphomas
Terms: (1) agranulocytosis: acquired lack of neutrophils, usually from
a drug; (2) Auer rod: crystal of azurophilic granules stuff, proof of
granulocyte origin; (3) Bence-Jones protein: free immunoglobulin light
chains produced by plasma cell myeloma; (4) blast: baby white cell with
all-euchromatin, some nucleoli, scanty cytoplasm; if easy to find,
think of acute leukemia; (5) bcr/abl oncogene: the cancer gene produced
by the Philadelphia translocation; (6) chloroma / granulocytic sarcoma:
The solid phase of acute granulocytic leukemia; (7) cleaved (clefted)
lymphocyte: a B-cell on its way to becoming an antibody producer; (8)
convoluted lymphocyte: A T-cell in Sezary/mycosis fungoides; (9)
cryoglobulin: marginally soluble plasma protein that precipitates in
the cold; (10) D hle body: rough ER masses in some turned-on white
cells; (11) monoclonal gammopathy: extreme overproduction of exactly
one particular antibody; (12) polyclonal gammopathy: too much of many
antibodies being overproduced (lupus, AIDS, liver failure, rheumatoid
arthritis, bad infections); (13) leukemia: cancer of the white cell
precursors, cancer of the bone marrow; (14) aleukemic leukemia: no
leukemia cells in the blood; (15) leukocyte alkaline phosphatase:
marker high in leukemid reaction, low in chronic granulocytic leukemia;
(16) leukocytosis: increased absolute total white count; (17)
leukoerythroblastic smear: teardrops and nucleated reds, i.e.
something's crowding the marrow; (18) leukopenia: decreased absolute
white count; (19) lymphadenopathy: big lymph nodes for any reason; (20)
lymphoma: solid cancer of the lymphocytes, not in the marrow; (21) M-
protein: the particular antibody or chain overproduced in monoclonal
gammopathy; (22) myeloid / myelogenous: derived from granulocytic
precursors; (23) myeloma ("multiple myeloma", "plasma cell myeloma"):
cancer of the plasma cells; (24) neutropenia: absolute lack of
neutrophils; (25): paraprotein: consider this the same as M-protein;
(26): Pautrier microabscess: clusters of convoluted lymphocytes in the
epidermis in mycosis fungoides / Sezary's; (27) Philadelphia
chromosome: the famous translocation in chronic granulocytic leukemia;
(28) absolute polycythemia: too much red cell mass; (29) relative
polycythemia: too little plasma, causing too high hematocrit; (30)
primary polycythemia: absolute polycythemia due to overproduction of
red blood cells bearing mutations; (31): secondary polycythemia:
absolute polycythemia due to low oxygen tension or excess
erythropoietin or taking gym steroids or high-affinity hemoglobin; (32)
pseudolymphoma: ugly-looking chronic inflammation that fooled the other
pathologist; (33) tingible body macrophage: a macrophage that has eaten
debris in an inflamed lymph nodes; (34) toxic granulation: exaggerated
granules in neutrophils during sepsis.
T-cell zones: thymus, lymph node parafollicular cortex, splenic white
pulp near arteriole
B-cell zones: germinal centers and their mantles, splenic white pulp at
its margins
Among circulating lymphocytes, 80% are T-cells, and 20% are B-cells.
Healthy absolute counts:
Basophils: * few- 100/æL
Eosinophils: few- 400
Lymphocytes: 1500-7000 (*3000-7000 for kids)
T4 helper lymphocytes: >1000
Monocytes: few- 800
Neutrophils: 1800-7000
"95% lymphocytes" might mean either agranulocytosis (if the total white
count is 2000) or chronic lymphocytic leukemia (if the total white
count is 100,000).
Somebody might actually have the crust to ask you about white cell
markers.
PAS+ chunks ("blocks"): immature lymphocytes or M6 leukemia
TdT: immature lymphocytes
E-rosettes: T-cells
CD4, CD8, others: T-cells (various kinds)
CD1 (T6) T-cells, Langerhans macrophages
Surface Ig(M, etc): B-cells
kappa, lambda: B-cell, plasma cells
cytoplasmic Ig: plasma cells
nonspecific esterase: monocytes
Fc receptor: B-cells, monocytes
TRAP: hairy-cell leukemia (tartrate resistant
acid phosphatase)
HLA-D/DR /Ia: Langerhans cells and other antigen-
presenting macrophages; some other cells
lysozyme: monocytes
à1-antichymotrypsin: monocytes
erythrophagocytosis: monocytes
(myelo-)peroxidase: granulocytes
Sudan black granulocytes
chloroacetate esterase: neutrophils, basophils, mast cells
platelet markers: megakaryocytes
PAS+ diffusely: erythrocytes, megakaryocytes/platelets

Even worse, someone might ask about the development of a B-cell:

Resting small B-lymphocyte

Small cleaved ("clefted", i.e., folded-nucleus) B-lymphocyte

Large cleaved B-lymphocyte

Small non-cleaved B-lymphocyte
[NOTE: This cell is as large as a large cleaved B-lymphocyte]

Large non-cleaved B-lymphocyte

B-immunoblast
 
Memory B-cell Plasma cell
Neutropenia: The aplastic anemias, space-occupying lesions in marrow,
the megaloblastic anemias, radiation, chemotherapy, typhoid,
hypersplenism, phenylbutazone, other drugs. Agranulocytosis (extreme
neutropenia) presents as mouth ulcers.
Left-shift: Immature neutrophils appearing in the blood, usually from
bad infection. Extreme case: Leukemoid reaction; distinguish from
granulocytic leukemia.
Leukemoid reaction Chronic granulocytic leukemia
High leuk alk phos Low leuk alk phos
Normal basophils High basophils
No Philadelphia chr. Ph' or at least bcr/abl
Chediak-Higashi: Problems with neutrophil membranes.
Pelger-Huet: Poor segmentation of neutrophils, not a clinical problem.
Alder-Reilley: Conspicuous neutrophil granules in
mucopolysaccharidosis.
Non-Hodgkin's lymphoma rules. All monoclonal lymphocyte proliferations
are malignant. Most lymphomas are of unknown cause. The majority are
of B-cell origin. Fever, weight loss, night sweats,
hypogammaglobulinemia are from cytokine production by the tumor.
Enlarged, non-tender nodes, less often gut or lung lymphoid tissue.
Uniform overgrowth of cells, often not bizarre. Nodular (follicular)
lymphoma means B-cell origin, better prognosis than diffuse
counterpart. Pathologists diagnose lymphoma based on effaced
architecture, cell uniformity, invasion, necrosis, monoclonality,
chromosome rearrangements. Prognosis depends on subtype. High-grade
ones are curable with chemotherapy. Low-grade ones are indolent but
non-curable.
Small lymphocytic lymphoma: indolent disease of older folks.
Richter's: turns aggressive (Jackie Kennedy's disease).
Plasmacytoid small lymphocytic lymphoma: Often Waldenstrom's, makes
IgM, leading to hyperviscosity.
T-lymphoblastic lymphoma: teenaged boys, in the thymus.
Burkitt's: 8:14 translocation, Epstein-Barr virus, starry-sky (the
white "stars" are macrophages devouring the lipid-rich debris); jaws of
kids in Africa; sporadic cases in the U.S. are not Epstein-Barr
related.
Mycosis fungoides: T-cells with convoluted nuclei in the skin; disease
progressively gets worse, from just red skin to horrible tumors
("toadstools"). Sezary's: mycosis fungoides-type cells circulating in
the blood.
Hodgkin's: Malignant cell is the Reed-Sternberg cell, cancerous
counterpart of certain cells ordinarily found in excited nodes.
You must recognize the classic Reed-Sternberg cell:
-- 15-45 æ across
-- multilobed nucleus (often appears "binucleate"), with lobes
appearing as mirror images of one another
-- large, red owl-eye nucleoli, surrounded by clear nuclear sap
 -- pink-to-lavender cytoplasm
Reed-Sternberg variants appear in various subtypes. The elegant Rye
classification is less prognostic than the stage of the disease.
Staging simplified (they might ask):
I: One group of nodes
II: One side of the diaphragm
III: Both sides of the diaphragm
IV: Bone or 2 extra-nodal organs.
A: No fever, weight loss, or night sweats
B: Fever, weight loss, or night sweats
Histologic types:
Lymphocyte predominance: Only a few Reed-Sternberg cells,
among many benign lymphocytes
Nodular sclerosis: Lacunar Reed-Sternberg variants,
mediastinum, mixed background
Mixed cellularity: Lots of different cells, enough
Reed-Sternberg cells
Lymphocyte depletion: Horrible-looking cancer
One type tends to become a worse type, with nodular sclerosis the most
stable. Eosinophils tend to come out in large numbers in Hodgkin's.
Acute leukemia: lots of blasts, presents abruptly as one of the
cytopenias (anemia, neutropenia, and/or thrombocytopenia). Bone pain
is likely to result from expansion of the marrow and infiltration of
the periosteum.
Chronic leukemia: few or no blasts, presents as cytopenia, or over-
abundant white cells plugging vessels.
Acute lymphoblastic leukemia: Kids' leukemia. Down's, radiation are
the risk factors, otherwise strikes at random. Most are B-cell, some
T-cell or null. Usually curable.
Acute myeloblastic (granulocytic) leukemia: Down's, benzene, previous
chemotherapy, preleukemia, "blast crisis" of chronic granulocytic
leukemia / polycythemia vera / "aplastic anemia", "the fragile
chromosome syndromes". I don't expect them to ask you the M1-M7
scheme, or about the myelodysplastic syndromes ("preleukemia").
Chronic granulocytic (myelogenous) leukemia: Benzene, previous
radiation, most appear random. Huge spleens, Philadelphia chromosome.
The disease smolders until blast crisis (i.e., more mutations, acute
disease and death) supervenes.
Chronic lymphocytic leukemia: Usually normal-appearing B-cells
circulating. No risk factors, not even radiation. Anemia,
thrombocytopenia, autoimmune hemolysis, Richter's.
Hairy-cell leukemia: fuzzy lymphocytes, dry tap, positive stain for
tartrate-resistant acid phosphatase, probably an infection, HTLV-II is
one suspect, good response to anti-viral drugs.
Polycythemia vera rubra: low-grade neoplasm of normoblasts, which
(news) have their low-erythropoietin signals stuck "on". Actually a
stem-cell problem; neutrophils and platelets are also up. Older-
middle-age. Hyperviscous blood. Treatment is phlebotomy.
Agnogenic myeloid metaplasia: Proliferative disease in marrow and
spleen; marrow looks normal. Teardrops and red cell precursors.
Later, marrow fibrosis.
Plasma cell myeloma: Older folks, no known risk factors, minority have
the punched-out lesions, but all have some bone rarification. Some
make Bence-Jones protein, some make a complete antibody, a few make
nothing. Bence-Jones protein eventually plugs kidney tubules. Patients
have anemia and suppression of normal antibody production. IgG is most
common paraprotein. Amyloidosis B. Hypercalcemia from some unknown
bone-destroying hormone.
Langerhans cell histiocytosis ("histiocytosis X"): Cancer of the
dendritic macrophages. Archaic names: "Hans-Schuller-Christian;
Letterer-Siwe, eosinophilic granuloma". Giveaway is CD1 / T6 stain,
Birbeck granules (pentalaminar tennis rackets) on electron microscopy.
Hypersplenism: Takes out neutrophils, red cells, and platelets. Think
of cirrhosis, Felty's (rheumatoid arthritis), Gaucher's.
All diseases of hemostasis have spontaneous bleeding (petechiae,
purpura, mucous membranes, GI bleeding, hematuria, into joint spaces)
and/or excessive bleeding after trauma or surgery.
Testing hemostasis:
Platelet count
Bleeding time: tests number and function of platelets.
Thrombin time: fibrinogen
Prothrombin time: I, II, V, VII, X
aPTT I, II, V, VIII, IX, X, XI, XII
Clot retraction: fibrinogen, platelet count, and Glanzmann's
factor
Urea solubility: XIII (cross-linker)
Fibrin split pr. DIC?
D-dimer Better test for DIC
Platelet aggreg. Not very useful clinically; exception is that
von Willebrand's respond poor to ristocetin
Increased vascular fragility: amyloidosis, scurvy, Cushing's, Osler-
Weber-Rendu, Ehlers-Danlos, endothelial infections, rickettsia, viral
hemorrhagic fevers, type III immune injuries
Platelets <40,000: bleed after surgery. Platelets <20,000: bleed
spontaneously. Platelets <10,000: bleed bad, spontaneously.
Thrombopoietin was finally cloned in 1994. Thrombocytopenia of
decreased production (few megakaryocytes): drugs, chemotherapy, marrow
disease, megaloblastic anemia. Increased destruction (many
megakaryocytes): autoimmune, isoimmune, hypersplenism, massive
bleeding.
Idiopathic thrombocytopenic purpura: Acute form in kids with virus-
antivirus immune complexes adsorbed on the platelets; seen also in
AIDS. Chronic ITP: real anti-platelet antibodies, adults.
Thrombotic thrombocytopenic purpura (TTP): Fibrin-platelet microthrombi
all over the vascular system. Mysterious. Confusion and CNS signs,
fever, thrombocytopenia, kidney failure, red cell fragmentation, death.
Administering fresh-frozen plasma controls it.
Bernard-Soulier: Giant platelets that don't work.
Von-Willebrand's: Lack of VIII-R, the stuff made in endothelium that
keeps platelets working and VIII-C in the plasma. Very common, if you
look.
Glanzmann's tired-platelet thrombasthenia: Lack of a factor that makes
platelets work, particularly in their role in clot retraction.
Aspirin lesion stays for the 9-day life of the platelet.
Thrombocytosis of seldom of interest, unless it's due to "essential
thrombocythemia", in which the megakaryocytes have a mutation; this is
preleukemic, and the platelets may not work well.
Hereditary coagulation disorders: Classic hemophilic factor VIII.
Christmas disease factor IX.
Lack of vitamin K: malabsorption, little babies, coumadin, liver
failure. Factors II, VII, IX, X.
"Circulating anticoagulants" cannot be neutralized by adding the good
factor; problem for hemophiliacs.
Hypercoagulable blood: Factor C deficiency, factor S deficiency, lupus
anticoagulant, protein C cofactor deficiency, antithrombin III
deficiency (hereditary, birth control pills), hyperactive V (news),
hyperhomocysteinemia (news).
Memory work:
Defects of the extrinsic pathway (normal aPTT, prolonged PT)
usually indicate early liver disease or coumarin therapy
(congenital factor VII deficiency is rare)
Defects of the intrinsic pathway (normal PT, prolonged aPTT)
include factor VIII and IX deficiencies or circulating
anticoagulants (congenital factor XI and XII deficiencies are
rare)
Defects of both pathways (prolonged PT and aPTT): usually indicate
heparin or coumadin therapy, advanced liver disease, or
circulating anticoagulants (congenital factor II, V, and X
deficiencies are rare)
Defects of neither pathway (normal PT and aPTT): fragile vessels,
platelet problem, or factor XIII deficiency (remember urea
solubility test)
Tooth decay: Dental caries, strep mutans hiding under a film (plaque)
made of polymerized carbohydrates (sucrose is best), making acid,
eroding teeth. Risk factors: high-sucrose diet, dry mouth from any
cause. Fluoride in the drinking water protects. Eroded teeth may
abscess, etc. Ludwig's angina: infection spreads to floor of mouth,
neck structures.
Periodontal disease: Plaque accumulates in the gingival sulcus,
calcified is calculus, causes inflammation and resorption of the
attachments of tooth to bone, tooth loss in older folks.
Trench mouth (necrotizing gingivitis): Mixed borrelia and fusobacterium
infection; severe cases (noma) destroys face.
Leukoplakia: Any white lesion on the mucosa; may be nothing, or may be
carcinoma in situ; smokeless tobacco. Squamous cell carcinoma of oral
mucosa: tobacco, alcohol, herpes simplex.
Lichen planus: White lines on oral mucosa.
Aphthous stomatitis: White "canker sores" on the oral mucosa, nothing
to do with herpes; local immune complex vasculitis probably strep
antigens; rule out Crohn's, Bechet's (mouth and genital sores),
agranulocytosis, lupus. (Erythema multiforme and pemphigus have their
own looks.)
Herpes stomatitis: First infection with type I. Herpes labialis:
induced by stress, sunlight, hormonal chaos, fever, injury.
Herpangina: Coxsackie A blisters on anterior tonsillar pillars.
Salivary gland neoplasms: Pleomorphic adenoma is a cartilage-based
mixed tumor. Warthin's tumor is benign. A variety of cancers occur
here; only known risk factor is radiation.
Ameloblastoma: the common semi-cancer of the jaws, simulates developing
tooth, no tendency to metastasize.
Gut words! (1) achalasia: failure of the gastroesophageal sphincter to
relax, causing the esophagus to fill up with a few day's dinner; (2)
hernia: gut (usually) pooching out where it doesn't belong; (3) polyp:
a bump sticking up from the mucosa; (4) tenesmus: unpleasant spasms of
the anal sphincter, continuous urge to defecate; any inflammation here
can produce this.
Tracheo-esophageal fistula: Kid chokes on feeding. Zenker's pulsion
pseudodiverticulum: Esophagus pooches out next to cricophagyngeus
muscle, traps yesterday's spaghetti. Mega-esophagus: Achalasia or
Chagas's. Webs: little fibrous scars that may obstruct. Hiatus
hernia: Stomach in the chest; sliding (common) from shortened esophagus
(years of reflux; obesity; congenital), rolling (less common; think of
obesity stretching the diaphragm wide) alongside esophagus of normal
length.
Reflux: familiar heartburn, damage from acid, lysolecithin, pepsin.
Hyperplastic basal cells, eosinophils in the epithelium, tall papillae.
Barrett's esophagus: Columnar metaplasia at the gastroesophageal
junction, caused by healing of reflux in the setting of a mutation
giving advantage to cells of glandular phenotype, hence the
adenocarcinoma risk.
Esophagitis: Candida, herpes, less often CMV. Lacerated esophagus: Bad
vomiting. Mallory-Weiss: Several longitudinal tears in the distal
esophagus from vomiting. Boerhaave's: Badly ruptured esophagus.
Varices: from portal hypertension; prone to heavy bleeding. Esophageal
angina: Popular new diagnosis to explain chest pain.
The causes of portal hypertension....
Pre-hepatic
 Thrombosis of the portal vein
Hypercoagulability
Polycythemia vera, sickle cell, others
Invasion by tumor (hepatocellular carcinoma)
Tumor compressing the portal vein
Intra-hepatic
Cirrhosis from any cause
Other obstructive disease
Bad alcoholic liver disease without cirrhosis
Schistosomiasis without cirrhosis
Central hyaline sclerosis in alcoholism
Post-hepatic
Budd-Chiari (thrombosis of hepatic veins)
Causes as for thrombosis of portal vein
Squamous cell carcinoma of esophagus: Alcohol, tobacco, and herpes; old
lye strictures, Red China (mystery). Adenocarcinomas arise in
Barrett's.
Diaphragmatic hernia: Stomach all the way up in the chest at birth.
Pyloric stenosis (congenital): Boy has projectile vomiting at one
month, surgeon feels an olive-like mass.
Acute gastritis: Multifactorial, several mechanisms (ischemia, low pH,
dead epithelial cells, compromised defenses). Causes include alcohol,
aspirin, caffeine, chemotherapy, food allergy, helicobacter, radiation
injury, lysolecithin refluxing from the duodenum, shock, spicy foods,
staph food poisoning, tobacco, viruses, stress.
Chronic gastritis:
Type A: Autoimmune, fundic; stomach cancer common; pernicious
anemia, intestinal metaplasia
Type B: Hypersecretory, antral, lots of stomach acid,
helicobacter
Type AB: "Environmental", helicobacter, stomach cancer fairly
common, but not as a bad as A; Japan, Chile, others.
Menetrier's: Hypertrophy-hyperplasia of mucosa from helicobacter
Zollinger-Ellison: Hyperplasia and worse from a gastrinoma.
Stress ulcers: Common. In the burn unit, called "Curling's ulcers".
In the neurosurgery unit, called "Cushing's ulcers".
Peptic ulcer: Helicobacter is key; other risks are alcohol, aspirin,
blood type O, smoking, cirrhosis, emphysema, gastrinoma.
Gastric adenocarcinoma: dietary factors (smoked food, ethnic pickled
stuff, lack of green vegetables, lack of animal fat), old ulcer
surgery, chronic gastritis A or AB, blood groups A or AB (convenient).
Epidemics now in Japan and Chile; helicobacter antibodies may be growth
factor. Linitis plastica: Stomach cancer replacing the wall ("leather
bottle"). Krukenberg tumor: Massive stomach cancer metastases to the
ovaries.
Meckel's diverticulum (persistent omphalomesenteric duct): 2% of folks
have it, 2 feet proximal to the ileocecal valve, 2 types of ectopia are
pancreas and stomach; ulcers, bleed, infection, volvulus.
Mucosal infarcts ("hemorrhagic gastroenteropathy"): stress, shock,
digitalis, long runs.
Crohn's disease: mycobacterial origin now seems plausible; skip
lesions, transmural involvement, string sign, fistulas, creeping fat,
linear fissuring and cobblestone change of the mucosa, small cancer
risk, aphthae, lesions anywhere from lips to anus, favored site is
terminal ileum, B12 and folate malabsorption.
Malabsorption has many causes.
Cannot break down food to simple molecules ("mal-digestion")
Exocrine pancreatic disease (duct obstruction by stone or cancer,
damaged parenchyma in "chronic pancreatitis")
Lack of bile salts (bile duct obstruction, liver failure;
bacterial overgrowth in diverticula, stasis, after gastrectomy)
Disaccharidase (lactase, etc.) deficiency
Problems with the small bowel mucosa
Sprue
Tropical
Non-tropical ("celiac disease" "gluten enteropathy")
Crohn's
Whipple's
Acute infections
Parasites
Giardia (the usual cause of "malabsorption secondary to
hypogammaglobulinemia")
Less often, strongyloides, schistosomes
Allergic gastroenteritis
Kinks in the metabolism (abetalipoproteinemia, inability to absorb
a particular molecule)
Collagenous enteritis / scleroderma
Amyloidosis
Lymphomas
Radiation sickness / B12 / folate deficiency (epithelium cannot
replenish itself)
Super-fast transit time
Laxatives
Mechanical problems
Blocked lymphatics (cancer, TB)
After re-routing surgery (gastrectomy, bypass)
Celiac sprue: Gluten induces autoantibodies against reticulin, which
somehow flattens the villi and microvilli. Skin manifestation is
dermatitis herpetiformis; many get lymphoma of gut. Tropical sprue:
Vicious cycle of malabsorption, folate deficiency, and bacterial
overgrowth.
Whipple's disease: Infection with Tropheryma whippli bacteria, which
pack macrophages (see on PAS stain) in gut and anywhere else.
Abetalipoproteinemia: no apolipoprotein B; acanthocytes, cannot absorb
fat which stays in the intestinal epithelial cells.
Intussusception: Telescoping of bowel into itself, as if it mistook a
polyp or lymphoid mass for food. Volvulus: Twisted bowel. Adhesions:
fibrous scarring, most often from surgery.
Appendicitis: Pain migrating from crampy-around-navel to knife-at-
Mcburney's-point. Cause is obstruction of appendix by fecalith or
lymphoid tissue. Carcinoid tumors of the appendix are common, low-
malignancy.
Hirschsprung's aganglionic megacolon: Failure of Auerbach's and
Meissner's plexi to develop over a segment of colon. Constipation is a
problem.
Diverticulosis: mucosa pooches out through the colonic wall where the
arteries enter. Low-residue diet requires more force to push small,
hard stools. Prone to bleed and/or get bacterial infections
(diverticulitis). (Really pseudo-diverticula). Functional bowel
syndrome (spastic colon): Uncoordinated peristalsis leads to ischemia
and pain.
Idiopathic ulcerative colitis: Rule out amebiasis, ischemia, shigella,
bad E. coli. Inflammatory disease of the colonic mucosa, increasing
distally without skip lesions. Bloody diarrhea. Pseudopolyps are
surviving mucosa among coalescent ulcers. Large cancer risk after many
years. Probable cause is some bacterial product.
Here is the inevitable comparison:
CROHN'S DISEASE ULCERATIVE COLITIS
Etiology? Unknown / infect? Unknown / infect?
Sex?
>
>
Ethnic group?  among Jewish  among Jewish
Hereditary? Contributes Contributes
Exacerbate/remit? Yes Yes
Stress exacerbates? Yes Yes
Location? Variable Rectum and upwards
Bowel? Small > Large Large only
Terminal ileum? Favorite site "Backwash"
Colon? Right>left, if any Left > right
Bile ducts? May be damaged May be damaged
Anal troubles? Common No
Oral lesions? Maybe No
Skip lesions? Yes No; continuous
Layers? All three Mucosa only
Ulcers? Linear fissures Broad / irregular
Pseudopolyps? Yeah, sort of Yes unless very mild
Fibrosis? Severe No
Fistulas? Yes No
Creeping fat? Yes No
Granulomas? Often No
Bleeding? Subtle Heavy-duty
Pain? Wretched Not so much
Malabsorption? Maybe No
Bowel obstruction? Maybe No
B-12 deficiency? Maybe No
Lymphs/plasma cells? Yes Yes
Arthritis, uveitis? Yes Yes
Ankylosing spondylitis? if (+) for HLA-B27 if (+) for HLA-B27
Diagnosis? Tough Easy
Surgery? Avoid Cures
Carcinoma risk? Minor High
Pseudomembranous colitis: Clostridium difficile overgrows normal flora
at times of stress or antibiotic coverage; pseudomembrane is fibrin,
and diarrhea may be followed by toxic megacolon.
Necrotizing enterocolitis: Babies, especially bottle-fed preemies.
Inflammation nad necrosis of gut.
Hyperplastic colon polyps are harmless bumps. Peutz-Jegher's polyps
are hamartomas in the small and large gut; look for freckles on the
lips. True colonic adenomas are tubular or villous, depending on the
shapes of their glands, may be mixed. Villous are more likely to be
sessile, more likely to secrete potassium, more likely to turn
malignant.
Colorectal cancer: Major killer, almost always adenocarcinoma, except
in Lynch's hereditary nonpolyposis colon caner syndrome the origin is
almost always n a polyp. Diet is a risk factor but exactly how is
unclear; the "red meat" hasn't held up recently; lack of roughage
(i.e., complex carbohydrate that holds water) seems more plausible.
News: an aspirin a day cuts colon cancer risk by about half. The
majority of colon cancers, like polyps, arise in the rectosigmoid,
present as narrowed stool. Those in the cecum present as iron
deficiency anemia. Marker: CEA.
* "You thing of no bowels!"
-- Shakespearean insult
Anal cancer: HPV-related, passive anal intercourse. Basaloid cancer:
from the transitional zone.
Hollow-organ pain is crampy-colicky and poorly-localized; patients tend
to squirm. Peritoneal pain (remember it's the parietal peritoneum that
feels it best) is knife-like and is exacerbated by movement (the
patient lies still). Peritonitis can and does follow most intra-
abdominal catastrophes. Most any bacterium can do it; fortunately, gas
gangrene is rare. Spontaneous bacterial peritonitis: In cirrhotics, E.
coli or enterococcus. Nephrotic syndrome: pneumococcus.
Pseudocyst: A lesser sac or other cavity with its wall digested by
lipase from a damaged pancreas.
Retroperitoneal fibrosis ("sclerosing retroperitonitis"): idiopathic,
ergot misuse.
Pseudomyxoma peritonei: mucin-secreting, low-grade adenocarcinoma
throughout the peritoneum. The primary is usually in the appendix,
ovary, or pancreas.
Sorting out food poisoning: A guide for future physicians and victims
You ingested a bug that then made toxin
E. coli
Water, tacos from street vendors, anything else.
Diarrhea in 24-72 hours.
C. perfringens
Ill-cooked food. Diarrhea in 8-14 hours.
Vibrio cholerae
Epidemic. Really bad diarrhea. This can kill anybody
unless their fluids and electrolytes are managed.
Vibrio parahemolyticus
The raw oyster bug. Vomiting, diarrhea, fever in 8-96
hours.
You ingested a bug that then invaded
Salmonella
Water, poultry, shellfish, most anything else. Fever,
vomiting, diarrhea in 8-24 hours.
E. coli
Enteroinvasive type. Diarrhea in 8-96 hours.
You ingested pre-formed toxin
Staph. aureus
Dairy products, custards. Impressive vomiting /
diarrhea in 2-4 hours. Ever had it? Betcha you have.
Beware, toxin is heat-stable.
Bacillus cereus
The fried-rice bug. Vomiting / diarrhea in 2-14 hours.
Beware, toxin is heat-stable.
C. perfringens as above.
C. botulinum
Sausage, ill-canned goods. Paralysis in 24-96 hours.
This can kill you.
Liver words: (1) Asterixis: liver flap of hepatic encephalopathy,
probably from octopamine rather than ammonia; (2) bile acids / salts:
cause the itching of cholestatic jaundice; (3) bridging necrosis: from
the portal to the central areas; (4) chronic active hepatitis:
inflammation plus piecemeal necrosis plus fibrosis, lasting six months
or more; will lead to cirrhosis; (5) chronic persistent hepatitis:
lymphocytes in the portal areas for more than six months, without
necrosis or fibrosis; (6) Councilman body: apoptotic hepatocyte in
hepatitis; (7) Giant mitochondria: alcoholism; (8) ground glass cell:
homogeneous cytoplasm seen in hepatitis B infection; (9) limiting
plate: the row of hepatocytes next to the portal area; it should be
uniform and smooth; (10) lobular disarray: sign of acute hepatitis; the
liver cords are indistinguishable; (11): Piecemeal necrosis: death of
groups of cells in the limiting plate; (12): Cirrhosis: enough scarring
of the liver to disrupt or scramble the normal blood circulation within
the liver; there will be regenerative nodules of hepatocytes; (13)
Peliosis: dilated veins, as in anabolic steroid use
Hepatocytes regenerate, but disrupted stroma doesn't.
Causes of jaundice:
TOO MUCH BILIRUBIN BEING PRODUCED ("hemolytic jaundice")
"Ineffective hematopoiesis", i.e., normoblasts dying in the bone
marrow
Thalassemias
Megaloblastic anemias
Intravascular hemolysis (many, many kinds)
Extravascular hemolysis
Big hematomas
GI bleeding
Red infarcts
LIVER FAILS TO TAKE UP AND/OR CONJUGATE BILIRUBIN ("hepatocellular
jaundice")
Newborns
Hypoperfusion
Bad alcoholism
Hepatitis (many causes)
Cirrhosis (many causes)
Gilbert's non-disease, the Crigler-Najjar syndromes
LIVER DOESN'T SEND BILIRUBIN TO THE RIGHT PLACE ("cholestatic
jaundice")
Problems with the liver cells
Drugs (estrogen, anabolic steroids)
Dubin-Johnson (pigmented) non-disease
Rotor (non-pigmented) non-disease
"Benign familial recurrent cholestasis"
Really bad cases of other liver diseases (hepatitis,
cirrhosis, alcoholism; i.e., when the liver fails, the
picture is likely to be mixed)
Problems with the bile ducts in the liver
Biliary cirrhosis
Biliary atresia
Problems with the bile ducts beyond the liver (call a surgeon)
Gallstone in the common duct
Cancer (i.e., biliary, pancreatic, ampullary)
Iatrogenic (i.e., the surgeon nicked the common bile duct)
In bile duct obstruction, expect clay-colored stools, smelly
steatorrhea.
Liver failure: Hypoalbuminemia, high ammonia, coagulopathy (VII goes
first), fetor hepaticus smell, hepatorenal syndrome (kidney fails yet
retains sodium), bad hypotension.
Shock and heart failure from any cause produce central hepatic
necrosis, raising enzymes ("ischemic hepatitis"); this regenerates upon
recovery. "Cardiac sclerosis" is longstanding scarring, usually from
tricuspid insufficiency.
Hepatic necrosis:
Central: Ischemia, carbon tetrachloride, chloroform, acetaminophen
Mid-zonal: Yellow fever.
Peripheral necrosis: Phosphorus, eclampsia
Acute hepatitis histology: lobular disarray, lysis of liver cells
individually or in small groups, Councilman bodies, some inflammatory
cells, prominent Kupffer cells, regenerating hepatocytes.
Massive necrosis ("acute yellow atrophy", unlucky hepatitis B, some
poisonings): apoptosis of all hepatocytes.
Cirrhosis: Problems include liver failure and portal hypertension
(varices, caput medusae, hemorrhoids, ascites) because of the scrambled
blood flow in the liver. Size of the regenerative nodules: <3 mm:
Micronodular (cause involved all lobules uniformly, i.e., alcohol,
hemochromatosis, primary biliary cirrhosis, other biliary tract
disease; >1 cm: macronodular (hepatitis B or C, autoimmune lupoid
hepatitis). Either pattern: Wilson's, galactosemia, antitrypsin
deficiency. Post-necrotic cirrhosis: it's mostly scar.
Hepatitis A: non-lethal, fecal-oral route, enterovirus; IgM is acute
antibody, IgG means old infection; vaccine finally available.
Hepatitis B: blood-borne, very infectious. You already have a chart;
here's the antigens and antibodies....
HBsAg ("Australia antigen"): Surface antigen. Envelope protein.
HBcAg: Core antigen. Nucleocapsid. Stays in liver nuclei, will
not see in blood.
HBeAg: Another nucleocapsid antigen, which means the virus is
being replicated; marker for seriousness and infectivity.

HBsAg first appears in the blood shortly before symptoms begin (if
they are to begin). It remains in the blood for the duration of
the infection, whether it is acutely symptomatic, slowly-
progressive / subclinical, or merely the carrier state.
HBeAg appears in the blood just after HBsAg, and before symptoms
start. It remains as long as there is acute viral replication,
marker for being very contagious, and disappears if (and only if)
viral replication stops. The patient is still sick when HBeAg
disappears, but can take comfort in the good news.
Anti-HBeAg appears soon after viral replication and HBeAg
production stop (if they stop). The patient can still be sick,
but this is another piece of good news.
 Anti-HBcAg, in its IgM form, appears in the blood typically before
symptoms begin, and generally remains present for years (IgG anti-
HBcAg will eventually take over, maybe). If a person with
clinical hepatitis has cleared his blood of HBsAg, but has not yet
developed detectable anti-HBsAg, the presence of IgM anti-HBcAg
confirms that the infection is, indeed, hepatitis B and is in the
core window.
Anti-HBsAg generally appears when the infection is pretty much
over, and is a sure sign of recovery.
Treat chronic persistent hepatitis B with masterful inactivity, chronic
active hepatitis B with interferon. Hepatitis D: An incomplete virus
only capable of causing disease in the presence of hepatitis B.
Hepatitis C: Same routes of transmission as hepatitis B, not so
catching. Antibody does not clear the infection; liver disease
smolders for decades and may turn to cirrhosis.
Hepatitis E: Water-borne, not much in the U.S.
Autoimmune "lupoid" hepatitis: Chronic active hepatitis, perhaps
triggered by virus or drugs; anti-smooth muscle autoantibodies.
Primary biliary cirrhosis: Destruction of the small bile ducts, leading
to scarring and cirrhosis; bad cholestasis causes itching from bile
salts; anti-mitochondrial antibodies (i.e., anti pyruvate
dehydrogenase).
Cholangitis: Usually ascending, often E. coli; underlying cause is
biliary obstruction. Polys in the bile ducts. May lead to liver
abscess; do not confuse with (minimally-inflamed) amoebic abscesses.
"Sir, I have known more old drunkards than old
doctors." -- Dr. Rabelais
Alcoholic liver disease: Fatty change after a case of beer, alcoholic
hepatitis (Mallory bodies, neutrophils, giant mitochondria, necrosis,
possible portal hypertension and/or liver failure) while on a drunk,
cirrhosis (maybe) after many years of heavy abuse.
Iron overload: Primary hemochromatosis is caused by too much iron being
absorbed by the duodenum, autosomal dominant (one dose, mild) or
recessive (two doses, severe), gene in HLA complex. Secondary
hemochromatosis is from hyperabsorption of iron in hemolyzers, or in
the over-transfused. Problems include liver cirrhosis, heart rhythm
disturbances and cardiomyopathy, "bronze" diabetes, arthritis
(knuckles), lost libido, skin pigment change, hepatocellular carcinoma.
Porphyria cutanea tarda from inhibition of porphyrin synthesis in those
carrying the gene. Treat primary hemochromatosis by phlebotomy.
Wilson's: Autosomal recessive, cannot dispose of copper via the bile.
Copper overload in liver and basal ganglia. Liver failure, mental
changes, hemolysis.
Other liver poisons: Toadstools, halothane, huge doses of acetaminophen
(massive necrosis); old tetracycline (fatty change); isoniazid,
methyldopa, many others (hepatitis).
Reye' syndrome: poorly-understood syndrome, follows viral infection
(especially if aspirin was given) in kids. Cerebral edema, extreme
elevations of serum ammonia, hepatic fatty change and failure; evidence
of generalized mitochondrial failure.
Biliary atresia: Grim birth defect; these kids get transplants.
Neonatal hepatitis: Many causes. Antitrypsin deficiency, CMV, bad
cystic fibrosis, galactosemia, hepatitis A, hepatitis B, herpes
simplex, syphilis, toxoplasmosis, total parenteral nutrition. Look for
giant multinucleated hepatocyte formation.
Liver cell adenomas: Sex hormones (oral contraceptive pill, gym
steroids), prone to rupture.
Hepatocellular carcinoma ("Mickey Mantle's disease"): risk factors are
iron overload, hepatitis B and C, aflatoxin, old radioactive studies
("thorotrast"). Invades portal vein and obstructs it. Hepatocellular
carcinoma is a dominant, non-umbilicated mass in a cirrhotic liver.
Metastatic carcinoma is several umbilicated masses in a non-cirrhotic
liver.
Hepatic angiosarcoma: Vinyl chloride exposure in industry.
Cholangiocarcinoma: cancer of biliary ducts, always a desmoplastic
adenocarcinoma. Klatskin tumor plugs the junction of the hepatic
ducts. Cholestasis.
Gallstones: Don't trust the fat, fair-skinned, fertile, female,
fortyish stereotype, anybody can have them. Cholesterol stones
(yellow) are poorly understood. Bilirubinate stones (black) suggest
ongoing hemolysis. Gallstones cause acute and chronic cholecystitis,
may plug cystic or common bile duct, erode into duodenum ("gallstone
ileus" or at least a fistula), cause gallbladder cancer.
Courvoisier's law: Obstructive jaundice plus palpable gall bladder:
cancer of the pancreas. Obstructive jaundice plus non-palpable gall
bladder: common duct stone, because the scarred-up gallbladder cannot
expand.
Acute cholecystitis: probable cause is ischemic damage to the mucosa
from gallstones (pressure, straining to push them out); lysolecithin
compounds the damage, bacteria may supervene. Chronic cholecystitis:
hypertrophied muscular wall, pseudodiverticula ("Rokitansky-Aschoff
sinuses").
Acute pancreatitis: Alcohol (reflux of duodenal contents up pancreatic
duct?), common duct stone, trauma; milder in mumps, hyperlipidemia I
and V. Elevated amylase and lipase; fat necrosis, hypocalcemia
(calcification of fat), hemorrhage (elastase). "Chronic pancreatitis":
scarring after acute pancreatitis, pain syndrome from nerve
involvement, pseudocyst formation.
Cancer of the pancreas: Adenocarcinoma. Risk factors include cigarette
smoking, maybe chemicals (garage mechanics). Back pain, jaundice,
weight loss, depression, diabetes (amylin production by the tumor),
Trousseau's migratory thrombophlebitis; Whipple procedure (your only
chance for a cure) and death.
Diabetes mellitus (MELL-uh-tuss, please): Systemic problems from
glucose intolerance. Type I primary diabetes: autoimmune destruction
of the islets by antibody-influenced T-cell mediated cytotoxicity;
strikes at random. Type II primary diabetes: insulin resistance plus
disordered insulin secretion; genetically programmed disease modifiable
by lifestyle (known genetic synromes include maturity-onset diabetes of
the young, which is mutant glucokinase, and some others). Secondary
diabetes: from some other obvious disease, like Cushingism, cancer of
the pancreas, hemochromatosis, acromegaly, severe pancreatitis damage.
Gestational diabetes is a special case. The ultimate trivia question:
eosinophils abound in the island of Langerhans in the children of
diabetic mothers.
Complications of diabetes: (1) ketoacidosis (mostly type I's), with
osmotic diuresis from high glucose and ketone levels; (2) hyperosmolar
nonketotic coma (mostly type II's, insulin reserve gives up and massive
hyperglycemia causes diuresis); (3) accelerated atherosclerosis
(stroke, gangrene, heart attack); (4) microvascular disease (hyaline
arteriolar sclerosis, makes gangrene worse); (5) liability to bacterial
infections (neutrophils slow down in hyperglycemia); (6) neuropathy:
from accumulation of sorbitol, pain and dysautonomia; (7) retinopathy
(microaneurysm, exudates, bleeds, later proliferation of vessels and
blindness); (8) sorbitol cataract; (9) nephropathy
("glomerulosclerosis", thick glomerular basement membrane, nodular
Kimmelstiel-Wilson disease, kidney infections); (10) reduced capillary
lipoprotein lipase, which is insulin-dependent; this raises
lipoproteins. Non-enzymatic glycosylation of proteins (as with HgbA1c)
is important in most of these.
Hypoglycemia: post-prandial "hypoglycemia" is really due to an overly
brisk epinephrine response. Fasting hypoglycemia is suspicious for
insulinoma; also consider addisonism, von Gierke's, secret insulin
injection, some others. Glucagonoma: dermatitis, glossitis, diabetes.
VIPoma (vasoactive intestinal peptide): Pancreatic cholera.
Gastrinoma: Zollinger-Ellison ulcers.
Kidney is my favorite area and I'll restrain myself. The seven renal
syndromes:
1. NEPHRITIC SYNDROME. An inflamed glomerulus. Hematuria, oliguria,
hypertension, mild edema, azotemia. Prototype is post-
streptococcal glomerulonephritis, remember also lupus IV.
2. NEPHROTIC SYNDROME. A glomerulus leaking protein. Heavy
proteinuria (selective for albumin, or not), hypoalbuminemia, high
LDL, severe edema, fatty casts in urine. Causes are foot process
disease (i.e., minimal change disease = nil disease = lipoid
nephrosis, focal-segmental glomerulosclerosis), diabetes,
amyloidosis, membranous glomerulopathy.
3. RAPIDLY-PROGRESSIVE GLOMERULONEPHRITIS. Severely injured
glomeruli leaking fibrin, producing crescents. Nephritic syndrome
becomes renal failure in a few weeks. Goodpasture's, bad immune-
complex disease, Wegener's / polyarteritis.
4. FANCONI SYNDROMES. The proximal tubule is alive but incapable of
reabsorbing some or all of the things it should. You lose things
in the urine. Birth defects, cadmium poisoning, others.
5. LOOP FAILURE. The loop of Henle is damaged, urine cannot be
concentrated, nocturia.
6. ACUTE TUBULAR NECROSIS: Dead tubules (mostly proximal tubule).
Seen in shock, poisoning (drugs, remember the aminoglycosides and
the NSAID family), pigment (hemoglobin or myoglobin free in
bloodstream). Dead cells plug the tubules, glomerular filtrate
leaks back. Oliguria, isosthenuria, azotemia. Recovery passes
through a diuretic phase, with intact tubules (i.e., no backleak)
unable to function (i.e., no reabsorption of glomerular filtrate).

7. RENOVASCULAR HYPERTENSION: Narrowed arteries cause ischemia of the

glomeruli, leading to renin release and hypertension. A vicious
cycle; all hypertension damages and narrows the small renal
arteries. "Goldblatt hypertension".

Azotemia: high BUN and creatinine. Uremia: symptomatic kidney failure.

Volume overload, hypertension, heart failure, pulmonary edema,
metabolic acidosis (sulfate, phosphate), calcium problems (cannot
active vitamin D), phosphate retention, metastatic calcification,
secondary hyperparathyroidism, osteomalacia, fibrinous pericarditis,
platelet failure, mild anemia (no erythropoietin), nausea and vomiting,
GI bleeds, pruritus, uremic frost (urea crystals), yellow color,
peripheral neuropathy, amyloidosis H, general unhappiness.
Cystic renal dysplasia: failure of drainage during intrauterine life,
fibrous tissue, tubules, and cartilage.
Autosomal recessive polycystic kidney: babies, cysts like daisy petals;
uremia.
Autosomal dominant polycystic kidney: football-sized kidneys, masses of
cysts like grapes; hypertension progressing to renal failure in later
life.
Medullary sponge kidney: small cysts, place for kidney stones to form.
End-stage kidney ("acquired dialysis cystic disease"): shrivelled
kidney, breeding-ground for renal cell carcinoma.
Hemolytic-uremic syndrome: When the cause is known, it's verocytotoxin
from E. coli or Shigella ("Jack in the Box" undercooked hamburgers);
endothelial cell damage with accumulation of platelet debris, plugging
glomeruli and disrupting red cells.
Acute pyelonephritis usually from E. coli swimming up from the bladder.
Honeymoon cystitis, stones, diabetes, pregnancy, reflux.
Chronic pyelonephritis: scar contraction, tubular atrophy,
"thyroidization".
Papillary necrosis: Phenacetin abuse, sicklers, diabetes.
Urate nephropathy: Tubular failure in gout. Oxalate nephropathy:
Tubular failure in vitamin C abuse or antifreeze drinking. Myeloma
kidney: Bence-Jones protein plugs tubules.
"Benign essential high blood pressure": variable mix of overworking
heart, excess renal sodium retention, inappropriate vasoconstriction.
Still mysterious, but causes encephalopathy (seizures, headache), heart
failure, hyaline arteriolar sclerosis, intimal fibrosis, accelerated
atherosclerosis, brain hemorrhages. "Malignant hypertension":
hypertension from any cause leading to vascular necrosis, worse
hypertension, and rapid death; heralded by papilledema.
Endocrine secondary hypertension: Cushingism, Conn's, salt-retaining
adrenal hyperplasia, pheochromocytoma, reninoma, hypercalcemia
(constricts vessels), licorice abuse (inhibits 11-beta hydroxylase);
diabetes contributes.
Poorly-perfused kidney causing hypertension: most renal diseases,
coarctation of the aorta, stenotic renal artery from atherosclerosis or
other disease.
Widened pulse pressure: Stiff aorta (atherosclerosis, Monckeberg's),
aortic valve insufficiency,
Hydronephrosis: dilated renal pelvis from any cause.
Kidney stones: Most are calcium oxalate, i.e., somebody who absorbs too
much calcium via the gut and/or drinks too little water. Cystine
stones: hereditary inability of the proximal tubule to resorb cystine
properly; hexagons in the urine. Magnesium ammonium phosphate stones:
Proteus infection, coffin-lid crystals in the urine.
Nephrogenic diabetes insipidus: Inability of the collecting duct to
respond to hADH. Pseudohypoparathyroidism: inability of the proximal
tubule to respond to parathyroid hormone.
Casts are kidney boogers. Hyaline casts mean nothing. Red cell cast
mean glomerulonephritis. White cell casts mean pyelonephritis.
NOTE: Do not worry right now about changes in blood chemistry (blood
urea nitrogen, creatinine, creatinine clearance, etc.). Except for
glycosuria, hematuria, proteinuria, pyuria, and casts, do not worry at
all about other abnormalities found on urinalysis. You will learn
about these soon enough.
Vocabulary
One thing that makes kidney pathology so hard is that many of the words
sound alike. Here are the most troublesome words:
Collagenized glomeruli: These glomeruli have been obliterated by dense
type I collagen. Most often, the collagen has been laid down
concentrically on Bowman's capsule, as in longstanding
arterial/arteriolar disease. Collagenized glomeruli are more often
called hyalinized or obsolescent, despite the fact that these terms are
less specific.
Diffuse: As applied to glomerular disease, all the glomeruli are
involved.
Fibrosis: Dense, type I collagen deposited in the glomeruli and/or
interstitium and/or vessels.
Focal: As applied to glomerular disease, some glomeruli are involved
and some are not.
Global: As applied to glomerular disease, if a glomerulus is involved,
all portions of it are involved.
Glomerulonephritis: As usually used, this implies that the glomeruli
are sufficiently inflamed to cause at least a few of them to lose blood
into the tubules.
("Glomerulonephritis" without nephritic syndrome -- i.e.,
"membranous glomerulonephritis", "minimal-change
glomerulonephritis", etc. -- is a less-common usage. Better to
call these "glomerulopathy".)
Glomerulopathy: Any primary problem with the glomeruli.
Glomerulosclerosis, diffuse: Thickening of the basement membrane as a
result of diabetes mellitus.
Glomerulosclerosis, focal/segmental: A pattern of injury with foot
process fusion and hyalinization of some lobules in some glomeruli. It
has nothing to do with diabetes mellitus.
Glomerulosclerosis, nodular: Diabetes mellitus with Kimmelstiel-Wilson
disease. Always superimposed on diffuse glomerulosclerosis.
*Hyalinosis: A distinctive, homogeneous pink blob seen in certain sick
glomeruli, notably those damaged by FSGS, diabetes, or other causes of
hyperfiltration.
Hyalinized glomeruli: A term which can mean collagenized or sclerotic
glomeruli.
Hypernephroma: Obsolete term for renal cell carcinoma.
Nephritis: Used by itself, this means "glomerulonephritis".
Nephritis, interstitial: Inflammation of the kidney that spares the
glomeruli. Includes cases formerly diagnosed as "chronic
pyelonephritis". Causes U-shaped cortical scars.
Nephroblastoma: The common childhood cancer of the kidney -- Wilms
tumor.
Nephrocalcinosis: Calcification of the basement membranes of the
tubules in the medullae. It has nothing to do with calcium stones. A
little calcification here is common, especially in older people.
Extensive calcification suggests hypercalcemia ("metastatic
calcification").
Nephrolithiasis: Stones (calculi) in the pelvis of a kidney
Nephropathy: Anything wrong with the kidney -- glomeruli, tubules, or
vessels.
Nephrotic syndrome: The sequelae of heavy protein leakage at the
glomerular capillaries.
Nephrosclerosis: Disease of the renal arteries and/or arterioles.
Nephrosclerosis, arterial: Multiple small infarcts destroying scattered
groups of glomeruli. Causes V-shaped cortical scars. Usually caused
by atheroembolization.
Nephrosclerosis, arteriolar: Vascular disease that destroys scattered
individual nephrons. Causes sandpaper-surface kidney. "Benign
nephrosclerosis". Caused by high blood pressure and/or diabetes.
Nephrosclerosis, benign: Arteriolar nephrosclerosis due to "benign
essential hypertension".
Obsolescent glomeruli: Another term which can mean collagenized or
sclerotic glomeruli.
Pyelonephritis: Inflammation of the interstitium of the kidney.
Current usage mostly limits this to bacterial infection.
Sclerosis: As applied to kidney, this means increased basement
membrane/mesangial matrix material obliterating loops of a glomerulus.
Sclerotic glomeruli: These glomeruli are fully replaced by basement
membrane/mesangial matrix material, as in advanced diffuse, nodular, or
focal-segmental glomerulosclerosis. They are also called hyalinized or
obsolescent.
Segmental: As applied to glomerular disease, some portions of some
glomeruli are involved and some other portions of the same glomeruli
are spared.
Here is a list of the more important entities that are likely to be
associated with a particular pattern; if you didn't learn them then...
Subepithelial, large, irregularly-spaced ("coarse granules")
Diffuse proliferative GN (especially post-streptococcal)
Mesangiocapillary (membranoproliferative) GN type I (tramtracks)
Lupus, class IV
Subepithelial, uniform, evenly-spaced ("fine granules evenly spaced")
Membranous glomerulopathy (any cause) Lupus, class V
Anti-GBM diseases ("smooth linear" -- don't expect to see these on EM)
Goodpasture's, others
Subendothelial (various descriptions, you will only need to recognize
on EM)
Mesangiocapillary (membranoproliferative) GN type I (tramtracks)
Lupus, especially class IV ("wire loops")
Cryoglobulinemia
Hemolytic-uremic syndrome ("fluff")
Also look here for amyloid deposits.
Intramembranous (various descriptions, depends on the disease)
Dense deposit disease (mesangiocapillary GN type II)
Late membranous glomerulopathy
Late stages of any other progressive immune complex disease
Mesangial ("mesangial pattern")
 IgA nephropathy
IgM mesangial-proliferative glomerulopathy
* Mesangiocapillary (membranoproliferative) GN type I
Lupus, any class
Also look here for amyloid deposits.
Renal cell carcinoma: Common kidney cancer, "hypernephroma", "Grawitz
tumor", 3p deletion, failed kidney, von Hippel Lindau and smoking are
risk factors, yellow mass, cells rich in lipid and glycogen, invades
renal vein and vena cava.
Wilms tumor: Pediatric tumor of primitive kidney, mixed carcinoma-
sarcoma histology is common, syndrome with aniridia and
hemihypertrophy; good response to chemotherapy.
Angiomyolipoma of the kidney is a tuberous sclerosis hamartoma;
transitional cell carcinoma mirrors common bladder cancer.
Exstrophy of the bladder: failure of the symphysis to close; runs with
epispadias. Persistent urachus: urine out the navel. Cystocele:
drooping bladder, as after childbirth. Hypertrophy of bladder wall:
from obstruction, usually prostatism. Bladder diverticula: usually
from mucosa going between bands of hypertrophied muscle. Bladder
stones: usually magnesium ammonium phosphate, from proteus infection.
Cystitis: Young women (short urethra, intercourse, etc.), older men
(prostatism). Cyclophosphamide, Hunner's idiopathic interstitial
ulcerative cystitis, and radiation are other causes of inflamed
bladder. Squamous metaplasia: schistosoma hematobium.
Hyperplasia of transitional epithelium: More than eight nuclear
layers. Papillomas: benign seaweed-like tumors. Transitional cell
carcinoma: the common bladder cancer; risks are smoking, aniline dye
exposure, phenacetin abuse, cyclophosphamide exposure. Adenocarcinoma:
from urachal remnants. Squamous cell carcinoma: schistosomiasis.
I used to pray, "Lord, give me chastity, but not
yet." -- St. Augustine, Confessions
While you are away, movie stars are taking your
women. Robert Redford is dating your girlfriend.
Tom Selleck is kissing your lady. Bart Simpson is
making love to your wife.
-- "Baghdad Betty", Iraqui disk jockey,
during the Gulf War
Hypospadias: urethral opening somewhere short of the end of the glans.
Epispadias: urethral opening on the dorsum of the penis, more serious.
Phimosis: tight foreskin. Balanoposthitis: dirty infected glans from
tight foreskin. Paraphimosis: foreskin is retracted, flips back and
gets stuck. Priapism: persistent, non-pleasurable erection, usually
from blockage of corpora veins, as in sicklers. Peyronie's: mysterious
fibrosing process causing curved erection. Urethritis is gonococcal,
chlamydial, mycoplasma, Mexican peppers. Lymphogranuloma venereum:
wicked chlamydia producing watering-can perineum, ask about a Frei skin
test. Gonorrhea's probably meaner because it produces an IgA-
destroying enzyme. Reiter's: usually chlamydial urethritis which gives
rise (somehow) to arthritis, conjunctivitis, horny rash on glans, palms
and soles, low back pain in HLA-B27 men. Cancer of the penis: HPV-
related, almost all are uncircumcised. Erythroplasia and Bowen's:
premalignant. Cryptorchidism: nobody knows why they fail to descend;
high rate of malignant change, risk of torsion, infertility. Torsion
of testis: cremaster spasm leads to venous infarct. TB, gonorrhea,
chlamydia: epididymitis; syphilis, mumps: orchitis. Hydrocele: fluid
in the tunica vaginalis. Varicocele: varicose veins in the pampiniform
plexus.
Germ cell tumors are often mixed. Seminoma: fried egg cells,
lymphocyte, excellent response to radiation or chemotherapy. Embryonal
cell carcinoma: anaplastic carcinoma, alpha-fetoprotein.
Choriocarcinoma: hCG, very malignant, mix of malignant cytotrophoblast
and malignant syncytiotrophoblast.
Prostatitis: gonorrhea, common bacteria, trichomonas, chlamydia.
Prostatic hyperplasia ("benign prostate hypertrophy"): mysterious
process that all intact, surviving men get sooner or later; heroic
abstinence is a risk factor. Hyperplasia of glands and stroma
especially periurethral; obstruction causes difficulty with urination,
frequency, urgency, dysuria, residual volume, infection, renal
shutdown. Every man is sitting on a time bomb #1.
Prostate adenocarcinoma: Common prostate cancer. Risk factors include
cadmium exposure. "Most commonly starts in posterior lobe", i.e.,
probably because that's where the doctor feels it first. Markers:
prostatic acid phosphatase, prostate-specific antigen. Treatment
includes hormonal manipulations.
"If I were asked to what the singular prosperity
and growing strength of [the Americans] ought
mainly to be attributed, I should reply, "To the
superiority of their women".
-- Alexis de Tocqueville 1789
"Not from Adam's brain, to have the same mind as
him, nor from Adam's foot, to be subordinate to
him, but from the rib next to Adam's heart, to love
and be loved by him."
-- Anonymous
Vulvar dystrophy includes lichen sclerosus (mysterious atrophy of the
mucosa over dense collagen; male counterpart is balanitis xerotica) and
squamous hyperplasia-dysplasia (mysterious, some malignant potential,
non-HPV-related); both are leukoplakias.
Bartholin duct abscess: think gonorrhea. Bartholin cyst: medial to
labia minora. Gartner's duct cyst (mesonephric cysts): Wolffian duct
remnants along anterolateral vagina.
Vulvar squamous carcinoma arises in HPV (strains 16, 18, 31), or
hyperplastic vulvar dystrophy. Vulvar adenocarcinoma may present as
extramammary Paget's, with adenocarcinoma cells invading the epidermis.
Melanoma.
Vaginal adenosis: from high estrogen exposure (i.e.,
diethylstilbestrol) before birth. A small percentage of these people
get clear-cell adenocarcinoma of the vagina.
Sarcoma botryoides: embryonal rhabdomyosarcoma of childrens' vaginas.
Pap smear: parabasal cells indicate no estrogen or progesterone effect
(think post-menopausal woman); superficial squamous cells indicate
estrogen effect (if predominant, think of Stein-Leventhal, anovulatory
cycles, estrogen-secreting tumor), intermediate squamous cells indicate
progesterone effect (if predominant, think of prepubertal child,
pregnant woman). A normal, non-pregnant woman has a mix depending on
the stage of her cycle.
Cervicitis: gonorrhea, chlamydia, herpes, trauma, intrauterine device,
streptococcus B after childbirth.
Transformation zone of cervix, i.e., squamo-columnar junction, is site
where dysplasias and cancers arise. Finding HPV: colposcopy with
acetic acid ("acetowhite"), look for koilocytes (clear halo around
wrinkled-raisin nucleus) on pap smear. Most cancers here are squamous,
and most are caused by HPV. First symptoms: bleeding on intercourse.
I can't review the anatomy, histology, or physiology of menstruation
and pregnancy. Menorrhagia: periods too heavy (>80 mL) or too long,
metrorrhagia: bleeding at irregular intervals. Dysfunctional uterine
bleeding: abnormal bleeding with no anatomic cause; think of
anovulatory cycles (follicle never ruptures but keeps making estrogen),
persistent luteal phase (i.e., the corpus luteum fails to involute),
inadequate luteal phase (i.e., corpus luteum fails to form.)
Stein-Leventhal: secondary amenorrhea, hirsutism, insulin resistance,
often obesity); ovaries with thick capsules, high LH, low FSH.
Acute endometritis: post-partum, polys, from common bacteria. Chronic
endometritis: plasma cells in endometrium; think of chlamydia,
gonorrhea, TB, intrauterine device.
Endometrial polyps: mutant areas, may be hyperplasia ("cystic") and/or
responsive to estrogen but not progesterone; tend to slough
irregularly. Endocervical polyps: similar, hang out cervix and present
route of infection.
Cystic hyperplasia of endometrium: big, dilated, busy-looking glands
(swiss cheese). Adenomatous hyperplasia: folded, benign glands.
Atypical hyperplasia: anaplasia, crowding, cancer risk.
Asherman's syndrome: endometrial cavity scarred shut after dilatation
and curettage (diagnosis, legal abortion).
Adenomyosis: outpouching of endometrium into the myometrial wall.
Endometriosis: functioning endometrium outside the uterine cavity;
bleed during menstruation. Chocolate cst of the ovary, dyspareunia
from uterine ligament involvement, blood in the pouch of Douglas, low
back pain, pain on defection, bowel obstruction, infertility. To
diagnose, must see two of these: glands, stroma, hemosiderin.
Leiomyomas ("fibroids"): tough, white, watered-silk look; subserosals
cause bleeding and infertility, numerous or large make pregnancy and
delivery difficult.
Endometrial adenocarcinoma: risk factors are high unopposed estrogen
(thecoma, replacement, anovulatory cycles), obesity, diabetes,
hypertension, never pregnant, tamoxifen. More common in older woman.
Postmenopausal bleeding.
"Pelvic inflammatory disease": gonorrhea, chlamydia, sometimes other
infections involving and damaging the oviducts. Increased risk for
infertility, faulty implantation (i.e., ectopic pregnancy).
Placenta over the os during childbirth: placenta previa (bleeds).
Placenta detaches from the wall prematurely: abruption (catastrophe).
Ectopic pregnancy: becoming more common; the more prevalent gonorrhea
is, the more prevalent are ectopic pregnancies.
Ovarian cysts: non-neoplastic, poorly-understood, may arise from
follicles, corpus luteum, or who knows.
Ovarian tumors fall in three groups, and tend to be mixtures of the
types within one group.
Coelomic:
Serous (mostly malignant; papillary, cilia, psammoma bodies,
common ovary cancer, often bilateral, recapitulates oviduct)
Mucinous (mostly benign, usually unilateral, recapitulates
endocervix, can be huge)
Clear-cell (malignant, resembles kidney cancer)
Brenner (mostly benign, resembles transitional cells in balls in a
dense stroma)
Endometrioid (malignant, same risk factors and histology as
endometrial adenocarcinoma)
Coelomic cancers tend to spread over the peritoneal surface, and
be positive for CA-125 in blood.
Sex-cord / stromal:
Fibroma (twisted, with ascites and pleural effusion: Meig's)
Thecoma (mostly benign, often estrogen-producers)
Granulosa cell tumor (low-grade cancer, simulate the cells that
encase the egg, Call-Exner bodies, coffee-bean nuclei)
Arrhenoblastoma (Sertoli-Leydig tumor, often testosterone-
producing; Reinke crystalloids are marker for Leydig cells)
Germ cell:
Choriocarcinoma
Dysgerminoma (counterpart of male seminoma)
Teratoma (common, "dermoid cyst", teeth, 3 germ layers, etc.; may
have preponderance of thyroid, or carcinoid, or squamous cell
carcinoma)
Twins: if there is a single amnionic sac, or the amnionic sacs are
fused without a layer of chorion between, the twins must be identical.
If the placentas are separate, or if there is a layer of chorion
between the amniotic sacs, then you cannot tell.
Chorioamnionitis may cause, or result from, premature rupture of the
membranes. Strep B.
Pre-eclampsia and eclampsia (both "toxemia of pregnancy") are poorly-
understood; probably a vicious cycle between narrowing of the spiral
arteries of the uterus and production of vasoconstrictors / production
of endothelial poisons / non-production of vasodilators (nitric oxide,
prostaglandin G) by the placenta. Patients have hypertension, edema,
and proteinuria and eventually azotemia; eclampsia is the development
of seizures. Toxemia of pregnancy is more common in first pregnancies,
twins, hydatidiform mole.
Gestational trophoblastic disease: hydatidiform mole, invasive mole,
choriocarcinoma. All are baby's cells, i.e., some of dad's genes.
According to some, a complete mole is all Dad's chromosomes (usually
XX, sometimes XY, two sperms, and Mom's chromosomes are deleted); in
partial mole, there's trisomy.
Hydatidiform mole: very common in Asia (1/100), rare in the U.S.
(1/2000); edematous ("hydropic") villi look like grapes; excess hCG
production.
"Invasive mole" can invade and metastasize, but bears villi; officially
"benign", I've never understood why; this entity is falling out of
fashion.
Choriocarcinoma: 1/2 arise from hydatidiform moles, 1/4 from abortions,
1/4 from normal pregnancies. No villi, but lots of syncytiotrophoblast
and cytotrophoblast. Lots of metastases, chemotherapy cure is usual.
"Hirsutism": terminal (big thick) hairs on androgen-sensitive areas,
more than most folks of your gender. "Virilization": a woman has an
enlarged clitoris, and perhaps also temporal balding (all men lose
their temple hair around age 20), muscles, deep voice, increased
libido. "Hypertrichosis": increased fine hair, as in porphyria,
anorexia nervosa, phenytoin therapy, diazoxide, minoxidil.
Breast development.... Estrogen: Ducts. Progesterone: Lobules. Milk
production: Prolactin / placental lactogen. Milk comes down: Oxytocin.
"Fibrocystic disease" affects all women if you look hard enough. Cysts
("blue dome"), fibrosis, epithelial hyperplasia, papillae, sclerosing
adenosis; tenderness before periods; malignant potential only if
epithelial hyperplasia is "atypical".
Fibroadenomas: Common, banal, benign tumor of younger women. Phyllodes
tumor ("cystosarcoma") is a fibroadenoma with an atypical stroma and
some potential to metastasize as sarcoma.
Acute mastitis: staph abscess acquired during lactation.
(Non-enzymatic) fat necrosis: considered "mysterious", probably results
from wife-beating and girlfriend-beating. Tends to calcify.
Plasma cell mastitis: near nipple, cheesy material in ducts, benign.
Blood from the nipple: usually intraductal papilloma has twisted and
infarcted itself. Galactorrhea: prolactinoma, dopamine blockers
(phenothiazine, methyldopa).
Risk factors for breast cancer: Previous cancer in other breast, family
history (especially BRCA1, BCRA2, retinoblastoma family), radiation,
atypical ductal hyperplasia, atypical lobular hyperplasia. In the poor
nations, women who are pregnant much or most of their reproductive
lives do not get breast cancer; translating this effect to the U.S.
(early menarche, late menopause, nulliparity) has yielded conflicting
results. The "legal abortion" and "high-fat low-fiber" diet haven't
held up last time I did my reading.
Infiltrating ductal carcinoma (75% of breast cancers): scirrhous
(desmoplasia, Indian-files), medullary (many lymphocytes), colloid
(mucin lakes), tubular (well-differentiated, good prognosis),
inflammatory (plugged lymphatics, raging-red breast, terrible
prognosis).
Intraductal carcinoma: cribriform (swiss cheese), and squeeze-the-
blackheads (comedocarcinoma); better prognosis. Paget's of breast:
cancer cells growing from duct into epidermis of nipple, producing a
red "eczematous" rash.
Lobular carcinoma: more desmoplasia and Indian-files circling the
lobules, tends to be bilateral; "lobular carcinoma-in-situ" is cells
filling the lobules.
Prognostication: Most important is presence or absence of axillary
metastases; next is size of primary. After this, presence of c-erb2
(neu, HER-2) is bad, aneuploid is bad, no estrogen receptors is bad, no
progesterone receptors is bad.
Gynecomastia: breast duct development in a man. XXY, cirrhosis, guy at
puberty, malnutrition, testicular tumors (extra hCG from
choriocarcinoma or seminoma, estrogen from Leydigoma), spironolactone,
cimetidine, flutamide.
"No one is born wise."
-- Ptahhotpe, c. 2350 B.C.
Hypopituitarism ("Simmond's disease"): loss of some of the anterior
pituitary hormones. Panhypopituitarism: loss of most or all of them.
Pituitary adenomas: Only known risk factor is MEN-I. Some feedback
control. Endocrine problems, visual problems (chiasm compression
causes bitemporal hemianopsia), enlarged sella on x-ray, less often
signs of increased intracranial pressure (headache, nausea, vomiting).
Acidophil adenomas: growth hormone, prolactin. Basophil adenomas:
ACTH, gonadotropin. Chromophobe adenomas: usually prolactin. These
distinctions are unreliable.
Prolactinoma: lost libido; galactorrhea-amenorrhea in women; obesity.
Growth hormone: gigantism before the epiphyses close, acromegaly after;
glucose intolerance. Acromegalics suffer joint problems, precocious
atherosclerosis, diabetes, neuropathy, myopathy; spot them by huge jaw
(prognathism), oily skin, deep voice, frontal bossing, spade fingers.
ACTH: Cushing's disease (definition).
Gonadotropin: usually silent (secret: most "non-secreting pituitary
adenomas" produce gonadotropins).
TSH: Secondary hyperthyroidism, rare.
Empty sella: infarcted pituitary gland, necrotic adenoma, post-surgery,
arachnoid herniated downward compressing the gland.
Panhypopituitarism: Loss of growth hormone makes kids short, adults
atrophy. Loss of gonadotropins remove sexual features. Loss of TSH
produces secondary hypothyroidism. Loss of ACTH produces secondary
adrenal insufficiency. If the posterior pituitary is lost, diabetes
insipidus.
Causes of hypopituitarism: Sheehan's (necrosis of pituitary during
post-partum shock), empty-sella syndromes, pituitary adenoma, surgery,
radiation, trauma, rarely autoimmunity.
Pituitary dwarfism (miniature adults): "Idiopathic dwarfs" often had
obstetrical mishaps with possible damage to pituitary stalk; Laron
dwarves have defective growth hormone receptors; pygmies have a
different kind of tissue resistance; other dwarfs lack somatomedin;
some just-plain-short folks have mild growth hormone receptor defects.
Craniopharyngioma: benign tumor in a bad place, Rathke's pouch
remnants, recapitulates tooth, machine-oil cysts, keratin, calcium.
Froehlich's syndrome: the fat, simple boy in gym class who didn't get
his pubic hair. Hypothalamic problem of some kind; several syndrome
are known.
McCune-Albright: polyostotic fibrous dysplasia of bone, cafe-au-lait
spots with rough edges, precocious puberty, other gland problems, no
two cases the same. Post-zygotic mutation causes growth signals (cGMP)
to be translated into make-hormone signals (cAMP).
Thyroglossal duct cysts mark the track of the gland's descent from the
back of the tongue. Goiter: any large thyroid, also "struma".
Hyperthyroidism: Hypermetabolism, excess heat production, increased
appetite, diarrhea, hyperdynamic heart, uncoupling of oxidative
phosphorylation, enhanced epinephrine effect, lid lag, atrial
fibrillation, cardiomyopathy, osteoporosis, low LDL, fine tremor.
Primary hyperthyroidism: Gland makes too much thyroxine and/or tri-
iodothyronine (Graves', hot Hashimoto's, hot "Plummer's" adenoma, Jod-
Basedow; rarely thyroid follicular carcinoma, autonomous struma
ovarii). Secondary hyperthyroidism: TSH-oma of the pituitary, "TSH"-
production by choriocarcinoma, rare. Tertiary hyperparathyroidism:
TRH-producing tumor, rare. Remember factitious hyperthyroidism.
Jod-Basedow: hyperthyroidism from sudden administration of iodine to an
iodine-starved goiter.
Cretinism: Hypothyroidism affecting the unborn child or baby.
Inexcusable unless the cause is lack of thyroid receptors. Other
causes include maternal hypothyroidism (especially iodine deficiency,
epidemic in Communist boondocks and among most "indigenous peoples"
living away from the ocean), problems synthesizing thyroxine (chemical,
or failure of the gland to form; become symptomatic after birth, which
is why we screen by TSH levels). Cretins may be myxedematous, or just
remain childlike.
Hypothyroidism: Slowing of mind and body, constipation, cold skin,
obesity, coarse voice, myxedema (increased ground substance), insanity,
"depression", coarse facial features, big tongue, high LDL,
atherosclerosis, hypercarotenemia with yellow skin, cold intolerance,
delayed "hung" deep tendon reflexes, dry skin, coarse and brittle hair.
Primary hypothyroidism: Thyroid cannot make the hormone despite lots of
TSH (iodine deficient, gland never formed, biochemistry problems, gland
was removed, gland was radiated, Hashimoto's, occasional DeQuervain's,
TSH-receptor-blocking autoantibodies, goitrogens). Secondary
hypothyroidism: Pituitary failure. Tertiary hypothyroidism:
Hypothalamic failure.
Hashimoto's thyroiditis: Antibody-related T-cell-mediated havoc in the
thyroid. Goiter with lots of lymphocytes, germinal centers, epithelial
cells packed with mitochondria. Breeding-ground for thyroid lymphoma.
Commonest cause of acquired hypothyroidism in adults. Many have
concurrent autoimmune addisonism and/or type I diabetes and/or
pernicious anemia. A forme-fruste (?) is lymphocytic thyroiditis,
common in Down's and sporadically.
DeQuervain's subacute granulomatous thyroiditis: some virus attacks the
thyroid epithelium, and there's a brisk foreign-body reaction to the
thyroglobulin colloid. Common, passes in a few weeks; may render you
temporarily hyperthyroid or hyothyroid.
Riedel's struma: A fibrous "woody" proliferation mimicking sarcoma.
Graves' disease ("diffuse toxic goiter"): Stimulatory autoantibodies
against the TSH receptor; nobody knows why extra ground substance
accumulates behind the eyes ("ophthalmopathy") or on the shins
("pretibial myxedema").
"Diffuse nontoxic goiter": Common, usually idiopathic. Most patients
remain euthyroid though the gland may be huge and/or turn multinodular.
Mutations are present but there's little or no extra cancer-potential.
Thyroid adenomas: Most are non-functioning and "just happen". Hot ones
may produce hyperthyroidism (T4, T3).
Papillary adenocarcinoma of the thyroid: "Orphan Annie's tumor". Young
women, slow-grower, seldom kills, "Orphan Annie eye" nuclei, psammoma
bodies (sand-like, Orphan Annie's dog is named Sandy).
Follicular adenocarcinoma of the thyroid: More aggressive, tendency to
invade veins and metastasize to lungs; takes up iodine, thyroglobulin a
tumor marker.
Medullary carcinoma of the thyroid: from C-cells, produces calcitonin,
which is beta-pleated to amyloid in the stroma. Seldom lowers blood
calcium, but may produce ACTH or VIP.
Anaplastic carcinoma of the thyroid: arises in a papillary or
follicular carcinoma, dismal prognosis.
Adrenal cortex layers: Salt sugar and sex. The deeper you go, the
sweeter it gets.
Addisonism now means chronic primary hypoadrenocorticism regardless of
cause (Dr. Addison's had bovine TB, most common nowadays are iatrogenic
and autoimmune). Also remember leprosy, TB, CMV in AIDS, amyloid,
hemochromatosis, metastatic lung cancer, adrenal leukodystrophy
("Lorenzo's oil").
Autoimmune addisonism (Jack Kennedy's disease) is antibody-related T-
cell attack on the adrenal cortex; antigen is 21-hydroxylase. Runs
with Hashimoto's, pernicious anemia, and type I diabetes.
Chronic hypoadrenocorticism: weakness, hyperkalemia, hypoglycemia,
nausea, weight loss, hypotension, sudden death. If the problems is
primary in the adrenal, excess ACTH will turn the skin brown.
Acute hypoadrenocorticism: meningococcemia, stressing an Addison's
patient, rapid withdrawal of glucocorticoids, Waterhouse-Friderichsen,
sudden death.
Cushing's syndrome: Iatrogenic (most common), Cushing's disease (ACTH-
oma), ACTH-producing cancer (oat cell, carcinoid, medullary carcinoma
of thyroid), autonomous cortisol-producing adrenal adenoma, a few
obscure entities.
Cushing's folks: truncal obesity, buffalo hump, increased appetite,
insomnia, mental changes, thinning of dermis, fragile vessels,
diabetes, red round face, hypertension, hypokalemia, osteoporosis,
acne, cellulitis, hirsutism, oligomenorrhea, muscle wasting, ringworm.
Nelson's syndrome: After removing the hyperplastic adrenals in someone
with an ACTH-producing pituitary adenoma, the adenoma becomes huge and
blinds the person in short order.
Primary hyperaldosteronism: Conn's, from an autonomous adenoma or
"mysterious hyperplasia of the zona glomerulosa". Hypertensives with
hypokalemia before you start a diuretic. Since atrial natriuretic
peptide overrides aldosterone in regulating total body water, these
patients do not have edema (for that matter, neither do patients with
syndrome of inappropriate ADH). Glucocorticoid-correctable Conn's
results from a chimeric gene that makes aldosterone in large quantities
when stimulated by ACTH.
Secondary hyperaldosteronism: Any time you have low effective
circulating volume. Seen in CHF, nephrotic syndrome, cirrhosis,
Goldblatt hypertension.
Congenital adrenal hyperplasia: Six enzyme deficiencies, any one of
which cause difficulty making cortisol, resulting in lots of ACTH, and
shunting of steroids into the male-hormone pathways. 21-hydroxylase
deficiency: excess male hormones, salt-waster. 11-hydroxylase
deficiency: excess male hormones, salt-retainer (deoxycorticosterone is
a potent mineralocorticoid). Ambiguous genitalia in girls, or
hirsutism in women, depending on severity. Infant Hercules in boys.
Adrenal cortical carcinoma: Usually makes a mix of unpleasant hormones,
bad prognosis.
Pheochromocytoma ("chromaffinoma"): 10% bilateral, 10% metastasize, 10%
familial (i.e., MEN-II, neurofibromatosis). Very vascular, produce
epinephrine, norepinephrine, or both. Headache, hypertension, "panic
attacks"; screening tests include vanillyl-mandelic acid (VMA),
metanephrines, more.
Neuroblastoma: pediatric tumor, present in one baby in 50; most regress
spontaneously. Tumor of small blue cells, look for rosettes (attempts
at neural tubes). Cures with chemotherapy in many, but not all, cases.
Likely to suddenly mature into ganglioneuromas. Older age, bone
involvement, myc-gene amplification are ominous. Marker: homovanillic
acid (HVA).
Parathyroids: Most folks have somewhere around four, somewhere around
the neck; anatomy books are idealized.
Primary hyperparathyroidism: usually an adenoma, except in familial
syndromes. Hypercalcemia, hypertension, depression, kidney stones,
pancreatitis, gastric ulcer, bone lesions ("osteitis fibrosa cystica"),
low serum phosphate, high urinary cAMP, high urinary 24-hour calcium
excretion.
To know you have an adenoma rather than hyperplasia, you must find a
normal parathyroid gland (if it were hyperplasia, all would be
hyperplastic).
Secondary hyperparathyroidism: parathyroid glands enlarge because of
phosphate retention by failing kidneys. Normal or low calcium, high
phosphate. Tertiary hyperparathyroidism: Autonomous hyperfunction in
the setting of secondary hyperparathyroidism.
Parathyroid carcinomas are rare and not very aggressive.
Hypoparathyroidism: usually iatrogenic (thyroidectomy mishap), less
often DiGeorge's or autoimmune; hypocalcemia and tetany.
Pseudohypoparathyroidism: defective adenyl cyclase renders proximal
tubule unresponsive to parathyroid hormone, also skeletal
abnormalities. Pseudopseudohypoparathyroidism: the skeletal
abnormalities without the calcium problem.
Thymic hyperplasia: germinal centers in the gland. Thymoma: tumor of
the epithelial cells of the thymus. Think of lupus (hyperplasia),
myasthenia gravis (either), "pure red cell aplasia" (thymoma, i.e.,
something is making normoblasts undergo apoptosis),
hypogammaglobulinemia (thymoma, mysterious).
Pineal: remember that testicular-type tumors are prone to occur here.
Multiple endocrine adenoma (neoplasia) syndromes:
MEA (MEN) I: PPP (Wermer's syndrome)
Parathyroid adenomas, often multiple (rarely hyperplasia)
Pituitary adenoma (anterior)
Pancreatic islet cell adenoma (gastrinoma)

MEA II: PAC (Sipple's syndrome); gene is RET

Parathyroid adenomas (some books still say "hyperplasia" too)
Adrenal medullary tumor (pheochromocytoma) or hyperplasia
Calcitonin-producing hyperplasia-carcinoma of thyroid

MEA III (was IIb):

Similar to MEA II; the patients have Marfanoid body habitus and
mucosal (ganglio)neuromas (bumps on the edges of their tongues and
elsewhere), and are less likely to have parathyroid problems.
Same locus, different allele.
It will be easy to recognize Ed's bleached bones in the desert, since
his are bright, fluorescent yellow from years on tetracycline (acne).
Bone words: (1) Diaphysis: The long shaft, remote from both growth
plates; (2) Epiphysis: Between the growth plate and the nearest joint;
(3) Metaphysis: Between the growth plate and the diaphysis. In kids,
this is where most of the bone growth is taking place, so this is where
most pediatric bone disease (infections, tumors) will occur; (4) woven
bone: crisscross fibers, never normal in an adult; (5) lamellar bone:
parallel fibers.
Osteogenesis imperfecta: problems making collagen. Fractures during
birth, or after; short statue, brittle bones.
Osteopetrosis ("marble bones"): osteoclast failure, bones become
brittle, marrow cavity obliteration leads to pancytopenia. Hereditary
forms with severe skull deformities.
Achondroplasia: Long bones fail to grow; common achondroplastic
dwarfism is caused by lack of fibroblast growth factor receptor 3.
Osteomyelitis: pus-producing infection in the marrow cavity. Bad,
since when the pressure rises, bone infarcts and acts like a foreign
body. Brodie's abscess: hiding place for bacteria after osteomyelitis
is supposedly cured. Pott's disease: TB osteomyelitis, typically of
the spine. Psoas abscess: Think TB.
Osteoporosis: Rarification of cortical and spongy bone, in old age, or
from disuse, cortisol, plasma cell myeloma, prolonged hyperthyroidism,
hypogonadism, anorexia nervosa, prolonged heparin therapy, or being
weightless for months in space. About 75% of the unexplained
variability in osteoporosis from person to person is now known to be
due to variations in the vitamin D receptor (big news).
Osteomalacia: failure of bone to mineralize in an adult.
Trivia... but it makes sense. Where do bone tumors arise?
Diaphysis: enchondromas
some chondrosarcomas, Ewing's, and
eosinophilic granulomas
Epiphysis: chondroblastomas
some giant cell tumors
Metaphysis: all other primary bone tumors
Osteomas arise from the cortical bone of the face. Plasma cell myeloma
produces its "punched-out" lesions throughout bone.
Paget's osteitis deformans: slow-virus infection, probably measles or
canine distemper, of osteoblasts and osteoclasts, which go crazy
remodeling bone. Soft woven bone with mosaic lines, thickening skull,
arteriovenous shunting, osteosarcoma risk. Pelvis, femurs, spine.
Beethoven's deafness, bulbous forehead, and heart failure.
Fibrous dysplasia: Woven bone in a fibrous stroma, a bone hamartoma.
Monostotic tends to be in the jaw; polyostotic means McCune-Albright.
For your patient histories on USMLE:
Metastatic neuroblastoma: infants and toddlers
Ewing's sarcoma: older children and adolescents
Osteosarcoma: adolescents and young adults
 Giant cell tumors: young adults and middle age
Chondrosarcoma: middle age
Metastatic cancer: middle and old age
Osteoma: Bone bump on you skull somewhere.
Osteoid osteoma: Painful nidus of miniature bone, surrounded by a
sclerotic rim.
Osteosarcoma: Commonest primary bone cancer, malignant osteoblasts are
making osteoid. Teenagers' knees or elsewhere, Paget folks.
Most bone tumors arise for no apparent reason; radiation (remember
strontium 90 and leukemia/osteosarcoma?), retinoblastoma family
(osteosarcoma). "Codman's triangle" is elevated periosteum near the
primary. Majority are cured nowadays.
Exostosis: A little ectopic epiphysis, a bony knob capped with
cartilage.
Enchondroma: A hunk of hyaline cartilage in the center of a bone shaft.
Chondrosarcoma: Typically in the pelvis of middle-aged men, slow-
grower.
Ewing's sarcoma: Teenager's tumor of small blue cells, glycogen-loaded,
very aggressive, liquid, simulates osteomyelitis.
Giant cell tumor / osteoclastoma: common in the knees.
Chordoma: benign tumor of notochord remnants, unfortunately it's
located on the clivus and is inoperable, destroys the cranial nerves
over years.
Prostate metastases to bone tend to be blastic, others tend to be
lytic, but there are many exceptions.
Malignant fibrous histiocytoma: the commonest soft-tissue sarcoma.

Bone alkaline phosphatase: elevated whenever osteoblasts are working

overtime. Urinary hydroxyproline reflects total-body collagen
synthesis.
Systemic diseases affecting joints: amyloidosis (especially
amyloidosis H of renal failure), gout (complement-fixing chemotactic
crystals), lupus, Lyme disease, hemochromatosis (osteoarthritis),
hemophilia (hemarthrosis, mutilation), scurvy (hemarthrosis),
ochronosis-alkaptonuria (osteoarthritis), rheumatic fever (synovitis),
scleroderma (synovitis), sickle cell disease (infection, infarcts),
syphilis (gummas), viremias (type III immune injury with synovitis),
peripheral neuropathies (nobody knows why, but joints without sensory
input tend to become deformed "Charcot joints", as in leprosy,
diabetes, syringomyelia).
Osteoarthritis: supposedly non-inflammatory (but ever see a red
Heberden's node?), limits movement, painful; wear-and-tear and
destruction of cartilage; worst in knees, hips, and first metacarpal
joint (so much for "the cause of weight-bearing..."). Fibrillation and
loss of cartilage, eburnation and "cysts" in underlying bone,
osteophyte formation, lipping, joint-mice (detached fragments).
Kashin-Beck in Central Asia is from fulvic acid toxicity and selenium
deficiency.
Rheumatoid arthritis: common, dread inflammatory synovitis.
Proliferated, inflamed synovium is "pannus". Rheumatoid factor is IgM
directed against Fc portions of IgG, usually but not always present.
Joint deformities include the familiar ulnar deviation, swan-neck and
variants. Mediators of the disease are probably macrophage products.
Complications include Felty's hypersplenism, rheumatoid fibrotic lung,
cryoglobulins, amyloidosis A, vasculitis (gangrene, heart attacks),
rheumatoid nodules (granulomas around injured collagen), Sjogren's,
pleuritis, others.
Juvenile rheumatoid arthritis ("Still's"): same histopathology,
different immunology, some are slow-virus infections with influenza A.
"The reactive enthesopathies" (HLA-B27 family): ankylosing spondylitis
(Marie-Strumpell, poker-back), Reiter's, arthropathy of inflammatory
bowel disease.
Pseudogout: calcium pyrophosphate crystals. Dupuytren's contracture:
palmar fibromatosis, locks one or more fingers in flexion. Osgood-
Schlatter's: repeated avulsions of the periosteum of the attachment of
the quadriceps tendon to the anterior tibia.
Ankylosis: Joint is fused and immobile. Pseudarthrosis: fracture that
healed with fibrous scar rather than bone.
Infectious arthritis: Think of gonorrhea in anyone, salmonella in
sicklers.
"One slow red ox". Type I fibers are slow-twitch, for posture, dark
meat, red muscle, oxidative phosphorylation for steady energy
expenditure. Type II fibers are fast-twitch, for sudden bursts of
hard work, white muscle, glycogen (why white meat on chickens is
sweeter), glycolytic enzymes abundant to burn lots of glucose fast.
Fiber type is determined by its current axons, and will change if
reinnervated; if only a few axons remain, type-grouping results.
Muscle atrophy: disuse, ischemia, damaged nerve, glucocorticoids. Lose
volume, keep nuclei. Angular fibers: denervation, other problems.
Target fibers mean denervation-reinnervation. Ring fibers: think of
myotonic dystrophy. Group atrophy: probably denervation.
Myasthenia gravis: antibodies and/or angry T-cells directed against the
NMJ. Tensilon test and thymic hyperplasia/thymoma.
Werdnig-Hoffman: apoptosis of the anterior horn cells, far-along at
birth, continues until death a few years later. Charcot-Marie-Tooth:
autosomal dominant (defects in myelin proteins) atrophy of lower legs.
Duchenne's muscular dystrophy: X-linked, pseudohypertrophy of calves,
lumbar lordosis, progression to severe disability and death. Variable
fiber size, fiber degeneration, fibrosis, fatty ingrowth. Muscles are
yellow (i.e. almost all fat and scar) at death. Lack of dystrophin, a
membrane protein. Milder alleles produce Becker's. Affected boys and
carrier Mom's have elevated creatine kinase.
Rhabdomyolysis: alcoholism, weekend athletes, heat stroke, seizures,
cocaine abuse, crush injury, malignant hyperthermia (hereditary
disease, anesthesiologist's nightmare), electrical injury.
Myositis ossificans: localized form is ectopic bone production at site
of injury. Generalized involves new bones bridging joints; rare and
miserable.
Muscle membrane diseases and semi-diseases: Myotonia congenita
(chloride channel disease) often features hypertrophied muscles in non-
exercisers, eventually cramps and atrophy become a problem. Periodic
paralysis: sodium channel problems, currently being sorted out.
Eosinophilia-myalgia: followed ingestion of tainted "health food"
tryptophan.
Vitiligo: autoimmunity against melanocytes; Michael Jackson's
depigmentation; runs with addisonism and pernicious anemia, but most
often alone.
Freckle: extra pigment, especially in response to tanning. Lentigo:
extra melanocytes with some acanthosis. Nevocellular nevi:
intradermal, junctional (dermal-epidermal), or mixed (compound). Blue
nevus: spindle-shaped, darkly-pigmented, in deep dermis. Halo nevus:
being cleared, along with nearby melanocytes, by immunity. Congenital
nevus: can be huge, follow dermatomes, some melanoma risk. Dysplastic
nevi: junctional nevi which are irregularly pigmented and with
irregular borders; often multiple and familial, melanoma risk.
Melanoma: risk factors are sunlight, fair skin, dysplastic nevus
syndrome, xeroderma pigmentosum. Look for irregular borders,
variegated pigmentation, bleeding, rapid growth. When in doubt, cut it
off.
Melanoma types: Hutchinson's lentigo-maligna freckle is in-situ,
single-cell growth, no invasion until late. Superficial spreading
melanoma: clusters of cells at dermal-epidermal junction, invades
(grows vertical) sooner or later. Nodular melanoma: vertical growth
from the onset. Clark's levels are replaced by Breslow's thickness
(less then 0.75 mm: safe).
Seborrheic keratosis: crusty keratotic lesions, old folks; sudden
eruption of dozens heralds colon cancer.
Keratoacanthoma: rapidly-growing volcano-shaped hyperkeratotic lesion;
benign.
Actinic keratosis: squamous cell carcinoma in situ. Sunlight, arsenic,
xeroderma pigmentosum. Bowen's disease: Very anaplastic carcinoma in
situ.
Squamous cell carcinoma: sunlight, osteomyelitis sinuses, arsenic,
xeroderma pigmentosum, coal tar, immune suppression for a long time
(the last are caused by KSHV, news). Metastasize late.
Basal cell carcinoma: pearly-bordered "rodent ulcers" on sun-exposed
skin, locally destructive but do not metastasize.
Dermatofibroma: fibrous nodule of histiocyte (?) origin; pinch it and
the overlying skin dimples since it is not attached to the epidermis.
Xanthomas: Masses of lipid-laden macrophages, including the familiar
xanthelasma.
Eczema: Acute inflammation of the epidermis, with edema in and between
cells, some cell loss, inflammatory cells, dried protein-rich exudate
("crusts"). Includes contact dermatitis (allergic, irritant), atopic
eczema (cracks in creases of elbows and knees), many drug rashes
(haptens?)
Erythema multiforme: T-cells angry with the epidermis. Triggers
include drugs, herpes simplex, mycoplasma, lymphoma, lupus, or just
plain idiopathic. Target lesions, variable course, worst is Stevens-
Johnson syndrome.
Psoriasis: Hyperkeratosis, parakeratosis, long rete pegs, pustules in
epidermis and dermal papillae tips, thin epidermis over distended
dermal papillae (peel it off and the pinpoint bleeds are Auspitz's
sign), Koebner phenomenon (scratch anywhere and psoriasis appears
there). Silvery scales, pitted nails; arthritis; HLA-B27 types get
ankylosing spondylitis.
Lichen planus: purple polygonal pruritic papules. Hyperkeratosis,
apoptosis, band-like infiltrate.
Acne vulgaris: Propionibacterium thriving on free fatty acids in sebum
gets the process started. When your epidermis gets hyperkeratotic and
your sebaceous glands enlarge during puberty, the problem begins.
Basic lesion is the "comedome" keratin-and-sebum plug.
Pemphigus vulgaris: antibodies against desmosomes; tombstone basal
layer. Nikolsky's sign on rubbing the skin.
Pemphigoid: antibodies against hemidesmosomes, milder than pemphigus
vulgaris.
Dermatitis herpetiformis: IgA in the dermal papillae; symmetric itchy
blisters.
Pompholyx ("dyshydrotic eczema") is blisters on palms and soles, a
nuisance disease; ask about nickel allergy, offer low-zinc diet.
Epidermolysis bullosa: no type VII collagen in the basal lamina of the
skin (genetic defect, autoimmunity).
Molluscum contagiosum: acanthotic, itchy lesions with a central plug
made of poxvirus. Transmitted by touch.
Impetigo: infectious, often mixed staph-strep, of the horny layer of
the epidermis. Honey crusts.
Seborrhea: caused by pityrosporum yeast. Tinea versicolor: another
superficial yeast. Jock itch and athlete's foot require no
description. Itchy glans and finger webs suggest scabies.

"It must be inconvenient to be made of flesh,"

said the Scarecrow, thoughtfully, "for you must
sleep, and eat and drink. However, you have
brains, and it is worth a lot of bother to be able
 to think properly."
-- The Wizard of Oz
Selective vulnerability:
Purkinje cells
Mammilaries, Purkinje cells
DM of thalamus
Hippocampus
Cerebellar granular layer
Retina
Anterior horn cells
Globus pallidus
Posterior columns
Caudate
Prefrontal, temporal
Deep brain
Intermediolateral cord
Substantia nigra
Left-center temporal cortex
Upper motor neurons
Alcoholism, carbon monoxide
Wernicke's
Korsakoff's
Alzheimer's, hypoxia, hypoglycemia
Mercury, radiation injury
Methanol
Polio, bad cassava, lower-ALS
Carbon monoxide, Wilson's,
kernicterus (baby jaundice)
B12 deficiency, syphilis (tabes)
Huntington's
Pick's
Progressive supranuclear palsy
Shy-Drager dysautonomia
Idiopathic Parkinson's, von Economo
Schizophrenia
Upper-ALS

Neural tube defects: folic acid deficiency at conception. Arnold-

Chiari: long cerebellar tonsils out the foramen magnum, beak-shaped
tectum, platybasia, maybe hydrocephalus, maybe neural tube defects.
Dandy-Walker: No good cerebellar vermis; prominent occiput.
Syringomyelia: acquired tube-shaped deformity down center of cervical
spine; etiology is obscure, loss of spinothalamic tracts at this level.
Red neuron: ischemia, hypoglycemia; this is coagulation necrosis of
neurons.
Neurofibrillary tangles: Twisted filaments of tau protein inside cells;
stain with silver, think of Alzheimer's, post-influenzal parkinsonism
("Awakenings"), progressive supranuclear palsy, boxers.
Lewy bodies: Pink spheroids inside cells; substantia nigra of
Parkinsonism, cortex in Lewy dementia, others.
Pick bodies: Big silver-staining barrel-shaped intraneuronal
inclusions. Pick's disease (easy).
Granulovacuolar degeneration: Silver-staining spheres of tau protein,
surrounded by a vacuole, inside neurons, in Alzheimer's.
Lafora bodies: sunflower-shaped masses of carbohydrate in neurons,
myoclonus epilepsy.
Negri bodies: eosinophilic inclusions in rabies.
Central chromatolysis (axonal reaction): neuron swells, endoplasmic
reticulum ("Nissl substance") moves to the periphery of the cell.
Axonal degeneration: Changes in the neuron cell body and other points
proximal to where an axon is cut. Wallerian degeneration: changes
distal to where an axon is cut. Axonal spheroids: stainable balls
typical of diffuse axonal injury.
Gliosis: astrocytes proliferate and heal injured brain. Sclerosis:
oligodendroglia die off, axons are preserved, and astrocytes replace
the lost volume. Spongiosis: reactive astrocytes plus edema.
Alzheimer type I glia: monstrously enlarged astrocytes in progressive
multifocal leukoencephalopathy (JC papovavirus) and subacute sclerosing
panencephalitis (slow measles virus). Alzheimer's type II glia:
astrocytes with swollen nuclei from hyperammonemia (liver failure,
Reye's).
Leukodystrophy: disease primarily affecting diffusely oligodendroglia,
usually hereditary.
Microglia: CNS macrophages. Giant-cell encephalitis: HIV. Rod cells:
elongated microglia in syphilis and rickettsial disease. Gitter cells:
microglia eating dead lipid. Microglial nodules: viruses and
rickettsia.
Increased intracranial pressure presents as headache, dullness, nausea
and vomiting.
Cingulate (subfalcine) gyrus herniation: under the falx; lose anterior
cerebral artery, weak leg on opposite side.
Uncal (hippocampal, transtentorial) herniation: under the tentorium,
lose III (dilated pupil), posterior cerebral artery (contralateral
homonymous hemianopsia).
Tonsillar herniation: out the foramen magnum, compress medulla,
autonomic death.
Duret hemorrhages: in brainstem following herniation, from damage to
arteries.
Vasogenic edema: hurt or leaky capillaries, as in infarcts, infection,
lead poisoning, trauma, "ring enhancement" around tumors or abscesses.
Cytotoxic edema: ischemia, acidosis, Reye's, Cerebral edema is bad
since the brain has nowhere to expand.
Interstitial edema: from obstructed flow of spinal fluid.
Hydrocephalus: any increase in volume of CSF. Hydrocephalus ex vacuo:
loss of cortex. Non-communicating hydrocephalus: blockage within the
brain. Communicating hydrocephalus: too much fluid produced, scarring
in the subarachnoid space, problems with arachnoid villi (i.e.,
sagittal sinus thrombosis).
Cerebral infarcts may be hemorrhagic or pale, depending on how much
reperfusion takes place.
Blood in the subarachnoid space is very painful. Bleeding in the brain
itself is toxic, but recovery is better than from ischemia. Blood in
the ventricles is a disaster.
Intracerebral bleeds: blamed on "hypertension", the common site is the
putamen ("lenticulostriate artery of Charcot"). Less often,
congophilic angiopathy, vascular malformations, others.
Subarachnoid hemorrhages: usual cause is berry aneurysms; risk factors
include polycystic kidneys; "defects in the elastica" are ubiquitous
even in folks who do not have berries; we don't understand how they
form. Most common site is anterior communicating artery, next is
middle cerebral, next is posterior communicating. (The other cause of
subarachnoid bleeds is AV malformations in the meninges.)
Germinal plate bleeds: Premature babies, especially with lung disease;
cor pulmonale raises the venous blood pressure, rupturing the fragile
baby-veins in the wall of the ventricles.
Subdural hematoma: from avulsion of the bridging veins. Acute subdural
hematoma: catastrophic injury. Chronic subdural hematoma: slow leaks,
especially in atrophic brains (stretched vessels); mass of granulation
tissue diverts blood from the underlying cortex.
Epidural hematoma: blow to the head fractures skull, nicking middle
meningeal artery. Upon regaining consciousness, the patient feels
okay, then drifts into coma, herniates, and dies. Why we monitor head
injury patients.
Concussion: blow to the head causing loss of consciousness. Contusion:
bruise to the brain, perhaps damaging it. Coup contusion: under the
impact. Contrecoup contusion: opposite the impact, typical when the
head strikes something bigger than itself, i.e., the ground. Typical
contrecoup sites are the occiput (fall on face), bottom of prefrontal
lobes (fall backwards off bar stool), temporal lobe above the petrous
ridge (hit on top of head).
Diffuse axonal injury is tearing of axons. Brain damage with no
radiologic correlates. At autopsy, we look for petechiae in the
reticular formation and the corpus callosum, axonal retraction
spheroids.
You will be quizzed frequently on the most common etiologic agents of
meningitis:
E. coli Newborns (strep B too)
H. 'flu 1 month to 3-5 year old kids
Meningococcus Older kids and younger adults (remember
epidemics, military recruits, Waterhouse-
Friderichsen syndrome)
Pneumococcus Oldsters and drinkers
Anything The immunosuppressed -- tough diagnosis
Disastrous effects of meningitis include brain damage, cranial nerve
loss, spinal nerve loss, hydrocephalus.
Acute lymphocytic meningitis: virus, leptospira; the familiar "stiff
neck", photophobia, and so forth. Recovery is the norm.
TB meningitis: around circle of Willis, where the oxygen is. Damage to
cranial nerves.
Cryptococcal meningitis: Bugs thrive in spinal fluid nad Virchow-Robin
spaces. India ink prep.
Brain abscess: after dirty wound, mastoiditis, lung abscess, right-to-
left shunts.
Von Economo's encephalitis: after influenza. Herpes simplex I:
necrosis of the temporal lobes, notably the hippocampus and amygdala;
herpes incisions in oligodendroglia. Herpes simplex II encephalitis:
why you deliver babies of a woman with active herpes by C-section.
Poliomyelitis: attacks anterior horn cells. Rabies: follows the axons
up to the brain. CMV: periventricular calcifications in the unborn.
HTLV-1: a spastic paralysis endemic in the Caribbean.
Spongiform encephalopathies: scrapie (sheep), mink encephalopathy and
mad cow disease (from eating scrapie sheep carcasses), kuru
(cannibals), Creutzfeldt-Jacob disease (sporadic, iatrogenic), and
Gerstmann-Straussler are the same disease. The cause is prions,
twisted PrP protein which catalyzes the transformation of normal PrP
into copies of itself, equally infectious, i.e., a chain reaction.
Gerstmann-Straussler is a hereditary disease with PrP prone to
transform spontaneously into prion, and this can happen to anyone who's
unlucky. Myoclonus, ataxia, dementia. Histopathology: neuronal
dropout with intracellular and extracellular water vacuoles
("spongiform encephalopathy").
The most common causes of headache are probably caffeine withdrawal,
hangover, and eyestrain (needing glasses). Worry about the unusual
headache, i.e., the one that's not typical for that patient. Migraine
is a pain syndrome inside the brain; what you've heard about vasospasm
and vasodilatation is simplistic.
Alzheimer's: "Just plain senile", or "presenile dementia".
Neurofibrillary tangles in the cortical neurons. Senile plaques
(masses of amyloid made of beta-A4 protein and apolipoprotein E)
surrounded by neurofilaments with altered tau protein in them.
Granulovacuolar degeneration. Amyloid in the vessels. Cortical
atrophy. Mutant beta-A4 for early-onset disease, mutant apolipoprotein
E4 is a risk factor for late-onset disease.
Pick's disease: Alzheimer-like dementia, only selectively involving the
prefrontal and temporal lobes ("walnut atrophy"). Pick bodies, swollen
cells.
Huntington's: degeneration of the caudate head, usually in young adult
life. Autosomal dominant with complete penetrance, shows genetic
anticipation. Dance-like (chorea) gait disturbance, dementia, a bad
way to die.
Parkinsonism: familiar movement disorder, difficulty initiating or
stopping movement, mask-like face, pill-rolling tremor. Lewy bodies,
or neurofibrillary tangles if post-influenzal. Shy-Drager: Parkinson's
plus dysautonomia, often including impressive orthostatic hypotension.
Progressive supranuclear palsy: Under-recognized degenerative disease
of basal ganglia and deep brain structures; eye movement disorders and
dementia.
Benign familial tremor: 1% of people, comes on around age 20, autosomal
dominant, a beer or a tiny dose of propranolol abolishes the intention
tremor.
Friedreich's ataxia: degeneration of spinal tracts and cerebellum, with
foot deformities and cardiomyopathy.
Amyotrophic lateral sclerosis: Lou Gehrig's, actually a family of
diseases in which upper and/or lower motor neurons die off.
Schizophrenia: Obviously a neurologic problem rather than "your mother
looked and talked to you funny"; old psychologist models are now
totally discredited. Loss of cells in the cortex, most notably the
center of the temporal lobe; hydrocephalus ex vacuo is usual. Autism
("rain man": Also obviously a neurologic problem rather than "bad
parenting"; deformities of the vermis are usual.
Subclavian steal ("Robin Hood"): stenosis of the subclavian artery
proximal to the thyrocervical trunk results in diversion of blood from
the brain when you exercise the corresponding arm.
Vascular dementias: Severe atherosclerosis can and does produce
dementia. Binswanger's subcortical leukoencephalopathy: brain failure
from hyaline arteriolar sclerosis in hypertensives; under-recognized.
Most brain tumors in kids are infratentorial (medulloblastomas,
cerebellar astrocytomas). Most brain tumors in adults are
supratentorial. They present as personality changes, then headache,
nausea-vomiting, etc.
All gliomas are malignant. Astrocytomas may be hard to see, simply
extra astrocytes in an area. Oligodendrogliomas tend to calcify, and
exhibit fried-egg cells (lipid). Ependymomas sit on the walls of
ventricles and make little tubes, cilia, and so forth. All tend to
transform into glioblastoma multiforme, an extremely malignant tumor,
with necrosis, hemorrhage, vascular proliferation, palisading of
bizarre cells, and rapid death.
Medulloblastoma: small blue cells, arising in cerebellar vermis,
spreads up and down neuraxis.
Meningioma: arises from arachnoid cap cells, along sphenoid ridge or
sagittal sinus, sometimes elsewhere. Whorls, psammoma bodies; most are
benign, tend to recur, may result from trauma.
Brain lymphomas: usually from Epstein-Barr infection in the immune-
suppressed.
Metastatic cancer: the most common brain tumor. Usually at the gray-
white junction, where vessel size drops off.
Multiple sclerosis: the dread demyelinating disease of young adults.
T-cells go after the myelin. Most likely cause of Epstein-Barr virus
mimicking myelin. The farther away from the equator that you grew up,
the more likely you are to get multiple sclerosis. Hereditary Finnish
MS maps to the myelin gene. Plaques appear, especially near the
ventricles, then may partly heal, accounting for the exacerbations and
remissions; the ultimate course is downhill though the final degree of
disability is widely variable. Classic signs are optic neuritis,
dysconjugate eye movements. Devic's: optic neuritis and spinal cord
lesions.
Acute disseminated encephalomyelitis: after a virus or immunization,
the immune system tears up the brain's myelin, especially around
vessels. Recovery may be partial or complete. There is a necrotizing
version.
Central pontine myelinolysis: in the center of the basis pontis; takes
out the descending motor tracts, currently blamed (sometimes) on too-
rapid correction of hyponatremia ("osmotic myelinolysis").
Blood alcohol levels....
gm/dL (=%) effect
0.05-0.1 happy
0.1-0.2 drunk
0.2-0.35 kisses mother-in-law, shoots best friend
0.35 & up books say "coma & death"; some are still
driving
Korsakoff's: nice fantasy life, damaged dorsomedian nucleus.
Wernicke's: damage mammillary bodies.

Guillain-Barr : autoimmunity against the spinal motor nerves, with

ascending paralysis lasting up to months.
Other peripheral neuropathies: alcoholism / thiamine deficiency;
diabetes; lead; Charcot-Marie-Tooth; paraneoplastic, more.
Neurilemmoma (schwannoma): Tumor of perineurium; sits on nerve with
fibers passing alongside the tumor. The familiar acoustic neuroma, or
anywhere else. Verocay bodies, Antony A (dense palisades) and Antoni B
(myxoid) areas.
Neurofibroma: Tumor of endoneurium. Fibers pass through it, with
ropelike transformation of nerves; those on the skin of
neurofibromatosis patients look like erasers.
[Mind and brain: Our brain is clearly our interface with the familiar
world, and handles the automatic stuff that our minds do for us. But
I've seen and heard enough to hold, as a reasonable working hypothesis
(and probably the best available), that what makes us who we really are
is something fundamentally different from, and separable from, our
brains. I am not the only science-jock to reach this tentative
conclusion. I'd add that we should probably try to be kind and decent
to each other, just for this reason.]
Serum Iron TIBC Serum Ferritin
Iron deficiency   0
Anemia of chronic
disease   typically 
Hemochromatosis
(1ø or 2ø)  N typically 

T3 resin uptake value is inversely proportional to the number of

unbound sites on the thyroid binding globulins.
What's in those vacuum-filled blood sample tubes? I could see them
asking....
Red-top: Nothing. The blood will clot, and we'll extract
the serum. Used for most routine chemistries.
Purple-top: EDTA (calcium-chelating anticoagulant). Best for
blood cell counting.
Blue-top: Citrate (calcium-chelating anticoagulant, readily
neutralized). Best for routine coagulation
 studies.
Gray-top: Fluoride-oxalate. Inhibits glycolytic enzymes.
Best for glucose and routine toxicology.
Green-top: Heparin anticoagulant. Less popular than the
others.
The porphyrias: Acute intermittent and its variants feature
neurotoxicity from delta-amino levulininc acid and porphobilinogen;
somtach aches and insanity; exacerbate the enzyme deficicy by further
inhibiting it with barbiturates. Cutanea tarda and its worse relatives
feature photosensitivity, with scarring, extra hair, and blistering,
from buildup of porphyrins themselves.
LDH isoenzymes: 1 (1-2 flip) is heart, red cells, kidney; 3 is lung; 5
is liver and skeletal muscle.
SGOT (AST): Up in liver cell injury, heart cell injury, red cells,
skeletal muscle. SGPT (ALT): Liver only.
Creatine kinase (CK, CPK): MM is skeletal muscle, MB is heart (or fit-
person's skeletal muscle), BB is brain.
Alkaline phosphatase: bone, liver, placenta, less often intestine. If
of hepatic origin, 5' nucleotidase, leucine aminopeptidase, and gamma-
glutamyl transpeptidase will be up as well.
Prerenal azotemia: BUN/creatinine ratio around 20, low urine sodium.
Renal shutdown: BUN/creatinig ratio around 10, urine soidum mEq/L.
"RDW" is red-cell distribution width, measure of size differences;
early detection of iron deficiency and most other stuff.
High LDH, high potassium: Hemolyzed specimen.
The titer of a substance measured in the serology lab is the maximum
dilution (of a series of dilutions) at which the substance can be
detected. Thus a titer of 1:2 or 1:10 is a "low titer" and indicates
that not very much of the substance is present. And a titer of
1:128000 is probably a "high titer". Depending on what you are
measuring, a titer of 1:100 might be "high" or "low".
"A significant rise in titer" suggests a recent infectious disease.
"Significant" is usually considered to be a "fourfold rise". If a
titer rises from 1:16 to 1:64 during an episode of acute illness, or
when a titer rises from 1:10000 to 1:80000, the patient probably had
the acute disease to match.
To screen for malabsorption, do a fecal fat stain. To distinguish
pancreatic malabsorption from intestinal malabsorption, do a d-xylose
test. To find the cause of intestinal malabsorption, do a biopsy.
Analytic sensitivity: how little of the substance you can detect.
Analytic specificity: how sure you can be that you're not looking at
something else instead. Accuracy: How close to a known true value.
Precision: How reproducable your results are, right or wrong.
DIAGNOSTIC SENSITIVITY ("Bayesian sensitivity") is the percentage of
positive results in patients with a particular disease.
 True Positives
Diagnostic sensitivity = ________________________________ x 100
True Positives + False Negatives
DIAGNOSTIC SPECIFICITY ("Bayesian specificity") is the percentage of
negative results in patients without a particular disease.
True Negatives
Diagnostic specificity = ________________________________ x 100
True Negatives + False Positives
Sensitive tests are best for the diagnosis of treatable diseases:
bacterial infections, early cancer, phenylketonuria. You want a very
sensitive test when the benefits of detecting the disease are great
(curing it, preventing new cases, etc).
Specific tests are best for the diagnosis of non-treatable
diseases: chronic neurologic disease, disseminated cancer, etc. You
want a very specific test when the risks of a wrong diagnosis are great
(getting very upset, losing your insurance, getting cancer
chemotherapy, etc.)
These are appalling over-generalizations, but there is always a
tradeoff between sensitivity and specificity. If a new test is both
more sensitive and more specific than an old test (and not much more
expensive), it replaces it. Otherwise, whether we are a pathologist
setting a "reference range" or "decision level", or a clinician
ordering a lab test, we must remember that sensitive tests lack
specificity and specific tests lack sensitivity. Clinicians commonly
order the sensitive tests first, followed by the specific ones.
Predictive value: the percent chance that a result correctly
identifies the patient as diseased or non-diseased.
True Positives
Predictive Value of = ________________________________ x 100
a Positive Result True Positives + False Positives
True Negatives
Predictive Value of = ________________________________ x 100
a Negative Result True Negatives + False Negatives
Diagnostic accuracy ("diagnostic efficiency"): the percent of
patients correctly identified as diseased or non-diseased by the test.
True Positives + True Negatives
Diagnostic accuracy = _______________________________ x 100
All Results
Prevalence: the percent of those tested who actually have the
disease.
True Positives + False Negatives
Prevalence = ________________________________ x 100
All Results
Prevalence may be expressed in different units. Contrast
incidence: the fraction of new cases of the disease in a population
over a given time.
 Prevalence = Incidence x Average Duration
Bayes' Theorem
(Sensitivity)(Prevalence)
Predictive Value of=_____________________________________________
a Positive Result Sensit.)(Prev.)+(1-Specif.)(1-Prev.)

"Don't take life too serious. It ain't

nohow permanent."
-- Walt Kelly, Pogo
* * *
Also Available.....
ED'S PATHOLOGY MELTDOWN
Part I -- General Pathology