Cyberfriends: The help you're looking for is probably here.
Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected.
DoctorGeorge.com is a larger, full-time service.
There is also a fee site at
www.afraidtoask.com.
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With one of four large boxes of "Pathguy" replies. |
I'm still doing my best to answer
everybody.
Sometimes I get backlogged,
sometimes my E-mail crashes, and sometimes my
literature search software crashes. If you've not heard
from me in a week, post me again. I send my most
challenging questions to the medical student pathology
interest group, minus the name, but with your E-mail
where you can receive a reply.
Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource. Someday you may be able to access these pictures directly from this page.
Also:
KCUMB Pathology Club
Freely have you received, freely give. -- Matthew 10:8. My
site receives an enormous amount of traffic, and I'm
handling about 200 requests for information weekly, all
as a public service.
Pathology's modern founder,
Rudolf
Virchow M.D., left a legacy
of realism and social conscience for the discipline. I am
a mainstream Christian, a man of science, and a proponent of
common sense and common kindness. I am an outspoken enemy
of all the make-believe and bunk that interfere with
peoples' health, reasonable freedom, and happiness. I
talk and write straight, and without apology.
Throughout these notes, I am speaking only
for myself, and not for any employer, organization,
or associate.
Special thanks to my friend and colleague,
Charles Wheeler M.D.,
pathologist and former Kansas City mayor. Thanks also
to the real Patch
Adams M.D., who wrote me encouragement when we were both
beginning our unusual medical careers.
If you're a private individual who's
enjoyed this site, and want to say, "Thank you, Ed!", then
what I'd like best is a contribution to the Episcopalian home for
abandoned, neglected, and abused kids in Nevada:
My home page
Especially if you're looking for
information on a disease with a name
that you know, here are a couple of
great places for you to go right now
and use Medline, which will
allow you to find every relevant
current scientific publication.
You owe it to yourself to learn to
use this invaluable internet resource.
Not only will you find some information
immediately, but you'll have references
to journal articles that you can obtain
by interlibrary loan, plus the names of
the world's foremost experts and their
institutions.
Alternative (complementary) medicine has made real progress since my
generally-unfavorable 1983 review linked below. If you are
interested in complementary medicine, then I would urge you
to visit my new
Alternative Medicine page.
If you are looking for something on complementary
medicine, please go first to
the American
Association of Naturopathic Physicians.
And for your enjoyment... here are some of my old pathology
exams
for medical school undergraduates.
I cannot examine every claim that my correspondents
share with me. Sometimes the independent thinkers
prove to be correct, and paradigms shift as a result.
You also know that extraordinary claims require
extraordinary evidence. When a discovery proves to
square with the observable world, scientists make
reputations by confirming it, and corporations
are soon making profits from it. When a
decades-old claim by a "persecuted genius"
finds no acceptance from mainstream science,
it probably failed some basic experimental tests designed
to eliminate self-deception. If you ask me about
something like this, I will simply invite you to
do some tests yourself, perhaps as a high-school
science project. Who knows? Perhaps
it'll be you who makes the next great discovery!
Our world is full of people who have found peace, fulfillment, and friendship
by suspending their own reasoning and
simply accepting a single authority that seems wise and good.
I've learned that they leave the movements when, and only when, they
discover they have been maliciously deceived.
In the meantime, nothing that I can say or do will
convince such people that I am a decent human being. I no longer
answer my crank mail.
This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.
This page was last updated February 9, 2008.
During the thirteen years my site has been online, it's proved to be
one of the most popular of all internet sites for undergraduate
physician and allied-health education. It is so well-known
that I'm not worried about borrowers.
I never refuse requests from colleagues for permission to
adapt or duplicate it for their own courses... and many do.
So, fellow-teachers,
help yourselves. Don't sell it for a profit, don't use it for a bad purpose,
and at some time in your course, mention me as author and KCUMB as my institution. Drop me a note about
your successes. And special
thanks to everyone who's helped and encouraged me, and especially the
people at KCUMB
for making it possible, and my teaching assistants over the years.
Whatever you're looking for on the web, I hope you find it,
here or elsewhere. Health and friendship!
I am presently adding clickable links to
images in these notes. Let me know about good online
sources in addition to these:
MedEdPORTAL -- American Association of Medical Colleges. Primarily for medical school faculty.
Pathology Education Instructional Resource -- U. of Alabama; includes a digital library
Pathopic -- Swiss site; great resource for the truly hard-core
Syracuse -- pathology cases
Alabama's Interactive Pathology Lab
"Companion to Big Robbins" -- very little here yet
Alberta
Pathology Images --hard-core!
Alberta Tumor Photos -- and lots more. Highly recommended.
Bristol Biomedical
Image Archive
EMBBS Clinical
Photo Library
Chilean Image Bank -- General Pathology -- en Español
Chilean Image Bank -- Systemic Pathology -- en Español
Connecticut
Virtual Pathology Museum
Australian
Interactive Pathology Museum
Semmelweis U.,
Budapest -- enormous pathology photo collection
Iowa Skin
Pathology
Loyola
Dermatology
History of Medicine -- National Library of Medicine
KU
Pathology Home
Page -- friends of mine
The Medical Algorithms Project -- not so much pathology, but worth a visit
National Museum of Health & Medicine -- Armed Forces Institute of Pathology
Telmeds -- brilliant site by the medical students of Panama (Spanish language)
U of
Iowa Dermatology Images
U Wash
Cytogenetics Image Gallery
Urbana
Atlas of Pathology -- great site
Visible
Human Project at NLM
Karolinska Institutet -- pathology links
Johns Hopkins CPC's
U. of Virginia Case Studies
Oklahoma Teaching Cases
Indiana U. Teaching Cases
SUNY Histopathology
West Virginia Case of the Month
Upstate NY Cases -- works only on some browsers
Society for Ultrastructural Pathologi -- electron microscope cases
WebPath:
Internet Pathology
Laboratory -- great siteEd Lulo's Pathology Gallery
Bryan Lee's Pathology Museum
Dino Laporte: Pathology Museum
Tom Demark: Pathology Museum
Dan Hammoudi's Site
Claude Roofian's Site![]()
Medmark Pathology -- massive listing of pathology sites
Pathology Handout -- Korean student-generated site; I am pleased to permit their use of my cartoons
Estimating the Time of Death -- computer program right on a webpage
Pathology Field Guide -- recognizing anatomic lesions, no pictures
St.
Jude's Ranch for Children
I've spent time there and they are good. Write "Thanks
Ed" on your check.
PO Box 60100
Boulder City, NV 89006--0100
More of my notes
My medical students
Clinical
Queries -- PubMed from the National Institutes of Health.
Take your questions here first.
HealthWorld
Yahoo! Medline lists other sites that may work well for you
We comply with the
HONcode standard for trustworthy health
information:
verify
here.
What's a 'double-blind study'? Two pathologists trying to read an EKG!
--Anonymous
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
Does CPR work better if you do your compressions with a toilet plunger? The great controversy, including a frank admission that CPR....: JAMA 273: 1299, 1995.
Out-of-hospital CPR survivors do twice as well (i.e., after you exclude those that were already obviously hopeless, maybe 6% of them are alive without obvious brain damage a month later) if you DON'T do the mouth-to-mouth stuff...: Lancet 369: 920, 2007.
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QUIZBANK Heart (all)
Cardovascular Pathology
Sampurna Roy, MD
Lots of photos and good text
Congenital: Heart 24-53
Cardiomyopathies / CHF / Myocarditis / Pericardium / Tumors: 9-23, 116-127, 169-181
Valves: 54-115
Ischemia: 1-8, 128-168
Tulane Pathology Course
Great for this unit
Exact links are always changing
Gross Cardiovascular Photos
Great pictures from Tulane
Drs. McLay & Harrison
Cardiovascular Pathology
Virginia Commonwealth U.
Great pictures
Cardiovascular Diseases
Mark W. Braun, M.D.
Photomicrographs
Myocardium
Slide from Andrea McCollum MD
Cuyahoga County Coroner's Office
Define and use the following terms:
Describe the changes in the myocardium in a trained aerobic athlete, and recognize that these are desirable rather than harmful.
Review the general pathology of congestive heart failure. You should probably already know this from your earlier studies of cardiac physiology and the pathology of the body fluids.
Describe the clinical spectrum of atherosclerotic coronary artery disease.
Tell how the various kinds of angina pectoris arise. Explain how myocardial infarcts occur, why they are so serious, and what the pathologist will see at autopsy under varying circumstances. Tell how subendocardial infarcts occur. Describe the typical picture of chronic ischemic cardiac disease. Tell what a pathologist will find in classic coronary "sudden death", and when the diagnosis can and cannot be made.
Mention the other causes of ischemic heart disease, and tell about how they operate. Tell about the other causes of sudden death.
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Define and use the following terms:
atresia
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Alan Shepard |
Recall the upper limit of normal weight of the sedentary adult's heart, left ventricular thickness, and right ventricular thickness.
List the minimal anatomic criteria for hypertensive heart disease. Describe the role of pressure overload (clear) and chronic catecholamine stimulation (probable) as causes of this hypertrophy. Describe the gross and microscopic changes typical of the hypertensive's heart. Appreciate that this is a very common finding, both clinically and at autopsy. Explain the difficulty of making the diagnosis when left ventricular failure confuses the picture.
Distinguish cor pulmonale from right heart enlargement caused by left ventricular failure or by congenital malformations. Recognize pulmonary embolization as the only setting for true "acute cor pulmonale". Describe the hypoxic vascular response, and describe how the shape of the right ventricle on cross section differs from normal in this setting. Recognize cor pulmonale as a sufficient explanation for sudden death cases coming to autopsy. Appreciate the tremendous clinical importance of cor pulmonale in many settings.
Recall the two principal causes of serious congenital heart disease. Recall the incidence per thousand live births, and the risk of recurrence. List the problems common to all these children, and the hazards presented by jet lesions.
List tetralogy of Fallot (most common), transposition of the great arteries, persistent truncus arteriosus, and tricuspid atresia as the four most important forms of congenital cyanotic heart disease, and clearly explain the abnormal anatomy and physiology of each. Explain the seriousness of the right-to-left shunt, the most dreaded consequences of paradoxical embolization, and other problems faced by these patients.
Diagram tetralogy of Fallot, listing the four features that define the syndrome.
Describe the usual pattern in transposition of the great vessels, and how a septal defect permits survival after birth. Distinguish "corrected transposition".
Define truncus arteriosus, and recall that it leads eventually to pulmonary hypertension.
Recall ventricular septal defect, atrial septal defect, and patent ductus arteriosus as the major causes of congenital left-to-right shunt. Explain the associated hazards, and especially why cyanosis develops weeks to years after birth in patients with left-to-right shunts.
Recall the location of most ventricular defects. Explain the reason that a "VSD" is unwholesome. Give the meaning of "Roger's disease" and the spontaneous closure rate.
Describe the usual clinical course in atrial septal defect, and tell why these are so seldom recognized in youth. Distinguish ostium primum ("endocardial cushion"), ostium secundum, and sinus venosus atrial septal defects. Recognize ostium primum as the usual form in Down's syndrome, as ostium secundum as most common in other people.
Locate the normal ductus arteriosus and define its function and fate. Identify prostaglandin E as maintaining the patency of the normal ductus. Recognize that in congenital heart disease with impaired blood flow to the lungs, it is good for the ductus to remain open.
Describe patent ductus arteriosus, mentioning its relationship to other defects and to Turner's syndrome, and its most common location. Tell why preductal coarctation can cause right sided heart failure in utero. Describe how it causes hypertension, and mention clinical findings that would alert the pediatrician to post-ductal coarctation. Mention the reasons for getting it fixed surgically.
Recognize pulmonary stenosis with intact interventricular septum as a common, serious cardiac malformation.
Describe the problems caused by a bicuspid aortic valve. Describe the aortic valve in congenital valvular aortic stenosis, and the defect in congenital sub-valvular stenosis. Explain why aortic stenosis commonly produces sudden death.
Give a short account of each:
Anitschkow cell / Aschoff body
antihyaluronidase
antistreptolysin O ("ASO")
Barlow's syndrome
caterpillar cell
dextrocardia with situs inversus
dextrocardia, isolated
erythema marginatum
friable
Kartagener's syndrome
lines of closure
MacCallum's patches of the left atrium
mid-systolic click
regurgitation
Roth spots
situs inversus totalis
splinter hemorrhages
Sydenham's chorea ("St. Vitus Dance")
tamponade
valvular insufficiency
valvular stenosis
vegetations
Relate dextrocardia, Kartagener's syndrome, immotile cilia, and situs inversus totalis.
Remember that mitral stenosis is virtually always caused by scarring from rheumatic fever.
List the important causes all eight valvular syndromes.
List the three important causes of acquired aortic valve stenosis. Sketch a normal (three cusp) aortic valve with calcific stenosis, mention the age of onset, and explain why the process is so serious. Sketch a bicuspid valve with the same thing, and mention which kind of valve is more prone to this.
Describe Barlow's "syndrome" of the mitral valve. Tell how prevalent the disease is, describe the relationship to Marfan's syndrome, and tell what makes the mid-systolic "click". Describe the four complications (bacterial endocarditis, mitral insufficiency, rhythm disturbances, and cardiac neurosis) that can result.
Describe the essential pathogenesis of rheumatic fever and rheumatic pancarditis, and the typical time of onset. List the six principal findings, and describe the changing incidence of the disease in the U.S. and globally. Mention the recurrence rates cited after repeat strep throat. Describe a typical Aschoff body, and tell where it is located. Explain why rheumatic endocarditis is considered more serious in the long run than the myocarditis or pericarditis, and describe the locations of the lesions on the valves in the acute illness.
Describe the pathologic anatomy in chronic mitral valve deformity and chronic aortic valve deformity following rheumatic fever.
Explain why infective (i.e., bacterial) endocarditis is so serious. Tell ways in which the blood becomes seeded with microbes, and times and places where the fibrin-platelet thrombi form inside the heart. Describe acute infective endocarditis, the types of valves that may be involved, its usual cause, and the fatality rate. Name the bacterium most often responsible for subacute bacterial endocarditis. Tell what you will see grossly and microscopically. Tell what valve are most often involved in IV drug-users and in other people. Mention why bacterial endocarditis might be "culture negative". Describe the dread complications of bacterial endocarditis in some detail, and mention clues to the diagnosis. Tell what healed bacterial endocarditis looks like.
Describe typical settings for nonbacterial thrombotic endocarditis ("marantic endocarditis"). Describe the gross and microscopic lesions.
Describe calcification of the mitral annulus as seen in some older individuals, and describe its clinical significance.
Describe the gross, microscopic, and functional lesions in carcinoid syndrome, and explain why we think that the lesions usually occur only on the right side.
Recognize the five complications of valve replacement.
Give a short account of each:
adriamycin
cardiomyopathy
Chagas's disease
daunorubicin
doxorubicin
effusion
myocarditis
Distinguish "myocarditis" (i.e., inflammatory, i.e., autoimmune or infection) and "cardiomyopathy" (i.e., a noninflammatory disorder).
Describe the gross and microscopic pathology and clinical course of a typical case of myocarditis.
Recall viruses, especially Coxsackie A
& B
as the most important causes of significant acute
myocarditis, and that this is (fortunately) rare. Mention why we think much of the damage is
immune-mediated. Explain why we think many cases of "idiopathic dilated cardiomyopathy"
("Barney Clark's disease") result from Coxsackie myocarditis.
Given a cardiomyopathy, subclassify it as dilated ("flabby heart"), hypertrophic ("muscle-bound heart"), or restrictive-infiltrative-obliterative (i.e., amyloid, "stiff heart").
Recall "dilated-congestive" cardiomyopathy as an end-stage of various longstanding cardiac injuries, and describe the way this heart looks and functions. Describe the histology, and why mural thrombi form.
Cite the clinical features of alcoholic cardiomyopathy, and relate it to cobalt toxicity and beriberi. Recognize alcohol itself as a controversial cause of cardiomyopathy.
Mention the typical setting for peripartum cardiomyopathy, and explain why we suspect a nutritional deficiency.
Recall that disarray of the myocardial fiber arrangement as the typical, though not invariable, feature of hypertrophic cardiomyopathy. Recognize "asymmetric septal hypertrophy" and "idiopathic hypertrophic subaortic stenosis" as the classic hypertrophic cardiomyopathy in which the septum is primarily involved. Recognize "obstructive hypertrophic cardiomyopathy" as the feared consequence of an over-thick septum, and describe this syndrome. Cite the gene responsible for many of these cases.
Briefly describe the heart disease seen in sarcoidosis and systemic amyloidosis, and recall the prevalence of minor amyloid deposits in the hearts of the elderly.
Describe endomyocardial fibrosis as seen in the apices of hearts of young Africans. Describe Loeffler's endocarditis ("with eosinophils") clinically and histologically. Describe endocardial fibroelastosis as seen in U.S. infants, both grossly and clinically.
Describe cardiac damage from anthracyclines (adriamycin and its relatives), and from cocaine.
Recall ruptured MI, penetrating injury, and backwards rupture of an aortic dissection as the only common causes of hemopericardium.
Tell how much fluid is required to produce cardiac tamponade, and under what circumstances it must accumulate.
Recognize the causes of pericarditis from table 13-9 of "Big Robbins". Mention the classic posture assumed by patients with pericarditis. Mention some of the organisms (TB, viruses) that may come from a serous pericardial effusion.
Recognize myocardial infarcts, uremia, radiation, lupus, rheumatic fever and trauma as the causes of fibrinous pericarditis, describe the origin of the distinctive physical sign, give the gourmet comparisons, and mention the anatomic progression and clinical prognosis.
Describe the causes and outcome of purulent (suppurative) pericarditis. List the significant causes
of hemorrhagic pericarditis (i.e., TB
and cancer) and
caseous
pericarditis (TB).
Recognize the cancers that tend to metastasize to heart. Be aware of the problems that such metastases can cause, and the difficulty of making the diagnosis.
Recall atrial myxomas ("wrecking balls") as the only common primary tumors of the heart. Tell where they arise and how they cause problems. Recognize their gross and microscopic appearances.
Recognize any good example of each of the types of lesions depicted in the videodisc series.
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.
The heart has its reasons of which Reason knows nothing. -- Pascal
INTRODUCTION
Cardiac pathology is relatively straightforward, if you understand the heart's physiology.
There are only a few important diseases and patterns of injury, and most of these are fairly well understood.
Looking at pictures of the heart? Remember:
I think that the pathology of the heart presents fewer difficulties than any other organ system except
GI tract, as long as you understand the physiology.
A variety of genetic syndromes produce various problems with the cardiovascular system. I have tried to resist the tremendous temptation to describe all my favorites. Instead, I've included only the ones that a generalist should know.
* THE PROARRHYTHMIAS FIASCO
Had CAST not included a placebo group, the erroneous conclusion that drug therapy did no harm might have been reached.
--NEJM, cited above.
"Proarrhythmias" are rhythm disturbances generated or made worse by anti-arrhythmic drugs. And they are quite common. In past decades, there have been fads for prescribing anti-arrhythmic drugs to asymptomatic people with ordinary ventricular ectopic beats (PVC's) and who have never had a heart attack. This is indefensible (Am. J. Card. 64: 50-J, 1989; NEJM 312: 193, 1985), and we can only guess how many thousands of people have died worldwide as a result.
ATHLETE'S HEART (is good: Eur. Heart. J. 17: 127, 1996).
The heart is special, because one of the most common "abnormalities" is the desirable result of
vigorous aerobic training.
Further, the athlete develops tremendous collateral circulation. If something happens to one
coronary artery, the percentage of lost myocardium (if any), and the absolute mass of lost
myocardium, are likely to be less. Surviving a major rhythm disturbance may still be a problem, but
death from cardiogenic shock in the acute phase is unlikely.
Also, exercise does offer some protection from coronary artery atherosclerosis. Most runners also
avoid tobacco and cholesterol-raising foods, and exercise tends to keep hypertension
and adult-onset
diabetes at bay, making it harder to sort out the benefit of exercise itself.
Nevertheless, even the best runners enjoy no
absolute immunity to coronary artery atherosclerosis, with all its
serious side-effects.
People who weren't thinking (including some physicians in the 1950's) used to talk about "athlete's heart syndrome" as
if it were something to be avoided. The "reasoning" was that failing hearts in disease tend to be
hypertrophied, and.... Silly, okay. Probably the only common situation in which a person
should avoid heavy aerobic training is some birth defects in which cardiac hypertrophy is likely to
impair outflow from the left ventricle. (Outstanding among these is hypertrophic cardiomyopathy).
* One group reports that athletes' hearts do not hypertrophy to a thickness
of more than 12 mm unless their chambers are also dilated, which should help
make the distinction from diseased hearts: J. Am. Coll. Card. 40: 1431, 2002;
this surprises me, as it does not square with my own experience after having
autopsied a few athletes.
CONGESTIVE HEART FAILURE ("CHF"; review Am. Heart J.
138: 5, 1999)
Inability of the heart to handle the volume of blood returned to it.
Either the heart muscle cannot pump because of intrinsic disease, or the blood is flowing in the
wrong way, or the heart must pump against excessive resistance, or the heart must pump a
preposterously large amount of blood (the latter is "high output failure").
Physiologists speak of "forward failure" (i.e., inability to perfuse the arteries) and "backward
failure" (i.e., congestion and its problems). Both occur simultaneously, of course, but one or the
other may be more obvious clinically.
The distinction between "congestive heart failure" and "cardiogenic shock" is admittedly artificial.
"Cardiogenic shock" is a term reserved for the acute situation (usually a myocardial infarct);
"failure" can simply mean inability to handle the ordinary venous return.
Exactly why the over-burdened heart's strength starts to fail is often unclear, and its response to
pharmacologic interventions often makes the picture more mysterious. There is talk of induction of
an abnormal myosin isoenzyme which is a poor ATP-ase, as well as decreased numbers of beta
sympathetic receptors, etc.
There's much interest in the effects of heart failure itself on the heart, both changes in the shape of
the heart that render its pumping and/or filling less effective ("remodelling"; Am. Heart J. 130: 153, 1995), and
problems with the cells themselves (notably failure of reuptake of calcium from the sarcoplasmic
reticulum; see Am. Heart J. 129: 684, 1995).
* Why is the heart of a fat person bigger? Is it simply from
the extra exercise of carrying around 100-200 or more pounds of weight?
Or is it the result of lack of adiponectin secretion by overstuffed
adipocytes (Nat. Med. 10: 1384, 2005)? How can anybody tell?
Tumor necrosis factor is one of the "usual suspects" here as well,
and there are some efforts to help CHF by administering its receptor
("etanercept": Circulation 99: 3213, 1999).
You can help out a congestive-heart-failure person, somewhat, by improving aerobic muscle tone
(i.e., more efficient burning of fuel), but exercise is no panacea (J. Am. Coll. Card. 25: 1239, 1995;
J. Am. Coll. Card. 27: 140, 1996; JAMA 283: 3095, 2000).
* Future pathologists: Serum cardiac troponin T (already in use
pre-hospital to screen for MI's: Am. Heart J. 138: 45, 1999)
as a marker for how
bad my congestive heart failure is today: Am. Heart J 138: 95, 1999.
Nesiritide, a natriuretic peptide originally found in brain,
helps CHF: NEJM 343: 246, 2000; you can also measure levels
to detect CHF (NEJM 347: 161, 2002); B-type natriuretic peptide
triumphs as a way to distinguish CHF from other causes of dyspnea:
NEJM 350: 647, 2004. No surprise.
You'll need to know this somewhat artificial classification of
cardiac hypertrophies, since
a clinician or radiologist may ask you about it, and as there's more talk
about "remodelling of the heart" (NEJM 358: 1370, 2008, it may eventually come down to a real science.
Eccentric hypertrophy: The heart too bitand it is not able
to empty properly. The cardiac myocyates are LONGER,
with new sarcomeres laiddown BEYOND existing ones.
Thick wall, chamber is very expanded and does not empty adequately.
Perhaps the heart is pumping too much blood
(anemia, AV shunts, thyroid disease, others) and/or
it refills (aortic regurgitation)
and/or there's a dead zone from an old infarct
and/or it's
doing its best but can't keep up for whatever reason
(i.e., congestive heart failure from most causes).
Looks bigger than a concentrically hypertrophied heart of the same weight
on a chest x-ray. (Why?)
Physiologic hypertrophy: Aerobic athlete; also late in pregnancy.
Thick wall, the chamber can fill tremendously but empties very well.
Word on the street is that hypertrophied cells are longer than they are thicker,
but since so few specimens come in for study, the question's not settled.
Watch for the molecular biology -- including expressions of variant myosins --
to be uncovered as we learn more about conditioning.
Hypertrophic cardiomyopathy: Uneven fiber
enlargement and scrambling
not to be confused with any of the above. Bumps
on the heart muscle notably around the aortic outflow
track.
Measurements for future pathologists:
350 gm...
Traditional normal upper limit of weight for an adult couch potato's heart
1.5 cm...
Traditional normal upper limit of thickness for an adult couch potato's left ventricle
0.5 cm...
Traditional normal upper limit of thickness for an adult couch potato's right ventricle
Measurements don't include the trabeculae carnae.
* Fun to know: If the heart was once very hypertrophic but is so no longer
(i.e., an athlete gone to seed, a hypertensive or valve-disease patient
successfully treated), the anterior and posterior descending coronaries are
very wiggly "accordion arteries". Why?
Less fun: When someone dies suddenly with only a large heart -- concentric or
eccentric hypertrophy, and the medical examiner finds no other cause of death,
it's considered acceptable to blame a rhythm disturbance
(NEJM 358: 1370, 2008 -- the article makes the point that in athletic/physiological
hypertrophy, you do NOT get rhythm problems as a result). I've always been shy about doing this,
but it comes up often in high-profile "sudden deaths of athletes."
Left-sided congestive heart failure
Failure of the left side of the heart to pump sufficient blood.
Except in the case of pure mitral stenosis (why?) or amyloidosis (why?), the left ventricle will be
hypertrophied and dilated. The left atrium will usually be, also (and especially in mitral valve
disease, why?)
The common causes of left-sided failure
Ischemia (old or recent myocardial infarct, ischemic muscle disease)
Aortic or mitral valve disease
Systemic hypertension
Myocardial disease / cardiomyopathy
NOTE: Of these, uncontrolled "systemic hypertension" (i.e., too much blood to push through too-narrow arterioles) is the
most common; when the heart fails, blood pressure drops, making the true cause
less obvious. See JAMA 273: 1363, 1996 (Framingham). How it progresses: JAMA 275: 1557,
1996; J. Am. Coll. Card. 25: 888, 1995.
The common effects of left-sided failure
First, on exertion
Later, paroxysmal nocturnal dyspnea ("cardiac dyspnea"); on lying down for a while, fluid
redistributes itself in the body, resulting in pulmonary edema. I think that the
reason that it's paroxysmal (i.e., comes on all of a sudden)
is that as the lungs become heavier (i.e., congestion, maybe edema)
their weight presses on the pulmonary veins which in turn
makes them more congested. 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?
Diastolic heart failure is a special situation in which the ejection
fraction is normal but the person is still in failure. The ventricle will not relax / is too
stiff to fill properly. It is not rare; the pathophysiology is being worked out
(NEJM 350: 1953, 2004).
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. You'll see dependent edema probably
because the veins of the body constrict extra-hard to return blood to the heart.
The causes:
Anemia
Hyperthyroidism
High fever
Shunts between an artery and a vein
Beriberi (poor autonomic control)
Paget's disease of bone (abnormal bone vasculature)
Iatrogenic (i.e., shunts in dialysis)
Right-sided congestive heart failure
Failure of the right side of the heart to pump enough blood.
As you'd expect, the right ventricle and atrium will usually be hypertrophied and dilated.
The common causes of right-sided failure
Pulmonary emboli (acute or chronic)
Any disease interfering seriously with lung ventilation
Emphysema
Cystic fibrosis
Fibrosing lung
Most others
NOTE: The mechanism, of course, is increased pulmonary vascular resistance (due to fibrosis
and/or the hypoxic vascular response; remember this?)
Left-sided heart failure!
Cardiac defects with left-to-right shunts (why?)
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: "Cardiac cirrhosis" of the liver, often discussed in textbooks as the result of right-sided
failure, almost never happens. The one time you might see it is in longstanding, severe tricuspid
insufficiency, with or without right-sided failure (why?)
NOTE: Some pathophysiologists include cardiac tamponade as a type of right-sided failure.
* Good news: In contrast to studies of selected patient populations
with various illnesses from decades ago, black and white
people with congestive heart failure seem to get equally good treatment (JAMA 289: 2517, 2003).
This seems to be part of a general trend to eliminate (and even reverse)
the past tendency to undertreat minority patients (NEJM 354: 1147, 2006).
ISCHEMIC HEART DISEASE
The cause of around 750,000 deaths annually in the U.S. In 90% or more of the cases, the problem
is coronary artery atherosclerosis (ASCVD).
In the setting of acute ischemia, one common mechanism of death is cardiac rhythm disturbances
("arrhythmias", one of the great misnomers in medicine). Don't worry about the details here; just
remember what you've already learned about (1) ischemia making membranes abnormally
permeable to ions, and (2) action potentials and how they result from altered permeability to ions.
Cigaret It's also worth remembering that coronary arteries usually increase their diameters substantially as
atherosclerosis worsens (study from my old department at Bowman-Gray: JAMA 271: 289,
1994), a phenomenon that saves lots of lives.
Future pathologists: We (unlike angiographers) refer to coronary artery stenosis in terms of
percentage of cross-sectional area occluded. Why?
You know the dominant coronary artery is whichever
supplies the posterior descending coronary
artery.
Angina pectoris: Pain in the chest from coronary insufficiency, in the absence of myocardial
infarction
Regardless of its category, all angina is due to some combination of coronary stenosis (usually
atherosclerotic), coronary spasm (demonstrable on angiogram), thromboxane A2 release and platelet
aggregation, and temporarily increased myocardial work load.
Stable ("classic", "typical", "Heberden") angina generally results from increased work in a patient
with coronary atherosclerosis, and relieved by rest.
Generally, three-vessel disease with >75% stenosis in each of three coronary arteries is sufficient to
cause problems. Of course, finding 90+% stenosis is commonplace in the U.S. Ask patients about
exacerbation of pain on climbing stairs or walking against cold wind.
Unstable ("pre-infarction", "crescendo", "acute coronary insufficiency") angina
In most cases, this is probably due to a thrombus developing, by fits and starts (white regions,
organization, etc.), over a ruptured plaque. Untreated, many of these people get an MI soon.
* "Is it really a heart attack?" Sometimes it's tough to know, especially
without an autopsy. "Infarctlets" / "CK leaks" / "troponin-positive acute coronary syndrome"
are now discussed as being coronary ischemic events that raise
cardiac enzymes but do not produce the EKG changes of a "true MI".
No one knows exactly what to do with these patients (Br. Med. J. 324: 377, 2002; the traditional
rx of calcium channel blockers fails more often than not Chest 123: 380, 2003).
* The endothelial nitric oxide synthetase gene has a mutant allele
that is a strong predictor for coronary artery spasm: Circulation 99:
2864, 1999.
* A "mouse model" (?) for Prinzmetal's has a mutation in a minor
potassium pump; sudden cardiac death and coronaries that over-react to
minor vasoconstrictors characterize this mouse: Nat. Med. 8:
466, 2002; J. Clin. Invest. 110: 203, 2002.
Cardiac syndrome X ("microvascular angina"), with classical clinical
angina and wide-open coronary arteries, and a generally good prognosis,
is an autonomic (?) disturbance in which the smooth
muscle of blood vessels does not dilate appropriately and/or constricts
too easily. These people may not get the red flush on re-perfusing a forearm made
ischemic by a blood pressure cuff. More about this arcane syndrome,
which is quite common and seems to have something to do with insulin
resistance, in Lancet 342: 136, 1992, and
Am. J. Card. 79: 961, 1997; NEJM 346: 1948, 2002; Hosp. Pract. 35(2):
75, Feb 15, 2000.
* You can supposedly diagnose microvascular angina in the lab by injecting acetylcholine.
Microvascular angina update: Lancet 351: 1165, 1998. "Coronary microvascular
disease" and how difficult it is to study: NEJM 356: 830, 2007 -- causes include
the familiar arteriolar sclerosis of hypertension, the strange muscling
of the little arteries in hypertrophic cardiomyopathy, a poorly-understood change
caused by aortic stenosis, and Fabry's (extreme; Heart 92: 357, 2006).
Don't confuse it with metabolic syndrome X, which is the poorly-understood, all-too-common
syndrome of obesity, hypertriglyceridemia, low HDL,
hypertension, and insulin resistance.
This common (maybe 1 million/year in the U.S.) catastrophe underlies many, but by no means all,
fatal cases of ischemic heart disease.
There are fewer myocardial infarcts nowadays than in the past, and the odds for a patient with a
myocardial infarct are much better, too, especially once he or she has made it to the hospital (NEJM
334: 884, 1996). Causes of myocardial infarcts
Atherosclerosis: Makes up 90% of coronary artery disease
{03476} atherosclerosis, coronary artery
The pathologist can usually find either a ruptured plaque (often with an overlying thrombus, hence
the archaic name "coronary thrombosis"; review of coronary thrombi Am. J. Card. 68: 28B, 1991),
or (less often) a hemorrhage into a plaque, ballooning its cap against the opposite wall. If neither are
present, but there's horrendous atherosclerosis and no other explanation, we assume the thrombus
lysed.
No surprise: The Armed Forces Institute of Pathology
documents
that sudden cardiac death occurring during intense
physical exertion typically results from a ruptured plaque:
JAMA 281: 921, 1999.
Long afterwards, look for a recanalized thrombus.
*Space-age medicine! Viewing the thrombus by angioscopy NEJM 326: 287, 1993. Unstable
angina thrombi are likely to be white fibrin-platelet thrombi or organizing thrombi (why?), etc. And
the thrombi overlie plaques that are lipid-rich and/or disrupted (no surprise): Am. J. Card. 79:
1106, 1997.
The recreational drug (1) produces coronary artery constriction (spasm, or whatever, nobody really
understands it NEJM 333: 1267, 1995; Am. J. Card. 79: 492, 1997) and cardiac ischemia
and even infarction (Circulation 99: 2737, 1999),
especially when combined with cigaret Future pharmacologists: The drug opens sodium channels, perhaps opens calcium channels, and
prevents synaptic re-uptake of catecholamines. Crystal meth probably does
the same thing (J. Tox. 41: 981, 2003).
* Hopefully no one was surprised by the results of a huge study
that showed that cocaine's effects on the heart are not mediated by its
causing precocious atherosclerosis (Am. Heart. J. 150: 921, 2005).
Prinzmetal's coronary spasm
Myocardial bridge and diving coronary artery, especially involving a portion of the left
anterior coronary artery. Vasculitis
Remember (1) lupus; (2) polyarteritis nodosa; (3) rheumatoid arthritis; (4) Kawasaki's;
(5) Takayasu's; (6) mycotic aneurysms (remember what those are? seen in bacterial endocarditis);
(7) rarely, exotic infections.
{06569} polyarteritis nodosa of a coronary artery
{03525} syphilis. Nice plasma cells.
Dissecting hematoma
A "dissecting aneurysm" can slide right up through a coronary ostium and cause occlusion. Or
trauma can induce this change in an artery.
{06575} coronary artery dissection
Shock and left-sided failure, even if mild, in the setting of subtotal coronary occlusion.
A drop in blood pressure from any cause is likely to produce a subendocardial infarct.
(By definition, a subendocardial infarct is less than 50% as thick as the wall).
This is a
watershed infarct of the myocardium farthest from the coronary, but not close enough to the
chamber to get its nutrients from the blood in the chamber.) If all three coronaries are stenotic, the
infarct is likely to be circumferential.
* A favorite place to find subendocardial infarcts is in the tips
of the mitral valve's papillary muscles. Why?
*Amyloid of the coronaries shouldn't cause an infarct, as the lumen is open
and the endothelium undamaged.
{03386} coronary artery amyloidosis
Clinical picture of the "MI" patient
Everyone knows the "typical" uncomplicated heart attack victim. There is chest pain (maybe,
perhaps "crushing") radiating to the (left arm? jaw? abdomen? wherever?), perhaps with
diaphoresis, perhaps with shortness of breath, perhaps with a feeling of fear, or perhaps with none of
these ("silent infarct").
Serum enzymes (troponin, CK, perhaps with an "MB" cardiac isoenzyme band) begin to rise in perhaps 2-4
hours, but may be normal in a day or two. Ask your cardiologist how often to check. Later, look
for the famous "LDH1>LDH2" isoenzyme flip.
The EKG changes depend on the location. Remember the subendocardial infarcts are notoriously
hard to pinpoint by EKG, and that posterior wall infarcts are easy to miss, too.
You'll learn of the management and treatment of these patients while in the "unit". Remember that
education about reducing risk factors is an important part of cardiac rehabilitation.
*Speaking of "cardiac rehabilitation": As a med student, I watched heart-attack survivors participate
at great expense in kindergarten-level exercise programs in special hospital areas, supervised by
boarded cardiologists. Not surprisingly, this is being replaced (under the much-maligned "managed
care") by expenditures on prevention (Am. J. Card. 79: 1075, 1997); for the "medically indigent"
who need to change their lifestyles, good results are obtained simply by talking and explaining
nicely (Am. J. Card. 79: 281, 1997). Pathology
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.
4-8 hours Earliest nuclear changes, polys appear; you may see a bit of dark mottling grossly
8-24 hours First clear gross changes, i.e., pallor; good
coagulation necrosis 24-72 hours Looks terrible, 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
10 days Nice granulation tissue; macrophage cleanup team may be removing the dead fibers, or the dead fibers
may persist for
weeks
7 weeks Nice scar.
* Today's standard for autopsy reports: "Acute" means polys, "Healing" means
the polys are gone but there are monocytes, "Healed" means the monocytes are gone.
"Microscopic" means less than 10% of the left ventricle (sic.), medium is 10% to 30%,
large is more than 30% (Am. Heart. J. 144: 957, 2001).
Among these, the only items that may be unfamiliar are wavy fibers (they had stopped beating and
were roughed-up by the beating of the rest of the heart) and contraction bands ("myofibrillar
degeneration"; densely eosinophilic cross-bands that probably result from calcium entering
membrane-damaged cells during reperfusion, i.e., reperfusion injury. Remember that?)
*The AFIP has finally documented what real-world pathologists have known and used for decades:
contraction bands let you know that a sudden death is of cardiac ischemic origin (gee whiz, Lancet 347:
1710, 1996)
* Future pathologists also note: Contraction bands can probably result from
epinephrine administration and/or electric shocks in CPR.
NOTE: Classically, the coronary arteries have the following distribution, and their occlusion will
result in transmural (across-the-wall, or
at least more than 50%) infarcts in the corresponding distribution
Right: Posterior-inferior wall, posterior 1/3 of septum
Left anterior descending: Anterior wall, anterior 2/3 of septum
Left circumflex: Lateral wall
There's plenty of variability. Especially when there's atherosclerosis, collateral formation may result
in the "best" artery supplying most of the heart, with minor occlusions producing "infarction at a
distance". Don't worry yet about "which gives you a bundle branch block", etc., etc.
NOTE: Infarcts almost never involve the right ventricle, unless it is extremely hypertrophied (why
do you think?) If the infarct extends as a result of more mayhem in the coronaries, expect a mix of
ages.
* Future pathologists: Try the nitroblue tetrazolium technique to demonstrate early myocardial
infarcts. Drop a slice of heart in the solution, and viable heart, containing an oxidizing enzyme, will
stain brown, and dead heart remain pale. I could never get this to work.
* Future pathologists: Don't mistake livor mortis for a posterior
wall MI!
{10103} myocardial infarct, acute
Complications occur in many but not all myocardial infarcts.
Rhythm disturbances may begin at any time until the damage to the conduction system is healed.
Formerly the great killer of "MI" patients, pharmacologic therapy is now generally successful in
managing these.
Left-sided congestive heart failure results from extensive damage to the heart. Whether or not there's
been a known episode of infarction, a person with severe coronary disease can get intractable heart
failure on the basis of ischemic scarring.
Cardiogenic shock results from necrosis of more than >40% of a non-athlete's myocardium. This is
usually fatal.
Rupture (ouch!) of the heart may occur, typically when the damaged heart is most soft (days 3-7 or thereabouts), but
day 1 ruptures are not unheard-of.
Rupture of the free wall will result in hemopericardium, tamponade, and instant death.
Rupture of the septum will result in a sudden left-to-right shunt.
Rupture of the papillary muscle produces severe mitral regurgitation.
{03614} ruptured wall
Aneurysm formation, mural thrombus formation, and embolization are dread, common side-effects
of myocardial infarcts. Ventricular aneurysms begin with the paradoxical movement of the necrotic
myocardium outward during systole; later the fibrous scar balloons. Large infarcts can produce large aneurysms that continue to
balloon out. Having a big aneurysm following a myocardial infarct greatly interferes with pump
effectiveness. Embolization from a mural thrombus (with or without an aneurysm) is often
devastating.
{06323} myocardial ventricular aneurysm
* Dressler's pericarditis / postpericardiotomy syndrome,
is pericarditis (sometimes with life-threatening effusion)
that supposedly
occurs weeks to years after an MI or cardiac surgery.
Dressler's is rare at best (Heart 80: 98, 1998),
and some cardiologists don't believe in it (Angiology 47:
83, 1996).
Chronic ischemic heart disease is cardiac muscle insufficiency
due to scarring from old infarcts, not necessarily large or known to have occurred.
It is a major cause of congestive heart failure. Think of this especially
if your patient has nighttime symptoms but the heart is perhaps not enlarged.
Sudden cardiac death
Definition: Death from cardiac causes in previously-asymptomatic person, within 1 (or 24) hours
after onset of symptoms. Most often, the person feels odd, then falls over dead. Either there's a
rhythm disturbance (most often, and typically "ventricular fibrillation"), or there's some sudden,
severe outflow obstruction. (Of course, the "forme fruste" of sudden cardiac death is a "fainting
spell"!)
Every day, around 1000 people in the U.S. get "sudden cardiac death". (Some of these are probably
included in the "1 million MI's" statistic; some probably aren't.)
Here's a rule: "Sudden death" means "sudden cardiac death". (Of course that includes
pulmonary emboli.) Apart from extreme trauma, severing of a major body vessel,
seizure death,
anaphylactic shock, super-fast poisons, or a hemorrhage that destroys the medulla,
there's probably nothing that can kill a human being in less than an hour that isn't on this list.
Here's another rule: There's almost always at least some warning
in the weeks beforehand. See Circulation 114: 1146, 2006.
The causes of sudden cardiac death
NOTE: Usually 75% stenosis of all 3 coronaries, often more
Being stressed (epinephrine -- no wonder, see Lancet 370: 1089, 2007) and having tobacco on
board probably exacerbate the rhythm disturbance, in
ischemia due to atherosclerosis or anything else.
* Future whole-person-oriented medical examiners: When somebody drops dead
with no pathology except three narrow coronary arteries, ask "Why today rather than yesterday?"
You will almost always find out if you ask about the circumstances.
For example, I hope no one was surprised that firemen are much more
likely to have heart attacks while fighting fires than at any other
time (NEJM 356: 1207, 2007 -- a firefighter seems to be almost equally
in danger from the fire and from his coronaries).
Vasospasm
Fiber necrosis
Rhythm disturbances
For example, having only one (Pete Maravich had no left main, also J. For. Sci. 35: 981, 1990), or having one
come off the pulmonary artery. These birth defects can cause other problems, too.
Ask a forensic pathologist about sudden death due to a "diving coronary artery", i.e., one which
enters the myocardium too soon, and "myocardial bridging" (very common in hypertrophic
cardiomyopathy and common enough in "normal people"), in which a band of heart muscle overlies a coronary
artery (NEJM 339: 1201, 1998; Chest 116: 574, 1999).
Atrial myxoma or thrombus obstructing the mitral valve
Hypertrophic cardiomyopathy
Aortic valve stenosis from most any cause
NOTE: This is important. The mechanism is acute coronary insufficiency. (1) The intra-myocardial branches of the coronary
arteries fill only during diastole. In aortic valve stenosis, diastole is
greatly shortened (why?). (2) Bernoulli's principle (remember that?) results in blood being sucked
out of the coronary arteries by the super-fast jet of blood passing through the narrowed aortic valve.
Cor pulmonale
Pulmonary embolus ("Do you think that should count as sudden cardiac death?"; maybe 50,000
extra "sudden death" cases among previously-healthy people in the U.S. per year)
Wolff-Parkinson-White, others ("bypass fibers", bundle of Kent; you'll learn about these on rotations; surgery Sci.
Am. 269(1): 68, July 1993; gene NEJM 344: 1823, 2001)
Amyloid in the bundle of His (real frequency as cause of death is unknown, may be high)
Anti-Ro/SSA disease of the unborn and babies ("neonatal lupus").
After surgically-induced trauma
Commotio cordis (myocardial concussion): Piezoelectric effect after a blow to the
chest on top of the T-wave. See
NEJM 333: 382, 1995.
Special hazard for
basketball, baseball catchers,
hockey goalies, other activities: JAMA 287: 1142, 2002.
Recreational inhalant use (i.e., glue sniffing, etc.)
sensitizes the heart to rhythm disturbances. This one's
easy to miss, especially if the family or friends have
removed the evidence. Finding this at autopsy is hard (Am. J. For. Med. Path. 27: 188, 2006);
in fact, it's a famous cause of "negative autopsy" that you'll never solve.
Iron overload (rhythm disturbances)
* Endocardial fibroelastosis (Am. J. For. Med. Path. 20: 357, 1999).
Ventricular septal defect involving bundle of His
* Familial syndromes with apoptosis of the sinus node and AV node
(Circulation 93: 1424, 1996).
Right ventricular dysplasia (see below)
Channelopathies
The unusual EKG is not always expressed, so keep a high index
of suspicion.
Whenever you suspect long-QT, either on EKG or
family history (i.e., unexplained
sudden death, including SIDS, or an episode of
torsade de pointes) or personal history
(torsade, syncope), get consultation; genetic screening for suspected families
will be routine probably by 2005.
This business is very tricky.
You'll learn on rotations what medications are contra-indicated
in which syndromes, when to place a defibrillator, and so forth.
You shouldn't need to be reminded to do an EKG on all pre-sports
physicals where there's a history of syncopal spells or sudden
unexplained death in a family member under age 30.
Swimming seems to trigger sudden death when the mutation is in the
potassium channel KCNQ1 (Mayo Clin. Proc. 74: 1088, 1999),
while loud noises trigger when the mutation is in the potassium channel KCNH2 / HERG.
When the mutation is in the SCN5A channel (same as a Brugada locus
but a different allele), death is likely to occur during sleep.
Although some old-time pathologists remain skeptical,
your lecturer believes that it will soon be standard practice to
check all first- and second-degree relatives of a person (especially
someone under age 18) who dies suddenly and has a negative autopsy, or who
has near-sudden-death.
In a 2005 Dutch study of the families of under-40 sudden death victims,
17 of 43 had a gene (catecholaminergic polymorphic V-tach was most common,
followed by long-QT,
Brugada, arrhythmogenic right ventricular dysplasia, hypertrophic
cardiomyopathy Circulation 112: 207, 2005).
Check includes EKG, exercise testing, and echocardiography.
In a 2007
series limited to youngsters who died, a hereditary disease was found in 14 of 25 families (Pediatrics 120: 3967, 2007).
European pathologists suggest professional standards for medical examiners
inclding molecular examination of "negative autopsies" in the young (For. Sci. Int. 156:
138, 2006; I don't predict this will become standard in today's cost-conscious USA medical examiners' offices.)
You also know that prolongation of the QT interval
in response to antipsychotic drugs predicts sudden unexpected
death from drug-induced rhythm disturbance: Lancet 355: 1048, 2000.
Sudden ventricular fibrillation with no anatomic findings
at autopsy.
Previous EKG's showed:
Usually men, more common among people of Asian ancestry, usually
die in their sleep at night.
Runs in families of course, and worth getting an implanted defibrillator for
if you have it (Am. J. Card. 83: 98-D, 1999).
About 3% of Thai and Laotian males have Brugada, and this
accounts for the flap about "delayed death from yellow rain
in Laotian immigrants" in
the 1980's.
The sodium channel mutation (LQT3 / SCN5A,
"idiopathic ventricular fibrillation" --
Nature 392: 293, 1998)
is the Brugada gene.
* Less deadly, but interesting to scientists: KVLQT1 is a gene for
familial atrial fibrillation (Science 299: 251, 2003).
* "Catecholamine-sensitive / catecholaminergic polymorphic V-tach" is a childhood disease in which
exercise reproducibly causes the arrhythmias. As I predicted, it's a
channelopathy, around half of cases it's in RYR2 (Mayo Clin. Proc. 79: 1367, 2004.
* "Idiopathic ventricular fibrillation", not familial and not caused by
stress, surely covers a few entities that have not yet been discovered.
Update on this and other causes of sudden cardiac death in structurally
normal hearts: J. Am. Coll. Card. 43: 1137, 2004.
NOTE: Syncope can warn of most of these. How?
NOTE: The other major causes of sudden unexpected
death are pulmonary emboli,
anaphylaxis, brain hemorrhages,
and epileptic seizures ("SUDEP"; Lancet 353: 888, 1999; Neurology 57:
430, 2001; Neurology 64: 1131, 2005; future medical
examiners see Am. J. For. Med. Path. 23: 307, 2002).
Other problems in cardiac ischemia
There's no room here to talk about the various rhythm disturbances and kinds of heart block that
may result from coronary insufficiency.
Worth remembering: Atrial fibrillation is a troublesome rhythm disturbance seen in coronary disease,
mitral valve disease (why?), hyperthyroidism (George Bush Sr.; why?),
ectopic (and ablatable) foci in the pulmonary veins
(NEJM 339: 659, 1998; now mainstream NEJM 354: 934, 2006), etc. It is especially dangerous
because thrombi tend to form in the quivering atria and embolize; this causes 1/3 of strokes in older
folks. (* Hereditary a-fib: NEJM 336: 905, 1997).
Serious degrees of heart block can cause people with coronary disease (or other problems; remember
amyloid) to drop over suddenly ("Stokes-Adams attacks", etc.) Get them pacemakers.
Despite the slight statistical
advantage of a one-drink-a-day person over a non-drinker with the same other risk factors (Br. Med.
J. 312: 1200, 1996; Br. Med. J. 314: 18, 1997), "your heart" is no reason to drink if you'd prefer not
to. Because of the media hype over red wine ("tannins in wine protect the heart, the French
paradox"), a couple of groups have looked at the cardioprotective properties of how-much vs. what-kind of alcohol (Br. Med. J.
312: 731 & 736, 1996); it's how much alcohol, not the kind of
beverage.
It's now painfully clear that a
person's successful return to near-normal living after a heart attack is largely a function of his or her
knowledge about the disease. Fatalism turns you into a cardiac neurotic, a bad way to live.
Education is the key to success. The implications for a primary-care physician are clear (Br. Med. J.
312: 1191, 1996).
No, it's probably not going to
happen because you were having sex, even if you have angina or had a myocardial infarct (JAMA
275: 1405, 1996).
The Cambridge Heart Anti-Oxidant Study finds a good
protective effect from vitamin E (Lancet 347: 781, 1996).
Hibernating myocardium: The most interesting discovery in "heart
pathology" in several years (NEJM 339, 173, 1998; update Am. J. Path. 160: 1425, 2002).
This seems to be an adaptation that allows fairly good survival
despite poor oxygenation (Am. J. Card. 98: 1574, 2006).
Pathologists can spot hibernating cells (at autopsy, of course) by...
* You can usually find a few of cells with the same morphology
normally in the subendocardium.
HYPERTENSIVE HEART DISEASE
In systemic hypertension, the left ventricle undergoes hypertrophy and, later, dilatation.
Probably the hypertrophy is mostly the result of pushing against the greatly increased load (more blood,
more vascular resistance). Some
hypertensives do have abnormally high cardiac outputs, so perhaps in these folks the heart is over-working for its own reasons.
There are rumors that some hypertensives suffer from chronic excess of catecholamines, and perhaps
this exacerbates the hypertrophy.
Ultimately, the hypertensive's left ventricle will probably fail. To make the diagnosis, the heart must
weigh more than 350 gm, and the left ventricle be more than 1.5 cm thick, with no other reason.
You remember the microscopic appearance of the hypertrophied myocardial cell (thick fibers, many-ploid squared "boxcar
nuclei"). It helps if the patient has a history of "high blood pressure", but
when congestive heart failure supervenes on the salt-overloaded, hyper-constricted vascular system,
"the high blood pressure may be cured".
NOTES: Despite "Big Robbins", I doubt that "hypertrophy" itself causes myocyte injury or
heart failure. I think that these result from the underlying hypertension.
NOTE: We talk about the
etiologies of systemic hypertension under "Kidney".
NOTE: Somebody may tell you that most congestive heart failure in the elderly is due to
coronary atherosclerosis, even in the absence of ischemic scarring, and that the ischemia causes the
hypertrophy. This pathologist doesn't follow this logic. If that were true, then probably you could
build muscle by holding your breath.
Remember that hypertension is also an important risk factor for atherosclerosis, stroke, and so forth.
COR PULMONALE
A quaint name for a very serious problem.
Any right-heart problem resulting from increased pulmonary vascular
resistance (usually poor ventilation, less often fibrosis or primary
vascular problems).
The cause of the poor ventilation may be anything from emphysema to a kyphoscoliosis.
"Cor pulmonale" would also include right-sided heart extra burden from narrowing of the pulmonary
vascular tree (Wegener's, pulmonary plexiform angiopathies, etc.) Whether "cor pulmonale"
includes failure due to pulmonary emboli is a question for semantics experts.
You already know how pulmonary ventilation causes increased
pulmonary vascular resistance
("causes pulmonary hypertension"). The right ventricle undergoes hypertrophy ("Feel that sternal
heave!"), dilates, loses its familiar crescent shape and becomes more rounded, and eventually fails.
The polycythemia that accompanies hypoxia make the blood more viscous and prone to clot. This
doesn't make the heart's job easier.
Increased pulmonary vascular resistance is a great impediment to a person's well-being. Often the
right ventricle's problems set the real limit on quality of life in lung disease.
NOTE: The strained right ventricle is extremely vulnerable to rhythm disturbances. Patients with
emphysema and cor pulmonale typically die very suddenly and unexpectedly as a result of an
electrical storm in their strained ventricle. This mechanism probably underlies many (if not most)
deaths from pulmonary emboli.
CONGENITAL HEART DISEASE: INTRODUCTION
Around 6-8 babies out of every 1000 has some kind of significant cardiac malformation.
Worth remembering:
Most of the time, nobody really knows why one heart forms normally and the next one doesn't (even folks
who study the molecular biology have no breakthroughs: Ped. Clin. NA 53: 989, 2006). If
onesibling has a defect, the next sibling has a 5% chance of having some (not necessarily the same)
defect.
Around 5% of cardiac defects are attributed to the chromosomal abnormalities, and the others now
account for <1% of new cases.
Classic "SIDS" cases (i.e., the child was reported to be asleep)
seldom reveal a cardiac malformation, but in the much less common
situation in which a child falls dead while awake is often
caused by a cardiac anomaly (and remember long QT): J. Ped. 141: 336, 2002.
A "shunt", of course, is abnormal flow of blood from one part of the circulation to another, which
aren't supposed to communicate directly. Intracardiac shunts are usually the result of birth defects.
Remember that intra-cardiac shunts that produce turbulence are also prone to get infected
(bacterial endocarditis; why?) As with other lesions with abnormal flow, look for jet lesions where
turbulence leads to endocardial thickening, and sometimes fibrin deposition and even infection.
"Cyanosis", you remember, refers to a concentration of >5 gm/dL of unoxygenated hemoglobin in
the arterial blood. Kids who are chronically hy
Athletic heart
Tom Demark's Site
The athlete's heart is hypertrophied, often remarkably so. You can feel the apex beat far lateral to
the mid-clavicular line. The pulse is slow (50-60 beats at rest), and the QRS complex often
tremendously large (why?).
* The myosin heavy chain in hypertrophied heart is beta, rather
than alpha as in a couch potato. Slower, more efficient.
As the heart is forced to work extra-hard, it undergoes hypertrophy (i.e., more muscle
mass) and perhaps dilatation (i.e., chamber enlargement, which helps pump the blood; remember Starling's
Law?) Eventually, however, the heart's strength cannot increase further, and the organ appears to
give up (i.e., it stops "obeying Starling's Law"). Now the chamber does not
empty fully.
* One team identifies urotensin II in remodelling heart (Lancet 359;
1990, 2002); maybe this is a protein involved in muscle hypertrophy; great
pictures in any case.
Its presence in the blood in a questionable death
correlates well with the presence of a myocardial infarction
(Am. J. For. Med. Path. 27: 175, 2006 -- curious study with
no "sudden cardiac death without myocardial necrosis" cases).
Left ventricular hypertrophy
Perhaps from hypertension
KU Collection
Concentric hypertrophy: The heart is bigger
but emptying fine. The cardiac myocytes are THICKER, with new sarcomeres
laid down ALONGSIDE existing ones.
Thick wall, chamber volume
is not excessively expanded, chamber empties fine.
Think of aortic valve stenosis and/or
increased systemic resistance in early hypertension
and/or "it's just happening and causing early hypertension.".
Coronary Artery Exhibit
Virtual Pathology Museum
University of Connecticut
Easy to remember: Mortality from coronary artery atherosclerosis dropped in the US
by about 50% between 1980 and 2000; of deaths prevented, about half were due to
healthier lifestyles and half were due to evidence-based medical interventions
(NEJM 356: 2388, 2007).
smoking is a risk factor for coronary atherosclerosis, and also
sensitizes the myocardium to be susceptible to rhythm disturbances in the setting of ischemia.
Prinzmetal's ("variant") angina is primarily attributable to vasospasm. Perhaps it's the cardiac
equivalent of migraine (if you believe migraine is caused by vasospasm).
Remember that scleroderma patients may have microvascular cardiac disease
due to the thickening of the intimal layers of the small arteries.
Acute MI
Photo and mini-review
Brown U.
Acute Myocardial Infarct
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery
Myocardial Infarct, Healed
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery
{06531} ruptured plaque with thrombus
Coronary with atherosclerosis
Decide yourself about obesity
WebPath photo
Atherosclerotic coronary artery
Serial sections
WebPath photo
Cocaine: Rough on the heart, and (your lecturer believes) the second most common cause of myocardial
infarction and sudden cardiac death in the U.S. Review Med. Clin. N.A. 89:
1323, 2005; South. Med. J. 98: 794, 2005.
smoking (NEJM 330: 454, 1994), which is bad because both
increase the heart's need for oxygen; (2) makes the heart more prone to rhythm disturbances, perhaps
by enhancing the effects of endogenous catecholamines; (3) can produce single-fiber necrosis and
contraction bands (something to do with ion channels), perhaps leading to myocarditis and/or dilated
cardiomyopathy. It is also known to produce (4) a dilated
cardiomyopaty (Lancet 369: 1574, 2007).
See below.
Do you believe these rather familiar autopsy findings
actually kill people? I don't know. Insurance studies show that
most people with myocardial bridges (i.e., bands of muscle across
a coronary artery; picture NEJM 358: 3921, 2008)
never have trouble. Since the bridge constricts the artery
worst during systole, and since the coronaries actually fill during diastole,
you wouldn't think so... However, the anecdotal reports are interesting (Clin. Card. 20
1032, 1998).
{06587} aspergillus
infection of a coronary artery
Kawasaki disease
Article and photos
AAFP
Epstein-Barr
coronary aneurysm
Advanced students
Yutaka Tsutsumi MD
{06584} amyloid (special stain)
{17483} amyloid myocardium
;
often good contraction bands;
definitely feels soft by 24 hours
Myocardial ischemic scar
Slide from Andrea McCollum MD
Cuyahoga County Coroner's Office
Subendocardial ischemic scar
Slide from Andrea McCollum MD
Cuyahoga County Coroner's Office
{06639} very early MI (bottom only)
{06428} myocyte degeneration (hydropic change)
{06431} myocyte degeneration (hydropic change)
{06642} contraction bands
{06651} contraction bands
{06645} necrosis and polys
{06630} subendocardial MI
{06654} good necrosis and polys (NOTE: the myocyte are
homogenized rather than pyknotic; that still means "dead")
{06443} road-kill, lots of polys, fibers very dead; good contraction bands remain
{06446} nice granulation tissue
{06663} nice granulation tissue
{06666} nice granulation tissue (left)
{06449} nice scar
{06338} nice scar
{06455} nice scar (trichrome)
You will learn how treat myocardial infarction on rotations.
In 2004, the first reports came in from experiments in which stem
cells (from bone marrow, not embryos) were injected into the injured
myocardium. After recovery, treated patients got about 6% new muscle,
with controls getting almost none (Lancet 364: 121 & 141, 2004).
The use of marrow stem
cells in reperfused tissue has enjoyed
further success, with patients seemingly
benefitting (NEJM 355: 1210, 2006).
{07141} hemopericardium
{03617} ruptured septum
{53285} ruptured septum
Ventricular aneurysm with thrombus
WebPath photo
Although there are no accepted immunologic criteria,
Dressler's is supposed
to have an
autoimmune basis, since anti-heart antibodies supposedly appear in the blood
and the response to steroids is
good.
Extreme straining against a closed glottis while upright (i.e.,
constipation death)
In keeping with the
idea that lupus involves defective clearance of apoptotic bodies, one group
found that heart cells themselves clear heart cells that undergo apoptosis,
and this clearing is inhibited by anti-Ro/SSA and anti-La/SSB: J. Clin. Inv. 116:
2413, 2006.
Myocarditis (even a little patch can cause rhythm problems and
even death: "Hank Gathers's disease"); I "buy this" when you see necrotic myocytes
along with a lymphocytic infiltrate ("Dallas criteria")
The long QT interval diseases (NEJM 339:
960, 1998; Circulation 99: 3165, 1999; stratifying risk NEJM 348:
1866, 2003; JAMA 289: 2120, 2003; Nat. Med. 10: 463, 2004;
NEJM 358: 169, 2008 -- there are now ten different loci and over a hundred
alleles).
Several different
channelopathies including some sodium channel mutations
(Circulation 101: 1698, 2000;
Circulation 102: 584 & 921, 2000) and a common
potassium channel mutation (Circulation 100: 1264, 1999).
This is now known to be a common cause of sudden death with no
anatomic findings at autopsy; this includes SIDS cases.
An episode of torsade de pointes may tip the alert
clinician, or the first sign may just be sudden death.
Updates Am. J. Med. 110: 50 & 385, 2001; Arch. Path. Lab. Med. 125:
116, 2001; Ann. Int. Med. 137: 981, 2002.
You need to be alert to these; presently the estimate is that
they cause about 4000 deaths in the US per year, i.e., around three
times as many as die of thyroid cancer.
Future pathologists: See Am. J. For. Med. Path. 22: 105, 2001
for "the molecular autopsy" (i.e., gene searches for long QT and so forth;
see J. Am. Coll. Card. 43: 1625, 2004)
that follows your performing an autopsy on a young
person who has died suddenly without a previous EKG or any anatomic or
toxicologic explanation for death. You can conact the Sudden Death Genomics
Lab at the Mayo Clinic (Mayo Clin. Proc. 80: 596, 2005; in particular
they're finding a great deal of long QT J. Am. Coll. Card. 49: 240, 2007.).

Brugada syndrome (mutated sodium channel; see below, clinical features
Circulation 99: 666, 1999; Lancet 355:
808, 2000).
While we are talking about sudden cardiac death...
When there is longstanding,
sublethal ischemia of a portion of the myocardium, the fibers
do not beat, but do not die.
A similar subject is the "myocardial stunning" seen after heart surgery;
the cause is apoptosis of cells (Ann. Thor. Surg. 73: 1229, 2002).
If circulation is restored, the fibers reconstitute themselves
and begin beating, though it may take several months.
syndrome produces a plethora of cardiac defects;
CONGENITAL HEART DISEASE WITH RIGHT-TO-LEFT SHUNTS ("early cyanosis"; "blue
baby", "cyanotic congenital heart disease")