Just as we said the Blood Vessel chapter was 1) atherosclerosis and 2) everything else We can now say the heart chapter is 1) ischemic heart disease and 2) everything else
This is the chapter outline, fairly logical
Remember 1.5 cm is considered to be the AVERAGE LV wall thickness, RV is 1/3 that, and atria are ½ RV.
This is a section from “Shotgun Histology”, in other words, the terms on the left describe the entire myocardium. Atrial natriuretic peptide (ANP), atrial natriuretic factor (ANF), atrial natriuretic hormone (ANH), or atriopeptin, is a powerful vasodilator, and a protein (polypeptide) hormone secreted by heart muscle cells. It is involved in the homeostatic control of body water, sodium, potassium and fat (adipose tissue). It is released by muscle cells in the upper chambers (atria) of the heart (atrial myocytes), in response to high blood pressure. ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressure.
The specialized myocytes of the heart’s conduction system, Purkinje fibers, running sub-endocardially, have this unique appearance. I do not recall any pathologist ever pinpointing an EKG abnormaility to a specific histopathologic abnormality of a Purkinje fiber.
Whichever artery winds up supplying the posterior interventricular septum is said to be “DOMINANT”. A thrombosis of WHICH coronary artery would usually result in sudden death? Ans: MAIN left coronary artery.
The myocardial perfusion is a good test of coronary artery and myocardial function.
These features are seen so commonly in autopsies of elderly people no matter what they died from. Also keep in mind that most people who do not die ACUTELY, die in cardiac failure. Also keep in mind that even though atherosclerosis is NOT considered normal aging, many of the atherosclerotic changes cannot be completely separated from “normal” aging, because it is so common.
One very key philosophical question is whether atherosclerosis is part of aging or not. We can leave that for the philosophers.
The pigment which accumulates with age is called lipofucsin, and caused the heart to appear “browner” than normal. This is called “brown” atrophy of the heart. Lipofucsin is another typical example of a golden brown, slightly refractile, INtrinsic pigment, which looks like hemosiderin, melanin, or bile, but accumulates, as a rule, on opposite poles of the myocyte nucleus. It is also called, appropriately, AGING pigmernt. It appears to be the product of the oxidation of unsaturated fatty acids.
This is the same analogy as the “straw” we talked about in the last chapter on blood vessels. You can classify cardiac diseases functionally into these 5 “pump” categories, like we had only 2 categories with the blood vessels described as straws or conduits.
ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressure
Very FEW hearts of elderly people at autopsy weigh the normal 250-300 gm. Atherosclerotic or CHF hearts weigh twice as much, hypertensive hearts weight three times as much, and cardiomyopathic hearts often weigh more.
LVH, how do you know this is probably NOT a cardiomyopathy? Ans: Thickening limited to LV
A good general diagram.
Note that not only is the FIBER thick, but so are the nuclei. Note squaring off of the nuclei, so called “BOXCAR” effect.
Can you understand why all of these findings can be related to LEFT sided heart failure? Ans: YES, primarily PULMONARY.
Can you understand why all of these findings can be related to RIGHT sided heart failure? Ans: YES, primarily STSTEMIC.
Does this look like it covers all bases? Ans: YES You can always logically remember heart diseases as being in one of these 5 categories.
Do the NAMES of these congenital heart conditions adequately describe the pathology? Ans: YES Why have I highlighted the “D”s and the “T”s? Ans: D = LR shunt, T= RL shunt (cyanosis, or “blue” babies). # kinds of Congenital heart diseases LR shunts RL shunts Stenoses of Aorta or Pulmonary Artery
LEFT to RIGHT SHUNTS, NON-cyanotic
All the RL congenital shunts are CYANOTIC, and have T’s in their names. CYANOSIS means UN-oxygenated blood is BYPASSING the lungs.
CLASSICAL “TETROLOGY” of FALLOT: 1) VSD, large 2) OBSTRUCTION to RV flow 3) Aorta OVERRIDES the VSD 4) RVH, including subpulmonic (causing stenosis to Pulmonary Artery)
In TRUNCUS ARTERIOSUS, the embryological structure known as the truncus arteriosus fails to properly divide into the pulmonary trunk and aorta
This is our THIRD category of congenital heart diseases after L—R and RL shunts. In this THIRD type, there is NO LR or RL shunting.
Can ATRESIA be thought of, anatomically, as being SEVERE stenosis? Ans: YES
Would you expect LVH in all cases? YES
If you would like to think of this as a spectrum, be my guest.
CHRONIC plaque PLUS acute thrombosis = Acute coronary syndromes.
Back to the inflammation saga?
IHD “spectrum” It is NOT unusual for the stenosis of stable angina to be MORE than the stenosis of an acute coronary syndrome on which there is plaque disruption!
What happens to myocardium when arteries are suddenly occluded, much of which is gotten from animal research. Note that the above changes are way earlier than gross or microscopic changes!
Why does the necrosis spread from the endocardium to the pericardium (i.e., epicardium)? Ans: Because the subendocardium is the LEAST well perfused by the subepicardial arteries. The “furthest away” theory, BOTH furthest away from the artery and furthest away from the base. The APEX of the myocardium is like the FOOT of a human being, it is the most likely to receive the brunt of ischemic and infarctive phenomena, no matter WHERE along the course of the artery the disease occurs. The apex therefore the most common site of wall motion abnormalities, logically.
NOTE: In ischemia, NO gross or microscopic findings are seen, visible changes are seen only with INFARCTION. You cannot see ISCHEMIA!!! When might myocardial rupture occur? Why?
Coagulative necrosis is PALE early. Or purple. Yellow when macrophages chew up the dead tissue. Sometimes red and soft again with organization or neovascularation. White and firm with fibrosis.
In “reperfusion”, not only are you oxygenating dead myocardial cells, but you are oxygenating the often destructive inflammatory process too.
C-reactive protein (CRP) is a protein found in the blood, made by the liver, the levels of which rise in response to inflammation (i.e. C-reactive protein is an acute phase reactant). Its physiological role is to bind to phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system.
All logical, I hope?
Even though myopathies are regarded as separate from IHD, you can have an ischemic myocardiopathy.
With the exception of the last two* items, all are easily demonstrated by autopsy.
Why might there NOT be an easily demonstrated thrombus or myocardial changes?
A chamber wall is only as thick as it has to be, i.e., more pressure more thickness. Please remember LVH does NOT CAUSE the hypertension, it is the adaptive REACTION to it! CHF causes HYPERTENSION, and HYPERTENSION causes CHF!
LV should be no more than 1.5 cm. LV should be no more than 1.5 cm. LV should be no more than 1.5 cm. LV should be no more than 1.5 cm. LV should be no more than 1.5 cm. LV should be no more than 1.5 cm. LV should be no more than 1.5 cm. LV should be no more than 1.5 cm. LV should be no more than 1.5 cm.
*Answer: owing to left atrial enlargement (i.e., dilatation, i.e. “stretching”)
Is this LV primarily hypertrophic, or dilated? What is an EDV?
As the alveoli EXPAND in COPD, the arterioles NARROW! In which type of cor pulmonale, might there be NO RVH, acute (such as massive PE or “saddle” embolism”), or chronic?
A reasonably logical way of looking at COR PULMONALE, or RIGHT HEART FAILURE
Why do BOTH stenosis and regurgitation cause hypertrophy of the chamber proximal to the valve?
If you have 4 valves and 2 possibilities of each valve (stenosis or regurgitation), then you have 8 possibilities, but these 2/8 cover 70% of all. So that mean, practically, clinically, R>L and Stenosis>Regurgitation Would a stenosis be more likely than a regurg to be chronic? Ans: YES
LVH is almost a reflex knee jerk conclusion to AS, but in this case there may be NO systemic hypertension. The LV extra work is at the aortic level, not the arteriolar level!
A GREAT classical Sydenham chorea (St. Vitus “Dance”) can be seen at www.youtube.com/watch?v=RnxqqW_nH0k
The great BRIDGE between infectious and autoimmune diseases! Also note this is a PAN-carditis, i.e., : 1) Endocardium 2) Myocardiom 3) Pericardium
What is a haček?
What is difference between “ACUTE” and “SUBACUTE” bacterial endocarditis? Ans: RATE and SEVERITY. The histology may be identical.
Vegetations: 1) rheumatoid = small, at chordae tendinae junction, 2) infectious = big (>5 mm), 3) lupus (Libman-Saks) = BOTH sides 4) NBTE = non-bacterial thrombotic endocarditis (<5 mm)
Another diagram which shows “quantification” of a diagnosis
Splinter hemorrhages, Janeway lesions (palms, soles), Osler’s “nodes” (raised), Roth’s spots (eye). Do you think that for every skin lesion you see there may be 10 visceral lesions which you do NOT see? Ans: Yes, I believe so!
Which valves would you expect to see Swan-Ganz vegetations? Ans: RIGHT HEART
Most carcinoids are from the GI tract, but only 10% of carcinoids produce “carcinoid syndrome”. Why are carcinoids selectively nasty to the RIGHT heart intima? ANS: Lungs break down serotonin. NOTE WELL: The CCPP for carcinoids!
Note the six ETIOLOGIC classes on the LEFT, And 3 FUNCTIONAL classes on the RIGHT
A “restrictive” cardiomyopathy is a wall which is NOT thickened or dilated necessarily, but RIGID in diastolic relaxation, i.e., loss of “compliance”. EF=1/EDV
LVEF = (EDV-ESV)/EDV, strictly a PERCENTAGE LVEF usually differentiateds the HYPERTROPHIC from the DILATED cardiomyopathies. EF=1/EDV
I hope as we run down the list all these etiologic explanations seem logical?
DILATED may be a misleading classification, because these hearts are HYPERTROPHIC also.
A genetic disease
How can you have decreased SV, decreased diastolic filling, but HIGH LVEF?
When you think RESTRICTIVE, think ↓↓↓ COMPLIANCE
The “bread and butter” pericarditis is classically and most often described in uremia or pericardial infections. What is the exudate? Ans: Fibrin “Bread and butter” pericarditis = fibrinous pericarditis.
Minarcik robbins 2013_ch12-heart
– Heart Failure: L, R
– Heart Disease
Congenital: LR shunts, RL shunts, Obstructive
Ischemic: Angina, Infarction, Chronic Ischemia, Sudden Death
Hypertensive: Left sided, Right sided
Valvular: AS, MVP, Rheumatic, Infective, Non-Infective,
Carcinoid, Artificial Valves
Cardiomyopathy: Dilated, Hypertrophic, Restrictive, Myocarditis,
Pericardium: Effusions, Pericarditis
Tumors: Primary, Effects of Other Primaries
40% of all deaths (2x cancer)
Wall thickness ~ pressure
(i.e., a wall is only as thick as it has to be)
– LV=1.5 cm
– RV= 0.5 cm
– Atria =.2 cm
• Starling’s Law
– DILATATION, any chamber, or all
– HYPERTROPHY, and chamber, or all
• Faulty embryogenesis (week 3-8)
• Usually MONO-morphic (i.e., SINGLE
lesion) (ASD, VSD, hypo-RV, hypo-LV)
• May not be evident until adult life
• Overall incidence 1% of USA births
• INCREASED simple early detection via
non invasive methods, e.g., US, MRI,
Incidence per Million Live
Patent ductus arteriosus
Tetralogy of Fallot
Coarctation of aorta
Atrioventricular septal defect
Transposition of great arteries
Total anomalous pulmonary venous connection
Ventricular septal defect
Atrial septal defect
• Gene abnormalities in only 10% of CHD
• Trisomies 21, 13, 15, 18, XO
• Mutations of genes which encode for
• Region of chromosome 22 important in
heart development, 22q11.2
deletionconotruncus, branchial arch,
• LR SHUNTS: all “D’s” in their names
– NO cyanosis
– Pulmonary hypertension
– SIGNIFICANT pulmonary hypertension is
• RL SHUNTS: all “T’s” in their names
– CYANOSIS (i,.e., “blue” babies)
– VENOUS EMBOLI become SYSTEMIC
• OBSTRUCTIONS: aorta or pulomnary
IS THE MOST
• NOT patent foramen ovale
• Usually asymptomatic until adulthood
• SECUNDUM (90%): Defective fossa
• PRIMUM (5%): Next to AV valves, mitral
• SINUS VENOSUS (5%): Next to SVC
with anomalous pulmonary veins
draining to SVC or RA
By far, most common CHD defect
Only 30% are isolated
Often with TETRALOGY of FALLOT
90% involve the membranous septum
If muscular septum is involved, likely to
have multiple holes
• SMALL ones often close spontaneously
• LARGE ones progress to pulmonary
• 90% isolated
• HARSH, machinery-like murmur
• LR, possibly RL as pulmonary
hypertension approaches systemic
• Closing the defect may be life saving
• Keeping it open may be life saving
(Prostaglandin E1). Why? Ans: TGA,
• Associated with defective,
inadequate AV valves
• Can be partial, or COMPLETE
(ALL 4 CHAMBERS FREELY
• Tetralogy of Fallot
• Transposition of great arteries
• Truncus arteriosus
• Total anomalous pulmonary venous
• Tricuspid atresia
• TETRALOGY of FALLOT most COMMON
– 1) VSD, large
– 2) OBSTRUCTION to RV flow
– 3) Aorta OVERRIDES the VSD
– 4) RVH
– SURVIVAL DEPENDS on SEVERITY of
– Can be a “PINK” tetrology if pulmonic
obstruction is small, but the greater the
obstruction, the greater is the RL shunt
of GREAT ARTERIES)
• NEEDS a SHUNT for
– PDA or PFO (65%),
– VSD (35%), “stable” shunt
– RV>LV in thickness
– Fatal in first few months
– Surgical “switching”
• Number of plaques
• Distribution of plaques
• Size, structure of plaques
ACUTE CORONARY SYNDROMES
• “The acute coronary syndromes are
frequently initiated by an
unpredictable and abrupt conversion
of a stable atherosclerotic plaque to
an unstable and potentially lifethreatening atherothrombotic lesion
through superficial erosion,
ulceration, fissuring, rupture, or deep
hemorrhage, usually with
(same as atherosclerosis)
• ½ million die of IHD yearly in USA
• 1 million in 1963. Why?
– Prevention of control controllable risk factors
– Earlier, better diagnostic methods
– PTCA, CABG, arrythmia control
• 90% of IHD patients have
ATHEROSCLEROSIS (no surprise here)
• ACUTE PLAQUE CHANGE *******
******* MOST IMPORTANT
ACUTE PLAQUE CHANGE
• Erosion/Ulceration, exposing ECM
• Acute Hemorrhage
NB: Plaques do NOT have to be severely stenotic to
cause acute changes, i.e., 50% of AMI results from
thromboses of plaques showing LESS THAN 50%
• Endothelial cells release CAMs,
• T-cells release TNF, IL-6, IFN-gamma to
stimulate and activate endothelial cells
• CRP (α-2 globulin) predicts the
probability of damage in angina
• Total occlusion
• Circulating adrenergic agonists, i.e., α
• Platelet release products, e.g., ADP
• Endothelially released factors, such as
Coronary Artery Pathology in Ischemic Heart Disease
Nonocclusive, often with thromboemboli
Widely variable, may be absent,
partial/complete, or lysed
Often small platelet aggregates or thrombi
15 sec.15 min.
Reduced perfusion, but NO infarction
– STABLE: relieved by rest or nitro
– PRINZMETAL: SPASM is main feature, responds to
nitro, S-T elevation.
Often younger with
people not much atherosclerotic narrowing.
– UNSTABLE (crescendo, PRE-infarction, Q-wave
angina): perhaps some thrombosis, perhaps some
non transmural necrosis, perhaps some
embolization, but DISRUPTION of PLAQUE is
universally agreed upon
• Transmural vs. Subendocardial (inner 1/3)
• DUH! EXACT SAME risk factors as
• Most are TRANSMURAL, and MOST are
caused by coronary artery occlusion
• In the 10% of transmural MIs NOT associated
– Emboli, e.g., mural thrombus
Onset of ATP depletion
Loss of contractility
to 50% of normal
to 10% of normal
Irreversible cell injury
TIMING of Gross and Microscopic Findings
Usually none; variable waviness of fibers at border
Occasionally dark mottling
Beginning coagulation necrosis; edema; hemorrhage
Ongoing coagulation necrosis; pyknosis of nuclei;
myocyte hypereosinophilia; marginal contraction
band necrosis; beginning neutrophilic infiltrate
Mottling with yellow-tan
Coagulation necrosis, with loss of nuclei and striations;
interstitial infiltrate of neutrophils
Hyperemic border; central
Beginning disintegration of dead myofibers, with dying
neutrophils; early phagocytosis of dead cells by
macrophages at infarct border
Maximally yellow-tan and
soft, with depressed redtan margins
Well-developed phagocytosis of dead cells; early
formation of fibrovascular granulation tissue at
Red-gray depressed infarct
Well-established granulation tissue with new blood
vessels and collagen deposition
Gray-white scar, progressive
from border toward core
Increased collagen deposition, with decreased
Dense collagenous scar
1 day (pyknosis, “waviness”)
3-4 days (neutrophils)
7 days (macrophages)
• Reperfusion CANNOT restore necrotic
or dead fibers, only reversibly injured
ones, and prevent further necrosis.
• REPERFUSION “INJURY”
– Free radicals
• EKG 1) Q-waves, 2) T-wave inversion, 3)
• (10% of MIs are “SILENT” with Qwaves)
• CKMB gold standard enzyme
• Troponin-I, Troponin-T better
• CRP predicts risk of AMI in angina
CIHD, aka, ischemic
• Progress to CHF often with no
pathologic or clinical evidence of
– Extensive atherosclerosis
– No infarct
– Hypertrophy & Dilatation present
SUDDEN CARDIAC DEATH
• 350,000 in USA yearly from atherosclerosis
• NON-atherosclerotic sudden cardiac death includes:
– Congenital coronary artery disease
– Aortic stenosis
– MVP, i.e., mitral valve prolapse
– Cardiomyopathy (sudden death in young athletes)
– Pulmonary hypertension
– *Conduction defects
– *HTN, hypertrophy of UNKNOWN etiology
AUTOPSY findings in SCD
• >75% narrowing of 1-3 vessels
• Healed infarcts 40%
• “ARRHYTHMIA” is often a very
convenient conclusion when no
anatomic findings are present, i.e.,
• EKG in LVH
Summary of LVH Criteria
1) R-I + S-III >25 mm
2) S-V1 + R-V5 >35 mm
3) ST-T depr. in L lead
4) R-wave in L lead >11 mm
5) LAE + other criteria
Positive Criteria: 1=possible
CHF, cardiac dilatation, pulmonary
venous congestion and dilatation
• NORMAL longevity, death from
• Progressive IHD
• Progressive renal damage,
hemorrhagic CVA (Which arteries?)
DIAGNOSIS=MMm, Mmmm, mmmmm
Positive blood culture(s) indicating characteristic organism or persistence of unusual organism
Echocardiographic findings, including valve-related or implant-related mass or abscess, or
partial separation of artificial valve
New valvular regurgitation
Predisposing heart lesion or intravenous drug use
Vascular lesions, including arterial petechiae, subungual/splinter hemorrhages, emboli, septic
infarcts, mycotic aneurysm, intracranial hemorrhage, Janeway lesions
Immunologic phenomena, including glomerulonephritis, Osler nodes, Roth spots, rheumatoid
Microbiologic evidence, including single culture showing uncharacteristic organism
Echocardiographic findings consistent with but not diagnostic of endocarditis, including new
valvular regurgitation, pericarditis
• <5 mm
• Trousseau syndrome (migratory
thrombophlebitis with malignancies)
• s/p Swan-Ganz
• Libman-Saks with SLE (both sides of
Episodic skin flushing
Nausea & Vomiting
• ↑serotonin, ↑ 5HIAA in urine
• FIBROUS INTIMAL THICKENING
– RV, Tricuspid valve, Pulmonic valve (all RIGHT side)
– Similar to what Fen-Phen does on the LEFT side
• Xenografts (porcine)
• 60% have complications within
Arrhythmogenic Right Ventricular Cardiomyopathy
(Arrhythmogenic Right Ventricular Dysplasia)
This is an uncommon dilated cardiomyopathy predominantly RIGHT ventricle.
So is NAXOS syndrome.
• Also called IHSS, (Idiopathic Hypertrophic
– GENETIC defects involving:
• Beta-myosin heavy chain
• Troponin T
• Myosin binding protein C
– PATHOLOGY: Massive hypertrophy, Asymmetric
septum, DISARRAY of myocytes, INTERSTITIAL
↓chamber volume, ↓SV, ↓ diastolic
↓ ventricular compliance
Chiefly affects DIASTOLE
NORMAL chamber size and wall
• THREE similar diseases affecting
– Endomyocardial Fibrosis (African
– Loeffler Endomyocarditis (eosinophilic
– Endocardial Fibroelastosis (infants)
• INFLAMMATION of MYOCARDIUM
• Chiefly microbial
–COXACKIE A & B, CMV, HIV
Trypanosoma cruzi (Chagas dis.), 80%
Lyme disease (5%)
• IMMUNE: Post-viral, rheumatic, SLE, drug
hypersensitivityalpha-methyl dopa, sulfas
LYMPHOCYTIC INFILTRATES are the USUAL pattern of ALL myocarditis, but
eosinophils, giant cells, and even trypanosomes can be seen occasionally
Amyloid, systemic or primary cardiac
– Congo red stain: green birefringence with
• Amyloid, aging
– Congo red stain: green birefringence with
• Hemochromatosis (Prussian Blue)
HYPER-, HYPO- -thyroidism