Ischemic Heart Disease Flashcards
1
Q
What does this show?
A
- Gross pathology of classical MI
- Acute = light brown, tan
- Subacute = yellow
- Old = white
1
Q
When is chronic rheumatic heart disease more common? About when do people typically get symptoms?
A
- More common with: recurrent carditis, severe carditis, and carditis at an early age
- Symptoms an average of 20 years after carditis
2
Q
What are the general principles of MI pathology (i.e., gross death, infiltration, time to heal)?
A
- Usually takes about 12 hours for dead cardiac muscle to show macroscopic (gross) manifestations of death
- Acute inflammation (neutrophils), clean-up (macros), and repair (fibroblasts) all come in from edge ofan MI bc no blood supply within it to bring them there (that is why it infarcted)
- Bigger the infarct, the longer it takes to heal and be converted to an acellular fibrous scar -> really big one can take 3 months
3
Q
What is a transmural infarction?
A
- Involves the full thickness of the heart wall
- 90% associated w/occlusive thrombosis super-imposed on atherosclerotic plaque with an acute change -> disruption of unstable, vulnerable plaque by rupture or erosion
3
Q
What is a subendocardial infarction?
A
- Involving inner portion of heart wall
- More likely to be patchy, and to have episodic extension
- Becoming more common than transmural
3
Q
What is acute rheumatic heart disease? What are the Jones criteria?
A
- Inflammation of endocardium, myocardium and epicardium (aka, pancarditis) after group A beta-hemolytic streptococcal pharyngitis
- 5 major diagnostic criteria (Jones criteria):
1. Fever
2. Polyarthritis
3. Sydenham’s chorea (rapid, uncoordinated jerking mvmts of hands and face)
4. Subcutaneous nodules
5. Erythema marginatum: pink rings on trunk and inner surfaces of limbs
4
Q
What do you see here?
A
- Very late subacute infarct
- Almost completely converted to a scar
- Just a few lymphos left (surveying work of macros and fibros)
4
Q
How do the leads help you localize an MI?
A
- LAD: anterior; V1-V4
- RCA: inferior; 2, 3, aVF
- LCX: lateral; 1, aVL, V5, V6
5
Q
What is the mPTP? Why is it so central to mito collapse in reperfusion injury?
A
- Opening the mPTP undoes the mito mem potential essential for generating ATP, wrecking its ability to provide energy for the cell
- mPTP is a voltage-dependent channel regulated by Ca and oxidative stress. Three different proteins influence the function of the mPTP:
1. Voltage-dependent anion channel (VDAC): outer mem
2. Adenine nucleotide translocator (ANT): inner mem
3. Cyclophilin D (CypD): matrix side, inner mem - Together, these proteins span the 2 mito mems, providing a path from the mito matrix to cytoplasm
5
Q
What do you see?
A
- Aschoff body
- Microscopic lesion of fibrinoid necrosis with histiocytes and Anitschkow cells (like a necrotizing granuloma, kind of)
6
Q
What do you see?
A
- Subcutaneous nodule: one of the 5 diagnostic criteria for rheumatic heart disease (Jones criteria)
7
Q
What do you see here? Why are there very few neutrophils?
A
- Viable myocytes with myocytolysis (aka, hibernating myocardium)
- Non-viable (dead) myocytes w/coagulation necrosis (showing loss of striations, hypereosinophilia, and loss of nuclei)
- Few polys bc they come in from the edges (where there is still blood flow; not from the subendocardial edge) -> lymphos, macros, fibroblasts that follow in the subacute healing phase also come from edges
8
Q
How does reperfusion injury involve the mitochondria?
A
- In ischemic cardiomyocytes, lack of oxygen causes electron transport in mito to back up, priming various components of ETC to generate oxygen free radicals when oxygen returns
- With reperfusion, a form of oxidative burst provokes a massive diversion of electrons from the electron transport system to generation of oxygen radicals
- Simultaneously, a large influx of Ca occurs
- A prime target of the excess oxygen radicals and Ca is the mito permeability transition pore (mPTP), which opens mPTP, collapsing mito function -> this is a central event in ischemic reperfusion injury
9
Q
What do you see?
A
- Hibernating myocytes: chronically ischemic myocytes that have cleared cytoplasm due to catabolism of their contractile proteins and need time to regenerate their contractile proteins before they work normally again
- Myocytolysis: light microscopic appearance of hibernating myocytes
10
Q
What do you see?
A
- Erythema marginatum: one of the 5 diagnostic criteria for rheumatic heart disease (Jones criteria)
11
Q
What is the microscopic pathology of reperfused MI?
A
- Subacute phase
- Days 4-10:
1. Lymphocytes (+/- eosinophils, plasma cells), then granulation tissue, collagen
2. Accelerated inflammation and repair: appears about 1 day older at 2 days, 2 at 4, and 4 at 6 - Days 11-end:
1. Healing of lg infarct can be accelerated from 12 to 7 weeks (small one done by 2 wks)
2. Patches of preserved myocardium commonly interspersed with scar -> may make re-entrant ventricular arrhythmias more common
12
Q
What is the molecular basis for ischemic preconditioning?
A
- Begins w/activation of various G-protein coupled receptors by autocoids, incl. adenosine, bradykinin, and opioids, which are released during brief periods of ischemia and reperfusion
- Activation of these receptors initiates a complex signaling cascade, incl. multiple kinases, that leads to opening of K channels in mito mem and maintenance of mPTP and electrical potential of inner mito mem
- Preservation of mito function and ATP production is primary mech for protective effect of conditioning
12
Q
What is the pathology of mitral stenosis?
A
- Almost all rhematic (i.e., chronic rheumatic heart disease); marked female predominance
- Slitlike fishmouth or round buttonhole stenosis with fibrous thickening and rigidity of valve
- +/- fusion of commissures
- Thickening, retraction, and fusion of chordae
14
Q
What do you see?
A
- Acute neutrophilic response to MI
- Typically reaches max around 2 days
16
Q
What do you see?
A
- Cardiac myocyte coagulative necrosis in narrow window after hypereosinophilia (and loss of striations, not evident here bc myocytes sectioned on end)
- Have signaled necrosis, but before neutrophils have responded to the necrosis
17
Q
What is the no reflow phenomenon?
A
- Failure of relieving obstruction at arterial level to restore blood flow
- Attributed to microvascular obstruction or edema
19
Q
How old is this infarct?
A
- Healing infarct (around 2-3 weeks old)
- Subacute (healing phase) MI with numerous fibroblasts and multiple new-grown blood vessels (neovascularization), which tend to come about the same time as fibroblasts, later than lymphocytes and macros
20
Q
What is the reperfusion injury salvage kinase pathway?
A
- Protective effect of conditioning involves, among other things, activation of a reperfusion injury salvage kinase (RISK) pathway in the mitochondria
- One component of this pathway is the action of phosphatidylinositol-3 kinase (PI-3K) on Akt (protein kinase B) and mammalian target of rapamycin (mTOR)
- Other component involves mitogen-associated protein kinase (MAPK) and p42/p44 extracellular signal-related kinase (ERK)
- 2 arms of pathway converge on p70s6 kinase to activate glycogen synthase kinase beta, which acts to prevent opening of the mPTP
20
Q
What are 2 reasons marantic endocarditis is a bad deal?
A
- Embolization from marantic endocarditis causes: strokes (cerebral infarcts w/irreperable brain losses), and infarcts of heart, kidneys, spleen, and other organs
- Worst thing: precursor for infective endocarditis
21
Q
What are the gross and microscopic pathology of acute rheumatic heart disease?
A
- Gross: tiny (1-2 mm) verrucous (wartlike) vegetations lined up on line of valve closure and fibrinous pericarditis
- Microscopic: fibrin + platelet thrombi on valves and Aschoff bodies with Anitschkow cells (caterpillar cells)
23
Q
Describe the myocytolysis and karyorrhexis debris shown here.
A
- Polys only live for a day or 2 in acute MI, then contribute their breakdown debris after a few days
1. They yield much more karyorrhexic debris than cardiac myocytes, so extensive nuclear dust is a feature of infarcts 3-6 days old - Thin subendocardial layer of cardiac myocytes can get enough O2 and nutrients from cardiac luminal blood before it is pumped out to survive an infarct (but not prosper) -> commonly catabolize their cytoplasmic contractile proteins
1. Cytoplasmic clearing of contractile proteins is called MYOCYTOLYSIS; might better be called “myoctyoplasmolysis” bc only cytoplasmic contractile proteins are broken down
25
Q
When do cardiac myocytes deprived of oxygen start to die? Where does this start and end? What does it look like on an ECG?
A
- Begin dying after about 20 minutes
- In transmural MI, starts in subendocardial zone, spreads in a wavefront to subepicardial zone, and is usually complete in about 3 hours
- ECG evidence includes ST-segment depression and T-wave inversion
26
Q
What is marantic endocarditis?
A
- Nonbacterial thrombotic endocarditis
- Common with:
1. Cancer (especially adenocarcinomas)
2. Disseminated intravascular coagulation (DIC)
3. Hyper-coagulable states
4. Long-term central venous catheterization
27
Q
What do you see?
A
- Tiny (1-2mm) verrucous (wartlike) vegetations lined up on valve closure
- Part of gross pathology of acute rheumatic heart disease
29
Q
Which leads are lateral, inferior, septal, and anterior?
A
- Lateral: 1, aVL, V5, V6
- Inferior: 2, 3, aVF
- Septal: V1, V2
- Anterior: V3, V4
30
Q
Describe the timeline for the arrival of “repair” cells at the site of an MI.
A
- Classic MI: unreperfused
- Day 2: infiltration by lymphocytes (bosses)
- Day 3: macros (garbage collectors) arrive
- Day 4: fibroblasts (collagen engineers) show up (+/- eosinophils and plasma cells)
- Begin at the periphery
- Early subacute phase: days 4-10
31
Q
What do you see?
A
- Mitral stenosis
- Almost all rheumatic; marked female predominance
- Murmur would be during diastole
32
Q
What is ischemic preconditioning?
A
- Resistance to mild-moderate ischemia due to induction of protective proteins by brief episodes of ischemia
33
Q
What are stunned myocytes?
A
- Myocytes injured by acute ischemia that look normal microscopically, but need time (several days) to repair before they can work normally again
34
Q
What do you see?
A
- ST-segment elevation going to Q-wave
- ST-elevation MI (STEMI)
35
Q
What do you see?
A
- Anitschkow cells
- Also called caterpillar cells bc they have clumped chromatin, resembling a caterpillar
36
Q
What do you see?
A
- Thin, wavy myocytes
- Sometimes present, sometimes the earliest microscopic evidence of MI
- As early as 30 minutes after it has occurred
37
Q
What do dead cardiac myocytes look like? How long does it take to see evidence of this?
A
- Usually takes about 4 hours for microscopic manifestations
1. BUT, dead thin, wavy myocytes may be visible as early as 1/2 hour after infarction - Dead myocytes in unreperfused MI usually show coagulative necrosis, which has 3 components:
1. Loss of normal cytoplasmic striations
2. Cytoplasmic hypereosinophilia
3. Nuclear changes (pyknosis, karyorrhexis, loss)
38
Q
What are the reperfusion effects in an MI?
A
- Smaller than it would have been
- More patchy than it would have been
- Hemorrhage into it
- More contraction band necrosis
- Accelerated inflammation and repair
- Diffusion of inflammation and repair
- Fewer neutrophils
- More macrophages
- More interstitial fibrosis
40
Q
What do you see? What is its pathology?
A
- Marantic endocarditis
- Pathology:
1. Small (1-5 mm) fibrin + platelet thrombi
2. Most common on atrial side of mitral valve
3. Second most common on ventricular side of aortic valve, usually on line of valve closure
41
Q
What is reperfusion injury?
A
- Hemorrhage and other injurious phenomena associated with bringing oxygen and calcium to injured tissue
- Attributed to reactive oxygen species (ROS) and the metabolic effects of calcium
