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
What are the gross and microscopic pathology of acute rheumatic heart disease?
- _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
Describe the myocytolysis and karyorrhexis debris shown here.
- 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
When do cardiac myocytes deprived of oxygen start to die? Where does this start and end? What does it look like on an ECG?
- 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
What is marantic endocarditis?
- 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
What do you see?
- Tiny (1-2mm) verrucous (wartlike) vegetations lined up on valve closure
- Part of gross pathology of acute rheumatic heart disease
29
Which leads are lateral, inferior, septal, and anterior?
- Lateral: 1, aVL, V5, V6
- Inferior: 2, 3, aVF
- Septal: V1, V2
- Anterior: V3, V4
30
Describe the timeline for the arrival of "repair" cells at the site of an MI.
- 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
What do you see?
- Mitral stenosis
- Almost all rheumatic; marked female predominance
- Murmur would be during diastole
32
What is ischemic preconditioning?
- Resistance to mild-moderate ischemia due to induction of protective proteins by brief episodes of ischemia
33
What are stunned myocytes?
- Myocytes injured by acute ischemia that look normal microscopically, but need time (several days) to repair before they can work normally again
34
What do you see?
- ST-segment elevation going to Q-wave
- ST-elevation MI (STEMI)
35
What do you see?
- Anitschkow cells
- Also called caterpillar cells bc they have clumped chromatin, resembling a caterpillar
36
What do you see?
- Thin, wavy myocytes
- Sometimes present, sometimes the earliest microscopic evidence of MI
- As early as 30 minutes after it has occurred
37
What do dead cardiac myocytes look like? How long does it take to see evidence of this?
- 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
What are the reperfusion effects in an MI?
- 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
What do you see? What is its pathology?
- 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
What is reperfusion injury?
- 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
