ICL 4.5: Pathology of Acute Coronary Syndromes Flashcards
what are hematoxylin bodies?
naked nuclei
septic infarct
infectious endocarditis embolism from the friable vegetations
what is ischemic heart disease?
it’s an imbalance between the supply/perfusion and the demand of the heart for oxygenated blood
this imbalance usually occursd due to reduced blood flow due to obstructive atherosclerosis of the coronary arteries (coronary artery disease)
what are the clinical manifestations of ischemic heart disease?
- MI (tissue death)
- angina (no necrosis)
- chronic ischemic heart disease with CHF
- sudden cardiac death
what are the pathological causes of ischemic heart disease?
- reduced coronary flow (atherosclerosis)
- increased myocardial demand (hypertrophy)
- reduced availability of o2 in the blood
how common is ischemic heart disease?
leading cause of death in the US with 500,000 deaths a year
there has been a decline in cases due to:
1. lifestyle modifactions
- elmiinating risk factors like smoking, hyperlipidemia, HTN
- technology has allowed for early diagnosis
- advanced therapies like angioplasty, stents, and CABGs
what is the pathogenesis of ischemic heart disease?
reduced coronary perfusion relative to myocardial demand
this can be caused by:
1. acute plaque change
- inflammation
- thrombosis
- vasoconstriction
how can acute plaque change cause ischemic heart disease?
- acute plaque change is rupture/fissuring exposing the highly thrombogenic plaque constituents
changes in plaques are triggered by stress, abrupt changes in BP, adrenergic stimulation, or increased platelets reactivity
- erosion/ulceration exposing the thrombogenic subedothelial BM to blood
- hemorrhage in the atheroma which leads to expanding its volume
how can inflammation cause ischemic heart disease?
inflammation plays a huge role in atherosclerosis which then plays a role in ischemic heart disease
endothelial cells interaction with circulation leucocytes leads to accumulation of t cells and macrophages in the arterial wall
macrophages then release chemical mediators which leads to atherosclerosis and eventually ischemia
**high sensitivity CRP is the major acute phase reactant and predicts the risk of coronary heart disease!! it’s a marker of atherosclerosis
how can thrombosis cause ischemic heart disease?
thrombosis in a partially occluded artery leads to complete occlusion of the coronary arteries
thrombosis can also embolize!
how can vasoconstriction cause ischemic heart disease? what are 3 causes of vasoconstriction?
vasoconstriction leads to disruption of plaques and ischemia
causes of vasoconstriction:
1. circulating adrenergic agonists
- locally released platelet contents
- impaired secretion of endothelial cell relaxing factors
what are the consequences of myocardial ischemia?
- stable angina
- unstable angina
- MI
- sudden cardiac death
what is stable angina?
results from an increase in myocardial oxygen demand
no plaque disruption
what is unstable angina?
plaque disruption
results in thrombosis and vasoconstriction
severe but transient reduction in blood flow which is why it doesnt cause necrosis
what is an MI?
- acute plaque change
- abrupt thrombotic occlusion
- myocardial necrosis
what is sudden cardiac death?
- regional myocardial ischemia
2. fatal ventricular arrhythmia
what is the coronary artery pathology in ischemic heart disease?
STABLE ANGINA
stenoses, no plaque disruption, no plaque associated thrombus
UNSTABLE ANGINA
some stenoses, frequent plaque disruption, nonocclusive plaque associated thrombus
TRANSMURAL MI
some stenoses, frequent plaque disruption, occlusive plaque associated thrombus
SUBENDOCARDIAL ENFARCT
variable stenoses, variable plaque disruption, variable plaque associated thrombus
SUDDEN DEATH
usually severe stenoses, frequent plaque disruption, small platelet aggregates or thrombi
what is angina pectoris?
it’s transient ischemia with paroxysmal pain and no necrosis
what type of pain do you feel with ischemia?
pressure pain
this is things like MI or angina
what pain do you feel with pericarditis pain?
pins and needles
stabbing pain
what pain do you feel with dissecting aneurysms or cardiac tamponade?
tearing my chest apart and radiating pain to the back
what are the 3 types of angina?
- stable
- unstable
- prinzmetal
what is the cause and effect of stable angina?
cause = chronic coronary stenosis of an atherosclerotic coronary artery
effects = pain on exertion
what is the cause and effect of unstable angina?
cause = disruption of plaque with superimposed partial thrombosis
effect = pain at rest and on exertion for prolonged period
what is the cause and effect of prinzmetal angina?
cause = coronary artery spasm
effect = pain at rest
A 55-year-old male, obese banker develops sudden crushing chest pain after a Board Dinner
The pain radiates to his left shoulder. His friends drive him to the emergency room upon arrival, he is found to be diaphoretic and his blood pressure is 80/40
The patient has been a heavy smoker for 40 years
obese, crushing chest pain, radiates to the left shoulder, diaphoretic, heavy smoker, stress from Board dinner
patient is in shock 80/40 BP and sweaty because the heart isn’t pumping properly
what are the risk factors for MI?
- HTN
- DM
- hyperlipidemia
- obesity
- smoking
10% < 40 years old
45% < 65 years old
what is the pathogenesis of MI?
sudden change in a plaque
platelet adhesions and aggregation and release of serotonin and platelet factors 3-4 = vasospasm mediated by factors released from platelets
activation of extrinsic coagulation pathway
occlusion of coronary artery by the newly formed thrombus
BUT 10% of transmural MI have no thrombus and are caused by vasospasm, emboli,or disorders of intramural coronary vessels so just because you don’t find a thrombus doesn’t mean your coronary artery hasn’t been occluded
what part of the heart is damaged when the LAD is occluded?
- anterior wall of the LV
2. anterior septum
what part of the heart is damaged when the RCA is occluded?
- posterior wall of LV
- posterior septum
- papillary muscles –> can cause arrhythmia
what part of the heart is damaged when the LCX is occluded?
lateral wall of LV
what is a transmural MI?
necrosis of the full thickness of the ventricular wall
this usually happens in an area of the heart that is perfused by a single coronary artery and there’s coronary atherosclerosis, plaque disruption or a thrombus
what is a subendocardial MI?
necrosis of 1/3 to 1/2 of the ventricular wall
this usually happens in an area of the heart that is perfused by more than one coronary artery
usually caused by shock, HTN or a transient thrombus
what is the evolution of morphological changes in an MI?
0-1 hr: relaxation of myofibrils, glycogen loss, mitochondrial swelling –> reversible injury
4 hrs: variable waviness of fibers at the border, sarcolemmal disruption, mitochondrial amorphous densities
4-12 hrs: dark mottling, early coagulation necrosis, edema, hemorrhage
12-24 hrs: dark mottling, ongoing coagulation necrosis, pyknosis of nuclei, myocyte hypereosinophilia, marginal contraction band necrosis, early neutrophilic infiltrate
1-3 days: mottling with yellow-tan infarct center, coagulation necrosis, loss of nuclei and attractions, brisk interstitial infiltrate of neutrophils
3-7 days: hyperemic border, ventral yellow-tan softening, beginning disintegration of dead myofibers with dying neutrophils, early phagocytosis of dead cells by macrophages at infarct border
7-10 days: maximally yellow-tan and sot with depressed red-tan margins, well-developed phagocytosis of dead cells, granulation tissue at margins forms
10-14 days: red-grey depressed infarct borders, well-established granulation tissue with new blood vessels and collagen deposition
2-8 weeks: gray-white scar progressive from border toward core of infarct, increased collagen deposition with decreased cellularity
2+ months: scarring complete, dense collagenous scar
what is coagulative necrosis?
denaturation of proteins inside the cell
so you can still see the cell but there’s fading of the nucleus because the cell is dying
what is the summary of evolution of morphological changes in an MI?**
4 hours: no changes that we can see
12-14 hours: dark mottling, neutrophils begin to invade, coagulation necrosis
1-3 days: neutrophils everywhere, inflammatory cascade has begun
3-7 days: yellow-tan softening meaning coagulation necrosis, neutrophils are gone, macrophages have come in
5-7 days is the most vulnerable time for the myocardium to rupture and cause a tamponade that could kill the patient
10-14 days: well established granulation tissue
2-8 weeks: scar
what is granulation tissue composed of?
- collagen
- fibroblasts
- blood vessels
- monocytes
a 50 year old male one week post acute mI present with sharp chest pain which increases with inspiration. his troponin levels are coming down.
CK MB normal, myoglobin normal
diagnosis?
tests?
sharp pain = pericardium pain
fibrinous pericarditis because it’s post MI! uremia and RF also cause fibrinous pericarditis
Dressler syndrome! occurs usually 10 days after MI and it’s a fibrinous pericarditis –> you’ll hear a friction rub because the damaged pericarditis is exposed to the immune system and when the antibodies eventually develop against the pericardium, they’ll attack it and cause a pericarditis
what are the non-specific lab findings you’ll see post-MI?
- increased ESR
2. increased WBCs (neutrophils)
how do creatinine kinase levels change post MI?
CKMB starts to go up at 4 hours post-MI but peaks at 12 hours
by 72 hours it’s back to baseline
how do myoglobin levels change post MI?
myoglobin starts to go up 2-4 hours post-MI but peaks at 9-12 hours
it’s back to baseline by 24-36 hours
what do myoglobin levels tell you about an MI?
myoglobin levels provide you information about:
- size of the infarct
- type of MI
transmural will have higher myoglobin than subendocardial
what are the advantages of measuring troponin-i levels post-MI?
Troponin-i is a cardiac marker that is truly cardiac specific, unlike CK-MB and Total CK.
Troponin-i, has a specificity of 99.4% vs. CK-MB which has a specificity of 92.8%.
Troponin-i, unlike other cardiac markers, will not show elevation in trauma or other disease states
troponin > 0.5 indicates an MI
how do troponin levels change post MI?
troponin-i starts to elevate 4-6 hours after onset of chest pain and remains elevated for 6-9 days after onset of chest pain
the fact that it remains elevated for 6-9 days will lend itself as a useful tool in diagnosis of those patients who present to the E.D. much later
troponin-i, due to the above facts, will eventually eliminate the need for Total-CK, CK-MB and LD Iso-enzymes
LDH is present in various tissues including the heart and during an MI, LDH-1 which is in the heart, the levels increase but now that we have troponin-i we don’t need to measure LDH1
what are the complication of MI?
- cariogenic shock and sudden death –> you go into shock because the necrotic heart fails and doesn’t pump so you have poor perfusion and the BP goes down due to pump failure
- contractile dysfunction –> heart failure
- arrhythmia if there’s papillary muscle rupture
- ruptured myocardium –> cardiac tamponade
- pericarditis
- mural thrombus
- ventricular aneurysm
- rupture of papillary muscles
how would a patient with cardiac tamponade present?
they can’t pump their heart because it’s being compressed by heart so you can’t feel their pulse BUT if you do an EKG though you can see electrical signals = pulsus paradoxicus
might also see distention of the jugular veins
what happens when the papillary muscles rupture?
- arrhythmias
2. mitral valve regurgitation
what is chronic ischemic heart disease?
aka ischemic cardiomyopathy
it’s a condition of the elderly who develop progressive heart failure as a result of ischemic myocardial damage
what are the predisposing factors to chronic ischemic heart disease?
- post-infarction
2. severe atherosclerosis without infarction but have myocardial dysfunction
what things can cause sudden cardiac death?
- acute myocardial ischemic arrhythmias
- congenital anomalies
- aortic stenosis
- mitral prolapse
- myocarditis
- cardiomyopathies
- hypertensive heart
- cocaine (vasoconstriction)
A 45 year old football coach is rushed to the ER after he collapses at the end of the game.
He is not responsive and has no pulse. EKG reveals abnormal electric signals.
diagnosis?
cardiac tamponade
pulsus paradoxicus
51 year old executive for a shipping company has been feeling some chest pain over the last year, particular after climbing up the stairs to the office. he had a cholesterol level of 250 and HDL of 25. his fasting glucose is 145. he smokes half pack of cigarettes a day. he’s overweight. he is admitted to the hospital after onset of severe chest pain that was substernal and described as crushing. he died 12 hours after admission
differential?
what was responsible for his symptoms?
acute MI!
pain with exercise = stable angina –> crushing pain = ischemic heart pain aka MI
risk factors = high cholesterol, low HDL, smoker, obese, sedentary lifestyle, DM
anginas pain due to poor perfusion of the myocardium secondary to coronary artery occlusion
when do neutrophils first appear in an MI?
1 day
when do macrophages first appear in an MI?
3-5 days
what is the most vulnerable time for a ruptured myocardium post-MI?
5-7 days
verrucus endocarditis
RF
people with pancreatic cancer and develop marantic endocarditis?
Trousseu’s sign
