Ischemia Flashcards
How long does it take for cardiac myocytes to die when they are deprived of blood supply?
20 minutes
transmural MI
full thickness of wall
most due to occlusive thrombosis superimposed on atherosclerotic plaque
death starts in subendocardial zone and spreads to subepicardial zone (complete in 3 hours)
How long does it take for dead myocytes to show microscopic manifestations of their death?
4 hours: loss of striation, hypereosinophilia, nuclear pyknosis, karyorrhexis, karyolysis and loss
exception: dead thin wavy myocytes visible at 1/2 hour
nuclear dust
feature of infarcts 3-6 days: breakdown debris of nuetrophils
myocytolysis
hibernating myocardium
subendocardial myocytes get enough O2 from cardiac lumen to survive, but they catabolize their cytoplasmic contractile proteins
early sub acute MI
4-10 days see first few cells coming from the periphery day 2: lymphocytes day 3: macrophages day 4: fibroblasts
subacute MI
2-3 weeks after MI
lots of fibroblasts, neovascularization
late subacute MI
mostly scar tissue
How long does it take to see gross manifestations of MI? What does MI look like grossly?
12 hours inflammation in from edges can take up to 3 months to heal and form fibrous scar acute (hrs): light brown to tan subacute (days): yellow old (wks to yrs): white
subendocardial infarction
involves inner portion of wall
more likely to be patch and have episodic extension
reperfusion effects of MI
- smaller
- patchy
- hemorrhage
- contraction band necrosis
- accelerated inflammation and repair
- diffusion of inflammation and repair
- fewer neutrophils
- more macrophages
- more interstitial fibrosis
reperfused subacute MI
days 4-10
lymphocytes, then granulation, then collagen
appears older than non-reperfused MI
healing accelerated
PATCHES of preserved myocardium: make re-entry ventricular arrhythmias more common
neutrophilic response to acute MI
12 hours
max at 2 days
stunned myocytes
injured by acute ischemia
look normal but need several days to work normally
reperfusion injury
bring oxygen (free radicals) and Ca to injured tissue target mPTP: opens mPTP and collapses mitochondrial function
mPTP
mitochondrial permeability transition pore
voltage-dependent channel
made of VDAC, ANT, and CypD proteins that provide path from mitochondrial matrix to cytoplasm
essential for generating ATP
VDAC
voltage-dependent anion channel
located on outer mitochondrial membrane
ANT
adenine nuucleotide translocator
located on inner mitochondrial membrane
CypD
cyclophilin D
matrix side of mitochondrial membrane
ischemic preconditioning
resistance to mild-moderate ischemia due to induction of protective proteins by brief episodes of ischemia
How does ischemic preconditioning work?
ischemia-> adenosine, bradykinin, opioids -> GPCR-> signaling cascade-> open K channels in mitochondrial membrane-> maintain mPTP and electrical potential of inner mitochondrial membrane -> maintainATP production
reperfusion injury salvage kinase (RISK) pathway
part of ischemic preconditioning
RISK-> PI-3K-> Akt-> mTOR
RISK-> MAPK-> ERK
both pathways prevent opening of mPTP
acute rheumatic heart disease
fibrinous pancarditis
after infection with group A beta-hemolytic streptococcal pharyngitis
Sx: fever, polyarthrits, Sydenham’s chorea, subcutaneous nodules, erythema marginatum
vegetations, aschoff bodies
sydenham’s chorea
rapid, uncoordinated jerking movements in primarily hands, feet and face
erythema marginatum
pink rings on inner surface of limbs and trunk
aschoff bodies
fibrinoid necrosis with histiocytes and anitschkow cells
anitschkow cells
caterpillar cells: clumped chromatin
chronic rheumatic heart disease
more common in carditis that is: severe, recurrent or at early age
Sx: 20 years after carditis, mitral stenosis (fibrous with thickening, retraction and fusion of chordae)
more common in women
marantic endocarditis
nonbacterial thrombotic endocarditis
common in: cancer (adenocarcinoma), DIC, hypercoaguability, long term cath
small platelet and fibrin thrombi: most common on atrial side of mitral valve; next ventricular side of aortic valve
precursor for infective endocarditis and embolism
treadmill test
see if angina upon exertion is heart related
Do NOT use for patients that have angina at rest/sleep
stable angina pectoris
chest discomfort on exertion
unstable angina
acute coronary syndrome
ruptured atherosclerotic thrombus
NO ST elevation
Tx: aspirin +heparin or clopidogrel
STEMI
crushing or squeezing chest pain
hyperadrenergic state: white as a ghost (vasoconstriction), diaphoresis, nausea, dyspnea
CK-MB, troponin, LDH
Tx: streptokinase
major determinants of MvO2 demand
HR and BP
How much of an artery is occluded before symptoms/angina occurs?
70%
factors contributing to plaque vulnerability
large lipid core, thin cap, lots of macrophages, low smooth muscle number
