ischemic heart disease Flashcards
causes of IHD
MI
when blood flow to a region is reduced?
usually obstruction due to - atheroma -thrombosis -Spasm -Embolus -Coronary ostial stenosis -Coronary arteritis
why could IHD occur when blood flow is not obstructed?
could be a general decrease of OXYGENATED blood flow to myocardium due to
anemia
Carboxyhaemoglobulinaemia
Hypotension causing decreased coronary perfusion pressure
MI due to decrease in oxygenated blood occurs with what?
anemia
hypotension = decreased coronary perfusion pressure
what triggers atherogenesis?
endothelial dysfunction
mechanical sheer stresses
Genetic alteration
what triggers atherogenesis?
Biochemical abnormalities
(elevated and modified LDL, DM, elevated plasma homocysteine)
what triggers atherogenesis?
Immunological factors
Inflammation
(free radicals from smoking) (infection such as chlamydia, Helicobacter)
atherosclerosis can be defined as a
inflammatory process
- cytokine storm in covid -
plaques build in adventitia in atherosclerosis
T/F?
False
build in Tunica intima in large and medium sized coronary arteries
why do atherosclerotic plaques cause IHD?
narrow artery lumen
features of Atherosclerotic plaque
necrotic rich core
SMC [these proliferate]
fibrous cap around
foam cells
how are foam cells created
lipoproteins [such as LDL] are retained into dysfunctional endothelium
these then form foam cells - this process is mediated by macrophages, immune cells
there is increased expression for monocyte interaction into dysfunctional endothelium intimal space
via increased selectins on endothelium which attract chemokines on monocytes - VCAM;ICAM-1
why do the tunica media smooth muscle cells proliferate?
response to injurv [plaque formation w necrotic core is injury]
SMC’s are recruited to the luminal side of the lesion to form a barrier between lesional prothrombotic factors
tunica of vessel wall? from lumen
intima ; endothelium
media ; smooth muscle cells , internal +external elastic membrane
adventitia ; vasa vasorum ; nerves
what is an important regulator of fibrous cap formation?
why?
TGF-B - Transforming Growth Factor
IL-10
produced by T-reg cells and macrophages
potent stimulator of collagen production in SMC
why is formation of a fibrous cap good for an atherosclerotic plaque?
= stable plaque - avoid rupture
contains necrotic core
limits thrombus formation
how is a necrotic core produced?
noninternalized apoptotic macrophage foam cells.
why is plaque rapture bad?
necrotic core comes into contact with blood exposing it to prothrombotic components to platelets and pro-coagulation factors
stimulates inflammatory state in blood = increasing thrombus formation
DIC
why doe plaque rupture happen?
thinning of the fibrous cap
this occurs due to no resolution of inflammation
chronic stable angina defined as?
fixed atherosclerotic plaque
= reduced blood flow through narrowed lumen
but stable
Acute
coronary syndromes?
Unstable angina
Non Stemi
STEMI
platelet aggregation
thrombus formation
progression of events in IHD?
Asymptomatic Chronic stable angina Acute Coronary syndromes HF Sudden death
Acute coronary occlusion
plaque breaks through endothelium [from intima]
> pro-thrombotic factors introduced to blood so platelets aggregate; adhere
haemostasis does its thing
= fibrin clot formation
= thrombus/ blood clot
artery occludes vessel = hypoxia of that region
= infarct - necrosis / death of region if oxygen supply not restored
if it moves away - emboli of distal vessels
collaterals are?
local anastamosis of heart arteries
dilate within seconds of acute episode
= aim to reach normal coronary flow
chronic atherosclerotic patients
- slow occlusion-collateral vessels develop as atherosclerosis develops
collaterals cannot cope with demand
why do you still get ACS with role collaterals play?
The collaterals can also get atherosclerosis or the damage become so extensive that even the collaterals can not help
collaterals dilate = HF as weakens the heart and cannot maintain blood supply
infarction defn?
area that in ischemic state has zero or little flow of blood[oxygen]
infarcted
Pathogenesis: Soon after infarction
Small amount of collaterals open and blood seep into the infarcted area
Local blood vessels dilate and area becomes overfilled with stagnant blood
Muscle fibres use all the remaining oxygen, hemoglobin becomes totally deoxygenated giving bluish brown hue & blood vessels appear engorged despite lack of blood flow
later stages of infarction?
Vessels walls permeability increases, fluid leak and local tissue oedematous
Cardiac muscle cells swell and due to no blood supply die within few hours
causes of death after MI
decreased CO
damming of blood in bodys venous system
V fibrillations
rupture of infarcted area
why does decreased cardiac output occur after MI?
loss of elasticity of infarcted smooth muscle ; cannot contract just forced outwards by pressure inside
lack of pumping force > cardiac failure = peripheral ischemia , cardiac shock
Damming of blood in body’s venous system
Can die after few days of doing well.—-because of low cardiac flow —low blood flow to kidneys a –fail to excrete add to blood volume and congestive symptoms—-pulmonary oedoma die after few hours of symptoms
after an acute MI will CO remain the same?
technically yes due to reserves; collaterals
normal areas of heart hypertrophy to compensate
but exertional CO will not be the same
what biomarkers are most informative with CVD?
B-type natriuretic peptide
urinary albumin-to-creatinine ratio
IHD clinical history?
chest pain
age,sex,ethnicity,smokinh,alcohol
SES
family history
lab tests for CVD/IHD?
basics lipid profile
LDL, HDL, Triglycerides, lipoprotein a, C-reactive proteins etc
Serum markers in patients with suspected acute cardiac events (ACS, MI)
Troponins(I or T)
Creatine kinasewith MB isozymes
Lactate dehydrogenase and lactate dehydrogenase isozymes
Serumaspartate aminotransferase
biomarkers for predicting death after an MI?
B-type natriuretic peptide CRP Homocysteine Renin Urinary albumin-to-creatinine ratio
unstable angina?
ECG changes
st depression and t wave inversion
acute MI ecg changes?
infarct - transmural so
ST elevation with T wave inversions
pharmacological treatments for IHD?
targeting LDL
HMG-CoA reductase inhibitors:
These agents lower LDL-C levels. They also lower triglyceride levels and raise serum HDL levels.
ATORVASTATIN
what do Bile acid sequestrants do?
Cholestyramine
prevent recycling of bile acids
so you use up more cholesterol - fecal
ACE inhibitors and CCB?
Hypertension and atherosclerosis may be intimately linked through their effects on vascular endothelial dysfunction
CCB : amlodipine
dilatory effect on coronary SMC - vasodilation
= improves myocardial oxygen delivery
CABG?
coronary artery bypass grafting
A vessel from another part of your body to create a graft that allows blood to flow around the blocked or narrowed coronary artery. This type of open-heart surgery is usually used only for people who have several narrowed coronary arteries.
Percutaneous coronary Intervention
Involves angiography and stent placement:
Common to treat stable CAD
Improves blood flow by placing a stent and compressing the plaque
acute anginal symptoms
pharmacological treatment?
anti-ischemic effect of nitrates is to decrease myocardial oxygen demand by producing systemic vasodilation
“reducing myocardial cellular sodium and calcium overload via inhibition of the late sodium current of the cardiac action potential”
what drug does this?
ranolazine
antianginal agents
how do B-blockers work
Beta-blockers inhibit sympathetic stimulation of the heart, reducing heart rate and contractility; this can decrease myocardial oxygen demand and thus prevent or relieve angina in patients with CAD
which drug inhibits platelet function
why is this useful in IHD?
- prevents atherosclerosis
antiplatelet drugs
aspirin
clopidogrel
