PBL 5 - cardiac remodelling following a MI Flashcards
(32 cards)
what are the 2nd most common causes of MI?
- rupture of an atherosclerotic plaque in a coronary artery
- formation of intracoronary thrombus
- cause infarction downstream of the occluded blood vessel
how does blockage of a coronary artery lead to heart failure?
- blockage of coronary artery
- ischaemia and MI
- necrosis
- inflammation response to remove dead cells
- infarct healing and scar formation
- hypertrophy, dilation, reduced function
- HF
what does death in a proportion of the LV wall and the development of scar tissue lead to?
- heart undergoes this adverse remodelling to result in a change in the heart shape (chamber dilation)
- chamber dilation leads to deterioration in cardiac function
loss of a significant amount of cardiac muscle ultimately leads to what?
scar formation
is myocardium endogenous regernative captacity good or bad?
bad
what does cells dying by necrosis cause?
- release of IC contents
- initiates an intense inflammatory response
what is used as a diagnostic tool?
release of troponins — not usually found in circulation
describe the rise in troponin levels
- levels rise within 4-8 hours of MI
- remain elevated for 4-7 days
what is the inflammatory response to an infarct?
- neutrophils infiltrate infarct
- secrete MMPs (matrix metalloproteinases) and phagocytose debris
- pro-inflammatory cytokine levels increase
- leads to recruitment of other inflammatory cells
- pro-reparative phase: neutrophils undergo apoptosis — further recruitment of inflammatory cells — initiation of the healing process
describe the inflammatory phase where dead cells are starting to be cleared away
- neutrophils infiltrate the infarct
- secrete MMPs and phagocytose debris
- pro-inflammatory cytokine levels increase (IL-1B, IL-6, IL-18, IFN-y, TNFa)
- leads to recruitment of other inflammatory cells
— further clearing of dead cells by recruited macrophages
— recruitment of other leukocytes — NKC, T and B lymphocytes, dendritic cells
— transition to pro-reparative phase
describe the pro-reparative phase (day 3 of infarction)
- neutrophils undergo apoptosis — reduction in pro-inflammatory macrophages in infarct zone
- further recruitment of inflammatory cells
- increased expression of IL-10 and TGF-B — inhibit pro-inflammatory cytokines
- initiation of healing process
what is a negative effect of the whole process of clearing away dead cells and debris?
makes the infarct zone very weak and prone to rupture —
cardiac rupture accounts for 10-20% of acute death following an MI, usually 4-7 days post MI
what replaces cardiomyocytes in the infarct zone?
a collagen-rich scar
what do cardiac fibroblasts turn into?
myofibroblasts
what do myofibroblasts do?
secrete new ECM proteins such as collagen
what can too much collagen result in?
increase in wall stiffness, leading to cardiac dysfunction
what does too little scar deposition result in?
a thin infarct wall — thin ventricular wall at risk of aneurysm or even rupture
what happens at the end of the collagen deposition process?
clearance of myofibroblasts by apoptosis
what is the ventricle left with after being strengthened by the scar?
a non-contracting region of the LV wall
what happens to the remaining healthy part of the myocardium?
LV undergoes hypertrophy to compensate for the lost muscle mass in the infarct area in order to maintain cardiac function
what happens in concentric hypertrophy?
- cardiomyocytes are thickened by the addition of more sarcomeres
- over time the heart can’t maintain this increased workload on the remaining healthy bits of the LV
- heart undergoes dilation
- LV chamber expands — heart looses its pump function
- loose the rhythmic contraction and relaxation of the heart wall
WALLS THICKEN BUT CAPACITY IS REDUCED
how does ejection fraction correlate its survival post MI?
the lower the ejection fraction (amount of blood pumped from the heart), the higher the death rate post MI
what joins adjacent cardiomyocytes?
gap junctions
within mins/hours of an MI, how does irreversible cell damage increase risk of ventricular arrhythmias?
- irreversible cell damage —> disruption of gap junctions causing electrical uncoupling of cardiomyocytes
- increased risk of ventricular arrhythmias eg.. ventricular tachycardia
