Ischemia and Infarction Flashcards
Factors contributing to decreased incidence of coronary artery disease and stroke in recent decades
- Prevention through changes in lifestyle, including reduced smoking, altered dietary habits, control of hypertension
- Improved treatment of myocardial infarction and related complications
- Prevention of recurrence in patients with history of atherosclerosis
Approximately ___ of deaths in the Western world are attributed to atherosclerosis.
Approximately ⅓ of deaths in the Western world are attributed to atherosclerosis.
Two most common pathologic consequences of atherosclerosis
- Myocardial infarction
- Stroke
Ischemia is an imbalance of ____ and ____.
Ischemia is an imbalance of blood supply and blood demand.
If ____ cannot be increased to meet an increase in demand, then ischemia will result
If perfusion cannot be increased to meet an increase in demand, then ischemia will result
Causes of decreased blood supply
- Vascular narrowing or obstruction
- Acutely decreased blood pressure (hemorrhage or shock)
Causes of increased blood demand
- Exercise
- Hypertrophy
- Tachycardia
- Dilation of the heart
Biochemical components of ischemia
- Hypoxia
- Inadequate supply of metabolic substrates
- Accumulation of metabolic waste products
Four intracellular systems most vulnerable to ischemia
- Genetic substrate integrity
- Cell membrane structure and function
- Aerobic respiration system
- Synthesis and maintenance of structural proteins
Three distributions of heart infarction
Strokes tend to be ___ in origin.
Strokes tend to be embolic in origin.
Myocardial infarctions tend to be ___ in origin.
Myocardial infarctions tend to be thrombotic in origin.
Common causes of shock
- Sepsis
- Cardiac failure
- Hypovolumetric shock
Shock can be thought of as essentially ____.
Shock can be thought of as essentially whole-body hypoperfusion.
Watershed Infarction
Watersheds are tissues which have poor perfusion at baseline. Typically these areas do not have their own vasculation system, but are sandwiched between the vascular territories of two other tissues. These are the tissues most at risk during shock.
Many watersheds are in the brain, and the subendocardium is another prominent example.
Prolonged or repeated shock may result in ____.
Prolonged or repeated shock may result in ischemic encephalopathy. This is associated with gradual degradation of watershed areas and decline in brain function.
“Bubbles” shown in picture attached are areas of necrosis.
The liver receives __% of its blood supply from portal circulation and __% from the hepatic arteries.
The liver receives 80% of its blood supply from portal circulation and 20% from the hepatic arteries.
Tissues with dual blood supplies
- Liver (portal veins, hepatic arteries)
- Lungs (pulmonary arteries, bronchial arteries)
____ is classically seen in organs with either a dual blood supply, or extensive collateral circulation.
Hemorrhagic infarction is classically seen in organs with either a dual blood supply, or extensive collateral circulation.
Ischemic cardiac myocytes shift to anaerobic respiration within ___ of ischemia onset. Cell death does not occur until after ___.
Ischemic cardiac myocytes shift to anaerobic respiration within 3-5 minutes of ischemia onset.
Cell death does not occur until after at least 20-30 minutes.
Although myocardium does not have a true dual circulation, there is extensive ____, providing a potential lifeline to ischemic cells at ____.
Although myocardium does not have a true dual circulation, there is extensive collateral circulation, providing a potential lifeline to ischemic cells at the periphery of an infarct zone (sometimes called the “penumbra”).
This results in a gradient of ischemic damage
Tissue viability and functionality as a function of bloodflow and time
Plaques causing around 60% stenosis are ____ to rupture than those causing 90% stenosis
Plaques causing around 60% stenosis are more likely to rupture than those causing 90% stenosis
Plaques at highest risk of rupture may be ____
Plaques at highest risk of rupture may be asymptomatic
Early changes in myocardial infarction
- Loss of glycogen
- Sarcomere relaxation
These are both reversible changes.
___ is the key event that results in the shift from reversible to irreversible injury
Cell membrane damage is the key event that results in the shift from reversible to irreversible injury
Troponin I (TnI)
Component of the cardiac myocyte contractile apparatus. Upon irreversible myocardial injury and loss of membrane integrity, it is released into circulation.
Serum troponin I is a highly sensitive and specific marker of myocardial infarction.
Most hospital MI protocols require ____, over a period of at least ____, before “ruling out” MI in a patient. This is because ___.
Most hospital MI protocols require three negative troponin I tests, over a period of at least four to six hours, before “ruling out” MI in a patient. This is because troponin I may not appear abnormal early in MI, prior to cell rupture and prior to escape from the tissue into the bloodstream.
Myocardial infarction histology: Day 1 to Day 10
Myocardial infarction histology: Week 2 to Week 8 and beyond
Wavefront of myocardial damage
The penumbra of myocardial damage can be ____.
The penumbra of myocardial damage can be saved if perfusion is restored quickly.
The goal of therapy for myocardial infarction should be . . .
. . . to intervene as early as possible, to reperfuse tissue and limit infarct size.
Clinical benefit of reperfusing therapy drops off precipitiously if greater than ___ pass between the initiating event and reperfusion.
Clinical benefit of reperfusing therapy drops off precipitiously if greater than 3 hours pass between the initiating event and reperfusion.
“Door to needle” time goal for most hospitals
30 minutes
Reperfusion was first accomplished using ___.
Reperfusion was first accomplished using thrombolytic drugs – first streptokinase and urokinase, and later tPA
Today, reperfusion is usually accomplished by ___
Today, reperfusion is usually accomplished by percutaneous coronary intervention (PCI)
Essentially, this means physically opening the vessel by inserting a catheter into the vasculature and inflating a balloon at the site of the obstruction (angioplasty) to reopen the vessel
contraction bands
The remnants of reperfusion injury
Myocardial stunning
Function of reperfused myocardium is not fully restored immediately, resulting in a period of post-ischemic ventricular dysfunction. May create turbulent flow that predisposes to aneurysm or mural thrombus.
Ischemic pre-conditioning
One potential way to reduce the risk of myocardial stunning and reperfusion injury
Deliberately causing brief episodes of myocardial ischemia and reperfusion prior to a major and predictable period of ischemia (e.g. cardiac surgery) to allow the myocardium to “adapt” in advance
Currently in clinical trials. Experimental trials in mammals have produced astounding results (~6 fold smaller infarct size)
Coronary Artery Disease: the big picture
Hemosiderin. Deposit of free, oxidized heme groups that broke off of hemoglobin following erythrocyte lysis. Cleared by macrophages.
Common in myocardial infarction H and E.
Treatment for acute coronary artery thrombosis
- If <3 hours since incidence, ONAH + stenting
- If >3 hours since incidence, hemolytic treatment: streptokinase, urokinase, tPA
ONAH
Oxygen (100%, gas mask)
Nitroglycerin (vasodilator)
Aspirin (Irreversibly inhibit TxA2 synthase in thromboytes)
Heparin (hemolytic activator and inhibitor of platelet aggregation)
Strokes: When to give tPA?
If there is hemorrhage/intracranial bleeding, DO NOT give tPA.
tPA should be given for nonhemorrhagic lesions, particularly thrombosis, atherosclerotic ischemia, or thromboembolism.
