Atherosclerosis : Pathophysiology of Ischaemia + Infarction Flashcards
<p>What is meant by hypoxia?</p>
<p>•Relative lack of blood supply to tissue/organ leading to inadequate O2 supply to meet needs of tissue/organ: hypoxia</p>
<p>What is hypoxic hypoxia?</p>
<p>(a) Low inspired O2 level</p>
<p>(b) Normal inspired O2 but low PaO2 – impairment of diffusion.</p>
<p>What is anaemic hypoxia?</p>
<p>•Normal inspired O2 but blood abnormal</p>
<p>What is stagnant hypoxia?</p>
<p>•Normal inspired O2 but abnormal delivery</p>
<p>(a)Local e.g. occlusion of vessel</p>
<p>(b)Systemic e.g. shock</p>
<p>What is cytotoxic hypoxia?</p>
<p>•Normal inspired O2 but abnormal at tissue level – Something not working with oxygen delivery to the cells</p>
<p>What are the factors afecting oxygen supply?</p>
<p>1. Inspired O2</p>
<p>2. Pulmonary function</p>
<p>3. Blood constituents (haemoglobin)</p>
<p>4. Blood flow (hypotension impairs supply)</p>
<p>5. Integrity of vasculature (atheroma, thrombus/embolus)</p>
<p>6. Tissue mechanisms – deliver oxygen to respiring organelles</p>
<p>What are the factors affecting oxygen demand?</p>
<p>Tissue itself - different tissues have different requirements – fat, bone, connective tissue have lower demand than brain and heart</p>
<p>Activity of tissue above baseline value</p>
<p>What are the two mechanisms for heart ischaemia?</p>
<p>Supply malfunction</p>
<p>Demand Malfunction</p>
<p>Describe supply issues that can cause heart ischaemia</p>
<p>Coronary artery atheroma</p>
<p>Cardiac failure</p>
<p>Pulmonary function - disease and pulmonary oedema</p>
<p>Anaemia</p>
<p>Previous MI</p>
<p>Where is the localised accumulation of lipid and fibrous tissue in atheroma?</p>
<p>In the intima of the arteries</p>
<p>What is the link between atheroma and:</p>
<ul> <li>Stable angina</li> <li>Unstable angina</li> <li>Thrombosis <ul> <li>Aneurysm</li> </ul> </li></ul>
<p>Stable angina - <u>established</u> atheroma in the coronary artery - pain on excertion</p>
<p>Unstable angina - <u>complicated</u> atheroma in coronary artery</p>
<p>Thrombosis - Ulcerated/fissured plaques - thrombosis - ischaemia and infarction</p>
<p>Aneurysm - Atheroma in aorta - walls of aorta become weakened and dilate</p>
<p>What are the clinical consequences of atheroma?</p>
<p>MI</p>
<p>Transient ischaemic attack</p>
<p>Cerebral infarction</p>
<p>Abdominal aortic aneurysm</p>
<p>Peripheral vascular disease</p>
<p>Cardiac failure</p>
<p>Coronary artery disease - MI - Cardiac failure</p>
<p>What are the</p>
<ul> <li>Functional</li> <li>General</li> <li>Biochemical</li> <li>Cellular</li> <li>Clinical</li></ul>
<p>Effects of Ischaemia?</p>
<p><strong>Functional</strong> - Blood/O2 supply fails to meet demands of tissue - (can be because of a reduction in supply or an increase in demand)</p>
<p><strong>General</strong></p>
<p>•Acute</p>
<p>•Chronic - claudication</p>
<p>•Acute-on-chronic – sudden worsening of an already chronic condition</p>
<p><strong>Biochemical</strong></p>
<p>Results in Lactate production -</p>
<p>Lactate to pyruvate takes energy</p>
<p>Lactate can cause death of the cell</p>
<p><strong>Cellular</strong></p>
<p>Variable susceptibility to O2 depending on tissue type and the metabolic rate</p>
<p><strong>Clinical</strong></p>
<p>Dysfunction</p>
<p>Pain</p>
<p>Physical damage to specialised cells</p>
<p></p>
<p></p>
<p>What are the outcomes of Ischaemia?</p>
<p>No clinical effect</p>
<p>Resolution / therapeutic intervention</p>
<p>Infarction</p>
<p>What is meant by infarction?</p>
<p>•Ischaemic necrosis within a tissue/organ in living body produced by occlusion of either the arterial supply or venous drainage</p>
<p>What are the possible aetiologies for infarction?</p>
<p>1. Thrombosis</p>
<p>2. Embolism</p>
<p>3. Strangulation e.g. gut</p>
<p>4. Trauma - cut/ruptured vessel</p>
<p>What does the scale of damage of ischamia/infarction depend on?</p>
<p>1.Time period</p>
<p>2.Tissue/organ</p>
<p>3.Pattern of blood supply (consider collateral circulation – whereby one branch can still supply cells if one is blocked)</p>
<p>4.Previous disease</p>
<p>What is the mechanism of tissue breakdown caused by infarction?</p>
<p>Anaerobic metabolism - cell death - liberation of enzymes</p>
<p>What are the two types of necrosis?</p>
<p>Coagulative</p>
<p>Colliquitive</p>
<p>Where do you find coagulative necrosis?</p>
<p>Heart, lung (most organs)</p>
<p>What is coagulative ischaemia?</p>
<p>Typically caused by ischaemia or infarction</p>
<p>Architecture of the dead tissue is preserved for at least a coupls of days.</p>
<p></p>
<p>Injury denatures structural proteins and lysosomal enzymes - blocks proteolysis of damaged cells - maintains coagulated morphology.</p>
<p>What is liquefactive necrosis/colliquitive necrosis?</p>
<p>Necrosis which results in a transformation of the tissue into a liquid viscous mass. Affected cell is completely digested by hydrolytic enzymes - circumscribed lesion of pus and fluid remains of necrotic tissue - debris is removed by white blood cells and a fluid space is left</p>
<p>How does myocyte death occur as a result of infarction?</p>
<div>•Coronary arterial obstruction leads to a decreasedblood flow to region of myocardium. Results inischaemia, rapid myocardial dysfunction andmyocyte death</div>
<p>What happens within seconds of myocardial ischaemia?</p>
<p>•Anaerobic metabolism, onset of ATP depletion</p>
<p>What happens in under two minutes of myocardial ischaemia?</p>
<p>•Loss of myocardial contractility (heart failure)</p>
<p>What happens within a few minutes of myocardial ischaemia?</p>
<p>•Ultrastructural changes (myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling) ?reversible</p>
<p>How long does it take for ischaemia to cause irreversible damage to the heart?</p>
<p>20-30 minutes</p>
<p>•Myocyte necrosis (disruption of integrity of sarcolemmal membrane leading to the leakage of intracellular macromolecules: blood tests) - Troponin?</p>
<p>•Injury to the microvasculature - over 1 hour</p>
<p>What do areas of infarction look like less than 24 hours after insult?</p>
<p>•No change on visual inspection</p>
<p>•A few hours to 12 hours post insult, see swollen mitochondria on Electron Microscopy</p>
<p>What organs do you see a plae infarct between 24 and 48 hours?</p>
<div>•Myocardium, spleen, kidney, solid tissues</div>
<p>What organs show a red infarct?</p>
<p>Lung and the liver</p>
<p>Loose tissues, previously congested tissue; second/continuing blood supply, venous occlusion</p>
<p>What can you see microscopically between 24 and 48 hours after infarction?</p>
<p>•Acute inflammation initially at edge of infarct; loss of specialised cell features</p>
<p>What changes do you see in a pale and a red infarct about 72 hours after infarction?</p>
<p>Pale - yellow/white and red rim periphery</p>
<p>Red infarct - little change</p>
<p>•Microscopically: chronic inflammation; macrophages remove debris; granulation tissue; fibrosis</p>
<p>What is the end result of infarction?</p>
<p>•Scar replaces area of tissue damage</p>
<p>•Shape depends on territory of occluded vessel</p>
<p>•Reperfusion Injury – damage when blood supply is restored – after period of ischaemia – inflammation and damage from free radicals</p>
<p>What is the reparative process of myocardial infarction?</p>
<p>•Cell death</p>
<p>•Acute inflammation</p>
<p>•Macrophage phagocytosis of dead cells</p>
<p>•Granulation tissue – new vessel formation</p>
<p>•Collagen deposition (fibrosis)</p>
<p>•Scar formation</p>
<p>What happens after 4-12 hours of myocardial infarction?</p>
<p>•Early coagulation necrosis, oedema, haemorrhage</p>
<p>What happens 12-24 hours after myocardial infarction?</p>
<p>•Ongoing coagulation necrosis, myocyte changes, early neutrophilic infiltrate</p>
<p>What happens 1-3 days after myocardial infarction?</p>
<p>•Coagulation necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate</p>
<p>What happens between 3-7 days of myocardial infarction?</p>
<p>•Disintegration of dead myofibres, dying neutrophils, early phagocytosis</p>
<p>What happens during 7-10 days of myocardial infarction?</p>
<p>•Well developed phagocytosis, granulation tissue at margins (red rim if pale infarct)</p>
<p>What happens between days 10-14 of myocardial infarction?</p>
<p>Well established granulation tissue with new blood vessels and collagen</p>
<p>What happens during weeks 2- 8 after myocardial infarction?</p>
<p>•Increased collagen deposition, decreased cellularity</p>
<p>What happens over 2 months of myocardial infarction?</p>
<p>•Dense collagenous scar</p>
<p>What is meant by a transmural infarction?</p>
<p>ischaemic necrosis affects full thickness of the myocardium</p>
<p>What is meant by a subendocardial infarction?</p>
<p>•ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart – just under the endocardial surface</p>
<p>What are the histological features of transmural and subendocardial infarction?</p>
<div>•Histological features are the same </div>
<div>(repair time - granulation tissue stage followed by fibrosis - in subendocardial infarct possibly slightly shortened compared to transmural infarct)</div>
<p>How are acute infarcts clasified?</p>
<p>•according to whether there is elevation of the ST segment on the ECG</p>
<p>What are the features of a NSTEMI?</p>
<p>(non st elevating myocardial infarction)</p>
<p>no ST segment elevation but a significantly elevated serum troponin level</p>
<p>What does a non-stemi correlate with?</p>
<p>subendocardial infarct</p>
<p>What do the effects of infarction depend?</p>
<p>Site</p>
<p>Size of infarct</p>
<p>Death and dysfunction (pain)</p>
<p>Contribution of previous disease and infarction</p>
<p>What are the complications of myocardial infarction?</p>
<p>•Immediate; early; late</p>
<p>•Sudden death; arrhythmias; angina; cardiac failure; cardiac rupture - ventricular wall, septum, papillary muscle; reinfarction; pericarditis; pulmonary embolism secondary to DVT; papillary muscle dysfunction - necrosis/rupture leads tomitral incompetence; mural thrombosis; ventricular aneurysm; Dressler's syndrome</p>
