Pathophysiology of Ischaemia and Infarction Flashcards
What is hypoxia?
Relative lack of blood supply to the tissue/organ, leading to inadequate oxygen supply to meet the needs of that tissue/organ
What are the main types of hypoxia?
Hypoxic
Anaemic
Stagnant
Cytotoxic
What is seen in hypoxic hypoxia?
Low inspired O2 level
or
Normal inspired O2 but low PaO2
What is seen in anaemic hypoxia?
Normal inspired O2 but abnormal blood
What is seen in stagnant hypoxia?
Normal inspired O2 but abnormal delivery, either local e.g. occlusion of a vessel or systemic e.g. shock
What is seen in cytotoxic hypoxia?
Normal inspired O2 but abnormal at tissue level
What factors affect oxygen supply?
Inspired O2 Pulmonary function Blood constituents Blood flow Integrity of vasculature Tissue mechanisms
What factors affect oxygen demand?
The tissue itself - different tissues have different requirements
Activity of the tissue above baseline value e.g. in exercise
What is ischaemia?
Inadequate blood supply to an organ or tissue
What is infarction?
Obstruction of the blood supply to an organ or tissue resulting in local cell death
Ischaemic necrosis within a tissue or organ in the living body
What is atheroma?
A localised accumulation of lipid and fibrous tissue in the intima of arteries
What does established atheroma in coronary arteries result in?
Stable angina
What does complicated atheroma in coronary arteries result in?
Unstable angina
What do ulcerated or fissured atheromatous plaques result in?
Thrombosis, causing ischaemia or infarction
What can atheroma in the aorta result in?
Aortic aneurysm
What are the clinical consequences of atheroma?
MI TIA Cerebral infarction Abdominal aortic aneurysm Peripheral vascular disease Cardiac failure
What is the effect of atheroma on blood flow, according to Poiseuille’s formula?
Atheroma leads to narrowing of the vessel lumen due to occlusion or thrombus
A reduction in vessel radius in an atheromatous vessel results in a 16 fold reduction in blood flow
This reduced blood and therefore oxygen flow leads to ischaemia or infarction
What are the functional consequences of ischaemia?
Blood/O2 supply fails to meet demand due to low supply, high demand or both
What are the general consequences of ischaemia?
Acute - obvious signs and symptoms
Chronic - may go unnoticed over a long period of time, insidious onset
Acute on chronic - acute signs/symptoms on already compromised tissues
What are the biochemical consequences of ischaemia?
Normal aerobic metabolism affected
Anaerobic metabolism occurs, causing cell death
What are the cellular consequences of ischaemia?
Different tissues have variable O2 requirements so are variably susceptible to ischaemia
Cells with high metabolic rate e.g. cardiac cells and neurons are greatly and quickly affected by ischaemia
Cells with low metabolic rate e.g. fat cells are much less affected by ischaemia
What are the clinical consequences of ischaemia?
Dysfunction
Pain
Physical damage of specialised cells
What are the potential outcomes of ischaemia?
No clinical effect
Resolution
Therapeutic intervention
Infarction
What might result in supply issues in IHD?
Coronary artery atheroma Cardiac failure Pulmonary function due to another disease causing pulmonary oedema e.g. left ventricular failure Anaemia Previous MI
What results in demand issues?
Increased exertion and stress
What causes infarction?
Occlusion of the arterial supply or the venous drainage
What might cause the cessation of blood flow?
Thrombosis
Embolism
Strangulation
Trauma
What does the scale of damage resulting from ischaemia or infarction depend on?
Time period
Tissue/organ affected
Pattern of blood supply
Previous disease
What is the basic process of infarction?
Anaerobic metabolism Cell death Liberation of enzymes Breakdown of tissue Coagulative necrosis e.g. heart, lung Colliquitive necrosis e.g. brain
What occurs in myocardial ischaemia?
Anaerobic metabolism - within seconds
Loss of myocardial contractility - in under 2 minutes
Ultrastructural changes - within a few minutes
Severe ischaemia - within 20-30 minutes
Myocyte necrosis - within 20-40 minutes
Injury to microvasculature - over 1 hour
What is transmural infarction?
Ischaemic necrosis which affects the full thickness of the myocardium
What is subendocardial infarction?
Ischaemic necrosis which is mostly limited to a zone of myocardium under the endocardial lining of the heart
What is the difference in the histological features of a transmural and subendocardial infarction?
Histological features are the same
Repair time, granulation tissue stage followed by fibrosis, is possibly slightly shorter in a subendocardial infarct
What are acute infarcts classified according to?
Whether there is elevation of the ST segment on the ECG
What is the class of acute infarct if there is no ST elevation but significantly elevated serum troponin level?
Non-STEMI
What are NSTEMIs thought to correlate with?
Subendocardial infarct
What is the appearance of an infarct at < 24 hours?
No change on visual inspection
From a few hours - 12 hours post-insult you will see swollen mitochondria on electron microscopy
What is the appearance of an infarct at 24-48 hours?
Pale infarct will develop in tissues such as myocardium, spleen and kidneys
Red infarct will develop in more solid tissues such as liver and lungs
Continuing blood supply and venous occlusion occurs in loose tissues or previously congested tissues
Acute inflammation initially at the edge of the infarct, loss of specialised cell features, and death/breaking apart of nuclei seen microscopically
What is the appearance of an infarct at 72 hours onwards?
Pale infarct develops a yellow/white and red peripheral (hyperaemic rim)
Red infarcts show little change
Microscopically there is chronic inflammation, macrophages remove the debris and granulation tissue and fibrosis develops
What is the effect of an infarct dependent on?
Site
Size
Death/dysfunction
Contribution of previous disease/infarction
What is the basic reparative process which occurs following myocardial infarction?
Cell death Acute inflammation Macrophage phagocytosis of dead cells Granulation tissue formation Collagen deposition, fibrosis Scar formation
What occurs in the reparative process of MI from 4-12 hours post-insult?
Early coagulation necrosis
Oedema
Haemorrhage
What occurs in the reparative process of MI from 12-24 hours post-insult?
Ongoing coagulation necrosis
Myocyte changes
Early neutrophilic infiltrate
What occurs in the reparative process of MI from 1-3 days post-insult?
Coagulation necrosis
Loss of nuclei and striations
Brisk neutrophilic infiltrate
What occurs in the reparative process of MI from 3-7 days post-insult?
Disintegration of dead myofibrils
Dying neutrophils
Early phagocytosis
What occurs in the reparative process of MI from 7-10 days post-insult?
Well-developed phagocytosis
Granulation tissue at margins
What occurs in the reparative process of MI from 10-14 days post-insult?
Well-established granulation tissue with new blood vessels and collagen deposition
What occurs in the reparative process of MI from 2-8 weeks post-insult?
Increased collagen deposition
Decreased cellularity
What occurs in the reparative process of MI from over 2 months post-insult?
Dense collagenous scar forms
What are the complications of myocardial infarction?
Sudden death Arrhythmias Angina Cardiac failure Cardiac rupture Reinfarction Pericarditis Pulmonary embolism secondary to DVT Papillary muscle dysfunction Mural thrombosis Ventricular aneurysm Dressler's syndrome
