Lecture 22: Ischaemia And Infarction Flashcards
What is hypoxia?
One of many consequences of ischaemia
A deficiency of oxygen which causes cell injury by reducing aerobic respiration
What is ischaemia?
Inadequate local blood supply to a tissue
I,e, an insufficient quantity of blood
What is anoxia?
The complete lack of oxygen
In addition to causing tissue hypoxia. What does ischaemia also cause?
Reduced transfer of metabolic substances e.g. Glucose into tissues and metabolic substances like glucose into cells and catabolites like H+ out of tissues
What is infarction?
Necrosis
What is necrosis?
Cell murder
Non programmed cell death of tissue due to ischaemia
What are the possible causes of ischaemia
External occlusion of vessels Internal occlusion of vessels Spasm of vessel Capillary blockage Shock
What is an example of external occlusion of vessels?
Tumour, compression (bedsores)
What is an example of internal occlusion of vessels
Atherosclerosis, thrombosis or embolism
What is an example of spasm of vessels
E.g. Due to cold, frost bite not actually due to cells freezing but due to soasms
What is an example of capillary blockage
Sickle cell anaemia, cerebral malaria
What is shock
Circulatory failure with low arterial blood pressure which causes impaired perfusion of tissues
Why do different cell types have different susceptibilities to ischaemia
Highly differentiated cells (e.g. In brain, heart, kidneys) depend on aerobic respiration to make ATP
What is the susceptibility of different cell types in decreasing order of sensitivity to ischaemia?
Neurons Renal proximal tubular epithelium Myocardium Skeletal muscle Fibroblasts and macrophages Neutrophils
Describe the susceptibility of neurons to ischaemia
Very sensitive
Irreversibly damaged by only 3 minutes of anoxia
Neurons in brain require almost continuous supply of blood
Describe the sensitivity of renal proximal tubular epithelium
Sensitive
Renal ion reabsorption is rapidly impaired
Describe the sensitivity of myocardium to ischaemia
Sensitive
Irreversible after 20mins of anoxia
Functional impairment (with risk of dysrhythmia within 1minute)
Describe the sensitivity of skeletal muscle to ischaemia
Less sensitive to ischaemia ,
Capable of anoxia work
Exercise causes ischaemia. Muscles undergo anaerobic respiration producing lactic acid
Describe fibroblast and macrophage sensitivity to ischaemia
Insensitive.
Describe the sensitivity of neutrophils to ischaemia
Neutrophils are weird
Their resistance to cell death is enhanced by hypoxia
Tis s allows them to function in damaged or infected tissues which are often hypoxic
What does the outcome of vessel occlusion depend on?
Types of cells present in the tissue supplied by occluded vessel
Anatomy of blood supply to organ
Size of occluded vessel
Speed of onset
Duration of occlusion
Metabolic demands of tissue
General adequacy if circulatory system
How does anatomy of blood supply affect the outcome of vessel occlusion?
Collateral circulation (more than one vessel supplying the organ ) Will reduce the susceptibility of the organ to ischaemia
Organs supplied by multiple vessels are relatively resistant to ischaarmia
How does the size of the occluded vessel affects the tissue susceptibility to ischaemia?
The larger the vessel blocked, the greater the volume of ischaemic tissue,
Tissues and organs more susceptible to ischaemia if its a large vessel which supplies it is blocked
How does the duration of the occlusion affect the organs susceptibility to ischaemia?
Cells may survive short periods of occlusion better than long periods of occlusion
Even if they survive a period of occlusion they may be killed by damage which occurs when blood flow is restored (reperfusion injury)
How do the metabolic demands of the tissue at the time of ischaemia affect the tissues susceptibility to ischaemia?
An ischaemic tissue under pressure has more severe ischaemia than a tissue at rest
How does the general adequacy of the circulatory affect organs susceptibility to ischaemia.
If body has coexisting heart failure or anaemia the outcome of the blockage is worsened
As heart can’t pump as much or not as much Hb to bring oxygen to tissues have a disproportional large effect.
What are the range of outcomes of ischaemia on tissue in order of decreasing damage
Infarction- necrosis of most/all cells in a tissue due to overwhelming injury
Apoptosis - isolated cells. (Strange because this requires energy which is limited in infarction)
Reversible damage - to isolated cells
Adaptation - fatty change, atrophy and shut down. Like changing from aerobic to anaerobic respiration
Functional defect - due to suboptimal tissue perfusion e.g, myocardial dysrhythmia, renal insufficiency
No effect
When does infarction occur
When perfusion of tissue is so severely ducked that most cells within the tissue are killed
In practice, what do most infarctions result from ?
Thrombotic or embolism events
What are the two types of infarction?
Red infarcts
White infarcts
Where does red infarction occur?
In tissues with dual blood supply like lungs
Or tissues where blood flow is reestablished after previous arterial occlusion
Where does white infarction occur?
Slid tissues supplied by single artery
These are often wedged shaped
The apex of the wedge is at the point of occlusion and the base is at the organ surface
What is coagulative necrosis?
Dominant appearance after infarction in many solid organs
What other kind of necrosis may develop in the brain?
Liquefactive necrosis
What develops in the viable margins of infarcts?
Acute inflammation
How soon does acute inflammation develop?
Within 24 hours usually
What does acute inflammation involve?
The recruitment of neutrophils
After 1-3 days macrophages and some lymphocytes start to enter margins of infarcts tissue
Fibroblasts and ECs are recruited (organisation) which repair infarcts tissue by granulation tissue formation
Granulation tissue over the following weeks is remodels into no function fibrous scar
Some tissues like the liver attempt regeneration of original tissue instead of forming fibrous scar
What is organisation
The recruitment of fibroblasts and endothelial cells
What is ischaemic heart disease usually caused by?
Atherosclerotic narrowing of coronary arteries
Tsk s leads to reduced blood flow to heart muscle
Leading to several clinical syndromes
What are the clinical syndromes of ischaemic heart disease in order of increasing severity?
Angina pectoris
Chronic ischaemic heart disease
Myocardial infarction
