Ischaemia, Infarction and Shock Flashcards
What are the 2 types of hypoxia?
GENERALISED - whole body (e.g. anaemia, altitude)
REGIONAL - specific tissues
What is ischaemia?
Pathological reduction in blood flow to tissues.
|»_space; hypoxia
What are the main causes of ishaemia?
Thrombosis/embolism.
What are the main types of ischaemia? (2)
- REVERSIBLE CELL INJURY (short duration)
- IRREVERSIBLE CELL INJURY (prolonged duration; cell death by necrosis)
Is therapeutic reperfusion of ischaemic tissue beneficial?
Beneficial is ischaemia is reversible.
-no effect on infarcted tissues (permanent cell damage)
How can reperfusion of ischaemic tissue be harmful?
Reperfusion of non-infarcted tissue can cause production of reactive oxygen species by inflammatory cells.
» REPERFUSION INJURY
What is infarction?
Ischaemic necrosis due to occlusion of arterial supply/venous drainage.
What are the main causes of infarction?
Thrombosis and embolism.
-mainly within arteries
What are other causes of infarction? (4)
- Vasospasm
- Atheroma expansion
- Extrinsic compression
- Venous occlusion (rare)
What are the morphological classifications of infarction?
by colour
- RED - haemorrhagic
* WHITE - anaemic
When does red (haemorrhagic) infarction occur?
Dual blood supply / venous infarction.
When does white (anaemic) infarction occur?
Single blood supply.
-totally cut off
What shape are most infarctions?
Wedge-shaped.
-tissue nearest blockage still has some perfusion
What are the histological characteristics of infarction? (2)
- Coagulative necrosis (» pale pink cells)
- Colliquative necrosis (brain; cells break down)
If a person dies suddenly (e.g. massive heart attack) what do you see in the tissues?
Nothing.
-no time to develop haemorrhage/inflammatory response
What factors influence the degree of ischaemic damage? (4)
- Nature of blood supply
- Rate of occlusion
- Tissue vulnerability to hypoxia
- Blood oxygen content
How does the nature of the blood supply influence ischaemic damage?
Organs with a single supply are more vulnerable to infarction.
-e.g. kidneys, spleen, testis
Give 3 examples of organs with alternative bloody supplies.
- LUNGS (pulmonary/bronchial arteries)
- LIVER (hepatic artery/portal vein)
- HAND (radial/ulnar arteries)
How does the rate of occlusion influence ischaemic damage?
Slowly developing occlusions are less likely to cause damage.
- more development of alternative/collateral perfusion pathways
(e. g. coronary arteries)
How does tissue vulnerability to hypoxia influence ischaemic damage?
- BRAIN; very vulnerable to injury, 3-4 minutes of hypoxia»_space; irreversible damage
- HEART; more resistant, 20-30 minutes of hypoxia»_space; myocyte death
How much of the body’s cardiac output and O2 consumption is required by the brain?
15% cardiac output.
20% oxygen consumption.
How does blood oxygen content influence ischaemic damage?
Reduced oxygen increases the chances of infarction.
-e.g. congestive heart failure
What are watershed regions?
Areas of the body that receive dual blood supply from the most distal branches of two large arteries.
-e.g. splenic flexure, brain
How does infarction present in the heart?
Ischaemic heart disease.
-angina/MI
How does infarction present in the brain?
Cerebrovascular disease.
-TIA/CVA
How does infarction present in the intestines?
Ischaemic bowel.
How does infarction present in the extremities?
- Peripheral vascular disease
- Gangrene
What is the leading cause of death in the West?
Ischaemic heart disease.
What is the 3rd leading cause of death in the West?
Cerebrovascular disease.
What is cerebrovascular disease?
Any abnormality that affects the circulation of blood to the brain, causing limited or no blood flow to affected areas.
Give an example of haemorrhagic cerebrovascular disease.
Bleeding.
Give an example of ischaemic cerebrovascular disease.
Thrombosis/embolism.
What causes an ischaemic stroke?
- Thrombosis 2* to atherosclerosis
- Embolism
What are the causes of a haemorrhagic stroke?
- Intracerebral haemorrhage
- Ruptured aneurysm in circle of Willis (subarachnoid)
What is a mural thrombus?
A stationary blood clot along the wall of a blood vessel, frequently causing vascular obstruction.
What usually causes ischaemic bowel disease?
Thrombosis/embolism in superior/inferior mesenteric arteries.
» abdominal pain
What are the different types of limb ischaemia/infarction?
- Gangrene
- Dry gangrene
- Wet gangrene
- Gas gangrene
What is gangrene?
Localized death and decomposition of body tissue.
-due to obstructed circulation / bacterial infection.
What is dry gangrene?
Due to vascular insufficiency.
» ischaemic coagulative necrosis
» black, dry tissue
What is wet gangrene?
Due to untreated infection»_space; lack of blood supply.
What is gas gangrene?
Superimposed infection with gas-producing organism.
-e.g. clostridium perfringens
What is shock?
A physiological state characterised by a significant reduction of systemic tissue perfusion (severe hypotension)»_space; decreased oxygen delivery to the tissues.
What critical imbalance does shock lead to?
Critical imbalance between oxygen delivery and oxygen consumption.
What are the cellular effects of shock? (5)
- Membrane ion pump dysfunction
- Intracellular swelling
- Leakage of intracellular contents
- Poor intracellular pH regulation
- Anaerobic respiration (» lactic acid)
What are the systemic effects of shock? (4)
- Alteration of serum pH (acidaemia)
- Endothelial dysfunction (vascular leakage)
- Stimulation of inflammatory cascades
- Ischaemia
Is shock reversible?
Initially reversible but rapidly becomes irreversible.
What is the sequential result of shock?
- Cell death
- End-organ damage
- Multi-organ failure
- Death
What are the main types of shock? (3)
- Hypovolaemic
- Cardiogenic
- Distributive
What is the mortality rate of septic shock?
35-60% die within one month.
What is the mortality rate of cardiogenic shock?
60-90% mortality.
What is hypovolaemic shock?
Severe intra-vascular fluid loss (e.g. blood)
» decreased pre-load (venous return to heart)
» decreased stroke volume
» decreased cardiac output
» low mean arterial pressure.
How do the body compensate for hypovolaemic shock?
Vasoconstriction»_space; increased systemic vascular resistance.
What are the causes of hypovolaemic shock? (2)
- Haemorrhage (e.g. trauma, aneurysm)
- Non-haemorrhagic fluid loss (diarrhoea, burns)
What is third spacing?
Acute loss of fluid from blood vessels to internal body cavities.
» oedema and hypotension
What is cardiogenic shock?
Cardiac pump failure»_space; decreased cardiac output.
-can no longer meet body’s needs
How can you compensate for cardiogenic shock?
Increased systemic vascular resistance.
What are the 4 categories of cardiogenic shock?
- Myopathic
- Arrhythmia-related
- Mechanical
- Extra-cardiac
What is myopathic cardiogenic shock, and what causes it?
Heart muscle failure.
-MI, right ventricular infarction, prolonged ischaemia
What is arrhythmia-related cardiogenic shock, and what causes it?
Abnormal electrical activity.
-arrhythmias, AF, ventricular tachycardia, complete heart block
What causes mechanical cardiogenic shock? (3)
- Valvular defects
- Ventricular septal defects
- Atrial myxomas
What is extra-cardiac cardiogenic shock, and what causes it?
Obstruction to blood flow (cardiac filling and ejection).
-pulmonary embolism, tension pneumothorax, pericarditis
What is distributive shock?
Severe vasodilation causes decreased systemic vascular resistance.
-leads to abnormal distribution to smaller vessels
How does the body compensate for distributive shock?
Increase cardiac output»_space; flushed/bounding heart.
How do patients with distributive shock normally appear?
Flushed, warm and tachycardic.
What are the sub-types of distributive shock? (4)
- Septic shock
- Anaphylactic shock
- Neurogenic shock
- Toxic shock syndrome
What is septic shock?
Severe systemic infection (bacteria/fungi)»_space; low BP and abnormal metabolism.
What role do cytokines and mediators play in septic shock?
Increased cytokines and mediators»_space; vasodilation.
What is anaphylactic shock?
Severe type 1 hypersensitivity reaction to an antigen.
-e.g. peanut allergy
What happens during an anaphylactic shock?
- Allergen»_space; IgE cross-linking
- Massive mast cell degranulation
- Vasodilation
What is neurogenic shock?
Loss of sympathetic vascular tone in spinal cord»_space; vasodilation and low BP.
-e.g. spinal injury
What is toxic shock syndrome?
S. aureus/S. pyogenes produce exotoxins
» non-specific binding of class II MHC to T cell receptors.
» lots of cytokine release
» decreased systemic vascular resistance
Why are the exotoxins produced by S. aureus and S. pyogenes known as ‘superantigens’?
- Don’t require processing by APCs
- Non-specific binding of class II MHC to T cell receptors
Can you have a combination of shock sub-types?
Yes.
-e.g. septic and cardiogenic (myocardial dysfuntion)
