What is meant by hypoxia, and what are the 2 types?
Any state of reduced oxygen availability
Generalised - whole body eg. altitude or anaemia
Localised - specific tissue affected
What is meant by ischaemia?
Pathological reduction in blood flow to tissues, ischaemia results in tissue hypoxia
What is the most common cause of ischaemia?
Usually as a result of obstruction to arterial flow commonly as a result of thrombosis/embolism
What are the consequences of limited compared to prolonged ischaemia?
Limited - cell injury is reversible
Prolonged - irreversible cell damage
-Cell death occurs by necrosis
When would therapeutic tissue reperfusion be used?
Only if the ischaemia is reversible
Why is therapeutic reperfusion not used in infarcted tissues?
Reperfusion of infarcted tissues will have no effect
Why could reperfusion of ischaemic non infarcted tissues be harmful?
Whilst the tissue is hypoxic inflammatory cells produce reactive oxygen species
When the tissue is reperfused these reactive oxygen species can travel around the body and cause damage
What is meant by infarction?
Ischaemic necrosis caused by occlusion of the arterial supply or venous drainage
What is infarct?
An area of infarction in tissues
Other than thrombosis and embolism, name 7 other causes of infarction?
1) Vasospasm
2) Atheroma expansion
3) Extrinsic compression eg. tumour
4) Twisting of vessel roots eg. volvulus
5) Rupture of vascular supply eg. AAA
6) Vasculitis
7) Hyperviscosity
How can infarction be classified by colour?
White infarction (anaemic)
Single blood supply hence totally cut off
Red infarction
Dual blood supply/venous infarction
Loss of one blood supply, tissue starts to undergo necrosis, damages blood vessels of other supply and blood leaks into tissues
What shape are most infarcts and why?
Wedge-shaped
Obstruction usually occurs at an upstream point, the entire down-stream area will therefore be affected
Infarction is normally what type of necrosis?
Normally coagulative necrosis - maintains tissue structure
Colliquative necrosis occurs in the brain
If a person died suddenly of an MI what would be seen in the tissues?
Nothing as there is no time to develop haemorrhage or inflammatory response
What 4 factors influence the degree of ischaemic damage?
1) Nature of blood supply
2) Rate of occlusion
3) Tissue vulnerability to hypoxia
4) Blood oxygen content
How does the nature of the blood supply influence the degree of ischaemic damage?
- An alternative blood supply will mean less damage hence severe ischeamia is required for infarction
- Tissues with a single blood supply are more vulnerable to infarction
eg. kidneys, spleen, testis
Name 3 tissues with dual blood supply (and those supplies) which are thus less vulnerable to infarction?
1) Lungs (pulmonary and bronchial arteries)
2) Liver (hepatic artery and portal vein)
3) Hand (radial and ulnar artery)`
Why are slow developing occlusions less likely to lead to infarction?
Allows time for the development of alternative collateral perfusion pathways
How does rate of occlusion affect coronary arteries?
- Small anastamoses connect major branches and have minimal flow
- If a coronary arterial branch is slowly occluded flow can be directed through these channels
- Infarction can therefore be avoided even if the main arterial branch is totally occluded
Why is the brain typically very vulnerable to hypoxia?
If a neurone is deprived of O2 irreversible cell damage occurs in 3-4 mins
Brain is 1-2% of total body weight but requires 15% of cardiac output
Therefore very vulnerable to injury
Why is the heart less vulnerable to hypoxia than the brain?
The heart is more resistant with cardiac myocyte death taking 20-30 minutes
How does blood oxygen content affect infarction?
Reduced oxygen supply in the blood (anaemia etc.) increases the chances of infarction
Why does congestive heart failure make people more vulnerable to infarction?
- Poor cardiac output and impaired pulmonary ventilation
- May develop an infarct with a normally inconsequential narrowing of vessels
Name 4 clinical manifestations of infarction?
1) Ischaemic heart disease
2) Cerebrovascular disease
3) Ischaemic bowel
4) Peripheral vascular disease/ gangrene
What is the leading cause of deaths in the west?
Ischaemic heart disease
What are 90% of cases of cardiac ischaemia due to?
Impaired coronary artery flow following complications of atherosclerotic disease
What is the 3rd leading cause of death in the west?
Cerebrovascular disease
What does cerebrovascular disease refer to?
Any abnormality of the brain caused by a pathological process involving the blood vessels
Includes thrombosis and embolism (ischaemic)
and Bleeding (haemorrhagic)
What is a cerebrovascular accident?
A stroke
Name 2 causes of an ischaemic stroke?
Thrombosis secondary to atherosclerosis
Embolism eg. mural thrombus
Name 2 causes of a haemorrhagic stroke?
1) Intracerebral haemorrhage (hypertensive)
2) Ruptured aneurysm in the circle of Willis (subarachnoid)
What is ischaemic bowel disease usually caused by and how does it present?
- Usually caused by a thrombosis or embolism in the superior or inferior mesenteric arteries
- Presents with abdominal pain
What is gangrene and what are the 3 types?
1) Gangrene - infarction of entire portion of a limb or organ
2) Dry gangrene - Ischaemic coagulative necrosis only
3) Wet gangrene - superimposed infection
4) Gas gangrene - superimposed infection with gas producing organism eg. clostridium perfringens
What is shock?
A physiological state characterised by a significant reduction of systemic tissue perfusion (severe hypotension) resulting in decreased O2 delivery to tissues
What can shock eventually lead to?
The impaired tissue perfusion and ultimately prolonged oxygen deprivation leads to cellular hypoxia and derangement of critical biochemical processes at first cellular and eventually systemic levels
What are the 6 cellular effects of shock?
1) Membrane ion pump dysfunction
2) Intracellular swelling
3) Leakage of intracellular contents into the extracellular space
4) Inadequate regulation of intracellular pH
5) Anaerobic respiration - lactic acid
What are the 4 systemic effects of shock?
1) Alterations in serum pH (acidaemia)
2) Endothelial dysfunction - vascular leakage
3) Stimulation of inflammatory and anti-inflammatory cascades
4) End-organ damage (ischaemia)
Is shock reversible?
Shock is initially reversible but rapidly becomes irreversible
What is the sequential result of shock one it becomes irreversible?
1) Cell death
2) End-organ damage
3) Mutli-organ failure
4) Death
What is hypovolaemic shock?
Intra-vascular fluid loss (blood, plasma etc.)
1) Get decreased venous return to the heart thus reduced pre-load
2) Decreased stroke volume thus decreased cardiac output
How can the body compensate for hypovolaemic shock?
it increases the systemic vascular resistance through vasoconstriction - pt appears cool and clammy - ‘shut down’
Give the 2 main causes of hypovolaemic shock (and some example of them)?
1) Haemorrhage - trauma, GI bleeding, ruptured haematoma, haemorrhagic pancreatitis, fractures, ruptured AAA, ruptured left ventricular free wall
2) Non-haemorrhagic fluid loss: diarrhoea, vomiting, heat stroke, burns
What is meant by ‘third spacing’ when referring to non-haemorrhagic fluid loss causing hypovolaemic shock and when does it commonly occur?
Acute loss of fluid into internal body cavities
Third space losses are common postoperatively and in intestinal obstruction, pancreatitis or cirrhosis
What is meant by cardiogenic shock?
Cardiac pump failure leading to reduced cardiac output
How does the body compensate for cardiogenic shock?
Increasing systemic vascular resistance
What are the 4 categories of causes of cardiogenic shock?
1) Myopathic (heart muscle failure)
2) Arrythmia related (abnormal electrical activity)
3) Mechanical
4) Extra-cardiac (obstruction to blood flow)
Give 4 causes of myopathic cardiogenic shock?
1) MI (>40% left venticular myocardium)
2) Right ventricular infarction
3) Dilated cardiomyopathies
4) “Stunned myocardium” following prolonged ischemia or cardiopulmonary bypass
Give 5 causes of arrhythmia-related cardiogenic shock and briefly describe mechanism?
1) atrial fibrilation - decreased CO by impairment of coordinated atrial filling of ventricles
2) Ventricular tachychardia - decreased CO
3) Bradyarrhythmias - decreased CO
4) Complete heart block - decreased CO
5) Ventricular fibrilation - abolishes CO
Give 4 causes of mechanical cardiogenic shock?
1) Valvular defects eg. prolapse
2) Ventricular septal defects
3) Atrial myxomas
4) Ruptured ventricular free wall aneurysm
Give 4 causes of extra-cardiac cardiogenic shock?
Anything that impairs cardiac filling or ejection of blood from the heart
1) Large PE
2) Tension pneumothorax
3) Severe constrictive pericarditis
4) Pericardial tamponade
What is meant by distributive shock?
decreased systemic vascular resistance due to severe vasodilation
How does the body compensate for distributive shock, thus how does the patient appear?
Increased cardiac output
patient appears flushed with a bounding heart
What are 4 familiar sub types of distributive shock?
1) Septic shock
2) Anaphylactic shock
3) Neurogenic shock
4) Toxic shock syndrome
What is meant by septic shock?
Severe overwhelming systemic infection with gram +ve, gram -ve or fungi, typically in the immunocompromised, very elderly, very young etc.
Get an increase in cytokines/mediators leading to vasodilation
Also get pro-coagulation DIC leading to ischaemia
What is meant by anaphylactic shock?
A severe type I hypersensitivity reaction
occurs in sensitized individuals, such as in hospital due to drugs, or in the community due to peanuts, shellfish or insect toxins
What is the mechanism of anaphylactic shock?
Sensitized indivduals
Small doses of allergen leads to IgE cross-linking leading to massive mast cell degranulation
Leading to vasodilation, contraction of bronchioles/respiratory distress, laryngeal oedema and circulatory collapse which leads to shock and possibly death
What is neurogenic shock and what is it typically caused by?
Loss of sympathetic vascular tone leading to vasodilation
Typically caused by spinal injury/ anesthetic accidents
Is toxic shock syndrome the same as septic shock?
No
What is the mechanism of toxic shock syndrome?
S.aureus/ S.pyogenes produce exotoxins (superantigens) which do not require processing by APCs
There is non-specific binding of Class II MHC to T cell receptors, up to 20% of T cells can be activated at one time
Wide spread release of massive amounts of cytokines leading to decreased systemic vascular resistance
Different type of shock can co-exist, give an example of how distributive, hypovolaemic and cardiogenic components can all play a role in a patient with septic shock?
Primary distributive shock - inflammatory and anti-inflammatory cascades lead to increased vascular permeability/vasodilation
Hypovolaemic component - decreased oral intake, insensible losses, vomiting, diarrhoea
Cardiogenic component - sepsis-related myocardial dysfunction
What percentage of patients die within one month of the onset of septic shock?
35-60%
What percentage of patients die from cardiogenic shock?
60-90%
