Ischaemia, Infarction & Shock Flashcards
How harmful is ischaemia?
Limited= cell injury reversible
Prolonged= irreversible cell damage, necrosis
What is therapeutic reperfusion? When will it work/not work?
- Only if ischaemia is reversible
- Will have no effect if not reversible (permanent damage)
- Causes generation of reactive oxygen species by inflammatory cells causing further damage
Define infarction & infarct
Infarction=Ischaemic necrosis caused by occlusion of the arterial supply or venous drainage
Infarct=An area of infarction in tissues
What causes infarctions?
- Majority= thrombosis & embolism most common within arteries
- Other causes= vasospasm, atheroma expansion, twisting of vessels (volvulus), extrinsic compression (tumour), rupture of vascular supply (AAA), Venous occlusion
Describe the morphology of infarction
- Red infarction (haemorrhagic)=dual blood supply/ venous infarction
- White infarction (anaemic) = single blood supply hence totally cut-off
- Most wedge shaped= obstruction occurs at upstream point, downstream area will be infarcted
Describe the histology of infarction
- Coagulative necrosis
- Colliquative necrosis (brain)
What factors influence the degree of ischaemic damage?
- Nature of the blood supply
- Rate of occlusion
- Tissue vulnerability to hypoxia
- Blood oxygen content
How does nature of blood supply influence degree of ischaemic damage?
- Alternative blood supply will mean less damage
- Severe ischaemia required for infarction (lungs, liver, hands)
- Kidneys, spleen, testis have single supplies hence vulnerable to infarction
How does rate of occlusion influence degree of ischaemic damage?
- Slow developing occlusions less likely to infarct tissue
- Allow time for development of alternative perfusion pathways
- Coronary arteries
How does tissue vulnerability to hypoxia influence the degree of ischaemic damage?
- The brain= very vulnerable, high O2 consumption
- The heart=slightly more resistant with cardiac myocyte death
How does blood O2 content influence the degree of ischaemic damage?
- Reduced O2 in blood inc chances of infarction
- Congestive cardiac failure=poor cardiac output
- Watershed regions occurring at anastamosis
What clinical manifestations can occur in ischaemia in specific organs?
- Heart (IHD, angina)
- Brain (TIA/CVA)
- Intestines (ischaemic bowel)
- Extremities (peripheral vascular disease/gangrene)
Describe what cerebrovascular disease is
- Any abnormality of the brain caused by a pathological process involving blood vessels
- Includes thrombosis & embolism
- Bleeding
- Third leading cause of western death
What are the 2 types of cerebrovascular accident?
- Causes of an ischaemic stroke=thrombosis secondary to atherosclerosis, embolism
- Causes of haemorrhagic stroke=intracerebral haemorrhage, ruptured aneurysm in circle of Willis
What are the types of gangrene?
- Wet= Superimposed infection
- Dry= Ischaemic coagulative necrosis
- Gas= Superimposed infection w/gas producing organism
Define shock
- Physiological state characterized by a significant reduction of systemic tissue perfusion (severe hypotension) resulting in decreased O2 delivery to tissues.
- Critical imbalance between O2 delivery & O2 consumption
What are the cellular effects of shock?
- Membrane ion pump dysfunction
- Intracellular swelling
- Leakage of intracellular contents into extracellular space
- Inadequate regulation of intracellular pH
- Anaerobic respiration= lactic acid
- Initially reversible but quickly becoming irreversible
What are the systemic effects of shock?
- Alterations in the serum pH=acidaemia
- Endothelial dysfunction= vascular leakage
- Stimulation of inflammatory & anti-inflammatory cascades
- End-organ damage=ischaemia
What are the types of shock?
- Hypovolaemic
- Cardiogenic
- Distributive (anaphylactic, septic, toxic shock syndrome, neurogenic)
Describe hypovolaemic shock
- intra-vascular fluid loss (blood, plasma)
- dec venous return
- dec stroke volume so dec cardiac output
- inc systemic vascular resistance = vasoconstriction
What are causes of hypovolaemic shock?
- Haemorrhage (trauma, GI bleeding, ruptured haematoma, AAA)
- Non-haemorrhagic fluid loss (diarrhoea, vomiting, heat stroke, burns)
- Acute loss of fluid into internal body cavities
- Third-space loss= common postoperatively & intestinal obstruction, pancreatitis, cirrhosis
What is cardiogenic shock?
- Cardiac pump failure
- dec cardiac output
- inc systemic vascular resistance
What are the 4 categories of cardiogenic shock?
- 60-90% mortality
- Myopathic (heart muscle failure)
- Arrhythmia-related
- Mechanical
- Extra-cardiac (obstruction to blood outflow)
What are the causes of myopathic cardiogenic shock?
- Myocardial infarction
- Right ventricular infarction, dilated cardiomyopathies
- stunned myocardium
What are causes of arrhythmia-related cardiogenic shock? What does this lead to?
- Atrial & ventricular arrhythmias
- Atrial fibrillation/flutter
- Ventricular tachycardia, bradyarrhythmia, complete heart block
- Leads to dec cardiac output
What are causes of mechanical cardiogenic shock?
- Valvular defects (prolapse)
- Ventricular septal defects
- Atrial myxomas
- Ruptured venticular free wall aneurysm
What are causes of extra-cardiac cardiogenic shock?
- Anything that impairs cardiac filling/ ejection of blood from heart
- Massive pulmonary embolism
- Tension pneumothorax
- Severe constrictive pericarditis
- Pericardial tamponade
What happens in distributive shock?
- dec systemic vascular resistance due to severe vasodilation
- inc cardiac output = flushing
What is septic shock?
- 35-60% mortality within 1 month
- Severe over-whelming systemic infections w/gram +ve/-ve bacteria or fungi
- inc cytokines/mediators= vasodilation
- Pro-coagulation=ischaemia
What is anaphylactic shock?
- Severe type I hypersensitivity reaction
- Sensitized individuals (penicillin, peanuts)
- Small doses of allergen= IgE cross-linking
- Laryngeal oedema
- Massive mast cell degranulation
- vasodilation
- Contraction of bronchioles/ respiratory distress
- Circulatory collapse-shock/death
What is neurogenic shock?
- Spinal injury/anaesthetic accident
- Loss of sympathetic vascular tone
- Vasodilation=shock
What is toxic shock syndrome?
- S.aureus/S.pyogenes produce exotoxins(superantigens)
- Don’t require processing by antigen-presenting cells
- Non-specific binding of class II MHC to T cell receptors
- Widespread release of massive amounts of cytokines= dec systemic vascular resistance
What are the combinations of shock that can occur and what happens in them?
- Primary distributive component (inflammation & anti-inflammatory cascades inc vascular permeability/vasodilation)
- Hypovolemic component (dec oral intake, insensible losses, vomiting, diarrhoea)
- Cardiogenic component (sepsis-related myocardial dysfunction)
