14 - Ischaemia, infarction and shock Flashcards
Why is reperfusion of non-infarcted but ischaemic tissues not always good?
Generation of reactive oxygen species by inflammatory cells causes further cell damage === reperfusion injury
Main causes of infarctions
Thrombosis and embolism
Other causes of infarctions
vasopasm artheroma expansion extrinsic compression twisting of vessel roots (volvulus) rupture of vascular supply (AAA)
Infarction morphology
Red (haemorrhagic)
White (anaemic)
what necrosis in the brain
colliquative
most popular necrosis
coagulative
if someone dies of a sudden heart attack what histology do you see?
nothing! as no time to develop haemorrhage / inflammatory response
factors affecting the degree of ischaemic damage
nature of the blood supply
rate of occlusion
tissue vulnerability to hypoxia
blood o2 content
most vulnerable organs for infarction
kidneys, spleen, testis
a slow rate of occlusion makes you more or less likely to have an infarct?
less likely as it allows development of collateral perfusion pathways
blood oxygen content
anaemia increases chance of infarction
congestive heart failure - poor CO and impaired pulm. vent. may develop an infarct with normally inconsequential narrowing of the vessels
shock definition
physiological state characterised by significant reduction of systemic tissue perfusion (severe hypotension) resulting in decreased O2 delivery to the tissues
shock’s effects at a cellular level
Membrane ion pump dysfunction
Intracellular swelling
Leakage of intracellular contents into the extracellular space
Inadequate regulation of intracellular pH
Anaerobic resp –> lactic acid
shock’s effects at a systemic level
Alterations in the serum pH (acidaemia)
Endothelial dysfunction -> vascular leakage
Stimulation of inflammatory and anti-inflammatory cascades
End-organ damage (ischaemia)
Shock and reversibility
Shock is initially reversible but rapidly becomes irreversible
Result of shock
Cell death
End-organ damage
Multi-organ failure
Death
Classification of shock
Hypovolaemic
Cardiogenic
Distributive
Types of distributive shock
Anaphylactic
Septic
Toxic shock syndrome
Neurogenic
Hypovolaemic shock
Intra-vascular fluid loss (blood, plasma etc)
Decrease in venous return to heart aka pre-load
Lower stroke volume therefore low CO
How to compensate for hypovolaemic shock
Increase blood volume
Causes of hypovolaemic shock
Haemorrhage - trauma, GI, rupture, fractures, aneurysm rupture
Non-haemorrhagic - diarrhoea, vomiting, heat stroke, burns
Third spacing
What is third spacing?
Acute loss of fluid into internal body cavities
Third-space losses are common post-op and in GI obstruction, pancreatitis or cirrhosis
Cardiogenic shock - why? how to compensate?
Cardiac pump failure with low CO
How to compensate -> increase in systemic vascular resistance
Causes of cardiogenic shock
Myopathic (heart muscle failure)
Arrythmia related
Mechanical
Extra cardiac (obstruction to blood flow)
Extra cardiac cardiogenic shock e.g.s
Anything that impairs cardiac filling or ejection of blood from heart
Massive PE, tension PT, severe constrictive pericarditis, pericardial tamponade
Distributive shock
Decrease in systemic vascular resistance due to severe vasodilation
Compensate via increasing CO
Septic shock which organisms? who’s at risk? pathophysiogical features
Gram +ve, -ve bacteria or fungi and affects immunocompromised, elderly, very young
Increase in cytokines/mediators leading to vasodilation
Pro-coagulation (DIC)
Anaphylactic shock - pathophysiology
Severe type I hypersensitivity rxn
Small doses of allergen = IgE cross-linking
Massive mast cell degranulation which = vasodilation
Anaphylactic shock - body’s rxn
Contraction of bronchioles/ resp. distress
Laryngeal oedema
Circulatory collapse -> shock/death
Neurogenic shock
Spinal injury / anaesthetic accidents = loss of sympathetic vascular tone
Vasodilation -> shock
Toxic shock syndrome
NOT SAME AS SEPTIC SHOCK
Toxic shock syndrome - causative organism
S. aureus
S. pyogenes
Toxic shock syndrome - pathophysiology
do not require processing by APCs
non-specific binding of MHC II to T cell receptors with up to 20% of T cells being activated at once
Widespread cytokine release = decrease in SVR
