What is hypoxia?
–Any state of reduced tissue oxygen availability
•Generalised - whole body e.g. altitude, anaemia
•Regional - specific tissues affected
What is ischaemia and why is it worse than hypoxia alone?
–Pathological reduction in blood flow to tissues
–Usually as a result of obstruction to arterial flow
commonly as a result of thrombosis / embolism
–Ischaemia results in tissue hypoxia
Worse as there's no removal of waste products in addition to hypoxia.
What is PCI for MI?
Percutaneous intervention for myocardial infarction. Only suitable for reversible ischaemia.
What is reperfusion injury?
Generation of ROS by inflammatory cells causes further cell damage.
What is infarction?
–Ischaemic necrosis caused by occlusion of the arterial supply or venous drainage
What causes the majority of infarctions?
Thrombosis and emobolisms. Most common within arteries.
What are the other causes of infarction?
Vasospasm, atheroma, extrinsic compression (eg tumour), twisiting of vessel roots, rupture of vascular supply (eg AAA)
Why do lung infarctions look red?
Dual blood supply. One supply blocked, the vessels for the other are damaged and leak blood into the infarcted area.
What is the difference between coagulative necrosis and liquefactive necrosis?
In coagulative necrosis the tissue retains it's basic arcitecture, Tissue arcitecture lost in liquefactive as there is no collagen (brain).
What factors influence the severity of the ischaemic damage?
1.Nature of the 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 severity of the ischaemic damage?
•An alternative blood supply will mean less damage hence severe ischaemia required for infarction
–Lungs (pulmonary and bronchial arteries)
–Liver (hepatic artery and portal vein)
–Hand (radial and ulnar artery)
•Kidneys, spleen, testis etc. have single supplies hence are vulnerable to infarction
How does the rate of occlusion effect the severity of ischaemic damage?
•Slow developing occlusions are less likely to infarct tissues
•Allows time for the development of alternative (collateral) perfusion pathways
–Small anastomoses connect major branches and have minimal flow
–If a coronary arterial branch is slowly occluded flow can be directed through these channels
–Infarction can be avoided even if the main arterial branch is totally occluded
How does the tissue vulnerabilty to hypoxia influence the severity of ischaemic damage?
–If a neurone is deprived of oxygen irreversible cell damage occurs in 3 to 4 minutes
–Brain is 1 to 2% of total body weight but requires 15% of cardiac output and 20% of body oxygen consumption
–Therefore very vulnerable to injury
–Slightly more resistant with cardiac myocyte death taking 20 to 30 minutes
How does the blood oxygen content influence the severity of ischaemia?
•Reduced oxygen in the blood (anaemia etc.) increases the chances of infarction
•Congestive cardiac failure
–Poor cardiac output and impaired pulmonary ventilation
–May develop an infarct with a normally inconsequential narrowing of the vessels!
•Watershed regions occur at the point of anastomosis between two vascular supplies
–E.g. Splenic flexure and brain
What are the most common causes of an ischaemic stroke?
–Thrombosis secondary to atherosclerosis
–Embolism (e.g. mural thrombus)
What are the most common causes of a haemmorhagic stroke?
–Intracerebral haemorrhage (hypertensive)
–Ruptured aneurysm in the circle of Willis (subarachnoid)
What is the usual cause of ischaemic bowel disease?
•Usually caused by thrombosis or embolism in the superior or inferior mesenteric arteries
•Presents with abdominal pain
What are the different types of gangrene?
–Infarction of entire portion of limb (or organ)
–Ischaemic coagulative necrosis only
–Superimposed infection with gas producing organism
e.g. clostridium perfringens
What is the definition of shock?
•A physiological state characterised by a significant reduction of systemic tissue perfusion (severe hypotension) resulting in decreased oxygen delivery to the tissues.
•Shock results in a critical imbalance between oxygen delivery and oxygen consumption.
•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. Initially reversible but rapdly becomes irreversible.
What is hypovolaemic shock?
•Intra-vascular fluid loss (blood, plasma etc)
•↓ venous return to heart AKA “pre-load”
•↓ stroke volume à ↓ cardiac output
•How could you compensate for this? - increase systemic vascular resistence by increasing HR and arterial muscle tone (sympathetic - clammy, olgouria).
Patient will be very pale, cool, tachy, clammy and have long cap refill
What is third spacing?
Where you loose your blood volume into internal body cavities (eg bowel)
What are the causes of hypovolaemic shock?
–Trauma, gastrointestinal bleeding, ruptured haematoma,
–Haemorrhagic pancreatitis, fractures
–Ruptured aortic, abdominal, or left ventricular free wall aneurysm
•Non-haemorrhagic fluid loss
–Diarrhoea, vomiting, heat stroke, burns, third spacing
What is cardiogenic shock?
•Cardiac pump failure
•How could you compensate for this?
What are the causes/categories of cardiogenic shock?
–Myopathic (heart muscle failure)
–Arrythmia-related (abnormal electrical activity)
–Extra-cardiac (obstruction to blood outflow)
What are the causes of myopathic shock?
•Any causes of myopathic cardiogenic shock??
–Myocardial infarction (> 40% left ventricular myocardium)
–Right ventricular infarction, dilated cardiomyopathies
–“Stunned myocardium” following prolonged ischemia or cardiopulmonary bypass.
What are the causes of arrthymia-related shock?
•Arrhythmia-related cardiogenic shock
–Atrial and ventricular arrhythmias
–Atrial fibrillation / flutter à ↓CO by impairment of co-ordinated atrial filling of the ventricles.
–Ventricular tachycardia, bradyarrhythmias, and complete heart block ↓ CO, while ventricular fibrillation abolishes CO.
What are the causes of mechanical cardiogenic shock?
•Mechanical cardiogenic shock
–Valvular defects (e.g. prolapse), ventricular septal defects
–Atrial myxomas, ruptured ventricular free wall aneurysm.
What are the causes of extra-cardiac cardiogenic shock?
–Anything that impairs cardiac filling or ejection of blood from heart
–Massive pulmonary embolism, tension pneumothorax, Severe constrictive pericarditis, pericardial tamponade
What is distributive shock and what are the different types?
•↓ SVR due to severe vasodilation
•How could you compensate for this?
•↑ CO Flushed / bounding heart
•TOXIC SHOCK SYNDROME
What are the features of septic shock?
•Severe, over-whelming systemic infections with...
–Gram+ve, gram-ve bacteria or fungi
•Immunocompromised, elderly, very young etc.
•↑ Cytokines / mediators
What are the features of anaphylactic shock?
•Severe type I hypersensitivity reaction
•Hospital e.g. drugs (penicillin etc)
•Community e.g. peanuts, shellfish, or insect toxins
–Small doses of allergen à IgE cross-linking
–Massive mast cell degranulation à
–Contraction of bronchioles / respiratory distress
–Circulatory collapse à shock / death
What are the features of neurogenic shock?
•Spinal injury / anesthetic accidents
•Loss of sympathetic vascular tone
•Vasodilation -> shock
What are the features of toxic shock syndrome?
•NOT the same as septic shock!!!!
•S. aureus / S. pyogenes produce exotoxins “superantigens”
•Do not require processing by antigen-presenting cells
•Non-specific binding of class II MHC to T cell receptors
•Up to 20% of T cells can be activated at one time!!!!!
•Widespread release of massive amounts of cytokines ↓SVR
How might different types of shock combine?
–Primary distributive component
•Inflammatory and anti-inflammatory cascades ↑ vascular permeability / vasodilation
•Decreased oral intake
•Sepsis-related myocardial dysfunction