Ischaemia, Infarction & Shock Flashcards
What is the definition of hypoxia?
When the oxygen saturation of tissues falls
What is the definition of ischaemia?
the interruption/disturbance of blood flow to cells and tissues
What is the relationship between ischaemia and hypoxia?
ischaemia ALWAYS results in hypoxia
hypoxia can occur without ischaemia e.g. anaemia
How is the oxygen supply and metabolite supply affected in hypoxia?
There is an impaired oxygen supply only
Other metabolites are still supplied to the tissue
How is the metabolite supply affected in ischaemia?
There is a decreased supply of metabolites, including glucose
What is the consequence of lack of glucose in ischaemia?
glycolytic anaerobic respiration fails due to lack of glucose
the build up of metabolites impairs anaerobic respiration further
What is the consequence of the reduced metabolite supply in ischaemia on the tissues?
Ischaemia will injure tissues faster and more severely than hypoxia
What is the main cause of ischaemia?
vascular occlusion
this can be arterial or venous
What are the 3 main causes of vascular occlusion?
- severe atherosclerosis
- thrombosis
- embolism
What are the 6 rarer causes of ischaemia?
- vasospasm
- vasculitis
- extrinsic compression (e.g. tumour)
- twisting of vessel roots (e.g. volvulus)
- rupture of vascular supply
- cardiac failure
What happens if ischaemia is limited and only occurs for a short duration?
Any cell injury is reversible
What is primary percutaneous coronary intervention used for?
Myocardial ischaemia/infarction
It allows for rapid restoration of blood flow to allow for reversible cell injury
What happens if ischaemic injury is prolonged or sustained?
Irreversible cell damage
This leads to necrosis
What is tissue necrosis called when it is caused by ischaemia?
infarction
What do the variable effects of vascular occlusion depend on (4 factors)?
- nature of the blood supply
- the rate of occlusion
- tissue vulnerability to hypoxia
- blood oxygen content
How does the nature of the blood supply affect whether vascular occlusion will cause damage?
an alternative blood supply means that vascular occlusion causes less damage
severe ischaemia is required for infarction
In which 3 organs is severe ischaemia less likely to occur due to a dual blood supply?
- lungs = pulmonary and bronchial arteries
- liver - hepatic artery and portal vein
- hand - radial and ulnar artery
In general, what kind of tissues are resistant to infarction of a single vessel?
tissues with a dual blood supply
Why are the kidneys, spleen and testis more vulnerable to both arterial and venous infarction?
they have end-arterial circulations
this means an artery only blood supply
What type of organs are more vulnerable to venous infarction?
organs with a single venous outflow (testis/ovary)
How does the rate of occlusion affect the severity of the effects of vascular occlusion?
Why?
Slow developing occlusions are less likely to lead to infarction
This allows time for the development of alternative perfusion pathways (collateral supply)
What is the state of the anastomoses in the heart under normal circumstances?
there are small anastomoses that connect the major branches of the coronary artery system
they have minimal flow
What is significant about the anastomoses in the coronary artery system when a coronary arterial branch becomes occluded?
If a coronary arterial branch becomes slowly occluded, the flow can be directed through the anastomoses
Infarction can be avoided even if the main arterial branch is totally occluded
If a neurone in the brain is deprived of oxygen, how long does it take for it to undergo irreversible cell damage?
3 - 4 minutes
If a cardiac myocyte or cardiac fibroblast is deprived of oxygen, how long does it take for irreversible cell damage to occur?
cardiac myocyte - 20-30 mins
cardiac fibroblast takes hours
Why does it take longer for irreversible cell damage to occur in a cardiac fibroblast compared to a myocyte?
fibroblasts are not as metabolically active as heart muscle cells
How does blood oxygen content affect the severity of the effects of vascular occlusion?
reduced oxygen content in the blood means that tissues are more vulnerable to infarction
e.g. anaemia
Why does an infarct occur in a normally inconsequential narrowing of vessels in congestive heart failure?
There is poor cardiac output and impaired pulmonary ventilation
Infarct occurs due to impaired oxygenation of the tissues
What 5 categories are looked for when looking at morphological changes of an infarct?
- location
- colour
- shape
- type of necrosis
- histological changes over time
What is the name of the locations that are looked for when identifying an infarct?
watershed regions
What is a watershed region?
a point of anastomoses between 2 vascular supplies
Infarcts are more likely to occur here
What are examples of common watershed regions?
- splenic flexure in colon
- myocardium
- regions in the brain
What are the two types of infarction and their colour?
- red infarction (haemorrhagic)
2. white infarction (anaemic)
Where do red infarctions tend to be found?
In regions with a dual blood supply
or venous infarctions
Where do white infarctions tend to be found?
in regions with a single blood supply
What shape are most infarcts?
wedge shaped
Why are most infarcts wedge-shaped?
- vascular supply is up-stream in the tissue
- the vascular branches expand as you get deeper into the tissue
- if obstruction occurs at an upstream point, the entire down-stream area will be infarcted
What is the main type of necrosis seen in infarction?
coagulative necrosis
What is the type of necrosis seen in an infarction of the brain?
colliquative/liquefactive necrosis
As duration of cellular injury progresses, what are the 4 events that occur?
- biochemical alterations leading to cell death
- ultrastructural changes
- light microscopic changes
- gross morphological changes
What gross and microscopic features will be seen 0-4 hours after cellular injury?
there will be no changes seen
Between 4-12 hours, what gross and microscopic features will be seen in coagulative infarction?
gross - occasional dark mottling
microscopic - oedema, haemorrhage - this is the start of coagulative necrosis
Between 12-24 hours, what gross and microscopic features will be seen in coagulative infarction?
gross - dark mottling
microscopic - ongoing coagulative necrosis
Between 1-3 days, what gross and microscopic features will be seen in coagulative infarction?
gross - yellow with haemorrhagic edge
microscopic - oedema with early neutrophil infiltration
Between 3-7 days, what gross and microscopic features will be seen in coagulative infarction?
gross - yellow centre becomes soft
microscopic - dying neutrophils with macrophage infiltration
Between 1-2 weeks, what gross and microscopic features will be seen in coagulative infarction?
gross - red-grey colour
microscopic - granulation tissue formation
Between 2-8 weeks, what gross and microscopic features will be seen in coagulative infarction?
gross - fibrous scar
microscopic - increased collagen leading to scar formation
Under what conditions is therapeutic reperfusion of ischaemia a good thing?
tissue reperfusion is generally good
ONLY if the ischaemia is reversible
What happens if ischaemia is NOT reversible, but therapeutic reperfusion is still performed?
reperfusion of infarcted tissues has no effect
this is because the damage caused by infarction cannot be reversed
What is reperfusion injury?
the generation of reactive oxygen species by sudden reperfusion of ischaemic (dysfunctional) tissues
this damages the tissues
How can reperfusion injury affect the function of salvaged tissue?
the function of the salvaged tissue may be delayed for hours to days
Why is reperfusion injury clinically relevant?
around 50% of the final infarct may be due to reperfusion injury
generally, reperfusion is better than infarction
What is the definition of shock?
a pathophysiological state of reduced systemic tissue perfusion resulting in decreased oxygen delivery to the tissues
How does shock affect oxygen balance of tissues?
it causes a critical imbalance between oxygen delivery and oxygen requirements of the tissues
What can impaired tissue perfusion and prolonged oxygen deprivation in shock lead to?
- cell death due to hypoxia
- end-organ damage
- multi-organ failure
- death
Can shock be reversible?
It is initially reversible, but rapidly becomes irreversible
Essentially, what is shock the result of?
decreased systemic tissue perfusion
or mean arterial pressure
What factors contribute to mean arterial pressure (MAP)?
MAP = CO x SVR
systemic vascular resistance is the same as total peripheral resistance
What factors affect cardiac output?
heart rate and stroke volume
What is the main factor influencing SVR?
arteriolar radius
this depends on how dilated or constricted the vessels are
What are the causes of shock?
anything that causes either:
- decreased cardiac output
- decreased systemic vascular resistance
What are the 3 types of shock?
- hypovolaemic
- cardiogenic
- distributive
What are the stages involved in hypovolaemic shock?
- there is intravascular fluid loss (blood, plasma)
- reduced venous return to the heart
- this reduces stroke volume, and therefore cardiac output
How does the body compensate for hypovolaemic shock?
vasoconstriction increases SVR
this means blood is directed away from the peripheries and towards vital organs
heart rate is increased
How would a patient in hypovolaemic shock feel/present?
cool/clammy due to less blood going to the peripheries
due to compensation, they may have normal blood pressure
What are the 2 categories of causes of hypovolaemic shock?
- haemorrhage
2. non-haemorrhagic fluid loss
What tends to cause haemorrhage that leads to hypovolaemic shock?
- trauma, GI bleeding, ruptured haematoma
- haemorrhagic pancreatitis, fractures
- ruptured aortic, abdominal or left ventricular wall aneurysm
What tends to cause non-haemorrhagic fluid loss?
- diarrhoea, vomiting, heat stroke, burns
2. third spacing
What is third spacing?
acute loss of fluid into internal body cavities
When are third-space losses common?
- post-operatively
2. in intestinal obstruction, pancreatitis or cirrhosis
What causes cardiogenic shock?
cardiac pump failure
this leads to reduced cardiac output
How is cardiogenic shock compensated for?
increase in SVR
this reduces blood flow to the extremities
What are the 4 categories of cardiogenic shock?
- myopathic
- arrhythmia-related
- mechanical
- extra-cardiac
What causes myopathic cardiogenic shock?
failure of the heart muscle
What causes arrhythmia related cardiogenic shock?
abnormal electrical activity
What causes mechanical cardiogenic shock?
acquired or developmental defects
What causes extra-cardiac cardiogenic shock?
obstruction to blood outflow
In what conditions can myopathic cardiogenic shock be seen?
- myocardial infarction
- cardiomyopathies
- “stunned myocardium” following cardiopulmonary bypass
What is arrhythmia-related cardiogenic shock and in what conditions is it seen?
there is nothing wrong with the cardiac muscle, but it is not beating correctly
seen in atrial or ventricular arrhythmias
there is impaired ventricular contraction/filling, reducing cardiac output
In what conditions is mechanical cardiogenic shock seen?
any defects relating to blood flow through the heart
- valvular defects
- ventricular septal defects
- atrial myxomas
What are examples of conditions that cause extra-cardiac cardiogenic shock?
anything outside the heart that impairs cardiac filling or ejection of blood from the heart
- massive pulmonary embolism
- tension pneumothorax
- severe constrictive pericarditis
- pericardial tamponade
What causes distributive shock?
there is a decrease in systemic vascular resistance due to severe vasodilation
How does the body compensate for distributive shock and how would this present?
Increase in cardiac output
Patient appears warm and flushed with a bounding heart beat
What are the 4 sub-types of distributive shock?
- septic shock
- anaphylactic shock
- neurogenic shock
- toxic shock syndrome
What causes septic shock and toxic shock syndrome?
cytokines causing severe vasodilation
What causes anaphylactic shock and neurogenic shock?
anaphylactic shock is due to mast cells
neurogenic shock is due to loss of sympathetic tone
What is meant by “mixed shock”?
when different types of shock can co-exist
