Lecture 10: Ischaemia, Infarction and shock Flashcards
Define ischaemia:
the interruption/ disturbance of blood flow to cells, reducing supply of oxygen and metabolites
Define infarction:
Tissue necrosis due to ischaemia
Why does reduced oxygen supply lead to infarction?
reduced oxygen means less oxidative phosphorylation which means less ATP required for cell function
What is the effect of cells switching to anaerobic respiration on lactate levels?
lactate levels increase
What is the effect of cells switching to anaerobic respiration on lactate levels?
lactate levels increase
Give four consequences of a lack of ATP in cells:
1) Na+ pumps stop working, causing an accumulation of Na+
2) the plasma membrane is damaged causing leakage of proteins
3) Ca2+ pump stops, causing an influx of Ca2+ into the cell
4) protein synthesis halts
Give two chemical markers for ischaemia that can be found in blood:
1) increased lactate
2) leakage of intracellular proteins
Give two examples of intracellular proteins that if found in the blood, indicate cardiac muscle damage:
1) creatine kinase
2) troponins
Give two examples of intracellular proteins that if found in the blood, indicate liver damage:
1) transaminases
2) alkaline phosphate
Give 6 causes of ischaemia:
1) vascular occlusion
2) vasospasm
3) vascular damage
4) extrinsic compression
5) mechanical interruption
6) hypoperfusion
What is the most common of ischaemia?
vascular occlusion
Give 4 structures that can lead to occlude blood vessels:
1) severe atherosclerosis
2) thrombosis
3) embolism
4) hyper-viscous blood
What is vasospasm?
sudden constriction of a blood vessel, reducing its diameter and flow rate
How can vascular damage lead to ischaemia? (2)
1) a rupture in a vessel reduces flow to tissues
2) vasculitis can cause inflammation, also reducing flow
Give an example of a structure that could cause extrinsic compression to a vessel:
Tumour
Give three examples of mechanical interruptions that cause ischaemia:
1) volvulus
2) torsion of a blood vessel
3) intussusception
What is volvulus?
twisting of the bowel, leading to ischaemia
What is intussusception?
where the intestine folds into a section next to it
Give two causes of hypoperfusion:
1) cardiac failure
2) cardiac malformation
Give two complications caused by arterial ischaemia:
1) myocardial infarction
2) stroke
Give an example of a complication caused by venous ischaemia:
pulmonary embolism
Give two examples of complications caused by capillary ischaemia:
1) frostbite
2) disseminated intravascular coagulation
What is disseminated intravascular coagulation (DIC)?
a condition in which clots form in numerous small vessels around the body
Give 5 factors that affect the outcomes of ischaemia?
1) the nature of the blood supply
2) duration of the ischaemia
3) rate of vascular occlusion
4) tissue vulnerability
5) blood oxygen content
Describe how the nature of blood supply can affect the outcomes of ischaemia:
tissues with a dual vascular supply are generally resistant to infarction to a single vessel
Give three examples of organs with dual blood supplies:
1) lungs
2) liver
2) hand
Give the dual blood supply of the lungs:
pulmonary and bronchial arteries
Give the dual blood supply of the liver:
hepatic and portal arteries
Give the dual blood supply of the hand:
radial and ulnar arteries
What is the term used to describe circulations where there is just a single artery supplying blood?
end arterial circulation
Give 3 examples of that have end arterial circulations:
1) kidneys
2) spleen
3) testes
Describe how the duration of ischaemia can affect the outcome of ischaemia:
prolonged ischaemia can lead to irreversible necrosis while limited ischaemia leads to reversible ischaemic injury
Describe how the rate of vascular occlusion can affect the outcome of ischaemia:
slow developing occlusions are less likely to cause infarction in tissues as the slow development allows for the development of alternative perfusion pathways
What is a term to used alternative blood supplies to tissues?
collateral circulation
Describe how tissue vulnerability can affect the outcome of ischaemia:
certain tissues like the brain are more sensitive to ischaemia as it is more metabolically active
How long does it take for ischaemia to cause irreversible damage in the brain?
3-4 minutes
How long does it take for ischaemia to cause irreversible damage in the heart?
20-30 minutes
Describe how blood oxygen content can affect the outcome of ischaemia:
reduced oxygen in the blood e.g. from anaemia makes individuals more vulnerable to infarction
What are the two types of infarcts?
1) coagulative
2) liquefactive
What cell process creates a coagulative infarct?
denaturation of cells where enzymes become unable to break down the cell structure
How does a coagulative infarct appear under a microscope?
the basic outlines of cells are preserved but it appears pale and lacks content (ghost cell)
Are necrotic tissues firm or soft in coagulative infarcts?
firm
What colour are coagulative infarcts?
white
What cell process creates liquefactive infarcts?
enzyme digestion
In which tissue are liquefactive infarcts formed?
brain
Describe a liquefactive infarct:
cells are completely digested and broken down into a mushy mess until it is liquefied, creating a cavity of cyst in the brain
What makes some infarcts white?
the blood is trapped in the infarct, denaturing, causing it to lose its red colour
What makes some infarcts red?
fresh blood is still able to enter the infarcted area
In which type of circulation supply are red infarcts created?
dual blood supply
In which type of circulation supply are white infarcts created?
single blood supply
What shape are most infarcts?
wedge-shaped
Why are most infarcts wedge-shaped?
because obstructions often occur at proximal vessels of a tissue affecting the entire downstream fan-shaped network of vessels
What gross and microscopic features can be seen in an infarct after 0-4 hours?
no gross or microscopic changes
What gross and microscopic features can be seen in an infarct after 4-24 hours?
1) gross: dark mottling
2) microscopic: oedema, haemorrhage
What gross and microscopic features can be seen in an infarct after 1-3 days?
1) gross: yellow colour with haemorrhagic edge
2) microscopic: oedema with early neutrophil infiltration
What gross and microscopic features can be seen in an infarct after 3-7 days?
1) gross: yellow centre will become soft
2) microscopic: dying neutrophils with macrophage infiltration can be seen
What gross and microscopic features can be seen in an infarct after 1-2 weeks?
1) gross: a grey-red colour can be seen on the organ
2) microscopic: granulation tissue formation can be seen and recruitment of fibroblasts for collagen production
What gross and microscopic features can be seen in an infarct after 2-8 weeks?
1) gross: a fibrous scar can be seen on the organ
2) microscopic: increased collagen can be seen
Why is the heart at risk of rupture following acute myocardial ischaemia?
the heart tissue is weakened
Why is the heart at risk of heart failure following acute myocardial ischaemia?
the scarred tissue is non-functional
What four factors cause reperfusion injury?
1) free radical damage
2) cytokine recruitment of inflammatory cells
3) activation of the compliment pathway
4) build-up of Ca2+ ions
Why is it that ischaemic tissue is susceptible to free radical damage?
healthy cells use antioxidants to control free radical formation but damaged cells have less of these
Define shock:
a pathophysiological state of reduced systemic tissue perfusion (generalised tissue effect) due to cardiovascular collapse
What is the key factor in causing shock?
reduced mean arterial pressure
What two factors determine mean arterial pressure?
1) cardiac output
2) total peripheral resistance
What two factors determine mean arterial pressure?
1) cardiac output
2) total peripheral resistance
What factors can contribute to shock? (2)
1) any factors that affect cardiac output (heart rate and stroke volume)
2) any factors that affect peripheral resistance (arteriolar radius)
Give the three broad types of shock:
three broad types of shock:
1) hypovolaemic
2) cardiogenic
3) distributive
What is hypovolaemic shock?
intra-vascular fluid loss causing reduced pre-load/ venous return to the heart, reducing blood pressure
What are three key presentations associated with hypovolaemic shock?
1) tachycardia
2) pallor
3) cool skin (due to vital organs being prioritised)
True or false: an individual in hypovolaemic shock may present with a normal blood pressure due to compensation
True
Give 5 haemorrhagic causes of hypovolaemic shock:
1) trauma
2) gastrointestinal bleeding
3) haemorrhagic pancreatitis
4) fractures
5) ruptures in vessels
Give 5 non-haemorrhagic causes of hypovolaemic shock:
1) diarrhoea
2) heat stroke
3) burns
4) vomiting
5) third spacing
What is third spacing?
When fluid accumulates in a portion of the body
What is cardiogenic shock?
cardiac pump failure meaning a healthy blood pressure cannot be maintained
What are the four types of cardiogenic shock?
1) myopathic
2) arrhythmia
3) mechanical
4) extracardiac
What is myopathic-related cardiogenic shock?
heart muscle failure due to cardiomyopathies and myocardial infarctions causing reduced blood pressure and shock
What is arrhythmia-related cardiogenic shock?
electrical abnormalities or atrial or ventricular arrhythmias e.g. fibrillation not allowing enough blood to fill the heart, causing reduced blood pressure and shock
What is mechanical-related cardiogenic shock?
defects relating to blood flow in the heart causing reduced cardiac output and blood pressure and thus shock
Give three mechanical defects that can lead to cardiogenic shock:
1) valvular defects
2) ventricular septal defects
3) atrial myxoma
What is an atrial myxoma?
a non-cancerous tumour of the heart
What is extracardiac cardiogenic shock?
anything outside of the heart impairing cardiac filling or ejection, causing reduced blood pressure and shock
Give 3 extracardiac changes that can cause cardiogenic shock:
1) massive pulmonary embolism
2) tension pneumothorax
3) pericardial tamponade
What is pericardial tamponade?
Fluid accumulating around the heart, slowly stops the heart from contracting
What is distributive shock?
reduced systemic vascular resistance due to severe vasodilatation
Give four types of distributive shock:
1) septic
2) anaphylactic
3) neurogenic
4) toxic shock
Describe the heartbeat in a patient suffering distributive shock:
bounding heartbeat
True or false: a patient can have mixed shock (a combination of 2 or 3 different types of shock
True
