L14- Ischaemia, Infarction & Shock

Question 1

What is Hypoxia

Answer 1

Any state of reduced tissue oxygen availability

• Generalised - whole body e.g. altitude, anaemia
• Regional - specific tissues affected

Question 2

What is Ischaemia

Answer 2

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

Question 3

How harmful is ischaemia? (Limited vs prolonged duration)

Answer 3

If limited / short duration —> cell injury reversible

Prolonged / sustained —> irreversible cell damage
Cell death occurs by necrosis (infarction)

Question 4

Why can reperfusion of non-infarcted but ischaemic tissue be bad?

Question 5

Whats is Infarction

Answer 5

Ischaemic necrosis caused by occlusion of the arterial supply or venous drainage

Question 6

Other causes of infarction?

Answer 6

Vasospasm (sudden blood vessel contraction)

Atheroma expansion

Extrinsic compression (e.g. tumour)

Twisting of vessel roots (e.g. volvulus)

Rupture of vascular supply (e.g. AAA)

Question 7

Morphology of infarction : Red infarct vs White

Answer 7

Red infarction (haemorrhagic)
Dual blood supply / venous infarction

White infarction (anaemic)
Single blood supply hence totally cut-off

Question 8

Why are most infarcts wedge shaped?

Answer 8

Obstruction usually occurs at an upstream point

The entire down-stream area will therefore be infarcted

Question 9

What are the histological characteristics of infarcts

Answer 9

Coagulative necrosis (usually)
Colliquative necrosis (in the brain)

Question 10

If a person dies suddenly (e.g. massive heart attack) what do you see in the tissues?

Answer 10

Nothing —>

No time to develop haemorrhage / inflammatory response

Question 11

What factors influence the degree of ischaemic damage?

Answer 11

Nature of the blood supply (e.g is there a collateral supply present?)

Rate of occlusion (slow forming ones are less likely to infarct tissues)

Tissue vulnerability to hypoxia (The brain is vulnerable/ the heart is a bit more resistant)

Blood oxygen content (Reduced oxygen in the blood (anaemia etc.) increases the chances of infarction)

Question 12

Clinical Manifestations of Ischaemia?

Answer 12

Ischaemic heart disease (angina / MI)

Cerebrovascular disease (TIA / CVA)

Ischaemic bowel

Peripheral vascular disease / gangrene

(Remember THE 5 Ps as well)

Question 13

What is Cerebrovascular disease

Answer 13

Any abnormality of the brain caused by a pathological process involving the blood vessels

Includes

• Thrombosis and embolism (ischaemic)
• Bleeding (haemorrhagic)

Question 14

What is a Cerebrovascular accident

Answer 14

Stroke

Causes of an ischaemic stroke:

• Thrombosis secondary to atherosclerosis
• Embolism (e.g. mural thrombus)

Question 15

What are the causes of a haemorrhagic stroke

Answer 15

Intracerebral haemorrhage (hypertensive)

Ruptured aneurysm in the circle of Willis (subarachnoid)

Question 16

What is Ischaemic bowel disease

Answer 16

Usually caused by thrombosis or embolism in the superior or inferior mesenteric arteries

Presents with abdominal pain

Question 17

Limb ischaemia / infarction presentation

Answer 17

Gangrene
Infarction of entire portion of limb (or organ)

Dry gangrene
Ischaemic coagulative necrosis only

Wet gangrene
Superimposed infection

Gas gangrene
Superimposed infection with gas producing organism e.g. clostridium perfringens

Question 18

What is Shock

Answer 18

A physiological state characterised by a significant reduction of systemic tissue perfusion (severe hypotension)

Which results in decreased oxygen delivery to the tissues.

Question 19

What can impaired tissue perfusion and oxygen deprivation lead to?

Answer 19

cellular hypoxia and derangement of critical biochemical processes at first cellular and eventually systemic levels.

Question 20

Cellular effects of shock…

Answer 20

Membrane ion pump dysfunction

Intracellular swelling

Leakage of intracellular contents into the extracellular space

Inadequate regulation of intracellular pH

Anerobic respiration —> build up of lactic acid

Question 21

Systemic effects of shock…

Answer 21

Alterations in the serum pH (acidaemia)

Endothelial dysfunction —> vascular leakage

Stimulation of inflammatory and anti-inflammatory cascades

End-organ damage (ischaemia)

Question 22

Is shock reversible?

Answer 22

Initially it is, but then becomes irreversible as:

• Cells start to die
• End organs are damaged
• Organs begin to fail
• –> eventually leading to DEATH

Question 23

Types of shock

Answer 23

HYPOVOLAEMIC
(severe blood and fluid loss)

CARDIOGENIC
(heart suddenly can’t pump enough blood to meet your body’s needs)

DISTRIBUTIVE
(Anaphylactic, septic, toxic shock syndrome, neurogenic)

Question 24

What is Hypovolaemic shock

Answer 24

Intra-vascular fluid loss (blood, plasma etc)

↓ venous return to heart AKA “pre-load”

↓ stroke volume —> ↓ cardiac output

Question 25

What is the body's response to Hypovolaemic shock?

Answer 25

Systemic vascular Resistance

Question 26

What are the causes of Hypovolaemic shock?

Answer 26

Haemorrhage: -Trauma, gastrointestinal bleeding, ruptured haematoma , aneurysm Non-haemorrhagic fluid loss: -Diarrhoea, vomitting, heat stroke, burns

Question 27

What is Cardiogenic shock ?

Answer 27

Cardiac pump failure

Question 28

The 4 categories of Causes of Cardiogenic shock?

Answer 28

Myopathic (heart muscle failure e.g after M.I) Arrythmia-related (abnormal electrical activity e.g AF) Mechanical (problems with the valves) Extra-cardiac (obstruction to blood outflow e.g PE, Anything that impairs cardiac filling or ejection of blood from heart)

Question 29

What is third spacing?

Answer 29

Acute loss of fluid into internal body cavities

Question 30

Types of Distributive shock: What is Septic shock and what happens during it

Answer 30

Severe, over-whelming systemic infections with Gram+ve, gram-ve bacteria or fungi Inc in Cytokines / mediators ---> VASODILATION Pro-coagulation (DIC) ---> Ischaemia

Question 31

Types of Distributive shock: What is Anaphylactic shock and what can cause it?

Answer 31

Severe type I hypersensitivity reaction Sensitized individuals Hospital e.g. drugs (penicillin etc) Community e.g. peanuts, shellfish, or insect toxins Small doses of allergen ---> IgE cross-linking (stimulates mast cells) ---> Vasodilation Contraction of bronchioles / respiratory distress Laryngeal oedema Circulatory collapse ---> shock / death

Question 32

Types of Distributive shock: What is Neurogenic shock

Answer 32

Spinal injury / anesthetic accidents Loss of sympathetic vascular tone Vasodilation ---> shock

Question 33

Types of Distributive shock: What is Toxic shock syndrome

Answer 33

NOT the same as septic shock!!!! S. aureus / S. pyogenes produce exotoxins “superantigens” 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 leading to a decrease ↓SVR (systemic vascular resistance)