Ischaemia, Infarction, Shock

infarction

• ischaemic necrosis

• tissue necrosis due to ischaemia

ischaemia

• interruption/disturbance of blood flow to cells and tissues

• reduces oxygen supply and metabolism

how does ischaemia lead to infarction

1. reduced blood flow leads to cell injury

2. sustained cell injury leads to cell death

3. individual cell death in ischaemic injury→ necrosis

ischaemic cell injury

1. less O₂ = less oxidative phosphorylation= less ATP

2. switch to anaerobic resp.

   1. more lactate

   2. depleted glycogen stores= less anaerobic resp.

3. failure of Na⁺ pump= accumulation of Na⁺

4. membrane damage

   1. leakage of cellular proteins

   2. enzymic digestion of cell

5. failure of Ca²⁺ pump= influx of Ca⁺⁺

6. decreased protein synthesis

markers of ischaemia

• lactate→ non-specific marker of ischaemia

• leakage of intracellular proteins→ cardiac muscle damage

• transaminases, Alk phosphate→ liver damage

causes of ischaemia

1. vascular occlusion

2. vasospasm

3. vascular damage e.g. vasculitis

4. extrinsic compression

5. mechanical interruption

6. hypoperfusion

ischaemia

• processes can effect arteries, veins and capillaries

• arterial

  • MI

  • stroke

• venous

  • PE

• capillary

  • DIC

  • frostbite

what is the outcome of ischaemia dependant on

• nature of blood supply

• rate of vascular occlusion

• tissue vulnerability

• duration of ischaemia

duration of ischaemia

• prolonged/sustained ischaemia= irreversible cell injury occurs (necrosis)

• limited/short duration= reversible

• rapid restoration of blood flow= reperfusion

reperfusion paradox

• reperfusion may augment tissue damage

• known as reperfusion injury

mechanisms of reperfusion

• free radical damage

• cytokine recruitment of inflammatory cells

• activation of complement pathways

• build up of Ca²⁺ ions

free radical damage

• healthy cells use antioxidants to control free radical formation

• damaged cells have less antioxidants

• influx of O₂ to damaged cells= uncontrolled generation of free radicals

reperfusion injury

• responsible for element of injury seen in ischaemia

  • up to 50% can be due to reperfusion injury

  • return of function may also be delayed for hours to days

shape of infarcts

• often wedge-shaped

  • vascular supply is proximal in tissue

  • deeper into tissue vascular branches expand

  • if obstruction occurs proximally, entire downstream area will be infarcted

coagulative necrosis

• predominant mode of cell injury is denaturation

• includes enzymes

  • unable to break down cell structure

  • basic outline is preserved

• and haemoglobin→ blood cells lose their red colour

liquefactive necrosis

• predominant mode of injury is enzyme digestion

• cells digested and broken down

• tissue is liquefied

• creates cavity or cyst within brain

white vs red infarcts

• white

  • blood is trapped and denatures (loses colour)

  • organs with single blood supply

• red

  • fresh blood still able to enter infarcted area

  • organs with dual blood supply/venous infarction/ infarction of loose tissue e.g. lungs

morphology of MI between 0 and 4 hours

• no gross or microscopic changes

morphology of MI between 4 and 12 hours

• gross features→ occasional dark mottling

• microscopic→ oedema, haemorrhage, start of coag. necrosis

morphology of MI between 12 and 24 hours

• gross→ dark mottling

• microscopic→ ongoing coag. necrosis

morphology of MI between 1 and 3 days

• gross→ yellow with haemorrhagic edge

• oedema with early neutrophil infiltration

morphology of MI between 3 and 7 days

• gross→ yellow centre becomes soft

• microscopic→ dying neutrophils with macrophage infiltration

morphology of MI between 1-2 weeks

• gross→ reg-grey colour

• microscopic→ granulation tissue formation

morphology of MI between 2-8 weeks

• gross→ fibrous scar

• microscopic→ increased collagen leading to scar formation

shock

• final common pathway for a number of conditions

• initially reversible but rapidly becomes irreversible

pathophysiology of shock

• systemic tissue hypoperfusion

• reduced mean arterial pressure

  • anything that causes:

    • dec. cardiac output

    • dec. systemic vascular resistance

types of shock

• hypovolaemic

• cardiogenic

• distributive

  • anaphylactic

  • septic

  • toxic shock syndrome

  • neurogenic

hypovolaemic shock

• Intra vascular fluid loss (blood, plasma etc)

  • dec. venous return to heart AKA ‘preload’

  • dec. stroke volume→ dec. cardiac output

causes of hypovolaemic shock

• haemorrhage

  • trauma

  • GI bleed

  • haemorrhagic pancreatitis

  • fractures

• non-haemorrhagic fluid loss

  • diarrhoea ± vomiting

  • heat stroke

  • burns

  • third spacing

cardiogenic shock

• cardiac pump failure

causes of cardiogenic shock

• myopathic

• arrythmia related

• mechanical

• extra-cardiac

myopathic cardiogenic shock

• heart muscle failure

• MI

• cardiomyopathies

arrhythmia-related cardiogenic shock

• electrical abnormalities

• atrial and ventricular arrhythmias

• impaired ventricular contraction/filling

mechanical cardiogenic shock

• defects relating to blood flow through the heart

• valvular defects

• VSD

• atrial myxomas, ruptured ventricular free wall aneurysm

extra-cardiac cardiogenic shock

• anything outside heart that impairs filling/ejection

• PE, tension pneumothorax

• tamponade, constrictive pericarditis

mixed shock

• different types of shock can co-exist in combination

• e.g. in septic shock

  • primary distributive component

  • hypovolemic component

  • cardiogenic component

presentation of shock

• signs and symptoms of underlying conditions + compensation

  • tachycardia

  • warm, flushed, bounding heartbeat

• evidence of end organ derangement/ cellular damage

• blood flow diverted to heart and brain