ISCHAEMIA AND INFARCTION Flashcards
ISCHAEMIA
- Decreased blood supply to an organ
- Resulting in hypoxic damage
- To susceptible cell
FUNCTIONAL CHANGES OF ISCHAEMIA
- Lack of oxygen -> oxidative metabolism stops -> reduction in ATP
- Anaerobic glycolysis takes over
- Stores of glucose and glycogen depleted (cannot be replenished as no blood supply)
- Anaerobic glycolysis slows and stops – inhibited by low levels of ATP
- Membrane pump failure
- Influx of sodium and water into cell
MORPHOLOGIC CHANGES OF ISCHAEMIA
- Mitochondrial swelling
- Cell swelling
- Necrosis
- Inflammation
Ischaemia - reperfusion Injury
Reperfusion following ischaemia
• Promote recovery of cells if reversibly injured
Or
• Exacerbate cell injury (myocardial and cerebral infarction)
• Cells that would have been viable are now injured
• Re-oxygenation – increase generation of reactive oxygen & nitrogen species
• Inflammation, cytokine production & recruitment of inflammatory cells further tissue injury
• Activation of complement system IgM deposits in ischaemic tissues and complement
proteins bind to antibodies, become activated & cause tissue injury
PATTERNS OF NECROSIS
- Coagulative necrosis
- Liquefactive necrosis
- Gangrenous necrosis:
- Dry gangrene
- Wet gangrene
- Caseous necrosis
- Fat necrosis
- Fibrinoid necrosis
INFARCTION
Definition:
• Area of ischaemic necrosis due to occlusion of arterial supply or venous drainage
Common sites: • Myocardial • Pulmonary • Bowel • Extremities (NB in DM)
Pathogenesis OF INFARCTION
- Arterial occlusion
- Arterial narrowing
- Venous occlusion
ARTERIAL OCCLUSION
MAIN CAUSES:
Embolism & thrombosis
Effects depend on anatomy of an organ’s arterial supply
Other causes:
Vasospasm
Hge into atheromatous plaque
ARTERIAL NARROWING
g. Atheroma in wall of coronary
artery, extrinsic compression by a tumour
Can cause frank infarction or only ischaemic effects
Allows time for collateral blood supply to develop if occlusion builds up slowly
VENOUS OCCLUSION
If bypass channels available:
Congestion -> opening of bypass
channels -> arterial inflow restored
If single outflow vein:
Blood able to pump in via arteries but cannot exit via veins
Pressure increases -> can eventually exceed arterial pressure -
> necrosis
Eg. Torsion or thrombosis(testicular torsion)
classification of infarction
- Colour red/white
* Presence/absence of infection septic/bland
RED INFARCTS
- Venous occlusion
- Loose tissues/those with rich anastomotic supply blood collects in infarcted zone
- In tissues with dual circulation blood flow into necrotic zone
- Tissues previously congested by sluggish venous outflow eg. torsion
- Flow re-established to site of previous arterial occlusion and necrosis
RED INFARCTS
- Venous occlusion
- Loose tissues/those with rich anastomotic supply blood collects in infarcted zone
- In tissues with dual circulation blood flow into necrotic zone
- Tissues previously congested by sluggish venous outflow eg. torsion
- Flow re-established to site of previous arterial occlusion and necrosis
EXAMPLE
Pulmonary infarct is haemorrhagic because of the dual blood supply:
some blood still flows from the non-occluded bronchial arteries, but
does not prevent the infarction
WHITE INFARCT
• Arterial occlusion in solid organs with endarterial circulation i.e.
heart,kidneys,spleen etc
• Initially a small area of haemorrhage -> once rbc are lysed, area becomes pale
EXAMPLE:
Loss of blood supply coagulative necrosis
Myocardial infarction from occlusion of a major coronary artery
GROSS MORPHOLOGY
• Infarcts tend to be wedge-shaped with occluded vessel at the apex and the
periphery of the organ forming the base
EXAMPLE:
Spleen:
These infarcts are typical of ischaemic infarcts: they are based on the capsule, pale, and wedge-shaped. The remaining splenicparenchyma appears dark red.
When the base is the serosal surface overlying fibrinous exudate
• Acute infarcts: poorly defined and slightly haemorrhagic over time
margins become better defined by a narrow rim of congestion (due to
inflam)
blood supply morphology
Morphology
• Without dual blood supply progressively paler and more sharply defined
• Dual blood supply (e.g. lung) haemorrhagic infarcts
• RBCs phagocytosed by macrophages: haem iron haemosiderin firm brown residuum
Microscopic feautures
Microscopic features
• Dominant microscopic characteristic of infarction = ischaemic
coagulative necrosis
• 4-12 hrs for tissue to show frank necrosis
• Acute inflam at margins within few hours, well defined in1-2d
• Inflammation followed by reparative process begins at margins
• Repair is by parenchymal regeneration or scar formation
• Brain: infarction results in liquefactive necrosis
• Septic infarctions:
• Infected cardiac valve vegetations embolize Abscess
• Microbes seed necrotic tissue
acute infarct
Interventricular septum of the heart has been sectioned to reveal an extensive
acute myocardial infarction
Dead muscle is tan-yellow with a surrounding hyperemic border
EXAMPLE: Cerebral infarction typically results in liquefactive necrosis, as
shown here with beginning cystic resolution of the infarct
SEPTIC INFARCT
Infected infarct: contains 2 abscesses appearing as cavitary lesions
FACTORS THAT INFLUENCE DEVELOPMENT OF INFARCT
Vulnerability to hypoxia
Nature of vascular supply
Rate of occlusion development
O2 content of blood
Nature of vascular supply
• Most NB determinant • Dual blood supply is protective against infarction • Dual blood supply: lung, liver, hand and forearm • End-arterial: kidney, spleen
Vulnerability to hypoxia
• Neurons irreversible damage 3-
4mins
• Myocardial cells 20-30mins
• Fibroblasts hours
Rate of occlusion development
• Slow which can lead to developing alternate perfusion pathways (collaterals
O2 content of blood(factors that influence the development of infarct)
- Anaemia
- Chronic lung disease
- Shock
