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What are the causes of cell injury?
- Oxygen deficiency - hypoxia
- Physical agents e.g. excessive cold / heat, trauma
- Infectious agents e.g. viruses, parasites, bacteria, prions
- Nutritional deficiencies and imbalances
- Genetic derangements
- Workload imbalance
- Chemicals, drugs, toxins
- Immunologic dysfunction
- Ageing
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What are the different types of reversible cell injury?
Hydropic change, fatty change, glycogen overload, chromatolysis
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What is hydopic change / vacuolar degeneration?
When cells become overloaded with water due to failure of energy-dependent ion pumps in the plasma membrane
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What affect does hydropic change have on cell organelles?
The increase in water squishes the organelles and they disintegrate
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With hydropic degeneration what can be seen on a) gross examination b) microscopic examination?
- a) organs enlarged, pale, turgid
- b) cytoplasm pale, finely vacuolated (cloudy swelling)
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What is fatty change / fatty degeneration?
Lipid vacuoles in cells
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What cells are more likely to undergo fatty change?
Cells involved in fat metabolism e.g. hepatocytes, myocardial cells, renal tubule cells
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What are the causes of hepatic lipidosis (fatty change in the liver)?
- Increased mobilisation of fat stores e.g. during late pregnancy (pregnancy toxaemia in sheep) or in early lactation (ketosis in dairy cows)
- Nutritional disorders eg obesity (increased transport of dietary lipids and mobilisation from adipose tissue)
- Endocrine diseases eg diabetes mellitus (increased mobilisation of triglycerides)
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With fatty change what can be seen on a) gross examination b) microscopic examination?
- a) organs enlarged, pale, greasy
- b) circular cytoplasmic clear vacuoles
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What causes glycogen overload?
- Abnormalities in glucose or glycogen metabolism
- Poorly controlled diabetes mellitus
- Long term glucocorticoids
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What can be seen on microscopic examination of samples with neurone chromatolysis?
The Nissl substance around the edge of the neurone is gone (left with an area of pallor)
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What are the morphological changes associated with reversible cell injury?
- Generalised cell and organelle swelling
- Blebbing or the plasma membrane
- Detachment of ribosomes from ER
- Clumping of nuclear chromatin
- (These changes are associates with decreased generation of ATP, loss of cell membrane integrity, defects in protein synthesis, cytoskeletal dame and DNA damage)
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What are the morphological changes associated with irreversible cell injury?
- Severe ER swelling
- Sever mitochondrial swelling
- Lysosome rupture
- Membrane fragmentation
- Nuclear membrane rupture and chromatin fragmentation
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What morphological changes can be seen in necrosis?
- The cytoplasm is homogeneous and eosinophilic (bright pink)
- The nucleus breaks down
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What are the different types of nuclear changes in necrosis?
- Pyknosis - nucleus is shrunken, dark, homogenous and round
- Karyorrhexis - nuclear envelope ruptured, dark nuclear remnants released into cytoplasm
- Karyolysis - nucleus very pale, dissolution of chromatin by RNAses and DNAses
- Absence - completely dissolved or lysed
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What is hypoxia?
Partial reduction in oxygen concentration supplied to cells or tissues
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What is anoxia?
Complete reduction in oxygen concentration supplied to cells or tissues
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What are the possible causes of hypoxia?
- Heart failure, respiratory failure
- Loss of blood supply (ischaemia)
- Reduced oxygen transport in blood - anaemia, CO toxicity
- Blockage of cell respiratory enzymes - cyanide toxicosis
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What determines whether cell damage is reversible / irreversible?
An increase in cytosolic calcium concentration
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What is oxidative stress?
Cell injury induced by free radicals / reactive oxygen species
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How are free radicals / ROS generated?
- Reduction-oxidation reactions during normal metabolic processes
- Absorption of radiant energy e.g. UV light, x-rays
- Rapid bursts of ROS by activated leucocytes during inflammation
- Enzymatic metabolism of exogenous chemicals or drugs that generate free radicals that are not ROS but have similar effects
- Nitric oxide is a chemical mediator generated by endothelial cells, macrophages, neurones and other cell types. It can act as a free radical and can also be converted to highly retain peroxynitrite anion
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