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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
What are the different types of reversible cell injury?
Hydropic change, fatty change, glycogen overload, chromatolysis
What is hydopic change / vacuolar degeneration?
When cells become overloaded with water due to failure of energy-dependent ion pumps in the plasma membrane
What affect does hydropic change have on cell organelles?
The increase in water squishes the organelles and they disintegrate
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)
What is fatty change / fatty degeneration?
Lipid vacuoles in cells
What cells are more likely to undergo fatty change?
Cells involved in fat metabolism e.g. hepatocytes, myocardial cells, renal tubule cells
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)
With fatty change what can be seen on a) gross examination b) microscopic examination?
- a) organs enlarged, pale, greasy
- b) circular cytoplasmic clear vacuoles
What causes glycogen overload?
- Abnormalities in glucose or glycogen metabolism
- Poorly controlled diabetes mellitus
- Long term glucocorticoids
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)
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)
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
What morphological changes can be seen in necrosis?
- The cytoplasm is homogeneous and eosinophilic (bright pink)
- The nucleus breaks down
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
What is hypoxia?
Partial reduction in oxygen concentration supplied to cells or tissues
What is anoxia?
Complete reduction in oxygen concentration supplied to cells or tissues
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
What determines whether cell damage is reversible / irreversible?
An increase in cytosolic calcium concentration
What is oxidative stress?
Cell injury induced by free radicals / reactive oxygen species
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