Pathology: Cell Injury Flashcards
What can cause cell injury?
Hypoxia Mechanical trauma Electricity/radiation Chemicals/drugs Pathogens Immunolgic reactions Genetic and nutritional deficiencies
What causes hypoxia to cells?
Reduced blood. flow (Ischaemia)
Inadequate oxygenation of the blood (CR failure)
Decreased oxygen carrying capacity of the blood (Anaemia, carbon monoxide poisoning, hypovolaemia)
Is degeneration reversible?
Yes
What happens to a cell when the ATP is depleted (degeneration)?
The cell swells due to failure of the energy dependent ion pumps in the plasma membrane leading to a a loss of K+ and gain of Ca, Na and water
Steatosis (fatty change) where there is abnormal accumulations of neutral lipids (triglycerides) within the parenchymal cells - often seen in the liver
What causes steatosis (fatty change)?
Excessive production/mobilisation of lipids: Diabetes mellitus (depleted carb stores lead to a breakdown of fats and protein - increase in FFA’s)
Defective metabolism and export of lipids
Is necrosis reversible?
No
When biochemical changes occur in the cell is it reversible?
No
What happens when a cell necroses?
Denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell (enzymes one from the lysosomes of the dying cells and also from leukocytes)
When a cell necroses and leaks cellular contents what can happen?
Inflammation
How can cell necrosis be detected in the blood?
Leaked enzymes and proteins can be detected in the blood (Creatinine kinase, alkaline phosphatase…)
What are the biochemical/ultrastuctural changes that occur during necrosis?
Depletion of ATP
Mitochondrial damage
Influx of calcium and loss of calcium homeostasis
Accumulation of oxygen derived free radicals
Defects in membrane permeability
Damage to DNA and proteins
What causes depletion of ATP in necrosis?
Reduced supply of oxygen, mitochondrial damage, toxins
What causes mitochondrial damage in necrosis?
Hypoxia and toxins
It causes a depletion of ATP and a release of pro-apoptotic proteins (cytochrome C)
What causes the influx of calcium in necrosis?
Ischaemia and toxins
It causes an increase in mitochondrial permeability (causing mitochondrial damage) and release of cellular enzymes (Phospholipases, proteases, endonuclease ATPases)
Where is most of the calcium in the cell?
Low concentrations in the cytoplasm and most intracellular calcium is sequestered in the mitochondria and the endoplasmic reticulum
What causes accumulation of oxygen-derived free radicals?
Inflammation, radiation, chemicals
What are reactive oxygen species?
ROS are produced normally in cells doing mitochondrial respiration and energy generation but they are degraded and removed by the cellular defences (antioxidant and enzymes)
What are free radicals?
Chemicals that have single unpaired electron in an outer orbit, energy created by this unstable configuration is released through reactions with adjacent molecules
What causes the defects in membrane permeability during necrosis?
Ischaemia, toxins, viruses, physical/chemical agents
It causes mitochondrial damage, ATP depletion, apoptosis
What are the cytoplasmic and nuclear changes that occur in necrosis?
Cytoplasmic changes: Increases eosinophilia in HE and cytoplasmic vacuolation
Nuclear changes: Karyolysis/ Pyknosis /Karyorrhexis
What is karyolysis?
Nuclear fading
What is pyknosis?
Nuclear shrinkage
What is karyorrhexis?
Nuclear fragmentation
What is coagulative necrosis?
The architecture of the dead tissues is preserved as injury denatures the structural proteins but also enzymes so blocks proteolysis
Has a firm texture eg. Infarct
