10 - Cell Injury and Necrosis Flashcards
Central axiom of Western medicine
All symptoms and signs of disease are caused by changes in the structure and function of cells and tissues
Four aetiologies of necrosis
1) Hypoxia/anoxia
2) Microbial infection
3) Drug/toxin damage
4) Physical trauma
Most important cause of necrosis
Hypoxia/anoxia
Most-common cause of cell injury in medicine
Ischaemia
Infarction
Hypoxia induced by reduced blood flow, often due to an occluded artery
Speed with which ischaemia can lead to cell death
20-30 minutes
Mechanism of acute myocardial infarction
Occlusion of one or both coronary artery branches.
Results in ischaemia, possible necrosis of cardiac tissue
Key event in cellular injury
Depletion of mitochondrial ATP production
Conceptual point at which cell death occurs
When mitochondrial ATP production stops
Two broad types of cellular injury
1) Reversible
2) Irreversible
Reversible stage of cellular injury
Depletion of mitochondrial ATP production leads to failure of membrane ion pumps, resulting in swelling of cell and organelles.
Stages of irreversible cell injury 1) 2) 3) 4) 5)
1) Depletion of mitochondrial ATP production leads to failure of membrane ion pumps, resulting in swelling of cell and organelles.
2) Cell membrane breakdown
3) Protein synthesis stops (needs ATP)
4) Nuclear, cytoplasmic contents undergo dissolution
5) ROS production leads to lipid, protein, nucleic acid damage
Five mechanisms of cell injury
1) ATP production depleted
2) Increase in ROS production
3) Uncontrolled Ca2+ entry into cell
4) Membrane damage
5) Protein misfolding, DNA damage
Effects of uncontrolled Ca2+ entry into cell
1)
2)
1) Increase in mitochondrial permeability. Further reduces capacity to generate ATP
2) Activation of multiple intracellular enzymes (EG: phospholipases damage cell membranes, proteases disrupt membrane proteins)
Effects of membrane damage
1)
2)
3)
1) Plasma membrane damage leads to influx of Ca2+, loss of organelles.
2) Lysosomal membrane damage leads to digestion of intracellular components
3) Organelle membrane damage reduces organelle capacity to work