Basic Pathology Q from BRS Path readings

[BlondeCookie]

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Hypoxic Cell Injury leads to cell death via necrosis. On p3 of the BRS Path 3rd edition book, the key point states that in regards to cell death "the point of no return is marked by irreversible damage to cell membranes, leading to massive calcium influx, extensive calcification of the mitochondria, and cell death"

I don't quite understand the mechanism by which there is calcium influx into the cell. Can someone explain that simply? Thanks. 😕

 

[chintu]

I don't think its known very well. Here are my thoughts: Lack of ATP would cause failure of Na/K pump, which results in massive swelling of cell and damage to cell membrane. And since concentration of ca++ outside is higher than inside it would be freely permeable due to lack of intact cell membrane. Also, lack of ATP would cause failure of ca++ pump on membrane which might explain it somehow. Again this is my hypothesis and I couldn't find a source to explain it.

 

[keeping-it-real]

did you say you wanted to hear what goljan's RR has to say about this? alrighty then.

"Impaired Ca-ATPase pump results in increased cytosolic Calcium which leads to:
1) Enzyme Activation
-Activates phospholipase
-Activates proteases
-Activates endonucleases
2) Re-entry of Calcium into mitochondria increases mitochondrial membrane permeability, with release of cytochrome c and subsequent apoptosis."

 

[LAZYGUY]

Ca2+ membrane permeability can also be created via lipid peroxidation mediated by free-radical damage & carbon tetrachloride (damage is actually do to CCl3, a free radical, due to transformation by p450), whose mechanism is primarily membrane & organelle damage as opposed to hypoxia which shuts down the pumps & causes dissipation of ionic gradients.

I believe CCl4 is a chemical that they use in dry cleaning