Cellular Injury Flashcards
How many pathways does apoptosis have?
2 Pathways. Intrinsic (mitochondrial) and extrinsic (death receptor) path way
Describe the Intrinsic pathway
The intrinsic pathway occurs when the cell is exposed to stress such as radiation, hypoxia and oxidative stress.
In this pathway, proteins BAC and BAX poke pores into the outer cell membrane of the mitochondria, which leads to 2 proteins SMACS and CYT-C to leak out into the cytoplasm.
SMACS binds to proteins that inhibit apoptosis where as CYT-C binds to ATP and another protein known as APAF-1 leading to the formation of what is known as an apoptosome. The APAF-1 portion of the apoptosome then Cleaves a “Pro-Caspase 9” enzyme into its active CASPASE 9 form, which then activates Caspase 3, which then activates other caspases in a caspase cascade which leads to Apoptosis
What does Caspase do?
Caspases cleave the cells responsible for making up the cells organelles, nuclei and cytoskeleton. The cell breaks down into pieces calls BLEBS which are broken down by macrophages.
Describe the extrinsic pathway
The extrinsic pathway comes about when the signal is from outside the cell.
TNF ALPHA binds to what is known as a death receptor located on the cell surface membrane of the cell, such as TNF receptor one, and this activates its “Death domain” causing it to change shape and bind to FAS associated protein with death domain(FADD) and TRADD forming the DEATH INDUCING SIGNALING COMPLEX (DISK). This structure then cleaves Pro caspase 8 leading to the caspase cascade.
If a cytotoxic T-cell notices the cell is expressing foreign antigens then the T cell will express fas ligand protein which binds to FAS receptor on the cell, leading to the formation of the DISC and followed by the Caspase cascade
Describe Oncosis
Oncosis occurs when toxins or ischemia damage the mitochondria, preventing it from releasing ATP. This stops the ion channels from working allowing ions and water to flow into the cells, causing it to burst. Its contents then fall onto other cells, triggering an inflammatory response which involves the release of proteases and reactive oxygen species.
Describe Coagulative necrosis
Happens due to hypoxia or ischemia. Structural proteins bend out of shape and no longer work. Lysosomal enzymes also stop working and cannot remove affected proteins hence although the cell is dead, some of its structure remains. The dead tissue becomes pale and gel like with a wedge shape. Occasionally whatever caused the obstruction in the blood vessels leading to the tissue can open up allowing blood to flow through, leaving a red mark known as a RED INFARCT. It can occur in any cell
Describe liquefactive necrosis
This happens when hydrolytic enzymes completely digest the dead cells and leave behind a creamy substance full of dead immune cells. Its most commonly seen in the brain but may occur in pancreatic cells. The brain contains Microglial cells which completely destroy any damaged cells, liquifying them
In the pancreas, a protein known as trypsin is present which can be activated during chronic inflammation causing it to damage the pancreas itself. In abscesses, neutrophils use their proteolytic enzymes to liquify the tissue, leading to formation of pus.
Describe gangrenous necrosis
Usually formed by hypoxia and is seen as a form of coagulative. It commonly affects the lower limbs as well as gastrointestinal tract. It cause the tissue to dry up and is referred to as dry gangrene in this case. However if it becomes infected, then liquefactive necrosis can occur and this is known as wet gangrene.
Describe Caseous necrosis
Usually caused by fungal of bacterial infection. The cells are disintegrated but not fully digested leading to a cottage cheese like consistency hence it is a mixture of coagulative and liquefactive.
Describe fat necrosis
This happens when there is trauma to fatty organs. The damaged cell membranes of the adipose tissue caused fatty to leak out into the extracellular space, and mixed with calcium, they lead to dystrophic calcification of the tissue, which looks like theres chalk in the tissue.
The pancreas can undergo fat necrosis in a condition known as PANCREATITIS, where by pancreatic cells spill lipases which break down fat, and this causes fatty acid to spill out of FATTY RETROPERITONEAL TISSUE which is adjacent to the pancreas.
Describe fibrinoid necrosis
Found in malignant hypertension and vasculitis.
In malignant hypertension, high blood pressure damages the wall of the small arteries , which causes fibrin to come in and it damages the walls of the blood vessels
In vasculitis there is an inflammatory reaction in the walls of the blood vessels which causes destruction.
