Growth Adaptations, Cellular Injury, Cell Death Flashcards
Compare the processes of hypertrophy vs. hyperplasia and the situations in which these processes are utilized. Why are “permanent tissues” an exception?
Hypertrophy involves increase in cell size via increased gene activation, protein/organelle synthesis. Hyperplasia involves generation of new cells from stem cells.
Both are a response to increased stress and often occur concurrently (i.e. uterus during pregnancy). However, in permanent tissues (e.g. cardiac/skeletal muscles and nerves) ONLY undergo hypertrophy and not hyperplasia.
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What are the two processes by which atrophy occurs?
Decrease in organ size by decrease in cell number or size.
Cell number –> apoptosis
Cell size –> ubiquitin-proteosome degradation of cytoskeleton and autophagy of cellular components.
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Describe the pathophysiology of how Vitamin A is involved with the development of acute promyelocytic leukemia.
APL involves a 15-17 translocation that disrupts the Vitamin A receptor/retinoic acid necessary for proper immune cell maturation. Disruption of the receptor results in cells remaining “trapped” in an immature blast state.
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Describe the pathophysiology of Vitamin A and the development of metaplastic changes, specifically keratomalacia?
Vitamin A is important for differentiation of specialized epithelial surfaces such as the thin squamous conjunctiva of the eye. Deficiency results in keratinization/thickening of the membrane–keratomalacia.
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What is methemoglobinemia and how does it lead to hypoxia? Common clinical findings and treatment?
Condition in which iron in heme is oxidized to Fe3+ (non-oxygen binding state) as opposed to the “normal” Fe2+ oxygen-binding state.
Commonly seen in setting of oxidant stress (sulfas, nitrate drugs) and newborns, who have immature mechanisms to reduce Fe3+ back to Fe2+.
Classic clinical findings are cyanosis with chocolate-colored blood.
Treat with methylene blue, which reduces Fe3+ back to Fe2+.
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What are the hallmark findings of reversible and irreversible injuries?
Reversible = cellular swelling –> loss of microvilli, membrane blebbing, swelling of RER (loss of protein synthesis)
Irreversible = membrane damage –> impaired plasma, mitochondrial, and lysosomal damage
What is the consequence of leakage of cytochrome C as a result of damage mitochondrial membrane?
Cytochrome C in cytosol will activate apoptosis.
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What is the morphologic hallmark of cell death and the three stages leading up to it?
Hallmark = loss of nucleus
1) Pyknosis - nuclear condensation
2) Karyorrhexis - nuclear fragmentation
3) Karyolysis - nuclear dissolution
How does the brain differ from other organs when undergoing necrosis?
Organs usually undergo coagulative necrosis in the setting of ischemic infarction. However, the brain undergoes liquefactive necrosis, the reason being the release of proteolytic enzymes by microglial cells.
What are the common findings of fat necrosis of the breast?
On biopsy, breast mass with giant cell reaction (fat necrosis), fat, and calcification that gives “chalky-white appearance.”
Calcification is a result of trauma or lipase-mediated release of fatty acids that bind to Ca2+.
Dystrophic calcification vs. metastatic calcification?
Dystrophic calcification (saponification being an example of it) is the process by which calcium is deposited on dead tissue under NORMAL serum calcium/phosphate concentrations. We see this with psammoma bodies.
Metastatic calcification involves calcium deposition on NORMAL tissues under abnormally HIGH serum calcium/phosphate levels.
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Intrinsic mitochondrial pathway of apoptosis?
Caspase activated by cytochrome C. Normally Bcl2 stabilizies mitochondrial membrane to prevent cytochrome C leakage.
However, under circumstances of cellular injury, DNA damage, or decreased hormonal stimulation (i.e. during endometrial sloughing of menstruation), Bcl2 becomes inactivated.
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Extrinsic receptor-ligand pathway of apoptosis?
FAS ligand binds FAS death receptor (CD95). Classic example is negative selection of thymocytes in thymus.
TNF binds TNF receptor.
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Cytotoxic CD8 T cell-mediated pathway of apoptosis?
CD8 T-cells secrete perforin that create pores in target (virally-infected) cells. Granzymes, also secreted from CD8s, enter pores to activate caspases that lead to apoptosis.
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How does oxidative phosphorylation, ionization radiation, inflammation, metals, drugs/chemicals generate free radicals?
Oxidative phosphorylation: partial reduction of oxygen with Cytochrome C mediated electron transfer.
Ionization radiation: radiation hits water in tissues to generate hydroxyl free radical (most potent).
Inflammation: neutrophilic oxygen-dependent mechanism of killing –> generation of superoxidase from oxygen with NADPH oxdiase.
Metals: Free/unbound Fe or Cu generates hydroxyl free radicals that damage tissues –> underlying mechanism of damage for hemochromatosis and Wilson’s disease.
Drugs/chemicals: generation of free radicals from metabolism via CYP450 (i.e. acetominophen, resulting in liver damage/necrosis; CCl4)
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