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List 5 biochemical themes in cell injury
ATP depletion, generation of ROS, loss of Ca homeostasis, altered plasma membrane permeability, mitochondrial damage
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Hypoxia causes what type of morphogenic change? Why?
Hypoxia impairs oxidative phosph. leading to decreased ATP. Lack of ATP causes a disruption in homeostasis and a net gain of solute causing the cell to swell.
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Isoosmotic gain of water has what effect on organelles?
mitochondrial swelling, dilation of the ER causing decreased protein synthesis and increased lipid deposition
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How does hypoxia effect cellular metabolism?
decreased ox. phosph. and increased glycolysis. increased glycolysis decreases intracellular pH leading to chromatin clumping
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what effect does hypoglycemia produce on cells?
lack of ATP production bc no substrate to use for energy (loss of homeostasis)
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list 3 types of ROS
Superoxide (O2), Hydrogen peroxide, hydroxyl radicals
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how is superoxide inactivated?
superoxide is inactivated by superoxide dismutase to form hydrogen peroxide
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how is hydrogen peroxide metabolized?
detoxified by glutathione peroxidase and catalase
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how are hydroxl radicals generated?
by hydrolysis of water by ionizing radiation or by transitional metals Fe or Cu
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how do ROS damage cells?
lipid peroxidation, protein cross-linking, thymidine and guanine single strand DNA breaks
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what intracellular antioxidant systems exist?
Superoxide dismutase (O2), catalase (H2O2), glutathione peroxidase (H2O2)
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what extracellular antioxidant systems exist?
vitamins A, C, E
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what type of cell injury occurs by increased cytoplasmic Ca?
high Ca levels will activate various degradative enzymes
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list 4 degradative enzymes activated by high Ca levels
phospholipases, proteases, endonucleases, ATPase
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list 3 outcomes of cellular injury
reversible cell injury, adaptation, cell death
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what is the single biochemical event influencing cell death
there is no single biochemical event that equates with cell death
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what morphologic changes occur during necrosis?
cell swelling, protein denaturation, organelle breakdown, inflammation, nuclei changes (karyolysis, pyknosis, karyorrhexis, or total loss)
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Describe Coagulative Necrosis
most common form of necrosis, cytoplasmic proteins are coagulated, nucleus is lost
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Describe Liquefactive necrosis
has lots of pus (purulence) and the tissue is totally digested by release of lysosomal enzymes during acute inflammatory response
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describe caseous necrosis
associated with M. tuberculosis infection. loss of tissue architecture and amorphous pink granular material
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describe fat necrosis
dead adipocytes give a "soap bubble" histological appearance, common in breast trauma or pancreatitis
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describe 4 morphologic features of apoptosis
cell shrinkage, chromatin condensation/fragmentation, apoptotic bodies formation, phagocytosis without inflammatory response
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what are 5 ways a cell can be signaled to start apoptosis
intrinsic, Fas Ligand-receptor binding, removal of trophic signals, ROS/radiation/toxins, cytotoxic T cells
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what is the function of the Bcl-2 gene family?
regulation of permeability of the mitochondrial membrane
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how do the Bcl-2 and Bcl-x genes affect apoptosis?
inhibit
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how do the bax and bak genes affect apoptosis?
stimulate
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what effect does cytochrome-c have?
it is released from outer mt membrane and disrupts inhibitory function of Bcl-2, in other words it stimulates apoptosis
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what effect do caspases have on the cell? what substrates does it have?
apoptosis, substrates include cytoskeletal and nuclear matrix proteins, DNase and transcription proteins
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what are the differences between apoptosis and necrosis in terms of stimuli?
apoptosis: physiologic and pathologic; necrosis: hypoxia and toxins
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what are the differences between apoptosis and necrosis in terms of cellular morphology
apoptosis: single cells, shrinkage; necrosis: multiple cells, swelling
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what are the differences between apoptosis and necrosis in terms of ATP
apoptosis: ATP dependent; necrosis: ATP independent
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list 4 cellular adaptations
cell size (atrophy vs hypertrophy), cell number (hyperplasia), cell differentiation (metaplasia), intracellular accumulations
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what are two etiologies of hypertrophy?
response to trophic signals, response to increased functional demand
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list 2 examples of abnormal hormone stimulation
anabolic steroids: hypertrophy; overproduction of TSH due to iodine deficiency and induces thyroid follicle hypertrophy (goiter)
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define barrett's esophagitis and explain what type of cellular adaptation it displays
normal stratified squamous epithelium of esophagus replaced due to prolonged exposure to gastric reflux---metaplasia
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list 4 mechanisms of intracellular accumulations
abnormal metabolism, lack of an enzyme, abnormal protein folding/transport, ingestion of indigestibile material
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define steatosis
fatty liver; abnormal accumulation of triglycerides within parenchymal cells of the liver, heart, kidney and skeletal muscle
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list 6 etiologies of steatosis
obesity, diabetes, alcohol, anorexia, toxins, protein malnutrition
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xanthoma is a result from what?
cholesterol accumulation
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atheromas of atherosclerosis in vessels are caused by what?
cholesterol accumulation in macrophages
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list 3 results from abnormal protein accumulation
a1-anti-trypsin deficiency (impaired folding), mallory bodies (impaired secretion), neurofibrillary tangles in Alzheimer's (accumulation of microtubule-associated proteins)
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what is Lipofuscin
endogenous brown-yellow pigment, lipoprotein complex due to ROS peroxidation of membranes
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what is hemosiderin
yellow-brown pigment due to aggregates of ferritin micelles from excess iron. can lead to hemosiderosis
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define hemochromatosis
genetic disease associated with cell death due to uncompensated hemosiderin accumulation
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what is bilirubin
end product of heme metabolism that accumulates in hepatocytes and bile ducts due to hemolysis, obstructed bile flow and/or hepatocellular disease
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