PATH: Irreversible Cell Injury and Cellular Death Flashcards Preview

1 Foundations of Disease and Therapy > PATH: Irreversible Cell Injury and Cellular Death > Flashcards

Flashcards in PATH: Irreversible Cell Injury and Cellular Death Deck (36):

What cellular damage must occur for irreversible damage to be inevitable?

Unrecoverable mitochondrial damage occurs with loss of ATP synthetic capacity and cell membrane damage of such severity that regulation of internal milieu is impossible


Describe the feed-forward cycle of irreversible cell injury

Membrane dysfunction leads to influx of Ca++ which activates phospholipases, which further contribute to membranal damage and further influx of Ca++


The detection of what hepatocyte enzymes are non-specific indicators of liver inflammation?



What pancreas proteins can be only detected in the serum in cases of pancreatitis?

Lipase and amylase


What are the morphological changes of irreversible mitochondrial injury?

Marked swelling, dense body formation (calcium phosphate)


What is karyolysis?

Marker of irreversible nuclear damage where the nucleus "fades away"


What is pyknosis?

Marker of irreversible nuclear damage where the nucleus is hard and dark and becomes "clumped" and actually shrinks


What is karyorrhexis?

Marker of irreversible nuclear damage where there is random breakup of nucleus into many fragments


How long can it take for nuclear morphological signs of damage to be clinically observed?

6-12 hours


What is reperfusion injury? What is thought to be the underlying mechanism of this damage?

Damage that occurs upon resumption of blood supply and reoxygenation of previously ischemic tissue; thought to be due to generation of ROS, including oxygen-derived free radicals


What are three common examples of oxygen-derived free radicals?

Superoxide anion, hydrogen peroxide, and hydroxyl radical


What are physiologic generators of ROS?

Oxidative phosphorylation, Neutrophilic respiratory burst, xanthine oxidase


What types of damage can be induced by ROS?

Lipid peroxidation (form lipid peroxides); Protein-protein cross-linking; single-stranded DNA breaks


What are the antioxidant mechanisms that protect from ROS?

Superoxide Dismutase (mitochondria) , Glutathione peroxidase and reductase (mitochondria), and catalase (peroxisomes)


How does carbon tetrachloride cause cellular damage?

CCl4 is metabolized by cyP450 to form CCL3-, which is esp. damaging to the rER, inhibiting protein synthesis and export (esp. apoproteins), resulting in lipid accumulation within injured hepatocytes


What vitamins serve as free radical scavengers?

Vit. E and A


How does the cell regulate molecules that propagate free radical production?

Fe is bound by transferrin and/or ferritin; Cu is bound by ceruloplasmin


After cell death via necrosis what two concurrent processes may be present in the cell?

Protein denaturation and enzymatic digestion of cell constituents


What is the difference is autolysis and heterolysis?

Autolysis is enzymatic digestion of cellular contents by the cell's own lysosome; Heterolysis is by inflammatory cells


What cytoplasmic change can be observed following cell necrosis? Why does this happen?

Increased eosinophilia dueto loss of basophlic ribosomes and increased uptake of eosin dye by denatured proteins


What is coagulation necrosis?

Cell necrosis in which denaturation (coagulation) of cellular proteins predominates, typically by autolysis


What is an infarct? What is the difference between a pale/anemic infarct and hemorrhagic /red infarct?

An infarct is a circumscribed area of an organ undergoing coagulation necrosis due to ischemia; Pale infarcts are found in end organs (spleen, heart, kidney) which have no dual blood supply; Red infarcts happen in organs with dual blood supply (lung) or with large amounts of CT (gut)


What kind of necrosis is gangrene? What is the cause?

A special type of coagulation necrosis caused by gradual ischemia of the distal extremities


In which type of necrosis occurs in tissues in which the initial digestion of cells and tissue predominates, with resulting loss of tissue structure? What is the mechanism of this digestion?

Liquefactive necrosis; heterolysis


In which organ is liquefactive necrosis seen following infarction rather than coagulation necrosis?



What are the causes of caseous necrosis and what are the common characteristics they share?

Mycobacterial (TB) and some fungal infections; difficult for the body to eliminate, resulting in chronic inflammation


What is the appearance of caseous necrotic tissue, grossly?

Necrotic tissue is walled off and transformed into focus of granular "cheesy" material, surrounded by granulomatous inflammation and fibrosis


In which organ is fat necrosis likely to occur? What is the mechanism?

Pancreatic cells undergo necrosis and spill their hydrolytic enzymes, esp. lipases, which act on adjacent adipocytes to release fatty acids, which combine with calcium to undergo saponification


Where does fibrinoid necrosis occur? When does it occur?

Arterial walls; Occurs in extreme hypertension or immune complex deposition in arterial walls


True or False: Both Necrosis and Apoptosis are energy-requiring?

False- Apoptosis is energy-requiring but not necrosis


What are the morphologic changes associated with apoptosis?

Cell shrinks and detaches from neighbors, blebbing, chromatin condensation, fragmentation into apoptotic bodies, little to no inflammatory response


What class of proteins are caspases and what are their cellular functions? Which are initiators and which are effectors?

Cysteine proteases which cleave cytoskeletal proteins and cleave nuclear scaffolding; initiators are -2,-8, and -9; executioners are capases-3, -6, - and -7


What is the function of Bcl-2 and where can it be found?

Bcl-2 is an anti-apoptotic protein normally found in the outer mitochondrial membrane, which stabilizes the membrane, prevents pore formation, prevents release of cytochrome c, binds to and sequesters Apaf-1


What are the common pro-apoptotic members of the Bcl-2 family?

Bax and Bad


What proteins form the apoptosome?

Apaf-1, cytochrome-c, and proCaspase 9


What are the best known triggers of the extrinsic apoptotic pathway? What is the mechanism of activation?

Fas and TNFR1 receptors binding to their ligands (Fas-L or TNF-alpha); Interaction with the appropriate ligand results in trimerization, and trimerization of Fas interact with Fas Associated Death Domain which activates proCaspase 8 and triggers the cascade