Cellular pathology Flashcards
22114 – Regarding normal cell division
1: activation of a growth factor receptor may stimulate a quiescent cell to divide
2: tumour necrosis factor may act as an inhibitor of cell division
3: growth factor receptors are almost always located in the cell nucleus
4: cells in the G\bo phase of the cell cycle are not able to undergo further cell division
TTFF
Robbins 5th ed. PAGES: 36-40
15631 – Apoptosis
1: is the major mechanism of cell death in viral hepatitis
2: stimulates an acute inflammatory reaction
3: is seen in pancreatic acinar cells due to duct obstruction
4: is mediated through calcium-dependent endonuclease
TFTT
15621 – Apoptosis
1: causes cell death by enzyme-induced membrane injury
2: occurs in prostatic epithelial cells following castration
3: is the common mechanism of cancer cell death following chemotherapy
4: results in a predominantly eosinophil leukocyte inflammatory reaction
FTTF
Apoptotic cell death is mediated through calcium-sensitive endonuclease; the mechanism of activation of this reaction differs according to the inducing stimulus. Withdrawal of the appropriate hormone induces apoptosis in the dependent tissue. Chemotherapy (appropriate to the cancer, of course) and radiotherapy induce apoptosis in the susceptible tumour. There is usually no inflammation induced by apoptotic cell death, unless extensive (eg in massive chemical-induced
tumour lysis).
15606 – Apoptosis
1: has important regulatory influence on normal cell population
2: is the mechanism causing menopausal ovarian follicle atresia
3: commonly causes polymorphonuclear leukocyte reaction
4: induces cell death through lysosomal enzyme activation
TTFF
Responses 1 and 2 deal with some normal ‘uses’ of apoptotic cell death in normal body economy - physiological functions, if you like. Apoptosis induces cell death through causing activation of endogenous endonuclease which causes denaturation of DNA as the lethal action. Endonucleases are activated by a number of different mechanisms, depending on the stimulus causing the apoptosis. The only reaction which is stimulated by apoptotic cell death is phagocytosis by adjacent cells (any cells - epithelial, mesenchymal, macrophages etc) activated by the expression of ‘phagocytosis ligands’ (perhaps opsonins) on the cell membrane component of the cell fragments or ‘apoptotic bodies’.
15616 – Apoptosis
1: mediates development of endothelial injury in Gram-negative sepsis
2: results from plasma membrane ‘ionic pump’ failure
3: mediates the vascular injury causing ‘fibrinoid’ necrosis
4: is a major mechanism of cell injury in graft-versus-host reactions
FFFT
Graft-versus-host reactions are Tc-lymphocyte-mediated and, as with transplant allograft cellular rejection and some viral infections, cell death is mediated by activation of host endonuclease in target cells. Ionic pump failure is commonly induced by hypoxia and leads to ionic imbalance and cell swelling. Fibrinoid necrosis is usually an expression of the Arthus reaction. Endothelial injury in Gram-negative sepsis is possibly IL-1 / TNF-mediated and has (as far as is known) no connection to apoptosis!
15626 – Apoptosis
1: is a determinant of growth rate of many cancers
2: is a major cause of shock in Gram-negative bacteraemia
3: will result from carbon tetrachloride (CCI4) cell poisoning
4: is a form of programmed cell destruction in normal body processes
TFFT
Certain genes involved in growth and genesis of cancer (oncogenes & suppressor genes) have a regulatory role in apoptosis: eg bcl-2 gene (inhibits hormone- and cytokine-induced apoptosis), or mutation of p53 (normally stimulates apoptosis in radiation-damaged cells). Activation of bcl-2 or loss of activity of p53 product allows cell survival following radiation which would ordinarily induce apoptotic death in that cell. Apoptosis plays a major role in regulation of normal cell populations. Mediation of shock in Gram-negative bacteraemia is complicated, multi-factorial and involves many mediators involved in acute inflammation; apoptosis appears to have no role. CCl4 cell poisoning is membrane-damaging and when severe enough to cause cell death, induces necrosis.
15763 – Apoptosis is cell death which
1: is caused by activation of endogenous endonuclease
2: results in ‘haematoxylin body’ formation in systemic lupus erythematosus (SLE)
3: may result from virus-induced Tc cytotoxic effect
4: induces a brisk acute inflammatory reaction
TFTF
Apoptosis is ‘death by endonuclease’ - activated in quite a variety of ways, including such things as activation of p53 gene and also the attentions of Tc cells interacting with virion-MHC I complex on the
surface of virus-infected cells. The haematoxylin body is produced from coating of a naked (usually lymphocyte) nucleus by anti-DNA antibody and then its phagocytosis. Inflammation does not follow, apoptosis - it is ‘death without fuss’.
21873 – Apoptosis is cell death that
1: is commonly seen during hormone-dependent involution
2: results in haematoxylin body production in systemic lupus (SLE)
3: may result from virus-induced cytotoxic T lymphocyte effect
4: induces a brisk acute inflammatory response
TFTF
Robbins 5th ed. Chapter: 1 Pages: 17-21
15611 – Apoptosis is the major mechanism causing
1: hepatocyte death in acute viral hepatitis
2: cell death due to chemical poisons
3: renal tubule cell death in cell-mediated transplant rejection
4: cancer cell death induced by radiotherapy
TFTT
Cell death in many viral infections is due to apoptosis. In the liver, this results in the Councilman body - surrounded by lymphocytes which have induced the cell death. Lymphocyte (Tc)-induced cell death of similar pathogenesis is also the mechanism of cell death in ‘acute’ or cell-mediated transplant rejection. Apoptosis is induced by radiation cell injury in normal and cancer cells (also by chemotherapy) providing these injuries are not too vigorous. Although cytotoxic (anticancer) drugs in therapeutic dosage induce apoptosis, severe chemical injury causes cell necrosis with all the consequent trappings of acute inflammation.
15641 – Apoptosis is the mechanism of cell attrition seen in
1: menopausal ovarian follicle atrophy
2: salivary gland atrophy caused by duct obstruction
3: prostatic epithelial cells following castration
4: lactating breast epithelium during weaning
TTTT
Responses 1, 3 and 4 illustrate apoptosis induced by hormone withdrawal. Pressure atrophy of epithelial cells (2) is also apoptosis-induced. Inflammation will not ensue - this is ‘death without
drama’.
15636 – Important mechanisms which mediate cell death by apoptosis include
1: lysosomal enzyme release and activation
2: denaturation of cell and cytoplasmic organelles
3: Ca2+-dependent, endonuclease-induced DNA denaturation
4: endogenous activation of oxidising free radicals
FFTF
Apoptosis and necrosis have major differences, both in pathogenesis and in consequences.
Apoptosis involves a primary attack on the cell DNA, usually by enzyme induction leading to increase in intracellular Ca++ and endonuclease activation. Responses 1 and 2 obviously refer to primary membrane injury (necrosis) as does endogenous oxygen free radical induction (cell oxidase systems).
15706 – Necrosis
1: causes rapid development of intracellular alkalosis
2: is often haemorrhagic if blood flow is rapidly restored following lethal ischaemia (‘reperfusion’)
3: never occurs as a result of T-lymphocyte-mediated reactions
4: in brain tissue does not elicit an acute inflammatory response
FTFF
The early response to lethal cell damage is acceleration of glycolysis (because of ATP decrease) with cytoplasmic acidosis. Alkalosis may or may not occur as a late development when cell derangement is far advanced. Haemorrhagic infarction is almost the rule with rapid reperfusion (spontaneous eg in the brain following embolic lysis, or induced by tPA or streptolysin-induced coronary thrombolysis). Many Tc responses result in apoptosis, but brisk TH2 reactions to antigen frequently result in necrosis (eg Mantoux reaction) and TH1 ‘help’ results in maximised immunoglobulin production, facilitating complement activation, chemotaxis, etc. Necrosis always elicits an acute inflammatory reaction, large or small, in all tissues.
15696 – Necrosis
1: always induces an acute inflammatory reaction
2: on occasion serves an essentially physiological function
3: usually results in rapid depletion of cytoplasmic glycogen
4: has its usual common pathway of causation through membrane damage
TFTT
Response 1 is true; there is always acute inflammation - mild or marked - after necrosis of one or many cells. Necrosis is always pathological. Interference with cell oxygen supply usually results in rapid glycolysis (with attendant lactate accumulation and acidosis). Whatever cause, evidence strongly favours the current hypothesis that the final pathway leading to cell demise in necrosis-inducing damage is cell membrane injury - specifically either plasma membrane or mitochondrial membrane. Breach of lysosomal membranes and acidic activation of enzymes then leads on to what is essentially autolysis.
15691 – Necrosis
1: commonly induces a moderate lymphocytic infiltration
2: is not caused by any of the ‘reactive’ body processes (immune, inflammatory, etc)
3: if solid and structureless (‘caseous’), is diagnostic of tuberculosis
4: may form a nidus for deposition of calcium salts
FFFT
Necrosis always induces an acute inflammatory reaction as the first response; the response is never lymphocytic (although the cause may be, if Tc-lymphocyte mediated). Immune and acute inflammatory reactions can (and commonly do) result in tissue necrosis. Caseous necrosis is a species of ‘carcass degeneration’ found due to many infective diseases (and some non-infective: eg Wegener’s granulomatosis). Calcium deposition in necrotic tissues is common (eg comedo carcinoma, tuberculous foci etc).
15701 – Necrosis
1: can be confidently diagnosed if one observes nuclear pyknosis
2: usually rapidly causes cytoplasmic acidosis
3: is pathogenetically different in neurones and myocardial cells
4: is most commonly induced by nuclear DNA damage
TTFF
Nuclear signs (pyknosis [condensation shrinkage], karyolysis [DNA dissolution] and karyorrhexis [nuclear fragmentation]) are the ‘hard’ signs of cell death. Acidosis is induced by failure of aerobic metabolism, plus activation of glycolytic enzyme systems (particularly with hypoxic cell death).
‘Necrosis is necrosis is necrosis’ (response 3 is FALSE ). DNA damage can cause necrosis, but this is the common pathogenesis of the onset of apoptosis.
