Term
| At what level do aetiological agents act? |
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Definition
| Cellular level - disrupt homeostasis |
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Term
| When does cell injury occur? |
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Definition
when the level of stress is so severe that the cell can not adapt
-may be reversible i.e. degenerative, or irreversible and result in cell death i.e. necrosis and apoptosis |
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Term
| Damage at the cellular level may be inflicted on which structures? |
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Definition
cell membranes - affects their integrity, affecting homeostasis
-cytoskeleton - resulting in loss of shape and form, which may affect ability to move
-nucleus i.e. DNA damage or loss
-energy production systems i.e. oxidative phosphorylation in mito. decr. or stops |
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Term
| What are the consequences of mito. dysfunction? |
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Definition
-decr. oxidative phosphorylation
-ATP decr.
-shifts to anaerobic glycolysis if poss.
-depletes glycogen stores and lactate accumulates, so pH decr.
-when ATP runs out Na/K pumps fail and loose homeostasis
- ion influx (Na+ and Ca++ in, K+, Mg++ out) and so osmosis and water influx
-cellular sweiling
-PLUS mito. further damaged by influx of Ca++ |
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Term
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Definition
Indicates NON-lethal cell damage involving disruption of mito. function and so SWELLING
-most cells can return to normal if oxygen supplied and membrane damaged repaired before too late |
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Term
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Definition
abnormal accumulations of trigs, chol, phospholipids WITHIN parenchymal cells
-type of degenerative change i.e. reversible
NB can be physiological e.g. pregnancy |
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Term
| Where does fatty change occur? |
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Definition
-most commonly in liver ("fatty liver"
-also heart, skeletal muscle, kidney |
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Term
| When does fatty change occur? |
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Definition
1) defects in FFA uptake
- severe calorie restriction so excessive FFA release from adipocytes eg. starvation, anorexia, late pregnancy
2)defects in FFA catabolism
-due to damage to hepatocytes
e.g. anoxia, toxins, cofactor deficiency
3) defect in secrection of lipids in lipoproteins
- due to protein deficiency and so impaired apoprotein synthesis
- due to lipotrope deficiency - required for apoprotein synthesis |
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Term
| What is the significance of fatty change? |
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Definition
-reversible providing underlying cause brought under control
-if not, then may develop to necrosis |
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Term
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Definition
| Adipocytes infiltrate between cells in an inappropriate site / organ |
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Term
| In necrosis, what causes cell death? |
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Definition
-mito. irreversibly damaged
-severe disruption to membrane function so that mito. and lysosomal enzymes enter the cytoplasm, digest the cell, and some of the cell contents then leak out
-massive influx of Ca++ due to lack of ATP to run ion pumps and so catabolic enzymes are activated |
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Term
| In necrosis, Ca++ influx activates which catabolic enzymes? |
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Definition
-phospholipase - degrades phospholipids in cell memb. causing further memb. damage, and generates arachidonic acid
-ATPases - dec. ATP levels further
-Proteases - break down memb. and cytoskeleton
-Endonucleases - break down DNA |
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Term
| What is the consequence of restoring bloof flow to necrotic tissue? |
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Definition
Acclerates the damage - huge influx of Ca++ w. associated further memb. damage etc
This is REPERFUSION INJURY |
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Term
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Definition
| When blood flow is restored to necrotic tissue it acclerates the damage due to huge influx of Ca++ w. associated further memb. damage etc |
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Term
Necrosis summary:
-Basis
-No. of affected cells
-Effect on plasma memb
-Morphology
-Inflam?
-Fate of cells
-Biochem mechanism |
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Definition
-Basis - always pathological
-No. of affected cells - groups of cells due to leakage of cellular enzymes into EC space
-Effect on plasma memb - loss of integrity and so enzymes and proteins pass out, Ca++ floods in
-Morphology- cell swelling and lysis
-Inflam? yes w. neutophils and macrophages
-Fate of cells - enzymatic digestion and phagocytosis
-Biochem mechanism - E-independent, loss of ion homeostasis |
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Term
| Gross morphological changes in necrosis |
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Definition
-tissue is pale, soft and/or friable
-if necrotic tissue is focal, it is sharply demarcated oft. w. peripheral red rim due to incr. blood flow |
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Term
| When are gross morphological changes in necrosis visible? |
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Definition
| 24-48 hours post-necrosis |
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Term
| Micro morphological changes in necrosis |
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Definition
-usually swollen cytoplasm and eosinophilic (pink) cells, sl. detached from one another
-changes to nuclei |
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Term
| When are micro morphological changes in necrosis visible? |
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Definition
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Term
| How can nuclei be affected in necrosis? |
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Definition
-Pyknosis (condensation)
-Karyorrhexis (fragmentation)
-Karyolysis (dissolution) |
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Term
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Definition
nucl. shrunken and condensed, dark basophilic (blue)
-seen in necrosis and apoptosis |
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Term
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Definition
| nucl. memb. ruptures and nucl. basophilic (blue) fragments are in the cytoplasm |
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Term
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Definition
| nucl. dissolved or pale or just a ghost outline |
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Term
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Definition
usually implies hypoxic or toxic injury
e.g. infarction |
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Term
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Definition
More chronic necrosis than coagulative w. loss of architecture, cytoplasmic and nucl. debris and often calcified
e.g. TB, caseous lymphadenitis |
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Term
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Definition
necrosis that affects the CNS, in abscesses and bacterial infections
-may follow coagulative necrosis once neutrophils arrive |
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Term
| Why can the presnce of neutrophils in coagulative necrosis result in the development of liquefactive necrosis? |
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Definition
| neutrophils release enzymes which digest / liquefy affected tissues |
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Term
| Why does the CNS always have liquefactive necrosis? |
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Definition
| high lipid, little c.t. so structure disintegrates |
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Term
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Definition
clinical term often applied to extremities which have lost their blood supply and undergone coagulative necrosis
-may be dry, wet or gas |
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Term
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Definition
tissue is dry and there is no bact. growth
-tissue looks mummified, black/brown, crispy |
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Term
| Wet/gas gangrenous necrosis |
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Definition
| Involves bacterial inf/ putrefaction and may involve enzymativc liqufaction |
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Term
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Definition
| necrosis to focal areas of fat usually due to release of pancreatic lipases e.g. pancreatitis or pancreatic necrosis |
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Term
| What are different types of fatty necrosis? |
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Definition
-traumatic
-lipomatosis in cattle
-fatty necrosis may result in saponification |
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Term
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Definition
| when fatty acids released in fatty necrosis combine with Ca++ to form soaps |
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Term
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Definition
when fat is crushed
e.g. fat in pelvic canal of heifers crushed during parturition |
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Term
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Definition
-in cattle
-when adipose tissue in ab. cavity or retroperitoneum becomes necrotic and can obstruct intestinal lumens due to ext. pressures, or affect motility |
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Term
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Definition
-slit like empty spaces left by dissolution of chol xlls in histological preparation
-often surrounded by macrophages, incl. giants |
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Term
| When do cholesterol clefts appear? |
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Definition
-subsequent to necrosis and haemorrhage
-chol. comes from dead cells |
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Term
| What are the outcomes of necrosis? |
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Definition
-stimulates inflam in adjacent tissues which still have a blood supply
-necrotic cells and debris usually disappear due to enzymatic digestion and fragmentation, followed by phagoc. by neutro. and macro.
-necrotic tissue by be replaced by or become encapsulated in fibrous tissue
-if poss., necrotic tissue may regenerate
-necrotic tissue may be sequestrated away
-if necrotic tissue is on a surface there may be desquamation or sloughing
-if not prompty removed, tends to attract calcium |
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Term
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Definition
-an isolated mass of necrotic tissue (potential consequence of necrosis)
-usually applies to bone, can be other tissues e.g. lung
-may fragment and pass to surface via a sinus tract
-may remain in a cavity inside tissue |
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Term
| What happens if necrotic tissue is not prompty removed? |
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Definition
tends to attract calcium and other minerals and become calcified
i.e.DYSTROPHIC CALCIFICATION |
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Term
| How can you distinguish between PM autolysis and antemortem necrosis? |
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Definition
| Autolysis does not cause inflammation |
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Term
| What causes autolysis PM changes? |
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Definition
| the release of lysosomal enzymes |
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Term
Apoptosis summary:
-Basis
-No. of affected cells
-Effect on plasma memb
-Morphology
-Inflam?
-Fate of cells
-Biochem mechanism |
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Definition
-Basis - pathological or physiological
-No. of affected cells - individual cells
-Effect on plasma memb - remains intact until end stages, but altered so that recongnised by phagoc.
-Morphology - cell shrinkage and nucl. condensation / fragmentation
-Inflam? no
-Fate of cells - phagocytosed
-Biochem mechanism - E dependent endonuclease activity (caspases) |
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Term
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Definition
| programmed cell death involving activation of enzymes in a genetically determined pathway which degrade the cells' own proteins and DNA |
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Term
| When does apoptosis occur normally? |
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Definition
-embryogenesis and development
e.g. thymic involution, in epiphyseal growth plates
-involultion of hormone-responsive tissues
e.g. endometrium, glands, elimination of self-reactive LCs |
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Term
| Describe the process of apoptosis |
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Definition
1) Initition - activiation of caspases
2)Execution - caspases cause cell death
-Cytoplasmic buds form w. portions of cell memb and cellular organelles, which break away to form APOPTOTIC BODIES which are taken up by phagocytic cells |
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Term
| In apoptosis, how do caspases cause cell death? |
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Definition
-activate proteases and endonucleases in the cell
-these breakdown the cytoskeleton and degrade DNA |
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Term
| What factors can induce apoptosis? |
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Definition
-tumour necrosis factor (TNF)
-withdrawal of growth factors
-cytotoxic T-cells
-cell injury e.g. DNA damage due to irradiation, UV light, mutagenic chemicals |
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Term
| In apoptosis, what happens when DNA damage is beyond repair? |
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Definition
-a tumour suppressor gene P53 is recruited
-several enzymes are activated and the tumour suppressor protein p53 is phosphorylated
-p53 unfolds and binds to DNA, acting as a transcription factor
-p53 stimulates the transcription of several genes that mediate cell cycle arrest and apoptosis |
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