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58 Cards in this Set

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define necrosis
the morphologic changes that follow cell death within living tissue (necrobiosis)
=Antemortem autolysis + heterolysis
where does necrosis occur?
in lethally-injured cells
from what does necrosis occur?
from the progressive degradative action of proteolytic lysosomal enzymes
where do proteolytic lysosomal enzymes needed for necrosis come from?
-dead cells temselves (autolysis)
-leukocytes recruited during inflammation (heterolysis)
The morphologic appearance of necrosis is due to....
- denaturation of intracellular protein
- enzymatic digestion of the cell
- inflammation (not present in post mortem autolysis)
what can cause irreversible cell injury?
-inherited (genetic)
-physical (thermal, trauma, radiant energy)
-toxic -infectious
-metabolic (endocrinologic, immunologic, degenerative)
-nutritional -neoplastic
list two main pathways of cell death
1. oncosis: cell death by swelling
2. apoptosis: cell death by shrinkage, programmed cell death
List histologic features of oncosis
Nuclear changes:pyknosis, karyorrhexis, karyolysis

Cytoplasmic changes: cell swelling, increased eosinophilia, pallor(蒼白), vacuolation
What does pyknosis lead to?
shrunken, irregular, dark nucleus
What does karyorrhexis lead to?
fragmentation of the nucleus (nuclear envelope ruptured, with release of dark nuclear fragments into cytoplasm)
what does karolysis lead to?
basohilia of nuclear chromatin fades (hydrolysis from DNAse activity)
Why does cell swelling occur during oncosis? what does it indicate?
due to accumulation of water, fat, glycogen
swelling reflects membrane damage of irreversible cell injugy
why do eosinophilia increase during oncosis?
due to increased binding of eosin to denatured intracytoplasmic proteins, and loss of normal basophilia of ribosomal RNA
Why do cells show pallor appearance during oncosis?
due to loss of intracellular proteins, glycogen stores and organelles
What does glassy appearance of cell during oncosis reflect?
relfects glycogen loss
Why does vacuolation occur during oncosis?
since organelles are digested by enzymes, calcification and cell replacement by whorled phospholipids masses called myelin figures which may be phagocytosed, or further degraded into fatty acids, which can form calcium soaps
Describe sequences of oncosis (necrosis) of small area
-resorption & phagocytosis of necrotic material
-regeneration of tissue from labile/stable cell populations
-replacement and repair by fibrous tissue (fibrosis)
-replacement by fat (fat infiltration)
Describe sequences of oncosis (necrosis) of large area
-limited resorption & inflammation
-fibrosis and scar formation
-encapsulation surrounded and contained within a fibrous capsule to form
what are gross features of necrosis?
2.loss in strength (soft, friable)
3.A zone of inflammation may border the necrotic tissue
4patterns of necrosis within the tissues
Why are there several types (patterns) of necrosis?
due to the different causative agent & local conditions, particularly the fluid or blood flow present in the lesion
List 7 types of necrosis
1. coagulative necrosis
2. liquefactive necrosis
3. Caseous necrosis
4. Gangrenous necrosis
5. fat necrosis
6. fibrinoid necrosis
7. collagen necrosis
What are gross features of coagulative necrosis?
tissues appear pale, often with a cooked apprearance
What are histological features of coagulative necrosis?
-tissues architecture is retained
-cell outlines preserved, but cells are shrunken
-cytosol is homogenenous and hyper-eoshinophilic
-nuclei are pyknotic, karyorrhectic, karyolytic or absent
Why does coagulation necrosis occur?
common acute hanges of hypoxic death of cells in acute bacterial or viral infections, anoxia or acute toxicoses
(it is characteristic of hypoxic cell death in all tissues except brain)
What is a gross feature of liquefactive necrosis?
liquefied areas
What is a histological feature of liquefactive necrosis?
-eosinophilic proteinaceous debris
-normal tissu architecture is lost
What are causes of liquefactive necrosis?
focal infection by pyogenic(化膿性の)bacteria that promote intense accumulation of inflammatory cells such as neutrophils and enzymic digestion
where is liquefactive necrosis usually found?
in the brain and cord (also intestinal mucosa, and pancreas)
Liquefactive necrosis is characteristic of hypoxic cell death of the brain and cord
What are gross features of caseous necrosis?
friable(もろい), granular to amorphous, off-white to pale yellow material with the consistency of cottage cheese
What are histological features of caseous necrosis?
-fragmented, coagulated cells
-tissue architecture is gone
-amorphous to granular nuclear -cytoplasmic degris
what is the cause of caseous necrosis?
rapidly growing tumors,fungal infections, and in some chronic bacterial infections
What does dry gangrene imply?
ischaemic coagulative necrosis without any fluid and gas built up.
What does wet gangrene imply?
ischiaemic necrosis mofified by the liquefactive action of putrefactive bacteria and the leukocytes they attract
Where can dry gangrene be found?
in extremities such as ears and udder
Where is fat necrosis be seen?
only in fat tissues
-common in ruminants
What are clinical signs of fat necrosis?
painful skin lumps and obstruction of GI and urinary tracts
What are gross features of fat necrosis?
-fat contains white, yellow to pink foci of calcium soap deposition at site of lipid breakdown
-chronic lesions are firm(fibrosis), white (Ca soaps) and chalky
what are histological features of fat necrosis?
-necrotic fat is not removed during preparation of paraffin-imbedded sections
-necrotic fat cells themselves are eosinophilic, but become basophilic when free fatty acids combine with Ca ions to form soaps
-chronic inflammation
-formation of multinucleate giant cells, fibrosis, and deposition of cholesterol
What are spindle-shaped clear clefts which are found in histological section of cell experiencing fat necrosis?
deposition of cholesterol
what makes fat necrosis calcified?
calcium soap foarmaiton
what are causes of fat necrosis?
-Vit E deficiency
-Chronic inflammation
-Pancreatic disease
Where is fibrinoid necrosis seen?
blood vessels, especially medium-sized arteries
Fibrinoid necrosis is often associated with ....
-thrombosis of the vessel lumen
-haemorrhage into adjacent tissue due to vascular leakage
What are histologic features of fibrinoid necrosis?
stains positively with fibrin stains such as PTAH & lendrums stain
What are possible causes of fibrinoid necrosis?
-sever vascular injury
-coagulation necrosis of the blood vessel wall mixed with blood clotting proteins which leak through a damaged intima
-seen in immune-mediated vasculitis, endotoxic shock, septicaemia, infection by endotheliotropic viruses
What are histological features of collagen necrosis?
-appears as condensed, fragmented, brightly eosinophilic denatured collagen
-damaged collagen is phagocytosed
What are possible causes of collagen necrosis?
-hypersensitivity reaction
-insect, spider bites
-mast cell tumours
What is apoptosis responsible for?
for both physiologic (eg. regression of the thymus, involusion of mammary gland, and regression of luteal cells)and pathologic events (eg.injuries)
What is oncosis (necrosis) responsible for?
only for pathologic events
What are histologic features of apoptosis?
-cell shrinkage
-chromatin condensation
-formation of cytoplasmic blebs (水泡)and apoptotic bodies
-rapid phagocytosis of apoptotic cells or apoptotic bodies by adfacent cells (usually macrophages)
The histological features of apoptosis are conspicuous. Why?
Because they usually involve only individual cells or small groups of cells, occur rapidly, and do not dlicit an inflammatory reaction
what are gross features of apoptosis?
only microscopic changes are seen in apoptosis
List biochemical features of apoptosis
-protein cleavage
-DNA breakdown
-Phagocytic recognition
How apoptotic cells prompt recognition and phagocytosis without release of pro-inflammatory cell components?
since apoptotic cells undergo membrane translocation - the phospholipid, phosphatidlserine, flips out from the inner layers of the plasma membrane to be expressed on the outer layer of the cell
List possible pathways for caspases activations
-Extrinsic (death receptor-initiated)pathway
-Intrinsic (mitochondorial) pathway
-Cytotoxic T lymphocytes
-Establishment of apoptotic threshold
How does extrinsic pathway activate caspases?
by signalling to cells via 'death receptors' (members of the tumor necrosis factor receptor) on the cell surface.
How does intrinsic pathway activate caspases?
by signalling to cells via withdrawal of growth factors or hormones, and diverse forms of injury
List stages of apoptosis
1.Initiation phase: commitment to cell death by activation of caspases
2.Execution(執行)phase: executioner caspases activate laent cytoplasmic endonucleases and proteases
3.Removal of dead cells: apoptotic bodies bud off and phagocytosis