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54 Cards in this Set

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Oxygen deficiency interfering with aerobic oxidative respiration
Loss of blood supply or mismatch of blood supply and tissue demand
T/F Ischemia can be caused by either impeded arterial flow or reduced venous drainage
What is most common cause of tissue hypoxia?
T/F During hypoxia, anaerobic glycolysis can continue.
TRUE. This is why hypoxia is less severe than ischemia.
T/F Ischemia injures tissues faster than hypoxia because delivery of both oxygenated blood and substrates for glycolysis ceases
Infarction: defn
Irreversible injury/cell death resulting from ischemia
What are the steps that lead to ER Swelling, cellular swelling, loss of microvilli, and blebs from ischemia?
1) Decreased oxygen delivery meants decreased oxidative phosphorylation

2) Decreased ATP

3) Decreased activity of Na+ pump

4) Influx of Ca, H20, and Na (water follows sodium);
Efflux of K

5) ER Swelling, cellular swelling, loss of microvilli, and blebs
What are the steps that lead to clumping of nuclear chromatin from ischemia?
1) Decreased oxygen delivery meants decreased oxidative phosphorylation

2) Decreased ATP

3) Increased anaerobic glycolysis

4) Decreased glycogen, Increased lactic acid

5) Decrease pH

6) Clumping of chromatin in nucleus
What are the steps that lead to lipid deposition from ischemia?
1) Decreased oxygen delivery meants decreased oxidative phosphorylation

2) Decreased ATP

3) Detachment of ribosomes

4) Decrease in protein synthesis

5) Lipoproteins not produces, tryglycerides can't get out of the cell

6) Lipid deposition in cell
What types of things leads to mitochondrial injury or dysfunction?
Increased cytosolic Ca2+, Reactive oxygen species, and lipid peroxidation
How does increased intracellular Ca2+ lead to cell damage?
1) Causes increase in mitochondrial permeability leading to decreased production of ATP

2) Causes activation of cellular enzymes that cause damage to membranes and nucleus (e.g., phospholipases, endonucleases, etc)
How are ROS generated?
Incomplete reduction of O2 --> superoxide radical in presence of inflammation, radiation, chemicals, reperfusion injury, etc.
Superoxide dismutase converts superoxide radicals to what?
H202 hydrogen peroxide
Glutathione peroxidase in mitochondria converts hydroxyl radical to what?
hydrogen peroxide then to water and O2
What does catalase do?
Converts hydrogen peroxide to water and O2
Where are the following found?
1) Catalase
2) Superoxide dismutase
3) Glutathione peroxidase
1) Peroxisomes
2) and 3) Mitochondria
What histologic abnormalities does cellular swelling due to failure of ion pumps and water influx cause?
hydropic change (accumulation of water in the cell); vacuolar degeneration (formation of nonlipid vacuoles in cytoplasm, most frequently due to accumulation of water)
What does early/mild injury that may be reversible look like?
Related to reduced ox-phos with depleted ATP. Include swelling of ER and mitochondria, membrane blebbing, clumping of chromatin
What are the two main morphologic correlates of early/mild cellular injury?
1) Cellular swelling due to failure of ion pumps and resultant water influx

2) Fatty change, mainly in cells involved with fat metabolism
T/F Gross morphologic changes occur early in cell death
False. these are the last to occur
What is the order or these in duration of injury?

A) Ultrastructural changes
B) Gross Morphologic Changes
C) Light microscopic changes
D) Biochemical alterations --> Cell death
D, A, C, B
Two forms of irreversible injury/cell death
1) Necrosis
2) Apoptosis
T/F Both necrosis and apoptosis may be physiological
False. Necrosis is always pathological; apoptosis may be physiologic
What happens to cytoplasm and cell membrane in necrosis?
Loss of membrane integrity and leakage of cytoplasm; Digestion of cell by enzymes from cell's lysosomes or leukocytes; phospholipids phagocytosed and degraded to FAs
What happens to nucleus in necrosis?
(These changes occur due to breakdown of DNA and chromatin)

3 patterns:

Karyolysis: fading of nucleus, due to deoxyribonuclease activity

pyknosis: nuclear shrinkage and increased basophilia due to DNA condensation

karyorrhexis: fragmentation and eventual disappearance of pyknotic nucleus
Karyolysis: defn
fading of nucleus, due to deoxyribonuclease activity
Pyknosis: defn
nuclear shrinkage and increased basophilia due to DNA condensation
destructive fragmentation of the nucleus of a dying cell[1] whereby its chromatin is distributed irregularly throughout the cytoplasm. It is usually preceded by pyknosis and is followed by karyolysis and can occur as a result of either programmed cell death or necrosis.
Increased basophilia is part of what phase of nuclear death?
Why is there no proteolysis in coagulative necrosis?
The injury causing the necrosis also destroyed enzymes
What type of necrosis is typical of ischemic infarcts?
Coagulative necrosis. The infarct is defined by the tissue that was supplied by the ischemic vessel.
What happens in coagulative necrosis?
This type is typical for ischemic infarcts. Basic tissue architecture is preserved and structural as well as enzymatic proteins are degraded. Necrotic cells are eventually phagocytozed by leukocytes that infiltrate the area.
What happens in liquefactive necrosis?
Usually it occurs in setting of microbial infections. Inflammatory cells release enzymes that digest/liquefy tissue. Associated with formation of pus and is typical of cerebral infarcts.
What type of necrosis is typical of cerebral infarcts?
What type of necrosis is characterized by Inflammatory cells release enzymes that digest/liquefy tissue?
What does gangrene refer to?
Usually to ischemic necrosis of a limb
Dry gangrene is ______ necrosis while wet gangrene is _______ necrosis
Coagulative; liquefactive
What happens in caseous necrosis?
Most often associated with tuberculous infection; refers to cheese-like appearance on gross exam; cells fragmented, lysed, tissue architecture not identifiable. usually surrounded by granuloma
Type of necrosis generally found with amorphous pink material surrounding it, unidentifiable tissue architecture
Caseous necrosis
What happens in fat necrosis?
Focal areas of fat destruction, found in association with acute pancreatitis, with release of lipases into pancreas and peritoneal cavity, also, any traumatized fatty tissue. Adipocyte membranes liquefied, released fatty acids combined with calcium (fat saponification)
Acute pancreatitis is likely to demonstrate what type of necrosis?
Fat necrosis due to release of lipases into peritoneal cavity
What happens in fibrinoid necrosis?
Usually seen in immune reactions involving blood vessels; Deposition of antigen-antibody complexes in vessel wall; fibrin leaks out of vessel; bright pink, amorphous appearance ("fibrin-like")
What does the bright pink/fibrin-like appearance represent in fibrinoid necrosis?
Immune complexes
Type of necrosis most likely seen in immune reactions involving blood vessels
Type of necrosis almost always in vessel walls
T/F Liquefactive necrosis leads to dissolution of the cell outline
Type of necrosis usually related to TB or fungal infection
T/F Apoptosis requires energy
T. This means it's NOT associated with ATP depletion
T/F In apoptosis the cell membrane bursts
False. It's largely maintained.
What is characterized by nuclear dissolution, fragmentation of the cell, followed by removal of cell debris?
What are the two major apoptotic pathways?
1) Mitochondrial (intrinsic)
2) Death receptor (extrinsic)
T/F In apoptosis, you will see little fragments microscopically
What are caspases?
Very important proteins for initiating apoptosis