Class #2 - cell injury

Question 1

T or F all disease involve cell injury?

Answer 1

T

Question 2

4 common target of cell injury?

Answer 2

Mitochondria
Plasma membrane
ER
Nucleus

Question 3

ROS?

Answer 3

Reactive Oxygen Species = free radial = Oxygen molecule with an unpaired electron, an extra electron that can fuck things up.

Question 4

Injury depends on?

Answer 4

Type, length and severity of stressors.

Question 5

Causes of cell injury?

Answer 5

1-hypoxia: Inadequate access to O2 in tissues.
2- physical injury
3-Chemical injury: ETOH
4- Biological agents :b and virus
5-Immune reaction
6-Genetic abnormalities
7-Inadequate nutrition

Question 6

hypoxemia vs hypoxia vs ischemia vs anemia vs anoxia

Answer 6

1- lack O2 in arterial blood
2- Lack O2 in tissues
3 - Restriction in blood supply to tissue
4- Decrease in total amount of Hb in blood
5- Complete deprivation of O2 in tissue

Question 7

Mechanisms of cell injury (6)?

Answer 7

1- Depletion ATP
2- Influx Calcium
3- Mitochondrial damage and dysfunction
4- Accumulation of ROS
5- Defect in membrane permeability
6-Damage DNA/p+

Question 8

How depletion of ATP in hypoxic injury leads to cell injury?

Answer 8

1) ion pumps (leading to cell swelling, and influx of Ca2+, with its deleterious consequences); (2) depletion of glycogen stores and accumulation of lactic acid, thus lowering the intracellular pH; and (3) reduction in protein synthesis.

Question 9

Hypoxic injury steps?

Answer 9

decrease O2 -> decrease oxidative phosphorylation of mitochondria -> reduce ATP prod. -> Na/K pump not working properly -> increase intracellular Na -> increase attraction of H2O intracellular -> increase cellular swelling -> Ribosome on ER detach due to swelling -> impaired p+ synthesis

also: reduce ATP prod. -> anaerobic glycolysis -> increase lactic acid -> decrease pH

Also: Reduce ATP -> release of Ca2+ from ER/mitochondria stores + Ca2+ (atp dependant) pump not working -> increase intracell. Ca2+ -> Activation of Enz. -> results in: membrane damage and nuclear damage

Question 10

Cells most vulnerable to hypoxia?

Answer 10

Neurons

Question 11

Free radical injury causes?

Answer 11

Hypoxia and chemical injury

Question 12

two major pathways of ROS prod.?

Answer 12

1- Redux in mitochondria to produce ATP

2- Produced by phagocytic Leukocytes: Neutrophiles and macrophages during inflammation.

Question 13

Reactive oxygen species cause cell injury by three main reactions?

Answer 13

-Lipid peroxidation of membranes. Double bonds in membrane polyunsaturated lipids are vulnerable to attack by oxygen-derived free radicals. The lipid–radical interactions yield peroxides, which are themselves unstable and reactive, and an autocatalytic chain reaction ensues.
• Cross-linking and other changes in proteins. Free radicals promote sulfhydryl-mediated protein cross-linking, resulting in enhanced degradation or loss of enzymatic activity. Free radical reactions may also directly cause polypeptide fragmentation.
• DNA damage. Free radical reactions with thymine in nuclear and mitochondrial DNA produce single-strand breaks. Such DNA damage has been implicated in cell death, aging, and malignant transformation of cells.

Question 14

ROS chain

Answer 14

O2 -> superoxide ->hydrogen peroxide -> hydroxyl radical

Question 15

Enz. eliminating ROS intracell?

Answer 15

Superoxide dismutase and glutathione peroxidase

Question 16

Two types of cell death?

Answer 16

Apoptosis and necrosis

Question 17

Types of necrosis?

Answer 17

Coagulative: cell retain barriers
Liquefactive: Full neutrophiles, result in hole in tissues, absec
Caseous: caog + liqu necrosis, cheese like. In tuberculosis
Gangrene: Ischemic necrosis followed by bacterial attack

Question 18

Necrosis involves…. and triggers….

Answer 18

1-Autolysis: dissolving itself

2-Inflammation