1
Advanced Pathophysiology
Study Guide for Test #1
Unit-1
Cellular adaptation, injury, and death
- Apoptosis Vs necrosis
Apoptosis = Programmed cell death (suicide) Necrosis = Unregulated enzymatic digestion of cell
components
- Maintains a balance between cell proliferation and cell - Interferes with cell replacement and tissue regeneration
death - Non-distinguishing cell death
– Functions to remove cells so new cells can replace them - Starts by swelling of the cell
– Highly selective process that eliminates injured and aged - There is loss of cell membrane integrity >> Lysosomal
cells enzymes are released extracellularly (blood)
- Affects scattered, single cells - Triggers inflammatory response in the surroundings
- Starts by shrinkage of the cell
- There is membrane-bound fragmentation of the cell
(CELL MEMBRANE STAYS INTACT). As a result,
intracellular enzymes are NOT released into
circulation
- Not associated with inflammatory reaction
- Role of Na + and Ca ++ in hypoxic cell injury
Steps and mechanisms of cell injury
1. Hypoxia > reduced ATP production inside the cell
2. Failure of Na/K pump > more Sodium (Na) moves into the cell
3. High osmotic pressure > water moves into the cell > cell swelling
4. Dilation of endoplasmic reticulum and detachment of ribosomes > reduced protein synthesis
5. Increased lipid deposition, glycolysis, lactate formation, lowered pH, clumping of nuclear chromatin, increased
membrane permeability
>> Lecture:
Recall > Where sodium goes, water goes. Water will follow sodium and accumulate within the cell, resulting in cellular
edema. With sodium, the cell swells to a certain degree, and the cell membrane gives way/breaks (#6), allowing calcium
to get inside (#7).
When cells are hypoxic, they will accumulate lactic acid. The Na/K pump is a protein molecule and will denature
(breakdown) when exposed to lactic acid, to stop functioning altogether.
6. Loss of cell membrane integrity
7. Increased Calcium (Ca) influx > enzymatic activation > cell damage
8. Disruption of cytoskeleton
9. Mitochondrial membrane damage, lysosome swelling and rupture
10. Cell death (necrosis!)
>> Lecture:
Calcium is the “killer.” Calcium inside the cell is very restricted and is always kept outside the cell. The cell membrane
keeps calcium out; however, in the above scenario, calcium can come in. Calcium activates cellular enzymes and leads
to self-destruction (necrosis!).
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- Aerobic Vs anaerobic metabolism: effects in cell injury
Anaerobic metabolism Aerobic metabolism
- Anaerobic metabolism occurs when little to no oxygen is - Aerobic metabolism occurs when sufficient oxygen is
available to the body (e.g., hypoxia, ischemia, infarct) available to the body (normal functioning!).
- 1 unit of glucose produces 2 units of ATP - 1 unit of glucose produces 32-36 units of ATP
- Lactic acid is a byproduct which damages the cell - No lactic acid w/ aerobic metabolism
>> Anaerobic metabolism occurs with hypoxia (e.g.,
ischemia or infarct). Decreased ATP production (only 2
units) due to lack of oxygen supply causes failure of the
Na/K pump and Na-Ca exchanger, which leads to cellular
swelling. Aerobic shutdown, or power failure, occurs >>
converting to anaerobic metabolism. Na/K cannot work
well. There is increased intracellular sodium (increased
water as well because water follows sodium) contributing
to cellular swelling. Cellular damage is caused by the
increased lactic acid. More free radicals are produced >>
more cell damage.
- Adaptation (Metaplasia)
Metaplasia: Reversible replacement of one cell by another cell type
Bronchial metaplasia (in smokers!)
- Normal columnar ciliated epithelial cells, are replaced by stratified squamous epithelial cells (no mucous
secretion, no cilia)
- Can be reversed (if the person stops smoking)
- Can be transformed into cancer (if the person continues to smoke, metaplasia can continue to dysplasia)
Barrett esophagus
- Normal squamous epithelial lining of the esophagus, is replaced by columnar epithelium (goblet cells of the
intestines)
- Occurs as an adaptation to the chronic irritation of GERD
- Predisposes to esophageal adenocarcinoma
- Dysplasia
Dysplasia: Atypical hyperplasia
- Deranged cell growth of a specific tissue that results in cells that vary in size, shape, and organization
- Epithelial tissue of the respiratory tract
- Epithelial tissue of the uterine cervix
- Precursor of cancer
- Grading (low or high grade) (e.g., Pap smear)
- Adaptive as it potential reversible
Questions from PPT
Advanced Pathophysiology
Study Guide for Test #1
Unit-1
Cellular adaptation, injury, and death
- Apoptosis Vs necrosis
Apoptosis = Programmed cell death (suicide) Necrosis = Unregulated enzymatic digestion of cell
components
- Maintains a balance between cell proliferation and cell - Interferes with cell replacement and tissue regeneration
death - Non-distinguishing cell death
– Functions to remove cells so new cells can replace them - Starts by swelling of the cell
– Highly selective process that eliminates injured and aged - There is loss of cell membrane integrity >> Lysosomal
cells enzymes are released extracellularly (blood)
- Affects scattered, single cells - Triggers inflammatory response in the surroundings
- Starts by shrinkage of the cell
- There is membrane-bound fragmentation of the cell
(CELL MEMBRANE STAYS INTACT). As a result,
intracellular enzymes are NOT released into
circulation
- Not associated with inflammatory reaction
- Role of Na + and Ca ++ in hypoxic cell injury
Steps and mechanisms of cell injury
1. Hypoxia > reduced ATP production inside the cell
2. Failure of Na/K pump > more Sodium (Na) moves into the cell
3. High osmotic pressure > water moves into the cell > cell swelling
4. Dilation of endoplasmic reticulum and detachment of ribosomes > reduced protein synthesis
5. Increased lipid deposition, glycolysis, lactate formation, lowered pH, clumping of nuclear chromatin, increased
membrane permeability
>> Lecture:
Recall > Where sodium goes, water goes. Water will follow sodium and accumulate within the cell, resulting in cellular
edema. With sodium, the cell swells to a certain degree, and the cell membrane gives way/breaks (#6), allowing calcium
to get inside (#7).
When cells are hypoxic, they will accumulate lactic acid. The Na/K pump is a protein molecule and will denature
(breakdown) when exposed to lactic acid, to stop functioning altogether.
6. Loss of cell membrane integrity
7. Increased Calcium (Ca) influx > enzymatic activation > cell damage
8. Disruption of cytoskeleton
9. Mitochondrial membrane damage, lysosome swelling and rupture
10. Cell death (necrosis!)
>> Lecture:
Calcium is the “killer.” Calcium inside the cell is very restricted and is always kept outside the cell. The cell membrane
keeps calcium out; however, in the above scenario, calcium can come in. Calcium activates cellular enzymes and leads
to self-destruction (necrosis!).
, 2
- Aerobic Vs anaerobic metabolism: effects in cell injury
Anaerobic metabolism Aerobic metabolism
- Anaerobic metabolism occurs when little to no oxygen is - Aerobic metabolism occurs when sufficient oxygen is
available to the body (e.g., hypoxia, ischemia, infarct) available to the body (normal functioning!).
- 1 unit of glucose produces 2 units of ATP - 1 unit of glucose produces 32-36 units of ATP
- Lactic acid is a byproduct which damages the cell - No lactic acid w/ aerobic metabolism
>> Anaerobic metabolism occurs with hypoxia (e.g.,
ischemia or infarct). Decreased ATP production (only 2
units) due to lack of oxygen supply causes failure of the
Na/K pump and Na-Ca exchanger, which leads to cellular
swelling. Aerobic shutdown, or power failure, occurs >>
converting to anaerobic metabolism. Na/K cannot work
well. There is increased intracellular sodium (increased
water as well because water follows sodium) contributing
to cellular swelling. Cellular damage is caused by the
increased lactic acid. More free radicals are produced >>
more cell damage.
- Adaptation (Metaplasia)
Metaplasia: Reversible replacement of one cell by another cell type
Bronchial metaplasia (in smokers!)
- Normal columnar ciliated epithelial cells, are replaced by stratified squamous epithelial cells (no mucous
secretion, no cilia)
- Can be reversed (if the person stops smoking)
- Can be transformed into cancer (if the person continues to smoke, metaplasia can continue to dysplasia)
Barrett esophagus
- Normal squamous epithelial lining of the esophagus, is replaced by columnar epithelium (goblet cells of the
intestines)
- Occurs as an adaptation to the chronic irritation of GERD
- Predisposes to esophageal adenocarcinoma
- Dysplasia
Dysplasia: Atypical hyperplasia
- Deranged cell growth of a specific tissue that results in cells that vary in size, shape, and organization
- Epithelial tissue of the respiratory tract
- Epithelial tissue of the uterine cervix
- Precursor of cancer
- Grading (low or high grade) (e.g., Pap smear)
- Adaptive as it potential reversible
Questions from PPT
