Cell Response to Stress and Injury + Mechanisms of Cell Injury

Question 1

What are the four types of adaptations to cellular stress, and how do they differ in terms of cellular changes?

Answer 1

1. Hypertrophy: Increase in cell size due to increased cellular components (e.g., muscle cells enlarging in response to increased workload).
2. Hyperplasia: Increase in cell number due to cell proliferation (e.g., papilloma (wart) from excessive cell growth).
3. Atrophy: Decrease in cell size due to reduced use, blood supply, or nutrients (e.g., muscle shrinkage after prolonged disuse OR programmed atrophy of structures in embryonic development).
4. Metaplasia: Change in cell type/ phenotype in response to chronic irritation or stress (e.g., columnar to squamous cells in the respiratory tract from smoking).

Question 2

Describe the pathway of a normal cell that is undergoing cell stress or injury.

Answer 2

Question 3

Describe the types of cell death

Answer 3

Apoptosis
* Membrane intact
* Condensation of chromatin
* Membrane blebbing
* DNA fragmentation

Necrosis
* Cell Swells
* Membrane breaks down
* Contents spill out
* Loss of ATP (bc of damage to mitochondria)

Question 4

Describe the mechanisms of injury for:
1. Decreased ATP
2. Mitochondrial damage
3. Entry of Ca+
4. Increase ROS
5. Membrane Damage
6. Protein misfolding, DNA damage

Answer 4

Question 5

What is pathology and why is it important? What do we start with and what is the next step after?

Answer 5

Pathology is the study of the structural, biochemical, and functional changes in cells, tissues, and function that underline disease.
Its important bc it serves as the bridge between the basic sciences and clinical medicine; is an important diagnostic.

You always start with gross path + staining and then move onto microscopy to see things at a cellular level.

Question 6

What ate the different aspects of disease?

Answer 6

There are 4:
1. Etiology- cause of disease (genetic or acquired)

2. Pathogenesis- sequence of events in the cell/tissue response to etiologic agent; ends at expression of disease.
   - ex: parkinsons: slow cellular changes in the brain.
3. Morphological (structural) and molecular (disease states) changes
4. Functional derangements and clinical manifestations- these are the symptoms of disease

Question 7

What is homeostasis and adaptation?

Answer 7

Homeostasis- range of steady state; can be pushed a little bit.

Adaptation- reversible changes to severe stressors and stimuli where the range of homeostasis is shifted –> allows cell to survive and continue functioning. (altered but steady state)

Question 8

Cell injury

Answer 8

Is reversible up to a certain point!
If the stimuli persists or is severe enough from the beginning–> cell suffers irreversible injury and eventually cell death.

Question 9

Tell me what the cellular responses for these injury/ stimuli would be

Answer 9

Question 10

Hypertrophy is caused by

Answer 10

increased functional demand or by stimulation by hormones and growth factors.
- ex: increase in hemodynamic load = larger/enlarged heart muscle, decrease CO bc of smaller lumen.
- reversible for a time.

Question 11

When does hyperplasia take place?

Answer 11

If the cell population is capable of dividing thus increasing the number of cells. not all cells can divide
- can be physiologic or pathologic.
- Ex: endometrial hyperplasia from hormone imbalance.

Question 12

Describe examples of pathological atrophy

Answer 12

Pathological atrophy depends on the underlying cause and can be local or generalized.

• use it or lose it: atrophy of disuse.
• tissue, muscle, or organ nerve damage or disconnect/ loss of innervation: denervation atrophy.
• atrophy from diminished/ decreased blood supply (ischemia) to a tissue bc of arterial occlusive disease.

Question 13

Diseases that cause vascular issues affect what the most?

Answer 13

The brain bc it is very vascular.

Question 14

example of ischemic injury/senile atrophy

Answer 14

alzheimer’s = large gaps in brain due to reduced blood supply (ischemia)

Question 15

What type of change is metaplasia?
What can it represent?

Answer 15

Metaplasia is a reversible changes in which one differentiated cell type is replaced by another cell type.
- It can represent an adaptive substitution of cells that are sensitive to stress by cell types that are better able to withstand the adverse environment. –> most common: cobblestones (squamous) takes over columns (columnar epi)

Question 16

What are the different causes of cell death?

Answer 16

We talked about 6!
1. Oxygen Deprivation
2. Physical agents: mechanical trauma, temp extremes, changes in atmospheric pressure, radiation.
3. Infectious agents
4. Immunologic rxns: immune reactions in response to toxic agents.
5. Genetic abnormalitiesL enzyme defects
6. Nutritional imbalances

Question 17

What are reversible injuries?

Answer 17

1. cellular swelling- this appears whenever cells are incapable of maintaining ionic and fluid homeostasis THUS is the result of failure of eneryy-dependent ion pumps in the plasma membrane.
2. Fatty changes

Question 18

Cellular swelling is the first manifestation of

Answer 18

Almost ALL forms of injury to cells.

Question 19

Define ultrastructural

Answer 19

Ultrastructural refers to the fine details of a cell or tissue that can only be observed using an electron microscope. This term is used to describe the minute structures within cells, such as organelles (like mitochondria, the endoplasmic reticulum, or lysosomes), membranes, and other subcellular components, that are not visible with a standard light microscope.

Question 20

What are ultrastructural changes of REVERSIBLE cell injury?

Answer 20

There are 4!
1. Plasma membrane alterations: like blebbing, blunting, and loss of microvilli.
2. Mitochondria changes: like swelling.
3. Dilation fo ER/ ER swelling.
4. Nuclear alterations: this is what differentiates necrosis and apoptosis.

Question 21

Tell me about necrosis

Answer 21

• Its morphological appearance is due to denaturation of intracellular proteins and enzymatic digestion of lethally injured cells.
• Necrotic cell are UNABLE to maintain membrane integrity and their contents often leak out–> elicit inflammation in surrounding tissues (affect neighboring tissues and cells).
  -the enzymes that digest necrotic cells are derives from the lysosomes of dying cells and leukocytes that are called in as part of the inflammatory reactions.
  -looks white bc proteins are being liquified !

Question 22

What are the features of necrosis and apoptosis for the following features?

Answer 22

Question 23

What are the types of necrosis discussed?

Answer 23

1. Coagulative necrosis: architecture of dead tissues is preserved for a span of at least some days.
2. Liquefactive necrosis: digestion of the dead cells –> tissue becomes liquid viscous mass.
3. Caseous necrosis: in foci of TB infection; cheesy!
4. Fat necrosis: focal areas of fat destruction; cause loss of blood supply over time.
5. Fibrinoid necrosis: special form of necrosis usually seen in immune reactions involving vessels.

Question 24

what is this

Answer 24

Coagulative necrosis

Question 25

What is this

Answer 25

liquefactive necrosis

Question 26

What is this

Answer 26

Caseous necrosis; CHEESE

Question 27

What is this

Answer 27

fat necrosis

Question 28

what is this

Answer 28

fibrinoid necrosis

Question 29

What about the liver makes it able to survive loss of oxygen and decrease oxidative phosphorylation better than other tissues?

Answer 29

It has greater glycolytic capacity. –> can produce ATP via glycolysis w/o O2.

Question 30

Describe the mechanism of injury of ischemia and decreased intracellular ATP during said cell injury.

Answer 30

Question 31

What are the pathological effects of free radicals ?

Answer 31

1. lipid peroxidation in membranes
2. Oxidative modification of proteins
3. Lesions in DNA (strand breakage, cross-linking of DNA strands, and formation of adducts).

Question 32

What is apoptosis in physiologic situations?

Answer 32

1. Programmed destruction of cells during embryogenesis.
2. Involution of hormone-dependent tissues upon hormone withdrawal.
   - regression of lactating breast after weaning,
3. Cell loss in proliferating cell populations –> avoid auto-immune disorders.

Question 33

Describe the pathological effects of ROS when it reacts with:
1) fatty acids
2) proteins
3) DNA

Answer 33

1) Fatty acids –> oxidation –> lipid peroxidase generation–> disruption of plasma membrane, organelles.

2) Proteins –> oxidation–> loss of enzymatic activity and abnormal folding.

3) DNA –> oxidation –> mutation, strand breakage.

Question 34

Give examples of apoptosis in physiologic situations

Answer 34

1) programmed destruction of cells during embryogenesis like developmental involution.
2) Involution of hormone-dependent tissues upon hormone withdrawal like regression of lactating breast after weaning.
3) Cell loss in proliferating cell populations- get rid of useless cells so the body doesn’t attack it–> how to avoid auto-immune disorders.

Question 35

What triggers apoptosis?

Answer 35

intrinsic and extrinsic stimuli.

Question 35

When there’s cytochrome c leakage, does that cause necrosis or apoptosis?

Answer 35

Cytochrome c leakage triggers apoptosis by activating a cascade of proteolytic enzymes (caspases) that result in programmed cell death. * remember extrinsic and intrinsic pathways*

This is distinct from necrosis, which is an uncontrolled form of cell death that does not involve cytochrome c and leads to cell lysis and inflammation.

Question 36

elevated albumin= ?
lowered = ?

Answer 36

dehydration or diarrhea
kidney and liver dysfunction

Question 37

elevated globulins=?
lowered= ?

Answer 37

infection, autoimmune disease, cancer
hepatotoxicity or renal disease

Question 38

duration of exposure:
- acute
- subacute
- subchronic

Answer 38

• acute: single dose, observed over 14 days.
• subacute: repeated dosing for 14 days.
• subchronic: 90 day exposure

Question 39

On what effects are we observing for acute exposure?

Answer 39

BW, food consumption, behavior, morbidity.

Question 40

what are the goals if subacute testing?

What’s monitored?

Answer 40

• Maximum tolerated dose –> no more than 10% decrease in BW–> figure out what really works.
  -BW, bloodwork and UA.

Question 41

What happens if histopathology is observed in the subacute study?

Answer 41

additional measurements may be indicated in a subchronic test –> Thyroid fucntion, adrenal activity, pancreatic function, renal parameters, and bile formation.

Question 42

for subchronic testing, if nothing happens in 90 days=?

Answer 42

nothing is gonna happen PERIODT.

Question 43

What are the goals of subchronic toxicity testing?

Answer 43

• long term effects on organs.
• if theres a NOAEL dose and LOAEL dose. –> predict safe levels of exposure–> guides dose selection if chronic toxicity tests are needed.

Question 44

What are the toxic effects on health?

Answer 44

6!
Developmental
Reproductive
Neurological
Immunological
Mutagenesis
Carcinogenesis

Question 45

What are the goals of acute, subacute, subchronic, and chronic toxicity testing?

Answer 45

• Acute: Identify immediate toxic effects and lethal doses from a single or short-term exposure.
• Subacute: Examine short-term repeated exposure for cumulative toxic effects and target organ toxicity.
• Subchronic: Assess medium-term exposure for more detailed dose-response information and identify NOAEL.
• Chronic: Evaluate long-term toxicity and potential for serious health outcomes like cancer or chronic organ damage from prolonged exposure.