lectures 28-29

Question 1

Understand how cells respond to injury (entire process).

Answer 1

Normal cell (homeostasis): cells maintain their intracellular environment within a narrow range of physiological parameters

Adaptation: as cells encounter physiological and pathological stimuli, they can undergo adaptation, achieving a new steady state and preserving viability and function by changing their size, number, and form (atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia)

Cell injury: occurs when cells are stressed to the point that they are unable to adapt (reversible cell injury, sub-cellular alterations, and apoptosis)

Cell death (2 kinds): one of the most crucial events in the evolution of disease in any tissue or organ (e.g., ischemia, infections, toxin and immune responses)

1. Apoptosis: specific programmed cell death, no immediate immune response
2. Necrosis: cell contents are released, triggering an immune response to the area and inflammation

Question 2

Understand five major cellular adaptations in response to injury or stimuli. Pay close attention to definition, possible causes, outcomes, and the differences in these adaptations.

Answer 2

1. Atrophy:
   - shrinkage in the cell size by the loss of cell substance; decrease in the size of a tissue or organ; no decrease in cell number
   - frequently caused by decreased workload, loss of innervation, reduced blood supply, inadequate nutrition, or aging (senile atrophy)
   - decreased cell size is caused by _____ or _____.
2. Hypertrophy:
   - an increase in the size of cells resulting in increase in the size of the organ; no increase in cell number
   - only occurs in cells that are incapable of dividing (striated muscle cells in both skeletal muscle and the heart)
   - commonly caused by increased workload (physiological stimuli or pathological conditions)
   - characterized by increased protein synthesis
3. Hyperplasia:
   - increase in the number of cells (not cell size)
   - can be physiological and pathological
   - physiologic hormonal hyperplasia, such as the proliferation of the female mammary epithelium during puberty
   - proliferation of connective tissue cells during wound healing
   - physiologic compensatory hyperplasia, such as the regeneration of a partially resected liver by the remaining hepatocytes
   - pathologic hyperplasia is typically the result of excessive hormonal or growth factor stimulation, hyperplastic tissue may eventually become malignant
4. Metaplasia:
   - a reversible change in which _____
   - often a response to chronic irritation and inflammation that makes the cells better able to withstand stress
   - frequently a precursor to malignancy
   - may be caused by reprogramming of stem cells rather than by transdifferentiation of mature cells
   - examples: Ciliated columnar epithelial cells of the trachea and bronchi help clear foreign materials and mucous. In smokers, they are replaced by squamous epithelial cells, which are more rugged but not ciliated. This leads to coughing and an increase in infections.
5. Dysplasia:
   - characterized by deranged cell growth of a specific tissue that results in cells that vary in size, number, shape, and organization

Question 3

Understand 8 causes of cell injury and examples for each of them.

Answer 3

1. oxygen deprivation- hypoxia, ischemia
2. chemical agents- poisons, air pollutants, CO, asbestos
3. infectious agents- viruses, bacteria, fungi, parasites
4. immunological reactions- immunological defects
5. genetic defects- sickle cell anemia, familial hypercholesterolemia
6. physical agents- trauma, heat, cold, electric shock
7. nutritional imbalances- nutritional deficiencies, excess nutrition, diabetes, atherosclerosis
8. aging- accumulation of damage by ROS, loss of telomerase function

Question 4

The characteristics of reversible versus irreversible cell injury.

Answer 4

reversible injury:
- _____ is the result of failure of energy-dependent ion pumps in the plasma membrane, leading to an inability to maintain ionic and fluid homeostasis
- _____ occurs in hypoxic injury and various forms of toxic or metabolic injury, and is manifested by the appearance of small or large lipid vacuoles in the cytoplasm. It mainly occurs in cells involved in metabolism such as hepatocytes and myocardial cells

irreversible injury:
- inability to reverse _____ (lack of oxidative phosphorylation and ATP generation)
- profound disturbances in membrane function (_____)

Question 5

Understand the mechanisms of cell injury (ATP depletion, mitochondria damage, membrane damage, calcium influx, increased ROS).

Question 6

Understand the inducers and mechanisms of the two apoptotic pathways.

Question 7

Understand the difference between apoptosis and necrosis.

Question 8

Understand the role of major players in the two apoptotic pathways (Bcl-2, Bax, caspase-3, 7, 9, cytochrome c) and DNA fragmentation.