Cellular adaptation and cellular injury Flashcards
How are cells injured/die?
when the stressors increase to an extent that the cell is incapable to adapt
What is meant by cellular adaptation and what are the ways a cell can adapt with?
Adaptation is when physiologic/pathologic stressors induce a new state that changes the cell, preserving its viability against all exogenous stimuli:
1) Hypertrophy: Expansion in size
2) Atrophy: shrinkage in size
3) Hyperplasia: Increased cell count
4) Hypoplasia: reduction in cell number
5) Metaplasia: alteration in the cell type
What are the different forms of atrophy, and what bodily structure do they affect?
- Loss of cell substance causing the cell to shrink in size
1) Physiologic:
- Development: (Thyroglossal duct)
- Uterus following parturition
2) Pathologic:
- Decreased workload (Disuse tissue)
- Loss of innervation (denervation atrophy)
-Decreased blood supply (Brain atrophy)
- Loss of endocrine function (Endocrine gland
2) Aging (Senile atrophy)
What is the mechanism behind atrophy?
The biochemical mechanism behind atrophy is simply the imbalance between protein synthesis and degradation, like in the head it will reduce the gyri size and widen the sulcus
What is meant by downsizing?
For example in muscle ischemic atrophy, the number of muscle cells is the same but fiber size is reduced, it is a response to injury as it requires less and survives for a longer period of time
What is meant by senile atrophy?
atrophy that is caused by aging
What is hypertrophy?
- The increase of cell size via the gain of cellular substance
- Due to increased demand or endocrine stimuli
What is the mechanism of hypertrophy?
Involves signal transduction pathway, which leads to the induction of genes that stimulate the synthesis of numerous cellular proteins
What are some bad examples of hypertrophy?
1) Heart (for example; Left ventricle thickening due to high blood pressure, but this isn’t supported by the blood volume which can lead to ischemia/MI)
2) Liver
Is Adaptation a reversible process?
yes but to an extent
What is Hyperplasia?
It is an increase in the number of cells in an organ
- It often predisposes neoplasia (as it can lead to uncontrolled proliferation, malignancy-neoplasia-cancer)
- Mechanism: If the cellular population is capable of synthesizing DNA permitting mitotic division
What can cause hyperplasia?
1) Physiologic
2) Pathologic
What are the types of physiologic hyperplasia?
1) Hormonal hyperplasia: increases the functional capacity of tissue when needed (physiologic hyperplasia occurring in a pregnant uterus)
2) Compensatory hyperplasia: Increases tissue mass after damage/partial resection (after unilateral nephrectomy), it depends on regenerative and proliferative capacity
What causes pathologic hyperplasia?
The main reason is the excessive hormonal stimulation/growth factors that are acting on target cells (nodule-like structure is seen)
What is metaplasia?
Reversible change where an adult cell is replaced by an adult cell but of a different type, which is more suited to tolerate a specific abnormal environment (smoking, changes ciliated epithelium into the squamous type)
- Normal protective mechanisms may be lost, if the signal persists it might lead to neoplasia
What are the different cellular injury mechanisms?
1) Mitochondrial Injury:
- Decreased ATP
- Increase in ROS that can damage lipids, proteins, and DNA
2) Loss of Ca2+ homeostasis:
(Increases mitochondrial permeability and activates multiple cellular enzymes)
3) Membrane damage:
- In the plasma membrane we will lose the cellular components
- In the lysosomal membrane the enzymes in it will digest cellular components
4) Protein misfolding, DNA damage:
- Activates pro-apoptotic proteins
What are the causes of cellular injury?
Physical, chemical, or biological insults or a vital substrate deficiency
1) Hypoxia (O2 deficiency) or Ischemia (reduced blood supply)
2) Toxins (air pollutants, insecticides, CO, etc)
3) Infectious agents
4) Immunologic reactions
5) Genetic abnormalities
6) Nutritional imbalances
7) Physical agents (radiation, extreme temperature)
8) Aging
What are the marks of a reversible cell injury?
1) Swelling of endoplasmic reticulum and mitochondria
2) Membrane plebs
3) Fatty changes
What are the structural changes that happen in a reversible cell injury?
1) Small clear vacuoles (distending the ER)
2) The cytoplasm becomes redder (Eosinophilic)
3) The alteration in the plasma membrane (blebbing, microvilli distortion, etc)
4) Mitochondrial changes (Swelling)
5) Dialation of (ER)
6) Nuclear alteration (clumping of the chromatin)
What causes a cell to be irreversibly damaged? and what is the fate of an irreversibly damaged cell?
- Severe/progressive injurious stimuli cause the cell to become irreversibly damaged
- It can lead to cell death (either Necrosis or Apoptosis)
What happens in reversible cellular injury?
1) Decrease in ATP
2) Decrease in Na/K pump activation
3) Increase of Na in the cell
4) Increase in water uptake inside the cell (osmosis, due to energy-dependant failure of the pump)
5) cell will swell
- This is an example of a reversible cell injury
What are the types of cell death?
- When cells die they die in different ways depending on the nature and severity of the insult:
1) Necrosis
2) Apoptosis
Define necrosis
- Morphologic manifestation of accidental cell death
- Rapid and uncontrollable
- Injuries that stimulate this type of cell death include (ischemia, toxins, various infections, and trauma)
What is the main difference between apoptosis and necrosis?
1) Cell Size:
- Necrosis: Enlarged (Swelling)
- Apoptosis Reduced (shrinkage)
2) Nucleus:
- Necrosis: Pyknosis - karorhexis - kharyolysis
- Apoptosis: fragmentation
3) Plasma membrane:
- Necrosis: Disrupted
- Apoptosis: instact
4) Cellular contents:
- Necrosis: enzymatic digestion, might leak out of cell
- Apoptosis: Intact but released in apoptotic bodies
5) Adjacent inflammation:
- Necrosis: Frequent
- Apoptosis: No
6) Physiologic/pathologic role:
- Necrosis: accumulation of irreversible cell damage (invariably pathologic)
- Apoptosis: Often physiologic
