Cellular adaptation and cellular injury

Question 1

How are cells injured/die?

Answer 1

when the stressors increase to an extent that the cell is incapable to adapt

Question 2

What is meant by cellular adaptation and what are the ways a cell can adapt with?

Answer 2

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

Question 3

What are the different forms of atrophy, and what bodily structure do they affect?

Answer 3

• 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)

Question 4

What is the mechanism behind atrophy?

Answer 4

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

Question 5

What is meant by downsizing?

Answer 5

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

Question 6

What is meant by senile atrophy?

Answer 6

atrophy that is caused by aging

Question 7

What is hypertrophy?

Answer 7

• The increase of cell size via the gain of cellular substance
• Due to increased demand or endocrine stimuli

Question 8

What is the mechanism of hypertrophy?

Answer 8

Involves signal transduction pathway, which leads to the induction of genes that stimulate the synthesis of numerous cellular proteins

Question 9

What are some bad examples of hypertrophy?

Answer 9

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

Question 10

Is Adaptation a reversible process?

Answer 10

yes but to an extent

Question 11

What is Hyperplasia?

Answer 11

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

Question 12

What can cause hyperplasia?

Answer 12

1) Physiologic

2) Pathologic

Question 13

What are the types of physiologic hyperplasia?

Answer 13

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

Question 14

What causes pathologic hyperplasia?

Answer 14

The main reason is the excessive hormonal stimulation/growth factors that are acting on target cells (nodule-like structure is seen)

Question 15

What is metaplasia?

Answer 15

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

Question 16

What are the different cellular injury mechanisms?

Answer 16

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

Question 16

What are the causes of cellular injury?

Answer 16

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

Question 16

What are the marks of a reversible cell injury?

Answer 16

1) Swelling of endoplasmic reticulum and mitochondria
2) Membrane plebs
3) Fatty changes

Question 16

What are the structural changes that happen in a reversible cell injury?

Answer 16

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)

Question 16

What causes a cell to be irreversibly damaged? and what is the fate of an irreversibly damaged cell?

Answer 16

• Severe/progressive injurious stimuli cause the cell to become irreversibly damaged
• It can lead to cell death (either Necrosis or Apoptosis)

Question 16

What happens in reversible cellular injury?

Answer 16

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

Question 16

What are the types of cell death?

Answer 16

• When cells die they die in different ways depending on the nature and severity of the insult:

1) Necrosis

2) Apoptosis

Question 16

Define necrosis

Answer 16

• Morphologic manifestation of accidental cell death
• Rapid and uncontrollable
• Injuries that stimulate this type of cell death include (ischemia, toxins, various infections, and trauma)

Question 17

What is the main difference between apoptosis and necrosis?

Answer 17

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

Question 17

Describe Apoptosis

Answer 17

• Programmed cell death which appears when the injury is less severe, or we need to eliminate the cells during a normal process
• Activates a precise cellular pathway to activate this type of cell death

Question 17

What characterizes necrosis?

Answer 17

• Loss of membrane integrity
• Enzymatic digestion of cells
• Leakage of cellular contents
• Produce a reaction within the host

Question 17

What characterizes Apoptosis?

Answer 17

• The cell’s active enzyme degrades the cell’s own nuclear DNA and cytoplasmic proteins
• Fragments of the cell then fall off
• Fragments are rapidly cleared out by phagocytes making them not induce an inflammatory reaction

Question 17

What are the cytoplasmic changes that occur in necrosis?

Answer 17

• Increased eosinophilia
• Denaturation of cytoplasmic proteins
• Loss of basophilic (RNA) in the cytoplasm
• When enzymes digest the cytoplasmic organelles, the cytoplasm becomes vacuolated and appears (mouth-eaten)

Question 17

What are the types of necrosis?

Answer 17

• Necrosis (irreversible): The tissue appears opaque, firm and dry

1) Coagulative - Infarction
2) Liquefaction - Brain, abscess
3) Caseous - Bacterial / Tuberculosis
4) Fat Necrosis
5) Gangrene

Question 17

What are the nuclear changes that occur in necrosis?

Answer 17

• Due to DNA & chromatin breakdown

1) Karyolysis “Nuclear fading” (Basophilia fades, due to DNA digestion by deoxyribonuclease (DNase & RNase) activity)

2) Pyknosis “Nuclear shrinkage” (Increased basophilia, DNA condenses into a shrunken basophilic mass)

3) Karyorhexis “Nuclear fragmentation” (pyknotic nucleas ruptures & undergoes fragmentation)

Question 17

What are the different types of intracellular accumulations?

Answer 17

1) Abnormal constituents:
- Hemosiderin (in iron overload)
- Copper (Wilsons disease)

2) Exogenous Constituents:
- Carbon pigment in lungs
- Silicosis

3) Lipofuscin ()spots on very old skin):
- Wear & tear pigment in aging (Brown atrophy)

Question 17

What is special regarding lipid accumulation? and how does it accumulate?

Answer 17

• Defects in any of the steps in uptake, catabolism, or secretion results in lipid accumulation (alcohol stimulates its accumulation)
• What is special about it is that it does not accumulate inside the cell but outside
• For example, atherosclerosis is due to the accumulation of cholesterol/cholesterol esters above the membrane

Question 17

What causes abnormal pigmentation?

Answer 17

1) Exogenous (tattoos)

2) Endogenous: synthesized within the body

• Some times like in carbon once it enters to the body the macrophages captures it and do not know what to do with it causing the black color in the lungs due to the inability of carbon to go out of the body

Question 17

What are the ways where calcium deposition might occur?

Answer 17

1) Dystrophic calcification:
- In nonviable(wounded)/dying tissue, in the presence of normal calcium serum levels (occurs in atherosclerosis, damaged valves, areas of necrosis)

2) Metastatic calcification:
- in Viable tissue, associated with hypercalcemia

Question 17

What is meant by abnormal calcification?

Answer 17

• The abnormal tissue deposition of calcium

Question 18

What is the name of the process that occurs in the breast, allowing a mother to breastfeed?

Answer 18

Lobular hyperplasia

Question 19

Brain atrophy is caused by which type of necrosis?

Answer 19

Liquifactive necrosis

Question 20

What is the difference between cytokeratins and vimentin?

Answer 20

1) Cytokeratin is found in carcinoma which is derived from epithelium, while vimentin is found in sarcoma derived from mesenchymal cells

Question 21

A deficiency in which vitamin can cause epithelial metaplasia?

Answer 21

Vitamin A

Question 22

What is the main cause of increased cell size of the uterus during pregnancy?

Answer 22

myometrium hyperplasia