Cellular Adaptation

Question 1

Depending on the nature of stimulus/injury, by cellular responses can be mainly divided into four types

Answer 1

1. Cellular adaptations
   •2. Cell injury
   •–– Reversible cell injury
   •–– Irreversible cell injury
   •3. Intracellular accumulations
   •4. Pathologic calcification.

Question 2

Cellular response to injury depends on:

Answer 2

•1. Type of injury
•2. Duration of injury
•3. Severity of injury

Question 3

CELLULAR ADAPTATION

Answer 3

•When the cell is exposed to pathological stimuli, the cells can achieve a new, steady altered state that allows them to survive and continue to function in an abnormal environment.
•These are reversible changes and constitute cellular adaptations.

Question 4

Different patterns of cellular adaptations include:

Answer 4

•• Hypertrophy
•• Hyperplasia
•• Atrophy
•• Metaplasia

Question 5

Adaptation may be

Answer 5

physiological or pathological

Question 6

Fate of adapted tissue

Answer 6

•1. If the stress is eliminated-can return to its original state.
•2. If exposed to injurious agents or stress beyond the tolerable limits results in cell injury.

Question 7

HYPERTROPHY

Answer 7

•Definition: Increase in the size of the tissue or organ due to increase in the size of cells.
•Hypertrophy: Occurs in tissues incapable of cell division.
•Hypertrophy without hyperplasia occurs in non-dividing cells such as cardiac, skeletal and smooth muscle as a response to increased workload.

Question 8

Physiological Causes of hypertrophy

Answer 8

:
•Increased functional demand/workload.
••• Physiological:
•–– Hypertrophy of skeletal muscle: e.g. the bulging muscles of body builders and athletes.
•–– Hypertrophy of smooth muscle: e.g. growth of the uterus during pregnancy from estrogenic stimulation.

Question 9

Pathological causes of hypertrophy

Answer 9

Pathological:
•–– Hypertrophy of cardiac muscle: e.g. left ventricular hypertrophy due to hypertension or damaged valves (aortic stenosis, mitral incompetence).
•–– Hypertrophy of smooth muscle: e.g. hypertrophy of urinary bladder muscle in response to urethral obstruction (e.g. prostate hyperplasia), hypertrophy of muscular layer of stomach due to pyloric stenosis.

Question 10

• Steps involved in biochemical mechanisms of hypertrophy

Answer 10

Hypertrophy is due to increased synthesis of cellular proteins.
• Steps involved in biochemical mechanisms of hypertrophy, e.g. myocardial (cardiac muscle) hypertrophy are :
•1. Activation of the Signal Transduction Pathways
•2. Activation of transcription factors.

Question 11

MECHANISM OF PHYSIOLOGIC HYPERTROPHY

Answer 11

MECHANISM OF HYPERTROPHY
Physiologic Hypertrophy:
••• Mechanical stretch: Increased work load on the myocardium produces mechanical stretch and is the major trigger for physiological hypertrophy.

Question 12

MECHANISM OF HYPERTROPHY in
Pathologic Hypertrophy

Answer 12

MECHANISM OF HYPERTROPHY
Pathologic Hypertrophy:

*Growth factors (e.g., TGF-β, IGF-1, FGF) and hypertrophy agonists (e.g., α-adrenergic agonists, endothelin-I, angiotensin II, nitric oxide (NO), and bradykinin) are involved in pathologic hypertrophy.

*Mechanical sensors also stimulate production of growth factors and agonists. They cause increased synthesis of muscle proteins.

Mechanical stretch, growth factors and hypertrophy agonists activate the signal transduction pathways and transcription factors (e.g. Myc, Fos, Jun).
*The activated transcription factors results in:-
- Increased synthesis of cellular contractile proteins
- Induction of embryonic/fetal genes (ANF)
- Increased production of growth factors.

Question 13

HYPERTROPHY- MORPHOLOGY

Answer 13

•Gross: Involved organ is enlarged.
•Microscopy: Increase in size of the cells as well as the nuclei.

•Hypertrophy of subcellular organelle can sometimes occur (e.g. hypertrophy of the smooth endoplamic reticulum in hepatocytes by barbiturates and alcohol).

Question 14

HYPERPLASIA

Answer 14

•Definition: Increase in the number of cells in an organ or tissue, resulting in increased size/mass of the organ or tissue.
•Hyperplasia occurs in cells capable of replication namely labile/stable or stem cells.
•Not in permanent cells.

Question 15

Physiological causes of hyperplasia

Answer 15

Causes
••• Physiological hyperplasia: Hormonal stimulation, or as compensatory process.
•–– Hyperplasia due to hormones: e.g. hyperplasia of glandular epithelium of the female breast at puberty, pregnancy and lactation, hyperplasia of the uterus during pregnancy from estrogenic stimulation.
•–– Compensatory hyperplasia: e.g. in liver following partial hepatectomy

Question 16

Cause of Pathological hyperplasia

Answer 16

Pathological hyperplasia: Due to excess endocrine stimulation or chronic injury/irritation.
•–– Excessive hormonal stimulation: e.g. endometrial hyperplasia (due to estrogen) and benign prostatic hyperplasia (due to androgens).

•–– Chronic injury/irritation: Long-standing inflammation or chronic injury may lead to hyperplasia especially in skin or oral mucosa.
•Pathological hyperplasia can progress to cancer, e.g. endometrial hyperplasia can develop into endometrial cancer.

Question 17

Hyperplasia mechanism

Answer 17

Hyperplasia is characterized by cell proliferation mostly of mature cell mediated through stimulation by growth factor or hormones.
••• Some instances, the new cells may be derived from tissue stem cells.

Question 18

HYPERPLASIA-MORPHOLOGY

Answer 18

•Morphology
••• Gross: Size of the affected organ is increased.
••• Microscopy: Increased number of cells with increased number of mitotic figures.

•Hyperplasia unlike neoplasia can regress, if the stimulation is eliminated.

Question 19

ATROPHY

Answer 19

•Definition: Atrophy is the reduced size of an organ or tissue resulting from a decrease in cell size and number.
•The size/weight of the involved tissue /organ is reduced.
•Function of an organ is also reduced.

Atrophy may be reversible but with irreversible loss of cells and the size of the organ cannot be restored.
•In atrophy cell death is mainly due to apoptosis.

Question 20

Causes of Physiological atrophy

Answer 20

Causes
•Physiological atrophy: Common during normal fetal development, and in adult life.
••• During fetal development: e.g. atrophy of embryonic structures such as thyroglossal duct.
••• During adult life: e.g. involution of thymus, atrophy of brain and heart due to aging (senile atrophy).

Question 21

Cause of Pathological atrophy

Answer 21

Pathological atrophy: Local or generalized.
•1. Local
••• Disuse atrophy (decreased workload): e.g. atrophy of limb muscles immobilized in a plaster cast (as treatment for fracture) or after prolonged bed rest

•• Denervation (loss of innervation) atrophy: e.g. atrophy of muscle due to damage to the nerves (e.g. poliomyelitis).
••• Loss of endocrine stimulation: Occurs in hormone-responsive tissues such as breast and reporductive organs (e.g., loss of estrogen stimulation after menopause results in physiologic atrophy of the endometrium, vaginal epithelium and breast.

••• Ischemic (diminished blood supply) atrophy: e.g. brain atrophy produced by ischemia due to atherosclerosis of the carotid artery.
••• Pressure atrophy: e.g. atrophy of renal parenchyma in hydronephrosis due to increased pressure.

Question 22

Generalized cause of atrophy

Answer 22

Starvation (inadequate nutrition) atrophy: e.g. protein-calorie malnutrition.

Question 23

ATROPHY-MECHANISM

Answer 23

•Atrophic cells have diminished function. There is decreased protein synthesis and increased protein degradation in cells.

•Decreased synthesis of cellular proteins or increased breakdown of cellular organelles.

Question 24

ATROPHY-MORPHOLOGY

Answer 24

•Morphology
••• Gross: The organ is small and often shrunken.
••• Microscopy: The cells are smaller in size due to reduction in cell organelles
•Atrophied cells have increased lipofuscin (wear and tear) pigment.

Question 25

METAPLASIA

Answer 25

•Definition:
• Metaplasia is a reversible change in which one adult cell type is replaced by another adult cell type.

Question 26

METAPLASIA-CAUSES

Answer 26

•Causes
••• Metaplasia is usually fully reversible adaptive response to chronic persistent injury.
• If the noxious stimulus is removed (e.g. cessation of smoking), the metaplastic epithelium may return to normal.

Metaplasia is mainly seen in association with tissue damage, repair, and regeneration.
••• The replacing cell type is usually more suited to a change in environment.

Question 27

METAPLASIA-TYPES

Answer 27

EPITHELIAL METAPLASIA
Connective tissue METAPLASIA

Question 28

1. EPITHELIAL METAPLASIA types

Answer 28

Most Common Type. It includes:
A. Squamous metaplasia: Original epithelium is replaced by squamous epithelium.
••• Respiratory tract: e.g. chronic irritation due to tobacco smoke, the normal ciliated columnar epithelial cells of the trachea and bronchi undergo squamous

B. Columnar metaplasia: Original epithelium is replaced by columnar epithelium.
••• Squamous to columnar: In Barrett esophagus, the squamous epithelium of the esophagus replaced by columnar cells.
••• Intestinal metaplasia: The gastric glands are replaced by cells resembling those of the small intestine.

Question 29

CONNECTIVE TISSUE METAPLASIA

Answer 29

••• Osseous metaplasia: Formation of new bone at sites of tissue injury is known as osseous metaplasia.
•Bone formation in muscle, known as myositis ossificans, occasionally occurs after intramuscular hemorrhage.