Lect.2

Cellular response to Cellular response to injuryinjury

adaptation and injuryadaptation and injury

Cellular response to Cellular response to injuryinjury

adaptation and injuryadaptation and injury

• Normal cell is in a steady state “Homeostasis”

• Cells constantly adjust structure and function to accommodate changing demands and extracellular stress.

• But within a relatively narrow range of physiologic parameters.

• Change in Homeostasis due to prolonged stimuli Injury

FUNCTIONAL DEFINITION FUNCTIONAL DEFINITION OF DISEASEOF DISEASE

ABNORMAL HOMEOSTASIS

CELLULAR ADAPTATIONCELLULAR ADAPTATION• A new altered state between normal,

unstressed cell and the injured, overstressed cell due to excessive physiologic stresses & some pathologic stimuli.

• A new abnormal state but remains functional i.e. preserving the viability of the cell.(i.e. able to maintain homeostasis.

• Reversible

Types of adaptationTypes of adaptation

HyperplasiaHyperplasia - ↑ organ size due - ↑ organ size due to ↑ cell no.to ↑ cell no.

HypertrophyHypertrophy - ↑ organ size due - ↑ organ size due to ↑ cell mass or size.to ↑ cell mass or size.

AtrophyAtrophy - ↓ organ size due to ↓ - ↓ organ size due to ↓ cell mass & no. cell mass & no.

MetaplasiaMetaplasia – change from one – change from one adult tissue to anotheradult tissue to another

HYPERPLASIAHYPERPLASIA• An organized increase in number of cells (versus: dysplasia, which An organized increase in number of cells (versus: dysplasia, which

is disorganized growth, and neoplasia, which is new growth).is disorganized growth, and neoplasia, which is new growth).

• It occurs in tissues with cells that are capable of mitotic division “i.e. Hyperplasia essentially does not occur in the brain , heart & skeletal Hyperplasia essentially does not occur in the brain , heart & skeletal muscle.muscle.

HYPER-PLASIAHYPER-PLASIAIN-CREASE IN NUMBER OF CELLS

HYPERTROPHYHYPERTROPHY• Increase in the sizes of cells, and hence the size of the organ ultimately increase in the amount of functioning

tissue mass

HYPER-TROPHYHYPER-TROPHYIN-CREASE IN SIZE OF CELLS

Cellular adaptation (con’t)Cellular adaptation (con’t)

**Hyperplasia and hypertrophy can be difficult **Hyperplasia and hypertrophy can be difficult to separate--not possible by gross exam; to separate--not possible by gross exam; difficult by microscopic exam. In most cases, difficult by microscopic exam. In most cases, both hyperplasia and hypertrophy occur both hyperplasia and hypertrophy occur together (e.g., breast and uterus during together (e.g., breast and uterus during pregnancy).pregnancy).

Hyperplasia essentially does not occur in the Hyperplasia essentially does not occur in the brain , heart and skeletal muscles.brain , heart and skeletal muscles.

HyperplasiaHyperplasia PhysiologicPhysiologic: ( Hormonal & compensatory): ( Hormonal & compensatory)

• Breast enlargement during pregnancy&puberty Breast enlargement during pregnancy&puberty (and hypertrophy)(and hypertrophy)

• Uterine enlargement during pregnancy (and Uterine enlargement during pregnancy (and hypertrophy)hypertrophy)

• Liver re-growth after partial resection Liver re-growth after partial resection Pathologic:Pathologic: ( mostly hormonal )( mostly hormonal )

• Benign prostatic hyperplasia ( due to androgens)Benign prostatic hyperplasia ( due to androgens)• Endometrial hyperplasia (due to estrogen)Endometrial hyperplasia (due to estrogen)• Viral infections (warts due to human papilloma Viral infections (warts due to human papilloma

virus). Effects of locally produced GFs on target virus). Effects of locally produced GFs on target cells. cells.

• Endocrine organs with increased stimulus (e.g., Endocrine organs with increased stimulus (e.g., goiter)goiter)

Thyroid goiter (Diffuse thyroid hyperplasia)

Insufficient available dietary iodine cannot make enough thyroid hormones. Extra demand by pituitary TSH cause thyroid enlargement

HypertrophyHypertrophy

PhysiologicPhysiologic• Skeletal muscle hypertrophy associated with Skeletal muscle hypertrophy associated with

exerciseexercise• Compensatory hypertrophy of kidney after removal Compensatory hypertrophy of kidney after removal

of other kidneyof other kidney PathologicPathologic

• Cardiac hypertrophy due to hypertension, valvular Cardiac hypertrophy due to hypertension, valvular stenosis or insufficiencystenosis or insufficiency

• Asthma--smooth muscle hypertrophyAsthma--smooth muscle hypertrophy• Hypertrophy of bladder associated with prostatic Hypertrophy of bladder associated with prostatic

gland hyperplasiagland hyperplasia

Hypertrophy of the muscles of a strength athlete                                                       

Heart Heart hypertrophy in hypertrophy in hypertension:hypertension:

Left VentricleLeft Ventricle

Lt. Ventricular hypertrophyLt. Ventricular hypertrophy

Hypertrophy of the Uterus

ATROPHYATROPHY

• atrophy is defined as decrese in the size or function of an organ due to decrease in

cell size 1st and number of cells 2nd. • Can be physiologic or pathologicCan be physiologic or pathologic

AtrophyAtrophy PhysiologicPhysiologic

• Regression in size of breasts and uterus after Regression in size of breasts and uterus after pregnancy, thymus atrophy at adulthood.pregnancy, thymus atrophy at adulthood.

PathologicPathologic• Disuse or ↓ workload (skeletal muscle atrophy in Disuse or ↓ workload (skeletal muscle atrophy in

fracture)fracture)• Loss of endocrine stimulus (adrenal atrophy in Loss of endocrine stimulus (adrenal atrophy in

patients on steroids)patients on steroids)• Denervation ( polimyelitis ,paraplasia).Denervation ( polimyelitis ,paraplasia).• Inadequate nutritionInadequate nutrition• Decreased blood supply or Ischemia (atrophy of Decreased blood supply or Ischemia (atrophy of

kidney due to renal artery stenosis).kidney due to renal artery stenosis).• Aging or Senile atrophy.Aging or Senile atrophy.• Compression atrophy. Compression atrophy.

Morphology of atrophyMorphology of atrophy

*Reduction in the number of *Reduction in the number of cell’s organelles.cell’s organelles.

*Increase in the number of *Increase in the number of autophagic vacuoles.autophagic vacuoles.

*Lipofuscin granules (Brown *Lipofuscin granules (Brown atrophy)atrophy)

Cerebral atrophy - Alzheimers:Cerebral atrophy - Alzheimers:

Normal Atrophic

Lipofuscin granules

Skeletal muscle atrophy:Skeletal muscle atrophy:

Hydronephrosis

Metaplasia "A reversible adaptive change in which one adult or fully differentiated cell type replaced by another adult cell type.“ "Conversion of a differentiated cell type into another" of same or less functional activity.of same or less functional activity. genetic reprogramming of stem cells.genetic reprogramming of stem cells.Always pathologicAlways pathologic

•Squamous metaplasiaSquamous metaplasia

•Glandular metaplasiaGlandular metaplasia

Bronchial epitheliaBronchial epithelia

Epithelia in bile ductEpithelia in bile duct

Cervical epitheliaCervical epithelia

Epithelial metaplasia Epithelial metaplasia

Columnar epithelium

Squamous epithelium

Squamous epithelium

Barrett’s esophagitis

significance of metaplasia

o A two-edged sword

o An undesirable change

o Cells survive but some important protective mechanism is lost.

o The influences that predispose to such squamous metaplasia, if persistent, may promote cancer transformation in metaplastic epithelium.

All Cellular adaptation types All Cellular adaptation types are reversibleare reversible

Both Both Hyperplasia & Metaplasia Hyperplasia & Metaplasia are preneoplastic:are preneoplastic:

i.e. fertile soil for neoplastic transformation.i.e. fertile soil for neoplastic transformation.

while while hypertrophy & atrophy hypertrophy & atrophy are NOT preneoplastic .are NOT preneoplastic .