Cellular Adaptations

Cellular adaptations • Cells respond to excessive physiologic/path stimuli by undergoing a number of physiologic & morphologic cellular adaptations, in which a new but altered state is achieved which preserves the morphology of cell and modulates its function.

Contd… • • • • •

HyperplasiaHypertrophy Atrophy Metaplasia Intracellular accumulations of lipids,proteins, carbohydrates & pigments

Hyperplasia • An increase in no of cells in an organ or tissue , which then may have an increased volume • Physiologic – • Hormonal – proliferation of glandular epith of female breasr at puberty or hyperplasia of pregnant uterus • Compensatory - partial hepatectomy

Pathologic hyperplasia • Excessive hormonal stimulationendometrial hyperplasia • Response of connective tissue cells in wound healing • Skin warts – in cetain viral infections like papilloma viruses.

Hypertrophy • An increase in size of cells & thus an increase in the size of the organ. • No new cells just larger cells. • Physiologic or pathologic • eg. - Growth of uterus during pregnancy, -prolactin &estrogen induced hypertrophy of breasts during lactation • -striated muscle cells in both the heart & skeletal muscles responding to work overload

Atrophy • Shrinkage in the size of cell by loss of cell substance after attaining its normal size. • If sufficient no of cells are involved,entire organ is reduced in size. • Physiological causes• During foetal development-notochord or thyroglossal duct atrophied • Uterus decreases in size after parturition

Pathological causes of atrophy Disuse atrophy Denervation atrophy- due to damage to nerves Diminished blood supply& inadequate nutrition Loss of endocrine stimulation as in breast & reproductive organs • Ageing –senile atrophy esp in brain & heart • Pressure atrophy • • • •

Metaplasia • Reversible change in which one adult cell type (epithelial or parenchymal) is replaced by another adult cell type • Most common – columnar to squamous occurs in resp tract in response to chronic irritation as in smokers • Stones in excretory ducts of salivary glands, pancreas or bile ducts • Defi of vit A causes squamous meta in resp epithelium

Significance of metaplasia • If influences which predispose to metaplasia persists, may induce cancer transformation in metaplastic epithelium • Eg metaplasia from squamous to columnar type as in Barrett esophagitis results in glandular (adeno)carcinomas • Connective tissue metaplasia • All these metaplasia arise from a reprogramming of cells that are known to exist in most epithelia- called reserve cells or undiff mesenchymal cells in connective tissue

Intracellular accumulations • Metabolic derangements in cells leads to intracellular accumulation of abnormal amts of various substances which falls in 3 cate• Normal cellular constituent in excess – which may be produced at a normal or increased rate but rate of metabolism is inadequate to remove it. • eg fatty change in liver due to accumulation of triglycerides

Contd… • An abnormal substance either exogenous – mineral or products of infectious agent or endogenous- product of an abnormal synthesis or metabolism due to genetic or acquired defects in metabolism, packaging , transport or secretion .eg storage diseases, alpha-1-antitrypsin deficiency • Abnormal exogenous pigment deposited b’coz cell is not able to degrade it eg. Carbon/silica particles

Fatty change • Steatosis & fatty change describe abnormal accumulations of triglycerides in parenchymal cells of liver,heart & kidney. • Causes – • most common- alcohol abuse , • toxins , protein energy malnutrition, DM , obesity & anoxia

Contd… • Liver- enlarges,becomes yellow,soft,greasy • Lipid droplets accumulate in cytoplasm & push the nucleus to the periphery – signet ring app • Fat can be demonstrated by using special stainsSudan- 3 / 4 , Oil red O • Heart- tigered effect- bands of yellowed myocardium alternating with red uninvolved myo

Pigments • Colored substances which may be normally present in cells eg melanin or abnormal • Can be exogenous or endogenous pigments • Exogenous-eg.carbon or coal dust which is inhaled& taken up by alveolar macrophages in lungs- blacken lung tissues- anthracosis • Tatooing- localised exo pigmentatn of skin

Contd… • Endogenous-eg lipofuschin (fuscus-brown)–an insoluble pigment – wear & tear or aging pigment • Derived from lipid peroxidation of polyunsaturated lipid • Yellowish brown, finely granular,intracyto • Seen in cells undergoing slow retrogressive changes as in liver & heart of aging patients or with severe malnutritn or cancer cachexia

Contd… • Melanin –endogenous brown black pigment formed in melanocytes by oxidation of tyrosine to dihydroxyphenylalanine. • Homogentisic acid-black pigment occurs in alkaptonuria a metabolic disease- deposits in skin, connective tissues &cartilageochronosis

Contd… • Hemosiderin- hb-derived golden –yellow to brown pigment in which form iron is stored in cells • Hemosiderosis- systemic overload of iron,hemosiderin is deposited in organs & tissues as occurs in transfusions & hemolytic anemias or increased absorption of dietary iron.

Pathologic calcification • Abnormal deposits of calcium salts alongwith smaller amounts of iron,magnesium& other mineral salts • 2 forms of pathologic calcifications• 1)dystrophic-locally in dead/ dying tissues -normal level of serum calcium • 2)metastatic- deposits in vital tissues -some disturbance in Ca metabolism

Dystrophic calcification Seen in areas of necrosis- coagulative,caseous, liquefactive,fat In atheromas of advanced atherosclerosis Ageing or damaged heart valves Grossly-fine,white granule,gritty deposits H & E- basophilic,amorphous granular clumped appintra/extracellular • Progressive acquisition of outer layers –lamellated configuration called psamomma bodies • • • • •

Metastatic calcification • May occur in normal tissues whenever there is hypercalcemia. • Causes• 1)increased secretion of parathyroid hormone(PTH) as in hyperparathyroidism due to parathyroid or other tumors • 2)destruction of bone tissue- primary tumors of bone tissue(myeloma,leukemia)or diffuse skeletal metastasis(eg.breast cancer)

Contd… • 3)vitamin D related disorders • 4)renal failure- retention of phosphate2ndary hyperparathyroidism • Occurs widely throughout tissues but mainly in gastric mucosa , kidneys,lungs,sys arteries,pulm veins

Hyaline change • Defn- alteration within cells or extracellular space, which gives a homogenous or glassy app in routine H & E stained sections • Eg of I/C (epithelial) hyaline deposits-seen in renal tubular cells, • liver cells( mallory alcoholic hyaline), • prostate( corpora amylacea)

Contd… • E/C hyaline(connective tissue)- hyalinisatn of collagenous fibrous tissue in old scars • -longstanding HT & DM –hyalinisatn of walls of arterioles esp in kidney • - amyloid also has a hyaline app

Cellular ageing • A number of cell functions decline progressively with age eg. Reductn of oxidative phosphorylatn in mitochondria, synthesis of nucleoic acids 7 structural & enzymatic proteins, cell receptors & transcription factors . • Senescent cells have a decreased capacity for uptake of nutrients & for repair of chromosomal damage.

Contd… • Steady accumulation of pigment lipofuschin & e/o oxidative damage • Advanced glycation end products- result from nonenzymatic glycosylation & are capable of cross linking proteins- abnormally folded proteins • -eg glycosylation of lens proteins – senile cataract • Important in pathogenesis of DM.

Contd… • After a fixed number of divisions, all cells become arrested in a terminally nondividing state – kn as cellular senescence.

• How do these cells can count their divisons?

Contd… • Telomere shortening-a growth checkpoint allowing the cells to become senescent • Clock genes- clk-1 a gene of a nematode app to alter the growth rate & timing of developmental processes • Werner’s syndrome- rare disease ch by premature ageing, the defective gene product is a DNA helicase- a protein involved in DNA replication & repair.