Persistent prelethal stress leads to cellular adaptation. 1-Adaptation of growth. a) Increased growth and cellular activity e. g.Hypertrophy & Hyperplasia b) Decreased growth and cellular activity e.g. Atrophy. c-Disturbances of cellular differentiation and morphology e.g. Metaplasia 2-Intra and Extra cellular accumulations e. g. a) Lipids as in fatty change & Cholesterol deposits. b) Proteins as in Hyaline change& Amyloidosis. c) Calcium as in Pathologic Calcification d) Pigments as in Pathologic pigmentation. Intracellular Accumulations Endogenous normal substance produced at normal or increased rate/rate of metabolism inadequate for removal (fatty liver) Exogenous cell cannot degrade substance (carbon) Intracellular Accumulations Fatty Change (Steatosis) the liver is one of the main organs of the body involved in pathways involving metabolism of fats or lipids. Accumulation of lipids in hepatocytes is termed fatty change (also known as, hepatic steatosis, fatty liver,. Another example of accumulation of lipids in cells is atherosclerosis characterized by the accumulation of lipid-laden foam cells in the walls of arteries. The significance of atherosclerosis in humans is obviously reflected in the high incidence of myocardial and cerebral infarction (heart attack and stroke). Intracellular Accumulations Fatty Change (Steatosis) Liver increased weight, yellow color fat vacuoles within cytoplasm of hepatocytes Another example of accumulation of an endogenous substance, is the accumulation of protein in tubular epithelial cells of the kidney known as,amyloidosis Glycogen: Abnormal accumulation occurs in liver, muscles and kidney in case of:Diabetes mellitus ( hyperglycemia) defect in metabolism of glucose or glycogen Pigment disorders: Pigments are colored substances, synthesized within the body (endogenous) or coming from outside (exogenous). Endogenous pigments: include melanin, lipofuscin and Hemosiderin Intracellular Accumulations Endogenous Pigments Lipofuscin (“wear and tear pigment) ..) It contains complexes of lipid and protein derived from peroxidation of lipids by free radicals. insoluble brownish-yellow granular intracellular material that accumulates in a variety of tissues (particularly the heart, liver, and brain) as a function of age or atrophy( ageing pigment) when appear in tissue grossly it is called brown atrophy Intracellular Accumulations Endogenous Pigments Melanin brown-black pigment produced in melanocytes It is synthesized exclusively by melanocytes located in the epidermis and acts as a screen against harmful ultraviolet radiation Albinism: absence of melanin. Such individuals have melanocytes but are unable to synthesize melanin. These patients are vulnerable to cancer. Intracellular Accumulations Endogenous Pigments Hemosiderin golden-yellow pigmen accumulate in tissues when there is local or systemic excess of iron Local excesses of iron and hemosiderin result from hemorrhages or vascular congestion,. With lysis of the erythrocytes, the hemoglobin eventually undergoes transformation to hemosiderin. hemosiderin 1. 2. 3. hemosiderosis hemosiderin is systemic deposited in many organs and tissues [ liver, bone marrow, spleen, and lymph nodes occurs in increased absorption of dietary iron, hemolytic anemias, transfusions hemochromatosis hereditary more extensive accumulations of iron with tissue injury including liver fibrosis, heart failure, and diabetes mellitus. Intracellular Accumulations Exogenous Pigments Carbon (anthracosis) When inhaled, it is phagocytosed by alveolar macrophages and transported by lymphatics to lymph nodes mild accumulations usually are of no consequence--heavy accumulations may induce a fibroblastic response Exogenous pigments Most of these are dust particles in the inhaled air, deposited in the lungs and associated lymph nodes. The dust particles act as mild irritants and induce proliferation of fibrous connective tissue( FCT)(fibrosis) and collection of macrophages.