Intracellular Accumulations n Fatty Change Steatosis Abnormal accumulation
Intracellular Accumulations n Fatty Change (Steatosis): Abnormal accumulation of triglycerides within parenchymal cells seen in liver, kidneys, heart, muscles n Causes n n alcohol abuse, other toxins, anoxia, obesity, protein malnutrition Pathogenesis n n n Normally: various steps involved in liver triglyceride metabolism hepatic triglycerides requires complexing with apoproteins to form lipoproteins Triglycerides accumulation in hepatocytes may result from defects at any step from fatty acid entry to lipoprotein exit
Liver, normal Liver, fatty change
Liver, fatty change
Intracellular Accumulations n Cholesterol and Cholesterol Esters n Atherosclerosis n n macrophages and smooth muscle cells filled with lipid vacuoles (cholestrol & cholestrol esters) appear as foam cells atherosclerotic plaques (in aorta and other blood vessels) Xanthomas n macrophage accumulation/hereditary and acquired hyperlipidemias clusters of foamy cells in skin xanthomas
Aorta, atherosclerosis
SKine, xanthomas
Pathologic Calcification n n Abnormal deposition of calcium salts (with smaller amounts of iron, Mg, & others) Two types: dystrophic and metastatic calcification 1) Dystrophic Calcification n Areas of necrosis or injury n Normal serum calcium n Intracellular or extracellular n Examples: n n Areas of necrosis (T. B. , fat necrosis) Morphology n n Appears as chalky white granules grossly Microscopic: Intracellular or extracellular blue (basophillic) deposits
Pathologic Calcification 2) Metastatic Calcification n Occurs in normal tissue n Occurs with hypercalcemia n n Hyperparathyroidism n bone catabolism with tumors involving bone n vitamin D intoxication, sarcoidosis; renal failure Primarily affects blood vessels, kidneys (nephrocalcinosis), lungs, and gastric mucosa
Center of granuloma, dystrophic calcification
Cellular Aging n n Reduced Mitochondrial Function Reduced Synthesis of Structural, Enzymatic, and Receptor Proteins Diminished Capacity for Nutrient Uptake Diminished Capacity for DNA Repair
Cellular Aging n Morphologic Alterations n n n Irregular and abnormal lobed nuclei Pleomorphic vacuolated mitochondria Decreased endoplasmic reticulum Distorted Golgi apparatus Accumulation of lipofuscin pigment
Cellular Aging n Theories n Wear-and-tear n n n Defects in DNA repair free radical damage throughout life nonenzymatic glycosylation of proteins n n cross-linking of adjacent proteins Intrinsic cellular aging n predetermined genetic programming n n Telomere shortening Clock genes ? ?
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