1. Intracellular Accumulations Fatty Change (Steatosis): Fatty Change (Steatosis): Abnormal accumulation of triglycerides within parenchymal cells seen in liver, kidneys, heart, muscles Causes alcohol abuse, other toxins, anoxia, obesity, protein malnutrition Pathogenesis Normally: various steps involved in liver triglyceride metabolism hepatic triglycerides requires complexing with apoproteins to form lipoproteins defects at any step from fatty acid entry to lipoprotein exit Triglycerides accumulation in hepatocytes may result from defects at any step from fatty acid entry to lipoprotein exit

3. Liver, fatty change Liver, normal

4. Liver, fatty change

5. Intracellular Accumulations Cholesterol and Cholesterol Esters Cholesterol and Cholesterol Esters Atherosclerosis 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 macrophage accumulation/hereditary and acquired hyperlipidemias  clusters of foamy cells in skin  xanthomas

6. Aorta, atherosclerosis

7. SKine, xanthomas

8. Pathologic Calcification Abnormal deposition of calcium salts (with smaller amounts of iron, Mg, & others) Abnormal deposition of calcium salts (with smaller amounts of iron, Mg, & others) Two types:dystrophic and metastatic calcification Two types:dystrophic and metastatic calcification 1) Dystrophic Calcification Areas of necrosis or injury Normal serum calcium Intracellular or extracellular Examples: Areas of necrosis (T.B., fat necrosis) Morphology Appears as chalky white granules grossly Microscopic: Intracellular or extracellular blue (basophillic) deposits

9. Pathologic Calcification 2) Metastatic Calcification Occurs in normal tissue Occurs with hypercalcemia Hyperparathyroidism bone catabolism with tumors involving bone vitamin D intoxication, sarcoidosis; renal failure Primarily affects blood vessels, kidneys (nephrocalcinosis), lungs, and gastric mucosa

10. Center of granuloma, dystrophic calcification

11. Cellular Aging Reduced Mitochondrial Function Reduced Synthesis of Structural, Enzymatic, and Receptor Proteins Diminished Capacity for Nutrient Uptake Diminished Capacity for DNA Repair

12. Cellular Aging Morphologic Alterations Irregular and abnormal lobed nuclei Pleomorphic vacuolated mitochondria Decreased endoplasmic reticulum Distorted Golgi apparatus Accumulation of lipofuscin pigment

13. Cellular Aging Theories Wear-and-tear Defects in DNA repair free radical damage throughout life nonenzymatic glycosylation of proteins cross-linking of adjacent proteins Intrinsic cellular aging predetermined genetic programming Telomere shortening Clock genes ??