Intracellular AccumulationsIntracellular 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 Triglycerides accumulation in hepatocytes may result from defects defects

at any step from fatty acid entry to lipoprotein exit at any step from fatty acid entry to lipoprotein exit

Liver, fatty change

Liver, normal

Liver, fatty change

Intracellular AccumulationsIntracellular Accumulations

Cholesterol and Cholesterol EstersCholesterol 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

Aorta, atherosclerosis

SKine, xanthomas

Pathologic CalcificationPathologic Calcification

Abnormal deposition of calcium salts (with smaller amounts of iron, Mg, Abnormal deposition of calcium salts (with smaller amounts of iron, Mg, & others)& others)

Two types:Two types: dystrophic and metastatic calcificationdystrophic and metastatic calcification

1) Dystrophic Calcification1) 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

Pathologic CalcificationPathologic Calcification

2) Metastatic Calcification2) 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

Center of granuloma, dystrophic calcification

Cellular AgingCellular Aging

Reduced Mitochondrial Function Reduced Synthesis of Structural, Enzymatic,

and Receptor Proteins Diminished Capacity for Nutrient Uptake Diminished Capacity for DNA Repair

Cellular AgingCellular Aging

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

Cellular AgingCellular 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 ??