Intracellular Accumulations PDF

INTRACELLULAR ACCUMULATIONS  cells may accumulate abnormal amounts of various substances, which may be harmless or may cause varying degrees of injury.  The substance may be located in the cytoplasm, within organelles (typically lysosomes), or in the nucleus, and it may be synthesized by the affec...

INTRACELLULAR ACCUMULATIONS  cells may accumulate abnormal amounts of various substances, which may be harmless or may cause varying degrees of injury.  The substance may be located in the cytoplasm, within organelles (typically lysosomes), or in the nucleus, and it may be synthesized by the affected cells or it may be produced elsewhere. Three main pathways for intracellular accumulation: 1- A normal substance is produced at abnormal or an increased rate, but metabolic rate is inadequate to remove it Example: Fatty change in the liver 2-A normal or abnormal endogenous substance accumulates because of genetic or acquired defects in its folding, packaging, transport or secretion Example:Accumulation of proteins in anti-trypsin deficiency 3-An abnormal exogenous substance is deposited and accumulates because the cell has neither the enzymatic machinery to degrade the substance nor the ability to transport it to other sites. Example: Accumulation of carbon or silica particles Fatty Change (Steatosis):  Refers to any abnormal accumulation of triglycerides within parenchymal cells  Most often seen in the liver but may also occur in the heart, skeletal muscle, kidney and other organs  May be caused by toxins, protein malnutrition, diabetes mellitus, obesity and anoxia  Alcohol abuse and diabetes associated with obesity are the most common causes of fatty liver Fatty Liver Cholesterol and Cholesteryl Esters:  Result of defective catabolism and excessive intake  Present in lipid vacoules of smooth muscle cells and macrophages in atherosclerosis  Give atherosclerotic plaques their characteristic yellow color and contribute to the pathogenesis of the lesion Xanthomas  Xanthomas are hypercholesterolemic tumurous masses found in the connective tissue of the skin or tendons Proteins: Less common than lipid accumulations Occur because excess are presented to the cells or because the cells synthesize excessive amounts 1) accumulation of newly synthesized imunoglobulins in some plasma cells forming rounded, eosinophilic Russell bodies 3) Mallory body or “ alcoholic hyalin” is an eosinophilic cytoplasmic inclusion in liver cells highly characteristic of alcoholic liver disease 4) Neurofibrillary tangle found in the brain in Alzheimer disease Glycogen : Accumulations of these are associated with abnormalities in the metabolism of either glucose or glycogen Example: 1) In poorly controlled diabetes mellitus, glycogen accumulates in renal tubular epithelium, cardia myocytes, and β cells of Islets of langerhans 2) Glycogen storage diseases or glycogeneses are genetic disorders where glycogen accumulates in macrophages of patients with defects in lysosomal enzymes Pigments: colored substances that are either exogenous or endogenous Exogenous Pigments: -Carbon ,most common air pollutant - Aggregates of the pigment blacken the draining lymph nodes and pulmonary parenchyma (Anthracosis) Endogenous Pigments: 1- Lipofuscin : - synthesized within the body itself -an insoluble brownish-yellow granular intracellular material that accumulates in the heart, liver, & brain as a function of age or atrophy -represents complexes of lipid & protein that derive from the free radical-catalyzed peroxidation of polyunsaturated lipids  it is not injurious to the cell but is important as a marker of past freeradical injury  the brown pigment when present in large amounts, imparts an appearance to the tissue that is called brown atrophy The pale golden brown finely granular pigment seen here in nearly all hepatocytes is lipochrome (lipofuscin). 2- Melanin:  An endogenous, brown-black pigment synthesized exclusively by melanocytes when the enzyme tyrosinase catalyzes tyrosine to (DOPA) dihydroxyphenylalanine located in the epidermis  Acts as a screen against harmful ultraviolet radiation 3-Hemosiderin A hemoglobin-derived granular pigment that is golden yellow to brown and accumulates in tissues when there is a local or systemic excess of iron   Iron is normally stored within cells in association with the protein apoferritin, forming ferritin micelles Iron can be identified by the Prussian blue reaction Hemosiderosis:   a condition where hemosiderin is deposited in many organs and tissues whenever there is systemic overloadof iron It occurs in the following settings: -Increased absorption of dietary iron -Impaired utilization of iron -Hemolytic anemias -Transfusions Hereditary Hemochromatosis:  A condition where there is extensive accumulations of iron with tissue injury  Characterized principally by 1-the deposition of hemosiderin in liver, pancreas,myocardium, pituitary, adrenal, thyroid, joints & skin 2-cirrhosis 3-pancreatic fibrosis