General Pathology #5 PDF

0795372799 “General Pathology” #5 Intracellular Accumulation and Calcification Intracellular Accumulation Cells may accumulate abnormal amounts of various substances under some circumstances Harmless or associated with varying degrees of...

0795372799 “General Pathology” #5 Intracellular Accumulation and Calcification Intracellular Accumulation Cells may accumulate abnormal amounts of various substances under some circumstances Harmless or associated with varying degrees of injury. The substance may be located in: - Cytoplasm - Within organelles (typically lysosomes) - Nucleus. Mechanisms: 1. Inadequate removal of a normal substance secondary to defects in mechanisms of packaging and transport: Fatty change in the liver 2. Accumulation of an abnormal endogenous substance as a result of genetic or acquired defects in its folding, packaging, transport, or secretion: Certain mutated forms of α1- antitrypsin. 3. Failure to degrade a metabolite due to inherited enzyme deficiencies: Storage diseases “lysosomal storage disease, glycogen storage diseases” 4. Deposition and accumulation of an abnormal exogenous substance when the cell has neither the enzymatic machinery to degrade the substance nor the ability to transport it to other sites: Accumulation of carbon or silica particles.  0795372799 Fatty Change (Steatosis) Abnormal accumulation of triglycerides within parenchymal cells Caused by Excessive intake or defects in synthesis of transport proteins Most often seen in the liver (major organ involved in fat metabolism) May occur in heart, skeletal muscle, kidney, and other organs. Alcohol abuse and diabetes associated with obesity are the most common causes. Cholesterol and Cholesteryl Esters Cholesterol deposition because of defective catabolism and excessive intake. - Seen in macrophages and smooth muscle cells of vessel walls in atherosclerosis. Proteins In the kidney, trace amounts of albumin filtered through the glomerulus are normally reabsorbed. In disorders with heavy protein leakage across the glomerular filter (e.g., nephrotic syndrome) - Larger reabsorption of the protein - Pink, hyaline cytoplasmic droplets. Marked accumulation of newly synthesized immunoglobulins of some plasma cells, forming rounded, eosinophilic bodies >>>> Russell bodies. Neurofibrillary tangles in neurons “aggregates of microtubules binding protein tau”  0795372799 Pigments “colored substances” - Exogenous: The most common exogenous pigment is Carbon Anthracosis: Aggregates of the pigment blacken the draining lymph nodes and pulmonary parenchyma. - Endogenous: lipofuscin, melanin, and certain derivatives of hemoglobin. Lipofuscin, or “wear-and-tear pigment”: - Insoluble brownish-yellow granular material - Accumulates in heart, liver, and brain as a function of age or atrophy. - Complexes of lipid and protein that derive from the free radical– catalyzed peroxidation of polyunsaturated lipids of subcellular membranes. - It is not injurious to the cell but is a marker of past free radical injury. Melanin: - Endogenous, brown-black pigment - Synthesized by melanocytes located in the epidermis Hemosiderin: - Hemoglobin-derived granular pigment - Golden yellow to brown - Accumulates in tissues when there is a local or systemic excess of iron. - Represents large aggregates of ferritin micelles. ❖ The iron can be identified by the Prussian blue histochemical reaction. >> Golden yellow to blue. ❖ Small amounts of this pigment are normal in the mononuclear phagocytes of the bone marrow, spleen, and liver, where aging red cells are normally degraded. ❖ Excessive deposition of hemosiderin: hemosiderosis ❖ More extensive accumulations of iron seen in: hereditary hemochromatosis. ‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ Pathologic calcification Abnormal deposition of calcium salts, together with smaller amounts of iron, magnesium, and other minerals. Dystrophic calcification: Metastatic calcification: - Occurs in dead or dying tissues - Deposition of calcium salts in normal tissues - Normal serum levels of calcium - Almost always secondary hypercalcemia May be an incidental finding indicating Metastatic calcification can occur widely throughout the insignificant past cell injury body but principally affects the interstitial tissues of the May also be a cause of organ dysfunction. vasculature, kidneys, lungs, and gastric mucosa. - Can develop in aging or damaged heart valves, Generally do not cause clinical dysfunction resulting in severely compromised valve motion. Extensive calcifications in the lungs may be evident on - Dystrophic calcification of the aortic valves is an radiographs and may produce respiratory deficits important cause of aortic stenosis in elderly persons. Massive deposits in the kidney (nephrocalcinosis) can lead to renal damage. Morphology Gross examination: Calcium salts are seen as fine white granules or clumps, often felt as gritty deposits. Histologic examination: Intracellular and/or extracellular basophilic deposits.  0795372799 Cellular Aging Individuals age because their cells age. Age is one of the strongest independent risk factors for many chronic diseases, such as cancer, Alzheimer disease, and ischemic heart disease. Cellular aging is the result of a progressive decline in the life span and functional capacity of cells. Several mechanisms are responsible for cellular aging: 1-DNA damage. - Variety of metabolic insults may result in DNA damage. - Most DNA damage is repaired by DNA repair enzymes; some persists and accumulates as cells age. 2- Decreased cellular replication. - All normal cells have a limited capacity for replication, and after a fixed number of divisions cells become arrested in a terminally nondividing state, known as replicative senescence. - Replicative senescence: reduced capacity of cells to divide secondary to progressive shortening of chromosomal ends (telomeres), which ultimately results in cell cycle arrest. - Aging is associated with progressive replicative senescence of cells. Telomeres are short repeated sequences of DNA present at the ends of linear chromosomes - Important for ensuring the complete replication of chromosome ends - Protecting the ends from fusion and degradation. As the telomeres become shorter, the ends of chromosomes cannot be protected and are seen as broken DNA, which signals cell cycle arrest. 3- Defective protein homeostasis. - Over time: increased turnover and decreased synthesis of proteins. - Affects cell survival, replication, and functions. - May lead to accumulation of misfolded proteins, which can trigger apoptosis.