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Intracellular Accumulation Pathophysiology B Pharm 2nd Semester
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Intracellular Accumulation | Pathophysiology | B Pharm 2nd Semester | Pathophysiology B Pharm 2nd Semester • DOWNLOAD PDF: https://www.slideshare.net/Rohittrive... • FACEBOOK: / rohitkrtrivedi • INSTAGRAM: / rohit_kumar_trivedi • SLIDESHARE: https://www.slideshare.net/Rohittrive... • #RohitKumarTrivedi • Pathophysiology B Pharm 2nd Semester • CHAPTERS • 0:00 Introduction • 2:35 Classification of Intracellular Accumulation • 5:20 Mechanisms of Intracellular Accumulation • 7:15 Accumulation of Lipids • 12:54 Accumulation of Proteins • 14:26 Accumulation of Carbohydrates • 17:25 Accumulation of Pigments • CONTENT: • It is the manifestation of metabolic derangement. • It is the Accumulation of abnormal amounts of various substances may be endogenous or exogenous. • A normal or abnormal endogenous substance accumulates because it cannot be metabolized. • An abnormal exogenous substance is deposited and accumulates because the cell has neither the enzymatic machinery to degrade the substance not the ability to transport it to other sites • Accumulation may be transient reversible or permanent. • Effects range from harmless to toxic. • All major classes of lipids can accumulate in cells: • triglycerides, • cholesterol/cholesterol esters • phospholipids • Abnormal complexes of lipids and carbohydrates accumulate in the lysosomal storage diseases • • *Lysosomal storage diseases (LSDs): • are a group of about 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. • Steatosis (Fatty Change) • It is the abnormal accumulations of triglycerides within parenchymal cells. • Seen in the liver because it is the major organ involved in fat metabolism, but it also occurs in heart, muscle, and kidney. • Causes: • Toxins • Protein malnutrition • Diabetes mellitus • Obesity • Anoxia • • The cellular metabolism of cholesterol is tightly regulated such that most cells use cholesterol for the synthesis of cell membranes without intracellular accumulation of cholesterol or cholesterol esters. • Atherosclerosis: A build up of cholesterol plaque in the walls of arteries, causing obstruction of blood flow. Plaques may rupture, causing acute occlusion of the artery by clot. • Xanthomas: Intracellular accumulation of cholesterol within macrophages in the skin • Cholesterolosis: This refers to the accumulations of cholesterol-laden macrophages in the lamina propria of the gallbladder • Primarily occurs in epithelial cells of the proximal convoluted tubules (PCT) of the kidney and in plasma cells. • Russel Bodies- excessive synthesis of immunoglobulin Plasma cells. • Excessive accumulation of protein in the kidney, produce leakage of proteins from glomeruli into the glomerular filtrate. • The main protein involved in the accumulation is albumin. • In the kidney, trace amounts of albumin filtered through the glomerulus are normally reabsorbed by pinocytosis in the proximal convoluted tubules. • Carbohydrate or glycogen accumulation intracellularly are associated with abnormalities in the metabolism of either glucose or glycogen. • It can be divided into two basic categories: • Glycogen Infiltration • Glycogen Storage • They differ mainly in their pathogenetic mechanisms. • Glycogen Infiltration: • Accumulation of glycogen that occurs due to excessive amounts of glucose in the circulation (hyperglycemia). • Hyperglycemia is usually encountered in Diabetes mellitus and it is due to: • insufficient insulin concentrations • or tissue insensitivity to insulin • The tissues involved in glycogen infiltration are: • the epithelial cells of the distal portion of the proximal convoluted tubule and in the loop of Henle in the kidney, • leukocytes within inflamed or necrotic tissue, • the liver and, • on rare occasions cardiac muscle fibers • Identification of Glycogen deposition: • In Hematoxylin and Eosin (H E) stained sections, deposits of glycogen produce clear vacuoles in the cytoplasm of the affected cells. • Best’s carmine and periodic acid-Schiff (PAS) staining may be used to confirm the presence of glycogen in the cell. • 2. Glycogen Storage: • Defects in the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types are known as glycogen storage disease. • It occurs due to genetic disorders. • This disease mainly retard the growth of child. • Pigments are colored substances, some of which are normal constituents of cells (e.g., melanin), whereas others are abnormal and accumulate in cells only under special circumstances. • They are either normal constituent of the cell or accumulate under special circumstances. • e.g. Melanin, Alkaptonuria, Haemoprotein-derived, lipofuscin. • Melanin: • Brown-black, non-haemoglobin-derived pigment • Present in hair, skin, mucosa at some places (oral cavity, oesophagus, anal canal)
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