1. Week 3 Adaptations and Accumulations Dr.İ.Taci Cangül Bursa-2008

2. Adaptations Hyperplasia: Increase in number of cells Hypertrophy: Increase in size of cells Atrophy: Decrease in size Metaplasia: Cellular differentiation Dysplasia: Disordered growth patterns

3. Hyperplasia Physiologic hyperplasia: –Hormonal stimulation (breast and uterus) –Extra workloads Pathologic hyperplasia: –Excessive hormonal stimulation (endometrial hyperplasia)

5. Hypertrophy Increase in size of an organ as a result of an increase in the size of individual cells Physiologic: When muscles are worked Pathologic: Hypertension causes hypertrophy of the heart, specifically of the left ventricle

11. Atrophy A shrinkage in the size of the cell by loss of cell substance Physiologic atrophy: Loss of the ductus arteriosus in utero Pathologic atrophy: Shrinkage of our brains as we age Local atrophy: Most often the result of decreased blood flow to that area Disuse atrophy: Essentially when an organ is underused, it undergoes atrophy. Another example of this is an immobilized limb, which undergoes muscle wasting upon casting.

14. Metaplasia One mature adult tissue is replaced by another. Smoking: Replacement of pseudo ‑ stratified columnar epithelium of the lungs by stratified squamous epithelium Metaplasia may also be seen within mesenchymal tissue. Soft tissues that undergo trauma may be replaced by mature bone.

16. Dysplasia Abnormal epithelial maturation which is characterized by alterations in cell size, shape and organization

18. Accumulations and Pigmentations

19. Intracellular Accumulations Under certain circumstances, in normal or injured cells Most often occurs in the cytoplasm and usually contained within lysosomes Mostly, substances that are produced by the cell –Either their rate of production is increased or their rate of utilization and/or elimination is reduced In other instances, substances that originate in other organs or tissues accumulate in cells because of an inability on the part of that cell to eliminate or metabolize the substance at a rate exceeding its acquisition

20. Fatty Change Abnormal accumulation of fat within parenchymal cells Fatty degeneration, fatty infiltration Most notedly in hepatocytes The liver plays a pivotal role in the metabolism of fat because it is largely responsible for the conversion of free fatty acids into a lipoprotein which is more readily utilizable by other cells

21. Causes of Fatty Change 1. Excessive entry of lipids into the liver 2. Enhanced fatty acid synthesis by hepatocytes 3. Decreased oxidation of fatty acids by mitochondria 4. Increased esterification of fatty acids to triglycerides 5. Decreased apoprotein synthesis 6. Impaired lipoprotein excretion

25. Other Lipid Accumulations Cholesterol and cholesterol esters In atherosclerosis, cholesterol accumulates in smooth muscle cells and macrophages in the intima of arteries In hereditary hyperlipemia, cholesterol accumulates in macrophages, usually under the skin, forming tumor-like structures known as xanthomas

27. Intracellular Accumulation of Proteins Primarily in epithelial cells of the proximal convoluted tubules of the kidney and in plasma cells In the kidney, this excessive accumulation occurs subsequent to leakage of proteins from glomeruli into the glomerular filtrate Plasma cells actively engaged in the production of immunoglobulins sometimes become overloaded with these immunoglobulins and large eosinophilic inclusions, called Russell Bodies, appear in their cytoplasm

28. Intracellular Accumulation of Glycogen Glycogen Infiltration and Glycogen Storage Glycogen appears as clear vacuoles in the cytoplasm of cells Hyperglycemia 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 Liver Cardiac muscle fibers

29. Intracellular Accumulations of Complex Lipids and Carbohydrates Lysosomal storage diseases Mainly in reticuloendothelial cells, neurons, myocardial fibers and the parenchymal cells of the liver and kidneys Sphingolipids, mucopolysaccharides, mucolipases, complex carbohydrates, cholesterol esters and triglycerides. Tay-Sachs disease, Niemann-Pick disease, Gaucher's disease, etc.

30. Inclusion Bodies Intracellular or intracytoplasmic Eosinophilic or basophilic Major significance in making an etiologic diagnosis Aggregates of virions which tend to have characteristic stain affinities

31. Inclusion Bodies Lead poisoning: Acid fast intranuclear inclusions in renal tubular epithelial cells Chediak-Higashi syndrome: Autosomal recessive genetic disorder, large intracytoplasmic granules (abnormally fused versions of normal granule subpopulations)

33. Extracellular Accumulations Calcification Hyaline change Amyloid and amyloidosis Gout Fibrinoid

34. Calcification “Deposition of calcium salts in vital or dying/dead tissues” Dystrophic and metastatic

35. Dystrophic Calcification “Deposition of calcium salts in dead or dying tissues” Principally in areas of coagulative, liquefactive, caseous and/or fat necrosis that persist for rather long periods of time. Normal levels of serum calcium (around 10 mg/100 ml) and in the absence of derangement in calcium metabolism

37. Metastatic Calcification Deposition of calcium salts in vital tissues in association with a defect in calcium metabolism that is characterized by hypercalcemia Usual causes: (1) Hyperparathyroidism, either primary or secondary (2) Vitamin-D intoxication (3) Deficiency of magnesium (4) Hypercalcemia of malignancy

38. Metastatic Calcification Principally in interstitial tissue of blood vessels, kidneys, lungs and gastric mucosa The fundamental abnormality is the pathologic entry of large amounts of ionic calcium into cell organelles, chiefly the mitochondria (it is suggested that mitochondria are the organelles first involved in the pathogenesis of metastatic calcification)

39. Hyaline Change “A homogeneous, glassy, pink appearance in tissues or cells stained with H&E” Widely used descriptive histologic term rather than a specific marker for cell injury Connective tissue hyaline Epithelial hyaline Kerato-hyaline

40. Amyloid and Amyloidosis Deposition of amyloid protein fibrils in tissue Chronic antigenic stimulation and plasmacytosis reticuloendothelial and immune system dysfunction Abnormal processing of components of immunoglobulins, insulin, growth hormone and an acute-phase reactant of inflammation called the serum amyloid associated protein (SAA)

41. Detection of Amyloid Small amounts: Virtually undetectable Large amounts: Organ enlargement and a yellowish to greyish discoloration Rubbery consistency Painting the cut surface organs with iodine: A brownish to yellow-red color Application of dilute sulfuric acid: Colour changes to blue or violet

43. Histologically Amyloid Homogeneous, eosinophilic material that stains reddish pink with the Congo red stain. Under polarized light, the Congo red-stained amyloid has a green birefringence Compression atrophy

45. Ultrastructurally Amyloid Amyloid fibrils are 7.5-10 nm in diameter Rigid, nonbranching, hollow-cored tubules of indeterminate length Beta-pleated sheet configuration: Responsible for the previously described birefringence. Probably also responsible for its resistance to proteolytic digestion

46. Gout “Deposition of uric acid and urate crystals in tissues subsequent to defective purine metabolism” The condition occurs primarily in humans and in birds. In birds, articular and visceral forms of gout are recognized

47. Articular Gout Uric acid and urate crystals are deposited in joint spaces over the serous membranes Affected joints are enlarged, and white, chalky masses (“tophil”) may be observed when opened. The condition may result in severe pain

49. Visceral Gout Uric and urate crystals are deposited over the serous surfaces within the body cavity (pleural, pericardium, etc.) Deposits are also found in the renal tubules Grossly, serous membranes are encrusted by a thin grayish layer having a metallic sheen

52. Fibrinoid Amorphous, eosinophilic, sometimes granular deposit that resembles fibrin. It is typically seen in a focus of tissue injury (especially in vessel walls or in connective tissue) With H&E stains, fibrinoid appears as a deeply eosinophilic, amorphous material which sometimes entraps leukocytes or other necrotic cells. It is most often located in the intima and media of vessel walls