Ch 2 adaptations, cell injury, cell death

This is a presentation on the topic of Adaptations, Cell injury and cell death, prepared by Dr Ashish Jawarkar, he is MD in pathology and a teacher at Parul institute of Medical sciences and research Vadodara.

1. Chapter 2 ADAPTATIONS, CELL INJURY, CELL DEATH PART 2 Dr. Ashish Jawarkar, MD

2. Overview Homeostasis Adaptations

3. Homeostasis

4. Homeostasis In the same way, the normal cell is confined to a fairly narrow range of function and structure by its state of metabolism, differentiation, specialization; by constraints of neighboring cells by the availability of metabolic substrates

5. INJURY (ALTERED HOMEOSTASIS)

6. Adaptations- Reversible Injury – Irreversible injury – Cell death

7. Adaptations

8. ADAPTATIONS

9. HYPERTROPHY Hypertrophy refers to an increase in the size of cells, that results in an increase in the size of the affected organ. The increased size of the cells is due to the synthesis and assembly of additional intracellular structural components Cells synthesize more proteins and the number of myofilaments increases. This increases the amount of force each myocyte can generate, and thus increases the strength and work capacity of the muscle as a whole Eg. Cells that cannot multiply Muscles in body builders Cardiac muscle in hypertension

10. MECHANISMS

11. HYPERPLASIA Hyperplasia is defined as an increase in the number of cells in an organ or tissue in response to a stimulus Physiologic Female breast during pregnancy (epithelium) Liver - In individuals who donate one lobe of the liver for transplantation, the remaining cells proliferate so that the organ soon grows back to its original size Bone marrow in response to supplements Endometrium – after menstruation Pathologic Endometrium – in response to hormones Hyperplasia of prostate in old age Epidermal hyperplasia (warts) in response to viral infection

12. THE MYTH OF PROMETHEUS

13. Mechanisms of Hyperplasia Hyperplasia is the result of growth factor-driven proliferation of mature cells and by increased output of new cells from tissue stem cells

14. ATROPHY Atrophy is defined as a reduction in the size of an organ or tissue due to a decrease in cell size and number Physiologic Embryonic structures – notochord, thyroglossal duct Post partum uterus Pathologic Disuse atrophy Denervation atrophy Ischemic atrophy Loss of nutrition – Marasmus, cachexia Loss of endocrine stimulation Breast after menopause Pressure atrophy Tumor compressing normal tissue

15. Mechanisms

16. Metaplasia Reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another differentiated cell type the influences that predispose to metaplasia, if persistent, can initiate malignant transformation in metaplastic epithelium Barret’s esophagus – squamous to columnar Respiratory epithelium – columnar to squamous

17. Mechanism reprogramming of stem cells that are known to exist in normal tissues

18. TRIVIA What does a cell do first when it is exposed to stress? More than 1 options can be correct It undergoes dysplasia It undergoes metaplasia It tries adapts It tries to achieve homeostasis again

19. TRIVIA Why physiotherapy is required after a plaster cast is removed after healing of fracture?

20. TRIVIA Give one example of an organ that can undergo both hyperplasia and hypertrophy; and atrophy when not in use..

21. TRIVIA What does cigarette smoke do to the lining of the respiratory mucosa? Atrophy Hypertrophy Metaplasia Hyperplasia

22. CELL INJURY

23. CELL INJURY Source: Robbins Textbook of pathology, 9E

24. TIMELINE Source: Robbins Textbook of pathology, 9E

25. MORPHOLOGY OF REVERSIBLE CELL INJURY Best examples are cellular swelling and fatty change Cellular swelling Cellular swelling is the first manifestation of almost all forms of injury to cells Gross - It causes some pallor, increased turgor, and increase in weight of the organ Light microscopy - small clear vacuoles may be seen within the cytoplasm; these represent distended and pinched-off segments of the ER Source: Robbins Textbook of pathology, 9E

26. The terms steatosis and fatty change describe abnormal accumulations of triglycerides within parenchymal cells Fatty change is often seen in the liver because it is the major organ involved in fat metabolism, but it also occurs in heart, muscle, and kidney. MORPHOLOGY OF REVERSIBLE CELL INJURY ( Fatty change)

27. IRREVERSIBLE CELL INJURY

28. CAUSES OF CELL INJURY (NECROSIS/APOPTOSIS) Hypoxia – lack of blood supply or lack of oxygen Physical agents – Heat, Mechanical trauma Chemical agents – glucose or salt in high concentrations, poisons Microorganisms causing infections Autoimmunity Genetic derangements – accumulation of damaged DNA can trigger apoptosis Nutritional defects – PCM, anorexia nervosa, Atheroscleosis

29. MECHANISMS OF CELL INJURY (NECROSIS/APOPTOSIS) Source: Robbins Textbook of pathology, 9E

30. 1. Mitochondrial damage Source: Robbins Textbook of pathology, 9E

31. 2. Influx of calcium Source: Robbins Textbook of pathology, 9E

32. 3. Membrane damage Source: Robbins Textbook of pathology, 9E

33. 4. Protein misfolding and DNA damage Source: Robbins Textbook of pathology, 9E

34. MORPHOLOGY OF NECROSIS The morphology of necrosis can be explained in following tissue patterns Coagulative necrosis Liquefactive necrosis Gangrenous necrosis Caseous necrosis Fat necrosis Fibrinoid necrosis

35. Coagulative necrosis (infarct) Coagulative necrosis is a form of necrosis in which the architecture of dead tissues is preserved. The injury denatures not only structural proteins but also enzymes and so blocks the proteolysis of the dead cells Cause is mainly Ischemia caused by obstruction in a vessel Source: Robbins Textbook of pathology, 9E

36. Liquefactive necrosis Liquefactive necrosis , in contrast to coagulative necrosis, is characterized by digestion of the dead cells, resulting in transformation of the tissue into a liquid viscous mass The necrotic material is frequently creamy yellow because of the presence of dead leukocytes and is called pus Best example is necrosis in brain Source: Robbins Textbook of pathology, 9E

37. Gangrenous necrosis (wet gangrene) It is a type of coagulative necrosis with superimposed bacterial infection. It is seen in multiple tissue planes Best example is a limb, generally the lower leg, that has lost its blood supply Source: Robbins Textbook of pathology, 9E

38. Caseous necrosis Caseous necrosis is encountered most often in foci of tuberculous infection The term “caseous” (cheese like) is derived from the friable white appearance of the area of necrosis Source: Robbins Textbook of pathology, 9E

39. Fat necrosis It refers to focal areas of fat destruction, typically resulting from release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity. This occurs in acute pancreatitis Source: Robbins Textbook of pathology, 9E

40. Fibrinoid necrosis Fibrinoid necrosis is a special form of necrosis usually seen in immune reactions involving blood vessels. This pattern of necrosis typically occurs when complexes of antigens and antibodies are deposited in the walls of arteries. Deposits of these “immune complexes,” together with fibrin that has leaked out of vessels, result in a bright pink and amorphous appearance in H&E stains, called “fibrinoid” (fibrin-like) by pathologists. Source: Robbins Textbook of pathology, 9E

41. Morphology of necrosis – cytoplasmic changes Gross Microscopy Ultrastructure (Electron microscopy) Increased eosinophilia due to Loss of cytoplasmic RNA that binds hematoxylin When enzymes have digested the cytoplasmic organelles, the cytoplasm becomes vacuolated and appears moth-eaten Cellular swelling Inflammation

42. Source: Robbins Textbook of pathology, 9E

43. TRIVIA Arrange the following changes in necrosis according to timeline Gross changes Biochemical alterations Ultrastructure changes Light microscopic changes

44. TRIVIA What is liquefactive necrosis?

45. TRIVIA Which event is event for activating enzymes of cell lysis Activation of ATPase Influx of calcium Break down of lysosomal barrier Protein misfolding

46. TRIVIA Fat necrosis can be seen in which organ other than omentum Prostate Breast Testis Seminal Vescicle

47. Apoptosis - Suicide Apoptosis occurs normally both during development and throughout adulthood, and serves to remove unwanted, aged, or potentially harmful cells. Physiologic apoptosis Pathologic apoptosis

48. Physiologic apoptosis

49. Pathologic apoptosis

50. Morphology Cell shrinkage Chromatin condensation Formation of cytoplasmic blebs and apoptotic bodies Phagocytosis of apoptotic cells or cell bodies, usually by macrophages

51. Mechanisms of apoptosis

52. WELCOME

53. Chapter 2 ADAPTATIONS, CELL INJURY, CELL DEATH PART 3 Dr. Ashish Jawarkar, MD

54. Intracellular accumulations Metabolic derangements lead to accumulation of different substances in the cytoplasm or in organelles or in nucleus

55. Pathways Source: Robbins Textbook of pathology, 9E

56. Intracellular accumulations

57. Lipid Fatty change Atherosclerosis Xanthomas Cholesterosis Neimann Pick disease type C Source: Robbins Textbook of pathology, 9E

58. Atherosclerosis In atherosclerotic plaques, smooth muscle cells and macrophages within the intimal layer of the aorta and large arteries are filled with lipid vacuoles, most of which are made up of cholesterol and cholesterol esters. Such cells have a foamy appearance (foam cells) Source: Robbins Textbook of pathology, 9E

59. Xanthomas Clusters of foamy cells are found in the subepithelial connective tissue of the skin and in tendons Source: Robbins Textbook of pathology, 9E

60. Cholesterosis This refers to the focal accumulations of cholesterol-laden macrophages in the lamina propria of the gallbladder Source: Robbins Textbook of pathology, 9E

61. Neimann pick disease type C This lysosomal storage disease is caused by mutations affecting an enzyme involved in cholesterol trafficking, resulting in cholesterol accumulation in multiple organs

62. Proteins Resorption droplets in proximal renal tubules in proteinuria Russel bodies α1 antitrypsin deficiency Neurofibrillary tangle found in Alzheimer’s Source: Robbins Textbook of pathology, 9E

63. Hyaline Change An alteration within cells or in the extracellular space that gives a homogeneous, glassy, pink appearance in routine histologic sections stained with hematoxylin and eosin This morphologic change is produced by a variety of alterations and does not represent a specific pattern of accumulation

64. Hyaline Change Intracellular Hyaline Intracellular accumulations of protein, described earlier (reabsorption droplets, Russell bodies, alcoholic hyaline), are examples of intracellular hyaline deposits. Extracellular Hyaline Collagenous fibrous tissue in old scars may appear hyalinized In long-standing hypertension and diabetes mellitus, the walls of arterioles, especially in the kidney, become hyalinized, resulting from extravasated plasma protein and deposition of basement membrane material

65. Glycogen Glycogen is a readily available energy source stored in the cytoplasm of healthy cells. Excessive intracellular deposits of glycogen are seen in patients with an abnormality in either glucose or glycogen metabolism – Diabetes mellitus/Glycogen storage disorders Source: Robbins Textbook of pathology, 9E

66. Pigments Exogenous Carbon Lipofuscin Melanin Hemosiderin Melanin Homogentisic acid Bilirubin and biliverdin

67. Carbon The most common exogenous pigment is carbon (coal dust), a ubiquitous air pollutant in urban areas. ANTHRACOSIS When inhaled Carbon is picked up by macrophages within the alveoli and is then transported through lymphatic channels to the regional lymph nodes Accumulations of this pigment blacken the tissues of the lungs and the involved lymph nodes. COAL WORKER’S PNEUMOCONIOSIS In coal miners the aggregates of carbon dust may induce a fibroblastic reaction or even emphysema and thus cause a serious lung disease (Chapter 15). TATTOOING is a form of localized, exogenous pigmentation of the skin. The pigments inoculated are phagocytosed by dermal macrophages, in which they reside for the remainder of the The pigments do not usually evoke any Inflammatory response. Source: Robbins Textbook of pathology, 9E

68. Lipofuscin It is seen in cells undergoing slow, regressive changes and is particularly prominent in the liver and heart of aging patients Tell-tale sign of free radical injury and lipid peroxidation not injurious to the cell or its functions Source: Robbins Textbook of pathology, 9E

69. Hemosiderin Hemosiderin, a hemoglobin -derived, golden yellow to-brown, granular or crystalline pigment derived from iron Under normal conditions small amounts of hemosiderin can be seen in the mononuclear phagocytes of the bone marrow, spleen, and liver, which are actively engaged in red cell breakdown Local excesses of hemosiderin - Common bruise Systemic overload of iron - HEMOSIDEROSIS Hemochromatosis - increased absorption of dietary iron due to an inborn error of metabolism called Hemolytic anemias - premature lysis of red cells leads to release of abnormal quantities of iron Repeated blood transfusions - transfused red cells constitute an exogenous load of iron Source: Robbins Textbook of pathology, 9E

70. Melanin brown-black, pigment formed when the enzyme tyrosinase catalyzes the oxidation of tyrosine to dihydroxyphenylalanine in melanocytes

71. Homogentisic acid Black pigment that occurs in patients with alkaptonuria Here the pigment is deposited in the skin, connective tissue, and cartilage, and the pigmentation is known as oochronosis Source: Robbins Textbook of pathology, 9E

72. Pathologic calcification Pathologic calcification is the abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium, and other mineral salts Types Dystrophic deposition occurs locally in dying tissues it occurs despite normal serum levels of calcium In absence of derangements in calcium metabolism Metastatic deposition of calcium salts in otherwise normal tissues results from hypercalcemia secondary to some disturbance in calcium metabolism.

73. Dystrophic calcification Examples in the atheromas of advanced atherosclerosis develops in aging or damaged heart valves Morphology Gross - fine, white granules or clumps, often felt as gritty deposits Microscopy – intracellular or extracellular, basophilic, amorphous granular, sometimes clumped appearance The progressive acquisition of outer layers may create lamellated configurations, called psammoma bodies – In papillary lesions of thyroid, meningiomas etc In asbestosis of the lung, iron and calcium deposition creates dumbbell shaped forms Source: Robbins Textbook of pathology, 9E

74. Metastatic calcification Causes Increased secretion of parathyroid hormone (PTH) with subsequent bone resorption hyperparathyroidism due to parathyroid tumors , and ectopic secretion of PTH-related protein by malignant tumors Resorption of bone tissue primary tumors of bone marrow (e.g., multiple myeloma, leukemia ) diffuse skeletal metastasis (e.g., breast cancer), accelerated bone turnover (e.g., Paget disease) Immobilization Vitamin D–related disorders vitamin D intoxication, sarcoidosis (in which macrophages activate a vitamin D precursor idiopathic hypercalcemia of infancy (Williams syndrome) - characterized by abnormal sensitivity to vitamin D Renal failure which causes retention of phosphate, leading to secondary hyperparathyroidism.

75. Metastatic calcification Principally affects the interstitial tissues of the gastric mucosa, kidneys, lungs, systemic arteries, and pulmonary veins All of these tissues excrete acid and therefore have an internal alkaline compartment that predisposes them to metastatic calcification

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