The basis of Disease

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1 General Curriculum The basis of Disease ZHOU REN 周韧 Prof., M.D., Ph.D. Institute of Pathology & Forensic Medicine Department of Pathology & Patho-physiology Zhenjiang University Judicial Evidence & Evaluation Center Zhejiang University School of Medicine

2 2. Cell Death I. Necrosis Def. Necrosis may be defined as the morphology of cell death in living body. Autolysis Heterolysis

3 Fundamental changes 1Nuclear changes: Pyknosis, karyorrhexis, Karyolysis. 2Cytoplasmic changes: acidophilic, granular, opaque mass.

4 Gross appearances of necrosis in earlier stage

5 Classification of necrosis 1Coagulative necrosis 2Caseous necrosis 3Liquefactive necrosis 4 Fat necrosis Fibrinoid necrosis (Fibrinoid change ) Gangrene a)dry gangrene b)moist gangrene c)gas gangrene

6 1 Coagulative necrosis 2 Liquefactive necrosis 3 Types of Special necrosis Caseous necrosis Gangrene a) Dry gangrene b) Moist gangrene c) Gas gangrene Fat necrosis Fibrinoid necrosis (Fibrinoid change )

7 Types of necrosis. 1Coagulative necrosis Conception: Coagulative necrosis implies preservation of the basic outline of the coagulated cell for some days with the disappearance of fine structures (cellular details) within cell.

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9

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11 Mechanism: Intracellular acidosis denatures not only structural proteins but also enzymic proteins and so blocks the proteolysis of the cell.

12 Morphology: 2Caseous necrosis Conception: A distinctive form of coagulative necrosis, most often occurs in tuberculosis. The term caseous is derived from the gross appearance of the necrotic area. i.e. white and cheesy. Characteristic morphology: disappearance of both basic outline and fine structures (cellular details) within cell of the affected cell.

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15 3Liquefactive necrosis Conception: The damaged cells are lysed by autolysis or heterolysis leaving amorphous, fluid or semifluid material. Morphology:

16 4 Fat necrosis a)enzymatic fat necrosis: In acute pancreatitis, activated pancreatic enzymes are released from pancreas resulting in destruction of fat tissue. b)traumatic fat necrosis: Trauma induce rupture of fat cells. The released fat causes chronic inflammation and foreign body reaction.

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18 Fibrinoid necrosis(fibrinoid change) Conception: Accumulation of pink staining homogenous masses of fibrin, immunoglobulins, and other plasma proteins within the vascular wall, connetive tissue is known as fibrinoid change.

19 Gangrene Def. Massive necrosis of body surface or organs with a passage to the body surface with putrefaction superadded is known as gangrene.

20 Classification: a)dry gangrene Conception: Dry gangrene occurs in the extremities due to occlusion of large artery with intact venous returns. The necrotic area is well dermacated black and mummification.

21 Morphology:

22 b)moist gangrene Conception: Blockage of venous return and artery supply massive necrosis followed by liquefaction caused by bacterial enzyme purplish black color with fouel smelling.

23

24 c)gas gangrene Conception: A serious complication of war wounds. deep contaminated wound(massive necrosis) + clostridia group bacterial infection gas production through the action of saccharolytic and proteolytic enzyme released from bacteria.

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26 Cellular aging functional alteration morphorlogy Aging clock telomeres: its length life span telomerase: control of the length

27 II. Apoptosis Conception: Apoptosis is a distinct type of cell death(cell suicide). It usually involves single cells, or cluster of cells. It is thought to be responsible for numerous physiologic events as well pathologic including the programmed destruction of cells during embryo-genesis.

28 Course of Basic Medical Sciences Chapter 1

29 生化特点 : 由基因调控, 是耗能的主动过程 Ca 2+ /Mg 2+ 依赖的核酸内切酶活化 DNA 断裂以核小体为单位 DNA 电泳呈阶梯状图谱

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33 凋亡率增加导致的疾病 AIDS Alzheimer s disease

34 凋亡率减少导致的疾病 某些肿瘤 : CLL/SLL, 某些自身免疫性疾病, SLE

35 Causes of Cell injury--- 自学 (1)Hypoxia 1Loss of blood supply(ischemia) 2Decrease of oxygenation of blood: cardiorespiratory failure 3Decrease of oxygen carrying capacity of blood: CO poisoning

36 (2)Chemicals and drugs Excessive water intake: water intoxication. (3)Physical agents Extreme heat or cold, radiant energy, change of atmospheric pressure.

37 (4) Biological factors Bacteria Virus Parasites (5) Immunologic reactions: anaphylactic reaction to foreign protein

38 (6)Genetic defects Inhereditary deficiency: vwf(von Willbrand factor) deficiency Hemophilia ( VIII factor deficiency) (7)Nutritional imbalances Vit. D insufficiency: osteomalacia Vit D intoxication: Urolithiasis

39 (8) Others psychosomatic Bio-psycho-social Neurosis Psychosis Aging Senile emphysema Alzheimer s disease

40 Summary: Forms and morphology of cell injury 1. reversible injury intracellular accumulation: cellular swelling, fatty change, pigments,et al. pathological calcification subcellular responses to injury: cytoskeletal abnormality, heterophagy, autophagy, et al. 2. irreversible injury necrosis: coagulative necorsis, caseous necrosis fat necrosis, et al apoptosis Acute injury and chronic injury

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