SECTION 2 CELL INJURY

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Adapted myocyte Normal myocyte Reversibly-injured myocyte SECTION 2 CELL INJURY Cell death 5/4/2014 1 5/4/2014 2 Reversible Degeneration Irreversible Cellular Swelling Fatty Change Hyaline Change Amyloid Change Mucoid Change Pathologic Pigmentation Pathologic Calcification Cell Death Reversible Cell Injury Degeneration Intracellular &/or extracellular abnormal accumulation: Excess amounts of various normal substances (water,lipids,proteins,pigments) Abnormal substances (exogenous, endogenous) 5/4/2014 3 5/4/2014 4 Cellular Swelling (1) Cellular Swelling (2) (hydropic degeneration) Intracellular accumulation Sodium Water Morphology the organs NE: Cloudy swelling Increase in the weight LM: EM: 5/4/2014 5 5/4/2014 6 1

Cellular Swelling (3) Morphology Cellular swelling of liver NE: LM: the cells Large Small & fine granules in the cytoplasm Ballooning change EM: 5/4/2014 7 5/4/2014 8 Cellular swelling in kidney cells 5/4/2014 9 Cellular swelling in liver cells 5/4/2014 10 Cellular Swelling (4) Morphology NE: LM: Swelling Endoplasmic reticulum EM: Mitochondria 5/4/2014 11 5/4/2014 12 2

Mechanism Injurious agents Fatty Change (1) Mitochondria damage Steatosis ATP Water & sodium within the cells Cellular swelling Intracellular abnormal accumulation: Triglycerides Often occurred in the liver and the heart 5/4/2014 13 5/4/2014 14 Fatty Change (2) Morphology Fatty Change (2) Morphology NE: LM: NE: LM: Large Yellow Soft Greasy EM: EM: 5/4/2014 15 5/4/2014 16 Fatty Change (3) Morphology Fatty Change (4) Morphology NE: Fat vacuoles LM: Round, clear vacuoles Orange-red color by staining with Sudan Ⅲ or Oil Red O (Frozen tissue EM: sections!) NE: LM: EM: Liposomes Membrane-bound inclusions 5/4/2014 17 5/4/2014 18 3

Fatty Change of the Liver (1) Fatty change in liver cells 5/4/2014 19 NE Mild fatty change: Not affect the gross appearance With progressive accumulation: Large Yellow Soft Greasy Fatty Liver: Severe & diffuse fatty change 5/4/2014 20 Fatty Change of the Liver (2) LM Fat vacuoles Small, in the cytoplasm around the nucleus Displacing the nucleus to the cell periphery Fatty liver 5/4/2014 21 Fatty cysts 5/4/2014 22 Fatty change of the liver 5/4/2014 23 Fatty change of the liver(sudan Ⅲ) 5/4/2014 24 4

Mechanism Fatty Change of the Liver (3) NE Fatty Change of the Myocardium Mild fatty change: Not affect the gross appearance With progressive accumulation: Tigered effect Apparent bands of yellowed myocardium alternating with bands of dark,red-brown,uninvolved myocardium 5/4/2014 25 5/4/2014 26 Fatty change of heart muscle (tigered effect) 5/4/2014 27 Fatty change of heart muscle (tigered effect) Sudanhematoxylin 5/4/2014 28 Hyaline Change (1) A descriptive morphologic term Intracellular or extracellular abnormal accumulation: Proteins A homogeneous, translucent, pink appearance in HE staining 5/4/2014 29 5/4/2014 30 5

Hyaline Change (2) Hyaline change in arteriolosclerosis e.g. Hypertension, Diabetes Hyaline change in connective tissues e.g. Old scars Hyaline change within the cytoplasm e.g. Nephrotic syndrome, Russell bodies, Mallory body 5/4/2014 31 Hyaline change in arteriolosclerosis 5/4/2014 32 Vascular pathology in hypertension. A, Hyaline arteriolosclerosis. The arteriolar wall is hyalinized, and the lumen is markedly narrowed. 5/4/2014 33 Chronic glomerulonephritis 5/4/2014 34 Protein reabsorption droplets in the renal tubular epithelium 5/4/2014 35 Mallory bodies in liver cells 5/4/2014 36 6

Amyloidosis Extracellular abnormal accumulation: Amyloid Hyaline Change 5/4/2014 37 5/4/2014 38 Physicochemical characteristics of amyloid +Iodine--- a brown color--- +H 2 SO 4 --- blue Staining: Congo red--- red, HE--- homogeneous pink EM: nonbranching fibrils 7.5-10 nm wide X-ray: a pleated sheet structure (rendering protein very resistant to enzymatic degradation, contributing to its accumulation in tissues) This is a Congo red stain to reveal orange-red deposits of amyloid. 5/4/2014 39 5/4/2014 40 Mucoid Change Extracellular abnormal accumulation: Mucopolysaccharide (Glycosaminoglycans, Hyaluronic Acid) 5/4/2014 41 5/4/2014 42 7

Pathologic Pigmentation Intracellular & extracellular abnormal accumulation: Colored substances Exogenous Endogenous Pathologic Pigmentation Exogenous Carbon Endogenous Hemosiderin Lipofuscin Melanin 5/4/2014 43 5/4/2014 44 Hemosiderin Carbon Hemosiderin granules in macrophages in the alveolus 5/4/2014 45 5/4/2014 46 Lipofuscin Hemosiderin granules in liver cells. A, H&E B, Prussian blue reaction 5/4/2014 47 5/4/2014 48 8

Pathologic Calcification (1) Melanin 1. Except for the bones and teeth 2. Pathologic conditions Intracellular & extracellular abnormal accumulation: Calcium salts 5/4/2014 49 5/4/2014 50 This is dystrophic calcification in the wall of the stomach. 5/4/2014 51 5/4/2014 52 Pathologic Calcification (2) Dystrophic Calcification In areas of necrosis No calcium metabolic derangements Metastatic calcification In normal tissues Some calcium metabolic derangements Adapted myocyte Normal myocyte Reversibly-injured myocyte Cell death 5/4/2014 53 5/4/2014 54 9

Irreversible Cell Injury 1. Necrosis Cell Death A sequence of morphologic changes that follow cell death in living tissue 2. Apoptosis A distinctive and important mode of cell death regulated by genes Necrosis (1) Two essentially concurrent processes to produce the morphologic changes : 1. Enzymatic digestion of the cell Autolysis Heterolysis 2. Denaturation of proteins 5/4/2014 55 5/4/2014 56 Necrosis (2) Basic pathologic changes Types of necrosis Sequences of necrosis Necrosis (3) Basic Pathologic Changes Pyknosis Nuclear changes Karyorrhexis Karyolysis Cytoplasm Increased eosinophilia 5/4/2014 57 5/4/2014 58 Normal Pyknosis Necrosis (4) Types of Necrosis Karyorrhexis Karyolysis Coagulative necrosis Liquefactive necrosis Caseous necrosis Fat necrosis Gangrene Fibrinoid necrosis Nuclear changes of necrosis 5/4/2014 59 5/4/2014 60 10

Coagulative Necrosis A mass of coagulated, pink-staining, homogeneous cytoplasm Preservation of the basic structure outline of the coagulated cell or tissue for several days In solid organs (kidney, heart, spleen ) 5/4/2014 61 5/4/2014 62 Liquefactive Necrosis Liquefaction of necrotic cells Condition: Presence of more abundant proteolytic enzymes Most often in suppurative inflammation & in the brain 5/4/2014 63 5/4/2014 64 A small abscess in the liver Liquefactive necrosis of the brain (Encephalomalacia) 5/4/2014 65 5/4/2014 66 11

Caseous Necrosis A distinctive form of coagulative necrosis Cheese-like An amorphous coarsely granular eosinophilic debris Most often in foci of TB 5/4/2014 67 A tuberculous lung with a large area of caseous necrosis. The caseous debris is yellow-white and cheesy. 5/4/2014 68 Fat Necrosis A special type of liquefactive necrosis Focal areas of fat destruction Calcium soaps Enzymatic fat necrosis(acute pancreatitis) Nonenzymatic fat necrosis (following direct trauma to adipose tissue & extracellular liberation of fat) 5/4/2014 69 5/4/2014 70 Foci of fat necrosis with saponification in the mesentery. The areas of white chalky deposits represent calcium soap formation at sites of lipid breakdown. 5/4/2014 71 This is fat necrosis of the pancreas. Cellular injury to the pancreatic acini leads to release of powerful enzymes which damage fat by the production of soaps, and these appear grossly as the soft, chalky white areas seen here on the cut surfaces. 5/4/2014 72 12

Gangrene Extensive tissue necrosis Secondary bacterial infection Dry gangrene Wet gangrene Gas gangrene Microscopically, fat necrosis is seen here. Though the cellular outlines vaguely remain, the fat cells have lost their peripheral nuclei and their cytoplasm has become a pink amorphous mass of necrotic material. 5/4/2014 73 5/4/2014 74 This is gangrene, or necrosis of many tissues in a body part. In this case, the toes were involved in a frostbite injury. This is an example of "dry" gangrene in which there 5/4/2014 75 is mainly coagulative necrosis from the anoxic injury. Toxic megacolon. Complete cessation of colon neuromuscular activity has led to massive dilatation of the colon and black-green discoloration signifying gangrene and impending rupture. 5/4/2014 76 Fibrinoid Necrosis A type of connective tissue necrosis Loss of normal structure A homogeneous,bright pink-staining necrotic material that resembles fibrin microscopically The small intestine is infarcted. The dark red to grey infarcted bowel contrasts with the pale pink normal bowel at the bottom. Some organs such as bowel with anastomosing blood supplies, or liver with a dual blood suppy, are hard to infarct. This bowel was caught in a hernia and the mesenteric 5/4/2014 77 blood supply was constricted by the small opening to the hernia sac. 5/4/2014 78 13

5/4/2014 79 Sometimes the small arteries and arterioles can be damaged so severely in malignant hypertension that they demonstrate necrosis with a pink fibrin-like quality that gives this process its name--fibrinoid necrosis. 恶性高血压病的肾脏小动脉 5/4/2014 80 Necrosis (5) Consequences of Necrosis Autolysis & inflammation Dissolution & absorption Sloughing Ulcer, Cavity, Sinus, Fistula Organization & encapsulation Calcification 5/4/2014 81 5/4/2014 82 5/4/2014 83 5/4/2014 84 14

CHAPTER 1 Normal Adaptation Reversible Injury Irreversible Injury 5/4/2014 85 5/4/2014 86 15