中国医科大学病理学英文课件1

nullnull Chapter I Adaptation and injury of cell or tissuenullAdaptable cellCell death Necrosis apoptosisatrophy hypertrophy hyperplasia metaplasiadegenerationreversibly injured cell Relationship of normal cell, adaptable cell and injured cellNormal cellnullnull 一、Cell adaptation 1 . Definition: a non-injurious reaction of cells, tissues and organs to exogenous and endogenous harmful stimuli.§1. Cell adaptation and aging2. Morphologic manifestation2. Morphologic manifestation Hypertrophy Hyperplasia Atrophy Metaplasia （一）Hypertrophy（一）Hypertrophy 1. Definition: an increase in the size of a tissues or organ due to increased size of individual cellsnull 2.Types (1) Physiologic hypertrophy: pregnancy → uterus↑ (endocrine hypertrophy)Physiologic hypertrophy of uterusPhysiologic hypertrophy of uterus(2) Pathologic hypertrophy (2) Pathologic hypertrophy Hypertension → heart hypertrophy GN → residual nephron hypertrophy 3. EM cell components mitochondria ↑ endoplasmic reticulum microfilament↑ protein synthesis↑ Myocardial hypertrophy Myocardial hypertrophyMyocardial hypertrophyMyocardial hypertrophy（二）Hyperplasia（二）Hyperplasia1. Definition: constitutes an increase in the number of cells in an organ or tissue, which may then have increased volume. 2. Types: (1) Physiologic hyperplasia null ① Hormonal hyperplasia: SMC of uterus during pregnancy ② Compensatory hyperplasia →partial hepatectomy (2) Pathologic hyperplasia: excessive hormonal stimulation the effects of growth factors on target cellsHyperplasia of mucosal epithlium(gastric ulcer)Hyperplasia of mucosal epithlium(gastric ulcer) Subacute severe hepatitis Subacute severe hepatitis Gastric polyp Gastric polypGastric polypGastric polyp Hepatic cirrhosis Hepatic cirrhosisnull3. Distinguish between hyperplasia and neoplasia proliferation (1) Hyperplasia: stimuli abates→hyperplasia disappears (2) Neoplasia proliferation: continuousnull1.Definition: Normal formed organ or tissue diminished in size due to decrease in the size of the parenchymal cells or in the number of cells. 2. Hypoplasia: organ or tissue can’t develop fully to normal size Aplasia: state of non-developing（三）Atrophy3. Types:3. Types:(1) Physiologic atrophy (2) Pathological atrophy: according to different causes, divided into following types Physiologic atrophy of brainPhysiologic atrophy of brainnull① Insufficient nutritive atrophy: whole body: malignant tumor ② Atrophy of disuse: decreased workload → skeletal muscle fiber decrease in number as well as in size when a patient is restricted to complete bed rest.null③ Denervation atrophy: damage to the nerves leads to rapid atrophy of keletal muscle supplied by those nerves. ④ Pressure atrophy: an enlarged tumor can cause atrophy in the surrounding compressed tissue. null⑤ Endocrine atrophy: loss of endocrine (estrogen) stimulation atrophy of endometrium, vaginal epithelium and breast ⑥ Endocrine atrophy: AS → brain4. Morphologic changes4. Morphologic changes(1) Gross appearance: volume ↓ weight↓null Pressure atrophy of kidney nullPressure atrophy of brainnull(2) Histological changes: Decrease in the size and number of cells. Lipofuscin → brown atrophy (heart or liver) nullAtrophy of myocardiumNormal myocardiumAtrophy of skeletal muscleAtrophy of skeletal musclenull (3) EM: increases in the number of autophagic vacuoles cell debris within autophagic vacuoles residual body (membrane-bound vacuoles)（四）Metaplasia（四）Metaplasia 1.Definition: a process in which one matured tissue type (epithelial or mesenchymal) is replaced by another matured tissue type. 2. Causes: chronic stimulation→activated or suppressed of related genes if persistent→ induce canceration3. Epithelial metaplasia3. Epithelial metaplasia (1) Squamous metaplasia: occurs in the respiratory tract chronic irritation deficiency of Vit A cigarette smoker nullHyperplasia of reserve cells in cervical epitheliumHyperplasia of reserve cells in cervical epitheliumnull(2) From squamous to columnar type: Barret esophagitis squamous cell intestinal–like columnar cell Columnar metaplasia of barret esophagitis Columnar metaplasia of barret esophagitis (3) Glandular metaplasia (3) Glandular metaplasiaIntestinal mataplasia 4.Mesenchymal tissue metaplasia4.Mesenchymal tissue metaplasia Epithelial metaplasia → reversible Bone cartilage → irreversibleOsseous metaplasia 二、Cellular aging(senescence)二、Cellular aging(senescence) Definition: the maturation and differentiation of the organs and its cells lead to the progressive loss of functional capacityAgingAgingnull (一) Aging clock: 1. Timing of the aging process – the concept of a clock: ① Controlling the rate and timing of aging is supported by the identification of clock genes.null② Telomeres: short repeated DNA sequences telomerase ensuring the complete replication of chromosomal ends protecting chromosomal termini from fusion and degradationnull Clock genes Telomerase activity decreasing ( Telomerase activity is expressed in germ cells and is present at low levels in stem cells, but it is usually absent in most somatic tissues.)telomere shortening（older of the cell and shorter of the telomere ） cell aging(二) Metabolic events, genetic damage and aging(二) Metabolic events, genetic damage and agingCellular life may also be determined by the balance between cellular damage repairment Free radical → oxidative damage Metabolic substances Toxic substances DNA damagenull Accumulating of metabolic substancestoxic substances DNA damage （ DNA damage is repaired by endogenous DNA repair enzymes, some damage persists and accumulates Cellular aging§2 Injury of cells and tissues§2 Injury of cells and tissues 一. Causes （一）Hypoxia (commom and important) 1. Ischemia 2. Heart Lung failure 3. Loss of the oxygen – carrying capacity of the bloodinadequate oxygenationnull(二) Physical agents 1. Mechanical trauma 2. Extremes of temperature : burns or exceeded cold 3. Changes in atmospheric pressure 4. Radiation（三） Chemical agents and drugs（三） Chemical agents and drugs All chemical agents and drugs Simple chemicals ( glucose or salt )in hypertonic concentrations Cell injury （四）Biologic agents (most common)（四）Biologic agents (most common)1. viruses 2. bacteria 3. others：fungi (fungus); parasites （五）Immunologic reactions 1.Anaphylactic reaction to foreign protein drugs 2. Endogenous self-antigen →autoimmune diseases （六）Genetic defect （六）Genetic defect Chromosomal aberration or gene mutation Errors of metabolism arising from enzymatic abnormalities null（七）Nutritional imbalance 1. Nutritional deficiency: protein ,Vitamin 2. Nutritional excesses Excesses of lipid → AS Fat↑→ obesity Vitamin D →calcification null1. ATP depletion 2. Irreversible mitochondria damage 3. Loss of membrane permeability 4. Overload of intracellular calcium and loss of calcium homeostasis 5. Accumulation of free radicals 二. Mechanisms of cell injuryCauses of cell injuryCauses of cell injury Mechanisms of cell injury Mechanisms of cell injurynull三.Morphologic changes of cell injury三.Morphologic changes of cell injury (一) Reversible injury (Degeneration) Definition: Morphologic changes of cell or extracellular stromal damage due of metabolic disorder the deposition of some abnormal substance excessive normal substance in cell or stroma (二) Substance accumulation in intra(extra)cellular space (二) Substance accumulation in intra(extra)cellular space Excessive normal substance in cell or stroma Water, lipid, protein The deposition of some abnormal substance Infectious products, mineral substance1. Hydropic degeneration (cellular swelling ) 1. Hydropic degeneration (cellular swelling ) The first manifestation of cell injury (1) The common site: liver, kidney , heart (2) Causes: hypoxia,infection,intoxication Mi injury →Na+-K+ pump dysfunction Na+, H2O↑ (3) Pathologic changes : (3) Pathologic changes : ① Gross appearance: increased in the weight of the organ cutting surface pallor in color capsule tense, section bulgy, cutting edge bulging, Cellular swelling of liver Cellular swelling of liver ② LM: ② LM:cell swelling fine, red-stained granules within cytoplasm small clear vacuoles Ballooned change clear cytoplasm cell swelling obviously ③ EM Mitochondria ERswellingCellular swelling of hepatocyteCellular swelling of hepatocyteBallooned change Swelling of endoplasmic reticulum Swelling of endoplasmic reticulumCellular swelling of hepatocyte(EM)Cellular swelling of hepatocyte(EM) 2. Fatty change (steatosis): 2. Fatty change (steatosis):(1) The common site: liver, heart , kidney, muscle (2) Causes hypoxia infection intoxication obesitynull(3) Definition: abnormal accumulations of fat (triglyceride, cholesterol, phospholipid) within parenchymal cells. (4) Morphology ① Gross: enlarged, yellow,soft,greasy ② LM: clear vacuoles in the cytoplasm around the nucleusnull Accumulation of fat, glycogen, water vacuoles PAS(Periodic acid-schiff) (+) →glycogen Oil Red-0 (+) Sudan Ⅲ (+) ③ EM: liposome membrane-bound round body fatnull(1) Fatty liver :most often seen in the liver ① Causes toxins protein malnutrition , diabetes , obesity alcohol abuse in industrialized nations the most common causenull② Gross: Enlarged , yellow , soft (section) →greasynull③ LM: Small vacuoles around nucleus ↓coalesce large vacuoles that displace the nucleus to the periphery of the cell.Fatty liver （SudanⅢ stained）Fatty liver （SudanⅢ stained）(2) Fatty change of myocardium(2) Fatty change of myocardium① Local type The common site Subendocardium papilary muscle Gross: Tigered effect apparent bands of yellowed myocardium alterating with bands of darker, red- brown(uninvolved) myocardiumleft ventriclenullLM: string of bead-like small droplets near the nucleus ② Diffuse type: Cause: severe hypoxia or poisoning Lesion: diffuse light yellowFatty change of myocardiumFatty change of myocardiumMyocardial fatty infiltration: Myocardial fatty infiltration: Different from myo-fatty change: In subpericardial, excessive fat accumulating and inserting among myocardial bandles. Causes: obvious obesity, alcohol abuse Sudden death Myocardial fatty infiltration Myocardial fatty infiltration(3) Fatty change of renal tubule epithelium (3) Fatty change of renal tubule epithelium Causes lipoprotein↑ reabsorption of lipoprotein↑ LM: droplets within proximal tubule epithelium(4) Cholesterol or cholesterol ester(4) Cholesterol or cholesterol ester① Atherosclerosis: cholesterol crystal ② Xanthoma: Macrophage phagocyte cholesterol foam-like ③ Inflammation and necrosis:foam cell ④Type C Manni-Pick Disaese: Deposition of cholesterol 3.Hyaline change(degeneration)3.Hyaline change(degeneration) Definition: an alteration within cells, in the extracellular space and walls of arterioles which gives a homogeneous glassy, pink appearance(1) Walls of arterioles:(1) Walls of arterioles:① Hypertension: walls of arterioles, in the kidney, brain, spleen, retina ② Diabetes: walls of arterioles of all body, especially in the kidney Hyaline change of central artery Hyaline change of central artery Sclerossis of renal afferent arterySclerossis of renal afferent artery(2) Connective tissue:(2) Connective tissue:① Site: old scars, glomerulus fibrosis, fibrous plaque (AS) ② Gross: gray, glassy appearance ③ LM: homogeneous ,pink ,beam-like substenceHyaline change of pleuraHyaline change of pleura (3) Within cells: (3) Within cells:① Reabsorbed droplets: varies in size red droplets in proximal tubule cells Hyaline change of proximal tubule cell ( Masson stain )Hyaline change of proximal tubule cell ( Masson stain )null②Mallory bodies (Alcoholic hyaline body): alcoholic liver disease red stained inclusion ③Russell body: within plasma cells Ig accumulated in ERMallory bodies (Alcoholic hyaline body)Mallory bodies (Alcoholic hyaline body)