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1、 CHAPTER 4 3/23/2022PATHOLOGY FOR 7 1Liqin Ma (马丽琴)Institute of Pathology, Zhejiang University School of MedicineEmail: CHAPTER 4 3/23/2022PATHOLOGY FOR 7 2 Master the definition and basal pathological changes of inflammation. Master the morphologic characteristics of inflammation of different types

2、. Comprehend the course and result of inflammation. Purpose CHAPTER 4 3/23/2022PATHOLOGY FOR 7 31. Overview of inflammation 2. Basal pathological changes of inflammation3. Classification of inflammation4. Outcomes of inflammation Contents CHAPTER 4 3/23/2022PATHOLOGY FOR 7 4SECTION 1 OVERVIEW OF INF

3、LAMMATION CHAPTER 4 3/23/2022PATHOLOGY FOR 7 5Inflammation is a Protective response of living tissue which developed blood system to injury. Definitionnaturecausecondition site CHAPTER 4 3/23/2022PATHOLOGY FOR 7 6 A Protective Response in Vascularized Connective TissuesVascular ChangesInvolves: vasc

4、ular ,neurological, humoral, cellular response Definition Definition CHAPTER 4 3/23/2022PATHOLOGY FOR 7 7 Blood vessel and other components CHAPTER 4 3/23/2022PATHOLOGY FOR 7 8 Beneficial :a. Elimination the initial cause of cell injury: diluting or neutralizing the harmful agentsb. Promotion the re

5、pair of damaged tissue: regeneration of parenchymal cells or filling with fibrous scar tissue Harmful: causing the tissues damage, e.g. hypersensitive response, pericardial inflammation-dense scar-impairing cardiac function Why the human body can emerge the inflammation? CHAPTER 4 3/23/2022PATHOLOGY

6、 FOR 7 9 Plasma proteins (albumin, globulin, ) and circulating cells exudation caused by vascular reactions. Core changes CHAPTER 4 3/23/2022PATHOLOGY FOR 7 10 CHAPTER 4 3/23/2022PATHOLOGY FOR 7 11 CHAPTER 4 3/23/2022PATHOLOGY FOR 7 12Causes of inflammationA. Microbial or Biological agents B. Physic

7、al agentsC. Chemical agentsD. Immunological agents Causes of inflammation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 13 Causes of inflammation 1. Microbial agents：bacteria, virus, fungus, ricketts organism, parasite (infection) The commonest cause of inflammation Causes of inflammation CHAPTER 4 3/23/2022PA

8、THOLOGY FOR 7 14tooth extraction CHAPTER 4 3/23/2022PATHOLOGY FOR 7 152. Chemical agents：acids, alkalis, oxidising agents, reducing agents, bacterial toxins 3. Physical agents: physical trauma, ionising radiation, burn, excessive cooling. Causes of inflammation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 16e

9、xcessive cooling CHAPTER 4 3/23/2022PATHOLOGY FOR 7 17exfoliation by Burn CHAPTER 4 3/23/2022PATHOLOGY FOR 7 18physical trauma CHAPTER 4 3/23/2022PATHOLOGY FOR 7 194. Immunological reaction: hypersensitivity reactions( pollen, medicine, food,) ,inappropriate or excessive immune reaction5. Endogenous

10、 agents：tissue necrosis 6. Exogenous agents: foreign bodies- splinter, sutures, hemostat，Causes of inflammation Causes of inflammation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 20pollen hypersensitivityDrug/food hypersensitivity CHAPTER 4 3/23/2022PATHOLOGY FOR 7 21Clinical signs of inflammation Local clin

11、ical signs Systemic clinical signs CHAPTER 4 3/23/2022PATHOLOGY FOR 7 22 Heat (calor) Redness (rubor) Swelling (tumor) Pain (dolor) Loss of function (functio laesa) Local Signs Of Inflammation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 23 Heat Redness Swelling Pain Loss of function INFLAMMATION CHAPTER 4 3/

12、23/2022PATHOLOGY FOR 7 24redness(ruber); due to dilatation of small blood vessels CHAPTER 4 3/23/2022PATHOLOGY FOR 7 25Eyelid Swelling (tumor) CHAPTER 4 3/23/2022PATHOLOGY FOR 7 26 heat (calor): contain increase of local temperature and systemic fever pain (dolor) : cause by stretching and distortio

13、n of tissues+ chemical mediators loss of the function was added by Virchow (1821-1902) CHAPTER 4 3/23/2022PATHOLOGY FOR 7 27A. Fever B. Changes in the Peripheral White Blood Cell Count Systemic clinical signs CHAPTER 4 3/23/2022PATHOLOGY FOR 7 28A. Fever Exogenous pyrogens Endogenous pyrogens System

14、ic clinical signsInterleukin-1,6 (IL-1,IL-6),TNF CHAPTER 4 3/23/2022PATHOLOGY FOR 7 29Cause of Pyrexia: endogenous pyrogens hypothalamus(下丘脑下丘脑) thermoregulatory mechanisms increasing the temperaturetriggerevokeinduce CHAPTER 4 3/23/2022PATHOLOGY FOR 7 30B. Changes in the Peripheral White Blood Cell

15、 Count 1520X103 cells/microliter (normal range:410X103microliter) Systemic clinical signs Systemic clinical signs CHAPTER 4 3/23/2022PATHOLOGY FOR 7 31Haematological change Neutrophilia: purulent infections ,acute inflammation Eosinophilia: allergic disorders or parasitic infection Lymphocytosis: ch

16、ronic infection or viral infection Monocytosis: infectious mononucleosis CHAPTER 4 3/23/2022PATHOLOGY FOR 7 32 Proliferation of mononuclear phagocyte system Pathological changes： 1.local or systemic lymph nodes enlargement,2.splenomegaly (enlarged spleen) CHAPTER 4 3/23/2022PATHOLOGY FOR 7 33 Pay at

17、tention to: Local manifestations often companied with general reactionsHeatIncreasing of white blood cells CHAPTER 4 3/23/2022PATHOLOGY FOR 7 34 Types of Inflammatory Cells来源；形态；功能来源；形态；功能NeutrophilsLymphocytesPlasmocytesMonocytesEosinophilsBasophilsGiant cells CHAPTER 4 3/23/2022PATHOLOGY FOR 7 35T

18、ype of inflammation cells CHAPTER 4 3/23/2022PATHOLOGY FOR 7 36Left, Eosinophils. Middle, Lymphocytes. Right, Plasma Cells.Inflammatory cells CHAPTER 4 3/23/2022PATHOLOGY FOR 7 37 Inflammatory cell Neutrophils: Conception: Granular leukocytes having a nucleus with three to five lobes connected by sl

19、ender threads of chromatin, and cytoplasm containing fine inconspicuous granules . early stage of acute inflammation and purulent inflammation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 38Neutrophils- threeleaf nuclear CHAPTER 4 3/23/2022PATHOLOGY FOR 7 39 Inflammatory cell Eosinophils : Conception: Granula

20、r leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. allergy and parasitic infection CHAPTER 4 3/23/2022PATHOLOGY FOR 7 40Eosinophils CHAPTER 4 3/23/2022PATH

21、OLOGY FOR 7 41Inflammatory cell Basophils : Conception: Granular leukocytes characterized by a relatively blue-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. acute and persisting inflammation, anaphylactic reaction CHAPTE

22、R 4 3/23/2022PATHOLOGY FOR 7 42Inflammatory cell Lymphocytes : Conception: The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is little and typically pale blue with azurophilic (if any) granules. (Most lymphocytes can be classified as either T or B), those w

23、ith characteristics are called null cells. viral infection, all forms of chronic inflammation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 43Identify the segmented neutrophil, band neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet in the image CHAPTER 4 3/23/2022PATHOLOGY FOR 7 44Inflammato

24、ry cell Plasmacytes : Conception: Specialized forms of antibody-producing B-LYMPHOCYTES. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses. Its nucleus is round or ovoid with coarse, regularly clumped chromatin (rotiform or wheel-like

25、) while the cytoplasm is bulk. viral infection, all forms of chronic inflammation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 45Inflammatory cell Monocytes: Conception: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewh

26、at indented nucleus surrounded by voluminous cytoplasm and numerous organelles. later stage of acute inflammation, some special infectious disease CHAPTER 4 3/23/2022PATHOLOGY FOR 7 46 Macrophages:Macrophages are derived from blood monocytes that emigrate from blood vessels under influence of chemot

27、actic factors.Commonly seen in later stage of inflammation, chronic inflammation, non-purulent inflammation, and viral, or protozoal, or fungal infections. And macrophages are also related to specific immune response.Inflammatory cell CHAPTER 4 3/23/2022PATHOLOGY FOR 7 47 dusty cell foamy cell Macro

28、phages epithelioid cell heart failure cell Multinucleate giant-cells Inflammatory cellforeign-body giant cell , Langhans giant cell CHAPTER 4 3/23/2022PATHOLOGY FOR 7 48A macrophage , B foreign body giant cell, C heart failure cell, D. Langhanstype giant cells, E. foam cells, F. typhoid cell, G dust

29、 cell Different kinds of cell derived from macrophage. CHAPTER 4 3/23/2022PATHOLOGY FOR 7 49Proliferation of giant macrophages with multiple nuclei in Foreign-body granuloma. CHAPTER 4 3/23/2022PATHOLOGY FOR 7 50Hoof-likeChaplet-like CHAPTER 4 3/23/2022PATHOLOGY FOR 7 51 SECTION 2BASIC PATHOLOGICAL

30、CHANGES CHAPTER 4 3/23/2022PATHOLOGY FOR 7 52two main courses: vascular response cellular changesThree changes: Alteration , Exudation, Proliferation Basic pathological changes CHAPTER 4 3/23/2022PATHOLOGY FOR 7 53AlTERATION CHAPTER 4 3/23/2022PATHOLOGY FOR 7 54 Conception : The tissues or cells in

31、the inflammatory site become degeneration and/or necrosis. CHAPTER 4 3/23/2022PATHOLOGY FOR 7 55Alteration CHAPTER 4 3/23/2022PATHOLOGY FOR 7 56Parenchymal cells Hydropic change Fatty change Hyaline change Coagulative necrosis Caseous necrosis Liquefactive necrosis Gangrene CHAPTER 4 3/23/2022PATHOL

32、OGY FOR 7 57Interstitial cells Hyaline change Amyloidosis Mucoid change Fibrinoid necrosis CHAPTER 4 3/23/2022PATHOLOGY FOR 7 58 Morphological: swelling, redness, accumulation of fluid in the extra vascular space CHAPTER 4 3/23/2022PATHOLOGY FOR 7 59Hydropic change/ Ballooning degeneration CHAPTER 4

33、 3/23/2022PATHOLOGY FOR 7 60Fatty /adipose degeneration CHAPTER 4 3/23/2022PATHOLOGY FOR 7 61Caseous necrosismultinucleated giant cell CHAPTER 4 3/23/2022PATHOLOGY FOR 7 62Neurocyte and gliocyte net necrosisBrain Parenchyma CHAPTER 4 3/23/2022PATHOLOGY FOR 7 63EXUDATION CHAPTER 4 3/23/2022PATHOLOGY

34、FOR 7 64Process of the movement of fluid, proteins and blood cells from the vascular systeminto the interstitial tissues or body cavities onto the surface of skin or mucosa surfaceConception of Exudation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 65 Inflammatory exudate: Fluid exudate out of blood vessel in

35、 inflammation area Inflammatory edema: exudate fluid into the space of tissue Inflammatory hydrops: Accumulation of exudate fluid within the body cavity (bloated) and the arthritic space (arthrocele) Type of Exudation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 66 Changes in vascular caliber and flow Increas

36、ed vascular permeability Exudation of fluid Cellular responseProcess of Exudation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 67a.Inconstant and transient vasoconstriction of arterioles. Seconds or minutesb. Persistent Vasodilatation Increased local metabolism, redness and warmth. CHAPTER 4 3/23/2022PATHOLOG

37、Y FOR 7 68normalInconstant and TransientVasoconstrictionSeconds or minutes Persistent Vasodilatation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 69 a. Initially rapid as a result of vasodilatation (active hyperemia)b. Slowing and disturbance of axial flow as a result of increased blood viscosity secondary to

38、 loss of plasma into the tissue (congestion and edema) CHAPTER 4 3/23/2022PATHOLOGY FOR 7 70c. Stasis: With the exudation of protein-rich fluid into the extravascular tissue, the blood become more concentrated and the viscosity increased, thereby slowing the blood circulation. CHAPTER 4 3/23/2022PAT

39、HOLOGY FOR 7 71VasodilatationNormal Vasodilatation, exudation slowing the blood circulation, exudation slowing the blood circulation, exudation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 72Increased Vascular Permeability Gaps due to endothelial contraction Direct injury (Endothelial injury) Leukocyte-depend

40、ent injury Increased transcytosis (protein tissue) New blood vessel formation (Immature)Causes or mechanisms : CHAPTER 4 3/23/2022PATHOLOGY FOR 7 73five mechanisms of increased vascular permeability in inflammation CHAPTER 4 3/23/2022PATHOLOGY FOR 7 74Endothelial cell contractionEndothelial injuryIn

41、creased transcytosisprotein CHAPTER 4 3/23/2022PATHOLOGY FOR 7 75Cause of fluid exudation during inflammation a. Increased vascular permeability b. Increased microcirculation hydrostatic pressure. c. Decreased effective colloid osmotic pressure. Exudation of Fluid CHAPTER 4 3/23/2022PATHOLOGY FOR 7

42、76Balance Unbalance CHAPTER 4 3/23/2022PATHOLOGY FOR 7 77intra-alveolar exudate with few neutrophils CHAPTER 4 3/23/2022PATHOLOGY FOR 7 78 Exudate: extravascular fluid collection that is rich in protein and/or cells. Fluid appears grossly cloudy. Transudate: extravascular fluid collection that is ba

43、sically an ultrafiltrate of plasma with little protein and few or no cells. Fluid appears grossly clear. CHAPTER 4 3/23/2022PATHOLOGY FOR 7 79 CHAPTER 4 3/23/2022PATHOLOGY FOR 7 80Exudates vs Transudates Exudate Transudate Vascular permeability Increased Normal Protein content 1.5-6 g/Deciliter 0-1.

44、5 g/dL Protein types All Albumin Rivalta test (mucoprotein) (+) (-) Fibrin (+) (-) Specific gravity 1.020 1.012 CHAPTER 4 3/23/2022PATHOLOGY FOR 7 81Exudates vs Transudates Exudate Transudate Permeability increased normal Leukocyte 0.1109/L 0.1109/L Coagulability self-coagulation non self-coagulatio

45、n Transparency cloudy clear CHAPTER 4 3/23/2022PATHOLOGY FOR 7 82 Transudate Exudate blood CHAPTER 4 3/23/2022PATHOLOGY FOR 7 83d) The significance of fluid exudatesAdvantage of exudation ：a. Dilution of toxin and carrying off harmful materialb. Entry of numerous antibodies and complement components

46、; transport of drugsc. Fibrin formation: suppress the spread of pathogen, beneficial for phagocytosis and repair;d. Inducing Immune response to the inflammation agent CHAPTER 4 3/23/2022PATHOLOGY FOR 7 84Disadvantage： Disadvantage of exudation ： Oppression, adhesion and swelling in closed space such

47、 as the cranial cavity: acute meningitisraise intracranial pressureischemic damage , anoxic encephalopathy coma, death CHAPTER 4 3/23/2022PATHOLOGY FOR 7 85Suppurative meningitis raise intracranial pressure CHAPTER 4 3/23/2022PATHOLOGY FOR 7 86A “ bread and butter” appearance in visceral and parieta

48、l pericardiumFibrin exudationHairy heart /cor villosum CHAPTER 4 3/23/2022PATHOLOGY FOR 7 87Fibrin exudation in visceral pericardium CHAPTER 4 3/23/2022PATHOLOGY FOR 7 88organization of the exudate in lung CHAPTER 4 3/23/2022PATHOLOGY FOR 7 89 Inflammatory infiltration: Leukocytes traverse blood wal

49、l and enter interstitial space to exert phagocytosis during inflammation. inflammatory cellsCellular Response CHAPTER 4 3/23/2022PATHOLOGY FOR 7 90 Margination & Rolling Adhesion & Transmigration Chemotaxis Phagocytosis & degradationCourse of Inflammatory infiltration CHAPTER 4 3/23/2022

50、PATHOLOGY FOR 7 91 Margination and Rolling Margination: accumulation process of leukocytes to periphery of bloodflow; from axial flow to margin Rolling: The process of leukocytes tumble on the endothelial surface, transiently sticking along the way. Selectin Family: E- Selectin: endothelium P- Selec

51、tin: endothelium+ platelets L- Selectin: leukocytes CHAPTER 4 3/23/2022PATHOLOGY FOR 7 92Margination & Rolling CHAPTER 4 3/23/2022PATHOLOGY FOR 7 93Margination & Rolling CHAPTER 4 3/23/2022PATHOLOGY FOR 7 94Margination & Rolling CHAPTER 4 3/23/2022PATHOLOGY FOR 7 95 AdhesionConception: l

52、eukocytes firmly stick to endothelial surface by the binding of adhesion molecules (selectins, immunoglobulins, intergrins, mucin-like glycoproteins)Cell adhesion molecule: immunoglobin superfamily; It consist of at least three identified families: cytoadhesin receptors, leukocyte adhesion receptors

53、 , and very late antigen receptors.They interact with a wide variety of ligands including extra cellular matrix proteins ,complement, and others. CHAPTER 4 3/23/2022PATHOLOGY FOR 7 96Adhesion & Transmigration CHAPTER 4 3/23/2022PATHOLOGY FOR 7 97 Emigrating It refers to the process by which moti

54、le white cells migrate out of blood vessels. Although all leukocytes are more or less motile, the most active are neutrophils, than monocytes; the most sluggish are lymphocytes. While cells emigration is an active, energy-dependent process. Red blood cell out of blood vessels, is believed to be pass

55、ive loss of red blood cells through the points of rupture (blooding). CHAPTER 4 3/23/2022PATHOLOGY FOR 7 98TransmigrationActive amoeboid movementTransmigration: crawling between endothelial cellsand through the basement membrane into the extravascular space CHAPTER 4 3/23/2022PATHOLOGY FOR 7 99Adhes

56、ion & Transmigration CHAPTER 4 3/23/2022PATHOLOGY FOR 7 100Margination ,Rolling, Adhesion Inflammatory infiltration CHAPTER 4 3/23/2022PATHOLOGY FOR 7 101CHEMOTAXISConception : A process of leukocytes migrating toward the sites of injury along a chemical gradient CHAPTER 4 3/23/2022PATHOLOGY FOR

57、 7 102Chemotaxis CHAPTER 4 3/23/2022PATHOLOGY FOR 7 103Chemical substance which can induce leukocytes to directionally emigrate. Chemotactic factors CHAPTER 4 3/23/2022PATHOLOGY FOR 7 104 Chemotactic agents bind to specific receptors and induce an intracellular cascade of phospholipid metabolism whi

58、ch eventually culminating in increased intracellular calcium and triggers the assembly of cytoskeletal contractile elements necessary for movement. CHAPTER 4 3/23/2022PATHOLOGY FOR 7 105 Chemotactic factors Type Endogenous chemotactic agents Exogenous chemotactic agents CHAPTER 4 3/23/2022PATHOLOGY

59、FOR 7 106 Exogenous chemotactic agents: soluble bacterial products Endogenous chemotactic agents： Components of the complement system:C5a Products of lipoxygenase pathway of arachidonic acid metabolism; Cytokines: Interleukin-8(IL-8) Chemotactic factors CHAPTER 4 3/23/2022PATHOLOGY FOR 7 107 CHAPTER

60、 4 3/23/2022PATHOLOGY FOR 7 108Conception : The processes leukocyte phagocytose pathogenic microorganism,foreign body and tissue debris in inflammatory foci. Phagocyte ：1) Neutrophil (microphage): phagocytose many kinds of pathogenic microorganism and tissue debris.2) Macrophage (large phagocyte): Phagocytosis CHAPTER 4 3/23/2