04炎症

nullnullChapter 4： InflammationDepartment of Pathology Peking University Health Science Center Zheng JienullSkin blister result from burningSerous effusion accumulated within and underneath the epidermis of skinnullFuruncle（疖）Carbuncle（痈)Outlines of inflammationOutlines of inflammationGeneral Considerations Definition; Inflammatory agents; Basic pathological changes of inflammation; Local and systemic manifestations of Inflammation Acute inflammation The process of vascular and cellular events in inflammation, Inflammatory mediators The classification and outcomes of acute inflammation Chronic inflammation Part 1 General ConsiderationsPart 1 General Considerations DefinitionDefinitionInflammation is a protective response intended to eliminate the initial cause of cell injury as well as the necrotic cells and tissues resulting from the original insult. nullComponents of acute and chronic inflammationInflammatory agentsInflammatory agentsInfections (bacterial, viral, parasitic) and microbial toxins Physical agents (e.g., irradiation, burns) and Trauma (blunt and penetrating) Chemical agents (some environmental chemicals) Ischemic and necrotic tissues Foreign particle (dirt, sutures) Allergic reactionsThe basic pathological changes The basic pathological changes Alteration (degeneration, necrosis) Exudation (hallmark, vascular change, leukocyte reaction, inflammatory mediators ) Proliferation (parenchymal and strmal cells)nullExudation of plasma proteins Exudate and transudate Exudate and transudateCause inflammation non-inflammation Gross cloudy clear Gravity >1.018 <1.018 Protein >30g/L < 30g/L Cell no. >100/mm3 <100/mm3 Coagulation + - Mucoprotein + - null Local manifestations of Inflammation Local manifestations of Inflammation rubor (redness) tumor (swelling) calor (heat) dolor (pain)Systemic manifestations of inflammation Fever Increased acute-phase proteins Leukocytosis Others: increased pulse and blood pressure; decreased sweating; rigors; anorexia Systemic manifestations of inflammation nullPart 2 Acute inflammation The process of acute inflammation The process of acute inflammation Vascular events Cellular events Molecular events Vascular EventsVascular EventsChanges in vascular caliber and flow Transient vasoconstriction of arterioles at the site of injury Vasodilation of precapillary arterioles then increases blood flow to the tissue Increased vascular permeabilitynullThe major local manifestations of acute inflammation: (1) vascular dilation; (2) extravasation of plasma fluid and protein; (3) leukocyte emigration and accumulation in the site of injury Cellular Events1) Recruitment of leukocytes to sites of infection and injury 2) Recognition of microbes and dead tissues 3) Removal of the offending agents 4) Release of leukocyte products and leukocyte-mediated tissue injuryCellular Events1) Recruitment of leukocytes to sites of infection and injuryMargination, rolling and adhesion to endothelium Leukocyte migration through endothelium Chemotaxis and activation 1) Recruitment of leukocytes to sites of infection and injurynullThe multiple process of leukocyte migration through blood vessels. Robbins and Cotran Pathologic Basis of Disease 7th edition Chemotaxis ChemotaxisAfter extravasating from the blood, leukocytes migrate toward sites of injury along a chemical gradient in a process called Chemotaxis. Chemotactic Factors including bacterial products, chemokines, C5a, leukotriene B42) Recognition of microbes2) Recognition of microbesLeukocyte receptors and responses3) Removal of the offending agents3) Removal of the offending agentsPhagocytosis Engulfment Killing and degradationnullRobbins Basic PathologyA. Phagocytosis: Attachment Engulfment Fusion with lysosomes B. oxygen- dependent bactericidal mechanism4) Release of leukocyte products and leukocyte-mediated tissue injury 4) Release of leukocyte products and leukocyte-mediated tissue injury Acute inflammation: e.g., acute respiratory distress syndrome; acute transplant rejection; reperfusion injury Chronic inflammation: e.g., arthritis; asthma; chronic lung disease Inflammatory MediatorInflammatory MediatorFunction of chemical mediators: directing the vascular and cellular events in inflammation Cell-derived or Plasma-derived mediators Act as a complicated network nullCell-derived mediatorsnullGeneration of arachidonic acid metabolites and their roles in inflammation Robbins and Cotran Pathologic Basis of Disease 7th editionMajor effects of IL-1 and TNF Robbins Basic PathologyMajor effects of IL-1 and TNF nullplasma protein-derived mediators nullInterrelationships between the four plasma mediators null Role of Mediators in Inflammation Inflammatory MediatorInflammatory MediatorVasodilatation Vascular permeabilityEDEMAVESOACTIVE MEDIATORS Histamine Bradykinin C3a C5a LT PG PAF NOTISUE INJURY Trauma Ischemia Neoplasm Infectious agents Foreign particlePRODUCTION OF INFLAMMATORY MEDIATORSCHEMOTACTIC FACTORS C5a LTB4 IL-8, TNFinflammatory cellsACUTE INFLAMMATION Neutrophils, Platelets,Mast cell CHRONIC INFLAMMATION Macrophages, Lymphocytes, Platelets Classification of inflammationClassification of inflammationClinical classification Pathological classification nullClinical Classification Acute inflammation Chronic inflammationCharacteristics of Acute InflammationCharacteristics of Acute InflammationShort duration: days to months Acute injuries induced by inflammatory agents Exudation: fluid, plasma proteins, neutrophils Abscess formation Complete resolution can be reached if the injury is limited or short-lived Severe injury healing by scar formation Spreading : septicemia, pyemia,( metastatic abscess) Progression to chronic inflammation Characteristics of Chronic Inflammation Characteristics of Chronic Inflammation Long duration: months to years Persistent infection, prolonged exposure to harmful agents Prolonged tissue destruction, loss of normal structure and function chronic inflammatory cell Infiltration : Macrophages, Lymphocytes, Plasma cells persistent new vessel regeneration and fibroblast proliferation : Resulting in fibrosisPathological ClassificationPathological ClassificationAlteration Inflammation (acute) Exudation Inflammation (acute) Proliferation Inflammation (chronic)Alteration InflammationViral hepatitis (hepatocyte necrosis) Epidemic Type B Encephalitis (neuronal necrosis) Poliomyelitis (neuronal necrosis) Alteration InflammationnullAlteration inflammation----Viral hepatitisExudation InflammationExudation InflammationSerous Inflammation Fibrinous Inflammaion Suppurative Inflammation Phlegnomous Inflammation Superficial Suppuration Abscess Hemorrhagic InflammationSerous InflammationSerous InflammationFeatures: Outpouring of a watery, relatively protein-poor fluid (effusion, with 3%-5% plasma proteins, Albumin) Location: Mucosa, body cavities (peritoneal, pleural & pericardial cavities) , Loose connective tissues Pathologic changes: Inflammatory edema, blister, hydrops, Catarrh Outcome: complete resolutionSerous InflammationSerous InflammationnullFibrinous InflammationFibrinous InflammationCauses: More severe injuries can result in greater vascular permeability. Larger molecules(esp. fibrinogen)come out through the endothelial cells. Pathologic changes: Eosinophilic meshwork of threads or sometimes as an amorphous coagulum. Location: Mucosa, pericardium , peritonium, body cavities, LungExudation InflammationFibrinous InflammationFibrinous InflammationPathologic changes: Mucosa: Pseudomembraneous Pericardium: Shaggy heart Lung: lobar pneumonia Outcome: Resolution: Restore normal tissue structure Organization: scar formation Exudation Inflammation Fibrinous Inflammation of Larynx & Trachea due to diphtheria Fibrinous Inflammation of Larynx & Trachea due to diphtheria Fibrinous Inflammation of Intestine Pseudomembrane (Bacillary Dysentery)Fibrinous Inflammation of Intestine Pseudomembrane (Bacillary Dysentery)Fibrinous Inflammation of Pericardial CavityFibrinous Inflammation of Pericardial CavitynullnullPulmonary CarnificationAdhesive PleuritisSuppurative or Purulent InflammationSuppurative or Purulent InflammationFeatures: The presence of large number of neutrophils and varying degrees of tissue necrosis and pus formation. Causes: Pyogenic (pus-producing) bacteria subclass: Superficial Suppuration, Abscess, Phlegmonous Inflammation Exudation InflammationAbscessAbscessDefinition: Focal localized collections of purulent inflammatory tissues caused by suppuration buried in a tissue, an organ, or a confined space. Reason: a deep seeding of pyogenic bacteria into a tissue Features: Mass of necrotic neutrophils and tissue cells (pus) in the central part, surrounding is cellular proliferation. Exudation Inflammation　Abscess of Lung　Abscess of Lung Abscess of liver 　Abscess of cerebrum Abscess of liver 　Abscess of cerebrumExudation InflammationAbscess of SkinAbscess of Skin Furuncle：the localized suppurative inflammation of haircyst, sebaceous gland & surrounding tissues. Carbuncle：Fusion of quite a few furuncles. Caused by StaphylococciExudation InflammationSuperficial SuppurationSuperficial SuppurationLocation: Mucosa, Serosal Membrane. Features: Pus formation, Suppurative Catarrh, Empyema(积脓) Examples: Gall bladder, Fallopian tube, Suppurative meningitis. Exudation InflammationEmpyema of Fallopian TubeEmpyema of Fallopian TubeSuppurative meningitis (subarachnoid empyema)Suppurative meningitis (subarachnoid empyema)Phlegmonous InflammationPhlegmonous InflammationLocation: Loose connective tissues: Appendix, Skin. Examples: Phlegmonous appendicitis Features: large numbers of neutrophils infiltration. Outcome: heal without sequelaeExudation InflammationAcute phlegmonous appendicitisAcute phlegmonous appendicitisExudation InflammationErysipelasErysipelasAn acute disease of the skin and subcutaneous tissue caused by a species of hemolytic streptococcus and marked by localized inflammation and fever. Also called: Saint Anthony's fireExudation InflammationHemorrhagic InflammationHemorrhagic Inflammation Features: large numbers of RBC in the exudation. Generally: It’s not an independent inflammation In some instances: epidemic hemorrhagic fever、leptospirosis (钩端螺旋体病) and plague (鼠疫)Exudation InflammationnullThe Outcomes of Acute InflammationResolution Progression to chronic inflammation Dissemination Local spread Lymphatic spread Hematogenous spread null Events in the complete resolution of inflammation Return to normal vascular permeability Removal of fluid and protein Macrophage pinocytosis Phagocytosis by neutrophils Necrotic debris by macrophages Eventual exodus by macrophagesnullSinusUlcerFistulaOutcomes of Suppurative InflammationulcerulcerHematogenous Spread of Acute InflammationHematogenous Spread of Acute InflammationBacteremia: bacteria enter systemic circulation Toxemia ： Toxins enter systemic circulation Septicemia: bacteria reproduce in systemic circulation, release endotoxin, induce systemic manifestrations Pyemia：sepicemia results from pyegenic bacteria, embolic abscesses occur in multiple organsMultiple Embolic Abscesses of KidneyMultiple Embolic Abscesses of KidneynullPart 3 Chronic inflammation Proliferation inflammationProliferation inflammation Characterized by cellular proliferation parenchymal cell proliferation mesenchymal cell proliferation lymphoid tissue proliferation granulomatoue inflammation proliferation of macrophage and its derivatives Inflammatory pseudotumor Inflammatory polypnullChronic inflammation in lungGranulomatous InflammationGranulomatous InflammationDefinition: Distinctive pattern of chronic inflammation characterized by aggregates of activated macophages that assume a squamous cell-like appearance (epithelioid cell) Macrophage derivatives: Foamy cell, epithelioid cell, typhoid cell, Aschoff cell, multinuclear giant cell (Langhans’ giant cell, foreign body giant cell) Granulomatous InflammationGranulomatous InflammationTuberculosis Tubercle Leparosy Tuberculoid granuloma Syphilis Gumma (syphiloma) Typhoid Fever Typhoid nodule (typhoid granuloma) Sarcoidosis Noncaseating Epithelioid granuloma Crohn Disease Noncaseating Epithelioid granuloma Rheumatic fever Aschoff body Cat-scratch disease Activated Macrophages in Granulomas Activated Macrophages in GranulomasSpecial type of Macrophage Epithelioid cells: Tuberculosis, Sarcoidosis, Crohn disease, Leparosy Typhoid cells Typhoid fever Aschoff cells Rheumatic fever Multinuclear giant cells Langhans cells : Tuberculosis Foreign body giant cells: Foreign body granulomaChronic InflammationTubercle/ Tuberculous Granuloma Central focus: Caseous necrosis Surrounding: Epithelioid cells Langhans gaint cells Rim: Lymphocytes FibroblastsTubercle/ Tuberculous GranulomanullnullForeign body giant cellsInflammatory PseudotumorInflammatory PseudotumorTumor-like proliferation of local tissues (parenchymal, stromal, even inflammatory cells) resulting from chronic inflammation It is not a real tumor Occur in the orbit, lung, liver and spleenChronic InflammationInflammatory PolypInflammatory PolypPolypoid lesion of mucosa result from Chronic inflammation composed of mucosal glands, granulation tissue, and inflammatory cells. Commonly seen in nasal, cervical & colorectal mucosa.Chronic InflammationnullCauses and outcomes of acute and chronic inflammation