病理生理学：Inflammation

1、Chapter Four,Inflammation,Definition,The defending reaction of vascularized living tissue to local injury,Response to injury vascularized living tissue defending,Causes of Inflammation,infective factors immune reactions physical factors chemical factors traumatic factors,Fundamental Pathologic Chang

2、es,Fundamental Pathologic Changes,1, Alteration Degeneration and necrosis,Alteration,Parenchymal cells Cellular swelling, fatty degeneration Necrosis Interstitial tissues Edema, mucoid degeneration fibrinoid necrosis,Fundamental Pathologic Changes,2, Exudation The escape of fluid, proteins, and bloo

3、d cells from the vascular system into the interstitial tissue or body cavities,Fundamental Pathologic Changes,3, Proliferation 1) the parenchymal cells 2) fibroblasts and capillary endothelial cells 3) inflammatory cells, e.g. Plasma cells and macrophages,General Featuresof Inflammation,Local Signs

4、of Inflammation,redness swelling heat pain loss of function,Systemic Manifestations,Fever and leukocytosis,Classification-according to time course,Peracut inflammation Acute inflammation - the initial and often transient series of tissue reaction to injury Chronic inflammation - the subsequent and o

5、ften prolonged tissue reaction following the initial response Subacute inflammation - in between acute and chronic inflammation,Acute Inflammation,Vascular changes,1, Changes in vascular caliber and blood flow. Inconstant and transient vasoconstriction of arterioles Vasodilation and increase of bloo

6、d flow; Dilatation of capillaries and venules, slowing of blood flow (stasis,Vascular changes,2. Increased Vascular Permeability leading to the escape of a protein-rich fluid (exudate) into the interstitium the hallmark of acute inflammation,Vascular changes,Increased Vascular Permeability Mechanism

7、 Formation of endothelial gaps in venules (endothelial contraction) Increased transcytosis Endothelial injury,Increased Vascular PermeabilityExudate and Transudate Edema denotes an excess of fluid in the interstitial or serous cavities; it can be either an exudate or transudate,Increased Vascular Pe

8、rmeability,An exudate is an inflammatory extravascular fluid that has a high protein concentration, much cellular debris, and a specific gravity over 1.020 A transudate is a fluid with low protein content (most of which is albumin) and a specific gravity of less than 1.012,渗出液与漏出液,Increased Vascular

9、 Permeability,Significance of Exudate Defending Dilute toxin, carry nutrition and remove metabolic products Contain antibodies and complements Fibrin formation Negative effects,Cellular Events: Leukocyte Extravasation and Pahgocytosis,Extravasation: The sequence of events in the journey of leukocyte

10、s from the lumen to the interstitial tissue,Cellular Events: Steps of Extravasation,In the lumen: margination, rolling, and adhesion Transmigration across the endothelium Migration in interstitial tissues toward a chemotactic stimulus,Cellular Events: Adhesion and Transmigration,Leukocyte adhesion a

11、nd transmigration are largely determined by the binding of complementary adhesion molecules on the leukocyte and endothelial surface and chemical mediators,Cellular Events: Mechanisms of Adhesion,Redistribution of adhesion molecules to the cell surface Induction of adhesion molecules on endothelium

12、Increased avidity of binding,Cellular Events: Chemotaxis,After extravasation, leukocytes emigrate in tissues toward the site of injury by a process called chemotaxis, defined as locomotion oriented along a chemical gradient,Cellular Events: Chemoatractants,Exogenous bacterial products Endogenous 1)

13、C5a 2) leukotriene B4 3) Cytokines (e.g. IL-8,Cellular Events: Phagocytosis,Steps of Phagocytosis Recognition and attachment Engulfment Killing or degradation,Cellular Events: Recognition and Attachment,opsonins The Fc fragment of IgG C3b, the opsonic fragment of C3 Lectins,Cellular Events: Killing

14、or Degradation,Oxygen-dependent Mechanisms - H2O2 - MPO - halide system 2O2+NADPH 2O2-+NADP+H+ 2O2-+2 H+ H2O2+O2 MPO H2O2+CL- HOCL+H2O,Cellular Events: Killing or Degradation,Oxygen-independent Mechanisms Bactericidal permeability increase protein (BPI) lysozyme lactoferrin major basic protein defen

15、sins,Cellular Events: Inflammatory Cells,Neutrophils Monocytes and macrophages Lymphocyts and plasma cells Eosinophilic leukocytes Basophilic leukocytes and mast cells,Cellular Events: Leukocyte Functions,Phagocytosis and immune reactions Leukocyte-induced injury Defects in Leukocyte Function,Chemic

16、al Mediators of InflammationPlasma derived Mediators,Kinin system: bradykinin, kallikeins Complement system: C3a, C5a, C567 Clotting system and fibrinopeptides,Chemical Mediators of InflammationCell-derived mediators,Vasoactive amines: histemin, serotonin (5-HT) Arachidonic acid metabolites: postgla

17、ndins, leukotrienes Lysosomal components:cationic protein, neutral proteases,Chemical Mediators of InflammationCell-derived mediators,Oxygen metablolites: oxygen derived free radicals Platelet activating factor (PAF) Cytokines: IL-1, TNF,Mediators in InflammationVasodilation,Prostaglandins Nitric ox

18、ide,Mediators in InflammationIncreased vascular permeability,Vasoactive amines C3a and C5a Bradykinin Leukotrienes C4, D4, E4 PAF,Mediators in InflammationChemotaxis, leukocyte activation,C5a Leukotriene B4 Chemokines Bacterial products,Mediators in InflammationFever,IL-1, IL-6, TNF Prostaglandins,M

19、ediators in InflammationPain,Prostaglandins Bradykinin,Mediators in InflammationTissue damage,Neutrophil and macrophage lysosomal enzymes Oxygen metabolites Nitric oxide,Morphologic Patterns of Acute Inflammation,Morphologic Patterns of Acute Inflammation,Serous inflammation Excessive clear watery f

20、luid, with a variable protein content “Catarrh” mon cold,Morphologic Patterns of Acute Inflammation,Fibrinous inflammation With more severe injuries and the resulting greater vascular permeability, larger molecules such as fibrin pass the vascular barrier, e.g. Acute pleurisy, lobar pneumonia, fibri

21、nous pericarditis,Morphologic Patterns of Acute Inflammation,Fibrinous inflammation *Pseudo-membranous inflammation A membranous film consisting mainly of fibrin with necrotic cells admixed, forms on a mucosal surface e.g. Diphtheria and bacillary dysentery,Morphologic Patterns of Acute Inflammation

22、,Suppurative or purulent inflammation Characterized by the production of large amounts of pus or purulent exudate consisting of neutrophils, necrotic cells, and edema fluid,Morphologic Patterns of Acute Inflammation,Suppurative or purulent inflammation a, Superficial suppuration and empyema e.g. Sup

23、purative tonsillitis, empyema of gallbladder, empyema of pericardium and thoracic empyema,Morphologic Patterns of Acute Inflammation,Suppurative or purulent inflammation b. Phlegmonous inflammation Pathogen: hemolytic streptococci, e.g. Acute appendicitis,Morphologic Patterns of Acute Inflammation,S

24、uppurative or purulent inflammation C. Abscess a localized purulent inflammation Pathogen: staphylococcus aureus,Morphologic Patterns of Acute Inflammation,Suppurative or purulent inflammation C. Abscess: Outcomes *Absorption, healing by granulation tissue *Ulceration *Sinus *Fistula,Morphologic Patterns of Acute Inflammation,Hemorrhagic Inflammation,Outcomes of Acute Inflammation,Complete resolution Incomplete resolution with scar formation Persistence or relapse to become chronic inflammation Local e