acute inflammation-

Exudates are typical of inflammation, transudates accumulate in various noninflammatory conditions。

acute inflammation

• general introduction
  • the acute inflammatory response rapidly delivers leukocytes and plasma proteins to the site of injury,（leukocyte extravasation) leukocytes clear the invaders and start digesting and eliminating necrotic tissue
  • 2 major components
    • vascular changes:Increased blood flow (vasodilation) and increased vascular permeability血管扩张和渗透性增加
      • 在损伤或感染后血管改变很快的开始，在一个短暂的vasoconstriction(few seconds),小动脉的血管扩张开始，造成了局部增加的血流，微血管变得更有通透性and protein-rich fluid moves into the extra-vascular tissues，Red cells become then more concentrated—— stasis淤积
        • 血管通透性增加导致富含蛋白质的液体甚至血细胞进入血管外组织•这反过来又增加了间质液的渗透压，导致更多的水从血液流出到组织
        • exudate:resulting protein-rich accumulation is called an exudate
        • transudate:are interstitial fluid accumulation caused by increased hydrostatic pressure, usually as a consequence of reduced venous return. low concentration of proteins and few or no blood cells
        • Exudates are typical of inflammation, transudates accumulate in various noninflammatory conditions
      • As stasis develops, leukocytes accumulate along the vascular endothelial surface (margination)
    • cellular events:emigration of leukocytes(especially polymorphonucleates)from circulation and accumulation in the site of injury白细胞的迁移和聚集
      • Leukocyte recruitment
        • margination and rolling along the vessel wall
        • firm adhesion to the endothelium
        • transmigration between endothelial cells
        • migration in interstitial tissue towards a chemotactic stimulus
      • 迁移的白细胞类型随炎症反应的年龄和刺激类型的不同而不同
        • In most forms of acute inflammation, neutrophils predominate in the inflammatory infiltrate during the first 6 to 24 hours
        • From 24 to 48 hours monocytes are instead more abundant
  • 3 steps
    • alterations in vascular calibre血管口径的改变that lead to changes in blood flow(vasodilation）
      • cause erythema红斑(redness) and heat
    • structural changes in small vessels小血管结构的改变that allow plasma proteins and cells to leave circulation(increased permeability)
      • cause swelling(oedema)
      • mechanisms4
        • endothelial cell contraction leading to intercellular gaps in post-capillary venules
        • endothelial injury
        • increased transcytosis转胞 of proteins
        • leakage from new blood vessels
    • cellular changes细胞的改变
      • emigration of leukocytes from circulation
      • accumulation of area of injury
      • activation of leukocytes to destroy injurious agent
        • 一旦被激活，they may induce tissue damage and prolong inflammation, so the activation and recruitment are strictly controlled
        • leukocyte activation
          • Leukocyte activation results in enhancement of the following functions:
            • Phagocytosis3
            • Intracellular destruction of microbes
            • Liberation of substances for extracellular microbes
            • Production of mediators
        • 子主题
• 急性炎症反应的刺激物
  • infections(bacterial, viral, fungal, parasitic)
    • Recognition of microbes
      • 特定的细胞类型(吞噬细胞，树突状细胞，上皮细胞…)表达的受体能够感知感染性病原体的存在和死亡细胞释放出的物质
      • two most important families
        • Toll-like receptors(TLRs),mainly recognize pathogens
        • inflammasome炎症体，recognize products of dead cells
  • Trauma (blunt and penetrating)
  • Physical and chemical agents (i.e. thermal injury, irradiation, toxicity…)
  • Tissue necrosis, including ischemia and chemical and physical injury
  • Foreign bodies
  • Immune reactions (hypersensitivity reactions)
• 白细胞
  • Leukocyte-induced tissue injury
    • 因为白细胞能够分泌潜在的有害物质(如酶和活性氧)，它们是在几种情况下损伤正常细胞和组织的重要原因:
      • Bystander tissues are injured during defense reaction against microbes
      • As a normal attempt to clear damaged and dead tissues
      • When inflammatory response is directed against ‘self’ (autoimmune diseases)
  • Defects in leukocyte function
    • increased susceptibility to infections， causes may be bone marrow suppression(caused by tumors or chemo- and radiotherapy), metabolic diseases, genetic diseases
• outcomes3
  • resolution解决
    • regeneration and repair(restoration to structural and fuctional mormality)
  • chronic inflammation
    • if the agent is not removed
  • scarring
    • (repair after substantial tissue destruction),fibrosis occurs if excess connective tissue deposition compromises the function of tissue
• phagocytosis
  • Recognition and attachment
    • Recognition is mediated by specific surface receptors Enhanced by opsonisation (coating of microbes,dead cells) to favour phagocytosis – Opsonins (receptors to host cells) include:
      • IgG antibodies recognised by Fc receptor
      • C3 fragment of complement
      • fibronectin纤连蛋白, fibrinogen,complememt receptor
  • Engulfment
    • Cytoplasmic pseudopods flow round particle and form phagosome • Fuses with a lysosomal granule in leukocyte– phagolysosome
  • – Killing and degradation
    • Mainly through oxygendependent mechanisms • Leads to generation of Reactive Oxygen Intermediates (ROIs)
• 4
  • Margination, rolling and adhesion
    • • Normally blood flow is axial • With increased vascular permeability stasis develops • This leads to cells occupying a more peripheral position (margination) • If the endothelial cells are activated, they express adhesion molecules to which the leukocytes attach loosely • Leukocytes start to roll along endothelium – Associated with transient adhesion The transient interactions involved in rolling are mediated by the selectin family of adhesion molecules
      • E-selecting：endothelial cells
      • P-selectin:endothelium and platlet
      • L-selectin:leukocytes
      • bind to sialylated glycoproteins on various cells.Mediated rolling
  • Leukocyte adhesion
    • • Firm adhesion to endothelial cells is mediated by integrins expressed on the surface of leukocytes that interact with specific ligands on endothelial cells • They are normally expressed on leukocytes as low-affinity proteins and do not adhere their ligands if the leukocytes are not activated Endothelial cells express ligands for integrins whose expression is increased during inflammation:
      • ICAM-1(intercellular cell adhesion molecular 1)
      • VCAM-1(vascular cell adhesion molecular 1)
  • Transmigration
    • Leukocytes migrate through the vessel wall primarily by squeezing between cells at intercellular junctions • This extravasation of leukocytes is called diapedesis血细胞渗出 • Platelet endothelial cell adhesion molecule 1 (PECAM 1 or CD31) expressed by endothelial cells and leukocytes, mediates leukocyte migration through endothelium
  • Chemotaxis
    • Leukocytes move towards site of injury along a chemical gradient. This process is called chemotaxis • Exogenous and endogenous substances may be chemotactic
      • exogenous
        • bacterial products
      • endogenous
        • components of complementsC5
        • products of lipoxygenase pathwayLTB4
        • cytokines(especially chemokines)