• first line of defense designed to
  • eliminate cause of injury
  • remove necrotic debris
  • repair damage

• defense (neutralize and kill pathogens)
• immediate (within seconds)
• nonspecific (no pre sensitization)
• localized (limits injury)

• dilation of blood vessels leads to increased blood flow (hyperemia)
  • heat
  • redness(rubor)
• nerve stimulation and increased blood flow
  • pain
• increased vascular permeability
  • swelling/eduma
    • loss of function (also caused by pain)

• vascular
  1. smooth muscle relaxes in arteries/ arterioles
  2. vascular dilation of capillaries and arterioles cause increase blood flow (hyperemia)
  3. endothelial cells contract
  4. increase in vascular permeability as endothelium contraction cause gaps at post-capillary sinusoids (venules
     • leak out Na, water (osmotic P)
     • then, low molecular weight proteins like Ig's, fibrinogen leak out
     • forms the exudate

• cellular response (neutrophils are major effector cells in acute inflam)
  1. marginate and roll
     • margination- roll out of periphery of vessel
     • rolling- move along endothelial lining being drawn by chemoattractant stimulus
  2. adhere to endothelial cell
  3. transmigrate through endothelial cell gaps
  4. move to site of injury along chemoattractant gradient

• L selectin (leukocytes) and P selectin (platelets) bind to E selectin (endothelium)

• beta 1-2 integrins (ex: LFA, Mac 1) bind to VCAM-1 and ICAM-1 on endothelium

• exogenous- bacterial products
• endogenous
  • necrotic cells
  • fibrinopeptides
  • C5a (chemoattractant)
  • LTB4
  • chemokines
    • IL-8 (for neutrophils)
    • MCP-1 (monocyte)
    • C3a (for eosinophils)

• leaks out of vessels into excudate and polymerizes to fibrin in EC tissue
• forms a gel like clot
• this clot forms a strand like scaffold for migrating neutrophils

• trauma burns
• direct cell injury
• complement and factor XII activation

• stimulates mast cells
• mast cells immediately degranulate and release preformed histamine

• direct cell injury cause release of mediators of macrophages and endothelial cells
  • NO
  • PG's
  • leukotriens
  • PAF
  • cytokines
    • IL-8
    • TNF alpha
    • IL-1

• bradykinin
• C3a,b
• C3b
• C5a
• fibrinopeptides

• vasodilation, increase permeability
• antimicrobial activity in macrophages
• Loc.
  • constitutively produced in endothelium
  • macrophage synthesis from Arg when iNOS upregulated by cytokines

• Function
  • cause vasodilation more so than permeability
  • also responsible for fever and pain
• metabolite of arachodonic acid

• metabolite of arachadonic acid (lipoxygenase)
• function
  • permeability
  • chemotactic to neutrophils (LTB4)

• vasodilation and permeability
• platelet activation with multiple effects

vasodilation

permeability

pain

• C5a- chemotactic
• C3b- opsonin

Both increase vasodilation and permeability

vascular permeability

chemotaxin

• anaerobic
  1. binding of matter to cell surface
     • nonspecific- opsonin (C3b) coats particle
     • specific- particle specific ligand (endotoxin) via tole like receptor (bind pathogen), FcR-Ab
     • engulfed into phagocytic vacuole (phagosome)
  2. fusion with lysosome to form phagolysosome and discharge o digestive enzymes
• aerobic
  • respiratory burst where oxygen turned ito superoxide anion
  • superoxide anion produce hydrogen peroxide
  • than it could from halide or myeloperoxidase from azurophilic granules produce:
    • form hypochlorite ion
    • form hydroxyl radical

serous

purulent

fibrinous

mucinous

sanguinous

• clear, few cells
• protein rich
• signifies inflammatory edema

• if within body cavity, empyema
• cloudy viscid fluid
• neutrophils and necrotic tissue
• common with bacteria

• fibrin rich
• common in serous sacs

• mucin rich
• common in mucinous epithelium

• localized liquifactive necrosis of tissue within an organ or body cavity, surrounded by normal body tissue
• will see suppurative exudate (pus) entrapped within necrotic focus (will see neutrophils)

• localized site of inflammation
• located on tissue surface
• results in gap along surface
  • exudate accumulates within area of focal necrosis or sloughs away
• extend beyond epidermis or mucosa into deeper tissue layers

• leukocytosis increase
  • cytokines, mainly IL 1
  • increased release of neutrophils from marrow
• increase fever
  • PG's and IL-1
  • effect thermoreg. by hypothal, associated with increased pulse rate
• increase C reactive protein (CRP)
  • cytokines, mainly IL-1
  • stimnulate increase liver synthesis of acute phase proteins
• increase erythrocyte sedimentation rate (ESR)
  • cytokines, mainly, IL-1
  • increase liver synthesis of acute phase proteins (includes fibrinogen)
  • increased fibrinogen leads to RBC aggregation