Inflammation: Brahma

Anmerkungen:

• A protective response of vascularized tissues to injury

1. Acute inflammation

   Anmerkungen:

   • Sequential steps: 1.An offending agent located in the interstitial tissue, which are recognized by host cells. 2.Leukocytes and plasma proteins are recruited from the circulation to the site of injury 3.Leukocytes and plasma proteins are activated and work together to destroy and eliminate the offending agent 4.The reaction is controlled and terminated 5.The damaged tissue is repaired
   1. Reactions in the blood vessels

      Anmerkungen:

      • Changes in Vascular Flow and Caliber Increased Vascular Permeability (Vascular Leakage) Emigration of leukocytes from the microcirculation towards the site of injury
      1. Increased vascular permeability

         Anmerkungen:

         • Histamine and NO secreted by the endothelial cells. 1. Endothelial cell contraction 2. Endothelial necrosis 3. Transcytosis
         1. Transudate

            Anmerkungen:

            • Ultrafiltration of the plasma without increase in the vascular permeabilty: E.g. Heart failure Nephrotic syndrome
         2. Exudate

            Anmerkungen:

            • Increased vascular permeability Escape of plasma protein and cells Cell rich protein rich E.g. Inflammation Infections
            1. Lights criteria

               Anmerkungen:

               • •Increase in protein levels more than serum protein levels (ratio >0.5) or •Increased effusion LDH  > 2/3 of serum  normal upper limit or •Effusion LDH to serum LDH ratio >0.6
      2. Vasodilation

         Anmerkungen:

         • Histamine, NO and prostaglandins
   2. Cellular events in acute inflammation
      1. Margination
      2. Transmigration
      3. Rolling
      4. Adhesion
         1. LAD-1

            Anmerkungen:

            • Defect in LFA1 OR CD18 B2-integrins on the neutrophils There is no firm adhesion. Dealyed umbilical cord seperation Recurrent bacterial infections
         2. LAD-2

            Anmerkungen:

            • Not that severe : Defect in selectins or Sialylewis-x on the neutrophils Defect in rolling
      5. Chemotaxis
      6. Phagocytosis
         1. O2-Mediated killing
            1. Chronic granulomatous disease

               Anmerkungen:

               • X-linked recessive Defect in NADPH Oxidase No superoxide No hydrogen peroxide
               1. Catalase + organisms

                  Anmerkungen:

                  • Staph, Nocardia, serratia,aspergillus produce catalases that can degrade the hydrogen peroxide produced by the bacteria They will be able to phagocytose but are unable to kill the bacteria
               2. catalase neg
               3. NBT

                  Anmerkungen:

                  • Non specific test for CGD: NBT Positive : blue colored dots in the neutrophils signify respiratory burst Negative NBT: No color in CGD
            2. Myeloperoxidase def

               Anmerkungen:

               • Defective formation of bleach. Can produce superoxide, hydrogen peroxide
         2. Non O2mediated killing

            Anmerkungen:

            • Nitric oxide gives peroxynitrite as a free radical Major basic protein secreted by the eosinophils against parasites
         3. Opsonization

            Anmerkungen:

            • C3b, IgG
         4. Phagolysosome fusion
            1. Chediak-Higashi

               Anmerkungen:

               • Defective lysosomal trafiicking LYST gene encodes for microtubulin function for the fusion Oculocutaneous albinism Neurological manifestations Recurrent infections
   3. Acute phase reactants

      Anmerkungen:

      • C-reactiveprotein Ferritin Fibrinogen Hepcidin Serum amyloid A Produced by IL-1 and IL-6 from activated macrophages acts on liver to produce
   4. Mediators of a/c inflmm

      Anmerkungen:

      • Vasodilatation: Histamine, PGI2, NO Fever: PGE2, IL-1, TNF Vasoconstriction: TXA2 Pain: Bradykinin Chemotaxis: C5a, IL-8, LTB4 ,bacterial products
   5. Morphological types
      1. Serous

         Anmerkungen:

         • Thin serous without much of fibrin E.g. Burns
      2. Fibrinous

         Anmerkungen:

         • Commonly seen in body cavities: Due to increase in capillary permeability, plasma proteins fibrin leak out.
      3. Purulent

         Anmerkungen:

         • Pus forming: Due to colonization of bacteria
      4. Pseudomembranous

         Anmerkungen:

         • Formation of dead shaggy membranes. Diptheria C. Difficile infections
2. Signs of a/c inflammation
   1. Rubor

      Anmerkungen:

      • Redness: Histamine mediated vasodilation
   2. Calor

      Anmerkungen:

      • Heat: Increased blood flow again histamine mediated
   3. Tumor
   4. Dolor

      Anmerkungen:

      • Pain:  PGE2 and bradykinin
   5. Loss of function
3. Chronic inflammation

   Anmerkungen:

   • Body response to persistent stimuli for months to years. E.g. TB Autoimmune diseases
   1. Role of macrophages
      1. Circulating monocytes

         Anmerkungen:

         • Follow the same pathway as neutrophils i.e. Margination, rolling, adhesion, diapedesis, chemotaxis
      2. Tissue macrophages

         Anmerkungen:

         • They are formed in the fetal liver and yolk sac: Classified on their location Liver: Kupffer cells Lungs: Alveolar macrophages Skin: Langerhan cell CNS: Microglia
      3. M1-Macrophages

         Anmerkungen:

         • Activate inflammation recruits more netrophils: Activated by interferon-gamma
      4. M2-Macrophages

         Anmerkungen:

         • Inhibits inflammation by secreting IL-10 and promotes repair by secreting TGF-B. Indirect signal by IL-4
   2. Role of lymphocytes

      Anmerkungen:

      • Amplify the inflammation by secreting cytokines
      1. TH-1

         Anmerkungen:

         • Produce interferon gamma classical pathway of macrophage activation
      2. TH-2

         Anmerkungen:

         • Secrete IL-13, IL-5 recruits and activates eosinophils for parasitic infections
      3. TH17

         Anmerkungen:

         • Produce IL-17 for more neutrophilic recruitment
   3. Granuloma

      Anmerkungen:

      • Comprised of epithelioid cells, multinucleated giant cells, lymphocyes and plasma cells
      1. Caseating granuloma

         Anmerkungen:

         • Central pink amorphous debri surrounded by palisading epithelioid cells, Langhans giant cells, Seen in TB, fungal infection
      2. Noncaseation granuloma

         Anmerkungen:

         • Solid granulomas E.g. Chrons Sarcoidosis Cat scratch disease Leprosy Rheumatoid arthritis
      3. Immunopathology

         Anmerkungen:

         • IL-12 Activate T- cells to form TH1 cells to secrete more IF-Gamma
4. Repair and healing
   1. Regeneration

      Anmerkungen:

      • Seen in tissues with replicating potentials. Skin, intestinal epithelial cells Hepatocytes are produced from the mitogenic signals of Kupffer cells and production of new hepatocytes by cells of ito in canals of Hering
   2. scar formation
      1. Keloid

         Anmerkungen:

         • Scar extends beyond the borders of primary wound Disorganized collagen bundles Seen in earlobe, sternum and common in african americans Rx: Intralesional steroids       flurouracil injection
      2. Hypertrophied scar

         Anmerkungen:

         • scar is at the level of wound Organized collagen bundles May regress spontaneously
      3. Wound dehiscence

         Anmerkungen:

         • Sutured wounds when increased compartmental pressures recurrent cough after a surgery for hernia
      4. Proud flesh

         Anmerkungen:

         • Increased production of granulation tissue with reduced reepitheliazation
   3. Healing by primary intention

      Anmerkungen:

      • Clean uninfected wounds Suture wounds 0- bleeding and clot that acts as a scaffold 1day: Neutrophils and basal epidermal cells starts to proliferate: Re-epithelization 3day: Macrophages , granulation tissues weeks: Remodeling Appx 80% strength by 3months
      1. Factors influence healing

         Anmerkungen:

         • Immune status: Steroids reduce healing Diabetes Scurvy: Vit C deficiency Copper deficiecy: Menkes disease Bacterial infection
   4. Healing by secondary intention

      Anmerkungen:

      • Occurs when there is extensive tissue loss. Robust inflammation, wound contraction and healing