Inflammation: Brahma

Annotations:

• A protective response of vascularized tissues to injury

1. Acute inflammation

   Annotations:

   • 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

      Annotations:

      • 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

         Annotations:

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

            Annotations:

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

            Annotations:

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

               Annotations:

               • •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

         Annotations:

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

            Annotations:

            • 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

            Annotations:

            • 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

               Annotations:

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

                  Annotations:

                  • 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

                  Annotations:

                  • 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

               Annotations:

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

            Annotations:

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

            Annotations:

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

               Annotations:

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

      Annotations:

      • 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

      Annotations:

      • 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

         Annotations:

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

         Annotations:

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

         Annotations:

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

         Annotations:

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

      Annotations:

      • Redness: Histamine mediated vasodilation
   2. Calor

      Annotations:

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

      Annotations:

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

   Annotations:

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

         Annotations:

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

         Annotations:

         • 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

         Annotations:

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

         Annotations:

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

      Annotations:

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

         Annotations:

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

         Annotations:

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

         Annotations:

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

      Annotations:

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

         Annotations:

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

         Annotations:

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

         Annotations:

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

      Annotations:

      • 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

         Annotations:

         • 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

         Annotations:

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

         Annotations:

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

         Annotations:

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

      Annotations:

      • 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

         Annotations:

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

      Annotations:

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