Inflammation Part 2 PDF

Inflammation Part 2 Neelam Maheshwari Asso Prof Pathology Bond University 2024 Few terminologies Edema (Odema) Transudate (Fluid like) Exudate (Pus like) Abscess TRANSUDATE OR EXUDATE Ultrafiltra...

Inflammation Part 2 Neelam Maheshwari Asso Prof Pathology Bond University 2024 Few terminologies Edema (Odema) Transudate (Fluid like) Exudate (Pus like) Abscess TRANSUDATE OR EXUDATE Ultrafiltrate of blood plasma Low specific gravity No endothelial contraction= seeping of fluid only due to pressure difference High specific gravity Endothelial contraction= loss of cells and proteins through gaps  Edema: Transudate Pitting Non pitting Pus: Exudate rich in pus cells (neutrophils), dead cells, microbes Abscess: Pus in a closed inflammatory cavity Morphological patterns of Acute inflammation (Clinical examples)  1. Serous Inflammation Thin pink watery tissue fluid: more fluid, less proteins or cells=TRANSUDATE e.g.: Burns/Viral blisters /Heart failure congestion/ Peritoneal, pericardial, pleural effusions  2. Seropurulent (Exudate) Appendicitis Normal appendix 3. Purulent inflammation-Severe form Abscess/Empyema Pyogenic (pus forming organisms )causing central necrosis due to pus made of dead pathogen and damaged tissue, and inflammatory cells which is Walled off by fibrous wall ( Hence always nick (open) it and then give antibiotics , as fibrous tissue is avascular) Abscess/Septic arthritis  4. Fibrinous Inflammation Pericarditis Severe and longer injury Pericardial cavity ( Heart cavity-Image below) Peritonitis ( abdominal cavity ) Mesothelial cells secrete fibrinogen that gets deposited in between two layers of the cavity lining Pericarditis: Bread and butter appearance Chronic inflammation Chronic inflammation Inflammation of prolonged duration (>6 weeks to years) characterised by  Mononuclear cell infiltration  Tissue destruction  Repair ( Resolution) by angiogenesis and fibrosis Causes of chronic inflammation Persistent infection (specific pathogens) Tuberculosis Leprosy Syphilis Certain viruses Fungi Parasites Need intracellular killing Prolonged exposure to toxins/foreign material Silicosis, Asbestosis Atherosclerosis: against cholesterol deposits Obesity: Free fatty acids Suture material Uric acid crystals Immune mediated Autoimmunity: Autoantigens evoke self-perpetuating immune reaction leading to tissue damage and persistent inflammation Rheumatoid arthritis Inflammatory bowel disease Psoriasis Systemic lupus erythematosus Hashimoto’s thyroiditis Pernicious anemia Abnormal immune response Inflammatory bowel disease -  Chest X-ray Case history A 41-year-old male presents to GCUH outpatients with 4 months history of low-grade fever of 37.7 ◦C, bilateral dull aching upper chest pain, productive cough with yellow sputum. He recently noticed blood in his sputum. He has recently lost 8 kg of weight. The clinician runs a battery of tests including Chest Xray. His Hgb is 10 g/L (RR: 15-18 g/L), total WCC count is 19,600 cells/cmm (4000-11,000 cells/cmm) with mainly lymphocytes (80%) ( RR 20-30%) on differentials. He is advised to submit early morning sputum’s on three consecutive days which is positive for a pathogen on a special stain (Image). Sputum –ZN stain What is happening here? What more history would you ask? What symptoms bring him to the hospital now? What is the special stain and describe the pathogen ? What is the significance of total WCC and differentials? Why does he submit three sputum samples What does the Chest X ray show? What is the stimulus here? What is the type of inflammation ? Example : Mycobacterium tuberculosis Slender beaded pink Acid fast bacilli on ZN stain ( not gram stainable) as Cell wall rich in mycolic acid (complex lipids) M.tuberculosis hominis ( MTb) Slow growing ( takes 10 weeks in solid media - Lowenstein Jensen media) but 2 weeks in liquid culture media (MGIT) Transmission: airborne (respiratory droplets) from an active open case Risk factors: overcrowding, poverty, immunosuppression, malnutrition  Pathogenesis of TB Flu like prodrome in non sensitised individuals Prevention of phagolysosome formation and hence no bacterial killing Effector phase Sensitisation phase Development of CMI=Delayed type 4 hypersensitivity This TH1 CMI response, while largely effective, comes at the cost of -Delayed Type 4 hypersensitivity (Tuberculin/Mauntoux test principle) -accompanying tissue destruction (caseation) Pathology: Gross -TB lungs Primary Tuberculosis Ghon complex Secondary Tuberculosis ( Re-activated TB) Caseation/Cavity Pathology: Microscopy-Caseating granulomas Caseous necrosis ( centre) Epithelioid macrophages Foamy plump activated macrophages/monocyt es Multinucleate Langhans giant cells Activated lymphocytes Walled off by fibroblasts Non caseating granulomas EFFECTS of Inflammation on body Haemodynamic shock Sepsis, DIC Pyrogens Biomarkers C-RP Procalcitoni n ESR These parameters are used for diagnosing inflammation: type and severity Anti-Inflammatory agents Used when too much Inflammation (foe) Degradative enzymes to inactivate cytokines/mediators Lipoxins Tyrosine PO4 Aspirin –Acetyl salicylic acid IL-1 antagonists Corticosteroids Antagonise vasodilatation (↓Prostaglandins effect locally) Redistribute granulocytes ( Push extravasated WBC into circulation ) Stabilise lysosomal membranes Summary-Take home message Inflammation Complex interplay between all 4 components and sequences Acute: short onset & duration; vascular events and neutrophils are the main components Chronic: longer duration and onset; mononuclear cells, tissue damage and fibrosis are the main components Inflammation is not always infection Inflammation can be a friend or foe ! References :Textbook Robbins Basic pathology 9th edition Underwood General and Systemic Pathology 5th What is the difference between an inflammation, infection and a disease  Quiz- Case 1 A-Peripheral blood B –Gram stain blood A 45-year-old female presents with smear culture fever of 39◦ C with rigors, severe pain in her right upper quadrant abdomen. She complains it all started after a big fatty meal 3 days ago. The doctor performs several investigations. Her total WBC count is 17,800 cells/cmm (Ref range : 4000-11,000 cells/cmm)with prominent WCC’s as shown in the peripheral blood smear (A). Her C-RP is 140 mg/L ( Normal Range: 0-10 mg/L) and her blood culture bleeps positive for a pathogen as shown on the gram stain (B) The intraoperative image of her removed tissue pathology is shown(C). Spot the features of inflammation in the clinical history. Explain the type of inflammation, explain? C- Intraoperative gross Identify the stimulus pathology E-Normal gall bladder to (aetiology/cause) using VINDICATE compare with abnormal Which process of inflammation is prominent in Gross(C) in C Explain the significance of C-RP, fever ?  Quiz- Case 2 A –Hands A 55-year-old female presents with low grade fever 37.6 C, pain and increasing deformity of her hands for 3 months (A). She complains difficulty in doing house chores. Her total WBC count is 15,800 cells/cmm (RR: 4000-11,000 cells/cmm)with prominent cells as shown in the peripheral blood smear (B). Her ESR is 200 mg/L ( RR: 0-10 mg/L) and Serum Rheumatoid factor (autoantibodies against tissue protein) is 500 IU/ml ( RR: upto 15 IU/ml). B-Peripheral blood Describe the cardinal signs seen in her smear hands. Justify the type of inflammation. Outline her cause (stimulus/aetiology) using VINDICATE? Which stages of inflammation are prominent ? What is the significance of ESR. Chemical mediators of Inflammation Extra slide, Not for exam Principal actions/role of mediators : Refer Robbins Table 2-5 & 2-7  Plasma factors in inflammation Extra slide, Not for Pain exam Plasmin lyses fibrin into fibrin split products affecting vascular Fac XII when in contact permeability with basal lamina of the endothelial lining and bacterial products activates kinin, fibrinolytic and coagulation system