ACUTE INFLAMMATION- CHEMICAL MEDIATORS AND ROLE OF LYMPHATICS AN OVER-VIEW

Basic concepts in Humane pathology

1. INFLAMMATION Prof DR AHSAN KAZMI Pathology Department Sahara Medical College Narowal

2. SOURCES OF CHEMICAL MEDIATORS

3. KININ SYSTEM Leads to formation of bradykinin from cleavage of precursor High molecular-weight Kininogen ( HMWK) and rapidly inactivate kininase. A circulating plasma protein which participates in the initiation of blood coagulation , and in the generation of the vasodilator bradykinin via the kallikrein-kinin system . HMWK is inactive until it either adheres to binding proteins beneath an endothelium disrupted by injury, thereby initiating coagulation; or it binds to intact endothelial cells or platelets for functions other than coagulation. Activation of this system results in pain initiation by increasing vascular permeability and smooth muscle contraction.

4. Function of complement product C3a,C5a…….. anaphylatoxin , chemotaxis C3b…… opsonization. fix the bacterial cell wall ,act as opsonin causing phagocytosis C5b-9…… membrane attack complex MAC

5. Opsonization MAC

6. Vasodilation Prostaglandins Histamine Nitric oxide Increased vascular permeability Vasoactive amines C3a C5a Bradykinin Leukotrienes C4, D4, E4 PAF Substance P Chemotaxis, leukocyte recruitment and activation C5a Leukotriene B4 Chemokines IL-1, TNF Bacterial products Fever IL-1, TNF Prostaglandins Pain Prostaglandins Bradykinin Tissue damage Lysosomal enzymes Oxygen metabolites Nitric oxide Inflammation Events And Related Chemicals

7. Task A photomicrograph of inflamed tissue showing a vessel and surrounding interstitium. Describe the sequence of vascular and cellular events which have resulted in accumulation of fluid and neutrophils in the interstitium What is the purpose of this process?

8. Defects in leukocyte function Following Defects in: Adhesion : genetic defects in integrins selectins Chemotaxis : Lazy leukocyte syndrome (abnormal neutrophil motility) Phagolysosome function e.g . Chediak –Higashi syndrome Microbicidal activity Acquired deficiencies: immunosuppression

9. Response of Lymphatic Vessels and Lymph Nodes Lymphatics drain the small amount of extravascular fluid that seeps out of capillaries under normal circumstances In inflammation, lymph flow is increased to help drain edema fluid that accumulates because of increased vascular permeability Lymphatic vessels, like blood vessels, proliferate during inflammatory reactions to handle the increased load. Leukocytes cell debris and microbes , may also find their way into lymph

10. Responses of Lymphatic Vessels and Lymph Nodes Lymphangitis- The lymphatics may become secondarily inflamed Lymphadenitis- inflammation of draining lymph nodes Inflamed lymph nodes are often enlarged because of increased cellularity. This constellation of pathologic changes is termed Reactive, Or Inflammatory Lymphadenitis

11. Responses of Lymphatic Vessels and Lymph Nodes For clinicians The presence of red streaks near a skin wound is a telltale sign of an infection in the wound. indicates the presence of lymphangitis It may be accompanied by painful enlargement of the draining lymph nodes, indicating lymphadenitis

12. Outcomes/Consequences Of Acute Inflammation Complete resolution Little tissue damage Capable of regeneration Abscess formation occurs with some bacterial or fungal infections Scarring (fibrosis) In tissues unable to regenerate and excessive damage Progression to chronic inflammation

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14. Comparison of Acute and Chronic Inflammation Chronic inflammation Persistent injurious agent Non-degradable foreign matter Auto-immune reactions T- lymophocytes & macrophage products- cytokines and GF’s Proteases and reactive oxygen Complement, lipid mediators Acute inflammation Microbial surfaces & fragments Injured tissue & tissue fragments Mast cell products (histamine) Bradykinin Lysosomal components Complement, lipid mediators Process Initiators Mediators

15. Comparison of Acute and Chronic Inflammation Chronic inflammation Angiogenesis Monocytes/Macrophages, Plasma cells, Fibroblasts Insidious onset, weeks  years Resolution, Tissue destruction fibrosis Acute inflammation Vasodilatation & permeability Neutrophils Acute onset, minutes  days Resolution, Abscess formation Chronic inflammation Process Vascular changes Cell populations Time course Outcome

16. SYSTEMIC EFFECTS OF INFLAMMATION ACUTE-PHASE RESPONSE: Fever cytokines (TNF, IL-1) stimulate production of prostaglandins in hypothalamus Elevated plasma levels of Acute-phase Proteins : C-reactive protein (CRP) Fibrinogen Serum Amyloid A (SAA) protein Leukocytosis raised WBC count 15,000 to 20,000 cells/µL . leukemoid reactions 40,000 to 100,000 cells/µL

17. Laboratory Diagnosis Leukocytosis: Acute Inflammation Neutrophilia: Bacterial infection Eosinophilia: Parasitic infection Lymphocytosis: Viral infection , Chronic infection ESR: raised in inflammation CRP: raised in inflammation

18. Blood CP

19. Morphological patterns of Acute Inflammation

20. Types/ Morphological patterns of Acute Inflammation Serous inflammation: inflammation in which there is out pouring of thin serous fluid derived from plasma or mesothelial secretion . e.g. Skin blister skin blister showing the epidermis separated from the dermis by a focal collection of serous effusion

21. Morphological patterns Fibrinous inflammation: inflammation in which exudate contains a lot of fibrin. Present in body cavities, e.g. meningitis, pericarditis , pleuritis , peritonitis Fibrinous pericarditis . A, Deposits of fibrin on the pericardium. B, A pink meshwork of fibrin exudate (F) overlies the pericardial surface (P).

22. Morphological patterns Purulent inflammation/abscess: characterized by production of pus consisting of neutrophils, liquefactive necrosis and edema fluid. An abscess, containing neutrophils and cellular debris and is surrounded by congested blood vessels.

23. Morphological patterns Ulcer: a local defect or excavation of surface of organ or tissue produced by sloughing of inflamed necrotic tissue Ulcer. A: A chronic duodenal ulcer. B: Low-power crosssection of a duodenal ulcer crater with an acute inflammatory exudate in the base

24. A 68-year old man presents with fever, shaking chills, and shortness of breath. Physical examination shows rales and decreased breath sounds over both lung fields. The sputum displays numerous neutrophils. Removal of bacteria from the alveolar air spaces in this patient involves opsonization. This is an important step in mediating which of the following leukocyte functions? ( A) Chemotaxis (B) Diapedesis (C) Stasis (D) Margination (E) Phagocytosis

25. ANSWER This is an important step in mediating which of the following leukocyte functions? (E) Phagocytosis

26. Why are there numerous neutrophils in the sputum? What might be the duration of his illness ? Why did the physician find rales and decreased breath sounds over both lung fields? What will you find in blood CP report in this patient?

27. THANK YOU