inflammation ppt for medical purpose………….

Inflammation

1. inflammation

2. Learning Objectives At the end of the session, the student should be able to: 1. Define inflammation and explain its role in the body's defense mechanism. 2. Describe the stages of inflammation, including initiation, amplification, and resolution. 3. Differentiate between acute and chronic inflammation and their respective pathological features. 4. Discuss the Ayurvedic perspective on inflammation, including the role of Doshas and Dhatus . 5. Explain the clinical manifestations and management of inflammatory conditions using Ayurvedic and modern approaches. Domain CK (Cognitive Knowledge) Miller's Pyramid Must know Level Knows how Learning Objectives with CO CO2: Understand and analyze the processes and outcomes of inflammation in various conditions. CO5: Apply Ayurvedic and modern principles to diagnose and treat inflammatory conditions.

3. Inflammation INFLAMMATION is defined as local response of body tissue to injury due to any agents. AGENTS OF INFLAMMATION Physical agents – heat,cold,radiation Chemical agents-organic –inorganic poisons Infective agents-bacteria ,virus, parasites Immunological agents-antigen –antibody reaction.

4. Signs of inflammation – Rubor -redness Tumor-swelling Calor -heat Dolor-pain Functio laesa -loss of function

5. purpose 1)to bring more blood to injured area 2)to bring more defence mechanism to area. For what? 1)remove or neutralise the cause of injury 2)to wall of the cause of injury 3)to remove the dead cell caused by injury 4)to pave the way for repair processe

6. Types of inflammation Acute and chronic inflammation. Acute is of short duration and represent early body reaction is usually followed by repair. Chronic inflammation is of long duration and occurs either after the causative agent of acute inflammation persists for long time.

7. Acute inflammation It can be described under 3 heading 1)hemodynamic change 2) altered vascular permeability Both comprise of vascular event 3)cellular events

8. 1) hemodynamic change A)transient vasoconstriction of arterioles.-Last for 3 to 5 sec in mild injury and up to 5 min in severe injury. B)persistent progressive vasodilatation –it result in increase in blood volume in micro vascular beds of the area which in turn increase the local hydrostatic pressure resulting in transudation of fluid in to extracellular space.

9. Acute inflammatory processe Tissue Tissue has arterioles arterioles break up in to capillaries and end up on venous side,which drain into venous system. Tissue has parenchymal cells ,there are other cells which support the parenchymal cells called stromal cells for ex in skin epidermal cel is parenchymal cell but dermal cell is stromal cell. Also there are mast cell ,some resident macrophages,lymphocyte in this tissue.

10. What happens when tissue get injured? Bacteria-toxic substances-damage parenchymal cell , stromal cells- prstaglandin will be released,leucotrines will be released Mast cell injured release-preformed histamin,release proteolytic enzyme,release prostaglandin,leucotrines,platlet activation factor Resident macrophage,lymphocyte release cytokines and synthesis intrleukine 1 , TNalpha . IT MEANS ALL THESE LOCAL CELL START RELEASING SUBSTANCES WHICH MEDIATE LOCAL INFLAMMATION.

11. NOW LETS SEE WHAT THE CHEMICAL MEDIATORS DO? They will control two major steps of inflammation. Vascular events Cellular events.

12. Vascular events- arteriols have lot of smooth muscles and arteriol smooth muscle tone controls blood flow to any tissue.so at injured site we need more or less blood? So chemical mediators which are produce will 1)act on vascular smooth muscle. Transient vasoconstriction is due to neurogenic mechanism usually followed by vasodilation .

13. Why these arteriols dilate? Many chemical mediators like histamine prostaglandin nitric oxide are produced at the site of injury, these are strong smooth muscle relaxant for arteriols . By receptor mechanism,more blood shifted towards injured area so 1 st vascular event is arteriolar dilation will take place

14. What will happen after arteriols dilate? Change in different forceses which control the fluid exchange Starlings force,hydrostatic force,osmotic pressure. Normal

15. normal Arterial side of capillary venous side of capillary. Hydro-on arterial is 35mm/hg and venule is 15mm/hg Osmotic pressure exerted by plasma protein is approx 28mm/hg-stable Hydro is more osmo is less at the early part of arteiol fluid will go out. At venule end hydro is less and osmo is more so fluid is coming back to circulation,so whatever amount of fluid sips out again come in so volume does not change. Some proteins leak out and are drained in lymphatic system.

16. abnormal What happens to microcirculation during inflammation? Chemical mediator-intra endothelial gap development Hydro -55mmhg Loss of protein drop of osmotic presure around 20mm/hg More loss of fluid/,high leak of protein rich fluid( exudate )

17. Exudation is loss of protein rich fluid from vascular compartment to extra vascular compartmment,it has high sp.gravity (1.020). Transudation-if hydrostatic pressure is increase and osmotic pressure fall and permieability of microcirculation is normal what willl happen. Protein poor fluid

18. How increased permeability occurs? the process which make microcirculation more leaky endothelial cell have receptor for chemical mediator,and when they are acted by these chemical procese , they undergo contraction,formation of endothelial gaps.-increase microcirculation permeability

19. Cellular events of inflammation. Aim –to learn how the wbc comes at the site of injury from circulation and deal with cause of injury. Axial blood flow. Haemoconcentration -viscosity-stasis. Rbc sticking-dash Margination Rolling Pavementing .

20. Chemical mediator from injured cell act on endothelium-endothelium cell activation and some CM act on wbc so they become sticky? Histamin -rapidly produced by preformed granules of mast cell Leukotrine –cell membrane of mast cell Thrombine -derived from coagulation factors of blood. All these act on endothelial cell for what reason?

21. Leukotrine act on endothelial cell,endothelial cell have special receptor for these substances,when activated endothelial cell have granules and these cell when activated by CM they move towards the surface and plant some molecules,which acts like hooks. These hooks will hook on wbc ( weibal palate bodies) Few minute processe .(preformed). Wbc have some cytoplasmic extension and on these extension there are special molecule which are like hooks and they are sticky molecule. This molecule is called oligosialyated sugar.

22. P selectin is expressed on endothelial cell, As soon as P SELECTIN are expressed the wbc which are marginated will touch it and get hooked. No long time commitment?why . Rolls forward.

23. As time passes another group of CM , interleukine and tumor necrosis factor are produced within few hours. What will happen? The CM will activate endothelial cell and receptor on endothelial cell will give signal to nucleus of endothelium and nucleus is activated ,and they will start producing another molecule and better class of hook are produced and they are called E – selectin , Now wbc can stick to E or P selectin but cannot? Bond is week and they roll forward .this is called rolling.

24. Mean while another change occur,more cytokine come from injured site( chemokines interleukin 8-(attraction for neutrophills ). Endothelial cell have special type of receptor to hold chemokine molecule, these chemokine molecule bind on the these special receptor or chemokine holders. On the WBC there are special type of molecule ,which are not working,these are two peptide,now when wbc while rolling touch the endothelial cell holding chemokines,then wbc will change its configuration of integrins.integrins open.

25. The endothelial cell will express another molecule called I CAM or V-CAM and when integrins open their pockets they will grab that molecule. Now this is a strong bond,now wbc cannot roll further ,and now wbc will stick to the endothelium and spread over it and this processes is called pavementing .

26. Clinical imp.

27. AIM What is Extravasation,emmigration,diapedessis . CHEMOTAXIS WBC ACTIVATION PHAGOCYTOSIS

28. Now wbc is resting on endothelial cell as time passes another class of cytokine are acting on endothelial and wbc cell ,now a special molecule is expressed on both surface and that molecule is called P CAM. Both molecule are same and they start rubbing each other and act as molecular motor and wbc start slipping down and rest on basement memmbrane .

29. extravasation Wbc start relaesing enzyme( collagenesis ) and they digest collagen and wbbc comes out, and this processe through which wbc comes from vascular compartment to extravascular compartment is called extravasation .

30. Now wbc should move to focus of injury and question is how they move at the site of injury? At the site of injury there is more concentration of CM and wbc can sense these CM and the direction of movement under the influence of chemoattractant molecule is called chemotaxis . Ex bacterial toxins,injured cell – leukotrine b4 all these are chemotactic agents. Exogenous chemotactic agent and endogenous chemotactic agents .

31. chemotaxis Now when chemmoattractant bind on receptor of leucocyte a reaction takes place and the leucocyte extend filopodia which pull the cell in direction of extension and leucocyte moves forward towards the source of chemoattractant and whole processes is called chemotaxis .

32. wbc activationa As leucocyte come near the site of injury they develop a specila type of integrin molecule and bind with extracellular cd44molecule,which act as foot stone for wbc and this is called wbc activation.

33. phagocytosis It is the processes of recognition ,engulfment and digestion of microbes ,dead cell and foreignbodies .(cell eating) 3 steps of phago Recognition Engulfment killing

34. Recognition-there are various type of receptor on phagocyte,like scavanger receptor,opsonin receptor , manomose receptor etc, The microbe gets bind to such receptor and it will lead to membrane remodeling and change in cytoskeleton and that result in polymerisation of actin filament . This will lead to extension of cytoplasam of phagocyte to produce psuedopod

35. These psuedopods gradually they extend around the microbe and finally plasma membrane pinches off to form a vesicle and this vesicle is called as phagosome . Phagosome eventually fuses with lysome and forms a single vesicle called phagolysosome . Now the granules which are present in lysosome go toward the microbes and break down the microbe. Killing occur by reactive oxygen specises,nitrogen species and lysomal enzymes,the killing occurs in phagolysosome thus to avoid damage to cell cytoplasam and nucleus.

36. Fate of acute inflamation 1) resolution -it means complete return to normal tissue following acute inflammation. 2) healing by scarring -this take place when the tissue destruction in acute inflammation is extensive so that there is no tissue regeneration but there is healing by fibrosis. 3) suppuration - pyogenic bacteria cause acute inflammation result in severe tissue necrosis leading to suppuration .there is intense neutrophilic infiltration there is pus formation to form cavity and then abscess ,the abscesse when not drained gets organised by dense fibrous tissue and in time get calcified. 4) chronic inflammation -the acute progresses to chronic inflammation

37. Chemical mediators Mediators are the substancese which initiate and regulate the steps of inflammation.

38. Archidonic acid metabolites when there is injury there is influx of calcium within the cell and this lead to activation of enzyme phospholipase A2,and activation leads to release of archadonic acid metabolites which are , prostaglandins,thromboxane,leukotrine and lipoxins .