3.INFLAMMATION Of Nursing Second Students

pathiophysiology
Inflammtion

1. 1 INFLAMMATION DR.SHIFERAW D(MD) 2017

2. Inflammation 2 What is inflammation? It is Protective response intended to eliminate the initial cause of cell injury and the necrotic cells and tissues arising from the injury Inflammation is intimately associated with the repair process which includes parenchymal cell regeneration and scarring

3. Inflammation and repair may however be potentially harmful:- E.g. Rheumatoid arthritis, lung fibrosis,and Hypersensitivity reactions It consists of two main components, 1 - vascular reaction 2 - cellular reaction Inflammation is terminated when:- - The offending agent is eliminated , -The secreted mediators are broken down and -By an additional anti inflammatory mechanism . 3

4. Nomenclature Indicated by adding the suffix ‘ itis ’ to the cell origin. Eg . Inflammation of the:- Appendix  Appendicitis Meninges  Meningitis. Cervix  Cervicitis. Exceptions Lung  Pneumonia 5/8/2017

5. Inflammation of : 1)Bladder 2)Gallbladder 3)Endocardium 4)Liver 5)Systemic inflammation caused by S.typhi 6)Subcutaneous tissue 7)Fallopian tube 8) Skin 9) Kidney Answers

6. . 1) Cystitis 2) Cholecystitis 3) Endocarditis 4) Hepatitis 5Typhoid fever 6) Cellulitis 7) Salpingitis 8) Dermatitis 9) Pyelonephritis

7. Chemical mediators of inflammations Account for the vascular & cellular changes. Derived from plasma or locally from the cells. Perform their activity by initially binding to specific receptor on target cells. Can act on one or few target cell types, or may even have differing effects on different types of cells. Most are SHORT lived .

8. Locally produced Histamine Serotonin Cytokines Chemokines Prostaglandins* Leukotriene * Plasma derived Kinins Complements Coagulation system Fibrinolytic system

9. Arachidonic Acid Leukotrienes Cyclooxygenase 5-Lipoxygenase Prostaglandins Prostacyclins Cell Damage Cell Membrane Phospholipids 5-LO inhibitors Steroids NSAID

10. Classification Based on DURATION of the lesion & HISTOLOGICAL appearance. 1-Acute inflammation 2-Chronic inflammation 5/8/2017

11. ACUTE INFLAMATION Acute inflammation is rapid in onset and is of relatively short duration, lasting for minutes, several hours, or a few days 12

12. CAUSES OF ACUTE INFLAMMATION Include :-    • Infections and microbial toxins    •  Physical agents(Trauma (blunt and penetrating),burn)    • Chemical agents    •  Tissue necrosis (from any cause)    •  Foreign bodies (splinters, dirt, sutures)    •  Immune reactions (hypersensitivity reactions) 13

13. The five cardinal signs of acute inflammation are : 1 ) Redness ( rubor ) which is due to dilation of small blood vessels within damaged tissue as it occurs in cellulitis. 2) Warm ( calor ) which results from increased blood flow (hyperemia) due to regional vascular dilation. 3) Swelling (tumor) which is due to accumulation of fluid in the extravascular space which, in turn, is due to increased vascular permeability .

14. 4) Pain (dolor), which partly results from the stretching & destruction of tissues due to inflammatory edema , and in part from pus under pressure in as abscess cavity. Some chemicals of acute inflammation, including bradykinins , prostaglandins and serotonin are also known to induce pain. 5) Loss of function: The inflamed area is inhibited by pain while severe swelling may also physically immobilize the tissue.

15. Cardinal Signs of Inflammation(5 ) Calor : Warm – Hyperaemia . Rubor : Redness – Hyperaemia . Dolor : Pain – Nerve, Chemical med. Tumor : Swelling – Exudation Functio laesa : Loss of function 5/8/2017

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17. Pneumonia:- Inflammation of lung parenchyma 5/8/2017 Acute Enteritis

18. Events of acute inflammation Acute inflammation has 3 major components: 1- Alterations in vascular caliber :- increase in blood flow 2- Structural changes in the microvasculature permeability :-permit plasma proteins and leukocytes to leave the circulation 3-E migration of the leukocytes from the microcirculation to site of injury, and their activation to eliminate the offending agent . 19

19. Vascular changes 1-Changes in Vascular Flow and Caliber a) Transient and immediate vasoconstriction in seconds due to neurogenic or chemical stimuli. b)- Vasodilatation of arterioles and venules resulting in increased blood flow. -Develop at varying rates depending on severity of injury -I nduced by the action of several mediators, on vascular smooth muscle. e.g. Histamine and NO 20

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21. 2-Increased Vascular Permeability It is hallmark of acute inflammation leads to the escape of a protein-rich fluid (exudate) into the extravascular tissue. Together with increased hydrostatic pressure, exudation results in Edema 22

22. Edema: denotes an excess of fluid in the interstitial space or serous cavities; it can be either an exudative or a transudative . Transudate: is a fluid with low protein content (most of which is albumin) An exudate: is an inflammatory extravascular fluid that has a high protein concentration Pus ,: a purulent exudate, is an inflammatory exudate rich in leukocytes ( mostly neutrophils ), the debris of dead cells and, in many cases, microbes . 23

23. EXUDATE TRANSUDATE CAUSE Acute inflammation Non-inflammatory disorder APPEARANCE Colored, turbid , hemorrhagic Clear, translucent or pale yellow PROTEIN CONTENT > 3 gram CELLS Abundant WBC, RBC, & Cell debris usually present Only few mesothelial cells BACTERIA Present Absent

24. 3. Cellular changes(Emigration of leuckocytes and their activation) Emigration of leukocytes from vessel lumen in to interstitial space is called extravasation . Can be divided into the following steps; A - Margination , rolling & adhesion B - Diapedesis -transmigration across the endothelium C - Chemotaxis - migration in interstitial tissues toward a chemotactic stimulus D -leukocyte activation and phagocytosis 25

25. M orphologic Patterns of acute inflammation 1.SEROUS INFLAMMATION -Is characterized by the outpouring of a watery , relatively protein-poor fluid that, derives either from the serum or from the secretions of mesothelial cells lining the peritoneal, pleural, and pericardial cavities. The skin blister resulting from a burn or vesicles from viral infection Fluid in a serous cavity is called an effusion . Serous inflammation resolves without reactions. 26

26. BLISTER, “Watery”, i.e., SEROUS

27. 2. Fibrinous inflammation More severe injury resulting in greater vascular permeability which leads to exudation of larger molecules like fibrinogen . Most common sites of fibrinous exudate are meninges, pericardium and pleura .

28. The fates of fibrinous exudate could be:- (A) Resolution: degraded by fibrinolysis, → and the accumulated debris may be removed by macrophages, → resulting in restoration of the normal tissue structure. (B) Organization: failure to completely remove the fibrin results in the ingrowth of fibroblasts and blood vessels . (C) Organization leads ultimately to scarring 29

29. 3.SUPPURATIVE OR PURULENT INFLAMMATION Characterized by the production of large amounts of pus or purulent exudate consisting of neutrophils, necrotic cells, microbes and edema fluid. Usually result from pyogenic bacterial infection E.g. Staphylococcus, Streptococcus … Abscess:- localized collections of purulent inflammatory tissue in a confined space . 30

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31. 4. Catarrhal inflammation Mild and superficial inflammation of mucus membrane. E.g. Rhinitis.

32. 5.ULCERS It is a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflammatory necrotic tissue. An ulcer is most commonly found in : (1) inflammatory necrosis of the mucosa of the mouth, stomach, intestines, or genitourinary tract; and E.g. PUD (2) tissue necrosis and subcutaneous inflammation of the lower extremities in older persons who have circulatory disturbances that predispose to extensive necrosis. E.g.- Diabetic foot ulcer 33

33. Outcomes of Acute Inflammation Acute inflammation have 3 outcomes; 1 -Complete resolution 2 -Healing by connective tissue replacement (fibrosis) 3 - Progression to chronic inflammation 34

34. 1-Complete resolution It is restoration of the site of acute inflammation to normal. Is the usual outcome when; -The injury is limited or short-lived -There has been little tissue destruction and -Damaged parenchymal cells can regenerate to replace lost tissue. 35

35. 2- Healing by connective tissue replacement Occurs many circumstances such as; -After substantial tissue destruction -When the inflammatory injury involves tissues that are incapable of regeneration . -When there is abundant fibrin exudation which failed to be cleared. 36

36. 3-Progression to chronic inflammation Acute to chronic transition occurs when the acute inflammatory response cannot be resolved. This may be due to: -The persistence of the injurious agent or -Some interference with the normal process of healing E.g. Pneumonia Lung abscess Acute PUD  Chronic PUD 37

37. Chronic Inflammation It is inflammation of prolonged duration (weeks or months) characterized by:- - Active inflammation , tissue destruction , and attempts at repair are proceeding simultaneously . 38

38. CAUSES Persistent infections by certain microorganisms E.g. TB, Syphilis, Fungi… Autoimmunity E.g. - Rheumatoid arthritis -SLE Progression from acute inflammation: 39

39. MORPHOLOGIC FEATURES Chronic inflammation is characterized by: A- Infiltration with mononuclear cells B- Tissue destruction C- Attempts at healing by connective tissue replacement of damaged tissue 40

40. MONONUCLEAR CELL INFILTRATION Emigrate into extravascular tissues quite early in acute inflammation, and within 48 hours they may constitute the predominant cell type. Extravasation of monocytes occurs with similar mechanism as neutrophils. Once in the tissue they transform to macrophages 41

41. Classification of Chronic inflammation - Two type based on histologic type 1. Non specific -Involves a diffuse accumulation of macrophages and lymphocytes Eg . Chronic cholecystitis 2. Specific(Granulomatous) inf.

42. Granulomatous inflammation Definition: Granulomatous inflammation is characterized by the presence of granuloma. A granuloma is a microscopic aggregate of epithelioid cells. Epithelioid cell is an activated macrophage, with a modified epithelial cell-like appearance (hence the name epithelioid ). The epitheloid cells can fuse with each other & form multinucleated giant cells. So, a granuloma is 1) basically a collection of epithelioid cells , 2) containing multinucleated giant cell & 3) surrounded by a cuff of lymphocytes and occasional plasma cells . 43

43. causes Bacterial - Tuberculosis , Leprosy ,Syphilitic gumma ….. Parasitic:- Schistosomiasis Fungal -Cryptococcus neoformans Foreign Body -Suture, breast prosthesis, vascular graft 44

44. Systemic effects of inflammation Result from reactions to cytokines ,bacterial products or other inflammatory stimuli. The systemic changes associated with inflammation are collectively called the acute phase response or SIRS. These consists of several clinical and pathologic changes such as; 45

45. 1.Fever- Elevation of body temperature, usually by 1° to 4°C -Is produced in response to substances called pyrogens -Coordinated by hypothalamus & by cytokines like:- - IL-1 - TNF-a -Tachycardia & decreased BP(blood pressure) -Other manifestations - Rigors ,Chills, Anorexia, 46

46. 2. Leukocytosis/leukopenia leukocyte count typically increases to 15,000 or 20,000 cells per μL (normal = 4000 to 11,000 The cells per μL ) but may climb as high as 40,000 to 100,000 cells per μL , a so-called leukemoid reaction . Leukocytosis initially results from the release of cells from the bone marrow (caused by IL-1 and TNF) and is associated with an increased number of relatively immature neutrophils in the blood ("left-shift").

47. Most bacterial infections induce a relatively selective increase in polymorphonuclear cells ( neutrophilia ), while parasitic infections (as well as allergic responses) characteristically induce eosinophilia . Certain viruses, such as infectious mononucleosis mumps, and rubella, engender selective increases in lymphocytes ( lymphocytosis ). Typhoid fever are associated with a decreased number of circulating white cells ( leukopenia ). Leukopenia is also encountered in infections that overwhelm patients debilitated by, for example, disseminated cancer, RVI pts.

48. Defective and Excessive Inflammation Defective inflammation It is inadequate mounting of inflammatory response Results in -Increased susceptibility to infections -Delayed healing of wounds -Tissue damage 49

49. 3. Increased serum level of acute phase proteins E.g.- -C-reactive protein (CRP) -Fibrinogen -Sepsis and septic shock -DIC -Organ failures E.g.-heart failure -Hepatic failure -ARDS 50

50. Excessive inflammation Are responsible for many morbidities due to there destructive behavior . Involved in; - Hypersensitivity reactions * Unregulated immune responses against commonly encountered environmental antigens, - Autoimmune reactions * Immune responses develop against normally tolerated self- antigens - Other disease conditions E.g. Cancer, Atherosclerosis, IHD 51

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