C. HPCT File Week 4; Inflammation and Repair.pptx

Inflammation of tissue

1. Inflammation and Repair Prepared by: Billy Africa, RMT, MPH

2. Learning Objectives: At the end of the session, the students are expected to be able to: 1. Explain terms related to inflammation and repair. 2. Discuss the importance of body response to inflammation. 3. Identify the clinical manifestations in the presence of inflammation. 4. Identify the causes of inflammation and its preventive measures and possible management. 5. Explain the Healing process, the pattern of healing and the complication of tissue healing and repair

3. Inflammation - is a response of vascularized tissues to infections and damaged tissues that brings cells and molecules of host defense from the circulation to the sites where they are needed, in order to eliminate the offending agents.

4. The typical inflammatory reaction develops through a series of sequential steps: • The offending agent-_____________________________________ • Leukocytes and plasma proteins- ___________________________ • The leukocytes and proteins- _______________________________ • The reaction is controlled and ______________________________ • The damaged tissue is __________________________________

5. Fundamental Properties of Inflammatory process Components of the inflammatory response. Harmful consequences of inflammation. Local and systemic inflammation Mediators of inflammation

6. Fundamental Properties of Inflammatory process Components of the inflammatory response. - The major participants in the inflammatory reaction in tissues are blood vessels and leukocytes Harmful consequences of inflammation. - Protective inflammatory reactions to infections are often accompanied by local tissue damage and its associated signs and symptoms Local and systemic inflammation Mediators of inflammation

7. Features of Acute and Chronic Inflammation Features Acute Chronic Onset ______________ Slow, days Cellular infiltrate Mainly neutrophil ___________________ Tissue injury fibrosis ________________ May be severe and progressive Local and systemic signs Prominent _______________

8. The external manifestations of inflammation (cardinal signs) Redness (rubor) Heat (calor) Swelling (tumor) Pain (dolor) • chemicals of acute inflammation, –bradykinins, – prostaglandins –serotonin Loss of function

9. Causes of Inflammation •Infections(bacterial, viral, fungal, _______________) are among the most common and medically important causes of inflammation •Trauma (blunt and penetrating) and physical and chemical agents (thermal injury, e.g.________________; irradiation; ________________) injure host cells and elicit inflammatory reactions. •Tissue necrosis (from any cause), including ischemia (________________) and physical and _______________ •Foreign bodies (_______________) •Immune reactions (also called hypersensitivity reactions) against environmental substances or against _______________.

10. The main components of inflammation: Vascular reaction Cellular response

11. Mechanism of Vascular response Vasoconstriction  Vasodilatation of arterioles and venules Stasis of blood blood flow due increased _________________ oozes protein-rich fluid into ________________  exudates clinically appears as ______________

12. Stages of Vascular response •Vascular dilation and increased blood flow o-(causing erythema and ____________), •Extravasation and deposition of plasma fluid and proteins (edema) •Leukocyte (mainly ____________) emigration and accumulation in the site of injury.

13. Stages of cellular response 1. Margination is a peripheral positioning of white cells along the endothelial cells. Rolling - ______________________ Pavementing - _________________  selectins, immunoglobulins, integrins. 2. Transmigration of leukocytes Diapedesis- -The movement of leukocytes by extending pseudopodia through the vascular wall.

14. 3. Chemotaxis: unidirectional attraction of leukocytes from vascular channels towards the site of inflammation within the tissue space guided by chemical gradients.  The important chemotactic factors for neutrophils: (C5a) – complement system mitochondrial products of arachidonic acid metabolism:  leukotriene B4 cytokines (IL-8). 4. Phagocytosis  Phagocytic cells:  polymorphonuclear leukocytes _____________, monocytes  Tissue macrophages.

15. Chemical mediators of inflammation a) Plasma-derived mediators: i) Complement activation  increases vascular permeability (__________)  activates chemotaxis (_____________)  opsonization (_____________) ii) Factor XII (_____________) activation  four systems:  the kinin  the clotting,  the fibrinolytic  the compliment systems.

16. Steps of Inflammatory response (1) Recognition of the ____________,  (2) Recruitment of ____________, (3) Removal of the agent,  (4) Regulation of ______________. (5) Resolution ______________

17. Morphologic Types of acute inflammation 1) Serous inflammation 2) Fibrinous inflammation 3) Suppurative Types of suppurative inflammation A) Abscess formation: B) Acute diffuse inflammation  diffuse spread of the exudate through tissue spaces.

18. The outcome of acute inflammation •Elimination of the ______________ •Decline of the reaction •Repair of the _________________ •Persistent injury resulting in chronic inflammation.

19. CHRONIC INFLAMMATION Causes of chronic inflammation: 1. Persistent infections- ___________________ 2. Prolonged exposure to nondegradable but partially toxic substances either endogenous lipid components which result in atherosclerosis or exogenous substances such as silica, asbestos. 3. Progression from acute inflammation: Acute inflammation almost always progresses to chronic inflammation following: a. Persistent suppuration as a result of uncollapsed abscess cavities, foreign body materials (dirt, cloth, wool, etc), sequesterum in osteomylitis, or a sinus/fistula from chronic abscesses. 4. Autoimmuniy.

20. Cells of chronic inflammation: Monocytes and Macrophages  Macrophages- scavenger cells of the body. Liver - ______________ spleen, lymph nodes - _______________ Lungs - ____________  bone marrow, brain - ________________ Skin (Langerhan’s cells), ….  cells constitute the mononuclear- ____________ Other cells in chronic inflammation: 1. T-Lymphocytes 2. B-lymphocytes and Plasma cells 3. Mast cells and eosinophils

21. Classification of chronic inflammation:  Nonspecific chronic inflammation:  Specific inflammation (granulomatous inflammation):  characterized by the presence of granuloma.  Granuloma - ______________________.  Epithelioid cell is an activated macrophage, with a modified epithelial cell-like appearance. The epitheloid cells can fuse with each other & form ________________

22. Types of giant cells: . Foreign body-type giant cells which have irregularly scattered nuclei in presence of ______________. . Langhans giant cells  the nuclei are arranged peripherally in a horse –shoe pattern which is seen typically in tuberculosis, and _____________.

23. Types of granulomas Foreign body granuloma  granulomas are initiated by inert foreign  Immune granulomas Antigen presenting cells (______________) engulf a poorly soluble inciting agent. Macrophage inhibitory factor helps to localize activated macrophages and epitheloid cells.

24. Major causes of granulomatious inflammation Bacterial: Tuberculosis, Leprosy, Syphilis, Cat scratch disease, _____________  Fungal: Histoplasmosis, Cryptococcosis, Coccidioidomycosis, _____________  Helminthic: ______________  Protozoal: Leishmaniasis, ________________  Chlamydia: ______________

25. SYSTEMIC EFFECTS OF INFLAMMATIONS a. Fever b. Endocrine & metabolic responses c. Autonomic responses d. Behavioral responses e. Leukocytosis f. Leukopenia g. Weight loss

26. Tissue repair = ____________________________ • Occurs in two ways: – Regeneration of injured tissue – Replacement by connective tissue _____________ - Usually, tissue repair involves both processes. • Involves: - cell proliferation - interaction between cells and ______________ Processes in the proliferation of cells 1.DNA replication 2.Mitosis

27. Mechanisms regulating cell populations • Cell numbers can be altered by: - increased or decreased rates of stem cell input - cell death due to apoptosis. • changes in the rates of proliferation or differentiation.

28. Cellular Proliferation (can be divided into: 1- Continuously dividing (labile) tissues - ___________________ • Can easily regenerate after injury • Contain a pool of stem cells •Examples: bone marrow, skin, epithelium 2- Stable tissues - _________________ • Limited ability to regenerate • Can proliferate if injured •Examples: liver, kidney, pancreas 3- Permanent tissues - ____________________ • Can’t regenerate ( injury always leads to scar) • Examples: neurons, cardiac muscle

29. Tissue for regeneration depends 1) proliferative ability 2) degree of damage to stromal framework 3) type and severity of the damage ue)

30. Repair - ___________________________ - lining epithelium - basement membrane - granulation tissue Three Phases in granulation – tissue 1. Phase of inflammation 2. Phase of demolition 3. Ingrowth of granulation tissue

31. Wound contraction is a mechanical reduction in the size of the defect. Contraction - ___________________________ If contraction is prevented, healing is slow and a large ugly scar is formed. Molecular control of healing process Growth factors –___________________________ • promote cell survival

32. Sources of Growth Factors: 1. Platelets, activated _____________ 2. Damaged epithelial cells ____________ 3. Circulating serum growth factors, 4. Macrophages, __________________ 5. Lymphocytes recruited to the area of injury

33. Wound Healing Healing of a wound demonstrates both epithelial regeneration (healing of the epidermis) and repair by scarring (healing of the dermis).

34. 1.Healing by first intention 1. (Primary union) - Occurs in small wounds that close easily • Epithelial regeneration predominates over fibrosis • Healing is fast, with minimal scarring/infection • Examples:______________ By 24 hours • clot forms • neutrophils come in • epithelium begins to _________ By 3-7 days • macrophages come in • granulation tissue is formed Ø new blood vessels Ø fibroblasts • collagen begins to bridge incision • epithelium increases in _________ Weeks later • granulation tissue gone • collagen is remodeled • epidermis full, mature • eventually, _________ forms

35. 2.Healing by second intention (secondary union) - _____________________ • Fibrosis predominates over epithelial regeneration • Healing is slower, with more inflammation and granulation tissue formation, and more scarring • Examples: – Infarction – Large burns and ulcers

36. Factors that influence wound healing Local Factors > Type, size, and location of the wound > Vascular supply > Infection •Movement •Ionizing radiation Systemic Factors; •Circulatory status •Infection •Metabolic status •Nutritional deficiencies

37. Complications of Wound Healing Infection Deficient Scar Formation Wound Dehiscence Ulceration Excessive Scar Formation oKeloid Formation oHypertrophic Scar

38. Tissue Repair • Repair, sometimes called healing, refers to the restoration of tissue architecture and function after an injury. (By convention, the term repair is often used for parenchymal and connective tissues and healing for surface epithelia)

39. Regeneration Some tissues are able to replace the damaged components and essentially return to a normal state

40. Connective tissue deposition (scar formation) The term fibrosis is most often used to describe the extensive deposition of collagen that occurs: 1.lungs, 2.liver, 3.kidney, 4.myocardium

41. References: Robbins Basic Pathology 9th Edition