Acute Inflammation I &II Classification Notes 2023 PDF

Anatomical Pathology Lecture 3 & 4 : Acute inflammation BDS 2 / GEMP 1 Dr Mark Keyter Anatomical Pathology NIOH / University of Witwatersrand General features of inflammation - It is a protective response, essential to survival and not always harmful but may b...

Anatomical Pathology Lecture 3 & 4 : Acute inflammation BDS 2 / GEMP 1 Dr Mark Keyter Anatomical Pathology NIOH / University of Witwatersrand General features of inflammation - It is a protective response, essential to survival and not always harmful but may be - Definition : “Response of vascularised tissue to infections and damaged tissues that brings cells and molecules of host defense from the sites of circulation to where they are needed in order to eliminate the offending agent” (Robbins and Cotran et al) The five ‘R’s : main steps of the inflammatory response 1. Recognition of the injurious agent ○ Epithelial cells, tissue macrophages, dendritic cells, leukocytes and other cell types which express receptors that sense the damage ie microbes 2. Recruitment of the leukocytes 3. Removal of the agent 4. Regulation (control) of the response 5. Resolution (repair) ○ Either : ○ 1. Elimination of the noxious stimulus followed by decline of the reaction and repair of the damaged tissue by complete resolution or scarring by fibrosis ○ 2. Persistent injury resulting in chronic inflammation Causes of inflammation - Mechanical injury eg. cut, crush - Chemical injury eg. acid - Physical injury eg. heat, electrical - Infective eg. bacteria, parasites - Adjacent necrosis – vital reaction - Immunologic reaction eg. hypersensitivity, autoimmune - Foreign material eg. sutures, splinters Classification according to site Tissue involved Suffix –itis Eg. appendicitis, pericarditis, colitis, meningitis Types of inflammation : acute and chronic Acute : - Initial, rapid response (hrs to days) - Exudation of fluid and plasma proteins (oedema) and emigration of leukocytes (neutrophils) - May resolve or persist which leads to chronic inflammation - Role in innate immunity Chronic : - Longer duration - More tissue destruction, lymphocytes and macrophages, proliferation of blood vessels, deposition of connective tissue - Role in adaptive immunity  Clinical signs of inflammation Rubor – Redness Calor – Heat Dolor – Pain Tumor – Swelling Functio laesa – loss of function Major components of acute inflammation 1. Dilation of small vessels leading to an increase in blood flow 2. Increased permeability of the vasculature enabling plasma proteins and leukocytes to leave the circulation 3. Emigration of the leukocytes from the circulation, their accumulation and their activation Vascular reactions in acute inflammation - Vasodilation - Induced by histamine - Cause of erythema (redness) and stasis of blood flow - Increased vascular permeability - Induced by histamine, kinins, etc - Produce gaps in endothelial cells by injury (direct or leukocyte-induced) - Increased passage of fluids through endothelium - Edema from fluid leakage and escape of plasma proteins and leukocytes - Response of lymphatics / lymph nodes - Due to drainage of fluid by lymphatics - Leads to reactive or inflammatory lymphadenitis, showing redness and swelling Leukocyte recruitment to sites of inflammation - Multistep process: - Loose attachment and rolling on endothelium (mediated by selectins) - Firm attachment to endothelium (mediated by integrins) - Migration through endothelial spaces - Expression mediators promoted by cytokines - Neutrophils initially predominate, followed by macrophages Leukocyte activation and removal of offending agent - Leukocytes can eliminate microbes and dead cells by phagocytosis - Further destruction by phagolysosomes - Destruction caused by free radicals (ROS,NO) generated in activated leukocytes and lysosomal enzymes - Elimination of microbes by neutrophils (extruding nuclear contents), enzymes and ROS - Damage to normal tissue can also occur - Termination of inflammatory response by anti-inflammatory mediators Important mediators - Chemotaxis – positive movement by white cells toward an attracting stimulus - Chemotactic agents: - Bacterial products - Complement proteins C5a - Lipoxygenase pathway of arachidonic acid metabolism components, eg. leukotriene - Phagocytosis - Recognition – opsonins (immunoglobulins, complement) - Ingestion - phagosomes - Killing/digestion – phagolysosomes, oxygen free radicals and enzymes - Degranulation - Lysosomal granules: - Small specific granules (lactoferrin, lysozyme, alkaline phosphatase, collagenase and adhesion molecules) - Large azurophil granules (myeloperoxidase, lysozyme, cationic proteins, acid hydrolases, elastase)  Principal mediators of inflammation Mediator Source Action Histamine Mast cells, basophils, platelets VD, VP, endothelial activation Prostaglandins Mast cells, leukocytes CD, pain, fever Leukotrienes Mast cells, leukocytes VP, chemotaxis, LA and activation Cytokines Macrophages, endothelial cells, mast Local : endothelial activation cells Systemic : fever, metabolic abn hypotension Chemokines Leukocytes, activated macrophages Chemotaxis, LA Platelet-activating Leukocytes, mast cells VD, VP chemotaxis, degranulation, oxidative burst factor Complement Plasma (from liver) LA, direct target killing, VD Kinins Plasma (from liver) VP, smooth muscle contraction, VD, pain Histamine response Histamine response (Lewis 1924) 1. Red line – localised capillary dilatation 2. Red flare – blotchy flush – more diffuse dilatation 3. Weal – raised area from oedema Polymorphonuclear leucocytes / neutrophils Smaller specific granules and larger azurophil granules 10-12µm Lobated nucleus First to arrive, short life Actively motile Pus formation – living and dead polymorphous, dead digested tissue cells, fluid exudate, +-organisms Eosinophils Bilobed Red granules Allergic conditions, parasitic infestations, drug reactions Basophils and mast cells Histamine, heparin Hypersensitivity (anaphylaxis)  Mononuclear phagocytes Scavenger cells – clear up foreign matter Immune function – present antigens for development of cell-mediated immunity, cytokine production Monocytes in blood , macrophages in tissue Derived from bone marrow Phagocytosis and production of inflammatory mediators May fuse to form multinucleated giant cells Lymphocytes 8-10µm Single small, round nucleus Recognise foreign material and antigens Activate macrophages T-lymphocytes – cytotoxic, regulatory B-lymphocytes - immunoglobulins  Plasma cells 10-12µm Dark, round, eccentric nucleus, “clock-face” chromatin, dark cytoplasm with a paranuclear pale hof Transformed B cells Synthesise antibodies Morphologic patterns of acute inflammation Hallmarks : dilation of small blood vessels and accumulation of leukocytes and fluid in the extravascular tissue There are special morphologic patterns superimposed May provide clues as to the underlying cause Morphologic patterns of acute inflammation Serous – high fluid content eg. blisters, burns Fibrinous – high fibrinogen / fibrin content eg. pleural effusion in pneumonia Haemorrhagic – high red blood cell content eg. meningococcal septicaemia Catarrhal – high mucus content eg. bronchitis Pseudomembranous – false membrane of necrotic debris and inflammation eg. diphtheria Suppurative – pus semiliquid substance composed of dead and living neutrophils, dead digested tissue and fluid exudate (abscess = localised collection of pus) Systemic reaction to acute inflammation Fever - Bacterial endotoxins, IL-1 - IL-1 acts on thermosensory centre and causes formation of prostaglandins - Aspirin blocks prostaglandin formation, reducing temperature Headache, lethargy, weakness, hyperaesthesia, loss of appetite Leucocytosis - Increase white cell count - Neutrophils, lymphocytes, eosinophils Protein synthesis - IL-1 and TNFα - C-reactive protein, fibrinogen, serum amyloid A complement  Outcome of acute inflammation Resolution (back to normal) Tissue destruction and suppuration Healing by regeneration and repair Fibrosis Chronic inflammation Septicaemia Death  Sources Rippey, JJ. General Pathology Illustrated Lecture notes. Witwatersrand University Press, 1999. Kumar V, Abbas A et al. Robbins and Cotran Pathologic Basis of Disease, 8th ed. Saunders Elsevier, 2010. Dr P.C. King lecture series.  Questions? [email protected]