Pathology of Inflammation PDF

# Pathology of Inflammation **Prof.Dr Shereen Fathy** ## Inflammation **Definition:** - Inflammation is a dynamic response of vascularized living tissue to injury. - It is physiologic, protective response. - Serves to bring defense and healing mechanisms to the site of injury. ## Aim of Inflam...

# Pathology of Inflammation **Prof.Dr Shereen Fathy** ## Inflammation **Definition:** - Inflammation is a dynamic response of vascularized living tissue to injury. - It is physiologic, protective response. - Serves to bring defense and healing mechanisms to the site of injury. ## Aim of Inflammation - Isolate injury - Destroy invading microorganisms - Inactivate toxins - Prepare the damaged tissue to repair and healing ## Causes of Inflammation - Infections - Trauma - Physical injury (heat, radiation) - Chemical injury - Immune-mediated - Adjacent to necrotic tissue ## Cardinal Signs of Inflammation - **Calor:** Warm — Hyperaemia - **Rubor:** Redness — Hyperaemia - **Dolor:** Pain — Nerve, chemical med. - **Tumor:** Swelling — Exudation - **Functio laesa:** Loss of function ## Types of Inflammation ### Acute - **Suppurative** - Localized: Abscess, furuncle and carbuncle. - Diffuse: Cellulitis - **Non-Suppurative** ### Chronic - **Non-specific** - Chronic abscess - **Specific** - Tuberculosis or bilharziasis | | Acute | Chronic | |---|---|---| | | Strong irritant | Mild | | | Rapid response | Gradual | | | Short duration | Prolonged | | | Vascular dilatation | Healing (fibrosis) | | | Excess fluid exudate | End arteritis obliterans | | | Polymorphs, eosinophils, macrophages | Scanty | | |   | Lymphocytes, plasma, macrophages, giant cells | ## Acute Inflammation **Definition:** It is a rapid host response serves to deliver leukocytes and plasma proteins, such as antibodies to sites of infection or tissue injury. **Tissue Response:** - Two main components of tissue response (inflammation) - Vascular response - Cellular response ### Major features: - **Vascular Responses** - Vasodilation with an increased blood flow - Increased vascular permeability (proteins and cells) - Leukocyte transmigration and chemotaxis ## Vascular Responses **Vasodilation and Endothelial Contraction:** - Histamine - Bradykinin - Prostaglandins and Leukotrienes - Platelet Activating Factor - Direct Endothelial Injury - Transudates - Exudates ### Vascular responses - Immediate vasoconstriction - Vasodilation - Increased vascular permeability - **Contraction of Endothelial Cells with Increased Inter-endothelial Cell Mediated by Histamine and Bradykinin:** - Endothelial cells undergo necrosis and detachment by either a direct effect of injurious agent or effect of neutrophils adherent to the wall. - **Transcytosis:** - Caused by interconnected uncoated vesicles and vacuoles called "vesiculo- vacuolar organelles" that increase in size in inflammation. - **Formation of Inflammatory Exudate** ## Inflammatory Fluid Exudate **Mechanism** - Vascular permeability - Capillary Hydrostatic pressure - Osmotic pressure **Amount** - Tissue - Irritant - Lymphatic obstruction | Variables | Transudate | Exudate | |----------|--------------------------|----------------------------------------------------------| | Definition | An ultrafiltrate of blood plasma | A filtrate of blood plasma mixed with inflammatory cells and cellular debris | | Capillary permeability | Normal | Increased | | Composition | - Fluid low in protein content < 3 gm/dl | - Fluid high in protein content > 3gm/dl | |   | - Clear | - Turbid | |   | - Liquid (like serum) | - Viscous (like pus) | |   | - Sp. Gravity< 1.015 | - Sp. Gravity>1.020 | |   | - Scant cellular content | - Contains numerous neutrophils | ## Exudate and Transudate | Variables | Transudate | Exudate | |----------|-------------|---------| | Definition | Oedema fluid | Inflammation fluid | | Capillary permeability | Normal | Increased | | Composition | - Fluid low in protein content < 3 gm/dl | - Fluid high in protein content > 3 gm/dl | |   | - Clear | - Turbid | |   | - Liquid (like serum) | - Viscous (like pus) | |   | - Sp. Gravity <1015 | - Sp. Gravity >1020 | |   | - Scant cellular content | - Contains numerous neutrophils | ## Extravasation of Cells is Divided into Three Steps **I - Intravascular:** - Margination - Rolling and adhesion of leukocytes to the endothelium - Transmigration across the endothelium **II- Extravascular** - Chemotaxis - Phagocytosis ## Cellular Responses ### Neutrophil Recruitment - Margination - Pavementing - Transmigration - Chemotaxis **Hemodynamic Changes:** - Adhesion molecules - Selectins, Integrans - ICAM-1, VCAM-1 - **Bacterial Products** - Complement components (C5a) - AA metabolites (leukotriene B4) - Platelet Activating Factor (PAF) - **Margination: due to stasis** ### Cellular responses - Vasoconstriction - Vasodilation - Stasis - Exudation - Edema - Emigration of cells - Chemotaxis - Phagocytosis - **Rolling:** Occurs by P-& E- selectin on endothelial cells and oligosaccharides on leukocytes. - **Stable Adhesion:** Depends on immunoglobulin family including ICAM-1 and VCAM-1 on endothelial cells, and integrins on leukocytes. - **Transmigration** (diapedesis) Depends on CD31 (PECAM-1) on both endothelial and leukocytes. ## Chemotaxis **Definition**: Is the directed movement of neutrophils and macrophages in the area of inflammation towards the irritant depending on: - Exogenous bacteria product - Endogenous mediators as complement, arachidonic acid metabolites and chemokines. ## Phagocytosis **Definition:** Is the ingestion and destruction of bacteria, necrotic debris and foreign particles by the phagocytic inflammatory cells. It is similar to the feeding process of amoeba. ## Cellular Responses **1-Recognition** ### Opsonization and phagocytosis - C3b receptor - Fc receptor - Complement Immunoglobulin ### Opsonization and phagocytosis - C3b - Fc ### Opsonization and phagocytosis **2-Engulfment** ### Opsonization and phagocytosis **3- Killing and Degradation** ### Oxidative burst, bacterial killing, and tissue injury - Reactive Oxygen Metabolites - Lysosomal Enzymes - Tissue Injury - AA metabolites - Prostaglandins - Leukotrienes - ↑ Inflammation - **NADPH Oxidase** - **Myeloperoxidase** - **H2O2** - **HOCl** - Hypochlorous radical ## 1-Suppurative Inflammation **(1) Localized** @ **(A) Abscess:** - Abscess is a type of localized suppurative inflammation characterized by the formation of a cavity containing pus. - It is commonly caused by staphylococcal infection. - It can occur in any organ, but is most common in the subcutaneous tissues. **Pus is formed of:** - Fluid exudate without fibrin (liquefied) - A large number of pus cells, neutrophils - Necrotic fragments (sloughs) and liquefied necrotic tissue - Bacteria and bacterial pigments ** (2) Diffuse** - **Caused by streptococcus haemolyticus bacteria which produce hyaluronidase (the spreading factor) and streptokinase (fibrinolysin) with dissolves fibrin.** - The most common forms of diffuse suppurative inflammation are: - **Cellulitis:** Is common in diabetics - **Suppurative appendicitis.** - **Septic peritonitis** ## Abscess and Cellulitis | Variables | Abscess | Cellulitis | |----------|----------|-----------| | Definition | Localized suppurative inflammation | Diffuse suppurative inflammation | | Etiology | Staph aureus | Strepthemolyticus | |   | Produces coagulase that localizes the infection | Produces fibrinolysis and hyaluronidase that lyses fibrin | | Site | Any organ, commonly subcutaneous tissue | Loose connective tissue, orbit areolar tissue (less liquefied fibrin), pelvis, and scrotum | | Pus is | Thick (more liquefied fibrin) | Thin (less liquefied fibrin) | | Spread of inflammation | Few RBCs | Many RBCs | |   | Less common | More common | ## 2-Non-Suppurative Inflammation - Catarrhal (rhinitis, appendicitis) - Memmberanous(diphtheria) - Sero-fibrinous (serous membranes) - Fibrinous(lobar pneumonia) - Serous (burn, herpes) - Haemorrhagic (hamolyt. Strept. Infect.) - Necrotizing (cancerum oris) - Allergic (anaphylactic shock, Br.asthma) ## Chronic inflammation **Character:** - Mild irritant with long duration. - Follow acute inflammation or start as chronic. - Mild vascular congestion and dilatation. - Scanty fluid exudate. - Healing by fibrosis. - Chronic inflammatory cells - @lymphocytes @plasma cells - @Macrophages @giant cell ### Types - **Non-specific** - Chronic abscess - **Specific (granuloma)** - Tuberculosis or bilharziasis ## Granuloma - **Type of chronic specific inflammation** - **Collection of a large number of:** - Macrophages, lymphocytes, plasma, giant cells and fibroblasts - **Forming tiny microscopic granules** - **Fuse to form tumor-like mass** ### Types - **Infective** - Bacterial: T.B.,leprosy, syphilis. - Parasitic: Bilharziasis. - Fungal:Madura foot, histoplasmosis. - **Non-Infective** - Silicosis and asbestosis. - **Granuloma of unknown cause:** Sarcoidosis