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LFS 319 – Pathophysiology Chapter 2: Inflammation Chapter 2: Inflammation 1. Acute Inflammation Introduction Inflammation is the response of living tissue to damage. Short-lasting (few days) The acute inflammatory response has 3 main functions. 1. The affected area is occupied by exudate helps mediate local defences 2. Removal of causative agent (e.g. bacteria 3. Removal of damaged tissue & debris from the site of damage. Causes of acute inflammation: Physical damage Chemical substances Micro-organisms Other agents The inflammatory response consists of: 1. Changes in blood flow 2. Increased permeability of blood vessels Examples of acute inflammation? Definition of inflammation "inflammation is complexly orchestrated response to injury that serves to destroy the source of injury, remove the accumulated debris, and trigger the repair process" Page 28 1 LFS 319 – Pathophysiology Chapter 2: Inflammation Cardinal signs: Redness (rubor) Heat (calor) Swelling (tumor) Pain (dolor) Loss of function Normal vascularised connective tissue The inflammatory process is focused in the vascularised loose connective tissue (ECM). The vessels that participate in the inflammatory response are the venules. Inflammation loosens endothelial junctions within postcapillary venules. Connective tissue contains fibroblasts, macrophages & mast cells Formation of tissue fluid (Fig. 2.3, P 30): 4 forces control fluid movement between blood and tissue spaces: a. Blood hydrostatic pressure (BHP) b. tissue hydrostatic pressure (THP) c. blood osmotic pressure (BOP) d. tissue osmotic pressure (TOP) fluid leaving blood vessels at the arteriolar end = fluid entering at venule end 2 LFS 319 – Pathophysiology Chapter 2: Inflammation Normal fluid shift: (Fig. 2.3 a): At the arteriolar end of the capillary: BHP + TOP > BOP + THP Fluid shifts from blood vessels to interstitial spaces. At the venule end of the capillary: BOP + THP > BHP + TOP Fluid shifts from interstitial spaces to blood vessels In acute inflammation, 2 changes occur (Fig. 2.3 b&c): 1. Hyperaemia due to dilation of arterioles BHP increased fluid filtration transudate 2. Permeability (esp. venules) filtration of blood proteins exudate Explain how high tissue osmotic pressure contributes to swelling? Net effect: low blood volume, high viscosity Stasis How do permeability changes differ in mild to moderate injury from that in more severe injury? 3 LFS 319 – Pathophysiology Chapter 2: Inflammation What are the benefits of accumulation of fluid and plasma proteins at an injury site? 1. dilution of toxins 2. limitation of use of affected part because of pain 3. presence of antibodies 4. stimulation of phagocytosis (by exudates proteins) Descriptive classification of acute inflammation: 1. Serous inflammation Only fluid escapes from capillaries Occurs in minor injuries, e.g. blisters of mild burns 2. Fibrinous exudates Presence of fibrinogen (a plasma protein) in the exudates Results in coagulation of exudates E.g. in pericarditis and pleurisy (seen in pneumonia) 3. Purulent (suppurative) inflammation: a. Caused by more severe injury b. Results in formation of Pus c. Pus is: Neutrophils, necrotic debris & fluid exudates d. Cellulitis: diffuse suppurative inflammation e. Abscess: localised accumulation of pus f. Cyst: a fluid-filled sac may remain after removal of injurious agent 4. Hemorrhagic inflammation 4 LFS 319 – Pathophysiology Chapter 2: Inflammation The formation of exudate: Cellular factors: Stages of movement of Leukocytes from blood vessels to tissue spaces: 1. Migration: movement towards vascular endothelium 2. Rolling, pavementing and adhesion: attachment to endothelium 3. Transmigration: movement of leukocytes from blood to tissue spaces Phagocytosis: Effective phagocytic activity involves: 1. Activation (chemotaxis) 2. Recognition & Attachment 3. Engulfment & destruction 5 LFS 319 – Pathophysiology Chapter 2: Inflammation 4. Chemical Mediation of Inflammation: Answer the following questions: a. What triggers the dilation and permeability changes that occur during acute inflammation? b. What activates phagocytic cells? c. How are these responses linked to the original injury? Injury ↓ Chemicals released or produced at site of injury ↓ Acute inflammatory changes Acute inflammation starts with triggering events, also called initiators (Table 2.1, page 38). Initiator(s) ↓ Chemical mediators ↓ Vascular & cellular events (Inflammatory response) 6 LFS 319 – Pathophysiology Chapter 2: Inflammation Cell-Derived Mediators: Chemical Released from Triggered by Causes Histamine Mast cells Cold, heat, trauma, Rapid, brief increase in [binds to H1 Platelets foreign antigens postcapillary venule permeability receptors] Serotonin platelets Contact with of Same as above platelets with basement membrane collagen fibres Eicosanoids All Injury Coagulation Leukocytes Pain [Metabolic especially Swelling transformation mast cells Tissue damage of arachidonic acid (AA)] 7 LFS 319 – Pathophysiology Chapter 2: Inflammation Plasma Cascades Bradykinin: contributes to pain Inflammation of inflammation. Kinin Fibrinolytic Inflammation & Function in both inflammation Coagulation and blood loss prevention Coagulation The complement system consists of 20 circulating proteins. Upon Inflammation & activation, a complex of 5 proteins Complement immune is formed called the membrane attack complex (MAC), which can destroy microorganisms by All four cascades can be directly or indirectly producing holes in their membranes. triggered by the presence of the active form of They also promote chemotaxis, circulating protein known as Hageman factor dilation, permeability changes, and (clotting factor no. XII) phagocytosis and histamine release by mast cells. 8 LFS 319 – Pathophysiology Chapter 2: Inflammation Systemic effects of acute inflammation: Fever Loss of appetite Rapid weight loss Fatigue Lymphadenitis Bacteremia Leukocytosis Therapeutic modification of acute inflammation: a. Temperature: Application of cold to damaged area ↓ swelling (how?) Application of heat phagocytosis Q. Explain why cold should not be applied for more than 10 minutes. Q. Explain why cold should be applied first then heat. b. Elevation and pressure: Elevation of a limb reduces swelling. Constrictive wrapping reduces exudate formation 9 LFS 319 – Pathophysiology Chapter 2: Inflammation c. Drug Therapy: Antihistamines block the action of histamine at its blood vessel receptors. NSAIDs prostaglandin synthesis, bradykinin Steroid prostaglandin synthesis ↓ vasodilation ↓ swelling ↓ phagocytic activity ↓ tissue damage ↓ release of lysosomal enzymes ↓ damage Potential complications of anti-inflammatory therapy: Interference with the healing process Greater susceptibility to infection 10 LFS 319 – Pathophysiology Chapter 2: Inflammation 2. Chronic Inflammation Subacute: Inflammation lasting > 1 week Chronic: Inflammation lasting > 6 weeks – months or years Development of chronic inflammation Injurious agent enters body Acute inflammatory response (both vascular and cellular) Agent not destroyed or removed Vascular response diminishes (↓ exudate) & cellular response dominates (↑ phagocytes and lymphocytes activity) Injurious agent attacks and defences = host attacks and defences Inflammatory response prolonged Chronic inflammation Tissue damage 11 LFS 319 – Pathophysiology Chapter 2: Inflammation Pathogenesis of chronic inflammation: (Fig. 2.20, P 47) Acute inflammatory response Response unable to eliminate injurious agent Lymphocytes are also attracted to the scene (so now both macrophages and lymphocytes are present) Injurious agent not destroyed or removed Lymphocytes (T-Helper) Lymphokines (MAF, MIF) Accumulation of macrophages Diffuse Focal Chronic Chronic Nonspecific Granulomatous inflammation inflammation. . 12 LFS 319 – Pathophysiology Chapter 2: Inflammation Explain how acute and chronic inflammation processes differ in the sequencing of healing. Classification of chronic inflammation: There are two patterns: a. Nonspecific chronic inflammation (most common): Diffuse accumulation of macrophages and lymphocytes at site of injury. b. Granulomatous inflammation: Focal accumulation of macrophages and lymphocytes granuloma Formation of a mass of epithelioid cells surrounded by lymphocytes and fibroblast. Central mass of necrotic tissue Multinucleated giant cells Give examples of agents that may cause chronic inflammation. 13
"Ch 2 - Inflammation - OH"