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Published by: kayexh on Aug 26, 2010
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Inflammation and Repair

Richard Allcock S chool of Pathology and Laboratory Medicine, UWA

At this end of this lecture you should be able to : 1. Describe the causes, features and signs of inflammation 2. Define the important chemical mediators involved in inflammatory reactions 3. Describe the different kinds of inflammatory reactions 4. Describe how inflammation resolves and affected tissues are repaired


consisting of vascular.Definition and General Features • Reaction to injurious agents. cellular and systemic responses • • • • Fluid and cells accumulate at injured site Primarily a protective response Rapid onset Effects mediated by chemical messengers • Inflammation is tightly controlled • Sensitive activation • Massive amplification • Controlled down-regulation Signs of Inflammation Calor Rubor Tumor Dolor 2 .

dirt. frostbite.Causes of Acute Inflammation • Infections and microbial toxins • bacterial. some environmental chemicals) • Tissue necrosis • Foreign bodies • splinters. viral. parasitic • Trauma • blunt and penetrating • Physical and chemical agents • Burns. sutures • Immune reactions • also called hypersensitivity reactions 3 . irradiation.

Initiating event (ie.Steps required for Inflammation 1. cells must move to the correct area (how?) The cells must do something (how do they decide?) • • Send out signals recruiting other cells Engulf and attempt to kill and remov e the offending organisms 2. a cause) • • • • Signal to the body that a response is needed Allow fluid and cells to move out of circulation into the injured site (what about capillary integrity?) At the site. Down-regulation of the response when finished • • Short-lived responses that only continues whilst needed Require s continual re-stimulation Movement of Cellular and Vascular Components 4 . A response 3.

What can cells do when they reach tissues? 1. Phagocytosis • Engulfment and removal of organisms/foreign material Direct lysis and killing of foreign organisms Can attract more cells to the area or activate cells already present 2. Activation • • 3. Release mediators Overview of Phagocytosis 5 .

Macrophage adhering to E. Coli 6 .

• • • • Arachidonic acid metabolite production Cy tokine secretion Modulation of adhesion molecules Phagocy tosis f ollowed by degranulation and secretion of lysosomal enzy mes 7 .Leukocyte activation • Leukocytes generally indiscriminate • Self-preservation • Require activation in order to do anything • Acti vation results from signals delivered from the cell surface • Many different receptor pathways • Many possibilities………….

require activation 8 .Sources of inflammatory mediators • Cell-derived • Act alone. active when secreted • Plasma Mediators • Act in interacting cascades.

Staph spp. Creamy–yellow colour. necrotic cells. short half-lives • Degrade quickly. so inflammation persists as long as stimulus persists Purulent Inflammation • Pus = dead white cells/bacteria.?Repair? ?Fibrotic wall? 9 . • Pyogenic bacteria (eg. edema fluid • Abscesses : collection of purulent inflammatory tissue in confined space (or deep within tissues) • • • • Central region w/ mass of necrotic cells Preserved zone of neutrophils Vascular dilation and fibroblast proliferation . which will then resolve differently • • • • Purulent Inflammation (suppurative) Fibrinous Inflammation Serous Inflammation Ulcerative Inflammation • Most mediators have v.) result in purulent inflammation • Purulent inflammation characterised by : • Large amounts of pus • Large amounts of neutrophils.Possible Courses of Acute Inflammation • Different stimuli cause different courses of inflammation.

pericardium • Fibrin can be broken down and removed (resolution) • When not removed. Functional consequences?? 10 . is cleaved to form fibrin • Eg. can lead to scarring. Inflammation of lining of meninges.Subcutaneous bacterial abscess Fibrinous Inflammation • Severe injury causes greatest vascular permeability • Fibrinogen enters tissues.

intestines. stomach. or genitourinary tract • Lower extremities of individuals with impaired circulation 11 . Blisters from burns or viral infections Ulcerous Inflammation • Excavation in tissue surface produced by shedding of necrotic inflammatory tissue • Mucosa of mouth. pleural and pericardial cavities • Eg.Serous Inflammation • Thin fluid from plasma or mesothelial cells in peritoneal.

Return to normal permeability • 2. Phagocytosis of necrotic debris • 6. Pinocytosis into macrophages • 4. Drainage of fluid and proteins into lymph • 3. susceptibility to infections • Delayed wound healing and repair • Excessive inflammation • Excessive tissue damage • ??Death to the host?? 12 .Complete Resolution of Inflammation • 1. Disposal of macrophages Consequences of Too Much or Too Little Inflammation • Defective inflammation • Inc. Phagocytosis of apoptotic neutrophils • 5.

Inflammation • Numerous chemical mediators and growth factors involved • New tissues must be formed • The newly formed tissue has to become vascularised – angiogenesis 13 .Diseases Associated with Inflammation Acute Acute respiratory distress syndrome Acute transplant rejection Asthma Glomerulonephritis Reperf usion injury Septic shock Vasculitis Chronic Arthritis Asthma Atherosclerosis Chronic lung disease Chronic rejection Genetic defects identified in almost all stages of inflammatory pathway General Comments on healing • Inflammation and healing/regeneration occur simultaneously • Integrated response of many cell types (cf.

Inflammation to remove damaged and dead tissue Entry and proliferation of CT and parenchymal cells Formation of new blood vessels Synthesis of new ECM proteins Tissue remodelling Wound contraction Acquisition of wound strength 14 .Overview of Healing • Fibroproliferative response that patches areas of damaged tissue 1. 6. 7. 2. 5. 4. 3.

so tissue edematous • Fibroinogen and plasma fibronectin form early stroma • Fibroblasts attracted by TGFβ. • Also clear debris. Inadequate vascularisation. pink. denervation. EGF. vitamin deficiency. intensity of the stimulus. FGF. anemia. drugs. granular Microscopic – angiogenesis and fibroblast proliferation New vessels leaky. trace metal deficiencies Formation of Scars 1 : Migration & Proliferation of Fibroblasts • “Granulation tissue” can start forming <24hrs after injury • • • • Vascular endothelial cells and fibroblasts Macroscopic – soft. nature of the injury. temperature. hormones.Factors Affecting Healing • Injury-related factors • Nature of the tissue. duration of the stimulus • Inflammatory factors • Foreign bodies. fibrin and foreign material from site 15 . surgical techniques • Host factors • Age. trauma. systemic infection. uremia. genetic disorders. mechanical stress. PDGF. necrotic tissue. diabetes. malnutrition. obesity. dressings. IL1 and TNF • Mφ are a source of GFs.

Formation of Scars 2 : ECM Deposition • Fibroblasts major source of ECM components • Collagen synthesis starts 3-5 days after injury • Collagen deposition depends on synthesis and degradation • Granulation tissue becomes the scar • Spindle-shaped fibroblasts • Dense collagen • Elastic tissue fragments • Vascular regression leads to scar becoming pale Collagen Prior to healing After healing 16 .

Healing by First and Second Intention Complications • Deficient scar formation • Mechanical stress or inadequate vascularisation • Can cause rupture and/or ulceration • Excessive formation of repair components • Excess collagen causes raised scars (hypertrophic) • Scar beyond original boundaries = keloid • Contractures • Too much contraction deforms the surrounding tissue 17 .

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