Acute and Chronic Inflammation

By Dr C A Okolo MBBS, FMCPath Dept of Pathology, College of Medicine University of Ibadan

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This is the response of living vascularised tissue to injury. Inflammation is fundamentally a protective response, the ultimate goal of which is to rid the body of both the initial cause of cell injury and the consequences of such injury The inflammatory process is closely intertwined with the process of repair Acute inflammation is of relatively short duration, lasting from minutes to a few days & its main characteristics are the exudation of fluid and plasma proteins and the migration of leukocytes

Historical Highlights
 Signs

of inflammation were 1st described in an Egyptian papyrus in 300BC  Cardinal signs of inflammation  Rubor – Redness  Tumor – Swelling  Calor – Heat  Dolor – Pain  Elie Metchnikoff (Russian) discovered “phagocytosis” in 1882

Acute Inflammation
  (3) (4)


This is the immediate or early response of of living vascularised tissues to an injurious agent. It has three major components Alteration in vascular caliber that leads to an increase in blood flow. Structural changes in the microvasculature that permits the plasma proteins and leukocytes to leave the circulation. Emigration of the leukocytes from the microcirculation & their accumulation at the focus of injury

Events in Acute Inflammation
 Vascular

events  Cellular events  Chemical mediators of inflammation

Vascular events
 Changes

in vascular flow and caliber.  Transient vasoconstriction (inconstant)  Vasodilation  Stasis  Increased vascular permeability

 Peripheral

orientation of leukocytes  Leukocyte margination  Rolling  pavementing

Increased vascular permeability
 Mainly

at the arterioles, capillaries and venules  Endothelial contraction  Cytoskeletal reorganisation  Direct injury  Leukocyte-dependent injury  Increased transcytosis  Angiogenesis with leaky blood vessels

Cellular events
 (2)



Leukocyte extravasation In the lumen – margination, rolling and adhesion Transmigration across the endothelium (diapedisis) Migration in the interstitial tissues towards the chemotactic stimulus

Adhesion and transmigration
 P-selectins

– rolling  E-selectins- rolling adhesion to activated endothelium  ICAM-1 - Adhesion, arrest, tranmigration  VCAM-1 – adhesion  GlyCam -1 - Homing

 This

is the movt of leukocytes towards the site of injury propelled by a chemical gradient  Chemoattractants – C5a, B4 Cytokins eg IL8, Bacterial products

Leukocyte Activation
 Production

of arachidonic acid metabolites from phospholipids  Degranulation and secretion of lysosomal enzymes and activation of the oxidative burst  Modulation of leukocyte adhesion molecules

 Recognition

and attachment – opsonins – C3b, IgG Fc fragment  Engulfment  Killing or degradation

Chemical mediators of inflammation
 Mediators

from plasma  Mediators from cells  Most mediators perform by initially binding to specific receptors on target cells  A chemical mediator can stimulate the release of mediators by target cells themselves  Mediators can act on one or few target cell types and have wide spread effect.

Preformed mediators
 Histamine  Serotonin  Lysosomal

enzymes  They are produced by mast cells, platelets and neutrophils and macrophages

Newly synthesised
 Prostaglandins  Leukotrienes  Platelet

activation factor  Activated O2 species  Nitric Oxide  Cytokins  Produced by all leukocyte

Complement factors
 C3a--

Anaphylatoxins  C5a-- ‘’  C3b  C5b-9

Clotting factors
 Factor

XII Hageman factor

Outcome of Acute Inflammation
 Resolution  Healing

by fibrosis  Abscess formation  Progression to chronic inflammation

Chronic Inflammation
 This

is inflammation of prolonged duration in which active inflammation, tissue destruction, and attempt at repair are proceeding simultaneously.  It frequently begins insidiously as a lowgrade, smoldering, often asymptomatic response  It is responsible for most common and disabling human diseases such as rheumatoid arthritis, tuberculosis etc

Chronic inflammation arises under the following setting
 Persistent

infection by certain microorganisms e.g. TB , Treponema pallidum, fungi  Prolonged exposure to potentially toxic agents either exogenous or endogenous e.g. silica –silicosis, toxic plasma lipid components – atherosclerosis  Autoimmunity – immune reactions are set up against the individuals own tissues

Histologic features
 Infiltration

by mononuclear cells which include macrophages, lymphocytes, eosinophils, mast cells and plasma cells – reflecting persistent reaction to injury  Tissue destruction induced by inflammatory cells  Attempt at healing by connective tissue replacement of damaged tissue

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These are the most important cells in chronic inflammation. Derived from blood monocytes, they home to different tissues as tissue macrophages Lung – alveolar macrophages Liver – kupffer cells Spleen – sinus histiocytes Bone – osteoclasts They undergo phagocytosis and are capable of activation into cell with larger cytoplasm, increased level of lysosomal enzyme production, greater ability to phagocytose & kill ingested microbes

 They

secrete a wide variety of biologically active products, e.g. enzymes, complement components, coagulation factors, reactive O2 species cytokines, growth factors, nitric oxide  Induce continued recruitment of monocytes from circulation  Local proliferation of macrophages  Immobilization of macrophages

 Mobilized

in both antibody mediated and cell mediated immune responses and also in non immune mediated chronic inflammation.  Various types of lymphocytes T & B  Lymphocytes can be activated on contact with antigen to produce lymphokines  Plasma cells produce antibodies directed at persistent antigen at the inflammatory site or against altered tissue components

Other cell types
 Mast

cells are widely distributed in connective tissue and participate in both acute and chronic inflammation eg asthma, parasitic infections  Eosinophils are also characteristic of immune reactions mediated by IgE and parasitic infections

Chronic non-specific inflammation of the cervix

Granulomatous inflammation
 This

is a special type of chronic inflammation in which the predominant cell type is an activated macrophage with modified epithelial-like appearance (epithelioid).  A granuloma is a focal area of inflammation consisting of aggregation of macrophages that are transformed into epithelioid cells surrounded by a rim of lymphocytes and sometimes plasma cells.

Types of granulomas
 Foreign

body granulomas – these are incited by relatively inert foreign bodies eg talc, suture or other fiber. Foreign body giant cells are typically formed.  Immune granulomas – caused by insoluble particles that are capable of inducing a cell mediated immune response

Examples of granulomas
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Tuberculosis- Caseating Leprosy Syphilis Cat-scratch disease Schistosomiasis Fungal granulomas Foreign body granulomas Lymphogranuloma venereum – chlamydia spp

Granulomatous inflammation

Histology of a granulomalanghans giant cells

Epithelioid cells in a granuloma

Caseous granuloma in TB

Foreign body type giant cell (suture material)

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