Inflammation

InflammationI Wayan Juli SumadiBagian/SMF Patologi Anatomi FK UNUD/RSUP SanglahInflammation???In flame ??

Inflammation Fundamentally a protective response, designed to rid the organism of both the initial cause of cell injury (e.g., microbes, toxins) and the consequences of such injury (e.g., necrotic cells and tissues) Inflammation is a complex reaction in tissues that consists mainly of responses of blood vessels and inflammatory cells (leukocytes, macrophages, lymphocytes, etc)Acute inflammation

Cardinal sign of acute inflammation

Inflammation due to gouthttp://www.whathealth.com/gout/picture-3.html

Acute inflammationRapid host response that serves to deliver leukocytes and plasma proteins (antibodies) to sites of infection or tissue injury Three major components: (1) vascular changes(2) structural changes in the microvasculature that permit plasma proteins and leukocytes to leave the circulation(3) emigration of the leukocytesVascular response + cellular response

NORMALACUTE INFLAMMATION(1) Vascular dilation and increased blood flow (causing erythema and warmth); (2) extravasation and extravascular deposition of plasma fluid and proteins (edema); (3) leukocyte emigration and accumulation in the site of injury. STIMULI FOR ACUTE INFLAMMATION InfectionTissue necrosis (ischemia, trauma, physical and chemical injury)Foreign bodiesImmune reaction

REACTIONS OF BLOOD VESSELS IN ACUTE INFLAMMATION Changes in Vascular Flow and Caliber vasodilation (heat and redness)increased permeability of the microvasculaturestasis increased levels of adhesion molecules (endothel)Increased Vascular Permeability (Vascular Leakage)

REACTIONS OF LEUKOCYTES IN INFLAMMATION In the lumen: margination, rolling, and adhesion to endothelium. Migration across the endothelium and vessel wall.Migration in the tissues toward a chemotactic stimulus.

Recognition of Microbes and Dead Tissues

Removal of the Offending Agents TERMINATION OF THE ACUTE INFLAMMATORY RESPONSE Mediators of inflammation are produced in rapid bursts, only as long as the stimulus persists, short half-lives, and are degraded after their release

Neutrophils have short half-lives in tissues

Active termination:switch in the type of arachidonic acid metabolite produced, from pro-inflammatory leukotrienes to anti-inflammatory lipoxins liberation of anti-inflammatory cytokines (TGF- and IL-10) from macrophages neural impulses (cholinergic discharge) that inhibit the production of TNF in macrophages.Mediators of Inflammation Cell-derivedPlasma protein-derivedCell - derived

Arachidonic Acid (AA) Metabolites: Prostaglandins, Leukotrienes, and Lipoxins

Cytokines and Chemokines Cytokines : proteins produced by many cell types (lymphocytes, macrophages, endothelial, epithelial, and connective tissue cells) that modulate the functions of other cell types

Chemokines are a family of small (8 to 10 kD) proteins that act primarily as chemo-attractants for specific types of leukocytes

Plasma protein - derivedComplement system

Outcomes of Acute Inflammation

Morphologic Patterns of Acute Inflammation

SEROUS INFLAMMATION

FIBRINOUS INFLAMMATION

SUPPURATIVE OR PURULENT INFLAMMATION; ABSCESS

ULCERS

Summary of Acute Inflammation

Chronic Inflammation Chronic inflammation is inflammation of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist, in varying combinations Chronic inflammation arises in the following settings:Persistent infections Immune-mediated inflammatory diseases Prolonged exposure to potentially toxic agentsMORPHOLOGIC FEATURES chronic inflammation is characterized by: Infiltration with mononuclear cells, which include macrophages, lymphocytes, and plasma cells

Tissue destruction, induced by the persistent offending agent or by the inflammatory cells

Healing by connective tissue replacement of damaged tissue, accomplished by proliferation of small blood vessels (angiogenesis) and, in particular, fibrosis

A, Chronic inflammation in the lung, showing all three characteristic histologic features: (1) collection of chronic inflammatory cells (*), (2) destruction of parenchyma (normal alveoli are replaced by spaces lined by cuboidal epithelium, arrowheads), and (3) replacement by connective tissue (fibrosis, arrows). B, By contrast, in acute inflammation of the lung (acute bronchopneumonia), neutrophils fill the alveolar spaces and blood vessels are congested. ROLE OF MACROPHAGES IN CHRONIC INFLAMMATION

Other cells in chronic inflammationLymphcytesPlasma cellsMast cellsEosinophils

GRANULOMATOUS INFLAMMATIONGranulomatous inflammation is a distinctive pattern of chronic inflammatory reaction.

Granuloma is a focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelium-like cells, surrounded by a collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells Foreign body granulomas are incited by relatively inert foreign bodies

Immune granulomas are caused by a variety of agents that are capable of inducing a cell-mediated immune response

Systemic Effects of Inflammation Fever CRP >>ESR >>LeukocytosisOther manifestations of the acute-phase response:increased pulse and blood pressure; decreased sweatingmainly because of redirection of blood flow from cutaneous to deep vascular beds, to minimize heat loss through the skin

chills (search for warmth), anorexia, somnolence, and malaiseprobably because of the actions of cytokines on brain cells. THANK YOU