Acute Inflammation

1.Adhesion and Transmigration

Margination

Leukocyte accumulation along vessel periphery

Endothelial activation

Inflmmatory mediators increase expression of selectins

Rolling

Rapid and relatively loose adhesion

Resulting from interaction between selectins and their ligands

Firm Adhesion

Activation of leukocytes, avidy of integrins to ligands increased

Transmigration

Mediated by leukocyte integrins & ligands on endothelial cells

Type of cell varies with age of inflammatory lesion

Neutrophils

predominate in most infections

Lymphocytes

First to arrive in viral infxn

Eosinophils

Main type in hypersensitivity rxn

2.Chemotaxis

Process by which leukocytes emigrate to cyte of injury

Chemoatractants

Exogenous

Bacterial products

Endogenous

Components of complement pathway

Cytokines

Migration determined by

Attractant receptors the leukocyte expresses

Sequence of chemokine gradients

3.Leukocyte Activation

Chemotactc factors induce

Production of arachidonic acid metabolites

Degranulation of lysosomal enzymes

Activation of Oxidative Burst

Increased no. and avidity of leukocyte adhesion molecules

Short duration

Few minutes to days

3 major components

1) Alteration in vascular caliber leading to increased blood flow

2) Changes in microvasculature permit plasma proteins and leukocytes to leave circulation

3) Emigration of leukocytes from circulation and accumulation in focus of injury

Characterized by exudation of fluid and predominance of neutrophils

Serves to remove source of injury and promote healing process

4.Phagocytosis

Recognition and attachment

Most organisms unrecognised till coated by opsonins

Opsonins

Fc Fragment of IgG

C3b, opsonin fragment of complement protein C3

Engulfment

Triggered by binding of opsonized particle ro receptor

Completely enclosed by extension of phagocyte cytoplasm

Discharge of granule content into phagosome

Degranulation

Killing or Degredation

Largely O2 dependent mechanisms

Activation of NADPH oxidase

Converted to HOCl (antimicrobial)

O2 independent mechanism

Lysozyme increases bacterial permeability

5.Release of Leukocyte products

Mediators of endothelial injury and tissue damage

Amplify effects of initial inflammatory stimulus

Responsible for pain and tissue injury during inflammation

Predominantly neutrophil products

Lysosomal enzymes

O2 derived active metabolites

Production of Arachidonic acid metab

Prostaglandins

Leukotrienes

Changes in Flow and Caliber

Vasodialation

Arterioles first, results in operning of new capillary beds

Increased blood flow

Causes

Heat

Swelling

Redness

Slowing of circulation

Increased permeability of microvasculature

Outporing of proteins into extravascular tissues

Incrased viscosity of blood due to concentration of red cells

Stasis

Peripheral orientation of leukocytes

Leukocytic margination

Leakage

Massive outflow of fluid

Loss of osmotic pressure by protein loss

Increase in hydrostatic pressure due to increased blood flow

Mechanisms

Formation of endothelial gaps

Cytoskeletal reorganization

Direct Injury

Complete restitution

Abcess formation

Healing by Fibrosis and Scarring

Chronic Inflammation