Acute Inflammation

Acute Inflammation

Outcome

Chronic Inflammation

Healing by Fibrosis and Scarring

Abcess formation

Complete restitution

Vascular Changes

Leakage

Mechanisms

Direct Injury

Cytoskeletal reorganization

Formation of endothelial gaps

Massive outflow of fluid

Increase in hydrostatic pressure due to increased blood flow

Loss of osmotic pressure by protein loss

Changes in Flow and Caliber

Stasis

Leukocytic margination

Peripheral orientation of leukocytes

Slowing of circulation

Incrased viscosity of blood due to concentration of red cells

Outporing of proteins into extravascular tissues

Increased permeability of microvasculature

Vasodialation

Increased blood flow

Causes

Redness

Swelling

Heat

Arterioles first, results in operning of new capillary beds

Cellular Events (B)

5.Release of Leukocyte products

Predominantly neutrophil products

Production of Arachidonic acid metab

Leukotrienes

Prostaglandins

O2 derived active metabolites

Lysosomal enzymes

Responsible for pain and tissue injury during inflammation

Amplify effects of initial inflammatory stimulus

Mediators of endothelial injury and tissue damage

4.Phagocytosis

Killing or Degredation

O2 independent mechanism

Lysozyme increases bacterial permeability

Activation of NADPH oxidase

Converted to HOCl (antimicrobial)

Largely O2 dependent mechanisms

Engulfment

Discharge of granule content into phagosome

Degranulation

Completely enclosed by extension of phagocyte cytoplasm

Triggered by binding of opsonized particle ro receptor

Recognition and attachment

Opsonins

C3b, opsonin fragment of complement protein C3

Fc Fragment of IgG

Most organisms unrecognised till coated by opsonins

Characteristic

Serves to remove source of injury and promote healing process

Characterized by exudation of fluid and predominance of neutrophils

3 major components

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

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

1) Alteration in vascular caliber leading to increased blood flow

Short duration

Few minutes to days

Cellular Events (A)

3.Leukocyte Activation

Chemotactc factors induce

Increased no. and avidity of leukocyte adhesion molecules

Activation of Oxidative Burst

Degranulation of lysosomal enzymes

Production of arachidonic acid metabolites

2.Chemotaxis

Migration determined by

Sequence of chemokine gradients

Attractant receptors the leukocyte expresses

Chemoatractants

Endogenous

Cytokines

Components of complement pathway

Exogenous

Bacterial products

Process by which leukocytes emigrate to cyte of injury

1.Adhesion and Transmigration

Transmigration

Eosinophils

Main type in hypersensitivity rxn

Lymphocytes

First to arrive in viral infxn

Neutrophils

predominate in most infections

Type of cell varies with age of inflammatory lesion

Mediated by leukocyte integrins & ligands on endothelial cells

Firm Adhesion

Activation of leukocytes, avidy of integrins to ligands increased

Rolling

Resulting from interaction between selectins and their ligands

Rapid and relatively loose adhesion

Endothelial activation

Inflmmatory mediators increase expression of selectins

Margination

Leukocyte accumulation along vessel periphery