Inflammation

Inflammation, Interally meaning burning, is the commonest of Pathogenic phenomena.

Defintion

Inflammation is defined as the local response of living mammalian tissues to Injury from any agent. -JA is a body defense reaction in order to eliminate or limit the spread of injurious agent, followed by stemoval of the necrosed cells and Resues.

Causes:

1. Infective agents like bacteria, viruses and there toxins fungi, parasites.
2. Tissue necrosis caused by various agents such as ischaemia physical agents (eg heat, cold, radiation and mechanical trauma)
3. Immunological agents the cell-mediated and antigen antibody reactions.
4. Inert materials such as fareign bodies, dirts etc.

* Inflammation involves a basic process with some overlapping viz early inflammation response and later followed by repair.

Signs of inflammation.

There are 4 cardinal signs of inflammation, which are as follows:

• Rubor (redness)  
• Tumor (Swelling)
• calor (heat) 
• dolor (pain)

fifth sign of inflammation is functio laesa (Loss of function).

Basic concepts

Injury

Response of body

• changes in blood vessels
• changes in cells (connective tissue)

– Response is usually protective, but sometimes it can be harmful.

Classification

Type of inflammation: CATARRHAL Inflammation

Sub types

Depending upon the defense capacity of the host and duration of response, inflammation can be classified as

• Acute Inflammation
• Chronic inflammation

Acute inflammation:

It is of short duration (lasting less than 2 weeks) and represents the early body reaction. This type of inflammation resolves quickly and is usually followed by healing.

Acute inflammation is usually for short duration including Neutrophils

main features of acute inflammation are:

• Accumulation of fluid and plasma at the affected sites. 
• Intravascular activation of platelets, and 
• Polymorphonuclear neutrophils as inflammatory cells.

Chronic inflammation

chronic inflammation – long duration including mono nuclear WBC (lymphocytes and monocytes)

It is of longer duration and occurs after a delay, either when the causitive agent of acute inflammation persists for a long time or the stimulus & such that Induces chronic inflammation from the beginning.

Characteristic features:

• Presence of chronic inflammatory cells such as lymphocytes, plasma cells and macrophagus.
• Granulation tissue formation.
• Specific situations as granulomatous inflammation.

Initiation of inflammation:

1. Recongnition system of receptors

• Receptor for recognition of microbes
• Receptors on leucocytes
• Receptors for recognition of necrotic cells

2. Circulating proteins.

Acute inflammatory response.

• Vascular events
• Cellular Events.

Vascular Events

Alteration in the microvasculature is the earliest supponse to the tissue injury. It includes

• Haemodynamic changes 
• Altered vascular permiability

Haemodynamic changes

The earliest features of inflammatory response result from changes in the vascular flow and calibre of small blood vessels in the injured tissue.

• Transient vasoconstriction of arterioles 
• Vasodilation
• Local hydrolytic pressure. 
• Slowing arstasis.

Vascular permeability→ Hemoconcentration→ Blood flow→ stasis

ALTERED VASCULAR PERMEABILITY

• Accumulation of oedema fluid in the interstitial compartment which comes from blood plasma by its escape through the endothelial wall of peripheral vascular bed.
• It is explained on the basis of starling’s hypothesis. 
• Fluid balance is maintained by two process

1. Forces that cause outward movement of fluid from microcirculation 
2. Forces that cause Inward movement of interstitial

fluid into circulation

Mechanism

• Endothelial cells constriction→ Immediate transient response→Thorn prict 
• Direct Endothelial cell injury→ Immediate sustained response→Sevene burn / sepicemia
• Endothelial cell refraction→ Delayed transient susponse→ Bacterial infections damage. 
• Endothelial damage→ Delayed prolonged leakage→ late sun burns

Cellular changes

• Intra vascular cellular changes 
• Extra vascular cellular changes.

Intra vascular cellular changes 

• Margination
• Rolling: peripherally marginated and pavemented neutrophils slowly roll over the endothelial cells lining the vessel walls.

Adhesion -Intersun Intexoction

{ICAN / VCAM ] Fism adhesion.

ICAM-Intracellular adhesion molecules

VCAM- Vasculea cellular adhesion molecules 

INTEGRINS made of subunits known as COII a12FA

Transmigration: 

After leucocyte endothelium adhesion neutrophils move along the endothelial surface till a suitable site between the endothelial cells is found where the neutrophils throw out cytoplasmic pseudopods. 

Extracellular changes.

• CHEMOTAXIS It is movement of leucocytes towards the disection of chemical molecules on factors called chamo attractants.
• Leukocyte activation Recognition of target call engulfment (pseudopode formation) opsonization → Bacteria becomes tastier→preferential eating Antibody formation
• Killing of bacteria The major function of phagocytes as Scavenger cells is killing and degradation of microbe to dispose of it.

Killing of bacteria→Lysosomal formation→O2 for killing

Intracellular mechanism

Reactive oxygen species

MPO-dependent MPO- Independent

Nitric oxide

Lysosomal granules

Extracellular mechanisms

Activated leucocytes, 

Neutrophil extracellular traps 

Immune mechanisms

Preormed chemical mediators

chemical mediators

Chronic inflammation

Chronic inflammation is defined as long lasting inflammatory response in which tissue destruction and Inflammation occurs at same time. 

• Chronic inflammation following acute inflammation 
• Recurrent attacks of acute sinflammation
• Chronic inflammation stasiting de novo.

Systemic features

1. fever
2. Anaemia 
3. Leucocytes
4. ESR
5. Amyloidosis

Types

Chronic non-specific inflammation: When the Irritant substance produces a non-specific chronic inflammatory reaction with formation of granulation tissue and tissue repair by fibrosis it is called as chronic non specific Inflammation. Example chronic osteomyelitis.

Chronic Granulomatous inflammation

In this the cliologic agent causes a characteristic

marphologic tissue response by formation of  granulomatous  eg. tuberculosis, leprosy and syphilis.

Marphology

• Epithelioid cells These are so called, because of their epithelial cell like apperance.
• Multinucleated giant cells: These are formed by fusion of adjacent epithelioid cells and may have 20 or more nuclei.
• Lymphoid cells – As a cell-mediated immune reaction to antigen. The host response by Lymphocytes is integral to composition of granuloma.
• Necrosis: Necrosis may be feature of some, e granulomatous conditions eg central cascation necrosis in tuberculosis 
• Fibrosis fibrosis is a feature of healing by proliferating fibroblasts at the periphery of granuloma.

Causes

Infectious causes: mycobacteria, bacteria, spiroctestes.

Non infectious causes

These include exogenous agents and immune causes.