Docs Network: September 2014

Inflammation

It is an immediate response to injury.

Types

Acute
Chronic

Events
Vascular events

Increased vessel caliber and permeability

Cellular events

Recruitment of different types of inflammatory cells

Chemical events

Production of different inflammatory mediators in the site of inflammation

Cardinal signs of inflammation

Redness Due to vasodilatation due to histamine
Heat
Swelling Due to increased vascular permeability in respone to different chemical mediators like histamine, prostaglandins etc.
Pain Due to bradykinin and p substance.
Loss of function

Hemodynamic changes

Initial transient vasoconstriction
Followed by massive vasodilation due to histamine, prostaglandins and bradykinin.

Increased vascular permeability due to

Vasoactive amines like histamine and serotonin
End product on kinin system like bradykinin
Cytokines like LTB4
Direct injury of the vascular endothelium
It increases the blood flow to the region and help in exudation as well as neutrophil migration.

Cellular event

The most important cellular event is the neutrophil migration.
It is the commonest cell in the acute inflammation.
It is also called as PMN.
It has different grannules that carry the mediators of inflammation

Azurophilic grannules-

that contains myeloperoxidase, phospholipase A2, lysozyme and acid hydrolase.

Secondary grannules-

that contain lysozyme, phospholipase A2, leucocyte alkaline phosphatase etc

Macrophage

It is after 48 to 72 hrs after the injury.
They are large cell derived from monocyte that has lifespan for 2 to 4 months.

They have

Elastase, acid hydrolases, and collagenases.
Produce different cytokines like interleukins and TNF, that mediate inflammation and promotes the healing.
They induce the production of different growth factors like FGF, EDGF, EGF and hence help in new tissue regeneration and repair.
They engulf the debris that is remaining after the tissue is dead.

Neutrophils migration and defence
Steps

Vasodilation and rolling
Marginalisation
Adhesion
Diapedesis
Chemotaxis
Phagocytosis and degranulation
Intracellular killing

Adhesion is due to the surface molecules on the endothelium and the neutrophils like selectin and integrin respectively.
These molecules are expressed due to other different chemicals like IL1, TNF etc.

Defect in adhesion occurs in

DM
Steroid therapy
Uremia
Alcohol intoxication
Leukocyte adhesion defect (autosomal recessive cond.)

Chemotaxis

It is the attraction of the inflammatory cells at the site of the tissue injury by the use of chemicals.

Types:

Bacteria products like N-formyl methionine
Inflammatory mediators like
LTB4- product of arachidonic acid
Complement proteins like C3a, C5a
Chemokines like IL1 produced by macrophages.

Leucocyte migration

Phagocytosis

It is the process of engulf the bacteria by neutrophils

How does neutrophil recognizes the bacteria? (opsonins)

Coated by antibody
Coated by complement C3b
Plasma proteins like collectins

The engulfed bacteria or product is called phagosome and when it combines with the lysosomes, it becomes phagolysosomes.

Intracellular killing

Types
Oxygen dependent-

Using superoxide radicals with the use of NADPH oxidase and producing superoxide and superchloride ions.

Oxygen independent killing

Using lysozyme, lactoferrin, acid hydrolases which make pore in the bacterial cell wall and then causing the lysis of the bacteria.
NADPH oxidase deficiency leads to the disease called as chronic granulomatous disease.

Chemical mediators of inflammation

Mediators of inflammation

Complement system

They are a group of proteins that are produced by the liver

They have different functions,

C3a, C5a- chemotaxis and anaphylotoxins
C3b- works as opsonin so it is target for phagocytosis and intra or extracellular killing
C5b-C9- they form membrane attack complex.

TNF and IL

They are produced by activated macrophages

They have the following function

Fever
Apoptosis
Decrease apetite and cachexia
Insomnia
Stimulate the production of the different growth factors like EDGF, FGF, TGF etc.
IL 8 is a chemoattractant.

Outcomes of inflammation

Complete resolution with regeneration
Complete recovery with scarring
Chronic inflammation
Abscess formation

Chronic inflammation
Causes

Acute inflammation
Persistent infections like TB
Autoimmune disease
Foreign body inside body
Malignancy

Key players in the chronic inflammation

Macrophage

Modified macrophage is called epithelioid cell.
Fused multiple macrophages makes giant cell.

Lymphocytes

Types, B cell and T cell.
B cell produce antibodies and T cells help B cells and also help cell mediated immunity.

Eosinophills and basophills

mainly in the allergic conditions and worm infestations.
Eosinophils has a protein in the cytoplasm called as major basic protein, that is toxic to the parasites.

Granulomatous inflammation

It is special type of inflammation in which the infecting organisms living or dead are surrounded by macrophages(epithelioid cell and giant cell) and lymphocytes Th1, as well as plasma cells.

Key mediators are

IFN gamma
TNF alfa
IL 2

All are produced by activated T cells and macrophages.
They convert the macrophages to epithelioid cells and giant cells.
Common example is TB. If someone is taking TNF inhibitor like in RA like Infliximab and Etarnacept , they should do PPD test, otherwise they reactivate the latent TB.

Histologic patterns/types of inflammation

Exudative inflammation