INFLAMATION

Inflammation is a protective response:

The purpose is:
1) To dilute, Localize and destroy the injurious agent.
2) To limit tissue injury and
3) To restore the tissue towards normality.
Inflammation may be harmful e.g: inflammation due to hypersensitivity reactions, autoimmune disease etc.
Types of Inflammation:
1 Acute inflammation 2 Chronic inflammation
ACUTE INFLAMMATION
It is the immediate and early response to an injurious agents and lasts for minutes, several hours or a'"few
days and its main characteristics are the exudation of fluid and plasma proteins (edema) and the emigration of
leukocytes. predominantly "heutrophils"(It is exudative lesion).

The major local manifestations of acute inflammation, compared to normal.

1.Vascular dilation and increased blood flow (causing Urythema and warmth).
(2) Extravasation and extravascular deposition of plasma fluid and proteins (edema).
(3) Leukocyte emigration and accumulation in the site of injury. (Ref. Robbin's 9* p-73 + Khaleque p-191
2. Endothelial cells 3. Mast cells 4. Eosinophils 3. Basophils 6. Monocyte or macrophage (No plasmaceu).
Causes/aetiology of acute inflammation: ) Infectious agents-NORN AL Occasional resident Bacteria:
Mycobacterium tuberculosis Streptococcus Pneumonia Borrelia Vincenti Neisseria Meningitidis 4 virus
INFLAMED GIncreased blood flow Arterole dilation a fungi M protozoa or helminthes Da microbial toxins
2/Immunologic injury: Hypersensitivity reaction (antigen-antibody, cell - mediated) eg-allergic. rhinitis, acule •
Neutrophil emigration () Leakage of plasma rheumatic fever etc. SBA: Mast cells ane widels distributed in both
acute and 2 chronie inflammation u sis, GENGSIS connective timsue. but not in granuloma.
3.Physical agents:burn, ionizing irradiation.
4. Chemical Agents:corrosives, Simple chemical poisons (acids), organic poisons (paraquat alkalies.
5) Foreign bodies like sutures, dirt, splinters.
6) Tissue necrosis: e.g-Infarct."SBA
Clinical or Cardinal signs of Acute Inflammation:
(Introduced by Celsus, a roman writer of first century.)
1.Rubor or redness
2) Calor or heat
1) Tumor or swelling
4) Dolor or pain
5) Loss of function (functio laesa)
Events or changes of acute inflammation:
Acute inflammation has three major components:
1.An Alterations in vascular caliber that lead to an increase in blood flow. (vascular changes)
2.Structural changes in the microvasculature that permits the plasma proteins and leukocytes to leave the
circulation.
3.Emigration of the leukocytes from the microcirculation and their accumulation in the focus of injury.
Vasoditation: Maint anterüole. (Most resistanteglin's 9'' p -731
JVascular Changes
A) Changes in vascular caliber and flow:
SBA
1. Transient Vasoconstriction: If is an inconstant finding and usually persists for few seconds"By the action of ~
Thromboxane A2.
V Leukotriene Ca, D4, Ba (CDE) 4
23 Vasodilatation:Vasodilation is induced by the action of several mediators, notably histamind, (on vascular
smooth muscle. It is one of the earliest manifestations of acute inflammation. Vasodilation first involves the
¡ancerist: and then leads to opening of new capillary beds in the area. FIRST EVENT VASODE LATATION" wuSS.
(3) Increased Arterial Blood Flow: Rapid and transitory increase of blood flow occurs leads to rubor (redness)
and calor (heat)
VI_SBA
DILATION- ARTERIOLES.
A) Slowing of blood flow or stasis: Stasis occurs due to
INCREASE PERMIABILITY- VENULES
At) Exudation of protein rich fluid
%) Microcirculation is packed with red blood cells
e) Increased viscosity of blood.
_
Thrombosis may sometimes supervene due to stasis.
SBA
- Last StEP
sMargination of Leucocytes. As stasis develops red cells are confined to a central axial column, displacing the
leucocytes toward the wall of the vessel, this is called leucocyte margination. Leucocytes then stick to the
endothelium transiently called rolling and then firmly called adhesion.
In mild injury, It takes 5 to 30 minuteS or these events, and with severe injury stasis may occur in a'hew
minutes."?
[Ref. Robbin's gt p-74 † Khaleque p-201
6. Lymphangitis
'B) Increased vascular permeability (vascular leakage):
Increased vascular permeability is a hallmark of acute inflammation. (USBA= MUsT _ SB A
Increased vascular permeability (vascular leakage) due to structural changes in microvasculature leads to a
marked outfow of protein-rich fluid and its accumulation into the extravascular tissue (fluid exudates) The net
increase of extravascular fluid results in oedema
SBA:NKC has perforin in its granules.
Mechanisms of Increased Vascular Permeability: H B S L".
1.Formation Of Endothelial Gaps In Post Capillary Venules: Most Commonest way-SBA
a.Endothelial cell contraction: leads to widened intercellular Junctions and intercellular gap. It is most
common, reversible, persists for 5 to 30 minutest S&otrs only in post capillary venules and caused by MUST
histamine, bradykinin. leukottiencs. sübstance EfThere oceúrs phosphorylation of contractile and
cytoskeletsl proteins such as myosin in endothelial cells leading to contraction of endothelial cells and
separation of intercellular junctions. post capillary venules. ShorF dúnation.
b.Endothelial cell retraction. It ocours due to cytoskeletal reorganization starts after 4 to 6 hours and persists
† 24 hours or more. Induced by LL-1, TNE, IN-
2.Direct endothelial injury: resulting in endothelial cell necrosis and detachment. This direct damage occurs
by necrotizing injurious stimulus eg. severe burn or lytic bacterial Infections. Immediate sustained respönse
occurs and there may be platelet adhesion and thrombosis. Long- durations
3.Delayed prolonged leakage: The leakage begins after 2 to 12 hours and lasts for several hours to days.
Venules and capillaries are involved due to:
Direct effect or injurious agent causing delayed cell damage, probably by apoptosis, or
Cytokines causing Endothelial retraction
Causes are mild to moderate thermal injury, X-ray, ultraviolet radiation and certain bacterial toxins.
Leucocyte- mediated endothelial injurif The injury is caused by toxic oxygen-species and proteolytic enzymes?
si Increased transcytosis: Increased transport of fluids and proteins, called transcytosis, through the
endothelial cell. This process may involve intracellular channels that may be stimulated by certain factors, such
as Yascular endothelial growth factor (VEGF), that promote vascular leakage.
% Leakage from new blood vessels it occurs during angiogenesis in early healing phases that follow
inflammation.
EXUDATION
Exudation is the leaking of blood constituents from blood vessels into interstitial tissue with formation of
exudates.
Fluid exudates are formed by the plasma constituents- fluid solute and proteins!
Mechanism of Formation of Fluid Exudates
Fluid exudates is formed due to
1) Increased vascular permeability,
2) Increased capillary hydrostatic pressure,
3) Breakdown of large molecule tissue protein and.
4) Increased fluidity of the tissue ground substance.
Pathogenesis of Inflammatory Oedema:
1.Vasodilation & Stasis.
2. Increase inter-endothelial space.
Effects of fluid Exudates
Beneficial Effects:
1. It dilutes the irritant and thus lowers injurious effect.
2. Helps to nourish the greatly increased number of cells.
3. It brings chemical mediators, natural immune products, antibodies, antimicrobial agents (eg. antibiotics)
and anti-enzymes which inhibit proteolytic enzymes.
4. Low ph due to lactic acid, formed by neutrophils inhibits bacterial growth.
5. If fibrin is produced, it acts as barrier against invasion of microorganisms, helps in surface phagocytosis,
and acts as\caffold in repair process,
6. Microorganisms and toxins are carried by the exudate to local lymph nodes where the antigens stimulate
immune response.
Harmful Effects:
1. Acts as a splendid medium for bacterial growth due to high protein content,
2. An excess fibrin may lead to adhesion.
3. Causes pain by chemical mediators like bradykinin and prostaglandins.
Difference between exudate and transudate

Features Exudate Transudate

Total protein count ~ High protein concentration (30 Less than 10 g/L
g/L to as plasma
Distribution of protein As in plasma Mostly albumin
Fibrinogen Present. It clots spontaneously Absent. No tendency to clot.
Specific gravity High (> 1.020) Low (> 1.012)
Cells Inflammatory cells and much tell Few present, nearly all are
debris mesothelial
Cause Increased vascular permeability Imbalance of hydrostatic pressure
along the vascular endothelium
Occurrence Inflammatory condition Non-inflammatory conditions.