ADITHIYAN UDAYASANKAR

INTRODUCTION DEFINITION CAUSES TYPES VASCULAR EVENTS REFERNCE CONCLUSION

Inflammation is fundamentally a protective response designed to get rid the organism of both the initial cause of cell injury(microbes) and the consequences of such injury(necrotic cell & tissues)

Inflammation is a complex reaction elicited in the vascularised connective tissues of body by various exogenous or endogenous stimuli that cause cell injury. It is a protective response that tend to isolate , eliminate, dilute causative factor as well as necrotic tissue that result from original damage.

HYPOXIA PHYSICAL CAUSES POISONS IMMUNE MEDIATED NUTRITIONAL IMBALANCE TISSUE NECROSIS INFECTIONS

Depending on severity of stimulus & effectiveness of initial response to neutralize the agent . It is classified into

ACUTE

•Short duration -several mins, to hrs, to days•Chacterized by edema

CHRONIC

• Prolonged duration –several days, to months, to years

• Characterized by infiltration of lymphocytes, macrophages

ACUTE INFLAMMATION is defined as immediate or early response to an injurious stimulus , the critical function of which is to deliver leukocytes, plasma proteins, antibodies to the site of injury.

The events in acute inflammation can be divided into

1) Vascular events 2) Cellular events

Certain vascular changes take place during inflammation .These are

Alteration in vascular caliber to increase blood flow

Alteration in vascular permeability with emigration of fluid & plasma proteins

Emigration of leukocytes (neutrophils)

The above vascular features are responsible for 5 cardinal signs of inflammation

RUBOR-REDNESS CALOR-HEAT TUMOR-SWELLING DOLOR-PAIN LOSS OF FUNCTIONS Redness &heat are due to increased blood flow Swelling is due to edema Loss of function is due to tissue damage

ALTERATION IN VASCULAR CALIBER & BLOOD FLOW:

As the injurious stimulus strikes there is immediate TRANSIENT vasoconstriction which lasts for few seconds.

It is followed by vasodilation Which involves arterioles followed by

opening of capillary beds which was carrying low blood flow ,so there is increased blood flow.

Increased blood flow is the cause of heat and redness (erythema). Vasodilation is induced by the action of histamine & nitric oxide (NO).

Vasodilation is quickly followed by slowing of circulation which is due to increased vascular permeability with the outpouring of protein rich fluid into extravascular tissues.

This increases the viscosity of blood and cause stasis.

STASIS: Dilation of blood vessels packed with slow moving rbc’s(red blood cells).

As stasis develops, the laminar blood flow is interrupted so the leukocytes principally neutrophils tend to fall out from centre to the periphery close to endothelial cell,this is known as MARGINATION.

As there is increased blood flow due to vasodilation, there is increased hydrostatic pressure with outpouring of fluid into extravascular space. This fluid is known as transudate.

Normally, the hydrostatic pressure at arteriolar end is 32mm hg while at venous end is 12mm hg. The COP of tissues is 25mm hg which is almost equal to mean capillary pressure. Hence the outflow is negligible.

In inflammation due to vasodilation & due to increased hydrostatic pressure causes transduateformation.

Transudate-ultra filtration of plasma due to increased hydrostatic pressure or decreased COP without alteration in vascular permeability.

Transduate contains 1. Low protein content 2. Low fibrinogen 3. Low specific gravity4. Low cell count Transduate is soon followed by increased

vascular permeability with outpouring of protein rich fluid into interstitium. This fluid is exduate.

A hallmark of acute inflammation is increased vascular permeability leading to escape of protein rich exudate causing edema .

Exudate –inflammatory extravascular fluid formed due to increased vasc. Permeability

Exudate contains 1. High protein content 2. High specific gravity 3. High cell count

Transudate• increased hydrostatic pressure I. congestive heart failureII. venous outflow obstruction • decreased colloidal osmotic pressure i. liver cirrhosis ii. nephrotic syndrome iii. protein losing enteropathy. Exudate – purulent (pus formation)

Several mechanisms are responsible for increased vascular permeability .

Endothelial cell contraction: occurs immediately in response to mediators like serotonin, bradykinin, substance P, histamine .

The endothelial cells contract widening the inter endothelial junction causing increased permeability

It is called immediate transient response. Short lived (15-30 mins) & reversible It Is mainly seen in post capillary venules.

It occurs in response to cytokines like IL-1 , TNF alpha .

They cause structural re-organisation of endothelial cytoskeleton disrupting the inter endothelial junction.

Begins in 2-4 hrs &lasts for 24 hrs. Arterioles, capillaries, venules can be

effected.

It may occur with severe injury causing endothelial cell necrosis & detachment.

For example burns , lytic bacterial infection . The leakage begins immediately & sustained

at high level until vessel is thrombosed or repaired. This is known as immediate sustained response.

Leakage begins in 2-12 hrs &persist for several hours.

As stasis occurs, leucocytes tend to fall towards endothelial cells . These leukocytes are activated &they produce reactive oxygen species(ROS)& PROTEOLYTIC ENZYME that can damage endothelial cells.

For example, pulmonary & glomerularcapillaries.

Inflammation associated with process of healing & repair in which there is vascular proliferation in response to mediators like VEGF .

The newly formed vascular sprout have a leaky endothelial junction .

The fluid can pass through endothelial cells in form of tiny vesicles.