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"Opportunities are usually disguised by hard work, so most people don't recognize

them."

- Ann Landers

Shashi-Mar 2000

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INFLAMMATI0N

Dr. SHAHILA JALEELHistopathologySZH,Lahore

Introduction:

“Inflame” – to set fire. Inflammation is “dynamic

response of vascularised tissue to injury.”

Is a protective response. Serves to bring defense & healing

mechanisms to the site of injury.

INTROD……….

Injurious stimuli cause a protective vascular connective tissue reaction called “inflammation”• Dilute• Destroy• Isolate• Initiate repair

Acute and chronic forms

Lewis Triple Response:

Flush: capillary dilatation. Flare: arteriolar dilatation. Weal: exudation, edema.

Gastric Ulcer:

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Laryngitis:

Acute Enteritis:

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Pneumonia

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Cardinal Signs of Inflammation

Rubor : Redness – Hyperaemia. Calor : Warm – Hyperaemia. Dolor : Pain – Nerve, Chemical

med. Tumor: Swelling – Exudation Loss of Function:

Heat Redness Swelling Pain Loss Of Func.

The 5 Cardinal Signs of

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Inflammation

Two main components:vascular reactioncellular reaction

Two main types: acute chronic

Chemical mediators

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Cells of inflammation

Circulating cells

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Connective tissue matrix

Made up of :

A)collagen fibers B)elastic fibers C)glycoproteins D)proteoglycans

Connective tissue cells

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Acute Inflammation - Mechanism

1.Alterations in vascular calibre leading to increased blood flow

2.Microvasculature structural changes

3.Leukocyte emigration

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Vascular changes

A Inconstant transient vasoconstriction of arterioles for few seconds followed by vasodilationAccounts for warmth and rednessOpens microvascular beds

Increased intravascular pressure causes an early transudate (protein-poor filtrate of plasma) into interstitium (vascular permeability still not increased yet)

Vascular permeability (leakiness) commencesTransudate gives way to exudate

(protein-rich)Increases interstitial osmotic pressure

contributing to edema (water and ions) slowing of circulation (increased

permeability of the vasculature) stasis Leukocyte migration

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Vascular changes continued

B)increased vascular permeabilityvascular leakage leading to escape of protein rich fluid into the interstitium is the hall mark of acute inflammation

exudatetransudateedemapus

An exudate is an extravascular fluid that has a

high protein concentration cellular debris high specific gravity. Its presence implies an increase in the normal

permeability of small blood vessels in an area of injury .

A transudate is a fluid with low protein content (most of which is albumin) little or no cellular material low specific gravity It is essentially an ultrafiltrate of blood plasma that

results from osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability

Edema denotes an excess of fluid in the interstitial tissue or serous cavities; it can be either an exudate or a transudate.

Pus, a purulent exudate, is an inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead cells and, in many cases, microbes.

IMMEDIATE TRANSIENT RESPONSE – RESPONSE TO

MINOR INJURY

IMMEDIATE SUSTAINED RESPONSE – RESPONSE

TO

MORE SERIOUS INJURY, CONTINUES FOR SEVERAL

DAYS, DAMAGE TO VESSELS

DELAYED RESPONSE – INCREASES IN CAPILLARY

PERMEABILITY, DELAYED 4-24 HR, RADIATION

INJURIES, SUNBURN

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Inflammation-37How does endothelium becomes leaky in inflammation?

1)formation of endothelial gaps in venules

2)cytoskeletal reorganization 3)increased transcytosis 4)direct endothelial injury 5)leukocyte dependent injury 6)delayed prolonged leakage 7)leakage from new blood vessels

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Mechanism of Inflammation:

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Leukocyte emigration/extravasation

Sequence of events in the journey of leukocytes from the lumen to the interstitial tissue

Margination Pavementing Rolling Adhesion Transmigration/diapedesis

Adhesion molecules

Play an important role in acute inflammation

4 families Family no 1: Selectins

E-selectin,P-selectin,L-selectinFamily no 2:Ig-family adhesion proteins

ICAM-I,ICAM-II,PECAM-I,VCAM-I

Adhesion molecules

Family no 3:IntegrinsLFAMAC-1VLA-4

Family no 4:Mucin like glycoproteinsCD-34Glycam-1

Margination and Rolling

Early rolling adhesion mediated by selectin family:• E-selectin (endothelium), P-selectin

(platelets, endothelium), L-selectin (leukocytes) bind other surface molecules (i.e.,CD34, Sialyl-Lewis X-modified GP) that are upregulated on endothelium by cytokines (TNF, IL-1) at injury sites

Adhesion

Rolling comes to a stop and adhesion results

Other sets of adhesion molecules participate:• Endothelial: ICAM-1, VCAM-1 • Leukocyte: LFA-1, Mac-1, VLA-4(ICAM-1 binds LFA-1/Mac-1, VCAM-1 binds VLA-4)

Ordinarily down-regulated or in an inactive conformation, but inflammation alters this

Transmigration (diapedesis)

Occurs after firm adhesion within the systemic venules and pulmonary capillaries via PECAM –1 (CD31)

Must then cross basement membrane• Collagenases• Integrins

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Neutrophil Margination

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Vascular changes

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Pneumonia - Exudation

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