Inflammation-1 "Opportunities are usually disguised by hard work, so most people dont recognize them." - Ann Landers DR EJAZ WARIS
Inflammation-2 INFLAMMATI0N Dr. SHAHILA JALEEL Histopathology SZH,Lahore Shashi-Mar 2000
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
Inflammation-28 Acute Inflammation - Mechanism 1.Alterations in vascular calibre leading to increased blood flow 2.Microvasculature structural changes 3.Leukocyte emigration DR EJAZ WARIS
Inflammation-29 Vascular changes A Inconstant transient vasoconstriction of arterioles for few seconds followed by vasodilation Accounts for warmth and redness Opens microvascular beds Increased intravascular pressure causes an early transudate (protein- poor filtrate of plasma) into interstitium (vascular permeability still not increased yet) DR EJAZ WARIS
Vascular permeability (leakiness) commences Transudate 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
Inflammation-31 Vascular changes continued B)increased vascular permeability vascular leakage leading to escape of protein rich fluid into the interstitium is the hall mark of acute inflammation exudate transudate edema pus DR EJAZ WARIS
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
Inflammation-37 How 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 DR EJAZ WARIS
Inflammation-39 Mechanism of Inflammation: DR EJAZ WARIS
Inflammation-41 Leukocyte emigration/extravasation Sequence of events in the journey of leukocytes from the lumen to the interstitial tissue Margination Pavementing Rolling Adhesion Transmigration/diapedesis DR EJAZ WARIS
Adhesion molecules Play an important role in acute inflammation 4 families Family no 1: Selectins E-selectin,P-selectin,L-selectin Family no 2:Ig-family adhesion proteins ICAM-I,ICAM-II,PECAM-I,VCAM-I
Adhesion moleculesFamily no 3:IntegrinsLFAMAC-1VLA-4Family 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
Inflammation-50 Neutrophil Margination DR EJAZ WARIS
Inflammation-51 Vascular changes DR EJAZ WARIS
Inflammation-52 Pneumonia - Exudation DR EJAZ WARIS
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