Inflammation Lecture PDF

LECTURE-1 PMED-DENT-PHARM Pathology Team By the end of this session students should be able to: Session’s Objectives ◦ Define, classify, and list the causes of inflammation. ◦ List cardinal signs of inflammation. ◦ Discuss in detail acute inflammation regarding definition, vascular changes, and cell...

LECTURE-1 PMED-DENT-PHARM Pathology Team By the end of this session students should be able to: Session’s Objectives ◦ Define, classify, and list the causes of inflammation. ◦ List cardinal signs of inflammation. ◦ Discuss in detail acute inflammation regarding definition, vascular changes, and cellular events up till rolling. ◦ Inflammation is a protective response of vascularized tissue to eliminate the cause of injury, necrotic cells & tissues resulting from the original insult. ◦ Acute Inflammation: Inflammation ◦ Rapid in onset & of short duration (a few minutes to few days). ◦ Characterized by a predominantly neutrophilic accumulation, fluid & plasma protein exudation. ◦ Chronic Inflammation: ◦ Longer duration (days to years) ◦ Characterized by influx of lymphocytes, plasma cells & macrophages with associated vascular proliferation & scarring. Acute vs Chronic Inflammation Signs of Inflammation Classic Cardinal Signs: ◦ 1.Calor (Warmth) ◦ 2.Rubor (Redness) ◦ 3.Tumor (Swelling) ◦ 4. Dolor (Pain) ◦ 5. Functio lease (Loss of function) Signs of Acute Inflammation Cardinal Signs ◦ 1.Calor (heat) ◦ 2.Rubor (red) ◦ 3.Tumor (swelling) ◦ 4. Dolor (Pain) ◦ 5. Functio lease (loss of function) Vascular Changes ◦ Hyperemia: As capillaries and venules dilate the blood flow to the injured area increases. Inflamed area appears red & hot because of hyperemia. ◦ As blood flow increases capillary Hydrostatic pressure rises, so fluid moves out of vessels into the tissues, leading to the swelling.i.e. Transudate formation. ◦ Increased permeability at postcapillary venules: This increases the outflow of fluid alongwith plasma proteins & WBCs from the capillaries into the tissues.This further increases the swelling. This fluid is Exudate. Fluid leads to pain in inflammation. ◦ Blood volume decreases and becomes viscous, with aggregation of RBCS. ◦ Infections: bacterial, viral, parasitic & fungal infections Causes of Inflammation ◦ Trauma physical(blunt & penetrating) & chemical agents, thermal injury (burns, frost bite), irradiation. ◦ Tissue necrosis due to any cause e.g. ischemia or trauma etc. ◦ Foreign bodies: splinter, dirt, sutures. ◦ Immune reactions or hypersensitivity reactions against environmental substances or self tissues. Also known as “immune-mediated inflammatory diseases” and have features of chronic inflammation. ◦ Rapid response to injury or microbes designed to deliver leukocytes & plasma proteins to the site of injury. WBCs clear the invaders & start digesting the necrotic tissue. Acute Inflammation ◦ Acute inflammation has two major components: 1.Vascular component 2. Cellular (leukocytes) component 1. Vascular component: Alteration in the vessel caliber i.e. vasodilatation leads to an increase in the blood flow to the inflamed area ◦ Acute Inflammation Increase in the vascular permeability leads to extravascular leakage of plasma proteins 2. Cellular component: Emigration of WBCS from the microcirculation & accumulation at the site of injury. The principal cell of acute inflammation is Neutrophil. Components of an Inflammatory Response ◦ Accumulation of fluid in the extra-vascular space is called edema. Inflammation: 1. Vascular Events ◦ In early phase of acute inflammation, arteriolar vasodilatation & increased volume of blood flow lead to a rise in the intravascular hydrostatic pressure. This causes movement of the fluid from the capillaries into the tissues. This fluid is called Transudate (an ultrafiltrate of blood plasma, with little proteins) ◦ Later increased vascular permeability leads to Exudate formation (plasma rich in proteins & cells) Protein loss from the blood decreases the osmotic pressure in the capillaries and increases the osmotic pressure in the interstitial tissues leading to an outflow of water & ions into the extravascular tissues. Inflammation: 1. Vascular Events ◦ Exudate: ◦ Fluid rich in proteins and cell debris ◦ High specific gravity ◦ Secondary to increased vascular permeability ◦ Transudate: ◦ Fluid with very little protein (mostly albumin) ◦ Low specific gravity. ◦ Secondary to increased hydrostatic pressure in vessels Process of Fluid Exudation ◦ Vasodilation ◦ Endothelial cell contraction typically most pronounced in post capillary VENULES. Vascular changes and fluid leakage during acute inflammation lead to Edema in a process called Exudation Transudate Result of increase in intravascular hydrostatic pressure. Ultrafiltrate of plasma Low protein content Specific gravity < 1.015 Exudate Result of inflammation Due to increased vascular permeability Increased interstitial osmotic pressure High protein content specific gravity >1.020 How does the permeability of small vessels increase during inflammation? ◦ 1. Formation of gaps between endothelial cells (Endothelial cell contraction): ◦ This leads to formation of widened intercellular junctions, or intercellular gaps. ◦ Mostly due to the effect of the chemical mediators (e.g. Histamine). How does the permeability of small vessels increase during inflammation? 2. Direct injury of endothelial cells: 3. Leukocyte-mediated endothelial injury: How does the permeability of small vessels increase during inflammation? 4. Increased transcytosis across the endothelial cytoplasm via vesicles and vacuoles: 5. Leakage from regenerating capillaries, during healing: RESPONSE OF LYMPHATICS in inflammation: Vascular Events ◦ Lymph flow is increased - drains edema fluid ◦ Secondary inflammation of the lymphatics lymphangitis & resulting inflammation in the draining lymph nodes -lymphadenitis. 2. Cellular Events A. Leukocyte recruitment B. Leukocyte activation Leukocyte Recruitment The sequence of events in the recruitment of leukocytes from the vascular lumen to the extravascular space consists of: 1. Margination, rolling along the vessel wall & weak adhesions to the endothelium. 2. Firm adhesions to the endothelium & Pavementing. 3. Transmigration between endothelial cells 4. Chemotaxsis i.e. Migration in interstitial tissue towards the chemotactic stimulus. Cellular Events 1. Margination & Rolling: Normal blood flow - central axial column. Cellular Events: Leukocyte Recruitment ◦ Margination: In stasis- leukocytes accumulate at the periphery of the vessels. ◦ Rolling: WBCs tumble down on the endothelial cells. ◦ Weak & transient adhesions: to vessel wall is by Selectins, which are receptors on the WBCs & endothelium. (L-selectin on leucocytes, E-selectin on endothelium) CELLULAR MIGRATION – free flowing. Leukocyte Direction of blood flow Vascular endothelium ROLLING- selectin adhesion. Selectins Leucocytes migrating to periphery of the lumen of blood vessel Summary