Acute Inflammation 2023-2024 Lecture Notes PDF

ACUTE INFLAMMATION -1 Prof. Dr. Hadi Al-mousawi Histopathologist F. I. C. M. Path. Session 3 L1 2023-2024 References Robbins basic pathology. Muir's Textbook of pathology. Objectives Major causes and biological purposes of acute...

ACUTE INFLAMMATION -1 Prof. Dr. Hadi Al-mousawi Histopathologist F. I. C. M. Path. Session 3 L1 2023-2024 References Robbins basic pathology. Muir's Textbook of pathology. Objectives Major causes and biological purposes of acute inflammation. Characteristic macroscopic features of acute inflammation. Characteristic microscopic features - Oedema. -Vasodilatation. -Neutrophil margination and migration. How the microscopic changes relate to the macroscopic ones.  Acute inflammation Definition: The local response of living tissues to injury due to any agent. So it is body defense reaction in order to : eliminate or limit the spread of injurious agents as well as to remove the consequent necrosed cells and tissues. Innate, immediate and early. Short duration –minutes/hours/few days  Acute Inflammation Major characteristics of acute inflammation 1. Vascular reaction Accumulation of fluid exudate and neutrophils in tissues 2.Controlled by a variety of chemical mediators derived from plasma or cells 3.Protective, but can lead to local complications and systemic effects 4. usually followed by repair. Objectives Major causes and biological purposes of acute inflammation. Characteristic macroscopic features of acute inflammation. Characteristic microscopic features - Oedema. -Vasodilatation. -Neutrophil margination and migration. How the microscopic changes relate to the macroscopic ones.  Causes of acute inflammation Microbial Infections (bacterial, viral, fungal, parasitic) are among the most common and medically important causes of inflammation. eg. pyogenic organisms Hypersensitivity reactions (acute phase) against environmental substances or against “self” tissues. Physical &Chemicals agents: (e.g., thermal injury, such as burns or frostbite; irradiation; toxicity from certain environmental chemicals) injure host cells and elicit inflammatory reaction. Tissue necrosis. including ischemia (as in a myocardial infarct) and physical and chemical injury Objectives Major causes and biological purposes of acute inflammation. Characteristic macroscopic features of acute inflammation. Characteristic microscopic features - Oedema. -Vasodilatation. -Neutrophil margination and migration. How the microscopic changes relate to the macroscopic ones.  Clinical features of acute inflammation Main clinical signs: –RUBOR = redness –TUMOR = swelling –CALOR = heat –DOLOR = pain & loss of function Objectives Major causes and biological purposes of acute inflammation. Characteristic macroscopic features of acute inflammation. Characteristic microscopic features - Oedema. -Vasodilatation. -Neutrophil margination and migration. How the microscopic changes relate to the macroscopic ones.  Acute inflammation has two major components: Vascular changes. Cellular events.  Vascular Changes 1. Transient vasoconstriction of arterioles (few sec.). 2. Vasodilatation of arterioles and then capillaries ---> increase in blood flow(heat and redness). 3. Increased permeability of blood vessels ---> exudation of protein -rich fluid into tissues ---> slowing of circulation. 4. Concentration of RBCs in small vessels and increased viscosity of blood = STASIS  Increased Vascular Permeability Increasing vascular permeability--------> movement protein-rich fluid and even blood cells into the extravascular tissues--->increases the osmotic pressure of the interstitial fluid ------- > leading to more outflow of water from the blood into the tissues. Fluid loss from vessels -Starling‟s Law Fluid flow across vessel walls is determined by the balance of hydrostatic pressure within the vessel and the difference in colloid osmotic pressure (protein content) between the plasma and interstitial fluid:- –Increase hydrostatic pressure ---> increase fluid flow out of vessel –Increase colloid osmotic pressure of interstitium ---> increase pulls fluid into vessel and/or prevents fluid from leaving  Fluid exudation Acute inflammation - –arteriolar dilatation leads to increase in hydrostatic pressure –increased permeability of vessel walls leads to loss of protein into interstitium Net flow of fluid out of vessels  Exudate vs Transudate Fluid loss in inflammation is an EXUDATE = high protein content, specific gravity above 1.02. Fluid loss due to hydrostatic pressure imbalance only (eg. venous outflow obstruction) is a TRANSUDATE = low protein content, specific gravity less than 1.012  Oedema Oedema = excess of fluid in interstitium, can be transudate or exudate (Oedema leads to increased lymphatic drainage) Pus = a purulent exudate, rich in neutrophils and cell debris  In inflammation, lymph flow is increased and helps drain edema fluid, leukocytes, and cell debris from the extravascular space. In severe inflammatory reactions, especially to microbes, the lymphatics may transport the offending agent, contributing to its dissemination.  Mechanisms lead increased vascular permeability in acute inflammatory reactions Endothelial cell contraction leading to intercellular gaps in postcapillary venules. is the most common cause of increased vascular permeability. Endothelial injury. vascular leakage occur due to endothelial cell necrosis and detachment. Endothelial cells are damaged in Sever burns. Infections as a consequence of leukocyte accumulation along the vessel wall.  Mechanisms lead increased vascular permeability in acute inflammatory reactions Increased transcytosis of proteins. occurs through channels formed by fusion of intracellular vesicles Leakage from new blood vessels. tissue repair involves new blood vessel formation (angiogenesis). These vessel sprouts remain leaky until proliferating endothelial cells mature sufficiently to form intercellular junctions.  Cellular Events LEUKOCYTES RECRRUTEMNT TO SITE OF INJURY. 1.Stasis causes neutrophils to line up at the edge of blood vessels along the endothelium = MARGINATION. 2.Neutrophils then roll along endothelium, sticking to it intermittently = ROLLING. 3.Then stick more avidly = ADHESION. 4.Followed by EMIGRATION of neutrophils through blood vessel wall. 5. MIGARTION in interstitial tissues toward a chemotactic stimulus.  Margination and Rolling. The smaller red cells tend to move faster than the larger white cells, leukocytes are pushed out of the central axial column and thus have a better opportunity to interact with lining endothelial cells, especially as stasis sets in.=== margination.  If the endothelial cells are activated by cytokines and other mediators produced locally, they express adhesion molecules to which the leukocytes attach loosely. These cells bind and detach and thus begin to tumble on the endothelial surface =====rolling.  The weak and transient interactions involved in rolling are mediated by the selectin family of adhesion molecules. The three members of this family are E- selectin , expressed on endothelial cells; P- selectin , present on platelets and endothelium; and L-selectin , on the surface of most leukocytes. Adhesion. The rolling leukocytes are able to sense changes in the endothelium that initiate the next step in the reaction of leukocytes, which is firm adhesion to endothelial surfaces. This adhesion is mediated by integrins expressed on leukocyte cell surfaces interacting with their ligands on endothelial cells  Emigration (Transmigration). leukocytes migrate through the vessel wall primarily by squeezing between cells at intercellular junctions. This extravasation of leukocytes, called diapedesis. occurs mainly in the venules of the systemic vasculature. migration (Chemotaxis) & phagocytosis After extravasating from the blood, leukocytes move toward sites of infection or injury along a chemical gradient. Both exogenous and endogenous substances can be chemotactic for leukocytes, including the followings : 1. Bacterial products. 2. Cytokines. 3. Components of the complement system. 4. Products of the lipoxygenase pathway of arachidonic acid (AA) metabolism  Neutrophils phagocytose microorganisms Activated neutrophils may release toxic metabolites and enzymes causing damage to the host tissue Neutrophil margination …. And emigration Migration Objectives Major causes and biological purposes of acute inflammation. Characteristic macroscopic features of acute inflammation. Characteristic microscopic features - Oedema. -Vasodilatation. -Neutrophil margination and migration. How the microscopic changes relate to the macroscopic ones. How do these changes combat injury? 1.Exudation of fluid Delivers plasma proteins to area of injury immunoglobulins inflammatory mediators fibrinogen Dilutes toxins Increases lymphatic drainage Delivers micro-organisms to phagocytes and antigens to immune system How do these changes combat injury? 2.Infiltration of Cells Removes pathogenic organisms, necrotic debris 3. Vasodilatation Increases delivery, increases temperature 4. Pain and loss of function Enforces rest, reduces chance of further traumatic damage.