Lecture 7: Inflammation - Introduction to Acute Inflammation (Batterjee Medical College) PDF

Lecture 7 Inflammation: Introduction Acute Inflammation Year/Level: D2 / Semester 1 Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students will be able to 1. Define inflammation 2. Discu...

Lecture 7 Inflammation: Introduction Acute Inflammation Year/Level: D2 / Semester 1 Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students will be able to 1. Define inflammation 2. Discuss the events and components of acute inflammatory response 2  What is Inflammation? outcome itis=Inflammation Appendicitis=inflam mation of appendix Arthritis=Inflammati on of joints Inflammation: Overview “Fundamentally, inflammation is a protective response” outcome The major goals of inflammation are: To get rid of the initial cause of cell injury (e.g., microbes, toxins…etc). To get rid of the consequences of cell injury (e.g., necrotic cells and tissues). To Initiate the process of repair. What will happen if the inflammation did not take place? Infections could not be restrained. Wounds would never heal. Injured tissue would remain permanent festering (suppurative/ pus forming) sores.  Cardinal Signs of Inflammation Latin word English Major causes and mediators outcome 1) Calor Heat. 1. Due to vasodilation, which results in increased blood flow. 2) Rubor Redness. Histamine, Prostaglandins, and Bradykinin. 3) Tumor Swelling/ 1. Due to accumulation of fluid. Edema. 2. Histamine, Tissue damage, 4) Dolor Pain. 1. Due to release of chemicals that stimulate nerve endings. 2. Bradykinin and PGE2 5) Functio Loss of Increased pain/swelling The first four were described by Celsus; the fifth was a later addition by Virchow in Laesa. function. the nineteenth century..  Causes and Types of Inflammation Infections– Bacterial, Viral, Fungal, Parasitic. Tissue Necrosis– Ischemia, Physical & Chemical Injury, Trauma. Foreign Bodies – Sutures, Splinters, Dirts. Immune Reactions – Hypersensitivity Reaction, Autoimmune Diseases Types: ❖ Acute inflammation ❖ Chronic inflammation - Granulomatous inflammation  The Steps of Inflammatory Response Recognition of the offending agent by host cells and molecules Recruitment of leukocytes and plasma proteins to the site where the offending agent is located Removal of the offending agent: Activated leucocytes and proteins eliminate the offending substance Regulation (control) of the reaction: Termination of response Repair (Resolution): The damaged tissue is repaired.c  Acute Inflammation Acute inflammation has 4 major events and components 1) Vascular Changes: Vasodilation (Increases blood flow) 2) Microvascular Changes: (Increased Vascular Permeability). Plasma proteins & WBC leakage 3) Cellular Events: Emigration, accumulation & activation of WBCs at the site of Injury (cellular recruitment and activation). 4) Chemical Mediators: Derived from plasma proteins and cells. me Recognition of Microbes, Necrotic Cells and Foreign Substances Danger signals are elicited by microbes and outcome dead cells Phagocytes, dendritic cells, epithelial cells express “pattern recognition receptors” that sense the presence of infectious agents Examples: Toll like receptors(TLR) Inflammasome Fc receptors Complement system: Lectin I. Vascular Changes: Alteration in Vascular Flow and Caliber Earliest manifestation is Vasodilation. Vasodilation: First occurs in arterioles Induced by histamine and nitric oxide (acts on vascular smooth muscle) Increased blood flow → redness (rubor sign) Heat(color sign) Increased Hydrostatic Pressure II.Microvascular Changes: Increased permeability of microvasculature A hallmark of acute inflammation. Induced by histamine, kinins, and other mediators Produce gaps between endothelial cells(Increased permeability) Allows plasma proteins and leukocytes to escape vessels and enter sites of infection or tissue damage Fluid leak through blood vessels results in Edema. (Tumor sign or swelling)  What is Edema? oDefinition: Edema means accumulation of excess amount of fluid in interstitial tissue or in serous cavities. Types of edema fluid: Transudate and Exudate. Differences between transudate and exudate  III.Cellular Events: WBC Extravasation and Phagocytosis. A critical function of inflammation is the delivery of leukocytes from the lumen of vessel to the site of injury/interstitium: Extravasation Steps in Extravasation 1: Margination of leukocytes in the lumen. 2: Rolling of leukocytes in the lumen. 3: Adhesion of leukocytes in the lumen. 4: Transmigration across the endothelium (also called diapedesis). 5: Chemotaxis: Migration in interstitial tissues along a chemical gradient outcome  Cellular events: WBC extravasation Step 1: Margination Normal state: Axial blood flow - Central stream: RBC, WBC. - Peripheral cell- free layer: Plasma During Margination. - Due to stasis, central stream of cells widens. - Plasma zone becomes narrower due to plasma loss. The process of leukocyte accumulation at the periphery of vessels is called margination.  Steps in WBC Extravasation Ut 2. Rolling 3. Adhesion 4. Transmigration come by proteins called Firm adhesion of WBCs to Mediated Migration of the leukocytes Selectins endothelial cells by integrins through the endothelium before transmigration E-selectin on endothelial Mediated by members of Ig Mediated by PECAM-1 cells. superfamily of endothelial (CD31), also of Ig P-selectin on endothelial cells (Ligands ICAM-1 and superfamily. cells and platelets. VCAM-1) L-selectin on most leukocytes Selectins bind Sialyl Lewis X Interact with leukocyte on Leukocytes. integrins (VLA-4, LFA-1).  Cellular events: WBC extravasation Rolling Adhesion Transmigration Rolling Adhesion  Step 5: Chemotaxis and WBC Activation Transmigrated leukocytes move to the site of injury along chemical gradients of chemotactic agents. Chemotactic agent can be exogenous or endogenous; Examples: Soluble bacterial products, components of the complement system (C5a), Leukotrienes (B4), Cytokines (IL-8) Note/ type of leukocytes emigrating depends on type of stimulus and age of inflammatory response. Example: ▪ Neutrophils in the first 6-24hrs. ▪ Macrophages replace neutrophils in 24-48hrs. ▪ Lymphocytes in viral infections. ▪ Eosinophils in allergies.  Leukocyte Activation Activated by Microbes, Necrotic cells, Ag-Ab complexes, Chemotactic factors, Cytokines. Activation leads to: - Production of Arachidonic acid metabolites. - Secretion of Lysosomal enzymes. - Degranulation. - Secretion of cytokines. - Modulation of cell adhesion molecules (CAM)  Phagocytosis ‘’Process of engulfment of solid particulate material Example: Bacteria, necrotic tissue or foreign material by phagocytic cells ‘’ Type of phagocytic cells: Neutrophils, Macrophages Three steps in phagocytosis 1) Recognition and attachment. 2) Engulfment 3) Killing or degradation  Phagocytosis (1) Recognition and Attachment Enhanced by coating of microorganism with opsonins: Opsonins: 1) Fc fragment of IgG. 2) C3b – opsonic fragment of C3. 3) Carbohydrate-binding proteins (lectins) (2) Engulfment: Phagocyte membrane zips up around microbe Plasma membrane pinches off to form a vesicle (phagosome) Fusion of phagosome with lysosome (Phagolysosome)  (3)Killing and degradation Oxygen – Dependent Killing: NADPH oxidase multiprotein enzyme complex. H2O2 – MPO - halide system. Oxygen – Independent Killing: Bacterial permeability increasing protein. Lysozyme. Lactoferrin. Major basic protein. Defensins. Degradation: Acid Hydrolase.  References 1. Robbins and Cotran Pathologic Basis of Disease; 10th ed. 2021 2. HarshMohan Textbook of Pathology. 7th edition. 26