D2 Lecture 8 Acute Inflammation PDF

D2 Lecture 8 Acute Inflammation; Chemical mediators Morphological patterns of inflammation Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students must be be able to 1. Enumerate the ce...

D2 Lecture 8 Acute Inflammation; Chemical mediators Morphological patterns of inflammation Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students must be be able to 1. Enumerate the cell derived and plasma derived chemical mediators of inflammation 2. Discuss about cytokines and their role in inflammation 3. Discuss the sources, and roles of various chemical mediators 4. Describe the various morphological patterns of inflammation 2  Components & Events of Acute Inflammation Acute inflammation has 4 major components: 1) Vascular Changes: Alteration in Vascular caliber with increased blood flow thus called Vasodilation. 2) Microvascular Changes: Alteration in permeability of microvasculature. Plasma proteins & WBC leakage (Increased Vascular Permeability). 3) Cellular Events: Emigration, accumulation & activation of WBCs in the site of Injury (cellular recruitment and activation). 4) Mediators, derived from plasma proteins and cells.  Mediators of inflammation Inflammatory mediators are chemical substances that trigger certain processes in an inflammatory reaction. Mediators are differentiated according to their origin: (A) Cell-derived mediators. (B) Plasma-derived mediators.  Principles of Mediators Initially bind to specific receptors and act. Stimulate the release of other mediators Can act on one or few target cell types. Once activated these are short lived. Potentially harmful.  Active Mediators Active Mediators are produced and released in response to various Injurious stimuli such as: Microbial products. Substances released from necrotic cells. Proteins of the complement, kinin, and coagulation systems which activated by microbes and damaged tissues. - Ensures that inflammation is normally triggered only when and where it is needed.  Roles of Mediators Multifunctional Effects on: ▪ The blood vessels. ▪ Inflammatory cells ▪ Other cells in the body  EFFECTS OF MEDIATORS Effects of mediators 1. Vasodilation. 2. Vasoconstriction. 3. Altered vascular permeability. 4. Activation of inflammatory cells. 5. Chemotaxis. 6. Cytotoxicity. 7. Degradation of tissue. 8. Pain. 9. Fever.  (A) Cell -derived mediators ▪ May be pre-formed and stored in granules of platelets and leukocytes (histamine)…or… ▪ May be synthesized as needed.  (A) Cell-derived mediators 1. Vasoactive amines (Histamine). 2. Arachidonic Acid derivatives (Prostaglandins & Leukotrienes). 3. Platelet-Activating Factor. 4. Cytokines. 5. Nitric Oxide. (A) Cell-Derived Mediators of Inflammation: 1. Vasoactive amines (Histamine) The most notable example is Histamine. Source: mast cells, basophils & platelets. Effects: (1) vasodilatation (2) venular permeability increase (3) Endothelial activation. (A) Cell-Derived Mediators of Inflammation: 2. Arachidonic Acid (AA) Metabolites (Prostaglandins & Leukotrienes). Prostaglandins (PGI2, PGD2 & PGE2). - Mediate vasodilation, pain, fever. Leukoterines (LTB4, LTC4, LTD4 & LTE4). - Mediate increased vascular permeability, chemotaxis, leukocytes adhesion & activation. Source: mast cells & leukocytes (mainly by neutrophils). Involved in all stages of inflammation. (A) Cell-Derived Mediators of Inflammation: 3. Platelet- Activating Factors (PAF) Source: Produced by mast cells and other leukocytes (mainly neutrophils). Effects: (1) Vasodilation. (2) Increased vascular permeability. (3) Leukocyte adhesion. (4) Oxidative burst. (5) Chemotaxis. (6) Induced platelet degranulation. (A) Cell-Derived Mediators of Inflammation: 4. Cytokines Cytokines are proteins produced by many cell types that modulate the functions of other cell types. Source: Produced by activated lymphocytes and macrophages that modulate the function of other cell types. Involved both in acute and chronic inflammation Cytokines include: ▪ Lymphokines – cytokines produced by lymphocyte. ▪ Monokines - cytokines produced by monocytes/ macrophages. ▪ Interleukins (IL) - cytokines that act between the leukocytes (more than 15 types). ▪ Interferons (INF) – inhibit replication of viruses within the cells and activates macrophages and natural killer (NK) cells. ▪ Growth factors. ▪ Tumor necrosis factors – kill tumor cells but also stimulate adipose and muscle catabolism leading to weight loss. Important Note/ Tumor necrosis factor alpha (TNFa) and IL-1 are key cytokines in acute inflammation. Cytokines Effects: (A) Cell-Derived Mediators of Inflammation: 5. Nitric Oxide (NO) Nitric oxide (NO) is a potent vasodilator. Source: Soluble gas produced by endothelial cells & macrophages. Nitric oxide acts as a regulator of inflammation, actively reducing the effect of other proinflammatory mediators. Role of Cell- mediators in different Reactions of Inflammation  (B) Plasma protein-derived mediators ▪ Circulate in an inactive form. ▪ Must be transformed into an active form by an activator. ▪ Numerous, specific and non-specific. ▪ All activators have natural in-activators to maintain balance.  (B) Plasma protein-derived mediators Three interrelated systems are involved in several aspects of inflammation: Proteins are derived from plasma 1. Complement 2. Bradykinin 3. Factor XII  Morphological Patterns of Acute Inflammation 1. Serous 2. Fibrinous. 3. Purulent. 4. Haemorrhagic. 5. Ulcers.  1. Serous Inflammation Outpouring of a thin fluid that is derived from either plasma or mesothelial cells lining the peritoneal, pleural, and pericardial cavities. Accumulation of Fluid in these serous cavities is called an effusion. For example: skin blisters.  Serous inflammation-Example: skin blister Serous fluid Serous inflammation. Low-power view of a cross-section of a skin blister showing the epidermis separated from the dermis by a focal collection of serous effusion (Blue arrow)  2. Fibrinous Inflammation Characterized by deposition of fibrin in the extracellular spaces. Occurs in cases of more severe injuries with greater vascular permeability allowing larger molecules like fibrinogen to come out of endothelial barrier For example: Fibrinous exudate in meninges, pericardium and pleura.  Fibrinous Inflammation Fibrinous pericarditis. A, Deposits of fibrin on the pericardium. B, A pink meshwork of fibrin exudate (F) overlies the pericardial surface (P).  3. Suppurative Inflammation & Abscess Production of large amounts of pus (purulent exudate), consist of neutrophils, liquefactive necrosis and edema fluid. For example: caused by pyogenic bacteria like staphylococci. Abscess are localized collection of purulent inflammatory exudate or pus  Purulent inflammation with abscess formation. Purulent inflammation with abscess formation. A, Multiple bacterial abscesses in the lung (arrows) in a case of bronchopneumonia. B, The abscess contains neutrophils and cellular debris and is surrounded by congested blood vessels.  4. Ulcer “ An ulcer is a local defect or excavation of the surface of an organ or tissue that is produced by the sloughing ( shedding ) of inflammatory necrotic tissue “ Occur when tissue necrosis and inflammation exist on or near a surface. Common Sites: Mucosa of the mouth, stomach, intestines, genitourinary tract. Skin & subcutaneous tissues  Ulcer A B Ulcer. A, A chronic duodenal ulcer. B, Low-power cross section of a duodenal ulcer crater with an acute inflammatory exudate in the base.  References 1. Robbins and Cotran Pathologic Basis of Disease; 10th ed. 2021 2. HarshMohan Textbook of Pathology. 7th edition. 32 Thank You 33