Acute Inflammation (Bahrain Version) October 2023 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Acute Inflammation Class Year 2 Course Pathology Lecturer Professor Paul Murray  LEARNING OUTCOME...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Acute Inflammation Class Year 2 Course Pathology Lecturer Professor Paul Murray  LEARNING OUTCOMES Define inflammation List the causes of inflammation Describe the clinical and microscopical features and outcome of inflammation List the pathophysiology mediators of inflammation Describe cascades in inflammation Describe cytokines in inflammation List the beneficial and harmful effects of inflammation List the outcomes of inflammation  INFLAMMATION Reaction of a vascularised living tissue to a local injury Protective response intended to eliminate the initial cause of cell injury and the necrotic cells and tissues arising from the injury May be harmful Inflammation is intimately associated with the repair process Inflammatory lesions usually indicated by suffix (ITIS)  INFLAMMATION Purpose: – Localise and eliminate the causative agent – Limit tissue injury – Begin the process of healing Causes – Infectious agents – Physical agents – Chemical agents – Immune reactions – Necrotic tissue  TYPES OF INFLAMMATION Acute - minutes to days  Immediate and early response to injury  Characterised by fluid and protein  Polymorphonuclear cells (neutrophils) Chronic - weeks to years  Mononuclear cells (macrophages, lymphocytes and plasma cells) ACUTE AND CHRONIC INFLAMMATION FIVE CLASSIC SIGNS OF ACUTE INFLAMMATION These were known to the Romans Heat Calor Redness Rubor Swelling Tumor Pain Dolor Loss of function Function laesa TWO MAJOR EVENTS IN ACUTE INFLAMMATION Vascular response  Transient vasoconstriction, followed by vasodilatation  Increased vascular permeability Cellular response  Extravasation of neutrophils (polymorphonuclear leucocytes) REASONS FOR INCREASED VASCULAR PERMEABILITY Increased hydrostatic pressure: Think of this as increased "pushing pressure" inside blood vessels that forces fluid out. Decreased intravascular osmotic pressure: There's less "pulling power" inside the blood vessels to retain the fluid. Endothelial cell changes: that make the vessel walls leaky. Contraction: Cells shrink, creating gaps. Junctional retraction: The connections between cells pull back, creating spaces. Injury: Damage to these cells can lead to gaps. OUTCOMES OF INCREASED VASCULAR PERMEABILITY Transudate: This is a watery fluid with few proteins. It forms when there is mainly an imbalance in pushing and pulling pressures. Exudate: A thicker fluid, rich in proteins and often with immune cells like neutrophils. It forms during inflammation. CELLULAR RESPONSE  CELLULAR RESPONSE: KEY POINTS Margination: as blood slows, leucocytes move from the centre of the vessel towards the periphery Endothelial cell activation: Cytokines activate the endothelium causing selectins and other mediators to move to the surface Rolling: Neutrophils roll along and transiently adhere to endothelial cells, mediated by selectins molecules (transiently bind to their receptors) Neutrophil activation: mediated e.g., by IL-8 Firm adhesion (pavmenting): Mediated by ICAM-1-LFA-1. Transmigration: mediated by PECAM-1…diapedesis (cells crawling) Chemotaxis: Movement toward the site of injury mediated by chemokines  FUNCTIONS OF NEUTROPHILS Primary granules – myeloperoxidases (MPO), and others Secondary granules –collagenase and CHI3L1, also known as chitinase 3-like 1 Tertiary granules – MMPs and others Neutrophils express cell surface receptors that recognise pathogen associated molecular patterns (PAMPs) produced by infectious agents and damage associated molecular patterns (DAMPs) from injured and dead cells  ANTIMICROBIAL MECHANISMS OF NEUTROPHILS Phagocytosis: ingestion of the microorganism into a phagocytic vacuole, fuses with lysosome to form phagolysosome. Microorganism is destroyed by oxidative burst with a sudden increase in oxygen consumption and glycogenolysis reactive oxygen species are released – >superoxide ion O2-, hydrogen peroxide (H2O2), hypochlorous acid (HOCL), hydroxyl radical (OH), nitric oxide (NO) Degranulation: Release of granule contents to the environment (tissue damage) Neutrophil extracellular traps (NETs): formed by DNA fibres, histones, etc.  REACTIVE OXYGEN SPECIES Elimination of bacteria Tissue damage CHEMICAL MEDIATORS OF INFLAMMATION Most bind to cell surface receptors, but some have direct enzymatic or toxic activity, all are tightly regulated  VASOACTIVE AMINES Histamine  Found in mast cells, basophils and platelets  Promotes arteriolar dilation and venular endothelial contraction -- - Results in widening of inter-endothelial cell junctions with increased vascular permeability Serotonin  Vasoactive effects similar to histamine  Found in platelets  Released when platelets aggregate  COMPLEMENT SYSTEM Classical pathway: requires antibodies to activate (Ag-Ab complex) C1 binds to IgG or IgM that is bound to antigen) Alternative pathway: does not require antibody to activate  MEMBRANE ATTACK COMPLEX Punches a hole in the membrane ROLE IN INFLAMMATION (C3A AND C5A) BLOOD COAGULATION SYSTEM  BLOOD COAGULATION SYSTEM Factor XII is activated by inflammation KALLIKREIN-BRADYKININ SYSTEM ARACHIDONIC ACID PATHWAY FEVER Beneficial effects of fever – oxygen-dissociation curve is shifted right. More oxygen is available. – Provides a hostile environment for bacterial and viral reproduction.  EFFECTS OF INFLAMMATION Beneficial: – Dilution of toxins – Stimulation of adaptive immunity, arrival of antibodies – Delivery of nutrients and oxygen, drug transport – Formation of fibrin (delays bacterial spread) – Destruction of microbial agent – Removal of tissue debris Harmful: – Mechanical effect e.g., epiglottitis – Impaired flow e.g., acute meningitis – Impaired function – Tissue destruction OUTCOMES OF ACUTE INFLAMMATION Resolution: healing and repair Abscess formation  Abscess is a walled off- collection of pus Progression to chronic inflammation