Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease PDF

Lecture Material is adapted from © 2022 Wolters Kluwer Health, Lippincott Williams & Wilkins Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease Chapter 3: Inflammation and Tissue Repair Module 1: Acute Inflammation Dr. Romeo Batacan Jr. MPAT12001 Medical Pathophysiology...

Lecture Material is adapted from © 2022 Wolters Kluwer Health, Lippincott Williams & Wilkins Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease Chapter 3: Inflammation and Tissue Repair Module 1: Acute Inflammation Dr. Romeo Batacan Jr. MPAT12001 Medical Pathophysiology Lecture Series Copyright © 2017 Wolters Kluwer Health | Lippincott Williams &Wilkins Inflammation and Tissue Repair All disease process cause injury Healing can only occur with an effective inflammatory response Two inflammatory process 1. Acute inflammation: expected body response to injury 2. Chronic inflammation: altered inflammatory process due to unrelenting injury Lines of Defense First: Skin and mucous membranes Physical barrier Mucus: chemically coated Second: Inflammatory response Non‐specific Identical regardless of cause Third: Immune response Specific response Depends on the invader  Inflammation “inflammare” – set on fire Reaction of vascularized tissues to injury Inflammatory conditions are named by adding the suffix – itis to the affected organ or system Appendicitis: inflammation of appendix Pericarditis: inflammation of pericardium Neuritis: inflammation of a nerve  Acute Inflammation Triggered by tissue injury Injury: any form of damage 3 goals of inflammation 1. Increase blood flow to site (vascular response) 2. Increase cells for healing at site (cellular response) 3. Remove injured tissue and prepare for tissue repair  Vascular Response Response required at/near the site of injury Facilitated by chemical mediators (inflammatory mediators) (after brief vasoconstriction) induces vasodilation and increases capillary permeability Objective is to get more blood flowing to the injured area Blood is composed of cells Active in phagocytosis Required for healing Developing immune response Increased blood flow dilutes harmful substances at the site of injury  Capillaries Capillaries: exchange of oxygen, nutrients, waste between blood and tissue Flow through capillaries are controlled by pre‐capillary sphincters Smooth muscle Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings  Arteriole end 5L blood 55% plasma (2.75L) 20ml / 2.75ml = 7.3 Venule end Marieb EN, Hoehn KN. Human Anatomy & Physiology. 9th ed. Boston, Pearson Education;© 2013 Pearson Education, Inc. 2013 Fluid movement: Exudate vs Transudate Kumar, Robbins & Cotran: Pathologic basis of disease. 8th ed. Philadelphia: Saunders;2010 Exudates Vary in fluid type, plasma protein content, presence of cells 1. Serous Watery fluid, low in protein content, plasma entering ry site inflammatory site 2. Hemorrhagic Severe tissue injury causes damage to blood vessels Significant leakage of RBCs from capillaries 3. Fibrinous Large amount of fibrinogen, sticky meshwork 4. Membraneous / Pseudomembraneous Develops on mucous membrane surfaces Necrotic cells enmeshed in fibropurulent exudate 5. Purulent or suppurative Contains pus (degraded WBs, proteins, tissue debris) Inflammatory Mediators Cell derived: generated in cell plasma membrane made up from proteins within the cell 1. Within White blood cells 2. Within Platelets 3. Within Endothelial or damaged cells Plasma derived: Continuously circulating Plasma proteins 1. Complement system 2. Kinin system 3. Clotting system Inflammatory mediators within plasma Circulating inflammatory mediators Craft AJ, Gordon C, Tiziani A. Understanding pathophysiology. 1st ed. Chatswood, Mosby; 2011 3 major interrelated system: 1. Complement 2. Clotting 3. Kinin Initial Steps in Inflammatory Response Tissue injury Blood vessel vasodilation Increased vascular permeability Clotting cascade activated Continued release and circulation of vasoactive inflammatory mediators Cellular Response After vessel dilation: cells are needed for healing Cellular response: regulated by inflammatory mediators 3 essential steps: 1. Chemotaxis Moving cells to the site of injury Chemotactic factors are activated 2. Cellular adherence Attraction and binding to migration site Regulated by chemotactic factors and receptors that binds leukocytes to the endothelial surface 3. Cellular migration Across/between endothelial cells: diapedesis  Phagocytosis Inflammatory cells release more inflammatory mediators to attract more neutrophils Neutrophils also release inflammatory mediators Aggressive process to destroy/phagocytize causative agents Healthy tissue is also damaged Summary Manifestations of Inflammation Local manifestations include the 5 cardinal sign: 1. Redness rubor 2. Heat calor 3. swelling (edema) tumor 4. Pain dolor 5. incapacitation (loss of function) function laesa Lymphadenitis: enlargement and inflammation of the lymph nodes Result of trying to filter harmful substances Painful palpable nodes (Non‐painful palpable: neoplasms) Manifestations of Inflammation Systemic manifestations may include fever (pyrexia) increased circulating leukocytes and plasma proteins weight loss fatigue headache lethargy Laboratory diagnosis 2 Non‐specific tests of inflammation 1. CRP:C‐reactive protein 2. ESR: erythrocyte sedimentation rate Elevated value indicate inflammation Will not identify source/location CRP: C‐reactive protein Preferred test of acute inflammation Presence of a specific protein (triggered by plasma protein system during inflammation)  Treatment of Inflammation Inflammatory response: multiple components, “overzealous” Damage to healthy surrounding tissue is common Treatment goal to minimize damage Initial treatment for acute inflammation 1. Reduce blood flow 2. Decrease swelling 3. Block the action of chemical mediators 4. Decrease pain Pharmacologic treatment Porth C. Pathophysiology : concepts of altered health states. 7th ed. Philadelphia, Lippincott Williams & Wilkins; 2005. Block inflammatory mediators Reduce swelling, pain, redness, warmth Non-pharmacologic treatment Initial treatment: RICE Nowak T, Handford AG. Pathophysiology: Concepts and Applications for Health Care Professionals. 3rd ed.New York, McGraw‐Hill; 2004 Rest, ice, compression and elevation Ice/Cold: cause vasoconstriction to prevent heat loss At the site of injury: reduced formation of exudate Rule of 10 on and 10 off (Heat e.g. sport injury: early on ice, later heat increase blood flow, reduce pain, help phagocytosis) Elevation: blood flow slows, work against gravity Compression: prevents exudate forming by increasing tissue pressure, promotes lymphatic drainage Optimal fluid and nutrient intake to help healing Resolution of acuteinflammation Acute inflammatory response is self‐limited Offending agent is destroyed/removed: Feedback system regulated by 3 plasma protein system Relevant inflammatory mediators Deactivate the inflammatory response Tissue is ready to heal, the stage is set If acute inflammatory response is unsuccessful: chronic inflammation Craft AJ, Gordon C, Tiziani A. Understanding pathophysiology. 1st ed. Chatswood, Mosby; 2011