Inflammation Chapter 9 Fall 2024 PDF

Inflammatio n Tissue Repair Wound Healing Pathophysiology Miranda Hawks, PhD, RN, CNL Compliments to Dr. Landerfelt Chapter 9 Inflammation: Complex, nonspecific response to tissue injury Acute inflammation - early response to injury Goals: Minimize effects of injury or...

Inflammatio n Tissue Repair Wound Healing Pathophysiology Miranda Hawks, PhD, RN, CNL Compliments to Dr. Landerfelt Chapter 9 Inflammation: Complex, nonspecific response to tissue injury Acute inflammation - early response to injury Goals: Minimize effects of injury or infection Remove damaged tissue Generate new tissue Facilitate healing Chronic inflammation Self-perpetuating Contributes to chronic disease Add ending –itis to affected organ or tissue Appendicitis, tendonitis, bronchitis This Photo by Unknown Author is licensed under CC Cells of Inflammation (figure 9-1, pg. 193) Endothelial cells Platelets Leukocytes Neutrophils Eosinophils Basophils and mast cells Monocytes/ Macrophages Extracellular matrix Cells of Inflammation: Endothelial Cell (figure 9-1, pg. 193) Single layer, lines blood vessels Functions: Produce antithrombotic agents, vasoconstrictors, and vasodilators Provide selectively permeable barrier Regulate leukocyte movement (extravasation) Synthesize and secrete inflammatory mediators Regulate immune cell proliferation ↑ endothelial permeability allows inflammatory products to migrate to tissue Cells of Inflammation: Platelets (figure 22-1, pg. 546) Thrombocytes Small, membrane-bound disks Hemostasis Release inflammatory mediators → ↑ vascular permeability Cells of Inflammation: Leukocytes (figure 9-1, pg. 193) Major cellular components Neutrophils Most numerous First to arrive Phagocytize bacteria Release enzymes Life span ~ 24 hours Eosinophils Allergic reactions Destroy parasitic worms Cells of Inflammation: Leukocytes (figure 9-1, pg. 193) Basophils Allergic reactions Mast cells Allergic reactions Reside in tissues Acute and chronic inflammation Release histamine Vasodilation and vascular permeability Cells of Inflammation: Leukocytes (figure 9-1, pg. 193) Monocyte Largest WBC Monocytes → macrophages in tissues Life span Monocytes Macrophages Macrophages Major phagocytic cells Cells of Inflammation: Other contributors (figure 9-1, pg. 193) Connective tissue: Ex. fibroblasts, mast cells, macrophages Extracellular matrix: Collagen and elastin  Acute Inflammation Early, immediate reaction Remove injurious agent and limit damage Local reaction 5 Cardinal signs: Rubor – redness Tumor – swelling Calor – heat Dolor – pain Functio laesa – loss of function Acute Inflammation Acute-phase response Systemic manifestations during acute inflammation Covid-19 Fever Fatigue Stages of Inflammation Vascular Cellular ↑ vasodilation Migration of ↑ vascular leukocytes to site permeability of injury or Plasma proteins infection leave vascular space Vascular Phase (pg. 194) Abrupt changes in blood vessels Brief vasoconstriction  rapid vasodilation ↑ capillary blood flow Heat and redness ↑ capillary permeability Fluid and proteins into tissue Swelling, pain, loss of function  Cellular Phase (pg. 195) Delivery of leukocytes to site of injury 1. Adhesion and margination ↓ speed, adhere to endothelial cells 2. Transmigration Extravasation 3. Chemotaxis Migration to site of injury Chemokines secrete chemoattractants Cellular Phase (pg. 195) 4. Leukocyte activation and phagocytosis Opsonin Circulating proteins that opsonize Opson Ancient Greek word for delicious side-dish Opsonization Coating of a microbe to facilitate recognition by neutrophils Think-Pair-Share (3 minutes) Partner Power-Up! 1.High-five the person next to you— Boom! You’ve got a partner! 2.Together, dive into the stages of inflammation. How are they similar? How are they different? 3.Get your ideas ready to share with the class, because we want to hear your brilliant breakdowns! Wait.... Did I hear prizes for first 3 teams to share? Wow! Inflammatory Mediators (figure 9-3, pg. 198)  Cell-Derived Mediators of Inflammation (figure 9-4, pg. 199) Histamine and serotonin Vasoactive Vasodilation and ↑ permeability 1st mediators released Arachidonic acid metabolites Lipoxygenase pathway Leukotrienes Cyclooxygenase pathway (COX) Prostaglandins Thromboxane A2  Cell-Derived Mediators of Inflammation (figure 9-4, pg. 199) Histamine and serotonin Vasoactive Block release of Vasodilation and ↑ permeability arachidon 1st mediators released ic acid Arachidonic acid metabolites Block COX pathway Lipoxygenase pathway Leukotrienes Cyclooxygenase pathway (COX) Prostaglandins Thromboxane A2  Omega-3 polyunsaturated fatty acids (PUFAs) Fish oil, flax seed, canola oil, green Cell- leafy vegetables, walnuts, soybeans Derived – can only be obtained through diet Anti-inflammatory Mediators Replace arachidonic cells in cell of membrane with eicosapentaenoic acid Inflammat Platelet-activating factor (PAF) ion Activates platelets Stimulates immune response ↑ prostaglandins and serotonin Cell-Derived Mediators of Inflammation (figure 9-5, pg. 200) Inflammatory cytokines Chemical messengers Autocrine and paracrine Produced by immune cells, endothelial cells, epithelial cells, fibroblasts Tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) Mediate local inflammation and systemic response Pleiotropic Chemokines Subgroup of cytokines Chemoattractant trail Recruit, direct migration of immune cells Cell-Derived Mediators of Inflammation Nitric oxide Reactive oxygen Vasodilator species Released by multiple immune cells Relaxes vascular smooth muscle ↑ inflammation Anti-platelet functions ↑ inflammatory cytokines synthesis and release ↓ cellular phase of inflammation Plasma Protein: Mediators of Inflammation Clotting proteins Vascular phase of inflammation Thrombin binds to protease-activated receptors on platelets ↑ production of chemokines, PAF, endothelial adhesion molecules, prostaglandin synthesis Complement proteins Vascular permeability, phagocytosis, vasodilation Vasoactive peptides Generated by kinin system Ex. Bradykinin: ↑vascular permeability, contraction of smooth muscle, vasodilation, and pain Local Manifestations of Inflammation: Exudates and Ulceration Exudates: Fluid that leaks out of blood vessels into nearby tissue Serous Low protein Hemorrhagic Fibrinous Membranous/pseudomembranous Necrotic cells in fibrinopurulent exudate Purulent/suppurative Ulceration Necrosis and erosion Chronic Inflammation Self-perpetuating Contributes to chronic disease Lasts for weeks  years Contributes to chronic disease by causing tissue damage Fibrosis Causes: Foreign agents, microbes, autoimmune disease Chronic diseases: Obesity, cardiovascular disease, diabetes  Systemic Manifestations of Inflammation Acute-phase response Acute-phase proteins: C-reactive protein (CRP) Inflammatory cytokine Fibrinogen ↑erythrocyte sedimentation rate (ESR) Leukocytosis ↑ white blood cells (WBCs) WBC differential Fever ↑ in body temperature Cytokine-induced upward displacement of thermoregulatory set point Tissue Repair and Wound Healing: Cell Proliferation and Differentiation Proliferation: ↑ cell numbers via mitotic division Differentiation: Structural and functional specialization of a cell Ex. hematopoietic stem cell  red blood cell (RBC) Tissue Types Parenchymal tissues: Functioning cells of organ or body part Heart cell, liver cell, etc. Stromal tissues: Interstitial space Connective tissues, blood vessels, fibroblasts, nerve fibers, extracellular matrix Tissue Repair and Wound Healing: Restoration of tissue structure and function after an injury Regeneration: Injured cells replaced with cells of same type Replacement: Injured cells replaced with connective, fibrous scar tissue (fibrosis)  Proliferative Capacity of Tissues Labile cells Continue to divide and replicate throughout life Need reserve pool of stem cells Ex. Skin, oral cavity, GI tract, bone marrow, female reproductive organs, urinary tract Stable cells Stop dividing when growth ceases Remain in G0 stage of cell cycle Proliferate with certain stimuli Ex. Liver, kidney, smooth muscle, vascular endothelial cells, fibroblasts Permanent cells Unable to proliferate Replaced with fibrous scar tissue Neurons, cardiac muscle, skeletal muscle Regulation of the Healing Process (figure 6-9, pg. 104) Chemical mediators Cytokines: Interleukins, interferons, TNF-α Arachidonic acid derivatives: Prostaglandins, leukotrienes Growth factors Control proliferation, differentiation, metabolism of cells Extracellular matrix (ECM) Growth Factor Signaling Pathway Regulation of the Healing Process: Growth Factors ↑ cell size, cell proliferation Regulate inflammation, angiogenesis, ECM Some growth factors involved in tissue regeneration and wound healing: Just FYI Regulation of the Healing Process: Extracellular Matrix Basement membrane Surrounds epithelial, endothelial, smooth muscle cells Interstitial ECM Fibrous structural proteins Collagen, elastin Water-hydrated gels Hyaluronic acid, proteoglycans Adhesive glycoproteins Fibronectin, laminin Fibroblasts Synthesize collagen Integrin Bind ECM components Initiate signaling cascade → proliferation and differentiation of cell Wound Healing: Filling of gap created by tissue death Depends on extent of tissue loss Regeneration of lost tissue Replacement with connective tissue scar Primary intention Healing when no tissue lost Ex. Surgical incision Wound Healing: Filling of gap created by tissue death Secondary intention Healing with tissue loss or infection Slower than primary intention Larger amount of scar tissue Granulation Red, moist connective tissue Angiogenesis Fibrogenesis Residual inflammatory cells Scar formation Fibroblasts ECM Case Study (3 minutes) – Partner Up! Case Study: Captain Heal and the Battle of Secondary Intention Meet Captain Heal, a 68-year-old gardening enthusiast, who fell while chasing a pesky squirrel and sustained a deep leg wound. This wound is healing slowly by secondary intention. The wound is red and moist with granulation tissue on the scene, fibroblasts are hard at work, and angiogenesis—the formation of new blood vessels—is creating new pathways for oxygen and nutrients. The process is slower, with scar tissue expected. Discussion Questions: How does angiogenesis help in the healing process? Why is Captain Heal’s wound taking longer to heal than a minor cut? Wound Healing Inflammatory phase Starts at time of injury Blood clot formation Migration of phagocytic WBCs Neutrophils First responders Macrophages Arrive within 24 hours Life span Initiate growth factor production Wound Healing Proliferative phase Begins on day 2 – 3 Lasts ~ 3 weeks Fill wound space with new tissue Fibroblasts Synthesize collagen, proteoglycans, glycoproteins Release growth factors Angiogenesis, endothelial cell proliferation and migration Epithelialization Wound edges heal, form new surface layer  Wound Healing Wound contraction and remodeling phase Begins ~ 3 weeks after injury Continues up to 6 months Fibrous scar develops  Malnutrition Adequate proteins, carbohydrates, and fats Factors Vitamins A, C, K, B Minerals Affecting Zinc, copper, electrolytes ↓ Blood flow and O2 delivery Wound Impaired inflammatory and immune Healing responses Infection, wound separation, foreign bodies Bite wounds  Wound Healing in Aging Adults Changes in skin structure ↓ dermal thickness, collagen content, elasticity ↓ fibroblasts Impaired wound contraction ↓ epithelialization ↑ vulnerability to chronic wounds Thank you for your attention Questions? 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