Inflammation, Injury, and Repair. Inflammation. Inflammation made simple. Inflammation 1/27/2015. Amelia Granberry, DMD. Common causes of inflammation

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1 , Injury, and Amelia Granberry, DMD Injury alteration in the environment that causes tissue damage Necrosis Hyperplasia Hypertrophy Atrophy Innate defenses Intact skin and mucosa Cilia and mucus in respiratory system Stomach acid Flushing action of tears, saliva, diarrhea Antimicrobials Microflora on skin Local or Systemic Acute or Chronic 5 Classic Signs of Redness (erythema or rubor) Heat (calor) Swelling (tumor) Pain (dolor) Loss of normal tissue function (function laesa) Common causes of inflammation Trauma Pathogenic organisms Allergens Foreign substances Extreme thermal changes (burns) Chemical exposure made simple Aids disposal of microbes, toxins, or foreign material at the site of injury, prevents their spread to other organs, and prepares site for tissue repair Nonspecific internal system of defense Response to accidental cut is similar to other tissue damage (burns, radiation, bacterial or viral invasion) 3 Basic Stages 1. Vasodilation and increased permeability of blood vessels 2. Phagocyte migration 3. 1 st Immediate reflex constriction of microcirculation in area of injury Within seconds, dilation of same blood vessels Hyperemia (responsible for erythema and heat) Permeability increases Plasma fluid enters tissue (transudate) Movement of WBCs to periphery (margination) WBCs line the walls (pavementing) After pavementing, WBCs escape vessels and enter tissue (emigration) Exudate (higher protein content than trasudate) now flows to injured tissues Exudate and transudate help dilute injurious agents and carry injurious agents to lymph nodes (where immune response is stimulated) WBCs ingest foreign substances (phagocytosis) 1

2 Exudate Serous exudate thin, clear fluid Purulent exudate thick, white to yellow pus; contains tissue debris and many WBCs, includes dead phagocytes Abscess collection of purulent exudate accumulated in cavity formed by tissue When tissue is shed many times, it produces and open sore, called and ulcer May interfere with repair of tissue if excessive Fistula Drainage passage formed that bores through tissue IND Incision and Drainage may be necessary with antibiotic 5 Substances that contribute to Vasodilation, Increased Permeability, and other aspects of 1. Histamine Especially in Mast Cells in CT, basophils, and blood platelets Released in response to injury by any cell that contains it (Phagocytes also stimulate its release) Causes Vasodilation and Increased permeability 2. Kinins polypeptides Induce Vasodilation and increased permeability Serve as chemotactic agents for phagocytes Affect some nerve endings, causing much of the pain associated with Continued 3. Prostaglandins (PGs) Released by damaged cells and intensify the effect of histamine and kinins May stimulate migration of phagocytes through capillary walls Increased vascular dilation, permeability, erythema, and pain (intensifies and prolongs) 4. Leukotrienes (LTs) Produced by basophils and mast cells by breakdown of membrane phospholipids Cause Increased permeability Also function in adherence and chemotactic agents for phagocytes Continued 5. Complement Protein stimulates histamine release Attracts neutrophils by chemotaxis Promote phagocytosis Can also destroy bacteria Phagocyte Migration Neutrophil 1 st type of WBC recruited to area of injury in response to chemotactic factors 60 70% of entire WBC population Derived from stem cells in bone marrow Main function Phagocytosis of substances such as pathogenic micro organisms and tissue debris Multi lobed nucleus Polymorphonuclear leukocytes Granular cytoplasm contains Lysosomal enzymes that destroy substances once engulfed Can immediately initiate phagocytosis because already mature cells Phagocytize up to 20 bacteria before dying Cannot phagocytize organisms larger than bacteria Predominate in early stages of infection but tend to die off rapidly Phagocyte Migration (cont) Monocyte 2 nd type of WBC to emigrate from blood vessels to injured tissue (hours later), where it becomes a Macrophage Monocytes also derived from stem cells in bone marrow Responds to chemotactic factors, capable of phagocytosis, is mobile, has lysosomal enzymes in cytoplasm Macrophage is larger than monocyte, 3 8% of WBC population, single round nucleus, NO granular cytoplasm Can destroy up to 100 bacteria Can ingest larger particles than phagocytes Survive and function for several months 2

3 Biochemical Mediators Essential to inflammatory response Can start or amplify response May come from blood, endothelial cells, WBCs, platelets, prod by pathogenic organisms 3 Systems of plasma proteins circulating in the blood can be activated during inflammation 1. Kinin System 2. Clotting Mechanism 3. Complement System Keep in Mind The Kinin, Clotting, and Complement Systems interact together because a protein from one system can activate one or both of the other systems Kinin System Most predominant member of this class Bradykinin Bradykinin is responsible for: Vasodilation Increased vascular permeability Leukocyte chemotaxis Contraction of smooth ms Actions of bradykinin are short lived and inactivated by kininase Clotting Mechanism Primary function clotting of blood Stops bleeding at sight of injury Forms fibrous meshwork that protects adjacent tissues and keeps foreign substances contained (prevents spread of infection), this also aids in phagocytosis Biochemically mediates inflammation Certain products cause vascular dilation and permeability by also activating kinin system Important in tissue repair because forms future framework for repair process (wound healing) Chemical playing important roles: thrombin, fibrinopeptides, and factor X Complement System Series of plasma proteins activated in cascade fashion Function during inflammation and immunity Can cause Mast Cells to release granules from their cytoplasm that contain histamine and other mediators Mast Cells usually in loose CT of skin and mucosa When histamine released from mast cells increase in vascular permeability and vasodilation Other components create holes in cell membrane and cause cell death (Cytolysis) Complement proteins can attach to surface of bacteria, stimulation WBCs to phagocytize them (opsonization) 1. Fever Body temp controlled by hypothalamic thermoregulatory center Higher than 98.6 degrees Assoc with systemic inflamm response Pyrogens fever producing substances produced by WBCs and pathogenic micro organisms that increase the synthesis and release of prostaglandins in the hypothalamus Moderately high fever may help combat infxn b/c increased temp slows growth of many pathogenic organisms Body can t tolerate high fever for long, seizures, may be fatal 3

4 2. Leukocytosis Increase in # of WBCs circulating in blood primarily involved neutrophils in response to chemical mediators, attempts to provide more cells for phagocytosis complete blood count will show WBC count (measures proportion of each WBC type) that can help distinguish bacterial from viral infxn Viral infxn=increase in lymphocytes Bacterial infxn=increase in neutrophils Allergic reaction=may be increase in eosinophils 3. Lymphadenopathy enlargement of lymph nodes results from changes in lymphocytes that reside in lymph nodes lymphocytes WBCs that mature in lymphoid tissue, main WBC of the immune system travel from the lymph node to tissues through circulation where involved with immune response changes in lymph nodes include hyperplasia and hypertrophy usually during chronic inflammation 4. Elevated C Reactive Protein produced in liver interacts with complement system and clotting mechanism measurement of C reactive protein is diagnostic test assoc with inflammation chronically elevated C reactive protein associated with high risk of cardio disease and marker of periodontal disease activity Regeneration vs Regeneration most favorable, return completely to normal structure and function when complete return of the tissue to normal is not possible because damage was too great Final defense mechanism of body to restore injured tissues to original state Cannot be completed until source of injury is removed or injurious agents destroyed Often results in scar tissue Usually complete in 2 weeks 3 phases of : 1)inflammation 2)proliferation 3)maturation Day of Injury Clot (meshwork composed of fibrin, aggregated red blood cells, and platelets) as result of Clotting mechanism Day After Injury Acute inflammation Neutrophils emigrate from microcirculation into injured tissue Phagocytosis of foreign substances and necrotic tissue 4

5 2 Days After Injury Monocytes enter injured area as macrophages Macrophages continue phagocytosis and secrete growth factors to stimulate growth of new blood vessels (angiogenesis) Fibroblasts become the most important cells during healing as they secrete collagen fibers using meshwork of clot as scaffold, known as fibroplasia Microcirculation establishes itself in immature connective tissue Granulation tissue initial CT formed, many more capillaries and fibroblasts, appears pink or red Epithelialization As epithelial cells divide and migrate across the injured tissue, using fibrinous meshwork of clot as guide to form new surface layer Important for clot to remain in place Perio Pack Dry Socket At end of 2 days, lymphocytes and plasma cells begin to emigrate as chronic inflamm and immune response begin 7 Days After Injury If source of injury removed, inflamm and immune responses in tissue are completed 1 wk after injury Surface remains redder (thin surface epithelium and increased vascularity Fragile and at risk for new injury Fibroblasts differentiate into myofibroblasts (similar to smooth ms) and the tissue begins to contract; this contracting peaks 5 15 days after injury and continues until site is reepithelialized 2 Weeks After Injury Initial granulation tissue and fibers remodeled=full Strength Matured fibrous CT is now scar tissue Tissue appears whiter or paler Because of increased collagen fibers and decreased vascularity Stronger collagen replaced immature collagen and is more organized Types of 1. Primary intention When wound edges are brought together (sutured/glued) so that they are adjacent to each other Minimizes scarring Most surgical wounds heal by primary intention healing Wound closure is performed with sutures (stitches), staples, or adhesive tape or glue Very little granulation tissue and more normal tissue Types of 2. Secondary intention Tissue is Lost Edges cannot be joined during healing Large clot followed by increased granulation tissue Surgeon may pack the wound with a gauze or use a drainage system Broader scar Examples: gingivectomy, gingivoplasty, tooth extraction sockets by Secondary Intention Keloid may form Excessive scarring appearing raised and extending beyond original borders Usually occurs in those with darker skin 5

6 Types of 3. Tertiary Intention delayed or secondary closure If the wound edges are not reapproximated immediately, delayed primary wound healing transpires Infection may occur at site of surgical incision that was healing by primary intention Enlargement of injured area, increase in magnitude and duration of inflammatory and immune responses The wound may be purposely left open until infection controlled 6