Tissue Repair and Inflammatory Response PDF

Tissue Repair and Inflammatory Response 1 Inflammatory Response ⚫ is defined as a response of the body to an injurious agent, characterized by cardinal signs such as: ◦ tumour or swelling ◦ dolor or pain ◦ calor or heat ◦ rubor or erythema (Rednes...

Tissue Repair and Inflammatory Response 1 Inflammatory Response ⚫ is defined as a response of the body to an injurious agent, characterized by cardinal signs such as: ◦ tumour or swelling ◦ dolor or pain ◦ calor or heat ◦ rubor or erythema (Redness) ◦ function laesa or loss of function (occurs rarely) ◦ Inflammation is the end-result of these inflammatory responses comprised of various physiologic reactions occurring in the body in its response to an injurious agent (e.g. viruses, microbes, mechanical or chemical trauma, etc.). 2 Inflammatory Response ⚫ Triggered whenever body tissues injured ⚫ Prevents spread of damaging agents ⚫ Disposes cell debris and pathogens ⚫ Alerts adaptive immune system ⚫ Sets the stage for repair 3 Inflammatory Response ⚫ Begins with chemicals released into extracellular fluid (ECF) by injured tissues, immune cells, blood proteins ⚫ Macrophages and epithelial cells of boundary tissues bear Toll-like receptors (TLRs) ⚫ 11 types of TLRs recognize specific classes of infecting microbes ⚫ Activated TLRs trigger release of cytokines that promote inflammation 4 ⚫ Figure 1 : Receptors that detect infection ⚫ Toll-like receptors (TLRs) recognize microbes by binding to pathogen-associated molecular patterns. Abbreviations: lipopolysaccharide (LPS), lipoteichoic acid (LTA), lipoproteins (LP), glycophosphatidylinositol (GPI). Other pattern-recognition receptors for pathogens have been identified, such as: transmembrane C-type lectin receptors (CLRs) which detect fungi; secreted receptors (collectins, ficolins, and pentaxins) which activate innate defenses involving complement and phagocytosis; cytosolic RIG-1-like receptors (RLRs) which detect viruses; and cytosolic nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) which detect pathogens and stress signals. 5 Inflammatory Response ⚫ Inflammatory mediators ◦ Histamine (from mast cells) ◦ Kinins, prostaglandins (PGs), and complement Dilate local arterioles (hyperemia) Causes redness and heat of inflamed region Make capillaries leaky Many attract leukocytes to area Some have inflammatory roles 6 Inflammatory Response: Edema ⚫ 🡪 Capillary permeability 🡪 exudate to tissues ◦ Fluid containing clotting factors and antibodies ◦ Causes local swelling (edema) ◦ Swelling pushes on nerve endings 🡪 pain Pain also from bacterial toxins, prostaglandins, and kinins ◦ Moves foreign material into lymphatic vessels ◦ Delivers clotting proteins and complement 7 Inflammatory Response ⚫ Clotting factors form fibrin mesh ◦ Scaffold for repair ◦ Isolates injured area so invaders cannot spread 8 Clinical Applications ⚫ Benadryl (an antihistamine) – blocks receptor site (H1) for histamine receptors ⚫ Aspirin/Ibuprofen – inhibits formation/action of prostaglandins – reduces pain and fever Cortisone cream – inhibits release/action of inflammatory chemicals ⚫ Naproxen – prevents formation of prostaglandins 9 Figure 1.1. Tissue repair of a nonextensive skin wound: regeneration and fibrosis. Slide 1 Scab Epidermis Vein Blood clot in incised wound Inflammatory chemicals Migrating white blood cell Artery 1 Inflammation sets the stage: Severed blood vessels bleed. Inflammatory chemicals are released. Local blood vessels become more permeable, allowing white blood cells, fluid, clotting proteins, and other plasma proteins to seep into the injured area. Clotting occurs; surface dries and forms a scab. 10 Tissue Repair ⚫ is defined as the physical or mechanical restoration of damaged tissues. It refers to the replacement of dead or damaged cells in a body tissue by healthy new cells. 11  Tissue Repair: Steps ⚫ Necessary when barriers are penetrated ⚫ Cells must divide and migrate ⚫ Occurs in two major ways ◦ Regeneration Same kind of tissue replaces destroyed tissue Original function restored ◦ Fibrosis Connective tissue replaces destroyed tissue Original function lost 12 Figure 1.2. Tissue repair of a nonextensive skin wound: regeneration and fibrosis. Slide 2 Regenerating epithelium Area of granulation tissue ingrowth Fibroblast Macrophage Budding capillary 2 Organization restores the blood supply: The clot is replaced by granulation tissue, which restores the vascular supply. Fibroblasts produce collagen fibers that bridge the gap. Macrophages phagocytize dead and dying cells and other debris. Surface epithelial cells multiply and migrate over the granulation tissue. 13 Steps in Tissue Repair: Step 3 ⚫ Regeneration and fibrosis ◦ The scab detaches ◦ Fibrous tissue matures; epithelium thickens and begins to resemble adjacent tissue ◦ Results in a fully regenerated epithelium with underlying scar tissue 14 Figure 1.3. Tissue repair of a nonextensive skin wound: regeneration and fibrosis. Slide 3 Regenerated epithelium Fibrosed area 3 Regeneration and fibrosis effect permanent repair: The fibrosed area matures and contracts; the epithelium thickens. A fully regenerated epithelium with an underlying area of scar tissue results. 15 Regenerative Capacity in Different Tissues ⚫ Regenerate extremely well ◦ Epithelial tissues, bone, areolar connective tissue, dense irregular connective tissue, blood-forming tissue ⚫ Moderate regenerating capacity ◦ Smooth muscle and dense regular connective tissue ⚫ Virtually no functional regenerative capacity ◦ Cardiac muscle and nervous tissue of brain and spinal cord ◦ New research shows cell division does occur Efforts underway to coax them to regenerate better 16 Aging Tissues ⚫ Normally function well through youth and middle age if adequate diet, circulation, and infrequent wounds and infections ⚫ Epithelia thin with increasing age so more easily breached ⚫ Tissue repair less efficient ⚫ Bone, muscle and nervous tissues begin to atrophy ⚫ DNA mutations possible 🡪 increased cancer risk 17 SUMMARY 18 19 THANK YOU FOR LISTENING ☺ 20