CHAPTER 4 Tissue: The Living Fabric: Part B 6/23/2012 Press Images © Annie Leibovitz/Contact MDufilho 1 Inflammatory Response • • • • • Triggered whenever body tissues injured Prevents spread of damaging agents Disposes of cell debris and pathogens Alerts adaptive immune system Sets the stage for repair 6/23/2012 MDufilho 2 Inflammatory Response • Cardinal signs of acute inflammation: 1. Redness 2. Heat 3. Swelling 4. Pain (Sometimes 5. Impairment of function) 6/23/2012 MDufilho 3 Inflammatory Response • Begins with chemicals released into 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 6/23/2012 MDufilho 4 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 6/23/2012 MDufilho 5 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 6/23/2012 MDufilho 6 Inflammatory Response • Clotting factors form fibrin mesh – Scaffold for repair – Isolates injured area so invaders cannot spread 6/23/2012 MDufilho 7 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 6/23/2012 MDufilho 8 Figure 4.12. 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. • 6/23/2012 Clotting occurs; surface dries and forms a scab. 9 MDufilho Tissue Repair • 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 6/23/2012 MDufilho 10 Figure 4.12. 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. 6/23/2012 MDufilho 11 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 6/23/2012 MDufilho 12 Figure 4.12. 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. 6/23/2012 MDufilho 13 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 6/23/2012 MDufilho 14 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 6/23/2012 MDufilho 15