4 Tissue: The Living Fabric: Part B 6/23/2012 MDufilho

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

Inflammatory Response Cardinal signs of acute inflammation: Redness Heat Swelling Pain (Sometimes 5. Impairment of function) 6/23/2012 MDufilho

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

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

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

Inflammatory Response Clotting factors form fibrin mesh Scaffold for repair Isolates injured area so invaders cannot spread 6/23/2012 MDufilho

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 MDufilho 6/23/2012

Scab Epidermis Vein Blood clot in incised wound Inflammatory chemicals 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. • Clotting occurs; surface dries and forms a scab. 6/23/2012 MDufilho

Necessary when barriers are penetrated Cells must divide and migrate 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

Organization restores the blood supply: Figure 4.12. Tissue repair of a nonextensive skin wound: regeneration and fibrosis. Slide 2 Regenerating epithelium Area of granulation tissue ingrowth Macrophage Budding capillary Fibroblast 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. 2 6/23/2012 MDufilho

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

Regeneration and fibrosis effect permanent repair: 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

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

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