REGENERATION AND REPAIR

HOW TISSUES ARE RESTORED

REMOVAL OF EXUDATE REMOVAL OF CELLULAR AND TISSUE DEBRIS REPLACEMENT OF CELLS AND TISSUES LOST

REPLACEMENT OF CELLS AND TISSUES =

Occurs before proceeding to one of the 3 final outcomes of acute inflammation.
REGENERATION = Growth of cells to replace lost tissue.
PHYSIOLOGICAL REGENERATION EPIDERMIS BLOOD VESSELS UTERINE MUCOSA GLANDULAR EPITHELIUM RENAL TUBULAR INTESTINAL REGENERATIVE ABILITY BEST = SUPPORTING TISSUE OTHER

CELLS = LOST ABILITY TO REGENERATE IN POST NATAL LIFE ATYPICAL ORGAN REGENERATION INABILITY TO REGENERATE FRAMEWORK DESTROYED ORGAN REGENERATION BEST = LIVER AND LUNGS KIDNEY SPLEEN

REPAIR OR HEALING = A reparative tissue response to a wound, inflammation or necrosis resulting in FIBROSIS.
REGENERATIVE CAPACITY LABILE = Proliferate throughout life STABLE = Divide in response to stimuli PARANCHYMOUS CELLS MESENCHYMOUS CELLS PERMANENT = Cant divide in postnatal life BY CONNECTIVE TISSUE AND GRANULATIVE TISSUE = May overlap inflammation

MECHANISMS INVOLVED IN REGENERATION AND REPAIR

CONTROL OF CELL PROLIFERATION
HORMONES AND GROWTH FACTORS = MITOGENIC HORMONES = estrogen, progesterone, somatotropin, insulin GROWTH FACTORS = Locomotion, Contractility, Differentiation and Angiogenesis
EGF bFGF PDGF VEGF IL-1 and IL-2 TNF TIGF NGF Macrophage Derived Growth Factors

CELL-CELL INTERACTIONS = CONTACT INHIBITION CELL-MATRIX INTERACTIONS = INTEGRINS LEUKOCYTE ADHESION MOLECULES PLATELET SURFACE RECEPTOR FIBRONECTIN RECEPTOR EXTRACELLULAR MATRIX COLLAGENS CAMs PROTEOGLYCANS ELASTIN

GLYCOSAMINOGLYCANS LAMININ FIBRONECTINS = GLYCOPROTEINS SEEN IN: Cell Surfaces, Basement Membranes and
Pericellular Matrices

MADE BY: Fibroblasts, Endothelial Cells and Monocytes IN WOUND HEALING Facilitate migration of epithelium Chemotactic for monocytes Chemotactic for fibroblasts Stimulate endothelial migration and organization Release bFGF from monocytes

COLLAGENIZATION AND WOUND STRENGTH = REPAIR BY CONNECTIVE TISSUE

I. ANGIOGENESIS = GRANULATION TISSUE = 3-5 days
From endothelial precursor cells From PRE-EXISTING vessels Mediated by VEGF and bFGF release = BASEMENT MEMBRANE damage

Edematous appearance = mesh of capillaries, fibroblasts, inflammatory cells and ECM

II. FIBROSIS = Fibroblast COLLAGEN DEPOSITION Growth Factors released by Inflammatory cells III. REMODELLING (SCARRING) Metalloproteinases + Collagenases Debridement + Digestion of (Collagen I-IV) and Fibronectin Inflammatory cells and epithelial cells (Collagenases)

SKIN WOUND HEALING

REPAIR OF SKIN WOUNDS
I. CRUST FORMATION II. REMOVAL OF DEAD TISSUE, OTHER DEBRIS AND EXUDATE = sloughing off and zone of demarcation IV. REPLACEMENT OF LOST CELLS AND TISSUES CELL PROLIFERATION = granulation tissue Endothelial MIGRATION = in arcs Epithelial MIGRATION = in sheets V. CICATRIZATION = Granulation tissue (III) SCAR (I)

ADULT TISSUE = COLLAGEN TYPE I GRANULATION TISSUE = COLLAGEN TYPE III CLOSING OF BLOOD VESSELS

PRIMARY REPAIR = Edges lined up

RESTITUTIO AD INTEGRUM

SECONDARY REPAIR = Edges not lined up More granulation More epithelialization MORE FIBROSIS

HEALING OVERVIEW
INFLAMMATION PROLIFERATION and MIGRATION of connective tissue cells ANGIOGENESIS Collagen and other ECM protein synthesis Tissue remodeling Wound contraction Increase in wound strength (scar = fibrosis)

FACTORS INFLUENCING THE RATE OF HEALING = DECREASED Blood Supply

LOCAL SYSTEMIC