Fundamentals of Pathology PDF

Www.Medicalstudyzone.com 20 FUNDAMENTALS OF PATHOLOGY C. Limited type-Skin involvement is limited (hands and face) with late visceral...

Www.Medicalstudyzone.com 20 FUNDAMENTALS OF PATHOLOGY C. Limited type-Skin involvement is limited (hands and face) with late visceral involvement. 1. Prototype is CREST syndrome: Calcinosis/anti-Centromere antibodies, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly (Fig. 2.4D), and Telangiectasias of the skin. D. Diffuse type-Skin involvement is diffuse with early visceral involvement. 1. Any organ can be involved. 2. Commonly involved organs include i. Vessels (Raynaud phenomenon) ii. GI tract (esophageal dysmotility and reflux) iii. Lungs (interstitial fibrosis and pulmonary hypertension) iv. Kidneys (scleroderma renal crisis) 3. Highly associated with antibodies to DNA topoisomerase I (anti-Scl-70). V. MIXED CONNECTIVE TISSUE DISEASE A. Autoimmune-mediated tissue damage with mixed features of SLE, systemic sclerosis, and polymyositis B. Characterized by ANA along with serum antibodies to U1 ribonucleoprotein WOUND HEALING I. BASIC PRINCIPLES A. Healing is initiated when inflammation begins. B. Occurs via a combination of regeneration and repair II. REGENERATION A. Replacement of damaged tissue with native tissue; dependent on regenerative capacity of tissue B. Tissues are divided into three types based on regenerative capacity: labile, stable, and permanent. C. Labile tissues possess stem cells that continuously cycle to regenerate the tissue. 1. Small and large bowel (stem cells in mucosal crypts, Fig. 2.5) 2. Skin (stem cells in basal layer, Fig. 2.6) 3. Bone marrow (hematopoietic stem cells) D. Stable tissues are comprised of cells that are quiescent (G 0) , but can reenter the cell cycle to regenerate tissue when necessary. 1. Classic example is regeneration of liver by compensatory hyperplasia after partial resection. Each hepatocyte produces additional cells and then reenters quiescence. Fig. 2.4C Lymphocytic sialadenitis, Sjögren Fig. 2.4D Sclerodactyly, scleroderma. Fig. 2.5 Intestinal crypts. syndrome.  Www.Medicalstudyzone.com Inflammation, Inflammation Inflammatory , Inflammatory Disorders, Disorders and Wound , and Wound Healing Healing 21 E. Permanent tissues lack significant regenerative potential (e.g., myocardium, skeletal muscle, and neurons). III. REPAIR A. Replacement of damaged tissue with fibrous scar B. Occurs when regenerative stem cells are lost (e.g., deep skin cut) or when a tissue lacks regenerative capacity (e.g., healing after a myocardial infarction, Fig. 2.7) C. Granulation tissue formation is the initial phase of repair (Fig. 2.8). 1. Consists of fibroblasts (deposit type III collagen), capillaries (provide nutrients), and myofibroblasts (contract wound) D. Eventually results in scar formation, in which type III collagen is replaced with type I collagen 1. Type III collagen is pliable and present in granulation tissue, embryonic tissue, uterus, and keloids. 2. Type I collagen has high tensile strength and is present in skin, bone, tendons, and most organs. 3. Collagenase removes type III collagen and requires zinc as a cofactor. IV. MECHANISMS OF TISSUE REGENERATION AND REPAIR A. Mediated by paracrine signaling via growth factors (e.g., macrophages secrete growth factors that target fibroblasts) B. Interaction of growth factors with receptors (e.g., epidermal growth factor with growth factor receptor) results in gene expression and cellular growth. C. Examples of mediators include 1. TGF-α - epithelial and fibroblast growth factor 2. TGF-β - important fibroblast growth factor; also inhibits inflammation 3. Platelet-derived growth factor - growth factor for endothelium, smooth muscle, and fibroblasts 4. Fibroblast growth factor - important for angiogenesis; also mediates skeletal development 5. Vascular endothelial growth factor (VEGF) - important for angiogenesis V. NORMAL AND ABERRANT WOUND HEALING A. Cutaneous healing occurs via primary or secondary intention. 1. Primary intention-Wound edges are brought together (e.g., suturing of a surgical incision); leads to minimal scar formation 2. Secondary intention-Edges are not approximated. Granulation tissue fills the defect; myofibroblasts then contract the wound, forming a scar. B. Delayed wound healing occurs in 1. Infection (most common cause; S aureus is the most common offender) Fig. 2.6 Basal layer of skin. Fig. 2.7 Myocardial scarring. (Courtesy of Fig. 2.8 Granulation tissue. Aliya Husain.MD)  Www.Medicalstudyzone.com 22 FUNDAMENTALS OF PATHOLOGY 2. Vitamin C, copper, or zinc deficiency i. Vitamin C is an important cofactor in the hydroxylation of proline and lysine procollagen residues; hydroxylation is necessary for eventual collagen cross-linking. ii. Copper is a cofactor for lysyl oxidase, which cross-links lysine and hydroxylysine to form stable collagen. iii. Zinc is a cofactor for collagenase, which replaces the type III collagen of granulation tissue with stronger type I collagen. 3. Other causes include foreign body, ischemia, diabetes, and malnutrition. C. Dehiscence is rupture of a wound; most commonly seen after abdominal surgery D. Hypertrophic scar is excess production of scar tissue that is localized to the wound (Fig. 2.9). E. Keloid is excess production of scar tissue that is out of proportion to the wound (Fig. 2.10). 1. Characterized by excess type III collagen 2. Genetic predisposition (more common in African Americans) 3. Classically affects earlobes, face, and upper extremities Fig. 2.9 Hypertrophic scar. (Reprinted with Fig. 2.10 Keloid. permission, http://emedicine.medscape.com/ article/1128404-overview)