Pathoma 2023 PDF Inflammation & Inflammatory Disorders

Www.Medicalstudyzone.com Inflammation, Inflammatory Disorders, and Wound Healing 19 2. Important antiphospholipid antibodies include anticardiolipin (false-positive VDRL and RPR syphilis screening test...

Www.Medicalstudyzone.com Inflammation, Inflammatory Disorders, and Wound Healing 19 2. Important antiphospholipid antibodies include anticardiolipin (false-positive VDRL and RPR syphilis screening tests), anti-β2-glycoprotein I, and lupus anticoagulant (falsely-elevated PTT). F. Antiphospholipid antibody syndrome is characterized by hypercoagulable state due to antiphospholipid antibodies (especially lupus anticoagulant). 1. Results in arterial and venous thrombosis including deep venous, hepatic vein, placental (recurrent pregnancy loss), and cerebral (stroke) thrombosis 2. Requires lifelong anticoagulation 3. Associated with SLE; however, more commonly occurs as a primary disorder G. Antihistone antibody is characteristic of drug-induced lupus. 1. Procainamide, hydralazine, and isoniazid are common causes. 2. ANA is positive by definition. 3. CNS and renal involvement are rare. 4. Removal of drug usually results in remission. H. First-line treatment includes avoiding exposure to direct sunlight and glucocorticoids for flares; other immunosuppressive agents are useful in severe or refractory disease. I. 5-year survival is > 90%; renal failure, infection, and accelerated coronary atherosclerosis (occurs late) are common causes of death. III. SJÖGREN SYNDROME A. Autoimmune destruction of lacrimal and salivary glands 1. Lymphocyte-mediated damage (type IV HSR) with fibrosis B. Classically presents as dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia), and recurrent dental caries in an older woman (50-60 years)-"Can't chew a cracker, dirt in my eyes" 1. May progress to ulceration of corneal epithelium and oral mucosa C. Can be primary (sicca syndrome) or associated with another autoimmune disorder, especially rheumatoid arthritis 1. Rheumatoid factor is often present even when rheumatoid arthritis is absent. D. Characterized by ANA and anti-ribonucleoprotein antibodies (anti-SSA/Ro and anti-SSB/La) 1. Anti-SSA and anti-SSB are associated with extraglandular manifestations (e.g., neuropathy). 2. Pregnant women with anti-SSA are at risk for delivering babies with neonatal lupus and congenital heart block. 3. Anti-SSA and anti-SSB are also seen in a subset of patients with SLE (screen pregnant patients) E. Lymphocytic sialadenitis on lip biopsy (minor salivary glands) is an additional diagnostic criterion (Fig. 2.4C). F. Increased risk for B-cell (marginal zone) lymphoma, which presents as unilateral enlargement of the parotid gland late in disease course IV. SYSTEMIC SCLEROSIS (SCLERODERMA) A. Autoimmune disorder characterized by sclerosis of skin and visceral organs 1. Classically presents in middle-aged females (30-50 years) B. Fibroblast activation leads to deposition of collagen. 1. Autoimmune damage to mesenchyme is possible initiating event. 2. Endothelial dysfunction leads to inflammation (increased adhesion molecules), vasoconstriction (increased endothelin and decreased NO), and secretion of growth factors (TGF-β and PDGF). 3. Fibrosis, initially perivascular, progresses and causes organ damage.  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.