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Gout
 

Gout

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    Gout Gout Presentation Transcript

    • GOUT Dr. Mohanad
    • Purines Purines are natural substances found in all of the body's cells, and in virtually all foods. The reason for their widespread occurrence is simple: purines provide part of the chemical structure of our genes and the genes of plants and animals
    • When cells die and get recycled, the purines in their genetic material also get broken down. Uric acid is the chemical formed when purines have been broken down completely.
    • Hyperuricemia  The condition when there are high concentrations of uric acid in the blood.  Serum levels of uric acid are >7mg/dL (Normally, 2.4-6mg/dL in females; 3.4- 7mg/dL in males)  At such a high level, uric acid tends to aggregate and form crystals  Primary Hyperuricemia: an innate defect in purine metabolism and/or uric acid excretion  Secondary Hyperuricemia: high uric acid levels due to medications/medical conditions such as diabetic ketoacidosis, psoriasis, chronic lead poisoning
    • Most uric acid dissolves in blood and travels to the kidneys, where it passes out in urine.  If your body produces too much uric acid or doesn't remove enough if it, you can get sick. High levels of uric acid in the body is called Hyperuricemia.
    • Purine nucleotides hypoxanthine xanthine Uric acid Xanthine oxidase Alimentary excretion Urinary excretion Tissue deposition in excess Urate crystal microtophi Phagocytosis with acute inflammation and arthritis uricosurics colchicine NSAID Allopurinol Oxypurinol
    • Uric Acid Uric acid is the end product in purine metabolism Excretion of uric acid removes nitrogenous wastes from body 2/3 of uric acid made is excreted via kidneys; 1/3 via GI tract Urate: protonated form of uric acid
    •  Uric acid can accumulate due to:  Overproduction of purine nucleotides  Enhanced cell turnover (purine degradation)  Decreased in purine salvage pathway  Underexcretion of uric acid  Predisposition to many diseases  People may live with elevated uric acid levels without experiencing any symptoms
    • GOUT Gout and gouty arthritis Transient attacks of acute arthritis initiated by crystallization of urates and neutrophils, followed by chronic gouty arthritis with tophi in joints and urate nephropathy Sites: 50% have initial attack in first metatarsophalangeal joint; also ankles, heels, knees, wrists, fingers, elbows
    • Gout Affects less than 0.5% of the population. It is a common condition, presenting in 1-4% of adult men. Due to familial disposition, incidence may be as high as 80% in families affected by disorder.
    • Alcohol and Gout alcohol metabolism contributes to urate retention some red wines contain purines or oxypurines, which lead to an increased purine load alcohol may contribute to obesity which is associated with under excretion of uric acid Patients with a history of gout are advised to drink plenty of fluid, approximately 2 litres per day (nonalcoholic).
    • GOUT Primary gout (90%): idiopathic with overproduction of uric acid Hyperuricemia in the absence of other disease Asymptomatic hyperuricemia can precede gout Impaired secretion by kidneys
    • Secondary gout (10%): increased nucleic acid turnover due to chronic renal disease, HGPRT deficiency( hypoxanthine-guanine phosphoribosyl transferase deficiency) Tumors Leukemias Lymphomas After chemotherapy Alcoholism Accelerated ATP catabolism
    • "se co n da ry go u t" H G P R T E n zym a tic d e ficie n cy "se co n d a ry g o u t" L e u ke m ia In crea se d n ucle ic a cid tu rn o ve r "p rim a ry g o u t" U n kn o w n d efe ct ca u sin g d e cre a se d excre tion H yp e ru rice m ia
    • GOUT Arthritis: synovial fluid is poorer solvent for sodium urate than plasma, so with hyperuricemia.  Urates in joint fluid crystallize, particularly in ankle due to lower temperature; crystals develop in synovial lining cells, stimulate formation of antibodies, which accelerates formation of new crystals. Release of crystals attracts neutrophils and complement, (generates c3a, c5a, attracts more neutrophils), Releases free radicals, releases lysosomal enzymes
    • GOUT  This will eventually causes acute arthritis that last days to weeks without treatment; repeated attacks of acute arthritis cause  Renal failure, urate stones
    •  Risk factors for gout with Hyperuricemia are:  Age > 30 years,  Male, familial history of gout,  Alcohol use,  Obesity,  Thiazide administration(reduce the clearance of uric acid)
    • Pathogenesis Enzymatic deficiencies and increased nucleic acid turnover account for only 10% of gout patients. Remaining 90% are “primary gout” due to an unknown defect limiting the ability to excrete uric acid.
    • Pathogenesis Uric acid normally dissolves in plasma Poorly soluble in synovial fluid and precipitates out as MSU crystals (monosodium urate crystals )
    • Pathogenesis Hyperuricaemia  May be asymptomatic  Deposition of monosodium urate crystals in synovial tissue (contain various Ig’s, complement, fibrinogen, fibronectin)  Complement activated  Neutrophils phagocytose & lyse crystals  Release chemical mediators (e.g. TNF-α; IL-1)  ACUTE GOUTY ARTHRITIS  May resolve & become asymptomatic (INTERCRITICAL GOUT)
    • May have recurrent episodes  Large deposits of chalky white urate  tophi  Chronic granulomatous inflammatory condition  Fibrosis of synovium  Erosion of articular cartilage  CHRONIC TOPHACEOUS ARTHRITIS  ankylosis  Tophi may be deposited in soft tissue  Can ulcerate if sub-cutaneous
    • Pathogenesis of Renal Involvement Hyperuricaemia  Freely filtered by glomerulus, but reabsorbed in proximal convulated tubules  Precipitation in renal tubules  Tubule obstruction  Crystal formation in interstitium  Renal stones  Recurrent pyelonephritis
    • Crystal Studies Sodium urate crystals viewed under polarized light with a red plate makes those in the plane of the long axis of the red plate yellow, which indicates that they are negatively birefringent.
    • Clinical features Acute gouty arthritis Painful Involves one joint initially, then polyarticular Podagra (painful, red metatarsophalangeal joint) Tophaceous gout Development of tophi Chalky, cheesy, yellow-white, pasty deposits of monosodium urate crystals Helix and antihelix of ear Achilles tendon
    • Stages of Gout Asymptomatic Hyperuricemia Acute Attack Intercritical Period Chronic Gout
    • Acute gout Sudden onset Lasts 1-2w May be triggered by – trauma, operation, alcohol, exercise Sites 1st MTP (75%) Ankle Finger Olecranon
    • Chronic gout  Polyarticular gout  Tophi may form around joints and often also in the pinna of the ear and with time may ulcerate and discharge  May cause joint stiffness and deformity as a result of joint erosion  May cause renal damage due to deposition of urate crystals in the renal parenchyma  Urate urolithiasis occurs in 10%; rarely chronic urate nephropathy with renal failure may develop
    • Acute on chronic gout
    • Diagnosis More than one attack Maximum inflammation in one day Monoarthritis Redness First MTP involved Unilateral first MTP Unilateral tarsal attack Tophus Hyperuricemia Asymmetric swelling MSU crystals in joint fluid Joint fluid culture negative
    • Diagnosis Based on history and physical examination Confirmed by arthrocentesis Urate crystals: needle-shaped negatively birefringent either free floating or within neutrophils & macrophages. Uric acid level non specific. 30% may show normal level Urine collection:
    • GOUT Gross: chalky white appearance of gouty deposits Micro: early - edematous synovium with acute and chronic inflammatory infiltrate  Late - tophi (large aggregates of urate crystals, granulomatous inflammation, hyperplastic fibrotic synovium); Gout crystals are long, slender, needle shaped, but difficult to visualize with routine staining because they are dissolved during formalin processing (crystals are water soluble); easier to identify on scrape or with alcohol fixation
    • GOUT With chronic disease, urate deposits may be present in soft tissue, ligaments, skin Gouty deposits may be surrounded by fibrous tissue and be rimmed by histiocytes and giant cells
    • Gout from sodium urate crystalsGout from sodium urate crystals deposited in joints.deposited in joints.
    • This is gout. Gouty arthritis results from deposition of sodium urate crystals in joints. The joint most often affected is the first MP joint (big toe) as seen here. Acute attacks are characterized by severe pain, swelling, and erythema of the joint.
    • Gout or pseudogout? Gout >40 small joints esp 1st MTP Severe joint pain swelling Uric acid crystals neg bifringent Rest, nsiad prohylaxis hyperuricaemia Pseudogout  Elderly  Large joints esp knee  Mod pain and swelling  Calcium pyrophosphate positively bifringent  Rest, nsaid, joint aspiration
    • Treatment Life style (food) Colchicine Prophylactic Probenecid & sulfinpyrazone Interfere with urate resorption Allopurinol Inhibitor of enzyme that converts the xanthine and hypoxanthine to uric acid