Pathophysiology of Gout

Hyperuricemia and Gout: etiology, types, pathogenesis, sign and symptoms

1. gout Pathophysiology Nem Kumar Jain MS (Pharm.) Pharmacology & Toxicology Assistant Professor, School of Pharmacy ITM University Gwalior

2. Gout Metabolic disease characterized by Monosodium urate crystal deposition within or around joints which results in inflammation in joints and surrounding tissue. Clinical appearance: Acute inflammatory arthritis Hyperuricemea Uric acid nephrolithiasis Commonly mono-articular (primarily affects metatarso -phalangeal joint (MTP) of big toe) Other locations for urate crystal deposition Elbows Knees Feets Ear pinna (helix of the ear) Etiology : Hyperuricemia (blood uric acid level > 6.8 mg/dl) Hyperuricemia is a condition when blood serum uric acid level gets increased Normal plasma uric acid level male: 3-7 mg/dl, Female: 2-6 mg/dl

3. Uric acid is product of purine metabolism Gout is of two types – Primary gout Secondary gout Primary gout : it is an inborn error of metabolism of purine due to over production of uric acid. This is mostly related to increased synthesis of purine nucleotides. Secondary gout : secondary hyperuricemia is due to various disease causing increased synthesis or decreased excretion of uric acid. Factors: Diseases because of defects of purine metabolism Lesch-Nyhan syndrome: partial or complete deficiency of HGPRT enzyme Severe combined immunodeficiency disease (SCID): deficiency of Adenosin deaminase Superactivity of Phosphoribosyl pyrophosphate synthetase activity Other Factors: cancer therapy, Dehydration, Lactic acidosis, starvation , Diuretic therapy Renal failure, Excessive purine intake , Alcohol intake, Carbohydrate ingestion

4. Diet rich in purines: Red meat and organ meats ( eg. liver) Yeasts and yeast extracts ( eg. beer and alcoholic beverages) Asparagus, spinach, beans, peas, lentils, oatmeal, cauliflower and mushrooms Coffee, tea etc.

5. pathogenesis The inflammation in gout is triggered by precipitation of urate crystals in the joints, stimulating the production of cytokines that recruit leukocytes.

6. Morphology Acute arthritis  is characterized by a dense inflammatory  infiltrate that permeates the synovium and synovial fluid crystals are frequently found in the cytoplasm of the neutrophils  and are arranged in small clusters in the synovium They are long,  slender, and needle-shaped, and are negatively birefringent synovium is edematous and congested, and it also contains scattered lymphocytes, plasma cells, and macrophages Chronic tophaceous arthritis: evolves from the repetitive  precipitation of urate crystals during acute attacks. The crystals  encrust the articular surface and form visible chalky deposits in  the synovium The synovium becomes hyperplastic,  fibrotic, and thickened by inflammatory cells and forms a pannus  that destroys the underlying cartilage. Tophi  in the articular cartilage, ligaments, tendons,  and bursae are pathognomonic of gout .They are formed  by large aggregations of urate crystals surrounded by an intense  foreign body giant cell reaction Gouty  nephropathy  refers  to  the  renal  complications  caused by urate crystals or tophi in the renal medullary  interstitium  or tubules. Complications include uric acid nephrolithiasis  and pyelonephritis.

7. Tophi

8. Sign and Symptoms Sudden onset of excruciating pain, localized hyperemia , warmth. Most first attacks are monoarticular; 50% occur in the first metatarsophalangeal joint. May become polyarticular if left untreated

9. Summary Food intake Cell breakdown Purines Uric acid HYPERURICAEMIA Kidney Soft tissue of the joints Other tissue Ear Overproduction Under excretion