Gout

Definition: It is a metabolic disease associated with overproduction of uric acid.

Where does this uric acid come from?

It is the end product of purine metabolism

Normal concentrations :

 Uric acid in serum of adults is 3-7 mg/dl.

Daily excretion 500-700 mg.

Abnormal Concentration:

Any rise in the serum levels of uric acid from the normal range is hyperuricemia. In severe hyperuricemia crystals of sodium urate (soluble form of uric acid) gets deposited in joints. These deposits are called as Tophi which cause an inflammatory condition called as Arthritis.

  1. Alcohol consumption
  2. High living
  3. Over eating
  4. Lead posioning → Kidney damage → decreased uric acid excretion → gout
  5. Diet of meat and sea foods.

Types Of Gout:

Reasons:

Increased purine nucleotide synthesis

Metabolic defects

  1. PRPP synthetase: Variant forms of this enzyme which are not subjected to feedback mechanism have been detected.
  1. PRPP glutamlyamidotransferase : Lack of feedback control of this enzyme leads to elevated synthesis.
  1. HGPRT deficiency: Causes Lesch Nyhan Syndrome

    Characterised by:

  • decreased utilization of purines by salavage pathway leading to PRPP accumulation and diversion for purine nucelotides.
  • Any defect in the purine salvage pathway leads to decreased levels of IMP and GMP causing impaired feeback regulation of their production.
  1. Gulcose 6 Phosphate Deficiency: This leads to increased utilization of G6PD by hexose monophosphate shunt resuting in elevated levels of ribose-5- phosphate and PRPP and ultimately leading to purine overproduction.
  1. Elevation of glutathione reductase: Generates more NADP+ utilized by HMP shunt leading to increased ribose-5-phosphate and PRPP synthesis.

(First three enzymes directly involved,

Last two indirectly)

Caused due to increased degradation of nucleic acids seen in cases of cancer , psoriasis , and increased tissue breakdown.

Uric Acid Pool In Gout:

Isotope N15 administered

Normal subjects : 1200 mg

Gout patients: 3000 mg

 

Treatment of Gout:

  1. Allopurinol : A drug which is a structural analogue of hypoxanthine that competitively inhibits the enzyme Xanthine oxidase

Allopurinol  → Alloxanthine (oxidation by xanthine oxidase)

Alloxanthine is a more effective inhibitor

This is also called suicide inhibition.

 

  1. Restriction in dietary intake of purines and alcohol.

 

  1. Consumption of plenty of water.

 

  1. Anti-Inflammatory Drugs: Colchicine , Phenylbutazone , Indomethacin etc..

 

Pseudogout: Depostion of Calcium Pyrophosphate Crystals in joints.

 

-Shivani Indrekar

Mimer Medical College

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