Gout
In gout the urate crystals accumulates in synovial fluid. The above conditionl eads to inflammation mediated acute arthritis. The solubility of uric acid is lowered to 4.5 mg/dl at 30°C. Thus the uric acid is deposited in cooler zone such as tophi. Deposition of uric acid crystrals are noticed with increase in excretion of uric acid in urine. The deposition of uric acid crystals leads to calculi or stone formation. The gout may be either primary or secondary in nature .
Primary gout
Primary gout may show familial incidence and are about 1:500 in total population. About 10 % of primary gout are idiopathic in nature. The main cause of primary gout is because of error in synthesis of enzymes such as
(a) 5-phosphoribosyl amido transferase
The error in 5-phospho ribosyl amido transferase leads to over production of purine nucleotides. Even though the abnormal nucleotide is active, they are not sensitive to feedback inhibition by inhibitory nucleotides.
(b) Phospho ribosyl phyrophosphate (PRPP) synthetase The abnormal leads to increase and accumulation of PRPP and are Xlinked recessive in inheritance.
(c) Glucose-6-phosphatase
Deficiency in glucose-6-phosphatase leads to a glycogen storage disease called as Gierke’s disease. In this case more glucose is channeled to the pentose-phosphate shunt pathway, leading increased availability of ribose5- phosphate. As a result of this there will be a increase in PRPP formation.
(d) Glutathione reductase
Abnormality in glutathione reductase leads to increased production of ribose-5-phosphate and thereby increases in PRPP.
Secondary gout
Secondary gout is characterized by increase in uric acid production and reduced
excretion rate. The increase in uric acid is due to increase in turnover rate of nucleic acids. The increase in nucleic acid turnover rate are seen in
(a) Rapidly growing malignant tissues
(b) Increase in tissue breakdown after treatment of large malignant tumors
(c) Increase in tissue damage due to trauma
(d) Increase in rate of catabolism as in starvation
Reduction in excretion rate as encountered in secondary gout during
(a) Renal failure
(b) Treatment with thiazide diuretics
(c) Interfrence of tubular secretion due to lactic acidosis and keto-acidosis.
