Uric acid ( urate) Dr.Ghulam Murtaza Resident Chemical Pathology DIMC
In human it’s a major product of catabolism of purine nucleoside ,adenosine & guanine . Purine from the catabolism of dietary nucleic acid is is directly converted int uric acid Daily synthesis rate of uric acid is approx . 400mg , dietary source contribute another 300mg .
In men ,consuming a free diet ,the total body pool of uric acid is 1200mg ,& in women it is estimated to 600mg By contrast Patient with Gouty arthritis, & tissue deposit of uric acid pool may increase up to 18000-30,000 mg . It is a weak organic acid that under physiologic conditions exists mainly as a monosodium salt.
Synthesis First step is formation of 5” phosphoribosyl amine Step is controlled by phosphoribosyl pyrophosphate (PRPP) The first Purine nucleotide formed by ring closure is INOSINE MONO PHOSPHATE , ADENOSINE & GAUNOSINE are derived from IMP.
Salvage pathways: Reutilization of major purine bases like Adenine ,Guanine ,& hypoxanthine . In which phosphorribolysation of the free bases leads to resynthesis of the respective nucleotide mono phosphate Adenine is converted into converted into adenosine mono phosphate thru the action of (APRT) adenosine phosphoribosyl transferase .
Renal excretion of uric acid
Uric acid is dibasic ,having two pka first pka value is 5.75 ,above this pH uric acid exits chiefly as URATE ION . is more soluble than uric acid, In kidney tubules mostly. 2 nd pka In blood ph. above 5.75 it exits in monosodium urate ,ten time more soluble than uric acid
two most common clinical use for urate is Gout & determination of therapy adequacy . Hyperuricemia : . Increased serum uric acid levels above 7 mg/dl in Men & above 6 mg/dl in women. Classification of hyperuricemia Serum uric acid. 24 hours urine uric acid Over Production Under excretion Serum uric acid high high Urine uric acid high Normal /low
Hyperuricemia
Gout : Is a metabolic disorder of purine catabolism, resulting in overproduction of uric acid so deposition of Monosodium urate crystals (MSU ) occurs . Classification of gout : Primary gout Secondary gout Primary gout : due inborn defect in purine metabolism or inherited defects in renal tubular secretion of urate . Secondary gout : attributed to several identifiable causes like CKD,DM,DKA,Diuretics ,& Lactoacidosis
Stages of classic Gout
Hypouricemia
Kidney stones
Analytical Method
Principles of the procedure
In our lab
Reference intervals Increase gradually with age 20-60 about 10 % . Pregnancy . In normal level In urine 32 weeks 36 weeks 38 weeks 1.9-5-5 mg/dl 2.0- 5.8 2.7- 6.5 mg/dl Men Women 3.5 – 7.2 mg/dl 2.6- 6.0 mg/dl Diet containing purines Purines free diet 250mg/dl – 750mg /dl Less than 400 mg/dl
Reference Tietz 6 th edition volume 1 st Chemical pathology for beginners ( Dr .Amir Ijaz )