Download Uric acid stones:

Uric acid stones:
When the concentration of uric acid in urine exceeds its solubility at the urine
pH, uric acid changes from a compound dissolved in solution to an insoluble
precipitate. Urate stones are formed by one of three general mechanisms:
overproduction, increased tubular secretion, or decreased tubular
reabsorption.
Uric acid results as a relatively insoluble endproduct of purine metabolism.
The concentration of uric acid in plasma depends on dietary ingestion, de
novo purine synthesis, and uric acid elimination by the kidneys and intestine.
Normal uric acid excretion is shown in the table.
Diseases producing uric acid nephropathy or pure uric acid stones in children
are rare. They may be considered in 5 basic groups. The evaluation should be
directed at identifying 1 of the following:
Group 1: The patient may have deficiencies in hypoxanthine-guanine
phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase, or
xanthine dehydrogenase enzymes. Mutations for these gene products occur
as autosomal recessive, spontaneous, or X-linked. Assess for a history of
deficiency of these enzymes, family history of gout at a young age, renal
stones with uric acid in other family members, or glycogen storage disease. A
previous history of painful gross hematuria is requested in the proband.
Group 2: The patient may have tissue breakdown, which can produce large
amounts of uric acid that precipitate in the nephron. This group includes
children with primary leukemia and lymphoma. Other malignancies may
produce uric acid nephropathy such as lung cancer, breast cancer, and
pancreatic cancer; however, these conditions are very rare in children.
Group 3: These children have genetic defects in renal tubular urate
reabsorption. The defects are X-linked or sporadic, and these patients have
hyperuricosuria with hypouricemia. The high urinary urate concentration in the
scenario of low urine volume and low urine pH tends to promote
crystallization. Uricosuric drugs (eg, cellulose sodium phosphate, colchicine,
probenecid, sulfinpyrazone) inhibit renal tubular urate reabsorption, producing
hyperuricosuria.
Group 4: These children have hyperuricemia and hypouricosuria secondary to
decreased renal excretion. This is due to decreased tubular secretion of uric
acid rather than decreased filtered load. Children with familial juvenile gouty
nephropathy are in this group. This condition is inherited in an autosomal
dominant fashion. Several other children with similar pathology, which occurs
in an isolated sporadic fashion, are reported. Glycogen storage disease type I
is also in this category.
Group 5: These children develop hyperuricosuria with, or without,
hyperuricemia secondary to oral purine intake. Although unusual, this may
occur with a diet rich in purines (eg, children with cystic fibrosis taking in
enzymes rich in purines). It may occur in children on the ketogenic diet
because the increase in ketoacids probably competes with uric acid via
organic anion secretory transporters. Several drugs, such as
hydrochlorothiazide (HCTZ), inhibit uric acid excretion in a similar manner.
History:


When obtaining the history, attempt to identify factors associated with
hyperuricosuria such as the following:
o
Lesch Nyhan disease
o
Familial gout
o
Uricosuric medications
o
Renal insufficiency
o
Malignancy
o
Polycythemia
o
Hemolysis
o
Lead exposure
o
Purine disorders
o
Sarcoid
o
Glycogen storage disease type I
o
Congestive heart failure
o
Dehydration
Infants with urate crystalluria may have pink-to-orange areas in their
diapers after urination. If Serratia marcescens is also present, the
diaper may appear red
Causes: Uric acid stones are produced when the urinary uric acid
concentration is increased secondary to overproduction, increased renal
tubular urinary uric acid secretion, decreased renal tubular urinary uric acid
reabsorption, decreased urinary water content, or increased hydrogen ion
concentration.

Specific causes include the following purine enzyme defects, which
lead to overproduction and increased urinary uric acid concentration:
o
HGPRT deficiency
o
o

Other causes include increased nucleotide turnover secondary to cell
death.
o
o
o


PRPP synthetase overactivity
Glucose-6-phosphatase deficiency
Myeloproliferative and lymphoproliferative disorders
Hemolytic anemia
Cytotoxic drugs
Other causes include the following:
o
Excessive dietary purine intake producing increased urinary uric
acid concentration
o
Decreased glomerular filtration, renal tubular uric acid
reabsorption, or both producing increased uric acid
concentration in urine (eg, renal failure, acidosis, drugs, lead
nephropathy)
Dehydration produces decreased urine water content (ie, increased
urine solute concentration) and increases urinary uric acid
concentration.