Urine overproduction

The average human produces 600 to 800 mg of uric acid daily and excretes less than 600 mg in urine. Individuals who excrete more than 600 mg after being on a purine-free diet for 3 to 5 days are considered overproducers. Hyperuricemic individuals who excrete less than 600 mg of uric acid per 24 hours on a purine-free diet are defined as underexcretors of uric acid. On a regular diet, excretion of more than 1,000 mg per 24 hours reflects overproduction less than this is probably normal. 

Hyperuricemia may be produced by overproduction of uric acid or under-excretion of uric add by the kidneys. Kyperuricemia may progress to acute and chronic gouty arthritis if uric acid (monosodium urate) is deposited in joints and surrounding soft tissue, where it causes inflammation, Uric add is produced from excess endogenous purines as shown in Figure 1-18-5, and is also produced from dietary purines (digestion of nucleic acid in the intestine) by intestinal epithe-lia. Both sources of uric acid are transported in the blood to the kidneys for excretion in urine. 

The hormones of the pituitary gland participate in the control of reproductive function, body growth, and cellular metabolism deficiency or overproduction of these hormones disrupts this control. Clinical use of protein hormones in the past was limited because preparations had to come from glands or urine. The ability to prepare at least some of these hormones in large quantities by recombinant DNA techniques and the development of more stable analogues that can be injected in a depot form permit increased and more effective use of these hormones. 

Acetone is volatile and is exhaled, and in uncontrolled diabetes, the breath has a characteristic odor sometimes mistaken for ethanol. A diabetic individual who is experiencing mental confusion due to high blood glucose is occasionally misdiagnosed as intoxicated, an error that can be fatal. The overproduction of ketone bodies, called ketosis, results in greatly increased concentrations of ketone bodies in the blood (ketonentia) and urine (lcetonuria). 

A 42-year-old male cancer patient undergoing radiation therapy develops severe pain in his right big toe. Laboratory analyses indicate an elevated serum uric acid level and urate crystals in his urine. This patient s pain is caused by the overproduction of the end product of which of the following metabolic pathways ... 

Several relatively common disorders result in aldosterone secretion abnormalities and aberrations of electrolyte status. In Addison s disease, the adrenal cortex is often destroyed through autoimmune processes. One of the effects is a lack of aldosterone secretion and decreased Na+ retention by the patient. In a typical Addison s disease patient, serum [Na+] and [CL] are 128 and 96 meq/L, respectively (see Table 16.2 for normal values). Potassium levels are elevated, 6 meq/L or higher, because the Na+ reabsorption system of the kidney, which is under aldosterone control, moves K+ into the urine just as it moves Na+ back into plasma. Thus, if more Na+ is excreted, more K+ is reabsorbed. Bicarbonate remains relatively normal. The opposite situation prevails in Cushing s disease, however, in which an overproduction of adrenocorticosteroids, especially cortisol, is present. Glucocorticoids have mild mineralocorticoid activities, but ACTH also increases aldosterone secretion. This may be caused by an oversecretion of ACTH by a tumor or by adrenal hyperplasia or tumors. Serum sodium in Cushing s disease is slightly elevated, [K+] is below normal (hypokalemia), and metabolic alkalosis is present. The patient is usually hypertensive. A more severe electrolyte abnormality is seen in Conn s syndrome or primary aldosteronism, usually caused by an adrenal tumor. Increased blood aldosterone levels result in the urinary loss of K+ and H+, retention of Na+ (hypernatremia), alkalosis, and profound hypertension. 

Enzymes of higher molecular weight, which preclude filtration, enter the urine from renal proximal tubuli. They are also indicators of Cd-induced renal damage, which confirm renal tubular damage even in clinical states where the overproduction of LMW... 

Additional markers of catecholamine overproduction have been employed to improve the biochemical detection of neuroblastomas. Free dopamine may be abnormal in urine from neuroblastoma patients with VMA and HVA excretion. Combined testing for VMA, HVA, and dopamine may therefore improve tumor detection, and in 1993 an international consensus report on neuroblastoma diagnosis added dopamine to the Hst of acceptable measurements to document the adrenergic nature of the tumor. Plasma measurements of dopamine and L-dopa, the amino acid precursor of dopamine, may also have clinical value and allow the alternate use of plasma. Measurement of methylated metabolites, especially normetanephrine, has also been explored. When urinary normetanephrine, metanephrine, methoxytyra-mine, dopamine, norepinephrine, VMA, and HVA were measured, clinical sensitivity for detection of neuroblastomas was 97% to 100% when results of normetanephrine testing were coupled either with VMA in the infants or with HVA in children greater than age 1. Even with an extended panel of catecholamines and metabolite measurements, a low incidence of nonsecreting tumors continues to be identified and should be considered in the interpretation of a negative test result. 

Most patients with autonomous aldosterone overproduction are hypokalemic, but most patients with hypokalemia do not have primary aldosteronism. In hyperaldosteronism, urinary potassium excretion is inappropriately high, and a random urine potassium >30mraol/L is usually indicative of primary aldosteronism or some type of mineralocorticoid excess condition. If hypokalemia can be shown to he due to nonrenal potassium loss, the diagnosis of aldosteronism does not need to be considered further. ... 

Secondary (or acquired) gout is caused by seemingly unrelated disorders. These conditions may cause hyperuricemia by either overproduction of uric acid or its undersecretion by the kidneys. For example, leukemia patients overproduce uric acid either because of massive cell destruction or the chemotherapy treatment required to destroy the cancerous cells. Hyperuricemia also results when certain drugs interfere with the renal secretion of uric acid into the urine. Patients with lead poisoning are also likely to develop gout because of renal damage. 

A patient with a tumor of the adrenal medulla experienced palpitations, excessive sweating, and hypertensive headaches. His urine contained increased amounts of vanillylmandelic acid. His symptoms are probably caused by an overproduction of which of the following ... 

The biochemical alteration includes overexretion of uric acid in urine (two or three times above normal). The hyperuricuria results from a massive overproduction of uric acid (two or three times above what is observed in gout patients). Studies of the incorporation of [ " Cjglycine into urinary uric acid clearly illustrate the uric acid overproduction, which is 100 and sometimes 200 times as great as in normal individuals. 

I shows that uric acid was almost completely absent from or urine, confirming the severity of the enz3mie defect in either direction. No significant increment was noted until guanine therapy commenced. Table I also shows the gross purine overproduction characteristic of this defect with a total purine end product of 2.4-3.8 mmol/mmol creatinine compared with <1.0 for controls. 

Plasma and urinary purines Uric acid, xanthine and hypoxanthine in plasma and urine in Family B are also given in Table 1. The plasma and urine uric acid levels were greatly increased in NB and his mother (CB) when compared with appropriate controls. Urinary hypo-xanthine levels were excessive in both (Table 1). The urine purine creatinine ratio confirmed gross purine overproduction in both, that in the mother (CB) being approximately twice normal for a healthy adult female. Values in the father (JB) were normal for age and sex. 

Detailed study revealed that she excreted 76O mg of urate per 2k hours in her urine and that her urate production amounted to 853 mg/ 2k hours. She also incorporated excessive glycine into urate and had a urate clearance of twice normal. This woman therefore demonstrates that the serum urate concentration may be normal in the presence of urate overproduction, provided urate excretion is able to keep pace with the urate production (Observation 3). 

Another patient with HGPRTase deficiency and minimal neurological signs presented with intractable gout at the age of 35 years and developed an episode of acute renal failure when his fluid intake was reduced below 3 litres/2U hours. This was attributed to the formation of uric acid crystals within his renal tubules so that an intense alkaline diuresis was instituted, resulting in a urine volume which, over one 2k hour period, exceeded 15 litres. This succeeded, however, in completely reversing his acute renal insufficiency and, when a regular urine volume of 5 litres/day was maintained, his renal function returned to normal. His usual 2k hour urinary urate excretion exceeded 2.5 g. Thus, an acute deterioration of renal function may occur in urate overproduction, which may be completely reversed by an intense diuresis (Observation k). 

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