Urine copper excretion

The chronic form of Wilson s disease is treated by oral chelating agents, such as penicillamine and trientine, that remove excess copper from tissue and increase urine copper excretion. Oral administration of zinc salts or ammonium molybdate, which block copper intestinal absorption, has also been successful. ... 

Treatment of active, symptomatic Wilson s disease is aimed at increasing urine copper excretion to eliminate excess copper from tissue. The primary therapy for Wilson s disease involves chelating agents such as o-penicillamine and trientine, which is now more widely used because of its lower rate of side effects. In patients with minimal symptoms or in asymptomatic family members, zinc is used to competitively inhibit copper absorption from the intestinal tract. Lifelong therapy with one of these types of treatment is required and is usually successful in limiting further damage. 

Urine copper excretion is markedly increased in patients with Wilson disease however, its usefulness in clinical practice is limited. The estimation of urinary copper excretion may be misleading due to incorrect collection of 24-h urine volume or to copper contamination. In presymptomatic patients urinary copper excretion may be normal, but increase after D-penicillamine challenge (Da Costa et al., 1992). This test is valuable in the diagnosis of Wilson disease with active Uver disease, but is unreliable to exclude the diagnosis in asymptomatic siblings (Muller et al., 2007). On the other hand urinary copper excretion is also increased in any disease with extensive hepatocellular necrosis. 

About 50% of copper in food is absorbed, usually under equitibrium conditions, and stored in the tiver and muscles. Excretion is mainly via the bile, and only a few percent of the absorbed amount is found in urine. The excretion of copper from the human body is influenced by molybdenum. A low molybdenum concentration in the diet causes a low excretion of copper, and a high intake results in a considerable increase in copper excretion (68). This copper—molybdenum relationship appears to correlate with copper deficiency symptoms in cattle. It has been suggested that, at the pH of the intestine, copper and molybdate ions react to form biologically unavailable copper molybdate (69). 

Increase in blood and urine Mo levels, increases in serum ceruloplasmin, increased xanthine oxidase activity (11) Increased uric acid, decreased copper excretion, high incidence of gout-like disease (11)... 

Uroporphyrins I and III are both excreted in small amounts in the urine. Another excretion product is coproporphyrin III, in which all of the carboxymethyl side chains have been decarboxylated to methyl groups. The feathers of the tropical touraco are colored with copper(II) complex of coproporphyrin III and this... 

Copper in plasma can be estimated following twenty-fold dilution with 0.1 normal HC1. Although few metals cause interference when using flame AAS [31] standards containing 6/xgCu per 100 ml should be made up in the plasma or mine equivalent [32]. Only very small amounts of copper are excreted in the urine of normal subjects and specimens are best aspirated undiluted. However, in Wilson s disease and especially during treatment urine copper may be high and appropriate dilution will be needed. 

Cupruria In pronounced liver cell decay, there is not only a rise in the copper value in serum, but more particularly in the amount of copper excretion in the urine. Cupruria of < 50 pg/day rules out the presence of Wilson s disease (differential diagnosis e.g. kidney disease). The penicillamine test has proved successful after administration of 600 mg penicillamine, copper excretion increases to > 300 pg/6 hr (> 600 pg/24 hr). However, it should be noted that this test may show similar positive results in cholestatic liver diseases. 

Confirmation The diagnosis is verified by laboratory parameters (determination of the serum values of copper and ceruloplasmin as well as of copper excretion in the urine, if necessary also by means of the penicillamine test) and by demonstration of the copper content of the liver, with simultaneous differentiation of existing liver damage. 

Between 0.5 and 2.0 mg of copper per day is excreted via bile into feces. Patients with cholestatic jaundice or other forms of hver dysfunction are therefore at risk of copper accumulation caused by failure of excretion. Copper losses in urine and sweat are <3% of dietary intalce. Urine copper output is normally less than 60pg/day. 

Very little copper is excreted in urine. Here the concentration values have little meaning the 24-hour excretion is shown in Table 4. The figures in this table were taken from the careful study of Butler and Newman (B33). Beam and Kunkel (B7) and Porter (P9) found similarly low urinary excretions. According to our own experience, the 24-hour urinary copper excretion does not exceed 40 ig in normal individuals. Others accept figures up to 60 or even 100 iig per 24 hours as normal (see references quoted in reference B33). 

P9. Porter, H., Copper excretion in the urine of normal individuals and of patients with hepatolenticular degeneration (Wilson s disease). Arch. Biochem. Biophys. 31, 262-265 (1951). 

Molybdenum and zinc are known antagonists of copper, so that high dietary doses of these elements can cause symptoms of copper deficiency. In the case of high doses of molybdenum, this is due to reduced resorption and increased copper excretion from the body in urine. Higher doses of dietary zinc lead to increased production of metallothionein in enterocytes, which leads to its retention in these cells, so that copper is released into the bloodstream to a lesser extent. 

The answer is 3 [III B 4 c IV E 3 a V F 3 VIIIC 3J. Of the choices presented, only arsenic toxicosis is not readily confirmed by detection of high concentrations In the blood. Arsenic in domestic animals has a high affinity for many epithelial tissues and is excreted rapidly in the urine. Copper accumulates in erythrocytes just prior to and during the acute hemolytic crisis. Iron is transported in the blood bound to transferrin, and both bound iron and total iron increase as dosage Increases. Selenium is present in both erythrocytes and serum or plasma and responds quickly to dietary or parenteral dosing. Lead is primarily associated with erythrocytes and is consistently elevated in lead poisoning. 

Treatment for Wilson disease consists of a diet low in copper along with Ufelong administration of penicillamine, which chelates copper, is excreted in the urine, and thus depletes the body of the excess of this mineral. 

The (n)-enantiomer of penicillamine is used clinically in man either as the hydrochloride or as the free amino acid [1], although the (L)-enantiomer also forms chelation complexes. Penicillamine is an effective chelator of copper, mercury, zinc, and lead, and other heavy metals to form stable, soluble complexes that are readily excreted in the urine [2,3]. 

Retention of radiocopper injected into humans is high only 10% is excreted within 72 h in urine and feces, and 50% in four weeks (Aaseth and Norseth 1986). Most (72%) of the unabsorbed copper is excreted in the feces primarily by way of the biliary duct, the salivary glands, or the intestinal mucosa a minor portion is excreted by way of sweat and menses (Schroeder et al. 1966 USEPA 1980 ATSDR 1990). In mammals, copper is excreted mainly via the bile in association with glutathione or unidentified high-molecular-weight molecules. However, the transport mechanisms of copper from liver cells into bile are essentially unknown (Aaseth and Norseth 1986). In rats, biliary excretion of copper is increased by increased flow of bile, increased body temperature, or administration of adrenal steroids (Sugawara et al. 1994). 

Because molybdenum is a copper antagonist, high levels of copper decrease the absorption of molybdenum. It is equally excreted in the urine and the faeces. 

Human volunteers who drank wine containing inorganic arsenic excreted methylarsonic and cacodylic acids in their urine (96). These two compounds also occur in the urine of copper smelters, the elevated arsenic content presumably coming from copper ores (97). Cacodylate ion forms when H34As04 is administered orally to dogs or hamsters (98-100). A Japanese group reported that various small animals will form methylar-sonate and cacodylate from H3ASO4 (101). On the basis of presently available data, it remains uncertain whether arsenic biomethylation occurs from the bodily processes of the mammals themselves or from microflora of the intestinal tract. 

The same investigators subsequently reported increased urinary excretion of copper and iron, as well as zinc, in patients receiving TPN (2). They also detected sugar-amine compounds in the TPN solutions and in the patients urine and plasma. 

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