Zinc deficiency plasma concentrations

Fdee Kand Kiechgessnee M (1996a) Effects of zinc deficiency on concentrations of lipids in liver and plasma of rats. Trace Flements and Electrolytes 13 60-65. 

An endemic zinc deficiency syndrome among young men has been reported from Iran and Egypt, and is characterized by retarded growth, infantile testes, delayed sexual maturation, mental lethargy, anemia, reduced concentration of zinc in plasma and red cells, enlarged liver and spleen, and hyperpigmentation oral supplementation of 30 mg Zn daily had a prompt beneficial effect (Prasad 1979 Elinder 1986). 

Cows and calves fed low-zinc diets of 25 mg Zn/kg ration showed a decrease in plasma zinc from 1.02 mg/L at start to 0.66 mg/L at day 90 cows fed 65 mg Zn/kg diet had a significantly elevated (1.5 mg Zn/L) plasma zinc level and increased blood urea and plasma proteins (Ram-achandra and Prasad 1989). Biomarkers used to identify zinc deficiency in bovines include zinc concentrations in plasma, unsaturated zinc-binding capacity, ratio of copper to zinc in plasma, and zinc concentrations in other blood factors indirect biomarkers include enzyme activities, red cell uptake, and metallothionein content in plasma and liver (Binnerts 1989). 

Domestic sheep (Ovis aries) fed a low-zinc diet (2.2 mg Zn/kg DW diet) for 50 days, when compared to those fed a zinc-adequate diet (33 mg Zn/kg DW diet), excreted less zinc (<4 mg daily vs. 23 to 25), consumed less food (409 g daily vs. 898), and had lower plasma zinc concentrations (0.18 mg/L vs. 0.53 to 0.58) a reduction in plasma alkaline phosphatase activity and an increase in plasma zinc binding capacity were also noted (Khandaker and Telfer 1990). Sensitive indicators of zinc deficiency in lambs include significant reductions in plasma alkaline phosphatase activity and plasma zinc concentrations signs were clearly evident in lambs fed 10.8 mg Zn/kg DW diet for 50 to 180 days (Vergnes et al. 1990). A normal diet for lambs contains 124 to 130 mg Zn/kg DW ration vs. 33 for adults (Vergnes et al. 1990). One recommended treatment for zinc-deficient sheep is ruminal insertion of zinc-containing boluses every 40 days bolus zinc release is about 107 mg daily (Khandaker and Telfer 1990). 

Other workers have determined zinc in serum by direct dilution 87> 88). McPherson and George 89) determined total copper and zinc of red cells and the free copper and zinc of plasma and dialysis fluids of patients undergoing regular hemodialysis, using atomic absorption spectroscopy. Spry and Piper 90) determined zinc in whole blood and plasma in blood cells of iron deficient rats. The zinc concentrations were raised in the iron deficient rats. 

A number of important and, as yet, unexplained discrepancies are apparent in tissue zinc concentrations in this syndrome. Patients with chronic renal disease, with clinical signs and symptoms of zinc deficiency show consistently elevated red blood cell zinc levels (40-42) whereas plasma zinc concentrations have been reported as either low, normal or elevated (40-44). Patients with Kwashiorkor and symptoms of zinc deficiency have... 

Interpretation of plasma concentrations of retinol is confounded by the fact that both RBP and transthyretin are negative acute phase proteins, and their synthesis falls, and hence the plasma concentration of retinol fall, in response to infection. Similarly, both protein-energy malnutrition and zinc deficiency result in a low plasma concentration, despite possibly adequate liver reserves as a result of impaired synthesis of RBP. 

Although there are still some discrepancies in the hterature regarding zinc levels in dialysis patients, most studies have found decreased levels of the element in serum [64,65] and muscles whereas the levels in bone [63] and other tissues seem to be normal or even increased suggesting translocation of the element in uremia. The dialysis treatment itself seems to have little or no effect on the serum zinc concentrations. Zinc deficiency in uremic patients has been associated with anorexia, disturbances in taste and sexual performance [66] whereas decreased plasma zinc seem to correlate with erythrocyte superoxide dismutase levels [67]. As evaluated by Tiirk et al. [68], zinc supplementation did not have any effect on the restoration of immune parameters or enhancement of the antibody response to multivalent influenza vaccine in hemodialysis patients. On the ofher hand however, has zinc supplementation been reported an effective means of improving serum levels of zinc and cholesterol in the hemodialysis patient [69]. 

In patients with renal failure, the occurrence of conditioned zinc deficiency may be the result of a mixture of factors, which at present are ill defined. If 1,25-dihydroxycholecalciferol plays a role in the intestinal absorption of zinc, an impairment in its formation by the diseased kidney would be expected to result in malabsorption of zinc. It seems likely that plasma and soft tissue concentrations of zinc may be "protected in some individuals with renal failure by the dissolution of bone which occurs as a result of increased parathyroid activity in response to low serum calcium. In experimental animals, calcium deficiency has been shown to cause release of zinc from bone. In some patients who are successfully treated for hyperphosphatemia and hypocalcemia, the plama zinc concentration may be expected to decline because of the deposition of zinc along with calcium in bone. Thus, in the latter group in particular, a diet low in protein and high in refined cereal products and fat would be expected to contribute to a conditioned deficiency of zinc. Such a diet would be low in zinc. The patients reported by Mansouri et al. (37), who were treated with a diet containing 20-30 g of protein daily and who had low plasma concentrations of zinc, appear to represent such a clinical instance. Presumably the patients of Halsted and Smith (38) were similarly restricted in dietary protein. In other patients with renal failure whose dietary protein was not restricted, plasma zinc concentration were not decreased. Patients on dialysis had even higher levels, particularly... 

Thus changes in the zinc concentration of plasma, erythrocytes, leucocytes, and urine and changes in the activities of zinc-dependent enzymes such as alkaline phosphatase, RNase in the plasma, and deoxythymidine kinase in the tissue during the zinc restriction phase, appear to have been induced specifically by a mild deficiency of zinc in the volunteers. One unexpected finding was with respect to plasma ammonia level which appeared to increase during the zinc-restricted period. We recently have reported a similar finding in zinc deficient rats (88). This... 

As we saw in Chapter 7, there are several plasma membrane zinc uptake transporters in yeast. Within the cell, a number of other proteins are involved in zinc transport within the cell. S. cerevisiae is unusual in that it does not appear to have any plasma membrane zinc efflux transporters. This is to a large extent compensated by the capacity of the vacuole to serve as a major site of zinc sequestration and detoxification, enabling wild-type cells to tolerate exogenous zinc concentrations as high as 5 mM. The zinc stored in the vacuole can attain millimolar levels, and can be mobilised under zinc-deficient conditions for use by the cell. Vacuolar zinc uptake is mediated by two members of the cation diffusion facility CDF family, Zrcl and Cotl (Fig. 8.16). 

Bradley JE, Baumgartner RJ Subsequent mental development of children with lead encephalopathy, as related to type of treatment. J Pediatr 53 311-315,1958 Bruhl HH, Foni J, Lee YH, et al Plasma concentrations of magnesium, lead, lithium, copper, and zinc in mentally retarded persons. American Journal of Mental Deficiency 92 103-111, 1987... 

The functional and structural abnormalities of zinc deficiency are associated with a wide variety of biochemical changes in the blood and tissues. As the zinc-deficient state develops, there is usually a small decline in the zinc concentration of several tissues, including liver, kidney, heart, bone and muscle, and a more marked decline in the blood plasma and pancreas and in hair, wool and feathers. Measurement of zinc concentrations in the blood serum or plasma serves as the most widely used indicator of zinc deficiency, but it lacks positivity and sensitivity as a diagnostic criterion. 

It is important to distinguish between changes in zinc metabolism which occur as a secondary effect of disease, injury, infection and drug therapy and alterations caused by a primary nutritional zinc deficiency. There is confusion in the literature because a number of unrelated causes can temporarily lower the concentration of zinc in plasma, and this is reported uncritically as evidence of nutritional depletion. Since a high proportion of zinc in plasma is albumin bound, any circumstance which lowers plasma albumin wiil also lower plasma zinc. For example, the changes seen in severe liver disease are primarily caused by a failure of hepatic synthesis of plasma proteins such as albumin. This results in problems in the distribution of zinc and eventual tissue depletion. It is questionable whether zinc supplementation of diet is worthwhile without some restoration of hepatocyte function, by effective treatment of the underlying disease (Mills et al., 1983). 

Acute zinc deficiency, with the signs of skin disease, abdominal pain and the other effects listed in Table 2, is seen at plasma zinc concentrations of less than 0.5 mg/L. The adults who developed the acrodermatitis-like condition during prolonged IVN had plasma zinc levels of 0.3-0.5 mg/L at the time when they began to gain body weight. 

This is likely to be a cause where the primary change is in the plasma albumin concentration and is not due to zinc deficiency per se. 

The test usually conducted to determine body zinc is the measurement of plasma zinc concentration. However, plasma zinc concentrations do not seem to reflect the concentration found in the liver parenchyma (Goksu Ozsoylu, 1986 Sato et al., 2005). This may be explained by the fact that there are very efficient homeostatic mechanisms to correct plasma or serum zinc deficiencies, which makes it difficult to diagnose marginal deficiency by using this method. Therefore, the investigation of zinc concentration in liver tissue is important. 

Zinc status is known to affect retinoid levels in the circulation [106,107]. It has been proposed that zinc plays a regulatory role in the synthesis of RBP in the liver. Zinc deficient rats have been shown to have a reduced rate of hepatic RBP synthesis [107], lower levels of plasma RBP-ROH and lower hepatocyte concentrations of RBP when compared with pair-fed zinc-sufficient rats [108]. In humans, a linkage between retinoid and zinc status has not been conclusively demonstrated in either observational or cross-sectional studies or through intervention trials... 

The prevalence of marginal zinc deficiency in human populations is unknown because of the lack of a good means of assessing zinc status. Measurement of plasma zinc is straightforward, but it does not serve as a reliable indicator of zinc status. Plasma zinc is a quantitatively minor pool that can be easily influenced by minor shifts in tissue zinc. Plasma concentrations do not fall with decreasing dietary intake, except at very low intakes. Plasma zinc can also be affected by factors unrelated to zinc status (e.g., time of day, stress, and infection). Cellular components of blood can be assayed, but erythrocyte concentrations of zinc are maintained in deficient states and variable results have been found with leucocytes. Hair zinc concentrations may reflect available zinc but will also depend on the rate of hair growth. 

Hypoproteinemia may result in low levels of serum calcium, ceruloplasmin, and transferrin. Because losses of iron are at most 0.5-1.0 mg/24 hr, even with the heaviest proteinuria, other factors must operate to produce iron deficiency and microcytic hypochromic anemia. Although the copper-binding protein ceruloplasmin is lost in the urine in nephrotic subjects and its plasma levels are low, plasma and red cell copper concentrations are usually normal. Zinc circulates mainly bound to albumin and also to transferrin, and thus the reported reduction zinc concentration in plasma, hair, and white cells in nephrotic patients is not surprising. 

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