Chapter 071. Vitamin and Trace Mineral Deficiency and Excess (Part 12) pps

Chapter 071. Vitamin and Trace Mineral Deficiency and Excess (Part 12) Zinc Zinc is an integral component of many metalloenzymes in the body; it is involved in the synthesis and stabilization of proteins, DNA, and RNA and plays a structural role in ribosomes and membranes. Zinc is necessary for the binding of steroid hormone receptors and several other transcription factors to DNA. Zinc is absolutely required for normal spermatogenesis, fetal growth, and embryonic development. Absorption The absorption of zinc from the diet is inhibited by dietary phytate, fiber, oxalate, iron, and copper, as well as by certain drugs including penicillamine, sodium valproate, and ethambutol. Meat, shellfish, nuts, and legumes are good sources of bioavailable zinc, whereas zinc in grains and legumes is less available for absorption. Deficiency Mild zinc deficiency has been described in many diseases, including diabetes mellitus, HIV/AIDS, cirrhosis, alcoholism, inflammatory bowel disease, malabsorption syndromes, and sickle cell disease. In these diseases, mild chronic zinc deficiency can cause stunted growth in children, decreased taste sensation (hypogeusia), and impaired immune function. Severe chronic zinc deficiency has been described as a cause of hypogonadism and dwarfism in several Middle Eastern countries. In these children, hypopigmented hair is also part of the syndrome. Acrodermatitis enteropathica is a rare autosomal recessive disorder characterized by abnormalities in zinc absorption. Clinical manifestations include diarrhea, alopecia, muscle wasting, depression, irritability, and a rash involving the extremities, face, and perineum. The rash is characterized by vesicular and pustular crusting with scaling and erythema. Occasional patients with Wilson's disease have developed zinc deficiency as a consequence of penicillamine therapy (Chap. 354). The diagnosis of zinc deficiency is usually made by a serum zinc level of <12 µmol/L (<70 µg/dL). Pregnancy and birth control pills may cause a slight depression in serum zinc levels, and hypoalbuminemia from any cause can result in hypozincemia. In acute stress situations, zinc may be redistributed from serum into tissues. Zinc deficiency may be treated with 60 mg elemental zinc, orally twice a day. Zinc gluconate lozenges (13 mg elemental zinc every 2 h while awake) have been reported to reduce the duration and symptoms of the common cold in adults, but studies are conflicting. Zinc deficiency is prevalent in many developing countries and usually coexists with other micronutrient deficiencies (especially iron). Zinc (20 mg/d) may be an effective adjunctive therapeutic strategy for diarrheal disease in children. Toxicity Acute zinc toxicity after oral ingestion causes nausea, vomiting, and fever. Zinc fumes from welding may also be toxic and cause fever, respiratory distress, excessive salivation, sweating, and headache. Chronic large doses of zinc may depress immune function and cause hypochromic anemia as a result of copper deficiency. Copper Copper is an integral part of numerous enzyme systems including amine oxidases, ferroxidase (ceruloplasmin), cytochrome-c oxidase, superoxide dismutase, and dopamine hydroxylase. Copper is also a component of ferroprotein, a transport protein involved in the basolateral transfer of iron during absorption from the enterocyte. As such, copper plays a role in iron metabolism, melanin synthesis, energy production, neurotransmitter synthesis, and CNS function; the synthesis and cross-linking of elastin and collagen; and the scavenging of superoxide radicals. Dietary sources of copper include shellfish, liver, nuts, legumes, bran, and organ meats. Deficiency Dietary copper deficiency is relatively rare, although it has been described in premature infants who are fed milk diets and in infants with malabsorption (Table 71-2). Copper-deficiency anemia has been reported in patients with malabsorptive diseases and nephrotic syndrome and in patients treated for Wilson's disease with chronic high doses of oral zinc, which can interfere with copper absorption. Menkes kinky hair syndrome is an X-linked metabolic disturbance of copper metabolism characterized by mental retardation, hypocupremia, and decreased circulating ceruloplasmin (Chap. 357). It is caused by mutations in the copper-transporting ATP7A gene. Children with this disease often die within 5 years because of dissecting aneurysms or cardiac rupture. Aceruloplasminemia is a rare autosomal recessive disease characterized by tissue iron overload, mental deterioration, microcytic anemia, and low serum iron and copper concentrations. The diagnosis of copper deficiency is usually made on the basis of low serum levels of copper (<65 µg/dL) and low ceruloplasmin levels (<20 mg/dL). Serum levels of copper may be elevated in pregnancy or stress conditions since ceruloplasmin is an acute-phase reactant and 90% of circulating copper is bound to ceruloplasmin. Toxicity Copper toxicity is usually accidental (Table 71-2). In severe cases, kidney failure, liver failure, and coma may ensue. In Wilson's disease, mutations in the copper-transporting ATP7B gene lead to accumulation of copper in the liver and brain, with low blood levels due to decreased ceruloplasmin (Chap. 354). . Chapter 071. Vitamin and Trace Mineral Deficiency and Excess (Part 12) Zinc Zinc is an integral component of many metalloenzymes in the body; it is involved in the synthesis and stabilization. valproate, and ethambutol. Meat, shellfish, nuts, and legumes are good sources of bioavailable zinc, whereas zinc in grains and legumes is less available for absorption. Deficiency Mild zinc deficiency. stabilization of proteins, DNA, and RNA and plays a structural role in ribosomes and membranes. Zinc is necessary for the binding of steroid hormone receptors and several other transcription