Anemia copper deficiency

Copper deficiency in humans and other mammals is characterized by slow growth, hair loss, anemia, weight loss, emaciation, edema, altered ratios of dietary copper to molybdenum and other metals, impaired immune response, decreased cytochrome oxidase activity, central nervous system histopathology, decreased phospholipid synthesis, fetal absorption, and eventually death (NAS 1977 Gallagher 1979 Kirchgessner et al. 1979 USEPA 1980 ATSDR 1990 Percival 1995). 

Humans given zinc supplements should be aware of possible complications (Fosmire 1990). Low intakes of 100 to 300 mg of zinc daily in excess of the recommended dietary allowance of 15 mg Zn daily may produce induced copper deficiency, impaired immune function, and disrupted blood lipid profiles. Patients treated with zinc supplements (150 mg daily) to control sickle cell anemia and nonresponsive celiac disease developed a severe copper deficiency in 13 to 23 months normal copper status was restored by cessation of zinc supplements and increased dietary copper (Fosmire 1990). 

Menkes disease Deficient cross-linking secondary to functional copper deficiency Depigmented (steely) hair Arterial tortuosity, rupture Cerebral degeneration Osteoporosis, anemia... 

Large amounts of copper are found in the liver, larger amounts in young individuals than in old. In cases of copper deficiency, anemia, hair discoloration, and other pathological symptoms have been observed. Increased levels of copper, which result from defense mechanism actions of the immune system, have been reported in infectious and cancer diseases (Sarkar, 1995). 

Several metal ions are essential or beneficial to life while others, such as lead, cadmium or mercury, are highly detrimental. Many diseases have been associated in a way or another to altered metal ion concentrations in the body. Deficiencies can be as damaging as overloads. Copper deficiency has been associated to anemia while excess copper can lead to Wilson s disease (liver cirrhosis). Anemia may also be caused by a lack of iron and overload of this same metal ion is connected to thalassemia and siderosis [122]. In vivo determination of metal ion distribution is thus highly desirable and progresses have been made towards the design of MRI contrast agents sensitive to the concentration of metal ions. 

Copper deficiency may present as hematological changes (anemia, leukopenia, and neutropenia) and skeletal demineralization. In severe cases, such as in Menkes syndrome, copper deficiency is further manifested as hypothermia, depigmentation of hair and skin, progressive mental deterioration, and growth retardation. Factors predisposing to copper deficiency include malabsorption states, protein-losing enteropathy, nephrotic syndrome, copper-free parenteral nutrition, and copper-deficient enteral nutrition. 

In addition, megadoses of zinc of up to 5 g per day (40) or chronic dosing with "therapeutic" amounts of zinc, 150 mg of zinc daily for 1 to 2 years (41), have been associated with overt copper deficiency anemias. 

Cartwright and Wintrobe and their co-workers suggested a link between copper deficiency and anemia in mammals 50 years ago (see Lahey et al., 1952). Cartwright subsequently demonstrated that this copper-dependent anemia was unresponsive to iron supplementation but was corrected on administration of ceruloplasmin (see Lee et al., 1968). The molecular basis of this link was indicated by Osaki and Friedan, who characterized the ferroxidase activity of ceruloplasmin and kinetically demonstrated that Cp could play a critical role in catalyzing trafficking of the potentially cytotoxic Fe(II) in the plasma to apoA f (see Frieden and... 

Copper deficiency Copper imbalance causes health disorders that include arthritis, fatigue, adrenal burnout, insomnia, scoliosis, osteoporosis, heart disease, cancer, migraine headaches, seizures, fungal and bacterial infections, gum disease, tooth decay, skin and hair problems, and female organ conditions including uterine fibroids and endometriosis. Copper deficiency is associated with atherosclerosis and other cardiovascular conditions, aneurysms, gout, and anemia. - - ... 

Cardiovascular Disorders and Copper. Sudden cardiac failure has been associated with copper deficiency (91J. There are two attractive mechanisms. First, the coronary arteries and aorta may become weakened from an inability to synthesize elastin due to a decrease in lysyl oxidase activity. Rupture of these major blood vessels has been shown to cause sudden death in animals suffering from copper deficiency. Second, a decrease in cytochrome oxidase activity during copper deficiency Impairs aerobic metabolism of the heart and increases the risk of hypertrophy. Hypertrophy, which may lead to high output congestive heart failure, is exacerbated by hypochromic anemia also caused by copper deficiency. 

The specific daily amounts of antioxidants and zinc used by the AREDS researchers were 500 mg vitamin C. 400 lU vitamin E, 15 mg beta-carotene (often labeled as equivalent to 25,000 lU vitamin A), 80 mg zinc as zinc oxide, and 2 mg copper as cupric oxide. Copper was added to thcAREDS formulations containing zinc to prevent copper deficiency anemia, a condition associated with high levels of zinc intake. (Retrieved March 28. 2007. from http //www.nei.nih.gOv/amd/summary.asp 2)... 

There is some evidence that ceruloplasmin is involved in iron metabolism. It has been suggested that ceruloplasmin and ferritin in plasma work together to reduce the levels of free ferrous ions in plasma. Here, the ceruloplasmin catalyzes the oxidation of Fe (ferrous) to (ferric), the form of the metal that binds to ferritin. Ceruloplasmin acts as an oxidant in this process. This proposed function may reduce damage to membrane lipids possibly inflicted by the small amount of Fe in the circulation. It is thought that ceruloplasmin may be used in the mobilization of iron from intracellular stores. Here, the protein may facilitate the transfer of iron from ferritin to transferrin [Frieden and Hsieh, 1976), A relationship between copper and irtm is suggested by the fact that copper-deficient rats may develop iron deficiency anemia, as revealed by measurements of hemoglobin and hematocrit (Johnson and Dufault, 19S9 Cohen et a ., 1985), Ceruloplasmin may also function in a unique iron transport mechanism, as mentioned in the Iron section. 

Experimentally induced copper deficiency produces anemia in a variety of animals. It produces an anemia. As one might expect, this type of anemia cannot be cured by iron. The heart may enlarge and the mitochondria of the heart may enlarge dramatically. The heart and arteries may rupture with deficiency, probably because of a drop in the activity of lysyl oxidase, a copper melallt enzyme involved in the synthesis of connective tissue proteins. Skeletal defects, such as osteoporosis, occur in experimental copper deficiency. Infections appear to affect copper metabolism. Infections can induce a threefold increase in plasma ceruloplasmin levels. Copper-deficient animals have a reduced ability to exercise, as measured by running on treadmills (Klevay and Medeiros, 1996). 

Because copper is excreted primarily in the bile, some experts advocate reducing or curtailing copper supplementation in patients with chronic hyperbUrrubinemia. The earliest signs of copper deficiency are peripheral blood cytopenias (typically anemia and neutropenia) and occasionally thrombocytopenia, caused by reduced bone marrow production. The authors recommended that serum copper should be monitored quarterly and that copper should be included in the parenteral nutrition mixture three times a week, adjusting the frequency in response to serum copper concentrations. 

Copper deficiency has been reported in a patient with Crohn s disease after removal of copper from the parenteral nutrition because of severe cholestasis (59). The patient developed pancytopenia with severely depressed serum copper concentrations after 8 weeks. Bone-marrow biopsy confirmed the cause as copper deficiency. Although intravenous replacement of copper improved the patient s anemia and other markers, he suddenly died of cardiac tamponade. 

Zinc sulfate can cause copper deficiency by inducing the production of metaUothionein in intestinal cells and thus lowering copper absorption copper deficiency can lead in turn to sideroblastic anemia (8), neutropenia, and osteopenia (9). 

Patterson WP, Winkelmann M, Perry MC. Zinc-induced copper deficiency megamineral sideroblastic anemia. Ann Intern Med 1985 103(3) 385-6. 

The effect of copper deficiency is not fully understood. The element is required for lysil oxidase activity which is necessary for cross-linking of collagen. Its deficiency has heen associated with growth retardation and anemia. Also has in dialysis patients a correlation heen demonstrated between serum copper levels and superoxide dismutase activity. 

Diseases of Copper Deficiency. Manifestations of copper deficiency have been described by several authors (16,32). The most common features in animals and man are anemia, ataxia, cardiovascular rupture, skeletal deformities, and achromotricia. Three systems in the body seem to suffer the consequences of copper deficiency the hemopoietic system, the vascular and skeletal system, and the central nervous system. 

It has been known for some time that copper deficiency leads to anemia and failure of the erythropoietic system to matiure (50,51). Although the exact mechanism involved is still not well defined, recent evidence suggests that copper may be essential for iron absorption and mobilization for hemoglobin synthesis. A ferrous-to-ferric cycle with respect to the role of copper in iron metabolism has been proposed by several workers. Role of ceruloplasmin in the spontaneous oxidation of... 

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