Copper deficiency anemia: review article

Abstract

Copper is a crucial micronutrient needed by animals and humans for proper organ function and metabolic processes such as hemoglobin synthesis, as a neurotransmitter, for iron oxidation, cellular respiration, and antioxidant defense peptide amidation, and in the formation of pigments and connective tissue. Multiple factors, either hereditary or acquired, contribute to the increase in copper deficiency seen clinically over the past decades. The uptake of dietary copper into intestinal cells is via the Ctr1 transporter, located at the apical membrane aspect of intestinal cells and in most tissues. Copper is excreted from enterocytes into the blood via the Cu-ATPase, ATP7A, by trafficking the transporter towards the basolateral membrane. Zinc is another important micronutrient in animals and humans. Although zinc absorption may occur by direct interaction with the Ctr1 transporter, its absorption is slightly different. Copper deficiency affects physiologic systems such as bone marrow hematopoiesis, optic nerve function, and the nervous system in general. Detailed pathophysiology and its related diseases are explained in this manuscript. Diagnosis is made by measuring serum copper, serum ceruloplasmin, and 24-h urine copper levels. Copper deficiency anemia is treated with oral or intravenous copper replacement in the form of copper gluconate, copper sulfate, or copper chloride. Hematological manifestations are fully reversible with copper supplementation over a 4- to 12-week period. However, neurological manifestations are only partially reversible with copper supplementation.

Anemia and leukopenia following intravenous colloidal silver infusions—Clinical and hematological features, unique peripheral blood film appearance and effective therapy with supplemental oral copper and apheresis

“…10 It is known that zinc and copper compete with each other for access to a common relatively weak excretion pathway and that excess oral zinc administration may cause copper deficiency anemia. [11][12][13][14][15] It appears from our three patients, that infused colloidal silver has no significant excretion pathway, as the markedly elevated serum silver levels remained constant over many weeks. However, its presence likely facilitates persistent excess urinary losses of both copper and zinc, and particularly for copper, into both the bile and urine.…”

“…In more current literature, that copper and zinc deficiency may both occur with silver poisoning has been commented upon . It is known that zinc and copper compete with each other for access to a common relatively weak excretion pathway and that excess oral zinc administration may cause copper deficiency anemia . It appears from our three patients, that infused colloidal silver has no significant excretion pathway, as the markedly elevated serum silver levels remained constant over many weeks.…”

Wilson disease: copper deficiency and iatrogenic neurological complications with zinc therapy

“…Zinc toxicity can cause copper deficiency through entrapment of copper in the enterocytes, which can subsequently cause sideroblastic anaemia and subacute combined degeneration of the spinal cord . Copper deficiency may occur at differing times after the commencement of zinc therapy, and hence regular neurological examination, copper metabolism and haematological monitoring is necessary.…”

Nutritional neuropathies

“…Copper deficiency most commonly follows Roux‐en‐Y surgery with a prevalence of 9.6% and an incidence of 18.8% . The use of parenteral nutrition may also result in copper deficiency . Other causes of deficiency include renal conditions such as glomerulonephritis and nephrotic syndrome as well as malabsorptive processes such as celiac disease and inflammatory bowel disease …”

“…Differences in bioavailability between these supplements is unknown. Neurological recovery is less complete than reversal of anemia …”