Zinc deficiency is common worldwide but is seen with greater frequency in developing countries. Zinc deficiency can be inherited or acquired and typically presents with infectious, inflammatory, gastrointestinal, or cutaneous involvement. Treatment is predominantly via oral replacement and usually results in quick clinical improvement. This activity reviews the evaluation and management of zinc deficiency and highlights the role of the interprofessional team in caring for affected patients.
Objectives:Describe the recommended treatment for zinc deficiency.Outline the typical presentation for a patient with zinc deficiency.Review the pathophysiology of zinc deficiency.Explain the interprofessional team strategies for improving care coordination and communication regarding managing patients with zinc deficiency.Access free multiple choice questions on this topic.
Zinc 4.0 Serial Key
Zinc is an essential micronutrient for humans and is extensively involved in protein, lipid, nucleic acid metabolism, and gene transcription.[1] Its role within the human body is extensive in reproduction, immune function, and wound repair. At the microcellular level, it has a significant effect on the normal functioning of macrophages, neutrophils, natural killer cells, and complement activity.[2][3][4] Despite being one of the most abundant trace elements in the human body, zinc cannot be stored in significant amounts and hence requires regular intake or supplementation. Zinc is found in various foods, including meat, fish, legumes, nuts, and other dietary sources, although its absorption varies by the substrate carrying it. Zinc deficiency is a major health problem worldwide, especially in developing countries, hence it is designated by the World Health Organization as a major disease contributing factor.[5][6] Zinc deficiency can present with growth impairment, sexual dysfunction, inflammation, gastrointestinal symptoms, or cutaneous involvement.[3]
Zinc is a divalent cation not synthesized within the human body and needs to be taken from outside to maintain adequate levels. The dietary intake of zinc increases from 3 mg/day in children to 8 mg/day in adult females and 11 mg/day in adult males. These requirements are even higher in pregnant and lactating women.
Zinc deficiency is commonly seen in developing regions that is attributable to malnutrition; however, in developed regions, it is found to be associated with aging and many chronic illnesses. Zinc deficiency can be acquired or inherited. Acquired deficiency can occur from decreased intake, inability to absorb the micronutrient, increased metabolic demand, or excessive loss. Patients with an acquired form of zinc deficiency usually have a combination of various factors, such as:
Increased demand occurs in multiple settings, one of which is during pregnancy and lactation.[5] Zinc requirements increase up to two-fold during these times and up to 2 mg/day of loss occurs, lasting up to two months postpartum. Preterm infants require higher zinc levels because of inadequate stores, decreased gut absorption, and higher metabolic rate.[17]
Acrodermatitis enteropathica is an inherited form of zinc deficiency from impaired absorption.[19] This is a rare disease with an incidence estimated at 1 per 500,000. It occurs as an autosomal recessive mutation of the SLC39A4 gene on chromosome 8q24.3 that encodes the Zip4 transporter.
It is estimated that up to 17% of the global population is at risk for inadequate zinc intake, while in South Asia, up to 30% of the population may be deficient. Other areas at risk include sub-Saharan Africa and Central America.[4] Worldwide trends and prevalence of zinc deficiency have largely been stable; however, notable reductions have been seen exemplified by countries like China with a decrease of prevalence from 17% to 8% recorded in 2005.[20][21]
Clay eating or 'pica' is commonly seen in children of certain communities and regions. Clay effectively binds zinc, causing a dramatic decrease in the bioavailability of zinc. Approximately two billion people in developing regions are deficient in zinc to some extent. The at-risk population is comprised of children and elderly adults.[23][24][25]
Zinc is a vital trace element. It plays multiple, indispensable roles within the human body including growth and tissue repair. Zinc is involved in molecular synthesis, including the formation of DNA, RNA, and proteins. It stabilizes ribosomes, cell membranes and has protective effects by decreasing lipid peroxidation and subsequent free radicals. Beyond the molecular nuances of function, it is required for spermatogenesis, embryogenesis, and fetal growth.[2][4] The absorption of zinc occurs primarily in the distal duodenum and proximal jejunum, while excretion is primarily gastrointestinal (GI) with some secretion through urine and sweat.
Zinc has a significant role in the skin and is found in higher concentrations in the epidermis than dermis, with the majority found in the stratum spinosum. Tight regulation of intracellular zinc is maintained by transporters encoded by solute-linked carrier genes, including zinc transporter (ZnT; SLC30A). Other regulators include Zrt-Irt-like proteins (ZIP; SLC39A). Within keratinocytes, zinc suppresses activation of tumor necrosis factor-alpha (TNF-alpha) and diminishes inducible nitric oxide synthase and nitric oxide production. Furthermore, chelation of intracellular zinc results in activation of caspase-3 and DNA fragmentation with resultant apoptosis of keratinocytes. The net effect is that zinc is required for normal keratinocyte proliferation and suppression of inflammation. Zip2 and Zip4 are present in keratinocytes facilitating appropriate proliferation and differentiation and are crucial in skin health.[26] Zip10 is expressed in the outer root sheath of hair and is involved in hair growth and preservation.[27]
Its role in immune function is also well described. Overall, it keeps the skin viable as an initial barrier to pathogens. It mediates innate immunity with the function of natural killer cells and neutrophils while influencing the acquired immune system through T-lymphocyte activation and regulation, Th1 cytokine production, B-lymphocyte function, and antibody production with subsequent immunoglobulin G formation. Macrophages utilize zinc for phagocytosis, intracellular killing, and cytokine production. Zinc potentiates programmed cell death through apoptosis.[4][28][29]
Risk factors and age of presentation will help to distinguish acquired versus inherited forms of zinc deficiency. Acquired forms will present with risk factors of inadequate supply, regional and geographic risk factors, excess loss, or increased demand as described earlier. The inherited disease presents earlier in life.
Multiple organ systems are affected by zinc deficiency. Its role within the reproductive system manifests clinically as hypogonadism and associated complications and oligospermia.[33][34][35] Central nervous system (CNS) involvement can present as emotional lability, mental disturbances, impaired taste, and smell, as well as photophobia.[36] Immune dysfunction predisposes individuals to a myriad of infectious complications.[37] GI symptoms may manifest as significant diarrhea.[18]
Inherited deficiency, as exemplified by acrodermatitis enteropathica, is a rare inherited form of zinc malabsorption and often becomes symptomatic 4 to 6 weeks after an infant has stopped breastfeeding. Clinical symptoms include irritability, withdrawn disposition, growth impairment, anorexia, night blindness, pica, and photophobia. Cutaneous involvement includes the periorificial, gluteal, perineal, acral predominant burn-like psoriasiform lesions. Nail dystrophy and paronychia occur, and alopecia may develop. Delayed wound healing, conjunctivitis, and increased susceptibility to infection may also be clues.[41]
Acrodermatitis enteropathica is suspected clinically and supported by laboratory findings and histopathology. Lab values will demonstrate low serum alkaline phosphatase (a zinc-dependent metalloenzyme) and low plasma zinc concentrations. They are helpful in the cases of severe zinc deficiency; however, they are not accurate in nominal deficiency, partly because of impaired protein binding.[43]
Serum studies and the ideal collection include using zinc-free vacuum tubes, stainless steel needles, avoiding contact with rubber stoppers, avoiding hemolysis, separating plasma, or serum from cells within 45 minutes, and using anticoagulants low in zinc concentration, as well as morning, fasting samples to optimize accuracy. Normal zinc levels are between 70 to 250 ug/dl in adults, and mild deficiency can manifest clinically when values decrease to 40 to 60 ug/dl. Urine zinc levels vary widely and are not a reliable marker for the acute state. Hair zinc level is also an unreliable marker in acute changes.[44]
Punch biopsy and histopathology of affected tissue can support the diagnosis of necrolysis seen as cytoplasmic pallor, vacuolization, ballooning degeneration, and confluent necrosis of keratinocytes in the upper epidermis. Confluent parakeratosis is often present with loss of the granular layer and with dermal edema. An associated neutrophilic crust may be present. Individual keratinocytes often have pyknotic nuclei. These findings are non-specific and are often seen with pellagra and necrolytic migratory erythema. Late lesions of zinc deficiency may mimic psoriasis. Clinical improvement to zinc supplementation can also be confirmatory.[45]
Zinc supplementation has been observed to decrease the risk of infection in various studies.[46] In a study conducted on children over 6 months old who were at risk of zinc deficiency, it was observed that zinc supplementation helped in reducing the duration of diarrhea.[47] As there exists relatively low sensitivity of plasma zinc levels in mild deficiency, it is wise to initiate oral supplementation if typical symptoms are present, even if test results are equivocal or normal. High-risk groups should be considered for empirical supplementation. 2ff7e9595c
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