Zinc is a component of certain important enzymes, such as carbonic anhydrase, lactic dehydrogenase, alkaline phosphatase, DNA and RNA polymerases, and d-aminolevulinic acid dehydratase. Zinc is obtained primarily through food. About 30% of that ingested is absorbed in the small intestine. About 80% of zinc in blood is found in RBCs, mostly as part of the enzyme carbonic anhydrase. Of that portion not in RBCs, about 50% is bound to albumin, about 30% is bound to alpha-2 macroglobulin or transferrin, and about 5% is bound to histidine and certain other amino acids, leaving about 15% free in plasma. Excretion occurs predominately in the stool, with a much smaller amount excreted in urine and sweat.

Zinc deficiency is usually not clinically evident until it becomes severe. Severe deficiency may produce growth retardation, delayed sexual development, acrodermatitis enterohepatica (dermatitis, diarrhea, and alopecia), decreased taste acuity, and poor wound healing. Acrodermatitis enterohepatica can either be congenital (autosomal recessive trait) or can appear in severe acquired zinc deficiency.

Conditions producing zinc deficiency include inadequate diet intake (most often in hospitalized patients on IV feeding, including hyperalimentation patients), conditions that interfere with intestinal absorption (high-fiber or phytate diet, prolonged severe diarrhea, steatorrhea), excess zinc loss (sickle cell anemia), increased zinc requirement (pregnancy, lactation, wound healing), and certain diseases such as alcoholism and cirrhosis.

Assay of plasma zinc is usually done by atomic absorption spectrophotometry. Contamination is a major problem. Rubber stoppers or gaskets are well known for this. Glassware must be specially prepared. Another major problem is considerable variation in reference range between laboratories for both adults and infants. Serum is reported to have slightly higher levels than plasma. Since a substantial amount of plasma zinc is bound to albumin, changes in albumin can change (total) plasma zinc levels without reflecting patient body zinc levels. Hemolysis invalidates zinc measurement due to the high levels in RBCs. There is a circadian rhythm, with values somewhat higher in the morning.


Normally, small amounts of aluminum are ingested with food. Other sources include aluminum leached from aluminum cooking utensils by acidic juices, and alum-containing baking soda, processed cheese, and beer. Aluminum in serum is predominantly bound to transferrin, with a small amount bound to citrate in extracellular fluid. The only source of excretion is the kidney. Most interest in aluminum is focused on aluminum toxicity in patients with renal failure. These patients develop microcytic anemia, osteodystrophy (osteomalacia) resistant to Vitamin D, and encephalopathy. The osteodystrophy is caused by deposition in bone of excessive aluminum, where it interferes with bone mineralization. Initially, aluminum toxicity was thought to be due to aluminum contamination of water used for renal dialysis. More recently, the source of aluminum has been traced to aluminum-containing preparations used to bind phosphates in the GI tract to prevent phosphate absorption, with subsequent phosphate accumulation and development of secondary hyperparathyroidism. The gold standard test for aluminum osteodystrophy is bone biopsy with either (or both) chemical analysis or histochemical staining for aluminum content. However, other procedures have been used to estimate likelihood of aluminum bone toxicity. The serum aluminum level has been most commonly used for this purpose. Values greater than 50 ng/ml are generally considered abnormal, and values greater than 100 ng/ml are generally considered suggestive of possible aluminum bone toxicity. However, in one series about 30% of patients with serum aluminum values greater than 100 ng/ml failed to show definite evidence of aluminum toxicity on bone biopsy (70% specificity), and about 20% with serum values less than 100 µg/ml had biopsy evidence of aluminum toxicity (80% sensitivity). Many patients with aluminum toxicity develop a microcytic anemia (although it must be emphasized that microcytic anemia is not specific for aluminum toxicity). In one series, about 20% of renal hemodialysis patients with a microcytic mean cell volume (MCV) had a serum aluminum level less than 50 ng/ml, about 40% had a level between 50 and 100 ng/ml and about 40% had a level more than 100 ng/ml. About 25% of patients with serum aluminum values greater than 100 ng/ml had a normal MCV. However, no patient with a value more than 140 ng/ml had a normal MCV. Another test involves infusion of a chelating drug desferrioxamine, which extracts some aluminum from tissues and increases serum aluminum levels by a certain amount over baseline if the tissues contain excess aluminum. Serum aluminum assay is difficult and is available only at large reference laboratories and some medical centers. The major problem is contamination by aluminum in laboratory apparatus and in the environment. Some sources of contamination include aluminum needles used for specimen collection, rubber stoppers on blood tubes, contaminated pipets or other glassware, and aluminum contamination of environmental dust.