plasma or blood levels of the metal

 urinary excretion of metals

 an associated biochemical abnormality related to the toxicity.

Lead

Inorganic lead has long been known to be toxic, but acute lead poisoning is rare. Chronic toxicity is related to industrial exposure, lead leached from water pipes, or the eating of lead-containing paints or dirt by children (pica). Only 5–10% of lead is absorbed from the gastrointestinal tract in adults but this proportion is higher in children.

Lead poisoning causes anaemia as well as hepatic, renal and neurological sequelae. In general, the consequences of organic lead poisoning are neurological, whereas inorganic lead poisoning results in constipation, abdominal colic, anaemia and peripheral and motor neuron deficiencies. Severe cases develop encephalopathy with seizures and coma.

Biochemical evidence of lead poisoning is by the finding of raised protoporphyrin levels in the erythrocytes due to the inhibition of a number of the synthetic enzymes of the haem pathway by lead (Fig 61.2). A clinical sign is the appearance of a blue line on the gums.

Lead is measured in whole blood or in urine (Table 61.1). Excretion can be enhanced using chelating agents such as NaEDTA, dimercaprol or N-acetyl-penicillamine. Because of their high toxicity the use and handling of organic lead compounds, such as tetra-ethyl-lead, the anti-knocking agent in petrol, is strictly regulated by law and they are being replaced by alternative compounds.

Mercury

Mercury poisoning may be acute or chronic and is related to exposure to elemental mercury vapour, inorganic salts or organic forms such as methyl-mercury. Metallic mercury is relatively non-toxic if ingested, but mercury vapour can give rise to acute toxicity. The symptoms are respiratory distress and a metallic taste in the mouth.

Mercurous salts, notably calomel, have been known to cause chronic toxicity following skin absorption from powders and other forms, but are less toxic than mercuric salts, notably mercuric chloride. This is highly toxic when ingested. The symptoms are nausea and vomiting, muscular tremors, CNS symptoms and renal damage.

Diagnosis is by estimation of blood and urine mercury concentrations (Table 61.1). Long-term monitoring of exposure, such as may be necessary with those working with dental amalgam, may be carried out using hair or nail clippings.

Organic mercury compounds are very toxic. In the oceans, the methyl-mercury concentration in the flesh of marine life increases as you move up the food chain. Thus, in top predators such as tuna and shark the concentration is such that organizations such as UK Food Standards Agency have issued advice to pregnant women to limit their intake.

Aluminium

Aluminium is very poorly absorbed from the gastrointestinal tract. Aluminium sulphate is used as a flocculating agent in the treatment of drinking water and aluminium hydroxide is used therapeutically as a phosphate-binding agent and an antacid.

Aluminium levels in water supplies are variable and may contain from less than 50 to more than 1000 µg/L. This is a potential hazard to renal dialysis patients when the aluminium can enter the body across the dialysis membrane, thus bypassing intestinal absorption. The water used in dialysis is now treated to remove contaminating metals. Acute aluminium toxicity is extremely rare. Aluminium toxicity in patients with renal dysfunction causes bone disease (aluminium osteodystrophy) and gradually failing cerebral function (dialysis dementia).

Diagnosis is by measurement of aluminium in a plasma specimen (Table 61.1). Aluminium content of bone biopsy material is also used, with levels greater than 100 µg/g dry weight indicating accumulation.

Treatment of aluminium toxicity is by prevention. In cases of toxicity, aluminium excretion may be enhanced by using the chelating agent desferrioxamine.

Arsenic

Arsenic never occurs as the free element, but as the ions As³⁺ and As⁵⁺ and may be found in some insecticides. Acute ingestion gives rise to violent gastointestinal pain and vomiting, with shock developing. Chronic ingestion is evidenced by persistent diarrhoea, dermatitis and polyneuropathy. Arsenic is sometimes used to treat colitis and this is probably the most frequent type of exposure. The best indicator of chronic arsenic exposure is hair analysis. The arsenic content will vary with time along the length of the hair. A level of >0.5 µg/g arsenic in hair indicates significant exposure. Urine arsenic measurements are also of value in assessing occupational exposure.

Cadmium

Chronic cadmium toxicity occurs in industrial workers exposed to cadmium fumes. The symptoms are those of nephrotoxicity, bone disease and, to a lesser extent, hepatotoxicity. Renal stone formation may be increased.

In diagnosis, indicators of renal damage, in particular β₂-microglobulin in urine, can be used to monitor the effects. Blood and urine cadmium estimates (Table 61.1) will give an objective index of the degree of exposure, and, in some cases, the cadmium content of renal biopsy tissue may be useful.

Treatment of chronic cadmium toxicity is by removal from exposure. The use of chelating agents is not recommended because mobilization of cadmium may cause renal damage.

The major source of cadmium exposure in the general population is tobacco smoke, with smokers having blood cadmium levels twice that of non-smokers.

Cobalt and chromium

Metal prostheses are being used in younger patients and in increasing numbers in orthopaedics. There is a lot of concern that cobalt and chromium released from ‘metal on metal’ units may result in toxicity. Thus some agencies, such as the UK Medicines and Healthcare Products Regulatory Agency (MHRA), have issued guidance recommending that cobalt and chromium should be measured in the blood of patients with some prostheses to detect potential toxicity.