Cadmium Toxicity

Etiology

Cadmium toxicity usually occurs after occupational, environmental, or hobby work exposure.  Environmental exposures can occur from contamination in the surrounding soil with the metal, and then the resultant food grown there is consumed.  This type of contamination can occur in areas where mining or refining of ores takes place. 

Something to this effect took place in Japan in the 1950s at the Jinzu River when a mine discharged a large amount of cadmium into the environment.  The rice grown in the area caused an epidemic of painful osteomalacia that occurred mostly in multiparous postmenopausal women.   The name given this condition was “itai-itai” disease which is “ouch-ouch” in Japanese since those affected would say this every time they took a step.[2]

Epidemiology

Welders, solderers, and jewelry worker are at risk for inhaling cadmium oxide fumes.  Significant toxicity is usually the result of metalworking in a closed space with improper ventilation.

Pathophysiology

Orally ingested cadmium is poorly bioavailable, but inhaled cadmium fumes are readily bioavailable.   Once in the bloodstream, cadmium binds to alpha-2-macroglobulin and albumin and gets distributed to the liver and kidneys.  Aside from these two main organs, cadmium also concentrates in the pancreas, spleen, heart, lung, and testes.[3]

Once in the liver, cadmium binds with metallothionein and this complex is slowly released from the liver.  Because of the slow release, its biologic half-life can be at least ten years. Cadmium then travels to the glomerulus, and large amounts concentrate in the proximal tubule–conferring its renal toxic effects.[4]

Histopathology

Metallothionein is protective, and the free cadmium cation is the damaging entity in this toxicity.  The cadmium ion causes mitochondrial damage via enzyme degradation and protein destruction.  This destructive effect makes the cell more susceptible to oxidative stress.  Also, cadmium affects cell adhesion and calcium transport that can lead to cell dysfunction and cell death.[5]

History and Physical

Acute Poisoning

Acute poisoning can occur by inhalation of cadmium fumes or ingestion of cadmium salts.  Cadmium pneumonitis can occur and look strikingly similar to metal fume fever.  Within six hours of soldering with cadmium alloys, patients may experience fever, chills, cough, and respiratory distress.  Patients may appear well on initial presentation but can progress from pneumonitis to acute respiratory distress syndrome (ARDS).  Death can occur in 3-5 days.  Survivors may suffer from lifelong restrictive lung disease.[6][7]

Acute ingestions occur more rarely than inhalational injury.  After ingestion, patients may develop gastrointestinal injury.  In high concentrations, it produces hemorrhagic necrosis of the gastrointestinal tract and multiorgan system failure.[8]

Chronic Poisoning

Nephrotoxicity

Most commonly, permanent proteinuria is seen after chronic cadmium exposure.  More specifically, beta-2-microglobulinuria is found in these workers.  Renal function has been reported to continue to deteriorate in some patients even after removal from cadmium contact[9].  Those with pre-existing renal disease or risk factors for developing renal disease (i.e., diabetes mellitus) are susceptible.[10]  Cadmium is also associated with hypercalciuria and nephrolithiasis.[11]

Pulmonary toxicity

The research is not clear on whether chronic cadmium inhalation causes pulmonary toxicity.  It is, however, agreed upon that exposure causes lung cancer.[12]

Musculoskeletal toxicity

Usually occurring after environmental exposure, painful osteomalacia has been seen mostly in postmenopausal women.  There appears to be a gender and age difference to those that are at risk.  This may account for the lack of occupational exposures as these workers tend to be younger men. 

Other organ systems

Hepatotoxicity is not reported with cadmium exposure likely because cadmium forms a complex with metallothionein which renders it inactivate.[13]  Neurologic dysfunction can occur in the form of parkinsonism, impaired higher cortical functioning, and olfactory disturbances.  Animal studies have shown a relationship with cadmium and hypertension, immunosuppression, and testicular dysfunction; however, these results have not translated to human studies.[14][15]

Evaluation

Cadmium blood concentrations have limited use other than for confirmation in acute exposure: history, physical exam, and symptoms guide diagnosis.  In chronic exposure, urinary cadmium is the test of choice to determine total body cadmium burden.  Anyone at high risk for chronic cadmium exposure should have routine urinary protein testing (beta-2-microglobulin).      

Treatment / Management

Acute Poisoning

Cadmium fumes pose a significant risk to the lungs.  Airway management is essential and supplemental oxygen applied.  Often, steroids area treatment of choice, though their benefit remains unproven. 

Ingestion of cadmium poses slightly different concerns.  Activated charcoal and gastric lavage are options.  The patient will require monitoring for gastrointestinal injury as well as renal and hepatic dysfunction.  Chelators, though promising, have not been definitively proven to be useful in cadmium toxicity.  However, it appears that if succimer is given early in the course, it has promising results.[16](B3)

Chronic Poisoning

These patients will have a known exposure, and their dysfunction typically discovered on routine screening.  The first intervention is always to remove the patient from the exposure.  Chelation is not currently recommended for these patients even though the effects can be permanent and progressive. 

Differential Diagnosis

For any environmental or occupational metal exposure, one must consider the other prevalent metal toxicities such as iron, lead, arsenic, mercury, thallium.  In acute toxicities, other causes of pneumonitis and ARDS are on the differential; metal fume fever is a diagnosis of exclusion.

Prognosis

In acute exposure, restrictive lung disease can be lifelong. In chronic exposure, kidney injury can be progressive and irreversible.