Cadmium pneumonitis results from inhalation of cadmium oxide fumes. The acute phase of cadmium pneumonitis may mimic metal fume fever (Chap. 124), but in fact, the two entities are distinctly different, with regard to both mechanism and clinical consequences. Whereas metal fume fever is benign and self-limited, acute cadmium pneumonitis can progress to hypoxia, respiratory insufficiency, and death.
Published case reports of patients who develop acute cadmium pneumonitis4,5,32,71,84,93,101,105 are strikingly similar in their presentation. Within 6 to 12 hours of soldering or brazing with cadmium alloys in a closed space, patients typically develop constitutional symptoms, such as fever and chills, as well as a cough and respiratory distress.
On initial presentation these patients may have a normal physical examination, oxygenation, and chest radiograph. This relatively benign presentation may lead both to the misdiagnosis of metal fume fever and the underestimation of the severity of illness. As the pneumonitis progresses to acute respiratory distress syndrome (ARDS) (Chap. 124), crackles and rhonchi develop, oxygenation becomes impaired, and the chest radiograph develops a pattern consistent with alveolar filling. Despite aggressive supportive care, death may occur, usually within 3 to 5 days.32,71,84,101
Patients who survive an episode of acute cadmium pneumonitis may develop chronic pulmonary disorders, including restrictive lung disease,4,5 diffusion abnormalities,4 and pulmonary fibrosis,93 although recovery without sequelae is also reported.105
Most acute cadmium exposures are inhalational, and acute ingestions are rare. Based on case report data, GI injury is likely to be the most significant clinical finding after acute ingestion, although other presentations are possible.
In one case,11 a 17 year-old student ingested approximately 150 g of cadmium chloride that she obtained from her school science stockroom. She presented to the emergency department with hypotension and edema of the face, pharynx, and neck. Her condition quickly deteriorated, and she suffered a respiratory arrest. She was intubated and underwent orogastric lavage, chelation with an unspecified agent, and charcoal hemoperfusion. Multisystem organ failure ensued, and she died within 30 hours of presentation. At autopsy, the most significant finding was hemorrhagic necrosis of the upper GI tract. Her blood cadmium concentration was more than 2000 times normal.
In a second reported case a 23 year-old man ingested approximately 5 g of cadmium iodide in a suicide attempt and presented with acute hemorrhagic gastroenteritis.102 His condition deteriorated, and despite treatment with calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA) and supportive measures, he died on hospital day 7. Autopsy did not reveal a specific cause of death.
A 51 year-old man taking multiple nutritional supplements who had no history to suggest cadmium exposure presented with a one month history of fatigue, with laboratory findings suggestive of autoimmune hemolytic anemia. He was treated aggressively for that condition, but developed progressive multisystem organ failure and expired one week after presentation. His blood cadmium concentrations were extraordinarily high, suggesting an acute ingestion, although the source of the cadmium was never determined.76
The most common finding in chronic cadmium poisoning is proteinuria. Low-molecular-weight proteinuria is usually more significant than, and generally precedes, glomerular dysfunction, although some cadmium exposed workers manifest predominantly glomerular proteinuria.7 There is a dose–response relationship between total body cadmium burden and kidney dysfunction,10,44,46,67,95 although this relationship may not be as strong at low doses.39 Patients with diabetes mellitus may be particularly susceptible to the nephrotoxic effects of cadmium.37 In most cases, proteinuria is generally considered to be irreversible even after removal from exposure,38,52,79 but improvement is sometimes reported.60,94 Less clear is the question of whether kidney dysfunction progresses after removal from exposure, with studies showing both stable38 and deteriorating42,78,79 function in cadmium exposed workers who are removed from exposure. The routes and duration of exposure, as well as blood and urine cadmium concentrations, differ markedly among these studies, limiting wider applicability of any analysis.
Occupational cadmium exposure is also associated with nephrolithiasis,45,82 likely as a result of hypercalciuria.83
Large studies of workers chronically exposed to relatively low concentrations of cadmium fail to demonstrate consistent effects on the lung. In one study of 57 workers with sufficient exposure to cadmium oxide to produce kidney dysfunction, there was no evidence of pulmonary dysfunction, even in those with the greatest cumulative cadmium exposure.27 In contrast, other studies have reported both restrictive17 and obstructive21,81 changes on pulmonary function tests. Interestingly, a follow-up study of the group with restrictive lung disease showed improvements after cadmium exposure was reduced.16 The discrepancies in these results may be partly a result of markedly different doses and durations of exposure among the various groups.
Cadmium is associated with pulmonary neoplasia; the carcinogenicity of cadmium is discussed separately (see Cancer below).
Cadmium-induced osteomalacia usually occurs in the setting of environmental exposure, as was true in Japan and Sweden.43 Although mentioned in case reports,8,52 osteomalacia is generally not a prominent feature of occupational exposure to cadmium. Gender and age differences may explain part of this apparent difference: victims of the original Itai-Itai epidemic were mostly older women, whereas occupational cadmium exposures typically occur in younger men. In addition, differences in cumulative dosing and in route of exposure (oral vs. pulmonary) may partly account for the unique prominence of osteomalacia in patients with environmental exposures. Cadmium exposure is associated with osteopenia and osteoporosis even in areas (such as the United States) where widespread environmental exposure is unlikely.103
Although the liver stores as much cadmium as any other organ, hepatotoxicity is not a prominent feature in humans with cadmium exposure, probably because hepatic cadmium is usually complexed to metallothionein.40 The liver is a potential target organ, however, as hepatotoxicity is easily inducible in animals.1,25,26,77
Cadmium exposure is linked to olfactory disturbances,64,80,89 impaired higher cortical function,98 and parkinsonism.68,98
Cadmium induces hypertension in rats,59 but human studies have only yielded unconvincing and conflicting results.31,58,69,92 Although there is evidence that cadmium may cause immunosuppression affecting both humoral and cell-mediated immunity in animals,24 a single human study showed no overt immunopathology in an occupationally exposed cohort.51 The testes are clearly a target organ in animal exposures,57 but they are not considered a major target organ in humans.
Cadmium induces tumors in multiple animal organs, an effect that is exacerbated by zinc deficiency.99 In humans, cadmium exposure is associated with lung cancer.70 The strength of this association has been questioned because most studies have methodologic problems, such as coexposure to arsenic, a known pulmonary carcinogen.9,53 Despite these confounding coexposures, cadmium is officially designated as a human carcinogen by the International Agency for Research on Cancer.41