Section 3 -

Acute Inorganic Mercury Inhalation Poisoning Komyo Eto National Institute for Minamata Disease Shigeyuki Asano Iwaki Kyoritsu General Hospital

Introduction Mercury contamination is a serious environmental problem worldwide. Two primary sources of contamination are the dumping of large quantities of inorganic mercury and the resultant exposure in the mining industry. There is also the serious environmental problem of mercury pollution, such as the dumping of large quantities of inorganic mercury along the Amazon River basin in Brazil [1, 2, 3]a nd the exposure to mercury of pit-workers in the gold mines of Tanzania, [4, 5] Indonesia, [6, 7] and the Philippines [8] or mercury miners in Slovenia. [9] There are two autopsy cases of chronic inorganic mercury poisonings in workers in the mercury mines of Hokkaido, Japan from 1967 to 1968. [10] In 1993, there were three fatal cases of acute inorganic mercury vapor poisoning in Iwaki City, Fukushima Prefecture, Japan. [11]Three men were exposed to highly concentrated mercury vapor, and acute lung injury was observed in all three men. Although the actual fatal level of mercury vapor is not known, exposure to more than 1-2 mg/m3 of elemental mercury vapor (Hg0) for a few hours causes acute chemical bronchitis and pneumonitis. Two hours after exposure, lung injuries appear as a hyaline membrane formation, and finally, extensive pulmonary fibrosis occurs. Clinical findings correlate with the duration of exposure, the concentration of mercury, and the survival time after exposure. Fatal Industrial Cases In 1993, twenty-seven men were cutting pipes using a high-temperature gas burner (over 1,000 degrees centigrade) in a cylindrical heat exchanger (3.8 m in diameter and 9 m in height) in a refinery that extracted zinc from ores. Three of the men were exposed to highly concentrated mercury vapor for 2-3 h in the central area of the heat exchanger. They complained of common cold-like symptoms, such as headache and a severe cough, along with shortness of breath, nausea, and vomiting. Chest X-rays revealed bilateral diffuse granular infiltrates. The men' died on day 12, 17, and 19 after vapor inhalation due to pulmonary insufficiency and acute renal failure, even though they had received corticosteroids, antibiotics, and anticoagulant therapy. The combined weight of the autopsied lungs ranged from 2,289 to 2,480 g. All specimens were grossly similar in that they had the elasticity of rubber and an airless firm appearance with partial honeycomb lesions. Histological features included significant disease in the air spaces, which had been replaced with extensive fibrosis or organized lesions. The lungs of the man who died on day 19 showed voluminous epithelial desquamation, fibrin, and exudation with patchy organized pneumonitis in the alveolar spaces. Mercury granules were detected diffusely in all lung tissues. Histological Characteristics in the Lungs The heating of mercury forms a mercury vapor, which is actively absorbed in the lungs. The vapor rapidly diffuses through the alveolar membrane, where the absorption rate is approximately 100%. [12] Subjects remain with 50-88 % of an inhaled dose in the lungs. [10, 13, 14, 15, 16] The absorption rate through the skin is approximately 2% of that of the lungs. [17, 18] Absorption at the alveolar and bronchiolar levels causes capillary damage, pulmonary edema, desquamation and proliferation of airway lining cells, leading to obliteration of air spaces. This reaction is believed to be a direct localized irritant effect of the inhaled mercury vapor. [19] The histological changes caused by acute inorganic mercury vapor inhalation can give rise to acute erosive and necrotizing bronchitis and severe interstitial pneumonitis with a hyaline membrane. [13, 20] These histological changes are similar to those seen in adult respiratory distress syndrome. [21] The lesions seem to correlate directly with survival time. [13] Pulmonary toxicity may be caused by mercuric oxide vapors, which more actively penetrate the respiratory tract. [19] The three histological stages of acute mercury lung injury are early, intermediate, and end-stage. [13, 14, 22] Early acute lung injury occurs during the first 2-48 h after exposure. It is characterized by swollen alveolar lining cells with a slight proliferation of pneumocytes, a pink fibrous hyaline membrane, and foci of fibrosis. In the intermediates stage of acute lung injury, there is marked pneumocyte hyperplasia and a significant decrease in the air spaces, the majority of which are replaced with extensive fibrosis. The bronchioles may become lined by stratified epithelium within 72 h of exposure. [23] Mercury apparently persists in the lung tissue for several months after exposure and may be significantly related to the interstitial fibrosis. [12] The remaining alveolar spaces gradually fill with mononuclear cells and alveolar macrophages, which trap fine mercury granules and lead to pulmonary fibrosis. In the end-stage of acute lung injury, the alveolar spaces are almost completely destroyed, and there is extensive mature interstitial fibrosis. The remaining alveolar spaces are filled with inflammatory cells, hyperplasic pneumocytes and alveolar macrophages. All cases involving acute lung injury in the various stages of progression are related to the length of time after exposure to the mercury vapor. Diffuse interstitial pulmonary fibrosis has also been reported in patients with acute mercury poisoning who survived for several weeks following exposure. [24] In addition, spontaneous tension pneumothorax has been reported, [13] as in the cases from the Iwaki refinery. References Akagi H. Studies on mercury pollution in the Amazon. Brazil Global Environ. Res. 1998; 2: 193-202. Akagi H, Malm O, Branches FJP. 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