Itai disease

The most severe form of chronic cadmium (Cd) poisoning caused by prolonged oral Cd ingestion is Itai-itai disease, which developed in numerous inhabitants of the Jinzu River basin in Toyama Prefecture, Japan in the 1950s (Figure 20.7). For the first time, cadmium pollution was shown to have severe consequences on human health, particularly in women. The most important effects were softening of the bones and kidney failure. The name of the disease is derived from the painful screams (Japanese /to/) caused by the severe pain in the... 

Figure 20.7 Itai-itai disease (left) the degree of Cd pollution and (right) the presence of the disease in women over 50 years of age.

Chronic exposure to high levels of cadmium in food has caused bone disorders including osteoporosis and osteomalacia. Long-term ingestion of water, beans, and rice contaminated with cadmium by a Japanese population was associated with a crippling condition, Itai-Itai disease. The affliction is characterized by pain in the back and joints, osteomalacia, bone fractures, and occasional renal failure, and it most often affected women with multiple risk factors such as multiparity and poor nutrition. ... 

Chronic exposure can result in obstructive lung disease, emphysema, and kidney disease. Cadmium may also be related to increases in blood pressure (hypertension) and is a possible lung carcinogen. Cadmium affects calcium metabolism and can result in bone loss. This condition has been referred to as Itai-Itai disease, which means Ouch-Ouch in Japanese and reflects the bone pain associated with cadmium effects on calcium. 

Human blood levels of selenium are reported to correlate somewhat with soil concentrations of the element (94). In addition, human ingestion of selenized vegetables and grain has resulted in signs of selenium toxicity (146). Ingestion of rice contaminated with cadmium from the effluent of a mining operation was hypothesized as the etiological factor in Itai-Itai disease in man (32). 

The most spectacular and publicized occurrence of cadmium poisoning resulted from dietary intake of cadmium by people in the Jintsu River Valley, near Fuchu, Japan. The victims were afflicted by itai, itai disease, which means ouch, ouch in Japanese. The symptoms are the result of painful osteomalacia (bone disease) combined with kidney malfunction. Cadmium poisoning in the Jintsu River Valley was attributed to irrigated rice contaminated from an upstream mine producing lead, zinc, and cadmium. 

Kjellstroem. T. 1986. Itai-itai Disease. In L, Friberg, C. G. Blinder, T. Kjellstroem, and G. F. Nordberg, Eds. Cadmium and Health A Toxicological and Epidemiological Appraisal, Vol. II. CRC Press, Boca Raton, FL, pp. 257-290. 

A classic example of essential metal deficiency resulting from nonessential metal exposure is Itai itai disease. Cadmium pollution in the Jinzu River basin in Japan resulted in severe nephrotoxicity in approximately 184 people. Renal tubule damage caused excessive loss of electrolytes and small proteins from the urine. In severe cases, urinary Ca loss was so severe that bone Ca was mobilized, resulting in osteomalacia. Renal tubular defects persisted for life and induced hypophosphatemia, hyperuricemia, and hyperchloremia, which are characteristic biochemical features of Itai-itai disease (see Section 21.6.1). 

Itai-itai disease was identified in residents of the Jinzu River Basin in Japan in the mid-1940s. A lead and zinc mine polluted the river with high levels of Cd. The river water was used in the irrigation of rice fields and for drinking water. People affected by the disease suffered severe kidney dysfunction and painful skeletal symptoms. In the worst cases, bones would break from slight pressure, even from simply coughing. It is important to note that the worst cases were presented in... 

Dangerous levels of human exposure from diet have occurred, most notably in Fuchu, in northern Japan where rice was eaten that was contaminated with cadmium derived from an old zinc mine and present in soil and water. Low calcium intake and vitamin D deficiency may also have been factors. The victims suffered from brittle bones, and it became known as itai-itai disease from the Japanese for ouch-ouch (see box). The village of Shipham in Somerset was, similarly, found to have very high levels of cadmium in the soil, which also derived from an old zinc mine. 

Cadmium is chemically similar to the metal zinc, and is absorbed from the gut in a similar way using the same system. It can interfere with zinc in the body and consequently may affect the male reproductive system where zinc is important. Cadmium interferes with the metabolism of calcium too, a critical mineral in the body with which it also has similarities. This interference leads to loss of calcium from the bones which then become brittle (osteomalacia). In the case of itai-itai disease, which was the result of cadmium poisoning in Japan, the exposure to cadmium was accompanied by a deficiency of vitamin D which made the problems with the bones worse. 

It has been observed in the past that the rate of emission of these trace metals into the atmosphere is low due to their low volatility. However, with the advent of large-scale metal mining and smelting as well as fossil-fuel combustion in the twentieth century, the emission rate of these metals has increased dramatically. As most of these emissions are released into the atmosphere where the mammals live and breathe, we see a great increase in the occurrence of health problems such as lead (Pb) poisoning, cadmium (Cd) Itai-itai disease, chromium (Cr), and nickel (Ni) carcinogenesis. 

In Japan, an unusual disease named "itai-itai byo" or ouch-ouch disease" was reported in 1955 [2]. This disease is characterized clinically by bone and kidney damage. In 1968, fhe Japanese Ministry of Health and Welfare concluded that itai-itai disease was caused by... 

As renal tubular damage progresses the concentration of serum creatinine increases. One of the most severe cases in the Cd-polluted Kakehashi River basin had a serum creatinine value of 4.4 mg/100 ml. Progression to renal failure was evidenced by high blood nitrogen, severe anemia, acidosis, hyponatremia, hyperphosphatemia and hypocalcemia [81]. It was reported that four out of six itai-itai disease patients died of uremia [82]. 

In 1967 and 1968, data of an extensive epidemiological investigahon involving 13,183 inhabitants (6,155 men and 7,028 women) aged 30 years and older living in the district where itai-itai disease occurred and adjacent districts were reported [83]. The prevalence of proteinuria and glucosuria in the endemic area was found to be markedly higher than that in the non-endemic district. 

Itai-itai disease is considered the most advanced stage of chronic Cd intoxication. Cadmium-induced bone effects are also suggested to occur in the more advanced stage. Originally, attention was focused on osteomalacia in the diagnosis of this disease. Recent studies, however, showed that osteopenia, a main characteristic of osteoporosis, can be detected in the early stage of chronic Cd intoxication. 

Bone density was analyzed in 28 women with itai-itai disease, 92 men and 114 women with Cd-induced renal dysfunction and 44 men and 66 women living in non-polluted areas using a microdensitometer [90]. To assess the degree of bone density by microdensitom-... 

Out of these results, one may deduce that itai-itai disease only represents the tip of the iceberg. Indeed, in the earlier stage of chronic Cd exposure, the presence of Cd-induced bone effects such as osteopenia may be reflected by both microdensitometry and biochemical indices of bone turn-over. The degree of bone damage closely parallels the degree of renal damage. 

However, in contrast, in a 20-year follow-up study in which (i) patients diagnosed as having itai-itai disease, (ii) subjects who were suspected of having... 

Nogawa K. itai-itai disease and follow-up studies, in Nriagu JO (editor). Cadmium in the environment. Part ii Fiealth effects. John Wiley Sons, New York 1981 p. 1-37. 

Nogawa K, Yamada Y, Honda R,Tsuritani I, Ishizaki M, Sakamoto M. Urinary N-acetyl-p-D-glucosaminidase and Pj-microglobulin in itai-itai disease.Toxicol Lett 1983 16 317-322. 

Kajikawa K, Kitagawa M, Nakanishi I, Ueshima H, Katsuda S, Kuroda K. A pathological study of"itai-itai disease". J Juzen Med Soc (in Japanese) 1974 83 309-347. 

Fukushima M. Environmental pollution by cadmium and its health effects an epidemiological approach to the itai-itai"disease. In New methods in environmental chemistry and toxicology. Coulston F, Koprte F, Goto M (editors). International Academic Printing Co,Tokyo 1973 p. 231-252. 

Nakagawa H,Tabata M, MorikawaY, Senma M, Kitagawa Y, Kawano S, KidoT. High mortality and shortened life-span in patients with itai-itai disease and subjects with suspected disease. Arch Environ Health 1990 45 283-287. 

---