Ingested mercury can injure the gut and cause ulcerations and bloody diarrhea. In the kidneys, mercury can cause acute tubular necrosis and renal failure.
Arsenic salts interfere with several aspects of cellular metabolism, leading to toxicities that are most prominent in the GI tract, nervous system, skin, and heart. Arsenic was poison of choice of skilled practitioners in the Borgia http://ebooksmedicine.net and Medici families in Renaissance Italy. Today, arsenic exposure is an important health problem in many areas of the world. Arsenic is found naturally in soil and water and is used in wood preservatives, herbicides, and other agricultural products. It may be released into the environment by the mining and smelting industries. Arsenic is present in Chinese and Indian herbal medicine, and arsenic trioxide is a frontline treatment for acute promyelocytic leukemia (Chapter 6). Large concentrations of inorganic arsenic are present in ground water in countries such as Bangladesh, Chile, and China. Between 35 and 77 million people in Bangladesh drink water contaminated with arsenic, constituting one of the greatest environmental cancer risks yet uncovered.
If ingested in large quantities, arsenic causes acute toxicity manifesting as severe abdominal pain, diarrhea; cardiac arrhythmias, shock and respiratory distress syndrome; and acute encephalopathy. GI, cardiovascular and CNS toxicity may be severe enough to cause death. These effects may be attributed to the interference with mitochondrial oxidative phosphorylation. Chronic exposure to arsenic causes hyper-pigmentation and hyperkeratosis of the skin, which may be followed by the development of basal and squamous cell carcinomas (but not melanomas). A symmetrical sensorimotor polyneuropathy can also develop. Arsenic-induced skin tumors differ from those induced by sunlight by appearing on palms and soles, and by occurring as multiple lesions. Arsenic exposure also is associated with an increased risk of lung carcinoma. The mechanisms of arsenic carcinogenesis in the skin and the lung are uncertain.
Cadmium is preferentially toxic to the kidneys and the lungs through uncertain mechanisms that may involve increased production of ROS. In contrast with the metals already discussed, cadmium is a relatively modern toxic agent. It is used mainly in nickel-cadmium batteries, which generally are disposed of as household waste. Cadmium can contaminate soil and plants directly or through fertilizers and irrigation water. Food is the most important source of exposure for the general population. Excessive cadmium intake can lead to obstructive lung disease and renal toxicity, initially as tubular damage that may progress to end-stage renal disease. Cadmium exposure can also cause skeletal abnormalities associated with calcium loss. Cadmium-contaminated water used to irrigate rice fields in Japan caused a disease in postmenopausal women known as “itai-itai” (ouch-ouch), a combination of osteoporosis and osteomalacia associated with renal disease. A survey showed that 5% of persons aged 20 years and older in the U.S. population have urinary cadmium levels that, according to research data, may produce subtle kidney injury and increased calcium loss.
Lead,mercury,arsenic,andcadmiumaretheheavymetalsmostcommonlyassociatedwithtoxiceffectsinhumans.
Childrenabsorbmoreingestedleadthanadults;themainsourceofexposureforchildrenislead-containingpaint.
ExcessleadcausesCNSdefectsinchildrenandperipheralneuropathyinadults.Excessleadcompeteswithcalciuminbonesandinterfereswiththeremodelingofcartilage;italsocausesanemia.
Themajorsourceofmercuryiscontaminatedfish.Thedevelopingbrainishighlysensitivetomethylmercury,whichaccumulatesinthebrainandblocksionchannels.