Arsenic poisoning
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| Arsenic Poisoning | |
|---|---|
| Classification and external resources | |
| ICD-10 | T57.0 |
| ICD-9 | 985.1 |
| eMedicine | emerg/42 |
| MeSH | D020261 |
Arsenic Poisoning interferes with cellular longevity by allosteric inhibition of an essential metabolic enzyme pyruvate dehydrogenase (PDH) complex which catalyzes the oxidation of pyruvate to acetyl-CoA by NAD+. With the enzyme inhibited, the energy system of the cell is disrupted resulting in a cellular apoptosis episode. Biochemically, arsenic prevents use of thiamine resulting in a clinical picture resembling thiamine deficiency. Poisoning with arsenic can raise lactate levels and lead to lactic acidosis. Low potassium levels in the blood increase the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide. Arsenic in cells clearly stimulates the production of hydrogen peroxide (H2O2). When the H2O2 reacts with certain metals such as iron or manganese it produces a highly reactive hydroxyl radical. Inorganic Arsenic trioxide found in ground water particularly affects voltage-gated potassium channels,[1] disrupting cellular electrolytic function resulting in neurological disturbances, cardiovascular episodes such as prolonged qt interval, neutropenia, high blood pressure,[2] central nervous system dysfunction, anemia, Leukemia,[3] and death. Arsenic trioxide is a ubiquitous molecule present in American drinking water.[4]
| “ | Arsenic exposure plays a key role in the pathogenesis of vascular endothelial dysfunction as it inactivates endothelial nitric oxide synthase, leading to reduction in the generation and bioavailability of nitric oxide. In addition, the chronic arsenic exposure induces high oxidative stress, which may affect the structure and function of cardiovascular system. Further, the arsenic exposure has been noted to induce atherosclerosis by increasing the platelet aggregation and reducing fibrinolysis. Moreover, arsenic exposure may cause arrhythmia by increasing the QT interval and accelerating the cellular calcium overload. The chronic exposure to arsenic upregulates the expression of tumor necrosis factor-α, interleukin-1, vascular cell adhesion molecule and vascular endothelial growth factor to induce cardiovascular pathogenesis. | ” |
—Pitchai Balakumar1 and Jagdeep Kaur, "Arsenic Exposure and Cardiovascular Disorders: An Overview", Cardiovascular Toxicology, December 2009[5] | ||
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[edit] Toxicity
Research has shown that the inorganic arsenites (trivalent forms) in drinking water have a much higher acute toxicity than organic arsenates (pentavalent forms).[6] The acute minimal lethal dose of arsenic in adults is estimated to be 70 to 200 mg or 1 mg/kg/day.[7] Most reported arsenic poisonings are caused by one of arsenic's compounds, also found in drinking water, arsenic trioxide which is 500 times more toxic than pure arsenic.
Arsenic is related to the first five leading causes of non-accidental death in the United States, bringing the total to 1,525,675 related mortalities. EPA efforts are underway to reduce drinking water exposure to zero.[8][9] heart disease[10] (hypertension related cardiovascular), cancer,[11] stroke[12] (cerebrovascular diseases), chronic lower respiratory diseases,[13] and diabetes. These diseases are all related to the alteration of voltage dependent potassium channels. Researchers, led by Ana Navas-Acien, MD, PhD, of the Johns Hopkins Bloomberg School of Health, studied 788 adults who had their urine tested for arsenic exposure in the 2003-2004 National Health and Nutrition Examination Survey. Participants with type 2 diabetes had a 26% higher level of total arsenic in their urine than those without the disease.[citation needed] Diabetes is also related to alteration of voltage dependent potassium channels due in part to the function of insulin and potassium in the cellular metabolism of glucose. Due to the regular appearance of arsenic in public drinking water supplies, it is likely that arsenic plays a part in about thirty percent of total all cause mortality in the United States.[citation needed] Arsenic prevalence in the water has been related to the occurrence of hypertension, erectile dysfunction and related conditions. Leading causes of mortality in the world are all related to arsenic. These are
Chronic exposure to inorganic arsenic may lead to hypertension, involuntary muscular dysfunction (including incontinence), diabetes, neuropathy, depression, obesity and any other condition related to the altered role of intercellular voltage-dependent potassium channels, including cutaneous hyperpigmentation.[14]:859
[edit] Symptoms of Arsenic Poisoning
Symptoms of arsenic poisoning begin with headaches, confusion and drowsiness. As the poisoning develops, convulsions and changes in fingernail pigmentation may occur. When the poisoning becomes acute, symptoms may include diarrhea, vomiting, blood in the urine, cramping muscles, hair loss, stomach pain, and more convulsions. The organs of the body that are usually affected by arsenic poisoning are the lungs, skin, kidneys, and liver. The final result of arsenic poisoning is coma or death.
[edit] Pathophysiology
Main article: Arsenic toxicity
Tissue culture studies have shown that arsenic blocks both IKr and Iks channels and, at the same time, activates IK-ATP channels. Arsenic also disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. These metabolic interferences lead to death from multi-system organ failure, probably from necrotic cell death, not apoptosis. A post mortem reveals brick red colored mucosa, due to severe hemorrhage. Although arsenic causes toxicity, it can also play a protective role.[15]
[edit] Diagnosis
There are tests available to diagnose poisoning by measuring arsenic in blood, urine, hair, and fingernails. The urine test is the most reliable test for arsenic exposure within the last few days. Urine testing needs to be done within 24–48 hours for an accurate analysis of an acute exposure. Tests on hair and fingernails can measure exposure to high levels of arsenic over the past 6–12 months. These tests can determine if one has been exposed to above-average levels of arsenic. They cannot predict, however, whether the arsenic levels in the body will affect health.[16]
Hair is a potential bioindicator for arsenic exposure due to its ability to store trace elements from blood. Incorporated elements maintain their position during growth of hair. Thus for a temporal estimation of exposure, an assay of hair composition needs to be carried out with a single hair which is not possible with older techniques requiring homogenization and dissolution of several strands of hair. This type of biomonitoring has been achieved with newer microanalytical techniques like Synchroton radiation based X ray fluorescence (SXRF) spectroscopy and Microparticle induced X ray emission (PIXE).The highly focused and intense beams study small spots on biological samples allowing analysis to micro level along with the chemical speciation. In a study, this method has been used to follow arsenic level before, during and after treatment with Arsenious oxide in patients with Acute Promyelocytic Leukemia.[17]
[edit] Treatment
Chemical and synthetic methods are now used to treat arsenic poisoning. Dimercaprol and dimercaptosuccinic acid are chelating agents which sequester the arsenic away from blood proteins and are used in treating acute arsenic poisoning. The most important side effect is hypertension. Dimercaprol is considerably more toxic than succimer.[18]
In the journal Food and Chemical Toxicology, Keya Chaudhuri of the Indian Institute of Chemical Biology in Kolkata, and her colleagues reported giving rats daily doses of arsenic in their water, in levels equivalent to those found in groundwater in Bangladesh and West Bengal. Those rats which were also fed garlic extracts had 40 percent less arsenic in their blood and liver, and passed 45 percent more arsenic in their urine. The conclusion is that sulfur-containing substances in garlic scavenge arsenic from tissues and blood. The presentation concludes that people in areas at risk of arsenic contamination in the water supply should eat one to three cloves of garlic per day as a preventative.[19][20][21]
