EFFECTS OF HEAVY METALS ON THE BONE MARROW & PORTAL SYSTEM


anatomy-of-the-bone-drawing-shows-spongy-bone-red-marrow-and- LYMPHOCYTESThe body’s goal is to keep the blood as clean as possible as this is essential to life.  One method of achieving this goal is to move extremely toxic substances out of the blood and eventually out of the body.  What cannot be removed from the body must be moved into areas such as the bone marrow where it can be stored and be less lethal as indicated in the picture to the left.   With their affinity for bone marrow, mercury, lead and cadmium will be stored there. ([1],[2],[3],[4],[5],[6])

Cadmium is an important environmental pollutant.  The environmental risk can lead to the absorption of large quantities of Cd and its toxic action on the organism. ([7]) Though there are still some questions about Cadmium’s individual effects on the blood cells in the bone marrow, there is evidence that Cd  presents a serious threat to the bone marrow when coupled with lead.  Bauchinger et al. reported subjects exposed to Pb (mean B-Pb 19±7, ug/100 ml) and Cd (B-Cd 0.40±0.27 p, g/100 ml) who experienced an increase of both chromatid and chromosome type aberrations.([8])

Lead is a major environmental pollutant that is well documented to be predominantly stored in the bone marrow within 30 days of exposure. ([9],[10])  Using the Alkaline Comet Assay to assesses DNA damage in individual cells, it was shown that, in the bone marrow,  lead acetate induces DNA damage in isolated human lymphocytes at 1–100M.  Lead acetate may induce single-strand breaks (SSB) and double-strand breaks (DSB) in DNA as well as DNA-protein cross-links. (Wosniak and Blasiak 2003)([11]) An assay was performed using lead-nitrate on whole mice blood at 24, 48, 72 h, 1st and 2nd week. Significant increase in mean tail-length of DNA was observed at all time intervals after treatment with lead-nitrate when compared to controls.  Increase in mean tail-lengths clearly gives evidence that lead-nitrate causes DNA damage effectively.  [Devi et al 2000([12])]

“Metallic mercury is extremely dangerous with a few drops generating enough fumes to contaminate the air in a room. Furthermore, skin contact with the metal results in the absorption of mercury into the blood stream and potential health problems.” ([13]) According to the International Academy of Oral Medicine and Toxicology, mercury is the most toxic non-radioactive substance on our planet.  Most human exposure results from fish consumption (organic mercury) or dental amalgam (elemental mercury). ([14])  Well water can also be a source of mercury.  ([15])  Mercury has the ability to cause aneuploidy which is present in some cancer cells. ([16],[17])

Cadmium, lead and mercury are synergistic in their effects on the human body.  All three metals are known to cause chromosomal aberrations. Deknudt and Leonard found an increased incidence of “complex chromosomal aberrations” in 23 men exposed to high levels of Cd (B-Cd 3.2, ug/100 ml) and Pb. ([18])  Bauchinger et al. reported subjects exposed to Pb (mean B-Pb 19±7, ug/100 ml) and Cd (B-Cd 0.40±0.27 p, g/100 ml) who experienced an increase of both chromatid and chromosome type aberrations. ([19])  This points to the very real possibility that when Cd, Pb and Hg are present, their ability to cause chromosomal abnormalities are synergistic. ([20]) We are expecting to see CLL diagnosed more in this population than in others.

Hepatic-Portal-Circulation - WITH MARROWThe liver is one of the primary organs involved in the elimination of Cd. ([21]) The spleen is a reservoir for lymphocytes as it collects them directly from the blood.  The lymphocytes are housed in the splenic red pulp portion of the spleen. ([22])  The spleen is also capable of producing lymphocytes. (Mayo Clinic [23])

Hepatic-Portal-Circulation - WITH MARROW and cellsEventually, the spleen will release the lymphocytes into the blood (Merck Manual)([24]) going into the liver (hepato-Hepatic-Portal-Circulation - LEUKEMIA portal system).

Since Pb has been shown to cause chromosomal abnormalities in the lymphocytes which in turn, result in the cell’s overproduction, it follows that this overproduction of abnormal lymphocytes will send an excess of these cells to the spleen and on to the liver.  Since the liver is especially sensitive to the toxic effects of Cd ([25]), we theorize that the liver can get overwhelmed with by the direct effects Cd and with the job of trying to clear the body of the metal.  This will leave the liver with less than an optimal amount of its resources available for breaking down the excessive lymphocytes.  The more Pb and Cd, the higher the percentage of the liver’s functionality that will be diverted into managing these metals.  This will elevate circulating lymphocytes and back up the spleen, with the resulting splenomegaly.  We theorize that the dermal chelation process keeps the blood clean enough to allow the liver to focus on assisting the spleen with managing the damaged white blood cells.  This, in turn will lower the total WBC count.  When the source of these metals has been eliminated and the majority of the Pb and Cd have been removed from the body, the subject will keep a normal white blood cell count without having to continue the DC process.

Chromium is an essential nutrient that plays a role in glucose, fat, and protein metabolism by potentiating the action of insulin ([26]).  However, according to Wilbur’s Toxicological Profile for Chromium  Table 3-1 exposure to high levels causes increased white blood cell count.

 


[1] M. Berlin, R. K. Zalups, and B. A. Fowler, “Mercury,” in Handbook on the Toxicology of Metals, G. F. Nordberg, B. A. Fowler, M. Nordberg, and L. T. Friberg, Eds., chapter 33, Elsevier, New York, NY, USA, 3rd edition, 2007

[2] Barry PSI. A comparison of concentrations of lead in human tissues. Br J Ind Med. 1975;32:119–139.

[3] Rasmussen K.L., Skytte L., Pilekær C. et al. The distribution of mercury and other trace elements in the bones of two human individuals from medieval Denmark – the chemical life history hypothesis.  herit sci (2013) 1: 10.

[4] Cretaccia Y, Parsons PJ. Localized accumulation of lead within and among bones from lead-dosed goats. Environ Res. 2010 Jan; 110(1): 26–32.

[5] Flood PR, Schmidt PF, et al. The distribution of lead in human hemopoietic tissue and spongy bone after lead poisoning and Ca-EDTA chelation therapy. Observations made by atomic absorption spectroscopy, laser microbeam mass analysis and electron microbeam X-ray analysis. Arch Toxicol. 1988;62(4):295-300. https://www.ncbi.nlm.nih.gov/pubmed/3149183

[6] Stelzer KJ, Pazdernik TL. Cadmium-induced immunotoxicity. Int J Immunopharmacol. 1983;5(6):541-8.

[7] Arroyo VS, Flores KM, Ortiz LB, Gómez-Quiroz LE, Gutiérrez-Ruiz MC (2012) Liver and Cadmium Toxicity. J Drug Metabol Toxicol S5:001. doi: 10.4172/2157-7609.S5-001.

[8] Bauchinger, M., Schmid, E., Einbrodt, H. J., and Dresp, J. Chromosome aberrations in lymphocytes after occupational exposure to lead and cadmium. Mutat. Res. 40: 57 (1976).

[9] Barry PSI. A comparison of concentrations of lead in human tissues. Br J Ind Med. 1975;32:119–139.

[10] McCabe MJ Jr, Lawrence DA. Lead, a major environmental pollutant, is immunomodulatory by its differential effects on CD4+ T cells subsets. Toxicol Appl Pharmacol. 1991 Oct;111(1):13-23.

[11] Wozniak, Katarzyna & Blasiak, Janusz. (2003). In vitro genotoxicity of lead acetate: Induction of single and double DNA strand breaks and DNA-protein cross-links. Mutation research. 535. 127-39. 10.1016/S1383-5718(02)00295-4.

[12] Devi KD, Banu BS, et al. Genotoxic effect of lead nitrate on mice using SCGE (comet assay).Toxicology. 2000 Apr 14;145(2-3):195-201.

[13] National Institute of Environmental Health Sciences.  “Mercury”. Last Reviewed: September 28,2017

[14] Bernhoft RA. Mercury Toxicity and Treatment: A Review of the Literature. Journal of Environmental and Public Health. 2012;2012:460508. doi:10.1155/2012/460508.

[15] NC Department of Health and Human Services- Division of Public Health. Protect Yourself from Mercury in your Well Water Fact Sheet. July 2009.

[16] Sen S. Aneuploidy and cancer. US National Library of Medicine National Institutes of Health. Curr Opin Oncol. 2000 Jan;12(1):82-8.

[17] Vainio H, Sorsa M. Chromosome aberrations and their relevance to metal carcinogenesis. Environmental Health Perspectives. 1981;40:173-180.

[18] Vainio H, Sorsa M. Chromosome Aberrations and Their Relevance to Metal Carcinogenesis. Environmental Health Perspectives Vol. 40, pp. 173-180, 1981.

[19] Bauchinger, M., Schmid, E., Einbrodt, H. J., and Dresp, J. Chromosome aberrations in lymphocytes after occupational exposure to lead and cadmium. Mutat. Res. 40: 57 (1976).

[20] Vainio H, Sorsa M. Chromosome aberrations and their relevance to metal carcinogenesis. Environmental Health Perspectives. 1981;40:173-180.

[21] Arroyo VS, Flores KM, Ortiz LB, Gómez-Quiroz LE, Gutiérrez-Ruiz MC (2012) Liver and Cadmium Toxicity. J Drug Metabol Toxicol S5:001. doi: 10.4172/2157-7609.S5-001.

[22] PubMed Health. A service of the National Library of Medicine, National Institutes of Health. “How does the liver work?” PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

[23] Mayo Clinic. “Enlarged spleen (splenomegaly).”  Mayo Foundation for Medical Education and Research (MFMER) 1998-2017.

[24] Jacob, Harry S. “Overview of the spleen.” Merck Manual. Last full review/revision November 2016.

[25] Arroyo VS, Flores KM, Ortiz LB, Gómez-Quiroz LE, Gutiérrez-Ruiz MC (2012) Liver and Cadmium Toxicity. J Drug Metabol Toxicol S5:001. doi: 10.4172/2157-7609.S5-001.

[26] Anderson RA. Nutritional role of chromium. Sci Total Environ. 1981;17:13–29. [PubMed]

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