Bone marrow nonneoplastic
Benign changes
Arsenic toxicity
Last author update: 1 July 2013
Last staff update: 4 October 2023
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PubMed Search: Bone marrow arsenic toxicity
Table of Contents
Definition / general | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Uses by pathologists | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Peripheral smear images | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Differential diagnosisCite this page: Zhao X. Arsenic toxicity. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowarsenic.html. Accessed April 19th, 2024.
Definition / general
- Arsenic intoxication is associated with acute and chronic adverse health effects
- Arsenic is pervasive in water, soil, air; has natural and anthropogenic sources
- Its metabolism involves reduction to a trivalent state and oxidative methylation to a pentavalent state; the trivalent arsenicals, including those methylated, have more potent toxic properties than the pentavalent arsenicals (Toxicol Lett 2002;133:1)
- Arsenic (As) belongs to fifth group of Mendeleyev's periodic table
- Free element of arsenic appears in two allotropic forms: grey and yellow (crystalline)
- Can also exist in various oxidation states, inorganic and organic forms, exposure to inorganic arsenic is associated with most cases of arsenic induced toxicity
Epidemiology
- Arsenic contamination in drinking water identified in Russia, New Zealand, Romania, USA
- Inorganic arsenic (e.g. arsenic trioxide) is present in air, usually due to volcanic eruption and purposeful human activities
- Arsenic also found as sulphuric compound in lead, copper, nickel and ferrous ores; also in soil in small quantities
- Also a medicinal used by physicians for 2000 years
Sites
- Oral toxicities predominate, cause GI irritation, peripheral neuropathy, vascular lesions, anemia, skin disease; cancer of bladder, kidney, liver, lung (Int J Occup Med Environ Health 2002;15:101)
- Exposure by inhalation is associated with increased risk of lung cancer
- Little information is available on effects of direct dermal contact (Environ Health Perspect 1993;101:79)
Pathophysiology
- Intracellularly, arsenic accumulates in mitochondria, where it inhibits succinic dehydrogenase and uncouples oxidative phosphorylation, resulting in low ATP levels
- May also down regulate certain cytochrome P450 enzymes and activate c-Jun / AP1 transcription complex
- High doses of inorganic arsenicals induce release of TNF alpha
- Arsenic can induce cross tolerance to cytotoxicity, genotoxicity and apoptosis induced by nickel and other metals (Toxicol Appl Pharmacol 2001;176:127)
Etiology
- Relative toxicities of arsenicals: As (III) > Mas (III) > DMAs (III) > DMAs (V) > Mas (V) > As (V); trivalent arsenicals increase cell proliferation at low concentrations (0.001 - 0.01 μmol) (Toxicol Appl Pharmacol 2001;172:225)
Clinical features
- Bone marrow depression: due to acute or more commonly chronic arsenic intoxication, may initially manifest as pancytopenia and be reversible; may have nonspecific clinical presentation of pancytopenia, fatigue / weakness (anemia), frequent infections (leukopenia) and easy bruising / petechia (thrombocytopenia)
- Anemia and leukopenia are common in chronic arsenic toxicity, are often accompanied by thrombocytopenia and mild eosinophilia
- Chronic arsenic exposure may be associated with immunosuppression (National Research Council: Arsenic in Drinking Water, 1999)
- Acute intoxication with arsine gas can cause fulminant intravascular hemolysis
- Most sensitive endpoint from arsenic exposure is dermal effects
Diagnosis
- Can measure arsenic in blood, urine, hair, fingernails
- Current biological exposure index for U.S. workers of 35 μg/L total urinary arsenic may easily be exceeded by a healthy person eating a seafood meal (The Agency for Toxic Substances and Disease Registry (ATSDR): Arsenic Toxicity)
- Urine test is most reliable method for arsenic exposure within past few days; needs to be done within 24 - 48 hours for accurate analysis of acute exposure
- Hair and fingernail tests measure exposure to high levels over past 6 - 12 months
- Newer microanalytical techniques include synchroton radiation based X ray fluorescence (SXRF) spectroscopy, microparticle induced X ray emission (PIXE) (Biochimie 2009;91:1260)
Uses by pathologists
- Arsenic trioxide approved for treatment of relapsed acute promyelocytic leukemia (APL) for remission induction
- May have activity for various solid tumors, myelodysplastic syndrome, myeloma, autoimmune disease (Ann Hematol 2013;92:719, Chin Med J (Engl) 2012;125:3556, Expert Opin Pharmacother 2012;13:1031, Leukemia 2012;26:1743)
Case reports
- 35 year old woman with megaloblastic, dyserythropoietic anemia following arsenic ingestion (Ann Clin Lab Sci 1980;10:515)
- 41 year old woman with arsenic intoxication presenting as myelodysplastic syndrome (Am J Hematol 1991;36:291)
- 2 cases of acute arsenic intoxication from contaminated well water (Arch Environ Health 1989;44:385)
- 3 cases of erythroid karyorrhexis in peripheral blood smear in severe arsenic poisoning (Am J Clin Pathol 1984;81:533)
- Chronic arsenic intoxication associated with hemoloytic anemia, megaloblastic anemia and hypoplastic bone marrow (Rinsho Ketsueki 1980;21:409)
- Folic acid deficiency in chronic arsenic poisoning (Lancet 1965;1:784)
Treatment
- Acute arsenic poisoning: dimercaprol and dimercaptosuccinic acid (DMSA) are chelating agents that sequester arsenic from blood proteins (Biochimie 2009;91:1260)
- Supplemental potassium decreases risk of life threatening arrhythmias from arsenic trioxide
- Sulfur containing substances in garlic may scavenge arsenic from tissue and blood
Clinical images
Images hosted on other servers:
Pigment changes and
palmoplantar hyperkeratoses
are characteristic of
chronic arsenic exposure
Arsenic keratosis -
so called "raindrops
on a dusty road"
Skin cancer
Microscopic (histologic) description
- Peripheral smear: leukopenia including granulocytopenia and absolute eosinophilia, and profound anemia (normocytic or macrocytic) with coarse basophilic stippling and karyorrhexis (N Engl J Med 1965;273:18, West J Med 1983;139:219, Am J Clin Pathol 1984;81:533, Blut 1985;50:51)
- Dyserythropoiesis including megaloblastic features and typical karyorrhexis in erythropoietic cells, accompanied by basophilic stippling and impairment of mitoses in megakaryocytes and granulopoietic components
- Bone marrow biopsy shows nonspecific changes
Microscopic (histologic) images
AFIP images
Bone marrow: erythroid
precursors have marked
dysplastic changes including
nuclear lobulation and karyorrhexis
Peripheral smear images
AFIP images
Erythroid precursor with
slightly lobulated
megaloblastoid nucleus
Electron microscopy description
- Arsenic intoxication induces megaloblastic erythropoiesis and other bone marrow changes similar to other dyserythropoietic states, including marked nuclear aberrations involving shape, chromatin distribution and nuclear envelope (Blood 1979;53:820)
Electron microscopy images
Images hosted on other servers:
Abnormal erythroblasts
Molecular / cytogenetics description
- No specific cytogenetic abnormalities
Differential diagnosis
- Other heavy metal intoxications, especially those associated with anemia / pancytopenia
- Other conditions associated with megaloblastic changes in erythroid precursors
