Pathophysiology Unit 2-Factors of Disease Environmental Factors Heavy Metal Toxicity Pathophysiology Unit 2-Factors of Disease Environmental Factors Arsenic Lead Mercury

Definitions ‘Metals’ originally included only gold, silver, copper, iron, lead, and tin. Dense, malleable, lustrous Conduct heat and electricity Many other elements since added to the list with some of these characteristics ‘Metalloids’ are elements with features intermediate between metals and non-metals. Examples: lead and arsenic

‘Heavy metal’ A metal having an atomic weight greater than sodium, a density greater than 5 g/cm3 Some notion of toxicity Includes cadmium, lead and mercury

Lead

Lead Paint The use of lead in residential paint was banned in 1977 Lead-containing pigments still are used for outdoor paint products because of their bright colors and weather resistant properties Tetraethyl and tetramethyl lead are still used as additives in gasoline in several countries

Sources of Exposure Soil and dust Paint chips Contaminated water Parents lead-related occupation Folk remedies Congenital exposure Pica Developmental delay

Toxicity Absorption: Lungs: depends on size particle GI: Adults: 20-30% Children: as much as 50% of dietary lead Inadequate intake of iron, calcium, and total calories are associated with higher lead levels Skin: Inorganic lead is not absorbed Organic lead is well absorbed Lead is carried bound to the RBC

Clinical Manifestation Acute toxicity Acute encephalopathy, renal failure and severe GI symptoms

General Signs and Symptoms of Lead Toxicity Fatigue Irritability Lethargy Paresthesis Myalgias Abdominal pain Tremor Headache Vomiting Weight loss Constipation Loss of libido Motor neuropathy Encephalopathy Cerebral edema Seizures Coma Severe abdominal cramping Epiphyseal lead lines in children (growth arrest) Renal failure

Range of Lead-induced Health Effects in Adults and Children Blood lead levels Adults Children 10 g/dL Hypertension may occur Crosses placenta Impairment IQ, growth Partial inhibition of heme synthesis 20 g/dL Inhibition of heme synthesis Increased erythrocyte protoporphyrin Beginning impairment of nerve conduction velocity 30 g/dL Systolic hypertension Impaired hearing() Impaired vitamin D metabolism 40 g/dL Infertility in males Renal effects Neuropathy Fatigue, headache, abd pain Hemoglobin synthesis inhibition 50 g/dL Anemia, GI sx, headache, tremor Colicky abd pain, neuropathy 100 g/dL Lethargy, seizures, encephalopathy Encephalopathy, anemia, nephropathy, seizures

Childhood Lead Poisoning Childhood lead poisoning is now defined as a blood lead level of 10 g/dl

The average lead level of American children is 2 g/dl 8.9% of American children have lead poisoning Lead intoxication is more prevalent in minority groups and among those living in the northeast

Neurotoxicity of Lead in Childhood Mental retardation in severe lead intoxication  5 points in IQ for every 10 g/dl  in blood lead level- population based studies Other adverse developmental outcomes: Aggression Hyperactivity Antisocial behaviors Learning disability- impairment in memory, auditory processing, and visual-motor integration. The IQ is normal. These effects has been demonstrated with blood lead levels as low as 6 g/dl

Diagnosis Evaluation of clinical symptoms and signs CBC Serum iron levelsAbdominal radiographs (for recent ingestion of lead-containing material) Whole blood lead level X-ray fluorescence (XRF)- to asses body burden

Treatment Environmental inspection/hazard reduction Nutritional supplementation Chelation therapy

Arsenic

Introduction Arsenic is common in the environment Sources Groundwater Arsenic containing mineral ores Industrial processes Semiconductor manufacturing (gallium arsenide) Fossil fuels Wood treated with arsenic preservatives Metallurgy Smelting (copper, zinc, lead) and refining of metals and ores Glass manufacturing

Manifestations of acute arsenic poisoning Bodily system affected Symptoms or signs Time of onset Systemic Thirst Hypovolemia, Hypotension Minutes Minutes to hours Gastrointestinal Garlic or metallic taste Burning mucosa Nausea and vomiting Diarrhea Abdominal pain Hematemesis Hematochezia, melena Rice-water stools Immediate Hours Hematopoietic system Hemolysis Hematuria Lymphopenia Pancytopenia Several weeks Pulmonary (primarily in inhalational exposures) Cough Dyspnea Chest Pain Pulmonary edema Liver Jaundice Fatty degeneration Central necrosis Days Kidneys Proteinuria Acute renal failure Hours to days Manifestations of acute arsenic poisoning

Acute Arsenic Poinsoning

Mercury

Mercury Occurs in three forms (elemental, inorganic salts, and organic compounds) Contamination results from mining, smelting, and industrial discharges. Mercury in water can be converted by bacteria to organic mercury (more toxic) in fish. Can also be found in thermometers, dental amalgams, fluorescent light bulbs, disc batteries, electrical switches, folk remedies, chemistry sets and vaccines.

Mercury - Exposure Elemental liquid at room temperature that volatizes readily rapid distribution in body by vapor, poor in GI tract Inorganic poorly absorbed in GI tract, but can be caustic dermal exposure has resulted in toxicity Organic lipid soluble and well absorbed via GI, lungs and skin can cross placenta and into breast milk

Elemental Mercury At high concentrations, vapor inhalation produces acute necrotizing bronchitis, pneumonitis, and death. Long term exposure affects CNS. Early: insomnia, forgetfulness, anorexia, mild tremor Late: progressive tremor and erethism (red palms, emotional lability, and memory impairment) Salivation, excessive sweating, renal toxicity (proteinuria, or nephrotic syndrome) Dental amalgams do not pose a health risk.

Diagnosis and Treatment Dx made by history and physical and lab analysis. Inorganic mercury can be measured in 24 hour urine collection; organic mercury is measured in whole blood. The most important and effective treatment is to identify the source and end the exposure Chelating agents (DMSA) may enhance inorganic mercury elimination. Dimercaprol may increase mercury concentration in the brain.

Mercury - Prevention Many mercury compounds are no longer sold in the United States. Elemental mercury spills: Roll onto a sheet of paper and place in airtight container Use of a vacuum cleaner should be avoided because it causes mercury to vaporize (unless it is a Hg Vac) Consultation with environmental cleaning company is advised with large spills. State advisories on public limit or avoid consumption of certain fish from specific bodies of water.