Wilson's Disease and Fluoride Overview

Wilson's Disease

• Autosomal recessive genetic disorder causing impaired biliary copper excretion
• Presents typically between ages 6 and 40
• Excess copper deposits in liver and brain basal nuclei, leading to sclerosis and hepatitis
• May affect kidneys, cornea, and brain
• Kayser-Fleischer rings (green-brown discoloration) in cornea due to copper deposition

Fluoride

• Used to prevent dental caries and minimize bone loss
• Stimulates bone formation
• Drinking water fluoridation decreased tooth decay incidence by over 60% in many US populations

Fluoride Toxicity

• Calcification of soft tissues
• Dental fluorosis (unsightly mottling of dental enamel) in children, possibly from fluoride-containing toothpaste

Iodine

• Dietary iodine (ingested as iodide) is crucial for thyroid hormone synthesis
• Transported to thyroid follicles, concentrated significantly
• Thyroid Stimulating Hormone (TSH) stimulates iodine trapping and incorporation into tyronines

Iodine Deficiency

• Leads to inadequate thyroid hormone and hypothyroidism
• Possible consequences:
  • Mental retardation and cretinism (congenital hypothyroidism in children)
  • Myxedema (hypothyroidism in adults with mental status changes and hypotension)
  • Goiter development

Manganese

• Component of several metalloenzymes (e.g., superoxide dismutase, pyruvate carboxylase, arginase, glycosyl transferases)
• Found in high concentrations in fat and bone
• Dietary sources: whole grains, nuts, leafy vegetables, soy, tea

Manganese Deficiency

• Low plasma cholesterol
• Impaired glucose tolerance
• Skeletal abnormalities
• Dermatitis
• Hair color changes
• Reduced blood clotting unresponsive to vitamin K

Manganese Toxicity

• Nausea, vomiting, headache, disorientation, memory loss, anxiety, compulsive laughing/crying
• Chronic toxicity resembles Parkinson's disease (akinesia, rigidity, tremors, mask-like faces)
• Brain deposition seen in biliary atresia in children
• "Manganese Madness" (Locura Manganica) described in Chilean manganese miners with acute manganese aerosol contamination

Iron

• Ferrous (Fe2+) and ferric (Fe3+) forms
• Fourth most abundant element in Earth's crust; abundant transition metal
• No excretory system for excess iron
• Primarily regulated by intestinal iron absorption
• Lost primarily through desquamation and red cell loss
• Women lose ~20-40 mg iron per menstrual cycle
• Excess free iron catalyzes toxic free radical formation, contributing to lipid peroxidation, atherosclerosis, DNA damage, and carcinogenesis
• Body iron distribution:
  • ~2-2.5g in hemoglobin (mostly in RBCs and precursors)
  • ~130mg in myoglobin
  • ~8mg in enzymes (e.g., peroxidases, cytochromes, Krebs cycle enzymes)
• Stored as ferritin or hemosiderin (bone marrow, spleen, liver)
• Hemosiderin formed when ferritin breaks down
• ~3-5mg in plasma (bound to transferrin, albumin, free hemoglobin)

Iron Deficiency

• Affects 15% of the global population
• At-risk groups: pregnant women, young children, adolescents, women of reproductive age
• Caused by increased blood loss, decreased intake, or decreased release from ferritin
• IDA (Iron Deficiency Anemia): most common anemia globally

Iron Toxicity

• Hemochromatosis: iron overload with or without tissue damage; associated with hereditary hemochromatosis, leading to increased iron absorption
• Affects liver function and often leads to hyperpigmentation of the skin
• Hemosiderosis: iron overload without demonstrable tissue damage

Lab Evaluation of Iron Metabolism Disorders

• Evaluated using hematocrit/hemoglobin, RBC count/indices
• Total iron level
• Percent saturation
• Transferrin
• Ferritin
• TIBC (Total Iron-binding Capacity)

Precautionary Measures (Trace Element Lab)

• Separate laboratory room
• Rigorous contamination control
• Sticky mats, non-shedding ceilings, controlled airflow
• Disposable booties
• Particulate monitoring equipment

Causes of Trace Element Deficiencies

• Decreased intake (nutritional)
• Total parenteral nutrition (inadequate supplementation)
• Increased utilization (increased catabolism)
• Interactions between trace elements (e.g., zinc and copper) or with other nutrients (e.g., zinc and vitamin C)
• Increased excretion
• Disease states (insufficient intestinal absorption, malabsorption syndromes, intestinal resection)
• Genetic mutations affecting element absorption (e.g., Menkes' kinky hair syndrome (copper), congenital atransferrinemia (iron), acrodermatitis enteropathica (zinc), xanthine & sulfite oxidase deficiencies (molybdenum))

Lab Methodologies for Trace Element Analysis

• Atomic Absorption Spectrometry (AAS):
  • Flame AAS (copper, iron, zinc; LOQ in ppm)
  • GFAAS (graphite furnace; selenium, cadmium, lead; broader application clinically)
  • Analyzes absorption of optical radiation by free atoms in gas phase
• Inductively Coupled Plasma Mass Spectrometry (ICP-MS): Highly sensitive, for multiple elements in a single run, uses ionized gas (argon), internal standard (Yttrium)
• Atomic Emission Spectroscopy (AES):
  • Uses flame or inductively coupled plasma source
  • Liquid sample converted to aerosol, atomized, excited, measured based on emitted radiation; Photographic film (obsolete), modern detectors (photomultipliers, arrays)
• Elemental Speciation: considers chemical form; Example: arsenic forms (e.g., arsenobetaine (nontoxic), methylated forms (intermediate toxicity), inorganic arsenic (toxic)) - crucial for toxicity assessment; Hyphenated techniques can determine elemental species.

This quiz covers key concepts in Wilson's disease, fluoride, fluoride toxicity, and the role of iodine in health. Explore how these substances affect the human body, including their chemical interactions and clinical implications. Test your knowledge on their significance in medical science.