Medical Quiz on Wilson's Disease, Fluoride, and Iodine

Wilson's Disease

• Autosomal recessive genetic disorder
• Impaired biliary copper excretion
• Presents typically between ages 6 and 40
• Excess copper deposited in liver and brain basal nuclei, causing sclerosis and hepatitis
• Kidney, cornea, and brain abnormalities possible
• Kayser-Fleischer rings (green-brown discoloration) in cornea from copper deposition

Fluoride

• Used to prevent dental caries and minimize bone loss
• Stimulates bone formation
• Drinking water fluoridation reduces tooth decay by over 60% in the US
• Primarily excreted through kidneys

Fluoride Toxicity

• Calcification of soft tissues
• Dental fluorosis (unsightly enamel mottling) in children's teeth from excessive fluoride intake

Iodine

• Dietary iodine (ingested as iodide) is fundamental for thyroid hormone synthesis
• Transported to thyroid follicles, concentrated significantly
• Thyroid-stimulating hormone (TSH) stimulates iodine trapping and incorporation into thyronines

Iodine Deficiency

• Leads to inadequate thyroid hormone and hypothyroidism
• Results in:
  • Mental retardation and cretinism (congenital hypothyroidism in children)
  • Myxedema (hypothyroidism in adults), affecting mental status and blood pressure
  • Goiter development

Manganese

• Component of metalloenzymes (e.g., superoxide dismutase, pyruvate carboxylase)
• Found in high levels in fat and bone
• Food sources include whole grains, nuts, leafy vegetables, soy, and tea

Manganese Deficiency

• Lowers plasma cholesterol
• Impairs glucose tolerance
• Causes skeletal abnormalities, dermatitis, hair color changes, and reduced blood clotting (not responsive to vitamin K)

Manganese Toxicity

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

Iron

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

Iron Deficiency

• Affects ~15% of the global population
• Those at risk: pregnant women, young children, adolescents, women of reproductive age
• Caused by increased blood loss, decreased intake, or decreased release from ferritin
• Iron-deficiency anemia (IDA) is the most common anemia worldwide

Iron Toxicity

• Hemochromatosis: iron overload with or without tissue damage, often due to hereditary hemochromatosis (abnormally high iron absorption) affecting liver function and skin hyperpigmentation
• Hemosiderosis: iron overload without tissue damage

Lab Evaluation of Metal Metabolism Disorders

• Assessed via hematocrit, hemoglobin, RBC count/indices, total iron level, percent saturation, transferrin, ferritin, and total iron-binding capacity (TIBC)

Precautionary Measures in Trace Element Labs

• Isolation of trace element labs with contamination controls (mats, non-shedding tiles, controlled airflow, disposable booties, particulate monitors)

Causes of Trace Element Deficiencies

• Decreased intake (nutritional deficiency)
• Inadequate supplementation (total parenteral nutrition)
• Increased utilization (increased catabolism)
• Interactions between trace elements (e.g., zinc interfering with copper absorption) or with other nutrients
• Increased excretion
• Disease states limiting intestinal absorption (malabsorption syndromes, intestinal resection)
• Genetic diseases preventing element absorption (e.g., Menkes' syndrome, congenital atransferrinemia, acrodermatitis enteropathica, xanthine/sulfite oxidase deficiencies)

Lab Methodologies

• Atomic Absorption Spectrometry (AAS):
  • Most common for trace/toxic metal analysis
  • Flame AAS for copper, iron, zinc (parts per million)
  • GFAAS (graphite furnace AAS) for selenium, cadmium, lead (widely used in clinical samples)

Lab Methodologies (cont.)

• Inductively Coupled Plasma Mass Spectrometry (ICP-MS): Highly sensitive and specific for multiple trace elements in a single run, ionizing argon to excite atoms
• Atomic Emission Spectroscopy (AES):
  • Uses flame or inductively coupled plasma sources
  • Liquid sample converted to aerosol, excited atoms yield wavelengths measured by detectors (photomultipliers and array systems)

Elemental Speciation

• Element toxicity depends on chemical form (e.g., arsenic—arsenobetine is non-toxic, methylated forms are intermediate, inorganic arsenic is toxic)
• Hyphenated techniques (combining multiple analytical techniques to separate elemental forms)

Test your knowledge on Wilson's Disease, fluoride's role in dental health, and the importance of iodine for thyroid function. This quiz covers the mechanisms, effects of deficiencies, and the consequences of excessive intake for each topic. Perfect for students of medicine and health sciences!