Minerals and trace elements

Calcium and bone mineral

• About 99% of body calcium is in bone, deposited on a collagen (osteoid) framework as hydroxyapatite, a calcium phosphate crystal [Ca₁₀(PO₄)₆(OH)₂]. Osteoid is the unmineralised matrix; osteoblasts mineralise it with the help of alkaline phosphatase, which provides phosphate by breaking down pyrophosphate (an inhibitor of mineralisation).
• Bone strength depends on both the collagen framework (defective in osteogenesis imperfecta) and mineral (defective in rickets and osteomalacia). Fluoride converts hydroxyapatite to the harder, more acid-resistant fluorapatite.
• Plasma calcium 2.2–2.6 mmol/L (8.8–10.4 mg/dL); about half is ionised (the active fraction), 40% bound to albumin.
• Low albumin lowers total but not ionised calcium; correct by adding 0.02 mmol/L for every g/L albumin below 40 (0.8 mg/dL per g/dL below 4). Alkalosis increases albumin binding and lowers ionised calcium, so hyperventilation causes tetany.
• Calcium needs about 1,000–1,200 mg/day; absorbed in duodenum, increased by calcitriol, reduced by phytates and oxalates.
• Hypocalcaemia: perioral tingling, carpopedal spasm, Trousseau (cuff) and Chvostek (facial tap) signs, prolonged QT, seizures.
• Hypercalcaemia: bone pain, stones, abdominal pain, constipation, confusion, polyuria, short QT; commonest causes are primary hyperparathyroidism (outpatients) and malignancy (inpatients).

Phosphate and magnesium

• Phosphate: bone, ATP, 2,3-BPG, nucleic acids, urinary buffer. The kidney excretes it under PTH and FGF23. In refeeding syndrome insulin drives phosphate into cells, causing hypophosphataemia: muscle weakness, respiratory failure, haemolysis, heart failure.
• Magnesium: cofactor for every ATP-using enzyme. Hypomagnesaemia (diuretics, PPIs, alcohol, diarrhoea, aminoglycosides, cisplatin) causes refractory hypocalcaemia (PTH release and action fail) and refractory hypokalaemia (renal potassium loss), arrhythmias and torsades de pointes (treat with IV magnesium).

Exam trap Hypocalcaemia or hypokalaemia that will not correct: check and replace magnesium first.

Iron: absorption and regulation

• Haem iron (meat, fish) is absorbed intact and well (15–35%). Non-haem iron (cereals, pulses, vegetables) is mostly ferric (Fe³⁺) and poorly absorbed (2–20%).
• Site: duodenum and upper jejunum. Ferric iron is reduced to ferrous by duodenal cytochrome b, enters via DMT1, and leaves the cell through ferroportin into blood, where it travels on transferrin. It is stored as ferritin and haemosiderin.
• Hepcidin from the liver blocks ferroportin. It rises in inflammation (causing anaemia of chronic disease) and falls in iron deficiency; it is inappropriately low in haemochromatosis.
• Body iron is regulated only at absorption; there is no excretion pathway apart from blood loss and shed cells.

• So a woman with iron deficiency who drinks tea with meals should take vitamin C-rich food or juice with meals and drink tea between meals, not with them.
• Phytates and oxalates bind iron, zinc and calcium in the gut, giving plant-based diets poor mineral bioavailability.

Remember Vitamin C with meals, tea between meals.

Iron deficiency anaemia

• The commonest anaemia worldwide; causes are blood loss (menstruation, GI bleeding, hookworm), poor intake, increased need (infancy, pregnancy) and malabsorption (coeliac, after gastrectomy, where iron deficiency is the commonest anaemia).
• Clinical: pallor, fatigue, koilonychia, glossitis, angular cheilitis, pica, Plummer–Vinson web.
• Blood film: microcytic hypochromic cells, pencil cells, anisocytosis.
• Serum ferritin is the best single test (low ferritin is diagnostic), but ferritin is an acute-phase protein and may be falsely normal in inflammation. Serum iron low, TIBC and transferrin high, transferrin saturation low. Bone marrow iron stain is the gold standard but rarely needed.

• Haemoglobin electrophoresis (raised HbA2) is the key test to separate β-thalassaemia trait from iron deficiency.
• Treatment: oral ferrous sulphate (taken with vitamin C, away from tea and antacids), and find the cause. Children: iron-rich weaning foods; prophylactic iron in pregnancy where deficiency is common.

Iodine

• Needed for thyroid hormone: intake about 150 µg/day (250 µg in pregnancy and lactation). Taken up by the sodium–iodide symporter, oxidised and attached to tyrosines on thyroglobulin (made by follicular cells) by thyroid peroxidase.
• Deficiency causes endemic goitre in particular geographic areas (mountains, far from the sea), hypothyroidism and cretinism; it is the commonest preventable cause of intellectual disability worldwide. Prevented by iodised salt; population status is measured by urinary iodine.
• Worldwide, iodine deficiency is the commonest cause of hypothyroidism; in iodine-sufficient regions, Hashimoto thyroiditis is.
• Goitrogens: cassava (thiocyanate), brassicas, lithium, amiodarone. Excess iodine can cause transient block (Wolff–Chaikoff) or hyperthyroidism in nodular glands (Jod–Basedow). Iodine excess from contrast or amiodarone reduces radioactive iodine uptake.

Trace elements

• Zinc given with ORS shortens childhood diarrhoea; TPN without trace elements causes zinc, copper, selenium and chromium deficiency. Delayed wound healing is linked to deficiency of vitamin C, zinc and copper.

Copper disorders and Wilson disease

• Menkes disease (ATP7A, X-linked): copper cannot be absorbed from gut, so lysyl oxidase and other copper enzymes fail: kinky hair, neurodegeneration.
• Wilson disease (ATP7B, autosomal recessive): the liver cannot excrete copper into bile or load it onto caeruloplasmin, so copper builds up in liver, brain (basal ganglia: tremor, dystonia, psychiatric change), cornea (Kayser–Fleischer rings) and kidney. Suspect it in anyone under 40 with unexplained liver disease or movement disorder.
• Diagnosis uses several tests because none is perfect: raised 24-hour urinary copper (the most useful supportive test when the picture is unclear), low serum caeruloplasmin, slit-lamp KF rings, and liver biopsy copper content (gold standard) or ATP7B genetic testing.
• A normal caeruloplasmin does not exclude Wilson disease (it is an acute-phase protein), and KF rings may be absent in liver-predominant disease.
• Treatment: chelation (penicillamine, trientine), zinc (blocks gut copper uptake), liver transplant for fulminant failure.

Exam trap Borderline caeruloplasmin and no KF rings do not rule out Wilson disease; measure 24-hour urinary copper.

How FCPS asks about this

• Best single test for iron deficiency: serum ferritin (low); TIBC is high.
• Separating iron deficiency from β-thalassaemia trait: haemoglobin electrophoresis (raised HbA2) with normal ferritin.
• Advice to improve iron absorption in a tea drinker: vitamin C with meals, tea between meals; phytates and calcium also reduce absorption.
• Chemical form of bone mineral: hydroxyapatite on a type I collagen framework.
• Hypocalcaemia not correcting with calcium: hypomagnesaemia.
• Commonest preventable cause of intellectual disability: iodine deficiency; prevented by iodised salt.
• Teen with liver disease and tremor but borderline caeruloplasmin and no KF rings: raised 24-hour urinary copper supports Wilson disease.