Biochemistry chapters
Minerals: iron, calcium, sodium, potassium and iodine
How the body absorbs, stores and controls iron, calcium and phosphate, sodium, potassium and iodine (plus zinc, copper, fluoride and selenium), what happens with too little or too much of each, and the bedside calculations doctors use: corrected calcium, iron deficit and potassium replacement.
- Iron is absorbed as ferrous (Fe²⁺) iron in the duodenum (helped by vitamin C and acid, blocked by tea, phytates and calcium), exported by ferroportin (blocked by hepcidin, raised in inflammation), carried by transferrin and stored as ferritin; iron deficiency shows low ferritin, high TIBC, low transferrin saturation and microcytic anaemia, while anaemia of chronic disease shows high or normal ferritin with low TIBC.
- Calcium is controlled by PTH (raises calcium, lowers phosphate), calcitriol (raises both) and calcitonin (lowers calcium); about 40% of serum calcium is albumin-bound, so total calcium is corrected for albumin; low calcium causes tetany (Chvostek, Trousseau signs) and high calcium causes "bones, stones, groans and moans".
- Potassium disorders show on the ECG (hypokalaemia: U waves, flat T; hyperkalaemia: peaked T, wide QRS → sine wave); emergency hyperkalaemia is treated with IV calcium gluconate (protects the heart), insulin with glucose and salbutamol (shift potassium into cells); iodine deficiency causes goitre, hypothyroidism and cretinism, prevented by iodised salt.
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Iron
Absorption
- Sources: haem iron (red meat, liver, fish) is absorbed well; non-haem iron (cereals, pulses, leafy vegetables) is absorbed poorly.
- Absorbed mainly in the duodenum and upper jejunum as ferrous (Fe²⁺) iron through DMT1; ferric iron is reduced by duodenal cytochrome b.
- Enhancers: vitamin C, gastric acid, meat protein.
- Inhibitors: tea (tannins), phytates (cereals, bran), calcium, antacids and PPIs, tetracyclines.
- Leaves the gut cell through ferroportin, oxidised by hephaestin, then bound to transferrin.
- Hepcidin (from the liver) blocks ferroportin, reducing absorption and trapping iron in macrophages; hepcidin rises in inflammation (IL-6) and iron overload, and falls in iron deficiency and increased red cell production.
There is no physiological route for iron excretion; balance is controlled at absorption. Daily losses are small (about 1 mg; more with menstruation, pregnancy).
Transport and storage
- Transferrin: plasma transport protein; total iron binding capacity (TIBC) measures it.
- Ferritin: soluble storage protein (liver, marrow, spleen); serum ferritin reflects stores (but rises in inflammation: an acute-phase protein).
- Haemosiderin: insoluble storage form in macrophages (Prussian blue stain).
| Test | Iron deficiency | Anaemia of chronic disease | Haemochromatosis / iron overload | Thalassaemia trait |
|---|---|---|---|---|
| Serum iron | ↓ | ↓ | ↑ | Normal |
| TIBC (transferrin) | ↑ | ↓ | ↓ | Normal |
| Transferrin saturation | ↓ | ↓ or normal | ↑↑ | Normal |
| Ferritin | ↓ (most useful single test) | Normal or ↑ | ↑↑ | Normal |
Iron deficiency anaemia
Causes: blood loss (menstruation, hookworm, peptic ulcer, colon cancer, NSAIDs), poor intake, pregnancy, malabsorption (coeliac), growth spurts. Features: fatigue, pallor, koilonychia, angular stomatitis, glossitis, pica, Plummer-Vinson syndrome (dysphagia, oesophageal web). Blood film: microcytic hypochromic, pencil cells.
Treatment: oral ferrous sulphate (or fumarate) taken away from tea and meals, with vitamin C; continue for about 3 months after haemoglobin normalises to refill stores. Haemoglobin should rise about 1 g/dL every 1–2 weeks (about 2 g/dL in 3–4 weeks). IV iron when oral fails or rapid repletion is needed.
Total iron deficit (mg) = weight (kg) × (target Hb − actual Hb) (g/dL) × 2.4 + iron stores
Iron stores ≈ 500 mg in adults over 35 kg
Woman 60 kg, Hb 8 g/dL, target 13 g/dL:
60 × (13 − 8) × 2.4 = 60 × 5 × 2.4 = 720 mg
+ 500 mg stores = 1220 mg total iron needed
Oral ferrous sulphate 200 mg contains 65 mg elemental iron
Iron poisoning (children taking tablets): vomiting, haematemesis, then apparent recovery, then shock, liver failure and gut strictures; antidote desferrioxamine.
Iron overload: hereditary haemochromatosis, repeated transfusions (thalassaemia major: chelation with desferrioxamine, deferasirox or deferiprone).
Calcium and phosphate
About 99% of body calcium is in bone. Normal serum calcium is about 8.5–10.5 mg/dL (2.2–2.6 mmol/L): about 45% ionised (active), 40% albumin-bound, 15% complexed.
Regulation
| Hormone | Stimulus | Effect on calcium | Effect on phosphate | How |
|---|---|---|---|---|
| PTH | Low ionised calcium | ↑ | ↓ | Bone resorption, kidney calcium reabsorption, phosphate excretion, stimulates 1α-hydroxylase |
| Calcitriol (1,25-(OH)₂D) | PTH, low phosphate | ↑ | ↑ | Gut absorption of both |
| Calcitonin (thyroid C cells) | High calcium | ↓ | ↓ | Inhibits osteoclasts (minor role in humans; marker for medullary thyroid cancer) |
Alkalosis increases albumin binding → lower ionised calcium → tetany (hyperventilation).
Corrected calcium
Corrected Ca (mg/dL) = measured Ca + 0.8 × (4.0 − albumin in g/dL)
Measured Ca 7.6 mg/dL, albumin 2.0 g/dL:
Corrected = 7.6 + 0.8 × (4.0 − 2.0) = 7.6 + 1.6 = 9.2 mg/dL → normal
SI version: corrected Ca (mmol/L) = measured Ca + 0.02 × (40 − albumin g/L)
Measured 1.90 mmol/L, albumin 20 g/L: 1.90 + 0.02 × 20 = 2.30 mmol/L
Hypocalcaemia
Causes: hypoparathyroidism (after thyroid or parathyroid surgery), vitamin D deficiency, chronic kidney disease, acute pancreatitis, low magnesium (impairs PTH release and action), massive transfusion (citrate), rhabdomyolysis, DiGeorge syndrome, pseudohypoparathyroidism.
Features: perioral and finger tingling, muscle cramps, tetany, carpopedal spasm, seizures, laryngospasm; Chvostek sign (tapping the facial nerve causes facial twitch), Trousseau sign (BP cuff inflated causes carpal spasm); prolonged QT.
Treatment: severe: IV calcium gluconate (10 mL of 10% over 10 minutes); correct magnesium; oral calcium and vitamin D (alfacalcidol or calcitriol in hypoparathyroidism and kidney disease).
Hypercalcaemia
Causes: primary hyperparathyroidism (commonest in outpatients) and malignancy (commonest in hospital: PTHrP, bone metastases, myeloma), vitamin D excess, sarcoidosis and TB, thiazides, immobilisation, milk-alkali syndrome, thyrotoxicosis.
Features: "bones (pain, fractures), stones (kidney), abdominal groans (constipation, pancreatitis, peptic ulcer), psychic moans (confusion, depression)", plus polyuria and thirst (nephrogenic diabetes insipidus), short QT.
Treatment: IV saline (rehydration first), then IV bisphosphonate (zoledronate, pamidronate); calcitonin (short-term); steroids for vitamin D-mediated causes (sarcoidosis, myeloma); treat the cause.
Phosphate
- Low phosphate: refeeding syndrome, alcohol, DKA treatment, hyperparathyroidism → muscle weakness, respiratory failure, haemolysis.
- High phosphate: chronic kidney disease (→ secondary hyperparathyroidism), tumour lysis, rhabdomyolysis.
Sodium and water
Sodium is the main extracellular cation (135–145 mmol/L) and determines extracellular fluid volume and plasma osmolality.
Plasma osmolality ≈ 2 × Na + glucose + urea (all in mmol/L; normal about 275–295 mOsm/kg).
Osmolality = 2 × Na + glucose + urea (mmol/L)
Na 140, glucose 5, urea 5: 2 × 140 + 5 + 5 = 290 mOsm/kg
Measured 320 → osmolar gap = 320 − 290 = 30 (normal < 10)
A high gap suggests an extra solute: methanol, ethylene glycol, ethanol
Hyponatraemia (below 135 mmol/L): the commonest electrolyte disorder in hospital.
- Hypovolaemic: vomiting, diarrhoea, diuretics (thiazides), Addison disease.
- Euvolaemic: SIADH (lung disease, CNS disease, drugs: carbamazepine, SSRIs, cyclophosphamide; small cell lung cancer), hypothyroidism, adrenal insufficiency, psychogenic polydipsia.
- Hypervolaemic: heart failure, cirrhosis, nephrotic syndrome, kidney failure.
- Pseudohyponatraemia: severe hyperlipidaemia or paraproteinaemia; hyperglycaemia lowers measured sodium (water shift).
- Features: nausea, headache, confusion, seizures, coma (cerebral oedema).
- Correction: slowly, no more than about 8–10 mmol/L in 24 hours in chronic hyponatraemia, to avoid osmotic demyelination (central pontine myelinolysis). Severe symptoms: hypertonic (3%) saline in small boluses.
Hypernatraemia (above 145 mmol/L): water loss (diarrhoea, fever, diabetes insipidus, poor access to water in infants and elderly). Correct slowly (risk of cerebral oedema if too fast).
Potassium
Potassium is the main intracellular cation (serum 3.5–5.0 mmol/L). Most is inside cells, so small shifts change serum levels greatly.
Shift into cells: insulin, β2 agonists, alkalosis. Shift out: acidosis, insulin lack (DKA), cell breakdown (haemolysis, rhabdomyolysis, tumour lysis), digoxin toxicity.
| Feature | Hypokalaemia (below 3.5) | Hyperkalaemia (above 5.5) |
|---|---|---|
| Causes | Vomiting and diarrhoea, diuretics (loop, thiazide), hyperaldosteronism (Conn), Cushing, insulin and salbutamol, alkalosis, low magnesium, renal tubular acidosis types 1 and 2 | Kidney failure, ACE inhibitors/ARBs, spironolactone, amiloride, trimethoprim, NSAIDs, Addison disease, acidosis, cell breakdown, haemolysed sample (false) |
| Symptoms | Muscle weakness, cramps, ileus, constipation, polyuria, arrhythmias; enhances digoxin toxicity | Weakness, paralysis, arrhythmias, cardiac arrest |
| ECG | Flat or inverted T waves, U waves, ST depression, long QU interval | Tall peaked T waves → flat P waves, long PR → wide QRS → sine wave → VF or asystole |
| Treatment | Oral or IV potassium chloride (IV usually no faster than 10 mmol/hour peripherally; concentrated solutions only in high-dependency settings); correct magnesium | See below |
Emergency treatment of hyperkalaemia (K⁺ above 6.5 mmol/L or ECG changes):
- IV calcium gluconate (10 mL of 10%, or calcium chloride): stabilises the heart membrane within minutes; does not lower potassium.
- Insulin + glucose (10 units soluble insulin in 25 g glucose): shifts K⁺ into cells (falls about 0.6–1 mmol/L).
- Nebulised salbutamol: shifts K⁺ into cells.
- Sodium bicarbonate if acidotic.
- Remove potassium: calcium resonium or newer binders, loop diuretics, dialysis.
- Stop causative drugs; monitor glucose.
In hyperkalaemia, calcium protects the heart; insulin-glucose and salbutamol shift potassium; dialysis and binders remove it.
Iodine
- Needed for thyroid hormones (T4 has 4 iodine atoms, T3 has 3). Adult need about 150 micrograms/day (more in pregnancy and lactation: about 250).
- Sources: iodised salt, seafood, dairy.
- Iodine deficiency disorders: goitre (endemic, especially in mountain areas such as northern Pakistan), hypothyroidism, and, if deficient in pregnancy, cretinism (intellectual disability, deafness, short stature), miscarriage and stillbirth. Iodine deficiency is the world's commonest preventable cause of intellectual disability.
- Prevention: universal salt iodisation, a long-running public health programme in Pakistan.
- Excess iodine: hypothyroidism (Wolff-Chaikoff) or hyperthyroidism (Jod-Basedow) in susceptible people.
Trace elements
| Element | Role | Deficiency | Excess or disorder |
|---|---|---|---|
| Zinc | Many enzymes (carbonic anhydrase, alcohol dehydrogenase), wound healing, immunity, growth, taste | Growth retardation, hypogonadism, poor wound healing, loss of taste, acrodermatitis enteropathica (rash around mouth and anus, alopecia, diarrhoea), diarrhoea; zinc is given in childhood diarrhoea (10–14 days) | Copper deficiency |
| Copper | Cytochrome oxidase, lysyl oxidase (collagen), superoxide dismutase, ceruloplasmin | Microcytic anaemia, neutropenia, neuropathy; Menkes disease (X-linked, copper transport: kinky hair, neurodegeneration) | Wilson disease (ATP7B; autosomal recessive): low ceruloplasmin, copper in liver (cirrhosis), brain (basal ganglia: tremor, dystonia, psychiatric) and cornea (Kayser-Fleischer rings); treat with penicillamine, trientine, zinc |
| Fluoride | Strengthens tooth enamel and bone | Dental caries | Fluorosis: mottled teeth, bone sclerosis (high-fluoride groundwater in parts of Pakistan) |
| Selenium | Glutathione peroxidase (antioxidant), deiodinases | Keshan disease (cardiomyopathy), Kashin-Beck disease | Hair and nail loss |
| Magnesium | ATP reactions, PTH release, nerve and muscle | Tetany, arrhythmias, refractory hypokalaemia and hypocalcaemia; causes: diuretics, PPIs, alcohol, diarrhoea | Weakness, loss of reflexes, respiratory depression (magnesium sulphate in eclampsia: antidote calcium gluconate) |
| Chromium | Insulin action | Impaired glucose tolerance | (none commonly tested) |
| Manganese, molybdenum, cobalt (in B12) | Enzyme cofactors | Rare | (none commonly tested) |
Expect: iron absorption (form, site, enhancers, inhibitors), hepcidin and ferroportin, ferritin and TIBC patterns, iron therapy, PTH, calcitriol and calcitonin actions, corrected calcium, causes and signs of hypo- and hypercalcaemia, osmolality, causes of hyponatraemia and safe correction, hypokalaemia and hyperkalaemia ECG changes and emergency treatment, iodine deficiency and iodised salt, zinc in diarrhoea, Wilson and Menkes disease, fluorosis.
Quick revision
- Iron: Fe²⁺, duodenum; vitamin C helps, tea and phytates block; hepcidin blocks ferroportin.
- Iron deficiency: low ferritin, high TIBC. Chronic disease: normal or high ferritin, low TIBC.
- PTH: ↑ Ca, ↓ PO₄. Calcitriol: ↑ both. Corrected Ca = Ca + 0.8 × (4 − albumin).
- Hypocalcaemia: Chvostek, Trousseau, long QT. Hypercalcaemia: bones, stones, groans, moans.
- Hyponatraemia: correct ≤ 8–10 mmol/L per day (osmotic demyelination).
- Hypokalaemia: U waves. Hyperkalaemia: peaked T; calcium gluconate, insulin-glucose, salbutamol.
- Iodine: goitre, cretinism; iodised salt. Zinc: childhood diarrhoea. Wilson: low ceruloplasmin.
Written by The House Job from standard biochemistry references (Lippincott Illustrated Reviews: Biochemistry).
FAQ
In what form and where is iron absorbed?
As ferrous (Fe²⁺) iron, mainly in the duodenum.
How is serum calcium corrected for albumin?
Corrected calcium (mg/dL) = measured calcium + 0.8 × (4.0 − albumin in g/dL).
What is given first in severe hyperkalaemia?
Intravenous calcium gluconate, to protect the heart, followed by insulin with glucose and salbutamol to move potassium into cells.
What is the best single test for iron deficiency?
Serum ferritin, which is low; it can be falsely normal in inflammation.