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BI9.1-3 | Minerals, electrolytes, Water and Acid base balance — SDL Guide
Learning Objectives
- Describe the absorption, transport, storage, and functions of clinically important minerals: iron, calcium, phosphorus, copper, zinc, and iodine
- Explain the causes, biochemical mechanisms, and clinical features of iron-deficiency anaemia, osteoporosis, and zinc deficiency
- Describe the distribution and regulation of body water and the major electrolytes (Na⁺, K⁺, Cl⁻, HCO₃⁻)
- Explain the Henderson-Hasselbalch equation and the three buffer systems for acid-base balance
- Diagnose and interpret the four primary acid-base disorders from blood gas values with compensation
INSTRUCTIONS
This is a dense module — take it section by section. The acid-base section is often challenging for first-time learners; use the systematic approach taught here. Estimated time: 55 minutes.
References
CLINICAL SCENARIO
Outpatient morning at a district hospital in Rajasthan. Three patients in consecutive beds:
Bed 1: A 22-year-old woman who is 28 weeks pregnant with pallor, fatigue, and dyspnoea on climbing stairs. Haemoglobin: 6.8 g/dL. Blood film: microcytic hypochromic red cells.
Bed 2: A 65-year-old man admitted after a fracture of the hip from a simple fall at home. DEXA scan shows T-score −3.2. He has been on long-term prednisolone for COPD.
Bed 3: A 45-year-old with severe diarrhoea and vomiting for 3 days. Blood gas: pH 7.28, pCO₂ 28 mmHg, HCO₃⁻ 13 mEq/L.
Three different mineral/electrolyte problems. Can you identify each one and explain the biochemistry?
WHY THIS MATTERS
Minerals, electrolytes, and acid-base balance are central to clinical practice at every level:
- Iron deficiency anaemia affects 50% of pregnant women in India and is the leading cause of maternal mortality
- Electrolyte disturbances (hypo/hypernatraemia, hypo/hyperkalaemia) are common in hospitalised patients and can be life-threatening
- Acid-base disorders occur in every ICU patient and in common conditions: diabetic ketoacidosis, diarrhoea, renal failure, respiratory failure
- Understanding calcium-phosphate metabolism underpins management of osteoporosis, CKD-mineral bone disease, and parathyroid disorders
These topics bridge Biochemistry directly to Medicine, Surgery, and Obstetrics — you will use them daily as a clinician.
RECALL
Recall from previous topics:
- Haemoglobin structure: haem (iron-porphyrin) + globin chains — from Biochemistry (proteins)
- Ca²⁺ and PTH/Vitamin D axis — from the Vitamins and Minerals chapter
- Buffer concept from Chemistry: weak acid + its conjugate base
- Kidney anatomy and filtration (from Anatomy/Physiology) — relevant to electrolyte regulation
- Henderson-Hasselbalch equation (from general chemistry): pH = pKa + log ([A⁻]/[HA])
Iron — Absorption, Transport and Storage
Iron is the most clinically important mineral in India — deficiency is the leading nutritional disorder.
Total body iron: ~3.5–4 g (adult male); 2–3 g (adult female)
- ~65% in haemoglobin
- ~10% in myoglobin and enzymes (cytochromes, succinate dehydrogenase, ribonucleotide reductase)
- ~20–25% stored as ferritin and haemosiderin (liver, spleen, bone marrow)
- ~0.1% in plasma bound to transferrin (transport protein)
Iron absorption (duodenum and proximal jejunum):
- Haem iron (Fe²⁺ from meat, fish): absorbed directly via HCP1 receptor → much more bioavailable (~20–30%)
- Non-haem iron (Fe³⁺ from vegetables, cereals): must first be reduced to Fe²⁺ by brush border ferrireductase (Dcytb) — enhanced by Vitamin C; inhibited by phytates (cereals), oxalates (spinach), tannins (tea)
- Divalent metal transporter 1 (DMT1): transports Fe²⁺ into enterocyte
- Ferroportin: basolateral transporter → Fe²⁺ into portal blood → oxidised by hephaestin → Fe³⁺ → bound to transferrin (carries 2 Fe³⁺ per molecule)
Hepcidin — the master regulator of iron homeostasis:
- Peptide hormone made by the liver
- Binds ferroportin → internalises it → blocks Fe release from enterocytes, macrophages, hepatocytes
- High hepcidin → iron trapped → anaemia of chronic disease
- Low hepcidin → iron flows freely → used in haemochromatosis, iron overload
Iron storage:
- Ferritin: soluble storage protein; serum ferritin is the best marker of iron stores (low = iron deficiency; high = inflammation, iron overload, liver disease)
- Haemosiderin: insoluble ferritin aggregate in iron overload
Figure: Iron — Absorption, Transport and Storage
Iron Deficiency Anaemia — Stages and Diagnosis
Iron deficiency anaemia (IDA) develops in three stages:
Stage 1 — Iron depletion: Iron stores (ferritin) depleted. No anaemia yet. Serum ferritin low (<12 µg/L).
Stage 2 — Iron-deficient erythropoiesis: Serum transferrin rises (body tries to capture more iron); transferrin saturation falls (<20%). Mild microcytosis. No significant anaemia.
Stage 3 — Iron deficiency anaemia: Haemoglobin falls. Microcytic hypochromic red cells (MCV <80 fL, MCH <27 pg). Pencil cells, target cells on film. Raised RDW (anisocytosis).
Biochemical diagnosis panel:
- Haemoglobin + RBC indices (MCV, MCH, MCHC)
- Serum ferritin (↓ in IDA, ↑ in ACD/inflammation)
- Serum iron (↓)
- Total Iron Binding Capacity — TIBC (↑ in IDA, ↓ in ACD)
- Transferrin saturation = serum iron ÷ TIBC × 100 (↓ in IDA)
- Reticulocyte haemoglobin content (RHC) — early, sensitive marker
India burden: ~50% of pregnant women, 20% of non-pregnant women, and 7% of men are iron-deficient. Causes: inadequate dietary intake (low meat in vegetarian diets), high phytate diet reducing absorption, chronic parasitic infestations (hookworm — significant in rural India, causes GI blood loss).
Government programme: Anaemia Mukt Bharat — weekly iron-folic acid supplementation for adolescents, daily supplementation in pregnancy.
Figure: Iron Deficiency Anaemia — Stages and Diagnosis
CLINICAL PEARL
Ferritin as an acute-phase reactant: Ferritin rises in inflammation, infection, liver disease, and malignancy — independent of iron stores. Therefore, a "normal" or "high" ferritin does NOT rule out iron deficiency in a patient with active infection or chronic disease. In such patients, transferrin saturation <20% and reticulocyte haemoglobin <28 pg are more reliable markers of functional iron deficiency. This distinction between true iron deficiency and anaemia of chronic disease (ACD) is clinically critical — ACD responds to treating the underlying condition, not iron therapy.
Calcium, Phosphorus, and Bone Mineral Metabolism
Calcium — the most abundant mineral in the body (~1 kg; 99% in bone as hydroxyapatite).
Blood calcium (total): 8.5–10.5 mg/dL
- ~50% ionised Ca²⁺ (physiologically active)
- ~40% protein-bound (mainly to albumin — low albumin → low total Ca but normal ionised Ca)
- ~10% complexed with citrate, phosphate
Calcium regulation (triple axis: PTH, Calcitriol, Calcitonin):
- ↓ serum Ca²⁺ → PTH released from parathyroid → ↑ renal Ca reabsorption, ↑ bone resorption, ↑ renal 1α-hydroxylase → ↑ calcitriol → ↑ intestinal Ca absorption → Ca²⁺ rises
- Calcitonin (from C-cells of thyroid) → opposes PTH → inhibits osteoclasts → ↓ Ca
Hypocalcaemia: paraesthesiae, muscle cramps, tetany (carpal spasm), positive Chvostek sign (tapping facial nerve → facial twitch), Trousseau sign (BP cuff inflation → carpal spasm). Causes: hypoparathyroidism, Vitamin D deficiency, renal failure.
Hypercalcaemia: "bones, stones, groans, psychic moans" — bone pain, renal stones (calcium oxalate), abdominal pain, confusion. Causes: primary hyperparathyroidism (commonest), malignancy (bone metastases, PTHrP), hypervitaminosis D.
Phosphate: 85% in bone, 15% intracellular. Reciprocal relationship with calcium (high phosphate → lowers calcium). Elevated in CKD (kidneys cannot excrete phosphate → secondary hyperparathyroidism → renal osteodystrophy).
Figure: Calcium, Phosphorus, and Bone Mineral Metabolism