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BI9.1-3 | Minerals, electrolytes, Water and Acid base balance — Part 2
Other Trace Minerals — Copper, Zinc, Iodine
Trace Minerals — Functions, Deficiency, and Toxicity
| Mineral | Key Functions | Deficiency Features | Toxicity / Excess |
|---|---|---|---|
| Copper | Ceruloplasmin (iron metabolism), lysyl oxidase (cross-linking), cytochrome c oxidase, tyrosinase | Menkes disease (X-linked): kinky hair, neurodegeneration, connective tissue defects | Wilson disease (AR): hepatolenticular degeneration, Kayser-Fleischer rings, cirrhosis |
| Zinc | >300 enzymes (carbonic anhydrase, DNA polymerase); zinc fingers in transcription factors; immune function | Growth retardation, acrodermatitis enteropathica, poor wound healing, hypogonadism, impaired immunity | Nausea, vomiting, copper deficiency (zinc blocks copper absorption) |
| Iodine | Thyroid hormone synthesis (T3, T4) | Goitre, hypothyroidism, cretinism (intellectual disability in children), endemic in Himalayan belt | Jod-Basedow phenomenon (iodine-induced hyperthyroidism), Wolff-Chaikoff effect (transient block) |
| Fluoride | Fluorapatite formation (acid-resistant tooth enamel) | Dental caries (increased susceptibility) | Dental fluorosis (mottled enamel), skeletal fluorosis (osteosclerosis) — endemic in Rajasthan, AP, Gujarat |
| Selenium | Glutathione peroxidase (antioxidant), thioredoxin reductase, deiodinases (T4→T3) | Keshan disease (cardiomyopathy), Kashin-Beck disease (osteoarthropathy) | Selenosis: garlic breath, nail/hair loss, neuropathy |
Copper:
- Cofactor for: lysyl oxidase (collagen cross-linking), caeruloplasmin (ferroxidase), superoxide dismutase, cytochrome oxidase, dopamine-β-hydroxylase, tyrosinase (melanin synthesis)
- Menkes disease: X-linked copper deficiency → defective lysyl oxidase → brittle, kinky hair, connective tissue defects, intellectual disability, tortuous arteries. Low serum copper + caeruloplasmin.
- Wilson's disease: autosomal recessive copper accumulation (defective ATP7B transporter → copper cannot be incorporated into caeruloplasmin or excreted in bile) → deposits in liver, brain, eye. Kayser-Fleischer rings (copper in cornea), hepatic cirrhosis, psychiatric symptoms. Low serum caeruloplasmin, high urine copper.
Figure: Other Trace Minerals — Copper, Zinc, Iodine
Zinc:
- Cofactor for >300 enzymes: carbonic anhydrase, carboxypeptidase, alcohol dehydrogenase, DNA polymerase, RNA polymerase
- Deficiency: Acrodermatitis enteropathica (genetic malabsorption), growth retardation, poor wound healing, hypogonadism, ageusia (loss of taste), anosmia, impaired immune function, alopecia
- Common in India: zinc deficiency in malnourished children impairs immunity and increases mortality from diarrhoea and pneumonia
Iodine:
- Essential for thyroid hormone synthesis
- Deficiency → hypothyroidism and goitre (see Organ Function Tests module for TFT details)
- India's National Iodisation Programme: iodised salt mandated since 1983; still suboptimal in some regions
SELF-CHECK — : Minerals
A 28-year-old woman is found to have haemoglobin 8.2 g/dL, MCV 65 fL (low), serum ferritin 4 µg/L (low), TIBC elevated. Which stage of iron deficiency does this represent?
A. Stage 1 — iron depletion only
B. Stage 2 — iron-deficient erythropoiesis without anaemia
C. Stage 3 — iron deficiency anaemia with microcytosis
D. Anaemia of chronic disease
Reveal Answer
Answer: C. Stage 3 — iron deficiency anaemia with microcytosis
A 12-year-old boy has stunted growth, delayed puberty, rough skin, and poor wound healing. His diet is largely cereals and vegetables with minimal animal protein. Serum zinc is low. What enzyme cofactor is most critically affected by zinc deficiency?
A. Lysyl oxidase
B. Prolyl hydroxylase
C. Carbonic anhydrase and DNA/RNA polymerases
D. Pyruvate dehydrogenase
Reveal Answer
Answer: C. Carbonic anhydrase and DNA/RNA polymerases
Body Water and Electrolytes
Major Electrolytes — Distribution and Clinical Significance
| Electrolyte | Major Compartment | Normal Plasma Range | Key Functions | Clinical Significance of Imbalance |
|---|---|---|---|---|
| Na+ | ECF (140 mEq/L) | 135-145 mEq/L | Osmolality, ECF volume, nerve conduction | Hyponatraemia → cerebral oedema, seizures; Hypernatraemia → cellular shrinkage |
| K+ | ICF (150 mEq/L) | 3.5-5.5 mEq/L | Resting membrane potential, cardiac rhythm | Hypokalaemia → arrhythmias, weakness; Hyperkalaemia → cardiac arrest |
| Cl- | ECF (100 mEq/L) | 95-105 mEq/L | Osmolality, acid-base (anion gap), gastric HCl | Hypochloraemia → metabolic alkalosis (vomiting); Hyperchloraemia → normal AG acidosis |
| HCO3- | ECF (24 mEq/L) | 22-26 mEq/L | Major ECF buffer, acid-base balance | Low → metabolic acidosis; High → metabolic alkalosis |
| Ca2+ | ECF (ionised 4.5-5.5 mg/dL) | 8.5-10.5 mg/dL (total) | Muscle contraction, coagulation, nerve function | Hypocalcaemia → tetany, Chvostek/Trousseau signs; Hypercalcaemia → stones, bones, groans, moans |
| PO43- | ICF (major anion) | 2.5-4.5 mg/dL | Bone mineral, ATP, nucleic acids, buffers | Hypophosphataemia → muscle weakness, haemolysis; Hyperphosphataemia → metastatic calcification (CKD) |
Total body water (TBW): ~60% of body weight in adult males; ~55% in females (more fat = less water).
- Intracellular fluid (ICF): ~2/3 of TBW (40% body weight) — K⁺ is the major cation
- Extracellular fluid (ECF): ~1/3 of TBW (20% body weight)
- Interstitial fluid (15%)
- Plasma (5%)
Figure: Body Water and Electrolytes
Electrolyte distribution:
| Electrolyte | Major Compartment | Normal Plasma | Function |
|---|---|---|---|
| Na⁺ | ECF (main cation) | 135–145 mEq/L | Osmolality, action potentials |
| K⁺ | ICF (main cation) | 3.5–5.0 mEq/L | Resting membrane potential |
| Cl⁻ | ECF (main anion) | 95–105 mEq/L | Accompanies Na⁺ |
| HCO₃⁻ | ECF (second anion) | 22–28 mEq/L | Primary blood buffer |
| Ca²⁺ | ECF (ionised) | 4.5–5.3 mg/dL | Muscle contraction, coagulation |
| Mg²⁺ | ICF | 1.5–2.5 mEq/L | ATP synthesis, cardiac rhythm |
Hyponatraemia (<135 mEq/L): Most common electrolyte disturbance in hospital. Causes: SIADH (excess ADH → water retention → dilution), heart failure, liver cirrhosis, diarrhoea. Symptoms: nausea, headache, confusion, seizures (if acute/severe).
Figure: Electrolyte distribution:
Hyperkalaemia (>5.5 mEq/L): Most dangerous electrolyte disturbance — can cause fatal cardiac arrhythmias. Causes: renal failure (K⁺ cannot be excreted), acidosis (H⁺ enters cells, K⁺ exits to maintain electroneutrality), ACE inhibitors. ECG: peaked T waves → wide QRS → sine wave → cardiac arrest.
Acid-Base Balance — Buffers and Physiology
Normal arterial blood pH: 7.35–7.45 (mildly alkaline)
Figure: Acid-Base Balance — Buffers and Physiology
Maintaining this narrow range is critical — enzyme activity, protein conformation, and oxygen delivery all depend on pH.
Three buffer systems:
1. Bicarbonate buffer (most important in ECF): H⁺ + HCO₃⁻ ⇌ H₂CO₃ ⇌ H₂O + CO₂
- CO₂ expelled by lungs (respiratory compensation)
- HCO₃⁻ regulated by kidneys (metabolic compensation)
- Henderson-Hasselbalch: pH = 6.1 + log ([HCO₃⁻] / 0.03 × pCO₂)
- Phosphate buffer (most important in ICF and urine): H₂PO₄⁻ / HPO₄²⁻ (pKa 6.8)
- Protein buffer (including haemoglobin): imidazole groups of histidine residues buffer H⁺ in red cells; deoxyhaemoglobin is a better buffer than oxyhaemoglobin (Haldane effect)
Physiological compensations:
- Respiratory: lungs adjust CO₂ within minutes (hyperventilation to blow off CO₂ in metabolic acidosis; hypoventilation to retain CO₂ in metabolic alkalosis)
- Renal: kidneys adjust HCO₃⁻ over hours to days (excrete acid + regenerate HCO₃⁻ in metabolic acidosis; excrete HCO₃⁻ in metabolic alkalosis)