Mineral Metabolism — Calcium, Phosphate, Magnesium, Iron, and Trace Elements

🟢 Lite — Quick Review (1h–1d)

Rapid summary for last-minute revision before your exam.

Mineral metabolism covers the absorption, transport, storage, and functions of essential minerals. Calcium and phosphate are the most clinically tested minerals — their homeostasis is tightly regulated by PTH, vitamin D, and calcitonin. INI CET frequently asks about calcium disorders, PTH action, and vitamin D metabolism.

High-Yield Facts for INI CET:

• Normal serum calcium: 8.5-10.5 mg/dL; 40% bound to albumin, 10% complexed (citrate, phosphate), 50% ionized (free, active)
• PTH increases Ca²⁺: Stimulates bone resorption, renal Ca²⁺ reabsorption, activates 1α-hydroxylase in kidney (produces active vitamin D)
• Vitamin D (calcitriol): Increases Ca²⁺ absorption from gut, increases bone resorption, increases renal Ca²⁺ reabsorption
• Calcitonin decreases Ca²⁺: Secreted by C-cells of thyroid; inhibits bone resorption
• Hypocalcemia symptoms: Perioral numbness, tingling (fingers, toes), muscle cramps, tetany, Chvostek sign (facial twitch on tapping facial nerve), Trousseau sign (carpopedal spasm with BP cuff inflation)

⚡ Exam tip: For hypocalcemia tetany — look for Chvostek sign (tap facial nerve → facial muscle twitch) and Trousseau sign (BP cuff → carpal spasm). Remember calcium is bound to albumin — hypoalbuminemia lowers total calcium but ionized calcium may be normal (corrected calcium = measured calcium + 0.8 × (4 - albumin)).

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🟡 Standard — Regular Study (2d–2mo)

Standard content for students with a few days to months.

Mineral Metabolism — INI CET (AIIMS PG) Study Guide

Calcium Metabolism

Total Body Calcium: ~1000-1200g; 99% in skeleton (hydroxyapatite: Ca₁₀(PO₄)₆(OH)₂) Serum Calcium Fractions:

• Ionized (free): 50% — physiologically active
• Protein-bound: 40% (mostly albumin; albumin binds ~80% of protein-bound Ca)
• Complexed: 10% (bound to citrate, phosphate, bicarbonate)

Functions of Calcium:

1. Bone and tooth mineralization (hydroxyapatite crystal)
2. Nerve impulse transmission (voltage-gated Ca²⁺ channels)
3. Muscle contraction (actin-myosin interaction via troponin C)
4. Blood coagulation (cofactor for factor IV in coagulation cascade)
5. Enzyme cofactor (α-amylase, lipase, some kinases)
6. Intracellular signaling (second messenger — calmodulin pathway)
7. Hormone secretion (exocytosis requires Ca²⁺)

Calcium Absorption:

• Primary site: Duodenum and jejunum
• Absorption requires: Active vitamin D (1,25-dihydroxyvitamin D)
• ~30-40% of dietary calcium absorbed normally; increases up to 60% in vitamin D-replete states
• Factors that INCREASE absorption: Vitamin D, protein-rich diet, acidic environment, pregnancy
• Factors that DECREASE absorption: Phytates (whole grains), oxalates (spinach), tannins (tea), high phosphate, low gastric acidity

Calcium Balance:

• Input: Diet (~1000 mg/day)
• Output: Feces (~800 mg/day), urine (~150 mg/day), sweat (~50 mg/day)

Hormonal Regulation of Calcium

1,25-Dihydroxyvitamin D (Calcitriol):

• Produced in kidney by 1α-hydroxylase (activated by PTH and low phosphate)
• Actions:
  • ↑ intestinal calcium absorption (↑ calbindin synthesis in enterocytes)
  • ↑ intestinal phosphate absorption
  • ↑ bone resorption (with PTH)
  • ↑ renal calcium reabsorption (minor)
• Regulation: PTH stimulates 1α-hydroxylase; fibroblast growth factor 23 (FGF23) inhibits it

Parathyroid Hormone (PTH):

• Secreted by chief cells of parathyroid glands
• Response to low serum calcium — primary regulator is the calcium-sensing receptor (CaSR) on parathyroid cells
• Actions:
  • ↑ bone resorption (osteoclast activation via RANKL)
  • ↑ renal calcium reabsorption (distal tubule)
  • ↓ renal phosphate reabsorption (proximal tubule → phosphaturic)
  • ↑ 1α-hydroxylase activity (↑ active vitamin D production)
• Secretion: Inhibited by high Ca²⁺ (via CaSR), stimulated by low Ca²⁺
• PTH-related peptide (PTHrP): Causes hypercalcemia in malignancy (humoral hypercalcemia of malignancy); similar PTH-like action on bone and kidney but does not activate 1α-hydroxylase

Calcitonin:

• Secreted by parafollicular C-cells of thyroid
• Actions:
  • Inhibits osteoclast activity (↓ bone resorption)
  • ↑ renal calcium excretion
  • Minor effect on intestinal absorption
• Regulation: Stimulated by high serum calcium
• Not clinically significant in humans (unlike in fish/birds)

Phosphate Metabolism

Total Body Phosphate: ~500-800g; 85% in skeleton (hydroxyapatite), 15% in soft tissues Serum Phosphate: 2.5-4.5 mg/dL (higher in children than adults)

Functions:

1. Bone mineralization (hydroxyapatite)
2. ATP, cAMP, GTP, DNA, RNA structure
3. Protein phosphorylation (signaling)
4. Oxygen transport (2,3-DPG in RBCs)
5. Buffer system (urine, intracellular)

Phosphate Absorption:

• Site: Jejunum (vitamin D-dependent)
• ~65-80% of dietary phosphate absorbed
• Phosphates in processed foods (preservatives) highly absorbable

Renal Phosphate Handling:

• Proximal tubule: Major reabsorption site (NaPi-IIa and NaPi-IIc cotransporters)
• PTH causes phosphaturia (inhibits NaPi reabsorption)
• Fibroblast growth factor 23 (FGF23): Secreted by osteocytes/osteoblasts in response to high phosphate → causes phosphaturia and inhibits 1α-hydroxylase

Disorders:

• Hypophosphatemia: Rhabdomyolysis, refeeding syndrome, diabetic ketoacidosis, hyperparathyroidism, vitamin D deficiency
• Hyperphosphatemia: Renal failure, hypoparathyroidism, tumor lysis syndrome, acromegaly

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🔴 Extended — Deep Study (3mo+)

Comprehensive coverage for students on a longer study timeline.

Magnesium Metabolism

Total Body Magnesium: ~25g; 50-60% in bone, 40% in muscle/soft tissues Serum Magnesium: 1.5-2.5 mEq/L (0.75-1.25 mmol/L)

Functions:

1. Cofactor for ATP-dependent reactions (ATP requires Mg²⁺ as a cofactor)
2. Neurological function (NMDA receptor regulation, neuromuscular transmission)
3. Cardiac ion channels (P waves, QRS complex)
4. Bone mineralization (hydroxyapatite)
5. Protein synthesis, DNA replication

Regulation:

• Absorbed in jejunum and ileum (passive diffusion, paracellular)
• PTH increases renal Mg²⁺ reabsorption (similar to Ca²⁺)
• Furosemide causes hypomagnesemia (loop diuretics increase Mg²⁺ loss)
• Thiazides also cause hypomagnesemia

Hypomagnesemia:

• Causes: Alcoholism, diuretics, malnutrition, chronic diarrhea, proton pump inhibitors
• Features: Tetany (can mimic hypocalcemia), arrhythmias (torsades de pointes), seizures, muscle weakness, Chvostek/Trousseau signs
• Also causes hypokalemia (impaired K⁺ reabsorption) and hypocalcemia (impaired PTH secretion and action)

Hypermagnesemia:

• Causes: Renal failure, lithium therapy, excessive antacid use
• Features: Loss of deep tendon reflexes (first sign), respiratory depression, hypotension, bradycardia, cardiac arrest in severe cases
• Treatment: IV calcium gluconate, dialysis if severe

Iron Metabolism

Total Body Iron: ~3-4g (in adults); ~2g in hemoglobin, ~1g as storage (ferritin, hemosiderin), ~0.3g in myoglobin, ~0.3g as enzymes

Iron Absorption:

• Site: Duodenum (upper small intestine) — acidic environment keeps Fe²⁺ soluble
• Only Fe²⁺ (ferrous) absorbed; Fe³⁺ (ferric) must be reduced by duodenal cytochrome B (Dcytb)
• Enhancers: Vitamin C (ascorbic acid), meat/fish protein (MFP factor), acidic environment, iron deficiency
• Inhibitors: Phytates, tannins, oxalates, high calcium, antacids, PPI
• Ferroportin: Exports Fe²⁺ from enterocyte to blood; hepcidin inhibits ferroportin (degrades it)

Iron Transport and Storage:

• Transferrin: Plasma transport protein; carries 2 Fe³⁺ atoms; total iron binding capacity (TIBC) ~250-370 μg/dL
• Transferrin saturation: Serum iron / TIBC × 100; normal 20-50%
• Ferritin: Soluble storage form; also acute phase reactant (elevated in inflammation)
• Hemosiderin: Insoluble storage form; visible on Prussian blue stain

Iron Recycling:

• Macrophages phagocytose old RBCs → extract iron → export via ferroportin → taken up by transferrin
• Very efficient: ~20-25 mg iron recycled per day (vs ~1-2 mg absorbed from diet)

Daily Iron Balance:

• Losses: ~1 mg/day (skin, GI mucosa, urinary tract)
• Men: ~10-15 mg dietary iron needed to maintain balance
• Women (menstruating): ~15-20 mg/day needed

Iron Deficiency:

• Stages: 1) Depleted storage (low ferritin, normal Hb); 2) Iron-deficient erythropoiesis (low ferritin, normal Hb, high TIBC, low serum iron); 3) Iron deficiency anemia (microcytic, hypochromic RBCs, low ferritin, high TIBC, low serum iron)
• Microcytic anemia causes (remember mnemonic “TICS”): Thalassemia, Iron deficiency, Chronic disease (anemia of), Sideroblastic anemia
• Lead poisoning: Can cause microcytic anemia + basophilic stippling on smear

Iron Overload:

• Hemochromatosis: Primary iron overload; HFE gene mutation (C282Y); causes cirrhosis, cardiomyopathy, diabetes (“bronze diabetes”), arthropathy, hypogonadism
• Secondary: Transfusion-dependent anemias (thalassemia major), sideroblastic anemia, chronic liver disease

Trace Elements

Zinc:

• Functions: Metalloenzyme cofactor (carbonic anhydrase, alcohol dehydrogenase, alkaline phosphatase), wound healing, immune function, taste/smell, protein synthesis
• Deficiency: Acrodermatitis enteropathica (inherited zinc malabsorption), growth retardation, alopecia, diarrhea, dermatitis
• Excess: GI irritation, interfere with copper absorption (neurological symptoms)

Copper:

• Functions: Ceruloplasmin (oxidase), cytochrome oxidase (electron transport), dopamine β-hydroxylase (NE synthesis), lysyl oxidase (collagen cross-linking)
• Deficiency: Menkes disease (X-linked; copper malabsorption → kinky hair, neurodegeneration)
• Excess: Wilson disease (ATP7B mutation → copper accumulation in liver, brain, cornea); Kayser-Fleischer rings; treatment: penicillamine

Selenium:

• Functions: Glutathione peroxidase (antioxidant), iodothyronine deiodinase (T4→T3 conversion), thioredoxin reductase
• Deficiency: Keshan disease (cardiomyopathy in China), myxedematous cretinism
• Excess: Selenosis (GI symptoms, hair loss, garlic breath)

Iodine:

• Functions: Thyroid hormone synthesis (T3, T4)
• Deficiency: Goiter, hypothyroidism, cretinism (in fetus if mother deficient)
• Excess: Rare; can cause hyperthyroidism (Jod-Basedow phenomenon)

Manganese:

• Functions: Arginase, pyruvate carboxylase, Mn-superoxide dismutase
• Deficiency: Rare (impaired gluconeogenesis, bone demineralization)
• Toxicity: Manganism (Parkinsonian features) — seen in miners of manganese ore

Chromium:

• Functions: Potentiates insulin action (glucose tolerance factor — GTF); enhances insulin binding to receptors
• Deficiency: Impaired glucose tolerance (in total parenteral nutrition without chromium supplementation)

⚡ INI CET High-Yield: Calcium is bound to albumin — hypoalbuminemia lowers total calcium but ionized (free) calcium remains normal. Corrected calcium = Measured Ca + 0.8 × (4 - albumin). PTH is the primary regulator of serum calcium — it responds to the calcium-sensing receptor (CaSR) on parathyroid cells. High calcium → inhibits PTH secretion; low calcium → stimulates PTH. The calcium-phosphate product (Ca × PO₄) > 70 suggests metastatic calcification risk in chronic kidney disease.

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