بسم الله الرحمن الرحيم

Calcium Homeostasis -II By Amr S. Moustafa, M.D., Ph.D. Ass. Prof. & Consultant Clinical Biochemistry & Molecular Biology College of Medicine and Obesity Research Center King Saud University

Objectives: Physiological importance of calcium Distribution and forms of calcium Regulation of blood level of calcium Measurement of calcium level Clinical problems: Hypo- and hyper-calcemia

Calcium: Physiological importance Neuromuscular excitability Blood coagulation Mineralization of bones Release of hormones & neurotransmitters Intracellular actions of some hormones

Distribution and Forms of Calcium One Kg of calcium in human body 99% in bone (mainly, hydroxyapatite crystals) 1% in blood and ECF 45% Free, ionized form 40% Bound to protein (mostly albumin) 15% Bound to HCO3-, PO4-, citrate, lactate

Regulation of Blood Level of Calcium Parathyroid hormone (PTH) Calcitriol: Active form of vitamin D ? Calcitonin

Calcium Homeostasis: PTH & Calcitriol Response to low blood calcium

Reference Ranges: Serum total calcium: Child (< 12 years): 2.20 – 2.7 mmol/L Adult: 2.15 – 2.5 Serum ionized calcium: Child (< 12 years): 1.20 – 1.38 mmol/L Adult: 1.16 – 1.32

Hypocalcemia: Primary hypoparathyroidism Pseudohypoparathyroidism Hypo- / hyper-magnesemia Hypoalbuminemia Acute pancreatitis Secondary hyperparathyroidism Vitamin D deficiency Renal disease Rhabdomyolysis

Hypocalcemia: 1. Primary hypoparathyroidism Parathyroid gland: Aplasia, destruction or removal PTH: Undetectable Increased calcium excretion Decreased activation of vitamin D: More hypocalcemia

Hypocalcemia: 2. Pseudohypoparathyroidism Rare hereditary disorder PTH target tissue response: Decreased Decreased Ca Normal PTH secretion No increase of cAMP Common physical features: Short stature Obesity Short metacarpals and metatarsals Abnormal calcification

Hypocalcemia: 3. Hypomagnesemia More frequent in hospitalized patients Mechanisms: Decreases PTH secretion Impairs PTH actions on bone receptors Vitamin D resistance

Hypocalcemia: 4. Hypermagnesemia More frequent in nursing homes patients Renal problems Mg-containing medications: Antacids, laxatives, enemas Mechanisms: Decreases PTH secretion Impairs PTH actions on bone receptors

Hypocalcemia: 5. Hypoalbuminemia Low total calcium (but not ionized Ca2+) 1.0 g/dL S. albumin 0.2 mmol/L total calcium Causes: Chronic liver disease Nephrotic syndrome Malnutrition

Hypocalcemia: 6. Acute Pancreatitis Intestinal lipase activity Intestinal FFAs and bound calcium

Hypocalcemia: 7. Secondary Hyperparathyroidism Vitamin D deficiency and malabsorption: Ca absorption and PTH secretion Chronic renal disease: Altered albumin, Mg2+, PO4 and pH PO4 binds and lowers ionized Ca2+ Mg2+ impairs PTH secretion and action Altered vitamin D metabolism Renal osteodystrophy

Hypocalcemia: 8. Rhabdomyolysis Major crush injury and muscle damage PO4 release from cells binds and lowers ionized Ca2+

Neonatal Hypocalcemia Abnormal PTH and vitamin D metabolism Hyperphosphatemia Hypomagnesemia Hypercholestrolemia

Hypocalcemia: Symptoms Neuromuscular irritability Parasethesia, muscle cramps, tetany Seizures Cardiac irregularities Arrhythmias Heart block Hypocalcemia: Total calcium < 1.88 mmol/L

Hypocalcemia: Laboratory Diagnosis Total and ionized blood calcium level Serum phosphorus and magnesium Serum alkaline phosphatase Serum PTH level Serum 25 hydroxycholicaciferol Renal function tests Serum albumin Labs for etiological diagnosis

Hypocalcemia: Treatment Oral or parenteral calcium Slow I.V. calcium injection Vitamin D Magnesium (with associated hypomagnesemia)

Hypercalcemia: Primary hyperparathyroidism Hyperplasia or adenoma Malignancy Benign familial hypocalciuria Thiazide diuretics Prolonged immobilization

Hypercalcemia: 1. Primary hyperparathyroidism Increased PTH blood level Adenoma (80%), Hyperplasia (19%) Older women Clinical signs or asymptomatic Increase total and/or ionized calcium Decreased serum phosphorus (Compare Lab results with secondary hyperparathyroidism)

Hypercalcemia: 2. Malignancy PTH-related peptide secreting tumors Binds to PTH receptors hypercalcemia Specific assays for PTH-rP Not detected by PTH assays e.g., Squamous cell carcinoma of lung Osteolytic metastases Severe hypercalcemia and low PTH: Exclude malignancy

Hypercalcemia: 3. Other Causes Thiazide diuretics: Calcium reabsorption Prolonged immobilization: Bone resorption Rare, benign, familial hypocalciuria Hyperthyroidism

Hypercalcemia: Symptoms Mild (2.6 – 3.0 mmol/L): Asymptomatic Neurologic: Drowsiness, lethargy & coma G.I.: Constipation, nausia, vomiting & peptic ulcer Renal: Nephrolithiasis (nephrocalcinosis) Nephrogenic diabetes insipidus: Polyuria & hypovolemia: Hypercalcemia

Hypercalcemia: Laboratory Diagnosis Total and ionized blood calcium level Serum phosphorus Serum alkaline phosphatase Serum PTH level and PTH-rP Serum 25 hydroxycholicaciferol Renal function tests Labs for etiological diagnosis

Hypercalcemia: Treatment Estrogen-replacement: Postmenopausal woman Surgical: Parathyroidectomy Measure to reduce blood calcium level: Salt and water intake: Calcium excretion Bisphosphanates: Bone resorption Discontinue thiazide diuretics

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