بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. 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

3. 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

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

5. 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

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

7. Calcium Homeostasis: PTH & Calcitriol Response to low blood calcium

8. 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

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

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

11. 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

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

13. 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

14. 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

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

16. 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

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

18. Neonatal Hypocalcemia • Abnormal PTH and vitamin D metabolism • Hyperphosphatemia • Hypomagnesemia • Hypercholestrolemia

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

20. 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

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

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

23. 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)

24. 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

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

26. 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

27. 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

28. 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

29. Thank You