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

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Presentation on theme: "By Amr S. Moustafa, M.D., Ph.D. Ass. Prof. & Consultant Clinical Biochemistry & Molecular Biology College of Medicine and Obesity Research Center King."— Presentation transcript:

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3 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 Calcium Homeostasis -II

4 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

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

6 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 HCO 3 -, PO 4 -, citrate, lactate

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

8 Calcium Homeostasis: PTH & Calcitriol Response to low blood calcium

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

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

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

12 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

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

14 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

15 Hypocalcemia: 5. Hypoalbuminemia  Low total calcium (but not ionized Ca 2+ )  1.0 g/dL S. albumin 0.2 mmol/L total calcium  Causes: Chronic liver disease Nephrotic syndrome Malnutrition

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

17 Hypocalcemia: 7. Secondary Hyperparathyroidism  Vitamin D deficiency and malabsorption: Ca absorption and PTH secretion  Chronic renal disease: Altered albumin, Mg 2+, PO 4 and pH PO 4 binds and lowers ionized Ca 2+ Mg 2+ impairs PTH secretion and action Altered vitamin D metabolism Renal osteodystrophy

18 Hypocalcemia: 8. Rhabdomyolysis  Major crush injury and muscle damage PO 4 release from cells binds and lowers ionized Ca 2+

19 Neonatal Hypocalcemia  Abnormal PTH and vitamin D metabolism  Hyperphosphatemia  Hypomagnesemia  Hypercholestrolemia

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

21 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

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

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

24 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)

25 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

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

27 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

28 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

29 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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