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بسم الله الرحمن الرحيم.

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Presentation on theme: "بسم الله الرحمن الرحيم."— Presentation transcript:

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): – 2.7 mmol/L Adult: – 2.5 Serum ionized calcium: Child (< 12 years): – mmol/L Adult: – 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 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

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