1. بسم الله الرحمن الرحيم

2. Calcium Homeostasis -IIBy
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