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Calcium Disorders Dr. Sohail Inam Consultant Endocrine & Diabetes Prince Sultan Military Medical City Riyadh.

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Presentation on theme: "Calcium Disorders Dr. Sohail Inam Consultant Endocrine & Diabetes Prince Sultan Military Medical City Riyadh."— Presentation transcript:

1 Calcium Disorders Dr. Sohail Inam Consultant Endocrine & Diabetes Prince Sultan Military Medical City Riyadh

2 Calcium Major intracellular ion Important for cellular function – Intracellular signaling – Muscle action potential – Hormone secretion – Coagulation cascade Major store is the bone (90%)

3 Calcium Serum calcium is tightly regulated Normal total Ca 2.2-2.5 mmol/l (8.5-10 md/dl) – Ionized (free) – Bound (Albumin and other proteins) Corrected calcium for albumin

4 Serum Calcium Urine calcium 300 100 600 980010000 1000 Dietary Calcium Fecal Calcium 800 200 Values mg/day

5 Regulation of calcium Parathyroid hormone Vitamin D Calcitonin

6 Parathyroid gland PTH Calcium Phosphate Reabsorbs Calcium Excretes Phosphate Activates 1 alpha hydroxylase 25 OH D3 → 1,25 Dihydoxy D3

7 PTH Stimulation – Hypocalcaemia & hypomagnesaemia – Decrease 1,25 D3 – Hyperphosphatemia –  adrenergic stimulation Inhibition – Hypercalcemia – Increased 1,25 D3 – Hypophosphatemia

8 Vitamin D 291-315 nm

9 Vitamin D 25 OH D 1,25 dihydroxy D ↑Calcium ↑Phosphate ↑Absorption Calcium Phosphate 25 hydroxylase 1 alpha hydroxylase

10 1 alpha Hydroxylase Activation –PTH –Low phosphate –Low calcium –IGF 1 Inhibition –1,25 (OH)2 D3 –High phosphate & High calcium –FGF23

11 Calcitonin Inhibits release of Ca from bone Increases Ca excretion by the kidney Stimulated by increase in Ca levels

12 Ca x PO4 PTH 1,25-D3 Serum Calcium Urine calcium PTH 1,25-D3 CT

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14 HYPOCALCEMIA

15 Hypocalcemia Causes Hypoparathyroidism – Autoimmune – Surgical damage – Radiation damage – Infiltrative Psudohypoparathyroidism (PTH resistance) CaSR mutation

16 Hypocalcemia Causes Vitamin D – Deficiency – Inability to activate Vitamin D – Resistance Renal disease Magnesium deficiency – Decrease PTH release – PTH resistance

17 Hypocalcemia Causes Calcium sequestration – Pancreatitis – Osteoblastic metastasis – High phosphate – Hungry bone disease Drugs Critical illness

18 Hypocalcemia Symptoms Paresthesia – Peri-oral – Limbs Muscle cramps & carpopedal spasm Seizures Laryngeal spasm Cardiac Psychiatric

19 Hypocalcemia Signs Tetany – Carpopedal spasm – Chvestok’s sign – Trousseau's sign Papilledema Cataracts Extrapyramidal ECG- Prolonged QTc

20 Investigations Corrected calcium Phosphate Alkaline phosphatase Renal function Parathyroid hormone Vitamin D Magnesium

21 Hypocalcemia PTH Low Hypoparathyroidism CaSR mutations Magnesium deficiency Hungry bone syndrome PTH High Vitamin D disorders Renal disease PTH resistance Ca sequestration Sepsis Drugs Magnesium deficiency

22 Hypocalcemia Phosphate, Alkaline Phosphatase, Magnesium, Creatinine, Vitamin D PTH HighNormal or low ↑ Phosphate↓ Phosphate↑ Phosphate↓ Phosphate Renal failure PTH resistance Rhabdomyolysis Vitamin D disordersHypoparathyroidism CaSR mutations Hungry bone

23 Treatment Severe symptomatic hypocalcemia – IV calcium (slow infusion) Mild symptoms – Oral calcium Vitamin D – Active form – Inactive form

24 Treatment Specific Magnesium Hypoparathyroidism – Active form of vitamin D – PTH replacement Renal failure – Phosphate binders – Active form of Vitamin D

25 HYPERCALCEMIA

26 Hypercalcemia Mechanisms Excess PTH hormone PTHrP – Tumors (Malignancy) – Pregnancy & lactation Vitamin D mediated – Intoxication – Granulomatous disease – Hematological malignancies

27 Hypercalcemia Mechsnisms Excess Ca absorption (Milk Alkali) Increased osteoclast activation – Cytokines – Immobilization – Adrenal insufficiency – Thyrotoxicosis

28 ↑ Serum Calcium Urine calcium

29 Causes Hyperparathyroidism Malignancy Vitamin D intoxication Milk Alkali syndrome Granulomatous diseases Endocrine

30 Causes Immobilization Drugs Parenteral nutrition Familial hypocalciuric hypercalcemia

31 Clinical features Polyuria & polydipsia GIT – Anorexia – Abdominal pain – Constipation Neuropsychiatric Musculoskeletal

32 Clinical features Renal dysfunction – Nephrocalcinosis – Nephrolithiasis – Renal tubular acidosis Cardiovascular – Arrthymias – Cardiac arrest

33 Hypercalcemia High PTH Hyperparathyroidism Ectopic PTH secretion FHH Drugs Low PTH Malignancy Vitamin D excess Immobilization Milk Alkali Syndrome Granulomatous disease Endocrine

34 Hypercalcemia Confirm on repeat sample Measure PTH Normal or ↑ PTH 24 hour urine Calcium & creatinine FHHHyperparathyroidism Low PTH (<20pg/ml) Measure PTHrP, Vit D metabolites, TFT CXR, CT scan, Myeloma Clinical evaluation & medication history low Normal or high

35 Hypercalcemia Principles of Therapy Increase renal Ca excretion – Saline diuresis (± frusemide) – Calcitonin – Dialysis Reduce Ca efflux from bone – Calcitonin – Bisphosphonates – Denusamab Treat underling cause

36 Treatment Mild hypercalcemia (Ca <3) – Treat underlying cause Moderate hypercalcemia (Ca 3-3.49) – Hydration – Bisphosphonate – Treat underlying cause

37 Treatment Severe Hypercalcemia (severe symptoms, Ca>3.5) – IV hydration 0.9% NaCl – Calcitonin – Bisphosphonates – Low calcium bath dialysis – Treat underlying cause

38 Specific Treatment Hyperparathyroidism – Surgery – Non-surgical ablation – Conservative approach – Calcimimetics Steroids – Hematological malignancies – Vitamin D intoxication

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