DISORDERS OF CALCIUM METABOLISM

1. DISORDERS OF CALCIUM
METABOLISM
Dr.LEKSHMI PRIYA J S

2. SPECIFIC LEARNING OBJECTVES
1. TO REVIEW CALCIUM METABOLISM
2. TO UNDERSTAND ABOUT HYPERCALCAEMIA
AND HYPOCALCAEMIA
3. TO UNDERSTAND KEY FEATURES OF OTHER
DISORDERS OF CALCIUM METABOLISM
Causes
Clinical features
Treatment aspects

3. INTRODUCTION
• Calcium is an important divalent cation.
• Required for many enzymatic & cellular functions.
• 99% of total body calcium resides in skeletal tissues.
• Of the fraction found in plasma:
Ionised & unbound
MOST PHYSIOLOGICALLY
IMPORTANT
SLO 1

4. NORMAL LEVELS IN BODY
• Normal range of total calcium 
9-11mg/dl(2.2-2.6mm0l/L)
• Normal serum ionised calcium
3.7-6mg/dl(0.95-1.5mmol/L)

5. • In labs usually total calcium is measured
(ionised + protein bound)
• Albumin  low,protein bound calcium will also
be low.
• But level of ionized calcium remains unchanged.
Corrected calcium = calcium measured + [0.8(4-albumin)]

6. DISORDERS OF CALCIUM
METABOLISM
Hypercalcaemia
Hypocalcaemia
SLO 2

7. HYPERCALCAEMIA
• Occurs when serum level of ionized calcium
increases.
• Total serum calcium level > 10.5 mg/dl
(2.5mmol/L) or ionized calcium level >5.6mg/dl
(1.4mmol/L)
Mild (11-11.5mg/dl)

8. • Primary hyper parathyroidism
• Teritiary hyperparathyroidism
PTH related
• Humoral hypocalcemia of malignancy
• Solid tumours(breast,ovary,lung,kidney)
• Local osteolysis eg: multiple myeloma
Malignancy related
• Vit D intoxication
• Granulomatous diseases
Vitamin D related
Genetic disorders
Medication related
Endocrine diseases
Others
•Familial hypocalciuric hypercalcemia- calcium
sensing receptor inactivating mutation.
•Vit D supplements,ca carbonate,vit A intoxication,
Lithoum.,theophylline,estrogen,tamoxifen
•Hyperthyroidism ,adrenal insufficiency,
Pheochromocytoma,acromegaly .
•c/c kidney disease,immobilisation,TPN

9. Milk Alkali Syndrome
Ingesting large amounts of calcium containing antacids.
•HYPERCALCEMIA
•HYPERPHOSPHATEMIA
•METABOLIC ALKALOIS
•RENAL SUFFICIENCY
Incidence now increased because of recommendation for use of
calcium carbonate for prevention & treatment of osteoporosis.
THIRD MOST COMMON CAUSE OF HYPERCALCAEMIA.

10. SIGNS & SYMPTOMS
• Severity depends on level and rate of rise of
serum calcium.
• Serum calcium <12mg/dl, often asymptomatic.
• If hypercalcaemia is chronic patient remain
asymptomatic with levels 12-14mg/dl.
• But a/c rise to 12-14mg/dl severe symptoms.
• Levels >14mg/dl  cannot be tolerated 
severe symptoms may develop including
coma.

11. Pathophysiology
• Hypercalcaemia is caused by
1.Increased bone resorption
2.Increased GI absorption of
calcium
3.Decreased renal excretion of
calcium
Hypercalcemia leads to hyperpolarisation of cell membranes.

12. Clinical manifestations
• Painful bones,renal stones,abdominal
groans,psychic moans & neuropsychiatric
overtones

13. • Fatigue
• Headache
• Lethargy
• Cognitive dysfn
• Muscle weakness
• Stupor
• coma
• Anorexia
• Constipation
• Nausea,vomting
• pancreatits
• Peptic ulcer d/s
• Bone pain
• Arthritis
• Osteitis fibrosa
cystica
• A/C &C/C Renal
Failure
• Nephrolithiasis
• Nephrogenic DI
Renal Skeletal
Neuro
psychiatric
GI
HYPERCALCEMIA
Ocular
Conjunctivitis &
band keratopathy

14. Cardiac features
• Hypertension
• Shortened QT interval
• Shortened ST segment
• Arrhythmias
• Vascular calcification

15. Investigations
• S.electrolytes.
• BUN,creatinine.
• PTH levels.

16. Treatment
1. Measures to increase urine excretion
• Saline diuresis-0.9% Nacl is used.
• Furosemide- forced diuresis
• Hemodialysis – in severe cases & in CRF
2.Measures to decrease bone resorption
• Bisphosphonates
• Plicamycin/mithormycin
• Calcitonin
3.Measures to decrease intestinal absorption
• Glucocorticoids
• Oral phosphates
4.Specific treatment
• Discontinue drugs resonsible
• Sx in primary hyper pthyroidism
• Specific rx in case of malignancy & granulomtous conditions

17. Treatment algorithm
• Restore normal hydration
• Isotonic saline infusion (upto 3-4 litres or more)
• Frusemide (40mg BD)
• Add calcitonin within 24hrs (2-8U/kg) &
bisphosphonates(zolendronate 4-8mg/5min infusion)
• More aggressive hydration (6 litres or more) and
frequent dosing of frusemide for life threatening
hypercalcaemia.

18. HYPOCALCAEMIA
• Occurs when ionised calcium in serum falls
below 1.16mmol/L(3-4.4mg/dl) TRUE
HYPOCALCAEMIA
• Or serm calcium <9.0 mg/dl or 8.5mg/dl
• FALSE HYPOCALCAEMIA – occurs from
reduction in serum albumin which decreases
total serum calcium level,but ionised Ca
remains stable .

19. Causes Hypoparathyroidism
• sx
• Autoimmune
• Magnesium deficiency
 Hyoalbuminemia
 Defect in vit D metabolism
• Nutritional
• Malabsorption
• Drugs
• Liver & renal disease
 Miscellaneous
• Metaboloc & respiratory alkalosis
• Sepsis
• Massive blood transfusion
• Tumor lysis

20. Approach

21. Pathophysiology
• Decrease in extracellular ca
• MP on outside becomes less negative
• Less amount of depolarisation required to
initiate AP
• Increased excitability of muscle & nerve tissue

22. Clinical features
Result from increased neuromuscular activity.
• Fatigue
• Circumoral parasthesia
• Distal extremity paraesthesia
• Muscle cramps
• Carpopedal spasm
• Tetany
• Seizures
• Laryngospasm stridor & apnoea in neonates.
• Cardiac rhythm disturbances.
• Chvostek’s sign
• Trousseau’s sign
• Irritability , depression , psychosis

23. ECG abnormalities

26. Tetany
• Causes
1. Hypocalcaemia
2. Hypomagnesaemia
3. Alkalosis

27. c/f
• Latent
• Manifest – c/f depend on age of patient
Children TRIAD
•Carpopedal
spasm
•Laryngeal stridor
•Convulsions

28. Adults –
• paraesthesias are most common
• Carpopedal spasm less common
• Laryngeal stridor & convulsions rare .

29. • Latent tetany
Typical symptoms absent
Can be unmasked by foll provocative tests .
1. Trousseau’s sign.
2. chvostek’s sign.
3. Erb’s sign - Increased excitability of moor
nerves to galvanic current .

30. Management of hypocalcaemia
• Depending on underlying cause & severity
• Administrn of calcium alone is transiently
effective
• Mild asymptomatic can be managed by
increasing dietary calcium by 1000mg/day.
• Symptomatic – should rx immediately.

31. Severe symptomatic cases
• 10ml of 10% ca gluconate IV over 10mts
• Then continous IV infusion of Ca gluconate at
0.1mmol/kg over 24hrs.
• Continous cardiac monitoring for bradycardia

32. Severe asymptomatic cases
• Oral calcium supplements upto 1-3gm/day.

33. Treatment of hypoparathyroidism
• Oral Ca suplements
• Active Vit D preparations
o 1,25 dihydroxy vitD (calcitriol)
o 1α dihydroxy vit D(alpha calcidiol)
• Monitor urinary Ca/creatinine & plasma
calcium.
• PTH extracts

34. 1. HYPOPARATHYROIDISM
2. PSEUDOHYPOPARATHYROIDISM
SLO 3
SX SPONTANEOUS DIGEORGE
SYNDROME
•PTH HIGH
•SERUM CALCIUM LOW
•FAULT IN PTH RECEPTORS

35. 3. HYPERPARATHYROIDISM
due to increased activity of parathormone .
•Increased seru Ca
•PT adenoma,hyperplasia,carcinoma
•Bonepain +++,osteoporosis
•Death due to hypercalcemic crisis
•Stones,moans,groans
Primary
•Increased PTH
•Decreased serum calcium
•Renal disease,malabsorption
Secondary
•Increased PTH
•Increased serum calcium
•Adenomas,gland enlargement
Teritiary

36. 4.VITAMIN D DEFICIENCY
RICKETS
 Interference in mineralisation of bone
 Deranged endochondral & intramembraneous
bone growth.
•Rickets in children
•Osteomalacia in adults

37. Osteomalacia
• Adult rickets
• Failure ofmineralisatio0n of osteoid matrix.
• Bone consiststs largely of osteoid,but poor
calcification.
• Renal rickets
• Type of osteomalacia d/t c/c kidney damage.
• Failure of damaged to form active form of VIT
D.
Osteoporosis- matrix normally calcified but reduced in quantity

38. 5.HETEROTOPIC CALCIFICATION
Deposition of calcium salts in tissues other than
osteoid or enamel.
2 types: DYSROPHIC & METASTATIC
Daed or
degenerated tissues
Calcium salts
precipitated in
previously
undamaged tissues

39. To summarize…
• Calcium ions play an imp role in many
physiological functions.

40. Extra points to note
• PTHrP.
• OSTEOPORPSIS.
• OSTEOPETROSIS.
• HOW 1,25 dihydroxy cholecalciferol.
• Short notes on hyperparathyroidism
,hypoparathyroidism.

41. References
1. Textbook of Medical Physiology by Guyton &
Hall 10th Edition
2. Review of Medical Physiology by William F.
Ganong 21st Edition
3.Davidsons principle & Practice Of Medicine.