1. Dr. Nicolette du Plessis Department Paediatrics University of Pretoria
Hypocalcemia
Dr. Nicolette du Plessis
Department Paediatrics
University of Pretoria

2. Introduction
Pathophysiology
Etiology
Diagnostic approach
Management principles

3. Introduction Calcium is the most abundant mineral in the body.
In pediatric ICU, hypocalcemia has higher mortality then normocalcemia.
We are interested in ionized calcium levels

4. Calcium homeostasis
Regulation of parathyroid function by calcimimetic compounds
E. Nemeth,

5. Introduction to Anatomy and Physiology, http://ncwcbio101. wordpress

6. Pathophysiology Ionized calcium is affected by: Albumin Blood pH
Serum phosphate
Serum magnesium
Serum bicarbonate
Exogenous factors
Citrate / free fatty acids (TPN)

7. Why do we need it? Calcium messenger system – regulates cell function
Activates cellular enzyme cascades
Smooth muscle and myocardial contraction
Nerve impulse conduction
Secretory activity of exocrine glands

8. Symptoms and signs of hypocalcemia
Neuromuscular irritability
Paresthesias
Laryngospasm / Bronchospasm
Tetany
Seizures
Chvostek sign
Trousseau sign
Prolonged QTc time on ECG

9. Tetany is not caused by increased excitability of the muscles.
Muscle excitability is depressed
hypocalcemia impedes ACh release at NM junctions
However, the increase in neuronal excitability overrides the inhibition of muscle contraction.

10. Signs & Symptoms: A 2-in-1 Reference for Nurses, Copyright © 2007 Lippincott Williams & Wilkins,

11. Trousseau sign: (very uncomfortable and painful)
A blood pressure cuff is inflated to a pressure above the patients systolic level.
Pressure is continued for several minutes.
Carpopedal spasm: * flexion at the wrist
* flexion at the MP joints
* extension of the IP joints
* adduction thumbs/fingers

12. Long QT interval with normal T waves
Prolongation of the ST segment with little shift from the baseline

13. History that suggests hypocalcemia
Newborns (can be unspecific)
Asymptomatic
Lethargy
Poor feeding
Vomiting
Abdominal distention
Children
Seizures
Twitching
Cramping
Laryngospasm

14. Neonatal hypocalcemia:
Etiology
Neonatal hypocalcemia:
Early neonatal hypocalcemia (48-72 hours)
Prematurity
Poor intake, hypoalbuminemia, reduced responsiveness to vitamin D
Birth asphyxia
Delay feeding, increased calcitonin, endogenous phosphate load high, alkali therapy
Infant to diabetic mother
Magnesium depletion → functional hypoparathyroidism → hypocalcemia
IUGR

15. Etiology Late neonatal hypocalcemia Exogenous phosphate load
Phosphate-rich formulas / cow’s milk
Magnesium deficiency
Transient hypoparathyroidism of newborn
Hypoparathyroidism
Gentamycin (24 hourly dosing schedule)

16. Etiology Infants and children Hypoparathyroidism
Impaired synthesis / secretion
Loss/ lack of PTH tissue or defective synthesis
Primary or acquired conditions
Defective calcium sensing receptor
End –organ resistance to PTH (pseudohypoparathyroidism)
Hypovitaminosis D (MUCH MORE COMMON)
Hypomagnesemia
Other

17. Synthesis / secretion of PTH
Genetic
Autosomal dominant
Autosomal recessive
X-Linked
HDR (hypoparathyroidism associated with sensorineural deafness and renal dysplasia)
DiGeorge's syndrome
Mitochondrial disorders:
MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episode),

18. Synthesis / secretion Autoimmune
APECED (autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy syndrome)
Hypoparathyroidism
Primary adrenal insufficiency
Chronic mucocutaneous candidiasis

19. Synthesis / secretion Acquired Thyroid surgery Parathyroidectomy
Iron deposition with chronic transfusions
Wilson’s disease
Gram negative sepsis, toxic shock, AIDS
? Macrophage-generated cytokines

20. Pseudohypoparathyroidism
Target organ insensitivity to PTH (bone / kidney)
Hypocalcemia
Hyperphosphatemia
Elevated PTH

21. Pseudohypoparathyroidism (PHP)
GNAS1 gene mutations – intracellular signals
Expression in tissues either paternally / maternally determined
Example: renal expression is maternal
Type 1a PHP
AD (maternal transmission)
Albright’s hereditary osteodystrophy

22. Albright’s Short stature & limbs Obesity Round, flat face
Short 4e/5e metacarpals
Archibald sign
Brachydactyly
Potter's thumb
Eye problems
IQ problems
Basal ganglia calcifications

23. Pseudopseudohypoparathyroidism
Phenotype of Albright’s
NORMAL serum calcium
NO PTH resistance
Paternal GNAS1 gene mutation

24. Pseudohypoparathyroidism
Type 1b
Hypocalcemia, no phenotypic abnormality
AD, maternal transmission
Type 1c
Looks like type 1a
Type 2
No features of Albright’s

25. PTH target tissues only
PHP Ia 
PHP Ib 
PHP II
 PPHP
Albright’s phenotype  +  - +
Serum calcium   NL
Response to PTH cAMP
NL 
Response to Phosphorus
()NL
Hormone Resistance 
All hormones 
PTH target tissues only 
None
Molecular defect 
Gsa 
?PTH R 
Unknown 
Gsa

26. Hypovitaminosis D Decrease intake or production Increased catabolism
Decrease 25-hydroxylation by liver
Decrease 1-hydroxylation by kidney

27. Delayed closure of fontanels
Bossing
Craniotabes
Delayed eruption of teeth
Rickety rosary
Pectus carinatum
Harrison sulcii
Splaying of distal ends of
long bones bones
Hypotonia
Weakness
Growth retarded
Recurrent chest infections

28. Magnesium is required for PTH release
Hypomagnesemia
Magnesium is required for PTH release
May also be required for effects on target organs
Mechanisms:
End-organ unresponsiveness to PTH
Impaired release of PTH
Impaired formation of 1,25-vitamin D3

29. Primary Secondary Hypomagnesemia Autosomal recessive
Present at 1 month age with seizures
Secondary
Intestinal absorption vs renal excretion

30. Pancreatitis Citrated products Hungry bone syndrome Hyperphosphatemia
Other
Pancreatitis
Citrated products
Hungry bone syndrome
Hyperphosphatemia
Fluoride poisoning

31. Following parathyroidectomy
Other
Hungry bone syndrome
After prolonged period of calcium absorption
Rebound phase
Avid uptake of calcium by bone
Parallel uptake of magnesium by bone
Following parathyroidectomy

32. Total and ionized calcium Magnesium Phosphate UKE and s-glucose PTH
Workup - blood
Total and ionized calcium
Magnesium
Phosphate
UKE and s-glucose
PTH
Vitamin D metabolite
Urine-CMP and –creatinine
S-ALP

33. Workup - imaging
CXR
Ankle and wrist XR

34. Karyotyping and family screening
Workup - other
ECG
Malabsorption workup
Karyotyping and family screening

35. Management Dependent on the underlying cause and severity
Administration of calcium alone is only transiently effective
Mild asymptomatic cases: Often adequate to increase dietary calcium by 1000 mg/day
Symptomatic: Treat immediately

36. Treatment of hypocalcaemia
Symptomatic hypocalcaemia
IV Calcium should only be given with close monitoring
Should be on cardiac monitor
Mix with NaCl or 5 % D/W (not bicarbonate/lactate containing solutions)
Risks
Tissue necrosis/calcification if extravasates
Calcium can inhibit sinus node  bradycardia + arrest
Stop infusion if bradycardia develops
Avoid complete correction of hypocalcaemia
With acidosis and  S-Ca – give Ca before correcting acidosis
If  Mg is cause of  S-Ca – treat and correct hypomagnesaemia

37. Treatment of hypocalcaemia
Symptomatic hypocalcaemia
Early neonatal hypocalcaemia
Neonates: Ca gluconate:10 mg/kg (1 ml/kg of 10% solution) Slowly IV + monitoring ECG
Occasionally associated transient hypomagnesaemia
Treat prior to Ca administration
Start oral Calcium as soon as possible
Early neonatal hypocalcaemia normalizes in 2-3 days
Oral Ca usually necessary for 1 week

38. Treatment of hypocalcaemia
Symptomatic hypocalcaemia
Late neonatal hypocalcaemia
Associated with  S-phosphate
Decrease phosphate intake
Give calcium containing phosphate binder
Oral calcium (gluconate) supplementation
100 mg/kg/dose 4 hourly per os

39. Hypocalcaemia in older children
Same dose IV as for neonates
More often require continuous infusion
Oral supplementation 50 mg/kg/24 hr elemental Ca
Ca binds with phosphate in gut   Ca absorption
Advantage in conditions with  s-phosphate
Renal failure
Hypoparathyroidism
Tumor lysis
Most need Vit D supplementation

40. References Acknowledgement: Dr. Ida van Biljon
Zalman et al. Treatment of hypocalcemia. May 2008.
Zalman et al. Diagnostic approach to hypocalcemia. May 2008.
Gernter JM. Disorders of calcium and phosphorus homeostasis. Pediatr Clin North Am. Dec 1990; 37(6):
Lorraine a et al. Hypocalcemia: Diagnosis and Treatment. Metabolic diseases. Sept 2002.
Jeha GS et al. Etiology of hypocalcemia in infants and children. May 2008.
Acknowledgement: Dr. Ida van Biljon
Consultant Paediatric Nephrology
Department Paediatrics and Child Health
Steve Biko Academic Hospital