Hypocalcemia

Dr. Nicolette du Plessis

Department Paediatrics

University of Pretoria
 Introduction
 Pathophysiology

 Etiology

 Diagnostic approach

 Management principles
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

Calcium homeostasis

Regulation of parathyroid function by calcimimetic compounds

E. Nemeth, http://www.ndt-educational.org/nemethslide.asp
Introduction to Anatomy and Physiology, http://ncwcbio101.wordpress.com/2008/11/23/14-
introduction-to-anatomy-and-physiology/
Pathophysiology
 Ionized calcium is affected by:
 Albumin

 Blood pH

 Serum phosphate

 Serum magnesium

 Serum bicarbonate

 Exogenous factors
 Citrate / free fatty acids (TPN)
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

Symptoms and signs of hypocalcemia
 Neuromuscular irritability
 Paresthesias
 Laryngospasm / Bronchospasm
 Tetany
 Seizures
 Chvostek sign
 Trousseau sign
 Prolonged QTc time on ECG
 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.
Signs & Symptoms: A 2-in-1 Reference for Nurses, Copyright © 2007 Lippincott Williams & Wilkins,
www.wrongdiagnosis.com/bookimages/14/4721.1.png
 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
 Long QT interval with
normal T waves
 Prolongation of the ST
segment with little shift
from the baseline
History that suggests hypocalcemia
 Newborns (can be unspecific)
 Asymptomatic
 Lethargy
 Poor feeding
 Vomiting
 Abdominal distention

 Children
 Seizures
 Twitching
 Cramping
 Laryngospasm
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
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)
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
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),
Synthesis / secretion
 Autoimmune
 APECED (autoimmune polyendocrinopathy-
candidiasis-ectodermal dystrophy syndrome)
 Hypoparathyroidism
 Primary adrenal insufficiency
 Chronic mucocutaneous candidiasis
Synthesis / secretion
 Acquired
 Thyroid surgery
 Parathyroidectomy
 Iron deposition with chronic transfusions
 Wilson’s disease
 Gram negative sepsis, toxic shock, AIDS
 ? Macrophage-generated cytokines
Pseudohypoparathyroidism
 Target
organ insensitivity to PTH (bone /
kidney)
 Hypocalcemia
 Hyperphosphatemia

 Elevated PTH
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
 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
Pseudopseudohypoparathyroidism
 Phenotype of Albright’s

 NORMAL serum
calcium

 NO PTH resistance

 Paternal GNAS1 gene

mutation
Pseudohypoparathyroidism
 Type 1b
 Hypocalcemia, no phenotypic abnormality
 AD, maternal transmission

 Type 1c
 Looks like type 1a

 Type 2
 No features of Albright’s
 PHP Ia  PHP Ib  PHP II  PPHP
Albright’s +  - - +
phenotype 
Serum    NL
calcium 
Response to    NL 
PTH cAMP
Response to   ()NL NL 
Phosphorus
Hormone All PTH target PTH target None
Resistance  hormones  tissues only  tissues only 
Molecular Gsa  ?PTH R  Unknown  Gsa
defect 
Hypovitaminosis D
 Decrease intake or production

 Increased catabolism

 Decrease 25-hydroxylation by liver

 Decrease 1-hydroxylation by kidney

 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
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
Hypomagnesemia
 Primary
 Autosomal recessive
 Present at 1 month age with seizures

 Secondary
 Intestinal absorption vs renal excretion
Other
 Pancreatitis

 Citrated products

 Hungry bone syndrome

 Hyperphosphatemia

 Fluoride poisoning
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
Workup - blood
 Totaland ionized calcium
 Magnesium
 Phosphate
 UKE and s-glucose
 PTH
 Vitamin D metabolite
 Urine-CMP and –creatinine
 S-ALP
Workup - imaging
 CXR
 Ankle and wrist XR
Workup - other
 ECG
 Malabsorption workup
 Karyotyping and family screening
Management
1. Dependent on the underlying cause and severity
2. Administration of calcium alone is only
transiently effective
3. Mild asymptomatic cases: Often adequate to
increase dietary calcium by 1000 mg/day
4. Symptomatic: Treat immediately
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
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
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
 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
References
 Zalman et al. Treatment of hypocalcemia. www.uptodate.com. May 2008.
 Zalman et al. Diagnostic approach to hypocalcemia. www.uptodate.com. May 2008.
 Gernter JM. Disorders of calcium and phosphorus homeostasis. Pediatr Clin North Am. Dec
1990; 37(6): 1441-65.
 Lorraine a et al. Hypocalcemia: Diagnosis and Treatment. Metabolic diseases. Sept 2002.
 Jeha GS et al. Etiology of hypocalcemia in infants and children. www.uptodate.com. May
2008.

Acknowledgement: Dr. Ida van Biljon

Consultant Paediatric Nephrology
Department Paediatrics and Child Health
Steve Biko Academic Hospital