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/2008/11/23/14introduction-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 feeding, increased calcitonin, endogenous phosphate load high, alkali therapy depletion functional hypoparathyroidism hypocalcemia

Birth asphyxia
Delay

Infant to diabetic mother

Magnesium

IUGR

Etiology

Late neonatal hypocalcemia

Exogenous phosphate load

Phosphate-rich

formulas / cows 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 ( CATCH 22 ) Mitochondrial disorders:

MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episode),

Synthesis / secretion

Autoimmune

APECED (autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy syndrome)

Hypoparathyroidism Primary adrenal insufficiency Chronic mucocutaneous candidiasis

Synthesis / secretion

Acquired

Thyroid surgery Parathyroidectomy Iron deposition with chronic transfusions Wilsons 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) Albrights hereditary osteodystrophy

Albrights

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 Albrights

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 Albrights

PHP Ia
Albrights phenotype +

PHP Ib
-

PHP II
-

PPHP
+

Serum calcium
Response to PTH cAMP Response to Phosphorus Hormone Resistance Molecular defect

All hormones Gsa

PTH target tissues only ?PTH R

()NL PTH target tissues only Unknown

NL
NL NL None Gsa

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

Total and 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. 2. 3. 4.

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

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