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 compoundsE. 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

PseudohypoparathyroidismType 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  PPHPAlbright’s phenotype 

+  - - +

Serum calcium 

NL

Response to PTH cAMP

NL 

Response to Phosphorus

()NL NL 

Hormone Resistance 

All hormones 

PTH target tissues only 

PTH target tissues only 

None

Molecular defect 

Gsa  ?PTH R  Unknown  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

HypomagnesemiaMagnesium 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

HypomagnesemiaPrimary

Autosomal recessive Present at 1 month age with seizures

Secondary Intestinal absorption vs renal excretion

OtherPancreatitis

Citrated products

Hungry bone syndrome

Hyperphosphatemia

Fluoride poisoning

OtherHungry 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 - bloodTotal and ionized calciumMagnesiumPhosphateUKE and s-glucosePTHVitamin D metaboliteUrine-CMP and –creatinineS-ALP

Workup - imagingCXRAnkle and wrist XR

Workup - otherECGMalabsorption workupKaryotyping 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 hypocalcaemiaSymptomatic 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 BiljonConsultant Paediatric Nephrology

Department Paediatrics and Child HealthSteve Biko Academic Hospital