Hypocalcemia

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 andPhysiology,

http://ncwcbio101.wordpress.com/2008/11/23/14-introduction-to-anatomy-and-

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 / 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
Mitochondrial disorders:

MELAS

(mitochondrial encephalopathy, lactic

acidosis and stroke-like episode),

Synthesis / secretion
Autoimmune

APECED (autoimmune
polyendocrinopathy-candidiasisectodermal 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

Looks like type 1a

Type

1c
2

No features of Albrights

Albrights
phenotyp
e
Serum
calcium
Response
to PTH
cAMP
Response
to
Phosphor
us

PHP Ia

PHP Ib

PHP II

PPHP

NL

NL

()NL

NL

Hormone
All
PTH target PTH target
Resistanc hormones
tissues
tissues

None

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
Hungry

products

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