Transcript Hypocalcemia

Hypocalcemia
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Introduction
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Pathophysiology
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Etiology
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Diagnostic approach
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Management principles
Introduction
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Calcium is the most abundant mineral in the body.
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In pediatric ICU, hypocalcemia has higher mortality then
normocalcemia.
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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-toanatomy-and-physiology/
Pathophysiology
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Ionized calcium is affected by:
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Albumin
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Blood pH
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Serum phosphate
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Serum magnesium
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Serum bicarbonate
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Exogenous factors
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Citrate / free fatty acids (TPN)
Why do we need it?
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Calcium messenger system – regulates cell function
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Activates cellular enzyme cascades
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Smooth muscle and myocardial contraction
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Nerve impulse conduction
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Secretory activity of exocrine glands
Symptoms and signs of hypocalcemia
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Neuromuscular irritability
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Paresthesias
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Laryngospasm / Bronchospasm
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Tetany
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Seizures
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Chvostek sign
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Trousseau sign
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Prolonged QTc time on ECG
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Tetany is not caused by increased excitability of the
muscles.
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Muscle excitability is depressed
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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)
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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
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Long QT interval with
normal T waves
Prolongation of the ST
segment with little shift
from the baseline
History that suggests hypocalcemia
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Newborns (can be unspecific)
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Asymptomatic
Lethargy
Poor feeding
Vomiting
Abdominal distention
Children
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Seizures
Twitching
Cramping
Laryngospasm
Etiology
 Neonatal hypocalcemia:
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Early neonatal hypocalcemia (48-72 hours)
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Prematurity
 Poor
intake, hypoalbuminemia, reduced responsiveness to
vitamin D
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Birth asphyxia
 Delay
feeding, increased calcitonin, endogenous phosphate
load high, alkali therapy
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Infant to diabetic mother
 Magnesium
depletion → functional hypoparathyroidism →
hypocalcemia
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IUGR
Etiology
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Late neonatal hypocalcemia
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Exogenous phosphate load
 Phosphate-rich
formulas / cow’s milk
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Magnesium deficiency
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Transient hypoparathyroidism of newborn
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Hypoparathyroidism
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Gentamycin (24 hourly dosing schedule)
Etiology
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Infants and children
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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)
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Hypomagnesemia
Other
Synthesis / secretion of PTH
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Genetic
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Autosomal dominant
Autosomal recessive
X-Linked
HDR (hypoparathyroidism associated with
sensorineural deafness and renal dysplasia)
DiGeorge's syndrome
Mitochondrial disorders:
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MELAS (mitochondrial encephalopathy, lactic acidosis
and stroke-like episode),
Synthesis / secretion
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Autoimmune
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APECED (autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy syndrome)
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Hypoparathyroidism
Primary adrenal insufficiency
Chronic mucocutaneous candidiasis
Synthesis / secretion
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Acquired
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Thyroid surgery
Parathyroidectomy
Iron deposition with chronic transfusions
Wilson’s disease
Gram negative sepsis, toxic shock, AIDS
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? Macrophage-generated cytokines
Pseudohypoparathyroidism
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Target organ insensitivity to PTH (bone /
kidney)
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Hypocalcemia
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Hyperphosphatemia
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Elevated PTH
Pseudohypoparathyroidism (PHP)
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GNAS1 gene mutations – intracellular signals
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Expression in tissues either paternally / maternally
determined
Example: renal expression is maternal
Type 1a PHP
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AD (maternal transmission)
Albright’s hereditary osteodystrophy
Albright’s
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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
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Phenotype of Albright’s
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NORMAL serum
calcium
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NO PTH resistance
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Paternal GNAS1 gene
mutation
Pseudohypoparathyroidism
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Type 1b
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Type 1c
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Hypocalcemia, no phenotypic abnormality
AD, maternal transmission
Looks like type 1a
Type 2
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No features of Albright’s
PHP Ia
PHP Ib
PHP II
PPHP
Albright’s
phenotype
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Serum
calcium
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NL
Response to
PTH cAMP
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NL
Response to
Phosphorus
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()NL
NL
Hormone
Resistance
All
hormones
PTH target
tissues only
PTH target
tissues only
None
Molecular
defect
Gsa
?PTH R
Unknown
Gsa
Hypovitaminosis D
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Decrease intake or production
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Increased catabolism
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Decrease 25-hydroxylation by liver
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Decrease 1-hydroxylation by kidney
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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
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Mechanisms:
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End-organ unresponsiveness to PTH
Impaired release of PTH
Impaired formation of 1,25-vitamin D3
Hypomagnesemia
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Primary
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Autosomal recessive
Present at 1 month age with seizures
Secondary
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Intestinal absorption vs renal excretion
Other
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Pancreatitis
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Citrated products
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Hungry bone syndrome
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Hyperphosphatemia
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Fluoride poisoning
Other
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Hungry bone syndrome
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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
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Workup - imaging
CXR
 Ankle and wrist XR
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Workup - other
ECG
 Malabsorption workup
 Karyotyping and family screening
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Management
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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
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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
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Tissue necrosis/calcification if extravasates
Calcium can inhibit sinus node  bradycardia + arrest
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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
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Neonates: Ca gluconate:10 mg/kg (1 ml/kg of 10% solution) Slowly
IV + monitoring ECG
Occasionally associated transient hypomagnesaemia
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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
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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
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Ca binds with phosphate in gut   Ca absorption
 Advantage in conditions with  s-phosphate
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Renal failure
Hypoparathyroidism
Tumor lysis
Most need Vit D supplementation