hypocalcemia dr. nicolette du plessis department paediatrics university of pretoria
TRANSCRIPT
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Hypocalcemia
Dr. Nicolette du Plessis
Department Paediatrics
University of Pretoria
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Introduction
Pathophysiology
Etiology
Diagnostic approach
Management principles
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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
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Calcium homeostasis
Regulation of parathyroid function by calcimimetic compoundsE. Nemeth, http://www.ndt-educational.org/nemethslide.asp
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Introduction to Anatomy and Physiology, http://ncwcbio101.wordpress.com/2008/11/23/14-introduction-to-anatomy-and-physiology/
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Pathophysiology Ionized calcium is affected by:
Albumin
Blood pH
Serum phosphate
Serum magnesium
Serum bicarbonate
Exogenous factors Citrate / free fatty acids (TPN)
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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
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Symptoms and signs of hypocalcemia
Neuromuscular irritability
Paresthesias
Laryngospasm / Bronchospasm
Tetany
Seizures
Chvostek sign
Trousseau sign
Prolonged QTc time on ECG
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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.
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Signs & Symptoms: A 2-in-1 Reference for Nurses, Copyright © 2007 Lippincott Williams & Wilkins, www.wrongdiagnosis.com/bookimages/14/4721.1.png
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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
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Long QT interval with normal T waves
Prolongation of the ST segment with little shift from the baseline
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History that suggests hypocalcemia Newborns (can be unspecific)
Asymptomatic Lethargy Poor feeding Vomiting Abdominal distention
Children Seizures Twitching Cramping Laryngospasm
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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
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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)
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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
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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),
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Synthesis / secretion Autoimmune
APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome) Hypoparathyroidism Primary adrenal insufficiency Chronic mucocutaneous candidiasis
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Synthesis / secretion Acquired
Thyroid surgery Parathyroidectomy Iron deposition with chronic transfusions Wilson’s disease Gram negative sepsis, toxic shock, AIDS
? Macrophage-generated cytokines
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Pseudohypoparathyroidism Target organ insensitivity to PTH
(bone / kidney) Hypocalcemia
Hyperphosphatemia
Elevated PTH
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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
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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
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Pseudopseudohypoparathyroidism
Phenotype of Albright’s
NORMAL serum calcium
NO PTH resistance
Paternal GNAS1 gene mutation
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PseudohypoparathyroidismType 1b
Hypocalcemia, no phenotypic abnormality
AD, maternal transmission
Type 1c Looks like type 1a
Type 2 No features of Albright’s
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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
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Hypovitaminosis D Decrease intake or production
Increased catabolism
Decrease 25-hydroxylation by liver
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
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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
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HypomagnesemiaPrimary
Autosomal recessive Present at 1 month age with seizures
Secondary Intestinal absorption vs renal excretion
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OtherPancreatitis
Citrated products
Hungry bone syndrome
Hyperphosphatemia
Fluoride poisoning
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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
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Workup - bloodTotal and ionized calciumMagnesiumPhosphateUKE and s-glucosePTHVitamin D metaboliteUrine-CMP and –creatinineS-ALP
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Workup - imagingCXRAnkle and wrist XR
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Workup - otherECGMalabsorption workupKaryotyping and family screening
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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
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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
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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
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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
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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
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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