calcium physiology and associated disorder in children
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Calcium physiology and associated disorder in childrenTRANSCRIPT
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Calcium physiology and Calcium physiology and associated disorder in associated disorder in
childrenchildren
By: Wong Ann Cheng By: Wong Ann Cheng
MD (UKM) MRCPCH (UK)MD (UKM) MRCPCH (UK)
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Calcium physiologyCalcium physiology
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Biological functions of calciumBiological functions of calcium
Structural as component of boneStructural as component of bone
Functional for normal neuromuscular Functional for normal neuromuscular activityactivity
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Multiple biological functions of calcium
•Cell signalling •Neural transmission •Cardiac and skeletal muscle contraction •Blood coagulation •Enzymatic co-factor •Secretion •Biomineralization
30% increase in free Ca,
nerves and muscles become unresponsive
35% decrease,
nerves overexcitable and convulsions occur; 50% fatal
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Sources of calciumSources of calcium
bones and teeth provide huge reservoir of Ca bones and teeth provide huge reservoir of Ca
98-99% Ca filtered from blood in kidneys is 98-99% Ca filtered from blood in kidneys is reabsorbed reabsorbed
10-20% Ca consumed as food is absorbed 10-20% Ca consumed as food is absorbed by brush border of intestinal cells by brush border of intestinal cells
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Distribution in the bodyDistribution in the body
99% deposited in bones and teeth 99% deposited in bones and teeth
0.5% bound to plasma proteins in blood 0.5% bound to plasma proteins in blood
0.5% free ionized calcium in extracellular fluid 0.5% free ionized calcium in extracellular fluid
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Calcium in the bloodCalcium in the blood
Free or ionized state Free or ionized state 45%45%
Bound to plasma protein (albumin)Bound to plasma protein (albumin) 45%45%
Bound to anion (phosphate, citrate)Bound to anion (phosphate, citrate) 10%10%
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Calcium concentrationCalcium concentration
Ionized Calcium is metabolically activeIonized Calcium is metabolically active
Most lab only report total calciumMost lab only report total calcium
Total calcium concentration fluctuate with Total calcium concentration fluctuate with serum albuminserum albumin
Corrected CaCorrected Ca22 = Ca = Ca22 + 0.02 (40 - Alb) + 0.02 (40 - Alb)
Normal value 2.1-2.6 mmol/LNormal value 2.1-2.6 mmol/L
Degree of protein binding of plasma CaDegree of protein binding of plasma Ca2 2
proportional to plasma pHproportional to plasma pH
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Beware correction acidosis in Beware correction acidosis in renal failurerenal failure
Total and ionized CaTotal and ionized Ca22 already low already low
Acute rise in pH with NaHCOAcute rise in pH with NaHCO3 3 increase protein bound Caincrease protein bound Ca22 reduce ionized Careduce ionized Ca2 2
tetanytetany
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Pseudo-hypercalcemiaPseudo-hypercalcemia
Dehydration or haemoconcentration during Dehydration or haemoconcentration during blood taking may elevate serum albumin blood taking may elevate serum albumin and hence falsely elevated total serum and hence falsely elevated total serum calciumcalcium
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Calcium HomeostasisCalcium Homeostasis
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Principle organs involvedPrinciple organs involved
1.1. IntestineIntestine
2.2. KidneysKidneys
3.3. BoneBone
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Principal hormones involvedPrincipal hormones involved
1.1. 1,25-dihydroxyvitamin D (1,25-OH1,25-dihydroxyvitamin D (1,25-OH22D)D)
2.2. Parathyroid hormone (PTH)Parathyroid hormone (PTH)
3.3. Calcitonin (CT)Calcitonin (CT)
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Effects of 1,25-OHEffects of 1,25-OH22D (1,25-dihydroxyvitamin D) D (1,25-dihydroxyvitamin D)
on Mineral Metabolismon Mineral Metabolism
BoneBonePromotes mineralization of osteoid Promotes mineralization of osteoid Increases resorption at high doses Increases resorption at high doses
KidneyKidneyDecreases calcium excretion Decreases calcium excretion Decreases phosphorus excretion Decreases phosphorus excretion
Gastrointestinal TractGastrointestinal TractIncreases calcium absorption Increases calcium absorption Increases phosphorus absorption Increases phosphorus absorption
BloodBloodIncreases calcium Increases calcium Increases phosphorus Increases phosphorus
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Effects of Parathyroid Hormone on Effects of Parathyroid Hormone on Calcium and Skeletal MetabolismCalcium and Skeletal Metabolism
BoneBoneIncreases resorption Increases resorption Increases formation, especially at low and intermittent concentrations Increases formation, especially at low and intermittent concentrations
KidneyKidneyDecreases calcium excretion (clearance) Decreases calcium excretion (clearance) Increases phosphorus excretion Increases phosphorus excretion
Gastrointestinal TractGastrointestinal TractIncreases calcium and phosphorus absorption Increases calcium and phosphorus absorption Indirect effect via 1,25-OHIndirect effect via 1,25-OH22D production D production
BloodBloodIncreases calcium Increases calcium Decreases phosphorus Decreases phosphorus
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Effects of Calcitonin on Mineral MetabolismEffects of Calcitonin on Mineral Metabolism
BoneBoneInhibits resorption Inhibits resorption ? Promotes formation ? Promotes formation
KidneyKidneyIncreases calcium excretion Increases calcium excretion Increases phosphorus excretion Increases phosphorus excretion
Gastrointestinal TractGastrointestinal Tract? Inhibitory effect on calcium/phosphorus absorption? Inhibitory effect on calcium/phosphorus absorption
Blood Blood Decreases calcium Decreases calcium Decreases phosphorus Decreases phosphorus
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VITAMIN D SYNTHESISVITAMIN D SYNTHESIS
SKIN LIVER KIDNEY
7-DEHYDROCHOLESTEROL
VITAMIN D3
VITAMIN D3
25(OH)VITAMIN D
u25-HYDROXYLASE
25(OH)VITAMIN D
1,25(OH)2 VITAMIN D
(ACTIVE METABOLITE)
1-HYDROXYLASE
TISSUE-SPECIFIC VITAMIN D RESPONSES
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CALCIUM HOMEOSTASISCALCIUM HOMEOSTASIS
DIETARY CALCIUM
INTESTINAL ABSORPTIONORGAN PHYSIOLOGY
ENDOCRINE PHYSIOLOGY
DIETARY HABITS,
SUPPLEMENTSBLOOD CALCIUM
BONE
KIDNEYS
URINE
THE ONLY “IN”
THE PRINCIPLE “OUT”
ORGAN PHYS.
ENDOCRINE PHYS.
ORGAN, ENDOCRINE
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CALCIUM, PTH, AND VITAMIN D CALCIUM, PTH, AND VITAMIN D FEEDBACK LOOPSFEEDBACK LOOPS
NORMAL BLOOD Ca
RISING BLOOD Ca
FALLING BLOOD Ca
SUPPRESS PTH
STIMULATE PTH
BONE RESORPTION
URINARY LOSS
1,25(OH)2 D PRODUCTION
BONE RESORPTION
URINARY LOSS
1,25(OH)2 D PRODUCTION
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Calcium disorder in childrenCalcium disorder in children
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HypercalcemiaHypercalcemia
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Differential Diagnosis of Hypercalcemia
Primary hyperparathyroidism
Malignant tumors With skeletal metastases Without skeletal metastases Arising from the marrow
• Myeloma • Leukemia with blastic crisis
Granulomatous diseases Sarcoidosis Active tuberculosis Histoplasmosis Coccidiomycosis Leprosy
Medications
Thiazide diuretics
Vitamin D intoxication
Vitamin A intoxication
Total parenteral nutrition
Aminophylline intoxication
Miscellaneous
Immobilization
Pheochromocytoma
William syndrome
Vasoactive intestinal peptide-producing tumor
Familial hypocalciuric hypercalcemia
Milk-alkali syndrome
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Differential diagnosis of hypercalcemia
PTH-mediatedHyperparathyroidism
Non-PTH-mediatedMalignancyGranulomatous diseasesEndocrine conditionsImmobilizationFamilial hypocalciuric hypercalcemiaDrugs or supplements
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Hypercalcemic disordersHypercalcemic disordersA. Endocrine Disorders Associated with HypercalcemiaA. Endocrine Disorders Associated with Hypercalcemia Endocrine Disorders with Excess PTH Production Endocrine Disorders with Excess PTH Production
Primary Sporadic hyperparathyroidism Primary Sporadic hyperparathyroidism Primary Familial Hyperparathyroidism Primary Familial Hyperparathyroidism
MEN I MEN I MEN IIA MEN IIA FHH and NSHPT FHH and NSHPT Hyperparathyroidism - Jaw Tumor Syndrome Hyperparathyroidism - Jaw Tumor Syndrome Familial Isolated Hyperparathyroidism Familial Isolated Hyperparathyroidism
Endocrine Disorders without Excess PTH Production Endocrine Disorders without Excess PTH Production Hyperthyroidism Hyperthyroidism Hypoadrenalism Hypoadrenalism Jansen's Syndrome Jansen's Syndrome
B. Malignancy-Associated Hypercalcemia (MAH)B. Malignancy-Associated Hypercalcemia (MAH)MAH with Elevated PTHrP MAH with Elevated PTHrP
Humoral Hypercalcemia of Malignancy Humoral Hypercalcemia of Malignancy Solid Tumors with Skeletal Metastases Solid Tumors with Skeletal Metastases Hematologic Malignancies Hematologic Malignancies
MAH with Elevation of Other Systemic Factors MAH with Elevation of Other Systemic Factors MAH with Elevated 1,25(OH)2D3 MAH with Elevated 1,25(OH)2D3 MAH with Elevated Cytokines MAH with Elevated Cytokines Ectopic Hyperparathyroidism Ectopic Hyperparathyroidism Multiple Myeloma Multiple Myeloma
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Hypercalcemic disordersHypercalcemic disordersC. Inflammatory Disorders Causing HypercalcemiaC. Inflammatory Disorders Causing HypercalcemiaGranulomatous Disorders AIDS
D. Disorders of Unknown EtiologyD. Disorders of Unknown EtiologyWilliams Syndrome Idiopathic Infantile Hypercalcemia
E. Medication-InducedE. Medication-InducedThiazides Lithium Vitamin D Vitamin A Estrogens and Antiestrogens Aluminium Intoxication Milk-Alkali Syndrome
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Disorder of vitamin D metabolismDisorder of vitamin D metabolism
Subcutaneous fat necrosisSubcutaneous fat necrosisTerm infant with mild birth asphyxiaTerm infant with mild birth asphyxiaDeveloped hardened lumps in skinDeveloped hardened lumps in skinInvaded by macrophages with inappropriately high 1Invaded by macrophages with inappropriately high 1αα--OHase activityOHase activity
SarcoidosisSarcoidosisAlso cause by inappropriate formation 1Also cause by inappropriate formation 1αα-OH-OH22D by D by macrophages in sarcoid tissue, usu in lungmacrophages in sarcoid tissue, usu in lung
Vitamin D toxicityVitamin D toxicity25-OHD formed from vitamin D, weak activity but sufficient 25-OHD formed from vitamin D, weak activity but sufficient to cause hypercalcemia if vitamin D is given in excessto cause hypercalcemia if vitamin D is given in excess11αα-OH-OH22D much more potentD much more potent
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William’s syndromeWilliam’s syndrome
Abnormality elastin gene on Abnormality elastin gene on chromosome 7chromosome 7
‘‘elfin-like’ facieselfin-like’ facies
‘‘cocktail party’ conversationcocktail party’ conversation
Developmental problems, Developmental problems, learning difficultieslearning difficulties
Supravalvular aortic stenosis, Supravalvular aortic stenosis, peripheral pulmonary stenosisperipheral pulmonary stenosis
Hypercalcemia, hypercalciuria, Hypercalcemia, hypercalciuria, assoc with FTT assoc with FTT (hypercalcemia usu does not (hypercalcemia usu does not extend beyond 1 year of life)extend beyond 1 year of life)
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Hyperparathyroidism
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Primary Primary hyperparathyroidismhyperparathyroidism
Secondary Secondary hyperparathyroidismhyperparathyroidism
Tertiary Tertiary hyperparathyroidismhyperparathyroidism
Autonomous Autonomous hypersecretion of PTHhypersecretion of PTH
- PTH hyperplasia- PTH hyperplasia
- PTH adenoma- PTH adenoma
Response to Response to hypocalcemiahypocalcemia
- PTH hypertrophy- PTH hypertrophy
PTH hypertrophy PTH hypertrophy persistent persistent
after removal of after removal of hypocalcemic stimulus hypocalcemic stimulus (renal transplantation)(renal transplantation)
High PTHHigh PTH
High CaHigh Ca
High PTHHigh PTH
Low CaLow Ca
High PTHHigh PTH
High CaHigh Ca
Hyperparathyroidism
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MEN type 1MEN type 1 MEN type 2aMEN type 2a MEN type 2bMEN type 2b
PTH adenomaPTH adenoma
Pituitary tumourPituitary tumour
Pancreatic tumourPancreatic tumour
(gastrinoma, insulinoma)(gastrinoma, insulinoma)
PTH hyperplasiaPTH hyperplasia
Medullary thyroid cancerMedullary thyroid cancer
PhaeochromocytomaPhaeochromocytoma
PTH hyperplasiaPTH hyperplasia
Medullary thyroid cancerMedullary thyroid cancer
PhaeochromocytomaPhaeochromocytoma
Mucocutaneous Mucocutaneous neurofibromaneurofibroma
Dysmorphic features Dysmorphic features (marfanoid habitus, (marfanoid habitus, skeletal abN, abN dental skeletal abN, abN dental enamel)enamel)
Parathyroid gland tumour associated with MEN
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Hypercalcemia of malignancyHypercalcemia of malignancy
The most frequent cause of hypercalcemia with The most frequent cause of hypercalcemia with nonmetastatic solid tumors is the release of nonmetastatic solid tumors is the release of PTHrP. PTHrP. This protein is immunologically distinct from PTH, This protein is immunologically distinct from PTH, yet is similar enough in structure to permit binding yet is similar enough in structure to permit binding to identical receptors and simulation of second to identical receptors and simulation of second messengers. messengers. Ability of PTHrP to induce most of the actions of Ability of PTHrP to induce most of the actions of PTH including increases in bone resorption and PTH including increases in bone resorption and inhibition of proximal tubule phosphate transport. inhibition of proximal tubule phosphate transport. In general, patients with PTHrP-induced In general, patients with PTHrP-induced hypercalcemia have advanced cancer and a poor hypercalcemia have advanced cancer and a poor prognosis.prognosis.
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Manifestations of Hypercalcemia
Acute Chronic
Gastrointestinal Anorexia, nausea, vomiting
Dyspepsia, constipation, pancreatitis
Renal Polyuria, polydipsia Nephrolithiasis, nephrocalcinosis
Neuro-muscular Depression, confusion, stupor, coma
Weakness
Cardiac Bradycardia, first degree atrio-ventricular
Hypertensionblock, digitalis sensitivity
Groans, moans, bones, stones
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Management of Acute Hypercalcemia
1.Hydration •Saline (0.9%) infusion, 2 - 4 L over 24 hours
2.Inhibition of Bone Resorption •Bisphosphonate
•Pamidronate (60 to 90 mg over 4 hours IV) or •Zoledronate (4 mg over 15 min IV)
•Calcitonin •4 IU/kg to 8 IU/kg q12h sc or IM x 1 to 2 days
3.Calciuresis •Loop diuretics
•Furosemide 10 to 20 mg IV every 6 to 12 hours 4.Glucocorticoids (when indicated)
•Hydrocortisone 200 - 300 mg IV daily for 3 to 5 days 5.Dialysis (in renal failure)
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HypocalcemiaHypocalcemia
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Causes of hypocalcemia in childrenCauses of hypocalcemia in children
Neonatal hypocalcemiaNeonatal hypocalcemiaVitamin D deficiencyVitamin D deficiency Vitamin D deficient ricketsVitamin D deficient rickets Vitamin D dependent ricketsVitamin D dependent rickets Vitamin D resistant ricketsVitamin D resistant rickets
Magnesium deficiencyMagnesium deficiencyRenal failureRenal failureParathyroid disorderParathyroid disorder Genetic: Di George syndrome, APECED syndromeGenetic: Di George syndrome, APECED syndrome Acquired: Surgical, irradiation, infiltrationAcquired: Surgical, irradiation, infiltration Pseudohypoparathyroidism (PTH resistance)Pseudohypoparathyroidism (PTH resistance)
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Neonatal hypocalcemiaNeonatal hypocalcemia
Fetal bone has high demand for calcium due to Fetal bone has high demand for calcium due to high rate of bone turnoverhigh rate of bone turnoverPhysiological hypocalcemia occur as plasma Ca Physiological hypocalcemia occur as plasma Ca falls to 2.0 mmol/L during first 24 - 48H before falls to 2.0 mmol/L during first 24 - 48H before recovering by end of 1recovering by end of 1stst week weekSymptomatic hypocalcemia more likely in Symptomatic hypocalcemia more likely in premature or unwell neonatespremature or unwell neonatesProfound and prolonged hypocalcemia if failure Profound and prolonged hypocalcemia if failure of PTH gland (Di George synd) or maternal of PTH gland (Di George synd) or maternal vitamin D deficient or hypercalcemicvitamin D deficient or hypercalcemic
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Vitamin D deficiencyVitamin D deficiency
Most common symptomatic hypocalcemia Most common symptomatic hypocalcemia outside neonatal period outside neonatal period
Nutritional vitamin D deficiency, esp in black Nutritional vitamin D deficiency, esp in black children with increase skin pigmentation children with increase skin pigmentation which inhibits synthesis of vitamin Dwhich inhibits synthesis of vitamin D
May present with May present with symptoms of hypocalcemia symptoms of hypocalcemia or ricketsor rickets
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Vitamin D Deficiency Vitamin D Deficiency RicketsRickets
Vitamin D Dependent Vitamin D Dependent RicketsRickets
Vitamin D Resistant Vitamin D Resistant RicketsRickets
CauseCause
Lack exposure to sunlightLack exposure to sunlight
Lack of intake Lack of intake
Anticonvulsant therapyAnticonvulsant therapy
Intestinal malabsorptionIntestinal malabsorption
CauseCause
Deficiency enzyme that Deficiency enzyme that convert 25-D3 to 1,25-D3convert 25-D3 to 1,25-D3
CauseCause
Phosphate leak at level of Phosphate leak at level of proximal tubulesproximal tubules
(not a disease of vitamin (not a disease of vitamin D metabolism)D metabolism)
Lab findingsLab findings
Low CaLow Ca22
Low POLow PO44
High ALPHigh ALP
High PTHHigh PTH
Low 1,25-D3Low 1,25-D3
Lab findingsLab findings
Low CaLow Ca22
Low POLow PO44
High ALPHigh ALP
High PTHHigh PTH
Low 1,25-D3Low 1,25-D3
Lab findingsLab findings
Normal CaNormal Ca22
Low POLow PO44
Normal PTHNormal PTH
TreatmentTreatment
Vitamin DVitamin D
TreatmentTreatment
Daily 1,25-D3Daily 1,25-D3
TreatmentTreatment
Phosphate supplementsPhosphate supplements
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Clinical features of hypocalcemia
•Muscle cramps•Paraesthesias •Laryngospasm •Bronchospasm •Tetany •Seizures
•Chvostek sign •Trousseau sign •Prolonged Q-T interval on ECG
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Findings of ricketsFindings of rickets
RReaction of the periosteum (may occur) eaction of the periosteum (may occur)
IIndistinct cortex ndistinct cortex
CCoarse trabeculation oarse trabeculation
KKnees, wrists, and ankles affected predominantly nees, wrists, and ankles affected predominantly
EEpiphyseal plates, widened and irregular piphyseal plates, widened and irregular
TTremendous metaphysis (cupping, fraying, splaying) remendous metaphysis (cupping, fraying, splaying)
SSpur (metaphyseal) pur (metaphyseal)
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Rickety rossary Frontal bossing
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BowingWidening of wrist
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Cupping and splaying of metaphysis
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Magnesium deficiencyMagnesium deficiency
Deficiency commonly cause by Deficiency commonly cause by malabsorptionmalabsorption
Causes hypoparathyroid state by Causes hypoparathyroid state by interfering with PTH secretioninterfering with PTH secretion
Biochem resembles hypoparathyroidism Biochem resembles hypoparathyroidism but with low plasma Mgbut with low plasma Mg
Corrected by treatment with MgCorrected by treatment with Mg
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Renal FailureRenal FailureDecreased glomerular filtration rate (GFR) Decreased glomerular filtration rate (GFR) decreased decreased filtration of phosphate, phosphate retention, and filtration of phosphate, phosphate retention, and increased serum phosphateincreased serum phosphateIncreased serum phosphate complexes with serum Increased serum phosphate complexes with serum calcium calcium decreased ionized serum calcium decreased ionized serum calciumDecreased production of active Vitamin D (1,25-Decreased production of active Vitamin D (1,25-dihydroxycholecalciferol) by diseased renal tissue also dihydroxycholecalciferol) by diseased renal tissue also contributes to decreased ionized calcium contributes to decreased ionized calcium Decreased serum calcium causes secondary Decreased serum calcium causes secondary hyperparathyroidismhyperparathyroidismThe combination of increased PTH levels and decreased The combination of increased PTH levels and decreased active Vitamin D produces renal osteodystrophy, in which active Vitamin D produces renal osteodystrophy, in which there is increased bone resorption and osteomalaciathere is increased bone resorption and osteomalacia
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Genetic hypoparathyroidismGenetic hypoparathyroidismDiGeorge SyndromeDiGeorge Syndrome
Catch 22 spectrumCatch 22 spectrumMicrodeletion long arm chromosome 22Microdeletion long arm chromosome 22AbN 3AbN 3rdrd and 4 and 4thth branchial arches branchial arches
Absent parathyroid, Absent parathyroid, Absent thymus gland, Absent thymus gland, Anomalies of aortic archAnomalies of aortic arch
APECED Syndrome (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal APECED Syndrome (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome)Dystrophy Syndrome) Autoimmune parathyroid gland failureAutoimmune parathyroid gland failureAbN AIRE (autoimmune regulator) gene on chrom 21AbN AIRE (autoimmune regulator) gene on chrom 21Triad ofTriad of
Adrenal insufficiency (Addison disease)Adrenal insufficiency (Addison disease) HypoparathyroidismHypoparathyroidism Chronic mucocutaneous candidiasisChronic mucocutaneous candidiasis
Associated with polyendocrinopathy: DM, hypogonadotrophic hypogonadism, Associated with polyendocrinopathy: DM, hypogonadotrophic hypogonadism, autoimmune thyroid diseaseautoimmune thyroid disease
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Acquired hypoparathyroidismAcquired hypoparathyroidism
InfiltrationInfiltrationIron in Beta thalassaemiaIron in Beta thalassaemiaCopper in Wilson’s diseaseCopper in Wilson’s disease
SurgerySurgeryDamage during thyroid surgeryDamage during thyroid surgeryRemoval of gland for hyperparathyroidismRemoval of gland for hyperparathyroidism
IrradiationIrradiation
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HypoparathyroidismHypoparathyroidism Pseudo-Pseudo-hypoparathyroidism hypoparathyroidism
Pseudopseudo-Pseudopseudo-hypoparathyroidismhypoparathyroidism
CauseCause
Deficiency PTHDeficiency PTH
CauseCause
End organ resistance to End organ resistance to raised PTHraised PTH
Autosomal dominantAutosomal dominant
PhenotypePhenotype
Normal phenotypeNormal phenotype
PhenotypePhenotype
Abnormal phenotype- Abnormal phenotype- short stature, obesity, short stature, obesity, intellectual delay, round intellectual delay, round face, short neck, face, short neck, shortened 4shortened 4thth and 5 and 5thth metacarpalmetacarpal
PhenotypePhenotype
Abnormal phenotypeAbnormal phenotype
Lab findingsLab findings
Low Ca2Low Ca2
High PO4High PO4
Low PTHLow PTH
Lab findingsLab findings
Low Ca2Low Ca2
High PO4High PO4
High PTHHigh PTH
Lab findingsLab findings
NormalNormal
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Pseudohypoparatyroidism type 1a – Albright hereditary osteodystrophy
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Management of Hypocalcemia
1.1. IV 10% Ca gluconateIV 10% Ca gluconate 0.2 ml/kg diluted 1:5 with 0.2 ml/kg diluted 1:5 with D5% over 10 minutes with ECG monitoring, D5% over 10 minutes with ECG monitoring, followed by IV infusionfollowed by IV infusion
2.2. Oral Ca supplementsOral Ca supplements
3.3. Vitamin D Vitamin D for vitamin D deficiencyfor vitamin D deficiency
4.4. Analogue alfacalcidolAnalogue alfacalcidol for defect in vitamin D for defect in vitamin D metabolism, hypoparathyroidism, renal failuremetabolism, hypoparathyroidism, renal failure
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Investigations of disorder of Investigations of disorder of calcium metabolismcalcium metabolism
CaCa22, PO, PO44, Mg, Mg33
ALP, AlbALP, AlbBUSE, CreatinineBUSE, CreatinineCapillary pHCapillary pHPTHPTH25-OHD25-OHDUrine Ca, PO4, creatinine, a.a, glucoseUrine Ca, PO4, creatinine, a.a, glucoseX-ray wrist and kneeX-ray wrist and knee
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