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)

Calcium physiologyCalcium physiology

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

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

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

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

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%

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

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

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

Calcium HomeostasisCalcium Homeostasis

Principle organs involvedPrinciple organs involved

1.1. IntestineIntestine

2.2. KidneysKidneys

3.3. BoneBone

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)

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

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

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

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

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

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

Calcium disorder in childrenCalcium disorder in children

HypercalcemiaHypercalcemia

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

Differential diagnosis of hypercalcemia

PTH-mediatedHyperparathyroidism

Non-PTH-mediatedMalignancyGranulomatous diseasesEndocrine conditionsImmobilizationFamilial hypocalciuric hypercalcemiaDrugs or supplements

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

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

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

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)

Hyperparathyroidism

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

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

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.

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

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)

HypocalcemiaHypocalcemia

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)

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

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

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

Clinical features of hypocalcemia

•Muscle cramps•Paraesthesias •Laryngospasm •Bronchospasm •Tetany •Seizures

•Chvostek sign •Trousseau sign •Prolonged Q-T interval on ECG

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)

Rickety rossary Frontal bossing

BowingWidening of wrist

Cupping and splaying of metaphysis

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

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

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

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

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

Pseudohypoparatyroidism type 1a – Albright hereditary osteodystrophy

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

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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