Upload
angela-austin
View
218
Download
2
Tags:
Embed Size (px)
Citation preview
Calcium Disorders
Dr. Sohail InamConsultant Endocrine & Diabetes
Prince Sultan Military Medical CityRiyadh
Calcium
Major intracellular ionImportant for cellular function– Intracellular signaling– Muscle action potential– Hormone secretion– Coagulation cascade
Major store is the bone (90%)
Calcium
Serum calcium is tightly regulatedNormal total Ca 2.2-2.5 mmol/l (8.5-10 md/dl)– Ionized (free)– Bound (Albumin and other proteins)
Corrected calcium for albumin
SerumCalcium
Urine calcium
300
100
600
600
980010000
1000
Dietary Calcium
FecalCalcium
800
200 Valuesmg/day
Regulation of calcium
Parathyroid hormoneVitamin DCalcitonin
Parathyroid gland
PTH
CalciumPhosphate
Reabsorbs CalciumExcretes Phosphate
Activates 1 alpha hydroxylase25 OH D3 → 1,25 Dihydoxy D3
PTH
• Stimulation– Hypocalcaemia & hypomagnesaemia– Decrease 1,25 D3– Hyperphosphatemia– adrenergic stimulation
• Inhibition– Hypercalcemia– Increased 1,25 D3– Hypophosphatemia
Vitamin D
291-315 nm
Vitamin D
25 OH D
1,25 dihydroxy D
↑Calcium↑Phosphate
↑AbsorptionCalcium
Phosphate
25 hydroxylase
1 alpha hydroxylase
1 alpha Hydroxylase
Activation– PTH– Low phosphate– Low calcium– IGF 1
Inhibition– 1,25 (OH)2 D3– High phosphate & High calcium– FGF23
Calcitonin
Inhibits release of Ca from boneIncreases Ca excretion by the kidneyStimulated by increase in Ca levels
Ca x PO4
PTH1,25-D3
SerumCalcium
Urine calcium
PTH1,25-D3
1,25-D3
CT
HYPOCALCEMIA
HypocalcemiaCauses
Hypoparathyroidism– Autoimmune– Surgical damage– Radiation damage– Infiltrative
Psudohypoparathyroidism (PTH resistance)CaSR mutation
HypocalcemiaCauses
Vitamin D– Deficiency– Inability to activate Vitamin D– Resistance
Renal diseaseMagnesium deficiency– Decrease PTH release– PTH resistance
HypocalcemiaCauses
Calcium sequestration– Pancreatitis– Osteoblastic metastasis– High phosphate– Hungry bone disease
DrugsCritical illness
HypocalcemiaSymptoms
Paresthesia– Peri-oral– Limbs
Muscle cramps & carpopedal spasmSeizuresLaryngeal spasmCardiac Psychiatric
HypocalcemiaSigns
Tetany– Carpopedal spasm– Chvestok’s sign– Trousseau's sign
PapilledemaCataractsExtrapyramidal ECG- Prolonged QTc
Investigations
Corrected calciumPhosphateAlkaline phosphataseRenal functionParathyroid hormoneVitamin DMagnesium
Hypocalcemia
PTH Low• Hypoparathyroidism• CaSR mutations• Magnesium deficiency• Hungry bone syndrome
PTH High• Vitamin D disorders• Renal disease• PTH resistance• Ca sequestration• Sepsis• Drugs• Magnesium deficiency
Hypocalcemia
Phosphate, Alkaline Phosphatase, Magnesium, Creatinine, Vitamin D
PTH
High Normal or low
↑ Phosphate ↓ Phosphate ↑ Phosphate ↓ Phosphate
Renal failurePTH resistance
Rhabdomyolysis
Vitamin D disorders HypoparathyroidismCaSR mutations
Hungry bone
Treatment
Severe symptomatic hypocalcemia– IV calcium (slow infusion)
Mild symptoms– Oral calcium
Vitamin D– Active form– Inactive form
TreatmentSpecific
MagnesiumHypoparathyroidism– Active form of vitamin D– PTH replacement
Renal failure– Phosphate binders– Active form of Vitamin D
HYPERCALCEMIA
HypercalcemiaMechanisms
Excess PTH hormonePTHrP– Tumors (Malignancy)– Pregnancy & lactation
Vitamin D mediated– Intoxication– Granulomatous disease– Hematological malignancies
HypercalcemiaMechsnisms
Excess Ca absorption (Milk Alkali)Increased osteoclast activation– Cytokines– Immobilization– Adrenal insufficiency– Thyrotoxicosis
↑ SerumCalcium
Urine calcium
Causes
HyperparathyroidismMalignancyVitamin D intoxicationMilk Alkali syndromeGranulomatous diseasesEndocrine
Causes
ImmobilizationDrugsParenteral nutritionFamilial hypocalciuric hypercalcemia
Clinical features
Polyuria & polydipsiaGIT– Anorexia– Abdominal pain– Constipation
NeuropsychiatricMusculoskeletal
Clinical features
Renal dysfunction– Nephrocalcinosis– Nephrolithiasis– Renal tubular acidosis
Cardiovascular– Arrthymias– Cardiac arrest
Hypercalcemia
High PTH• Hyperparathyroidism• Ectopic PTH secretion• FHH• Drugs
Low PTH• Malignancy• Vitamin D excess• Immobilization• Milk Alkali Syndrome• Granulomatous disease• Endocrine
Hypercalcemia
Confirm on repeat sample
Measure PTH
Normal or ↑ PTH
24 hour urineCalcium & creatinine
FHH Hyperparathyroidism
Low PTH (<20pg/ml)
MeasurePTHrP, Vit D metabolites, TFT
CXR, CT scan, Myeloma
Clinical evaluation & medication history
low Normalor high
HypercalcemiaPrinciples of Therapy
Increase renal Ca excretion– Saline diuresis (± frusemide)– Calcitonin– Dialysis
Reduce Ca efflux from bone– Calcitonin– Bisphosphonates– Denusamab
Treat underling cause
Treatment
Mild hypercalcemia (Ca <3)– Treat underlying cause
Moderate hypercalcemia (Ca 3-3.49)– Hydration– Bisphosphonate– Treat underlying cause
Treatment
Severe Hypercalcemia (severe symptoms, Ca>3.5)– IV hydration 0.9% NaCl– Calcitonin– Bisphosphonates– Low calcium bath dialysis– Treat underlying cause
Specific Treatment
Hyperparathyroidism– Surgery– Non-surgical ablation– Conservative approach– Calcimimetics
Steroids– Hematological malignancies– Vitamin D intoxication
Thank You