Disorders of Calcium and Phosphate Metabolism
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Transcript of Disorders of Calcium and Phosphate Metabolism
Disorders of Calcium and Disorders of Calcium and Phosphate MetabolismPhosphate Metabolism
OutlineOutline
1.1. Review of calcium and phosphate Review of calcium and phosphate metabolismmetabolism
2.2. Abnormalities of calcium balanceAbnormalities of calcium balance
3.3. Abnormalities of phosphate balanceAbnormalities of phosphate balance
4.4. Example casesExample cases
Major Mediators of Calcium and Major Mediators of Calcium and Phosphate BalancePhosphate Balance
Parathyroid hormone (PTH)Parathyroid hormone (PTH)
Calcitriol (active form of vitamin DCalcitriol (active form of vitamin D33))
Role of PTHRole of PTH
Stimulates renal reabsorption of calciumStimulates renal reabsorption of calcium
Inhibits renal reabsorption of phosphateInhibits renal reabsorption of phosphate
Stimulates bone resorptionStimulates bone resorption
Inhibits bone formation and mineralizationInhibits bone formation and mineralization
Stimulates synthesis of calcitriolStimulates synthesis of calcitriol
Net effect of PTH Net effect of PTH ↑ ↑ serum calciumserum calcium↓ ↓ serum phosphateserum phosphate
Regulation of PTHRegulation of PTH
Low serum [CaLow serum [Ca+2+2] ] Increased PTH secretion Increased PTH secretion
High serum [CaHigh serum [Ca+2+2] ] Decreased PTH secretion Decreased PTH secretion
Role of CalcitriolRole of Calcitriol
Stimulates GI absorption of both calcium Stimulates GI absorption of both calcium and phosphateand phosphate
Stimulates renal reabsorption of both Stimulates renal reabsorption of both calcium and phosphatecalcium and phosphate
Stimulates bone resorptionStimulates bone resorption
Net effect of calcitriol Net effect of calcitriol ↑ ↑ serum calciumserum calcium↑ ↑ serum phosphateserum phosphate
Regulation of CalcitriolRegulation of Calcitriol
Overview of Calcium-Phosphate RegulationOverview of Calcium-Phosphate Regulation
Different Forms of CalciumDifferent Forms of CalciumAt any one time, most of the calcium in the body exists as the At any one time, most of the calcium in the body exists as the mineral hydroxyapatite, Camineral hydroxyapatite, Ca1010(PO(PO44))66(OH)(OH)22..
Calcium in the plasma:Calcium in the plasma:45% in ionized form (the physiologically active form)45% in ionized form (the physiologically active form)45% bound to proteins (predominantly albumin)45% bound to proteins (predominantly albumin)10% complexed with anions (citrate, sulfate, phosphate)10% complexed with anions (citrate, sulfate, phosphate)
To estimate the physiologic levels of ionized calcium in states To estimate the physiologic levels of ionized calcium in states of hypoalbuminemia:of hypoalbuminemia:
[Ca[Ca+2+2]]CorrectedCorrected = [Ca = [Ca+2+2]]MeasuredMeasured + [ 0.8 (4 – Albumin) ] + [ 0.8 (4 – Albumin) ]
Overview of Biochemical HomeostasisOverview of Biochemical Homeostasis
Overview of Calcium BalanceOverview of Calcium Balance
Etiologies of HypercalcemiaEtiologies of Hypercalcemia
Increased GI AbsorptionIncreased GI AbsorptionMilk-alkali syndromeMilk-alkali syndromeElevated calcitriolElevated calcitriol
Vitamin D excessVitamin D excessExcessive dietary intakeExcessive dietary intakeGranuomatous Granuomatous
diseasesdiseasesElevated PTHElevated PTHHypophosphatemiaHypophosphatemia
Increased Loss From BoneIncreased Loss From BoneIncreased net bone resorptionIncreased net bone resorption
Elevated PTHElevated PTHHyperparathyroidismHyperparathyroidism
MalignancyMalignancyOsteolytic metastasesOsteolytic metastasesPTHrP secreting tumorPTHrP secreting tumor
Increased bone turnoverIncreased bone turnoverPaget’s disease of bonePaget’s disease of boneHyperthyroidismHyperthyroidism
Decreased Bone Mineralization
Elevated PTH
Aluminum toxicity
Decreased Urinary Excretion
Thiazide diuretics
Elevated calcitriol
Elevated PTH
Etiologies of HypocalcemiaEtiologies of HypocalcemiaDecreased GI AbsorptionDecreased GI Absorption
Poor dietary intake of calciumPoor dietary intake of calcium
Impaired absorption of calciumImpaired absorption of calcium
Vitamin D deficiencyVitamin D deficiency
Poor dietary intake of vitamin DPoor dietary intake of vitamin D
Malabsorption syndromesMalabsorption syndromes
Decreased conversion of vit. D to calcitriolDecreased conversion of vit. D to calcitriol
Liver failureLiver failure
Renal failureRenal failure
Low PTHLow PTH
HyperphosphatemiaHyperphosphatemia
Decreased Bone Resorption/Increased MineralizationDecreased Bone Resorption/Increased Mineralization
Low PTH (aka hypoparathyroidism)Low PTH (aka hypoparathyroidism)
PTH resistance (aka pseudohypoparathyroidism)PTH resistance (aka pseudohypoparathyroidism)
Vitamin D deficiency / low calcitriolVitamin D deficiency / low calcitriol
Hungry bones syndromeHungry bones syndrome
Osteoblastic metastasesOsteoblastic metastases
Increased Urinary Excretion
Low PTH
s/p thyroidectomy
s/p I131 treatment
Autoimmune hypoparathyroidism
PTH resistance
Vitamin D deficiency / low calcitriol
Overview of Phosphate BalanceOverview of Phosphate Balance
Etiologies of HyperphosphatemiaEtiologies of Hyperphosphatemia
Increased GI IntakeIncreased GI Intake
Fleet’s Phospho-SodaFleet’s Phospho-Soda
Decreased Urinary ExcretionDecreased Urinary Excretion
Renal FailureRenal Failure
Low PTH (hypoparathyroidism)Low PTH (hypoparathyroidism)
s/p thyroidectomy
s/p I131 treatment for Graves disease of thyroid cancer
Autoimmune hypoparathyroidism
Cell Lysis
Rhabdomyolysis
Tumor lysis syndrome
Etiologies of HypophosphatemiaEtiologies of HypophosphatemiaDecreased GI AbsorptionDecreased GI Absorption
Decreased dietary intake (rare in isolation)Decreased dietary intake (rare in isolation)Diarrhea / Malabsorption Diarrhea / Malabsorption Phosphate binders (calcium acetate, Al & Mg containing antacids)Phosphate binders (calcium acetate, Al & Mg containing antacids)
Decreased Bone Resorption / Increased Bone Mineralization Decreased Bone Resorption / Increased Bone Mineralization Vitamin D deficiency / low calcitriolVitamin D deficiency / low calcitriolHungry bones syndromeHungry bones syndromeOsteoblastic metastasesOsteoblastic metastases
Increased Urinary ExcretionIncreased Urinary ExcretionElevated PTH (as in primary hyperparathyroidism)Elevated PTH (as in primary hyperparathyroidism)Vitamin D deficiency / low calcitriolVitamin D deficiency / low calcitriolFanconi syndromeFanconi syndrome
Internal Redistribution (due to acute stimulation of glycolysis)Internal Redistribution (due to acute stimulation of glycolysis)Refeeding syndrome (seen in starvation, anorexia, and alcholism)Refeeding syndrome (seen in starvation, anorexia, and alcholism)During treatment for DKADuring treatment for DKA
Case 1Case 1
Mrs. T is a 59 year old woman with a past medical history Mrs. T is a 59 year old woman with a past medical history significant for hypertension who comes for a routine clinic visit. significant for hypertension who comes for a routine clinic visit. She initially states that she has no symptomatic complaints, She initially states that she has no symptomatic complaints, but later in the interview describes chronic fatigue and a mildly but later in the interview describes chronic fatigue and a mildly depressed mood. Her exam is unremarkable. Labs are as depressed mood. Her exam is unremarkable. Labs are as follows:follows:
Calcium (total) – 11.9 mg/dL Calcium (total) – 11.9 mg/dL (normal ~ 8.5-10.2 mg/dL)(normal ~ 8.5-10.2 mg/dL)Phosphate – 1.8 mg/dL Phosphate – 1.8 mg/dL (normal ~ 2.0-4.3 mg/dL)(normal ~ 2.0-4.3 mg/dL)Albumin – 3.8 g/dL Albumin – 3.8 g/dL (normal ~ 3.5-5.0 g/dL)(normal ~ 3.5-5.0 g/dL)PTH – 124 pg/mL PTH – 124 pg/mL (normal ~ 10-60 pg/mL)(normal ~ 10-60 pg/mL)Creatinine – 1.2 mg/dLCreatinine – 1.2 mg/dL
Case 2Case 2Mr. G is a 40 year old man with a history of alcoholism. He had not seen a Mr. G is a 40 year old man with a history of alcoholism. He had not seen a doctor for 15 years before police brought him to the ER after finding him doctor for 15 years before police brought him to the ER after finding him confused and disheveled behind a local convenience store. In the ER, he confused and disheveled behind a local convenience store. In the ER, he was thought to be confused simply due to intoxication, but was admitted for was thought to be confused simply due to intoxication, but was admitted for mild alcoholic hepatitis and marked malnutrition. His mental status cleared mild alcoholic hepatitis and marked malnutrition. His mental status cleared up about 8 hours after admission. During morning rounds on hospital day up about 8 hours after admission. During morning rounds on hospital day #2, he complained of feeling fatigued and weak. Later that day, the nurses #2, he complained of feeling fatigued and weak. Later that day, the nurses find him seizing. The seizures stop with low dose IV diazepam. Stat labs find him seizing. The seizures stop with low dose IV diazepam. Stat labs are sent:are sent:
Sodium – 136 meq/LSodium – 136 meq/LPotassium – 3.2 meq/LPotassium – 3.2 meq/LCalcium (total) – 6.8 mg/dL Calcium (total) – 6.8 mg/dL (normal ~ 8.5-10.2 mg/dL)(normal ~ 8.5-10.2 mg/dL)Phosphate – 0.7 mg/dLPhosphate – 0.7 mg/dL (normal ~ 2.0-4.3 mg/dL)(normal ~ 2.0-4.3 mg/dL)Albumin – 1.8 g/dLAlbumin – 1.8 g/dL (normal ~ 3.5-5.0 g/dL)(normal ~ 3.5-5.0 g/dL)Creatinine – 1.3 mg/dLCreatinine – 1.3 mg/dLCK – 3500 U/LCK – 3500 U/L
Case 3Case 3Mr. H is a 74 year old man with a past history significant for Mr. H is a 74 year old man with a past history significant for hypertension and COPD from smoking 2 packs per day for the hypertension and COPD from smoking 2 packs per day for the last 40 years. He presented to an urgent pulmonary clinic last 40 years. He presented to an urgent pulmonary clinic appointment with 2 months of increased cough and 5 days of appointment with 2 months of increased cough and 5 days of “mild” hemoptysis. Upon further obtaining further history, he “mild” hemoptysis. Upon further obtaining further history, he reports feeling fatigued, nauseous, and chronically thirsty for reports feeling fatigued, nauseous, and chronically thirsty for several weeks. His exam is significant for bilateral rhonchi (no several weeks. His exam is significant for bilateral rhonchi (no change from baseline lung exam) and absent reflexes. Stat change from baseline lung exam) and absent reflexes. Stat labs are ordered from clinic:labs are ordered from clinic:
Sodium – 138 meq/LSodium – 138 meq/L CBC, PT/PTT – WNL CBC, PT/PTT – WNL Potassium – 3.7 meq/LPotassium – 3.7 meq/L PTH - PendingPTH - PendingMagnesium – 1.8 mg/dLMagnesium – 1.8 mg/dL Albumin – 2.2 g/dL Albumin – 2.2 g/dL Calcium (total) – 13.1 mg/dL Calcium (total) – 13.1 mg/dL Phosphate – 1.3 mg/dLPhosphate – 1.3 mg/dLCreatinine – 2.8 mg/dL (baseline creatinine = 1.1)Creatinine – 2.8 mg/dL (baseline creatinine = 1.1)
Case 4Case 4Miss L is a 16 year old woman with no significant past medical Miss L is a 16 year old woman with no significant past medical history, who is brought to the ER by her mother after she noted history, who is brought to the ER by her mother after she noted her to be acting bizarrely for the past several weeks. Thought her to be acting bizarrely for the past several weeks. Thought to be actively psychotic, a psychiatry consult is asked to see to be actively psychotic, a psychiatry consult is asked to see the patient, who recommends checking routine labs:the patient, who recommends checking routine labs:
Sodium – 142 meq/LSodium – 142 meq/L Urine tox. screen – NegativeUrine tox. screen – NegativePotassium – 4.1 meq/LPotassium – 4.1 meq/L Urine pregnancy - NegativeUrine pregnancy - NegativeMagnesium – 2.3 mg/dLMagnesium – 2.3 mg/dLCalcium (total) – 6.9 mg/dLCalcium (total) – 6.9 mg/dLPhosphate – 4.4 mg/dLPhosphate – 4.4 mg/dLAlbumin – 4.2 g/dLAlbumin – 4.2 g/dLCreatinine – 0.8 mg/dLCreatinine – 0.8 mg/dL