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 balance3.3. Abnormalities of phosphate balanceAbnormalities of phosphate balance4.4. 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 calciumInhibits renal reabsorption of phosphateInhibits renal reabsorption of phosphateStimulates bone resorptionStimulates bone resorptionInhibits bone formation and mineralizationInhibits bone formation and mineralizationStimulates 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 phosphateStimulates renal reabsorption of both Stimulates renal reabsorption of both calcium and phosphatecalcium and phosphateStimulates 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 calcitriolVitamin D excessVitamin D excessExcessive dietary intakeExcessive dietary intakeGranuomatous diseasesGranuomatous diseasesElevated PTHElevated PTHHypophosphatemiaHypophosphatemia

Increased Loss From BoneIncreased Loss From BoneIncreased net bone resorptionIncreased net bone resorptionElevated PTHElevated PTHHyperparathyroidismHyperparathyroidismMalignancyMalignancyOsteolytic metastasesOsteolytic metastasesPTHrP secreting tumorPTHrP secreting tumorIncreased 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 calciumImpaired absorption of calciumImpaired absorption of calcium

Vitamin D deficiencyVitamin D deficiency Poor dietary intake of vitamin DPoor dietary intake of vitamin D

Malabsorption syndromesMalabsorption syndromesDecreased 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 MineralizationLow PTH (aka hypoparathyroidism)Low PTH (aka hypoparathyroidism)PTH resistance (aka pseudohypoparathyroidism)PTH resistance (aka pseudohypoparathyroidism)Vitamin D deficiency / low calcitriolVitamin D deficiency / low calcitriolHungry bones syndromeHungry bones syndromeOsteoblastic 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 IntakeFleet’s Phospho-SodaFleet’s Phospho-Soda

Decreased Urinary ExcretionDecreased Urinary ExcretionRenal FailureRenal FailureLow PTH (hypoparathyroidism)Low PTH (hypoparathyroidism)s/p thyroidectomys/p I131 treatment for Graves disease of thyroid cancerAutoimmune hypoparathyroidism

Cell LysisRhabdomyolysisTumor 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