Disorders of Calcium and Phosphate Metabolism (1)

8/6/2019 Disorders of Calcium and Phosphate Metabolism (1)

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Disorders of Calcium andDisorders of Calcium and

Phosphate MetabolismPhosphate Metabolism

Seminar 3Seminar 3

DRDR DeepaDeepa VV


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OutlineOutline

1.1. Review of calcium and phosphateReview of calcium and phosphate

metabolismmetabolism

2.2. Abnormalities of calcium balanceAbnormalities of calcium balance3.3. Abnormalities of phosphate balanceAbnormalities of phosphate balance

4.4. Example casesExample cases


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Major Mediators of Calcium andMajor Mediators of Calcium and

Phosphate BalancePhosphate Balance

Parathyroid hormone (PTH)Parathyroid hormone (PTH)

Calcitriol (active form of vitamin DCalcitriol (active form of vitamin D33))


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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 resorptionInhibits bone formation and mineralizationInhibits bone formation and mineralization

Stimulates synthesis of calcitriolStimulates synthesis of calcitriol

Net effect of PTHNet effect of PTH serum calcium serum calcium

serum phosphate serum phosphate


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Regulation of PTHRegulation of PTH

Low serum [CaLow serum [Ca+2+2]] Increased PTH secretionIncreased PTH secretion

High serum [CaHigh serum [Ca+2+2]] Decreased PTH secretionDecreased PTH secretion


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Role of CalcitriolRole of Calcitriol

Stimulates GI absorption of both calciumStimulates GI absorption of both calcium

and phosphateand phosphate

Stimulates renal reabsorption of bothStimulates renal reabsorption of bothcalcium and phosphatecalcium and phosphate

Stimulates bone resorptionStimulates bone resorption

Net effect of calcitriolNet effect of calcitriol serum calcium serum calcium

serum phosphate serum phosphate


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Regulation of CalcitriolRegulation of Calcitriol


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Overview of CalciumOverview of Calcium--Phosphate RegulationPhosphate Regulation


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Different Forms of CalciumDifferent Forms of Calcium

At any one time, most of the calcium in the body exists as theAt any one time, most of the calcium in the body exists as themineral 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 statesTo estimate the physiologic levels of ionized calcium in statesof hypoalbuminemia:of hypoalbuminemia:

[Ca[Ca+2+2]]CorrectedCorrected = [Ca= [Ca+2+2]]MeasuredMeasured + [ 0.8 (4+ [ 0.8 (4 Albumin) ]Albumin) ]


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Overview of Biochemical HomeostasisOverview of Biochemical Homeostasis


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Overview of Calcium BalanceOverview of Calcium Balance


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Etiologies of HypercalcemiaEtiologies of Hypercalcemia

Increased GI AbsorptionIncreased GI Absorption

MilkMilk--alkali syndromealkali syndrome

Elevated calcitriolElevated calcitriol

Vitamin D excessVitamin D excess

Excessive dietary intakeExcessive dietary intake

Granuomatous diseasesGranuomatous diseases

Elevated PTHElevated PTH

HypophosphatemiaHypophosphatemia

Increased Loss From BoneIncreased Loss From Bone

Increased net bone resorptionIncreased net bone resorption

Elevated PTHElevated PTH

HyperparathyroidismHyperparathyroidism

MalignancyMalignancy

Osteolytic metastasesOsteolytic metastases

PTHrP secreting tumorPTHrP secreting tumor

Increased bone turnoverIncreased bone turnover

Pagets disease of bonePagets disease of bone

HyperthyroidismHyperthyroidism

Decreased Bone Mineralization

Elevated PTH

Aluminum toxicity

Decreased Urinary Excretion

Thiazide diuretics

Elevated calcitriol

Elevated PTH


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Etiologies of HypocalcemiaEtiologies of Hypocalcemia

Decreased 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

MalabsorptionMalabsorption syndromessyndromes

Decreased conversion ofDecreased conversion of vitvit. D to. D to calcitriolcalcitriol

Liver failureLiver failure

Renal failureRenal failure

Low PTHLow PTH

HyperphosphatemiaHyperphosphatemia

Decreased BoneDecreased Bone ResorptionResorption/Increased Mineralization/Increased MineralizationLow PTH (akaLow PTH (aka hypoparathyroidismhypoparathyroidism))

PTH resistance ( pseudoPTH resistance ( pseudo hypoparathyroidismhypoparathyroidism))

Vitamin D deficiency / lowVitamin D deficiency / low calcitriolcalcitriol

Hungry bones syndromeHungry bones syndrome

OsteoblasticOsteoblastic metastasesmetastases

Increased Urinary Excretion

Low PTH

s/p thyroidectomy

s/p I131 treatment

Autoimmune hypoparathyroidism

PTH resistance

Vitamin D deficiency / low calcitriol


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Overview of Phosphate BalanceOverview of Phosphate Balance


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Etiologies of HyperphosphatemiaEtiologies of Hyperphosphatemia

Increased GI IntakeIncreased GI Intake

Fleets PhosphoFleets Phospho--SodaSoda

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


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Etiologies of HypophosphatemiaEtiologies of HypophosphatemiaDecreased GI AbsorptionDecreased GI Absorption

Decreased dietary intake (rare in isolation)Decreased dietary intake (rare in isolation)

Diarrhea / MalabsorptionDiarrhea / Malabsorption

Phosphate binders (calcium acetate, Al & Mg containing antacids)Phosphate binders (calcium acetate, Al & Mg containing antacids)

Decreased Bone Resorption / Increased Bone MineralizationDecreased Bone Resorption / Increased Bone Mineralization

Vitamin D deficiency / low calcitriolVitamin D deficiency / low calcitriolHungry bones syndromeHungry bones syndrome

Osteoblastic metastasesOsteoblastic metastases

Increased Urinary ExcretionIncreased Urinary Excretion

Elevated PTH (as in primary hyperparathyroidism)Elevated PTH (as in primary hyperparathyroidism)

Vitamin D deficiency / low calcitriolVitamin D deficiency / low calcitriol

Fanconi 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


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Case 1Case 1

Mrs. T is a 59 year old woman with a past medical historyMrs. T is a 59 year old woman with a past medical historysignificant 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 mildlybut later in the interview describes chronic fatigue and a mildly

depressed mood. Her exam is unremarkable. Labs are asdepressed mood. Her exam is unremarkable. Labs are asfollows:follows:

Calcium (total)Calcium (total) 11.9 mg/dL11.9 mg/dL (normal ~ 8.5(normal ~ 8.5--10.2 mg/dL)10.2 mg/dL)

PhosphatePhosphate 1.8 mg/dL1.8 mg/dL (normal ~ 2.0(normal ~ 2.0--4.3 mg/dL)4.3 mg/dL)AlbuminAlbumin 3.8 g/dL3.8 g/dL (normal ~ 3.5(normal ~ 3.5--5.0 g/dL)5.0 g/dL)

PTHPTH 124 pg/mL124 pg/mL (normal ~ 10(normal ~ 10--60 pg/mL)60 pg/mL)

CreatinineCreatinine 1.2 mg/dL1.2 mg/dL


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Case 2Case 2

Mr. G is a 40 year old man with a history of alcoholism. He had not seen aMr. G is a 40 year old man with a history of alcoholism. He had not seen adoctor for 15 years before police brought him to the ER after finding himdoctor for 15 years before police brought him to the ER after finding himconfused and disheveled behind a local convenience store. In the ER, heconfused and disheveled behind a local convenience store. In the ER, hewas thought to be confused simply due to intoxication, but was admitted forwas thought to be confused simply due to intoxication, but was admitted formild alcoholic hepatitis and marked malnutrition. His mental status clearedmild alcoholic hepatitis and marked malnutrition. His mental status clearedup about 8 hours after admission. During morning rounds on hospital dayup 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 nursesfind him seizing. The seizures stop with low dose IV diazepam. Stat labsfind him seizing. The seizures stop with low dose IV diazepam. Stat labsare sent:are sent:

SodiumSodium 136 meq/L136 meq/L

PotassiumPotassium 3.2 meq/L3.2 meq/L

Calcium (total)Calcium (total) 6.8 mg/dL6.8 mg/dL (normal ~ 8.5(normal ~ 8.5--10.2 mg/dL)10.2 mg/dL)PhosphatePhosphate 0.7 mg/dL0.7 mg/dL (normal ~ 2.0(normal ~ 2.0--4.3 mg/dL)4.3 mg/dL)

AlbuminAlbumin 1.8 g/dL1.8 g/dL (normal ~ 3.5(normal ~ 3.5--5.0 g/dL)5.0 g/dL)


CKCK 3500 U/L3500 U/L


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Case 3Case 3

Mr. H is a 74 year old man with a past history significant forMr. H is a 74 year old man with a past history significant forhypertension and COPD from smoking 2 packs per day for thehypertension and COPD from smoking 2 packs per day for thelast 40 years. He presented to an urgent pulmonary cliniclast 40 years. He presented to an urgent pulmonary clinicappointment with 2 months of increased cough and 5 days ofappointment with 2 months of increased cough and 5 days ofmild hemoptysis. Upon further obtaining further history, hemild hemoptysis. Upon further obtaining further history, hereports feeling fatigued, nauseous, and chronically thirsty forreports feeling fatigued, nauseous, and chronically thirsty for

several weeks. His exam is significant for bilateral rhonchi (noseveral weeks. His exam is significant for bilateral rhonchi (nochange from baseline lung exam) and absent reflexes. Statchange from baseline lung exam) and absent reflexes. Statlabs are ordered from clinic:labs are ordered from clinic:

SodiumSodium 138 meq/L138 meq/L CBC, PT/PTTCBC, PT/PTT WNLWNL

PotassiumPotassium 3.7 meq/L3.7 meq/L PTHPTH -- PendingPendingMagnesiumMagnesium 1.8 mg/dL1.8 mg/dL AlbuminAlbumin 2.2 g/dL2.2 g/dL

Calcium (total)Calcium (total) 13.1 mg/dL13.1 mg/dL

PhosphatePhosphate 1.3 mg/dL1.3 mg/dL

CreatinineCreatinine 2.8 mg/dL (baseline creatinine = 1.1)2.8 mg/dL (baseline creatinine = 1.1)


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Case 4Case 4

Miss L is a 16 year old woman with no significant past medicalMiss L is a 16 year old woman with no significant past medicalhistory, who is brought to the ER by her mother after she notedhistory, who is brought to the ER by her mother after she notedher to be acting bizarrely for the past several weeks. Thoughther to be acting bizarrely for the past several weeks. Thoughtto be actively psychotic, a psychiatry consult is asked to seeto be actively psychotic, a psychiatry consult is asked to seethe patient, who recommends checking routine labs:the patient, who recommends checking routine labs:

SodiumSodium 142 meq/L142 meq/L Urine tox. screenUrine tox. screen NegativeNegative

PotassiumPotassium 4.1 meq/L4.1 meq/L Urine pregnancyUrine pregnancy -- NegativeNegative

MagnesiumMagnesium 2.3 mg/dL2.3 mg/dL

Calcium (total)Calcium (total) 6.9 mg/dL6.9 mg/dLPhosphatePhosphate 4.4 mg/dL4.4 mg/dL

AlbuminAlbumin 4.2 g/dL4.2 g/dL


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Disorders of Calcium and Phosphate Metabolism (1)