Disorders of Calcium and Disorders of Calcium and

Phosphate Metabolism Phosphate Metabolism

utline utline
1. 1. Review of calcium and phosphate Review of calcium and phosphate
metabolism metabolism
2. 2. Abnormalities of calcium balance Abnormalities of calcium balance
3. 3. Abnormalities of phosphate balance Abnormalities of phosphate balance
4. 4. Example cases Example cases
Major Mediators of Calcium and Major Mediators of Calcium and
Phosphate Balance Phosphate Balance
Parathyroid hormone (PTH) Parathyroid hormone (PTH)
Calcitriol (active form of vitamin D Calcitriol (active form of vitamin D
3 3
) )
Role of PTH Role of PTH
Stimulates renal reabsorption of calcium Stimulates renal reabsorption of calcium
nhibits renal reabsorption of phosphate nhibits renal reabsorption of phosphate
Stimulates bone resorption Stimulates bone resorption
nhibits bone formation and mineralization nhibits bone formation and mineralization
Stimulates synthesis of calcitriol Stimulates synthesis of calcitriol
Net effect of PTH Net effect of PTH
serum calcium serum calcium
serum phosphate serum phosphate
Regulation of PTH Regulation of PTH
Low serum [Ca Low serum [Ca
+2 +2
] ] ncreased PTH secretion ncreased PTH secretion
High serum [Ca High serum [Ca
+2 +2
] ] Decreased PTH secretion Decreased PTH secretion
Role of Calcitriol Role of Calcitriol
Stimulates G absorption of both calcium Stimulates G absorption of both calcium
and phosphate and phosphate
Stimulates renal reabsorption of both Stimulates renal reabsorption of both
calcium and phosphate calcium and phosphate
Stimulates bone resorption Stimulates bone resorption
Net effect of calcitriol Net effect of calcitriol
serum calcium serum calcium
serum phosphate serum phosphate
Regulation of Calcitriol Regulation of Calcitriol
verview of Calcium verview of Calcium- -Phosphate Regulation Phosphate Regulation
Different Forms of Calcium Different Forms of Calcium
At 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, Ca mineral hydroxyapatite, Ca
10 10
(P (P
4 4
) )
6 6
(H) (H)
2 2
..
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
]]
Corrected Corrected
= [Ca = [Ca
+2 +2
]]
Measured Measured
+ [ 0.8 (4 + [ 0.8 (4 Albumin) ] Albumin) ]
verview of Biochemical Homeostasis verview of Biochemical Homeostasis
verview of Calcium Balance verview of Calcium Balance
Etiologies of Hypercalcemia Etiologies of Hypercalcemia
ncreased G Absorption ncreased G Absorption
Milk Milk- -alkali syndrome alkali syndrome
Elevated calcitriol Elevated calcitriol
Vitamin D excess Vitamin D excess
Excessive dietary intake Excessive dietary intake
Granuomatous diseases Granuomatous diseases
Elevated PTH Elevated PTH
Hypophosphatemia Hypophosphatemia
ncreased Loss From Bone ncreased Loss From Bone
ncreased net bone resorption ncreased net bone resorption
Elevated PTH Elevated PTH
Hyperparathyroidism Hyperparathyroidism
Malignancy Malignancy
steolytic metastases steolytic metastases
PTHrP secreting tumor PTHrP secreting tumor
ncreased bone turnover ncreased bone turnover
Paget's disease of bone Paget's disease of bone
Hyperthyroidism Hyperthyroidism
Decreased Bone Mineralization
Elevated PTH
Aluminum toxicity
Decreased Urinary Excretion
Thiazide diuretics
Elevated calcitriol
Elevated PTH
Etiologies of Hypocalcemia Etiologies of Hypocalcemia
Decreased G Absorption Decreased G Absorption
Poor dietary intake of calcium Poor dietary intake of calcium
mpaired absorption of calcium mpaired absorption of calcium
Vitamin D deficiency Vitamin D deficiency
Poor dietary intake of vitamin D Poor dietary intake of vitamin D
Malabsorption syndromes Malabsorption syndromes
Decreased conversion of vit. D to calcitriol Decreased conversion of vit. D to calcitriol
Liver failure Liver failure
Renal failure Renal failure
Low PTH Low PTH
Hyperphosphatemia Hyperphosphatemia
Decreased Bone Resorption/ncreased Mineralization Decreased Bone Resorption/ncreased Mineralization
Low PTH (aka hypoparathyroidism) Low PTH (aka hypoparathyroidism)
PTH resistance (aka pseudohypoparathyroidism) PTH resistance (aka pseudohypoparathyroidism)
Vitamin D deficiency / low calcitriol Vitamin D deficiency / low calcitriol
Hungry bones syndrome Hungry bones syndrome
steoblastic metastases steoblastic metastases
ncreased Urinary Excretion
Low PTH
s/p thyroidectomy
s/p
131
treatment
Autoimmune hypoparathyroidism
PTH resistance
Vitamin D deficiency / low calcitriol
verview of Phosphate Balance verview of Phosphate Balance
Etiologies of Hyperphosphatemia Etiologies of Hyperphosphatemia
ncreased G ntake ncreased G ntake
Fleet's Phospho Fleet's Phospho- -Soda Soda
Decreased Urinary Excretion Decreased Urinary Excretion
Renal Failure Renal Failure
Low PTH (hypoparathyroidism) Low PTH (hypoparathyroidism)
s/p thyroidectomy
s/p
131
treatment for Graves disease of thyroid cancer
Autoimmune hypoparathyroidism
Cell Lysis
Rhabdomyolysis
Tumor lysis syndrome
Etiologies of Hypophosphatemia Etiologies of Hypophosphatemia
Decreased G Absorption Decreased G 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 / ncreased Bone Mineralization Decreased Bone Resorption / ncreased Bone Mineralization
Vitamin D deficiency / low calcitriol Vitamin D deficiency / low calcitriol
Hungry bones syndrome Hungry bones syndrome
steoblastic metastases steoblastic metastases
ncreased Urinary Excretion ncreased Urinary Excretion
Elevated PTH (as in primary hyperparathyroidism) Elevated PTH (as in primary hyperparathyroidism)
Vitamin D deficiency / low calcitriol Vitamin D deficiency / low calcitriol
Fanconi syndrome Fanconi syndrome
nternal Redistribution (due to acute stimulation of glycolysis) nternal 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 DKA During treatment for DKA
Case 1 Case 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) Calcium (total) 11.9 mg/dL 11.9 mg/dL (normal ~ 8.5 (normal ~ 8.5- -10.2 mg/dL) 10.2 mg/dL)
Phosphate Phosphate 1.8 mg/dL 1.8 mg/dL (normal ~ 2.0 (normal ~ 2.0- -4.3 mg/dL) 4.3 mg/dL)
Albumin Albumin 3.8 g/dL 3.8 g/dL (normal ~ 3.5 (normal ~ 3.5- -5.0 g/dL) 5.0 g/dL)
PTH PTH 124 pg/mL 124 pg/mL (normal ~ 10 (normal ~ 10- -60 pg/mL) 60 pg/mL)
Creatinine Creatinine 1.2 mg/dL 1.2 mg/dL
Case 2 Case 2
Mr. 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. n the ER, he confused and disheveled behind a local convenience store. n 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 V diazepam. Stat labs find him seizing. The seizures stop with low dose V diazepam. Stat labs
are sent: are sent:
Sodium Sodium 136 meq/L 136 meq/L
Potassium Potassium 3.2 meq/L 3.2 meq/L
Calcium (total) Calcium (total) 6.8 mg/dL 6.8 mg/dL (normal ~ 8.5 (normal ~ 8.5- -10.2 mg/dL) 10.2 mg/dL)
Phosphate Phosphate 0.7 mg/dL 0.7 mg/dL (normal ~ 2.0 (normal ~ 2.0- -4.3 mg/dL) 4.3 mg/dL)
Albumin Albumin 1.8 g/dL 1.8 g/dL (normal ~ 3.5 (normal ~ 3.5- -5.0 g/dL) 5.0 g/dL)
Creatinine Creatinine 1.3 mg/dL 1.3 mg/dL
CK CK 3500 U/L 3500 U/L
Case 3 Case 3
Mr. 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 CPD from smoking 2 packs per day for the hypertension and CPD 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 Sodium 138 meq/L 138 meq/L CBC, PT/PTT CBC, PT/PTT WNL WNL
Potassium Potassium 3.7 meq/L 3.7 meq/L PTH PTH - - Pending Pending
Magnesium Magnesium 1.8 mg/dL 1.8 mg/dL Albumin Albumin 2.2 g/dL 2.2 g/dL
Calcium (total) Calcium (total) 13.1 mg/dL 13.1 mg/dL
Phosphate Phosphate 1.3 mg/dL 1.3 mg/dL
Creatinine Creatinine 2.8 mg/dL (baseline creatinine = 1.1) 2.8 mg/dL (baseline creatinine = 1.1)
Case 4 Case 4
Miss 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 Sodium 142 meq/L 142 meq/L Urine tox. screen Urine tox. screen Negative Negative
Potassium Potassium 4.1 meq/L 4.1 meq/L Urine pregnancy Urine pregnancy - - Negative Negative
Magnesium Magnesium 2.3 mg/dL 2.3 mg/dL
Calcium (total) Calcium (total) 6.9 mg/dL 6.9 mg/dL
Phosphate Phosphate 4.4 mg/dL 4.4 mg/dL
Albumin Albumin 4.2 g/dL 4.2 g/dL
Creatinine Creatinine 0.8 mg/dL 0.8 mg/dL