Calcium & Phosphorous Homeostasis

Question 1

calcium - roles

Answer 1

*myocardial & smooth muscle contraction
*blood coagulation
*intracellular messaging
*structural

Question 2

phosphate - roles

Answer 2

*energy production
*protein production
*skeletal/structural

Question 3

calcium distribution

Answer 3

99% in bone
1% intracellular
0.10% extracellular

Question 4

renal calcium reabsorption

Answer 4

1) proximal tubule: calcium reabsorption is passive, linked to sodium reabsorption
2) sodium absorbed in thick ascending loop of henle by furosemide-sensitive NKCC transporter with backleak of K+ → leads to increased paracellular calcium reabsorption
3) DCT: transcellular calcium reabsorption in the presence of PTH and calcitriol

Question 5

effects of thiazide diuretics on calcium

Answer 5

*cause sodium-wasting distally that is compensated for by proximal sodium uptake
*leads to INCREASED CALCIUM REABSORPTION and HYPOCALCIURIA (decreased calcium excretion), and rarely hypercalcemia

Question 6

effects of furosemide (loop diuretics) on calcium

Answer 6

*Loops LOSE calcium
*block the NKCC transporter & results in loss of electrochemical gradient
*results in DECREASED CALCIUM REABSORPTION and HYPERCALCIURIA (increased excretion of calcium); hypocalcemia

Question 7

furosemide (loop diuretics) - effects on urine calcium and serum calcium

Answer 7

*urine calcium: INCREASED
*serum calcium: decreased
*used to be used as a treatment for hypercalcemia (i.e. lowers serum calcium)

Question 8

thiazide diuretics - effects on urine calcium and serum calcium

Answer 8

*serum calcium: increased
*urine calcium: decreased
*may cause hypercalcemia (i.e. raises serum calcium)

Question 9

phosphate distribution

Answer 9

86% in bone
14% intracellular
.03% extracellular

Question 10

total serum calcium =

Answer 10

= protein-bound calcium + ionized calcium + complexed calcium

50% ionized
40% protein-bound
10% complexed

note - we are really interested in the ionized calcium

Question 11

factors affecting serum calcium

Answer 11

*albumin binding
*other protein binding
*pH

Question 12

total serum calcium vs. ionized calcium

Answer 12

*total serum calcium:
-part of basic metabolic panel
-inexpensive to test
-includes ionized calcium, complexed calcium, bound calcium
-low serum albumin affects total calcium but not ionized calcium

*ionized calcium:
-separate test
-collected in a different tube
-more expensive
-the “important” calcium level

Question 13

corrected serum calcium =

Answer 13

[(4 - serum albumin) x 0.8] + serum calcium

Question 14

hypocalcemia - clinical manifestations

Answer 14

*INCREASED neuromuscular excitability / tetany
1. Chvostek’s sign - tapping on the facial nerve results in contraction of ipsilateral facial muscles
2. tetany - diffuse involuntary muscle contractions
3. Trousseau’s sign - carpal-pedal spasm occurring with inflation of blood pressure cuff
4. PROLONGED QT interval

Question 15

hypercalcemia - clinical manifestations

Answer 15

“stones, bones, moans, and groans”:
*nephrolithiasis
*bone pain
*lethargy/anorexia
*constipation

Question 16

vitamin D metabolism

Answer 16

1. sunlight converts 7-dehydrocholesterol → cholecalciferol (vitamin D3)
2. liver converts cholecalciferol → 25-hydroxyvitamin D3 (this is what we MEASURE)
3. kidney converts 25-hydroxyvitamin D3 → 1,25-dihydroxyvitamin D3 (ACTIVE FORM)

Question 17

dietary sources of vitamin D

Answer 17

*concentrated source: liver of cold water fishes (trout, salmon)
*supplementation in milk (vitamin D3)

Question 18

active form of vitamin D

Answer 18

active form = 1,25-dihydroxy Vitamin D

made by conversion in the proximal tubules in the kidneys

Question 19

roles of 1,25-dihydroxy Vitamin D

Answer 19

*increased intestinal calcium & phosphate absorption
*increases calcium & phosphate resorption from bone
*overall: INCREASED SERUM Ca2+ and INCREASED SERUM phosphate

Question 20

rickets - overview

Answer 20

*caused by decreased 1,25 dihydroxy vitamin D
*results in decreased calcium absorption
*decreased calcium available for skeletal growth
*presents at 3-18 months of age

Question 21

rickets - causes

Answer 21

*breast feeding without vitamin D supplementation
*skin that is less able to let UV light penetrate in an environment with decreased sun
*celiac disease
*genetic causes

Question 22

7-dehydrocholesterol

Answer 22

*precursor to vitamin D
*converted in skin by sun to vitamin D3

Question 23

vitamin D3

Answer 23

*aka cholecalciferol
*made in humans (conversion from 7-dehydrocholesterol) or given as a vitamin D supplement in milk

Question 24

25 hydroxy vitamin D

Answer 24

*made from 25-hydroxylation of vitamin D3 (cholecalciferol) in the LIVER
*NOT the most active form
*we measure levels of this in most people to determine vitamin D status

Question 25

1,25 dihydroxy vitamin D

Answer 25

*made in the kidney
*ACTIVE FORM OF VITAMIN D
*if you have kidney failure, you cannot make this
*also called calcitriol
*can be given as vitamin to patients with kidney failure

Question 26

vitamin D2

Answer 26

*aka ergocalciferol
*not produced in humans
*has same efficacy as vitamin D3 as a supplement

Question 27

parathyroid hormone - overview

Answer 27

*released from parathyroid glands in response to hypocalcemia
*effect: increases serum calcium levels by:
1. stimulating osteoclast activity: promotes bone resorption → release of calcium & phosphate into blood
2. increases urinary excretion of phosphate

*overall: increased serum calcium, slightly decreases serum phosphate

Question 28

parathyroid hormone (PTH) - roles

Answer 28

*osteoBLASTS have PTH receptors → stimulate osteoCLAST resorption
*renal effects occur in distal tubule:
-stimulate calcium reabsorption → inreased serum calcium
-stimulates phosphate excretion → decreased serum phosphate

*result: INCREASED SERUM CALCIUM; NORMAL to LOW PHOSPHATE

Question 29

hyperparathyroidism - results

Answer 29

*hypercalcemia (high serum calcium)
*normal or low serum phosphate
*hypercalciuria:
-kidney stones in some individuals
-osteoporosis

Question 30

fibroblast growth factor 23 - overview

Answer 30

*produced by osteocytes in response to high serum phosphate levels
*effect = decreases serum phosphate levels
*decreased proximal tubular phosphate reabsorption → INCREASED EXCRETION OF PHOSPHATE IN URINE
*decreases 1,25 hydroxy vitamin D (calcitriol) production
*decreases PTH secretion

Question 31

calcitonin - overview

Answer 31

*hormone produced by the parafollicular cells of the thyroid
*“tones down” calcium: decreases serum calcium & serum phosphate
*opposes the effect of PTH
*inhibits osteoclast activity in bone
*inhibits tubular reabsorption of calcium & phosphate

Question 32

major problems in chronic kidney failure

Answer 32

1. decreased urinary phosphate excretion (decreased phosphate filtration)
   -results in increased FGF-23 production
   -occurs in stage 3 CKD
2. decreased calcitriol production (due to increased FGF-23 and increase serum phosphate)
   -less calcitriol → increased PTH
3. increased PTH production (due to decreased 1,25 dihydroxy vitamin D & increased serum phosphate)
   -causes bone resorption
4. dysregulation of calcium/phosphate metabolism; results in:
   -decreased bone mineralization (from increased PTH)
   -accelerated vascular calcification (from increased serum phosphate)

Question 33

chronic kidney failure - overview of problems

Answer 33

*decreased phosphate excretion / increased serum phosphate
*increased FGF-23
*decreased 1,25 OH Vit D (calcitriol) / decreased serum calcium
*increased PTH
*increased vascular calcification
*decreased bone mineralization
*increased alkaline phosphatase (bone enzyme)

Question 34

treating chronic kidney failure

Answer 34

1. decrease phosphate in diet
2. remove phosphate with dialysis
3. use phosphate binders with meals