Calcium and Phosphate Physiology and their roles in CKD

Question 1

role of calcium in the body

Answer 1

skeletal development

excitable tissues

action potentials

cardiac and muscle contractility

Question 2

roles of phosphate in the body

Answer 2

bone formation

ATP generation

membrane phospholipids

phosphorylation of second messengers - signaling

glycolysis

DNA/RNA synthesis

unloading O2 (2,3-BPG)

Question 3

When are people appropriately in calcium excess?

Answer 3

during growth phase

pregnant mothers

Question 4

What is the most common state of negative calcium balance?

Answer 4

osteoporosis - bone loss

Question 5

1,25-dihydroxyvitamin D (main role, stimulus, inhibitor)

Answer 5

primarily regulates gut mineral absorption

main stimulus is PTH

main inhibitor is FGF23

Question 6

calcium vs. phosphate absorption

Answer 6

20% calcium

67-75% phosphate

Question 7

calcium uptake in the gut

Answer 7

channels and binding proteins induced by vitamin D

trans-cellular transport

Question 8

phosphate uptake in the gut

Answer 8

paracellular transport

transcellular transport can be induced by 1, 25 vitamin D

transporter called NaPi2b (sodium/phosphate cotransporter)

linear absorption, nonsaturable function of intake

Question 9

Where is calcium reabsorbed?

Answer 9

proximal tubule (67%)

thick ascending limb - paracellular (25%)

distal convoluted tuble - TRPV5 channel, transcellular and vitamin D dependent (8%)

Question 10

What diseases impair calcium reabsorption?

Answer 10

mutations in ROMK and NKCC channels in the thick ascending limb

mutations of the calcium receptor

Question 11

calcium sensing receptor

Answer 11

transmembrane protein in the basolateral membrane of the tAL

extracellular domain that binds calcium - constantly senses the calcium concentration

when many sites are bound, inteprets as high amounts of calcium

a way for the cell to contribute to regulating serum calcium

Question 12

How does defects in the calcium receptor lead to polyuria?

Answer 12

calcium sensor activation stimulates calciuria

inactivates the ROMK channel as a result of activation

effectively impairs the NKCC channel

Question 13

phosphate reabsorption in the kidneys

Answer 13

NAPi2a and NAPi2c in the proximal tubule

when presence, phosphate is absorbed through the cells

otherwise, it is paracellular transport

if phosphate gets past the proximal tubule, then will be excreted

10-15% fractional excretion

Question 14

What ion is the collecting duct impermeable to?

Answer 14

chloride

this allows influx of sodium to promote efflux of potassium and hydrogen ions

Question 15

What is the primary regulator of calcium reabsorption?

Answer 15

PHT - parathyroid hormone

job is to increase the ionized calcium concentration

Question 16

What is the primary stimulus for PTH release?

Answer 16

concentration of ionized calcium in the blood

picked up by calcium receptors

Question 17

functions of PTH

Answer 17

primarily regulates ionized calcium

raises serum calcium

increase bone resorption of calcium

increase calcium reabsorption in the kidney

stimulates conversion of 25D into 1,25D (activates vitamin D)increased absorption in GI tract

decreased phosphate reabsorption (phosphaturia)

inhibits CYP24

inhibits calciuria

Question 18

How does PTH lead to decreased phosphate reabsorption?

Answer 18

decrease expression of NAPi2a anc NAPi2c in the proxmial tubule

Question 19

How does PTH increase calcium reabsorption?

Answer 19

stimulates TRPV5 calcium transport in the distal tubule

Question 20

What stimulates FGF23 expression?

Answer 20

increased phosphate intake

increased 1,25 D levels

serum phosphate may not be the primary stimulant

Question 21

What cells make FGF23?

Answer 21

osteocytes

Question 22

What cells make PTH?

Answer 22

chief cells int he parathyroids

Question 23

functions of FGF23

Answer 23

main effect is to lower serum phosphate

stimulates phosphaturia (decreased reabsorption)

blocks the activation of 25D to 1,25D

stimulates CYP24

inhibits PTH

Question 24

What are the functions of 1,25D

Answer 24

increased gut Ca absorption

increased gut phosphate absorption

feedback inhibition to suppress PTH

increased FGF23 production

stimulates 24-hydroxylase

Question 25

What is the metablism of vitamin D?

Answer 25

vitamin D2/3 -\> 25 vitamin D (liver) -\> 1,25 vitamin D (kidney)

Question 26

Where is aldosterone released from?

Answer 26

zona glomerulosa of the adrenal cortex

Question 27

primary hyperparathyroidism

Answer 27

caused by benign tumor that continuously produces PTH increased calcium decreased phosphate increased fracture risk increased urine calcium risk for stones

Question 28

How does increased PTH increase urine calcium?

Answer 28

effect of ability of tubuels to reabsorb calcium is overwhelmed by the high concentration of calcium in the blood higher filtered load leads to higher concentrations in the urine

Question 29

How does increased PTH lead to kidney stones?

Answer 29

high filtered calcium and inproper reabsorption leads to prediliction for stones

Question 30

What are the effects of primary hypothyroidism?

Answer 30

decreased calcium increased phosphate tetany - due to lack of calcium

Question 31

What is the normal range of PTH?

Answer 31

10-65 pg/m

Question 32

Does a PTH level of 60 pg/mL rule out primary parathyroidism?

Answer 32

a PTH of 60 in the setting of hypercalcemia does not rule out primary hyper parathyroidism - should be 0!

Question 33

Is a PTH level of 30 pg/mL in hypocalcemia normal?

Answer 33

no, should be much higher suggests hypoparathyrodism

Question 34

What is the normal range of calcium in the blood?

Answer 34

8.5-10.5 mg/dL

Question 35

What is the normal range of phosphate in the blood?

Answer 35

2.5-4.5 mg/dL

Question 36

Rickets syndrome

Answer 36

bone weakness due to either deficiency in vitamin D, low blood calcium, or low blood phosphate

Question 37

PTH related peptide

Answer 37

drives hypercalcemia comonly secreted by cancer cells

Question 38

organs involved in calcium/phosphate regulation

Answer 38

parathyroid bone gut kidney

Question 39

What is the normal fractional excretion of calcium?

Answer 39

about 2%

Question 40

What are the phosphate/calcium regulator features in CKD?

Answer 40

low 1,25D variable 25D high PTH high FGF23 low klotho expression low normal calcium high normal phosphate

Question 41

NPT2b (NaPi2b)

Answer 41

active transport of phosphate in the guy less important than passive phosphate transport human deletion has no phosphate phenotype

Question 42

NPT2a, NPT2c (NaPi2a,c)

Answer 42

in PCT NPT2a mutations - Fanconi syndrome NPT2c mutations - HHRH syndrome relative roles vary in mammalian species

Question 43

What is the time course of a disordered mineral metabolism in CDK?

Answer 43

1) increased FGF23 is the earliest alteration in mineral metabolism 2) gradually increasing FGF23 levels cause early decline in 1,25D levels 3) this frees PTH from feedback inhibition, leading to secondary hyperparathyroidism 4) all these changes occur long before increases in serum P levels are evident

Question 44

What is the key finding in HHRH?

Answer 44

hypophosphatemia that is not FGF23 or PTH mediated NaP12c deficiency

Question 45

What is the key finding in tumoral calcinosis?

Answer 45

hyperphosphatemia with low FGF23 and low PTH FGF23 deficiency

Question 46

What is the key finding in familial hypocalciuric hypercalcemia (FHH)?

Answer 46

hypercalcemia with non-suppressed PTH = primary hyperthyroidism

Question 47

What are the key findings in autosomal dominant hypoparathyroidism?

Answer 47

hypocalcemia + low PTH

Question 48

Key finding in Vitamin D - dependent rickets type I

Answer 48

hypocalcemia and hypophosphatemia with secondary hyperparathyroidism