Calcium and Phosphate Physiology and their roles in CKD Flashcards Preview

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Flashcards in Calcium and Phosphate Physiology and their roles in CKD Deck (48):
1

role of calcium in the body

skeletal development

excitable tissues

action potentials

cardiac and muscle contractility

2

roles of phosphate in the body

bone formation

ATP generation

membrane phospholipids

phosphorylation of second messengers - signaling

glycolysis

DNA/RNA synthesis

unloading O2 (2,3-BPG)

3

When are people appropriately in calcium excess?

during growth phase

pregnant mothers

4

What is the most common state of negative calcium balance?

osteoporosis - bone loss

5

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

primarily regulates gut mineral absorption

main stimulus is PTH

main inhibitor is FGF23

6

calcium vs. phosphate absorption

20% calcium

67-75% phosphate

7

calcium uptake in the gut

channels and binding proteins induced by vitamin D

trans-cellular transport

8

phosphate uptake in the gut

paracellular transport

transcellular transport can be induced by 1, 25 vitamin D

transporter called NaPi2b (sodium/phosphate cotransporter)

linear absorption, nonsaturable function of intake

9

Where is calcium reabsorbed?

proximal tubule (67%)

thick ascending limb - paracellular (25%)

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

10

What diseases impair calcium reabsorption?

mutations in ROMK and NKCC channels in the thick ascending limb

mutations of the calcium receptor

11

calcium sensing receptor

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

12

How does defects in the calcium receptor lead to polyuria?

calcium sensor activation stimulates calciuria

inactivates the ROMK channel as a result of activation

effectively impairs the NKCC channel

13

phosphate reabsorption in the kidneys

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

14

What ion is the collecting duct impermeable to?

chloride

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

15

What is the primary regulator of calcium reabsorption?

PHT - parathyroid hormone

job is to increase the ionized calcium concentration

16

What is the primary stimulus for PTH release?

concentration of ionized calcium in the blood

picked up by calcium receptors

17

functions of PTH

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

18

How does PTH lead to decreased phosphate reabsorption?

decrease expression of NAPi2a anc NAPi2c in the proxmial tubule

19

How does PTH increase calcium reabsorption?

stimulates TRPV5 calcium transport in the distal tubule

20

What stimulates FGF23 expression?

increased phosphate intake

increased 1,25 D levels

serum phosphate may not be the primary stimulant

21

What cells make FGF23?

osteocytes

22

What cells make PTH?

chief cells int he parathyroids

23

functions of FGF23

main effect is to lower serum phosphate

stimulates phosphaturia (decreased reabsorption)

blocks the activation of 25D to 1,25D

stimulates CYP24

inhibits PTH

24

What are the functions of 1,25D

increased gut Ca absorption

increased gut phosphate absorption

feedback inhibition to suppress PTH

increased FGF23 production

stimulates 24-hydroxylase

25

What is the metablism of vitamin D?

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

26

Where is aldosterone released from?

zona glomerulosa of the adrenal cortex

27

primary hyperparathyroidism

caused by benign tumor that continuously produces PTH

increased calcium

decreased phosphate

increased fracture risk

increased urine calcium

risk for stones

28

How does increased PTH increase urine calcium?

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

29

How does increased PTH lead to kidney stones?

high filtered calcium and inproper reabsorption leads to prediliction for stones

30

What are the effects of primary hypothyroidism?

decreased calcium

increased phosphate

tetany - due to lack of calcium

31

What is the normal range of PTH?

10-65 pg/m

 

32

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

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

33

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

no, should be much higher

suggests hypoparathyrodism

34

What is the normal range of calcium in the blood?

8.5-10.5 mg/dL

35

What is the normal range of phosphate in the blood?

2.5-4.5 mg/dL

36

Rickets syndrome

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

37

PTH related peptide

drives hypercalcemia

comonly secreted by cancer cells

38

organs involved in calcium/phosphate regulation

parathyroid

bone

gut

kidney

39

What is the normal fractional excretion of calcium?

about 2%

40

What are the phosphate/calcium regulator features in CKD?

low 1,25D

variable 25D

high PTH

high FGF23

low klotho expression

low normal calcium

high normal phosphate

41

NPT2b (NaPi2b)

active transport of phosphate in the guy

less important than passive phosphate transport

human deletion has no phosphate phenotype

42

NPT2a, NPT2c (NaPi2a,c)

in PCT

NPT2a mutations - Fanconi syndrome

NPT2c mutations - HHRH syndrome

relative roles vary in mammalian species

43

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

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

44

What is the key finding in HHRH?

hypophosphatemia that is not FGF23 or PTH mediated

NaP12c deficiency

45

What is the key finding in tumoral calcinosis?

hyperphosphatemia with low FGF23 and low PTH

FGF23 deficiency

46

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

hypercalcemia with non-suppressed PTH = primary hyperthyroidism

47

What are the key findings in autosomal dominant hypoparathyroidism?

hypocalcemia + low PTH

48

Key finding in Vitamin D - dependent rickets type I

hypocalcemia and hypophosphatemia with secondary hyperparathyroidism