Calcium-Phosphate Metabolism and Derrangment Flashcards Preview

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Flashcards in Calcium-Phosphate Metabolism and Derrangment Deck (49)
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1

About how much Ca2+ input is their per day?
• what are the main modes of output?

Input:
1000 mg

Output:
• Fecal Loss - 700 mg
• Renal Excretion - 300 mg

2

What is the normal range for serum Calcium?
• ionized Ca2+ component?

Serum Calcium conc. = 8.7 to 10.2 mg/dL
Ionized calcium component = 4.8 to 5.2 mg/dL

3

What is the distribution of most Ca2+ that is not sequested in the bone?
• what is the active component?

1% not sequestered in Bone

MOST = intracellular

Extracellular:
• 45% protein Bound
• 55% non-protein bound
-------> 45% Free Ionized*****ACTIVE******
-------> 10% complexed

4

How does calcium penetrate into an enterocyte from the GI tract?
•how does it exit the basolateral side?

• TRPV6 Channel used by Ca2+ from the brush border membrane along a the electrochrmical gradient.

Basolateral Side:
• Pumped OUT (uphill) by ATP powered Ca2+ pump (aka Ca2+ ATPase)

5

Compare the way that calcium leaves the cell on the basolateral side in times of normal intracytoplasmic calcium levels vs. when intracytoplasmic Ca2+ is super elevated.

Normal Ca2+ exit through the Basolateral Side:
• ATP powered Ca2+ ATPase pump pushes Calcium out into the blood

Elevated intracytoplasmic Ca2+ levels:
• Leaves the cell using the Na+/Ca2+ exchanger

6

What regulates the passive influx and efflux of Ca2+?
• what does this do?

• Passive Ca2+ influx and efflux are regulated by Calcitriol

• Calcitriol Binds the Vitamin D receptor

7

What parts of the filtration apparatus in the kidney play an important role in fine tuning renal excretion of Ca2+?

Distal Convoluted Tubule (DCT)
Connecting Tubule (CNT)

8

What Ca2+ channels/transporters are present on the Apical and Basolateral Membrane of cells in the DCT and Connecting Tubule?

Apical Membrane:
• TRPV5 => Ca2+ channel

Basolateral:
• NCX1 - Na+/Ca2+ exchanger on the basolateral side of the cell

• PMCA1 - ATP driven Ca2+ transporter

9

What role would increased activity of PTH-R and and NKA play in Ca2+ transport in the Kidney?

PTH-R:
• PTH stimulates the Receptor on the BASOLATERAL side of the DCT/CNT and stimulates activity of TRPV5.

NKA (sodium-potassium ATPase)
• Increased activity raises intracellular Na+ levels which means more Ca2+ export

10

What does Klotho do?

1. Acts on the Basolateral membrane to upregulate NKA activity and thus NCX1 activity.

2. Acts on Apical Membrane to increase TPRV5 activity

11

What role does BK2 play in Ca2+ import?
• which side of the cell is it found on?

BK2
• Stimulated by TK (Tissue Kallikrien) to activate TRPV5

12

What are the steps in suppression of PTH?

HIGH CALCIUM in serum =>
1. CaSR (calcium-sensing receptor) = GPCR

2. Stimulation = release of Phospholipase C leading to increased IP3

3. this INHIBITS PTH synthesis and secretion

13

What happens in the parathyroid cells when serum calcium is low?

LOW CALCIUM in serum =>
1. Inhibition of intracellular signaling

2. Increased PTH synthesis and secretion

14

What is the distribution of phosphorus in the body?

Bone - 85%
Soft Tissue - 14%
Extracellular Fluid - 1%

15

What are the main forms of Phosphorus in the plasma?
• ratio at physiological pH?

HPO4-- and H2PO4- are present in a 4:1 ratio at pH 7.4

16

What is the amount total phosphorus taken in per day?
• how much is absorbed at different levels of intake?

Phosphorus per day:
• 800 - 1500 mg

How much absorbed:
• at more than 10 mg/kg/day 70% absorbed
• at less than 10 mg/kg/day 80-90% absorbed

***Important to recognize that we are good at reabsorbing phosphorus because we need it for everything****

17

What are the normal serum levels of phosphorus?

2.5 to 4.5 mg/dL in people with a GFR greater than 25 mL/min

18

How much of dietary phosphorus is typically elminated?
• when do you see hyperphosphatemia?

typically 5-15% is eliminated daily

**Only time you see too much phosphate in serum is with severe renal insufficiency (GFR less than 25 mL/min**

19

What is the main method of phosphate loss (for someone with a daily intake of 1400mg)?
• in what ways is this different than Ca2+ elimination?

Renal Excretion - 900 mg
Fecal Excretion - 500 mg

***Most Ca2+ is excreted in the Feces while most PO4 is excreted in the urine***

20

What is the difference in the S1, S2, S3 portions of the proximal convoluted tubule as far as Phosphate Transporters go?

S1/S2 - Apical:
• 3Na+/HPO4- co-transporter
• 2Na+/HPO4- co-transporter
• 2Na+/H2PO4- co-transporter

S3 - Apical:
• 3Na+/HPO4- co-transporter
• 2Na+/H2PO4 co-transporter

BOTH BASOLATERAL:
• H2PO4-/HPO4- (unknown) channel
• NKA = DRIVES THE Na+ gradient

21

Where is most PO4 reabsorbed in the nephron?

Proximal Tubule = most common sight of reabsorption

22

T or F: tubular reabsorption of phosphate is saturable

True, look at diagrams to see a graph of this

23

How do we know that phosphate reabsorption is saturable?

• it is excreted LINEARLY with PLASMA concentration and depends on GFR

***if we compare it to inulin it will have the same slope just shifted down to account for the set amount of reabsorption that's occuring***

24

T or F: Vitamin D is an important hormone needed to regulate Ca2+ and Cl- homeostasis.

FALSE, Vitamin D is a PROHORMONE needed to regulate Ca2+ and PHOSPHORUS homeostasis

25

What are the steps in the endogenous formation of Vitamin D3?

Cholesterol => 7-dehydrocholesterol + Sunlight/UVB => Vitamin D3

26

What allows Vit. D3 to travel in the bloodstream?
• where is it delivered 1st?

Vit. D Binding Protein (VDBP) binds to Vit. D and carries Vit. D3 to the LIVER to be acted on by 25-hydroxylase

27

What are the 4 main places 1,25-(OH)2D - Active Vit. D is delivered?

• Intestine
• PTH gland
• Osteoclast Precursors
• Kidney

28

What receptors on kidney cells bind VDBP-25(OH)D?

• Cubulin
• Megalin

29

What Happens when Vitamin D enters a target cell?

Transcriptional Effects:
• Binds VDR (vitamin D receptor and diffuses into nucleus)

• Binds VDR-1,25(OH)2D binds RXR on DNA and upregulates transcription of proteins

Conversion of Calcitriol:
• CYPs act on 1,25 (OH)D2 (calcitriol) to turn it into calcitriolic acid

30

What are 3 factors that DOWN REGULATE PTH?
• how do they work?

1. Calcium => CaSR activation --> Ca2+ release from ER ---> Less PTH secretion

2. Calcitriol - 1) preproPTH transcription inhibition via VDR 2) also upregulates CaSR to indirectly inhibit

3. FGF23 - Direct inhibition of PTH mRNA generation