Ca2+,Pi,Mg2+ Regulation Flashcards
1
Q
- What is normal plasma Ca2+ level
A
- 5.0 mEq/L
2
Q
- Where is Ca2+ stored in the body?
A
- 99% Bone
- 1% ICF
- 0.1% ECF
3
Q
- Normal level of biologically active plasma?
A
- 2.4 mEq/L
4
Q
- How much of Ca2+ is filterable at the glomerulus?
- Which Ca2+ is NOT freely filterable at the glomerulus?
A
- 60% (the filtered Ca2+ is the calcium that is ionized or diffusible complexes)
- Protein bound Ca2+
5
Q
- H+ and Ca2+ compete for binding on which plasma protein?
- Which is the stronger of the two?
A
- Albumin
- H+
6
Q
- Hypoalbuminemia _ plasma Ca2+
- Hyperalbuminemia _ plasma Ca2+
A
- Increases
- Decreases
7
Q
- Acidosis _ plasma Ca2+ levels
- Alkalosis _ plasma Ca2+ levels
A
- Increases (More acid, more H+ binding to albumin, less binding sites for Ca2+)
- Decreases (predisposes to hypocalcemic tetany-also why acute alkalosis can mimic hypocalcemia)
8
Q
- What is the name of the biologically active form of Vitamin D?
A
Calcitriol
(Has other names, but she said to focus on this one)
9
Q
- What is the overall goal of calcitriol?
- Through which receptor does calcitriol work?
- Where are these receptors located?
A
- Increase serum Ca2+ and Pi
- VDR (Vitamin D receptors)
- Throughout the body (we will talk about bone, intestines, and kidney)
10
Q
- How does calcitriol act on bone?
A
- Promotes osteoid mineralization
- Osteoclastic mediated bone resorption (taking Ca2+ out of bone and putting it back into the blood stream-remember goal is to increase overall serum Ca2+ and Pi levels)
11
Q
- How does calcitriol act on the intestine?
A
- Increases Ca2+ absorption (30% dietary intake)
- Increases phosporus absorption
12
Q
- How does calcitriol act on the kidney?
A
- Stimulates phosphate reabsorption
- Stimulates Ca2+ reabsorption (by acting on NKCC?*)
13
Q
- What is the overall goal of calcitonin?
- What is it stimulated by?
A
- Increased excretion of Ca2+ and Pi
- Decreases activity and number of osteoclasts
- Stimulated by hypercalcemia (makes sense since the overall goal is to increase excretion of Ca2+)
- ALSO OPPOSES PTH
14
Q
- How does calcitonin act on bone?
A
- Inhibits osteoclast mediated bone resorption (so keeps the Ca2+ in the bones and prevents it from coming back out into the blood stream)
- Also decreases the activity and number of osteoclasts
15
Q
- How does calcitonin act on the kidney?
A
- Promotes phosphate and Ca2+ excretion
16
Q
- Pharmacological doses of Calcitonin can be used to treat:
A
- Hypercalcemia
- Paget’s disease
- Osteoporosis (leaves Ca2+ in bone)
17
Q
- What is the overall goal of PTH?
A
- Increase Serum Ca2+ and Decrease Serum Pi
18
Q
- How does PTH work on bone?
A
- Increased osteoclastic resorption (which increases Ca2+ going from bone back into the bloodstream)
19
Q
- How does PTH work on intestinal cells?
A
- Increases Ca2+ and Pi ABsorption INDIRECTLY via Calcitriol
20
Q
- How does PTH act on the kidney?
A
- Stimulates reabsorption of Ca2+ in the DCT
- Decreases reabsorption of Pi in the PCT
- Decreases activity of the Na+/H+ antiporter
- Decrease in bicarbonate reabsorption
21
Q
- Excess PTH can cause
A
- Hypercalcemia
- Hypophosphatemia
- Hyperchloremic metabolic acidosis
22
Q
- What is the CaSR?
- Where is it located?
- What is it’s function?
A
- Ca2+ sensing receptor
- Located on the basolateral membrane of the cells of the Thick Ascending Limb of the LOH
- Inhibits Ca2+ reabsorption when plasma Ca2+ is high
- (Also inhibits the NKCC and K+ leak channels on APICal membrane)
23
Q
- How do you calculate filtered load of Ca2+?
A
Remember that only 60% of Ca2+ is freely filtered at the glomerulus (other 40% is bound to proteins, which are not, under normal circumstances, freely filterable)
Filtered Load= GFR x [Plasma Conc] x (% Filterability)
Filtered Load of Ca2+= GFR x [Plasma Conc] x 0.6
24
Q
- In which areas of the neprhon is Ca2+ reabsorption passive?
- In which areas is it active?
A
- Passive in the PCT and the TAL of LOH
- Active in the distal tubule (major site of regulation)
25
Q
- How much Ca2+ is reabsorbed in the PCT?
- How is the Ca2+ reabsorbed?
A
- 65-70%
- Primarily Paracellularly
- Some reabsorbed transcellularly
- Diffuses down conc gradient into cell via Ca2+ channels on apical membrane
- Exits cell via Ca2+ ATPase or Na-Ca2+ antiporters located on the basolateral membrane
26
Q
- Volume contraction _ Ca2+ reabsorption
- Why?
A
- Increases
- Na+ and Ca2+ parallel each other in PT
27
Q
- How does Ca2+ reabsorption occur in the TAL?
- Which hormone acts on the TAL to increase Ca2+ reabsorption and how does it do so?
A
- Primarily paracellularly (reabsorption parallels Na+)
- Dependent on TEPD (lumen + voltage)
- ADH-because it increases NaCl reabsorption in the TAL, and Ca2+ parallels Na+ so it is also reabsorbed)
28
Q
Loop diuretics inhibit _ reabsorption in the TAL of the LOH. They can thus be used (indirectly) to treat _
A
- Na+
- Hypercalcemia (since Ca2+ reabsorption in the TAL parallels Na+ reabsorption)
29
Q
- Is the TEPD in the tubular lumen of the distal tubule positive or negative?
- How does this impact Ca2+ reabsorption in the distal tubule?
A
- Negative
- Requires Ca2+ reabsorption to be ACTIVE (requires ATP) since Ca2+ likes to be in the negatively charged lumen
30
Q
- How is Ca2+ reabsorbed in the distal tubule?
A
- Crosses apical membrane via TRPV5/TRPV6 channels
- Crosses basolateral membrane via Na+-Ca2+ exchanger
31
Q
- What conditions/hormones act on the TRPV5 to ENHANCE Ca2+ reabsorption?
- What conditions decrease activity of the TRPV5 and thus DECREASE Ca2+ reabsorption?
A
- PTH, Vitamin D, Calcitriol, Alkalosis
- Acidosis
32
Q
- How do you calculate filtered load of phosphate?
A
- Filtered load of phosphate= GFR x [Plasma conc of Pi] x 1
- Use 1 as % filterability since Pi is freely filtered at the glomerulus
33
Q
- How much Pi is reabsorbed in the proximal tubule?
- How is Pi reabsorbed in the proximal tubule?
A
- 80%
- Reabsorption is primarily driven by the Na+/K+ ATPase on the basolateral membrane
- This creates a gradient for Na+ to move into the cell
- Na+-Pi transporter on the APICAL membrane
- Pi crosses the BASOLATERAL membrane via its own unknown transporter
34
Q
- How does FGF23 regulate Pi reabsorption?
- When is it secreted?
A
- Secreted by bone in response to PTH, calcitriol and hyperphosphatemia
- inhibits activity of the Na+-Pi symporter on the APICAL surface of the early proximal tubule
35
Q
- Which enzyme converts Vitamin D into its highly active form?
- Where is this enzyme located
A
- CYP1alpha (renal one alpha hydroxylase)
- Proximal tubule of the kidney
36
Q
- What upregulates renal 1alpha-hydroxylase expression?*
A
- Low calcium
- Low phosphate
- High PTH
37
Q
- What inhibits renal 1 alphahydroxylase expression?
A
- High Ca2+ (via CaSR)
38
Q
- What happens to the vitamin D that is filtered at the glomeruls=us?
A
- Undergoes endocytosis
- Reabsorbed by PT
39
Q
- How does insulin impact Pi levels?
A
- Lowers serum levels by shifting Pi into cells
40
Q
_ is the most important hormone that regulates Pi excretion
A
- PTH
- PTH inhibits Na+-Pi symporter on the APICAL membrane of the proximal tubule and inhibits the Na+/H+ antiporter on the APICAL membrane
- PTH also works on the distal tubule to increase Ca2+ reabsorption
41
Q
- Where is Mg2+ reabsorbed in the neprhon?
- Where is most Mg2+ reabsorbed in the neprhon?
A
- Proximal tubule, thick ascending limb of LOH, Distal tubule
- Most reabsorption of Mg2+ occurs in the thick ascending limb of the LOH
42
Q
- How does Mg2+ reabsorption occur in the proximal tubule?
- How much Mg2+ is reabsorbed here?
A
- Mg2+ reabsorbed paracellularly, following movement of Na+ and H2O
- 20%
43
Q
- How is Mg2+ reabsorbed in the thick ascending limb of the LOH?
A
- Paracellularly
- Mg2+ reabsorption in TAL dependent on uptake of Na+ and K+ via NKCC2 (which depends on lumen positive voltage of TAL)
44
Q
- How is Mg2+ reabsorbed in the distal tubule?
A
- Crosses APICAL membrane via TRPM 6
- Crosses BASOLATERAL membrane via unknown mechanism
- Electrical potential is primary driver of Mg2+ influx into the cell (since Mg2+ concentration is similar intracellularly and extracellularly)
45
Q
- Regulators of Mg2+ reabsorption
A
- Dietary depletion (increases reabsorption)
- PTH (increases reabsorption)
- Metabolic acidosis (decreases reabsorption by decreasing membrane permeability of Mg2+)
- Metabolic alkalosis (increases reabsorption by increasing paracellular permeability of Mg2+)
- ECF volume expansion (decreases reabsorption-Na+ reabsorption also decreasing d/t decreased activity of the NKCC at TAL)
- ECF volume contraction (increases Mg2+ reabsorption)
