Lecture 10 - Renal Regulation of Potassium, Phosphate, and Calcium Homeostasis Flashcards

1
Q

Where is K+ found in the body?

A
  1. RBCs
  2. Muscle
  3. Liver
  4. Bone
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2
Q

How is K+ excreted?

A

Both urine (95%) and stool (5%)

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3
Q

Normal K+ kidney excretion rate?

A

90-95 mEq/day

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4
Q

Describe the pathway of K+ ingestion.

A

100 mEq/day => 5-10 mEq excreted in feces => rest is absorbed by the GIT (90 mEq) => 65 mEq left in ECF => either excreted in urine or stored in cells

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5
Q

Effect of increase in plasma K+?

A

Cell depolarization

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6
Q

What 3 hormones regulate the storage of K+ in cells?

A
  1. Insulin
  2. EPI
  3. Aldosterone
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7
Q

What 6 factors regulate the excretion/reabsorption of K+ by the kidneys?

A
  1. Plasma [K+]
  2. ADH
  3. Aldosterone
  4. Tubular flow rate
  5. Acid-base status
  6. Na+ intake
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8
Q

How is filtered K+ reabsorbed/secreted in the kidney?

A
  1. PCT: paracellular transport mostly, and also a little via primary active transport
  2. Thick ascending limb of the loop of Henle: very unique carrier (does not utilize energy) on the lumenal surface: 1Na+/1K+/2Cl- all pumped in due to drive of sodium gradient

COLLECTING DUCT:

3a. Principal cell of the collecting duct allows K+ to be secreted through: (1) lumenal channel and (2) lumenal K+/Cl- carrier (not active) - both after K+ has been brought in through the Na+/K+-ATPase on basolateral membrane
3b. Alpha-intercalated cell of the collecting duct allows K+ reabsorption via K+ primary active transport: simple K+ pump (then diffuses out basolateral membrane into blood)

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9
Q

What % of K+ filtered load is reabsorbed by the PCT and thick ascending limb of the loop of Henle? What does this mean?

A

90%

Means that by this point, if daily intake is normal, only 60 mmol of K+ are left (Fk=600 mmol/day), and since 90-95 mmol are excreted a day, K+ will need to be secreted by the rest of the nephron

BUT if daily intake is lower than normal, K+ might need to be reabsorbed

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10
Q

What is the filtered load?

A

= Filtration rate

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11
Q

How does aldosterone affect K+ homeostasis?

A

Stimulates K+ secretion at the collecting duct

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12
Q

How does dietary K+ intake affect K+ homeostasis?

A

Increase plasma [K+] => stimulation of cells of the adrenal cortex => increase aldosterone secretion => increase K+ secretion => increase K+ excretion

AND

Increase plasma [K+] => increase intracellular [K+] in collecting duct cells => increase K+ secretion => increase K+ excretion

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13
Q

How does tubular flow rate affect K+ homeostasis? What to note?

A

Flow rate increases in collecting duct => at higher luminal flow rates, the same amount of K+ secretion will be diluted by the larger volume such that the rise in luminal K+ concentration will be less => increased concentration gradient between blood and tubular fluid => increase K+ secretion => increase K+ excretion

To note: this effect is accentuated when dietary K+ is high and does not happen when dietary K+ is low

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14
Q

How do diuretics affect K+ homeostasis? Clinical implication?

A

Inhibition of NaCl/H2O reabsorption in proximal tubule and loop of Henle => increase rate of fluid delivery to distal tubule => increase in cell:lumen gradient for K+ diffusion => increase K+ secretion + inhibition of K+ reabsorption by diuretics in thick ascending limb => increase K+ excretion => can lead to K+ DEPLETION

Patients on diuretics need to increase their dietary K+ intake to avoid depletion (although some diuretics block the K+ channels in the distal tubule to inhibit secretion)

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15
Q

How does acid-base status affect K+ homeostasis? Explain in detail.

A
  1. Acidosis decreases the rate of K+ secretion (metabolic more so than respiratory): excess plasma H+ => H+ enters cells to be buffered => either Na+ or K+ needs to exit to compensate => cells have a lot of K+ => intracellular [K+] decreases => collecting duct gradient decreases => decrease K+ secretion
  2. Alkalosis increases the rate of K+ secretion (metabolic more so than respiratory): deficit in plasma H+ => H+ comes out of cells => K+ enters cells => intracellular [K+] increases => collecting duct gradient increases => increase K+ secretion
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16
Q

Effect of metabolic alkalosis + respiratory acidosis on K+ secretion?

A

Mild increase

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17
Q

How does Na+ intake affect K+ homeostasis?

A

Increase Na+ intake => increase in ECF volume => increase in distal tubule flow rate => increase in K+ secretion => increase in K+ excretion

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18
Q

Under normal K+ intake, is homeostasis maintained by regulating secretion or excretion?

A

SECRETION

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19
Q

Describe the pathway of phosphate ingestion.

A

900 mg in diet => 600 mg absorbed by GIT and 300 mg excreted in feces =>

  1. Stored in soft tissues (in and out)
  2. Used for bone remodeling (in and out)
  3. 600 mg excreted by the kidneys
20
Q

What % of filtered load of kidney does Na+ make up?

A

<1%

21
Q

What is the phosphate deprivation experiment?

A

No phosphate in diet + parathyroid gland removed => kidney excretion rate of phosphate would go to 0%

22
Q

What is the phosphate loading experiment?

A

High phosphate diet + PTH => kidney excretion rate of phosphate would go up to over 80%

23
Q

Can human kidneys secrete phosphate?

A

NOPE

24
Q

Where is Pi reabsorbed in the nephron? Provide %.

A
  1. Proximal tubule: 70-80%
  2. Distal convoluted tubule: 5-15%
  3. Collecting duct: 4-8%
25
Q

Plasma Pi?

A

1-2 mEq/L

26
Q

Proximal convoluted tubule cell [Pi]?

A

4 mEq/L

27
Q

How is Pi reabsorbed in the proximal tubule? What to note?

A

Na+-Pi co-transporter driven by Na+/K+-ATPase on basolateral membrane (rate-limiting step) => carrier is highly regulated

Under normal conditions, the rate of Pi delivery is easily handled by transport capacity in the proximal tubule so that no Pi is excreted

BUT, past this point, which is the tubular maximum for phosphate, TmP, the reabsorption is maximal and cannot be increased, so that we start excreting Pi

28
Q

Is the normal plasma Pi close to its Tm?

A

YUP

29
Q

Difference between reabsorption of Pi in S1 and S2 vs S3?

A

Lower capacity to reabsorb Pi in S3 due to decrease in transporter density

30
Q

What is special about the Pi Tm? Timing?

A

It is NOT fixed, but VARIABLE:

  1. Tm decreased by PTH/high Pi diet because transporters are removed from the proximal tubule lumenal membrane
  2. Tm increased by low Pi diet/decrease in PTH because transporters are inserted onto the proximal tubule lumenal membrane

=> this can happens within hours

31
Q

Effect of PTH + low Pi diet on Tm Pi?

A

Tm decreases because effect of PTH is more significant

32
Q

What is the maximal tubular reabsorptive capacity for a particular substance?

A

Tm/GFR

33
Q

How does PTH decrease proximal tubule Pi reabsorption?

A

Binds to membrane-bound receptor Gs: adenylyl cyclase –> cAMP –> PKA => removal of transporters from the proximal tubule lumenal membrane => increase Pi excretion

34
Q

On what parts of the nephron can PTH increase Pi excretion?

A
  1. Proximal tubule

2. DCT

35
Q

Describe the pathway of calcium ingestion.

A

1000 mg ingested daly => 350 mg absorbed in GIT/150 mg secreted in GIT => 800 mg excreted in feces => bone remodeling (in and out) + urinary excretion (200 mg = net amount absorbed)

36
Q

What % of filtered load of kidney does Ca++ make up?

A

2%

37
Q

Where is Ca++ reabsorbed in the nephron? Provide %.

A
  1. Proximal tubule: 60%
  2. Thick ascending limb of the loop of Henle: 20%
  3. Distal convoluted tubule: 10%
  4. Collecting duct: 5%
38
Q

Excretion fraction of Ca++ under normal conditions?

A

5%

39
Q

Between Pi, K+, and Ca++, which one can be reabsorbed in the STRAIGHT distal tubule?

A

Ca++ and K+

40
Q

Role of PTH on Ca++ reabsorption?

A

Stimulate Ca++ reabsorption in both the PCT and the distal convoluted tubule

41
Q

How is Ca++ reabsorbed in the thick ascending limb of the loop of Henle?

A

Intra and paracellularly

42
Q

How is Ca++ reabsorbed in the distal convoluted tubule?

A

Intracellularly only

43
Q

What regulates PTH secretion?

A

Plasma [Ca++]

Sensor on parathyroid gland senses it => higher Ca++ => decrease in PTH secretion rate

44
Q

4 effects of PTH on the body? Overall?

A
  1. Breaks down bone to release Ca++
  2. Increases Pi excretion
  3. Increases Ca++ reabsorption
  4. Stimulates kidney conversion of 25-hydroxy vitamin D to 1,25-dihydroxy vitamin D=> increases GIT Ca++ absorption

Purpose is to increase plasma [Ca++] BUT make sure to decrease plasma [Pi] because together they would form complex depositions

45
Q

Main regulatory organ(s) of Ca++ homeostasis?

A

GIT and bone

46
Q

What % of filtered load of kidney does Pi make up?

A

10-20% of filtered load of the kidney

47
Q

Is most filtered Ca++ passively reabsorbed?

A

YUP