Lecture #18: Renal Regulation of Ion Concentrations

Question 1

What is the normal intracellular concentration of potassium?

Answer 1

140 mEq/L

Question 2

What is the clinical significance of excess extracellular potassium?

Answer 2

> An increase of 3 to 4 mEq/L can lead to cardiac arrhythmias.

> Higher concentrations can lead to cardiac arrest or fibrillation.

Question 3

Why must the kidneys be able to rapidly adjust extracellular potassium concentration?

Answer 3

Kidneys must adjust potassium excretion rapidly and precisely in response to wide variations in intake.

 - mainly involves distal and collecting tubules 
 - intake of potassium from a single meal can be as high as 50 mEq 
           * extracellular fluid contains 2% of total body potassium

Question 4

What is the total amount of potassium in the extracellular and intracellular body compartments?

Answer 4

Extracellular = 4.2 mEq/L x 14L = 59 mEq

Intracellular = 140 mEq/L x 28 L = 3920 mEq

Question 5

What is the overall effect of aldosterone secretion on potassium excretion?

Answer 5

Increase in extracellular potassium stimulates increase in aldosterone secretion.

Question 6

What part of the renal tubule is responsible for potassium reabsorption and what part is responsible for potassium secretion?

Answer 6

Potassium Reabsorption:

  - proximal tubule 
  - ascending limb of Henle

Potassium Secretion:

  - late tubule 
  - collecting duct

Question 7

Describe the mechanism by which principal cells secrete potassium.

Answer 7

> NOTE: potassium secretion by principal cells is stimulated by potassium concentration and aldosterone.

> Na/K ATPase pumps sodium from intracellular into renal interstitial fluid of the kidney and pumps potassium into the principal cell. This creates a concentration gradient so that sodium can be reabsorbed from the tubular lumen into the principle cell through the ENaC channel. Potassium is then secreted into the tubular lumen because of the concentration gradient maintained by the Na/K ATPase.

***Figure 29-3 show this mechanism well.

Question 8

What cell in the kidney tubule system reabsorbs sodium and secretes potassium?

Answer 8

Principal Cells

Question 9

What factors stimulate principal cells to secrete potassium?

Answer 9

> potassium concentration

> aldosterone

** Note that potassium secretion by principal cells is stimulated by potassium concentration and aldosterone. **

Question 10

Describe the relationship between tubular flow rate and potassium secretion.

Answer 10

An increase in tubular flow rate leads to an increase in potassium secretion rate. Look at figure 29-9 because the relationship curves are different depending on high, low, or normal potassium diet.

Question 11

Describe and explain why high sodium intake has little effect on potassium excretion.

Answer 11

*This is answered by figure 29-10

Increased sodium intake decreases aldosterone secretion and, therefore, potassium excretion.

However, increased sodium intake also increases GFR and decreases proximal tubular reabsorption of sodium. This leads to an increase in distal tubular flow rate and increase in potassium excretion.

Therefore, high sodium diet leads to little change in potassium excretion.

**The increase in sodium intake leads to decreased aldosterone, which inhibits potassium secretion in cortical collecting ducts. Increased sodium intake also causes increased GFR and decreased proximal tubular sodium reabsorption, which both lead to an increased distal tubular flow rate, thus increasing potassium secretion in cortical collecting ducts. The effect of these two lead to an unchanged potassium excretion in the cortical collecting ducts.

Question 12

What is the overall effect of aldosterone secretion on potassium excretion?

Answer 12

Increase potassium excretion

Question 13

What is the normal extracellular concentration of potassium ion?

Answer 13

Precisely regulated at 4.2 mEq/L (+/- 0.3 mEq/L)

Question 14

How does plasma pH effect the amount of plasma calcium bound to plasma proteins?

Answer 14

> Changes in plasma pH on calcium binding:
- Acidosis -> less calcium is bound to the plasma proteins.

 - Alkalosis -> more calcium is bound to the plasma proteins. 

• low pH = less calcium binding
• high pH = more calcium binding

Question 15

List the effects that parathyroid hormone (PTH) have.

Answer 15

1) stimulates bone reabsorption
2) stimulates activation of vitamin D
3) indirectly increases tubular calcium reabsorption

Question 16

How much filtered calcium is reabsorbed, and where in the kidney tubule does this occur?

Answer 16

> Reabsorption in proximal tubule:

• About 99% of filtered calcium is reabsorbed!
  
  • 65% via paracellular route
  • 20% via transcellular route

> Reabsorption in loop of Henle:

• restricted to thick ascending limb
  
  • 50% through paracellular route
    
    • • passive diffusion and slight + charge of tubular lumen
  • 50% via transcellular route stimulated by PTH

> Reabsorption in distal tubule:

• almost entirely via active transport
• calcium-ATPase pump in basolateral membrane
• stimulated by PTH

Factors that regulate tubular calcium reabsorption
> increased levels PTH (decreases calcium excretion)
> plasma concentration of phosphate (decrease Ca excretion)
> metabolic acidosis (decreases Ca excretion)

Question 17

List the factors that decrease calcium reabsorption.

Answer 17

1) decreased levels of PTH
2) metabolic alkalosis
3) increased level plasma concentration of Ca

Question 18

What mechanism controls phosphate excretion?

Answer 18

Overflow Mechanism
* [phosphate] all filtered phosphate is reabsorbed

• [phosphate] > 0.1 -> excess is secreted
  • 75-80% reabsorbed in proximal tubule
    > transcellular pathway
  • 10% reabsorbed in distal tubule

Question 19

What is the role of PTH in phosphate reabsorption?

Answer 19

> PTH promotes bone reabsorption ->
- increased [phosphate] in extracellular fluid

> PTH -> decreases transport maximum for phosphate by renal tubules ->
- greater loss of phosphate in urine

Question 20

What effects do insulin and catecholamines have on extracellular potassium levels?

Answer 20

Insulin -> stimulates potassium uptake by cells.

Catecholamines:

 - > beta-adrenergic stimulation (epinephrine):
      - stimulates potassium uptake by cells 
 - > beta-adrenergic receptor blockers -> hyperkalemia

Question 21

What are the relationships of Conn’s syndrome and Addison’s disease to aldosterone secretion and potassium levels?

Answer 21

> Hypokalemia:

 - excess secretion of aldosterone (Conn's syndrome) 
 * low potassium/high aldosterone = Conn's syndrome

> Hyperkalemia:

 - deficiency in aldosterone secretion (Addison's disease) 
 * high potassium/low aldosterone = Addison's disease

Question 22

What effect does metabolic acidosis have on extracellular potassium concentration?

Answer 22

increase in [extracellular K+]

• increase [H+] -> reduction in activity of Na/K-ATPase pump, which causes a decrease in cellular uptake of K+, thus causing an increase in [extracellular K+]

Question 23

What effect does metabolic alkalosis have on extracellular potassium concentration?

Answer 23

decreased [extracellular K+]

Question 24

What effects do cell lysis, strenuous exercise, and increased extracellular fluid osmolarity have on extracellular potassium concentration?

Answer 24

Cell lysis, strenuous exercise, and increased extracellular fluid osmolarity all cause hyperkalemia, which is an increase in extracellular potassium concentration.

Question 25

Describe the role of intercalated cells in controlling potassium levels.

Answer 25

Intercalated cells reabsorb K+ during K+ depletion.

 - possible through a H/K-ATPase
 - secrete H+ into tubular lumen

Question 26

In which portion of the kidney tubule does the most potassium reabsorption occur?

Answer 26

proximal tubule

Question 27

Which of the following cells play a major role in the secretion of potassium?

a) intercalated cells
b) principal cells
c) chief cells
d) podocytes

Answer 27

b) principal cells

Question 28

Which of the following plays a major role in stimulating potassium secretion by the kidney tubule?

a) aldosterone
b) angiotensin II
c) sodium ion
d) PTH

Answer 28

a) aldosterone

Question 29

What percentage of calcium is stored in the bones?

Answer 29

99%

Question 30

What percentage of potassium is excreted in a normal human?

Answer 30

1%

Question 31

Which of the following cells reabsorb potassium during potassium depletion?

a) intercalated cells
b) principal cells
c) chief cells
d) podocytes

Answer 31

a) intercalated cells

Question 32

A high potassium intake would have which of the following effects on potassium excretion associated with increased renal tubular flow rate?

a) potassium excretion would increase with increased tubular flow rate
b) potassium excretion would decrease with increased tubular flow rate
c) there would be little effect
d) tubular flow rate would be decreased

Answer 32

a) potassium excretion would increase with increased tubular flow rate

Question 33

Which of the following describes a valid change in potassium distribution due to an acid/base abnormality?

a) metabolic acidosis decreases extracellular potassium
b) metabolic alkalosis increases extracellular potassium
c) metabolic acidosis increases extracellular potassium concentration
d) both A and B are valid

Answer 33

c) metabolic acidosis increases extracellular potassium concentration

Question 34

True or False:

At high levels of angiotensin II greater increases in arterial pressure are necessary to increase sodium excretion.

Answer 34

True

Question 35

True or False:

At reduced angiotensin II levels, normal levels of sodium can be maintained at reduced arterial pressures.

Answer 35

True

Question 36

What factors stimulate K+ secretion by principal cells?

Answer 36

> increased [extracellular K+]

 - stimulates Na/K-ATPase
 - increased K+ gradient from ECF to cellular fluid
 - stimulates aldosterone secretion

> increased aldosterone

> increased tubular flow rate

Question 37

What kind of cells secrete potassium?

Answer 37

Principal cells

Question 38

In which region of the tubule system are principal cells found?

Answer 38

Found in the late distal tubule and cortical collecting tubules.

** 90% of cells in these regions **

Question 39

What percentage of cells that make up the late distal tubule and cortical collecting tubules are principal cells?

Answer 39

90%

Question 40

How do principal cells secrete potassium?

Answer 40

> Na/K-ATPase pump in basolateral membrane

> Passive diffusion of potassium into tubular lumen

Question 41

What 3 processes determine renal potassium excretion?

Answer 41

> rate of potassium filtration
- normal = 180 L/day x 4.2 mEq/L = 756 mEq/day

> rate of potassium reabsorption
- 65% in proximal tubule; 25-30% in loop of Henle

> rate of potassium secretion

Question 42

What effect does aldosterone have on extracellular potassium levels?

Answer 42

Aldosterone

• increases potassium uptake by cells
• stimulates active reabsorption of Na by principal cells via Na/K-ATPase pump
• increase permeability of luminal membrane for K
• increase extracellular K -> aldosterone secretion

Question 43

True or False:

Aldosterone increases potassium secretion - the high potassium extracellular concentration causes aldosterone secretion.

Answer 43

True

Question 44

What percentage of the total body potassium in found in the extracellular fluid?

Answer 44

2%