Lecture #18: Renal Regulation of Ion Concentrations Flashcards
What is the normal intracellular concentration of potassium?
140 mEq/L
What is the clinical significance of excess extracellular potassium?
> An increase of 3 to 4 mEq/L can lead to cardiac arrhythmias.
> Higher concentrations can lead to cardiac arrest or fibrillation.
Why must the kidneys be able to rapidly adjust extracellular potassium concentration?
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
What is the total amount of potassium in the extracellular and intracellular body compartments?
Extracellular = 4.2 mEq/L x 14L = 59 mEq
Intracellular = 140 mEq/L x 28 L = 3920 mEq
What is the overall effect of aldosterone secretion on potassium excretion?
Increase in extracellular potassium stimulates increase in aldosterone secretion.
What part of the renal tubule is responsible for potassium reabsorption and what part is responsible for potassium secretion?
Potassium Reabsorption:
- proximal tubule - ascending limb of Henle
Potassium Secretion:
- late tubule - collecting duct
Describe the mechanism by which principal cells secrete potassium.
> 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.
What cell in the kidney tubule system reabsorbs sodium and secretes potassium?
Principal Cells
What factors stimulate principal cells to secrete potassium?
> potassium concentration
> aldosterone
** Note that potassium secretion by principal cells is stimulated by potassium concentration and aldosterone. **
Describe the relationship between tubular flow rate and potassium secretion.
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.
Describe and explain why high sodium intake has little effect on potassium excretion.
*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.
What is the overall effect of aldosterone secretion on potassium excretion?
Increase potassium excretion
What is the normal extracellular concentration of potassium ion?
Precisely regulated at 4.2 mEq/L (+/- 0.3 mEq/L)
How does plasma pH effect the amount of plasma calcium bound to plasma proteins?
> 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
List the effects that parathyroid hormone (PTH) have.
1) stimulates bone reabsorption
2) stimulates activation of vitamin D
3) indirectly increases tubular calcium reabsorption
How much filtered calcium is reabsorbed, and where in the kidney tubule does this occur?
> 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
- 50% through paracellular route
> 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)
List the factors that decrease calcium reabsorption.
1) decreased levels of PTH
2) metabolic alkalosis
3) increased level plasma concentration of Ca
What mechanism controls phosphate excretion?
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
- 75-80% reabsorbed in proximal tubule
What is the role of PTH in phosphate reabsorption?
> PTH promotes bone reabsorption ->
- increased [phosphate] in extracellular fluid
> PTH -> decreases transport maximum for phosphate by renal tubules ->
- greater loss of phosphate in urine
What effects do insulin and catecholamines have on extracellular potassium levels?
Insulin -> stimulates potassium uptake by cells.
Catecholamines:
- > beta-adrenergic stimulation (epinephrine):
- stimulates potassium uptake by cells
- > beta-adrenergic receptor blockers -> hyperkalemia
What are the relationships of Conn’s syndrome and Addison’s disease to aldosterone secretion and potassium levels?
> 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
What effect does metabolic acidosis have on extracellular potassium concentration?
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+]
What effect does metabolic alkalosis have on extracellular potassium concentration?
decreased [extracellular K+]
What effects do cell lysis, strenuous exercise, and increased extracellular fluid osmolarity have on extracellular potassium concentration?
Cell lysis, strenuous exercise, and increased extracellular fluid osmolarity all cause hyperkalemia, which is an increase in extracellular potassium concentration.
Describe the role of intercalated cells in controlling potassium levels.
Intercalated cells reabsorb K+ during K+ depletion.
- possible through a H/K-ATPase - secrete H+ into tubular lumen
In which portion of the kidney tubule does the most potassium reabsorption occur?
proximal tubule
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
b) principal cells
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
a) aldosterone
What percentage of calcium is stored in the bones?
99%
What percentage of potassium is excreted in a normal human?
1%
Which of the following cells reabsorb potassium during potassium depletion?
a) intercalated cells
b) principal cells
c) chief cells
d) podocytes
a) intercalated cells
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
a) potassium excretion would increase with increased tubular flow rate
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
c) metabolic acidosis increases extracellular potassium concentration
True or False:
At high levels of angiotensin II greater increases in arterial pressure are necessary to increase sodium excretion.
True
True or False:
At reduced angiotensin II levels, normal levels of sodium can be maintained at reduced arterial pressures.
True
What factors stimulate K+ secretion by principal cells?
> increased [extracellular K+]
- stimulates Na/K-ATPase - increased K+ gradient from ECF to cellular fluid - stimulates aldosterone secretion
> increased aldosterone
> increased tubular flow rate
What kind of cells secrete potassium?
Principal cells
In which region of the tubule system are principal cells found?
Found in the late distal tubule and cortical collecting tubules.
** 90% of cells in these regions **
What percentage of cells that make up the late distal tubule and cortical collecting tubules are principal cells?
90%
How do principal cells secrete potassium?
> Na/K-ATPase pump in basolateral membrane
> Passive diffusion of potassium into tubular lumen
What 3 processes determine renal potassium excretion?
> 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
What effect does aldosterone have on extracellular potassium levels?
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
True or False:
Aldosterone increases potassium secretion - the high potassium extracellular concentration causes aldosterone secretion.
True
What percentage of the total body potassium in found in the extracellular fluid?
2%
