Briefly
discuss the factors which regulate renal potassium excretion.
Outline:
·
Need for regulation of
renal potassium excretion
·
Regulatory factors:
- plasma K+ levels
- aldosterone
- tubular flow
·
Factors disrupting
potassium excretion:
- acid-base balance
- use of diuretics
Essay:
Potassium is one of the most abundant cations in the body and is critical
for many cell functions. The body contains between 3000-4000 mEq of K+.
99% (150 mEq/L) resides within the intracellular fluid and only 2% (3.5-5.0
mEq/L) within the extracellular fluid (ECF). This balance must be balanced to
ensure the normal functioning of excitable tissues such as nerves and muscles.
Regulation of K+ excretion is achieved mainly by alterations
in K+ secretion by principal cells of the distal tubule and
collecting duct. Plasma K+ and aldosterone are the major
physiological regulators of K+ secretion.
Plasma K+ is an important determinant of K+
secretion by the distal tubule and collecting duct. First, hyperkalemia
stimulates the Na+- K+-ATPase and thereby increases K+
uptake across the basolateral membrane. This uptake raises intracellular [K+]
and increases the electrochemical driving force for K+ exit across
the apical membrane. Second, hyperkalemia also increases the permeability of the
apical membrane to K+. Third, hyperkalemia stimulates aldosterone
secretion by the adrenal cortex. Lastly, hyperkalemia also increases the flow
rate of tubular fluid which enhances the excretion of K+.
A chronic elevation in plasma aldosterone levels enhances K+
secretion across the distal tubule and collecting duct by increasing the amount
of Na+- K+-ATPase in principal cells. Aldosterone also
increases the driving force for K+ exit across the apical membrane
and increases the permeability of the apical membrane to K+.
Aldosterone secretion is increased by hyperkalemia and by angiotensin II.
A rise in the flow of tubular fluid (e.g. diuretic therapy, ECF volume
expansion) rapidly stimulates K+ secretion, whereas a fall in flow (hemorrhage,
vomiting) reduces K+ secretion by the distal tubule and collecting
duct. Alterations in tubular fluid flow influence K+ secretion by
changing the driving force for K+ exit across the apical membrane. An
increase in tubular fluid flow minimizes the rise in tubular fluid [K+]
as the secreted K+ is washed downstream. A rise in tubular flow
increases the amount of Na+
entering the distal tubule and collecting duct, which in turn enhances Na+
reabsorption. The increase in Na+ reabsorption stimulates K+
uptake across the basolateral membrane by increasing the activity of the Na+-
K+-ATPase, which promotes K+ secretion. Because diuretic
drugs increase the flow of tubular fluid (e.g. thiazides) through the distal
tubule and collecting duct, they also enhance urinary K+ excretion.
However, hyperkalemia can result from the use of K+-sparing diuretics
such as spironolactone which inhibits the Na+- K+-ATPase
at the collecting duct.
Another factor that modulates K+ secretion is the pH of the
ECF. Alkalosis increases K+ secretion whereas acidosis decreases K+
secretion. Acute acidosis reduces K+ secretion by two mechanisms: it
inhibits Na+- K+-ATPase, thereby reducing cell [K+]
and the electrochemical driving force for K+ exit across the apical
membrane; and it reduces the permeability of the apical membrane to K+.
The effect of metabolic acidosis on K+ excretion is time dependent.
When a metabolic acidosis lasts for several days, urinary K+
excretion is stimulated. Chronic metabolic acidosis decreases water and NaCI
reabsorption by the proximal tubule by inhibiting the Na+- K+-ATPase
in the tubular cells. Hence the flow of tubular fluid is augmented through the
distal tubule and collecting duct. The inhibition of water and NaCI reabsorption
also causes a decrease in ECF, thereby stimulating aldosterone secretion. The
rise in tubular fluid flow and aldosterone offsets the effects of acidosis on
cell [K+] and apical membrane permeability and K+
secretion arises.