Role of Kidneys In Regulation Of
Potassium Levels In ECF
• Extracellular fluid potassium concentration normally is
regulated at about 4.2 mEq/L ±0.3 mEq/L
• More than 98 percent of the total body potassium is
contained in the cells and only 2 percent is in the
extracellular fluid
• Maintenance of balance between intake and output of
potassium depends primarily on excretion by the
kidneys because the amount excreted in the feces is
only 5 to 10 percent of the potassium intake
• Redistribution of potassium between the intracellular
and extracellular fluid compartments provides a first
line of defense against changes in extracellular fluid
potassium concentration
Regulation of Internal Potassium
Distribution
• Insulin stimulates Potassium uptake into cells
• Aldosterone increases Potassium uptake into cells
• β-adrenergic stimulation increases cellular uptake
of Potassium
• Metabolic acidosis increases extracellular
potassium concentration
• Metabolic alkalosis decreases extracellular fluid
potassium concentration
• Cell lysis causes increased extracellular potassium
concentration
• Strenuous exercise can Cause hyperkalemia by
releasing Potassium from skeletal muscle
• Increased extracellular fluid osmolarity causes
redistribution of Potassium from the cells to
extracellular Fluid
• About 65 percent of the filtered potassium is
reabsorbed in the proximal tubule
• Another 25 to 30 percent of the filtered potassium is
reabsorbed in the loop of Henle especially in the thick
ascending part where potassium is actively cotransported along with sodium and chloride
• Most of the day-to-day regulation of potassium
excretion occurs in the late distal and cortical collecting
tubules, where potassium can be either reabsorbed or
secreted, depending on the needs of the body
• When potassium intake is low, the secretion
rate of potassium in the distal and collecting
tubules decreases causing reduction in
urinary potassium secretion
• Intercalated cells can reabsorb Potassium
during Potassium depletion
• The most important factors that stimulate
potassium secretion by the principal cells
include
(1) increased extracellular fluid potassium
concentration
(2) increased aldosterone
(3) increased tubular flow rate
• Increased extracellular fluid potassium concentration
raises potassium secretion by three mechanisms
(1) Increased extracellular fluid potassium concentration
stimulates the sodium-potassium ATPase pump
(2) Increased extracellular potassium concentration
increases the potassium gradient from the renal
interstitial fluid to the interior of the epithelial cell; this
reduces back leakage of potassium ions from inside the
cells through the basolateral membrane
(3) Increased potassium concentration stimulates
aldosterone secretion by the adrenal cortex which further
stimulates potassium secretion by
o Stimulating sodium-potassium-ATPase pump
o By increasing the permeability of the luminal
membrane for potassium
Increased Distal Tubular Flow Rate Stimulates
Potassium Secretion
• A rise in distal tubular flow rate, as occurs with
volume expansion, high sodium intake or
treatment with some diuretics stimulates
potassium secretion
• The effect of tubular flow rate on potassium
secretion in the distal and collecting tubules is
strongly influenced by potassium intake
• When potassium intake is high, increased
tubular flow rate has a much greater effect to
stimulate potassium secretion than when
potassium intake is low
• The effect of increased tubular flow rate is important in
helping to preserve normal potassium excretion during
changes in sodium intake
• For example, with a high sodium intake, there is decreased
aldosterone secretion, which by itself would tend to
decrease the rate of potassium secretion and, therefore,
reduce urinary excretion of potassium. However, the high
distal tubular flow rate that occurs with a high sodium
intake tends to increase potassium secretion
• The two effects of high sodium intake, decreased
aldosterone secretion and the high tubular flow rate,
counterbalance each other, so there is little change in
potassium excretion
• Acute increases in hydrogen ion concentration of the
extracellular fluid (acidosis) reduce potassium secretion,
whereas decreased hydrogen ion concentration (alkalosis)
increases potassium secretion
• The primary mechanism by which increased hydrogen ion
concentration inhibits potassium secretion is by reducing
the activity of the sodium-potassium ATPase pump
• This in turn decreases intracellular potassium
concentration and subsequent passive diffusion of
potassium across the luminal membrane into the tubule
• Chronic acidosis leads to a loss of potassium whereas acute
acidosis leads to decreased potassium excretion
Role Of Kidneys In Regulation Of
Calcium Levels In ECF
• Calcium excretion is adjusted to meet the
body's needs
• With an increase in calcium intake there is
also increased renal calcium excretion
• With calcium depletion calcium excretion by
the kidneys decreases as a result of enhanced
tubular reabsorption
• About 65 percent of the filtered calcium is
reabsorbed in the proximal tubule, 25 to 30
percent is reabsorbed in the loop of Henle,
and 4 to 9 percent is reabsorbed in the distal
and collecting tubules
Proximal Tubular Calcium
Reabsorption
• Most of the calcium reabsorption in the proximal tubule occurs
through the paracellular pathway, dissolved in water and carried
with the reabsorbed fluid as it flows between the cells
• Only about 20% of proximal tubular calcium reabsorption occurs
through the transcellular pathway in two steps:
(1) calcium diffuses from the tubular lumen into the cell down an
electrochemical gradient due to the much higher concentration of
calcium in the tubular lumen, compared with the epithelial cell
cytoplasm and because the cell interior is negative relative to the
tubular lumen
(2) calcium exits the cell across the basolateral membrane by a
calcium-ATPase pump and by sodium-calcium counter-transporter
Loop of Henle and Distal Tubule
Calcium Reabsorption
• In the loop of Henle calcium reabsorption is
restricted to the thick ascending limb
Approximately 50% of calcium reabsorption in
the thick ascending limb occurs through the
paracellular route by passive diffusion due to the
slight positive charge of the tubular lumen
relative to the interstitial fluid
• The remaining 50% of calcium reabsorption in
the thick ascending limb occurs through the
transcellular pathway, a process that is stimulated
by PTH
• In the distal tubule there is diffusion across
the luminal membrane through calcium
channels and exit across the basolateral
membrane by a calcium-ATPase pump, as well
as a sodium-calcium counter transport
mechanism
Excretion Of Phosphate
• Renal phosphate excretion is controlled by an overflow mechanism
• when phosphate concentration in the plasma is below the critical
value of about 1 mmol/L, all the phosphate in the glomerular
filtrate is reabsorbed and no phosphate is lost in the urine
• But above this critical concentration, the rate of phosphate loss is
directly proportional to the additional increase
• The proximal tubule normally reabsorbs 75 to 80 percent of the
filtered phosphate
• The distal tubule reabsorbs about 10 percent of the filtered load,
and only very small amounts are reabsorbed in the loop of Henle,
collecting tubules, and collecting ducts
• Approximately 10 percent of the filtered phosphate is excreted in
the urine
Control of Renal Magnesium Excretion
and Extracellular Magnesium Ion
Concentration
• More than one half of the body's magnesium is
stored in the bones
• Most of the rest resides within the cells, with less
than 1 percent located in the extracellular fluid
• The total plasma magnesium concentration is
about 1.8 mEq/L, more than one half of this is
bound to plasma proteins
• Therefore, the free ionized concentration of
magnesium is only about 0.8 mEq/L
• Renal excretion of magnesium can increase
markedly during magnesium excess or decrease
to almost nil during magnesium depletion
• The proximal tubule usually reabsorbs only about
25 percent of the filtered magnesium
• The primary site of reabsorption is the loop of
Henle where about 65 percent of the filtered load
of magnesium is reabsorbed
• Only a small amount (usually <5 percent) of the
filtered magnesium is reabsorbed in the distal
and collecting tubules
Pressure Natriuresis and Pressure
Diuresis
• Pressure diuresis refers to the effect of
increased blood pressure to raise urinary
volume excretion
• Pressure natriuresis refers to the rise in
sodium excretion with increased blood
pressure
•
Sympathetic Nervous System Control
of Renal Excretion
• The kidneys receive extensive sympathetic
innervation
• changes in sympathetic activity can alter renal
sodium and water excretion as well as
extracellular fluid volume
• When blood volume is reduced by hemorrhage
there is reflex activation of the sympathetic
nervous system
• This in turn increases renal sympathetic nerve
activity which has several effects
(1) constriction of the renal arterioles with resultant
decrease in GFR
(2) increased tubular reabsorption of salt and water
(3) stimulation of renin release and increased
angiotensin II and aldosterone formation
Role of Angiotensin II in Controlling
Renal Excretion
• When sodium intake is elevated above normal,
renin secretion is decreased causing decreased
angiotensin II formation
• Reduced level of angiotensin II decreases tubular
reabsorption of sodium and water, thus
increasing the kidneys' excretion of sodium and
water
• The net result is to minimize the rise in
extracellular fluid volume and arterial pressure
that would otherwise occur when sodium intake
increases
• When sodium intake is reduced below normal,
increased levels of angiotensin II cause sodium
and water retention
• Changes in activity of the renin-angiotensin
system act as a powerful amplifier of the
pressure natriuresis mechanism for
maintaining stable blood pressures and body
fluid volumes
Role of Aldosterone in Controlling
Renal Excretion
• Aldosterone increases sodium reabsorption,
especially in the cortical collecting tubules.
The increased sodium reabsorption is also
associated with increased water reabsorption
and potassium secretion
Role of ADH
• Water deprivation strongly elevates plasma
levels of ADH that in turn increases water
reabsorption by the kidneys and helps to
minimize the decreases in extracellular fluid
volume and arterial pressure
Role of Atrial Natriuretic Peptide in
Controlling Renal Excretion
• The stimulus for release of this peptide is
increased stretch of the atria which can result
from excess blood volume
• It acts on the kidneys to cause small increase
in GFR and decrease in sodium reabsorption