Kati Sriwiyati, dr.

• Over 98 % of the total body K+ is contained in the

cells
• Only 2 % in the ECF
• ECF K+ concentration normally is regulated precisely
at about 4.2 mEq/L
• Rising or falling more than ± 0.3 mEq/L
• Failure to rapidly rid the ECF of the ingested K+ could
cause life-threatening hyperkalemia (increased plasma
K+ concentration)
• A small loss of K+ from the ECF could cause severe
hypokalemia (low plasma K+ concentration)
 Maintenance of K+ balance depends primarily on
excretion by the kidneys (90-95%)
 The amount excreted in the feces is only about 5 to 10
% of the K+ intake.
 Insulin Stimulates K+ Uptake into Cells
 Insulin deficiency (diabetes mellitus)  plasma K+
concentration after eating a meal is much greater than
normal
 Aldosterone Increases K+ Uptake into Cells
 K+ intake  stimulates secretion of aldosterone 
cell K+ uptake
• β-Adrenergic Stimulation Increases Cellular
Uptake of K+.
– Increased secretion of catecholamines, especially
epinephrine  movement of K+ from the EC to the ICF,
mainly by activation of b2-adrenergic receptors
• Acid-Base Abnormalities Can Cause Changes in
K+ Distribution.
– Increased H+ concentration  reduce the activity of the
Na-K ATPase pump  decreases cellular uptake of K+
and raises extracellular K+ concentration.
• Cell Lysis Causes Increased Extracellular K+
Concentration.
– As cells are destroyed, the large amounts of K+ contained in
the cells are released into the extracellular compartment.
• Strenuous Exercise Can Cause Hyperkalemia by
Releasing K+ from Skeletal Muscle.
– During prolonged exercise, K+ is released from skeletal
muscle into the ECF
• Increased Extracellular Fluid Osmolarity Causes
Redistribution of K+ from the Cells to Extracellular
Fluid.
– ECF osmolarity  osmotic flow of water out of the cells 
cellular dehydration  ICF K+ concentration  diffusion of
K+ out of the cells  ECF K+ concentration.
• 3 renal processes:
1. The rate of K+ filtration (GFR multiplied by the
plasma K+ concentration)
• The normal rate of K+ filtration is about 756 mEq/day (GFR,
180 L/day multiplied by plasma K+, 4.2 mEq/L)
2. The rate of K+ reabsorption by the tubules
3. The rate of K+ secretion by the tubules
 The cells in the late distal and cortical collecting
tubules that secrete K+ are called principal cells
 Make up about 90 % of the epithelial cells
• Control of K+ Secretion by Principal Cells.
– The primary factors that control K+ secretion by the
principal cells :
1. The activity of the Na-K ATPase pump,
2. The electrochemical gradient for K+ secretion from
the blood to the tubular lumen,
3. The permeability of the luminal membrane for K+
• Intercalated Cells Can Reabsorb K+ During K+
Depletion.
– H-K ATPase transport mechanism located in the luminal
membrane  transporter reabsorbs K+ in exchange for
H+ secreted into the tubular lumen, and the K+ then
diffuses through the basolateral membrane of the cell
into the blood.
– This transporter is necessary to allow K+ reabsorption
during extracellular fluid K+ depletion, but under
normal conditions it plays a small role in controlling the
excretion of K+
• The most important factors that stimulate potassium
secretion by the principal cells include :
1. Increased ECF K+ concentration,
2. Increased aldosterone,
3. Increased tubular flow rate
• 3 mechanisms by which increased ECF K+ concentration
raises K+ secretion:
1. Stimulates the Na-K+ ATPase pump by increasing K+
uptake across the basolateral membrane  increases IC
K+ concentration  K+ to diffuse across the luminal
membrane into the tubule.
2. Increases the K+ gradient from the renal interstitial
fluid to the interior of the epithelial cell  reduces
backleakage of K+ from inside the cells through the
basolateral membrane.
3. Stimulates aldosterone secretion by the adrenal cortex
 stimulates potassium secretion
1. Effect to control the rate at which the principal cells
secrete potassium
 Stimulates active reabsorption of Na+ ions by the
principal cells of the late distal tubules and collecting
ducts  mediated a Na-K ATPase pump  transports
Na+ outward through the basolateral membrane of the
cell and into the blood at the same time that it pumps
K+ into the cell.
2. Effect to increase K+
excretion
 Increase the permeability
of the luminal membrane
for K+ stimulating
potassium secretion.
 Aldosterone Regulation
 Increased plasma K+
 Decreased Na+ conc.
 Decreased ECF volume
 Decreased arterial pressure

Sherwood’s Human Physiology 14-25 5th Ed. &

14-22 6th Ed.
 The primary mechanism :
 Increased H+ concentration  inhibits K+ secretion is
by reducing the activity of the Na-K ATPase pump.
 decreases intracellular K+ concentration and
subsequent passive diffusion of K+ across the luminal
membrane into the tubule.
 ECF calcium ion concentration normal level, 2.4
mEq/L.
 Hypocalcemia  < 2,4 mEq/L  the excitability of
nerve and muscle cells increases markedly and can in
extreme cases result in hypocalcemic tetany (spastic
skeletal muscle contractions)
 Hypercalcemia  > 2,4 mEq/L  depresses
neuromuscular excitability and can lead to cardiac
arrhythmias
 Renal calcium excretion = Calcium filtered - Calcium
reabsorbed
 Only about 50 % of the plasma calcium is ionized
 Bound to the plasma proteins (about 40 %) the plasma
proteins or complexed in the non-ionized form with
anions such as phosphate and citrate (about 10 %)
 Only about 50 % of the plasma calcium can be
filtered at the glomerulus.
 Normally, about 99 % of the filtered calcium is
reabsorbed by the tubules,
 About 65 % is reabsorbed in the proximal tubule
 25 -30 % is reabsorbed in the loop of Henle
 4-9 % is reabsorbed in the distal and collecting
tubules.
 Only about 1 % of the filtered calcium being excreted.
Costanzo’s Physiology 6-31
 One of the primary controllers of renal tubular
calcium reabsorption  PTH.
 increased levels of PTH  increased Ca2+
reabsorption in the thick ascending loops of Henle
and distal tubules  reduces urinary excretion of
calcium.
 In the proximal tubule, calcium reabsorption usually
parallels Na and H2O reabsorption.
 Control of Renal Calcium Excretion

Guyton’s Textbook of Medical Physiology 29-10

 The total plasma magnesium concentration  1.8 mEq/L
 >1/2 bound to plasma proteins
 The free ionized concentration of magnesium is only about
0.8 mEq/L
 The normal daily intake of magnesium  250 to 300
mg/day
 Only ½ of this intake  absorbed by the gastrointestinal
tract
 To maintain balance, the kidneys must excrete about 1/2
the daily intake of magnesium, or 125 to 150 mg/day.
 Normally about 10% of the renal filtrate of magnesium
is excreted.
 Regulation of magnesium excretion is achieved by
changing the tubular reabsorption.
 25-30% of magnesium reabsorption occurs in the
proximal tubule.
 60-65% of magnesium reabsorption occurs in the loop of
Henle.
 ~5% of magnesium reabsorption occurs in the distal and
collecting tubules.
Costanzo’s Physiology 6-31
 The following disturbances lead to increased
magnesium excretion:
(1) increased extracellular fluid magnesium
concentration,
(2) extracellular volume expansion,
(3) increased extracellular fluid calcium concentration.
 Sodium Excretion Is Precisely Matched to Intake
Under Steady-State Conditions
 Sodium Excretion Is Controlled by Altering
Glomerular Filtration or Tubular Sodium
Reabsorption Rates
 Excretion = Glomerular filtration – Tubular reabsorption
 GFR normally is about 180 L/day,
 Tubular reabsorption is 178.5 L/day, and urine excretion
is 1.5 L/day.
 Small changes in GFR or tubular reabsorption
potentially can cause large changes in renal
excretion.
 Pressure diuresis  to the effect of increased blood
pressure to raise urinary volume excretion,
 Pressure natriuresis  to the rise in sodium excretion
that occurs with elevated blood pressure.
 Because pressure diuresis and natriuresis usually occur
in parallel, we refer to these mechanisms simply as
“pressure natriuresis”
 Sympathetic Nervous System Control of Renal
Excretion: Arterial Baroreceptor and Low-
Pressure Stretch Receptor Reflexes
 Kidneys receive extensive sympathetic innervation
 Changes in sympathetic activity can alter renal
sodium and water excretion
 Blood volume is reduced  the pressures in the pulmonary
blood vessels and other low-pressure regions of the
thorax decrease  reflex activation of the
sympathetic nervous system  increases renal
sympathetic nerve activity  several effects to
decrease Na and water excretion:
 Constriction of the renal arterioles, with resultant
decreased GFR;
 Increased tubular reabsorption of salt and water
 stimulation of renin release and increased
angiotensin II and aldosterone formation
 increase tubular reabsorption
 Reduction in blood volume is great enough to lower
systemic arterial pressure  decreased stretch ofthe
arterial baroreceptors located in the carotid sinus
and aortic arch  activation of the sympathetic
nervous system
 In Controlling Renal Excretion
 One of the body’s most powerful controllers of sodium
excretion
 Sodium intake is elevated 
renin secretion is
decreased decreased angiotensin II formation
 decreases tubular reabsorption of sodium
and waterincreasing the kidneys’ excretion of
sodium and waterminimize the rise in
extracellular fluid volume and arterial pressure
 in Increasing Effectiveness of Pressure
Natriuresis
 The high angiotensin II levels  sodium and
water
retention by the kidneys and a small increase in
extracellular fluid volumeinitiates a rise in
arterial pressure  quickly increases kidney
output of sodium and water re-establishing a
balance between intake and output of sodium at
a higher blood pressure.
 in Controlling Renal Excretion
 Aldosterone increases sodium reabsorption, especially
in the cortical collecting tubules
 increased sodium and water reabsorption and
potassium secretion
 Reduction in sodium intake the increased
angiotensin II levels stimulate aldosterone
secretionreduction in urinary sodium
excretion to the maintenance of sodium
balance
 in Controlling Renal Water Excretion
 An important role in allowing the kidneys to form a
small volume of concentrated urine while excreting
normal amounts of salt  especially important
during water deprivation strongly elevates
plasma levels of ADH  increase water
reabsorption by the kidneys and help to
minimize the decreases in extracellular fluid
volume and arterial pressure
 One of the most important of the natriuretic hormones is a
peptide referred to as atrial natriuretic peptide (ANP),
released by the cardiac atrial muscle fibers.
 The stimulus for release of this peptide appears to be
overstretch of the atria, which can result from excess
blood volume.
 Once released by the cardiac atria, ANP enters the
circulation and acts on the kidneys to cause small
increases in GFR and decreases in sodium
reabsorption by the collecting ducts increased
excretion of salt and water  helps to compensate for the
excess blood volume
 High Sodium Intake
Suppresses
Antinatriuretic Systems
and Activates Natriuretic
Systems
 mechanisms in the body
to increase sodium
excretion
SELAMAT BELAJAR