EXTERNAL BALANCE OF POTASSIUM
OVERVIEW
‣External balance of potassium is achieved through balancing dietary potassium intake,
intracellular and extracellular potassium levels and excretion by kidneys
‣Extracellular potassium concentration is usually maintained within 3.5-5 mmol/L
‣This narrow window of control is critically important as the difference between the
intracellular and extracellular potassium affects electrically excitable muscle and nerve
cells due to its effect on the resting membrane potential
‣Intracellular potassium levels, which are maintained within 120-150mmol/L, are
important for enzyme function, cell division and growth
‣It also contributes to acid-base and cell volume regulation
‣Learning Goal
‣To focus on the external balance of potassium within the body
EXTERNAL BALANCE OF POTASSIUM
RENAL HANDLING OF POTASSIUM
‣Potassium levels are controlled by regulating its secretion and
reabsorption
‣This is done by the kidneys to match potassium intake and
maintain an external balance of potassium
‣Potassium is freely filtered at the glomerulus and passes through
to the proximal convoluted tubule (PCT) and loop of Henle,
where most of it is reabsorbed
‣There is some reabsorption in the distal convoluted tubule and
collecting duct, but potassium secretion also occurs at these sites
EXTERNAL BALANCE OF POTASSIUM
REABSORPTION
‣The freely filtered potassium is then passed through the
kidney tubules
‣Two-thirds of the filtered K+ is reabsorbed in the PCT and
approximately 20% is reabsorbed in the thick ascending
limb of the Loop of Henle
‣This means a very small proportion of K+ reaches the
distal nephron
EXTERNAL BALANCE OF POTASSIUM
PROXIMAL CONVOLUTED TUBULE
‣K+ reabsorption occurs passively within the PCT and about two-thirds is
reabsorbed here
‣It occurs via a paracellular mechanism and is directly proportional to water and
Na+ movement
‣The Na+-K+-ATPase causes Na+ to move out of the proximal tubule cell and
drives K+ into the cell
‣The extrusion of Na+ creates an osmotic gradient and an electrochemical gradient
‣Water moves out of the PCT down the osmotic gradient and Cl– moves down the
electrochemical gradient
‣K+ is reabsorbed and follows Cl– into the bloodstream
EXTERNAL BALANCE OF POTASSIUM
THICK ASCENDING LIMB OF LOOP OF HENLE
‣In this section of the nephron roughly 20% of K+ is
reabsorbed through paracellular and transcellular
pathways
‣Paracellular mechanism
‣Movement of K+ through apical renal outer medullary
K+ (ROMK) channels
‣This leads to a positive voltage in the lumen which
provides a driving force for passive reabsorption of K+
EXTERNAL BALANCE OF POTASSIUM
THICK ASCENDING LIMB OF LOOP OF HENLE
‣Transcellular mechanism
‣Na+-K+-ATPase on the basolateral membrane pumps Na+ out
into the bloodstream and pumps K+ into the thick ascending
limb which keeps the sodium concentration in the cell low
‣This creates a gradient for the sodium-potassium-chloride
(NKCC2) cotransporter on the apical membrane
‣NKCC2 pumps Na+, K+ and 2 Cl– into the cell from the lumen
‣Intracellular K+ can enter the bloodstream through K+-Cl–
symporter or through the K+ uniporter
EXTERNAL BALANCE OF POTASSIUM
DISTAL CONVOLUTED TUBULE AND CORTICAL COLLECTING DUCT
‣Around 10% of filtered potassium is reabsorbed here when the
body is attempting to preserve potassium
‣It occurs via the transcellular pathway and is mediated by alpha
and beta intercalated cells
‣Structurally, the initial collecting tubule and cortical collecting
duct are both composed of 70% principal cells (secretion of K+)
and 30% intercalated cells (reabsorption of K+)
‣In this section, we are considering the intercalated cells in the
reabsorption of K+
EXTERNAL BALANCE OF POTASSIUM
DISTAL CONVOLUTED TUBULE AND CORTICAL COLLECTING DUCT
‣There are two steps in the reabsorption of potassium here:
‣1. The apical H+-K+-ATPase mediates the movement of H+ into
the lumen, driving K+into the intercalated cell
‣2. Then, the basolateral K+ channel allows the K+ inside
the intercalated cell to leak out into the bloodstream
‣In potassium depletion, the number of H+-K+-ATPase pumps
increase significantly in order to reabsorb as much K+ as possible
‣However, reabsorbing K+ drives H+ secretion into the lumen. This
leads to hypokalaemic alkalosis
EXTERNAL BALANCE OF POTASSIUM
SECRETION
‣Potassium secretion occurs mainly in the late distal collecting tubule
(DCT) and the collecting duct (CD)
‣The purpose of secretion is to control the serum potassium levels in
the long term
‣The rate of secretion is variable and can be increased or decreased
due to several factors (which will be considered later)
‣With a normal or high K+ diet, the substantial secretion varies
between 15-20%
‣However, with a low K+ diet or depletion, there is very little secretion
EXTERNAL BALANCE OF POTASSIUM
DISTAL CONVOLUTED TUBULE AND COLLECTING DUCT
‣Potassium secretion in the late DCT and CD mediated via principal
cells and the rate can be varied depending on need
‣The principal cells of the late DCT and collecting duct contain ENaC
on the apical membrane and Na+-K+-ATPase on the basolateral
membrane
‣The activity of Na+-K+-ATPase results in Na+ moving out into the
blood from the principal cell and in turn drives K+ into the principal
cell from the bloodstream
‣This leads to a decrease in intracellular Na+ concentration and an
accumulation of intracellular K+
EXTERNAL BALANCE OF POTASSIUM
DISTAL CONVOLUTED TUBULE AND COLLECTING DUCT
‣The high intracellular K+ in comparison to the luminal
K+ concentration creates a chemical gradient which is ideal for
potassium secretion from the principal cell into the lumen
‣Due to the action of Na+-K+-ATPase, the low intracellular [Na+] allows
for a concentration gradient between the lumen and principal cell
‣Na+ moves from the lumen into the cell down the concentration
gradient through ENaC
‣This creates a favourable electrochemical gradient which allows for
K+ secretion via K+ channels on the apical membrane
EXTERNAL BALANCE OF POTASSIUM
FACTORS AFFECTING SECRETION - TUBULAR FACTORS
‣High ECF [K+]
‣This stimulates the Na+-K+-ATPases, leading to increased
permeability of K+ channels on the apical membrane
‣This results in increased secretion of K+ into the lumen
‣Aldosterone
‣This stimulates the Na+-K+-ATPases in the basolateral membrane
‣This stimulates K+ channels and ENaCs in the apical membrane,
leading to increased K+ secretion
EXTERNAL BALANCE OF POTASSIUM
FACTORS AFFECTING SECRETION - TUBULAR FACTORS
‣Acidosis – This leads to increased H+ secretion into lumen to
correct acidosis
‣Due to H+-K+-ATPase, when H+ is secreted into lumen,
K+ is driven back into the cell, leading to decreased
K+ secretion
‣Alkalosis – The kidneys try to decrease secretion of H+,
increasing secretion of K+ in turn
‣Stimulates Na+-K+-ATPase, leading to increased K+ channel
permeability
EXTERNAL BALANCE OF POTASSIUM
LUMINAL FACTORS
‣High luminal flow
‣The increased flow rate washes away luminal K+, meaning
there is a constant concentration gradient available
‣This leads to increased K+ secretion
‣This increased luminal flow also increases Na+ delivery to
the tubule cells which stimulates Na+ uptake through ENaC
‣This leaves the lumen in a negative potential, encouraging
K+ to be secreted through the apical K+ channel
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Where is most potassium reabsorbed in the kidney?
‣Proximal tubule
‣Descending limb
‣Ascending Limb
‣Distal Convoluted Tubule
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Where is most potassium reabsorbed in the kidney?
‣Proximal tubule
‣Descending limb
‣Ascending Limb
‣Distal Convoluted Tubule
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which channel is mainly responsible for reabsorption of
Potassium from the lumen into the cell in the thick
ascending limb?
‣Sodium-Potassium ATPase
‣NKCC2
‣H+-K+-ATPase
‣K+-Cl- cotransporter
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which channel is mainly responsible for reabsorption of Potassium
from the lumen into the cell in the thick ascending limb?
‣Sodium-Potassium ATPase
‣NKCC2
‣H+-K+-ATPase
‣K+-Cl- cotransporter
‣The NKCC2 channel is responsible for reabsorption in the thick
ascending limb into the cell. From there, potassium ions can enter the
bloodstream via the K+ -Cl - cotransporter.
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which channel is mainly responsible for reabsorption of
Potassium from the lumen into the cell in the distal
convoluted tubule?
‣Sodium-Potassium ATPase
‣NKCC2
‣H+-K+-ATPase
‣K+-Cl- cotransporter
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which channel is mainly responsible for reabsorption of Potassium from the
lumen into the cell in the distal convoluted tubule?
‣Sodium-Potassium ATPase
‣NKCC2
‣H+-K+-ATPase
‣K+-Cl- cotransporter
‣In the distal convoluted tubule, potassium reabsorption is coupled to
hydrogen secretion. Therefore, the H+-K+-ATPase channel allows hydrogen
ions to be secreted, allowing potassium ions to move into the cell.
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which channel is mainly responsible for the transportation
of potassium ions into the cell from the bloodstream in the
late distal convoluted tubule and collecting duct?
‣Sodium-Potassium ATPase
‣NKCC2
‣H+-K+-ATPase
‣K+-Cl- cotransporter
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which channel is mainly responsible for the transportation of
potassium ions into the cell from the bloodstream in the late distal
convoluted tubule and collecting duct?
‣Sodium-Potassium ATPase
‣NKCC2
‣H+-K+-ATPase
‣K+-Cl- cotransporter
‣The Sodium-Potassium ATPase channel moves potassium into the cell
from the bloodstream in the location specified in the question.
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which of these factors would increase secretion of
potassium ions?
‣Acidosis
‣Alkalosis
‣Low aldosterone
‣Low luminal flow
EXTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which of these factors would increase secretion of potassium ions?
‣Acidosis
‣Alkalosis
‣Low aldosterone
‣Low luminal flow
‣Acidosis leads to increased hydrogen secretion and therefore increased
potassium reabsorption. High levels of Aldosterone increases Na+-K+-
ATPase channels in the basolateral membrane and therefore increases
secretion. High luminal flow increases potassium secretion.
INTERNAL BALANCE OF
POTASSIUM
INTERNAL BALANCE OF POTASSIUM
OVERVIEW
‣Potassium is a hugely important electrolyte within the body and plays a
vital role in maintaining the resting membrane potential of cells
‣Even a small change in the extracellular concentration of K+ could
significantly depolarize or hyperpolarize cells, which has big implications
for cardiac function, amongst other things
‣The concept of maintaining an internal balance of K+ refers to its
movement between the extracellular fluid (ECF) and intracellular fluid (ICF)
‣The normal concentrations of K+ are between 3.5-5.0 mmol/L in the ECF
and between 120-150 mmol/L intracellularly
‣98% of the body’s K+ is stored intracellularly
INTERNAL BALANCE OF POTASSIUM
MECHANISMS FOR SHIFTING K+ INTO CELLS
‣An increase in [K+] in the ECF will promote the movement
of K+ into cells, down its concentration gradient
‣However, the internal balance of K+ is not this simple and
there are other factors to consider
‣When we eat a meal, insulin is secreted by the pancreas in
response to increased K+ concentrations in the blood
‣This increases the activity of Na+/K+-ATPase, therefore
moving the excess K+ into cells
INTERNAL BALANCE OF POTASSIUM
MECHANISMS FOR SHIFTING K+ INTO CELLS
‣This homeostatic mechanism helps to prevent dangerous
rises in [K+] after eating
‣Other hormones which act on Na+/K+-ATPase channels
include aldosterone and catecholamines
‣Alkalosis will also cause a decrease in ECF [K+]
‣This is due to the close relationship of [K+] with the pH of
the ECF
INTERNAL BALANCE OF POTASSIUM
MECHANISMS FOR SHIFTING K+ INTO CELLS
‣A decrease in the concentration of H+ ions (i.e. an increase
in pH) will lead to H+ ions being transported out of cells
‣This causes a reciprocal shift of K+ into cells, thereby
lowering the concentration of K+ in the ECF
‣Conversely, an increase in H+ ion
concentration (acidosis) causes H+ to move into cells,
drawing K+ out
INTERNAL BALANCE OF POTASSIUM
MECHANISMS FOR SHIFTING K+ OUT OF CELLS
‣A low concentration of ECF K+ promotes the movement of K+ out of
cells, down its concentration gradient
‣During exercise, skeletal muscle contracts, causing a net release of
K+ from these cells
‣This leads to an increase in ECF [K+] proportional to exercise intensity
‣Hyperkalaemia is prevented due to the uptake of K+ by other non-
contracting cells
‣Furthermore, exercise causes the release of catecholamines e.g.
adrenaline which increases K+ uptake by other cells via Na+/K+-
ATPase channels as mentioned earlier
INTERNAL BALANCE OF POTASSIUM
MECHANISMS FOR SHIFTING K+ OUT OF CELLS
‣This can lead to short-term hypokalaemia when exercise is
stopped
‣Acidosis also cause an increase in the concentration of ECF K+
‣Cell lysis will also cause the release of intracellular K+ into the ECF
‣If plasma tonicity becomes increased, water will leave cells to
compensate
‣This will increase the intracellular concentration of K+, causing it to
leave the cell and enter the ECF down its concentration gradient
INTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣What is the normal concentrations of K+ in the ECF?
‣0.1 - 2.3 mmol/L
‣3.5-5.0 mmol/L
‣120-150 mmol/L
‣300-500 mmol/L
INTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣What is the normal concentrations of K+ in the ECF?
‣0.1 - 2.3 mmol/L
‣3.5-5.0 mmol/L
‣120-150 mmol/L
‣300-500 mmol/L
INTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which of the following is a mechanism that shifts
potassium out of cells?
‣An increase in [K+] in the ECF
‣Insulin is secretion by the pancreas
‣A decrease in the plasma concentration of H+ ions (i.e.
an increase in pH)
‣Cell lysis
INTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which of the following is a mechanism that shifts potassium out of
cells?
‣An increase in [K+] in the ECF
‣Insulin is secretion by the pancreas
‣A decrease in the plasma concentration of H+ ions (i.e. an
increase in pH) - alkalosis
‣Cell lysis
‣Cell lysis will also cause the release of intracellular K+ into the ECF
INTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which of the following is a mechanism that shifts
potassium into cells?
‣An decrease in [K+] in the ECF
‣An increase in the plasma concentration of H+ ions (i.e.
a decrease in pH) - acidosis
‣Exercise (skeletal muscle contraction)
‣Release of catecholamines
INTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which of the following is a mechanism that shifts potassium into cells?
‣An decrease in [K+] in the ECF
‣An increase in the plasma concentration of H+ ions (i.e. a decrease
in pH) - acidosis
‣Exercise (skeletal muscle contraction)
‣Release of catecholamines
‣Adrenaline increases K+ uptake by other cells via Na+/K+-
ATPase channels. This can lead to short-term hypokalaemia when
exercise is stopped.
INTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Adrenaline increases K+ uptake by other cells via Na+/K+-
ATPase channels. This can lead to short-term hypokalemia
when exercise is stopped. During exercise, skeletal muscle
contracts, causing a net release of K+ from these cells. This
leads to an increase in ECF [K+] proportional to exercise
intensity. Hyperkalemia is prevented during exercise due
to the uptake of K+ by other non-contracting cells.
INTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which of the following is NOT a feature of hypokalemia?
‣Muscle weakness
‣Paralytic ileus
‣Nephrogenic diabetes insipidus
‣Tall tented T waves
INTERNAL BALANCE OF POTASSIUM
REVIEW QUESTIONS
‣Which of the following is NOT a feature of hypokalemia?
‣Muscle weakness
‣Paralytic ileus
‣Nephrogenic diabetes insipidus
‣Tall tented T waves on ECG
‣Hypokalemia is associated with small or inverted T waves,
prominent U waves, and ST segment depression (when severe)
URINARY REGULATION
OF ACID-BASE BALANCE
URINARY REGULATION OF ACID-BASE BALANCE
OVERVIEW
‣The acid-base balance is vital for normal bodily functions
‣When this equilibrium is disrupted, it can lead to severe
symptoms such as arrhythmias and seizures
‣Therefore, this acid-base balance is tightly regulated
‣Learning Goal
‣To look at the buffering system, responses of the
urinary system and relevant clinical conditions
URINARY REGULATION OF ACID-BASE BALANCE
URINARY SYSTEM
‣The urinary system utilizes two methods to alter blood pH
‣Excretion of hydrogen (H+) ions as …
‣1. dihydrogen phosphate (H2PO4–)
‣2. ammonia
‣Production and reabsorption of bicarbonate (HCO3–)
ions
URINARY REGULATION OF ACID-BASE BALANCE
EXCRETION OF HYDROGEN IONS: H2PO4–
‣Excretion of H+ ions in the form of dihydrogen phosphate
(H2PO4–)
‣H+ ions are actively transported into the lumen via
hydrogen-ATPase pumps on alpha intercalated cells
‣Excess luminal phosphate (only 85% of total phosphate is
normally reabsorbed) can bind a large portion of hydrogen
ions, buffering them as H2PO4– before excretion
‣This excretion of H+ ions increases blood pH
URINARY REGULATION OF ACID-BASE BALANCE
EXCRETION OF HYDROGEN IONS: NH4+
‣Excretion of hydrogen ions in the form of ammonium (NH4+)
‣Glutamine is converted to glutamate and ammonium in the proximal
convoluted tubule (PCT)
‣The ammonium dissociates to ammonia and H+ ions, allowing it to
pass the membrane and enter the lumen
‣Once in the lumen, it reforms ammonium by picking up a luminal
H+ ion
‣This allows hydrogen to be excreted as ammonium ions, increasing
blood pH
URINARY REGULATION OF ACID-BASE BALANCE
EXCRETION OF HYDROGEN IONS: NH4+
‣Furthermore, ammonia secreted at the PCT can be used
further down to buffer and excrete H+ ions secreted by
alpha intercalated cells in the collecting duct
‣This is due to its ability to pass membranes and traverse the
nephron
‣The glutamate created from glutamine can also go on to
form bicarbonate (via its conversion to alpha-ketoglutarate)
which can then be reabsorbed to further increase pH
URINARY REGULATION OF ACID-BASE BALANCE
BICARBONATE (HCO3-) REABSORPTION
‣Bicarbonate ions can also be reabsorbed in the PCT, which aids in the buffering system
‣H+ ions are secreted into the lumen via the sodium-hydrogen (Na+-H+) exchanger to
combine with any filtered bicarbonate
‣This then forms carbonic acid (H2CO3), catalyzed by carbonic anhydrase on the luminal
side
‣Carbonic acid then dissociates into carbon dioxide and water, which both can diffuse
into the cell
‣Here, the reaction is undone, and carbonic anhydrase inside the cell converts carbon
dioxide and water to carbonic acid, which then dissociates into H+ and HCO3– ions
‣HCO3– can then be transported into the blood whilst the H+ ions can be transported
back into the lumen for the cycle to repeat
URINARY REGULATION OF ACID-BASE BALANCE
BICARBONATE (HCO3-) PRODUCTION
‣The kidney is also able to produce bicarbonate
‣The metabolic activity of cells produces large amounts of carbon
dioxide
‣This then reacts with water to produce HCO3– ions, which enter the
plasma, and H+ ions to be transported into the lumen
‣This is useful as it also provides H+ ions to drive HCO3–
reabsorption
‣In addition to this bicarbonate can also be produced from amino
acids, which produces ammonium ions which then enter the urine
URINARY REGULATION OF ACID-BASE BALANCE
REVIEW QUESTIONS
‣Which cells in the kidney tubules are responsible for the
excretion of hydrogen ions?
‣Proximal tubule cells
‣Loop of Henle
‣Principle cells
‣Alpha intercalated cells
URINARY REGULATION OF ACID-BASE BALANCE
REVIEW QUESTIONS
‣Which cells in the kidney tubules are responsible for the
excretion of hydrogen ions?
‣Proximal tubule cells
‣Loop of Henle
‣Principle cells
‣Alpha intercalated cells
‣Via the luminal Hydrogen-ATPase pumps
URINARY REGULATION OF ACID-BASE BALANCE
REVIEW QUESTIONS
‣Which cells in the kidney tubules are responsible for the
reabsorption of bicarbonate ions?
‣Proximal tubule cells
‣Loop of henle
‣Principle cells
‣Beta intercalated cells
URINARY REGULATION OF ACID-BASE BALANCE
REVIEW QUESTIONS
‣Which cells in the kidney tubules are responsible for the
reabsorption of bicarbonate ions?
‣Proximal tubule cells
‣Loop of henle
‣Principle cells
‣Beta intercalated cells
URINARY REGULATION OF ACID-BASE BALANCE
REVIEW QUESTIONS
‣Which of the following is a cause of respiratory alkalosis?
‣Pulmonary embolism
‣Respiratory depression
‣Polio
‣Asthma
URINARY REGULATION OF ACID-BASE BALANCE
REVIEW QUESTIONS
‣Which of the following is a cause of respiratory alkalosis?
‣Pulmonary embolism
‣Respiratory depression
‣Polio
‣Asthma
‣Respiratory depression, polio are both causes of respiratory acidosis,
as they cause hypoventilation. Asthma does not usually have a major
effect on pH, but is more likely to cause respiratory acidosis. Only a
pulmonary embolism will cause respiratory alkalosis.
URINARY REGULATION OF ACID-BASE BALANCE
REVIEW QUESTIONS
‣Hydrogen ions are secreted from the proximal convoluted
tubule as which of the following?
‣Dihydrogen phosphate (H2PO4-)
‣Ammonia (NH3)
‣Bircarbonate (HCO3-)
‣Carbonic anhydrase
URINARY REGULATION OF ACID-BASE BALANCE
REVIEW QUESTIONS
‣Hydrogen ions are secreted from the proximal convoluted tubule as which of
the following?
‣Dihydrogen phosphate (H2PO4-)
‣Ammonia (NH3)
‣Bircarbonate (HCO3-)
‣Carbonic anhydrase
‣Hydrogen ions can be excreted as dihydrogen phosphate (H2PO4-) ions.
They can also be excreted as ammonium ions, not ammonia. The bicarbonate
binds with hydrogen ions, so that the bicarbonate ions can be reabsorbed
more readily. Carbonic anhydrase is the enzyme that catalyses this process
References
These slide reflect a summary of the contents of
TeachMePhysiology.com and are to be used for educational
purposes only in compliance with the terms of use policy.
Specific portions referenced in this summary are as follows:
‣https://teachmephysiology.com/urinary-system/ion-balance/potassium-regulation/
‣https://teachmephysiology.com/urinary-system/ion-balance/internal-balance-
potassium/
‣https://teachmephysiology.com/urinary-system/ion-balance/urinary-acid-base/
Additional sources are referenced on the slide containing
that specific content.