Primal Pictures Ltd.

2010

FUNCTIONAL PROCESSES OF URINE FORMATION

Each nephron functions to filter the blood to produce urine, removing waste or unwanted substances from the
body, while retaining nutrients and other important substances. T his is achieved using several different
processes:
Glomerular filtration
T he blood is filtered and water and solutes move out, forming a fluid called glomerular filtrate (tubular
fluid). T his occurs in the renal corpuscle when the blood in the glomerulus is under pressure, provoking the
selective filtration of substances into the glomerular capsule.
Each individual nephron only filters a small volume of blood, but the combined activity of all the nephrons
in both kidneys enables the filtration of approximately 1200 ml of blood per minute.
Tubular reabsorption
Water and solutes are reabsorbed from the tubular fluid and move back into the blood. Approximately 99%
of the water filtered into the glomerular capsule is reabsorbed into the bloodstream . T his process occurs
throughout the length of the renal tubule, with the proximal convoluted tubule making the largest
contribution. Specific segments of the renal tubule have different functions and properties, and a variety of
transport mechanisms facilitate the movement of substances back into the blood.
Tubular secretion
Additional substances are secreted and move out of the blood and tubular cells into the renal tubular fluid
(filtrate). T his final function serves to remove particular chemicals and control the ionic composition of
blood.
T he number of particles moving into or out of the bloodstream per unit of time can be given as a 'rate'.
Excretion is defined as the process of removing the waste products from metabolism, whereas secretion is
defined as the process of moving materials that have a purpose within the body. For any given substance, the
rate of excretion relies on the total effect of the three different movements described above. T herefore, the
rate of excretion can be calculated as the rate of filtration, less the rate of reabsorption, plus the rate of
secretion. T his can be summarized thus:
Excretion = Filtration Reabsorption + Secretion
T hese processes are described in detail in this topic, and the regulation of these processes is described
subsequently in 'Urinary System: 'Regulation of Urine Formation'.

GLOMERULAR FILTRATION

Blood flows from the afferent arteriole into the glomerulus, where pressure forces fluids and specific solutes to
leave the blood and enter the glomerular capsule. T his is glomerular filtration.
T he fluid that leaves the glomerulus and enters the glomerular capsule is called glomerular filtrate. In

healthy adults, the mean daily volume of glomerular filtrate is 180 liters for males and 150 liters for females.
Only small molecules travel with the fluid into the glomerular capsule to become part of the glomerular
filtrate. Cells, and larger molecules with a diameter greater than 7 nm (atoms typically have diameters of
about 0.1 nm), are prevented from entering the glomerular capsule by the filtration membrane, and are thus
retained within the circulatory system and subsequently enter the efferent arteriole.

FILTRATION MEMBRANE

Not everything in the blood passes into the glomerular capsule during glomerular filtration. A selectively
permeable membrane, known as the filtration membrane, separates the glomerulus and the glomerular
capsule, through which certain larger molecules cannot pass.
T he filtration membrane is composed of three layers and they function to prevent the passage of
progressively smaller substances. T hese layers are: a layer of endothelium forming the wall of the
glomerulus, a basal lamina, and a visceral layer containing podocyte cells.
Glomerular endothelium
T he glomerulus wall is composed of a single layer of glomerular endothelial cells. T hese cells
have many fenestrations (holes) that measure 7 nm in diameter.

Function

Prevents substances with a diameter larger than 7 nm from entering the glomerular filtrate.
Most solutes in the blood can pass through with the exception of red blood cells and platelets.
T he majority of proteins however, are larger than 7 nm in diameter, and therefore cannot pass
into the filtrate.

Basal lamina
T he basal lamina is produced by the endothelial cells of the glomerulus, and consists of a
glycoprotein matrix containing collagen fibers and proteoglycans. T here are no holes in this
layer.

Function

Prevents large proteins from filtering out of the blood and into glomerular filtrate.

Slit membrane
Each podocyte cell has thousands of pedicels wrapped around the glomerular capillary. In
between each pedicel is a gap called a filtration slit.
A thin membrane covers the filtration slit and only small molecules with a diameter less than 7
nm can pass through it, meaning that the majority (99%) of molecules within the blood are
prevented from entering the capsular space.
Function

Prevents molecules of a certain size from filtering out of the blood into glomerular filtrate.

A significantly greater volume of liquid is filtered through the filtration membrane in the renal corpuscle than
in other capillary networks. T here are four reasons for this:
Surface area

T he glomerular capillary network is an extremely convoluted structure and has a very large
surface area.

Filtration
distance

T he combined width of the three layers of the filtration membrane is very small (100 nm),
giving a smaller distance for filtration to occur over.

Permeability

Despite the multiple layers of the filtration membrane, molecules do not have to pass
through multiple cell membranes, due to the fenestrations and filtration slits.

Pressure
gradient

T he difference in size between the afferent arterioles and the efferent arterioles means
that pressure is often much greater in the glomerular capillaries.

As noted above, a key determinant of the rate at which fluid filtered through the filtration membrane is
pressure, specifically the pressure promoting the movement of fluid from the glomerular capillaries through the
filtration membrane and into the capsular space. T his is known as the net filtration pressure.
Glomerular blood hydrostatic pressure
T he glomerular blood hydrostatic pressure (GBHP) is usually 55 mmHg, and in the glomerular
capillaries, it acts to force liquid through the filtration membrane.
It promotes filtration.
Blood colloid osmotic pressure
T he blood colloid osmotic pressure (BCOP) is usually 30 mmHg. It is caused by the presence
of large proteins, such as albumins, globulins, and fibrinogens, that cannot easily pass through
the filtration membrane, therefore preventing the passage of liquid through the filtration
membrane.
It opposes filtration.
Capsular hydrostatic pressure
T he capsular hydrostatic pressure (CHP) is usually 15 mmHg. It is caused by the presence of
fluid already inside the capsular space and the renal tubule, and therefore prevents the
passage of liquid through the filtration membrane.
It opposes filtration.
T he NFP may be calculated by combining the effects of these forces using the following equation:
Net filtration pressure (NFP)
Net filtration pressure = GBHP CHP BCOP.
Entering the values for each pressure (as given above, GBHP = 55 mmHg, BCOP = 30 mmHg,
CHP = 15 mmHg) into the equation results in:
Net filtration pressure = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg.
T he NFP is 10 mmHg, therefore the net effect is to promote filtration and push liquid through
the filtration membrane.
T hese factors, especially NFP, affect the glomerular filtration rate (GFR). T he GFR is the speed at which fluid
passes out of the blood and into the glomerular capsule. All renal corpuscles in both kidneys contribute to the
GFR. T he GFR is measured as the amount of glomerular filtrate produced (fluid entering the glomerular
capsule) per minute.
In healthy adults, the mean GFR is 125 ml/min for males, and 105 ml/min for females. T he GFR represents
how quickly fluid is filtered. To maintain homeostasis, GFR must be kept as close to constant as possible.

Increased
GFR

If fluid is filtered too quickly, fluid passes through the renal tubules too quickly. T his means
that the filtrate only spends a short amount of time in the renal tubules and proper
reabsorption cannot take place, resulting in insufficient reabsorption of vital substances which
are then lost from the body in the urine.

Decreased
GFR

If fluid is filtered too slowly, fluid passes through the renal tubules too slowly. T his means that
the filtrate spends too much time in the renal tubules and too much filtrate can be
reabsorbed, resulting in the reabsorption of unwanted waste products that should be excreted.

For more information, see 'Urinary system: Regulation of Urine Formation'.

TUBULAR REABSORPTION

T he typical adult male produces roughly 180 liters of filtrate per day, whilst the typical female produces 150
liters. T he volume of urine produced, however is generally less than 2 liters (depending on fluid intake).
T he bulk of glomerular filtrate must be reabsorbed back into the bloodstream. T his occurs in a process known
as tubular reabsorption, during which the fol lowing substances are reabsorbed:
1. Water (typically 99% of filtered w ater is reabsorbed).
+

2+

2-

2. Ions (Na , K , Ca , Cl , HCO 3 , and HPO 4 ).

3. Molecules (glucose, amino acids, and urea).
T he reabsorption of substances from the tubular fluid occurs through different mechanisms, including active
transport (requiring AT P) and passive transport (no AT P required). Substances may be absorbed by different
mechanisms at different points along the nephron. For this reason, all the major mechanisms of reabsorption
are considered first, before examining which mechanisms occur at specific regions of the nephron (for more
information, see 'Urinary System: Regulation of Urine Formation.').
Adjacent epithelial cells lining the tubules are firmly adjoined by tight junctions, allowing only certai n
substances to pass through them. T he apical membrane of each tubule epithelial cell is in contact with the
lumen of the renal tubule, and the basolateral membrane is in contact with the interstitial fluid surrounding
the peritubular capillaries and vasa recta. T his cellular configuration means that substances can pass around
the tubule epithelial cells, via tight junctions (paracellular reabsorption), or directly through the cell
(transcellular reabsorption), ultimately passing through the interstitial fluid and into the blood of the
peritubular capillaries and vasa recta.
PARACELLULAR REABSORPTION

Paracellular reabsorption is a passive process whereby substances pass around tubule epithelial cells, via
tight junctions, without passing through the cytosol. In certain regions of the renal tubule, this mechanism
can constitute up to 50% of the reabsorption of some ions. Paracellular reabsorption occurs by simple
diffusion.

Substances inv olv ed

2+

2+

Water and some small ions (Ca , Cl , Mg , K , and some Na ).

TRANSCELLULAR REABSORPTION

Transcellular reabsorption is the process whereby substances pass from the tubular fluid, through the tubular
cells, and into the peritubular capillaries. T his process occurs along the length of the nephron.
Substances inv olv ed

2+

2+

Water, ions (Ca , Mg , Cl , K , and Na ), and molecules (glucose, amino acids,

vitamins, and urea).

T he transcellular reabsorption of different substances occurs by different functionally distinct mechanisms.

T hese mechanisms can be classified on the basis of whether they require AT P (active transport) or not
(passive diffusion), whether a specific transporter protein is required, and the specific ion being
transported. T he major functional categories of transcellular reabsorption are detailed below:
Passiv e transport: simple diffusion
Simple diffusion is a form of passive transport, during which substances move unassisted
from the tubular fluid, across the plasma membrane, into the tubule cells.

Passiv e transport: facilitated diffusion

Facilitated diffusion is another form of passive transport. During facilitated diffusion,
substances are assisted in their movement across the plasma membrane of the tubule
epithelial cells, either by leakage channels or carrier proteins.

Leakage channels
T here are many leakage channels present in both the apical and basolateral membrane of
tubule cells throughout the nephron. T hey facilitate the passive diffusion of ions, down their
concentration gradients, across the plasma membrane of tubule cells.
+

K leakage channels are present in both the apical and basolateral membrane of tubule
+

cells, through which K ions diffuse out into tubular filtrate and medullary interstitial fluid,
respectively.
-

Cl leakage channels are present in the basolateral membrane of tubule cells of the
-

ascending limb of the loop of Henle, through which Cl ions diffuse out into medullary
interstitial fluid.
Glucose transporter
Glucose transporters are examples of carrier proteins. T hey are located in the basolateral
membrane of tubule cells and facilitate the passive movement of glucose along its
concentration gradient, out of tubule cells and into the interstitial fluid of the renal medulla.

Passiv e transport: osmosis

Osmosis is a form of passive transport. It is the movement of water across a selectively
permeable membrane, down its concentration gradient, from a region of high water
concentration (low solute concentration) to a region of low water concentration (high solute
concentration).
Aquaporin-1 and aquaporin-2 w ater channels
Water moves across tubule epithelial cells by osmosis, driven by the reabsorption of solutes.
As solutes are reabsorbed, an osmotic gradient is generated, causing water to be drawn into
interstitial fluid.
T he apical and basolateral plasma membranes of some tubule epithelial cells contain
transmembrane proteins known as aquaporin-1 or aquaporin-2 molecules. T hey contain
internal water channels that span the membrane, increasing the cells permeability to water.
Primary activ e transport
Primary active transport uses specific carrier proteins, or pumps, driven by energy produced
by the hydrolysis of adenosine triphosphate (AT P). T hese carrier proteins (pumps) move
various solutes across the plasma membrane against their concentration gradient.

Na /K ATPase pumps
+

Na is actively transported out of tubule epithelial cells throughout the nephron by Na /K

ATPase pumps in the basolateral m embrane. T his maintains a low cytoplasmic Na

concentration, generating a strong Na electrochemical gradient, which provides the driving

force behind the reabsorption of water by osmosis, and most other solutes by passive solute
+

diffusion and cotransport with Na .

+

T he K being pumped in immediately moves out again through leakage channels, leaving
the inside of the tubule epithelial cells negatively charged.
Secondary activ e transport (cotransport)
Secondary active transport, or cotransport, is the movement of a substance across a plasma
membrane, against its electrochemical gradient, coupled with another secondary substance
+

that is moving down its electrochemical gradient (in renal tubule cells, this is usually Na ).
Kinetic energy, produced by the secondary substance moving down its electrochemical
gradient, is used to drive the movement of the primary substance against its electrochemical
+

gradient. In renal tubule cells, an Na electrochemical gradient is set by Na /K AT Pase

pumps in the basolateral membrane.
Transmembrane proteins known as symporters and antiporters are used during cotransport.
+

Symporters transport two or more substances in the same direction (e.g., Na /glucose
symporters in the proximal convoluted tubule) whereas antiporters transport two or more
+

proteins in the opposite direction (e.g., Na /H antiporters).

+

Na /glucose symporter

Na /glucose symporters located in the apical membrane of proximal convoluted tubule cells
+

transport glucose, along with 2 Na , into the tubular epithelial cells. T he diffusion of Na
+

ions down the concentration gradient (established by Na /K AT Pase pumps) and into the
epithelial cells drives the movement of glucose.
+

Na /H antiporter
+

Na /H antiporters located in the apical membrane of tubule cells pump H

ions (protons)

out of tubule epithelial cells into the tubular fluid. Na ions diffuse down their concentration
+

gradient (established by Na /K AT Pase pumps) into the cytoplasm of tubule epithelial

cells, and protons are transported into the tubular fluid.
+

Na /K /2 Cl symporter
+

Na /K /2Cl symporters located in the apical membrane of tubule cells transport Na , K ,

-

and 2 Cl into tubule epithelial cells. T he diffusion of Na ions down the concentration
+

gradient (established by Na /K AT Pase pumps) and into the cytoplasm of tubule epithelial
+

cells simultaneously drives the transport of K and Cl into the tubular cells.

TUBULAR SECRETION
Excess quantities of dissolved substances are removed from blood in the peritubular capillaries and added to
tubular filtrate to be disposed of in the urine. T his occurs in a process known as tubular secretion, during
which the following substances are secreted into tubular filtrate:
+

1. Ions (K , H , HCO 3 , and NH4 ).

2. Creatinine and urea.
3. Some hormones and drugs.
Tubular secretion removes harmful or unwanted substances (waste) from blood plasma, whilst maintaining a
healthy blood pH. T he proximal convoluted tubules are the main site of secretion, with the late distal tubule
and collecting ducts also playing a role. As with tubular reabsorption, tubular secretion may be active or
passive.
For more information, see 'Urinary System: Regulation of Urine Formation'.

REABSORPTION AND SECRETION IN THE PROXIMAL CONVOLUTED TUBULE

T he mechanisms of tubular reabsorption and tubular secretion discussed above occur along the nephron.
However, different regions of the nephron are especially important for the reabsorption and secretion of
specific substances.
T he proximal convoluted tubule (PCT ) is the site of bulk solute and water reabsorption, with approximately
+

60-67% of water, Na , Cl , K , HCO 3 and urea present in the filtrate being reabsorbed, 100% of glucose,
amino acids, lactic acid, and water-soluble vitamins present in the filtrate also being reabsorbed, in addition

2-

to a variable amount of HPO 4 . T he function of the proximal convoluted tubule is facilitated by its structure: it
has a 'leaky' apical epithelium and is therefore highly permeable to water and solutes.
Within the proximal tubule, isosmotic reabsorption occurs: solutes are reabsorbed from the tubular fluid into
the tubule cells and water passively follows the solutes by osmosis. As both solutes and water are being
reabsorbed, the ionic concentration of the tubular filtrate does not change and is therefore referred to as being
isosmotic.
In addition, the secretion of substances, such as ammonium ions, back into tubular fluid also occurs.
Reabsorption of Na

+
+

Approximately 60% of sodium ions (Na ) present in the tubular filtrate are reabsorbed in the
proximal convoluted tubule.
+

Na ions are initially transported into the tubule cells from the tubular fluid, primarily by a
variety of secondary active transport mechanisms, detailed above. To maintain the
electrochemical gradient for the reabsorption from the tubular fluid, Na+ ions are then actively
transported out of the tubule cells by Na/K ATPases located in the basolateral membranes,
where it enters the interstitial space, and eventually is returned to the blood. T his maintains a
+

low intracellular Na concentration within the tubule cells, which in turn maintains the
+

electrochemical gradient for further reabsorption of Na ions (and the substances which are
cotransported with them) from the tubular fluid.
In addition, this electrochemical gradient drives the sustained reabsorption of water by
osmosis, as well as other solutes via passive diffusion.
Reabsorption of nutrients (glucose, amino acids, lactic acid, and w ater-soluble v itamins)
All glucose, amino acids, lactic acid, and water-soluble vitamins present in filtrate are
reabsorbed early in the proximal convoluted tubule. T hese substances are usually reabsorbed
+

by secondary active transport via Na symporters present in the apical membrane of tubule
cells, amongst the microvilli.
-

Reabsorption of bicarbonate (HCO 3 )

-

More than 60% of HCO 3 present in the tubular fluid is reabsorbed in the proximal convoluted
-

tubule. HCO 3 cannot directly cross the apical membrane of proximal convoluted tubule cells.
+

Instead, it combines with protons (H ) to produce CO 2 and H2O, both of which can diffuse
freely across the apical membrane into the tubule cells.
+

H + HCO 3 H2CO 3 H2O + CO 2

-

T herefore HCO 3 reabsorption is achieved by the movement of hydrogen ions out of tubule
+

cells into the filtrate. H ATPases (proton pumps) and Na /H antiporters on the apical
+

membrane of the tubule cells pump H ions out of the cells and into tubular filtrate, where it
-

combines with HCO 3 ions to form H2O + CO 2.

T he CO 2 diffuses into the tubule cells, where, in a reversal of the equation above, it reacts
with H2O (in the presence of the catalytic enzyme carbonic anhydrase) to make carbonic
acid, which dissociates to reform the bicarbonate ions and protons.
+

CO 2 + H2O H2CO 3 H + HCO 3

Between them, these reactions achieve two goals: HCO 3 ions are moved from the tubular fluid
+

into the tubule cells, and H is generated for transport into the tubular fluid.
-

T he reformed HCO 3 ions are transported across the basolateral membrane to the interstitial
fluid by Na+/HCO3- symporters, which transport three HCO3- ions out of the cell with every
one Na+ ion. T he bicarbonate ions move from the interstitial fluid to the bloodstream.
+

In addition, Na /K ATPases in the basolateral m embrane transport three Na ions out of the
+

tubule cell for every two K ions pumped in. T his helps maintains a low intracellular Na

concentration within the tubule cells, setting up the Na concentration gradient across the
+

apical membrane required to drive the H /Na antiporter.

+

For each H secreted into the renal tubule, one HCO 3 and one Na is reabsorbed.
Reabsorption of w ater
T he apical and basolateral plasma membranes of proximal convoluted tubule cells contain
many aquaporin-1 molecules. Aquaporins are water channels within the tubular cell
membrane, which serve to increase the permeability of the cell to water. Water can then pass
from the tubular fluid into the tubule cells, along the osmotic gradient. As solutes are
transported out of the tubular fluid and into the tubule cells, water is therefore able to follow
by osmosis via these aquaporin-1 channels.
As this reabsorption of water is not controlled by the proximal convoluted tubule directly, but is
a consequence of the active reabsorption of other solutes (primarily sodium ions), it is
sometimes referred to as obligatory water reabsorption.
-

2+

Reabsorption of Cl , K , Ca , and Mg

2+
+

As water is reabsorbed by osmosis (mainly driven by the reabsorption of Na ions) the

concentration of the various ions that remain in the tubular filtrate increases. T his increase in
concentration establishes a concentration gradient, favoring diffusion out of the tubular fluid.
As a result, the ions are drawn into the interstitial fluid by passive transport via transcellular
and paracellular routes.
-

T he diffusion of Cl ions into the interstitial fluid results in an increase in negative charge
within the interstitial fluid relative to the tubular fluid. T his establishes an electrical gradient,
+

2+

2+

giving further impetus to the passive diffusion of cations (K , Ca , and Mg ) out of the
tubular fluid.
Reabsorption of urea
Urea is reabsorbed from the tubular fluid by passive paracellular diffusion driven by an
electrochemical gradient. Some may also be reabsorbed by transcellular facilitated diffusion.

Reabsorption of small proteins

Small proteins are reabsorbed by endocytosis at the apical membrane of tubule cells, and
are digested into amino acids within these cells, for transportation across the basolateral
membrane by facilitated diffusion.

2-

Reabsorption of phosphate (HPO 4 )

Approximately 85% of phosphate in the tubular fluid is reabsorbed in the proximal convoluted
+

2-

tubule. It is transported into the cell by way of a Na /HPO 4 symporter present on the apical
membrane of the cell. T he phosphate ions are transported across the cell, whereby they leave
through the basolateral membrane into the blood vessel by an unknown method of diffusion.
2-

T he reabsorption of HPO 4 in the proximal convoluted tubule is inhibited by parathyroid

hormone, resulting in the excretion of phosphate and a net loss in plasma phosphate
concentration.
Secretion of ammonia
+

Ammonia is filtered out of the blood at the glomerulus in the form of ammonium ions (NH4 )
as a result of the deamination of amino acids. T hese ammonium ions are also secreted into
the tubular fluid from the tubule cells of the proximal convoluted tubule.
T he secretion of ammonium ions occurs in these cells as a result of the deamination of the
+

amino acid glutamine. NH4 then enters the proximal tubule cells from the peritubular
capillaries. T he metabolism of glutamine ultimately releases ammonia (NH3) and bicarbonate
-

(HCO 3 ). T he NH3 rapidly reacts with H ions to form NH4 .

+

T he Na /H antiporters will accept an NH4 ion in place of an H ion; therefore NH4 can be
+

secreted into the tubular fluid in exchange for Na .

-

T he HCO 3 produced in the deamination of glutamine is transported into the interstitial fluid
+

via secondary active transport with Na .

REABSORPTION AND SECRETION IN THE LOOP OF HENLE

By the time the tubular filtrate reaches the loop of Henle almost all glucose, amino acids, and a significant
proportion of ions and water have already been reabsorbed. T herefore the rate at which the filtrate moves is
considerably slower (40 - 45 ml/min).
DESCENDING LIMB

Reabsorption of w ater
T he cells lining the descending limb of the loop of Henle have many aquaporin-1 water
channels, increasing its permeability to water. Water undergoes obligatory reabsorption by
osmosis.

ASCENDING LIMB

T he ascending limb of the loop of Henle does not contain aquaporin-1 water channels and therefore the
reabsorption of water is greatly reduced. Solute reabsorption here occurs independently of water
reabsorption. Due to the continued reabsorption of ions, but not water, the osmolarity of the tubular fluid
progressively decreases towards the distal convoluted tubule.
T he reabsorption of similar ions occurs by two main mechanisms:
+

Reabsorption of Na , K , and Cl
+

Na /K /2Cl symporters that span the apical plasma membranes of the tubule cells, move
+

Na , K and 2 Cl ions from the tubular fluid into the cells of the thick ascending limb. Once
+

inside, the cells, Na , Cl , and K meet the following fates:

+

Na is actively transported into the interstitial fluid at the basolateral membrane by

+

Na /K ATPases, and ultimately diffuses into the vasa recta.

-

Cl diffuses out into the interstitial fluid, through leakage channels in the basolateral
membrane.
+

K leaves by way of leakage channels, the majority of which are located on the apical
+

membrane, therefore, K diffuses down its concentration gradient back into the tubular
fluid.
+

2+

Reabsorption of Na , K , Ca , and Mg

2+

T he leakage of K ions back into the tubular fluid results in the build up of positive charge
within the tubular fluid (and a relative negative charge within the interstitial fluid). T his
generates an electrical gradient which draws the positively-charged ions into the interstitial
fluid by passive paracellular or passive transcellular transport.

REABSORPTION AND SECRETION IN THE DISTAL CONVOLUTED TUBULE AND COLLECTING

DUCT
T he majority of filtrate has been reabsorbed prior to the distal convoluted tubule (80%), therefore the rate at
which it passes though decreases to 25 ml/min.
EARLY DISTAL CONVOLUTED TUBULE

Reabsorption of w ater
Water is reabsorbed in the distal convoluted tubule through aquaporin-1 water channels,
undergoing obligatory reabsorption by osmosis.

Reabsorption of Na and Cl
+

Na /Cl symporters in the apical membrane of cells lining the early distal convoluted tubule
+

reabsorb Na and Cl simultaneously into the tubule cell.

+

Na is then actively transported into the interstitial fluid via Na /K ATPases.

Cl passes through the Cl leakage channels into the interstitial fl uid, prior to diffusing into the
vasa recta.
Reabsorption of Ca

2+

T he apical membrane has Ca

2+
+

channels which allow Ca

the basolateral membrane, Na /Ca

ions move into the cell. Ca
paracellular transport.

2+

2+

2+

antiporters move Ca

2+

to diffuse into the tubule cells. On

into the interstitial fluid, as Na

can also diffuse into the interstitial fluid via passive

T he amount of calcium in the body can be partially regulated by the action of parathyroid
hormones on the distal convoluted tubule: parathyroid hormone stimulates reabsorption of
2+

Ca .
LATE DISTAL CONVOLUTED TUBULE AND COLLECTING DUCT

Reabsorption of w ater
T he remaining 15% of water in tubular filtrate within the late distal convoluted tubule and
collecting duct may or may not be reabsorbed: the amount of water reabsorbed in this region
is dependent on the bodys needs and is termed facultative water reabsorption. T he volume
of water reabsorption is controlled by antidiuretic hormone, which determines the
permeability of the collecting ducts to water by stimulating the insertion of additional
aquaporin-2 water channels into the apical membrane.
Reabsorption of Na

Na diffuses down its electrochemical gradient, through Na leakage channels in the apical
membrane of principal cells of the late distal convoluted tubule and collecting ducts.
+

Na is then pumped out into the interstitial fluid via Na /K ATPases.

+

Reabsorption of K and HCO 3

Intercalated cells of the late distal convoluted tubule and collecting ducts are responsible for a
+

small amount of K reabsorption, through the action of apical H /K ATPase.

-

HCO 3 can be reabsorbed into the tubule cells via the same process involved in the
-

reabsorption of HCO 3 in the proximal convoluted tubule. However, HCO 3 is transported out of
-

the tubule cells across the basolateral membrane via HCO 3 /Cl antiporters.
Reabsorption of urea
Urea is reabsorbed by facilitated diffusion, driven by concentration gradients in the deep
medullary region. Urea recycling occurs, promoting the creation of a medullary osmotic
gradient.

Secretion of K

K ions are actively pumped into principal cells of the late distal convoluted tubule and
+

collecting ducts from the interstitial fluid by Na /K ATPases located on the basolateral
+

membrane of these cells. K ions then diffuse into the tubular fluid through leakage channels
in the apical plasma membrane.
Secretion of H

T he intercalated cells found in the late distal convoluted tubule and collecting ducts are
+

responsible for H ion secretion. H ions are secreted into the filtrate by H /K ATPases,
located on the apical surface of the tubule cells.

SUMMARY OF TUBULAR REABSORPTION AND SECRETION

T he table below summarizes the substances reabsorbed and secreted in each section of the renal tubule and
the mechanisms that permit these actions.
GLUCOSE, AMINO ACIDS, AND PROTEINS
Proximal tubule

Loop of Henle

Distal tubule

Collecting duct

None

None

Distal tubule

Collecting duct

None

Basolateral membrane
Secondary active transport

Reabsorption
Apical membrane
None
Secondary active transport
+

(Na symporters)
Endocytosis (proteins)
Basolateral membrane
Facilitated diffusion
(carrier proteins)
-

HCO 3 (BICARBONATE)
Proximal tubule

Loop of Henle

Reabsorption
Basolateral membrane
None
Secondary active transport
+

(Na /HCO 3 symporters)

(HCO 3 /Cl antiporter)

Apical membrane

Na (SODIUM)
Proximal tubule

Loop of Henle (thick

ascending limb)

Distal tubule

Collecting duct

Reabsorption
Apical membrane
Passive solute diffusion
and secondary active
+

transport (Na symporters)

Apical membrane
Apical membrane
Apical membrane
Secondary active transport Secondary active transport Passive solute diffusion
+

(Na /K /2Cl symporters)

(Na /Cl symporters)

(Na leakage channels)

Basolateral membrane
Primary active transport
+

(Na /K AT Pase)

Basolateral membrane
Primary active transport
+

(Na /K AT Pase)

Basolateral membrane
Primary active transport
+

(Na /K AT Pase)

Basolateral membrane
Primary active transport
+

(Na /K AT Pase)
+

K (POTASSIUM)
Proximal tubule

Loop of Henle (thick

ascending limb)

Distal tubule

Collecting duct

Reabsorption
Passive solute diffusion

Apical membrane

Apical membrane
None
Secondary active transport
+

H /K AT Pase

(Na /K /2 Cl symporters)

Secretion
None

Basolateral membrane
+

Diffusion (K leakage
channels)

Basolateral membrane
Primary active transport
+

(Na /K AT Pase)

Basolateral membrane
Primary active transport
+

(Na /K AT Pase)
Facilitated diffusion
(leakage channels)
Apical membrane
+

Diffusion (K leakage
channels)
WATER
Proximal tubule

Loop of Henle
(descending limb)

Distal tubule

Collecting duct

Osmosis (aquaporin-1
water channels)

Osmosis (aquaporin-1
water channels)

Osmosis (aquaporin-2
water channels)

Loop of Henle

Distal tubule

Collecting duct

None

Facilitated diffusion

Facilitated diffusion

Facilitated diffusion

None

None

Loop of Henle

Distal tubule

Collecting duct

Reabsorption
Osmosis (aquaporin-1
water channels)
UREA
Proximal tubule
Reabsorption
Facilitated diffusion
Secretion
None
-

Cl (CHLORIDE)
Proximal tubule
Reabsorption
Passive solute diffusion
(paracellular)

Apical membrane
Basolateral membrane
Apical membrane
Secondary active transport Secondary active transport Secondary active transport
+

(Na /K /2Cl symporters)

(Na /Cl symporters)

(HCO 3 /Cl antiporter)

Basolateral membrane
-

Ca

2+

Basolateral membrane
-

Diffusion (Cl leakage

channels)

Diffusion (Cl leakage

channels)

Loop of Henle (thick

ascending limb)

Distal tubule

Passive solute diffusion

Apical membrane

(CALCIUM)

Proximal tubule

Collecting duct

Reabsorption
Passive solute diffusion

Ca AT Pase and Ca
channels

None
2+

Basolateral membrane
+

Na /Ca

Mg

2+

2+

antiporter

(MAGNESIUM)

Proximal tubule

Loop of Henle (thick

ascending limb)

Distal tubule

Collecting duct

Passive solute diffusion

None

None

Loop of Henle

Distal tubule

Collecting duct

None

None

Distal tubule

Collecting duct

Reabsorption
Passive solute diffusion
2-

HPO 4

(PHOSPHATE)

Proximal tubule
Reabsorption

Apical membrane
None
Secondary active transport
+

(Na /phosphate
symporters)
Basolateral membrane
Diffusion
+

NH4 (AMMONIUM)
Proximal tubule

Loop of Henle

Secretion
Secondary active transport None
+

(Na /H antiporters)

Secondary active transport None

(antiporters)

H (PROTONS)
Proximal tubule
Secretion

Loop of Henle

Distal tubule

Collecting duct

Apical membrane
None
Secondary active transport
+

(Na /H antiporters)

None

Apical membrane
Secondary active transport
+

(Na /H antiporters)
Basolateral membrane
Primary active transport
+

(H /K AT Pases)