Tubular Processing of the Glomerular Filtrate pdf - The Body Fluids and Kidneys

stances, such as glucose and amino acids, are almost completely reabsorbed

. Some sub-

Second, unlike glomerular filtration, which is relatively nonselective (that is,

glomerular filtration are closely coordinated, so that large fluctuations in urinary

remained constant. In reality, however, changes in tubular reabsorption and

reabsorption, from 178.5 to 160.7 L/day, would increase urine volume from 1.5

large change in urinary excretion. For example, a 10 per cent decrease in tubular

ative to urinary excretion for many substances. This means that a small change

From Table 27–1, two things are immediately apparent. First, the processes of

glucose reabsorption is also 180 g/day.

Because virtually none of the filtered glucose is normally excreted, the rate of

1 g/L, or 180 g/day.

amount of glucose filtered each day is about 180 L/day

to plasma proteins. For example, if plasma glucose concentration is 1 g/L, the

This calculation assumes that the substance is freely filtered and not bound

Filtration

The rate at which each of these substances is filtered is calculated as

tered in the kidneys and reabsorbed at variable rates.

Table 27–1 shows the renal handling of several substances that are all freely fil-

Tubular Reabsorption Is Selective and Quantitatively Large

few other substances that appear in the urine.

tion accounts for significant amounts of potassium ions, hydrogen ions, and a

does secretion in determining the final urinary excretion rate. However, secre-

For many substances, reabsorption plays a much more important role than

Tubular secretion

Tubular reabsorption

reabsorption, and tubular secretion—as follows:

represent the sum of three basic renal processes—glomerular filtration, tubular

lumen. Eventually, the urine that is formed and all the substances in the urine

back into the blood, whereas others are secreted from the blood into the tubular

Along this course, some substances are selectively reabsorbed from the tubules

before it is excreted as urine.

, and, finally,

, the

proximal tubule

As the glomerular filtrate enters the renal tubules,

by the Renal Tubules

Reabsorption and Secretion

Glomerular Filtrate

II. Tubular Processing of the

Urine Formation by the Kidneys:

327

it flows sequentially through the successive parts of
the tubule—the

loop of Henle,

the distal tubule

collecting tubule

the collecting duct—

Urinary excretion

= Glomerular filtration -

= Glomerular filtration rate ¥ Plasma concentration

glomerular filtration and tubular reabsorption are quantitatively very large rel-

in glomerular filtration or tubular reabsorption can potentially cause a relatively

to 19.3 L/day (almost a 13-fold increase) if the glomerular filtration rate (GFR)

excretion are avoided.

essentially all solutes in the plasma are filtered except the plasma proteins or
substances bound to them), tubular reabsorption is highly selective

the tubule, water is always reabsorbed by a passive

secondary active transport. Although solutes can be

. Reabsorp-

an energy source, such as that due to an ion gradient,

the renal tubule. Transport that is coupled

ATPase pump that functions throughout most parts of

. A good example of this is the sodium-potassium

triphosphate (ATP), is termed

an energy source, such as the hydrolysis of adenosine

from metabolism. Transport that is coupled directly to

Active Transport

and colloid osmotic forces. The peritubular capillaries

bulk flow

tubular epithelial cells into the interstitial fluid, water

). Then, after absorption across the

across other membranes of the body. For instance,

includes a series of transport steps. Reabsorption

(Figure 27–1). Thus, reabsorption of water and solutes

For a substance to be reabsorbed, it must first be trans-

Tubular Reabsorption

rates.

composition of body fluids. In this chapter, we discuss

excretion of solutes independently of one another, a

reabsorb different substances, the kidneys regulate the

Therefore, by controlling the rate at which they

tubules and excreted in relatively large amounts.

nine, conversely, are poorly reabsorbed from the

body. Certain waste products, such as urea and creati-

excretion are variable, depending on the needs of the

reabsorbed, but their rates of reabsorption and urinary

as sodium, chloride, and bicarbonate, are also highly

essentially zero. Many of the ions in the plasma, such

from the tubules, so that the urinary excretion rate is

328

Unit V

The Body Fluids and Kidneys

capability that is essential for precise control of the

the mechanisms that allow the kidneys to selectively
reabsorb or secrete different substances at variable

Includes Passive and
Active Mechanisms

ported (1) across the tubular epithelial membranes
into the renal interstitial fluid and then (2) through the
peritubular capillary membrane back into the blood

across the tubular epithelium into the interstitial fluid
includes active or passive transport by way of the same
basic mechanisms discussed in Chapter 4 for transport

water and solutes can be transported either through
the cell membranes themselves (transcellular route) or
through the junctional spaces between the cells (para-
cellular route

and solutes are transported the rest of the way through
the peritubular capillary walls into the blood by ultra-
filtration (

) that is mediated by hydrostatic

behave very much like the venous ends of most other
capillaries because there is a net reabsorptive force
that moves the fluid and solutes from the interstitium
into the blood.

Active transport can move a solute against an elec-
trochemical gradient and requires energy derived

primary active trans-

port

indirectly to

is referred to as secondary active transport
tion of glucose by the renal tubule is an example of

reabsorbed by active and/or passive mechanisms by

Table 27–1

Urea (g/day)

46.8

23.4

Potassium (mEq/day)

756

664

87.8

Chloride (mEq/day)

19,440

19,260

180

99.1

Sodium (mEq/day)

25,560

25,410

150

99.4

Bicarbonate (mEq/day)

4,320

4,318

Glucose (g/day)

180

100

Amount Filtered

Amount Reabsorbed

Amount Excreted

% of Filtered Load Reabsorbed

Filtration, Reabsorption, and Excretion Rates of Different Substances by the Kidneys

>99.9

Creatinine (g/day)

1.8

ATP

(diffusion)

FILTRATION

Transcellular

Tubular

Peritubular

capillary

cells

Lumen

Paracellular
path

path

Solutes

EXCRETION

REABSORPTION

Bulk

flow

Blood

Active

Passive

Osmosis

through the cells and between the tubular cells by osmosis. Trans-

the cells (paracellular route) by diffusion. Water is transported

cellular route) by passive diffusion or active transport, or between

back into the blood. Solutes are transported through the cells (trans-

across the tubular epithelial cells, through the renal interstitium, and

Figure 27–1

Reabsorption of filtered water and solutes from the tubular lumen

port of water and solutes from the interstitial fluid into the peri-
tubular capillaries occurs by ultrafiltration (bulk flow).

membrane. As one of the substances (for instance,

In secondary active transport, two or more substances

Secondary Active Reabsorption Through the Tubular Membrane.

osmotic pressure gradients.

peritubular capillaries by ultrafiltration, a passive

3. Sodium, water, and other substances are

by the sodium-potassium ATPase pump.

2. Sodium is transported across the basolateral

basolateral side of the membrane.

by the sodium-potassium ATPase pump on the

1. Sodium diffuses across the luminal membrane

Thus, the net reabsorption of sodium ions from the

as discussed later.

of other substances, such as glucose and amino acids,

the membrane into the cell. These sodium carrier pro-

facilitated diffusion

cell, providing

the surface area about 20-fold. There are also sodium

the cell. In the proximal tubule, there is an extensive

In certain parts of the nephron, there are additional

potassium ATPase occurs in most parts of the tubule.

high (140 mEq/L). (2) The negative,

into the cell, for two reasons: (1) There is a concen-

membrane of the cell, from the tubular lumen

70 millivolts within the cell. This pumping of

cell. The operation of this ion pump maintains low

cell into the interstitium. At the same time, potassium

ATPase system that hydrolyzes ATP and uses the

proximal tubular membrane, as shown in Figure 27–2.

calcium ATPase

, and

potassium ATPase

hydrogen ATPase

potassium ATPase

moves solutes across the cell membranes. The primary

way of membrane-bound ATPase; the ATPase is also

active transport comes from the hydrolysis of ATP by

The energy for this

against an electrochemical gradient.

primary active transport is that it can move solutes

Linked to Hydrolysis of ATP

Primary Active Transport Through the Tubular Membrane Is

between the cells.

ride ions, are carried with the reabsorbed fluid

the water, especially potassium, magnesium, and chlo-

paracellular pathway, and substances dissolved in

proximal tubule, water is also reabsorbed across the

pathway. In some nephron segments, especially the

moves through both routes, although most of the

. Sodium is a substance that

paracellular pathway

pathway

epithelial cells of the tubule. Solutes can be reabsorbed

. Lateral intercellular

Renal tubular cells, like other epithelial cells, are

Solutes Can Be Transported Through Epithelial Cells or Between

, which

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

329

(nonactive) physical mechanism called osmosis
means water diffusion from a region of low solute con-
centration (high water concentration) to one of high
solute concentration (low water concentration).

Cells.

held together by tight junctions
spaces lie behind the tight junctions and separate the

or secreted across the cells by way of the transcellular

or between the cells by moving across the

tight junctions and intercellular spaces by way of
the

sodium is transported through the transcellular

. The special importance of

a component of the carrier mechanism that binds and

active transporters that are known include sodium-

, hydrogen-

A good example of a primary active transport

system is the reabsorption of sodium ions across the

On the basolateral sides of the tubular epithelial cell,
the cell membrane has an extensive sodium-potassium

released energy to transport sodium ions out of the

is transported from the interstitium to the inside of the

intracellular sodium and high intracellular potassium
concentrations and creates a net negative charge of
about

sodium out of the cell across the basolateral membrane
of the cell favors passive diffusion of sodium across the
luminal

tration gradient favoring sodium diffusion into the cell
because intracellular sodium concentration is low
(12 mEq/L) and tubular fluid sodium concentration is

-70-millivolt,

intracellular potential attracts the positive sodium ions
from the tubular lumen into the cell.

Active reabsorption of sodium by sodium-

provisions for moving large amounts of sodium into

brush border on the luminal side of the membrane
(the side that faces the tubular lumen) that multiplies

carrier proteins that bind sodium ions on the luminal
surface of the membrane and release them inside the

of sodium through

teins are also important for secondary active transport

tubular lumen back into the blood involves at least
three steps:

(also called the apical membrane) into the cell
down an electrochemical gradient established

membrane against an electrochemical gradient

reabsorbed from the interstitial fluid into the

process driven by the hydrostatic and colloid

interact with a specific membrane protein (a carrier
molecule) and are transported together across the

sodium) diffuses down its electrochemical gradient,
the energy released is used to drive another substance

ATP

Tubular

Tight junction

Tubular

Peritubular

capillary

epithelial cells

Basement

membrane

Intercellular space

Interstitial

fluid

lumen

(

3 mv)

(

70 mV)

Brush border
(luminal
membrane)

Basal
channels

the tubular lumen into the cell through the brush border.

electrical potential. The low intracellular sodium concentration and

the interior of the cell across the basolateral membrane, creating a

epithelial cell. The sodium-potassium pump transports sodium from

Figure 27–2

Basic mechanism for active transport of sodium through the tubular

low intracellular sodium concentration and a negative intracellular

the negative electrical potential cause sodium ions to diffuse from

port process.

. This limit is due to saturation

the solute can be transported, often referred to as the

sorbed or secreted, there is a limit to the rate at which

For most substances that are actively reab-

Transport Maximum for Substances That Are Actively Reab-

Because pinocytosis requires energy, it is considered a

stituent amino acids, which are reabsorbed through the

inside the cell, the protein is digested into its con-

and a vesicle is formed containing the protein. Once

attaches to the brush border of the luminal membrane,

. In this process, the protein

proximal tubule, reabsorb large molecules such as

Some parts of the tubule, especially the

Pinocytosis—An Active Transport Mechanism for Reabsorption

in the opposite direction into the tubular lumen. The

interior of the cell, hydrogen ions are forced outward

of the luminal membrane. As sodium is carried to the

by sodium-hydrogen counter-transport. This transport

the proximal tubule. In this case, sodium entry into the

27–3, is the active secretion of hydrogen ions coupled

One example of counter-transport, shown in Figure

movement of one of the substances (for example,

transport, the energy liberated from the downhill

of the substance with sodium ions. In counter-

counter-transport

active transport. This often involves

Secondary Active Secretion into the Tubules.

capillaries.

occurs at the basolateral membrane, and passive

luminal membrane, but passive facilitated diffusion

reabsorption, secondary active transport occurs at the

the reabsorption process may be passive. For glucose

ary active transport, even though other steps in

to undergo “active” transport when at least one of the

gradient, but it is “secondary” to primary active trans-

is referred to as “secondary active transport” because

luminal membrane. Thus, this reabsorption of glucose

maintained, and it is this downhill diffusion of sodium

this pump, an electrochemical gradient for facilitated

basolateral membrane. Because of the activity of

primary active sodium-potassium ATPase pump in the

of glucose depends on energy expended by the

gradient does not directly use ATP, the reabsorption

tated diffusion, driven by the high glucose and amino

lumen. After entry into the cell, glucose and amino

or a glucose molecule at the same time. These trans-

both instances, a specific carrier protein in the brush

glucose and amino acids in the proximal tubule. In

Figure 27–3 shows secondary active transport of

energy phosphate sources. Rather, the direct source of

require energy directly from ATP or from other high-

gradient. Thus, secondary active transport does not

(for instance, glucose) against its electrochemical

330

Unit V

The Body Fluids and Kidneys

the energy is that liberated by the simultaneous facil-
itated diffusion of another transported substance
down its own electrochemical gradient.

border combines with a sodium ion and an amino acid

port mechanisms are so efficient that they remove vir-
tually all the glucose and amino acids from the tubular

acids exit across the basolateral membranes by facili-

acid concentrations in the cell.

Although transport of glucose against a chemical

diffusion of sodium across the luminal membrane is

to the interior of the cell that provides the energy for

the simultaneous uphill transport of glucose across the

glucose itself is reabsorbed uphill against a chemical

port of sodium.

Another important point is that a substance is said

steps in the reabsorption involves primary or second-

uptake by bulk flow occurs at the peritubular

Some sub-

stances are secreted into the tubules by secondary

sodium ions) enables uphill movement of a second
substance in the opposite direction.

to sodium reabsorption in the luminal membrane of

cell is coupled with hydrogen extrusion from the cell

is mediated by a specific protein in the brush border

basic principles of primary and secondary active trans-
port are discussed in additional detail in Chapter 4.

of Proteins.

proteins by pinocytosis

and this portion of the membrane then invaginates to
the interior of the cell until it is completely pinched off

basolateral membrane into the interstitial fluid.

form of active transport.

sorbed.

transport maximum
of the specific transport systems involved when the
amount of solute delivered to the tubule (referred to
as tubular load) exceeds the capacity of the carrier
proteins and specific enzymes involved in the trans-

Amino acids

ATP

Tubular

cells

70 mV

Co-transport

Interstitial

fluid

lumen

70 mV

Counter-transport

Glucose

membrane, provides the energy for transport of the hydrogen ions

movement of sodium ions into the cell, down an electrochemical gra-

counter-transport

facilitated diffusion through the basolateral membranes. The lower

through the apical side of the tubular epithelial cells, followed by

Mechanisms of secondary active transport. The upper cell shows the

Figure 27–3

co-transport of glucose and amino acids along with sodium ions

cell shows the

of hydrogen ions from the interior

of the cell across the apical membrane and into the tubular lumen;

dient established by the sodium-potassium pump on the basolateral

from inside the cell into the tubular lumen.

resulting in urinary glucose excretion. Some of the

glucose may rise to high levels, causing the filtered load

diabetes mellitus,

However, in uncontrolled

glucose in the urine, even after eating a meal.

The plasma glucose of a healthy person almost

sorb glucose.

nephrons have reached their maximal capacity to reab-

is normally about 375 mg/min, is reached when all

The overall transport maximum for the kidneys, which

glucose, and some of the nephrons excrete glucose

. One reason for the difference between

reached

for glucose.

This point is termed the

small amount of glucose begins to appear in the urine.

increasing the filtered load to about 250 mg/min, a

glucose in the urine. However, when the plasma con-

is at its normal level, 125 mg/min, there is no loss of

loss in the urine. Note that when the plasma glucose

transport maximum for glucose, and rate of glucose

centration of glucose, filtered load of glucose, tubular

Figure 27–4 shows the relation between plasma con-

passes into the urine.

min, the excess glucose filtered is not reabsorbed and

1 mg/ml). With large

glucose averages about 375 mg/min, whereas the fil-

In the adult human, the transport maximum for

tion of glucose does occur.

ity of the tubules to reabsorb glucose, urinary excre-

However, when the filtered load exceeds the capabil-

tered glucose is reabsorbed in the proximal tubule.

is a good example. Normally, measurable glucose does

The glucose transport system in the proximal tubule

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

331

not appear in the urine because essentially all the fil-

tered load of glucose is only about 125 mg/min (GFR
¥ plasma glucose = 125 ml/min ¥
increases in GFR and/or plasma glucose concentration
that increase the filtered load of glucose above 375 mg/

concentration is 100 mg/100 mL and the filtered load

centration of glucose rises above about 200 mg/100 ml,

threshold

Note

that this appearance of glucose in the urine (at the
threshold) occurs before the transport maximum is

threshold and transport maximum is that not all

nephrons have the same transport maximum for

before others have reached their transport maximum.

never becomes high enough to cause excretion of

plasma

of glucose to exceed the transport maximum and

important transport maximums for substances actively
reabsorbed by the tubules are as follows:

Lactate

75 mg/min

Urate

15 mg/min

Amino acids

1.5 mM/min

Sulfate

0.06 mM/min

Phosphate

0.10 mM/min

Glucose

375 mg/min

Substance

Transport Maximum

Transport Maximums for Substances That Are Actively

Plasma protein

30 mg/min

Secreted.

Substances that are actively secreted also

exhibit transport maximums as follows:

Creatinine

16 mg/min

Substance

Transport Maximum

the basolateral sodium-potassium ATPase pump is

proximal tubules, the maximum transport capacity of

maximum rate of active transport. For example, in the

sodium reabsorption in the proximal tubule. The

. An example is

Some actively transported substances also have char-

in turn depends on the tubular flow rate.

and the time that the substance is in the tubule, which

remains within the tubule. Transport of this type is

the permeability of the membrane for the substance,

diffusion of the substance across the membrane, (2)

factors, such as (1) the electrochemical gradient for

the tubular load increases.

The reason that actively trans-

Transport Maximum.

Substances That Are Actively Transported but Do Not Exhibit a

Para-aminohippuric acid

80 mg/min

ported solutes often exhibit a transport maximum is
that the transport carrier system becomes saturated as

Substances that are passively

reabsorbed do not demonstrate a transport maximum
because their rate of transport is determined by other

and (3) the time that the fluid containing the substance

referred to as gradient-time transport because the rate
of transport depends on the electrochemical gradient

acteristics of gradient-time transport

main reason that sodium transport in the proximal
tubule does not exhibit a transport maximum is that
other factors limit the reabsorption rate besides the

usually far greater than the actual rate of net sodium

Transport

800

Glucose filtered load, reabsorption

or excretion (mg/min)

Plasma glucose concentration

(mg/100 ml)

700

600

500

400

300

200

100

Filtered

load

Filtered

load

900

800

700

600

500

400

300

200

100

Normal

Threshold

maximum

Reabsorption

Excretion

begins to be excreted in the urine.

glucose can be reabsorbed from the tubules. The

in the urine. The

reabsorption by the renal tubules, and the rate of glucose excretion

Relations among the filtered load of glucose, the rate of glucose

Figure 27–4

transport maximum is the maximum rate at which

threshold for

glucose refers to the filtered load of glucose at which glucose first

(Figure 27–5). Thus, the active reabsorption of sodium

reabsorbed from the tubule by osmosis, thereby con-

. Additional reab-

paracellular pathway

fluid. This causes chloride ions to diffuse

negatively charged, compared with the interstitial

tials. That is, transport of positively charged sodium

epithelial cell, negative ions such as chloride are trans-

When sodium is reabsorbed through the tubular

Reabsorption of Chloride, Urea, and

low, depending on the presence or absence of ADH.

lecting tubules, and collecting ducts—can be high or

the last parts of the tubules—the distal tubules, col-

despite a large osmotic gradient. Water permeability in

always low, so that almost no water is reabsorbed,

the ascending loop of Henle, water permeability is

and water is reabsorbed as rapidly as the solutes. In

proximal tubule, the water permeability is always high,

water, no matter how large the osmotic gradient. In the

Thus, water movement across the tubular epithe-

distal and collecting tubules, as discussed later.

membrane by osmosis. However, antidiuretic hormone

Therefore, water cannot move easily across the tubular

also have a greatly decreased membrane surface area.

meable to water and solutes, and the epithelial cells

lecting tubule, the tight junctions become far less per-

In the more distal parts of the nephron, beginning

of water and many other solutes.

coupled to sodium reabsorption, changes in sodium

reabsorption of water, organic solutes, and ions is

. And because the

osmosis, it can also carry with it some of the solutes, a

calcium, and magnesium.

most ions, such as sodium, chloride, potassium,

proximal tubules, which have a high permeability for

of water and small ions. This is especially true in the

name would imply, and they allow significant diffusion

The reason for this, as already discussed, is that the

epithelial cells as well as through the cells themselves.

tubular membrane.

proximal tubule, are highly permeable to water, and

tium. Some parts of the renal tubule, especially the

ported, from the tubular lumen to the renal intersti-

while increasing in the renal interstitium. This creates

either primary or secondary active transport, their

When solutes are transported out of the tubule by

to Sodium Reabsorption

by Osmosis Is Coupled Mainly

Passive Water Reabsorption

in response to certain hormones, such as

Furthermore, this transport maximum can be increased

similar to that for other actively transported substances.

much smaller amounts of sodium. In these segments,

In the more distal parts of the nephron, the epithe-

the proximal tubules.

slower the flow rate of tubular fluid, the greater the

mal tubules, the greater its reabsorption rate. Also, the

maximum transport characteristics. This means that

the peritubular capillaries. Therefore, sodium trans-

interstitial physical forces, which determine the rate of

leak occurs depends on several factors, including (1)

epithelial tight junctions. The rate at which this back-

reabsorption. One of the reasons for this is that a sig-

332

Unit V

The Body Fluids and Kidneys

nificant amount of sodium transported out of the
cell leaks back into the tubular lumen through the

the permeability of the tight junctions and (2) the

bulk flow reabsorption from the interstitial fluid into

port in the proximal tubules obeys mainly gradient-
time transport principles rather than tubular

the greater the concentration of sodium in the proxi-

percentage of sodium that can be reabsorbed from

lial cells have much tighter junctions and transport

sodium reabsorption exhibits a transport maximum

aldosterone.

concentrations tend to decrease inside the tubule

a concentration difference that causes osmosis of
water in the same direction that the solutes are trans-

water reabsorption occurs so rapidly that there is only
a small concentration gradient for solutes across the

A large part of the osmotic flow of water occurs

through the so-called tight junctions between the

junctions between the cells are not as tight as their

water and a smaller but significant permeability to

As water moves across the tight junctions by

process referred to as solvent drag

reabsorption significantly influence the reabsorption

in the loop of Henle and extending through the col-

(ADH) greatly increases the water permeability in the

lium can occur only if the membrane is permeable to

Other Solutes by Passive Diffusion

ported along with sodium because of electrical poten-

ions out of the lumen leaves the inside of the lumen

passively

through the
sorption of chloride ions occurs because of a chloride
concentration gradient that develops when water is

centrating the chloride ions in the tubular lumen

is closely coupled to the passive reabsorption of chlo-
ride by way of an electrical potential and a chloride
concentration gradient.

Passive Cl

reabsorption

Passive urea

reabsorption

O reabsorption

Lumen
negative
potential

Luminal Cl

concentration

Luminal Cl

concentration

Luminal
urea
concentration

Mechanisms by which water, chloride, and urea reabsorption are

Figure 27–5

coupled with sodium reabsorption.

chloride (around 140 mEq/L) compared with the early

mainly with chloride ions. The second half of the prox-

to be reabsorbed. Instead, sodium is now reabsorbed

proximal tubule, little glucose and amino acids remain

acids, and other solutes. But in the second half of the

reabsorbed by co-transport along with glucose, amino

In the first half of the proximal tubule, sodium is

proximal tubular membrane.

chloride, and water throughout the proximal tubule,

Although the sodium-potassium ATPase pump pro-

, which then dissociates

to form H

in Chapter 30, the secretion of hydrogen ions into the

tubular lumen, especially hydrogen ions. As discussed

mechanisms, which reabsorb

counter-transport

such as amino acids and glucose. The remainder of the

The extensive membrane surface of the epithelial

other substances.

extensive labyrinth of intercellular and basal channels,

active transport processes. In addition, the proximal

acteristics, as shown in Figure 27–6. The proximal

The high capacity of the proximal tubule

Proximal Tubules Have a High Capacity for Active and Passive

different physiologic conditions, as discussed later.

These percentages can be increased or decreased in

tubule before the filtrate reaches the loops of Henle.

Normally, about 65 per cent of the filtered load of

Proximal Tubular Reabsorption

subsequent chapters, we discuss the reabsorption and

to the reabsorption of sodium, chloride, and water. In

most important are discussed, especially as they relate

perform their specific excretory functions. Only the

mind, we can now discuss the different characteristics

the tubular membrane. With these generalizations in

In the previous sections, we discussed the basic princi-

the Nephron

Along Different Parts of

Reabsorption and Secretion

the glomerulus is excreted in the urine.

sorbed, so that virtually all the creatinine filtered by

impermeant to the tubular membrane. Therefore,

Another waste product of metabolism, creatinine, is

passes into the urine, allowing the kidneys to excrete

sorbed from the tubules. The remainder of the urea

. Yet only about one half of the urea

duct, passive urea reabsorption is facilitated by specific

nephron, especially the inner medullary collecting

the tubule as readily as water. In some parts of the

sorption of urea. However, urea does not permeate

in the tubular lumen increases (see Figure 27–5). This

coupled to sodium reabsorption), urea concentration

but to a much lesser extent than chloride ions. As

Urea is also passively reabsorbed from the tubule,

the luminal membrane.

active transport. The most important of the secondary

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

333

Chloride ions can also be reabsorbed by secondary

active transport processes for chloride reabsorption
involves co-transport of chloride with sodium across

water is reabsorbed from the tubules (by osmosis

creates a concentration gradient favoring the reab-

urea transporters
that is filtered by the glomerular capillaries is reab-

large amounts of this waste product of metabolism.

an even larger molecule than urea and is essentially

almost none of the creatinine that is filtered is reab-

ples by which water and solutes are transported across

of the individual tubular segments that enable them to

tubular transport functions that are quantitatively

secretion of other specific substances in different parts
of the tubular system.

sodium and water and a slightly lower percentage of
filtered chloride are reabsorbed by the proximal

Reabsorption.

for reabsorption results from its special cellular char-

tubule epithelial cells are highly metabolic and have
large numbers of mitochondria to support potent

tubular cells have an extensive brush border on the
luminal (apical) side of the membrane as well as an

all of which together provide an extensive membrane
surface area on the luminal and basolateral sides of the
epithelium for rapid transport of sodium ions and

brush border is also loaded with protein carrier mole-
cules that transport a large fraction of the sodium ions
across the luminal membrane linked by way of the co-
transport mechanism with multiple organic nutrients

sodium is transported from the tubular lumen into the
cell by
sodium while secreting other substances into the

tubular lumen is an important step in the removal of
bicarbonate ions from the tubule (by combining H

with the HCO

into H

O and CO

vides the major force for reabsorption of sodium,

there are some differences in the mechanisms by
which sodium and chloride are transported through
the luminal side of the early and late portions of the

imal tubule has a relatively high concentration of

Proximal tubule

65%

Isosmotic

, organic acids, bases

, Cl

, HCO

, K

O, glucose, amino acids

tubules also secrete organic acids, bases, and hydrogen ions into the

essentially all the filtered glucose and amino acids. The proximal

of the filtered sodium, chloride, bicarbonate, and potassium and

proximal tubule. The proximal tubules reabsorb about 65 per cent

Figure 27–6

Cellular ultrastructure and primary transport characteristics of the

tubular lumen.

The thin segment of the ascending limb has a much

also reabsorbed in the thick ascending loop of Henle.

ions, such as calcium, bicarbonate, and magnesium, are

thick ascending limb. Considerable amounts of other

are reabsorbed in the loop of Henle, mostly in the

the filtered loads of sodium, chloride, and potassium

and potassium (see Figure 27–8). About 25 per cent of

are capable of active reabsorption of sodium, chloride,

begins about halfway up the ascending limb, has thick

The thick segment of the loop of Henle, which

trating the urine.

water, a characteristic that is important for concen-

and the thick portions, is virtually impermeable to

ing limb. The ascending limb, including both the thin

Henle, and almost all of this occurs in the thin descend-

fusion of substances through its walls. About 20 per

most solutes, including urea and sodium. The function

The descending part of the thin segment is highly

levels of metabolic activity (Figure 27–8).

with no brush borders, few mitochondria, and minimal

their names imply, have thin epithelial membranes

The thin descending and thin ascending segments, as

thick ascending segment

, and the

, the

tinct segments: the

The loop of Henle consists of three functionally dis-

Loop of Henle

Solute and Water Transport in the

cussed later.

can be used to estimate the renal plasma flow, as dis-

the urine. For this reason, the rate of PAH clearance

can clear about 90 per cent of the PAH from the

PAH is secreted so rapidly that the average person

proximal tubule is para-aminohippuric acid (PAH).

and salicylates, the rapid clearance by the kidneys

blood. In the case of certain drugs, such as penicillin

In addition to the waste products of metabolism, the

the urine.

tubules, all combined, contribute to rapid excretion in

be rapidly removed from the body. The

. Many of these sub-

catecholamines

, and

oxalate

The proximal tubule is also an important site for secre-

Secretion of Organic Acids and Bases by the Proximal Tubule.

meability of this part of the nephron to water.

osmolarity, remains essentially the same all along the

tubule. The total solute concentration, as reflected by

nine, increase their concentration along the proximal

permeant and not actively reabsorbed, such as creati-

the proximal tubule. Other organic solutes that are less

much more avidly reabsorbed than water, so that their

such as glucose, amino acids, and bicarbonate, are

with sodium reabsorption. Certain organic solutes,

markedly along the proximal tubule, the

various solutes along the proximal tubule. Although

Figure

Concentrations of Solutes Along the Proximal Tubule.

the proximal tubule, the higher chloride concentration

higher concentration of chloride. In the second half of

proximal tubule, leaving behind a solution that has a

glucose, bicarbonate, and organic ions in the early

sodium is reabsorbed, it preferentially carries with it

proximal tubule (about 105 mEq/L) because when

334

Unit V

The Body Fluids and Kidneys

favors the diffusion of this ion from the tubule lumen
through the intercellular junctions into the renal inter-
stitial fluid.

27–7 summarizes the changes in concentrations of

the amount of sodium in the tubular fluid decreases

concentration

of sodium (and the total osmolarity) remains relatively
constant because water permeability of the proximal
tubules is so great that water reabsorption keeps pace

concentrations decrease markedly along the length of

proximal tubule because of the extremely high per-

tion of organic acids and bases such as bile salts,

, urate

stances are the end products of metabolism and must

secretion of

these substances into the proximal tubule plus filtra-
tion into the proximal tubule by the glomerular capil-
laries and the almost total lack of reabsorption by the

kidneys secrete many potentially harmful drugs or
toxins directly through the tubular cells into the
tubules and rapidly clear these substances from the

creates a problem in maintaining a therapeutically
effective drug concentration.

Another compound that is rapidly secreted by the

plasma flowing through the kidneys and excrete it in

thin descending segment

thin

ascending segment

permeable to water and moderately permeable to

of this nephron segment is mainly to allow simple dif-

cent of the filtered water is reabsorbed in the loop of

epithelial cells that have high metabolic activity and

lower reabsorptive capacity than the thick segment,

100

ubular fluid / plasma concentration

% Total proximal tubule length

Glucose

Amino acids

Osmolality

Urea

Creatinine

HCO

5.0

2.0

1.0

0.5

0.05

0.2

0.1

0.01

sorbed to a lesser extent than water or is secreted into the tubules.

water, whereas values above 1.0 indicate that the substance is reab-

tubular fluid is the same as the concentration in the plasma. Values

of these substances in the plasma and in the glomerular filtrate. A

Figure 27–7

Changes in concentrations of different substances in tubular fluid
along the proximal convoluted tubule relative to the concentrations

value of 1.0 indicates that the concentration of the substance in the

below 1.0 indicate that the substance is reabsorbed more avidly than

water delivered to this segment remains in the tubule,

. Therefore, most of the

The thick segment of the ascending loop of Henle is

hydrogen counter-transport mechanism in its luminal

The thick ascending limb also has a sodium-

8 millivolts in the tubular lumen. This positive

sium ions into the lumen, creating a positive charge of

anions into the cell, there is a slight backleak of potas-

Although the 1-sodium, 2-chloride, 1-potassium co-

, in the thick

, and K

, Na

, Ca

cations, such as Mg

There is also significant paracellular reabsorption of

potassium co-transporter. These diuretics are dis-

which inhibit the action of the sodium 2-chloride,

, all of

, and

furosemide, ethacrynic acid

the site of action of the powerful “

The thick ascending limb of the loop of Henle is

(Figure 27–9). This co-transport protein carrier in the

2-chloride

the luminal membrane is mediated primarily by a

movement of sodium across

thick ascending loop

tion. The low intracellular sodium concentration in

capability of the sodium-potassium ATPase pump,

branes. As in the proximal tubule, the reabsorption of

ATPase pump in the epithelial cell basolateral mem-

nificant amounts of any of these solutes.

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

335

and the thin descending limb does not reabsorb sig-

An important component of solute reabsorption in

the thick ascending limb is the sodium-potassium

other solutes in the thick segment of the ascending
loop of Henle is closely linked to the reabsorptive

which maintains a low intracellular sodium concentra-

turn provides a favorable gradient for movement
of sodium from the tubular fluid into the cell. In the

1-sodium,

1-potassium co-transporter

luminal membrane uses the potential energy released
by downhill diffusion of sodium into the cell to drive
the reabsorption of potassium into the cell against a
concentration gradient.

loop” diuretics

bumetanide

cussed in Chapter 31.

ascending limb owing to the slight positive charge of
the tubular lumen relative to the interstitial fluid.

transporter moves equal amounts of cations and

about

charge forces cations such as Mg

and Ca

to diffuse

from the tubular lumen through the paracellular space
and into the interstitial fluid.

cell membrane that mediates sodium reabsorption and
hydrogen secretion in this segment.

virtually impermeable to water

Thick ascending

loop of Henle

25%

Hypo-

osmotic

, Cl

, K

, HCO

, Mg

Thin descending

loop of Henle

and magnesium. This segment also secretes hydrogen ions into the

and potassium, as well as large amounts of calcium, bicarbonate,

reabsorbs about 25 per cent of the filtered loads of sodium, chloride,

active reabsorption. The thick ascending limb of the loop of Henle

). The descending part of the thin segment

Figure 27–8

Cellular ultrastructure and transport characteristics of the thin
descending loop of Henle (top) and the thick ascending segment of
the loop of Henle (bottom
of the loop of Henle is highly permeable to water and moderately
permeable to most solutes but has few mitochondria and little or no

tubular lumen.

ATP

diffusion

Tubular

Paracellular

Renal

interstitial

fluid

lumen

(

8 mV)

cells

, Ca

, K

Loop diuretics
• Furosemide
• Ethacrynic acid
• Bumetanide

2Cl

from the lumen to the interstitial fluid via the paracellular pathway.

port. The positive charge (

transported into the tubular cell by sodium-hydrogen counter-trans-

down an electrochemical gradient into the cells. Sodium is also

the cells, using the potential energy released by diffusion of sodium

The 1-sodium, 2-chloride, 1-potassium co-transporter in the luminal

thick ascending loop of Henle. The sodium-potassium ATPase pump

Mechanisms of sodium, chloride, and potassium transport in the

Figure 27–9

in the basolateral cell membrane maintains a low intracellular
sodium concentration and a negative electrical potential in the cell.

membrane transports these three ions from the tubular lumen into

+8 mV) of the tubular lumen relative to

the interstitial fluid forces cations such as Mg

and Ca

to diffuse

sodium concentration inside the cell and, therefore,

membrane (Figure 27–12). This pump maintains a low

potassium ATPase pump in each cell’s basolateral

potassium ions into the lumen. The intercalated cells

(Figure 27–11). The principal cells reab-

two distinct cell types, the

characteristics. Anatomically, they are composed of

The second half of the distal tubule and the subse-

Collecting Tubule

Late Distal Tubule and Cortical

chloride co-transporter.

hypertension and heart failure, inhibit the sodium-

, which are widely used to treat disorders such as

nels in the basolateral membrane. The

brane (Figure 27–10). Chloride diffuses out of the cell

and the sodium-potassium ATPase pump transports

tubule. The sodium-chloride co-transporter moves

tually impermeable to water and urea. For this reason,

including sodium, potassium, and chloride, but is vir-

Henle. That is, it avidly reabsorbs most of the ions,

GFR and blood flow in this same nephron. The next

. The very first

The thick segment of the ascending limb of the loop

Distal Tubule

trate the urine under different conditions, as we

as it flows toward the distal tubule, a feature that is

despite reabsorption of large amounts of solute. The

336

Unit V

The Body Fluids and Kidneys

tubular fluid in the ascending limb becomes very dilute

important in allowing the kidneys to dilute or concen-

discuss much more fully in Chapter 28.

of Henle empties into the distal tubule
portion of the distal tubule forms part of the juxta-
glomerular complex that provides feedback control of

part of the distal tubule is highly convoluted and has
many of the same reabsorptive characteristics of the
thick segment of the ascending limb of the loop of

it is referred to as the diluting segment because it also
dilutes the tubular fluid.

Approximately 5 percent of the filtered load of

sodium chloride is reabsorbed in the early distal

sodium chloride from the tubular lumen into the cell,

sodium out of the cell across the basolateral mem-

into the renal interstitial fluid through chloride chan-

thiazide diuret-

ics

quent cortical collecting tubule have similar functional

principal cells and the inter-

calated cells
sorb sodium and water from the lumen and secrete

reabsorb potassium ions and secrete hydrogen ions
into the tubular lumen.

Principal Cells Reabsorb Sodium and Secrete Potassium.

Sodium reabsorption and potassium secretion by the
principal cells depend on the activity of a sodium-

favors sodium diffusion into the cell through special

ATP

Tubular

Renal

interstitial

fluid

lumen

(

10mV)

cells

Thiazide diuretics:

chloride diffuses into the interstitial fluid via chloride channels.

Sodium is pumped out of the cell by sodium-potassium ATPase and

the cell by a co-transporter that is inhibited by thiazide diuretics.

Mechanism of sodium chloride transport in the early distal tubule.

Figure 27–10

Sodium and chloride are transported from the tubular lumen into

Intercalated

cells

Early distal tubule

Late distal tubule

and collecting tubule

Principal

cells

, Cl

, Ca

, Mg

, Cl

(

ADH) H

HCO

ions into the lumen. The reabsorption of water from this tubular

potassium ions into the lumen. The intercalated cells reabsorb potas-

The principal cells reabsorb sodium from the lumen and secrete

two distinct cell types, the

and magnesium but is virtually impermeable to water and urea. The

ascending loop of Henle and reabsorbs sodium, chloride, calcium,

distal tubule and the late distal tubule and collecting tubule. The

Figure 27–11

Cellular ultrastructure and transport characteristics of the early

early distal tubule has many of the same characteristics as the thick

late distal tubules and cortical collecting tubules are composed of

principal cells and the intercalated cells.

sium and bicarbonate ions from the lumen and secrete hydrogen

segment is controlled by the concentration of antidiuretic hormone.

The epithelial cells of the collecting ducts are nearly

the final urine output of water and solutes.

fore, play an extremely important role in determining

are the final site for processing the urine and, there-

than 10 per cent of the filtered water and sodium, they

Medullary Collecting Duct

urine.

impermeable to water. This special characteristic

in the absence of ADH, they are virtually

tubular segments are permeable to water, but

. With high levels of ADH, these

, which is also called

4. The permeability of the late distal tubule and

in acid-base regulation of the body fluids.

tubule. Thus, the intercalated cells play a key role

concentration gradient, as much as 1000 to 1. This

hydrogen-ATPase mechanism. This process is

3. The

fluids.

tubular lumen, a process that is also controlled

time, these segments secrete potassium ions

hormones, especially aldosterone. At the same

collecting tubule segments reabsorb sodium ions,

2. Both the late distal tubule and the cortical

in the medullary collecting ducts.

collecting duct to be excreted in the urine,

thus, almost all the urea that enters these

almost completely impermeable to urea, similar

1. The tubular membranes of both segments are

The functional characteristics of the

ions.

The intercalated cells can also reabsorb potassium

across the basolateral membrane. A more detailed dis-

tubular lumen, and for each hydrogen ion secreted, a

ions. The hydrogen ions are then secreted into the

water and carbon dioxide to form carbonic acid, which

ATPase transport mechanism. Hydrogen is generated

Intercalated Cells Avidly Secrete Hydrogen and Reabsorb Bicar-

potassium-sparing diuretics.

tubular fluid. For this reason the sodium channel

the sodium-potassium ATPase pump. This, in turn,

sodium reabsorption and potassium secretion. Sodium

lactone, eplerenone, amiloride, and triamterene.

, including spirono-

potassium-sparing diuretics

The principal cells are the primary sites of action

(2) once in the cell, potassium diffuses down its con-

high intracellular potassium concentration, and then

sodium-potassium ATPase pump, which maintains a

steps: (1) Potassium enters the cell because of the

channels. The secretion of potassium by these cells

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

337

from the blood into the tubular lumen involves two

centration gradient across the luminal membrane into
the tubular fluid.

of the

Aldosterone antagonists compete with aldosterone for
receptor sites in the principal cells and therefore
inhibit the stimulatory effects of aldosterone on

channel blockers directly inhibit the entry of sodium
into the sodium channels of the luminal membranes
and therefore reduce the amount of sodium that can
be transported across the basolateral membranes by

decreases transport of potassium into the cells and
ultimately reduces potassium secretion into the

blockers as well as the aldosterone antagonists
decrease urinary excretion of potassium and act as

bonate and Potassium Ions.

Hydrogen ion secretion by

the intercalated cells is mediated by a hydrogen-

in this cell by the action of carbonic anhydrase on

then dissociates into hydrogen ions and bicarbonate

bicarbonate ion becomes available for reabsorption

cussion of this mechanism is presented in Chapter 30.

late distal tubule

and cortical collecting tubule can be summarized as
follows:

to the diluting segment of the early distal tubule;

segments passes on through and into the

although some reabsorption of urea occurs

and the rate of reabsorption is controlled by

from the peritubular capillary blood into the

by aldosterone and by other factors such as
the concentration of potassium ions in the body

intercalated cells of these nephron segments

avidly secrete hydrogen ions by an active

different from the secondary active secretion of
hydrogen ions by the proximal tubule because it is
capable of secreting hydrogen ions against a large

is in contrast to the relatively small gradient (4- to
10-fold) for hydrogen ions that can be achieved
by secondary active secretion in the proximal

cortical collecting duct to water is controlled by
the concentration of ADH
vasopressin

provides an important mechanism for controlling
the degree of dilution or concentration of the

Although the medullary collecting ducts reabsorb less

cuboidal in shape with smooth surfaces and relatively

Triamterene

Amiloride

ATP

Tubular

Renal

interstitial

fluid

lumen

(

50 mV)

cells

channel blockers

•
•

Aldosterone antagonists
• Spironolactone
• Eplerenone

inhibit the entry of sodium into the sodium channels.

sorption and potassium secretion. Sodium channel blockers directly

cell by the sodium-potassium ATPase pump. Aldosterone antago-

tion in the late distal tubules and cortical collecting tubules. Sodium

Figure 27–12

Mechanism of sodium chloride reabsorption and potassium secre-

enters the cell through special channels and is transported out of the

nists compete with aldosterone for binding sites in the cell and
therefore inhibit the effects of aldosterone to stimulate sodium reab-

lost in the urine.

body needs to conserve, and almost none of them are

strongly reabsorbed; these are all substances that the

of the figure, such as glucose and amino acids, are all

versely, the substances represented toward the bottom

ing especially great quantities into the urine. Con-

even to secrete them into the tubules, thereby excret-

adapted to reabsorb them only slightly or not at all, or

needed by the body, and the kidneys have become

in the urine. In general, these substances are not

27–14, such as creatinine, become highly concentrated

The substances represented at the top of Figure

been reabsorbed than water.

than 1.0, this means that relatively more solute has

more water is reabsorbed than solute, or if there has

As the filtrate moves along the tubular system, the

is assumed to be constant, any change in the ratio

a substance. If plasma concentration of the substance

several substances in the different tubular segments.

Figure 27–14 shows the degree of concentration of

percentage of the solute is reabsorbed, the substance

the substance becomes more concentrated. If a greater

water. If a greater percentage of water is reabsorbed,

Whether a solute will become concentrated in the

Tubular Segments

Different Solutes in the Different

acid-base balance.

cortical collecting tubule. Thus, the medullary

concentration gradient, as also occurs in the

3. The medullary collecting duct is capable of

a concentrated urine.

into the medullary interstitium, helping to raise

Therefore, some of the tubular urea is reabsorbed

2. Unlike the cortical collecting tubule, the

solutes in the urine.

into the medullary interstitium, thereby reducing

high levels of ADH, water is avidly reabsorbed

to water is controlled by the level of ADH. With

1. The permeability of the medullary collecting duct

few mitochondria (Figure 27–13). Special characteris-

338

Unit V

The Body Fluids and Kidneys

tics of this tubular segment are as follows:

the urine volume and concentrating most of the

medullary collecting duct is permeable to urea.

the osmolality in this region of the kidneys and
contributing to the kidneys’ overall ability to form

secreting hydrogen ions against a large

collecting duct also plays a key role in regulating

Summary of Concentrations of

tubular fluid is determined by the relative degree of
reabsorption of that solute versus the reabsorption of

becomes more diluted.

All the values in this figure represent the tubular fluid
concentration divided by the plasma concentration of

of tubular fluid/plasma concentration rate reflects
changes in tubular fluid concentration.

concentration rises to progressively greater than 1.0 if

been a net secretion of the solute into the tubular fluid.
If the concentration ratio becomes progressively less

Medullary

collecting duct

, Cl

Urea

HCO

(

ADH) H

centration of antidiuretic hormone.

urea, which is reabsorbed in these tubular segments. The reabsorp-

medullary collecting duct. The medullary collecting ducts actively

Figure 27–13

Cellular ultrastructure and transport characteristics of the

reabsorb sodium and secrete hydrogen ions and are permeable to

tion of water in medullary collecting ducts is controlled by the con-

PAH

ubular fluid/plasma concentration

Proximal

tubule

Loop of

Henle

Distal

tubule

Collecting

tubule

to 585

to 140

to 125

HCO

and Na

Cre

atinine

Cre

atinine

Glucose

Protein

Amino acids

Inulin

Urea

100.0

50.0

20.0

10.0

5.0

2.0

1.0

0.50

0.20

0.10

0.05

0.02

the tubules.

avidly than water, whereas values above 1.0 indicate that the sub-

Values below 1.0 indicate that the substance is reabsorbed more

substance in the plasma and in the glomerular filtrate. A value of 1.0

Figure 27–14

Changes in average concentrations of different substances at differ-
ent points in the tubular system relative to the concentration of that

indicates that the concentration of the substance in the tubular fluid
is the same as the concentration of that substance in the plasma.

stance is reabsorbed to a lesser extent than water or is secreted into

Figure 27–15 shows the approximate normal forces

), which opposes reabsorption.

), which favors reabsorption; and

outside the capillaries, which favors reabsorption; (3)

]), which opposes reabsorption;

laries. These forces include (1) hydrostatic pressure

The net reabsorptive force represents the sum of the

laries. The normal rate of peritubular capillary reab-

of the solutes are normally reabsorbed. Fluid and elec-

tubules, more than 99 per cent of the water and most

Normal Values for Physical Forces and Reabsorption Rate.

the renal tubules.

and, ultimately, reabsorption of water and solutes from

glomerular capillaries. Changes in peritubular capil-

of reabsorption across the peritubular capillaries,

Interstitial Fluid Physical Forces

homeostasis.

changes in GFR.) Working together, the autoregula-

cially tubuloglomerular feedback, which help prevent

includes the renal autoregulatory mechanisms, espe-

output. (The first line of defense, discussed earlier,

segments when GFR increases. Glomerulotubular

The importance of glomerulotubular balance is that

pletely isolated proximal tubular segments.

ing renal interstitium, as discussed later. It is clear that

of Henle. The precise mechanisms responsible for this

occurs in other tubular segments, especially the loop

as the filtered load increases, even though the

cent of GFR). Thus, glomerulotubular balance refers

min to 150 ml/min, the absolute rate of proximal

. For example, if GFR is increased from 125 ml/

This phenomenon is referred to as

to Increased Tubular Load

Ability of the Tubules to Increase

control mechanisms.

independently of others, especially through hormonal

tion. An important feature of tubular reabsorption is

tion, just as there are for control of glomerular filtra-

tion, there are multiple nervous, hormonal, and local

Regulation of Tubular

than 99% has been reabsorbed.

125 (see Figure 27–14), indicating that only 1/125 of

At the end of the collecting ducts, the tubular

sorbed as the fluid passes through the proximal tubule.

sorbed from the tubules, a tubular fluid/plasma con-

glomerular filtrate. Since inulin is not secreted or reab-

rises to about 3.0 at the end of the proximal tubules,

water present in the tubular fluid. For example, the

tubule, therefore, reflect changes in the amount of

sorbed or secreted by the renal tubules. Changes in

a polysaccharide used to measure GFR, is not reab-

to Measure Water Reabsorption by the Renal Tubules.

Tubular Fluid /Plasma Inulin Concentration Ratio Can Be Used

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

339

Inulin,

inulin concentration at different points along the renal

tubular fluid/plasma concentration ratio for inulin

indicating that inulin concentration in the tubular fluid
is 3 times greater than in the plasma and in the

centration ratio of 3.0 means that only one third of the
water that was filtered remains in the renal tubule and
that two thirds of the filtered water has been reab-

fluid/plasma inulin concentration ratio rises to about

the filtered water remains in the tubule and that more

Reabsorption

Because it is essential to maintain a precise balance
between tubular reabsorption and glomerular filtra-

control mechanisms that regulate tubular reabsorp-

that reabsorption of some solutes can be regulated

Glomerulotubular Balance—The

Reabsorption Rate in Response

One of the most basic mechanisms for controlling
tubular reabsorption is the intrinsic ability of the
tubules to increase their reabsorption rate in response
to increased tubular load (increased tubular inflow).

glomerulotubular

balance

tubular reabsorption also increases from about 81 ml/
min (65 per cent of GFR) to about 97.5 ml/min (65 per

to the fact that the total rate of reabsorption increases

percentage of GFR reabsorbed in the proximal
tubule remains relatively constant at about 65 per
cent.

Some degree of glomerulotubular balance also

are not fully understood but may be due partly to
changes in physical forces in the tubule and surround-

the mechanisms for glomerulotubular balance can
occur independently of hormones and can be demon-
strated in completely isolated kidneys or even in com-

it helps to prevent overloading of the distal tubular

balance acts as a second line of defense to buffer the
effects of spontaneous changes in GFR on urine

tory and glomerulotubular balance mechanisms
prevent large changes in fluid flow in the distal tubules
when the arterial pressure changes or when there
are other disturbances that would otherwise wreak
havoc with the maintenance of sodium and volume

Peritubular Capillary and Renal

Hydrostatic and colloid osmotic forces govern the rate

just as these physical forces control filtration in the

lary reabsorption can in turn influence the hydrostatic
and colloid osmotic pressures of the renal interstitium

the glomerular filtrate passes through the renal

trolytes are reabsorbed from the tubules into the renal
interstitium and from there into the peritubular capil-

sorption is about 124 ml/min.

Reabsorption across the peritubular capillaries can

be calculated as

Reabsorption

= K

¥ Net reabsorptive force

hydrostatic and colloid osmotic forces that either favor
or oppose reabsorption across the peritubular capil-

inside the peritubular capillaries (peritubular hydro-
static pressure [P

(2) hydrostatic pressure in the renal interstitium (P

)

colloid osmotic pressure of the peritubular capillary
plasma proteins (

(4) colloid osmotic pressure of the proteins in the renal
interstitium (

that favor and oppose peritubular reabsorption.

tubules.

tubules into the interstitium, especially in the proximal

proteins in the renal interstitium. These changes then

capillaries. This in turn raises renal interstitial fluid

colloid osmotic pressure, reduces the uptake of fluid

tive force across the peritubular capillary membranes,

the tubules. For example, a decrease in the reabsorp-

Ultimately, changes in peritubular capillary physical

rate.

conditions. Table 27–2 summarizes the factors that

tion. K

raise reabsorption, whereas

capillaries. Increases in K

cussed later.

plasma flow and increasing filtration fraction, as dis-

renal vasoconstrictors, such as angiotensin II, increase

increased GFR or decreased renal plasma flow. Some

tion is defined as the ratio of GFR/renal plasma flow,

lar capillary reabsorption rate. Because filtration frac-

the plasma that remains behind. Thus, increasing the

quently, the more concentrated the protein becomes in

plasma filtered through the glomerulus and, conse-

the filtration fraction, the greater the fraction of

reabsorption; and (2)

capillary colloid osmotic pressure, thereby increasing

is determined by

plasma in these capillaries; raising the colloid osmotic

The second major determinant of peritubular capil-

hydrostatic pressure.

hydrostatic pressure, it lowers peritubular capillary

reabsorption rate. Although constriction of the

blood vessels. (2) Increase in resistance of either the

decrease reabsorption rate. This effect is buffered to

. (1) Increases in arterial pressure tend to

sures of the peritubular capillaries. The

The two

Regulation of Peritubular Capillary Physical Forces.

normally is about 12.4 ml/min/mm Hg.

10 mm Hg, K

capillaries. Because the reabsorption rate is normally

The other factor that contributes to the high rate of

in the glomerular capillaries, but in the opposite

10 mm Hg. This is a high value, similar to that found

reabsorption. Therefore, subtracting the net hydro-

net colloid osmotic force of about 17 mm Hg, favoring

which opposes reabsorption, is 15 mm Hg, causing a

sure, which favors reabsorption, is about 32 mm Hg,

favor reabsorption. The plasma colloid osmotic pres-

which opposes fluid reabsorption. This is more than

lar capillary to the interstitial fluid of about 7 mm Hg,

hydrostatic pressure averages 6 mm Hg, there is a pos-

averages about 13 mm Hg and renal interstitial fluid

340

Unit V

The Body Fluids and Kidneys

Because the normal peritubular capillary pressure

itive hydrostatic pressure gradient from the peritubu-

counterbalanced by the colloid osmotic pressures that

and the colloid osmotic pressure of the interstitium,

static forces that oppose reabsorption (7 mm Hg) from
the net colloid osmotic forces that favor reabsorption
(17 mm Hg) gives a net reabsorptive force of about

direction.

fluid reabsorption in the peritubular capillaries is a
large filtration coefficient (K

) because of the high

hydraulic conductivity and large surface area of the

about 124 ml/min and net reabsorption pressure is

determinants of peritubular capillary reabsorption
that are directly influenced by renal hemodynamic
changes are the hydrostatic and colloid osmotic pres-

peritubular

capillary hydrostatic pressure is influenced by the arte-
rial pressure and resistances of the afferent and efferent
arterioles

raise peritubular capillary hydrostatic pressure and

some extent by autoregulatory mechanisms that main-
tain relatively constant renal blood flow as well as
relatively constant hydrostatic pressures in the renal

afferent or the efferent arterioles reduces peritubular
capillary hydrostatic pressure and tends to increase

efferent arterioles increases glomerular capillary

lary reabsorption is the colloid osmotic pressure of the

pressure increases peritubular capillary reabsorption.
The colloid osmotic pressure of peritubular capillaries

(1) the systemic plasma colloid

osmotic pressure; increasing the plasma protein con-
centration of systemic blood tends to raise peritubular

the filtration fraction; the higher

filtration fraction also tends to increase the peritubu-

increased filtration fraction can occur as a result of

peritubular capillary reabsorption by decreasing renal

Changes in the peritubular capillary K

can also

influence the reabsorption rate because K

is a

measure of the permeability and surface area of the

decreases in K

lower peritubular capillary reabsorp-

remains relatively constant in most physiologic

can influence the peritubular capillary reabsorption

Renal Interstitial Hydrostatic and Colloid Osmotic Pressures.

forces influence tubular reabsorption by changing the
physical forces in the renal interstitium surrounding

caused by either increased peritubular capillary hydro-
static pressure or decreased peritubular capillary

and solutes from the interstitium into the peritubular

hydrostatic pressure and decreases interstitial fluid
colloid osmotic pressure because of dilution of the

decrease the net reabsorption of fluid from the renal

Tubular

ATP

cells

lumen

Interstitial

fluid

Interstitial

fluid

Peritubular

capillary

Peritubular

capillary

10 mm Hg

Net reabsorption

pressure

10 mm Hg

Net reabsorption

pressure

13 mm Hg

32 mm Hg

15 mm Hg

6 mm Hg

Bulk

flow

Bulk

flow

, interstitial fluid colloid osmotic pressure.

, peritubular capillary colloid

, inter-

, peritubular capillary hydrostatic pressure; P

triphosphate; P

are transported across the renal tubular cells. ATP, adenosine

net reabsorptive pressure is normally about 10 mm Hg, causing fluid

cal values shown are estimates of the normal values for humans. The

mine fluid reabsorption by the peritubular capillaries. The numeri-

Figure 27–15

Summary of the hydrostatic and colloid osmotic forces that deter-

and solutes to be reabsorbed into the peritubular capillaries as they

stitial fluid hydrostatic pressure;

osmotic pressure;

kidney disease, increases in arterial pressure cause

GFR autoregulation is impaired, as often occurs in

increased arterial pressure on urine output. When

renal blood flow and GFR. The slight increase in GFR

pressure diuresis.

water, phenomena that are referred to as

Effect of Arterial Pressure on Urine

hemodynamic changes

Therefore, in general,

osmotic pressures of the renal interstitium, the uptake

Thus, through changes in the hydrostatic and colloid

sorption increases.

the tubular lumen is reduced, and net tubular reab-

stitium; therefore, backleak of water and solutes into

pressure. Both of these forces favor movement of fluid

The opposite is true when there is increased peri-

rate of net reabsorption (refer again to Figure 27–16).

backleak into the tubular lumen, thereby reducing the

tendency for greater amounts of solute and water to

tubular capillary reabsorption is reduced, there is

into the lumen of the tubule. However, when peri-

reabsorption, the net movement of water and solutes

With the normal high rate of peritubular capillary

can diffuse in both directions through these junctions.

actually leaky, so that considerable amounts of sodium

into the tubular lumen. The so-called tight junctions

once the water and solutes are in the interstitial spaces,

tubular lumen into the interstitium by osmosis. And

transport or passive diffusion, water is drawn from the

reabsorbed (Figure 27–16). Once the solutes enter the

The mechanisms by which changes in interstitial

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

341

fluid hydrostatic and colloid osmotic pressures influ-
ence tubular reabsorption can be understood by exam-
ining the pathways through which solute and water are

intercellular channels or renal interstitium by active

they can either be swept up into the peritubular cap-
illaries or diffuse back through the epithelial junctions

between the epithelial cells of the proximal tubule are

is into the peritubular capillaries with little backleak

increased interstitial fluid hydrostatic pressure and a

tubular capillary reabsorption above the normal level.
An initial increase in reabsorption by the peritubular
capillaries tends to reduce interstitial fluid hydrostatic
pressure and raise interstitial fluid colloid osmotic

and solutes out of the tubular lumen and into the inter-

of water and solutes by the peritubular capillaries is
closely matched to the net reabsorption of water and
solutes from the tubular lumen into the interstitium.

forces that increase peritubular

capillary reabsorption also increase reabsorption from
the renal tubules. Conversely,
that inhibit peritubular capillary reabsorption also
inhibit tubular reabsorption of water and solutes.

Output—The Pressure-Natriuresis and
Pressure-Diuresis Mechanisms

Even small increases in arterial pressure often cause
marked increases in urinary excretion of sodium and

pressure

natriuresis and

Because of the

autoregulatory mechanisms described in Chapter 26,
increasing the arterial pressure between the limits of
75 and 160 mm Hg usually has only a small effect on

that does occur contributes in part to the effect of

much larger increases in GFR.

Factors That Can Influence Peritubular Capillary

Table 27–2

Reabsorption

≠ P

Æ Ø Reabsorption

•

Ø R

Æ ≠ P

•

Ø R

Æ ≠ P

•

≠ Arterial Pressure Æ ≠ P

≠ p

Æ ≠ Reabsorption

•

≠ p

Æ ≠ p

•

≠ FF Æ ≠ p

≠ K

Æ ≠ Reabsorption

, peritubular capillary filtration coefficient.

, arterial plasma colloid osmotic pressure; FF, filtration fraction;

, peritubular capillary colloid osmotic

ent arteriolar resistances, respectively;

, afferent and effer-

, peritubular capillary hydrostatic pressure; R

and R

pressure;

ATP

Tubular

ATP

Decreased reabsorption

Normal

cells

Lumen

Backleak

Interstitial

fluid

Interstitial

fluid

Peritubular

capillary

Peritubular

capillary

Net

reabsorption

Net

reabsorption

Increased

backleak

Increased

backleak

Decreased net

reabsorption

Decreased net

reabsorption

lial cells, especially in the proximal tubule.

sorption, in turn, decreases the net reabsorption of solutes and water

). Reduced peritubular capillary reab-

Figure 27–16

Proximal tubular and peritubular capillary reabsorption under
normal conditions (top) and during decreased peritubular capillary
reabsorption (bottom) caused by either increasing peritubular cap-
illary hydrostatic pressure (P

) or decreasing peritubular capillary

colloid osmotic pressure (

by increasing the amounts of solutes and water that leak back into
the tubular lumen through the tight junctions of the tubular epithe-

loss of salt and water from the body fluids. The

cellular fluid volume, such as during hemorrhage or

19, angiotensin II formation increases in circumstances

sodium-retaining hormone. As discussed in Chapter

Angiotensin II is perhaps the body’s most powerful

Angiotensin II Increases Sodium and Water Reabsorption.

fluids. Thus, aldosterone is even more important as a

minimal levels of aldosterone are present, the inabil-

and potassium depletion. Although day-to-day regula-

Conn’s syndrome

secretion, as occurs in patients with adrenal tumors

lation of potassium. Conversely, excess aldosterone

), there

Addison’s disease

In the absence of aldosterone, as occurs with adrenal

The cellular mechanisms of aldosterone action are

permeability of the luminal side of the membrane.

membrane. Aldosterone also increases the sodium

stimulating the sodium-potassium ATPase pump on

. The mechanism by which

secretion by the renal tubules.

glomerulosa cells of the adrenal cortex, is an impor-

Aldosterone, secreted by the zona

tubular actions in the next few paragraphs.

Chapters 28 and 29, but we briefly review their renal

their effects on solute and water excretion. Some

their principal sites of action on the renal tubule, and

water. Table 27–3 summarizes some of the most impor-

major changes in excretion of other electrolytes.

when sodium intake is changed, the kidneys must

excretion of sodium and other electrolytes. Likewise,

potassium intake is increased, the kidneys must

independently of one another. For example, when

ent solutes and water at variable rates, sometimes

Hormonal Control of Tubular

increases sodium reabsorption. Therefore, decreased

stimulates aldosterone secretion,

which further

increases sodium reabsorption by the tubules; it also

reduced angiotensin II formation. Angiotensin II itself

arterial pressure rises.

leak of sodium into the tubular lumen, thereby reduc-

sure. As discussed earlier, an increase in the renal

vasa recta of the renal medulla, and a subsequent

tubular capillary hydrostatic pressure, especially in the

is reabsorbed by the tubules. The mechanisms respon-

342

Unit V

The Body Fluids and Kidneys

A second effect of increased renal arterial pressure

that raises urine output is that it decreases the per-
centage of the filtered load of sodium and water that

sible for this effect include a slight increase in peri-

increase in the renal interstitial fluid hydrostatic pres-

interstitial fluid hydrostatic pressure enhances back-

ing the net reabsorption of sodium and water and
further increasing the rate of urine output when renal

A third factor that contributes to the pressure-

natriuresis and pressure-diuresis mechanisms is

angiotensin II formation contributes to the decreased
tubular sodium reabsorption that occurs when arterial
pressure is increased.

Reabsorption

Precise regulation of body fluid volumes and solute
concentrations requires the kidneys to excrete differ-

excrete more potassium while maintaining normal

appropriately adjust urinary sodium excretion without

Several hormones in the body provide this specificity
of tubular reabsorption for different electrolytes and

tant hormones for regulating tubular reabsorption,

of these hormones are discussed in more detail in

Aldosterone Increases Sodium Reabsorption and Increases
Potassium Secretion.

tant regulator of sodium reabsorption and potassium

The primary site

of aldosterone action is on the principal cells of the
cortical collecting tubule
aldosterone increases sodium reabsorption while at
the same time increasing potassium secretion is by

the basolateral side of the cortical collecting tubule

discussed in Chapter 77.

destruction or malfunction (
is marked loss of sodium from the body and accumu-

(

) is associated with sodium retention

tion of sodium balance can be maintained as long as

ity to appropriately adjust aldosterone secretion
greatly impairs the regulation of renal potassium
excretion and potassium concentration of the body

regulator of potassium concentration than it is for
sodium concentration.

associated with low blood pressure and/or low extra-

increased formation of angiotensin II helps to return
blood pressure and extracellular volume toward
normal by increasing sodium and water reabsorption
from the renal tubules through three main effects:
1. Angiotensin II stimulates aldosterone secretion,

which in turn increases sodium reabsorption.

2. Angiotensin II constricts the efferent arterioles,

which has two effects on peritubular capillary
dynamics that raise sodium and water

Table 27–3

- - -

Parathyroid hormone

Proximal tubule, thick ascending loop of

Atrial natriuretic peptide

Distal tubule/collecting tubule and duct

Antidiuretic hormone

Distal tubule/collecting tubule and duct

tubule, collecting tubule

NaCl, H

Angiotensin II

Proximal tubule, thick ascending loop of Henle/distal

NaCl, H

Aldosterone

Collecting tubule and duct

Hormone

Site of Action

Effects

Hormones That Regulate Tubular Reabsorption

≠

O reabsorption,

≠ K

secretion

≠

O reabsorption,

≠ H

secretion

≠ H

O reabsorption

Ø NaCl reabsorption
Ø PO

reabsorption,

≠ Ca

reabsorption

Henle/distal tubule

of the plasma is “cleared” of the substance. Thus,

excreted into the urine each minute, then 1 ml/min

lowing example: If the plasma passing through the

To illustrate the clearance principle, consider the fol-

tion, and tubular secretion.

of the kidneys: glomerular filtration, tubular reabsorp-

later, can be used to quantify the rate at which blood

the excretory function of the kidneys and, as discussed

cleared of a substance. However,

. This concept is somewhat

that is completely cleared of the substance by the

various substances (Table 27–4). By definition, the

The rates at which different substances are “cleared”

formation, which adds to the overall effect to increase

renal tubule. And finally, sympathetic nervous system

loop of Henle, and perhaps in more distal parts of the

the proximal tubule, the thick ascending limb of the

the renal arterioles, thereby reducing GFR. Sympa-

Henle, as discussed in Chapter 29.

hormone also has other actions, including inhibition of

perhaps also in the loops of Henle. Parathyroid

tion of calcium, especially in the distal tubules and

calcium-regulating hormones in the body. Its principal

excretion, which helps to return blood volume back

especially in the collecting ducts. This decreased

sorption of sodium and water by the renal tubules,

Specific cells of the cardiac atria, when

Atrial Natriuretic Peptide Decreases Sodium and Water

reducing water permeability.

tled back to the cell cytoplasm, thereby removing the

of ADH decreases, the molecules of AQP-2 are shut-

ing AQP-2 gene transcription. When the concentration

AQP-2 protein in the renal tubular cells by stimulat-

increases in ADH levels also increase the formation of

are not believed to be regulated by ADH. Chronic

for water to rapidly exit the cells, although these

are other aquaporins, AQP-3 and AQP-4, in the baso-

permit rapid diffusion of water through the cells. There

water channels

membrane by exocytosis to form

ecules of AQP-2 cluster together and fuse with the cell

, to the luminal side of the cell membranes. The mol-

aquaporin-2 (AQP-

of an intracellular protein, called

protein kinases. This, in turn, stimulates the movement

increasing the formation of cyclic AMP and activating

tubules, collecting tubules, and collecting ducts,

degree of dilution or concentration of the urine, as dis-

the actions of ADH play a key role in controlling the

kidneys to excrete large amounts of dilute urine. Thus,

tubules and collecting ducts to water is low, causing the

In the absence of ADH, the permeability of the distal

lecting duct epithelia. This effect helps the body to

ability of the distal tubule, collecting tubule, and col-

renal action of ADH is to increase the water perme-

The most important

ADH Increases Water Reabsorption.

These multiple actions of angiotensin II cause

epithelial cell membrane in the tubules.

in the proximal tubule. Thus, angiotensin II

exchange in the luminal membrane, especially

the tubular epithelial cell basolateral membrane.

stimulate the sodium-potassium ATPase pump on

reabsorption in the proximal tubules

water.

the peritubular capillaries; this increases the

blood flow, raises filtration fraction in the

efferent arteriolar constriction, by reducing renal

especially from the proximal tubules. Second,

reduces peritubular capillary hydrostatic pressure,

reabsorption. First, efferent arteriolar constriction

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

343

which increases net tubular reabsorption,

glomerulus and increases the concentration of
proteins and the colloid osmotic pressure in

reabsorptive force at the peritubular capillaries
and raises tubular reabsorption of sodium and

3. Angiotensin II directly stimulates sodium

, the loops of

Henle, the distal tubules, and the collecting tubules.
One of the direct effects of angiotensin II is to

A second effect is to stimulate sodium-hydrogen

stimulates sodium transport across both the
luminal and the basolateral surfaces of the

marked sodium retention by the kidneys when
angiotensin II levels are increased.

conserve water in circumstances such as dehydration.

cussed further in Chapters 28 and 75.

ADH binds to specific V

receptors in the late distal

that

lateral side of the cell membrane that provide a path

water channels from the luminal membrane and

Reabsorption.

distended because of plasma volume expansion,
secrete a peptide called atrial natriuretic peptide.
Increased levels of this peptide in turn inhibit the reab-

sodium and water reabsorption increases urinary

toward normal.

Parathyroid Hormone Increases Calcium Reabsorption.

Parathyroid hormone is one of the most important

action in the kidneys is to increase tubular reabsorp-

phosphate reabsorption by the proximal tubule and
stimulation of magnesium reabsorption by the loop of

Sympathetic Nervous System
Activation Increases Sodium
Reabsorption

Activation of the sympathetic nervous system can
decrease sodium and water excretion by constricting

thetic activation also increases sodium reabsorption in

stimulation increases renin release and angiotensin II

tubular reabsorption and decrease renal excretion of
sodium.

Use of Clearance Methods
to Quantify Kidney Function

from the plasma provide a useful way of quantitating
the effectiveness with which the kidneys excrete

renal clearance of a substance is the volume of plasma

kidneys per unit time
abstract because there is no single volume of plasma
that is completely
renal clearance provides a useful way of quantifying

flows through the kidneys as well as the basic functions

kidneys contains 1 milligram of a substance in each mil-
liliter and if 1 milligram of this substance is also

, a polysac-

The GFR, therefore, can be calculated as the clearance

). Thus,

tubules, then the rate at which that substance is excreted

to Estimate GFR

Thus, renal clearance of a substance is calculated from

rate. Rearranging this equation, clearance can be

concentration of that substance, and V is the urine flow

plasma concentration of the substance, U

is the clearance rate of a substance s, P

in the urine per unit time. Stated mathematically,

344

Unit V

The Body Fluids and Kidneys

clearance refers to the volume of plasma that would be
necessary to supply the amount of substance excreted

¥ P

= U

¥ V,

where C

is the

is the urine

expressed as

the urinary excretion rate (U

¥ V) of that substance

divided by its plasma concentration.

Inulin Clearance Can Be Used

If a substance is freely filtered (filtered as freely as
water) and is not reabsorbed or secreted by the renal

in the urine (U

¥ V) is equal to the filtration rate of the

substance by the kidneys (GFR

¥ P

GFR

¥ P

= U

¥ V

of the substance as follows:

A substance that fits these criteria is inulin
charide molecule with a molecular weight of about

GFR

ltered. There is normally

tubules, so that the amount of creatinine excreted

However, creatinine clearance is not a perfect marker

used than inulin clearance for estimating GFR clinically.

sion into the patient, this method is much more widely

also be used to assess GFR. Because measurement of

ltration. Therefore, the clearance of creatinine can

creatinine.

determining GFR. Other substances that have been

ltered to deliver the inulin that appears in the urine.

tration, which yields a value of 125 ml/min. Thus, 125

urine. Then, inulin clearance is calculated as the urine

min. Therefore, 125 mg/min of inulin passes into the

concentration is 125 mg/ml, and urine

this example, the plasma concentration is 1 mg/ml, urine

17 shows the renal handling of inulin. In

Figure 27

5200. Inulin, which is not produced in the body, is found
in the roots of certain plants and must be administered
intravenously to a patient to measure GFR.

–

flow rate is 1 ml/

excretion rate of inulin divided by the plasma concen-

milliliters of plasma flowing through the kidneys must
be fi

Inulin is not the only substance that can be used for

used clinically to estimate GFR include radioactive
iothalamate and

Creatinine Clearance and Plasma
Creatinine Concentration Can Be
Used to Estimate GFR

Creatinine is a by-product of muscle metabolism and is
cleared from the body fluids almost entirely by glomeru-
lar fi

creatinine clearance does not require intravenous infu-

of GFR because a small amount of it is secreted by the

slightly exceeds the amount fi
a slight error in measuring plasma creatinine that
leads to an overestimate of the plasma creatinine

Table 27–4

Filtered load

mg/min, mmol/min, or mEq/min

Secretion rate

Excretion rate

mg/min, mmol/min, or mEq/min

Filtered load

Reabsorption rate

mg/min, mmol/min, or mEq/min

Excretion rate

ow (ERPF)

ml/min

Term

Equation

Units

Use of Clearance to Quantify Kidney Function

Clearance rate (C

)

ml/min

Glomerular filtration rate (GFR)

Clearance ratio

None

Effective renal plasma fl

Renal plasma flow (RPF)

ml/min

Renal blood flow (RBF)

ml/min

= U

= (GFR ¥ P

)

- (U

¥ V)

= Excretion rate -

, renal venous PAH concentration.

PAH

extraction ratio; V

, PAH

PAH

, renal arterial PAH concentration; E

PAH

ow rate; P, plasma concentration; PAH, para-aminohippuric acid; P

S, a substance; U, urine concentration; V, urine fl

1 Hematocrit

RBF

RPF

PAH

V P

RPF

C
E

PAH

(

)

(

)

ERPF

PAH

Clearance ratio

inulin

GFR

inulin

the plasma, the clearance rate of that substance is equal

Theoretically, if a substance is

PAH Clearance Can Be Used to

centration, as shown in Figure 27

GFR. However, this normal rate of creatinine excretion

rate of creatinine production, despite reductions in

state conditions, the creatinine excretion rate equals the

plasma creatinine to 8 times normal. Thus, under steady-

creatinine would increase to about 4 times normal, and

18. If GFR falls to one-fourth normal, plasma

Figure 27

increases to approximately twice normal, as shown in

is reestablished. This will occur when plasma creatinine

uids and raising plasma concentration. Plasma con-

nine, causing accumulation of creatinine in the body

If GFR suddenly decreases by 50%, the kidneys will

), which is inversely proportional to GFR:

in GFR, however, can be

changes

). An

In some cases, it may not be practical to collect urine

cancel each other. Therefore, creatinine clearance pro-

concentration, and fortuitously, these two errors tend to

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

345

vides a reasonable estimate of GFR.

in a patient for measuring creatinine clearance (C

approximation of
obtained by simply measuring plasma creatinine con-
centration (P

transiently filter and excrete only half as much creati-

fl
centration of creatinine will continue to rise until the fil-
tered load of creatinine (P

¥ GFR) and creatinine

excretion (U

¥ V) return to normal and a balance

between creatinine production and creatinine excretion

–

a decrease of GFR to one-eighth normal would raise

occurs at the expense of elevated plasma creatinine con-

–19.

Estimate Renal Plasma Flow

completely cleared from

GFR

diseased kidneys, this extraction ratio may be reduced

and averages about 90 per cent in normal kidneys. In

extraction ratio of PAH

leaves the kidneys. The percentage of PAH removed

the percentage of PAH that is still in the blood when it

ow. To be more accurate, one can correct for

of PAH can be used as an approximation of renal

cent cleared from the plasma. Therefore, the clearance

kidneys. One substance, however, PAH, is about 90 per

20). There is

ltration (Figure 27

ow, a substance that is completely cleared

V). Thus, renal

ow. In other words, the

to the total renal plasma fl
amount of the substance delivered to the kidneys in
the blood (renal plasma flow

¥ P

) would be equal to

the amount excreted in the urine (U

plasma flow (RPF) could be calculated as

Because the GFR is only about 20 per cent of the

total plasma fl
from the plasma must be excreted by tubular secretion
as well as glomerular fi

–

no known substance that is completely cleared by the

plasma fl

from the blood is known as the

RPF

inulin

= 125 mg/ml

inulin

= 1 mg/ml

V = 1 ml/min

Amount filtered = Amount excreted

GFR x P

inulin

= U

inulin

x V

inulin

x V

inulin

GFR =

GFR = 125 ml/min

, urine inulin concentration; V, urine flow

illaries but is not reabsorbed by the renal tubules. P

clearance of inulin. Inulin is freely filtered by the glomerular cap-

Measurement of glomerular filtration rate (GFR) from the renal

Figure 27–17

inulin

, plasma

inulin concentration; U

inulin

rate.

Positive balance

Production

Creatinine production and

renal excretion (g/day)

Days

Excretion GFR x P

Creatinine

Serum creatinine

concentration (mg/dl)

GFR (ml/min)

100

, plasma creatinine concentration.

Creatinine

rate when the production rate of creatinine remains constant.

on serum creatinine concentration and on creatinine excretion

Effect of reducing glomerular filtration rate (GRF) by 50 per cent

Figure 27–18

0.45), or 1182 ml/min.

650 ml/min, the total blood

(the percentage of red blood cells in the blood). If the

arterial PAH concentration:

) concentrations, divided by the renal

PAH

venous PAH (V

PAH

ference between the renal arterial PAH (P

PAH

The extraction ratio (E

Clearance of PAH/Extraction ratio of PAH

Total renal plasma

585 ml/min by 0.9, yielding a value of 650 ml/min. Thus,

If the extraction ratio for PAH is 90 per cent, the

concentration (0.01 mg/ml). Thus, clearance of PAH cal-

1 ml/min) divided by the plasma PAH

can be calculated from the rate of urinary PAH excre-

ow rate is 1 ml/min. PAH clearance

mg/ml, and urine

tion of PAH is 0.01 mg/ml, urine concentration is 5.85

following example: Assume that the plasma concentra-

The calculation of RPF can be demonstrated by the

because of inability of damaged tubules to secrete PAH

346

Unit V

The Body Fluids and Kidneys

into the tubular fluid.

tion (5.85 mg/ml

culates to be 585 ml/min.

actual renal plasma flow can be calculated by dividing

total renal plasma flow can be calculated as

flow

) is calculated as the dif-

) and renal

One can calculate the total blood flow through the

kidneys from the total renal plasma flow and hematocrit

hematocrit is 0.45 and the total renal plasma flow is

flow through both kidneys

is 650/(1

PAH

of tubular reabsorption. Assume the following labora-

The following example demonstrates the calculation

ltered load, then the rate

renal tubules. Conversely, if the excretion rate of the

), then some of

stance by the renal tubules. For example, if the rate of

of a substance are known, one can calculate whether

Calculation of Tubular Reabsorption

ow is 650 ml/min and GFR is 125 ml/min, the

clearance) and the GFR (inulin clearance). If renal

ow (PAH

brane, one must

ltration fraction, which is the fraction

To calculate the

from GFR Divided by Renal

Filtration Fraction Is Calculated

Plasma Flow

of plasma that filters through the glomerular mem-

first know the renal plasma fl

plasma fl
filtration fraction (FF) is calculated as

= GFR/RPF = 125/650 = 0.19

or Secretion from Renal Clearances

If the rates of glomerular filtration and renal excretion

there is a net reabsorption or a net secretion of that sub-

excretion of the substance (U

¥ V) is less than the fil-

tered load of the substance (GFR

¥ P

the substance must have been reabsorbed from the

substance is greater than its fi
at which it appears in the urine represents the sum of
the rate of glomerular filtration plus tubular secretion.

tory values for a patient were obtained:

100

125

150

Plasma creatinine concentration

(mg/100 ml)

Glomerular filtration rate

(ml/min)

Normal

and plasma creatinine concentration under steady-state conditions.

Figure 27–19

Approximate relationship between glomerular filtration rate (GFR)

Decreasing GFR by 50 per cent will increase plasma creatinine to
twice normal if creatinine production by the body remains constant.

PAH

= 5.85 mg/ml

PAH

= 0.01 mg/ml

V = 1 ml/min

PAH

x V

PAH

Renal plasma flow

Renal venous
PAH =
0.001 mg/ml

ow rate.

PAH concentration; V, urine

, urine

PAH

, arterial plasma PAH concentration; U

PAH

the kidneys. P

for the percentage of PAH that is still in the blood when it leaves

). To be more accurate, one can correct

PAH

the clearance of PAH (C

the urine. Therefore, the renal plasma

renal artery is about equal to the amount of PAH excreted in

into the tubular lumen. The amount of PAH in the plasma of the

aminohippuric acid (PAH). PAH is freely

Figure 27–20

Measurement of renal plasma flow from the renal clearance of para-

filtered by the glomerular

capillaries and is also secreted from the peritubular capillary blood

flow can be calculated from

be secreted by the nephron tubules. Listed below are

stance is greater than that of inulin, the substance must

nephron tubules; and (3) if the clearance rate of a sub-

ance, the substance must have been reabsorbed by the

ltered and not reabsorbed or secreted; (2) if the

rate of the substance equals that of inulin, the substance

ance of inulin, a measure of GFR: (1) if the clearance

The following generalizations can be made by

ltered load and urinary excretion, or

Therefore, tubular reabsorption of sodium is the differ-

Eq/min. Urinary

In this example, the

Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate

Chapter 27

347

Urine flow rate

= 1 ml/min

Urine concentration of sodium (U

)

= 70 mEq/L

= 70 mEq/ml

Plasma sodium concentration

= 140 mEq/L

= 140 mEq/ml

GFR (inulin clearance)

= 100 ml/min

filtered sodium load is GFR

¥ P

or 100 ml/min

¥ 140 mEq/ml = 14,000 m

sodium excretion (U

¥ urine flow rate) is 70 mEq/min.

ence between the fi
14,000

mEq/min - 70 mEq/min = 13,930 mEq/min.

Comparisons of Inulin Clearance with Clearances of Different
Solutes.

comparing the clearance of a substance with the clear-

is only fi
clearance rate of a substance is less than inulin clear-

the approximate clearance rates for some of the sub-
stances normally handled by the kidneys:

Inulin

125.0

Phosphate

25.0

Potassium

12.0

Chloride

1.3

Sodium

0.9

Glucose

Substance

Clearance Rate (ml/min)

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