Glomerular Filtration and Renal Blood Flow and Their Control pdf - The Body Fluids and Kidneys

30 mEq/day to a high level of 300 mEq/day. Within 2 to 3 days after raising the

match the intake of various substances. Figure 26–1 shows the response of the

and drinking habits, requiring the kidneys to adjust their excretion rates to

Intake of water and many electrolytes is governed mainly by a person’s eating

less than excretion, the amount of that substance in the body will decrease.

excretion, the amount of that substance in the body will increase. If intake is

tion of water and electrolytes must precisely match intake. If intake exceeds

For maintenance of homeostasis, excre-

Regulation of Water and Electrolyte Balances.

the body or ingested, such as pesticides, drugs, and food additives.

eliminated from the body as rapidly as they are produced. The kidneys also

These waste products must be

metabolites of various hormones.

bilirubin), and

end products of hemoglobin breakdown

metabolism that are no longer needed by the body. These products include

The kidneys are the primary means for eliminating waste products of

Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone Metabo-

Secretion, metabolism, and excretion of hormones

functions, including the following:

of renal excretion, it is important to recognize that the kidneys serve multiple

needs of the body. Ultimately, the kidneys “clear” unwanted substances from

and removing substances from the filtrate at variable rates, depending on the

The kidneys perform their most important functions by filtering the plasma

cells necessary for them to perform their various activities.

This regulatory function of the kidneys maintains the stable environment of the

excretion or metabolic consumption) is maintained in large part by the kidneys.

the body fluids. For water and virtually all electrolytes in the body, the balance

metabolism. A second function that is especially

Blood Flow, and Their Control

I. Glomerular Filtration, Renal

Urine Formation by the Kidneys:

307

Multiple Functions of the
Kidneys in Homeostasis

Most people are familiar with one important func-
tion of the kidneys—to rid the body of waste mate-
rials that are either ingested or produced by

critical is to control the volume and composition of

between intake (due to ingestion or metabolic production) and output (due to

the filtrate (and therefore from the blood) by excreting them in the urine while
returning substances that are needed back to the blood.

Although this chapter and the next few chapters focus mainly on the control

∑ Excretion of metabolic waste products and foreign chemicals
∑ Regulation of water and electrolyte balances
∑ Regulation of body fluid osmolality and electrolyte concentrations
∑ Regulation of arterial pressure
∑ Regulation of acid-base balance
∑
∑ Gluconeogenesis

lites.

urea

(from the metabolism of amino acids), creatinine (from muscle creatine), uric
acid (from nucleic acids),

(such as

eliminate most toxins and other foreign substances that are either produced by

kidneys to a sudden 10-fold increase in sodium intake from a low level of

delicate inner structures.

rounded by a tough, fibrous

where it is stored until emptied. The kidney is sur-

carries the final urine from the kidney to the bladder,

and vein, lymphatics, nerve supply, and ureter, which

grams and is about the size of a clenched fist. The

abdomen, outside the peritoneal cavity (Figure 26–2).

The two kidneys lie on the posterior wall of the

and Urinary Tract

the body fluid and electrolyte balances.

hemodialysis are initiated to restore, at least partially,

a few days, unless clinical interventions such as

failure, enough potassium, acids, fluid, and other sub-

composition rapidly occur. With complete renal

kidneys, these homeostatic functions are disrupted,

With chronic kidney disease or acute failure of the

prolonged periods of fasting rivals that of the liver.

The

gluconeogenesis.

fasting, a process referred to as

The kidneys synthesize glucose from

in Chapter 79, calcitriol plays an important role in

reabsorption by the gastrointestinal tract. As discussed

vitamin at the “number 1” position. Calcitriol is essen-

), by hydroxylating this

kidneys produce the active form of vitamin D, 1,25-

The

hemodialysis, severe anemia develops as a result of

people with severe kidney disease or who have had

the erythropoietin secreted into the circulation. In

The kidneys normally account for almost all

hypoxia.

blood cells, as discussed in Chapter 32. One important

The kidneys secrete

Regulation of Erythrocyte Production.

erated by the metabolism of proteins.

acids, such as sulfuric acid and phosphoric acid, gen-

body fluid buffer stores. The kidneys are the only

fluid buffers, by excreting acids and by regulating the

to acid-base regulation, along with the lungs and body

The kidneys contribute

ucts (e.g., angiotensin II).

secreting vasoactive factors or substances, such as

amounts of sodium and water. The kidneys also con-

19, the kidneys play a dominant role in long-term reg-

these amazing feats of homeostasis.

phate ions. In the next few chapters, we discuss the spe-

potassium, calcium, hydrogen, magnesium, and phos-

water and for most other electrolytes, such as chloride,

plasma sodium concentration. This is also true for

people, sodium intake can be increased to 1500 mEq/

mous. Experimental studies have shown that in many

The capacity of the kidneys to alter sodium excre-

days of renal adaptation to the high sodium intake,

output is re-established. However, during the 2 to 3

300 mEq/day, so that a balance between intake and

sodium intake, renal excretion also increases to about

308

Unit V

The Body Fluids and Kidneys

there is a modest accumulation of sodium that raises
extracellular fluid volume slightly and triggers hor-
monal changes and other compensatory responses
that signal the kidneys to increase their sodium
excretion.

tion in response to changes in sodium intake is enor-

day (more than 10 times normal) or decreased to
10 mEq/day (less than one tenth normal) with rela-
tively small changes in extracellular fluid volume or

cific mechanisms that permit the kidneys to perform

Regulation of Arterial Pressure.

As discussed in Chapter

ulation of arterial pressure by excreting variable

tribute to short-term arterial pressure regulation by

renin, that lead to the formation of vasoactive prod-

Regulation of Acid-Base Balance.

means of eliminating from the body certain types of

erythropoietin, which stimulates the production of red

stimulus for erythropoietin secretion by the kidneys is

their kidneys removed and have been placed on

decreased erythropoietin production.

Regulation of 1,25–Dihydroxyvitamin D

Production.

dihydroxyvitamin D

(calcitriol

tial for normal calcium deposition in bone and calcium

calcium and phosphate regulation.

Glucose Synthesis.

amino acids and other precursors during prolonged

kidneys’ capacity to add glucose to the blood during

and severe abnormalities of body fluid volumes and

stances accumulate in the body to cause death within

Physiologic Anatomy
of the Kidneys

General Organization of the Kidneys

Each kidney of the adult human weighs about 150

medial side of each kidney contains an indented region
called the hilum through which pass the renal artery

capsule that protects its

Time (days)

10 12

Sodium intake and

excretion

(mEq/day)

Extracellular

fluid volume

(Liters)

300

Sodium

retention

Intake

Excretion

Sodium

loss

200

100

intake and sodium excretion.

sodium loss, determined from the difference between sodium

The shaded areas represent the net sodium retention or the net

day) on urinary sodium excretion and extracellular fluid volume.

Effect of increasing sodium intake 10-fold (from 30 to 300 mEq/

Figure 26–1

peritubular capillaries, thereby changing the rate of

and efferent arterioles, the kidneys can regulate the

sorption. By adjusting the resistance of the afferent

60 mm Hg) causes rapid fluid filtration, whereas a

pressure in both sets of capillaries. High hydro-

efferent arterioles, which help regulate the hydrostatic

which are arranged in series and separated by the

illary beds, the glomerular and peritubular capillaries,

The renal circulation is unique in that it has two cap-

renal tubules.

peritubular capillaries,

network, the

efferent arteriole,

begin urine formation (Figure 26–3). The distal ends of

glomerular capillaries,

afferent arterioles,

arcuate arteries, interlobular arteries

interlobar arteries,

cent of the cardiac output, or 1100 ml/min. The renal

later in this chapter.

bladder,

calyces, pelvis, and ureter contain contractile elements

The walls of the

minor calyces,

ureter. The outer border of the pelvis is divided into

renal pelvis,

The base of

renal pyramids.

The medulla is divided into multiple cone-shaped

If the kidney is bisected from top to bottom, the two

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control

Chapter 26

309

major regions that can be visualized are the outer
cortex and the inner region referred to as the medulla.

masses of tissue called
each pyramid originates at the border between the
cortex and medulla and terminates in the papilla,
which projects into the space of the

funnel-shaped continuation of the upper end of the

open-ended pouches called major calyces that extend
downward and divide into

which collect

urine from the tubules of each papilla.

that propel the urine toward the

where urine

is stored until it is emptied by micturition, discussed in

Renal Blood Supply

Blood flow to the two kidneys is normally about 22 per

artery enters the kidney through the hilum and then
branches progressively to form the

(also called radial

arteries) and

which lead to the

where large amounts of fluid

and solutes (except the plasma proteins) are filtered to

the capillaries of each glomerulus coalesce to form the

which leads to a second capillary

that surrounds the

static pressure in the glomerular capillaries (about

much lower hydrostatic pressure in the peritubular
capillaries (about 13 mm Hg) permits rapid fluid reab-

hydrostatic pressure in both the glomerular and the

Nephron (enlarged)

Minor calyx

Major calyx

Papilla
Renal cortex

Renal medulla

Renal pelvis
Renal pyramid

Capsule

Kidney

Bladder

Urethra

Ureter

Kidney

Ureter

Renal

artery

kidneys and the urinary system.

General organization of the

Figure 26–2

Renal artery

Juxtaglomerular

apparatus

Efferent

arteriole

Bowman's

capsule

Glomerulus

Interlobar
arteries

Arcuate arteries

Cortical
collecting tubule

Collecting duct

Loop of
Henle

Proximal tubule

Interlobular
arterioles

Segmental

arteries

Afferent

arteriole

Arcuate

artery

Distal tubule

Arcuate

vein

Peritubular

capillaries

circulation of each nephron.

supply the blood flow to the kidney and schematic of the micro-

Figure 26–3

Section of the human kidney showing the major vessels that

urine.

the cortex and empty into the cortical veins. This

Like the loops of Henle, the vasa recta return toward

medulla, lying side by side with the loops of Henle.

tamedullary nephrons, long efferent arterioles extend

network of peritubular capillaries. For the jux-

the cortical nephrons. For the cortical nephrons, the

The vascular structures supplying the jux-

the tips of the renal papillae.

deeply into the medulla, in some cases all the way to

These nephrons have long loops of Henle that dip

juxtamedullary nephrons.

(Figure 26–5).

within the kidney mass. Those nephrons that have

ferences, depending on how deep the nephron lies

the components described earlier, there are some dif-

Juxtamedullary Nephrons.

collects urine from about 4000 nephrons.

250 of the very large collecting ducts, each of which

In each kidney, there are about

renal papillae.

The collecting

The initial parts of 8 to 10 cortical

cortical collecting tubule,

renal cortex. This is followed by the

which, like the proximal tubule, lies in the

distal tubule,

function. Beyond the macula densa, fluid enters the

As we discuss later, the macula

segment, which is actually a plaque in its wall, known

thick segment of the ascending limb.

cortex, its wall becomes much thicker, and it is referred

thin segment of the loop of Henle.

The

ascending limb.

which dips into the renal medulla. Each loop

of Henle,

From the proximal tubule, fluid flows into the

which lies in the cortex of the kidney (Figure 26–4).

proximal tubule,

Bowman’s capsule and then into the

Bowman’s capsule.

ies are covered by epithelial cells, and the total

pressure (about 60 mm Hg). The glomerular capillar-

pared with other capillaries, have high hydrostatic

and anastomosing glomerular capillaries that, com-

The glomerulus contains a network of branching

urine on its way to the pelvis of the kidney (see Figure

amounts of fluid are filtered from the blood, and (2) a

glomerulus,

electrolytes, and waste products, as discussed in

them to excrete the proper amounts of water,

did at age 40. This loss is not life threatening because

per cent every 10 years; thus, at age 80, many people

decrease in nephron number. After age 40, the number

injury, disease, or normal aging, there is a gradual

cannot regenerate new nephrons. Therefore, with renal

each capable of forming urine. The kidney

nephrons,

The Nephron Is the Functional Unit

leaves the kidney beside the renal artery and ureter.

arcuate vein, interlobar vein,

the venous system, which run parallel to the arteriolar

The peritubular capillaries empty into the vessels of

response to body homeostatic demands.

glomerular filtration, tubular reabsorption, or both in

310

Unit V

The Body Fluids and Kidneys

vessels and progressively form the interlobular vein,

and renal vein, which

of the Kidney

Each kidney in the human contains about 1 million

of functioning nephrons usually decreases about 10

have 40 per cent fewer functioning nephrons than they

adaptive changes in the remaining nephrons allow

Chapter 31.

Each nephron contains (1) a tuft of glomerular cap-

illaries called the

through which large

long tubule in which the filtered fluid is converted into

26–3).

glomerulus is encased in

Fluid

filtered from the glomerular capillaries flows into

loop

consists of a descending and an
walls of the descending limb and the lower end of the
ascending limb are very thin and therefore are called
the

After the ascend-

ing limb of the loop has returned partway back to the

to as the

At the end of the thick ascending limb is a short

as the macula densa.
densa plays an important role in controlling nephron

connecting tubule

and the

which lead to the cor-

tical collecting duct.
collecting ducts join to form a single larger collecting
duct that runs downward into the medulla and
becomes the medullary collecting duct.
ducts merge to form progressively larger ducts that

eventually empty into the renal pelvis through the tips
of the

Regional Differences in Nephron Structure: Cortical and

Although each nephron has all

glomeruli located in the outer cortex are called corti-
cal nephrons; they have short loops of Henle that
penetrate only a short distance into the medulla

About 20 to 30 per cent of the nephrons have

glomeruli that lie deep in the renal cortex near the
medulla and are called

tamedullary nephrons also differ from those supplying

entire tubular system is surrounded by an extensive

from the glomeruli down into the outer medulla and
then divide into specialized peritubular capillaries
called vasa recta that extend downward into the

specialized network of capillaries in the medulla plays
an essential role in the formation of a concentrated

Cortical
collecting tubule

Macula densa

Loop of Henle:
Thick segment of
ascending limb

Thin segment of
ascending limb

Descending limb

Distal tubule

Proximal tubule

Collecting duct

Medullary
collecting tubule

Medulla

Cortex

Cortical
collecting tubule

Bowman's capsule

Connecting tubule

different tubular segments are not drawn to scale.

Basic tubular segments of the nephron. The relative lengths of the

Figure 26–4

bladder.

the bladder, courses obliquely through the detrusor

Each ureter, as it enters

rugae.

is smooth, in contrast to the remaining bladder mucosa,

the inner lining of the bladder,

angles of the trigone. The trigone can be identified by

At the lowermost apex of the trigone,

trigone.

ately above the bladder neck, is a small triangular area

On the posterior wall of the bladder, lying immedi-

traction of the entire bladder at once.

muscle, from one muscle cell to the next, to cause con-

exist from one muscle cell to the other. Therefore, an

bladder to 40 to 60 mm Hg. Thus,

when contracted, can increase the pressure in the

sor muscle.

The smooth muscle of the bladder is called the

urethra. The lower part of the bladder neck is also called

extension of the body, passing inferiorly and anteriorly

neck,

urine collects, and (2) the

body,

muscle chamber composed of two main parts: (1) the

The urinary bladder, shown in Figure 26–6, is a smooth

Nervous Connections

cord reflex, it can also be inhibited or facilitated by

fails, at least causes a conscious desire to urinate.

that empties the bladder or, if this

elicits the second step, which is a nervous reflex called

tension in its walls rises above a threshold level; this

steps: First, the bladder fills progressively until the

empties when it becomes filled. This involves two main

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control

Chapter 26

311

Micturition

Micturition is the process by which the urinary bladder

the micturition reflex

Although the micturition reflex is an autonomic spinal

centers in the cerebral cortex or brain stem.

Physiologic Anatomy and

of the Bladder

which is the major part of the bladder in which

which is a funnel-shaped

into the urogenital triangle and connecting with the

the posterior urethra because of its relation to the
urethra.

detru-

Its muscle fibers extend in all directions and,

contraction of the

detrusor muscle is a major step in emptying the bladder.
Smooth muscle cells of the detrusor muscle fuse with
one another so that low-resistance electrical pathways

action potential can spread throughout the detrusor

called the
the bladder neck opens into the posterior urethra, and
the two ureters enter the bladder at the uppermost

the fact that its mucosa,

which is folded to form

muscle and then passes another 1 to 2 centimeters
beneath the bladder mucosa before emptying into the

Cortex

Medulla

Outer zone

Inner zone

Efferent

arteriole

Afferent

arteriole

Collecting

duct

Interlobar
artery

vein

Interlobar
artery
vein

Thick loop
of Henle

Juxtamedullary

nephron

Cortical

nephron

Duct of

Bellini

Vasa
recta

Thin loop
of Henle

nephrons.

tures and differences between cortical and juxtamedullary

Schematic of relations between blood vessels and tubular struc-

Figure 26–5

L1
L2
L3

L4
L5

S1
S2
S3
S4

Ureter

Body

Pudendal

Sympathetics

Parasympathetics

Trigone

Bladder neck
(posterior urethra)

External sphincter

Urinary bladder and its innervation.

Figure 26–6

minute. The pressure peaks may rise only a few cen-

causes the pressure to rise rapidly.

400 milliliters, collection of more urine in the bladder

intrinsic tone of the bladder wall itself. Beyond 300 to

pressure; this constant level of pressure is caused by

timeters of water. Additional urine—200 to 300 milli-

urine has collected, the pressure rises to 5 to 10 cen-

sure is about 0, but by the time 30 to 50 milliliters of

there is no urine in the bladder, the intravesicular pres-

vesicular pressure as the bladder fills with urine. When

Figure 26–7 shows the approximate changes in intra-

the Cystometrogram

and Bladder Wall Tone;

the pelvis of a kidney with a blocked ureter.

kidney. This effect is called the

arterioles, thereby decreasing urine output from the

with severe pain. Also, the pain impulses cause a sym-

stone), intense reflex constriction occurs, associated

When a ureter becomes blocked (e.g., by a ureteral

The ureters are well supplied with pain nerve fibers.

medulla, causing damage to these regions.

of the ureters and, if severe, can increase the pressure

backward into the ureter, a condition called

result, some of the urine in the bladder is propelled

always lead to complete occlusion of the ureter. As a

through the bladder wall is less than normal, so that

In some people, the distance that the ureter courses

allows urine to flow into the bladder.

compression. Each peristaltic wave along the ureter

tends to compress the ureter, thereby preventing back-

for several centimeters through the bladder wall. The

in Figure 26–6. Normally, the ureters course obliquely

in the trigone region of the bladder, as shown

The ureters enter the bladder through the

by sympathetic stimulation.

enhanced by parasympathetic stimulation and inhibited

smooth muscle,

the entire length of the ureters. As with other visceral

bladder. The walls of the ureters contain smooth

and then downward along the length of the ureter,

inherent pacemaker activity, which in turn initiates

calyces and ureters to the bladder.

lecting ducts; there are no significant changes in the

Kidney Through the Ureters

Transport of Urine from the

sensation of fullness and, in some instances, pain.

traction. Some sensory nerve fibers also pass by way of

spinal cord. These sympathetic fibers stimulate mainly

nerves,

ter. Also, the bladder receives

sphincter. These are

innervation are important in bladder function. Most

In addition to the pelvic nerves, two other types of

glionic nerves then innervate the detrusor muscle.

cells located in the wall of the bladder. Short postgan-

These terminate on ganglion

parasympathetic fibers.

The motor nerves transmitted in the pelvic nerves are

emptying.

the bladder wall. Stretch signals from the posterior

The sensory fibers detect the degree of stretch in

fibers.

segments S-2 and S-3. Coursing through the pelvic

sacral plexus,

pelvic nerves,

The principal nerve supply of the bladder is by way of

Innervation of the Bladder

ing to empty the bladder.

neck, which is entirely smooth muscle. The external

bladder. This muscle is a voluntary skeletal muscle, in

Beyond the posterior urethra, the urethra passes

posterior urethra empty of urine and, therefore, pre-

internal sphincter.

The muscle in this area is called the

muscle interlaced with a large amount of elastic tissue.

timeters long, and its wall is composed of detrusor

The bladder neck (posterior urethra) is 2 to 3 cen-

312

Unit V

The Body Fluids and Kidneys

Its natural tone normally keeps the bladder neck and

vents emptying of the bladder until the pressure in the
main part of the bladder rises above a critical threshold.

through the urogenital diaphragm, which contains a
layer of muscle called the external sphincter of the

contrast to the muscle of the bladder body and bladder

sphincter muscle is under voluntary control of the
nervous system and can be used to consciously prevent
urination even when involuntary controls are attempt-

the

which connect with the spinal cord

through the

mainly connecting with cord

nerves are both sensory nerve fibers and motor nerve

urethra are especially strong and are mainly re-
sponsible for initiating the reflexes that cause bladder

important are the skeletal motor fibers transmitted
through the pudendal nerve to the external bladder

somatic nerve fibers that innervate

and control the voluntary skeletal muscle of the sphinc-

sympathetic innervation

from the sympathetic chain through the hypogastric

connecting mainly with the L-2 segment of the

the blood vessels and have little to do with bladder con-

the sympathetic nerves and may be important in the

and into the Bladder

Urine that is expelled from the bladder has essentially
the same composition as fluid flowing out of the col-

composition of urine as it flows through the renal

Urine flowing from the collecting ducts into the

renal calyces stretches the calyces and increases their

peristaltic contractions that spread to the renal pelvis

thereby forcing urine from the renal pelvis toward the

muscle and are innervated by both sympathetic and
parasympathetic nerves as well as by an intramural
plexus of neurons and nerve fibers that extends along

peristaltic contractions in the ureter are

detrusor

muscle

normal tone of the detrusor muscle in the bladder wall

flow of urine from the bladder when pressure builds
up in the bladder during micturition or bladder

increases the pressure within the ureter so that the
region passing through the bladder wall opens and

contraction of the bladder during micturition does not

vesi-

coureteral reflux. Such reflux can lead to enlargement

in the renal calyces and structures of the renal

Pain Sensation in the Ureters, and the Ureterorenal Reflex

pathetic reflex back to the kidney to constrict the renal

ureterorenal reflex and

is important for preventing excessive flow of fluid into

Filling of the Bladder

liters—can collect with only a small additional rise in

Superimposed on the tonic pressure changes during

filling of the bladder are periodic acute increases in
pressure that last from a few seconds to more than a

timeters of water or may rise to more than 100

Atonic Bladder Caused by Destruction of Sensory Nerve Fibers.

Abnormalities of Micturition

more than 5 to 10 milliliters left in the bladder.

Ordinarily, all the urine will be emptied, with rarely

simultaneously inhibits the external urethral sphincter.

receptors, which excites the micturition reflex and

thus stretching their walls. This stimulates the stretch

bladder neck and posterior urethra under pressure,

her abdominal muscles, which increases the pressure

lowing way: First, a person voluntarily contracts his or

Voluntary urination

urination can occur.

3. When it is time to urinate, the cortical centers can

a convenient time presents itself.

if the micturition reflex occurs, by continual tonic

2. The higher centers can prevent micturition, even

partially inhibited, except when micturition is

1. The higher centers keep the micturition reflex

tion, but the higher centers normally exert final control

The micturition reflex is the basic cause of micturi-

but can become excitatory.

stem, located mainly in the pons,

by centers in the brain. These centers include (1)

spinal cord reflex, but it can be inhibited or facilitated

The micturition reflex is a completely autonomic

urination will occur. If not, urination will not occur

voluntary constrictor signals to the external sphincter,

it. If this inhibition is more potent in the brain than the

enough, it causes another reflex, which passes through

and more and more powerfully.

filled, micturition reflexes occur more and more often

reflex occurs. As the bladder becomes more and more

emptying the bladder, the nervous elements of this

pressure to the basal tone of the bladder. Once a mic-

period of sustained pressure, and (3) return of the

of (1) progressive and rapid increase of pressure, (2) a

Thus, the micturition reflex is a single complete cycle

reflex ceases, permitting the bladder to relax.

to fatigue and the regenerative cycle of the micturition

more than a minute, the self-regenerative reflex begins

degree of contraction. Then, after a few seconds to

traction of the bladder; thus, the cycle is repeated again

urethra, which causes a further increase in reflex con-

ative.” That is, initial contraction of the bladder acti-

Once a micturition reflex begins, it is “self-regener-

of the detrusor muscle.

bladder continues to fill, the micturition reflexes

tracting, and pressure falls back to the baseline. As the

a fraction of a minute, the detrusor muscles stop con-

When the bladder is only partially filled, these mic-

by way of these same nerves.

sures. Sensory signals from the bladder stretch recep-

in the bladder wall, especially

sensory stretch receptors

They are the result of a stretch reflex initiated by

begin to appear, as shown by the dashed spikes.

bladder fills, many superimposed

Referring again to Figure 26–7, one can see that as the

in the cystometrogram and are caused

centimeters of water. These pressure peaks are called

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control

Chapter 26

313

micturition waves
by the micturition reflex.

Micturition Reflex

micturition contrac-

tions

by the receptors in the posterior urethra when this
area begins to fill with urine at the higher bladder pres-

tors are conducted to the sacral segments of the cord
through the pelvic nerves and then reflexively back
again to the bladder through the parasympathetic
nerve fibers

turition contractions usually relax spontaneously after

become more frequent and cause greater contractions

vates the stretch receptors to cause a greater increase
in sensory impulses to the bladder and posterior

and again until the bladder has reached a strong

turition reflex has occurred but has not succeeded in

reflex usually remain in an inhibited state for a few
minutes to 1 hour or more before another micturition

Once the micturition reflex becomes powerful

the pudendal nerves to the external sphincter to inhibit

until the bladder fills still further and the micturition
reflex becomes more powerful.

Facilitation or Inhibition of Micturition
by the Brain

strong facilitative and inhibitory centers in the brain

and (2) several centers

located in the cerebral cortex that are mainly inhibitory

of micturition as follows:

desired.

contraction of the external bladder sphincter until

facilitate the sacral micturition centers to help
initiate a micturition reflex and at the same time
inhibit the external urinary sphincter so that

is usually initiated in the fol-

in the bladder and allows extra urine to enter the

Micturition reflex contraction cannot occur if the
sensory nerve fibers from the bladder to the spinal cord

100

200

300

400

Volume (milliliters)

Micturition

contractions

Basal cystom

etrogram

Intravesical pressure

(centimeters of water)

) caused by micturition reflexes.

Normal cystometrogram, showing also acute pressure waves

Figure 26–7

(dashed spikes

In panel C, the substance is freely filtered at the

for many of the electrolytes of the body.

tration rate minus the reabsorption rate. This is typical

In this case, the excretion rate is calculated as the fil-

than the rate of filtration at the glomerular capillaries.

blood. Therefore, the rate of urinary excretion is less

In panel B, the substance is freely filtered but is also

are handled by the kidneys in this manner, allowing

Certain waste products in the body, such as creatinine,

neither reabsorbed nor secreted. Therefore, its excre-

thetical substances. The substance shown in panel A is

Figure 26–9 shows the renal handling of four hypo-

peritubular capillaries into the tubules.

and passes through the tubules, it is modified by reab-

the plasma. As filtered fluid leaves Bowman’s capsule

filtrate in Bowman’s capsule is almost the same as in

filtered, so that their concentration in the glomerular

substances in the plasma, except for proteins, are freely

glomerular capillaries into Bowman’s capsule. Most

Filtration rate

mathematically,

from the blood into the renal tubules. Expressed

into the blood, and (3) secretion of substances

cesses, shown in Figure 26–8: (1) glomerular filtration,

The rates at which different substances are excreted

Tubular Secretion

Tubular Reabsorption, and

from Glomerular Filtration,

Urine Formation Results

elicits an uncontrollable micturition reflex, thereby pro-

of the inhibitory signals. Therefore, facilitative impulses

micturition. This condition derives from partial damage

tion is the so-called uninhibited neurogenic bladder,

Uninhibited Neurogenic Bladder Caused by Lack of Inhibitory

the genital region, which sometimes elicits a micturition

nounced) bladder emptying occurs.

micturition reflexes return; then, periodic (but unan-

caused by overstretching of the bladder, the excitability

stem and cerebrum. However, if the bladder is emptied

pressed because of the state of “spinal shock” caused by

cord has occurred, the micturition reflexes are sup-

they are no longer controlled by the brain. During the

typical micturition reflexes can still occur. However,

bladder.

tabes dorsalis,

destroying them. This condition is called

constrictive fibrosis around the dorsal root nerve fibers,

enter the spinal cord. For example, syphilis can cause

the sacral region of the spinal cord. Certain diseases can

overflow incontinence.

overflows a few drops at a time through the urethra.This

emptying periodically, the bladder fills to capacity and

neurogenic connections within the brain. Instead of

person loses bladder control, despite intact efferent

stretch signals from the bladder. When this happens, a

are destroyed, thereby preventing transmission of

314

Unit V

The Body Fluids and Kidneys

fibers from the cord to the bladder and despite intact

is called

A common cause of atonic bladder is crush injury to

also cause damage to the dorsal root nerve fibers that

and the resulting bladder condition is called tabetic

Automatic Bladder Caused by Spinal Cord Damage Above the
Sacral Region.

If the spinal cord is damaged above the

sacral region but the sacral cord segments are still intact,

first few days to several weeks after the damage to the

the sudden loss of facilitative impulses from the brain

periodically by catheterization to prevent bladder injury

of the micturition reflex gradually increases until typical

Some patients can still control urination in this con-

dition by stimulating the skin (scratching or tickling) in

reflex.

Signals from the Brain.

Another abnormality of micturi-

which results in frequent and relatively uncontrolled

in the spinal cord or the brain stem that interrupts most

passing continually down the cord keep the sacral
centers so excitable that even a small quantity of urine

moting frequent urination.

in the urine represent the sum of three renal pro-

(2) reabsorption of substances from the renal tubules

Urinary excretion rate

- Reabsorption rate + Secretion rate

Urine formation begins when a large amount of

fluid that is virtually free of protein is filtered from the

sorption of water and specific solutes back into the
blood or by secretion of other substances from the

freely filtered by the glomerular capillaries but is

tion rate is equal to the rate at which it was filtered.

excretion of essentially all that is filtered.

partly reabsorbed from the tubules back into the

glomerular capillaries but is not excreted into the

1. Filtration
2. Reabsorption
3. Secretion
4. Excretion

Peritubular
capillaries

Renal
vein

Urinary excretion

Excretion = Filtration – Reabsorption + Secretion

Glomerular

capillaries

Bowman's

capsule

Afferent

arteriole

Efferent

arteriole

rate at which it is secreted from the peritubular capillary blood into

which the substance is filtered minus its reabsorption rate plus the

urine. Urinary excretion rate of a substance is equal to the rate at

Basic kidney processes that determine the composition of the

Figure 26–8

the tubules.

volume and composition of the body fluids.

and processed about 60 times each day. This high GFR

is about 180 L/day, the entire plasma can be filtered

plasma volume is only about 3 liters, whereas the GFR

kidney many times each day. Because the entire

for effective removal from the body.

by the tubules and, therefore, depend on a high GFR

excretion. Most waste products are poorly reabsorbed

and then reabsorbing most of these substances. One

constant. In reality, changes in glomerular filtration

renal excretion. For example, an increase in glomeru-

excretion. Therefore, subtle adjustments of filtration or

For most substances, the rates of filtration and reab-

tion of the filtered sodium is reabsorbed, resulting in

when there is excess sodium in the body, the rate at

lated according to the needs of the body. For example,

tubular reabsorption, and tubular secretion—is regu-

capillaries.

amino acids and glucose, are completely reabsorbed

in the urine. Certain nutritional substances, such as

highly reabsorbed, so that only small amounts appear

as sodium ions, chloride ions, and bicarbonate ions, are

excretion rates are high. Conversely, electrolytes, such

secreted from the blood into the tubules, so that their

drugs are also poorly reabsorbed but, in addition, are

amounts in the urine. Certain foreign substances and

reabsorbed and are therefore excreted in large

as urea, creatinine, uric acid, and urates, are poorly

blood, especially the end products of metabolism such

urine. Most substances that must be cleared from the

urine, but secretion plays an important role in deter-

In general, tubular reabsorption is quantitatively more

Secretion of Different Substances

Filtration, Reabsorption, and

basic renal processes.

occurs. The rate at which the substance is excreted in

bination of filtration, reabsorption, and secretion

For each substance in the plasma, a particular com-

tubular secretion rate.

and excreted in large amounts in the urine. The excre-

This pattern often occurs for organic acids and bases,

the peritubular capillary blood into the renal tubules.

glomerular capillaries and is not reabsorbed, but addi-

The substance in panel D is freely filtered at the

to be conserved in the body fluids.

blood, such as amino acids and glucose, allowing them

from the tubules back into the blood. This pattern

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control

Chapter 26

315

urine because all the filtered substance is reabsorbed

occurs for some of the nutritional substances in the

tional quantities of this substance are secreted from

permitting them to be rapidly cleared from the blood

tion rate in this case is calculated as filtration rate plus

the urine depends on the relative rates of these three

important than tubular secretion in the formation of

mining the amounts of potassium and hydrogen ions
and a few other substances that are excreted in the

from the tubules and do not appear in the urine even
though large amounts are filtered by the glomerular

Each of the processes—glomerular filtration,

which sodium is filtered increases and a smaller frac-

increased urinary excretion of sodium.

sorption are extremely large relative to the rates of

reabsorption can lead to relatively large changes in

lar filtration rate (GFR) of only 10 per cent (from 180
to 198 L/day) would raise urine volume 13-fold (from
1.5 to 19.5 L/day) if tubular reabsorption remained

and tubular reabsorption usually act in a coordinated
manner to produce the necessary changes in renal
excretion.

Why Are Large Amounts of Solutes Filtered and Then Reab-
sorbed by the Kidneys?

One might question the wisdom

of filtering such large amounts of water and solutes

advantage of a high GFR is that it allows the kidneys
to rapidly remove waste products from the body that
depend primarily on glomerular filtration for their

A second advantage of a high GFR is that it allows

all the body fluids to be filtered and processed by the

allows the kidneys to precisely and rapidly control the

Substance A

Urine

Filtration only

Substance B

Urine

Filtration, partial

reabsorption

Substance C

Urine

Filtration, complete

reabsorption

Substance D

Urine

Filtration, secretion

renal tubules.

sorbed but is secreted from the peritubular capillary blood into the

The substance is freely filtered and is not reab-

because all the filtered substance is reabsorbed from the tubules

The substance is freely filtered but is not excreted in the urine

tered, but part of the filtered load is reabsorbed back in the blood.

The substance is freely fil-

is freely filtered but not reabsorbed.

Figure 26–9

Renal handling of four hypothetical substances. A, The substance

into the blood. D,

proteins.

proteins. Thus, all layers of the glomerular capillary

The epithelial cells, which also have negative charges,

through which the glomerular filtrate moves.

The foot processes are separated by gaps called

outer surface of the capillaries (see Figure 26–10).

long footlike processes (podocytes) that encircle the

glomerulus. These cells are not continuous but have

The final part of the glomerular membrane is a layer

proteoglycans.

filtration of plasma proteins, in part because of

filter. The basement membrane effectively prevents

brane,

the passage of plasma proteins.

fenestrations are relatively large, endothelial cells are

fenestrated capillaries found in the liver. Although the

fenestrae,

teristics. The capillary

The high filtration rate across the glomerular capil-

vents filtration of plasma proteins.

tion, the glomerular capillary membrane normally pre-

capillary membrane. Even with this high rate of filtra-

barrier, which, despite the three layers, filters several

26–10). Together, these layers make up the filtration

surface of the capillary basement membrane (Figure

basement membrane,

the capillary, (2) a

of the usual two) major layers: (1) the

of other capillaries, except that it has three (instead

The glomerular capillary membrane is similar to that

Filtration fraction

capillaries. The filtration fraction is calculated as

filtered (the filtration fraction) averages about 0.2; this

180 L/day. The fraction of the renal plasma flow that is

average adult human, the GFR is about 125 ml/min, or

. In the

The glomerular capillaries have a much higher rate of

meability and filtering surface area of the capillaries.

), the product of the per-

As in other capillaries, the GFR is determined by (1)

GFR Is About 20 Per Cent of the

are not filtered through the glomerular capillaries.

acids are bound to proteins, and these bound portions

partially bound to the plasma proteins. Almost one

fatty acids, that are not freely filtered because they are

low-molecular-weight substances, such as calcium and

plasma. Exceptions to this generalization include a few

molecules, are similar to the concentrations in the

glomerular filtrate, including most salts and organic

The concentrations of other constituents of the

cellular elements, including red blood cells.

proteins, so that the filtered fluid (called the glomeru-

into Bowman’s capsule. Like most capillaries, the

Composition of the Glomerular

First Step in Urine Formation

316

Unit V

The Body Fluids and Kidneys

Glomerular Filtration—The

Filtrate

Urine formation begins with filtration of large
amounts of fluid through the glomerular capillaries

glomerular capillaries are relatively impermeable to

lar filtrate) is essentially protein-free and devoid of

half of the plasma calcium and most of the plasma fatty

Renal Plasma Flow

the balance of hydrostatic and colloid osmotic forces
acting across the capillary membrane and (2) the cap-
illary filtration coefficient (K

filtration than most other capillaries because of a high
glomerular hydrostatic pressure and a large K

means that about 20 per cent of the plasma flowing
through the kidney is filtered through the glomerular

follows:

= GFR/Renal plasma flow

Glomerular Capillary Membrane

endothelium of

and (3) a layer

of epithelial cells (podocytes) surrounding the outer

hundred times as much water and solutes as the usual

lary membrane is due partly to its special charac-

endothelium is perforated by

thousands of small holes called

similar to the

richly endowed with fixed negative charges that hinder

Surrounding the endothelium is the basement mem-

which consists of a meshwork of collagen and

proteoglycan fibrillae that have large spaces through
which large amounts of water and small solutes can

strong negative electrical charges associated with the

of epithelial cells that line the outer surface of the

slit pores

provide additional restriction to filtration of plasma

wall provide a barrier to filtration of plasma

Efferent arteriole

Bowman's capsule

Bowman's space

Capillary loops

Afferent arteriole

Slit pores

Epithelium

Basement
membrane

Endothelium

Fenestrations

Proximal tubule

Podocytes

ponents: capillary endothelium, basement membrane, and epithe-

section of the glomerular capillary membrane and its major com-

Cross

Basic ultrastructure of the glomerular capillaries.

Figure 26–10

lium (podocytes).

The GFR can therefore be expressed as

is considered to be zero.)

colloid osmotic pressure of the Bowman’s capsule fluid

(Under normal conditions, the concentration of

), which promotes filtration.

Bowman’s capsule (

), which opposes filtration; and

outside the capillaries, which opposes filtration; (3) the

(2) the hydrostatic pressure in Bowman’s capsule (P

), which promotes filtration;

hydrostatic pressure, P

(Figure 26–12). These forces include (1) hydrostatic

The net filtration pressure represents the sum of the

. Expressed mathematically, the GFR equals the

net filtration pressure,

membrane, which gives the

The GFR is determined by (1) the sum of the hydro-

Determinants of the GFR

in the urine, a condition known as

proteins, especially albumin, are filtered and appear

membranes, some of the lower-molecular-weight

minimal change nephropathy.

noticeable changes in kidney histology, a condition

In certain kidney diseases, the negative charges on

including the plasma proteins.

for restricting large negatively charged molecules,

brane and the podocytes provide an important means

weight. The reason for these differences in filterability

more readily than negatively charged molecules.

radius, positively charged molecules are filtered much

positive charges. Note that for any given molecular

glomerulus. Dextrans are polysaccharides that can be

Figure 26–11 shows how electrical charge affects the

charges of the glomerular capillary wall proteoglycans.

from filtration, however, because of its negative charge

8 nanometers (80 angstroms). Albumin is restricted

is only about 6 nanometers, whereas the pores of

The molecular diameter of the plasma protein albumin

ing zero.

albumin, the filterability rapidly decreases, approach-

pounds such as glucose are freely filtered. As the

tered only 75 per cent as rapidly as water. Note that

terability of different molecules. A filterability of 1.0

Table 26–1 lists the effect of molecular size on fil-

based on their size and electrical charge.

is selective in determining which molecules will filter,

the high filtration rate, the glomerular filtration barrier

porous and therefore filters fluid at a high rate. Despite

than most other capillaries, but it is also much more

The glomerular capillary membrane is thicker

Filterability of Solutes Is Inversely Related to Their

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control

Chapter 26

317

Size.

means that the substance is filtered as freely as water;
a filterability of 0.75 means that the substance is fil-

electrolytes such as sodium and small organic com-

molecular weight of the molecule approaches that of

Negatively Charged Large Molecules Are Filtered Less Easily
Than Positively Charged Molecules of Equal Molecular Size.

the glomerular membrane are thought to be about

and the electrostatic repulsion exerted by negative

filtration of different molecular weight dextrans by the

manufactured as neutral molecules or with negative or

Neutral dextrans are also filtered more readily than
negatively charged dextrans of equal molecular

is that the negative charges of the basement mem-

the basement membrane are lost even before there are

referred to as

As a result

of this loss of negative charges on the basement

proteinuria or

albuminuria.

static and colloid osmotic forces across the glomerular

and

(2) the glomerular capillary filtration coefficient,
K

product of K

and the net filtration pressure:

GFR

= K

¥ Net filtration pressure

hydrostatic and colloid osmotic forces that either favor
or oppose filtration across the glomerular capillaries

pressure inside the glomerular capillaries (glomerular

)

colloid osmotic pressure of the glomerular capillary
plasma proteins (

(4) the colloid osmotic pressure of the proteins in

protein in the glomerular filtrate is so low that the

GFR

= K

¥ (P

– P

–

+ p

)

Table 26–1

Filterability of Substances by Glomerular Capillaries Based

Myoglobin

17,000

0.75

Inulin

5,500

1.0

Glucose

180

1.0

Sodium

1.0

Water

1.0

Substance

Molecular Weight

Filterability

on Molecular Weight

Albumin

69,000

0.005

Effective molecular radius (A)

Relative filterability

1.0

0.8

0.6

0.4

0.2

Polycationic dextran

Polyanionic dextran

Neutral dextran

charges and with varying molecular weights.

manufactured as neutral molecules or with negative or positive

that it is not filtered. Dextrans are polysaccharides that can be

stance is filtered as freely as water, whereas a value of 0 indicates

Effect of size and electrical charge of dextran on its filterability by

Figure 26–11

the glomerular capillaries. A value of 1.0 indicates that the sub-

28 mm Hg, this value usually rises to about 36 mm Hg

Bowman’s capsule,

thereby concentrating the

20 per cent (Figure 26–13). The reason for this is that

the glomerular capillaries to the efferent arterioles,

capsule pressure. This reduces GFR and eventually

outflow of the urinary tract and raising Bowman’s

urinary tract, often in the ureter, thereby obstructing

of uric acid may lead to “stones” that lodge in the

tion of GFR. For example, precipitation of calcium or

pressure can increase markedly, causing serious reduc-

obstruction of the urinary tract, Bowman’s capsule

However, changes in Bowman’s capsule pressure nor-

GFR, whereas decreasing this pressure raises GFR.

the hydrostatic pressure in Bowman’s capsule reduces

about 18 mm Hg under normal conditions. Increasing

estimate for Bowman’s capsule pressure in humans is

static pressure in Bowman’s capsule and at different

Direct measurements, using micropipettes, of hydro-

Increased Bowman’s Capsule

basement membrane and, eventually, by damaging the

ductivity. For example, chronic, uncontrolled hyper-

lation of GFR. Some diseases, however, lower K

reduces GFR, changes in K

about 0.01 ml/min/mm Hg per 100 grams. This high K

of most other capillary systems of the body; the

4.2 ml/min/mm Hg, a value about 400 times as high as

100 grams of kidney weight, it averages about

is expressed per

Hg of filtration pressure. When K

min and the net filtration pressure is 10 mm Hg, the

cannot be measured directly, but it is

laries. The K

The K

altered mainly in disease states, as discussed later.

different physiologic conditions, whereas others are

Glomerular capillary colloid osmotic pressure

Bowman’s capsule hydrostatic pressure

Bowman’s capsule colloid osmotic pressure

Glomerular hydrostatic pressure

Figure 26–12):

Based on the results in animals, the approximate

have been estimated in animals such as dogs and rats.

GFR have not been measured directly in humans, they

318

Unit V

The Body Fluids and Kidneys

Although the normal values for the determinants of

normal forces favoring and opposing glomerular fil-
tration in humans are believed to be as follows (see

Forces Favoring Filtration (mm Hg)

Forces Opposing Filtration (mm Hg)

Net filtration pressure

= 60 – 18 – 32 = +10 mm Hg

Some of these values can change markedly under

Increased Glomerular Capillary
Filtration Coefficient Increases GFR

is a measure of the product of the hydraulic

conductivity and surface area of the glomerular capil-

estimated experimentally by dividing the rate of
glomerular filtration by net filtration pressure:

= GFR/Net filtration pressure

Because total GFR for both kidneys is about 125 ml/

normal K

is calculated to be about 12.5 ml/min/mm

the K

average K

of many other tissues in the body is only

for the glomerular capillaries contributes tremen-
dously to their rapid rate of fluid filtration.

Although increased K

raises GFR and decreased K

probably do not provide

a primary mechanism for the normal day-to-day regu-

reducing the number of functional glomerular capil-
laries (thereby reducing the surface area for filtration)
or by increasing the thickness of the glomerular
capillary membrane and reducing its hydraulic con-

tension and diabetes mellitus gradually reduce K

increasing the thickness of the glomerular capillary

capillaries so severely that there is loss of capillary
function.

Hydrostatic Pressure Decreases GFR

points in the proximal tubule suggest that a reasonable

mally do not serve as a primary means for regulating
GFR.

In certain pathological states associated with

can damage or even destroy the kidney unless the
obstruction is relieved.

Increased Glomerular Capillary
Colloid Osmotic Pressure
Decreases GFR

As blood passes from the afferent arteriole through

the plasma protein concentration increases about

about one fifth of the fluid in the capillaries filters into

glomerular plasma proteins that are not filtered.
Assuming that the normal colloid osmotic pressure
of plasma entering the glomerular capillaries is

Glomerular
hydrostatic
pressure
(60 mm Hg)

Net filtration
pressure
(10 mm Hg)

–

Glomerular
oncotic
pressure
(32 mm Hg)

Bowman's
capsule
pressure
(18 mm Hg)

Afferent

arteriole

Efferent

arteriole

Bowman's

capsule

pressure

(18 mm Hg)

Bowman's

capsule

pressure

(18 mm Hg)

Glomerular
hydrostatic

pressure

(60 mm Hg)

Glomerular
hydrostatic

pressure

(60 mm Hg)

Glomerular

colloid osmotic

pressure

(32 mm Hg)

Glomerular

colloid osmotic

pressure

(32 mm Hg)

The values shown are estimates for healthy humans.

Summary of forces causing filtration by the glomerular capillaries.

Figure 26–12

(Figure 26–14).

Conversely, dilation of the afferent arterioles increases

pressure fluctuates.)

GFR. (However, as discussed later, this effect is

lar hydrostatic pressure and, therefore, to increase

efferent arteriolar resistance.

resistance,

arterial pressure,

control: (1)

three variables, each of which is under physiologic

pressure raise GFR, whereas decreases in glomerular

lation of GFR. Increases in glomerular hydrostatic

conditions. Changes in glomerular hydrostatic pres-

The glomerular capillary hydrostatic pressure has

lower rate of blood flow into the glomerulus tends to

flow into the glomerulus tends to increase GFR, and a

glomerular hydrostatic pressure, a greater rate of blood

Consequently, even with a constant

capillaries, causing a slower rise in the glomerular

With increasing renal blood flow, a lower fraction of

pressure.

reason, changes in renal blood flow can influence GFR

osmotic pressure and tend to reduce GFR. For this

GFR or by reducing renal plasma flow. For example, a

tration fraction is defined as GFR/renal plasma flow,

(see Figure 26–13). Because the fil-

colloid osmotic pressure, which in turn decreases

tion fraction). Increasing the arterial plasma colloid

Thus, two factors that influence the glomerular cap-

32 mm Hg.

is midway between 28 and 36 mm Hg, or about

capillaries. Therefore, the average colloid osmotic

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control

Chapter 26

319

by the time the blood reaches the efferent end of the

pressure of the glomerular capillary plasma proteins

illary colloid osmotic pressure are (1) the arterial
plasma colloid osmotic pressure and (2) the fraction
of plasma filtered by the glomerular capillaries (filtra-

osmotic pressure raises the glomerular capillary

GFR.

Increasing the filtration fraction also concentrates the

plasma proteins and raises the glomerular colloid
osmotic pressure

the filtration fraction can be increased either by raising

reduction in renal plasma flow with no initial change
in GFR would tend to increase the filtration fraction,
which would raise the glomerular capillary colloid

independently of changes in glomerular hydrostatic

the plasma is initially filtered out of the glomerular

capillary colloid osmotic pressure and less inhibitory
effect on GFR.

decrease GFR.

Increased Glomerular Capillary
Hydrostatic Pressure Increases GFR

been estimated to be about 60 mm Hg under normal

sure serve as the primary means for physiologic regu-

hydrostatic pressure reduce GFR.

Glomerular hydrostatic pressure is determined by

(2) afferent arteriolar

and (3)

Increased arterial pressure tends to raise glomeru-

buffered by autoregulatory mechanisms that maintain
a relatively constant glomerular pressure as blood

Increased resistance of afferent arterioles reduces

glomerular hydrostatic pressure and decreases GFR.

both glomerular hydrostatic pressure and GFR

Efferent

Afferent

Distance along

glomerular capillary

Distance along

glomerular capillary

Glomerular colloid

osmotic pressure

(mm Hg)

end

Filtration

fraction

Filtration

fraction

Normal

fraction have the opposite effect.

rises along the glomerular capillary; decreases in the filtration

increase the rate at which the plasma colloid osmotic pressure

the filtration fraction (glomerular filtration rate/renal plasma flow)

centrating the plasma proteins that are not filtered. Increases in

glomerular capillaries filters into Bowman’s capsule, thereby con-

glomerular capillary. Normally, about one fifth of the fluid in the

Increase in colloid osmotic pressure in plasma flowing through the

Figure 26–13

Efferent arteriolar resistance

(X normal)

Efferent arteriolar resistance

(X normal)

Glomerular filtration

rate (ml/min)

150

100

Renal blood flow

(ml/min)

2000

1400

800

200

Normal

Renal blood

flow

Glomerular

filtration

rate

Afferent arteriolar resistance

(X normal)

Afferent arteriolar resistance

(X normal)

Glomerular filtration

rate (ml/min)

250

100

150

100

Renal blood flow

(ml/min)

2000

1400

800

200

Normal

Renal blood

flow

Glomerular

filtration

rate

olar resistance on glomerular filtration rate and renal blood flow.

Effect of change in afferent arteriolar resistance or efferent arteri-

Figure 26–14

arteries, arterioles, capillaries, and veins (Table 26–3).

the individual vasculature segments, including the

vascular beds, the total vascular resistance through the

about 3 to 4 mm Hg under most conditions. As in other

arterial pressure, and renal vein pressure averages

sures), divided by the total renal vascular resistance:

Determinants of Renal Blood Flow

reflects the basic metabolic needs of the renal cells.

fourth normal. This residual oxygen consumption

pletely ceases, renal sodium reabsorption also ceases,

filtered (Figure 26–15). If glomerular filtration com-

portion to renal tubular sodium reabsorption, which in

Therefore, renal oxygen consumption varies in pro-

and GFR are reduced and less sodium is filtered, less

reabsorption by the renal tubules. If renal blood flow

other tissues.

metabolic needs, and the arterial-venous extraction of

almost seven times the blood flow of the brain. Thus,

On a per gram weight basis, the kidneys normally

Renal Blood Flow and Oxygen

and the excretory functions of the kidneys.

might be expected, the mechanisms that regulate renal

of body fluid volumes and solute concentrations. As

this need. The purpose of this additional flow is to

However, the high flow to the kidneys greatly exceeds

kidneys with nutrients and removes waste products.

As with other tissues, blood flow supplies the

pared with other organs.

per cent of the total body weight, one can readily see

about 22 per cent of the cardiac output. Considering

flow through both kidneys is about 1100 ml/min, or

In an average 70-kilogram man, the combined blood

Table 26–2 summarizes the factors that can decrease

striction; modest efferent constriction raises GFR, but

reduces GFR. However, the effect of efferent arterio-

To summarize, constriction of afferent arterioles

plasma proteins, which also exert an osmotic effect, as

tion, the more rapidly the colloid osmotic pressure

the Donnan effect; the higher the protein concentra-

protein concentration increases, there is a rapid, non-

striction, there is a decrease in GFR. The primary

there is a slight increase in GFR, but with severe con-

effect on GFR. At moderate levels of constriction,

Thus, efferent arteriolar constriction has a biphasic

for filtration actually decreases, causing a

efferent arteriolar constriction. When this occurs, the

increase in efferent arteriolar resistance), the rise in

increases. Therefore, if the constriction of efferent

arteriolar constriction also reduces renal blood flow,

slightly (see Figure 26–14). However, because efferent

reduce renal blood flow too much, GFR increases

This raises the glomerular hydrostatic pressure, and as

resistance to outflow from the glomerular capillaries.

320

Unit V

The Body Fluids and Kidneys

Constriction of the efferent arterioles increases the

long as the increase in efferent resistance does not

the filtration fraction and glomerular colloid osmotic
pressure increase as efferent arteriolar resistance

arterioles is severe (more than about a threefold

colloid osmotic pressure exceeds the increase in
glomerular capillary hydrostatic pressure caused by

net force
reduction in GFR.

cause of the eventual decrease in GFR is as follows:
As efferent constriction becomes severe and as plasma

linear increase in colloid osmotic pressure caused by

rises because of the interaction of ions bound to the

discussed in Chapter 16.

lar constriction depends on the severity of the con-

severe efferent constriction (more than a threefold
increase in resistance) tends to reduce GFR.

GFR.

Renal Blood Flow

the fact that the two kidneys constitute only about 0.4

that they receive an extremely high blood flow com-

supply enough plasma for the high rates of glomeru-
lar filtration that are necessary for precise regulation

blood flow are closely linked to the control of GFR

Consumption

consume oxygen at twice the rate of the brain but have

the oxygen delivered to the kidneys far exceeds their

oxygen is relatively low compared with that of most

A large fraction of the oxygen consumed by the

kidneys is related to the high rate of active sodium

sodium is reabsorbed and less oxygen is consumed.

turn is closely related to GFR and the rate of sodium

and oxygen consumption decreases to about one

Renal blood flow is determined by the pressure gradi-
ent across the renal vasculature (the difference
between renal artery and renal vein hydrostatic pres-

Renal artery pressure is about equal to systemic

kidneys is determined by the sum of the resistances in

Renal artery pressure Renal vein pressure)

Total renal vascular resistance

(

Table 26–2

Factors That Can Decrease the Glomerular Filtration Rate

hormones (e.g., norepinephrine,

Sympathetic activity, vasoconstrictor

ow, increased plasma

GFR

Urinary tract obstruction (e.g., kidney

GFR

Renal disease, diabetes mellitus,

Physical Determinants*

Physiologic/Pathophysiologic Causes

(GFR)

Ø K

Æ Ø

hypertension

≠ P

Æ Ø

stones)

≠ p

Æ Ø GFR

Ø Renal blood fl

proteins

Ø P

Æ Ø GFR

Ø A

Æ Ø P

Ø Arterial pressure (has only small effect

due to autoregulation)

Ø R

Æ Ø P

Ø Angiotensin II (drugs that block

angiotensin II formation)

≠ R

Æ Ø P

≠

endothelin)

, afferent arteriolar resistance.

resistance; R

, efferent arteriolar

, systemic arterial pressure; R

lary hydrostatic pressure; A

, glomerular capil-

, glomerular capillary colloid osmotic pressure; P

, Bowman

cient; P

, glomerular

* Opposite changes in the determinants usually increase GFR.
K

filtration coeffi

’s capsule hydrostatic pres-

sure;

bers. Strong activa-

ing the afferent and the efferent arterioles, are richly

Essentially all the blood vessels of the kidneys, includ-

feedback controls that are intrinsic to the kidneys.

released in the kidneys and act locally), and other

uenced by the sympathetic nervous system, hor-

colloid osmotic pressure. These variables, in turn, are

The determinants of GFR that are most variable and

Physiologic Control of

concentrated urine.

system. As discussed in Chapter 28, the vasa recta play

These vessels descend into

ow. Flow to the renal medulla is supplied

ow. Blood

The outer part of the kidney, the renal cortex, receives

with Flow in the Renal Cortex

Renal Medulla Is Very Low Compared

Blood Flow in the Vasa Recta of the

the kidneys, as discussed later in this chapter.

This capacity for autoregulation occurs

range between 80 and 170 mm Hg, a process called

ow, the kidneys have effec-

ow, whereas

mechanisms, as discussed later. An increase in the

various hormones, and local internal renal control

oles, and efferent arterioles. Resistance of these vessels

major segments: interlobular arteries, afferent arteri-

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control

Chapter 26

321

Most of the renal vascular resistance resides in three

is controlled by the sympathetic nervous system,

resistance of any of the vascular segments of the
kidneys tends to reduce the renal blood fl
a decrease in vascular resistance increases renal blood
flow if renal artery and renal vein pressures remain
constant.

Although changes in arterial pressure have some

influence on renal blood fl
tive mechanisms for maintaining renal blood flow and
GFR relatively constant over an arterial pressure

autoregulation.
through mechanisms that are completely intrinsic to

most of the kidney’s blood fl

flow in the renal

medulla accounts for only 1 to 2 per cent of the total
renal blood fl
by a specialized portion of the peritubular capillary
system called the vasa recta.
the medulla in parallel with the loops of Henle and
then loop back along with the loops of Henle and
return to the cortex before emptying into the venous

an important role in allowing the kidneys to form a

Glomerular Filtration and
Renal Blood Flow

subject to physiologic control include the glomerular
hydrostatic pressure and the glomerular capillary

infl
mones and autacoids (vasoactive substances that are

Sympathetic Nervous System
Activation Decreases GFR

innervated by sympathetic nerve fi
tion of the renal sympathetic nerves can constrict the
renal arterioles and decrease renal blood flow and

Oxygen consumption

(ml/min/100 gm kidney weight)

3.0

2.5

2.0

1.5

0.5

1.0

Sodium reabsorption

(mEq/min per 100 g kidney weight)

Sodium reabsorption

(mEq/min per 100 g kidney weight)

Basal oxygen consumption

during variations of blood pressure. Pflugers Arch Physiol

sorption in dog kidneys. (Kramer K, Deetjen P: Relation of renal

Relationship between oxygen consumption and sodium reab-

Figure 26–15

oxygen consumption to blood supply and glomerular filtration

271:782, 1960.)

Table 26–3

Interlobar, interlobular, and arcuate veins

Peritubular capillaries

Efferent arteriole

Glomerular capillaries

Afferent arteriole

100

Interlobar, arcuate, and interlobular arteries

Renal artery

100

Per Cent of Total Renal Vascular Resistance

Beginning

End

Vessel

Pressure in Vessel (mm Hg)

Approximate Pressures and Vascular Resistances in the Circulation of a Normal Kidney

~16
~26

~43
~10

Renal vein

ow. Under stressful

By opposing vasoconstriction of afferent arterioles,

afferent arterioles.

angiotensin II, especially their effects to constrict the

GFR in normal conditions, they may dampen the renal

These substances are discussed in Chapter 17.

Prostaglandins and Bradykinin Tend to Increase GFR.

constriction and increased blood pressure.

some hypertensive patients, impaired nitric oxide pro-

excretion, eventually causing high blood pressure. In

fore, administration of drugs that inhibit this normal

excrete normal amounts of sodium and water. There-

vasodilation of the kidneys. This allows the kidneys to

lial-derived nitric oxide.

creases renal vascular resistance and is released by the

Endothelial-Derived Nitric Oxide Decreases Renal Vascular

detail later in this chapter.

and blood pressure. This effect of angiotensin II in

sodium and water, which helps restore blood volume

the same time, the angiotensin II

ltration for their excretion; at

Thus, increased angiotensin II levels that occur with

water, as discussed in Chapter 27.

ow through the peritubular capillaries,

same time, though, the reduction in renal blood

in glomerular hydrostatic pressure and GFR; at the

constricting efferent arterioles, helps

cumstances, the increased level of angiotensin II, by

depletion, which tend to decrease GFR. In these cir-

ow.

oles, increased angiotensin II levels raise glomerular

as well as in the systemic circulation. Because

renal vasoconstrictor,

conditions.

of pregnancy, acute renal failure, and chronic uremia,

states associated with vascular injury, such as toxemia

and releases this powerful vasoconstrictor. Plasma

vessel is severed, which damages the endothelium

understood. However, endothelin may contribute to

cells of the kidneys as well as by other tissues. The

Another vasoconstrictor,

such as severe hemorrhage.

renal hemodynamics except under extreme conditions,

activity of the sympathetic nervous system; thus, nor-

general, blood levels of these hormones parallel the

released from the adrenal medulla. In

ow, include

afferent and efferent arterioles, causing reductions in

Blood Vessels and Decrease GFR.

Table 26

ow, as summarized in

There are several hormones and autacoids that can

of Renal Circulation

Hormonal and Autacoid Control

ow.

person, sympathetic tone appears to have little in

ischemia, or severe hemorrhage. In the healthy resting

such as those elicited by the defense reaction, brain

turbances lasting for a few minutes to a few hours,

important in reducing GFR during severe, acute dis-

The renal sympathetic nerves seem to be most

example, re

ow and GFR. For

little in

GFR. Moderate or mild sympathetic stimulation has

322

Unit V

The Body Fluids and Kidneys

fluence on renal blood fl

flex activation of the sympathetic nervous

system resulting from moderate decreases in pressure
at the carotid sinus baroreceptors or cardiopulmonary
receptors has little influence on renal blood flow or
GFR.

flu-

ence on renal blood fl

influence GFR and renal blood fl

–4.

Norepinephrine, Epinephrine, and Endothelin Constrict Renal

Hormones that constrict

GFR and renal blood fl

norepinephrine and

epinephrine

epinephrine and epinephrine have little influence on

endothelin, is a peptide

that can be released by damaged vascular endothelial

physiologic role of this autacoid is not completely

hemostasis (minimizing blood loss) when a blood

endothelin levels also are increased in certain disease

and may contribute to renal vasoconstriction and
decreased GFR in some of these pathophysiologic

Angiotensin II Constricts Efferent Arterioles.

A powerful

angiotensin II, can be consid-

ered a circulating hormone as well as a locally pro-
duced autacoid because it is formed in the kidneys

angiotensin II preferentially constricts efferent arteri-

hydrostatic pressure while reducing renal blood fl
It should be kept in mind that increased angiotensin
II formation usually occurs in circumstances associ-
ated with decreased arterial pressure or volume

prevent decreases

flow

caused by efferent arteriolar constriction contributes
to decreased fl
which in turn increases reabsorption of sodium and

a low-sodium diet or volume depletion help preserve
GFR and maintain normal excretion of metabolic
waste products such as urea and creatinine that
depend on glomerular fi

–induced constriction

of efferent arterioles increases tubular reabsorption of

helping to “autoregulate” GFR is discussed in more

Resistance and Increases GFR.

An autacoid that de-

vascular endothelium throughout the body is endothe-

A basal level of nitric oxide

production appears to be important for maintaining

formation of nitric oxide increases renal vascular
resistance and decreases GFR and urinary sodium

duction could be the cause of increased renal vaso-

Hor-

mones and autacoids that cause vasodilation and
increased renal blood flow and GFR include the
prostaglandins (PGE

and PGI

) and bradykinin.

Although these vasodilators do not appear to be of
major importance in regulating renal blood flow or

vasoconstrictor effects of the sympathetic nerves or

the prostaglandins may help prevent excessive reduc-
tions in GFR and renal blood fl

Hormones and Autacoids That Influence Glomerular

Table 26–4

Hormone or Autacoid

Effect on GFR

Filtration Rate (GFR)

Norepinephrine

Epinephrine

Endothelin

Angiotensin II

¨Æ (prevents Ø)

Endothelial-derived nitric oxide

≠

Prostaglandins

≠

otherwise occur. In many circumstances, this feedback

with the control of renal arteriolar resistance. This

To perform the function of autoregulation, the kidneys

in Autoregulation of GFR

Role of Tubuloglomerular Feedback

arterial pressure, as discussed in Chapters 19 and 29.

pressure natriuresis,

renal excretion of water and sodium; this is referred to

Even with these special control mechanisms, changes

rate when GFR rises, a phenomenon referred to as

changes in GFR that would otherwise occur, and (2)

two reasons: (1) renal autoregulation prevents large

But in reality, such a change in arterial pressure

volume.

Because the total plasma volume is only about 3 liters,

ow to 46.5 L/day

day, this would increase the urine

increase in GFR (from about 180 to 225 L/day). If

to 125 mm Hg) would cause a similar 25 per cent

excreted in the urine. In the absence of autoregulation,

sorption is 178.5 L/day, leaving 1.5 L/day of

Normally, GFR is about 180 L/day and tubular reab-

mechanisms.

sorption, and renal excretion and the changes in renal

ltration, tubular reab-

blood pressure. One can understand the quantitative

100 per cent perfect, but they do prevent potentially

The autoregulatory mechanisms of the kidney are not

Importance of GFR Autoregulation

ciently autoregulated under certain conditions.

regulated in parallel with GFR, but GFR is more ef

percentage points. In general, renal blood

s usual activities. For instance, a decrease in

remains relatively constant), despite considerable

The GFR normally remains autoregulated (that is,

renal excretion of water and solutes.

required for these functions. The major function of

despite changes in the arterial pressure. In the kidneys,

The primary function of blood

(Figure 26

constancy of GFR and renal blood

uences. This relative

body, independent of systemic in

pressure. These mechanisms still function in blood-

constant, despite marked changes in arterial blood

Feedback mechanisms intrinsic to the kidneys nor-

Autoregulation of GFR and

agents, such as aspirin, that inhibit prostaglandin syn-

conditions, such as volume depletion or after surgery,

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control

Chapter 26

323

the administration of nonsteroidal anti-inflammatory

thesis may cause significant reductions in GFR.

Renal Blood Flow

mally keep the renal blood flow and GFR relatively

perfused kidneys that have been removed from the

flow is referred to

as autoregulation

–16).

flow autoregulation

in most tissues other than the kidneys is to maintain
the delivery of oxygen and nutrients at a normal level
and to remove the waste products of metabolism,

the normal blood flow is much higher than that

autoregulation in the kidneys is to maintain a rela-
tively constant GFR and to allow precise control of

arterial pressure fluctuations that occur during a
person’

arterial pressure to as low as 75 mm Hg or an increase
to as high as 160 mm Hg changes GFR only a few

flow is auto-

fi-

in Preventing Extreme Changes in
Renal Excretion

large changes in GFR and renal excretion of water and
solutes that would otherwise occur with changes in

importance of autoregulation by considering the rela-
tive magnitudes of glomerular fi

excretion that would occur without autoregulatory

fluid to be

a relatively small increase in blood pressure (from 100

tubular reabsorption remained constant at 178.5 L/

(the difference between GFR and tubular reabsorp-
tion)—a total increase in urine of more than 30-fold.

such a change would quickly deplete the blood

exerts much less of an effect on urine volume for

there are additional adaptive mechanisms in the renal
tubules that allow them to increase their reabsorption

glomerulotubular balance (discussed in Chapter 27).

in arterial pressure still have significant effects on

as pressure diuresis or

and it is

crucial in the regulation of body fluid volumes and

have a feedback mechanism that links changes in
sodium chloride concentration at the macula densa

feedback helps ensure a relatively constant delivery of
sodium chloride to the distal tubule and helps prevent
spurious fluctuations in renal excretion that would

100

150

Renal blood flow

(ml/min)

1600

1200

800

400

Renal blood flow
Glomerular filtration
rate

Glomerular filtration

rate (ml/min)

160

120

Arterial pressure

(mm Hg)

Arterial pressure

(mm Hg)

200

Urine output

(ml/min)

rial pressure.

lack of autoregulation of urine flow during changes in renal arte-

Autoregulation of renal blood flow and glomerular filtration rate but

Figure 26–16

between the limits of 75 and 160 mm Hg.

points, even with large

together, the GFR changes only a few percentage

When both of these mechanisms are functioning

lation of GFR during changes in arterial pressure.

apparatus, provide feedback signals to both the affer-

feedback mechanism, operating together by way of the

These two components of the tubuloglomerular

rioles, thereby increasing glomerular hydrostatic pres-

Finally, the angiotensin II constricts the efferent arte-

angiotensin I, which is converted to angiotensin II.

sites for renin. Renin released from these cells then

and efferent arterioles, which are the major storage

return GFR toward normal, and (2) it increases renin

ow in the afferent arterioles,

18): (1) it decreases

that has two effects (Figure 26

macula densa cells. This decrease in sodium chloride

chloride ions in the ascending loop of Henle, thereby

Henle, causing increased reabsorption of sodium and

pletely understood. Experimental studies suggest that

The

be secreting a substance toward the arterioles.

toward the arterioles, suggesting that these cells may

oles. The macula densa cells contain Golgi apparatus,

efferent arterioles. The macula densa is a specialized

The juxtaglomerular complex consists of

(Figure

an efferent arteriolar feedback mechanism. These

The tubuloglomerular feedback mechanism has

ow, as discussed later.

the distal tubule, there are instances when GFR is

However, because this mechanism is speci

324

Unit V

The Body Fluids and Kidneys

autoregulates renal blood flow and GFR in parallel.

fically

directed toward stabilizing sodium chloride delivery to

autoregulated at the expense of changes in renal blood
fl

two components that act together to control GFR:
(1) an afferent arteriolar feedback mechanism and (2)

feedback mechanisms depend on special anatomical
arrangements of the juxtaglomerular complex
26–17).

macula

densa cells in the initial portion of the distal tubule and
juxtaglomerular cells in the walls of the afferent and

group of epithelial cells in the distal tubules that comes
in close contact with the afferent and efferent arteri-

which are intracellular secretory organelles directed

Decreased Macula Densa Sodium Chloride Causes Dilation of
Afferent Arterioles and Increased Renin Release.

macula densa cells sense changes in volume delivery
to the distal tubule by way of signals that are not com-

decreased GFR slows the flow rate in the loop of

reducing the concentration of sodium chloride at the

concentration initiates a signal from the macula densa

–

resistance to blood fl
which raises glomerular hydrostatic pressure and helps

release from the juxtaglomerular cells of the afferent

functions as an enzyme to increase the formation of

sure and returning GFR toward normal.

special anatomical structure of the juxtaglomerular

ent and the efferent arterioles for efficient autoregu-

fluctuations in arterial pressure

Juxtaglomerular
cells

Afferent
arteriole

Internal
elastic
lamina

Efferent

arteriole

Smooth

muscle

fiber

Distal

tubule

Glomerular
epithelium

Basement
membrane

Macula densa

sible feedback role in the control of nephron function.

Structure of the juxtaglomerular apparatus, demonstrating its pos-

Figure 26–17

Glomerular hydrostatic

pressure

GFR

Renin

Angiotensin II

Proximal

NaCl

reabsorption

Macula densa

NaCl

Efferent

arteriolar

resistance

Afferent

arteriolar

resistance

Arterial pressure

(GFR) during decreased renal arterial pressure.

glomerular hydrostatic pressure and glomerular filtration rate

Macula densa feedback mechanism for autoregulation of

Figure 26–18

naling. Annu Rev Physiol 65:481, 2003.

Bell PD, Lapointe JY, Peti-Peterdi J: Macula densa cell sig-

Annu Rev Physiol 42:531, 1980.

Beeuwkes R III: The vascular organization of the kidney.

in the urine.

uid solutes, and tubular

the proper rate of delivery of sodium chloride, other

the macula densa in these circumstances. These exam-

depletion.

One of the important compensatory

compensations, would quickly cause excessive volume

delivered to the distal tubule and, without appropriate

consequence, large amounts of sodium chloride are

ability to reabsorb sodium chloride is decreased. As a

or large doses of drugs, such as tetracyclines), their

a result of poisoning by heavy metals, such as mercury,

mal tubular reabsorption is reduced. For example, when

tion can be maintained (see Figure 26

ow and GFR, which

nal processing of the urine takes place. Thus, distur-

delivery of sodium chloride to the distal tubule, where

by the tubuloglomerular feedback mechanism. The

These examples demonstrate that renal blood

chloride to the macula densa, activating a tubu-

with glucose. This, in turn, decreases delivery of sodium

the proximal tubule, increased glucose delivery to the

amino acids, is also reabsorbed along with sodium in

Because glucose, like some of the

diabetes mellitus.

increases in renal blood flow and GFR that occur with

A similar mechanism may also explain the marked

products of protein metabolism, such as urea.

ow and GFR. This increased GFR

earlier. The decreased afferent arteriolar resistance then

in resistance of the afferent arterioles, as discussed

decreases sodium delivery to the macula densa, which

lates sodium reabsorption in the proximal tubules. This

tubules, increased amino acid reabsorption also stimu-

sorbed in the proximal tubule. Because amino acids

release of amino acids into the blood, which are reab-

tion is the following: A high-protein meal increases the

not completely understood, but one possible explana-

The exact mechanisms by which this occurs are still

growth of the kidneys. However, GFR and renal blood

such as one that contains large amounts of meat, the

With a chronic high-protein diet,

blood flow and GFR.

a high protein intake is known to increase both renal

cantly. For example,

stable under most conditions, there are circumstances in

Blood Flow and GFR: High Protein

ow or GFR per se.

ates in most arterioles throughout the body, its impor-

increases.

vascular resistance, helps prevent excessive increases

tention of the vessel and at the same time, by raising

cussed in Chapter 8. This contraction prevents overdis-

uid into the cells,

contraction of the vascular smooth muscle. Stretch

myogenic mechanism.

resist stretching during increased arterial pressure, a

Myogenic Autoregulation of Renal

not occur.

heart failure, and other conditions, as long as they are

agents in many patients with hypertension, congestive

some cases, cause acute renal failure. Nevertheless,

artery) is a severe decrease in GFR that can, in

Therefore, an important complication of using these

pressure falls below normal. The administration of

As discussed earlier, a preferential

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control

Chapter 26

325

Blockade of Angiotensin II Formation Further Reduces GFR During
Renal Hypoperfusion.

constrictor action of angiotensin II on efferent arteri-
oles helps prevent serious reductions in glomerular
hydrostatic pressure and GFR when renal perfusion

drugs that block the formation of angiotensin II
(angiotensin-converting enzyme inhibitors) or that
block the action of angiotensin II (angiotensin II antag-
onists) causes greater reductions in GFR than usual
when the renal arterial pressure falls below normal.

drugs to treat patients who have hypertension because
of renal artery stenosis (partial blockage of the renal

angiotensin II–blocking drugs can be useful therapeutic

monitored to ensure that severe decreases in GFR do

Blood Flow and GFR

Another mechanism that contributes to the main-
tenance of a relatively constant renal blood flow
and GFR is the ability of individual blood vessels to

phenomenon referred to as the
Studies of individual blood vessels (especially small
arterioles) throughout the body have shown that they
respond to increased wall tension or wall stretch by

of the vascular wall allows increased movement of
calcium ions from the extracellular fl
causing them to contract through the mechanisms dis-

in renal blood flow and GFR when arterial pressure

Although the myogenic mechanism probably oper-

tance in renal blood flow and GFR autoregulation has
been questioned by some physiologists because this
pressure-sensitive mechanism has no means of directly
detecting changes in renal blood fl

Other Factors That Increase Renal

Intake and Increased Blood Glucose

Although renal blood flow and GFR are relatively

which these variables change signifi

increases in GFR and renal blood flow are due partly to

flow increase 20 to 30 per cent within 1 or 2 hours after
a person eats a high-protein meal.

and sodium are reabsorbed together by the proximal

elicits a tubuloglomerular feedback–mediated decrease

raises renal blood fl
allows sodium excretion to be maintained at a nearly
normal level while increasing the excretion of the waste

large increases in blood glucose levels in uncontrolled

tubules causes them to reabsorb excess sodium along

loglomerular feedback–mediated dilation of the affer-
ent arterioles and subsequent increases in renal blood
flow and GFR.

flow

and GFR per se are not the primary variables controlled

main purpose of this feedback is to ensure a constant

fi
bances that tend to increase reabsorption of sodium
chloride at tubular sites before the macula densa tend
to elicit increased renal blood fl
helps return distal sodium chloride delivery toward
normal so that normal rates of sodium and water excre-

–18).

An opposite sequence of events occurs when proxi-

the proximal tubules are damaged (which can occur as

responses appears to be a tubuloglomerular feed-
back–mediated renal vasoconstriction that occurs in
response to the increased sodium chloride delivery to

ples again demonstrate the importance of this feedback
mechanism in ensuring that the distal tubule receives

tubular fl

fluid volume so that

appropriate amounts of these substances are excreted

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