Kidney Diseases and Diuretics pdf - The Body Fluids and Kidneys

causes rapid loss of fluid into the urine. In patients with diabetes mellitus, the high

instead, the excess glucose remains in the tubules, acts as an osmotic diuretic, and

centration of about 250 mg/dl, little of the extra glucose is reabsorbed by the tubules;

for glucose). Above a plasma glucose con-

(i.e., exceeds their

blood glucose concentration rises to high levels in diabetes mellitus, the increased

solutes that fail to be reabsorbed from the tubular fluid. For example, when the

tubular fluid into the urine.

of these solutes then greatly reduces water reabsorption, flushing large amounts of

concentration of osmotically active molecules in the tubules. The osmotic pressure

renal tubules, such as urea, mannitol, and sucrose, causes a marked increase in the

by Increasing Osmotic Pressure of Tubular Fluid

Osmotic Diuretics Decrease Water Reabsorption

in Table 31–1.

nephron. The general classes of diuretics and their mechanisms of action are shown

and, therefore, inhibit tubular reabsorption at different sites along the renal

The many diuretics available for clinical use have different mechanisms of action

prompted the use of diuretics in the first place.

cellular fluid volume have occurred, relieving the hypertension or edema that

becomes equal to intake, but only after reductions in arterial pressure and extra-

chronic effects of the diuretic on urine output. Thus, in the steady state, urine output

angiotensin II formation; all these responses, together, eventually override the

volume. For example, a decrease in extracellular fluid volume often reduces arterial

of salt and water subsides within a few days (Figure 31–1). This is due to activation

after they are administered. However, the effect of most diuretics on renal output

volume; therefore, diuretics are most often administered in clinical conditions in

Chapter 25, loss of sodium from the body mainly decreases extracellular fluid

especially in diseases associated with edema and hypertension. As discussed in

The most common clinical use of diuretics is to reduce extracellular fluid volume,

ondarily by sodium reabsorption, many diuretics raise renal output of these solutes

solutes, such as potassium, chloride, magnesium, and calcium, is also influenced sec-

decrease water reabsorption. Because the renal tubular reabsorption of many

sodium reabsorption, because sodium remaining in the tubules acts osmotically to

most cases, increased water output occurs secondary to inhibition of tubular

sodium output), which in turn causes diuresis (increased water output). That is, in

from the tubules, which causes natriuresis (increased

and chloride. In fact, most diuretics that are used clin-

increase urinary excretion of solutes, especially sodium

volume output, as the name implies. Most diuretics also

Diuretics and Their

402

Kidney Diseases and Diuretics

Mechanisms of Action

A diuretic is a substance that increases the rate of urine

ically act by decreasing the rate of sodium reabsorption

as well.

which extracellular fluid volume is expanded.

Some diuretics can increase urine output more than 20-fold within a few minutes

of other compensatory mechanisms initiated by decreased extracellular fluid

pressure and glomerular filtration rate (GFR) and increases renin secretion and

Injection into the blood stream of substances that are not easily reabsorbed by the

Large volumes of urine are also formed in certain diseases associated with excess

filtered load of glucose into the tubules exceeds their capacity to reabsorb glucose

transport maximum

minutes.

the urine, causing, under acute conditions, urine output

of Henle. Because of these multiple effects, 20 to 30 per

of the kidneys is also greatly reduced. In addition,

is decreased, so that the maximal concentrating ability

quently, reabsorption of fluid from the collecting ducts

fore renal medullary osmolarity, is reduced. Conse-

interstitial fluid concentration of these ions, and there-

excreted along with increased water excretion. Urinary

or dilute the urine. Urinary dilution is impaired because

interstitial fluid. Because of this effect, loop diuretics

tion as well; and (2) they disrupt the countercurrent

solutes delivered to the distal parts of the nephrons, and

two reasons: (1) they greatly increase the quantities of

potassium, and other electrolytes, as well as water, for

the loop diuretics raise urine output of sodium, chloride,

transport in the luminal membrane of the loop of Henle,

ically used diuretics.

These diuretics are among the most powerful of the clin-

located in the luminal membrane of the epithelial cells.

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

Furosemide, ethacrynic acid,

Ascending Loop of Henle

Reabsorption in the Thick

“Loop” Diuretics Decrease Active

Chapter 31

Kidney Diseases and Diuretics

403

urine output is balanced by a high level of fluid intake
owing to activation of the thirst mechanism.

Sodium-Chloride-Potassium

and bumetanide are power-

ful diuretics that decrease active reabsorption in the
thick ascending limb of the loop of Henle by blocking

By blocking active sodium-chloride-potassium co-

these act as osmotic agents to prevent water reabsorp-

multiplier system by decreasing absorption of ions from
the loop of Henle into the medullary interstitium,
thereby decreasing the osmolarity of the medullary

impair the ability of the kidneys to either concentrate

the inhibition of sodium and chloride reabsorption in
the loop of Henle causes more of these ions to be

concentration is impaired because the renal medullary

decreased renal medullary interstitial fluid osmolarity
reduces absorption of water from the descending loop

cent of the glomerular filtrate may be delivered into

to be as great as 25 times normal for at least a few

Time (days)

Extracellular fluid

volume (liters)

Sodium excretion or

sodium intake (mEq/day)

200

100

15.0

14.0

13.0

Excretion

Intake

Diuretic therapy

re-establishing sodium balance.

eventually return sodium excretion to equal sodium intake, thus

sodium intake is held constant, compensatory mechanisms will

accompanied by a decrease in extracellular fluid volume. If

administration. The immediate increase in sodium excretion is

Sodium excretion and extracellular fluid volume during diuretic

Figure 31–1

Table 31–1

reabsorption, and

(triamterene, amiloride)

membrane, decrease Na

channels of luminal

Collecting tubules

Sodium channel blockers

Block entry of Na

reabsorption, and decrease

(spironolactone, eplerenone)

decrease Na

Aldosterone antagonists

Inhibit action of aldosterone on tubular receptor,

Collecting tubules

(acetazolamide)

reduces Na

reabsorption, which Proximal

tubules

Carbonic anhydrase inhibitors

Inhibit H

co-transport in luminal membrane

Early distal tubules

Thiazide diuretics (hydrochlorothiazide,

Inhibit Na

co-transport in luminal membrane

Thick ascending loop of Henle

Loop diuretics (furosemide, bumetanide)

Inhibit Na

Osmotic diuretics (mannitol)

Inhibit water and solute reabsorption by increasing

Mainly proximal tubules

Class of Diuretic

Mechanism of Action

Tubular Site of Action

Classes of Diuretics, Their Mechanisms of Action, and Tubular Sites of Action

osmolarity of tubular fluid

-K

-Cl

chlorthalidone)

secretion and HCO

–

reabsorption

secretion

into Na

decrease K

secretion

Postrenal acute renal failure,

tubules.

those that affect the blood vessels, glomeruli, or

abnormalities within the kidney itself, including

blood pressure, such as severe hemorrhage.

the kidneys. This can be a

blood supply to the kidneys; this condition is

1. Acute renal failure resulting from decreased

The causes of acute renal failure can be divided into

Acute Renal Failure

important types of kidney diseases.

and bladder. In this chapter, we discuss specific physi-

urinary tract outside the kidney, including the ureters

glomeruli, tubules, renal interstitium, and parts of the

diseases that can affect the kidney blood vessels,

two general categories, there are many specific kidney

ually decreases overall kidney function. Within these

chronic renal failure,

may eventually recover nearly normal function, and

acute renal failure,

categories: (1)

to have chronic kidney disease.

throughout the world. For example, in 2004, more than

tubular fluid. For this reason, the sodium channel block-

adenosine triphosphatase pump. This decreased activity

therefore, decreased activity of the sodium-potassium-

into the epithelial cells, there is also decreased sodium

epithelial cells. Because of this decreased sodium entry

However, at the cellular level, these drugs act directly

tubules, similar to the effects of spironolactone.

Channels in the Collecting Tubules

contrast to the aldosterone antagonists, which “spare”

other diuretics cause loss of potassium in the urine, in

potassium-sparing diuretics.

centration to increase excessively. For this reason,

instances, this causes extracellular fluid potassium con-

sium from the cells to the extracellular fluid. In some

the tubules, they decrease the excretion of potassium.

well as sodium. Because these drugs also block the

osmotic diuretic, causing increased excretion of water as

sequence, sodium remains in the tubules and acts as an

secretion of potassium in this tubular segment.As a con-

therefore, can decrease the reabsorption of sodium and

Collecting Tubule

Secretion into the Cortical

Reabsorption from and Potassium

ions in the urine.

diuretic. Predictably, a disadvantage of the carbonic

sodium reabsorption. The blockage of sodium and

counter-transport mechanism in the luminal membrane,

lecting tubule.

tubular cells, such as in the intercalated cells of the col-

primary site of action of carbonic anhydrase inhibitors.

bonic anhydrase is abundant in the proximal tubule, the

the proximal tubule, as discussed in Chapter 30. Car-

carbonic anhydrase,

Acetazolamide

Tubules

Carbonic Anhydrase Inhibitors

normally reabsorbed by the distal tubules.

into the urine. This is about the same amount of sodium

tubular cells. Under favorable conditions, these agents

The thiazide derivatives, such as chlorothiazide, act

Distal Tubule

404

Unit V

The Body Fluids and Kidneys

Thiazide Diuretics Inhibit Sodium-
Chloride Reabsorption in the Early

mainly on the early distal tubules to block the sodium-
chloride co-transporter in the luminal membrane of the

cause 5 to 10 per cent of the glomerular filtrate to pass

Block Sodium-Bicarbonate
Reabsorption in the Proximal

inhibits the enzyme

which is critical for the reabsorption of bicarbonate in

Some carbonic anhydrase is also present in other

Because hydrogen ion secretion and bicarbonate

reabsorption in the proximal tubules are coupled to
sodium reabsorption through the sodium-hydrogen ion

decreasing bicarbonate reabsorption also reduces

bicarbonate reabsorption from the tubular fluid causes
these ions to remain in the tubules and act as an osmotic

anhydrase inhibitors is that they cause some degree of
acidosis because of the excessive loss of bicarbonate

Competitive Inhibitors of
Aldosterone Decrease Sodium

Spironolactone and eplerenone are aldosterone antago-
nists that compete with aldosterone for receptor sites
in the cortical collecting tubule epithelial cells and,

effect of aldosterone to promote potassium secretion in

Aldosterone antagonists also cause movement of potas-

spironolactone and other aldosterone inhibitors are
referred to as

Many of the

the loss of potassium.

Diuretics That Block Sodium

Decrease Sodium Reabsorption

Amiloride and triamterene also inhibit sodium reab-
sorption and potassium secretion in the collecting

to block the entry of sodium into the sodium channels
of the luminal membrane of the collecting tubule

transport across the cells’ basolateral membranes and,

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

ers are also potassium-sparing diuretics and decrease
the urinary excretion rate of potassium.

Kidney Diseases

Diseases of the kidneys are among the most important
causes of death and disability in many countries

20 million adults in the United States were estimated

Severe kidney diseases can be divided into two main

in which the kidneys

abruptly stop working entirely or almost entirely but

(2)

in which there is progressive

loss of function of more and more nephrons that grad-

ologic abnormalities that occur in a few of the more

three main categories:

often referred to as prerenal acute renal failure
to reflect the fact that the abnormality occurs
in a system before
consequence of heart failure with reduced cardiac
output and low blood pressure or conditions
associated with diminished blood volume and low

2. Intrarenal acute renal failure resulting from

resulting from

obstruction of the urinary collecting system

proliferate, but mainly the mesangial cells that lie

glomeruli, many of the cells of the glomeruli begin to

in the glomeruli, especially in the basement membrane

that damages the kidneys. Instead, over a few weeks, as

coccal infection of the skin. It is not the infection itself

cal sore throat, streptococcal tonsillitis, or even strepto-

streptococci. The infection may have been a streptococ-

body, usually caused by certain types of group A beta

patients with this disease, damage to the glomeruli

that damages the glomeruli. In about 95 per cent of the

of intrarenal acute renal failure are listed in Table 31–3.

can lead to damage of the renal blood vessels. Causes

lead to tubular damage, and primary tubular damage

interdependent, damage to the renal blood vessels can

tion refers to the primary site of injury, but because the

damage to the renal interstitium. This type of classifica-

renal tubular epithelium, and (3) conditions that cause

other small renal vessels, (2) conditions that damage the

This category of

intrarenal acute renal failure.

Within the Kidney

Caused by Abnormalities

Intrarenal Acute Renal Failure

failure.

patients. Table 31–2 shows some of the common causes

cussed later. Acute reduction of renal blood flow is a

can evolve into intrarenal acute renal failure, as dis-

persists longer than a few hours, this type of renal failure

tubular epithelial cells. If the cause of prerenal acute

damage or even death of the renal cells, especially the

decreases in renal blood flow, if prolonged, will cause

flow, the renal cells start to become hypoxic, and further

reduced below this basal requirement, which is usually

they are not reabsorbing sodium. When blood flow is

reduced. As the GFR approaches zero, oxygen con-

kidney. Therefore, as renal blood flow and GFR fall,

that must be reabsorbed by the tubules, which uses most

reduced. This decreases the amount of sodium chloride

blood flow is reduced, the GFR and the amount of

the renal cells occurs. The reason for this is that as renal

Unlike some tissues, the kidney can endure a relatively

20 to 25 per cent of normal, acute renal failure can

output can occur, a condition referred to as

blood flow is markedly reduced, total cessation of urine

mulation of water and solutes in the body fluids. If renal

the level of intake of water and solutes.This causes accu-

of water and solutes. Consequently, conditions that

Therefore, decreased renal blood flow is usually accom-

lation of body fluid volumes and solute concentrations.

cardiac output.The main purpose of this high blood flow

of about 1100 ml/min, or about 20 to 25 per cent of the

The kidneys normally receive an abundant blood supply

Prerenal Acute Renal Failure

calcium, urate, or cystine.

are kidney stones, caused by precipitation of

the bladder. The most common causes of

Chapter 31

Kidney Diseases and Diuretics

405

anywhere from the calyces to the outflow from

obstruction of the urinary tract outside the kidney

Caused by Decreased Blood Flow
to the Kidney

to the kidneys is to provide enough plasma for the high
rates of glomerular filtration needed for effective regu-

panied by decreased GFR and decreased urine output

acutely diminish blood flow to the kidneys usually cause
oliguria, which refers to diminished urine output below

anuria.

As long as renal blood flow does not fall below about

usually be reversed if the cause of the ischemia is cor-
rected before damage to the renal cells has occurred.

large reduction in blood flow before actual damage to

sodium chloride filtered by the glomeruli (as well as
the filtration rate of water and other electrolytes) are

of the energy and oxygen consumed by the normal

the requirement for renal oxygen consumption is also

sumption of the kidney approaches the rate that is
required to keep the renal tubular cells alive even when

less than 20 to 25 per cent of the normal renal blood

renal failure is not corrected and ischemia of the kidney

common cause of acute renal failure in hospitalized

of decreased renal blood flow and prerenal acute renal

Abnormalities that originate within the kidney and that
abruptly diminish urine output fall into the general cat-
egory of

acute renal failure can be further divided into (1)
conditions that injure the glomerular capillaries or

renal vasculature and tubular system are functionally

Acute Renal Failure Caused by Glomerulonephritis.

Acute

glomerulonephritis is a type of intrarenal acute renal
failure usually caused by an abnormal immune reaction

occurs 1 to 3 weeks after an infection elsewhere in the

antibodies develop against the streptococcal antigen,
the antibodies and antigen react with each other to form
an insoluble immune complex that becomes entrapped

portion of the glomeruli.

Once the immune complex has deposited in the

Table 31–2

Renal artery stenosis, embolism, or thrombosis of renal artery

Primary renal hemodynamic abnormalities

Sepsis, severe infections

Peripheral vasodilation and resultant hypotension

Valvular damage

Cardiac failure

Hemorrhage (trauma, surgery, postpartum, gastrointestinal)

Intravascular volume depletion

Some Causes of Prerenal Acute Renal Failure

Diarrhea or vomiting
Burns

Myocardial infarction

Anaphylactic shock
Anesthesia

or vein

Table 31–3

glycol, insecticides, poison mushrooms, carbon tetrachloride)

Acute tubular necrosis due to toxins (heavy metals, ethylene

Tubular epithelial injury (tubular necrosis)

Vasculitis (polyarteritis nodosa)

Small vessel and/or glomerular injury

Some Causes of Intrarenal Acute Renal Failure

Cholesterol emboli
Malignant hypertension
Acute glomerulonephritis

Acute tubular necrosis due to ischemia

Renal interstitial injury

Acute pyelonephritis
Acute allergic interstitial nephritis

of chronic renal failure. In general, chronic renal

Table 31–4 gives some of the most important causes

75 per cent below normal. In fact, relatively normal

versible loss of large numbers of functioning nephrons.

Nephrons

An Irreversible Decrease

Chronic Renal Failure:

failure.

as well as treatment with an artificial kidney, are dis-

metabolism. Other effects of diminished urine output,

retained water, electrolytes, and waste products of

plete anuria occurs. The patient will die in 8 to 14 days

In the most severe cases of acute renal failure, com-

failure develop metabolic acidosis, which in itself can

sufficient hydrogen ions, patients with acute renal

fatal. Because the kidneys are also unable to excrete

to patients with acute renal failure, because increases

of potassium, however, is often a more serious threat

lead to edema and hypertension. Excessive retention

can lead to water and salt overload, which in turn can

waste products of metabolism, and electrolytes. This

retention in the blood and extracellular fluid of water,

Physiologic Effects of Acute

bladder obstruction, and (3) obstruction of the urethra.

renal pelvises caused by large stones or blood clots, (2)

kidney damage. Some of the causes of postrenal acute

lasting for several days or weeks, can lead to irreversible

hours. But chronic obstruction of the urinary tract,

failure, normal kidney function can be restored if the

extracellular fluid volume. With this type of renal

output of only one kidney is diminished, no major

and other functions are initially normal. If the urine

Lower Urinary Tract

Caused by Abnormalities of the

Postrenal Acute Renal Failure

10 to 20 days.

of the membrane, so that the tubule repairs itself within

is destroyed. If the basement membrane remains intact,

tubules. In some instances, the basement membrane also

death of many of them. As a result, the epithelial cells

toxic action on the renal tubular epithelial cells, causing

certain cancers. Each of these substances has a specific

-platinum, which is used in treating

antibiotics, and

(such as tetracyclines) used as

insecticides,

is a major component in antifreeze), various

carbon tetrachloride, heavy

failure. Some of these are

There is a long list of renal poisons and medications that

Acute Tubular Necrosis Caused by Toxins or Medications.

this chapter.

associated with circulatory shock, as discussed earlier in

normal, as long as the tubules remain plugged. The most

blocked nephrons; the affected nephrons often fail to

nephrons, so that there is no urine output from the

happens, tubular cells “slough off” and plug many of the

destruction of the epithelial cells can occur. When this

cells, and if the insult is prolonged, damage or eventual

impairs the blood supply to the kidney. If the ischemia

Acute Tubular Necrosis Caused by Severe Renal

epithelial cells.

poisons, toxins, or medications that destroy the tubular

tubules. Some common causes of tubular necrosis are

sis,

Tubular Necrosis as a Cause of Acute Renal Failure.

described in a subsequent section of this chapter.

chronic renal failure,

continues indefinitely, leading to

percentage of patients, progressive renal deterioration

glomeruli are destroyed beyond repair, and in a small

weeks to few months. Sometimes, however, many of the

sides in about 2 weeks, and in most patients, the kidneys

The acute inflammation of the glomeruli usually sub-

almost complete renal shutdown occurs.

the glomerular filtrate. In severe cases, either total or

permeable, allowing both protein and red blood cells to

become blocked by this inflammatory reaction, and

entrapped in the glomeruli. Many of the glomeruli

tion, large numbers of white blood cells become

between the endothelium and the epithelium. In addi-

406

Unit V

The Body Fluids and Kidneys

those that are not blocked usually become excessively

leak from the blood of the glomerular capillaries into

return to almost normal function within the next few

Another

cause of intrarenal acute renal failure is tubular necro-

which means destruction of epithelial cells in the

(1) severe ischemia and inadequate supply of oxygen
and nutrients to the tubular epithelial cells and (2)

Ischemia.

Severe ischemia of the kidney can result from

circulatory shock or any other disturbance that severely

is severe enough to seriously impair the delivery of
nutrients and oxygen to the renal tubular epithelial

excrete urine even when renal blood flow is restored to

common causes of ischemic damage to the tubular
epithelium are the prerenal causes of acute renal failure

can damage the tubular epithelium and cause acute renal

metals (such as mercury and lead), ethylene glycol (which

various medications

cis

slough away from the basement membrane and plug the

new tubular epithelial cells can grow along the surface

Multiple abnormalities in the lower urinary tract can
block or partially block urine flow and therefore lead to

acute renal failure even when the kidneys’ blood supply

change in body fluid composition will occur because the
contralateral kidney can increase its urine output suffi-
ciently to maintain relatively normal levels of extracel-
lular electrolytes and solutes as well as normal

basic cause of the problem is corrected within a few

failure include (1) bilateral obstruction of the ureters or

Renal Failure

A major physiologic effect of acute renal failure is

in plasma potassium concentration (hyperkalemia) to
more than about 8 mEq/L (only twice normal) can be

be lethal or can aggravate the hyperkalemia.

unless kidney function is restored or unless an artifi-
cial kidney is used to rid the body of the excessive

cussed in the next section in relation to chronic renal

in the Number of Functional

Chronic renal failure results from progressive and irre-

Serious clinical symptoms often do not occur until the
number of functional nephrons falls to at least 70 to

blood concentrations of most electrolytes and normal
body fluid volumes can still be maintained until the
number of functioning nephrons decreases below 20
to 25 per cent of normal.

As discussed in Chapter 78, type II diabetes, which is

approximately 70 per cent of all chronic renal failure.

of end-stage renal disease, together accounting for

disease. In recent years,

stage renal disease. In the early 1980s,

Table 31–5 gives the most common causes of end-

angiotensin II antagonists.

hydrostatic pressure, especially by using drugs such

disease (Figure 31–2). The only proven method

remaining nephrons, and a slowly progressing vicious

kidney function, further adaptive changes in the

ate the glomerulus, leading to further reduction in

tissue). These sclerotic lesions can eventually obliter-

vasodilation or increased blood pressure; the chronic

glomeruli, which occurs as a result of functional

The cause of this additional injury is not known, but

of these nephrons.

the remaining nephrons, particularly to the glomeruli

normal. Over a period of several years, however, the

nephrons. These adaptive changes permit a person to

increased urine output in the surviving nephrons. The

that lead to increased blood flow, increased GFR, and

end-stage renal disease.

with a functional kidney to survive. This condition is

In many cases, an initial insult to the kidney leads to

Failure Leading to End-Stage

Vicious Circle of Chronic Renal

decrease in the number of functional nephrons.

failure, the end result is essentially the same—a

interstitium, and lower urinary tract. Despite the wide

disorders of the blood vessels, glomeruli, tubules, renal

failure, like acute renal failure, can occur because of

Chapter 31

Kidney Diseases and Diuretics

407

variety of diseases that can lead to chronic renal

Renal Disease

progressive deterioration of kidney function and
further loss of nephrons to the point where the person
must be placed on dialysis treatment or transplanted

referred to as

Studies in laboratory animals have shown that sur-

gical removal of large portions of the kidney initially
causes adaptive changes in the remaining nephrons

exact mechanisms responsible for these changes are
not well understood but involve hypertrophy (growth
of the various structures of the surviving nephrons) as
well as functional changes that decrease vascular
resistance and tubular reabsorption in the surviving

excrete normal amounts of water and solutes even
when kidney mass is reduced to 20 to 25 per cent of

renal functional changes may lead to further injury of

some investigators believe that it may be related in
part to increased pressure or stretch of the remaining

increase in pressure and stretch of the small arterioles
and glomeruli are believed to cause sclerosis of these
vessels (replacement of normal tissue with connective

circle that eventually terminates in end-stage renal

of slowing down this progressive loss of kidney func-
tion is to lower arterial pressure and glomerular

as angiotensin-converting enzyme inhibitors or

glomeru-

lonephritis in all its various forms was believed to be
the most common initiating cause of end-stage renal

diabetes mellitus and hyper-

tension have become recognized as the leading causes

Excessive weight gain (obesity) appears to be the

most important risk factor for the two main causes of
end-stage renal disease—diabetes and hypertension.

Table 31–4

Polycystic disease

Nephrotoxins (analgesics, heavy metals)

Tuberculosis

Polyarteritis nodosa

Renal vascular disorders

Metabolic disorders

Some Causes of Chronic Renal Failure

Diabetes mellitus
Obesity
Amyloidosis

Hypertension

Atherosclerosis
Nephrosclerosis-hypertension

Immunologic disorders

Glomerulonephritis

Lupus erythematosus

Infections

Pyelonephritis

Primary tubular disorders

Urinary tract obstruction

Renal calculi
Hypertrophy of prostate
Urethral constriction

Congenital disorders

Congenital absence of kidney tissue (renal hypoplasia)

Glomerular

sclerosis

Glomerular

pressure

and/or

filtration

Arterial

pressure

Nephron

number

Primary

kidney disease

Hypertrophy

and vasodilation

of surviving

nephrons

sclerosis and eventual loss of these glomeruli.

injure these “normal” capillaries as well, thus causing progressive

the surviving glomerular capillaries, which in turn may eventually

nephrons because of disease may increase pressure and flow in

Vicious circle that can occur with primary kidney disease. Loss of

Figure 31–2

the membranes, and eventual invasion of the glomeruli

membranes are inflammation, progressive thickening of

form of glomerulonephritis. The results of the accumu-

glomerulonephritis, streptococcal infections account for

plexes in the glomerular membrane. In contrast to acute

In most cases, chronic glomerulonephritis begins with

erythematosus.

may be secondary to systemic diseases, such as

kidney disease, following acute glomerulonephritis, or it

leads to irreversible renal failure. It may be a primary

trast to the acute form of this disease, chronic glomeru-

capillary loops in the glomeruli of the kidneys. In con-

degrees of severity of hypertension or diabetes.

reasons, the incidence of malignant nephrosclerosis and

occurring in the affected nephrons. For unknown

gressive thickening of the vessels, with severe ischemia

The characteristic histologi-

malignant nephrosclerosis.

ously. Thus, benign nephrosclerosis in association with

causes of end-stage renal disease, as discussed previ-

In fact, diabetes mel-

diabetes mellitus.

The frequency and severity of nephrosclerosis and

people, kidney plasma flow and GFR decrease by 40 to

in both renal blood flow and GFR. Even in “normal”

(Figure 31–3). This loss of glomeruli and overall

life, causing about a 10 per cent decrease in the number

glomerulosclerosis.

tissue. When sclerosis occurs in the glomeruli, the injury

number of nephrons. Therefore, much of the kidney

tion among the smaller renal arteries, occlusion of one

them. Because there is essentially no collateral circula-

tually constricts the vessels and, in some cases, occludes

develop in the medial layers of these vessels, followed

of these vessels. This causes fibrinoid deposits to

afferent arterioles of the kidney. It is believed to begin

die after the age of 60. This type of vascular lesion

kidney disease, is seen to at least some extent in about

Benign nephrosclerosis,

still normal, a condition analogous to “two-kidney”

kidney function. As discussed in Chapter 19, hyperten-

other and, therefore, cause unilaterally diminished

the smaller arteries, arterioles, and glomeruli.

nephrosclerosis,

large arteries, which also causes occlusion of the vessels;

ies, with progressive sclerotic constriction of the vessels;

ischemia and death of kidney tissue. The most common

Injury to the Renal Vasculature as a

kidney disease.

sion, obesity may have additive or synergistic effects

for developing hypertension in adults. In addition to

90 per cent of all diabetes mellitus. Excess weight gain

closely linked to obesity, accounts for approximately

408

Unit V

The Body Fluids and Kidneys

is also a major cause of essential hypertension,
accounting for as much as 65 to 75 per cent of the risk

causing renal injury through diabetes and hyperten-

to worsen renal function in patients with pre-existing

Cause of Chronic Renal Failure

Many types of vascular lesions can lead to renal

of these are (1) atherosclerosis of the larger renal arter-

(2) fibromuscular hyperplasia of one or more of the

and (3)

caused by sclerotic lesions of

Atherosclerotic or hyperplastic lesions of the large

arteries frequently affect one kidney more than the

sion often occurs when the artery of one kidney is
constricted while the artery of the other kidney is

Goldblatt hypertension.

the most common form of

70 per cent of postmortem examinations in people who

occurs in the smaller interlobular arteries and in the

with leakage of plasma through the intimal membrane

by progressive thickening of the vessel wall that even-

or more of them causes destruction of a comparable

tissue becomes replaced by small amounts of fibrous

is referred to as

Nephrosclerosis and glomerulosclerosis occur to

some extent in most people after the fourth decade of

of functional nephrons each 10 years after age 40

nephron function is reflected by a progressive decrease

50 per cent by age 80.

glomerulosclerosis are greatly increased by concurrent
hypertension or
litus and hypertension are the two most important

severe hypertension can lead to a rapidly progressing

cal features of malignant nephrosclerosis include large
amounts of fibrinoid deposits in the arterioles and pro-

severe glomerulosclerosis is significantly higher in
blacks than in whites of similar ages who have similar

Injury to the Glomeruli as a Cause
of Chronic Renal Failure—
Glomerulonephritis

Chronic glomerulonephritis can be caused by several
diseases that cause inflammation and damage to the

lonephritis is a slowly progressive disease that often

lupus

accumulation of precipitated antigen-antibody com-

only a small percentage of patients with the chronic

lation of antigen-antibody complex in the glomerular

Table 31–5

Polycystic kidney disease

Glomerulonephritis

Hypertension

Diabetes mellitus

Cause

Percentage of Total ESRD Patients

Most Common Causes of End-Stage Renal Disease (ESRD)

Other/unknown

Glomeruli (x 10

)

0.5

0.0

1.0

2.0

2.5

1.5

Age (years)

Effect of aging on the number of functional glomeruli.

Figure 31–3

nephrons that have been destroyed.The reason for this

products of metabolism, such as urea and creatinine,

In contrast to the electrolytes, many of the waste

however, leads to electrolyte and fluid retention, and

Further reduction in the number of nephrons,

accumulation of any of these in the body fluids.

solutes. Yet patients who have lost as much as 75 per

nephrons, which reduces the GFR, would also cause

to Excrete More Water and Solutes.

Loss of Functional Nephrons Requires the Surviving Nephrons

Nephron Function in Chronic

edema, as discussed in Chapter 25.

all over the body into most of the tissues, causing severe

plasma, large amounts of fluid leak from the capillaries

a normal value of 28 to less than 10 mm Hg. As a con-

below 2 g/dl, and the colloid osmotic pressure falls from

fore, the child’s plasma protein concentration often falls

which is an extreme amount for a young child. There-

40 grams of plasma protein loss into the urine each day,

of 2 and 6 years. Increased permeability of the glomeru-

Minimal change nephropathy can occur in adults, but

plasma proteins.

albumin, to pass through the glomerular membrane

glomerular capillaries allows proteins,

especially

from antibody attack on the membrane. Loss of normal

abnormal immune reactions in some cases, suggesting

membrane. Immunologic studies have also shown

26, minimal change nephropathy has been found to

detected with light microscopy. As discussed in Chapter

drome,

minimal change nephrotic syn-

of the glomeruli; and (3)

amyloidosis,

chronic glomerulonephritis,

brane can cause the nephrotic syndrome. Such diseases

permeability of the glomerular membrane. Therefore,

The cause of the protein loss in the urine is increased

it is associated with some degree of renal failure.

major abnormalities of kidney function, but more often

some instances, this occurs without evidence of other

large quantities of plasma proteins into the urine. In

, which is characterized by loss of

of Protein in the Urine Because of

can develop.

functional renal tissue are lost, and chronic renal failure

throughout the kidney. Consequently, large parts of

damage of renal tubules, glomeruli, and other structures

With long-standing pyelonephritis, invasion of the

have markedly impaired ability to concentrate the urine.

trating urine, patients with pyelonephritis frequently

than it affects the cortex, at least in the initial stages.

inflammation associated with pyelonephritis.

medulla, where they can initiate the infection and

is propelled upward toward the kidney, carrying with it

ureter during micturition; as a result, some of the urine

tion. This condition is called

or in some people, bacteria may reach the renal pelvis

may remain localized without ascending to the kidney,

Once cystitis has occurred, it

cystitis.

bacteria multiply and the bladder becomes inflamed, a

impaired ability to flush bacteria from the bladder, the

(2) the existence of obstruction of urine outflow. With

completely, leaving residual urine in the bladder, and

the bladder: (1) the inability of the bladder to empty

readily, there are two general clinical conditions that

ureters to the kidneys.

either by way of the blood stream or, more commonly,

of the urinary tract. These bacteria reach the kidneys

Escherichia coli

The infection can result

pyelonephritis.

bacterial infections.

damage to the renal interstitium by poisons, drugs, and

destroys individual nephrons, or it can involve primary

result from vascular, glomerular, or tubular damage that

In general, this can

interstitial nephritis.

Injury to the Renal Interstitium as a

tissue and are, therefore, unable to filter fluid.

the disease, many glomeruli are replaced by fibrous

thickened glomerular membranes. In the final stages of

by fibrous tissue. In the later stages of the disease, the

Chapter 31

Kidney Diseases and Diuretics

409

glomerular capillary filtration coefficient becomes
greatly reduced because of decreased numbers of filter-
ing capillaries in the glomerular tufts and because of

Cause of Chronic Renal Failure—
Pyelonephritis

Primary or secondary disease of the renal interstitium
is referred to as

Renal interstitial injury caused by bacterial infec-

tion is called
from different types of bacteria but especially from

that originate from fecal contamination

by ascension from the lower urinary tract by way of the

Although the normal bladder is able to clear bacteria

may interfere with the normal flushing of bacteria from

condition termed

because of a pathological condition in which urine is
propelled up one or both of the ureters during micturi-

vesicoureteral reflux and is

due to the failure of the bladder wall to occlude the

bacteria that can reach the renal pelvis and renal

Pyelonephritis begins in the renal medulla and there-

fore usually affects the function of the medulla more

Because one of the primary functions of the medulla is
to provide the countercurrent mechanism for concen-

kidneys by bacteria not only causes damage to the renal
medulla interstitium but also results in progressive

Nephrotic Syndrome—Excretion

Increased Glomerular Permeability

Many patients with kidney disease develop the
nephrotic syndrome

any disease that increases the permeability of this mem-

include (1)

which affects

primarily the glomeruli and often causes greatly
increased permeability of the glomerular membrane;
(2)

which results from deposition of an

abnormal proteinoid substance in the walls of the blood
vessels and seriously damages the basement membrane

which is associated with no major abnormality

in the glomerular capillary membrane that can be

be associated with loss of the negative charges that are
normally present in the glomerular capillary basement

that the loss of the negative charges may have resulted

negative charges in the basement membrane of the

with ease because the negative charges in the basement
membrane normally repel the negatively charged

more frequently it occurs in children between the ages

lar capillary membrane occasionally allows as much as

sequence of this low colloid osmotic pressure in the

Renal Failure

It would be reasonable

to suspect that decreasing the number of functional

major decreases in renal excretion of water and

cent of their nephrons are able to excrete normal
amounts of water and electrolytes without serious

death usually ensues when the number of nephrons
falls below 5 to 10 per cent of normal.

accumulate almost in proportion to the number of

large decreases in the total GFR, normal rates of renal

that cause the blood vessels to vasodilate. Even with

vessels and glomeruli, as well as functional changes

ing nephrons, owing to hypertrophy of the blood

as under normal conditions (Table 31–6).

nephrons, each surviving nephron must excrete four

For example, with a 75 per cent loss of functional

creasing tubular reabsorption of these electrolytes.

Figure 31–5). This is accomplished by greatly de-

In the case of sodium and chloride ions, their plasma

secretion rates.

sorption or, in some instances, by increasing tubular

as shown in curve B of Figure 31–5. Maintenance of

stances rise, but not in proportion to the fall in GFR,

Thereafter, the plasma concentrations of these sub-

gen ions, are often maintained near the normal range

Some solutes, such as phosphate, urate, and hydro-

Figure 31–5.

creatinine concentration, as shown in curve A of

tions in GFR; however, this normal rate of creatinine

equals the rate of creatinine production, despite reduc-

steady-state conditions, the creatinine excretion rate

is produced in the body (Figure 31–4). Thus, under

tion rate also transiently decreases, causing accumula-

Therefore, if GFR decreases, the creatinine excre-

Creatinine, for example, is not reabsorbed at all, and

they are not reabsorbed as avidly as the electrolytes.

largely on glomerular filtration for their excretion, and

410

Unit V

The Body Fluids and Kidneys

is that substances such as creatinine and urea depend

the excretion rate is equal to the rate at which it is
filtered.

Creatinine filtration rate

= GFR ¥ Plasma creatinine concentration
= Creatinine excretion rate

tion of creatinine in the body fluids and raising plasma
concentration until the excretion rate of creatinine
returns to normal—the same rate at which creatinine

excretion occurs at the expense of elevated plasma

until GFR falls below 20 to 30 per cent of normal.

relatively constant plasma concentrations of these
solutes as GFR declines is accomplished by excreting
progressively larger fractions of the amounts of these
solutes that are filtered at the glomerular capillaries;
this occurs by decreasing the rate of tubular reab-

concentrations are maintained virtually constant
even with severe decreases in GFR (see curve C of

times as much sodium and four times as much volume

Part of this adaptation occurs because of increased

blood flow and increased GFR in each of the surviv-

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

when the production rate of creatinine remains constant.

on serum creatinine concentration and on creatinine excretion rate

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

Figure 31–4

100

Plasma concentration

Glomerular filtration rate

(percentage of normal)

urate. Curve C shows the approximate concentrations for solutes

approximate concentrations for solutes such as phosphate and

urea that are filtered and poorly reabsorbed. Curve B shows the

in the plasma concentrations of solutes such as creatinine and

in chronic renal failure. Curve A shows the approximate changes

Representative patterns of adaptation for different types of solutes

Figure 31–5

such as sodium and chloride.

the high concentration of urea in the body fluids.

This total condition is called

bases.

phenols, sulfates, phosphates, potassium,

excreted by the kidney, including

end products of proteins, and (4)

—especially urea, creatinine, and uric acid—result-

products, (3)

water and salt retention, (2)

generalized edema

approximately those shown in Figure 31–7. Important

the same amounts of water and food, the concentrations

degree of impairment of renal function. Assuming that

The effect of complete renal failure on the body fluids

Effects of Renal Failure on the Body

restricted for 12 or more hours.

concentrate urine when a person’s water intake is

chronic renal failure, an important clinical test of renal

approach those of the glomerular filtrate. Because the

quence, the diluting capacity of the kidney is impaired,

tubular fluid of this part of the nephron. As a conse-

The diluting mechanism in the kidney is also

Figure 31–6.

specific gravity of the glomerular filtrate, as shown in

concentrating ability of the kidney declines, and urine

gressively more nephrons are destroyed, the maximum

medullary interstitial fluid solutes. Therefore, as pro-

ing ducts prevents adequate water reabsorption, and

ability to concentrate or dilute the urine. The concen-

rate at which the tubules reabsorb water and solutes.

Chapter 31

Kidney Diseases and Diuretics

411

excretion can still be maintained by decreasing the

Isosthenuria—Inability of the Kidney to Concentrate or Dilute
the Urine.

One important effect of the rapid rate of

tubular flow that occurs in the remaining nephrons of
diseased kidneys is that the renal tubules lose their

trating ability of the kidney is impaired mainly because
(1) the rapid flow of tubular fluid through the collect-

(2) the rapid flow through both the loop of Henle and
the collecting ducts prevents the countercurrent mech-
anism from operating effectively to concentrate the

osmolarity and specific gravity (a measure of the total
solute concentration) approach the osmolarity and

impaired when the number of nephrons decreases
because the rapid flushing of fluid through the loops
of Henle and the high load of solutes such as urea
cause a relatively high solute concentration in the

and the minimal urine osmolality and specific gravity

concentrating mechanism becomes impaired to a
greater extent than does the diluting mechanism in

function is to determine how well the kidneys can

Fluids—Uremia

depends on (1) water and food intake and (2) the

a person with complete renal failure continues to ingest

of different substances in the extracellular fluid are

effects include (1)

resulting from

acidosis resulting from

failure of the kidneys to rid the body of normal acidic

high concentration of the nonprotein nitro-

gens
ing from failure of the body to excrete the metabolic

high concentrations of

other substances

and guanidine

uremia because of

Total Kidney Excretion and Excretion per Nephron in

Table 31–6

Volume excreted per nephron

0.75

3.0

Volume excreted for all

1.5

Single nephron GFR (nl/min)

62.5

Total GFR (ml/min)

125

Number of nephrons

2,000,000

500,000

Normal

Nephrons

Renal Failure

75% Loss of

nephrons (ml/min)

(nl/min)

GFR, glomerular filtration rate.

500,000

2,000,000 1,500,000 1,000,000

Specific gravity of urine

Isosthenuria

Glomerular filtrate specific gravity

1.000

1.010

1.020

1.030

1.040

1.050

Number of nephrons in both kidneys

of functional nephrons.

Development of isosthenuria in a patient with decreased numbers

Figure 31–6

Water

Decrease

Increase

Kidney shutdown

Normal

NPN

Phenols

HPO

HCO

Days

nonprotein nitrogens.

Effect of kidney failure on extracellular fluid constituents. NPN,

Figure 31–7

mainly in the cortical collecting tubules.

secretion, which increases sodium reabsorption

thickening of the glomerular capillary membranes,

glomerulonephritis, which causes inflammation and

which reduces GFR. An example of this is chronic

hypertension caused by renal artery stenosis.

renal blood flow and GFR. An example is

Increased renal vascular resistance,

varying degrees. Some specific types of renal abnormal-

fore, lesions that either

and water almost invariably cause hypertension. There-

Sodium and Water Promote Hypertension.

following.

tension. A classification of kidney disease relative

uremia without hypertension. Nevertheless, some types

forth, until end-stage renal disease develops.

kidneys, further increases in blood pressure, and so

pressure, which in turn causes further damage to the

circle: primary kidney damage leads to increased blood

disease can, in some instances, propagate a vicious

19. Thus, the relation between hypertension and kidney

can cause hypertension, as discussed in detail in Chapter

disease. Conversely, abnormalities of kidney function

As discussed earlier in this chapter, hypertension can

bones, causing further demineralization of the bones.

secretion. This secondary hyperparathy-

calcium concentration, which in turn stimulates

ionized

plasma, thus decreasing the plasma serum

decreased GFR. This rise in serum phosphate causes

ability of calcium to the bones.

vitamin D, which in turn

calcium absorption from the intestine. Therefore,

first in the liver and then in the kidneys, into 1,25–

Vitamin D must be converted by a two-stage process,

absorbed and, therefore, become greatly weakened. An

Osteomalacia in Chronic Renal Failure Caused by Decreased

of erythropoietin, which leads to diminished red blood

damaged, they are unable to form adequate quantities

produce red blood cells. If the kidneys are seriously

The most im-

Anemia in Chronic Renal Failure Caused by Decreased Erythro-

drastically, and the patient will become comatose and

when this buffering power is used up, the blood pH falls

few thousand millimoles of hydrogen ion. However,

cellular fluid hydrogen ion concentration, and the phos-

to function, acid accumulates in the body fluids. The

than metabolic alkali. Therefore, when the kidneys fail

failure.

stances, especially of urea and creatinine, provides an

reason, measuring the concentrations of these sub-

the degree of reduction in functional nephrons. For this

weeks of total renal failure. With chronic renal failure,

cells. The concentrations of these, particularly of urea,

These, in general, are the end products of protein

acid, creatinine, and a few less important compounds.

The nonprotein nitrogens include urea, uric

Uremia—Increase in Urea and Other Nonprotein Nitrogens

group, removal of the ischemic kidneys usually corrects

excess sodium has been removed by dialysis. In this

by dialysis can control the hypertension. The remaining

develop hypertension. In most of these patients, severe

chronic renal failure. Almost all patients with kidney

kidney disease, often causes severe hypertension in

tion that does occur, along with increased secretion of

amounts of salt and water. Even the small fluid reten-

previously, is that the surviving nephrons excrete larger

cent of normal or lower. The reason for this, as discussed

are not excessive, until kidney function falls to 25 per

fluid may not be severe, as long as salt and fluid intake

With chronic partial kidney failure, accumulation of

and rapidly.

anisms, the body fluids begin to increase immediately

only slightly increased. If fluid intake is not limited and

failure begins, the total body fluid content may become

Water Retention and Development of Edema in Renal Failure.

412

Unit V

The Body Fluids and Kidneys

water intake is restricted immediately after acute renal

the patient drinks in response to the normal thirst mech-

renin and angiotensin II that usually occurs in ischemic

function so reduced as to require dialysis to preserve life

reduction of salt intake or removal of extracellular fluid

patients continue to have hypertension even after

the hypertension (as long as fluid retention is prevented
by dialysis) because it removes the source of excessive
renin secretion and subsequent increased angiotensin II
formation.

(Azotemia).

metabolism and must be removed from the body to
ensure continued normal protein metabolism in the

can rise to as high as 10 times normal during 1 to 2

the concentrations rise approximately in proportion to

important means for assessing the degree of renal

Acidosis in Renal Failure.

Each day the body normally pro-

duces about 50 to 80 millimoles more metabolic acid

buffers of the body fluids normally can buffer 500 to
1000 millimoles of acid without lethal increases in extra-

phate compounds in the bones can buffer an additional

die if the pH falls below about 6.8.

poietin Secretion.

Patients with severe chronic renal

failure almost always develop anemia.
portant cause of this is decreased renal secretion of
erythropoietin, which stimulates the bone marrow to

cell production and consequent anemia.

Production of Active Vitamin D and by Phosphate Retention by
the Kidneys.

Prolonged renal failure also causes osteo-

malacia, a condition in which the bones are partially

important cause of this condition is the following:

dihydroxycholecalciferol before it is able to promote

serious damage to the kidney greatly reduces the blood
concentration of active
decreases intestinal absorption of calcium and the avail-

Another important cause of demineralization of the

skeleton in chronic renal failure is the rise in serum
phosphate concentration that occurs as a result of

increased binding of phosphate with calcium in the

parathy-

roid hormone
roidism then stimulates the release of calcium from

Hypertension and Kidney Disease

exacerbate injury to the glomeruli and blood vessels of
the kidneys and is a major cause of end-stage renal

Not all types of kidney disease cause hypertension,

because damage to certain portions of the kidney cause

of renal damage are particularly prone to cause hyper-

to hypertensive or nonhypertensive effects is the

Renal Lesions That Reduce the Ability of the Kidneys to Excrete

Renal lesions that

decrease the ability of the kidneys to excrete sodium

decrease GFR or increase

tubular reabsorption usually lead to hypertension of

ities that can cause hypertension are as follows:
1.

which reduces

2. Decreased glomerular capillary filtration coefficient,

thereby reducing the glomerular capillary filtration
coefficient.

3. Excessive tubular sodium reabsorption. An example

is hypertension caused by excessive aldosterone

to the renal tubules.

orders, or it can occur as a result of widespread injury

metabolic acidosis, as discussed in Chapter 30. This type

ually lost in the urine. This causes a continued state of

result, large amounts of sodium bicarbonate are contin-

to secrete adequate amounts of hydrogen ions. As a

In this condition, the renal tubules are unable

Renal Tubular Acidosis—Failure of the Tubules to Secrete Hydro-

Chapter 79.

response of the usual type of rickets, as discussed in

tory to vitamin D therapy, in contrast to the rapid

person to develop rickets. This type of rickets is refrac-

causes diminished calcification of the bones, causing the

function. Over a long period, a low phosphate level

not cause serious immediate abnormalities, because

body fluids falls very low. This condition usually does

In renal hypophosphatemia,

the renal

ently has no major clinical significance.

to be reabsorbed; or (3)

renal stones; (2)

in which large amounts of cystine fail to be

sorption of all amino acids; more frequently, deficiencies

generalized aminoaciduria

distinct transport systems. Rarely, a condition called

reabsorption, whereas other amino acids have their own

making a diagnosis of diabetes mellitus.

is a relatively benign condition, must be ruled out before

presence of glucose in the urine, renal glycosuria, which

large amounts of glucose pass into the urine each day.

Consequently, despite a normal blood glucose level,

be normal, but the transport mechanism for tubular

In this condition, the blood glucose concentration may

can cause important renal tubular disorders.

through the tubular membrane. In addition, damage to

renal tubular epithelial cells. For this reason, many

happens to be absent or abnormal, the tubules may be

respective gene in the nucleus. If any required gene

Chapter 3, we also point out that each cellular enzyme

stances across the tubular epithelial membranes. In

In Chapter 27, we point out that several mechanisms are

Specific Tubular Disorders

case, the kidneys simply cannot clear adequate quanti-

imposed, such as eating a large amount of salt. In this

However, a patient with this type of abnormality may

to promote enough water and salt excretion in the urine,

not cause clinically significant hypertension, because

and the salt intake is not excessive, this condition might

is great enough. If the remaining nephrons are normal

of one kidney and part of another kidney, almost always

numbers of whole nephrons, such as occurs with the loss

Kidney Diseases That Cause Loss of Entire Nephrons Lead to Renal

pressure.

is maintained, but at the expense of high blood

excretion of sodium and water by the kidney, so that

hypertension develops, which restores the overall

nephrons to excrete sodium and water. As a result,

II formation. The high levels of angiotensin II then

amounts of renin, which causes increased angiotensin

portions of the kidneys. When this occurs, the ischemic

tension in the usual manner.

and water; and (3) excess salt and water cause hyper-

nonischemic kidney tissue, causing it also to retain salt

quent increased angiotensin II formation, affects the

the renin secreted by the ischemic kidney, and subse-

excretes less than normal amounts of water and salt; (2)

Chapter 19, is (1) the ischemic kidney tissue itself

of events in causing this hypertension, as discussed in

which can cause hypertension. The most likely sequence

This secretion leads to the formation of angiotensin II,

occurs when one renal artery is severely constricted, the

ischemic and the remainder is not ischemic, such as

Hypertension Caused by Patchy Renal Damage and Increased

arterial pressure.

Chapter 19, normal excretion of sodium and water at an

water other than the hypertension. As explained in

pressure rises. Thus, after hypertension develops, there

aldosterone secretion, the urinary excretion rate is ini-

reabsorption is increased, as occurs with excessive

arterial blood pressure rises. Likewise, when tubular

decreases in the glomerular capillary coefficient, the

and water become balanced once again. Even when

sure diuresis, so that intake and output of sodium

Once hypertension has developed, renal excretion of

Chapter 31

Kidney Diseases and Diuretics

413

sodium and water returns to normal because the high
arterial pressure causes pressure natriuresis and pres-

there are large increases in renal vascular resistance or

GFR may still return to nearly normal levels after the

tially reduced but then returns to normal as arterial

may be no sign of impaired excretion of sodium and

elevated arterial pressure means that pressure natriure-
sis and pressure diuresis have been reset to a higher

Renal Secretion of Renin.

If one part of the kidney is

ischemic renal tissue secretes large quantities of renin.

A similar type of hypertension can result when patchy

areas of one or both kidneys become ischemic as a
result of arteriosclerosis or vascular injury in specific

nephrons excrete less salt and water but secrete greater

impair the ability of the surrounding otherwise normal

balance between intake and output of salt and water

Failure But May Not Cause Hypertension.

Loss of large

leads to renal failure if the amount of kidney tissue lost

even a slight rise in blood pressure will raise the GFR
and decrease tubular sodium reabsorption sufficiently

even with the few nephrons that remain intact.

become severely hypertensive if additional stresses are

ties of salt with the small number of functioning
nephrons that remain.

responsible for transporting different individual sub-

and each carrier protein is formed in response to a

deficient in one of the appropriate carrier proteins or
one of the enzymes needed for solute transport by the

hereditary tubular disorders occur because of the trans-
port of individual substances or groups of substances

the tubular epithelial membrane by toxins or ischemia

Renal Glycosuria—Failure of the Kidneys to Reabsorb Glucose.

reabsorption of glucose is greatly limited or absent.

Because diabetes mellitus is also associated with the

Aminoaciduria—Failure of the Kidneys to Reabsorb Amino Acids.

Some amino acids share mutual transport systems for

results from deficient reab-

of specific carrier systems may result in (1) essential
cystinuria,
reabsorbed and often crystallize in the urine to form

simple glycinuria, in which glycine fails

beta-aminoisobutyricaciduria,

which occurs in about 5 per cent of all people but appar-

Renal Hypophosphatemia—Failure of the Kidneys to Reabsorb
Phosphate.

tubules fail to reabsorb large enough quantities of phos-
phate ions when the phosphate concentration of the

the phosphate concentration of the extracellular fluid
can vary widely without causing major cellular dys-

gen Ions.

of renal abnormality can be caused by hereditary dis-

flow may be several hundred milliliters per minute, and

one time is usually less than 500 milliliters, the rate of

The total amount of blood in the artificial kidney at any

In normal operation of the artificial kidney, blood

increasing the flow rate of the blood, the dialyzing fluid,

flow through the artificial kidney, the dissipation of the

with “hemodialysis,” in which blood and dialysate fluid

gradient is dissipated. In a flowing system, as is the case

Thus, the maximum rate of solute transfer occurs ini-

membrane.

area of the membrane, and (4) the length of time

meability of the membrane to the solute, (3) the surface

of the solute between the two solutions, (2) the per-

The rate of movement of solute across the dialyzing

fluid, there will be a

fluid back into the plasma. If the concentration of a sub-

the plasma proteins, to diffuse in both directions—from

enough to allow the constituents of the plasma, except

brane is a dialyzing fluid. The cellophane is porous

two thin membranes of cellophane; outside the mem-

Figure 31–8 shows the components of one type of arti-

channels bounded by a thin membrane. On the other

The basic principle of the arti-

kidneys usually remains significantly impaired. A better

kidneys, the health of patients maintained on artificial

with artificial kidneys. Because dialysis cannot maintain

to maintain life. In the United States alone, nearly

versible, it is necessary to perform dialysis chronically

their function. If the loss of kidney function is irre-

types of acute renal failure, an artificial kidney may be

plished by dialysis with an artificial kidney. In certain

and composition toward normal. This can be accom-

ically, is a threat to life and requires removal of toxic

Severe loss of kidney function, either acutely or chron-

Artificial Kidney

Treatment of Renal Failure

can cause damage.

drome caused by tubular injury, because these cells

tubular cells are especially affected in Fanconi’s syn-

tubular cells as a result of ischemia. The proximal

renal tubular epithelial cells, and (3) injury to the renal

port mechanisms, (2) toxins or drugs that injure the

tubular cells to transport various substances. Some of

There are multiple causes of Fanconi’s syndrome,

insipidus.

and sometimes calcium; and (3) nephrogenic diabetes

metabolic acidosis; (2) increased excretion of potassium

to reabsorb sodium bicarbonate, which results in

manifestations are also observed, such as (1) failure

acids, glucose, and phosphate. In severe cases, other

Fanconi’s syndrome is usually associated

Renal Tubules.

Fanconi’s Syndrome—A Generalized Reabsorptive Defect of the

adequate quantities of water are not available, the

dition seldom causes severe difficulty. However, when

as the person is supplied with plenty of water, this con-

large quantities of dilute urine to be excreted. As long

tubules do not respond to antidiuretic hormone, causing

Occasionally, the renal

414

Unit V

The Body Fluids and Kidneys

Nephrogenic Diabetes Insipidus—Failure of the Kidneys to
Respond to Antidiuretic Hormone.

person rapidly becomes dehydrated.

with increased urinary excretion of virtually all amino

which results from a generalized inability of the renal

these causes include (1) hereditary defects in cell trans-

reabsorb and secrete many of the drugs and toxins that

by Dialysis with an

waste products and restoration of body fluid volume

used to tide the patient over until the kidneys resume

300,000 people with irreversible renal failure or even
total kidney removal are being maintained by dialysis

completely normal body fluid composition and cannot
replace all the multiple functions performed by the

treatment for permanent loss of kidney function is to
restore functional kidney tissue by means of a kidney
transplant.

Basic Principles of Dialysis.

ficial kidney is to pass blood through minute blood

side of the membrane is a dialyzing fluid into which
unwanted substances in the blood pass by diffusion.

ficial kidney in which blood flows continually between

plasma into the dialyzing fluid or from the dialyzing

stance is greater in the plasma than in the dialyzing

net transfer of the substance from

the plasma into the dialyzing fluid.

membrane depends on (1) the concentration gradient

that the blood and fluid remain in contact with the

tially when the concentration gradient is greatest (when
dialysis is begun) and slows down as the concentration

concentration gradient can be reduced and diffusion of
solute across the membrane can be optimized by

or both.

flows continually or intermittently back into the vein.

Bubble

trap

Fresh dialyzing

solution

Used dialyzing

solution

Constant

temperature

bath

Semipermeable

membrane

Flowing

dialysate

Flowing

blood

Dialyzer

Blood in

Blood out

Dialysate

Dialysate
out

Waste

products

Water

Principles of dialysis with an artificial kidney.

Figure 31–8

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Wilcox CS: New insights into diuretic use in patients with

United States Renal Data System. http://www.usrds.org/.

289:747, 2003.

Singri N, Ahya SN, Levin ML: Acute renal failure. JAMA

284:F11, 2003.

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Shankar SS, Brater DC: Loop diuretics: from the Na-K-2Cl

www.kidneyatlas.org/.

Schrier RW: Atlas of Diseases of the Kidney. http://

Hypertension 42:1050, 2003.

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Sarnak MJ, Levey AS, Schoolwerth AC, et al: Kidney disease

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Molitoris BA: Transitioning to therapy in ischemic acute

WB Saunders, 2000, pp 567-570.

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What do we know? What do we need to learn? Where do

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Levey AS, Beto JA, Coronado BE, et al: Controlling the epi-

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Hostetter TH: Prevention of the development and progres-

11:41, 2004.

cause of chronic renal disease? Adv Ren Replace Ther

Hall JE, Henegar JR, Dwyer TM, et al: Is obesity a major

41:625, 2003.

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Fishbane SA, Scribner BH: Blood pressure control in dialy-

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Andreoli TE (ed): Cecil’s Essentials of Medicine, 6th ed.

secretion of erythropoietin, which is necessary for red

some of the other functions of the kidneys, such as

kidney replaces the normal kidneys. Also, it is important

three times a week. Therefore, the overall plasma clear-

the artificial kidney is used for only 4 to 6 hours per day,

together, whose urea clearance is only 70 ml/min. Yet

for the excretion of urea, the artificial kidney can func-

at a rate of 100 to 225 ml/min, which shows that at least

themselves to rid the body of unwanted substances.

discussed in Chapter 27, is the primary means for

cleared of different substances each minute, which, as

The effectiveness of the artificial kidney can be

Therefore, when a uremic patient is dialyzed, these sub-

or creatinine in the dialyzing fluid; however, these are

Note that there is no phosphate, urea, urate, sulfate,

solutes through the membrane during dialysis.

plasma. Instead, they are adjusted to levels that are

uremic plasma. Note that the concentrations of ions and

Table 31–7 compares the constituents in

bulk flow.

of the dialyzer; such filtration is called

tion to diffusion of solutes, mass transfer of solutes and

into the blood as it enters the artificial kidney. In addi-

the artificial kidney, a small amount of heparin is infused

square meters. To prevent coagulation of the blood in

Chapter 31

Kidney Diseases and Diuretics

415

the total diffusion surface area is between 0.6 and 2.5

water can be produced by applying a hydrostatic pres-
sure to force the fluid and solutes across the membranes

Dialyzing Fluid.

a typical dialyzing fluid with those in normal plasma and

other substances in dialyzing fluid are not the same as
the concentrations in normal plasma or in uremic

needed to cause appropriate movement of water and

present in high concentrations in the uremic blood.

stances are lost in large quantities into the dialyzing
fluid.

expressed in terms of the amount of plasma that is

expressing the functional effectiveness of the kidneys

Most artificial kidneys can clear urea from the plasma

tion about twice as rapidly as two normal kidneys

ance is still considerably limited when the artificial

to keep in mind that the artificial kidney cannot replace

blood cell production.

References

2003.

Table 31–7

Comparison of Dialyzing Fluid with Normal and Uremic

Urea

200

Glucose

100

125

100

0.5

0.3

1.2

35.7

107

105

107

1.5

3.0

1.0

142

133

142

Constituent

Plasma

Fluid

Plasma

Normal Dialyzing

Uremic

Plasma

Electrolytes (mEq/L)

–

HCO

–

Lactate

–

HPO

Urate

–

Sulfate

Nonelectrolytes

Creatinine