URINARY SYSTEM

Functions of the Urinary System

The major function of the urinary system is to control the composition and volume of body fluids. The
kidneys perform this function through multiple processes:

1. Excretion. The kidneys are the major excretory organs of the body. They remove waste products
from the blood. Many waste products are toxic, but most are metabolic by-products of cells and
substances absorbed from the intestine. The skin, liver, lungs, and intestines eliminate some of these
waste products, but they cannot compensate if the kidneys fail to function.

2. Regulation of blood volume and pressure. The kidneys play major role in controlling
the extracellular fluid volume in the body. They can produce either a large volume of dilute urine or a
small volume of concentrated urine. Thereby, the kidneys regulate blood volume and blood pressure.

3. Regulation of the concentration of solutes in the blood. The kidneys help regulate the
concentration of the major molecules and ions, such as glucose, Na+, Cl−, K+, Ca2+, HCO3−, and HPO42−.

4. Regulation of extracellular fluid pH. The kidneys excrete variable amounts of H+ to help
regulate extracellular fluid pH.

5. Regulation of red blood cell synthesis. The kidneys secrete a hormone, erythropoietin,
which regulates the synthesis of red blood cells in bone marrow.

6. Regulation of vitamin D synthesis. The kidneys play an important role in controlling

blood levels of Ca2+ by regulating the synthesis of vitamin D
ANATOMY OF THE KIDNEYS

The kidneys are bean-shaped organs, each about the size of a tightly clenched fist. They lie on
the posterior abdominal wall, behind the peritoneum, with one kidney on each side of the vertebral
column. Structures that are behind the peritoneum are said to be retroperitoneal. A layer of connective
tissue called the renal (derived from the Latin word for kidney) capsule surrounds each kidney. Around
the renal capsule is a thick layer of adipose tissue, which protects the kidney from mechanical shock.
On the medial side of each kidney is the hilum where the renal artery and nerves enter and where the
renal vein, ureter, and lymphatic vessels exit the kidney. The hilum opens into a cavity called the renal
sinus, which contains blood vessels, part of the system for collecting urine, and adipose tissue.

The kidney is divided into an outer cortex and an inner medulla, which surround the renal sinus.
The bases of several cone-shaped renal pyramids are located at the boundary between the cortex and
the medulla, and the tips of the renal pyramids project toward the center of the kidney. A funnel-shaped
structure called a calyx surrounds the tip of each renal pyramid. The calyces from all the renal pyramids
join to form a larger funnel called the renal pelvis. The renal pelvis then narrows to form a small tube,
the ureter, which exits the kidney and connects to the urinary bladder. Urine passes from the tips of
the renal pyramids into the calyces. From the calyces, urine collects in the renal pelvis and exits the
kidney through the ureter.

The functional unit of the kidney is the nephron, and there are approximately 1.3 million of them
in each kidney. Each nephron consists of a renal corpuscle, a proximal convoluted tubule, a loop of
Henle, and a distal convoluted tubule.

Fluid is forced into the renal corpuscle and then flows into the proximal convoluted tubule. From
there, it flows into the loop of Henle. Each loop of Henle consists of a descending limb and an ascending
limb. The limbs are further categorized into segments: the thin segment of the descending limb, the
thin segment of the ascending limb, and the thick segment of the ascending limb. The descending limb
extends toward the renal sinus, where it makes a hairpin turn, and the ascending limb extends back
toward the cortex. The fluid flows through the ascending limb of the loop of Henle to the distal
convoluted tubule. Several distal convoluted tubules empty into a collecting duct, which carries the
fluid from the cortex, through the medulla. Multiple collecting ducts empty into a single papillary
duct, and the papillary ducts empty their contents into a calyx.
The renal corpuscle and both convoluted tubules are in the renal cortex. The collecting duct and loop
of Henle enters the medulla. Approximately 15% of the nephrons, called juxtamedullary (next to the
medulla) nephrons, have loops of Henle that extend deep into the medulla of the kidney. The other
nephrons (85%), called cortical nephrons, have loops of Henle that do not extend deep into the
medulla.

The renal corpuscle of the nephron consists of the Bowman capsule and the glomerulus. The Bowman
capsule consists of the enlarged end of the nephron, which is indented to form a double-walled
chamber. The glomerulus is a tuft of capillaries that resembles a ball of yarn and lies within the
indentation of the Bowman capsule. The cavity of the Bowman capsule opens into the proximal
convoluted tubule, which carries fluid away from the capsule. The inner layer of the Bowman capsule
consists of specialized cells called podocytes which wrap around the glomerular capillaries. The outer
layer of the Bowman capsule consists of simple squamous epithelial cells.

The glomerular capillaries have pores in their walls, and the podocytes have numerous cell processes
with gaps between them.

The endothelium of the glomerular capillaries, the podocytes, and the basement membrane together
form a filtration membrane. In the first step of urine formation, fluid, consisting of water and solutes
smaller than proteins, passes from the blood in the glomerular capillaries through the filtration
membrane into the Bowman capsule. The fluid that passes across the filtration membrane is called
filtrate.
 The proximal convoluted tubules, the thick segments of the loops of Henle, the distal convoluted
tubules, and the collecting ducts consist of simple cuboidal epithelium. The cuboidal epithelial cells
have microvilli and many mitochondria. These portions of the nephron actively transport molecules and
ions across the wall of the nephron. The thin segments of the descending and ascending limbs of the
loops of Henle have very thin walls made up of simple squamous epithelium. Water and solutes pass
through the walls of these portions of the nephron by diffusion.

The thin segment of the descending limb of the loop of Henle is permeable to water and, to a
lesser degree, solutes, and the thin segment of the ascending limb is permeable to solutes, but not to
water.

Arteries and Veins

A system of blood vessels allows the exchange of materials that occurs in the kidneys. The renal
arteries branch off the abdominal aorta and enter the kidneys. They give rise to several branches.
The interlobar arteries pass between the renal pyramids and give rise to the arcuate arteries, which
arch between the cortex and the medulla. Interlobular arteries branch off the arcuate arteries and
project into the cortex. The afferent arterioles arise from branches of the interlobular arteries and
extend to the glomerular capillaries. Efferent arterioles extend from the glomerular capillaries to
the peritubular (around the tubes) capillaries, which surround the proximal convoluted and distal
convoluted tubules and the loops of Henle. The vasa recta are specialized portions of the peritubular
capillaries that extend deep into the medulla of the kidney and surround the loops of Henle and
collecting ducts. Blood from the peritubular capillaries, including the vasa recta, enters the inter- lobular
veins. The veins of the kidney run parallel to the arteries and have similar names.
A structure called the juxtaglomerular apparatus (pl. apparatuses) is formed where the distal
convoluted tubule comes in contact with the afferent arteriole next to the Bowman capsule. The
juxtaglomerular apparatus consists of specialized cells of the walls of the afferent arteriole and the distal
convoluted tubules. Certain cells of the juxtaglomerular apparatus secrete the enzyme, renin, and play
an important role in blood pressure regulation.

URINE PRODUCTION

The primary function of the kidney is regulation of body fluid composition. The kidney is the
organ that sorts the substances from the blood for either removal in the urine or return to the blood.
Substances that are waste products, toxins, and excess materials are permanently removed from the
body, whereas other substances need to be con-served to maintain homeostasis. The structural
components that per-form this sorting are the nephrons, the functional units of the kidney.

Filtration occurs when blood pressure non selectively forces water and other small molecules
out of glomerular capillaries and into the Bowman capsule, forming a fluid called filtrate.

Tubular reabsorption is the movement of substances from the filtrate across the wall of the nephron
back into the blood of the peritubular capillaries. Certain solute molecules and ions are reabsorbed by
processes such as active transport and cotransport into the cells of the nephron wall and then from
there into the interstitial fluid. Water reabsorption occurs by osmosis across the nephron wall. The
molecules and ions that enter the interstitial fluid surrounding the nephron pass into the peritubular
capillaries. In general, the useful substances that enter the filtrate are reabsorbed, and metabolic waste
products remain in the filtrate and are eliminated. For example, when proteins are metabolized,
ammonia is a by-product. Ammonia, which is toxic to humans, is converted into urea by the liver. Urea
forms part of the filtrate; although some of it is reabsorbed, much of it is eliminated in the urine.
Tubular secretion is the active transport of solutes across the nephron walls into the filtrate.
Consequently, urine consists of substances that are filtered across the filtration membrane and those
that are secreted from the peritubular capillaries into the nephron, minus the substances that are
reabsorbed.

Filtration

An average of 21% of the blood pumped by the heart each minute flows through the kidneys.
Of the total volume of blood plasma that flows through the glomerular capillaries, about 19% passes
through the filtration membrane into the Bowman capsule to become filtrate. In all the nephrons of
both kidneys, about 180 liters (L) of filtrate are produced each day, but only about 1% or less of the
filtrate becomes urine because most of the filtrate is reabsorbed.

Filtration is a nonspecific process whereby materials are separated based on size or charge. A
simple example of size filtration is demonstrated by a drip coffeemaker. In this case, the driving force
of filtration is gravity. The kidneys also use size filtration to remove substances from the blood by
filtering it, but in this case, the driving force of this filtration is blood pressure.

The filtration membrane allows some substances, but not others, to pass from the blood into the
Bowman capsule. Water and small solutes readily pass through the openings of the filtration membrane,
but blood cells and most proteins, which are too large, do not enter the Bowman capsule. One example
of a small blood protein that can enter the filtrate in very small amounts is albumin. Consequently, the
filtrate contains no cells and little protein

The formation of filtrate depends on a pressure gradient, called the filtration pressure, which
forces fluid from the glomerular capillary across the filtration membrane into the Bowman capsule. The
filtration pressure results from forces that move fluid out of the glomerular capillary into the Bowman
capsule minus the forces that move fluid out of the Bowman capsule into the glomerular capillary.
The glomerular capillary pressure is the blood pressure in the glomerular capillary. It is the major
force causing fluid to move from the glomerular capillary across the filtration membrane into the
Bowman capsule. There are two major forces opposing the movement of fluid into the lumen of the
Bowman capsule: capsular pressure and colloid osmotic pressure. The capsular pressure is caused by
the pressure of filtrate already inside the Bowman capsule, and the colloid osmotic pressure is within
the glomerular capillary. Because most plasma proteins do not pass through the filtration membrane,
they produce an osmotic pressure that favors fluid movement into the glomerular capillary from the
Bowman capsule. Thus, filtration pressure = glomerular capillary pressure – (capsular pressure and
colloid osmotic pressure).

The filtration pressure forces fluid from the glomerulus into the Bowman capsule because the
glomerular capillary pressure is greater than both the capsular and the colloid osmotic pressures. Under
most conditions, the filtration pressure remains within a narrow range of values. However, when the
filtration pressure increases, both the filtrate volume and the urine volume increase, and when the
filtration pressure decreases, both the filtrate volume and the urine volume decrease.

The filtration pressure is influenced by the blood pressure in the glomerular capillaries, the blood
protein concentration, and the pressure in the Bowman capsule. The blood pressure is normally higher
in the glomerular capillaries than it is in most capillaries. The filtration pressure increases if the blood
pressure in the glomerular capillaries increases further. The filtration pressure decreases if the blood
pressure in the glomerular capillaries decreases.

The filtration pressure is also influenced by the concentration of proteins in the blood. An increase in
blood protein concentration encourages the movement of water by osmosis back into the glomerular
capillaries and therefore reduces the overall filtration pressure. On the other hand, a decrease in blood
protein con-centration inhibits the movement of water by osmosis back into the glomerular capillaries,
which increases the overall filtration pressure.

Regulation of Filtration

The blood pressure within the glomerular capillaries is fairly constant because the afferent and
efferent arterioles either dilate or con-strict to regulate the blood pressure there, even though the
systemic blood pressure may fluctuate substantially. Also, the concentration of blood proteins and the
pressure inside the Bowman capsule are fairly constant. As a consequence, the filtration pressure and
the rate of filtrate formation are maintained within a narrow range of values most of the time.

However, the filtration pressure does change dramatically under some conditions. Sympathetic
neurons innervate the blood vessels of the kidney. Sympathetic stimulation constricts the arteries,
causing a decrease in renal blood flow and filtrate formation in proportion to the intensity of the
stimulation. It is possible to decrease filtrate formation to only a few milliliters per minute. Consequently,
only a small volume of urine is produced. For instance, during cardiovascular shock, the filtration
pressure and filtrate formation fall dramatically. One of the dangers of cardiovascular shock is that the
renal blood flow can be so low that the kidneys suffer from lack of O2. If the O2 level remains too low
for a long enough time, permanent kidney damage or complete kidney failure results. One important
reason for treating cardiovascular shock quickly is to avoid damage to the kidneys. Other conditions,
such as intense physical activity or trauma, also increase sympathetic stimulation of renal arteries and
decrease urine production to very low levels. On the other hand, increased blood pressure decreases
sympathetic stimulation of renal blood arteries, and urine volume increases.

Tubular Reabsorption

As the filtrate flows from the Bowman capsule through the proximal convoluted tubule, loop of
Henle, distal convoluted tubule, and collecting duct, many of the solutes in the filtrate are reabsorbed.
About 99% of the original filtrate volume is reabsorbed and enters the peritubular capillaries. The
reabsorbed filtrate flows through the renal veins to enter the general circulation. Only 1% of the original
filtrate volume becomes urine. Because excess ions and metabolic waste products are not readily
reabsorbed, the small volume of urine produced contains a high concentration of ions and metabolic
waste products.

The proximal convoluted tubule is the primary site for the reabsorption of solutes and water. The
cuboidal cells of the proximal convoluted tubule have numerous microvilli and mitochondria, and they
are well adapted to transport molecules and ions across the nephron wall by active transport and
cotransport. Substances transported from the proximal convoluted tubule include proteins, amino
acids, glucose, and fructose molecules, as well as Na+, K+, Ca2+, HCO3−, and Cl−. The proximal
convoluted tubule is permeable to water. As solute molecules are transported out of the proximal
convoluted tubule into the interstitial fluid, water moves by osmosis in the same direction. The solutes
and water then enter the peritubular capillaries. Consequently, 65% of the filtrate volume is reabsorbed
from the proximal convoluted tubule

The descending limb of the loop of Henle further concentrates the filtrate. The renal medulla
contains very concentrated interstitial fluid that has large amounts of Na+, Cl−, and urea. The wall of
the thin segment of the descending limb is permeable to water and moderately permeable to solutes.
As the filtrate passes through the descending limb of the loop of Henle into the medulla of the kidney,
water moves out of the nephron by osmosis, and some solutes move into the nephron by diffusion. By
the time the filtrate has passed through the descending limb, another 15% of the filtrate volume has
been reabsorbed, and the filtrate is as concentrated as the interstitial fluid of the medulla. The
reabsorbed water and solutes enter the vasa recta.

The ascending limb of the loop of Henle dilutes the filtrate by removing solutes. The thin
segment of the ascending limb is not permeable to water, but it is permeable to solutes. Consequently,
solutes diffuse out of the nephron

The cuboidal epithelial cells of the thick segment of the ascending limb actively transport
Na+ out of the nephron, and K+ and Cl− are cotransported with Na+. The thick segment of the
ascending limb is not permeable to water. As a result, Na+, K +, and Cl−, but little water, are removed
from the filtrate. Because of the efficient removal of these solutes, the highly concentrated filtrate that
enters the ascending limb of the loop of Henle is converted to a dilute solution by the time it reaches
the distal convoluted tubule. As the filtrate enters the distal convoluted tubule, it is more dilute than
the interstitial fluid of the renal cortex. Also, because of the volume of filtrate reabsorbed in the proximal
convoluted tubule and the descending limb of the loop of Henle, only about 20% of the original filtrate
volume remains. The solutes transported from the ascending limb of the loop of Henle enter the
interstitial fluid of the medulla and help keep the concentration of solutes in the medulla high. Excess
solutes enter the vasa recta.

The cuboidal cells of the distal convoluted tubule and collecting duct remove water and
additional solutes. Na+ and Cl− are reabsorbed. Sodium ions are actively transported, and chloride ions
are cotransported. Also, 19% of the original filtrate volume is reabsorbed by osmosis, leaving about 1%
of the original filtrate as urine. The reabsorbed water and solutes from the distal convoluted tubule
enter the peritubular capillaries and the vasa recta from the collecting ducts.

Tubular Secretion

Some substances, including by-products of metabolism that become toxic in high concentrations
and drugs or other molecules not normally produced by the body, are secreted into the nephron from
the peritubular capillaries. As with tubular reabsorption, tubular secretion can be either active or passive.
For example, ammonia diffuses into the lumen of the nephron, whereas H+, K+, creatinine, histamine,
and penicillin are actively transported into the nephron.

Hydrogen ions are actively transported into the proximal convoluted tubule. The epithelial cells actively
transport large quantities of H+ across the nephron wall into the filtrate. The secretion of H+ plays an
important role in regulating the body fluid pH.

In the proximal convoluted tubule, K+ is reabsorbed. However, in the distal convoluted tubule
and collecting duct, K+ is secreted, resulting in a net loss of K+ in the urine
REGULATION OF URINE CONCENTRATION AND VOLUME

The kidneys maintain the concentration of the body fluids by increasing water reabsorption from the
filtrate when the body fluid concentration increases and by reducing water reabsorption from the filtrate
when the body fluid concentration decreases. The volume and composition of urine therefore change,
depending on conditions in the body. If body fluid concentration increases above normal levels, the
kidneys produce a small volume of concentrated urine. This eliminates solutes and conserves water,
both of which help lower the body fluid concentration back to normal. On the other hand, if the body
fluid concentration decreases, the kidneys produce a large volume of dilute urine. As a result, water is
lost, solutes are conserved, and the body fluid concentration increases.

Urine production also maintains blood volume and therefore blood pressure. An increase in blood
volume can increase blood pressure, and a decrease in blood volume can decrease blood pressure.
When blood volume increases above normal, the kidneys produce a large volume of urine. The loss of
water in the urine lowers blood volume. Conversely, if blood volume decreases below normal, the
kidneys produce a small volume of urine to conserve water and maintain blood volume.

Hormonal Mechanisms

Three major hormonal mechanisms are involved in regulating urine concentration and volume

Renin-Angiotensin-Aldosterone Mechanism
Renin and angiotensin help regulate aldosterone secretion. Renin, an enzyme, is secreted by cells of
the juxtaglomerular apparatuses in the kidneys. Renin acts on angiotensinogen a plasma protein
produced by the liver, and converts it to angiotensin I. Angiotensin I is rapidly converted to a
smaller peptide called angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II acts
on the adrenal cortex, causing it to secrete aldosterone.

Aldosterone increases the rate of active transport of Na+ in the distal convoluted tubules and collecting
ducts. In the absence of aldosterone, large amounts of Na+ remain in the nephron and become part of
the urine. A high Na+ concentration in the filtrate causes water to remain in the nephrons and increases
urine volume. Therefore, when the rate of active transport of Na+ is slow, urine volume increases, and
the urine contains a high concentration of Na+. Because Cl− is attracted by the positive charge on Na+,
Cl− is cotransported with Na+.

When blood pressure suddenly decreases or when the concentration of Na+ in the filtrate becomes too
low, the kidney releases renin. The resultant increase in aldosterone causes an increase in Na+ and
Cl− reabsorption from the nephrons. Water follows the Na+ and Cl−. Thus, the volume of water lost in
the form of urine declines. This method of conserving water helps prevent a further decline in blood
pressure

Antidiuretic Hormone Mechanism

Antidiuretic hormone (ADH), secreted by the posterior pituitary gland, passes through the circulatory
system to the kidneys. ADH regulates the amount of water reabsorbed by the distal convoluted tubules
and collecting ducts. When ADH levels increase, the permeability of the distal convoluted tubules and
collecting ducts to water increases, and more water is reabsorbed from the filtrate. Consequently, an
increase in ADH results in the production of a small volume of concentrated urine. On the other hand,
when ADH levels decrease, the distal convoluted tubules and collecting ducts become less permeable
to water. As a result, less water is reabsorbed, and a large volume of dilute urine is produced

The release of ADH from the posterior pituitary is regulated by the hypothalamus. Certain cells of the
hypothalamus are sensitive to changes in solute concentration. When the solute concentration in the
blood increases, action potentials are sent along the axons of the ADH-secreting neurons of the
hypothalamus to the posterior pituitary, and ADH is released from the ends of the axons (figure 18.15;).
A reduced solute concentration in the blood causes inhibition of ADH release.

Baroreceptors that monitor blood pressure also influence ADH secretion. A large decrease in blood
pressure causes an increase in ADH secretion and a large increase in blood pressure decreases ADH
secretion.

Atrial Natriuretic Hormone

Atrial natriuretic hormone (ANH) is secreted from cardiac muscle cells in the right atrium of the heart
when blood pressure in the right atrium increases above normal. ANH acts on the kidney to decrease
Na+ reabsorption. Therefore, Na+ and water remain in the nephron to become urine. The increased
loss of Na+ and water as urine reduces the blood volume and the blood pressure.

URINE MOVEMENT

Anatomy and histology of the Ureters, Urinary Bladder, and Urethra

The ureters are small tubes that carry urine from the renal pelvis of the kidney to the posterior inferior
portion of the urinary bladder. The urinary bladder is a hollow, muscular container that lies in the pelvic
cavity just posterior to the pubic symphysis. It stores urine; thus, its size depends on the quantity of
urine present. The urinary bladder can hold from a few milliliters (mL) to a maximum of about 1000 mL
of urine. When the urinary bladder reaches a volume of a few hundred mL, its wall is stretched enough
to activate a reflex that causes the smooth muscle of the urinary bladder to contract, and most of the
urine flows out of the urinary bladder through the urethra.

The urethra is the tube that carries urine from the urinary bladder to the outside of the body. The
triangle-shaped portion of the urinary bladder located between the opening of the ureters and the
opening of the urethra is called the trigone.

The ureters and the urinary bladder are lined with transitional epithelium, which is specialized to stretch.
As the volume of the urinary bladder increases, the epithelial cells change in shape from columnar to
flat, and the number of epithelial cell layers decreases. As the volume of the urinary bladder decreases,
transitional epithelial cells assume their columnar shape and form a greater number of cell layers.

The walls of the ureter and urinary bladder are composed of layers of smooth muscle and connective
tissue. Regular waves of smooth muscle contraction in the ureters produce the force that causes urine
to flow from the kidneys to the urinary bladder. Contractions of smooth muscle in the urinary bladder
force urine to flow from the bladder through the urethra.

At the junction of the urinary bladder and the urethra, the smooth muscle of the bladder wall forms
the internal urinary sphincter in males. (There is no functional internal urinary sphincter in females.)
In males, the internal urinary sphincter contracts to keep semen from entering the urinary bladder
during sexual intercourse. In both males and females, the external urinary sphincter is formed of
skeletal muscle that sur-rounds the urethra as the urethra extends through the pelvic floor. The external
urinary sphincter is under voluntary control, allowing a person to start or stop the flow of urine through
the urethra.

In males, the urethra extends to the end of the penis, where it opens to the outside. The female urethra
is much shorter (approximately 4 cm) than the male urethra (approximately 20 cm) and opens into the
vestibule anterior to the vaginal opening.

Micturition Relex
The micturition reflex is activated by stretch of the urinary bladder wall. As the urinary bladder fills
with urine, pressure increases, stimulating stretch receptors in the wall of the urinary bladder. Action
potentials are conducted from the urinary bladder to the spinal cord through the pelvic nerves.
Integration of the reflex occurs in the spinal cord, and action potentials are conducted along
parasympathetic nerve fibers to the urinary bladder. Parasympathetic action potentials cause the urinary
bladder to contract

The external urinary sphincter is normally contracted as a result of stimulation from the somatic motor
nervous system. Because of the micturition reflex, action potentials conducted along somatic motor
nerves to the external urinary sphincter decrease, which causes the sphincter to relax. The micturition
reflex is an automatic reflex, but it can be inhibited or stimulated by higher centers in the brain. The
higher brain centers prevent micturition by sending action potentials through the spinal cord to
decrease the intensity of the autonomic reflex that stimulates urinary bladder contractions and to
stimulate nerve fibers that keep the external urinary sphincter contracted. The ability to voluntarily
inhibit micturition develops at the age of 2-3 years.

When a person feels the urge to urinate, the higher brain centers alter action potentials sent to the
spinal cord to facilitate the micturition reflex and relax the external urinary sphincter. Awareness of the
need to urinate occurs because stretch of the urinary bladder stimulates sensory nerve fibers that
increase action potentials carried to the brain by ascending tracts in the spinal cord. Irritation of the
urinary bladder or the urethra by a bacterial infection or some other condition can also initiate the urge
to urinate, even though the urinary bladder is nearly empty.

BODY FLUID COMPARTMENTS

Approximately 60% of the total body weight of an adult male consists of water. Approximately
50% of the total body weight of an adult female is water. Because the water content of adipose tis-sue
is relatively low, the fraction of the body’s weight composed of water decreases as the amount of
adipose tissue increases. A smaller percentage of the body weight of an adult female consists of water
because females generally have a greater percentage of body fat than do males. Water and the ions
dissolved in it are distributed in two major compartments: the intracellular fluid compartment and the
extracellular fluid compartment (table 18.2). Water and ions move between these compartments, but
their movement is regulated.
 The intracellular fluid compartment includes the fluid inside all the cells of the body. The cell
membranes of the individual cells enclose the intracellular compartment, which actually consists of
trillions of small compartments. Both the composition of the fluid in all these compartments and the
regulation of fluid movement across all these cell membranes are similar. Approximately two-thirds of
all the water in the body is in the intracellular fluid compartment.

The extracellular fluid compartment includes all the fluid outside the cells. It constitutes
approximately one-third of the total body water. The extracellular fluid compartment includes the
interstitial fluid, the plasma within blood vessels, and the fluid in the lymphatic vessels. A small portion
of the extracellular fluid volume is separated by membranes into subcompartments. These special
subcompartments contain fluid with a composition different from that of the other extracellular fluid.
Fluids within the subcompartments include the aqueous humor and vitreous humor of the eye,
cerebrospinal fluid, synovial fluid in the joint cavities, serous fluid in the body cavities, fluid secreted by
glands, renal filtrate, and bladder urine.

Composition of the fluid in the Body fluid Compartments

Intracellular fluid has a similar composition from cell to cell. It contains a relatively high concentration
of ions, such as K+, magnesium (Mg2+), phosphate (PO43−), and sulfate (SO42−), compared to the
extracellular fluid. It has a lower concentration of Na+, Ca2+, Cl−, and HCO3− than does the
extracellular fluid. The concentration of protein in the intracellular fluid is also greater than that in the
extracellular fluid. Like intracellular fluid, the extracellular fluid has a fairly consistent composition from
one area of the body to another.

Exchange Between Body Fluid Compartments

The cell membranes that separate the body fluid compartments are selectively permeable. Water
continually passes through them, but ions dissolved in the water do not readily pass through the cell
membrane. Water movement is regulated mainly by hydrostatic pressure differences and osmotic
differences between the compartments. For example, water moves across the wall of the capillary at the
arterial end of the capillary because the blood pressure there is great enough to force fluid into the
interstitial space. At the venous end of the capillary, the blood pressure is much lower, and fluid returns
to the capillary because the osmotic pressure is higher inside the capillary than outside it.

The major influence controlling the movement of water between the intracellular and extracellular
spaces is osmosis. For example, if the extracellular concentration of ions increases, water moves by
osmosis from cells into the extracellular fluid.

The intracellular fluid can help maintain the extracellular fluid volume if it is depleted. When a person
becomes dehydrated, the concentration of ions in the extracellular fluid increases. As a consequence,
water moves from the intracellular fluid to the extracellular fluid, thus maintaining the extracellular fluid
volume. Because blood is an important component of the extracellular fluid volume, this process helps
maintain blood volume. Movement of water from the intracellular fluid compartment to the extracellular
fluid compartment can help prolong the time a person can survive a condition such as dehydration or
cardiovascular shock.
REGULATION OF EXTRACELLULAR FLUID COMPOSITION

Homeostasis requires that the intake of substances equals their elimination. Needed water and ions
enter the body by ingestion; excess water and ions exit the body by excretion. The amounts of water
and ions entering and leaving the body can vary over the short term. For example, greater quantities of
water and ions are lost in the form of perspiration on warm days than on cool days, and varying amounts
of water and ions may be lost in the form of feces. However, over a long period, the total amount of
water and ions in the body does not change unless the individual is growing, gaining weight, or losing
weight. Regulating the amounts of water and ions in the body involves the coordinated participation
of several organ systems, but the kidneys are the most important, with the skin, liver, and digestive tract
playing supporting roles. Two mechanisms help regulate the levels of ions in the extracellular fluid:
thirst regulation and ion concentration regulation.

Thirst Regulation

Water intake is controlled by neurons in the hypothalamus, collectively called the thirst center. When
blood becomes more concentrated, the thirst center responds by initiating the sensation of thirst. When
water or another dilute solution is consumed, the blood becomes less concentrated and the sensation
of thirst decreases. Similarly, when blood pressure drops, as occurs during shock, the thirst center is
activated, and the sensation of thirstis triggered. Consumption of water increases the blood volume
and allows the blood pressure to return to its normal value. Other stimuli can also trigger the sensation
of thirst. For example, if the mucosa of the mouth becomes dry, the thirst center is activated. Thirst is
one of the important means of regulating extracellular fluid volume and concentration.

Ion Concentration Regulation

If the water content or concentration of ions in the extracellular fluid deviates from its normal range,
cells cannot control the movement of substances across their cell membranes or the composition of
their intracellular fluid. The consequence is abnormal cell function or even cell death. Keeping the
extracellular fluid composition within a normal range is therefore required to sustain life.

Regulating the concentrations of positively charged ions, such as Na+, K+, and Ca2+, in the body fluids
is particularly important. Action potentials, muscle contraction, and normal cell membrane permeability
depend on the maintenance of a narrow range of concentrations for these ions. Important mechanisms
control the concentrations of these ions in the body. Negatively charged ions, such as Cl−, are
secondarily regulated by the mechanisms that control the positively charged ions. The negatively
charged ions are attracted to the positively charged ions; when the positively charged ions are
transported, the negatively charged ions move with them.
Sodium Ions

Sodium ions (Na+) are the dominant ions in the extracellular fluid. About 90–95% of the osmotic
pressure of the extracellular fluid results from sodium ions and from the negative ions associated with
them.

The recommended intake of Na+ is 2.4 grams per day (g/day), because of its association with high
blood pressure in some people. Most people in the United States consume two to three times the
recommended amount of Na+. The kidneys provide the major route by which the excess Na+ is
excreted.

Stimuli that control aldosterone secretion influence the reabsorption of Na+ from nephrons of the
kidneys and the total amount of Na+ in the body fluids. Reabsorption of Na+ from the distal convoluted
tubules and collecting ducts is very efficient, and little Na+ is lost in the urine when aldosterone is
present. When aldosterone is absent, reabsorption of Na+ in the nephron is greatly reduced, and the
amount of Na+ lost in the urine increases. Aldosterone also plays an essential role in regulating the
extracellular K+ concentration

Sodium ions are also excreted from the body in perspiration, or sweat. Normally, only a small quantity
of Na+ is lost each day in the form of sweat, but the amount increases during heavy exercise in a warm
environment.

Because Na+ has such a large effect on the osmotic pressure of the extracellular fluid, mechanisms that
influence Na+ concentrations in the extracellular fluid also influence the extracellular fluid volume. The
mechanisms that play important roles in controlling these levels are the renin-angiotensin-aldosterone
mechanism, the atrial natriuretic (ANH) mechanism, and antidiuretic hormone (ADH). For example, low
blood pressure increases renin and ADH secretion. The result is an increase in Na+ and water
reabsorption in the kidney to bring blood pressure and the Na+ concentration back to their
normal ranges. Increased blood pressure inhibits renin and ADH secretion, and stimulates ANH
secretion. The result is a decrease in Na+ reabsorption and an increase in urine production to bring
blood pressure and the blood’s Na+ concentration into their normal ranges.

Potassium Ions

Electrically excitable tissues, such as muscles and nerves, are highly sensitive to slight changes in the
extracellular K+ concentration. The extracellular concentration of K+ must be maintained within a
narrow range for these tissues to function normally.

Aldosterone plays a major role in regulating the concentration of K+ in the extracellular fluid.
Dehydration, circulatory system shock resulting from plasma loss, and tissue damage due to injuries
such as severe burns all cause extracellular K+ concentrations to increase above normal. In response,
aldosterone secretion from the adrenal cortex increases and causes K+ secretion to increase.
 If the K+ concentration in the extracellular fluid decreases, aldosterone secretion from the adrenal
cortex decreases. In response, the rate of K+ secretion by the kidneys is reduced.

Calcium Ions

The extracellular concentration of Ca2+, like that of other ions, is maintained within a narrow range.
Increases and decreases in the extracellular concentration of Ca2+ have dramatic effects on the elec-
trical properties of excitable tissues. For example, decreased extra-cellular Ca2+ concentrations make
cell membranes more permeable to Na+, thus making them more electrically excitable. Decreased
extracellular concentrations of Ca2+ cause spontaneous action poten-tials in nerve and muscle cells,
resulting in hyperexcitability and muscle tetany. Increased extracellular Ca2+ concentrations make cell
membranes less permeable to Na+, thus making them less electrical-ly excitable. Increased extracellular
concentrations of Ca2+ inhibit action potentials in nerve and muscle cells, resulting in reduced
excitability and either muscle weakness or paralysis.

Parathyroid hormone (PTH), secreted by the parathyroid glands, increases extracellular

Ca2+ concentrations. The rate of PTH secretion is regulated by the extracellular Ca2+ concentration.
An elevated Ca2+ concentration inhibits the secretion of PTH and a reduced Ca2+ concentration
stimulates the secretion of PTH. PTH causes osteoclasts to degrade bone and release Ca2+ into the
body fluids. PTH also increases the rate of Ca2+ reabsorption from kidney nephrons.

Vitamin D increases Ca2+ concentration in the blood by increasing the rate of Ca2+ absorption by the
intestine. Some vitamin D is consumed in food, and the body produces the rest. PTH affects the
intestinal uptake of Ca2+ because PTH increases the rate of vitamin D production in the body.

Calcitonin is secreted by the thyroid gland. Calcitonin reduces the blood Ca2+ concentration when it
is too high. An elevated blood Ca2+ concentration causes the thyroid gland to secrete calcitonin, and
a low blood Ca2+ concentration inhibits calcitonin secretion. Calcitonin reduces the rate at which bone
is broken down and decreases the release of Ca2+ from bone

Phosphate and Sulfate Ions

Some ions, such as phosphate ions (PO43−) and sulfate ions(SO42−), are reabsorbed by active
transport in the kidneys. Therate of reabsorption is slow, so that if the concentration of these ions in
the filtrate exceeds the nephron’s ability to reabsorb them, the excess is excreted into the urine. As long
as the concentration of these ions is low, nearly all of them are reabsorbed by active transport. This
mechanism plays a major role in regulating the concentration of PO43− and SO42− in the body fluids
Acidosis and Alkalosis

Failure of the buffer systems, the respiratory system, or the urinary system to maintain normal pH levels
can result in acidosis or alkalosis.

Acidosis

Acidosis occurs when the blood pH falls below 7.35. The central nervous system malfunctions, and the
individual becomes disoriented and, as the condition worsens, may become comatose. Acidosis is
separated into two categories. Respiratory acidosis results when the respiratory system is unable to
eliminate adequate amounts of CO2. Carbon dioxide accumulates in the circulatory system, causing the
pH of the body fluids to decline. Metabolic acidosis results from excess production of acidic
substances, suchas lactic acid and ketone bodies, because of increased metabolism or decreased ability
of the kidneys to eliminate H+ in the urine.

Alkalosis

Alkalosis (al-kă-lō′ sis) occurs when the blood pH increases above 7.45. A major effect of alkalosis is
hyperexcitability of the nervous system. Peripheral nerves are affected first, resulting in spontaneous
nervous stimulation of muscles. Spasms and tetanic contractions result, as can extreme nervousness or
convulsions. Tetany of respiratory muscles can cause death. Respiratory alkalosis results from
hyperventilation, as can occur in response to stress. Metabolic alkalosis usually results from the rapid
elimination of H+ from the body, as occurs during severe vomiting or when excess aldosterone is
secreted by the adrenal cortex.