▪ The kidneys perform a chemical balancing act that would be tricky

even for the best chemical engineer. They maintain the body’s
internal environment by:
1. Regulating the total volume of water in the body and the total
concentration of solutes in that water (osmolality).
2. Regulating the concentrations of the various ions in the
extracellular fluids. (Even relatively small changes in some ion
concentrations such as K+ can be fatal.)
3. Ensuring long-term acid-base balance.
4. Excreting metabolic wastes and foreign substances such as
drugs or toxins.
5. Producing erythropoietin and renin, important molecules for
regulating red blood cell production and blood pressure,
respectively.
6. Converting vitamin D to its active form.
7. Carrying out gluconeogenesis during prolonged fasting
▪ The urine-forming kidneys are crucial components of the urinary
system. The urinary system also includes:
1. Ureters—paired tubes that transport urine from the kidneys to
the urinary bladder
2. Urinary bladder—a temporary storage reservoir for urine
3. Urethra—a tube that carries urine from the bladder to the body
exterior
▪ The bean-shaped kidneys lie in a retroperitoneal position in
the superior lumbar region. Extending approximately from
T12 to L3, the kidneys receive some protection from the
lower part of the rib cage. The right kidney is crowded by the
liver and lies slightly lower than the left.
▪ The lateral surface is convex. The medial surface is concave
and has a vertical cleft called the renal hilum that leads into
an internal space called the renal sinus. The ureter, renal
blood vessels, lymphatics, and nerves all join each kidney at
the hilum and occupy the sinus. Atop each kidney is an
adrenal (or suprarenal) gland, an endocrine gland that is
functionally unrelated to the kidney.
▪ Three layers of supportive tissue surround each kidney.
From superficial to deep, these are:
1. The renal fascia, an outer layer of dense fibrous
connective tissue that anchors the kidney and the
adrenal gland to surrounding structures
2. The perirenal fat capsule, a fatty mass that
surrounds the kidney and cushions it against blows
3. The fibrous capsule, a transparent capsule that
prevents infections in surrounding regions from
spreading to the kidney
▪ A frontal section through a kidney reveals three distinct
regions: cortex, medulla, and pelvis. The most superficial
region, the renal cortex, is light-colored and has a granular
appearance. Deep to the cortex is the darker, reddish-brown
renal medulla, which exhibits cone-shaped tissue masses
called medullary, or renal, pyramids. The broad base of each
pyramid faces toward the cortex, and its apex, or papilla
(“nipple”), points internally. The pyramids appear striped
because they are formed almost entirely of parallel bundles of
microscopic urine collecting tubules and capillaries. The
renal columns, inward extensions of cortical tissue, separate
the pyramids. Each pyramid and its surrounding cortical
tissue constitutes one of approximately eight lobes of a
kidney.
▪ The renal pelvis, a funnel-shaped tube, is continuous with
the ureter leaving the hilum. Branching extensions of the
pelvis form two or three major calyces. Each major calyx
subdivides to form several minor calyces, cup-shaped areas
that enclose the papillae. The calyces collect urine, which
drains continuously from the papillae, and empty it into the
renal pelvis. The urine then flows through the renal pelvis and
into the ureter, which moves it to the bladder to be stored. The
walls of the calyces, pelvis, and ureter contain smooth
muscle that contracts rhythmically to propel urine by
peristalsis.
▪ Nephrons are the structural and functional units of the kidneys.
Each kidney contains over 1 million of these tiny blood-processing
units, which carry out the processes that form urine. In addition,
there are thousands of collecting ducts, each of which collects
fluid from several nephrons and conveys it to the renal pelvis.
Each nephron consists of a renal corpuscle and a renal tubule. All
of the renal corpuscles are located in the renal cortex, while the
renal tubules begin in the cortex and then pass into the medulla
before returning to the cortex.
▪ Nephrons are generally divided into two major groups, cortical and
juxtamedullary:
▪ Cortical nephrons account for 85% of the nephrons in the
kidneys. Except for small parts of their nephron loops that dip
into the outer medulla, they are located entirely in the cortex.
▪ Juxtamedullary nephrons originate close to the cortex-
medulla junction, and they play an important role in the
kidneys’ ability to produce concentrated urine. They have long
nephron loops that deeply invade the medulla, and their
ascending limbs have both thin and thick segments.
▪ Nephrons are the structural and functional units of the kidneys. Each
kidney contains over 1 million of these tiny blood-processing units,
which carry out the processes that form urine. In addition, there are
thousands of collecting ducts, each of which collects fluid from several
nephrons and conveys it to the renal pelvis. Each nephron consists of a
renal corpuscle and a renal tubule. All of the renal corpuscles are
located in the renal cortex, while the renal tubules begin in the cortex
and then pass into the medulla before returning to the cortex.
▪ Each renal corpuscle consists of a tuft of capillaries called a
glomerulus and a cup-shaped hollow structure called the glomerular
capsule (or Bowman’s capsule). The glomerular capsule is continuous
with its renal tubule and completely surrounds the glomerulus, much
as a well-worn baseball glove encloses a ball.
▪ The endothelium of the glomerular capillaries is fenestrated
(penetrated by many pores), which makes these capillaries
exceptionally porous. This property allows large amounts of
solute-rich but virtually protein-free fluid to pass from the blood
into the glomerular capsule. This plasma-derived fluid or filtrate is
the raw material that the renal tubules process to form urine.
▪ The glomerular capsule has an external parietal layer (simple
squamous epithelium) and a visceral layer that clings to the
glomerular capillaries, consists of highly modified, branching
epithelial cells called podocytes. The octopus-like podocytes
terminate in foot processes, which interdigitate as they cling to
the basement membrane of the glomerulus.
• The renal tubule is about 3 cm (1.2 inches) long and has three major
parts. It leaves the glomerular capsule as the elaborately coiled
proximal convoluted tubule, drops into a hairpin loop called the
nephron loop, and then winds and twists again as the distal
convoluted tubule before emptying into a collecting duct.
• The walls of the proximal convoluted tubule are formed by cuboidal epithelial cells
with large mitochondria, and their apical (luminal) surfaces bear dense microvilli.
Just as in the intestine, this brush border dramatically increases the surface area
and capacity for reabsorbing water and solutes from the filtrate and secreting
substances into it.
• The U-shaped nephron loop (formerly called the loop of Henle) has descending
and ascending limbs. The proximal part of the descending limb is continuous with
the proximal tubule and its cells are similar. The rest of the descending limb, called
the descending thin limb, consists of a simple squamous epithelium. The epithelium
becomes cuboidal or even low columnar in the ascending part of the nephron loop,
which is therefore called the thick ascending limb. In most nephrons, the entire
ascending limb is thick, but in some nephrons, the thin segment extends around the
bend as the ascending thin limb. The thick and thin parts of the nephron loop are
also referred to as thick and thin segments.
• The epithelial cells of the distal convoluted tubule, like those of the PCT, are
cuboidal and confined to the cortex, but they are thinner and almost entirely lack
microvilli
• Each collecting duct contains two cell types. The more numerous principal cells
have sparse, short microvilli and are responsible for maintaining the body’s water
and Na+ balance. The intercalated cells are cuboidal cells with abundant microvilli.
There are two varieties of intercalated cells (types A and B), and each plays a role in
maintaining the acid-base balance of the blood. Each collecting duct receives
filtrate from many nephrons. The collecting ducts run through the medullary
pyramids, giving them their striped appearance. As the collecting ducts approach
the renal pelvis, they fuse together and deliver urine into the minor calyces via
papillae of the pyramids.
▪ Each nephron has a juxtaglomerular complex (JGC), a region
where the most distal portion of the ascending limb of the
nephron loop lies against the afferent arteriole feeding the
glomerulus (and sometimes the efferent arteriole). Both the
ascending limb and the afferent arteriole are modified at the
point of contact. The JGC includes three populations of cells that
help regulate the rate of filtrate formation and systemic blood
pressure.
1. The macula densa is a group of tall, closely packed cells
in the ascending limb of the nephron loop that lies
adjacent to the granular cells. The macula densa cells are
chemoreceptors that monitor the NaCl content of the
filtrate entering the distal convoluted tubule.
2. Granular cells (juxtaglomerular or JG cells) are in the
arteriolar walls. They are enlarged smooth muscle cells
with prominent secretory granules containing the enzyme
renin. Granular cells act as mechanoreceptors that sense
the blood pressure in the afferent arteriole.
3. Extraglomerular mesangial cells lie between the
arteriole and tubule cells and are interconnected by gap
junctions. These cells may pass regulatory signals
between macula densa and granular cells.
• Urine formation and the adjustment of blood composition
involve three processes:
1. Glomerular filtration. Glomerular filtration takes place in the
renal corpuscle and produces a cell- and protein-free filtrate.
2. Tubular reabsorption. Tubular reabsorption (“reclaiming
what the body needs to keep”) is the process of selectively
moving substances from the filtrate back into the blood. It
takes place in the renal tubules and collecting ducts. Tubular
reabsorption reclaims almost everything filtered—all of the
glucose and amino acids, and some 99% of the water, salt,
and other components. Anything that is not reabsorbed
becomes urine.
3. Tubular secretion. Tubular secretion (“selectively adding to
the waste container”) is the process of selectively moving
substances from the blood into the filtrate. Like tubular
reabsorption, it occurs along the length of the tubule and
collecting duct.
• Filtrate and urine are quite different. Filtrate contains
everything found in blood plasma except proteins. Urine
contains unneeded substances such as excess salts and
metabolic wastes.
• Tubular reabsorption is a selective
process. Given healthy kidneys, virtually
all organic nutrients such as glucose and
amino acids are completely reabsorbed to
maintain or restore normal plasma
concentrations. On the other hand, the
reabsorption of water and many ions is
continuously regulated and adjusted in
response to hormonal signals. Depending
on the substances transported, the
reabsorption process may be active or
passive. Active tubular reabsorption
requires ATP either directly (primary active
transport) or indirectly (secondary active
transport) for at least one of its steps.
Passive tubular reabsorption
encompasses diffusion, facilitated
diffusion, and osmosis—processes in
which substances move down their
electrochemical gradients.
▪ The most important way to clear plasma of unwanted substances is to
simply not reabsorb them from the filtrate. Another way is tubular
secretion—essentially, reabsorption in reverse. Tubular secretion moves
selected substances (such as H+, K+, NH4+, creatinine, and certain organic
acids and bases) from the peritubular capillaries through the tubule cells
into the filtrate. Also, some substances (such as HCO3−) that are
synthesized in the tubule cells are secreted.
▪ Tubular secretion is important for:
1. Disposing of substances, such as certain drugs and metabolites, that are
tightly bound to plasma proteins. Because plasma proteins are generally
not filtered, the substances they bind are not filtered and so must be
secreted.
2. Eliminating undesirable substances or end products that have been
reabsorbed by passive processes. Urea and uric acid, two nitrogenous
wastes, are both handled in this way
3. Ridding the body of excess K+. Because virtually all K+ present in the
filtrate is reabsorbed in the PCT and ascending nephron loop, nearly all K+
in urine comes from aldosterone-driven active tubular secretion into the
late DCT and collecting ducts.
4. Controlling blood pH. When blood pH drops toward the acidic end of its
homeostatic range, the renal tubule cells actively secrete more H+ into the
filtrate and retain and generate more HCO3− (a base). As a result, blood
pH rises and the urine drains off the excess H+. Conversely, when blood
pH approaches the alkaline end of its range, Cl− is reabsorbed instead of
HCO3−, which is allowed to leave the body in urine.
• Water accounts for about 95% of urine volume; the remaining 5%
consists of solutes. The largest component of urine by weight, apart from
water, is urea, which is derived from the normal breakdown of amino
acids. Other nitrogenous wastes in urine include uric acid (an end
product of nucleic acid metabolism) and creatinine (a metabolite of
creatine phosphate, which is found in large amounts in skeletal muscle
tissue where it stores energy to regenerate ATP).
• Normal solute constituents of urine, in order of decreasing
concentration, are urea, Na+, K+, PO43−, SO42−, creatinine, and uric
acid. Much smaller but highly variable amounts of Ca2+, Mg2+, and
HCO3− are also present. Unusually high concentrations of any solute, or
the presence of abnormal substances such as blood proteins, WBCs
(pus), or bile pigments, may indicate pathology.
• There are several types of diuretics, chemicals that enhance urinary
output. Alcohol encourages diuresis by inhibiting release of ADH. Other
diuretics increase urine flow by inhibiting Na+ reabsorption and the
obligatory water reabsorption that normally follows. Examples include
many drugs prescribed for hypertension or the edema of congestive
heart failure. Most diuretics inhibit Na+-associated symporters. “Loop
diuretics” [like furosemide (Lasix)] are powerful because they inhibit
formation of the medullary gradient by acting at the ascending limb of the
nephron loop. Thiazides are less potent and act at the DCT. An osmotic
diuretic is a substance that is not reabsorbed and that carries water out
with it (for example, the high blood glucose of a diabetes mellitus
patient).
▪ Color and Transparency Freshly voided urine is clear and pale to deep yellow. Its yellow color is due to
urochrome, a pigment that results when the body destroys hemoglobin. The more concentrated the urine, the
deeper the color. An abnormal color (such as pink, brown, or a smoky tinge) may result from eating certain
foods (beets, rhubarb) or from the presence of bile pigments or blood in the urine. Additionally, some
commonly prescribed drugs and vitamin supplements alter the color of urine. Cloudy urine may indicate a
urinary tract infection.
▪ Odor Fresh urine is slightly aromatic, but if allowed to stand, it develops an ammonia odor as bacteria
metabolize its urea solutes. Some drugs and vegetables alter the odor of urine, as do some diseases. For
example, in uncontrolled diabetes mellitus the urine smells fruity because of its acetone content
▪ pH Urine is usually slightly acidic (around pH 6), but changes in body metabolism or diet may cause the pH to
vary from about 4.5 to 8.0. A predominantly acidic diet that contains large amounts of protein and whole
wheat products produces acidic urine. A vegetarian (alkaline) diet, prolonged vomiting, and bacterial infection
of the urinary tract all cause the urine to become alkaline.
▪ Specific Gravity The ratio of the mass of a substance to the mass of an equal volume of distilled water is its
specific gravity. Because urine is water plus solutes, a given volume has a greater mass than the same
volume of distilled water. The specific gravity of distilled water is 1.0 and that of urine ranges from 1.001 to
1.035, depending on its solute concentration.
• The ureters are slender tubes that convey urine from
the kidneys to the bladder. Each ureter begins at the
level of L2 as a continuation of the renal pelvis. From
there, it descends behind the peritoneum and runs
obliquely through the posterior bladder wall. This
arrangement prevents backflow of urine because any
increase in bladder pressure compresses and closes
the distal ends of the ureters. The ureter plays an
active role in transporting urine. Incoming urine
distends the ureter and stimulates its muscularis to
contract, propelling urine into the bladder. (Urine does
not reach the bladder through gravity alone.) The
strength and frequency of the peristaltic waves are
adjusted to the rate of urine formation.
▪ The urinary bladder is a smooth, collapsible, muscular sac that
stores urine temporarily. The bladder is located
retroperitoneally on the pelvic floor just posterior to the pubic
symphysis. The prostate (part of the male reproductive system)
lies inferior to the bladder neck, which empties into the urethra.
In females, the bladder is anterior to the vagina and uterus.
▪ The interior of the bladder has openings for both ureters and the
urethra. The smooth, triangular region of the bladder base
outlined by these three openings is the trigone, important
clinically because infections tend to persist in this region.
▪ The bladder wall has three layers: a mucosa containing
transitional epithelium, a thick muscular layer, and a fibrous
adventitia (except on its superior surface, where it is covered by
the peritoneum). The muscular layer, called the detrusor,
consists of intermingled smooth muscle fibers arranged in inner
and outer longitudinal layers and a middle circular layer.
▪ A moderately full bladder is about 12 cm (5 inches) long and
holds approximately 500 ml (1 pint) of urine, but it can hold
nearly double that if necessary. When tense with urine, it can be
palpated well above the pubic symphysis. The maximum
capacity of the bladder is 800–1000 ml and when it is
overdistended, it may burst.
• The urinary bladder and ureters can be seen in a special X ray
called a pyelogram
▪ The urethra is a thin-walled muscular tube that drains urine from the bladder and
conveys it out of the body. The epithelium of its mucosal lining is mostly
pseudostratified columnar epithelium. However, near the bladder it becomes
transitional epithelium, and near the external opening it changes to a protective
stratified squamous epithelium.
▪ At the bladder-urethra junction, the detrusor smooth muscle thickens to form the
internal urethral sphincter. This involuntary sphincter, controlled by the
autonomic nervous system, keeps the urethra closed when urine is not being
passed and prevents leaking between voiding. The external urethral sphincter
surrounds the urethra as it passes through the urogenital diaphragm. This
sphincter is formed of skeletal muscle and is voluntarily controlled. The levator ani
muscle of the pelvic floor also serves as a voluntary constrictor of the urethra.
▪ The length and functions of the urethra differ in the two sexes. In females the
urethra is only 3–4 cm (1.5 inches) long and fibrous connective tissue binds it
tightly to the anterior vaginal wall. Its external opening, the external urethral
orifice, lies anterior to the vaginal opening and posterior to the clitoris. In males
the urethra is approximately 20 cm (8 inches) long and has three regions.
1. The prostatic urethra, about 2.5 cm (1 inch) long, runs within the prostate.
2. The intermediate part of the urethra (or membranous urethra), which runs
through the urogenital diaphragm, extends about 2 cm from the prostate to
the beginning of the penis.
3. The spongy urethra, about 15 cm long, passes through the penis and opens
at its tip via the external urethral orifice
▪ The male urethra has a double function: It carries semen as well as urine out of the
body
• Micturition, also called urination or voiding,
is the act of emptying the urinary bladder. For
micturition to occur, three things must
happen simultaneously: (1) the detrusor
must contract, (2) the internal urethral
sphincter must open, and (3) the external
urethral sphincter must open.
• The detrusor and its internal urethral
sphincter are composed of smooth muscle
and are innervated by both the
parasympathetic and sympathetic nervous
systems, which have opposing actions. The
external urethral sphincter, in contrast, is
skeletal muscle, and therefore is innervated
by the somatic nervous system.