RENAL SYSTEM

The urinary system consists of two kidneys, two ureters, one urinary bladder and one
urethra.
Function of Urinary system:
Regulation of blood ionic composition. The kidneys help regulate the blood levels of
several ions, most importantly sodium ions (Na+), potassium ions (K+), calcium ions (Ca2+),
chloride ions (Cl"), and phosphate ions (HPO42").
Regulation of blood pH. The kidneys excrete a variable amount of hydrogen ions (H+) into
the urine and conserve bicarbonate ions (HCO3"), which are an important buffer of H+ in
the blood. Both of these activities help regulate blood pH.
Regulation of blood volume. The kidneys adjust blood volume by conserving or
eliminating water in the urine. An increase in blood volume increases blood pressure; a
decrease in blood volume decreases blood pressure.
Regulation of blood pressure. The kidneys also help regulate blood pressure by secreting
the enzyme renin, which activates the renin-angiotensin-aldosterone pathway.
Maintenance of blood osmolarity. By separately regulating loss of water and loss of solutes
in the urine, the kidneys maintain a relatively constant blood osmolarity close to 300
milliosmoles per liter (mOsm/liter).
Production of hormones. The kidneys produce two hormones. Calcitriol, the active form
of vitamin D, helps regulate calcium homeostasis, and erythropoietin stimulates the
production of red blood cells.
Regulation of blood glucose level Like the liver, the kidneys can use the amino acid
glutamine in gluconeogene-sis, the synthesis of new glucose molecules.
Excretion of wastes and foreign substances. By forming urine, the kidneys help excrete
wastes—substances that have no useful function in the body. Like bilirubin, urea, uric acid,
Creatinine.
ANATOMY OF THE KIDNEYS
The paired kidneys are reddish, kidney-bean-shaped organs located just above the waist
between the peritoneum and the posterior wall of the abdomen. The kidneys are located
between the levels of the last thoracic and third lumbar vertebrae. The right kidney is
slightly lower than the left because the liver occupies considerable space on the right side
superior to the kidney.
External Anatomy of the Kidneys
A typical adult kidney is 10-12 cm long, 5-7 cm wide, and 3 cm thick. Near the center of
the concave border is an indentation called the renal hilum, through which the ureter
emerges from the kidney along with blood vessels, lymphatic vessels, and nerves.
Three layers of tissue surround each kidney.
Renal capsule: The deep layer, is a smooth, transparent sheet of dense irregular connective
tissue continue over ureter. It helps maintain the shape of the kidney.
Adipose capsule: The middle layer, is a mass of fatty tissue surrounding the renal capsule.
It also protects the kidney from jerks and holds it firmly in place within the abdominal cavity.
Renal fascia: The superficial layer, is another thin layer of dense irregular connective
tissue.
Internal Anatomy of the Kidneys
The outer red area is called the renal cortex and a deep, darker reddish-brown inner region
called the renal medulla. The renal medulla consists of several cone-shaped renal
pyramids. The apex (narrower end) of each pyramid called a renal papilla, points toward
the renal hilum. Each kidney consist of millions of nephrons, which are the structural and
functional units of kidney.
Urine formed by the nephrons drains into large papillary ducts, which drain fluid into
cuplike structures called minor and major calyces. From the major calyces, urine drains
into a single large cavity called the renal pelvis and then out through the ureter to the
urinary bladder.
Blood and Nerve Supply of the Kidneys
Kidneys are abundantly supplied with blood vessels. Although, they receive 20-25% of
the resting cardiac output via the right and left renal arteries.
Within the kidney, the renal artery divides into several segmental arteries, which supply
different segments (areas) of the kidney. Each segmental artery enter in to the parenchyma
and pass through the renal pyramids as the interlobar arteries. At the bases of the renal
pyramids, the interlobar arteries arch between the renal medulla and cortex; here they are
known as the arcuate arteries. Arcuate arteries produce a series of interlobular arteries.
These arteries are so named because they pass between renal lobules. Interlobular arteries
enter the renal cortex and give off branches called afferent arterioles.
Each nephron receives one afferent arteriole, which divides into capillary network called
the glomerulus. The glomerular capillaries then reunite to form an efferent arteriole that
carries blood out of the glomerulus.
The efferent arterioles divide to form the peritubular capillaries. The peritubular
capillaries eventually reunite to form peritubular venules and then interlobular veins.
Then the blood drains through the arcuate veins to the interlobar veins. Blood leaves the
kidney through a single renal vein that exits at the renal hilum and carries venous blood to
the inferior vena cava.
The Nephron Parts of a Nephron
Nephrons are the functional units of the kidneys. Each nephron consists of two parts:
Renal corpuscle: where blood plasma is filtered,
Renal tubule: into which the filtered fluid passes.
The two components of a renal corpuscle are the glomerulus (capillary network) and the
glomerular (Bowman’s) capsule, a double-walled epithelial cup
The renal tubule consists of a
(1) proximal convoluted tubule
(2) loop of Henle (nephron loop)
(3) distal convoluted tubule
About 80-85% of the nephrons are cortical nephrons. Their renal corpuscles lie in the
outer portion of the renal cortex, and they have short loops of Henle that lie mainly in the
cortex.
The other 15-20% of the nephrons are juxtamedullary nephrons. Their renal corpus-
cles lie deep in the cortex, close to the medulla, and they have a long loop of Henle that
extends into the deepest region of the medulla.
URINE FORMATION PROCESS
To produce urine, nephrons and collecting ducts perform three basic processes—
1. Glomerular filtration
2. Tubular reabsorption
3. Tubular secretion
1. Glomerular filtration. In the first step of urine production, water and most solutes in
blood plasma move across the wall of glomerular capillaries into the glomerular capsule
and then into the renal tubule.
2. Tubular reabsorption. As filtered fluid flows along the renal tubule and through the
collecting duct, tubule cells reabsorb about 99% of the filtered water and many useful
solutes. The water and solutes return to the blood as it flows through the peritubular
capillaries and vasa recta. Note that the term reabsorption refers to the return of substances
to the bloodstream.
3. Tubular secretion. As fluid flows along the renal tubule and through the collecting duct,
the tubule and duct cells secrete other materials, such as wastes, drugs, and excess ions, into
the fluid. Notice that tubular secretion removes a substance from the blood.
Solutes in the fluid that drains into the renal pelvis remain in the urine and are excreted.
Glomerular Filteration: The fluid that enters the capsular space is called the glomerular
filtrate.

GLOMERULAR FILTRATION RATE (GFR)

The amount of filtrate formed by the all the nephrons of both the kidney in each minute are
called GFR. GFR is 125 ml/minute in male and 105ml/minute in female.
On average, the daily volume of glomerular filtrate in adults is 150 liters in females and
180 liters in males. More than 99% of the glomerular filtrate returns to the bloodstream via
tubular reabsorption, so only 1-2 liters (about 1-2 qt) are excreted as urine.
If the GFR is too high, needed substances may pass so quickly through the renal tubules that
some are not reabsorbed and are lost in the urine. If the GFR is too low, nearly all the filtrate
may be reabsorbed and certain waste products may not be adequately excreted.
Glomerular endothelial cells are quite leaky because they have large fenestrations
(pores). This size permits all solutes in blood plasma to exit glomerular capillaries but
prevents filtration of blood cells and platelets.

The principle of filtration:

Glomerular capillaries present a large surface area for filtration because they are long and
extensive.
The filtration membrane is thin and porous. Despite having several layers, the thickness of
the filtration membrane is only 0.1 /nm. Glomerular capillaries also are about 50 times
leakier than capillaries in most other tissues, mainly because of their large fenestrations.
Glomerular capillary blood pressure is high. Because the efferent arteriole is smaller in
diameter than the afferent arteriole. As a result, blood pressure in glomerular capillaries is
considerably higher than in capillaries elsewhere in the body.
Net Filtration Pressure
Glomerular filtration depends on three main pressures. One pressure promotes filtration and
two pressures oppose filtration.
1. Glomerular blood hydrostatic pressure (GBHP) is the blood pressure in glomerular
capillaries. Generally, GBHP is about 55 mmHg. It promotes filtration by forcing water and
solutes in blood plasma through the filtration membrane.
2. Capsular hydrostatic pressure (CHP) is the hydrostatic pressure exerted against the
filtration membrane by fluid already in the capsular space and renal tubule. CHP opposes
filtration and represents a “back pressure” of about 15 mmHg.
3. Blood colloid osmotic pressure (BCOP), which is due to the presence of proteins such
as albumin, globulins, and fibrinogen in blood plasma, also opposes filtration. The average
BCOP in glomerular capillaries is 30 mmHg.
Net filtration pressure (NFP), the total pressure that promotes filtration, is determined as
follows:
Net Filtration Pressure (NFP) = GBHP — CHP — BCOP
By substituting the values just given, normal NFP may be calculated:
NFP = 55 mmHg — 15 mmHg — 30 mmHg = 10 mmHg
MECHANISM OF REGULATION OF GLOMERULAR FILTRATION
The mechanisms that regulate glomerular filtration rate operate in two main ways:
(1) By adjusting blood flow into and out of the glomerulus
(2) By altering the glomerular capillary surface area available for filtration

Three mechanisms control GFR:

1. Renal autoregulation
2. Neural regulation
3. Hormonal regulation
1. Renal Autoregulation of GFR:
The kidneys themselves help maintain a constant renal blood flow and GFR despite
normal, everyday changes in blood pressure. This capability is called renal autoregulation
and consists of two mechanisms
a. Myogenic mechanism
b. Tubuloglomerular feedback.

a. Myogenic mechanism: As blood pressure rises, GFR also rises because renal blood
flow increases. However, the elevated blood pressure stretches the walls of the afferent
arterioles. In response, smooth muscle fibers in the wall of the afferent arteriole contract,
which narrows the arteriole’s lumen. As a result, renal blood flow decreases, thus reducing
GFR to its previous level. Conversely, when arterial blood pressure drops, the smooth muscle
cells are stretched less and thus relax. The afferent arterioles dilate, renal blood flow
increases, and GFR increases. The myogenic mechanism normalizes renal blood flow and
GFR within seconds after a change in blood pressure.
b. Tubuloglomerular feedback mechanism; is so named because part of the renal
tubules—the macula densa—provides feedback to the glomerulus. When GFR is above
normal due to elevated systemic blood pressure, filtered fluid flows more rapidly along the
renal tubules. As a result, the proximal convoluted tubule and loop of Henle have less time
to reabsorb Na+, Cl-, and water. Macula densa cells are thought to detect the increased
delivery of Na+, Cl-, and water and to inhibit release of nitric oxide (NO) from cells in
the juxtaglomerular apparatus (JGA). Because NO causes vasodilation, afferent arterioles
constrict when the level of NO declines. As a result, less blood flows into the glomerular
capillaries, and GFR decreases. When blood pressure falls, causing GFR to be lower than
normal, the opposite sequence of events occurs. Tubuloglomerular feedback operates more
slowly than the myogenic mechanism.

2. Neural Regulation of GFR

Kidneys are supplied by sympathetic ANS fibers that release norepinephrine.
Norepinephrine causes vasoconstriction through the activation of alpha receptors.
At rest, sympathetic activity is moderately low, the afferent and efferent arterioles are dilated.
With moderate sympathetic stimulation, both afferent and efferent arterioles constrict to the
same degree. Blood flow into and out of the glomerulus is decrease to the same extent,
which decreases GFR only slightly.
With greater sympathetic stimulation, however, as occurs during exercise or hemorrhage,
vasoconstriction of the afferent arterioles. As a result, blood flow into glomerular
capillaries is greatly decreased, and GFR drops.
3. Hormonal Regulation of GFR
Two hormones contribute to regulation of GFR.
a. Angiotensin II reduces GFR
b. Atrial natriuretic peptide (ANP) increases GFR.

a. Angiotensin II is a very potent vasoconstrictor that narrows both afferent and efferent
arterioles and reduces renal blood flow, thereby decreasing GFR.
b. ANP: Cells in the atria of the heart secrete atrial natriuretic peptide (ANP).
Stretching of the atria, as occurs when blood volume increases, stimulates secretion of
ANP. ANP increases the capillary surface area available for filtration. Glomerular
filtration rate rises as the surface area increases.
TUBULAR REABSORPTION AND TUBULAR SECRETION
Tubular Reabsorption: Reabsorption—the return of most of the filtered water and many
of the filtered solutes to the bloodstream—is the second basic function of the nephron and
collecting duct. Normally, about 99% of the filtered water is reabsorbed. Solutes that are
reabsorbed by both active and passive processes include glucose, amino acids, urea, and
ions such as Na+ (sodium), K+ (potassium), Ca2+ (calcium), Cl- (chloride), HCO3-
(bicarbonate), and HPO42 (phosphate). The reabsorption of these substances are carried either
by symporters {exchange of sodium ions and glucose through the membrane} or by
antiporters {exchange of sodium and potassium ions in DCT and CD under the influence of
Aldosterone hormones}. Most small proteins and peptides that pass through the filter also
are reabsorbed, usually via pinocytosis.
Hormonal regulation of tubular reabsorption:
Five hormones affect the extent of Na+, Cl-, Ca2+, and water reabsorption as well as K+
secretion by the renal tubules. These hormones include angiotensin II, aldosterone,
antidiuretic hormone, atrial natriuretic peptide, and parathyroid hormone.
1. Renin-Angiotensin-Aldosterone System
When blood volume and blood pressure decrease, the walls of the afferent arterioles are
stretched less, and the juxtaglomerular cells secrete the enzyme renin into the blood.
Sympathetic stimulation also directly stimulates release of renin from juxtaglomerular cells.
Renin clips off a 10-amino-acid peptide called angiotensin I from angiotensinogen, which is
synthesized by he-patocytes. By clipping off two more amino acids, angiotensin converting
enzyme (ACE) converts angiotensin I to angiotensin II, which is the active form of the
hormone.
Angiotensin II affects renal physiology in three main ways:
a. It decreases the glomerular filtration rate by causing vasoconstriction of the afferent
arterioles.
b. It enhances reabsorption of Na+, Cl-, and water in the proximal convoluted tubule by
stimulating the activity of Na+/H+ antiporters.
c. It stimulates the adrenal cortex to release aldosterone, a hormone that in turn stimulates
the principal cells in the collecting ducts to reabsorb more Na+ and Cl- and secrete more
K+. The osmotic consequence of reabsorbing more Na+ and Cl- is excreting less water,
which increases blood volume.

2. Antidiuretic Hormone
Antidiuretic hormone (ADH or vasopressin) is released by the posterior pituitary. It
regulates facultative water reabsorption by increasing the water permeability of principal
cells in the last part of the distal convoluted tubule and throughout the collecting duct. In the
absence of ADH, the cells have a very low permeability to water hence large amount of
urine is formed. When ADH level declines, the kidneys produce a large volume of dilute
urine.
A negative feedback system involving ADH regulates the blood level. When the osmolarity
or osmotic pressure of plasma and interstitial fluid increases—that is, when water
concentration decreases—osmoreceptors in the hypothalamus detect the change. Their nerve
impulses stimulate secretion of more ADH into the blood, and the principal cells become
more permeable to water. As facultative water reabsorption increases, plasma osmolarity
decreases to normal. A second powerful stimulus for ADH secretion is a decrease in blood
volume, as occurs in hemorrhaging or severe dehydration. In the pathological absence of
ADH activity, a condition known as diabetes insipidus, a person may excrete up to 20 liters
of very dilute urine daily.
3. Atrial Natriuretic Peptide
A large increase in blood volume promotes release of atrial natriuretic peptide (ANP) from
the heart. it can inhibit reabsorption of Na and water in the proximal convoluted tubule and
collecting duct. ANP also suppresses the secretion of aldosterone and ADH. These effects
increase the excretion of Na+ in urine (natriuresis) and increase urine output (diuresis),
which decreases blood volume and blood pressure.
4. Parathyroid Hormone
A lower-than-normal level of Ca2+ in the blood stimulates the parathyroid glands to release
parathyroid hormone (PTH). PTH in turn stimulates cells in the early distal convoluted
tubules to reabsorb more Ca2+ into the blood. PTH also inhibits HPO42" (phosphate)
reabsorption in proximal convoluted tubules, thereby promoting phosphate excretion.

Tubular Secretion: The third function of nephrons and collecting ducts is tubular secretion,
the transfer of materials from the blood and tubule cells into tubular fluid. Secreted
substances include hydrogen ions (H+), K+, ammonium ions (NH4+), creatinine, and
certain drugs such as penicillin.

Tubular secretion has two important outcomes:

(1) The secretion of H+ helps control blood pH.
(2) The secretion of other substances helps eliminate them from the body.
As a result of tubular secretion, certain substances pass from blood into urine and may be
detected by a urinalysis
Ureters
Each of the two ureters transports urine from the renal pelvis of one kidney to the urinary
bladder. Peristaltic contractions of the muscular walls of the ureters push urine toward the
urinary bladder, but hydrostatic pressure and gravity also contribute.
The ureters are 25-30 cm long and are thick-walled, narrow tubes that vary in diameter
from 1 mm to 10 mm. At the base of the urinary bladder, the ureters curve medially and
pass obliquely through the wall of the urinary bladder. As the urinary bladder fills with
urine, pressure within it compresses the oblique openings into the ureters and prevents the
back flow of urine.

Urinary Bladder
The urinary bladder is a hollow, distensible muscular organ situated in the pelvic cavity.
In males, it is directly anterior to the rectum; in females, it is anterior to the vagina. When
slightly distended due to the accumulation of urine, the urinary bladder is spherical. When
it is empty, it collapses. As urine volume increases, it becomes pear-shaped and rises into
the abdominal cavity. Urinary bladder capacity averages 700-800 mL. It is smaller in
females because the uterus occupies the space just superior to the urinary bladder.

In the floor of the urinary bladder is a small triangular area called the trigone. Three coats
make up the wall of the urinary bladder.
a. Mucosa
b. Muscularis: Detrusor muscle
c. Adventitia
Around the opening to the urethra the circular fibers form an internal urethral sphincter;
inferior to it is the external urethral sphincter, which is composed of skeletal muscle

The Micturition Reflex

Discharge of urine from the urinary bladder, called micturition is also known as urination
or voiding. Micturition occurs via a combination of involuntary and voluntary muscle
contractions. When the volume of urine in the urinary bladder exceeds 200-400 mL,
pressure within the bladder increases considerably, and stretch receptors in its wall transmit
nerve impulses to the micturition center in sacral spinal cord segments and trigger a spinal
reflex called the micturition reflex.
In this reflex arc, parasympathetic impulses from the micturition center propagate to the
urinary bladder wall and internal urethral sphincter. The nerve impulses cause contraction
of the detrusor muscle and relaxation of the internal urethral sphincter muscle. Upon
contraction of the urinary bladder wall and relaxation of the sphincters, urination takes
place.
Glucosuria: Appearance of glucose in the urine, due to excess concentration of glucose in
blood is called glucosuria. The most common cause of glucosuria is diabetes mellitus.
Diabetes inspidus: Due to decrease the secretion of ADH.

Formation of Dilute Urine:

Glomerular filtrate has the same ratio of water and solute particles as blood; its osmolarity
is about 300 mOsm/liter. The fluid leaving the proximal convoluted tubule is still isotonic to
plasma. When dilute urine is being formed, the osmolarity of the fluid in the tubular lumen
increases.
FORMATION OF DILUTE URINE
When, water content in the body increases, kidney excretes dilute urine. This is achieved
by inhibition of ADH secretion from posterior pituitary. So water reabsorption from renal
tubules does not take place leading to excretion of large amount of water. This makes the
urine dilute.
FORMATION OF CONCENTRATED URINE
When the water content in body decreases, kidney retains water and excretes
concentrated urine. Formation of concentrated urine is not as simple as that of dilute
urine.
It involves two processes:
1. Development and maintenance of medullary gradient by countercurrent system
2. Secretion of ADH
1. DEVELOPMENT AND MAINTENANCE OF MEDULLARY GRADIENT
Countercurrent mechanism, which is responsible for the development and maintenance
of medullary gradient and hyperosmolarity of interstitial fluid in the inner medulla.
COUNTERCURRENT MECHANISM
COUNTERCURRENT FLOW
A countercurrent system is a system of ‘U’­shaped tubules in which, the flow of fluid is
in opposite direction in two limbs of the ‘U’­shaped tubules.
Divisions of Countercurrent System
Countercurrent system has two divisions:
1. Countercurrent multiplier formed by loop of Henle
2. Countercurrent exchanger formed by vasa recta.
COUNTERCURRENT MULTIPLIER
Role of Loop of Henle in Development of Medullary Gradient

Loop of Henle of juxtamedullary nephrons plays a major role as countercurrent multiplier

because loop of these nephrons is long and extends upto the deeper parts of medulla.

At ascending loop of henle active reabsorption of sodium, chloride and other solutes take
into the medullary interstitium. These solutes accumulate in the medullary interstitium
and increase the osmolarity. Now, due to the concentration gradient, the sodium and
chlorine ions diffuse from medullary interstitium into the descending limb of Henle loop
and reach the ascending limb again via hairpin bend.

Thus, recirculation of sodium and chlorine ions between the descending limb and
ascending limb of Henle loop and regular addition of more and more new sodium and
chlorine ions into descending limb by constant filtration results increase or multiply the
osmolarity of medullary interstitial fluid and medullary gradient.

Others Factor
Recirculation of urea
Fifty percent of urea filtered in glomeruli is reabsorbed in proximal convoluted tubule.
Collecting duct is impermeable to urea. However, due to the water reabsorption from
distal convoluted tubule and collecting duct in the presence of ADH, urea concentration
increases in collecting duct. Now due to concentration gradient, urea diffuses from inner
medullary part of collecting duct into medullary interstitium.

Due to continuous diffusion, the concentration of urea increases in the inner medulla
resulting in hyperosmolarity of interstitium in inner medulla.

Again, by concentration gradient, urea enters the ascending limb. From here, it passes
through distal convoluted tubule and reaches the collecting duct. Urea enters the
medullary interstitium from collecting duct. By this way urea recirculates repeatedly
and helps to maintain the hyperosmolarity of inner medullary interstitium.

COUNTERCURRENT EXCHANGER
Vasa Recta

Vasa recta acts like countercurrent exchanger because of its position. It is also ‘U’­shaped
tubule with a descending limb, hairpin bend and an ascending limb.
Vasa recta runs parallel to loop of Henle. Its descending limb runs along the ascending
limb of Henle loop and its ascending limb runs along with descending limb of Henle
loop.

The sodium chloride reabsorbed from ascending limb of Henle loop enters the medullary
interstitium.
From here it enters the descending limb of vasa recta. Simultaneously water diffuses from
descending limb of vasa recta into medullary interstitium.

The blood flows very slowly through vasa recta. So, a large quantity of sodium chloride
accumulates in descending limb of vasa recta and flows slowly towards ascending limb.
By the time the blood reaches the ascending limb of vasa recta, the concentration of
sodium chloride increases very much. This causes diffusion of sodium chloride into the
medullary interstitium. Simultaneously, water from medullary interstitium enters the
ascending limb of vasa recta. And the cycle is repeated.

Thus, vasa recta retains sodium chloride in the medullary interstitium and removes water
from it. So, the hyperosmolarity of medullary interstitium is maintained.

2. ROLE OF ADH
Final concentration of urine is achieved by the action of ADH. Normally, the distal
convoluted tubule and collecting duct are not permeable to water. But the presence of
ADH makes them permeable, resulting in water reabsorption. Water reabsorption
induced by ADH is called facultative reabsorption of water