Urine Formation

Introduction
• Urine formation is a blood cleansing function.
• Normally, about 1,300 mL of blood (26% of cardiac
output) enters the kidneys.
• Kidneys excrete the unwanted substances along with
water from the blood as urine.
• Normal urinary output is 1 L/day to 1.5 L/day.
Processes of Urine Formation

When blood passes through glomerular

capillaries, the plasma is filtered into the
Bowman capsule.
This process is called glomerular filtration.
•Filtrate from Bowman capsule passes through
the tubular portion of the nephron.
•While passing through the tubule, the filtrate
undergoes various changes both in quality and
in quantity.
•Many wanted substances like glucose, amino
acids, water and electrolytes are reabsorbed
from the tubules.
•This process is called tubular reabsorption.
•And, some unwanted substances are
secreted into the tubule from peritubular
blood vessels.
• This process is called tubular secretion or
excretion as shown in the Fig..
FIGURE : Events of urine formation
Thus, the urine formation includes three processes :

A. Glomerular filtration
B. Tubular reabsorption
C. Tubular secretion.
Among these three processes filtration is the
function of the glomerulus.
Reabsorption and secretion are the functions of tubular
portion of the nephron.
GLOMERULAR FILTRATION
• INTRODUCTION
• Glomerular filtration is the process by which the
blood is filtered while passing through the
glomerular capillaries by filtration membrane.
• It is the first process of urine formation.
• The structure of filtration membrane is well suited
for filtration.
Process of Glomerular Filtration
When blood passes through glomerular capillaries,
the plasma is filtered into the Bowman capsule.
All the substances of plasma are filtered except the
plasma proteins.
The filtered fluid is called glomerular filtrate.
Ultrafiltration
Glomerular filtration is called ultrafiltration because even
the minute particles are filtered.
But, the plasma proteins are not filtered due to their large
molecular size.
The protein molecules are larger than the slit pores
present in the endothelium of capillaries.
Thus, the glomerular filtrate contains all the substances
present in plasma except the plasma proteins
GLOMERULAR FILTRATION RATE

Glomerular filtration rate (GFR) is defined as the total

quantity of filtrate formed in all the nephrons of both the
kidneys in the given unit of time.
Normal GFR is 125 mL/minute or about 180 L/day.
FILTRATION FRACTION
Filtration fraction is the fraction (portion) of the renal
plasma, which becomes the filtrate.
It is the ratio between renal plasma flow and glomerular
filtration rate.
It is expressed in percentage.
PRESSURES DETERMINING FILTRATION
Pressures, which determine the GFR are:
1. Glomerular capillary pressure
2. Colloidal osmotic pressure in the glomeruli
3. Hydrostatic pressure in the Bowman
capsule.
These pressures determine the GFR by either
favoring or opposing the filtration.
1. Glomerular Capillary Pressure
Glomerular capillary pressure is the pressure exerted
by the blood in glomerular capillaries.
It is about 60 mm Hg and, varies between 45 and 70 mm
Hg.
Glomerular capillary pressure is the highest capillary
pressure in the body.
This pressure favors glomerular filtration.
2. Colloidal Osmotic Pressure
 It is the pressure exerted by plasma proteins in the
glomeruli.
 The plasma proteins are not filtered through the
glomerular capillaries and remain in the glomerular
capillaries.
 These proteins develop the colloidal osmotic pressure,
which is about 25 mm Hg.
 It opposes glomerular filtration.
3. Hydrostatic Pressure in Bowman Capsule
 It is the pressure exerted by the filtrate in Bowman
capsule.
 It is also called capsular pressure.
 It is about 15 mm Hg.
 It also opposes glomerular filtration.
Net Filtration Pressure
 Net filtration pressure is the balance between pressure
favoring filtration and pressures opposing filtration.
 It is otherwise known as effective filtration pressure
or essential filtration pressure.

Net filtration pressure is about 20 mm Hg and, it varies between 15 and 20 mm Hg

TUBULAR REABSORPTION
„INTRODUCTION
 Tubular reabsorption is the process by which water and
other substances are transported from renal tubules
back to the blood.
 When the glomerular filtrate flows through the tubular
portion of nephron, both quantitative and qualitative
changes occur.
 Large quantity of water (more than 99%), electrolytes
and other substances are reabsorbed by the tubular
epithelial cells.
The reabsorbed substances move into the
interstitial fluid of renal medulla
And, from here, the substances move into the
blood in peritubular capillaries.
Since the substances are taken back into the
blood from the glomerular filtrate, the entire
process is called tubular reabsorption.
SELECTIVE REABSORPTION
 Tubular reabsorption is known as selective
reabsorption because the tubular cells reabsorb
only the substances necessary for the body.
 Essential substances such as glucose, amino acids and
vitamins are completely reabsorbed from renal tubule.
 Whereas the unwanted substances like metabolic
waste products are not reabsorbed and excreted
through urine.
MECHANISM OF REABSORPTION
Basic transport mechanisms involved in tubular
reabsorption are of two types:
1. Active reabsorption
2. Passive reabsorption.
1. Active Reabsorption
 Active reabsorption is the movement of molecules
against the electrochemical (uphill) gradient.
 It needs liberation of energy, which is derived from
ATP.
• Substances reabsorbed actively
• Substances reabsorbed actively from the renal
tubule are sodium, calcium, potassium,
phosphates, sulfates, bicarbonates, glucose, amino
acids, ascorbic acid, uric acid and ketone bodies.
2. Passive Reabsorption
 Passive reabsorption is the movement of molecules
along the electrochemical (downhill) gradient.
 This process does not need energy.

Substances reabsorbed passively

 Substances reabsorbed passively are chloride, urea and
water.
ROUTES OF REABSORPTION
Reabsorption of substances from tubular lumen
into the peritubular capillary occurs by two
routes:
1. Trancelluar route
2. Paracellular route.
1. Transcellular Route
In this route the substances move through the
cell.
It includes transport of substances from:
a. Tubular lumen into tubular cell through
apical (luminal) surface of the cell membrane
b. Tubular cell into interstitial fluid
c. Interstitial fluid into capillary.
2. Paracelluar Route
In this route, the substances move through the
intercellular space.
It includes transport of substances from:
i. Tubular lumen into interstitial fluid present in lateral
intercellular space through the tight junction
between the cells
ii. Interstitial fluid into capillary (Fig).
SITE OF REABSORPTION
Reabsorption of the substances occurs in almost all the
segments of tubular portion of nephron.
1. Substances Reabsorbed from Proximal
Convoluted Tubule
 About 7/8 of the filtrate (about 88%) is reabsorbed
in proximal convoluted tubule.
 The brush border of epithelial cells in proximal
convoluted tubule increases the surface area and
facilitates the reabsorption.
Substances reabsorbed from proximal convoluted
tubule are glucose, amino acids, sodium, potassium,
calcium, bicarbonates, chlorides, phosphates, urea, uric
acid and water.
2. Substances Reabsorbed from Loop of Henle
Substances reabsorbed from loop of Henle are sodium and
chloride.
3. Substances Reabsorbed from Distal
Convoluted Tubule
Sodium, calcium, bicarbonate and water are
reabsorbed from distal convoluted tubule.
TUBULAR SECRETION
„INTRODUCTION
 Tubular secretion is the process by which the
substances are transported from blood into renal
tubules.
 It is also called tubular excretion.
 In addition to reabsorption from renal tubules, some
substances are also secreted into the lumen from the
peritubular capillaries through the tubular epithelial
cells.
 Dye phenol red was the first substance found to be
secreted in renal tubules in experimental conditions.
 Later many other substances were found to be secreted.

Such substances are:

1. Paraaminohippuric
acid (PAH)
2. Diodrast
3. 5hydroxyindoleacetic
acid (5HIAA)
4. Amino derivatives
5. Penicillin.
SUBSTANCES SECRETED IN DIFFERENT
SEGMENTS OF RENAL TUBULES
1. Potassium is secreted actively by sodium potassium
pump in proximal and distal convoluted tubules and
collecting ducts
2. Ammonia is secreted in the proximal convoluted tubule
3. Hydrogen ions are secreted in the proximal and
distal convoluted tubules. Maximum hydrogen ion
secretion occurs in proximal tubule
4. Urea is secreted in loop of Henle.
Thus, urine is formed in nephron by the processes
of glomerular filtration, selective reabsorption and
tubular secretion.
SUMMARY OF URINE FORMATION
Urine formation takes place in three processes:
1. Glomerular filtration
Plasma is filtered in glomeruli and the substances reach
the renal tubules along with water as filtrate.
2. Tubular Reabsorption
The 99% of filtrate is reabsorbed in different segments
of renal tubules.
3. Tubular Secretion
Some substances are transported from blood into the
renal tubule.
With all these changes, the filtrate becomes urine.
Concentration of Urine
 Every day 180 L of glomerular filtrate is formed with
large quantity of water.
 If this much of water is excreted in urine, body will
face serious threats. So the concentration of urine
is very essential.
 Osmolarity of glomerular filtrate is same as that of
plasma and it is 300 mOsm/L.
 But, normally urine is concentrated and its
osmolarity is four times more than that of plasma,
i.e. 1,200 mOsm/L.
Osmolarity of urine depends upon two factors:

1. Water content in the body

2. Antidiuretic hormone (ADH).

 Mechanism of urine formation is the same for

dilute urine and concentrated urine till the fluid reaches
the distal convoluted tubule.
 However, dilution or concentration of urine
depends upon water content of the body.
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 (see Fig.) leading to excretion of large
amount of water. This makes the urine dilute.
FIGURE 53.4: Mechanism for the formation of dilute urine. Numerical indicate osmolarity (mOsm/L)
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.
 MEDULLARY GRADIENT
MEDULLARY HYPEROSMOLARITY
 Cortical interstitial fluid is isotonic to plasma with the
osmolarity of 300 mOsm/L.
 Osmolarity of medullary interstitial fluid near the
cortex is also 300 mOsm/L.
 However, while proceeding from outer part
towards the inner part of medulla, the osmolarity
increases gradually and reaches the maximum at the
inner most part of medulla near renal sinus.
Here, the interstitial fluid is hypertonic with osmolarity of
1,200 mOsm/L (Fig.53.1).
FIGURE 53.1: Countercurrent multiplier.
Numerical indicate osmolarity (mOsm/L)

 This type of gradual increase

in the osmolarity of the
medullary interstitial fluid is
called the medullary gradient.
 It plays an important role in
the concentration of urine
DEVELOPMENT AND MAINTENANCE OF
MEDULLARY GRADIENT
Kidney has some unique mechanism called
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 (tubes) 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
Loop of Henle
•Loop of Henle functions as countercurrent
multiplier.
• It is responsible for development of
hyperosmolarity of medullary interstitial
fluid and medullary gradient.
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.
 Main reason for the hyperosmolarity of
medullary interstitial fluid is the active
reabsorption of sodium chloride and other
solutes from ascending limb of Henle loop
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, the sodium and chlorine ions are
repeatedly recirculated between the
descending limb and ascending limb of
Henle loop through medullary interstitial fluid
leaving a small portion to be excreted in the
urine.
 Apart from this there is regular addition of more
and more new sodium and chlorine ions into
descending limb by constant filtration.
 Thus, the reabsorption of sodium chloride from
ascending limb and addition of new sodium chlorine
ions into the filtrate increase or multiply the osmolarity
of medullary interstitial fluid and medullary gradient.
 Hence, it is called countercurrent multiplier.
Other Factors Responsible for Hyperosmolarity
of Medullary Interstitial Fluid
In addition to countercurrent multiplier action
provided by the loop of Henle, two more factors are
involved in hyperosmolarity of medullary interstitial
fluid.
i. Reabsorption of sodium from collecting duct
Reabsorption of sodium from medullary part of
collecting duct into the medullary interstitium, adds
to the osmolarity of inner medulla.
ii. Recirculation of urea
 Fifty percent of urea filtered in glomeruli is
reabsorbed in proximal convoluted tubule. Almost
an equal amount of urea is secreted in the loop of
Henle.

 So the fluid in distal convoluted tubule has as

much urea as amount filtered.
 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.
 Only a small amount of urea is excreted in urine.
 Urea recirculation accounts for 50% of
hyperosmolarity in inner medulla.
 Diffusion of urea from collecting duct into
medullary interstitium is carried out by urea
transporters, UTA1 and UTA3, which are
activated by ADH.
COUNTERCURRENT EXCHANGER
Vasa Recta
Vasa recta functions as countercurrent
exchanger.
It is responsible for the maintenance of
medullary gradient, which is developed by
countercurrent multiplier (Fig).
Role of Vasa Recta in the Maintenance
of Medullary Gradient
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.
 If the vasa recta would be a straight vessel
without hairpin arrangement, blood would leave
the kidney quickly at renal papillary level.
 In that case, the blood would remove all the
sodium chloride from medullary interstitium and
thereby the hyperosmolarity will be decreased.
 However, this does not happen, since the vasa recta
has a hairpin bend.
Therefore, when blood passes through the ascending
limb of vasa recta, sodium chloride diffuses out of
blood and enters the interstitial fluid of medulla and,
water diffuses into the blood.
Thus, vasa recta retains sodium chloride in the
medullary interstitium and removes water from it.
 So, the hyperosmolarity of medullary interstitium is
maintained.
The blood passing through the ascending limb of vasa
recta may carry very little amount of sodium chloride
from the medulla.
 Recycling of urea also occurs through vasa
recta.
 From medullary interstitium, along with sodium
chloride, urea also enters the descending limb
of vasa recta.
 When blood passes through ascending limb
of vasa recta, urea diffuses back into the
medullary interstitium along with sodium
chloride.
 Thus, sodium chloride and urea are exchanged for
water between the ascending and descending
limbs of vasa recta, hence this system is called
countercurrent exchanger.
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 (Refer Chapter 52 for details).
 A large quantity of water is removed from the fluid
while passing through distal convoluted tubule
and collecting duct.
 So, the urine becomes hypertonic with an
osmolarity of 1,200 mOsm/L (Fig. 53.3).
Role of ADH in the formation of concentrated urine. ADH increases the permeability for water in distal convoluted
tubule and collecting duct. Numerical indicate osmolarity (mOsm/L)
SUMMARY OF URINE CONCENTRATION
When the glomerular filtrate passes through renal
tubule, its osmolarity is altered in different segments
as described below (Fig. 53.4).
1. BOWMAN CAPSULE
 Glomerular filtrate collected at the Bowman capsule
is isotonic to plasma.
 This is because it contains all the substances of
plasma except proteins.
 Osmolarity of the filtrate at Bowman capsule is 300
mOsm/L.
2. PROXIMAL CONVOLUTED TUBULE
When the filtrate flows through proximal convoluted
tubule, there is active reabsorption of sodium and
chloride followed by obligatory reabsorption of
water.
So, the osmolarity of fluid remains the same as in the
case of Bowman capsule, i.e. 300 mOsm/L.
Thus, in proximal convoluted tubules, the fluid is isotonic
to plasma.
3. THICK DESCENDING SEGMENT
 When the fluid passes from proximal convoluted tubule into
the thick descending segment, water is reabsorbed
from tubule into outer medullary interstitium by means
of osmosis.
 It is due to the increased osmolarity in the medullary
interstitium, i.e. outside the thick descending tubule.
 The osmolarity of the fluid inside this segment is between
450 and 600 mOsm/L.
 That means the fluid is slightly hypertonic to plasma.
4. THIN DESCENDING SEGMENT
OF HENLE LOOP
 As the thin descending segment of Henle loop
passes through the inner medullary interstitium
(which is increasingly hypertonic) more water is
reabsorbed.
 This segment is highly permeable to water and
so the osmolarity of tubular fluid becomes equal to
that of the surrounding medullary interstitium.
 In the short loops of cortical nephrons, the
osmolarityof fluid at the hairpin bend of loop becomes
600 mOsm/L.
 And, in the long loops of juxtamedullary nephrons, at
the hairpin bend, the osmolarity is 1,200 mOsm/L.
 Thus in this segment the fluid is hypertonic to
plasma.
5. THIN ASCENDING SEGMENT
OF HENLE LOOP
 When the thin ascending segment of the loop
ascends upwards through the medullary region,
osmolarity decreases gradually.
 Due to concentration gradient, sodium chloride
diffuses out of tubular fluid and osmolarity decreases
to 400 mOsm/L.
 The fluid in this segment is slightly hypertonic to
plasma.
6. THICK ASCENDING SEGMENT
 This segment is impermeable to water.
 But there is active reabsorption of sodium and
chloride from this.
 Reabsorption of sodium decreases the osmolarity
of tubular fluid to a greater extent.
 The osmolarity is between 150 and 200 mOsm/L.
 The fluid inside becomes hypotonic to plasma.
7. DISTAL CONVOLUTED TUBULE AND
COLLECTING DUCT
 In the presence of ADH, distal convoluted tubule and
collecting duct become permeable to water resulting in
water reabsorption and final concentration of urine.
 It is found that in the collecting duct, Principal (P) cells are
responsible for ADH induced water reabsorption.
 Reabsorption of large quantity of water increases the
osmolarity to 1,200 mOsm/L.
 The urine becomes hypertonic to plasma.