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Biswash Sapkota (M.Pharm) (B.Pharm)
Lecturer, MBAHS
Unit IV
URINARY SYSTEM
Introduction
 It is one of the excretory systems of the body. It
consist of following structures
 2 kidneys, which secrets urine
 2 ureter which convey urine from kidney to the
urinary bladder
 1 urinary bladder where urine collects and is
temporarily stored
 1 urethra through which urine is discharged from
urinary bladder to exterior .
Functions of Urinary system
 Removes the metabolic waste
 Regulates the blood volume and blood pressure
 Regulates the plasma concentration of sodium,
potassium, chloride etc
 Helps to stabilize blood pH
 Conserves valuable nutrients
 Regulation of Acid-Base Balance.
 contribute to acid-base regulation, along with lungs and body
fluid buffers,
 by excreting acids
 by regulating the body fluid buffer stores.
 kidneys are the only means of eliminating certain types of
acids, such as sulfuric acid and phosphoric acid, generated
by the metabolism of proteins.
 Regulation of Arterial Pressure.
 long-term regulation
 by excreting variable amounts of sodium and water.
5
 short-term regulation
 by secreting vasoactive substances- renin, that lead to the formation of
vasoactive products (e.g. angiotensin II)
 Regulation of Erythrocyte Production.
 secrete erythropoietin, which stimulates the production of
RBC,
 account for almost all the erythropoietin secreted into the
circulation.
 In people with severe kidney disease or people with kidney removal,
and have been placed on hemodialysis, severe anemia develops as a
result of decreased erythropoietin production.
6
 Regulation of 1,25–Dihydroxyvitamin D3 Production.
 produce the active form of vitamin D- 1,25-
dihydroxyvitamin D3 (calcitriol).
 Calcitriol plays an important role in calcium and phosphate
regulation.
 Glucose Synthesis
 Kidneys synthesize glucose from amino acids and other
precursors during prolonged fasting, by the process
known as gluconeogenesis.
 The kidneys’ capacity to add glucose to the blood during
prolonged periods of fasting rivals that of the liver.
7
Functions of kidney
 Regulation of:
 body fluid osmolarity and
volume
 electrolyte balance
 acid-base balance
 blood pressure
 Secretion of :
 erythropoietin
 1,25-dihydroxy vitamin D3
(vitamin D activation)
 Renin
 prostaglandin
 Excretion of :
 metabolic products
 foreign substances (pesticides,
chemicals etc.)
 excess substance (water, etc)
8
Kidneys
 Lies on the posterior abdominal wall, one on each
side of vertebral column, behind the peritoneum
and below the diaphragm.
 They extend from 12th thoracic to the 3rd lumbar
vertebra
 The right is usually slightly lower then the left,
because of the considerable space occupied by
the liver.
 They are bean shaped organ about 11 cm long,
6cm wide, 3cm thick and weigh 150g
 They are embedded in held in position by a mass
of fat.
 A sheat of fibroelastic renal fascia encloses the
kidney and renal fat.
Gross structure of kidney
 When longitudinal section of kidney is viewed
with naked eyes following reasons and structure
are observed.
 A Fibrous capsule, surrounding the kidney
 The Cortex a reddish brown layer of the tissue
immediately below the capsule and outside of
pyramids
 The Medulla, the innermost layer consisting of
pale conical shaped striations, the renal pyramids
 The Hilum is the concave medial border of kidney
where the renal blood and lymph vessels, the
ureter and nerves enter
 The renal pelvis is funnel shaped structure which
acts as a receptacle for urine formed by kidney .
It has the number of branches called calyces,
which surround the pyramids. Urine formed in the
kidney passes through the papilla at the apex of
pyramid into minor calyx , then to major calyx
before passing through the pelvis into ureter.
 Pelvis has smooth muscle and lined with
transitional epithelium so this acts as the
pacemaker cells in the walls of the calyces
propels urine through the pelvis and the ureters to
the bladder .
Microscopic structure of Kidney
 The kidney is composed of about 1-2 million of
functional units, the nephrons and a smaller
number of collecting ducts
 The collecting ducts transport the urine through
the pyramids to the calyces and renal pelvis
 The collecting ducts are supported by small
amount of connective tissue, containing blood
vessels, nerves and lymph nodes .
The nephron
 The nephron consists of a tubule closed at one
end, the other end opening into a collecting
tubule.
 The closed end is indented to form cup shaped
glomerular capsule (Bowmans Capsule) which
almost completely encloses a network of tiny
arterial capillaries the glomerulus
 After glomerulus, the remainder of nephron is
about 3cm long and is described as :
 The proximal convoluted tubule
 The medullary loop (loop of Henle)
 The distal convoluted tubule, leading into a
collecting duct .
 The kidney receives 20% of cardiac output
 After entering the kidney at hilum the renal artery
divides into smaller arteries and arterioles .
 In cortex an arteriole, the afferent arteriole enters
each glomerular capsule and then subdivides into
cluster of tiny arterial capillaries forming
glomerulus.
 The blood vessels leading away from glomerulus
is efferent arteriole.
 The afferent arteriole has a larger diameter than
efferent arteriole which increase the pressure
inside the glomerulus and drives filtration across
glomerular capillary walls.
 The efferent arteriole divides into a second
peritubular capillary network which wraps around
the reminder of tubule allowing between the fluid
in tubule and blood stream.
 The blood vessels of the kidney are supplied by
both sympathetic and parasympathetic nerves.
The presence of both the branches of ANS
controls renal blood vessel diameter and renal
blood flow independently and autoregulation
NOTE (IMP)
 Glomerulus has fenestrated capillaries in
endothelium cells.
 Glomerulus basement membrane has middle
layer of lamina dense and the upper and lower
region has heparin sulfate (lamina rera interna
and externa). Basement membrane is negatively
charged.
 The lower region is attached with podocytes.
 Bowmans capsule has viscearal and parietal
layer
 Visceral region has podocytes (leg like structure).
The space between podocytes is called filtration
Formation of urine
 The kidneys form urine which passes through the
ureters to the bladder for storage prior to
excretion.
 The composition of urine reflects the activities of
nephrons in maintenance of homeostasis.
 Waste products of protein metabolism are
excreted, electrolyte balance is maintained and
pH is maintained by the excretion of hydrogen
ions. There are three processes involved in
formation of urine:
1. Simple filtration
2. Selective reabsorption
1. Simple filtration
 Filtration take place through the semipermeable
walls of glomerulus and glomerulus capsule.
 Water and large number of small molecules pass
through, although some are reabsorbed later.
 Blood cells, plasma proteins, and other large
molecules are unable to filter through and remain
in the capillaries.
 The filtrate in glomerulus is very similar in
composition to plasma with the important
exception of plasma proteins.
 The filtration occurs due to difference in blood
pressure in glomerulus and pressure of filtrate in
 The volume of filtrate formed by both kidneys
each minute is called the glomerular filtration rate
(GFR).
 In a healthy adult the GFR is about 125ml/min ie
180litres of dilute filtrate are formed each day by
two kidneys.
 In one minute around 1200ml of blood enters the
glomerulus, out of this only 625ml undergoes
filtration process while 575ml goes to efferent
arterioles.
 Out of 625ml only 20% get filtered which is 125ml
of the blood.
 GFR depends upon Net Filtration Pressure (NFP)
and filtration coefficient (KF).
 NFP = Pressure forcing out- pressure pulling in
 Pressure forcing out depends upon
1. Glomerular hydrostatic pressure (GHP) :
55mm/Hg
2. capsular osmotic pressure (COP) : 0mm/Hg
• Pressure pulling in depends upon
1. Colloid osmotic pressure (COP): 30mm/Hg
2. Capsular hydrostatic pressure (CHP): 15mm/Hg
• NFP is 10mm/Hg
 The filtration coefficient depends upon the
surface area of the glomerulus and the
permeability of glomerulus .
 Principal regulators of GFR:
1) Renal autoregulation of GFR
 The kidneys are able to maintain a relatively constant internal
blood pressure and GFR despite changes in systemic arterial
pressure.
 There is negative feedback from the juxtaglomerular apparatus
adjusting blood pressure and blood volume.
A. Angiotensin I & II
 Activated by renin released from JG cells and further by
ACE in the lungs
 5 important functions
 direct systemic vasoconstriction
  Na+ reabsorption in PCT (H2O follows
passively)
  thirst generated at the hypothalamus
  aldosterone secretion causes Na+
reabsorption
  ADH secretion – stimulates water
reabsorption in distal tubules and collecting
duct
 Net Effect  increased blood pressure and blood volume
2) Hormonal regulation of GFR
A. Atrial Natriuretic Peptide (ANP)
 Secreted by cells in atria of heart in response to stretch
  GFR, promotes excretion of H2O, Na+, but retention of
K+
 Suppresses output of ADH, aldosterone, and renin
 Net Effect  decreased blood pressure and blood
volume
B. Aldosterone
 Secreted by cells in adrenal cortex in response to
angiotensin I & II (and ACTH
(Adrenocorticotropic hormone))
  GFR, promotes retention of H2O, Na+, but excretion of
K+
 Antagonist to atrial natriuretic peptide
 Net Effect  increased blood pressure and blood
volume
3) Neural regulation
 Kidney’s blood vessels supplied by vasoconstrictor fibers from
Sympathetic Division of the ANS which release norepinephrine.
 Strong sympathetic stimulation causes JG cells to secrete renin
and the adrenal medulla to secrete Epinephrine
2. Selective reabsorption
 Selective reabsorption is the process by which
the composition and volume of the glomerular
filtrate are altered during its passage through
convoluted tubules, medullary loop and collecting
tubule.
 The general purpose of this process is to
reabsorb into the blood those filtrate constituents
needed by the body to maintain fluid and
electrolyte balance and pH of blood.
 Active transport is carried out at carrier sites in
epithelial membrane using chemical energy to
transport substances against the concentration
gradients.
 Some constituents of glomerular filtrate (glucose,
amino acid) do not normally appear in urine
because they are completely reabsorbed unless
they are present in blood in excessive quantities.
 The kidney has its own renal threshold ie its
maximum capacity for reabsorption. For eg
glucose level is 2.5 to 5.3 mmol/l, if the level rise
above the transport of about 9 mmol/l glucose
appears in the urine because all the carrier sites
are occupied and the mechanism for active
transfer out of tubules is overloaded.
 The substances reabsorbed by active transport
include amino acids and sodium, calcium,
potassium, phosphate and chloride.
 Parathyroid hormone from parathyroid gland and
calcitonin from thyroid gland together regulates
renal absorption of calcium and phosphate.
 Antidiuretic hormone from posterior lobe of
pituitary gland increases the permeability of DCT
and CD increasing water reabsorption .
 Aldosterone secreted by adrenal cortex increase
the reabsorption of sodium and excretion of
potassium .
 Nitrogenous waste product are only slightly
reabsorbed to slight extent .
More on Reabsorption
 PCT is site of most
electrolyte reabsorption
 ~100% of the filtered
glucose and other sugars,
AA's, lactic acid, and other
useful metabolites are
reabsorbed
Reabsorption in PCT
 The Na+/ K+-ATPase on
basolateral side is fundamental
 Requires ATP for energy
 Concentration of Na+ inside the
tubular cells is low
 Interior of the cell negatively
charged
 Na+ concentration is greater in
the filtrate than in the tubular
cells
 Na+ symporters in the apical
membrane power secondary active
transport systems
 Why secondary? They rely on
the Na+/ K+ ATPase pump.
Reabsorption of Na+ in PCT
Reabsorption of Glucose in PCT
 Glucose is actively transported
from the filtrate in tubule
lumen into tubular cells as Na+
moves down its concentration
gradient
Reabsorption of H2O in PCT
 H2O follows Na+ passively by osmosis from the filtrate through the
tubular cells into the peritubular capillaries
 The movement of water
back to the bloodstream
concentrates the
remaining solutes in the
filtrate.
[H2O]
[solutes]
 The new concentration gradients increase the diffusion of some of the
other remaining solutes in the filtrate from lumen to the blood stream.
Reabsorption of Nutrients in PCT
Renal Thresholds
 The Renal Threshold is the plasma concentration at
which a substance begins to spill into the urine because
its Tm (transport maximum) has been surpassed.
 If the plasma filtrate concentration is too high, all of the
substance cannot be reabsorbed.
 For example, glucose spills into the urine in untreated
diabetics.
 Tm for glucose = 375 mg/min
 If blood glucose > 400 mg/100 mL, large quantities of glucose
will appear in the urine
Reabsorption in the PCT
 By the end of the PCT the following reabsorption has occurred:
 100% of filtered nutrients (sugars, albumin, amino acids,
vitamins, etc.)
 80-90% of filtered HCO3
-
 65% of Na+ ions and water
 50% of Cl- and K+ ions
 Cells in the thin descending limb are
only permeable to water.
 H2O reabsorption is not coupled to
reabsorption of filtered solutes in this
area as it had been in the PCT.
Reabsorption in Loop of Henle
 Cells in the thicker ascending
Loop feature Na+/K+/2Cl-
symporters
 Reabsorb 1 Na+, 1 K+, 2 Cl-
 Depend on low cytoplasmic
Na+ concentration to function
 No H2O is reabsorbed from the
thick ascending Loop
 Loop reabsorbs 30% of K+, 20%
of Na+, 35% of Cl-, and 15% of
H2O
Reabsorption in Loop of Henle
Reabsorption in DCT and Collecting Ducts
 Filtrate reaching the DCT has already had ~80% of the solutes and
H2O reabsorbed
 Fluid now has the characteristics of “urine”
 DCT is the site of final adjustment of urine composition
 Less work to do, so no need for microvilli (brush border) to
increase surface area for transporters
 Na+/K+/Cl- symporter is a major DCT transporter
 DCT reabsorbs another 10% of filtrate volume
Reabsorption in DCT and Collecting Duct
 Principal cells are present in the distal DCTs and collecting ducts
 Three hormones act on principal cells to modify ion and fluid
reabsorption :
[1] Anti-Diuretic Hormone (ADH) (from neurohypophysis)
  H2O reabsorption by increasing permeability to H2O in the DCT and
collecting duct
Reabsorption in DCT and Collecting Duct
[2] Aldosterone (from
adrenal cortex)
  Na+ reabsorption; Cl-
and H2O follow
passively;  K+ reabsorption
  number & activity of basolateral
Na+/K+ ATPases
  number of luminal Na+ & K+
channels
Germann & Stanfield, 2005
Reabsorption in DCT and Collecting Duct
[3] Atrial Natriuretic Peptide (ANP) is the antagonist to
Aldosterone
  K+ reabsorption;
  Na+ reabsorption;
 Cl- and H2O follow passively; adding “salt” and water to urine
3. Secretion
 Filtration occurs as the blood flows through
glomerulus
 Substances not required and foreign materials eg
drugs including penicillin and aspirin are not
cleared by filtration . They remain in blood for
short time and cleared by secretion into
convoluted tubules and excreted from body in
urine.
 Tubular secretion of H+ is important in
maintaining homeostasis of blood pH.
More on secretion
Secretion of K+ ions
 Principal cells in collecting ducts secrete variable amount of K+ in
exchange for reabsorbed Na+
 Most animal diets contain excess K+ but scarce Na+
 Na+/K+ ATPases are the “ion pumps”
 Controlled by Aldosterone and Atrial Natriuretic Peptide
 Aldosterone is released from the adrenal cortex in response to
angiotensin I & II
 With excess K+, aldosterone secretion predominates: Na+
(and Cl-) are reabsorbed while considerable K+ is secreted
 Atrial Natriuretic Peptide is released from the atrial walls in the
heart in response to stretching when blood volume or blood
pressure increase
 With excess Na+, atrial natriuretic peptide secretion
predominates: K+ is reabsorbed while considerable Na+ (and Cl-) are
secreted
Secretion of H+ ions
 Cells of the renal tubule can elevate blood pH in three
ways:
 Secrete H+ ions into the filtrate
 Reabsorb filtered HCO3
-
 Produce more HCO3
-
 The key is the chemical relationship between H+ ions and
HCO3
- ions:
H2O + CO2  H2CO3  H+ + HCO3
-
 This reaction occurs spontaneously and it is also
catalyzed by the enzyme carbonic anhydrase.
Secretion of H+ ions
 In PCT
[1] Na+/H+ antiporter puts H+ ions into the filtrate
 H+ ions combine with HCO3
- in lumen to form CO2 and H2O
H+
1
1
Secretion of H+ ions
[2] CO2 from the filtrate or plasma enters the tubular cell where it
combines with H2O to form H2CO3
2
2
CO2
Secretion of H+ ions
[3] H+ is pumped into the lumen
[4] HCO3
- follows pumped Na+ back to the bloodstream
HCO3
-
H+
HCO3
-
3
4
Secretion of H+ ions
 Collecting ducts also secrete H+ ions
 H+ pumps are a primary active
transport process powered by
ATPs
 new bicarbonate ions are
reabsorbed by the basolateral
HCO3
-/Cl- antiporter
 adding new HCO3
- buffer to the
bloodstream
H+
HCO3
-
Secretion of NH3 and NH4
+
 Liver converts ammonia to urea, a much less toxic nitrogenous waste
 PCT cells can also deaminate certain amino acids and secrete
additional NH4
+ with a Na+/NH4
+ antiporter when blood pH becomes
acidic
Composition of urine
 Urine is clear and amber
in color due to presence
of urobilin, a bile pigment
altered in intestine .
 pH is around 6
 1000 to 1500 ml per day.
Water balance and urine output
 Water is taken in body through alimentary tract and a
small amount is formed by metabolic processes.
 Water is excreted as the constituent of the faeces,
through skin as a sweat and as a constituent of urine.
 The amount lost in expired air and in faeces is fairly
constant and amount of sweat produced is associated
with maintenance of normal body temperature.
 The balance between fluid intake and output is there
fore controlled by kidneys .
 The minimum urinary output ie the smallest volume
required to excrete body waste is about 500ml per
day.
 The amount produced in excess is controlled by
antidiuretic hormone (ADH) released by posterior
lobe of pituitary gland.
 The osmoreceptors stimulate the posterior lobe of
pituitary gland which detects the change in
osmotic pressure of blood and causes the release
of ADH.
 The ADH output is increased and as a result
water reabsorption by cells in DCT and CD is
increased reducing the osmotic pressure.
Electrolyte balance
 Sodium is most common cation in extracellular fluid
and potassium is most common intracellular cation.
 Sodium is a normal constituent of urine and the
amount excreted is regulated by hormone
aldosterone, secreted by adrenal cortex .
 The afferent arteriole in nephron are stimulated to
produce enzyme renin by low blood volume or low
arterial pressure.
 Renin converts the plasma protein angiotensinogen
produced by liver to angiotensinogen 1.
 Angiotensin converting enzyme (ACE) formed in
lungs, PCT and other tissues converts Angiotensin 1
to angiotensin 2 which is potent vasoconstrictor and
increased blood pressure.
 Renin and raised potassium level stimulate the
adrenal gland to secret aldosterone.
 Water is reabsorbed with sodium and together
they increase blood volume and leading to reduce
renin secretion.
 When sodium reabsorption is increased the
potassium excretion is increased indirectly
reducing intracellular potassium .
 When there is excess imbalance in the electrolyte
level of blood the cells of the PCT secret
Hydrogen ion.
Additional notes on acid
base balance
Role of kidneys in acid-base balance
 Kidneys helps in acid-base balance by:
 Reabsorption of bicarbonate ions(HCO3
-)
 Excretion of this much HCO3- in urine will affect the acid-base balance of
body fluids. So, HCO3 must be taken back from the renal tubule by
reabsorption.
 Secretion of hydrogen ions(H+)
 Sodium-hydrogen antiport pump
 ATP-driven proton pump
 Removal of hydrogen ions & acidification of urine.
 Bicarbonate mechanism
 Phosphate mechanism
 Ammonia mechanism
Acid-base balance
 Normally,urine is acidic in nature.
 Metabolic activities in the body produce lot of acids which
threaten to push the body towards acidosis.
 However, kidneys prevent this by excreting hydrogen ions (H+
)
and conserving bicarbonate ions (HCO3
-
).
 Conservation or reabsorption of HCO3
-
is an important process
because of the high quantity of filtered HCO3
-
.
 Excretion of much HCO3
-
through urine will affect the acid-
base balance of body fluids.
 So, HCO3
-
must be taken back from the renal tubule by
reabsorption.
 The reabsorption of filtered HCO3
-
utilizes secretion of H+
in
the renal tubules.
Secretion of Hydrogen ions
 Kidney is only route through which H+
can be eliminated
from body.
 Secretion of H+
into the renal tubules occurs by the
formation of carbonic acid.
 Carbonic anhydrase catalyses the production of carbonic
acid(H2CO3)from CO2 and H2O in renal tubular cell.
 H2CO3 then dissociated to H+
and HCO3
-
.
 PCT, thick segment of ascending loop of Henle and early
distal tubule all secrete H+
into tubular fluid by sodium-
hydrogen counter-transport.
Removal of Hydrogen ions and
Acidification of urine
 The H+
, which enters the renal tubules by filtration and
secretion, is removed by three mechanisms.
1. Bicarbonate mechanism
2. Phosphate mechanism
3. Ammonia mechanism
Bicarbonate mechanism
 All the filtered HCO3
-
into the renal tubules is reabsorbed.
 About 80% reabsorbed in PCT,15% in Henle’s loop and 5% in DCT
and collecting duct.
 The reabsorption of HCO3
-
utilizes the H+
present in renal
tubules,which combines with filtered HCO3
-
forming carbonic acid.
 H2CO3 is cleaved by carbonic anhydrase into CO2 and H2O.
 As CO2 concentration gradient built,it diffuses into tubular
cells,where CO2 combines with H2O to form H2CO3,which
dissociates into HCO3
-
and H+
.
 H+
is secreted into lumen in exchange of Na+
and HCO3
-
is
reabsorbed into plasma.
 Reabsorption of HCO3
-
is an important factor in maintaining pH of
the body fluids.
Phosphate mechanism
 The H+
, which is secreted into renal tubules, reacts with
phosphate buffer system.
 It combines with sodium hydrogen phosphate to form
sodium dihydrogen phosphate which is excreted in urine.
 The H+
, which is added to urine in the form of sodium
dihydrogen, makes the urine acidic.
 This happens mostly in distal tubule and collecting duct.
Ammonia mechanism
 This is the most important mechanism by which kidneys
excrete H+
and make the urine acidic.
 In the tubular epithelial cells,ammonia is formed when the
amino acid glutamine is converted into glutamic acid in
presence of enzyme glutaminase.
 NH3 secreted into tubular lumen in exchange for sodium
ion combines with H+
to form ammonium.
 The tubular cell membrane is not permeable to ammonium.
 So,it remains in the lumen and combines with sodium
acetoacetate to form ammonium acetoacetate,which is
excreted through urine.
 This process takes place mostly in the PCT.
Ureters
 The ureters are the tubes that convey urine from
the kidneys to the urinary bladder.
 They are about 25-30cm long with a diameter of
about 3mm
 The ureter is continuous with funnel shaped renal
pelvis and passes obliquely through posterior wall
of bladder.
 Because of this arrangement, when urine
accumulates and pressure in bladder rises, the
ureters are compressed and the openings
occluded.
 This prevent the reflux of urine into the ureters as
bladder fills and during micturition, when pressure
increases as muscular bladder wall contracts.
Structure:
The ureters has 3 layers
 outer covering of fibrous tissue
The middle layer has smooth muscle fibre
The inner layer mucosa, lined with
transitional epithelium
Functions:
To propel the urine from kidneys into
bladder by peristaltic contraction of smooth
muscle layer.
Urinary Bladder
 It is the reservoir for urine.
 It lies in pelvic cavity and its size and position
vary depending on the amount of urine it
contains. When distended, the bladder rises into
the abdominal cavity .
 It is roughly pear shaped, but become more oval
as it fills with urine.
 The bladder open into the urethra at its lowest
point the neck.
 The peritoneum covers the superior surface.
.
 The bladder has three layers:
1. Outer layer of connective tissues containing
blood and lymphatic vessels covered by upper
surface by peritoneum.
2. The middle layer of interlacing smooth muscle
fibers and elastic tissue and this is called
detrusor muscle and empties the bladder when
it contracts.
3. The inner layer is mucosa lined with transitional
epithelium. When the bladder is empty the inner
lining is arranged in folds or rugae and these
gradually disappear as bladder fills. The
bladder is distensible but when it contains 300
to 400ml , the awareness of need to pass urine
is felt. The total capacity is rarely more than
 The three orifices in the bladder wall form a
triangle or trigone. The upper two orifices on the
posterior wall are the opening of the ureters. The
lower orifice is the opening into the urethra. The
internal urethral sphincter a thickening of urethral
smooth muscle layer in upper part of urethra,
controls outflow of urine from the bladder.
Urethra
 The urethra is a canal extending from the neck of
the bladder to the exterior, at the external urethral
orifice, it is longer in the male than in female.
 The male urethra is associated with the urinary
and reproductive functions.
 Female urethra is approximately 4cm long and
6mm in diameter. It runs downwards and forwards
and opens at the external urethral orifice just in
front of vagina. The external urethral orifice is
guarded by external urethral sphincter which is
under voluntary control.
 The wall of female urethra has two main layers:
an outer muscle layer and an inner lining of
mucosa, which is continuous with that of bladder
.
 The muscle layer has two parts, an inner layer of
smooth muscle that is under autonomic nerve
control and outer layer of striated muscle
surrounding it. The striated muscle forms the
external urethral sphincter and is under voluntary
control.
Micturition
 When 300 to 400ml of urine have accumulated in
bladder, afferent autonomic nerve fibres in
bladder wall sensitive to stretch are stimulated.
In infant this initiates a spinal reflex and
micturition occurs.
 Urine passed in the response to parasympathetic
stimulation of the bladder, causing contraction of
the detrusor muscle and relaxation of internal
urethral sphincter and muscle of pelvic floor can
inhibit micturition until it is convenient to empty
the bladder.
 In adult, urine is passed when detrusor muscle
contracts and there is reflex relaxation of the
internal sphincter and voluntary relaxation of the
external sphincter. It can be assisted by
increasing the pressure within the pelvic cavity,
achieved by lowering the diaphragm and
contracting abdominal muscles. Over distension
of bladder is extremely painful and when this
stage is reached there is tendency for involuntary
relaxation of external sphincter to occur allowing
a small amount of urine to escape, provided there
is no mechanical obstruction.
 Involuntary loss of urine is known as
Filling of bladder
Stimulation of stretch receptors
Afferent impulses pass through pelvic nerve
Sacral segments of spinal cord
Efferent impulses through pelvic nerve
Contraction of detrusor muscle and relaxation of internal sphincter
Flow of urine into urethra and stimulation of stretch receptors
Afferent impulses through pelvic nerve
Inhibition of pudendal nerve
Relaxation of external sphincter
Voiding of urine
Mechanism of urine concentration and
dilution
 Presence of ADH-Urine
osmolality as high as
1400mosm/L of water
 Kidney operates intrinsic
mechanism to concentrate and
dilute urine.
 Absence of ADH- Urine
osmolality fall to as low as
30mosm/L of water
 Diabetes insipidus, ADH
deficiency urine out put is more
than 20 ltrs per day
 With adequate H2O, the
posterior pituitary releases little
ADH
 The glomerular filtrate
equilibrates with medullary
conditions while passing down
through the loop
 Meanwhile, tubular reabsorption
of solutes continues
Producing a Dilute Urine
 As the filtrate enters the
ascending limb of the loop, and
the DCT, and then the collecting
ducts, no water can diffuse out
of the filtrate
 Meanwhile, continuing tubular
reabsorption of solutes in the
DCT & CDs creates a dilute =
hypo-osmotic (hypotonic) urine
Producing a Dilute Urine
Producing a Concentrated Urine
 With inadequate H2O, the
posterior pituitary releases more
ADH
 The glomerular filtrate
equilibrates with medullary
conditions while passing down
through the loop
 Meanwhile, tubular reabsorption
of solutes continues
Producing a Concentrated Urine
 The ascending limb of the loop
remains impermeable to H2O
 However, as the filtrate enters
the DCT, and then the collecting
ducts, ADH causes the tubular
cells to become permeable to
H2O
 Water can diffuse in or out of
the filtrate
Producing a Concentrated Urine
 The filtrate becomes hypo-
osmotic (hypotonic) in the DCT
while H2O and solutes are
returned to the bloodstream
 However, the filtrate
equilibrates with medullary
conditions while passing down
through the collecting ducts
Producing a Concentrated Urine
 Even though the filtrate is still
losing urea and NaCl to active
transport, the other solutes
cannot leave
 The filtrate becomes hyper-
osmotic (hypertonic) as it
equilibrates with the osmotic
gradient surrounding the
collecting ducts
 Water is drawn into the vasa
recta and back to the
bloodstream
Producing a Concentrated Urine
 The effect of ADH is to create a concentrated =
 hyper-osmotic
(hypertonic) urine
Unit 4 urinary system

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Unit 4 urinary system

  • 1. Biswash Sapkota (M.Pharm) (B.Pharm) Lecturer, MBAHS Unit IV URINARY SYSTEM
  • 2. Introduction  It is one of the excretory systems of the body. It consist of following structures  2 kidneys, which secrets urine  2 ureter which convey urine from kidney to the urinary bladder  1 urinary bladder where urine collects and is temporarily stored  1 urethra through which urine is discharged from urinary bladder to exterior .
  • 3.
  • 4. Functions of Urinary system  Removes the metabolic waste  Regulates the blood volume and blood pressure  Regulates the plasma concentration of sodium, potassium, chloride etc  Helps to stabilize blood pH  Conserves valuable nutrients
  • 5.  Regulation of Acid-Base Balance.  contribute to acid-base regulation, along with lungs and body fluid buffers,  by excreting acids  by regulating the body fluid buffer stores.  kidneys are the only means of eliminating certain types of acids, such as sulfuric acid and phosphoric acid, generated by the metabolism of proteins.  Regulation of Arterial Pressure.  long-term regulation  by excreting variable amounts of sodium and water. 5
  • 6.  short-term regulation  by secreting vasoactive substances- renin, that lead to the formation of vasoactive products (e.g. angiotensin II)  Regulation of Erythrocyte Production.  secrete erythropoietin, which stimulates the production of RBC,  account for almost all the erythropoietin secreted into the circulation.  In people with severe kidney disease or people with kidney removal, and have been placed on hemodialysis, severe anemia develops as a result of decreased erythropoietin production. 6
  • 7.  Regulation of 1,25–Dihydroxyvitamin D3 Production.  produce the active form of vitamin D- 1,25- dihydroxyvitamin D3 (calcitriol).  Calcitriol plays an important role in calcium and phosphate regulation.  Glucose Synthesis  Kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, by the process known as gluconeogenesis.  The kidneys’ capacity to add glucose to the blood during prolonged periods of fasting rivals that of the liver. 7
  • 8. Functions of kidney  Regulation of:  body fluid osmolarity and volume  electrolyte balance  acid-base balance  blood pressure  Secretion of :  erythropoietin  1,25-dihydroxy vitamin D3 (vitamin D activation)  Renin  prostaglandin  Excretion of :  metabolic products  foreign substances (pesticides, chemicals etc.)  excess substance (water, etc) 8
  • 9. Kidneys  Lies on the posterior abdominal wall, one on each side of vertebral column, behind the peritoneum and below the diaphragm.  They extend from 12th thoracic to the 3rd lumbar vertebra  The right is usually slightly lower then the left, because of the considerable space occupied by the liver.  They are bean shaped organ about 11 cm long, 6cm wide, 3cm thick and weigh 150g  They are embedded in held in position by a mass of fat.  A sheat of fibroelastic renal fascia encloses the kidney and renal fat.
  • 10. Gross structure of kidney  When longitudinal section of kidney is viewed with naked eyes following reasons and structure are observed.  A Fibrous capsule, surrounding the kidney  The Cortex a reddish brown layer of the tissue immediately below the capsule and outside of pyramids  The Medulla, the innermost layer consisting of pale conical shaped striations, the renal pyramids  The Hilum is the concave medial border of kidney where the renal blood and lymph vessels, the ureter and nerves enter
  • 11.
  • 12.  The renal pelvis is funnel shaped structure which acts as a receptacle for urine formed by kidney . It has the number of branches called calyces, which surround the pyramids. Urine formed in the kidney passes through the papilla at the apex of pyramid into minor calyx , then to major calyx before passing through the pelvis into ureter.  Pelvis has smooth muscle and lined with transitional epithelium so this acts as the pacemaker cells in the walls of the calyces propels urine through the pelvis and the ureters to the bladder .
  • 13. Microscopic structure of Kidney  The kidney is composed of about 1-2 million of functional units, the nephrons and a smaller number of collecting ducts  The collecting ducts transport the urine through the pyramids to the calyces and renal pelvis  The collecting ducts are supported by small amount of connective tissue, containing blood vessels, nerves and lymph nodes .
  • 14.
  • 15. The nephron  The nephron consists of a tubule closed at one end, the other end opening into a collecting tubule.  The closed end is indented to form cup shaped glomerular capsule (Bowmans Capsule) which almost completely encloses a network of tiny arterial capillaries the glomerulus  After glomerulus, the remainder of nephron is about 3cm long and is described as :  The proximal convoluted tubule  The medullary loop (loop of Henle)  The distal convoluted tubule, leading into a collecting duct .
  • 16.  The kidney receives 20% of cardiac output  After entering the kidney at hilum the renal artery divides into smaller arteries and arterioles .  In cortex an arteriole, the afferent arteriole enters each glomerular capsule and then subdivides into cluster of tiny arterial capillaries forming glomerulus.  The blood vessels leading away from glomerulus is efferent arteriole.  The afferent arteriole has a larger diameter than efferent arteriole which increase the pressure inside the glomerulus and drives filtration across glomerular capillary walls.
  • 17.  The efferent arteriole divides into a second peritubular capillary network which wraps around the reminder of tubule allowing between the fluid in tubule and blood stream.  The blood vessels of the kidney are supplied by both sympathetic and parasympathetic nerves. The presence of both the branches of ANS controls renal blood vessel diameter and renal blood flow independently and autoregulation
  • 18.
  • 19. NOTE (IMP)  Glomerulus has fenestrated capillaries in endothelium cells.  Glomerulus basement membrane has middle layer of lamina dense and the upper and lower region has heparin sulfate (lamina rera interna and externa). Basement membrane is negatively charged.  The lower region is attached with podocytes.  Bowmans capsule has viscearal and parietal layer  Visceral region has podocytes (leg like structure). The space between podocytes is called filtration
  • 20. Formation of urine  The kidneys form urine which passes through the ureters to the bladder for storage prior to excretion.  The composition of urine reflects the activities of nephrons in maintenance of homeostasis.  Waste products of protein metabolism are excreted, electrolyte balance is maintained and pH is maintained by the excretion of hydrogen ions. There are three processes involved in formation of urine: 1. Simple filtration 2. Selective reabsorption
  • 21.
  • 22. 1. Simple filtration  Filtration take place through the semipermeable walls of glomerulus and glomerulus capsule.  Water and large number of small molecules pass through, although some are reabsorbed later.  Blood cells, plasma proteins, and other large molecules are unable to filter through and remain in the capillaries.  The filtrate in glomerulus is very similar in composition to plasma with the important exception of plasma proteins.  The filtration occurs due to difference in blood pressure in glomerulus and pressure of filtrate in
  • 23.  The volume of filtrate formed by both kidneys each minute is called the glomerular filtration rate (GFR).  In a healthy adult the GFR is about 125ml/min ie 180litres of dilute filtrate are formed each day by two kidneys.  In one minute around 1200ml of blood enters the glomerulus, out of this only 625ml undergoes filtration process while 575ml goes to efferent arterioles.  Out of 625ml only 20% get filtered which is 125ml of the blood.
  • 24.  GFR depends upon Net Filtration Pressure (NFP) and filtration coefficient (KF).  NFP = Pressure forcing out- pressure pulling in  Pressure forcing out depends upon 1. Glomerular hydrostatic pressure (GHP) : 55mm/Hg 2. capsular osmotic pressure (COP) : 0mm/Hg • Pressure pulling in depends upon 1. Colloid osmotic pressure (COP): 30mm/Hg 2. Capsular hydrostatic pressure (CHP): 15mm/Hg • NFP is 10mm/Hg
  • 25.  The filtration coefficient depends upon the surface area of the glomerulus and the permeability of glomerulus .
  • 26.  Principal regulators of GFR: 1) Renal autoregulation of GFR  The kidneys are able to maintain a relatively constant internal blood pressure and GFR despite changes in systemic arterial pressure.  There is negative feedback from the juxtaglomerular apparatus adjusting blood pressure and blood volume. A. Angiotensin I & II  Activated by renin released from JG cells and further by ACE in the lungs  5 important functions  direct systemic vasoconstriction   Na+ reabsorption in PCT (H2O follows passively)
  • 27.   thirst generated at the hypothalamus   aldosterone secretion causes Na+ reabsorption   ADH secretion – stimulates water reabsorption in distal tubules and collecting duct  Net Effect  increased blood pressure and blood volume
  • 28. 2) Hormonal regulation of GFR A. Atrial Natriuretic Peptide (ANP)  Secreted by cells in atria of heart in response to stretch   GFR, promotes excretion of H2O, Na+, but retention of K+  Suppresses output of ADH, aldosterone, and renin  Net Effect  decreased blood pressure and blood volume B. Aldosterone  Secreted by cells in adrenal cortex in response to angiotensin I & II (and ACTH (Adrenocorticotropic hormone))   GFR, promotes retention of H2O, Na+, but excretion of K+  Antagonist to atrial natriuretic peptide  Net Effect  increased blood pressure and blood volume
  • 29. 3) Neural regulation  Kidney’s blood vessels supplied by vasoconstrictor fibers from Sympathetic Division of the ANS which release norepinephrine.  Strong sympathetic stimulation causes JG cells to secrete renin and the adrenal medulla to secrete Epinephrine
  • 30. 2. Selective reabsorption  Selective reabsorption is the process by which the composition and volume of the glomerular filtrate are altered during its passage through convoluted tubules, medullary loop and collecting tubule.  The general purpose of this process is to reabsorb into the blood those filtrate constituents needed by the body to maintain fluid and electrolyte balance and pH of blood.  Active transport is carried out at carrier sites in epithelial membrane using chemical energy to transport substances against the concentration gradients.
  • 31.  Some constituents of glomerular filtrate (glucose, amino acid) do not normally appear in urine because they are completely reabsorbed unless they are present in blood in excessive quantities.  The kidney has its own renal threshold ie its maximum capacity for reabsorption. For eg glucose level is 2.5 to 5.3 mmol/l, if the level rise above the transport of about 9 mmol/l glucose appears in the urine because all the carrier sites are occupied and the mechanism for active transfer out of tubules is overloaded.  The substances reabsorbed by active transport include amino acids and sodium, calcium, potassium, phosphate and chloride.
  • 32.
  • 33.  Parathyroid hormone from parathyroid gland and calcitonin from thyroid gland together regulates renal absorption of calcium and phosphate.  Antidiuretic hormone from posterior lobe of pituitary gland increases the permeability of DCT and CD increasing water reabsorption .  Aldosterone secreted by adrenal cortex increase the reabsorption of sodium and excretion of potassium .  Nitrogenous waste product are only slightly reabsorbed to slight extent .
  • 35.  PCT is site of most electrolyte reabsorption  ~100% of the filtered glucose and other sugars, AA's, lactic acid, and other useful metabolites are reabsorbed Reabsorption in PCT
  • 36.  The Na+/ K+-ATPase on basolateral side is fundamental  Requires ATP for energy  Concentration of Na+ inside the tubular cells is low  Interior of the cell negatively charged  Na+ concentration is greater in the filtrate than in the tubular cells  Na+ symporters in the apical membrane power secondary active transport systems  Why secondary? They rely on the Na+/ K+ ATPase pump. Reabsorption of Na+ in PCT
  • 37. Reabsorption of Glucose in PCT  Glucose is actively transported from the filtrate in tubule lumen into tubular cells as Na+ moves down its concentration gradient
  • 38. Reabsorption of H2O in PCT  H2O follows Na+ passively by osmosis from the filtrate through the tubular cells into the peritubular capillaries  The movement of water back to the bloodstream concentrates the remaining solutes in the filtrate. [H2O] [solutes]
  • 39.  The new concentration gradients increase the diffusion of some of the other remaining solutes in the filtrate from lumen to the blood stream. Reabsorption of Nutrients in PCT
  • 40. Renal Thresholds  The Renal Threshold is the plasma concentration at which a substance begins to spill into the urine because its Tm (transport maximum) has been surpassed.  If the plasma filtrate concentration is too high, all of the substance cannot be reabsorbed.  For example, glucose spills into the urine in untreated diabetics.  Tm for glucose = 375 mg/min  If blood glucose > 400 mg/100 mL, large quantities of glucose will appear in the urine
  • 41. Reabsorption in the PCT  By the end of the PCT the following reabsorption has occurred:  100% of filtered nutrients (sugars, albumin, amino acids, vitamins, etc.)  80-90% of filtered HCO3 -  65% of Na+ ions and water  50% of Cl- and K+ ions
  • 42.  Cells in the thin descending limb are only permeable to water.  H2O reabsorption is not coupled to reabsorption of filtered solutes in this area as it had been in the PCT. Reabsorption in Loop of Henle
  • 43.  Cells in the thicker ascending Loop feature Na+/K+/2Cl- symporters  Reabsorb 1 Na+, 1 K+, 2 Cl-  Depend on low cytoplasmic Na+ concentration to function  No H2O is reabsorbed from the thick ascending Loop  Loop reabsorbs 30% of K+, 20% of Na+, 35% of Cl-, and 15% of H2O Reabsorption in Loop of Henle
  • 44. Reabsorption in DCT and Collecting Ducts  Filtrate reaching the DCT has already had ~80% of the solutes and H2O reabsorbed  Fluid now has the characteristics of “urine”  DCT is the site of final adjustment of urine composition  Less work to do, so no need for microvilli (brush border) to increase surface area for transporters  Na+/K+/Cl- symporter is a major DCT transporter  DCT reabsorbs another 10% of filtrate volume
  • 45. Reabsorption in DCT and Collecting Duct  Principal cells are present in the distal DCTs and collecting ducts  Three hormones act on principal cells to modify ion and fluid reabsorption : [1] Anti-Diuretic Hormone (ADH) (from neurohypophysis)   H2O reabsorption by increasing permeability to H2O in the DCT and collecting duct
  • 46. Reabsorption in DCT and Collecting Duct [2] Aldosterone (from adrenal cortex)   Na+ reabsorption; Cl- and H2O follow passively;  K+ reabsorption   number & activity of basolateral Na+/K+ ATPases   number of luminal Na+ & K+ channels Germann & Stanfield, 2005
  • 47. Reabsorption in DCT and Collecting Duct [3] Atrial Natriuretic Peptide (ANP) is the antagonist to Aldosterone   K+ reabsorption;   Na+ reabsorption;  Cl- and H2O follow passively; adding “salt” and water to urine
  • 48. 3. Secretion  Filtration occurs as the blood flows through glomerulus  Substances not required and foreign materials eg drugs including penicillin and aspirin are not cleared by filtration . They remain in blood for short time and cleared by secretion into convoluted tubules and excreted from body in urine.  Tubular secretion of H+ is important in maintaining homeostasis of blood pH.
  • 50. Secretion of K+ ions  Principal cells in collecting ducts secrete variable amount of K+ in exchange for reabsorbed Na+  Most animal diets contain excess K+ but scarce Na+  Na+/K+ ATPases are the “ion pumps”  Controlled by Aldosterone and Atrial Natriuretic Peptide  Aldosterone is released from the adrenal cortex in response to angiotensin I & II  With excess K+, aldosterone secretion predominates: Na+ (and Cl-) are reabsorbed while considerable K+ is secreted  Atrial Natriuretic Peptide is released from the atrial walls in the heart in response to stretching when blood volume or blood pressure increase  With excess Na+, atrial natriuretic peptide secretion predominates: K+ is reabsorbed while considerable Na+ (and Cl-) are secreted
  • 51. Secretion of H+ ions  Cells of the renal tubule can elevate blood pH in three ways:  Secrete H+ ions into the filtrate  Reabsorb filtered HCO3 -  Produce more HCO3 -  The key is the chemical relationship between H+ ions and HCO3 - ions: H2O + CO2  H2CO3  H+ + HCO3 -  This reaction occurs spontaneously and it is also catalyzed by the enzyme carbonic anhydrase.
  • 52. Secretion of H+ ions  In PCT [1] Na+/H+ antiporter puts H+ ions into the filtrate  H+ ions combine with HCO3 - in lumen to form CO2 and H2O H+ 1 1
  • 53. Secretion of H+ ions [2] CO2 from the filtrate or plasma enters the tubular cell where it combines with H2O to form H2CO3 2 2 CO2
  • 54. Secretion of H+ ions [3] H+ is pumped into the lumen [4] HCO3 - follows pumped Na+ back to the bloodstream HCO3 - H+ HCO3 - 3 4
  • 55. Secretion of H+ ions  Collecting ducts also secrete H+ ions  H+ pumps are a primary active transport process powered by ATPs  new bicarbonate ions are reabsorbed by the basolateral HCO3 -/Cl- antiporter  adding new HCO3 - buffer to the bloodstream H+ HCO3 -
  • 56. Secretion of NH3 and NH4 +  Liver converts ammonia to urea, a much less toxic nitrogenous waste  PCT cells can also deaminate certain amino acids and secrete additional NH4 + with a Na+/NH4 + antiporter when blood pH becomes acidic
  • 57. Composition of urine  Urine is clear and amber in color due to presence of urobilin, a bile pigment altered in intestine .  pH is around 6  1000 to 1500 ml per day.
  • 58. Water balance and urine output  Water is taken in body through alimentary tract and a small amount is formed by metabolic processes.  Water is excreted as the constituent of the faeces, through skin as a sweat and as a constituent of urine.  The amount lost in expired air and in faeces is fairly constant and amount of sweat produced is associated with maintenance of normal body temperature.  The balance between fluid intake and output is there fore controlled by kidneys .  The minimum urinary output ie the smallest volume required to excrete body waste is about 500ml per day.  The amount produced in excess is controlled by antidiuretic hormone (ADH) released by posterior lobe of pituitary gland.
  • 59.  The osmoreceptors stimulate the posterior lobe of pituitary gland which detects the change in osmotic pressure of blood and causes the release of ADH.  The ADH output is increased and as a result water reabsorption by cells in DCT and CD is increased reducing the osmotic pressure.
  • 60.
  • 61. Electrolyte balance  Sodium is most common cation in extracellular fluid and potassium is most common intracellular cation.  Sodium is a normal constituent of urine and the amount excreted is regulated by hormone aldosterone, secreted by adrenal cortex .  The afferent arteriole in nephron are stimulated to produce enzyme renin by low blood volume or low arterial pressure.  Renin converts the plasma protein angiotensinogen produced by liver to angiotensinogen 1.  Angiotensin converting enzyme (ACE) formed in lungs, PCT and other tissues converts Angiotensin 1 to angiotensin 2 which is potent vasoconstrictor and increased blood pressure.
  • 62.
  • 63.  Renin and raised potassium level stimulate the adrenal gland to secret aldosterone.  Water is reabsorbed with sodium and together they increase blood volume and leading to reduce renin secretion.  When sodium reabsorption is increased the potassium excretion is increased indirectly reducing intracellular potassium .
  • 64.  When there is excess imbalance in the electrolyte level of blood the cells of the PCT secret Hydrogen ion.
  • 65. Additional notes on acid base balance
  • 66. Role of kidneys in acid-base balance  Kidneys helps in acid-base balance by:  Reabsorption of bicarbonate ions(HCO3 -)  Excretion of this much HCO3- in urine will affect the acid-base balance of body fluids. So, HCO3 must be taken back from the renal tubule by reabsorption.  Secretion of hydrogen ions(H+)  Sodium-hydrogen antiport pump  ATP-driven proton pump  Removal of hydrogen ions & acidification of urine.  Bicarbonate mechanism  Phosphate mechanism  Ammonia mechanism
  • 67. Acid-base balance  Normally,urine is acidic in nature.  Metabolic activities in the body produce lot of acids which threaten to push the body towards acidosis.  However, kidneys prevent this by excreting hydrogen ions (H+ ) and conserving bicarbonate ions (HCO3 - ).  Conservation or reabsorption of HCO3 - is an important process because of the high quantity of filtered HCO3 - .  Excretion of much HCO3 - through urine will affect the acid- base balance of body fluids.  So, HCO3 - must be taken back from the renal tubule by reabsorption.  The reabsorption of filtered HCO3 - utilizes secretion of H+ in the renal tubules.
  • 68. Secretion of Hydrogen ions  Kidney is only route through which H+ can be eliminated from body.  Secretion of H+ into the renal tubules occurs by the formation of carbonic acid.  Carbonic anhydrase catalyses the production of carbonic acid(H2CO3)from CO2 and H2O in renal tubular cell.  H2CO3 then dissociated to H+ and HCO3 - .  PCT, thick segment of ascending loop of Henle and early distal tubule all secrete H+ into tubular fluid by sodium- hydrogen counter-transport.
  • 69. Removal of Hydrogen ions and Acidification of urine  The H+ , which enters the renal tubules by filtration and secretion, is removed by three mechanisms. 1. Bicarbonate mechanism 2. Phosphate mechanism 3. Ammonia mechanism
  • 70. Bicarbonate mechanism  All the filtered HCO3 - into the renal tubules is reabsorbed.  About 80% reabsorbed in PCT,15% in Henle’s loop and 5% in DCT and collecting duct.  The reabsorption of HCO3 - utilizes the H+ present in renal tubules,which combines with filtered HCO3 - forming carbonic acid.  H2CO3 is cleaved by carbonic anhydrase into CO2 and H2O.  As CO2 concentration gradient built,it diffuses into tubular cells,where CO2 combines with H2O to form H2CO3,which dissociates into HCO3 - and H+ .  H+ is secreted into lumen in exchange of Na+ and HCO3 - is reabsorbed into plasma.  Reabsorption of HCO3 - is an important factor in maintaining pH of the body fluids.
  • 71.
  • 72. Phosphate mechanism  The H+ , which is secreted into renal tubules, reacts with phosphate buffer system.  It combines with sodium hydrogen phosphate to form sodium dihydrogen phosphate which is excreted in urine.  The H+ , which is added to urine in the form of sodium dihydrogen, makes the urine acidic.  This happens mostly in distal tubule and collecting duct.
  • 73.
  • 74. Ammonia mechanism  This is the most important mechanism by which kidneys excrete H+ and make the urine acidic.  In the tubular epithelial cells,ammonia is formed when the amino acid glutamine is converted into glutamic acid in presence of enzyme glutaminase.  NH3 secreted into tubular lumen in exchange for sodium ion combines with H+ to form ammonium.  The tubular cell membrane is not permeable to ammonium.  So,it remains in the lumen and combines with sodium acetoacetate to form ammonium acetoacetate,which is excreted through urine.  This process takes place mostly in the PCT.
  • 75.
  • 76. Ureters  The ureters are the tubes that convey urine from the kidneys to the urinary bladder.  They are about 25-30cm long with a diameter of about 3mm  The ureter is continuous with funnel shaped renal pelvis and passes obliquely through posterior wall of bladder.  Because of this arrangement, when urine accumulates and pressure in bladder rises, the ureters are compressed and the openings occluded.  This prevent the reflux of urine into the ureters as bladder fills and during micturition, when pressure increases as muscular bladder wall contracts.
  • 77. Structure: The ureters has 3 layers  outer covering of fibrous tissue The middle layer has smooth muscle fibre The inner layer mucosa, lined with transitional epithelium Functions: To propel the urine from kidneys into bladder by peristaltic contraction of smooth muscle layer.
  • 78. Urinary Bladder  It is the reservoir for urine.  It lies in pelvic cavity and its size and position vary depending on the amount of urine it contains. When distended, the bladder rises into the abdominal cavity .  It is roughly pear shaped, but become more oval as it fills with urine.  The bladder open into the urethra at its lowest point the neck.  The peritoneum covers the superior surface. .
  • 79.  The bladder has three layers: 1. Outer layer of connective tissues containing blood and lymphatic vessels covered by upper surface by peritoneum. 2. The middle layer of interlacing smooth muscle fibers and elastic tissue and this is called detrusor muscle and empties the bladder when it contracts. 3. The inner layer is mucosa lined with transitional epithelium. When the bladder is empty the inner lining is arranged in folds or rugae and these gradually disappear as bladder fills. The bladder is distensible but when it contains 300 to 400ml , the awareness of need to pass urine is felt. The total capacity is rarely more than
  • 80.
  • 81.  The three orifices in the bladder wall form a triangle or trigone. The upper two orifices on the posterior wall are the opening of the ureters. The lower orifice is the opening into the urethra. The internal urethral sphincter a thickening of urethral smooth muscle layer in upper part of urethra, controls outflow of urine from the bladder.
  • 82. Urethra  The urethra is a canal extending from the neck of the bladder to the exterior, at the external urethral orifice, it is longer in the male than in female.  The male urethra is associated with the urinary and reproductive functions.  Female urethra is approximately 4cm long and 6mm in diameter. It runs downwards and forwards and opens at the external urethral orifice just in front of vagina. The external urethral orifice is guarded by external urethral sphincter which is under voluntary control.
  • 83.  The wall of female urethra has two main layers: an outer muscle layer and an inner lining of mucosa, which is continuous with that of bladder .  The muscle layer has two parts, an inner layer of smooth muscle that is under autonomic nerve control and outer layer of striated muscle surrounding it. The striated muscle forms the external urethral sphincter and is under voluntary control.
  • 84. Micturition  When 300 to 400ml of urine have accumulated in bladder, afferent autonomic nerve fibres in bladder wall sensitive to stretch are stimulated. In infant this initiates a spinal reflex and micturition occurs.  Urine passed in the response to parasympathetic stimulation of the bladder, causing contraction of the detrusor muscle and relaxation of internal urethral sphincter and muscle of pelvic floor can inhibit micturition until it is convenient to empty the bladder.
  • 85.  In adult, urine is passed when detrusor muscle contracts and there is reflex relaxation of the internal sphincter and voluntary relaxation of the external sphincter. It can be assisted by increasing the pressure within the pelvic cavity, achieved by lowering the diaphragm and contracting abdominal muscles. Over distension of bladder is extremely painful and when this stage is reached there is tendency for involuntary relaxation of external sphincter to occur allowing a small amount of urine to escape, provided there is no mechanical obstruction.  Involuntary loss of urine is known as
  • 86. Filling of bladder Stimulation of stretch receptors Afferent impulses pass through pelvic nerve Sacral segments of spinal cord Efferent impulses through pelvic nerve Contraction of detrusor muscle and relaxation of internal sphincter Flow of urine into urethra and stimulation of stretch receptors Afferent impulses through pelvic nerve Inhibition of pudendal nerve Relaxation of external sphincter Voiding of urine
  • 87. Mechanism of urine concentration and dilution  Presence of ADH-Urine osmolality as high as 1400mosm/L of water  Kidney operates intrinsic mechanism to concentrate and dilute urine.  Absence of ADH- Urine osmolality fall to as low as 30mosm/L of water  Diabetes insipidus, ADH deficiency urine out put is more than 20 ltrs per day
  • 88.  With adequate H2O, the posterior pituitary releases little ADH  The glomerular filtrate equilibrates with medullary conditions while passing down through the loop  Meanwhile, tubular reabsorption of solutes continues Producing a Dilute Urine
  • 89.  As the filtrate enters the ascending limb of the loop, and the DCT, and then the collecting ducts, no water can diffuse out of the filtrate  Meanwhile, continuing tubular reabsorption of solutes in the DCT & CDs creates a dilute = hypo-osmotic (hypotonic) urine Producing a Dilute Urine
  • 90. Producing a Concentrated Urine  With inadequate H2O, the posterior pituitary releases more ADH  The glomerular filtrate equilibrates with medullary conditions while passing down through the loop  Meanwhile, tubular reabsorption of solutes continues
  • 91. Producing a Concentrated Urine  The ascending limb of the loop remains impermeable to H2O  However, as the filtrate enters the DCT, and then the collecting ducts, ADH causes the tubular cells to become permeable to H2O  Water can diffuse in or out of the filtrate
  • 92. Producing a Concentrated Urine  The filtrate becomes hypo- osmotic (hypotonic) in the DCT while H2O and solutes are returned to the bloodstream  However, the filtrate equilibrates with medullary conditions while passing down through the collecting ducts
  • 93. Producing a Concentrated Urine  Even though the filtrate is still losing urea and NaCl to active transport, the other solutes cannot leave  The filtrate becomes hyper- osmotic (hypertonic) as it equilibrates with the osmotic gradient surrounding the collecting ducts  Water is drawn into the vasa recta and back to the bloodstream
  • 94. Producing a Concentrated Urine  The effect of ADH is to create a concentrated =  hyper-osmotic (hypertonic) urine