Chapter 26
The
Urinary System
The Urinary System
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Renal Anatomy
§ The kidneys are located between the peritoneum and
the posterior wall of the abdomen (in the
retroperitoneal space).
l
They are partially protected by the eleventh and
twelfth pairs of ribs.
l
Because of the position of the liver, the right
kidney is slightly lower than the left.
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Transverse
plane
ANTERIOR
Large intestine
Stomach
Pancreas
Liver
Renal artery
and vein
View
Layers
Inferior vena cava
Peritoneum
Abdominal
aorta
RENAL
HILUM
Body of
L2
RENAL FASCIA
LEFT KIDNEY
ADIPOSE CAPSULE
RENAL CAPSULE
Spleen
Rib
RIGHT KIDNEY
POSTERIOR
(a) Inferior view of transverse section of abdomen (L2)
Quadratus
lumborum
muscle
Location & layers
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Renal Anatomy
§ A frontal section through the kidney reveals two distinct
regions of internal anatomy, the cortex and medulla.
l
The main function of the cortex
is filtration to form urine.
l
The main function of
the medulla is to
collect and
excrete urine.
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PATH OF URINE DRAINAGE:
Nephron
Collecting duct
Renal
hilum
Minor calyx
Renal cortex
Renal medulla
Renal artery
Renal vein
Major calyx
Renal pelvis
Renal column
Renal pyramid
in renal medulla
Renal papilla
Ureter
Renal capsule
Urinary bladder
(a) Anterior view of dissection of right kidney
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Renal Anatomy
§ The renal pyramids within the medulla contain the kidney’s
tubules. The renal papilla is the
location where the
pyramids empty urine
into cuplike structures
called minor calyces.
2-3 minor calyces empty into a
major calyx
§ From the major calyces, urine drains into
§ the renal pelvis and then out through
the ureter
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Renal Blood Flow
§ The renal artery and renal vein pass into the substance of
the kidney at the hilum.
◦ The renal arteries are
very large branches
of the aorta, and up
to a third of total
cardiac output can pass
through them to be filtered by the kidneys.
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Renal
Blood
Flow
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The Nephron
§ Nephrons are the
structural and
functional units that
form urine
1 million in each
kidney- consist of:
l
Renal corpuscle
associated with a
l
Renal tubule
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The Nephron: Renal Corpuscle
§ The Renal Corpuscle consists of two structures:
l
The glomerular capillaries
l
The Bowman’s capsule– a double-walled epithelial cup
that surrounds the glomerular capillaries.
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§ Each nephron receives one afferent arteriole, which
divides into a tangled, ball-shaped capillary network
called the glomerulus.
l
The glomerular capillaries then reunite to form an
efferent arteriole that carries blood out of the
glomerulus.
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§ Bowman’s capsule consists of visceral and parietal layers.
l
The visceral layer is made of epithelial cells called
podocytes.
l
The parietal layer of the glomerular capsule is a simple
squamous epithelium and forms the outer wall of the
capsule.
l
Fluid filtered from the glomerular capillaries enters
Bowman’s space, (the space between the two layers of the
glomerular capsule)
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Renal corpuscle
(external view)
Parietal layer of glomerular
(Bowman’s) capsule
Afferent arteriole
Mesangial cell
Juxtaglomerular cell
Capsular space
Macula densa
Ascending limb
of loop of Henle
Proximal
convoluted
tubule
Mesangial cell
Efferent arteriole
Podocyte of visceral layer of
glomerular (Bowman’s) capsule
Endothelium of
glomerulus
Pedicel
(a) Renal corpuscle (internal view)
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Glomerular capsule:
Glomerulus
Parietal layer
Podocytes of visceral
layer of glomerular
capsule
Visceral layer
Afferent arteriole
Juxtaglomerular cell
Capsular
space
Ascending limb of loop
of Henle
Macula densa cell
Simple squamous
epithelial cells
Efferent arteriole
Proximal convoluted
tubule
LM 1380x
(b) Renal corpuscle
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The Nephron: Tubule
l
Filtered fluid passes into
the renal tubule, which
has three main sections:
◦1. the proximal convoluted
tubule (PCT)
◦2.the loop of Henle; consists of:
◦the descending limb
◦the ascending limb
◦3.the distal convoluted
tubule (DCT)
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Microvilli
Lining epithelium
Mitochondrion
Apical surface
Proximal convoluted tubule (PCT)
Loop of Henle: descending limb and
thin ascending limb
Loop of Henle: thick ascending limb
Most of distal convoluted tubule
(DCT)
Last part of DCT and all of
collecting duct (CD)
Intercalated
cell
Principal
cell
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The Nephron
§ The distal convoluted tubules of several nephrons empty
into a single collecting duct.
l
Collecting ducts
unite and converge
into large papillary ducts
which drain into the
minor calyces.
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The Nephron
§ Nephrons can be sorted into two populations:
cortical nephrons ( 85%) with short loops of Henle
their blood supply is from peritubular capillaries that arise from
efferent arterioles.
juxtamedullary nephrons ( 15%):
§ nephrons with long loops of Henle enable the kidneys to
create a concentration gradient in the renal medulla and to
excrete concentrated urine.
Their loops of Henle receive their blood supply from the vasa
recta
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The Cortical Nephron
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Juxtamedullary Nephron
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Juxtaglomerular Apparatus (JGA)
§ JGA is located where the distal tubule lies near the
afferent arteriole
§ JGA consists of:
§ 1.Juxtaglomerular (JG) cells)- in the wall of afferent
arterioles:
l
l
l
Are enlarged, smooth muscle cells
Have secretory granules containing renin
Sensitive to blood pressure changes
§ 2.Macula densa
l
l
l
Tall, distal tubule cells
Lie adjacent to JG cells
Sensitive to NaCl concentration in filtrate
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Juxtaglomerular Apparatus (JGA)
§ The JGA helps regulate blood pressure within the
kidneys.
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Kidney functions
§ Removes toxins, nitrogenous metabolic wastes ( urea, uric
acid, creatinine)
§ Regulates blood volume & blood pressure (produces
Renin)
§ Maintains electrolyte balance
§ Maintains acid base balance
§ Role in erythropoiesis (produces EPO)
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Mechanisms of Urine Formation
§ Urine formation involves
three major processes:
l
l
l
1.Glomerular filtration
2.Tubular reabsorption
3.Secretion
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Glomerular Filtration: Filtration
Membrane
§ Composed of three
layers
l
Fenestrated
endothelium of the
glomerular
capillaries- blocks
formed elements
l
Basement membrane
between the two
layers- blocks large
proteins
l
Podocytes slit
membranes
l
(visceral layer of the
glomerular capsule)blocks intermediate
sized proteins
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Glomerular Filtration
§ Glomerular filtration is the formation of a protein-free
filtrate (ultrafiltrate) of plasma across the glomerular
membrane.
l
Only a portion of the blood plasma delivered to the
kidney via the renal artery is filtered.
l
Plasma which escapes filtration, along with its protein
and cellular elements, exits the renal corpuscle via the
efferent arterioles
l
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Glomerular Filtration
A passive process, by which fluids and solutes are pushed through the
filtration membrane
§ The kidneys produce 180L of filtrate/day
§ The glomerulus is more efficient filter than other capillary beds
because:
l
Its filtration membrane has higher surface area & is more
permeable
l
Glomerular blood pressure is higher- higher net filtration
pressure
§ Blood cells & plasma proteins not filtered (occasional small proteins
may leak out)
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Glomerular Filtration
§ Filtration is controlled by Starling forces.
l
Blood hydrostatic pressure (55mmHg) is the main force that
“pushes” water and solutes through the filtration membrane -
(this is the blood pressure in glomerular capillaries)
l
Capsular hydrostatic pressure (15 mmHg) is exerted against the
filtration membrane by fluid in the capsular space (opposes
filtration).
l
Colloidal osmotic pressure (30 mmHg) is the pressure of plasma
proteins “pulling” on water (opposes filtration).
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Net Filtration Pressure
Net Filtration pressure = Blood Hydrostatic Pressure – Blood
Osmotic Pressure – Capsular Hydrostatic Pressure
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Net Filtration pressure = 55-30-15 = 10 mmHg
Glomerular Filtration Rate (GFR)
The total volume of filtrate formed per minute
by the kidneys- 120-125ml/min
GFR mainly determined by:
•Net filtration pressure- any change in the
3 pressures influences NFP & therefore
GFR
•Changes in GFR normally result from
changes in blood hydrostatic pressure
(glomerular blood pressure)
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Regulation of GFR
§ Regulation of the GFR is critical to maintaining homeostasis
and is regulated by local and systemic mechanisms:
l
Renal autoregulation occurs when the kidneys themselves
regulate GFR.
l
Neural regulation occurs when the sympathetic nerve
supply regulates renal blood flow and GFR.
l
Hormonal regulation involves angiotensin II and atrial
natriuretic peptide (ANP).
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Renal Autoregulation of GFR
§ Under normal conditions, renal autoregulation maintains a
constant GFR despite fluctuations in BP
§ Two local mechanisms in the kidney that control GFR (Renal
autoregulation)
◦ Myogenic mechanism
◦ Tubuloglomerular feedback
§ Myogenic – VC of afferent arteriole in response to increase in
BP, & VD in response to fall in BP, therefore maintaining GFR
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Renal Autoregulation of GFR
§ Tubuloglomerular feedback – macula densa cells of JGA
respond to NaCl concentration in the filtrate
§ As GFR increases- less time for Na reabsorption- high
NaCl concentration in filtrate
§ macula densa cells release VCs--- VC of afferent arteriole
----leading to fall in GFR
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Tubuloglomerular
feedback
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Regulation of GFR
§ Neural regulation of GFR is possible because the renal
blood vessels are supplied by sympathetic fibers that
release norepinephrine causing vasoconstriction.
§ Decreases GFR
l
Sympathetic input to
the kidneys is most
important with extreme
drops of B.P. (as occurs
with hemorrhage).
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Regulation of GFR
§ Two hormones contribute to regulation of GFR
l
Angiotensin II is a potent vasoconstrictor of both
afferent and efferent arterioles (reduces GFR).
l
Atrial natriuretic peptide (ANP).
l
A sudden large increase in BP stretches the cardiac atria
and releases ANP causes the
afferent arterioles to dilate &
glomerulus to relax,
increasing the surface
area for filtration. (increases GFR).
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Tubular Reabsorption
§ Tubular reabsorption is the process of returning important
substances (“good stuff”) from the filtrate back into the
renal blood vessels... and ultimately back into the body.
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Tubular Reabsorption
§ The “good stuff” is glucose, electrolytes, vitamins, water,
amino acids, and any small proteins that might have
escaped from the blood into the filtrate.
§ Ninety nine percent of the glomerular filtrate is reabsorbed
(most of it before the end of the PCT)!
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Tubular Reabsorption
Amount in 180 L
of filtrate (/day)
Amount
returned to
blood/d
(Reabsorbed)
Amount in
Urine (/day)
3L
180 L
178-179 L
1-2 L
Protein (active)
200 g
2g
1.9 g
0.1 g
Glucose (active)
3g
162 g
162 g
0g
Urea (passive)
1g
54 g
24 g
30 g
(about 1/2)
(about 1/2)
0.03 g
1.6 g
0g
1.6 g
(all filtered)
(none reabsorbed)
Total
Amount in
Plasma
Water (passive)
Creatinine
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Tubular Reabsorption
§ Reabsorption into the interstitium has two routes:
l
Paracellular reabsorption is a passive process that occurs
between adjacent tubule
Cells
Transcellular reabsorption
is movement through an
individual cell.( must pass
through apical & basal
membranes)
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Tubular Reabsorption; transport
mechanisms
Reabsorption of fluids, ions, and other substances occurs
by active and passive means including:
Diffusion
Osmosis (water)- from high water to low water ( from low
osmolarity to high osmolarity)
Primary active transport- energy derived from ATP is used to
“pump” a substance across a membrane
Secondary active transport- energy stored in an ion’s
electrochemical gradient drives another substance across the
membrane.
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Transport mechanisms
Reabsorption of water can be obligatory or facultative
Obligatory reabsorption of water occurs when it is obliged to
follow solutes as they are reabsorbed Occurs in PCT( always
permeable to water)
Facultative reabsorption (upto 10% of total water
reabsorption) is variable water
reabsorption, adapted to specific needs.
It is regulated by of ADH on
the principal cells of DCT & collecting
ducts (without ADH they are not
permeable to water)
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Reabsorption in the Proximal Convoluted
Tubule
The majority of solute and water reabsorption from filtered
fluid occurs in the PCT which reabsorbs, 65% Na+, water,
K+, 80-90% of bicarbonate ions
Most absorptive processes involve Na+reabsorption
PCT Na+ reabsorption promotes reabsorption of; water,
K+; Cl- and other ions
Normally, 100% of filtered glucose, amino acids, and other
nutrients are reabsorbed in the PCT by Na+ symporters. (
co-transported with sodium)
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Reabsorption of
glucose due to
active pumping of
Na+
Na+ symporters help reabsorb
materials from the tubular filtrate
Glucose is completely reabsorbed
in the first half of the PCT
Sodium levels are kept low inside
the cells due to Na+/K+ pump----
Reabsorption of Nutrients
sodium moves in from tubular
fluid down the gradient, cotransporting glucose
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Transport Maximum
A transport maximum (Tm) is maximum reabsorption rate,
i.e. rate when all the carriers are saturated- in mg/min
When the carriers are saturated, excess of that substance is
excreted in urine
In DM, due to hyperglycemia-when all carriers are
saturated glucose starts appearing in urine--glucosuria
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Reabsorption of water, other ions, due to
active pumping of Na+
Water follows sodium by osmosis
through aquaporins in PCT
(obligatory water reabsorption)
Passive diffusion of anions Cl-, K+,
Ca++, to maintain
electroneutrality
Urea, fat-soluble substances- move
down their gradient as filtrate
becomes more concentrated due to
PCT
water movement
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PCT-Reabsorption of Bicarbonate, Na+ & H+ secretion
Na+/H+ antiporters reabsorb Na+
and secrete H+
PCT cells produce the H+ &
release bicarbonate ion to the
peritubular capillaries
important buffering system
For every H+ secreted into the
tubular fluid, one filtered
bicarbonate eventually returns to
the blood
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Reabsorption in the Loop of Henle
Water reabsorption: about 15% of the filtered water is
reabsorbed in the descending limb, little or no water is
reabsorbed in the ascending limb
Solute reabsorption occurs in ascending limb
Na+-K+-Cl- symporters reclaim Na+, Cl-, and K+ ions from
the tubular lumen fluid in the thick part of ascending limb
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Reabsorption in the Loop of Henle
Fluid in
tubule
lumen
Vasa recta
Thick
ascending limb
cell
Na+
ATP
Main result is reabsorption
of Na+ and Cl-.
Na+
ADP
Na+
2Cl–
K+
Cations:
Na+
K+
Ca2+
Mg2+
Na+
Na+
2Cl–
2Cl–
2Cl–
K+
Cations
Key:
Na+–K+–2Cl– symporter
Apical
membrane
(impermeable to
water)
Interstitial fluid is
more negative than
fluid in tubule lumen
Leakage channels
Sodium–potassium pump
Diffusion
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Reabsorption and Secretion in the late DCT
& Collecting Ducts
DCT & Collecting ducts- most reabsorption depends on
needs of the body & regulated by hormones:
Aldosterone for Na+
Aldosterone for water (by ADH release )
ADH for water- otherwise impermeable to water
PTH for Ca2+
ANP-Acts on CDs to inhibit Na+ reabsorption
reduces blood Na+ & BP
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Tubular Secretion
Substances move from peritubular capillaries into the filtrate
Main site of secretion is PCT (except for K+ )
It is by active transport.
Tubular secretion is important for:
Disposing of drugs, metabolites- not filtered because bound to
plasma proteins
Eliminating undesirable substances such as urea, uric acid,
creatinine
Ridding the body of excess K+ ions ( by aldosterone in DCTs
& CDs)
+
Controlling blood pH- (secreting H+), NH
ions
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Copyright
Wiley & Sons, Inc. All rights reserved.
Hormonal Regulation of Tubular
Reabsorption & Secretion
Antidiuretic Hormone (ADH) :
affects 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, these are almost impermeable
to water.
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Hormonal Regulation
Renin- Angiotensin and aldosterone system:
When blood volume and blood pressure decreases, JGA
secretes renin.
Promotes aldosterone production which causes principal cells:
◦ to reabsorb more Na+ followed by water ( through ADH
release)
◦ To secrete K+ ions
◦ Decreases urine output & increases blood volume by
increasing water reabsorption
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Hormonal Regulation
Atrial natriuretic peptide
◦ inhibits reabsorption of Na+ and water
◦ increase excretion of Na+ which increases urine
output and decreases blood volume
◦ Parathyroid hormone:
◦ In response to low blood calcium, PTH stimulates
cells in DCT to reabsorb more calcium.
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Production of Dilute and
Concentrated Urine
The rate at which water is lost from the body depends
mainly on ADH
When ADH level is very low, the kidneys produce dilute
urine and excrete excess water
When ADH level is high, the kidneys secrete concentrated
urine and conserve water; a large volume of water is
reabsorbed from the tubular fluid and the solute
concentration of urine is high.
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Production of Dilute and
Concentrated Urine
Production of concentrated urine involves:
1.The presence of ADH which makes the distal part of
nephron permeable to water
2.The countercurrent mechanism which creates high
osmotic gradient for maximal water reabsorption
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The Countercurrent Mechanism
Creates a high osmotic gradient
from the cortex to the medulla
It includes:
Countercurrent multiplication
Involves long loops of Henle of
juxta medullary nephrons
Countercurrent exchange.
Involves blood flow in the Vasa
recta around the loops of Henle
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The Countercurrent Mechanism
Countercurrent multiplication is the process by which a
progressively increasing osmotic gradient is formed in the
interstitial fluid of renal medulla as a result of
countercurrent flow (opposing fluid flow in adjacent
limbs of long loops of Henle of juxtamedulary nephrons)
Countercurrent exchange is the process by which solutes
and water are passively exchanged between the blood of
the vasa recta and interstitial fluid of the renal medulla
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The Countercurrent Mechanism
The gradient from cortex to
medulla is 300-1200mOsm
The solute concentration in the
PCTs is 300 mOsm
Water only leaves descending limbfiltrate osmolarity increases to 1200
Salt only reabsorbed in ascending
limb- osmolarity of filtrate decreases
to 100 at top of loop
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The Countercurrent Mechanism
The descending loop of Henle:
Is impermeable to solutes & permeable to water
Water passes out by osmosis and tubular fluid increases in
osmolarity reaching an equilibrium with the Interstitial fluid
of medulla
The ascending loop of Henle:
Is permeable to solutes & impermeable to water
Na Cl is pumped out - tubular fluid becomes progressively
more dilute - by the time it reaches the DCT osmolarity is
100 mOsm/L
The vasa recta maintain the high osmolarity in the
medulla
Blood flows down the descending limb then up the
ascending limb of Vasa recta- exchanges a lot of fluid and
solute- but does not carry away any excess salt
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The vasa recta help maintain the high osmolarity
in the medulla; exchanges a lot of fluid and solutebut do not carry away any excess salt
H2O
H2O
H2O
H2O
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The Countercurrent Mechanism
Contributes to high osmolarity of medulla
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Formation of Dilute Urine
Filtrate is dilute at the end of the ascending loop of
Henle
Dilute urine is created by allowing this filtrate to
continue into the renal pelvis
This will happen as long as (ADH) is not being
secreted
Collecting ducts remain impermeable to water; no
further water reabsorption occurs
Urine osmolarity can be as low as 65 mOsm (one-sixth
that of plasma)
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Formation of Concentrated Urine
ADH-acts on CDs to cause further reabsorption of
water
In the presence of ADH, most of the water in filtrate
can be reabsorbed
High medullary osmolarity provides an osmotic
gradient necessary for water reabsorption to occur in
the presence of high levels of ADH
Small volume of concentrated urine formed (can be
1200mOsm)
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Vasa
recta
Loop of
Henle
Juxtamedullary nephron
and its blood supply
together
Glomerular (Bowman’s) capsule
H2O
Na+CI–
Blood flow
Glomerulus
Afferent
arteriole
Distal convoluted tubule
Presense of Na+-K+-2CI–
symporters
Interstitial
fluid in
renal cortex
200
HO
H2O 2
Efferent
arteriole
300
300
Collecting
duct
300
300
100
H2O
320
Na+CI–
400
Interstitial fluid
in renal medulla
380
200
H2O
400
3 Principal cells in
Osmotic
gradient
H2O
collecting duct
reabsorb more
water when ADH
is present
Na+CI–
400
500
H2O
600
H2O
580
600
320
300
H2O
Proximal
convoluted
tubule
Flow of tubular fluid
400
H2O
Na+CI–
600
1 Symporters in thick
ascending limb cause
buildup of Na+ and Cl–
800
700
780
600
Urea
H2O
980
1000
H2O
800
800
H2O
800
900
4 Urea recycling
1000
causes buildup
of urea in the
renal medulla
Na+CI–
H2O
1000
1100
H2O
1200
2 Countercurrent flow
through loop of Henle
establishes an osmotic
gradient
1200
Loop of Henle
1200
Papillary
duct
1200
Concentrated urine
(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron
1200
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©of
John
Wiley
& Sons,
All
rights
(b)
Recycling
salts
and urea
in theInc.
vasa
recta
reserved.
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Renal function tests
Two blood tests are commonly done clinically to assess
the adequacy of renal function.
Blood urea nitrogen (BUN)
Serum Creatinine levels
Renal Clearance: the volume of plasma that is cleared
of a particular substance in a given time-used to
determine GFR
Creatinine clearance test: for approximate measure of
GFR
Because creatinine is freely filtered and not reabsorbed at
all (some more added by secretion)
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Urinary bladder
The ureters transport urine from
the renal pelvis of the kidneys to
the bladder.
The urinary bladder is a hollow,
distensible muscular organ with
a capacity that averages 700800mL.
The urethra is a small tube
leading from the internal
urethral orifice in the bladder
floor to the exterior.
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Copyright © John Wiley & Sons, Inc. All rights reserved.
Copyright © John Wiley & Sons, Inc. All rights reserved.
Micturition Reflex
When volume of urine in bladder is between 200 to 400 mLstretch receptors activated --impulses relayed along sensory
axons to stimulate micturition reflex center in sacral spinal
cord
Parasympathetic stimulation causes detrusor muscle to
contract and internal urethral sphincter to open
• Conscious control of urination
• If desired, voluntary signal from the cortex sent
–
Signals go through pudendal nerve--cause relaxation of external
urethral sphincter
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