Renal system –L1
Faisal I. Mohammed, MD, PhD
University of Jordan
1
Objectives






List the functions of the renal system
Give an anatomical overview of the urinary
system
Describe the renal system functional unit –
Nephron- and its types
Outline the process of urine formation and define
GFR
Introduce the principle of clearance
Describe GFR regulation
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Overview of kidney functions

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

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Regulation of blood ionic composition
Regulation of blood pH
Regulation of blood volume
Regulation of blood pressure
Maintenance of blood osmolarity
Production of hormones (calcitrol and erythropoitin)
Regulation of blood glucose level
Excretion of wastes from metabolic reactions and foreign
substances (drugs or toxins)
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Organs of the urinary system
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Internal anatomy of the kidneys
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Blood and nerve supply of the kidneys


Blood supply
 Although kidneys constitute less than 0.5% of total body mass, they
receive 20-25% of resting cardiac output
 Left and right renal artery enters kidney
 Branches into segmental, interlobar, arcuate, interlobular arteries
 Each nephron receives one afferent arteriole
 Divides into glomerulus – capillary ball
 Reunite to form efferent arteriole (unique)
 Divide to form peritubular capillaries or some have vasa recta
 Peritubular venule, interlobar vein and renal vein exits kidney
Renal nerves are part of the sympathetic autonomic nervous system
 Most are vasomotor nerves regulating blood flow
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Blood
supply of
the kidneys
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The nephron – functional units of
kidney
2 parts


Renal corpuscle – filters blood plasma
 Glomerulus – capillary network
 Glomerular (Bowman’s) capsule – doublewalled cup surrounding glomerulus
Renal tubule – filtered fluid passes into
 Proximal convoluted tubule
 Descending and ascending loop of Henle
(nephron loop)
 Distal convoluted tubule
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Nephrons




Renal corpuscle and both convoluted tubules in cortex, loop
of Henle extend into medulla
Distal convoluted tubule of several nephrons empty into
single collecting duct
Cortical nephrons – 80-85% of nephrons
 Renal corpuscle in outer portion of cortex and short loops
of Henle extend only into outer region of medulla
Juxtamedullary nephrons – other 25-20%
 Renal corpuscle deep in cortex and long loops of Henle
extend deep into medulla
 Receive blood from peritubular capillaries and vasa recta
 Ascending limb has thick and thin regions
 Enable kidney to secrete very dilute or very concentrated
urine
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Cortical
Nephron
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Juxtamedullary
Nephron
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Histology of nephron and collecting duct

Glomerular capsule
 Visceral layer has podocytes that wrap
projections around single layer of endothelial
cells of glomerular capillaries and form inner
wall of capsule
 Parietal layer forms outer wall of capsule
 Fluid filtered from glomerular capillaries enters
capsular (Bowman’s) space
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Renal corpuscle
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Renal tubule and collecting duct



Proximal convoluted tubule cells have microvilli with
brush border – increases surface area
Juxtaglomerular appraratus helps regulate blood pressure
in kidney
 Macula densa – cells in final part of ascending loop of
Henle
 Juxtaglomerular cells – cells of afferent and efferent
arterioles contain modified smooth muscle fibers
Last part of distal convoluted tubule and collecting duct
 Principal cells – receptors for antidiuretic hormone
(ADH) and aldosterone
 Intercalated cells – role in blood pH homeostasis
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Overview of renal physiology
1.
2.
3.
4.
5.
Glomerular filtration
 Water and most solutes in blood plasma move across the wall of the
glomerular capillaries into glomerular capsule and then renal tubule
Tubular reabsorption
 As filtered fluid moves along tubule and through collecting duct,
about 99% of water and many useful solutes reabsorbed – returned to
blood
Tubular secretion
 As filtered fluid moves along tubule and through collecting duct,
other material secreted into fluid such as wastes, drugs, and excess
ions – removes substances from blood
Solutes in the fluid that drains into the renal pelvis remain in the fluid
and are excreted
Excretion of any solute = glomerular filtration + secretion - reabsorption
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Structures and functions of a nephron
Renal tubule and collecting duct
Renal corpuscle
Afferent
arteriole
Glomerular
capsule
Urine
(contains
excreted
substances)
Fluid in
renal tubule
1 Filtration from blood
plasma into nephron
2 Tubular reabsorption
from fluid into blood
Efferent
arteriole
Peritubular capillaries
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3 Tubular secretion
from blood into fluid
Blood
(contains
reabsorbed
substances)
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Glomerular Filtration
GFR = 125 ml/min = 180 liters/day
• Plasma volume is filtered 60 times per day
• Glomerular filtrate composition is about the
same as plasma, except for large proteins
• Filtration fraction (GFR / Renal Plasma Flow)
= 0.2 (i.e. 20% of plasma is filtered)
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Glomerular filtration


Glomerular filtrate – fluid that enters capsular space
 Daily volume 150-180 liters – more than 99% returned to
blood plasma via tubular reabsorption
Filtration membrane – endothelial cells of glomerular
capillaries and podocytes encircling capillaries
 Permits filtration of water and small solutes
 Prevents filtration of most plasma proteins, blood cells and
platelets
 3 barriers to cross – glomerular endothelial cells
fenestrations, basal lamina between endothelium and
podocytes and pedicels of podocytes create filtration slits
 Volume of fluid filtered is large because of large surface
area, thin and porous membrane, and high glomerular
capillary blood pressure
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Podocyte
Podocyte
of visceral
of visceral
layerlayer
of glomerular
of glomerular
(Bowman’s)
(Bowman’s)
capsule
capsule
Filtration
Filtrationslit
slit
Pedicel
Pedicel
1
1 Fenestration
Fenestration
(pore) of(pore)
glomerular
of glomerular
endothelial
endothelial
cell: prevents
cell: prevents
filtrationfiltration
of
of
blood cells
blood
butcells
allows
butall
allows
components
all components
of bloodofplasma
blood to
plasma
pass to
through
pass through
2
Basal
Basalof
lamina
glomerulus:
of glomerulus:
2 lamina
preventsprevents
filtrationfiltration
of largerofproteins
larger proteins
3
Slit membrane between pedicels:
prevents filtration of medium-sized
proteins
(a)
(a) Details
Details of
of filtration
filtration membrane
membrane
The
filtration
membrane
Pedicel
Pedicel
of podocyte
of podocyte
Filtration
Filtrationslit
slit
Basal
Basal
lamina
lamina
Lumen
Lumen
of glomerulus
of glomerulus
Fenestration
Fenestration
(pore)(pore)
of
of
glomerular
glomerular
endothelial
endothelial
cell cell
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(b) (b)
Filtration
Filtration
membrane
membrane
78,000x
TEM
TEM78,000x
19
Glomerular Filtration
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Net filtration pressure

Net filtration pressure (NFP) is the total pressure that promotes
filtration
 NFP = GBHP – CHP – BCOP
 Glomerular blood hydrostatic pressure is the blood pressure
of the glomerular capillaries forcing water and solutes
through filtration slits
 Capsular hydrostatic pressure is the hydrostatic pressure
exerted against the filtration membrane by fluid already in
the capsular space and represents “back pressure”
 Blood colloid osmotic pressure due to presence of proteins
in blood plasma and also opposes filtration
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1 GLOMERULAR BLOOD
HYDROSTATIC PRESSURE
(GBHP) = 55 mmHg
2 CAPSULAR HYDROSTATIC
PRESSURE (CHP) = 15 mmHg
3 BLOOD COLLOID
OSMOTIC PRESSURE
(BCOP) = 30 mmHg
Afferent arteriole
Proximal convoluted tubule
Efferent
arteriole
NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP
= 55 mmHg 15 mmHg 30 mmHg
= 10 mmHg
Glomerular
(Bowman's) Capsular
capsule
space
The pressures that drive glomerular filtration
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Glomerular filtration

Glomerular filtration rate – amount of filtrate formed in all the
renal corpuscles of both kidneys each minute
 Homeostasis requires kidneys maintain a relatively constant
GFR
 Too high – substances pass too quickly and are not
reabsorbed
 Too low – nearly all reabsorbed and some waste products
not adequately excreted
 GFR directly related to pressures that determine net
filtration pressure
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Clearance
• “Clearance” describes the rate at which substances
are removed (cleared) from the plasma.
• Renal clearance of a substance is the volume of
plasma completely cleared of a substance
per min by the kidneys.
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Clearance Technique
Renal clearance (Cs) of a substance is the volume of
plasma completely cleared of a substance per min.
Cs x Ps = Us x V
Cs
= Us x V = urine excretion rate s
Ps
Plasma conc. s
Where : Cs = clearance of substance S
Ps = plasma conc. of substance S
Us = urine conc. of substance S
V = urine flow rate
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Use of Clearance to Measure GFR
For a substance that is freely filtered, but not reabsorbed or
secreted (inulin, 125 I-iothalamate, creatinine), renal clearance is
equal to GFR
amount filtered = amount excreted
GFR x Pin
GFR =
= Uin x V
Uin x V
Pin
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Calculate the GFR from the following data:
Pinulin = 1.0 mg / 100ml
Uinulin = 125 mg/100 ml
Urine flow rate = 1.0 ml/min
U
x
V
in
GFR = Cinulin =
Pin
GFR =
125 x 1.0 = 125 ml/min
1.0
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Use of Clearance to Estimate Renal
Theoretically,
if a substance
Plasma
Flow is completely cleared
from the plasma, its clearance rate would equal
renal plasma flow
Cx = renal plasma flow
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Use of PAH Clearance to Estimate Renal Plasma Flow
Paraminohippuric acid (PAH) is freely filtered and secreted
and is almost completely cleared from the renal plasma
1. amount enter kidney =
RPF x PPAH
2. amount entered ~
=
3. ERPF x Ppah
ERPF =
amount excreted
= UPAH x V
~ 10 % PAH
remains
UPAH x V
PPAH
ERPF = Clearance PAH
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Calculation of Tubular Reabsorption
Reabsorption = Filtration -Excretion
Filt s = GFR x Ps
Excret s = Us x V
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Calculation of Tubular Secretion
Secretion = Excretion - Filtration
Filt s = GFR x Ps
VPAH = 0.1
Excret s = Us x V
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Use of Clearance to Estimate Renal
Plasma Flow
Theoretically, if a substance is completely cleared from
the plasma, its clearance rate would equal renal plasma flow
Cx = renal plasma flow
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Clearances of Different Substances
Substance
inulin
PAH
glucose
sodium
urea
Clearance (ml/min
125
600
0
0.9
70
Clearance of inulin (Cin) = GFR
if Cx < Cin : indicates reabsorption of x
if Cx > Cin : indicates secretion of x
Clearance creatinine (Ccreat) ~ 140 (used to estimate GFR)
Clearance of PAH (Cpah) ~ effective renal plasma flow
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GFR regulation : Adjusting blood
flow
• GFR is regulated using three mechanisms
1. Renal Autoregulation
2. Neural regulation
3. Hormonal regulation
All three mechanism adjust renal blood pressure
and resulting blood flow
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Local Control of GFR and renal
blood flow
1. Autoregulation of GFR and Renal Blood Flow
• Myogenic Mechanism
• Macula Densa Feedback
(tubuloglomerular feedback)
• Angiotensin II ( contributes to GFR but
not RBF autoregulation)
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Renal Autoregulation
120
Renal Artery
Pressure
(mmHg)
100
80
Glomerular
Filtration Rate
Renal Blood
Flow
0
1
2
3
Time (min)
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5
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3 Mechanisms regulating GFR
1.
Renal autoregulation
a. Kidneys themselves maintain constant renal blood flow
and GFR using
1. Myogenic mechanism – occurs when stretching
triggers contraction of smooth muscle cells in afferent
arterioles – reduces GFR
2. Tubuloglomerular mechanism – macula densa
provides feedback to glomerulus, inhibits release of
NO causing afferent arterioles to constrict and
decreasing GFR
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Myogenic Mechanism
Arterial
Pressure
Stretch of
Blood Vessel
Blood Flow
and
GFR
Vascular
Resistance
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Cell Ca++
Entry
Intracell. Ca++
38
Structure of
the juxtaglomerular
apparatus:
macula densa
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Macula Densa Feedback
GFR
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption
(macula densa feedback)
Afferent Arteriolar Resistance
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Macula Densa Feedback
Proximal NaCl
Reabsorption
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption
(macula densa feedback)
Afferent Arteriolar Resistance
GFR
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Regulation of GFR by Ang II
GFR
Macula
Densa NaCl
Renin
Blood
Pressure
AngII
Efferent Arteriolar
Resistance
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Ang II Blockade Impairs GFR Autoregulation
1600
Renal
Blood Flow
( ml/min)
1200
800
Normal
Ang II Blockade
400
0
Glomerular
Filtration
Rate (ml/min)
120
80
40
0
0
50
100
150
Arterial Pressure (mmHg)
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200
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Macula densa
feedback
mechanism for
regulating GFR
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Tuboglomerular
feedback
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Mechanisms regulating GFR
2.
Neural regulation
 Kidney blood vessels supplied by sympathetic ANS fibers that
release norepinephrine causing vasoconstriction
 Moderate stimulation – both afferent and efferent arterioles
constrict to same degree and GFR decreases
 Greater stimulation constricts afferent arterioles more and GFR
drops
3. Hormonal regulation
 Angiotensin II reduces GFR – potent vasoconstrictor of both
afferent and efferent arterioles
 Atrial natriuretic peptide increases GFR – stretching of atria
causes release, increases capillary surface area for filtration
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Summary of neurohumoral control of
GFR and renal blood flow
Effect on GFR
Effect on RBF
Sympathetic activity
Catecholamines
Angiotensin II
EDRF (NO)
Endothelin
Prostaglandins
increase
decrease
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Thank You
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Renal system –L3
Faisal I. Mohammed, MD, PhD
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Tubular reabsorption and tubular secretion

Reabsorption – return of most of the filtered water
and many solutes to the bloodstream




About 99% of filtered water reabsorbed
Proximal convoluted tubule cells make largest
contribution around 67%
Both active and passive processes
Secretion – transfer of material from blood into
tubular fluid


Helps control blood pH
Helps eliminate substances from the body
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Reabsorption routes and transport mechanisms

Reabsorption routes

Paracellular reabsorption





Between adjacent tubule cells
Tight junction do not completely seal off interstitial fluid from tubule
fluid
Passive
Transcellular reabsorption – through an individual cell
Transport mechanisms


Reabsorption of Na+ especially important
Primary active transport


Secondary active transport


Symporters, antiporters
Transport maximum (Tm)


Sodium-potassium pumps in basolateral membrane only
Upper limit to how fast it can work
Obligatory vs. facultative water reabsorption
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Reabsorption
routes:
paracellular
reabsorption
and
transcellular
reabsorption
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Reabsorption and secretion in proximal
convoluted tubule (PCT)
Largest amount of solute and water reabsorption two thirds
+
+
 Secretes variable amounts of H , NH4 and urea
+
 Most solute reabsorption involves Na
 Symporters for glucose, amino acids, lactic acid, water-soluble
vitamins, phosphate and sulfate
 Na+ / H+ antiporter causes Na+ to be reabsorbed and H+ to be
secreted
 Solute reabsorption promotes osmosis – creates osmotic gradient
 Aquaporin-1 in cells lining PCT and descending limb of loop of
Henle
 As water leaves tubular fluid, solute concentration increases
 Urea and ammonia in blood are filtered at glomerulus and secreted
by proximal convoluted tubule cells
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Glucose
Transport
Maximum
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Transport Maximum
Some substances have a maximum rate of tubular transport
due to saturation of carriers, limited ATP, etc
• Transport Maximum: Once the transport maximum is
reached for all nephrons, further increases in tubular
load are not reabsorbed and are excreted.
• Threshold is the tubular load at which transport maximum is
exceeded in some nephrons. This is not exactly the same
as the transport maximum of the whole kidney because
some nephrons have lower transport max’s than others.
• Examples: glucose, amino acids, phosphate, sulphate
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Reabsorption
and secretion in
the proximal
convoluted
tubule
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Reabsorption
and secretion in
the proximal
convoluted
tubule
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Reabsorption
and secretion in
the proximal
convoluted
tubule
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Changes in concentration in proximal
tubule
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Reabsorption in the loop of Henle





Chemical composition of tubular fluid quite different from
filtrate
 Glucose, amino acids and other nutrients reabsorbed
Osmolarity still close to that of blood
 Reabsorption of water and solutes balanced
For the first time reabsorption of water is NOT
automatically coupled to reabsorption of solutes
 Independent regulation of both volume and osmolarity of
body fluids
Na+-K+-2Cl- symporters function in Na+ and Clreabsorption – promotes reabsorption of cations
Little or no water is reabsorbed in ascending limb –
osmolarity decreases
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Na+–K+-2Clsymporter in the
thick ascending
limb of the loop
of Henle
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Early Distal Tubule
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Early Distal Tubule
Functionally similar to thick ascending loop
 Not permeable to water (called diluting segment)
Active reabsorption of Na+, Cl-, K+, Mg++
Contains macula densa (tubuloglomerular balance)
Major site where parathyroid hormone stimulates
reabsorption of Ca+ depending on body’s needs
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Reabsorption and secretion in the late distale
convoluted tubule and collecting duct


Reabsorption on the early distal convoluted tubule
 Na+-Cl- symporters reabsorb Na+ and Cl Major site where parathyroid hormone stimulates reabsorption
of Ca+ depending on body’s needs
Reabsorption and secretion in the late distal convoluted tubule
and collecting duct
 90-95% of filtered solutes and fluid have been returned by now
+
+
 Principal cells reabsorb Na and secrete K
 Intercalated cells reabsorb K+ and HCO3- and secrete H+
 Amount of water reabsorption and solute reabsorption and
secretion depends on body’s needs
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Reabsorption
and secretion
in the late
distale
convoluted
tubule and
collecting duct
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Late Distal and Cortical Collecting
Tubules Principal Cells – Secrete K+
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Late Distal and Cortical Collecting Tubules
Intercalated Cells –Secrete H+
Tubular Cells
Tubular Lumen
H2O (depends on
ADH)
K+
H+
K+
ATP
ATP
Na +
K+
H+
ATP
ATP
ATP
Cl -
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Changes in
concentrations of
substances in the
renal tubules
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Hormonal regulation of tubular reabsorption
and secretion



Angiotensin II - when blood volume and blood pressure
decrease
 Decreases GFR, enhances reabsorption of Na+, Cl- and
water in PCT
Aldosterone - when blood volume and blood pressure
decrease
 Stimulates principal cells in late distal and collecting
duct to reabsorb more Na+ and Cl- and secrete more K+
Parathyroid hormone
 Stimulates cells in DCT to reabsorb more Ca2+
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Regulation of facultative
water reabsorption by ADH


Antidiuretic hormone (ADH or
vasopressin)
 Increases water permeability of
cells by inserting aquaporin-2 in
last part of DCT and collecting duct
Atrial natriuretic peptide (ANP)
 Large increase in blood volume
promotes release of ANP
 Decreases blood volume and
pressure by inhibiting reabsorption
of Na+ and water in PCT and
collecting duct, suppress secretion
of ADH and aldosterone
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Production of dilute and concentrated
urine



Even though your fluid intake can be highly variable,
total fluid volume in your body remains stable
Depends in large part on the kidneys to regulate the
rate of water loss in urine
ADH controls whether dilute or concentrated urine is
formed
 Absent or low ADH = dilute urine
 Higher levels = more concentrated urine through
increased water reabsorption
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Formation of dilute urine



Glomerular filtrate has same osmolarity as blood
300 mOsm/liter
Fluid leaving PCT is isotonic to plasma
When dilute urine is being formed, the osmolarity
of fluid increases as it goes down the descending
loop of Henle, decreases as it goes up the ascending
limb, and decreases still more as it flows through
the rest of the nephron and collecting duct
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THANK YOU
Renal system –L4
Faisal I. Mohammed, MD, PhD
University of Jordan
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Control of Extracellular Osmolarity
(NaCl Concentration)
• ADH
• Thirst
]
ADH -Thirst Osmoreceptor System
Mechanism:
increased extracellular osmolarity (NaCl)
stimulates ADH release, which increases
H2O reabsorption, and stimulates thirst
(intake of water)
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Formation of
dilute urine




Osmolarity of interstitial fluid
of renal medulla becomes
greater, more water is
reabsorbed from tubular fluid
so fluid become more
concentrated
Water cannot leave in thick
portion of ascending limb but
solutes leave making fluid more
dilute than blood plasma
Additional solutes but not much
water leaves in DCT
Low ADH makes late DCT and
collecting duct have low water
permeability
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Formation of a dilute urine
• Continue electrolyte
reabsorption
• Decrease water
reabsorption
Mechanism:
Decreased ADH release and
reduced water permeability
in distal and collecting
tubules
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Formation of concentrated urine




Urine can be up to 4 times more concentrated than blood
plasma i.e maxinmal osmolarity is 1200 mOsm/liter
Ability of ADH depends on presence of osmotic gradient in
interstitial fluid of renal medulla
3 major solutes contribute – Na+, Cl-, and urea
2 main factors build and maintain gradient
 Differences in solute and water permeability in different
sections of loop of Henle and collecting ducts
 Countercurrent flow of fluid though descending and
ascending loop of Henle and blood through ascending and
descending limbs of vasa recta
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Formation of a Concentrated Urine when
antidiuretic hormone (ADH) are high.
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Countercurrent multiplication







Process by which a progressively increasing osmotic
gradient is formed as a result of countercurrent flow
Long loops of Henle of juxtamedullary nephrons function as
countercurrent multiplier
Symporters in thick ascending limb of loop of Henle cause
buildup of Na+ and Cl- in renal medulla, cells impermeable
to water
Countercurrent flow establishes gradient as reabsorbed Na+
and Cl- become increasingly concentrated
Cells in collecting duct reabsorb more water and urea
Urea recycling causes a buildup of urea in the renal medulla
Long loop of Henle establishes gradient by countercurrent
multiplication
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Countercurrent exchange





Process by which solutes and water are passively
exchanged between blood of the vasa recta and
interstitial fluid of the renal medulla as a result of
countercurrent flow
Vasa recta is a countercurrent exchanger
Osmolarity of blood leaving vasa recta is only slightly
higher than blood entering
Provides oxygen and nutrients to medulla without
washing out or diminishing gradient
Vasa recta maintains gradient by countercurrent
exchange
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Recirculation of urea absorbed from medullary
collecting duct into interstitial fluid.
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Urea Recirculation
• Urea is passively reabsorbed in proximal tubule
(~ 50% of filtered load is reabsorbed)
• In the presence of ADH, water is reabsorbed in
distal and collecting tubules, concentrating
urea in these parts of the nephron
• The inner medullary collecting tubule is highly
permeable to urea, which diffuses into the
medullary interstitium
• ADH increases urea permeability of medullary
collecting tubule by activating urea
transporters (UT-1)
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Mechanism of urine concentration in
long-loop juxtamedullary nephrons
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Summary of Tubule Characteristics
Tubule
Segment
Active NaCl
Transport
Proximal
Thin Desc.
Thin Ascen.
Thick Ascen.
Distal
Cortical Coll.
Inner Medullary
Coll.
Permeability
H2O
NaCl
Urea
++
0
0
+++
+
+
+
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+++
+++
0
0
+ADH
+ADH
+ADH
+
+
+
0
0
0
0
+
+
+
0
0
0
+++
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Changes in osmolarity of the tubular fluid
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Summary of
filtration,
reabsorption,
and secretion
in the nephron
and collecting
duct
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Evaluation of kidney function

Urinalysis
 Analysis of the volume and physical, chemical and
microscopic properties of urine
 Water accounts for 95% of total urine volume
 Typical solutes are filtered and secreted substances
that are not reabsorbed
 If disease alters metabolism or kidney function,
traces if substances normally not present or normal
constituents in abnormal amounts may appear
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Evaluation of kidney function

Blood tests



Blood urea nitrogen (BUN) – measures blood nitrogen that is part
of the urea resulting from catabolism and deamination of amino
acids
Plasma creatinine results from catabolism of creatine phosphate
in skeletal muscle – measure of renal function
Renal plasma clearance




More useful in diagnosis of kidney problems than above
Volume of blood cleared of a substance per unit time
High renal plasma clearance indicates efficient excretion of a
substance into urine
PAH administered to measure renal plasma flow
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Renal Handling of Water and Solutes
Filtration
Reabsorption
Water
(liters/day)
180
Sodium
(mmol/day)
25,560
25,410
Glucose
(gm/day)
180
180
Creatinine
(gm/day)
1.8
Excretion
179
1
0
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0
1.8
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Renal Regulation of Acid-Base
Balance
• Kidneys eliminate non-volatile
acids (H2SO4, H3PO4) (~ 80 mmol/day)
• Filtration of HCO3- (~ 4320 mmol/day)
• Secretion of H+ (~ 4400 mmol/day)
• Reabsorption of HCO3- (~ 4319 mmol/day)
• Production of new HCO3- (~ 80 mmol/day)
• Excretion of HCO3- (1 mmol/day)
Kidneys conserve HCO3- and excrete acidic
or basic urine depending on body needs
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Reabsorption of bicarbonate (and H+ secretion) in
different segments of renal tubule.
Key point:
For each HCO3reabsorbed, there
must be a H+
secreted
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Mechanisms for HCO3- reabsorption and Na+ H+ exchange in proximal tubule and thick loop
of Henle
Minimal pH
~ 6.7
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HCO3- reabsorption and H+ secretion in intercalated
cells of late distal and collecting tubules
Minimal
pH ~4.5
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Renal Compensations for
Acid-Base Disorders
• Acidosis:
- increased H+ secretion
- increased HCO3- reabsorption
- production of new HCO3-
• Alkalosis:
- decreased H+ secretion
- decreased HCO3- reabsorption
- loss of HCO3- in urine
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In acidosis all HCO3- is titrated and
excess H+ in tubule is buffered
Interstitial
Fluid
Cl-
Cl-
Cl-
new
HCO3-
H+
HCO3- + H+
ATP
H2CO3
CO2
Tubular
Lumen
Tubular
Cells
+ Buffers-
Carbonic
Anhydrase
CO2 + H2O
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Buffering of secreted H+ by filtered phosphate
(NaHPO4-) and generation of “new” HCO3-
“New” HCO3-
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Production and secretion of NH4+ and HCO3- by
proximal, thick loop of Henle, and distal tubules
H++NH3
“New” HCO3-
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Buffering of hydrogen ion secretion by ammonia
(NH3) in the collecting tubules.
“New” HCO3-
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Urine transportation, storage, and
elimination

Ureters
 Each of 2 ureters transports urine from renal pelvis of one
kidney to the bladder
 Peristaltic waves, hydrostatic pressure and gravity move
urine
 No anatomical valve at the opening of the ureter into
bladder – when bladder fills it compresses the opening and
prevents backflow
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Urinary bladder and urethra


Urinary bladder
 Hollow, distensible muscular organ
 Capacity averages 700-800mL
 Micturition – discharge of urine from bladder
 Combination of voluntary and involuntary muscle
contractions
 When volume increases stretch receptors send signals to
micturition center in spinal cord triggering spinal reflex –
micturition reflex
 In early childhood we learn to initiate and stop it voluntarily
Urethra
 Small tube leading from internal urethral orifice in floor of
bladder to exterior of the body
 In males discharges semen as well as urine
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Urinary bladder and its innervation
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Normal Cystometrogram
Figure 26-8
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Micturition
Once urine enters the renal pelvis, it flows through the ureters and
enters the bladder, where urine is stored.
Micturition is the process of emptying the urinary bladder.
Two processes are involved:
(1) The bladder fills progressively until the tension in its wall reses
above a threshold level, and then
(2) A nervous reflex called the micturition reflex occurs that
empties the bladder.
The micturition reflex is an automatic spinal cord reflex; however,
it can be inhibited or facilitated by centers in the brainstem and
cerebral cortex.
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Thank You
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