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Renal system
Faisal I. Mohammed, MD, PhD
Yanal Shafagoj, MD, PhD
University of Jordan
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Tubular reabsorption and tubular secretion

Reabsorption – return of most of the filtered
water and many solutes to the bloodstream

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About 99% of filtered water reabsorbed
Proximal convoluted tubule cells make largest
contribution
Both active and passive processes
Secretion – transfer of material from blood
into tubular fluid


Helps control blood pH
Helps eliminate substances from the body (K+)
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Reabsorption routes and transport mechanisms

Reabsorption routes

Paracellular reabsorption

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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

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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)

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Largest amount of solute and water reabsorption
Secretes variable amounts of H+, NH4+
Most solute reabsorption involves Na+

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Solute reabsorption promotes osmosis – creates osmotic gradient

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
Symporters with glucose, amino acids, lactic acid, water-soluble
vitamins, phosphate and sulfate
Na+ / H+ antiporter causes Na+ to be reabsorbed and H+ to be secreted
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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Reabsorption and secretion in the
proximal convoluted tubule
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Reabsorption in the loop of Henle
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Chemical composition of tubular fluid quite different from
filtrate
 Glucose, amino acids and other nutrients were already
reabsorbed in PT
At the entranc of LH Osmolarity still close to that of blood
 Reabsorption of water and solutes balanced
In the descending: 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
Ascending: Na+-K+-2Cl- symporters function in Na+ and Clreabsorption – promotes reabsorption of cations
No water is reabsorbed in ascending limb – osmolarity
decreases
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Na+–K+-2Cl- symporter in the thick
ascending limb of the loop of Henle…Lasix
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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- (Thiazide)
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


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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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Hormonal regulation of tubular reabsorption
and secretion

Angiotensin II - when blood volume and blood pressure
decrease


Aldosterone - when blood volume and blood pressure
decrease


Decreases GFR, enhances reabsorption of Na+, Cl- and water
in PCT
Stimulates principal cells in collecting duct to reabsorb more
Na+ and Cl- and secrete more K+ (Aldactone)
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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ANP



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Produced by atria due to stretching of walls.
Antagonist to aldosterone.
Increases Na+ and H20 excretion.
Acts as an endogenous diuretic.
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
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
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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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Formation of dilute urine


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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 concentrated urine
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
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Urine can be up to 4 times more concentrated than
blood plasma
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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Countercurrent multiplication
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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
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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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Mechanism of urine concentration in longloop juxtamedullary nephrons
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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
3 Principal cells in
400
380
200
H2O
400
Osmotic
gradient
Na+CI–
400
500
H2O
600
H2O
580
600
H2O
collecting duct
reabsorb more
water when ADH
is present
Na+CI–
Interstitial fluid
in renal medulla
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
causes buildup
of urea in the
renal medulla
1000
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
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(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron
1200
(b) Recycling of salts and urea in the vasa recta
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Summary of filtration, reabsorption, and secretion
in the nephron and collecting duct
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Na+ Reabsorption
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90% filtered Na+
reabsorbed in PCT.
In the absence of
aldosterone, 80% of
the remaining Na+ is
reabsorbed in DCT.
Final [Na+]
controlled in CD by
aldosterone.
When aldosterone
is secreted in
maximal amounts,
all Na+ in DCT is
reabsorbed.
Insert fig. 17.26
K+ Secretion

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90% filtered K+ is reabsorbed in early part of the
nephron.
Secretion of K+ occurs in CD.

Amount of K+ secreted depends upon:


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Amount of Na+ delivered to the region.
Amount of aldosterone secreted.
As Na+ is reabsorbed, lumen of tubule becomes –
charged.

Potential difference drives secretion of K+ into tubule.

Transport carriers for Na+ separate from transporters for K+.
K+ Secretion

Final [K+]
controlled in CD
by aldosterone.



When
aldosterone is
absent, no K+ is
excreted in the
urine.
High [K+] or low
[Na+] stimulates
the secretion of
aldosterone.
Only means by
which K+ is
secreted.
(continued)
Insert fig. 17.24
Renal Acid-Base Regulation


Kidneys help regulate blood pH by excreting
H+ and reabsorbing HC03-.
Most of the H+ secretion occurs across the
walls of the PCT in exchange for Na+.

Antiport mechanism.


Moves Na+ and H+ in opposite directions.
Normal urine normally is slightly acidic
because the kidneys reabsorb almost all
HC03- and excrete H+.

Returns blood pH back to normal range.
Reabsorption of HCO3
Apical membranes of tubule cells are
impermeable to HCO3-.


When urine is acidic, HCO3- combines with H+
to form H2C03-, which is catalyzed by ca
located in the apical cell membrane of PCT.

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Reabsorption is indirect.
As [C02] increases in the filtrate, C02 diffuses into
tubule cell and forms H2C03.
H2C03 dissociates to HCO3- and H+.
HCO3- generated within tubule cell diffuses into
peritubular capillary.
Acidification of Urine
Insert fig. 17.28
Urinary Buffers
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Nephron cannot produce a urine pH < 4.5.
In order to excrete more H+, the acid must be
buffered.
H+ secreted into the urine tubule and
combines with HPO4-2 or NH3.
HPO4-2 + H+
H2PO4NH3 + H+
NH4+
Diuretics

Increase urine volume excreted.

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Loop diuretics:

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Inhibit NaCl reabsorption in the 1st segment of the DCT.
Ca inhibitors:

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Inhibit NaCl transport out of the ascending limb of the LH.
Thiazide diuretics:


Increase the proportion of glomerular filtrate that is excreted as urine.
Prevent H20 reabsorption in PCT when HC0s- is reabsorbed.
Osmotic diuretics:

Increase osmotic pressure of filtrate.
Clinical Diuretics Sites of Action
Insert fig. 17.29
Evaluation of kidney function

Urinalysis

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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

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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

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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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Urine transportation, storage, and
elimination

Ureters

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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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Ireters, urinary bladder, and urethra in a
female
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Urinary bladder and urethra

Urinary bladder

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Hollow, distensible muscular organ
Capacity averages 700-800mL
Micturition – discharge of urine from bladder
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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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Comparison between female and male
urethras
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Glucose and Amino Acid Reabsorption

Filtered glucose and amino acids are normally
reabsorbed by the nephrons.

In PCT occurs by secondary active transport with
membrane carriers.

Carrier mediated transport displays:



Saturation.
T m.

[Transported molecules] needed to saturate carriers and
achieve maximum transport rate.
Renal transport threshold:

Minimum plasma [substance] that results in
excretion of that substance in the urine.

Renal plasma threshold for glucose = 180-200 mg/dl.
Kidney Diseases

Acute renal failure:

Ability of kidneys to excrete wastes and regulate
homeostasis of blood volume, pH, and electrolytes
impaired.

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Rise in blood [creatinine].
Decrease in renal plasma clearance of creatinine.
Glomerulonephritis:


Inflammation of the glomeruli.
Autoimmune disease by which antibodies have been
raised against the glomerulus basement membrane.

Leakage of protein into the urine.
Kidney Diseases

Renal insufficiency:


Nephrons are destroyed.
Clinical manifestations:

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(continued)
Salt and H20 retention.
Uremia.
Elevated plasma [H+] and [K+].
Dialysis:

Separates molecules on the basis of the ability to
diffuse through selectively permeable membrane.
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