Renal Physiology II

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Renal Physiology II

• Urination
• Tubular Transport
• Countercurrent

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Getting Urine from the kidney to the outside.
(Urination or micturition) Processed tubular
fluid is dumped by the collecting system into the
renal pelvis where it enters the
ureters. Ureters conduits that propel urine by
peristaltic contractions toward the
bladder. Bladder a muscular bag that holds
urine and forces it by contration. Urethra the
conduit for urine from the baldder to the
outside
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Pelvis Collects urine from collecting ducts. In
the pelvis there are electrical pacemaker cells
that initiate peristaltic waves in the (2) smooth
muscle sheaths of the ureteral wall. (The pelvis
to ureter is a functional syncitium, not unlike
the muscular wall of the heart). The frequency of
the waves is 2-6/min. The pacemaker cells seem to
be stimulated by the stretch of urine filling the
pelvis. The movement of the peristaltic wave is
about 2-6 cm/sec., traveling from its origin at
the pelvis down to the bladder.
Urethra ?
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Anatomy of the bladder and ureter. On the right
is the electrical profile of a peristaltic wave
passing down the muscular wall of the ureter.
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The peristaltic waves propel the urine along the
ureter, generating a pressure head of which
changes from a baseline of 2-5 cm H2O up to 20-80
cm H2O. While peristalysis is independent of
nerve input, the action of symapthetic nerves
innervating the ureter may modify the rate or
force of peristalsis. Interruption of the flow of
urine by an obstruction (such as a kidney stone)
stops flow, increases pressure which can back up
through the ureter into the pelvis, and increase
the nephron and subcapsular hydrostatic pressure.
This may result in the condition hydronephrosis
in which the medulla is damaged and may even be
sloughed off, leaving a hollow kidney. Obviously
this condition impares the concentrating ability
fo the kidney. There are autonomic pain fibers
in the ureter which account for the acute pain
when a kidney stone is formed.
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The bladder and its sphincters is also innervated
with sympathetic, parasympathetic and somatic
(voluntary) nerves. The wall of the bladder is
composed of three muscular layers, called the
detrusor muscle. A triangular membrane called
the trigone acts as a valve system along with
the internal sphinctors of the muscular wall to
prevent urine reflux into the ureters.
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Again, the anatomy of the bladder note trigone.
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Sympathetic nerves originate from the neurons ot
the intermediallateral cell column from T-10 to
L-2. they innervate the body of the bladder and
the trigone. Parasympathetic nerves originate
from S2-S4 of the sacral spinal cord. They
innervate the body and neck of the
bladder. Somatic innervation (voluntary or
pudendal) originates from the motor neurons
arising from S-2 to S-4. They innervate and
control the voluntary muscles of the external
sphinctor.
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Bladder tone is derived from the volume and
pressure exerted on the inside of the bladder
(intervesical pressure). Increasing bladder
volume by 50 ml increases pressure. As volume
inceases further, the intervesical pressure
increases, but not much until you get above 300
ml. then the pressure rises steeply with
additional volume. (see next slide-blue
line). This increase in volume and pressure
increases bladder tone triggering the
mictiurition reflex (open the flood-gates!) Effere
nt impulses from the brain supress the reflex (a
learned reflex) until a decision is made to relax
the external sphinctor using voluntary nerves.
Voiding begins with relaxation of the external
sphinctor, then the internal sphinctor.
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Next, the detrussor muscle of the bladder wall
contracts in waves (see red lines in previous
figure) to expell the urine. Voluntary
contraction of the abdonimal muscles further
contracts the bladder, increasing the
voiding. Once the bladder is empty, we are back
down to the no tone phase (in the lower left
corner of figure 32-14) and the sphinctors can
close again. The process is sterile until it
leaves the body. However, because of all the
organic and waste material, once out is it a good
culture media.
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SECTION II Transport along the nephron
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Transport of Sodium (Na) and Chloride (Cl-)
Chapter 34 The filtered load of Na is the
product of the glomerular filtration rate (GFR,
180 liters/day) and the plasma Na concentration
(142 mM), or approximately 25,500 mM/day
(equivalent to the Na in approximately 1.5 kg of
table salt, more than nine times the total
quantity of Na present in the body fluids. With
a typical Western diet consuming approximately
120 mM of Na per day, the kidneys reabsorb
approximately 99.6 of the filtered Na by the
time the tubule fluid reaches the renal pelvis.
Therefore, even minute variations in the
fractional reabsorptive rate could lead to
changes in total-body Na that markedly alter ECF
volume, sodium balance, blood pressure, body
weight and many other
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The filtered load of Na is 25,500 mM/day, but the
intake is only 120 mM/day and the output is 100
mM/day excreted plus about 20 mM in the feces and
sweat. Thus, the intake equals output, so the
body is in sodium balance.
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Reabsorption of filtered Na load along the each
nephron segment. Yellow boxes are the amount of
filtered which is reabsorbed. Green boxes
represent the amount of filtered which remains in
each portion of the nephron.
Pg 776
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• Transport of ions, and particularly of sodium
  from the lumen to the blood across the tubular
  wall is through two pathways transcellular and
  paracellular.
• Transport is driven by two general mechanisms
• active transport in an energy (ATP) utilizing
  fashion where ions are pumped against their
  electrochemical gradient (uphill), and
• passively down their electrochemical gradient
  (downhill) along the gradients created by the
  active transport.

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Tubular epithelial wall
Capillary wall
Start here with Na delivery
End here with sodium reabsorbed and recovered
Tubular lumen
Interstitial space
Capillary Lumen
Na
Apical Membrane
Basal-lateral membrane
Na
Na
Na
Na
Net pathway for sodium (Na) reabsorption from
tubular lumen to capillary
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Para-cellular movement incorporates The
transepithelial electrochemical Na gradient
drives passive Na reabsorption in the proximal
and thick ascending limb of the nephron. Not so
for later nephron segments where the net
(passive) force favors movement into the lumen.
Na can also move passively in the proximal
tubule (without active transport) via solvent
drag where the movement of water (driven by
active Na transport) sweeps additional Na and Cl
along with it (a sort of mass-action) out of the
lumen into the lateral intracellular space. The
leakiness of the nephron (facillitating passive
reabsorption) is greatest in the proximal, and
decreases along the nephron to the papillary
collecting ducts.
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Trans-cellular movement incorporates 1) passive
entry from the lumen via the apical membrane
into the cell down an electro-chemical gradient.
The proximal, TAL and DCT use various
co-transporters and exchangers, while in the
collecting ducts Na enters via Na channels. 2)
Active extrusion of Na out the basal-lateral
membrane via a Na-K pump which maintains
intracellular Na low and K high. This exchange
keeps the voltage at 70 mV (cell interior
negative vs interstitium, or lumen) depending on
pump activity and the voltage gradient it
creates.
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There is a net driving force due to the active
pump forcing Na into the interstitium, but a net
negative change favoring the lumen to draw Na
back via extracellular junctions.
Downhill refers to a passive flow along an
electrochemical gradient not requiring active
transport.
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Proximal the Na-K pump on the apical
(interstitial side) membrane is the driving force
for the electrochemical gradient which drives
passive transport into the cell and keeps
intracellular Na low, pumping against the
gradient into the basal-lateral space. Passive
entry into the cell is by diffusion, facillitated
diffusion through a transporter or
co-transporter, and by electroneutral exchange
with hydrogen ions (H).
Na
Na
Interstitial space
Tubular lumen
pump
Na
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Na reabsorption in different nephron segments
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The sodium movement across the thin limbs
(decending and ascending limbs) of the loop of
Henle are virtually entirely passive down its
electrochemical gradient and paracellular. Keep
this in mind when we return to the countercurrent
system!.
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• Thick Ascending Limb (TAL) of the loop of Henle.
• Transcellular Na reabsorption includes
• the Na/K/2Cl co-transporter (NKCC2) which couples
  inward movement of these three ions in an
  electroneutral (2 2-) process driven by the
  downhill gradient of Na and Cl into the cell.
  (Note that this pump is the target of loop
  diuretics). Much of the K entering the cell is
  extruded via K channels down its own gradient.
• The Na-H exchanger exchanging sodium for
  hydrogen in an electroneutral process.

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Na reabsorption in different nephron segments
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Paracellular sodium transport by the thick
ascending limb (TAL) (also known as the
diluting segment). Because the lumen of the TAL
is positive voltage due to the high density of K
channels in the apical membrane, unlike all other
nephron segment epithelia. This lumen-positive
voltage drives sodium (and other positively
charged ions) out of the lumen across the tight
junctions between the cells. This paracellular
pathway accounts for about half of the sodium
movement out of the lumen to the basalateral
spaces and the interstitium. The TAL has low
water permeability, so removal of ions without
water following leaves the lumen dilute
(hypoosmotic) and the interstitium concentrated
(hyperosmotic).
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Transcellular and paracellular Na reabsorption in
different nephron segments
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Distal Convoluted Tubule (DCT) Sodium
reabsorption in the distal tubule is almost
entriely due to transcellular transport. Electrone
utral passive apical Na entry is due to an Na/Cl
cotransporter (NCC). Unlike the NKCC2, this is
independent of K (this pump is the target of the
thiazide diuretics, which tqarget sodium
without wasting potassium) The net movement of
transcellular sodium in the DCT is driven by an
ATP-utilizing basal-lateral Na-K pump
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Transcellular and paracellular Na reabsorption in
different nephron segments
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Sodium transport in the Collecting Tubules The
relatively modest Sodium reabsorption in the
collecting tubules is entirely transcellular via
the principal cells. Na enters the apical
membrane via a voltage-gated sodium channel or
ENaC. The basolateral movement of sodium out
of the cell is driven by an energy requiring Na-K
pump which establishes the gradient driving
apical sodium entry. The movement of Na out of
the lumen into the cell makes the lumen
negatively charged, and the movement of K out of
the cell, primarily into the basolateral
interstitium makes the cell negative, for a net
transepithelial voltage of -40 mV. The hormones
aldosterone and vasopressin can change this site
of transport .
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Transcellular and paracellular Na reabsorption in
different nephron segments
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Medullary Collecting Duct The inner and outer
medulalry collecting ducts reabsorb only a small
amount of sodium (3 of filtered load) and this
is probably via ENaC on the apical membrane and
the Na-K pump driving Na movement on the basal
lateral membrane.
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Cl- transport and reabsorption Most Cl follows
along with Na reabsorption, but the exact nature
fo the movement is somewhat different. In the
Proximal tubule Early proximal tubule Cl
reabsorption is mostly paracellular via solvent
drag driven by the lumen negative
potential. However, in the late proximal it is
reabsorbed by a predominantly by transcellular
pathway, driven by apical H exchange and active
transport with Na and a K cotransporter. The
lumen becomes positive actually retarding Cl
reabsorption.
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Changes in proximal TFP ratio along the length
of the proximal tubule. Note that 65 of the
water is lost so inulin continues to concentrate,
while osmolality and Na are unchanged.
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Thick ascending limb (TAL) Cl is primarly
reabsorbed by the NaK2Cl co-transsporteracross
the apical membrane, and basal lateral Cl
channels along with active transport of sodium
drive Cl into the interstieium. Distal Tubule
Apical Cl reabsorption occurs via a Na/Cl
ccotransporter and is driven by Cl following Na
active extrusion via a Na/K pump. Collecting
ducts The principal cell has an electrogenic
pump that creates a -40 mV lumen negative
potential that drives Cl- out of the lumen via
paracellular routes. However, the other cell
type (the intercallated cell) drives
transcellular Cl movement powered by a
basalateral H pump.
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Water Reabsorption In the proximal tubule,
water follows sodium passibvely and isosmotically
because the proximal tubule is very permeable to
water. Water moves both transcellularly and
paracellularly. The transcellular movement is
facillitated by aquaporin water channels in
both the apical and basalateral membranes.
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Water reabsorption in the Thick Ascending Limb
and Distal nephrons. All the distal nephrons,
from TAL on, have a very low water permeability
(in the presence of vasopressin). This low water
permeability will be very important in
understanding countercurrent concentration of
the urine (coming later) The combination of Na
transport with low water permeability produce a
dilute tubular fluid with low Na and low
osmolality. This facillitates later passive water
reabsorption down a concentration gradient out of
the nephron and into the capillary blood.
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End of Na, Cl and water reabsorption lectures