Download Renal tubular transp..

 Excretion
refers to the removal of solutes
and water from the body in urine
 Reabsorption (movement from tubular fluid
to peritubular blood) and,
 Secretion (movement from peritubular
blood to tubular fluid) refer to direction of
movement of solutes and water across the
renal tubular epithelium
The
luminal cell membranes are
those that face the tubular lumen
(“urine” side)
The basolateral cell membranes are
those are in contact with the lateral
intercellular spaces and peritubular
interstitium (“blood” side)
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 Solute
reaborption in the proximal tubule is
isosmotic (water follows solute osmotically
and tubular fluid osmolality remains similar
to that of plasma).
 65%-70% of water and sodium reabsorption
occurs in the proximal tubule
 90% of bicarbonate, calcium, K+
 100% of glucose & amino acids
 Proximal
tubules: coarse adjustment
 Distal tubules: fine adjustment (hormonal
control).
 Responsible
for producing a concentrated urine by
forming a concentration gradient within the
medulla of kidney.
 When ADH is present, water is reabsorbed and
urine is concentrated.
 Counter-current multiplier
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Loop of Henle:
Acts in manner of
counter current
exchanger. Note that
each limb of loop has
fluid moving in opposite
directions (even though
connected at one end).
Further concentrates
urine.
Also means that salt
concentration will be
highest near bend in the
loop.
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Absorption through loop of Henle:
Descending limb: is water permeable and allow
absorption of 25% of filtered H2O. It is impermeable to
Na-CL.
Thin ascending limb: is impermeable to H2O, but
permeable to Na-Cl, where they are absorbed passively
in this part .
Thick ascending limb: is impermeable to H2O.
Na-K-2Cl co-transport occur in this part.
 What
happens here depends on hormonal control:
 Aldosterone affects Na+ and K+
 ADH – facultative water reabsorption
 Parathyroid hormone – increases Ca++ reabsorption
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Tubular
secretion to rid body of
substances: K+, H+, urea,
ammonia, creatinine and certain
drugs
Secretion of H+ helps maintain
blood pH
(can also reabsorb bicarb and
generate new bicarb)
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Na+ absorbed by active transport
mechanisms, NOT by TM
mechanism. Basolateral ATPases
establish a gradient across the
tubule wall.
 Proximal tubule is very
permeable to Na+, so ions flow
down gradient, across
membranes.
 Microvilli create large surface
area for absorption.
 Electrical gradient created also
draws Cl- across.
 H2O follows Na+ due to osmotic
force.
 Means fluid left in tubule is
concentrated.

Glucose absorption
also relies upon the
Na+ gradient.
 Most reabsorbed in
proximal tubule.
 At apical
membrane, needs
Na+/glucose
cotransporter
(SGLT)
 Crosses basolateral
membrane via
glucose transporters
(GLUT’s), which do
not rely upon Na+.

 K+
is major cation in
cells and balance is
essential for life.
Small change from 4 to
5.5 mmoles/l =
hyperkalaemia = ventric.
fibrillation = death.
Reabsorb K+ at proximal
tubule.
Changes in K+ excretion
due to changes in K+
secretion in distal tubule
K+ reabsorption along the
proximal tubule is largely
passive and follows the
movement of Na+ and fluid
(in collecting tubules, may
also rely active transport).
 K+ secretion occurs in
cortical collecting tubule
(principal cells), and relies
upon active transport of K+
across basolateral
membrane and passive exit
across apical membrane
into tubular fluid.

Countercurrent
is that, fluid flows down
the descending limb and up the ascending
limb.
The critical characteristics of the loops
which make them countercurrent
multipliers are:
1. The ascending limb of the loop of
Henle actively co-transports Na+ and Clions out of the tubule lumen into the
interstitium.
The ascending limb is
impermeable to H2O.
2. The descending limb is freely
permeable to H2O but relatively
impermeable to NaCl.
H2O that moves out of tubule into
intersitium is removed the blood vessels
called vasa recta – thus gradients
maintained and H2O returned to
circulation.
Mechanisms of tubular transport:
Active transport:
i. Primary active transport: e.g. Na-K-pump, H+-pump
ii. Secondary active transport : e.g. Na-K-2Cl cotransport, glucose-sodium co-transport, amino
acid-sodium co-transport.
Passive transport:
i. Simple diffusion.
ii. Facilitated diffusion.
Osmosis.
Pinocytosis.
Solvent drag.
 Movement
of a substance
across a membrane as a
result of random molecular
motion down concentration
and electrochemical
gradient. No energy needed.
 E.g. bicarbonate, chloride,
Movement
of a substance across a
membrane down its electrochemical
gradient after binding with a
specific carrier protein in the
membrane.
Needs a carrier.
Glucose,
amino acids: At
Basolateral membranes of proximal
tubules
Sodium: luminal membranes of
proximal tubules
Movement
of a substance across a
membrane in combination with a
carrier protein but against an
electrochemical gradient
Directly
requires metabolic energy (i.e.
hydrolysis of ATP)
Saturable (has a Vmax)
Structural specificity and affinity of the
carrier for the substance transported
 Na+-K+
ATPase
 H+ ATPase
 H+-K+ ATPase
 Ca+2 ATPase
In
renal tubular cells found only in
basolateral membrane
When ATP is hydrolyzed, 2 K+ ions are
pumped into the cell and 3 Na+ ions are
pumped out
Maintains favorable electrochemical gradient
for Na+ entry at luminal membrane
Maintains cell membrane potential
difference and intracellular osmolality
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+
Tubular lumen
Na+
pump
Interstitial space
Two
substances interact with one specific
carrier in the cell membrane and both
substances are translocated across the
membrane
 Co-transport
Transported substances move in
the same direction across the membrane
 Counter-transport Transported substances
move in opposite directions across the
membrane
Transcellular K+
50%
Paracellular = 50%
LUMINAL
Glucose, Pi
amino acids
Na+
HCO3-
Na+
+ H+
H2CO3
BASOLATERAL
2 K+
3 Na+
K+
“Uphill”
transport of one substance is
linked to “downhill” transport of
another substance
Carrier must be occupied by both
substances (or be unoccupied) to be
mobile in the membrane
Saturable (has a Vmax)
Glucose,
amino acids, or phosphate
with sodium in luminal membranes of
proximal tubules
Sodium and hydrogen ions in luminal
membranes of proximal tubules.
Na-K-2CL transport in the thick
ascending limb of Henle
Urea
is passively reabsorbed in the
proximal tubule
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.
What do the kidneys do?
Thick ascending : Na-K2Cl co-transport
Descending limb: 25%
H2O2 absorption
The glomeruli “non-discriminantly” filter the blood, and the tubules take back
what the body needs leaving the rest as waste to be excreted. Some wastes also
can be actively added to the tubular fluid.