Gilbert--Tubular Transport
Renal – 12.2.09
Ion
Na+
K+
Intracellular and extracellular ion conc
-knowing Na & K conc will help you work through
problems
Transport mechanisms:
Paracellular: between cells via diffusion
Transcellular: through cells via passive diffusion & active transport.
Transport
Definition
Renal location
Ions
Simple
Passive movement down conc
diffusion
grad directly through mem or
through channel
Facilitated
Substrate binding induces conf
Na transporters
diffusion
change in carrier protein, no ATP
used
Primary
ATP used to transport ions
Na/K ATPase on Na/K ATPase, H+,
Active
against grad. Antiporters,
basolateral mem and Ca++
transport
symporters & cotransporters
of tubular cells
Secondary
No ATP, need carrier protein,
Luminal mem of
Na/glucose,
active
often transported along gradient.
tubular cells.
Na+/Ca++,
transport
Cotransporters &
Na+/H+ countercountertransporters
transporters
Primary active transport
Intracellular
142 mEq/L
4 mEq/L
1
extracellular
10 mEq/L
140 mEq/L
Simple v. facilitated diffusion:
Simple: linear relationship, as
conc inc, diffusion rate inc. no
Vmax
Facilitated: Vmax occurs when
transporters are saturated.
Secondary active transport
Left: secondary
active transport
-Na/Glucose &
Na/AA
cotranasporters into
tubular cell from
lumen.
-Na grad maintained
by Na/K ATPase
pump
-Glucose & AA enter
interstium.
-Na/H
countertransporter.
Above: Reabsorption from renal tubules:
-water & solutes reabsorbed via paracellular &
trascellular processes from lumen  blood.
-move from interstium  bld vis bulk flow
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Gilbert--Tubular Transport
Renal – 12.2.09
Transporting solute and water from tubule to capillary (Left)
1: active extrusion of sodium into the interstitium which induces a
parallel transport of anions 
2: The movement of Na & anions generates an osmotic drive  3. that
causes reabsorption of water.  4. Finally, the inc vol in the interstitium
alters peritubular Starling forces & induces the bulk flow of water &
solute from interstitium into the peritubular capillary
Transport Maximum
Some substances have a max rate of tubular transport due
to saturation of carriers, limited ATP, etc.
• Transport Maximum: Once the transport maximum is
reached for all nephrons, further inc in tubular load are not
reabsorbed; they are excreted.
-example: sugar in bld, excess is excreted
•Threshold: 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
Left: Glucose transport max (Tm) -- good buffering system
-Filtration: via passive diffusion (linear, RED)
-reabsorption: via facilitated diffusion (Vmax, BLUE)
-excretion: what is left in lumen
-threshold dif from transport max due to nephron
heterogeneity.
Conc of solutes in different parts of the tubule depend on relative reabsorption of the solutes
compared to water
• if water is reabsorbed to a greater extent than the solute, the solute will become more
concentrated in the tubule (e.g. creatinine, inulin)
• if water is reabsorbed to a lesser extent than the solute, the solute will become less
concentrated in the tubule (e.g. glucose, amino acids)
Ion Reabsportion:
-Na reabsportion occurs mainly at proximal convoluted tubules, some at
distal convoluted
tubules, none in collecting duct.
-Water, chloride, and urea reabsorption are coupled with sodium
reabsorption
-WHEREVER THE Na GOES,
THE WATER WILL FOLLOW.
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Gilbert--Tubular Transport
Renal – 12.2.09
Transport Characteristics of dif portions of the nephron
Reabsorbed
secreted
Prox. Tubule
Cl-, Na, HCO3, K, H20,
Drugs (penicillin,
glucose, amino acids
salicylates), bile salts,
oxalate, urate,
Catecholamines, PAH
Loop of Henle:
3 seg listed below:
Thin descending LH Very permeable
to H2O, moderately
permeable to
Most solutes including urea
and sodium
Thin ascending LH
Thin Ascending limb not
permeable to H2O
Thick ascending LH 25% of filtered load!
Secretion of H+not
+
+
Reabsorption of Na , Cl , K ,
permeable to H2O
HCO3-, Ca++, Mg++
Early Distal Tubule
Active reabsorption of Na+,
Not permeable to water
Cl-, K+, Mg++
(called diluting segment)
• not very permeable to
• ~ 5% of filtered load
urea
NaCl reabsorbed
Late Distal Tubule
permeablility to H2O
depends on ADH
-Na, K, Ca, Bicarb
• not very permeable to
urea
-K & H+
Medullary collecting
duct
permeablility to H2O
depends on ADH
-Na, urea, bicarb, urea
H+
Pharm
Notes
In cortex, at top of
conc grad where
everything is
isosmotic
-loop diuretic hit
Na/2Cl/K transporter
Hypoosmotic
Thiazide Diuretics:
- chlorothiazide
- hydrochlorothiazide
blk Na/Cl cotransporter
Contains macula
densa: key for
tubulargolmerular
feedback,
Production of
renin-ang system
to maintain GFR.
-Principle cells:
aldosterone acts
on, secrete K
-intercalated cell:
respond to ADH,
acid/base –
secrete H+
Aldosterone antagonists
- Spironolactone
- Eplerenone
-blk Na/K ATPase & Na
channel
Na+ channel blockers:
- Amiloride
- Triamterene
Prox tubule
Left: Prox. Tubule transport
charac:
-Na & Cl: don’t change relative to
plasma cuz of isoosmotic cortex
-Creatine: inc cuz filtered but not
reabsorbed.
-bicarb, glucose & AA dec in
lumen cuz reabsorbed.
Loop of Henle
Gilbert--Tubular Transport
Renal – 12.2.09
Collecting Tubules
Below: Na, K, Cl transport in thick ascending
loop of Henle
4
Medullary collecting duct:
Gilbert--Tubular Transport
– 12.2.09
Lots of waterRenal
transport
but tightly reg
by ADH.
Regulation of Tubular Reabsorption
System/force
Effect
Glomerulotubular
-As tubular load inc, so
Balance
does tubular
reabsorption.
Reabsorption rate is
maintained, amt inc
-minimized changes in
urine vol as tubular
load changes
Peritubular Physical
-Balance of oncotic &
Forces
hydrostatic pressures
-net reabsorptive
pressure ~ 10 mmHg,
fluid & solutes to be
reabsorbed into the
peritubular caps
Aldosterone
-Inc Na reabs @
principle cells
-Inc K secrete @
principle cells
-inc H+ secrete @
intercalated cells
-inc Aldo secretion:
Ang II, K, ACTH,
dec Aldo secretion:
ANF, inc Na conc
Angiotensin II
Inc water and Na
retention
-inc Aldo secretion
Directly inc Na reabs
ADH
Atrial natriuretic horm
Parathyroid hormone
Sympathetic NS
- dec peritubular cap
hydrostatic P
- inc filtration fraction
 incs peritubular
colloid osmotic P
Inc perm to H20
Inc GFR
Dec renin, Ang II, Adlo
Dec NaCl & H2O reabs
Dec ADH secretion &
actions
Inc NaCl reabs
5
Location
Proximal tubule
notes
Peritubular caps
late distal, cortical and
medullary collecting
tubules
•deficiency - Addison’s
disease Na+ wasting,
hyperkalemia,
hypotension
• Excess - Conn’s
syndrome Na+
retention,
hypokalemia, alkalosis,
HTN
proximal, loop, distal,
collecting tubules
From constriction of
efferent arterioles
Blocking Ang II w/
ACEi & Ang II
antagonist  dec Aldo,
dec Na reabs, dec
efferent art R, 
naturesis & diuresis 
dec BP
CD  inc H20 reabs 
dec urine flow & inc
urine osmolarity
Glomerulus
JGA, adrenal cortex
Collecting duct (CD)
Post pituitary & CD
-Secreted by atria in
resp to stretch (inc vol)
-minimizes bld vol
expansion
Prox tubule, TAL, DT,
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Gilbert--Tubular Transport
Renal – 12.2.09
CD  inc H20 reabs
(not TAL cuz imperm)
Atrial Pressure
(pressure natriuresis)
Stim renin release
Dec GFR & renal bld
flow
• Inc peritubular cap
hydrostatic pressure
• Dec renin & aldo
• Inc release of
intrarenal natriuretic
factors: PG & EDRF
Afferent arteriole
constriction
Peritubular caps
Reabsorption by the Peritubular Capillaries
Kf = filtration coeffient (leakiness)
Colloid onoctic pressure = osmotic forces from proteins.
Osmotic pressure = from anything that has a charge.
Gilbert--Tubular Transport
Renal – 12.2.09
7
As there are inc in Na, your plasma vol inc, CO inc, if you have more vol in the
CV system the pressure will inc. The pressure inc until the pressure
naturesis mech is activated in kidney. When that occurs it will gradually
shift to the left over a couple of days. If the person is salt senstive, the curve
will shift right but reach a new steady state.
Aldosterone Escape: (Above)
Acute phase = excess Na retention  as the Na is retained
the BP will be inc once the BP maxes out Na excretion
will reach a steady state again
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Gilbert--Tubular Transport
Renal – 12.2.09
Practice Questions:
Know:
•Transport mechanisms: proximal tubule, loop of
Henle, distal and collecting tubules
• Physiological regulators of tubular transport
-Physiological Regulators of Tubular Reabsorption
-Factors that Cause Abnormal Increases in Tubular
Reabsorption (disordersO
Answers:
1. A.1/3 water remains
B. 1/8 water remains
C. 1/50 water remains
2. Renin tumor: Na reabs
3. Liddle’s syndrome: excessive Na reabs
4. Conn’s Syndrome: Na reabs
5. inappropriate ADH syndrome: water reabsorption