™The glomerulus has a high filtration rate: about
180 litres a day
(Glomerular Filtration Rate
- GFR)
Absorption Mechanisms of Salt
and Water in the Renal Tubule
™Sodium is high in the extracellular fluid and low
inside cells (intracellular).
™Therefore Na is high in plasma, and when
plasma is filtered by the glomerulus, the
resulting filtrate is also high in sodium
™Little Na reaches the final urine, so the bulk of
Na, and following water, is absorbed as the
filtrate travels along the renal nephron (tubule)
Conservation of sodium by the different segments of the
nephron
Distal tubule
5%
1260 mEq/day
Proximal tubule
67%
16,800 mEq/day
Collecting duct
3%
750 mEq/day
Thick ascending limb
25%
6300 mEq/day
Expression of Na and Water
Transporters/Channels Along
Nephron
™Expression of Na transporters is specific for
each segment of the nephron
™Some segments are only permeable to
water, other are impermeable to water,
some are permeable to both Na and water
Urine Flow = 1500ml/day
Urine Na Conc = 100mEq/L
Approx 0.6 % of filtered load excreted
Or 99.4% reabsorbed
Sodium Absorption in Proximal Tubule
Apical Renal Sodium Transporters and Water Channels
SGLT1
Sodium Glucose
Cotransporter
PT + TDL= AQP1
Cortex
Medulla
1
Sodium Absorption in Proximal Tubule
Renal tubules have a finite capacity
to reabsorb glucose
SGLT1
Sodium Glucose
Cotransporter
™If glucose concentrations in the blood exceed
the tubular transport capacity of SGLT
glucose is seen in the urine
™Urine test for diabetes – glucose stick
NHE3
Sodium Hydrogen
Exchanger
NaPi2
Sodium Phosphate
Cotransporter
AQP1
Aquaporin 1
Iso
- osmotic movement of Na and water
Proximal tubule
NHE3
AQP1
Glomerulus
Thin Descending Limb
™Only H20 transport in this region
™Aquaporin-1 present
™No Na movement in this segment
Only H20 Movement in Descending Limb
Apical Renal Sodium Transporters and Water Channels
Proximal tubule
NHE3
AQP1
Glomerulus
PT + TDL= AQP1
Cortex
Medulla
Thin Descending
Limb of
Henle’s Loop
AQP1
2
Sodium Absorption in Thick Ascending Loop
Proximal tubule
NHE3
X
NKCC2
Bumetanide/
Furosemide
AQP1
Thick
Ascending
Limb
Glomerulus
Diuretics (cause increased
urine flow) used to treat
high blood pressure
Sodium Potassium
2Chloride Cotransporter
Thin Descending
Limb of
Henle’s Loop
NHE3
Sodium Hydrogen
Exchanger
Sodium Absorption in Distal Convoluted Tubule
Apical Renal Sodium Transporters and Water Channels
X
Cortex
PT + TDL= AQP1
AQP1
Medulla
NaCl/TSC
Thiazides
Diuretic used to treat
high blood pressure
Sodium Chloride
Cotransporter/
Thiazide sensitive
cotransporter
Proximal tubule
NHE3
AQP1
Thick
Ascending
Limb
Distal Convoluted
Tubule
Apical Renal Sodium Transporters and Water Channels
Glomerulus
CCD= AQP2
AQP3
PT + TDL= AQP1
Cortex
Medulla
IMCD= AQP2
AQP4
Thin Descending
Limb of
Henle’s Loop
AQP1
3
Sodium Absorption in Collecting Duct
Proximal tubule
NHE3
AQP1
Thick
Ascending
Limb
Distal Convoluted
Tubule
Glomerulus
ENaC
X
Amiloride
Diuretic used to treat
high blood pressure
(potassium sparing)
Epithelial
Sodium Channel
Thin Descending
Limb of
Henle’s Loop
Apical Renal Sodium Transporters and Water Channels
AQP1
Collecting Duct Water
Permeability is regulated
CCD= AQP2
AQP3
Cortex
PT + TDL= AQP1
Collecting
Duct
™ADH – Anti Diuretic Hormone
also called vasopressin
Medulla
IMCD= AQP2
AQP4
Concentrating mechanism when vasopressin is low
NHE3 +AQP1
™Activates the insertion of the water channel,
aquaporin-2, into the apical membrane
High vasopressin = Formation of concentrated urine
NHE3 + AQP1
AQP2
AQP1
AQP1
A
Q
P
2
4
Vasopressin Secretion Pathway
Vasopressin signaling in collecting duct
Pituitary
AQP3/AQP4
Osmoreceptors
VP
Hypothalamus
Baroreceptor inputs
H20
AQP2
AQP2
H20
Gs
BLOOD
ADH
V2
AC
VI
ATP
LUMEN
cAMP
PKA
?
Gene regulation Nucleus
Urine is concentrated and flow reduced
5