Volume of Urine
Intake:
Na+ ~ 5-200 mmoles/day
K+~ 50-300
“
H20 ~ 0.5-3 L/day
H+ ~ 50-100 mEq/day
GFR
~ 50 200 L/d
Air water ~ 3000 mOsm/Kg H20
Extracellular Fluid
Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H20
Na+ 142 mM; K+ 4 mM; H+ 40 nM (pH 7.40)
Cells
Urine,
~ 0.5 – 15 L/d
How do we maintain ECF
Volume?
By keeping ECV Na+ content,
urine
Na+
EC
288
Na+
Cl- mOsm/kg
H2O intake
ADH
H2O excretion
IC
ECFV (~ 10-15 L) x [Na+] (140 mEq/L)
~ 1,400 – 2,100 mEq
Na+
H2O
fairly constant despite
variations on intake
Thirst
Osmol
EC
288
Na+
Cl- mOsm/kg
Thirst
Osmol
ADH
H2O excretion
IC
H2O
Effect of Changing NaCl in Diet
Renal Architecture
Weight
Kg
Na filtered
= GFR x PNa
10
Na+ intake
NaCl 5.0
gr
UNa+ • V
Na excreted
= V x UNa
Days
1
Nephron Segments
Fractional Na+in Urine along the Nephron
Fraction
in urine
(x 100)
% Reabsorption of Filtered NaCl
Sodium Absorption
Renal Oxygen Consumption
The Na + K + ATPase
Na
K
Entry into the Cell
down an electrochemical gradient
Na channel, or Na coupled solute carriers
Exit into the blood by the Na:K ATPase
Located in the basolateral membrane of Renal Tubular Cells
Inhibited by the cardiac glycosides digoxin and ouabain
Nielsen et al., Amer. J. Physiol.277:F257. 1999
2
Proximal Tubule Na+ Reabsorption
Tubular Segments
PCT
DCT
ThAL
CD
Glucose, AA
Na
K
Na
Na
H+
H O
2
HCO3
Na
Na/H exchanger
Na/solute co-transporter
Starling’s Forces in Peritubular Capillary
Driving Forces for Salt and Water
Absorption in the Proximal Tubule
Capillary
Trans-cellular
PR = Kf (BC - Bi) – (PC- Pi)
PR = Kf ()B - )P)
Lumen
Active transport of Na and HCO3
Intercellular Leak Starling Forces across capillary
(∆P − ∆Π )
Apical Transporters of the Thick Ascending Limb
Sodium Absorption in Thick Ascending
Limb
Na
K
CLC-Kb
NKCC
ROMK
NKCC
ROMK
NKCC
Na:K:2Cl Co-transporter
Furosemide sensitive cotransporter
ROMK K channel
CLC-Kb Chloride Channel
Nielsen et al., Amer. J. Physiol. 282: F34.2002
3
Sodium Absorption in Distal
Sodium Absorption in Collecting Duct
Tubule
TSC
Na
K
TSC
Na
K
ENaC
K
ENaC
Na:Cl Co-transporter
Thiazide sensitive cotransporter
K
Aldosterone Effect on Na+ and K+ in the
Collecting Duct
Epithelial Na Channel
Amiloride sensitive
K channel
Renin-Angiotensin System
angiotensinogen
Aldo
renin
angiotensin I
converting enzyme
angiotensin II
vasoconstriction
efferent constriction;
PT reabsorption
aldosterone; CD
reabsorption
Effect of Changing NaCl in Diet
Renal Handling of Glucose
Weight
Kg
10
Na+ intake
NaCl 5.0
gr
UNa+ • V
Days
4
Intake:
Na+ ~ 5-200 mmoles/day
K+~ 50-300
“
H20 ~ 0.5-3 L/day
H+ ~ 50-100 mEq/day
Air water ~ 3000 mOsm/Kg H20
Na+
EC
288
Na+
Cl- mOsm/kg
Thirst
H2O intake
ADH
H2O excretion
Osmol
IC
Extracellular Fluid
Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H20
Na+ 142 mM; K+ 4 mM; H+ 40 nM (pH 7.40)
Na+
H2O
Cells
EC
288
Na+
Cl- mOsm/kg
Thirst
Osmol
ADH
H2O excretion
IC
urine
H2O
Plasma ADH (AVP)
Urine/Plasma Osmolality in Rat
Posmol
290 mosm/Kg H20
Urine Osmolality as a function of Plasma
ADH
Tubular Fluid Osmolality
PCT
DCT
ThAL CD
Uosmol
max: 1200
min: 60 mosm/Kg H20
PCT iso-osmolar
ThAL hypo-osmolar
DCT hypo-osmolar
CD
hypo-osmolar in the absence of vasopressin (Antidiuretic Hormone)
hyper-osmolar in the presence of vasopressin
5
Cell Types of the Collecting Tubule
Mechanism of action of Vasopressin
Principal
Na + absorption
Water absorption
K + secretion
Intercalated H+ Transport
AQP2
ENaC
Aquaporin 2
ROMK
H + ATPase
V2R
Binds to V2 Receptor in collecting tubule
Increases production of cyclic AMP
Causes fusion of vesicles containing
Aquaporin 2 with the apical membrane
Urinary Concentration
NaCl
Urinary Concentration and Dilution
NaCl H2O H2O
NaCl
100
Descending
limb
60
H2 O
150
NaCl
Cortical
collecting
duct
Distal tubule
Cortex
300
NaClK
Medulla600
NaClK
H2 O
900
100
300
400
Ascending
limb
700
NaClK 1000
Urea
1200 H O
2
1200
H2 O
900
H2 O
900
NaCl
1000
H2 O
+ADH
600
Urea
NaClK
H2 O
H2 O
300
Medullary
collecting
duct
H2 O
25%
1200
1200
% water remaining
< 1%
900
600
Maximal
ADH
300
3%
35%
1000
Urea
1200
1400
Osmolarity (mOsm/L)
Active transport
Passive
Proximal
tubule
15%
Henle’s
loop
No ADH
Distal
tubule
Cortical
collecting
duct
10%
Medullary
collecting
duct
Urine/Plasma Osmolality in Rat
Posmol
290 mosm/Kg H20
Uosmol
max: 1200
min: 60 mosm/Kg H20
6