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Volume of Urine. GFR ~ 50 - 200 L/d. Urine, ~ 0.5 – 15 L/d. Intake : Na + ~ 5-200 mmoles/day K + ~ 50-300 “ H 2 0 ~ 0.5-3 L/day H + ~ 50-100 mEq/day. Air water ~ 3000 mOsm/Kg H 2 0. Extracellular Fluid Volume ~ 1/3 body water ; Osmol 290 mOsm/Kg H 2 0 - PowerPoint PPT Presentation
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Volume of Urine
GFR~ 50 -200 L/d
Urine, ~ 0.5 – 15 L/d
Cells
Extracellular FluidVolume ~ 1/3 body water; Osmol 290 mOsm/Kg H20Na+ 142 mM; K+ 4 mM; H+ 40 nM (pH 7.40)
Intake:Na+ ~ 5-200 mmoles/dayK+~ 50-300 “H20 ~ 0.5-3 L/dayH+ ~ 50-100 mEq/day
Air water ~ 3000 mOsm/Kg H20
urine
By keeping ECV Na+ content,
ECFV (~ 10-15 L) x [Na+] (140 mEq/L) ~ 1,400 – 2,100 mEq
fairly constant despite variations on intake
How do we maintain ECF Volume?
IC
EC Na+
Cl-288
mOsm/kgOsmol
Thirst
ADH
H2O intake
H2O excretion
EC Na+
Cl-288
mOsm/kgOsmol
Thirst
ADH H2O excretion
H2O
H2O
Na+
Na+
IC
Weight
NaClgr
10
5.0
Days
Na+ intake
UNa+ • V
Kg
Effect of Changing NaCl in Diet
Renal Architecture
Na filtered = GFR x PNa
Na excreted= V x UNa
Nephron Segments
Fractionin urine(x 100)
Fractional Na+in Urine along the Nephron
% Reabsorption of Filtered NaCl
Renal Oxygen Consumption
NaK
Entry into the Cell
down an electrochemical gradient
Na channel, or Na coupled solute carriers
Exit into the blood by the Na:K ATPase
Sodium Absorption
Located in the basolateral membrane of Renal Tubular CellsInhibited by the cardiac glycosides digoxin and ouabain
Nielsen et al., Amer. J. Physiol.277:F257. 1999
The Na + K + ATPase
PCT DCT
ThAL CD
Tubular Segments
NaK
Glucose, AA
Na
Na
H+
H2
O
Proximal Tubule Na+ Reabsorption
HCO3
Na
Na/H exchangerNa/solute co-transporter
PR = Kf (C - i) – (PC- Pi)
PR = Kf ( - P)
Starling’s Forces in Peritubular Capillary
LumenCapillary
Trans-cellular Active transport of Na and HCO3
Intercellular Leak Starling Forces across capillary(P
Driving Forces for Salt and WaterAbsorption in the Proximal Tubule
NaK
NKCC
ROMK
NKCC Na:K:2Cl Co-transporter
Furosemide sensitive cotransporter
ROMK K channel
CLC-Kb Chloride Channel
CLC-Kb
Sodium Absorption in Thick Ascending Limb
NKCC ROMK
Nielsen et al., Amer. J. Physiol. 282: F34.2002
Apical Transporters of the Thick Ascending Limb
NaK
TSC
TSC Na:Cl Co-transporter
Thiazide sensitive cotransporter
Sodium Absorption in Distal Tubule
NaK
ENaC
ENaC Epithelial Na Channel
Amiloride sensitive
K K channel
K
Sodium Absorption in Collecting Duct
Aldo
Aldosterone Effect on Na+ and K+ in the Collecting Duct
Renin-Angiotensin System
angiotensinogen
angiotensin I
converting enzyme
angiotensin II
renin
vasoconstriction aldosterone; CD reabsorption
efferent constriction; PT reabsorption
Weight
NaClgr
10
5.0
Days
Na+ intake
UNa+ • V
Kg
Effect of Changing NaCl in Diet
Renal Handling of Glucose
Cells
Extracellular FluidVolume ~ 1/3 body water; Osmol 290 mOsm/Kg H20Na+ 142 mM; K+ 4 mM; H+ 40 nM (pH 7.40)
Intake:Na+ ~ 5-200 mmoles/dayK+~ 50-300 “H20 ~ 0.5-3 L/dayH+ ~ 50-100 mEq/day
Air water ~ 3000 mOsm/Kg H20
urine
IC
EC Na+
Cl-288
mOsm/kgOsmol
Thirst
ADH
H2O intake
H2O excretion
EC Na+
Cl-288
mOsm/kgOsmol
Thirst
ADH H2O excretion
H2O
H2O
Na+
Na+
IC
Plasma ADH (AVP)
Urine Osmolality as a function of Plasma ADH
Urine/Plasma Osmolality in Rat
Posmol
290 mosm/Kg H20
Uosmol
max: 1200
min: 60 mosm/Kg H20
PCT DCT
ThAL CD
PCT iso-osmolarThAL hypo-osmolarDCT hypo-osmolarCD hypo-osmolar in the absence of vasopressin (Antidiuretic Hormone) hyper-osmolar in the presence of vasopressin
Tubular Fluid Osmolality
Binds to V2 Receptor in collecting tubule
Increases production of cyclic AMP
Causes fusion of vesicles containing
Aquaporin 2 with the apical membrane
AQP2
V2R
Mechanism of action of Vasopressin
Principal Na + absorption ENaCWater absorption Aquaporin 2K + secretion ROMK
Intercalated H+ Transport H + ATPase
Cell Types of the Collecting Tubule
DescendingDescendinglimblimb
300300
600600
900900
12001200
HH22OO
HH22OO
HH22OO
12001200
10001000
700700
NaClKNaClK
400400
100100
NaClKNaClK
NaClKNaClK
NaClKNaClK
100100
HH22OONaClNaCl HH22OONaClNaCl
6060 150150
NaClNaCl
HH22OO
NaClNaCl
CorticalCorticalcollectingcollecting
ductduct
Distal tubuleDistal tubule
Ascending Ascending limblimb
UreaUrea
300300HH22OO
600600HH22OO
UreaUrea
900900HH22OO
NaClNaCl10001000
HH22OO
UreaUrea12001200
HH22OO
300300
900900
10001000
12001200
MedullaryMedullarycollectingcollecting
ductduct
+ADH+ADH
Active transportActive transport
PassivePassive
Urinary Concentration
Cortex
Medulla
300300
600600
900900
12001200
14001400
35%35%
25%25%
15%15%
3%3%
< 1%< 1%
10%10%No ADHNo ADH
MaximalMaximalADHADH
Proximal Proximal tubuletubule
Henle’s Henle’s looploop
DistalDistaltubuletubule
Cortical Cortical collectingcollecting
ductduct
MedullaryMedullarycollectingcollecting
ductduct
Osm
olar
ity (
mO
sm/L
)O
smol
arity
(m
Osm
/L)
Urinary Concentration and Dilution
% water remaining
Urine/Plasma Osmolality in Rat
Posmol
290 mosm/Kg H20
Uosmol
max: 1200
min: 60 mosm/Kg H20