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