cells extracellular fluid volume ~ 1/3 body water; osmol 290 mosm/kg h 2 0 na + 142 mm; k + 4 mm; h...

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Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) 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 urine

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Page 1: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

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

Page 2: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Kidney

Page 3: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Kidney Vasculature

Page 4: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Glomerulus

Page 5: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Nephron Circulation

Page 6: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Blood Flow in Resting Human

Organ Weightkg

RestingBlood Flow

ml/min

RestingBlood Flowml/min/100g

CardiacOutput

%

Brain 1.4 750 55 14

Heart 0.3 250 80 5

Kidneys 0.3 1,200 400 22

Liver 1.5 1,300 85 23

Muscles 35.0 1,000 3 18

Skin 2.0 200 10 4

Bone,etc.

27.0 800 3 14

RPF ~ 600 m/mi = 36L/h = 864L/day

Page 7: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Volume of Urine

~0.5-2 L/day

GFR~ 200 L/day

Page 8: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Glomerular Capillary Wall

Page 9: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Fractional Clearance Across Glomerular Capillary

Page 10: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Glomerular “Sieve”

Page 11: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Electrical Charge Effect on Fractional Clearance Across Glomerular Capillary

Page 12: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Forces Driving Filtration

Page 13: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Filtration & Reabsorption In Systemic Capillary

Page 14: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Forces Determining GFR

Systemic capillary: F = Kf x [(Pc-Pi) - (c-I)]

Glomerular capillary: GFR = Kf x [(Pgc-Pu) – (gc-u)]

Because Pu is unregulated and believed to be constant and U = 0, then

GFR = Kf x (P - gc)

Page 15: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Permeability of Glomerular Capillary

Effective Hydraulic Permeability (k) of Various Capillaries

kCapillary (Source) nl/(sec-mm Hg-cm22)

RenalGlomerular (rat) 41Peritubular (rat) 1.0

ExtrarenalCremaster muscle (rat) 0.9Mesentery (frog) 0.65-1.0Omentum (rabbit) 0.3-9.0

_______________________________________________________Glomerular Ultrafiltration, W. M. Dean et al., 1974.

Page 16: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Pressures Inside the Renal Circulation

Page 17: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Filtration Pressures in Glomerular Capillary

Page 18: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

PUF

1010

2020

3030

4040

P = PGC-PU

mm Hg

Filtration Pressures in Glomerular Capillary

GC

GFR=Kf x (P - GC) = Kf x PUF

Page 19: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

PUF

PUF PUF P

GC

GC

GC

P P

Control Angiotensin II ANP

AA AA AAEE EE EE

Distance Along Glomerular Capillary

mm

Hg

1010

3030

Factors Regulating PGC

Page 20: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Volume of Urine

GFR~ 50 -200 L/d

Urine, ~ 0.5 – 15 L/d

Page 21: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Nephron Capillaries

Page 22: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Filtration & Reabsorption In Systemic Capillary

Page 23: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

PR = Kf (C - i) – (PC- Pi)

PR = Kf ( - P)

Starling’s Forces in Peritubular Capillary

Page 24: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

mm

Hg

PRPR

PUF

PUF

Control Angiotensin II

GC

Pglomerular

P (PGC – PU)

peritubular peritubularglomerular

P

GC

Distance Along Capillary

10

30

P

Glomerular and Peritubular Starling Forces

Page 25: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Renin-Angiotensin System

angiotensinogen

angiotensin I

converting enzyme

angiotensin II

renin

vasoconstriction

efferent constriction; net PT reabsorption

increases PT reabs

Page 26: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Angiotensin II Direct Effects on Kidney Function

1 - constricts Efferent Arteriole: PGC and GC ;

does not change GFR but peritubular

capillary and, therefore, net Proximal

Tubule sodium reabsorption

2- directly Proximal Tubule Na+ transport

Page 27: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Renin-Angiotensin System

angiotensinogen

angiotensin I

converting enzyme

angiotensin II

renin

vasoconstriction aldosterone; CD reabsorption

efferent constriction; PT reabsorption

Page 28: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Aldo

Aldosterone Effect on Na+ and K+ in the Collecting Duct

Page 29: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Fractionin urine(x 100)

Fractional Na+in Urine along the Nephron

Angio II Aldosterone

Page 30: Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) Intake: Na + ~ 5-200 mmoles/day K

Measurement of GFR

If a substance is freely filterable, then its rate of filtration is,

Plasma [x] x GFR vol/time

The rate of urinary excretion of any substance is,Urine [x] x Urine volume/time

If all of x that is filtered appears in the final urine, then we have

P[x] x GFR = U[x] x V and,

GFR = U[x] x V / P[x]