From Finch to Fish to Man: Role of Body Fluid Volume Regulation

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From Finch to Fish to ManRole of Body Fluid
Volume Regulation

• Robert W. Schrier, MD
• Professor of Medicine
• University of Colorado
• School of Medicine

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Darwins Origin of the Species
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The constancy of the Milieu Intérieur is the
condition of free and independent existence

• Claude Bernard
• 19th Century French Physiologist

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The kidney presents in the highest degree the
phenomenon of sensibility the power of
reacting to various stimuli in a direction which
is appropriate for the survival of the organism
a power of adaptation which gives one the idea
that its component parts must be endowed with
intelligence.

• E.H. Starling
• The Fluids of the Body
• The Harter Lectures, 1909

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BODY FLUID DISTRIBUTION

• COMPARTMENT AMOUNT
  VOLUME IN
• 70 KG MAN
• Total Body Fluid 60 of Body Weight 42.0
  liters
• Intracellular Fluid 40 of Body Weight
  28.0 liters
• Extracellular Fluid
• (ECF) 20 of Body Weight 14.0
  liters
• Interstitial Fluid Two-thirds of ECF
  9.4 liters
• Plasma Fluid One-third of ECF 4.6
  liters
• Venous Fluid 85 of Plasma Fluid 3.9
  liters
• Arterial Fluid 15 of Plasma Fluid 0.7
  liters

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Sodium and Water Retention with Plasma Volume
Expansion in Edematous Disorders
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Body Fluid Volume Regulation Hypothesis
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Volume Regulatory Hypothesis
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NEW YORK HEART ASSOCIATIONCLASSES OF CARDIAC
FAILUREASSOCIATED HEMODYNAMIC AND
HORMONAL CHANGES
CLASS II
CLASS III
CLASS IV

• Cardiac Index
• Plasma Hormones
• (AVP, Renin,
• Aldosterone, NE)
• Plasma Volume

Normal
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PRETREATMENT SERUM SODIUM CONCENTRATION
CORRELATES WITH PLASMA RENIN ACTIVITY IN PATIENTS
WITH SEVERE HEART FAILURE
r0.68 pPlasma Renin Activity (ng/ml/hr)
Pretreatment Serum Na Concentration (mEq/L)
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Pretreatment Hyponatremia Predicts an Unfavorable
Prognosis in Patients with Heart Failure
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Evidence for Non-Osmotic Release of Vasopressin
in Hyponatremic Patients with Congestive Heart
Failure
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Frank-Starling Curve in Normal Subjects and
Patients with Heart Failure
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Cardiac Index in Cardiac Failure Patients Before
and During After-Load Reduction
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Water Excretion in Cardiac Failure Patients
Before and During After-Load Reduction
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Plasma Effective Osmolality and Minimum Urinary
Osmolality in Cardiac Failure Patients Before and
During After-Load Reduction
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Arginine Vasopressin in Cardiac Failure Patients
Before and During After-Load Reduction
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AVP-mRNA in the Hypothalamus of Sham and Chronic
Cardiac Failure (CCF) Rats
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V2 Receptor Blockade Prevents the Impaired Water
Excretion in Rats with Heart Failure
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Selective V2 Receptor Antagonism Decreases
Urinary Osmolality in Patients with Chronic Heart
Failure
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Selective V2 Receptor Antagonism Increases Serum
Sodium in Patients with Chronic Heart Failure
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The Intracellular Action of the Antidiuretic
Hormone, Arginine-Vasopressin
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Effects of V2 Antagonist on AQP2 Protein in CHF
Rats
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The Relationships between Plasma AVP Levels and
Urinary Excretion of AQP2 in Normal Subjects
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Selective V2 Receptor Antagonism Decreases
24-Hour Urinary AQP2 Excretion in Human Heart
Failure
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Edematous Disorders
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Role of Distal Sodium Delivery in States of
Arterial Underfilling
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Reversal of Sodium Retention with Aldosterone
Antagonism in Heart Failure Patients
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Infused ANP Causes Natriuresis in Normal Subjects
but not in CHF Patients
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Plasma Atrial Natriuretic Peptide Correlates with
Urinary cGMP in Heart Failure Patients
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Effect of Renal Denervation to Reverse Atrial
Natriuretic Peptide Resistance in Experimental
Congestive Heart Failure in Rats
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Peripheral Arterial Vasodilation
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Baseline Hemodynamic Data in Control Rats and
Rats with High Output Cardiac Failure Secondary
to Aorto-Caval Fistula
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Hormonal Results in Control rats and Rats with
High Output Cardiac Failure Secondary to
Aorto-Caval Fistula
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Body Fluid Volume Regulation Hypothesis
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The Pathophysiology of Heart Failure
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