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

Regulation

Robert W. Schrier, MDProfessor of MedicineUniversity of Colorado

School of Medicine

Darwin’s Origin of the Species

“The constancy of the Milieu Intérieur is the condition of free and

independent existence”

Claude Bernard19th Century French Physiologist

“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. StarlingThe Fluids of the Body The Harter Lectures, 1909

BODY FLUID DISTRIBUTION

COMPARTMENT AMOUNT VOLUME IN 70 KG MAN

Total Body Fluid 60% of Body Weight 42.0 litersIntracellular Fluid 40% of Body Weight 28.0 litersExtracellular Fluid (ECF) 20% of Body Weight 14.0 litersInterstitial Fluid Two-thirds of ECF 9.4 litersPlasma Fluid One-third of ECF 4.6 litersVenous Fluid 85% of Plasma Fluid 3.9 litersArterial Fluid 15% of Plasma Fluid 0.7 liters

Sodium and Water Retention with Plasma Volume Expansion

in Edematous Disorders

Body Fluid Volume Regulation Hypothesis

Volume Regulatory Hypothesis

NEW YORK HEART ASSOCIATIONCLASSES OF CARDIAC FAILURE:

ASSOCIATED HEMODYNAMIC AND

HORMONAL CHANGES

Cardiac Index

Plasma Hormones

(AVP, Renin,

Aldosterone, NE)

Plasma Volume

CLASS II CLASS III CLASS IV

Normal

Plasma Renin

Activity

(ng/ml/hr)

r=0.68p<0.001logey=0l7x+24.32n=96SEE=0.94

Pretreatment Serum Na Concentration (mEq/L)

PRETREATMENT SERUM SODIUM CONCENTRATION CORRELATES WITH PLASMA RENIN ACTIVITY IN

PATIENTS WITH SEVERE HEART FAILURE

Pretreatment Hyponatremia Predicts an Unfavorable

Prognosis in Patients with Heart Failure

Evidence for Non-Osmotic Release of Vasopressin in Hyponatremic Patients with Congestive Heart Failure

Frank-Starling Curve in Normal Subjects and Patients with

Heart Failure

Cardiac Index in Cardiac Failure Patients Before and During

After-Load Reduction

Water Excretion in Cardiac Failure Patients Before and During After-Load Reduction

Plasma Effective Osmolality and Minimum Urinary

Osmolality in Cardiac Failure Patients Before and During

After-Load Reduction

Arginine Vasopressin in Cardiac Failure Patients Before and During After-Load Reduction

V2 Receptor Blockade Prevents the Impaired Water Excretion in

Rats with Heart Failure

Selective V2 Receptor Antagonism Decreases Urinary

Osmolality in Patients with Chronic Heart Failure

Selective V2 Receptor Antagonism Increases Serum

Sodium in Patients with Chronic Heart Failure

The Intracellular Action of the Antidiuretic Hormone, Arginine-

Vasopressin

Effects of V2 Antagonist on AQP2 Protein in CHF Rats

The Relationships between Plasma AVP Levels and

Urinary Excretion of AQP2 in Normal Subjects

Selective V2 Receptor Antagonism Decreases 24-

Hour Urinary AQP2 Excretion in Human Heart Failure

Edematous Disorders

Role of Distal Sodium Delivery in States of Arterial Underfilling

Reversal of Sodium Retention with Aldosterone Antagonism in

Heart Failure Patients

Infused ANP Causes Natriuresis in Normal Subjects but not in

CHF Patients

Plasma Atrial Natriuretic Peptide Correlates with Urinary cGMP in Heart Failure Patients

Effect of Renal Denervation to Reverse Atrial

Natriuretic Peptide Resistance in Experimental

Congestive Heart Failure in Rats

Peripheral Arterial Vasodilation

Baseline Hemodynamic Data in Control Rats and Rats with High

Output Cardiac Failure Secondary to Aorto-Caval

Fistula

Hormonal Results in Control rats and Rats with High Output Cardiac Failure Secondary to

Aorto-Caval Fistula

Body Fluid Volume Regulation Hypothesis

The Pathophysiology of Heart Failure