Regulation of Body Fluid Balance

Osmotic Relations Between Intracellular Fluid, Interstitial Fluid and Plasma

proteinNa+

protein

Na+

H2O

K+

H2O

K+

Na+

K+

Plasma

Intracellular fluid

Interstitial fluid

Crucial points

• Animal plasma membranes are so delicate that no osmotic gradient between ISF and ICF can exist.

• Only impermeant solutes can act as osmotic effectors• Cytoplasmic protein is the major osmotic effector of the

ICF; its osmotic effect is balanced by the transmembrane Na+ gradient, otherwise cells would swell.

• Plasma proteins are the major osmoeffectors of plasma – they counteract the effect of capillary hydrostatic pressure.

• Na+ is the major osmoeffector of ECF versus ICF. ECF volume closely tracks total body Na+ content.

Characteristics Of ICF and ECF Compartments

30 L total volume

9000 mOsm total solute

Posm = 300 mOsm

15 L total volume

4500 mOsm total solute

2175 mEq total Na+

[Na+] = 145 mEq/L

Posm = 300 mOsm

Intracellular Fluid Extracellular Fluid

The ECF consists of the ISF compartment and the plasma compartment

15 L total volume

4500 mOsm total solute

2175 mEq total Na+

Posm = 300 mOsm

Extracellular Fluid

Interstitial Fluid Plasma

11.25 L total volume

3375 mOsm total solute

Posm = 300 mOsm

3.75 L total volume

1125 mOsm total solute

Posm = 300 mOsm

There are three basic homeostatic challenges

• Gain or loss of isotonic solution– Affects only the ECF volume

• Gain or loss of pure water– Both ICF and ECF compartments change volume

proportionately – osmotic concentration changes in each are equal

• Gain or loss of pure salt– Na+ is confined to the ECF compartment – loss results

in volume shift from ECF to ICF; gain results in volume shift from ICF to ECF.

Regulation of Renal Function

• Intrinsic

• Baroreceptor Reflex

• Three endocrine systems– ADH system– Renin-Angiotensin-Aldosterone System– Atrial Natriuretic Hormone system

Intrinsic regulationBlood Volume

Arterial Blood Pressure

GFR

Intrinsic regulation + Baroreceptor reflex

Blood Volume

Arterial Blood Pressure

GFRBaroreceptor Reflex

Afferent arteriole dilates

ADH system“Peripheral volume receptors” are stretch receptors located in the right atrium – increased stretch signals a plasma volume increase and exerts an inhibitory effect on ADH secretion

Osmoreceptor cell bodies are in ventromedial hypothalamus – sensitive mainly to [Na+]

ADH = arginine vasopressin – an octapeptide with two major peripheral effects:

Increased water permeability of collecting duct

Vasoconstriction (at high levels)

Response of ADH system in gain of pure water

Response of ADH system to loss of pure water

The Renin-Angiotensin-Aldosterone System – response to loss of pure Na+ or loss of isotonic

solution

• Macula densa (Juxtaglomerular apparatus) secretes renin (a protease) when: – Blood [Na+] falls below normal– Glomerular blood volume flow decreases

Angiotensin cascade

Angiotensinogen

Angiotensin I

Angiotensin II

Aldosterone

Renin

Angiotensin Converting Enzyme (ACE) in lung

Adrenal Cortex

Distal tubule (also sweat glands, salivary glands, colon, etc. Increased Na+ reabsorption

3 Major factors that increase Aldo secretion

Adrenal Cortex

Angiotensin II

Increased Plasma [K+]

Adrenocorticotrophic Hormone (ACTH)

Kidney distal tubule

Na+ reabsorption

K+ secretion

H+ secretion

Aldosterone

Aldosterone effects

• Steroid hormone that increases expression of Na+/K+ ATPase in target epithelia

• Directly regulates total body Na+ - Indirectly regulates ECF volume.

• Also involved in K+ regulation – by a direct effect on the adrenal cortex: increased plasma [K+] increases aldo secretion

Atrial natriuretic peptide – response to gain of isotonic solution

• Stretched atria release 22 aa peptide which – increases GFR by vasodilating renal afferent

arterioles and constricting efferent arterioles– Inhibits Aldo secretion and antagonizes

tubular effect of aldosterone– Inhibits ADH secretion and blocks its action

• Causes marked diuresis (volume loss) and natriuresis (net loss of Na+ )

Study Goals

• Be able to trace the responses of each of the 3 major renal endocrine systems to each of the 3 simple homeostatic challenges.

• Integrate your understanding of these systems with what you know about the baroreceptor reflex and capillary filtration to arrive at a complete picture of whole-body responses to blood loss and plasma volume expansion – i.e. short term and long term regulation of mean arterial pressure.