1. Regulation of Body Fluid Balance

2. Osmotic Relations Between Intracellular Fluid, Interstitial Fluid and Plasma protein Na + protein Na + H2OH2O K+K+ H2OH2O K+K+ K+K+ Plasma Intracellular fluid Interstitial fluid

3. 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.

4. 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

5. 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

6. 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.

7. Regulation of Renal Function Intrinsic Baroreceptor Reflex Three endocrine systems –ADH system –Renin-Angiotensin-Aldosterone System –Atrial Natriuretic Hormone system

8. Intrinsic regulation Blood Volume Arterial Blood Pressure GFR

9. Intrinsic regulation + Baroreceptor reflex Blood Volume Arterial Blood Pressure GFR Baroreceptor Reflex Afferent arteriole dilates

10. 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)

11. Response of ADH system in gain of pure water

12. Response of ADH system to loss of pure water

13. 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

14. 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

15. 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

16. 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

17. 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 + )

18. 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.