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  1. 1. Control of Extracellular Fluid Osmolarity and Sodium Concentration<br />Regulation of extracellular fluid osmolarity and sodium concentration are closely linked <br />Osmolarity averages about 300 mOsm/L<br />Osmolarity must be precisely controlled because they determine the distribution of fluid between the intracellular and extracellular compartments.<br />
  2. 2. Estimating Plasma Osmolarity from Plasma Sodium Concentration<br />Plasma osmolarity (Posm) can be roughly approximated as<br /> Posm = 2.1 x Plasma Na concentration<br />The sodium ions in the extracellular fluid and associated anions are the principal determinants of fluid movement across the cell membrane<br />The control of osmolarity and control of sodium ion concentration are related<br />
  3. 3. Two primary systems are especially involved in regulating the concentration of sodium and osmolarity of extracellular fluid<br />The osmoreceptor-ADH system<br />(2) The thirst mechanism<br />
  4. 4. Osmoreceptor-ADH feedback system<br />When osmolarity increases above normal because of water deficit<br />An increase in extracellular fluid osmolarity causes the special nerve cells called osmoreceptor cells, located in the anterior hypothalamus to shrink. <br />Osmoreceptor cells send nerve signals to additional nerve cells in the supraoptic nuclei, which then relay these signals down the stalk of the pituitary gland to the posterior pituitary. <br />These action potentials stimulate the release of ADH, which is stored in secretory granules in the nerve endings. <br />
  5. 5. ADH enters the blood stream and is transported to the kidneys, where it increases the water permeability of the late distal tubules, cortical collecting tubules, and medullary collecting ducts. <br />The increased water permeability causes increased water reabsorption and excretion of a small volume of concentrated urine. <br />Water is conserved in the body while sodium and other solutes continue to be excreted in the urine and correcting the initial excessively concentrated extracellular fluid<br />
  6. 6. Osmoreceptor-antidiuretic hormone (ADH) feedback mechanism for regulating extracellular fluid osmolarity in response to water deficit<br />
  7. 7. ADH acts on Collecting Duct <br />
  8. 8. Cardiovascular Reflex Stimulation of ADH Release by Decreased Arterial Pressure and/or Decreased Blood Volume<br />ADH release is also controlled by cardiovascular reflexes that respond to decreases in blood pressure and/or blood volume<br />The arterial baroreceptor reflexes which originate in high-pressure regions of the circulation, such as the aortic arch and carotid sinus, and in the low-pressure regions, especially in the cardiac atria. <br />Afferent stimuli are carried by the vagus and glossopharyngeal nerves in the nuclei of the tractus solitarius. <br />Projections from these nuclei relay signals to the hypothalamic nuclei that control ADH synthesis and secretion<br />
  9. 9. Regulation of ADH secretion<br />
  10. 10. Role of Thirst in Controlling Extracellular Fluid Osmolarity and Sodium Concentration<br />Many of the same factors that stimulate ADH secretion also increase thirst, which is defined as the conscious desire for water <br />The most important stimulus is increased extracellular fluid osmolarity, which causes intracellular dehydration in the thirst centers<br />This helps to dilute extracellular fluids and returns osmolarity toward normal<br />
  11. 11. Control of thirst<br />
  12. 12. Effect of large changes in sodium intake on extracellular fluid sodium concentration in dogs under normal conditions (red line) and after the antidiuretic hormone (ADH) and thirst feedback systems had been blocked (blue line). Note that control of extracellular fluid sodium concentration is poor in the absence of these feedback systems<br />
  13. 13. Role of Angiotensin II and Aldosterone <br />Both angiotensin II and aldosterone play an important role in regulating sodium reabsorption by the renal tubules<br />When sodium intake is low, increased levels of these hormones stimulate sodium reabsorption by the kidneys<br />These hormones increase the amount of sodium in the extracellular fluid, they also increase the extracellular fluid volume by increasing reabsorption of water along with the sodium<br />Angiotensin II and aldosterone have little effect on sodium concentration<br />
  14. 14. Regulation of Potassium Excretion and Potassium Concentration in Extracellular Fluid<br />Extracellular fluid potassium concentration normally is about 4.2 mEq/L <br />Increase in plasma potassium concentration (Hyperkalemia) can cause cardiac arrhythmias, and higher concentrations can lead to cardiac arrest <br />Loss of potassium from the extracellular fluid (Hypokalemia) could cause muscle weakness and depress reflexes<br />
  15. 15. Regulation of Internal Potassium Distribution<br />Insulin Stimulates Potassium Uptake into Cells: Insulin increases cell potassium uptake<br />Aldosterone Increases Potassium Uptake into Cells: Increased potassium intake stimulate secretion of aldosterone which increase cell potassium uptake<br />Acid-Base Abnormalities Can Cause Changes in Potassium Distribution. Metabolic acidosis increases extracellular potassium concentration, one effect of increased hydrogen ion concentration is to reduce the activity of the sodium-potassium (ATPase) pump. This in turn decreases cellular uptake of potassium and raises extracellular potassium concentration. <br />
  16. 16. Cell Lysis Causes Increased Extracellular Potassium Concentration: As cells are destroyed, the large amounts of potassium contained in the cells are released into the extracellular compartment<br />Strenuous Exercise Can Cause Hyperkalemia by Releasing Potassium from Skeletal Muscle. During prolonged exercise, potassium is released from skeletal muscle into the extracellular fluid<br />Increased Extracellular Fluid Osmolarity Causes Redistribution of Potassium from the Cells to Extracellular Fluid. Increased extracellular fluid osmolarity causes osmotic flow of water out of the cells. The cellular dehydration increases intracellular potassium concentration, thereby promoting diffusion of potassium out of the cells and increasing extracellular fluid potassium concentration. <br />