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Aims • Regulation of extracellular fluid osmolarity • Readings; Guyton, Chapter 28 Osmolarity • The osmole is the unit of measure of the # of particles of a molecule in a solution – Osmole is used in place of grams • Osmolality – # of osmoles/ kg of H2O – Measurement not used to often due to difficulty in weighing H2O in a solution. • Osmolarity •1 osmole is 1g mol. wt. of an undissociated solute. •180g of glucose= 1 osmole of glucose •58.5g of NaCl= 2 osmoles of NaCl because it dissociates into 2 ions (Na and Cl) – # of osmoles/ L of H2O – Most frequently used – For dilute solutions in the body the difference between osmolality and osmolarity is less than 1%. Antidiuretic Hormone (ADH) Control Excess H2O in the body Extracellular fluid osmolarity is reduced. The secretion of ADH is reduced. This reduces the permeability of the distal tubules and collecting tubules for water and results in a dilution of the urine. Guyton’s Textbook of Medical Physiology 28-2 Formation of Dilute Urine • When there is excess water in the body, the extracellular fluid osmolarity is reduced. • In response the kidney excretes the excess water in the form of diluted urine. • The kidney can reduce the osmolarity of the urine (dilute the urine) 6-fold. • Conversely, when there is a deficit of water the kidneys can increase the osmolarity of the urine 4-fold. • The kidneys can also adjust the volume of urine secreted. Formation of Dilute Urine • Importantly, the kidneys can adjust the osmolarity and volume of urine without impacting the rate of excretion of solutes such as Na+. Guyton’s Textbook of Medical Physiology 28-1 Formation of Concentrated Urine • Obligatory urine volume – The minimum volume of urine which must be secreted in order to secrete the necessary amount of solute. • Example – Each day Dr. Donati must excrete 600 milliosmoles of solute. – Dr. Donati’s kidneys can concentrate urine up to 1200 milliosmoles/L. 600 milliosmoles 1200 milliosmoles/L = 500 ml (Obligitory Urine Volume) • Thus, Dr. Donati must eliminate a minimum of 500 ml per day Why is it bad to drink seawater? • Question • If Dr. Donati got stranded on a desert island with his pet Australian hopping mouse Wilbur (who by the way can concentrate it’s urine to 10,000 milliosmoles/L.) who should drink the water? • Answer • The salinity of sea water is ~2400 milliosmoles/L. • Since Dr. Donati can only concentrate his urine to 1200 milliosmoles/L, he will have to urinate out 2L for every 1L he drinks. A recipe for disaster. • Wilbur on the other hand can concentrate his urine to 10,000 milliosmoles/L. Thus he can drink to his hearts delight as he will have to urinate only ~250 ml per L of sea water drunk. Requirements for the concentration of urine • High osmolarity of the renal medullary interstitial fluid. • High levels of ___________________ High osmolarity of the renal medullary interstitial fluid. Sherwood’s Human Physiology 14-27 5th Ed. & 14-24 6th Ed. High osmolarity of the renal medullary interstitial fluid. • The Countercurrent mechanism – Descending limb of the loop of Henle. • Permeable to Water – Thin Descending limb of the loop of Henle • Passive reabsorption of sodium chloride • ____________ to water. Guyton’s Textbook of Medical Physiology table 28-1 High osmolarity of the renal medullary interstitial fluid. • The Countercurrent mechanism – Thick ascending limb of the loop of Henle. Active transport of Na+ and co-transport of K+ and Cl-. Can establish a 200 milliosmole concentration gradient between the tubular lumen and the interstitial fluid. Impermeable to water. Guyton’s Textbook of Medical Physiology table 28-1 • The process of the Countercurrent Multiplier involves the repetitive reabsorption of sodium chloride from the thick ascending limb and the continued inflow of new sodium chloride from the proximal tubules. Sherwood’s Human Physiology 14-28 5th Ed. & 14-25 6th Ed. • H2O continues to be reabsorbed in the descending limb of the loop of Henle and Na+ continues to be reabsorbed in the thick ascending limb. • This creates a high osmolarity in the medullary interstitium and a lower osmolarity as we ascend to the cortical interstitium. Sherwood’s Human Physiology 14-28 5th Ed. & 14-25 6th Ed. High osmolarity of the renal medullary interstitial fluid. Urea’s contribution • Urea is passively absorbed. • Urea gets trapped in the medullary interstitium. • Absorbed in the collecting ducts. • Secreted into _________________. Guyton’s Textbook of Medical Physiology 28-5 High osmolarity of the renal medullary Urea’s contribution interstitial fluid. Sherwood’s Human Physiology 14-5 High osmolarity of the renal medullary interstitial fluid. Vasa recta’s role • Medullary blood flow is low (~1-2% of total renal blood flow). • Countercurrent exchange. – Due to U shape. – Thus, no net dilution or “wash out” of interstitial fluid. – Does not create High osmolarity, just preserves it. Sherwood’s Human Physiology 14-31 5th Ed. & 14-28 6th Ed. High levels of ADH • The early and late distal tubule – Actively transports NaCl (early). – Relatively impermeable to H2O (both). • Cortical & Medullary collecting tubule – In absence of ADH mostly impermeable to H2O. – With high levels of ADH late distal and collecting tubules are very permeable to H2O. Guyton’s Textbook of Medical Physiology 28-4 Osmoreceptor-ADH feedback system • Net effect is that H2O is conserved while Na+ and other solutes continue to be excreted in the urine. Guyton’s Textbook of Medical Physiology 28-8 Osmoreceptor-ADH feedback system • Osmoreceptor – Senses increased osmolarity. • Hypothalamus – Synthesizes ADH. • Posterior pituitary – Releases ADH. • Kidney – Responds to ADH by reabsorbing H2O and increasing the concentration of solutes in the urine. Guyton’s Textbook of Medical Physiology 28-9 ADH Secretion • Other stimulators of ADH secretion. – Arterial baroreceptor reflex. • Increased signal ______________________________ ADH secretion. – Vice versa is true. – Cardiopulmonary reflex (volume reflex). • Decreased blood volume and decreased arterial pressure (decreased stretch of atria) results in an increase in ADH secretion. – Vice versa is also true. ADH Secretion • ADH secretion is more sensitive to small changes in osmolarity than similar changes in blood volume. Guyton’s Textbook of Medical Physiology 28-10 Summary of Excretion of Urine in the Presence and Absence of ADH ADH is present = Concentrated urine Sherwood’s Human Physiology 14-30 5th Ed. & 14-27 6th Ed. Summary of Excretion of Urine in the Presence and Absence of ADH ADH is absent = Dilute urine Sherwood’s Human Physiology 14-30 5th Ed. & 14-27 6th Ed. Thirst • Conscience desire for water. Thirst Center • In the preoptic nucleus and anteroventral wall of the third ventrical. – When stimulated electrically or with salt injections causes immediate drinking. Control of Thirst • Osmolarity – When the extracellular fluid Na+ concentration increases only 2 mEq/L above normal the thirst mechanism is activated. Guyton’s Textbook of Medical Physiology table 28-3 Renin-Angiotensin System Decreased arterial pressure Renin released from Kidneys Angiotensinogen Angiotensin I (mild vasoconstriction) Converting enzyme (in lung) Angiotensin II Angiotensinase (inactive) Increase Thirst Renal retention of salt and water Strong vasoconstriction Control Extracellular Osmolarity • When either the ADH or thirst mechanisms fail the other normally can still control extracellular osmolarity and sodium concentration. • If both fail regulation is lost. Guyton’s Textbook of Medical Physiology 28-11 Next Time • Potassium, phosphate, calcium, and magnesium excretion • Readings: Sherwood, Chapter 14. Objectives 1. Understand how dilute and concentrated urine is formed. 1. 2. 3. 4. Role of ADH Role of interstitial fluid osmolarity Countercurrent multiplier Obligatory urine volume 2. Understand the regional renal tubular permeability to H2O, NaCl, and urea. 3. Understand the role of the vasa recta regarding interstitial fluid osmolarity. 4. Understand the function of hypothalamic osmoreceptors and other stimulators of ADH secretion. 5. Understand the regulators of thirst.