1. Lecture 5 Regulation of Sodium and Water Excretion ….. essentially same as….. Regulating Plasma Volume and Osmolarity

2. Kidneys excrete salt and water Since the amounts of salt and water in body define blood volume & osmolarity, Kidney’s control blood volume and body fluid osmolarity.

3. Renal Role in Blood Pressure Regulation ►Short Term BP Control:seconds/minutes classic baroreceptor reflex sympathetic output changes vascular resistance ►Medium Term BP Control:minutes/hours renin release renin promotes angiotensin II formation circulating angiotensin II changes vascular resistance ►Long Term BP Control:hours/days changes in total body salt & H 2 0 changes blood volume The Kidney’s Role: 1) renin release (min/hrs) 2) controlling blood volume (hrs/days) Blood volume changes when H 2 0 moves in or out of the plasma. H 2 0 always moves down osmotic gradients. CONCEPT: CONCEPT: If you control Na, then you control blood volume. Most abundant osmotically active particle in plasma is Na +. Control of Na = control of H 2 0 movement = Control of volume

4. Regulation of Na + & H 2 0 Balance First a Conceptual Overview Parallel Bulk Handling Differential Hormonal Fine-Tuning Pressure Natriuresis Aldosterone ….. Na ADH ….. H 2 0

5. Regulation of Na + Balance Pressure Natriuresis Definitions: Natriuresis =  Na + excretion in Urine Pressure Natriuesis is caused by increased blood pressure & associated increase in GFR. More IN More OUT Simply Hemodynamics: More IN = More OUT No independent treatment of Na + & H 2 0 Good for simple bulk volume control Some Murky Mechanism Details: Some evidence that increased BP some how down regulates Na reabsorption from the proximal tubule Higher hydrostatic pressure in peritubular capillaries reduces reabsorption from the proximal tubule. Pressure Natriuresis: 1) driven by simple hemodynamics 2) proximal nephron phenomenon 3) no sensors or circulating factors

6. Regulation of Na + in Distal Nephron Aldosterone: Most important “H 2 0-independent” controller of Na + reabsorption & Na + balance Steroid hormone produced by adrenal cortex Acts on principle cells of the collecting duct Circulating Angiotensin II stimulates its release So…  BP trigger baroreceptor response … this in turn triggers renin release … renin leads to increased angiotensin II levels … this triggers aldosterone release … this stimulates Na reabsorption … this leads to increased blood volume … increased blood volume leads to  BP This is summarized in the next figure. Differential Hormonal Fine-Tuning Collecting Duct

7. …  BP triggers baroreceptor response …  BP & sympathetic inputs trigger renin release from granular cells … renin enters circulation and leads to increased angiotensin II levels … angiotensin II triggers aldosterone release from adrenal cortex … aldosterone stimulates Na reabsorption from collecting duct … the retained Na leads to increased blood volume which raises BP Aldosterone is not the only hormone that regulates the body’s Na + balance.

8. Atrial Natriuretic Peptide → released from heart when atria stretch due to high blood volume (  BP) → vasodilates afferent arteriole increasing GFR → inhibits Na reabsorption in from collecting duct → inhibits renin-angiotensin Now…. Let’s look at hormonal control H 2 0 balance

9. Regulation of H 2 0 Balance Key Hormone = Antidiuretic Hormone (ADH) sometimes called vasopressin Collecting Duct ADH : Peptide hormone Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly Released from posterior pituitary Increases H 2 0 Permeability of apical membrane by promoting the fusion of vesicles containing an aquaporin

10. Input Signals that Control ADH Release 1) cardiovascular baroreceptors  BP  less baroreceptor firing   ADH release  BP  more baroreceptor firing   ADH release 2) hypothalamic osmoreceptors  plasma osmolarity   ADH release  plasma osmolarity   ADH release

11. Input Signals that Control ADH Release 1) cardiovascular baroreceptors  BP  less baroreceptor firing   ADH release  BP  more baroreceptor firing   ADH release 2) hypothalamic osmoreceptors  plasma osmolarity   ADH release  plasma osmolarity   ADH release Baroreceptors

12. Input Signals that Control ADH Release 1) cardiovascular baroreceptors  BP  less baroreceptor firing   ADH release  BP  more baroreceptor firing   ADH release 2) hypothalamic osmoreceptors  plasma osmolarity   ADH release  plasma osmolarity   ADH release Osmoreceptors The cells that release ADH integrate the 2 input signals. “2 heads are better than 1”

13. Input Signals that Control ADH Release 1) cardiovascular baroreceptors  BP  less baroreceptor firing   ADH release  BP  more baroreceptor firing   ADH release 2) hypothalamic osmoreceptors  plasma osmolarity   ADH release  plasma osmolarity   ADH release Generally, osmolarity usually dominates unless there are very large changes in volume. Certain other brain level inputs can alter short-term ADH release (fear, pain, alcohol). Diabetes insipidus is due to abnormal ADH regulation. Origin could be brain problem or bad renal ADH receptors.

14. Free Water Clearance (C H20 ) means to access renal H 2 0 handling, not the usual clearance calculation The C H20 determination considers urine as having 2 parts: Urine Volume solute-free H 2 0 H 2 0 with solute  Can be calculate as Osmolar Clearance C OSM = U OSM · V P OSM solute-free H 2 0 H 2 0 with solute  This is the H 2 0 “cleared”  Volume in which solutes present would be iso-osmotic compared to plasma. v

15. Free Water Clearance (C H20 ) means to access renal H 2 0 handling, not the usual clearance calculation The C H20 determination considers urine as having 2 parts: Urine Volume solute-free H 2 0 H 2 0 with solute  Can be calculate as Osmolar Clearance C OSM = U OSM · V P OSM Thus…. C H20 = V - C OSM solute-free H 2 0 H 2 0 with solute  This is the H 2 0 “cleared”  Volume in which solutes present would be iso-osmotic compared to plasma. v

16. Free Water Clearance (C H20 ) means to access renal H 2 0 handling, not the usual clearance calculation The C H20 determination considers urine as having 2 parts: Urine Volume solute-free H 2 0 H 2 0 with solute  Can be calculate as Osmolar Clearance C OSM = U OSM · V P OSM Thus…. C H20 = V - C OSM solute-free H 2 0 H 2 0 with solute  This is the H 2 0 “cleared”  Volume in which solutes present would be iso-osmotic compared to plasma. v Note: C H20 could be negative !! This is when very concentrated urine is being produced.

17. Free Water Clearance (C H 2 0 ) means to access renal H 2 0 handling, not the usual clearance calculation The C H 2 0 determination considers urine as having 2 parts: Urine Volume solute-free H 2 0 H 2 0 with solute  Can be calculate as Osmolar Clearance C OSM = U OSM · V P OSM Thus…. C H20 = V - C OSM If… V = C OSM Then… C H20 is zero If… V < C OSM Then… C H20 is negative solute-free H 2 0 H 2 0 with solute  This is the H 2 0 “cleared”  Volume in which solutes present would be iso-osmotic compared to plasma. v If… V > C OSM Then… C H20 is positive Note: C H20 could be negative !! This is when very concentrated urine is being produced.

19. Renal Physiology Quiz for Lecture 5: Note that this and other Renal Physiology quizzes are simply provided to you to help you self- test your understanding of each lecture. They are not a substitute for studying the other learning materials presented to you. These questions are not intended to reflect the style or level of difficulty of questions on the Final Exam.

20. True/False Questions: 1. The looping configuration of the vasa recta is important to preserving the hypo- osmotic interstitium of the renal medulla. F 2. Renin is a proteolytic enzyme that cleaves the angiotensinogen produced by the liver. T 3. The kidney rapidly changes the body’s blood volume in pace with short-term (seconds/minutes) fluctuations in blood pressure. F 4.Pressure natriuresis is largely a proximal nephron phenomenon that does not involving any pressure sensing receptors. T 5.Aldosterone is a peptide hormone released from the adrenal medulla. F 6.Antidiuertic hormone (ADH) causes the water permeability of the collecting duct to decrease. F 7.Atrial Natriuretic Peptide (ANP) promotes the excretion of Na+ into the renal tubular fluid. T 8.A negative free water clearance means that the urine is dilute and excess water is being excreted in the urine. F

21. Multiple Choice Questions 9. Which of the following will result in triggering more renin release? a. decrease in renal afferent arteriolar pressure b. increase in sympathetic neural activity c. abnormally low NaCl level in the tubular fluid passing through the distal tubule d. answers a, b and c are all correct e..none of the above 10. Which of the following will result in triggering more aldosterone release? a. a decrease in plasma K+ levels b. a reduction in circulating angiotensin II levels c. block of angiotensin converting enzyme d. stimulation of renin release e. an elevation in mean arterial pressure 11. Which of the following will result in triggering more ADH release? a. an increase in blood osmolarity b. an increase in blood volume c. an increase in blood pressure d. answers a, b and c are all correct e. none of the above 12. What is the free water clearance considering the follow lab values? Urine volume = 2 ml/min Urine Osmolarity = 600 mOsm Plasma Osmolarity = 300 mOsm a. -2 b. +6 c. 0 d. -1 e. +3

23. The main goal of visualization and rendering is to effectively convey information to the viewer. For scientific visualization, this goal translates into determining which portions of data to highlight and how to render these portions to concisely convey the appropriate information to the specific audience. These are the tasks that medical and technical illustrators have undertaken for centuries. We have developed a system that builds upon and extends recent work in volume illustration to produce images that simulate pictorial representations for scientific and biomedical visualizations. Our system is designed in collaboration with a trained biomedical illustrator whose work focuses on visualization for clinical research and resident surgical training. The system combines traditional and novel volume illustration techniques. A high-level interface enables the user to specify the type of illustration and visualization goals to produce effective, illustrative rendering on commodity graphics hardware at nearly interactive rates.. This work has been published in IEEE Computer Graphics & Applications Journal, special issue "Smart Depiction in Visual Communication", May/June 2005. [PDF]. The demostration of the system has been included in SIGGRAPH 2005 conference half-day course, course #31 "Computer-Generated Medical, Technical, and Scientific Illustration".PDFSIGGRAPH 2005 conferenceComputer-Generated Medical, Technical, and Scientific Illustration