1. Aims Renal Regulation of Acid/Base Balance & Micturition Readings; Sherwood, Chapters 14 & 15

2. Renal Acid/Base Regulation Buffering Systems in the Body –Bicarbonate Buffer System Most important extracellular buffer –Phosphate Buffer System Important renal tubule & intracellular buffer –Proteins Important intracellular buffer

3. Renal Acid/Base Regulation Respiratory System –Alveolar ventilation of CO 2 Renal System –Excretion of acidic or basic urine Balance between the secretion and reabsorption of HCO 3 - and H + ions. Excretion of nonvolatile acids produced by protein metabolism (small component)

4. Renal Acid/Base Regulation 3 Fundamental mechanisms in which kidneys regulate ECF H + conc. –Secretion of H + –Reabsorption of filtered _________________________ –Production of new HCO 3 -

5. Renal Acid/Base Regulation HCO 3 - Reabsorption Requires H + Secretion 80-90% of HCO 3 - Reabsorption & H + Secretion occurs in the Proximal tubule Guyton’s Textbook of Medical Physiology 30-4

6. Renal Acid/Base Regulation H + Secretion Occurs in the in all parts of the renal tubules except the thin limbs of the loop of Henle. Occurs via 2 different mechanisms Guyton’s Textbook of Medical Physiology 30-4

7. Renal Acid/Base Regulation H + Secretion Occurs in the Proximal tubule, Thick ascending loop of Henle, & Early distal tubule by Na + - H + counter- transport. Guyton’s Textbook of Medical Physiology 30-4

8. Renal Acid/Base Regulation Na + -H + counter-transport. –Energy derived from Na + gradient established by Na + -K + ATPase H + combines with HCO 3 - to form H 2 CO 3 (carbonic acid) H 2 CO 3 dissociates into CO 2 & H 2 O in the lumen Guyton’s Textbook of Medical Physiology 30-5

10. Renal Acid/Base Regulation CO 2 diffuses into the renal epithelial cells and recombines with H 2 O to reform H 2 CO 3 via the enzyme carbonic anhydrase (ca) H 2 CO 3 dissociates into HCO 3 - and H + to create the pool of H + to be secreted & release an HCO 3 - into the blood Sherwood’s Human Physiology 15-10 HCO 3 - ions are indirectly reabsorbed in the renal tubules. Net result, most filtered HCO 3 - is replaced in the blood!

12. Renal Acid/Base Regulation H + Secretion Occurs in the Late distal tubules & Collecting tubules by Primary Active Transport via the H + ATPase 5-10% of total Guyton’s Textbook of Medical Physiology 30-4

13. Renal Acid/Base Regulation Primary Active Transport of H + ions occurs in ___________________________________ CO 2 from blood diffuses into the renal epithelial cells and recombines with H 2 O to reform H 2 CO 3 via the enzyme carbonic anhydrase H 2 CO 3 dissociates into HCO 3 - and H + to create the pool of H + to be secreted & release an HCO 3 - into the blood Guyton’s Textbook of Medical Physiology 30-6 This region is where maximal acidification of the urine occurs (increase H + conc. up to 900 fold) because H + is not combining with HCO 3 -. Net gain of 1 HCO 3 - in blood.

15. Renal Acid/Base Regulation Phosphate Buffering Used when HCO 3 - is insufficient. Allows for secretion of large amount of H + without reducing the urine pH below 4.5 Secreted H + combines with NaHPO 4 - to be excreted as NaH 2 PO 4 With the phosphate buffering system there is a net gain of 1 HCO 3 - into the blood because there is no HCO 3 - reabsorbed from the renal tubule. Sherwood’s Human Physiology 15-11

17. Renal Acid/Base Regulation Ammonia Buffering More important than the Phosphate system Glutamine is actively transported into the renal epithelium in the proximal tubule Glutamine is cleaved into 2 HCO 3 - & 2 NH 4 + The NH 4 + is secreted into the lumen via the NH 4 + -Na + Counter transporter The 2 HCO 3 - are absorbed into the blood Guyton’s Textbook of Medical Physiology 30-8 Net gain of 2 HCO3- into the blood!

19. Renal Acid/Base Regulation Ammonia Buffering In the collecting tubule NH 3 is secreted & combined with the secreted H + to produce NH 4 + which is excreted The Ammonia Buffer system accounts for 50% of H + excreted & 50% of new HCO 3 - produced! For each NH 4 + excreted, there is 1 new HCO 3 - generated and absorbed into the blood. Guyton’s Textbook of Medical Physiology 30-9

21. How do Plasma pH Levels Affect Renal Acid/Base Regulation? Sherwood’s Human Physiology Table 15-8

22. Micturition The process by which the urinary bladder empties when it becomes filled. The bladder fills progressively until tension in its walls rises above a threshold level. This elicits a nervous reflex called the micturition reflex which empties the bladder or causes a conscious desire to urinate.

23. Micturition Guyton’s Textbook of Medical Physiology 26-6 Urine travels from the kidneys to the bladder –due to ______________________.

24. Micturition Guyton’s Textbook of Medical Physiology 26-6 The normal tone of the detrussor muscles in the bladder wall compresses the ureter preventing backflow of urine when pressure builds up in the bladder.

25. Micturition Reflex Sherwoods’s Human Physiology 14-33 5th Ed. & 14-30 6th Ed. As the bladder fills, micturition contractions begin to appear. –Due to a stretch reflex initiated by stretch receptors in the bladder wall.

26. Micturition Reflex Sherwoods’s Human Physiology 14-33 5th Ed. & 14-30 6th Ed. When the bladder is only partially filled these contractions relax spontaneously after seconds. As the bladder fills the contractions become more frequent and stronger. The contractions are “self regenerative” in that each contraction stimulates the stretch receptor reflex. Once the bladder reaches a strong degree of contraction, the reflex can fatigue and the cycle of contraction can cease resulting in the relaxation of the bladder.

27. Micturition Reflex Once the micturition contraction runs this full cycle and the bladder is not emptied the reflex is inhibited for minutes to hours. As the micturition reflex becomes powerful enough it causes another reflex to inhibit the external sphincter. If this reflex can overpower the constriction by the external sphincter, micturition occurs. Guyton’s Textbook of Medical Physiology 26-6

28. Micturition Reflex Micturition is a completely ___________________________________ spinal cord reflex. In can be inhibited or facilitated by centers in the brainstem and cerebral cortex. Guyton’s Textbook of Medical Physiology 26-6

29. Voluntary Urination Voluntary contraction of abdominal muscles puts pressure on the bladder and stimulates stretch receptors. This excites the micturition reflex and inhibits the external sphincter. Urination ensues.

30. Summary of Micturition Sherwood’s Human Physiology 14-32 5th Ed. & 14-29 6th Ed.

31. Next Time Reproductive Physiology Readings; Sherwood, Chapter 20

32. Objectives 1.Describe the various buffer systems in the body. 2.Describe the mechanisms of renal regulation of extracellular H + conc. 1.Secretion of H + 1.Location and mechanisms 2.Reabsorption of filtered HCO 3 - 1.Location and mechanisms 3.Production of new HCO 3 - 1.Location and mechanisms 3.Describe the effect of plasma pH on renal acid/base regulation. 4.Describe the process of micturition. 1.Micturition reflex.