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Lecture7 RENAL HANDLING OF ACID-BASE BALANCE

Lecture7 RENAL HANDLING OF ACID-BASE BALANCE. Two ► Acidity is measured in terms of pH …. pH is the negative log of [H + ] pH = 4 means [H] is 0.0001 10 -4 moles/L pH = 7 0.0000001 10 -7 pH = 7.4 0.00000004 10 -7.4 pH = 11 0.00000000001 10 -11.

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Lecture7 RENAL HANDLING OF ACID-BASE BALANCE

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  1. Lecture7 RENAL HANDLING OF ACID-BASE BALANCE

  2. Two► Acidity is measured in terms of pH …. pH is the negative log of [H+] pH = 4 means [H] is 0.0001 10-4 moles/L pH = 7 0.0000001 10-7 pH = 7.4 0.00000004 10-7.4 pH = 11 0.00000000001 10-11 *Remember …. when free [H+]  the pH  Acid-Base Background Information Traditionally Confusing SEVEN GENERAL GUIDLINES One ► Balance principle applies …. acid/base input = acid/base output Three► Body fluids are buffered …. buffers are substances that bind H+ ions If you add H+ to a buffered solution, then the buffer binds the added H+ so that free H+ does not rise much. If you add H+ to unbuffered solution,then free H+ rises by amount added.

  3. Four ► Most important pH buffer system in body is …. C02-bicarbonate system C02 + H20 H2C03 HC03 + H+ ca ( Note: ca = carbonic anhydrase ) Usually consider only …. C02 + H20 HC03 + H+ Seven ► Plasma pH is defined by ratio of C02 and HC03 levels Henderson-Hasselbach Equation The 0.03 is solubility factor. Normal [HC03] = 24 mM Normal PCO2 = 40 mmHg 24/(0.03x40) = 20 ( Log 20 = 1.3 ) Five ► C02 is a volatile acid …. it generates a H+ by reacting with H20 Volatile because it can escape from solution as a gas Fixed acids (like lactic acid) can not simply blow off as a gas Six ► Gain/Loss of fixed acids alters body’s HC03 levels  Fixed Acid ….  HC03 level ( always ! )  Fixed Acid ….  HC03 level ( always ! ) Important Point: Keeping H+ balance is essentially same as keeping HC03 balance.

  4. Renal Handling of Bicarbonate Bicarbonate (HC03) is freely filtered. Normal plasma HC03 is 24 mM. Most filtered HC03 is reabsorbed. Reabsorption is transcellular. Most reabsorbed from proximal tubule. Reabsorption always involves a H+ secretion step.

  5. Bicarbonate Reabsorption from Proximal Tubule • Powered by Na+ gradient. • Apical H+ secretion by the • Na-H-antiporter • Secreted H+ binds to • filtered HC03 • Complex dissociates to • C02 and H20 H The H crank Electrogenic Pump 3HC03 & 1 Na powered by Vm • C02 and H20 re-associate • inside cell • Reformed HC03 transported • into interstitium ca

  6. Bicarbonate Reabsorption from Collecting Duct Type A Intercalated Cells • Not powered by Na+ gradient. • Powered by apical H+ pumps. • K-H-ATPase • H-ATPase • As before, secreted H+ binds • to filtered HC03 • Complex dissociates to • C02 and H20 H The H crank • C02 and H20 re-associate • inside cell • Reformed HC03 transported • into interstitium A Common Theme: HC03 reabsorption always involves a H+ secretion step.

  7. Collecting Duct Type B Intercalated Cell “looks like a flipped-around type A cell” • Powered by basolateral H+ pumps. • K-H-ATPase • H-ATPase • As H+ recycles across basolateral • membrane, a HC03 is reformed in • cell and a HC03 disappears from • the interstitium. H The H crank • Reformed HC03 is transported • into the tubular lumen. Secreting of Excess Base ( HC03 Secretion ) There are 2 ways to clear excess base: - reabsorb less HC03 - secrete HC03

  8. Secreting Excess Acid ( H+ excretion via phosphate ) Collecting Duct Type A Intercalated Cell “same that reabsorb HC03 earlier” • Secreted H+ binds to phosphate • not filtered HC03 • Bound H+ is excreted in urine. H • The H+ secretion still • results in HC03 formation • inside the tubular cell. • 4. The new HC03 is transported • into the interstitium. Important Note: Excreted H+ and simultaneous net HC03 gain act to alkalinize plasma.

  9. Phosphate is “Titratable Acid”: Titrate …. act of carefully and slowly adding a measured amounts of acid/base to a buffer solution. In essence, the collecting duct has titrated HP042- to H2P04- by adding H+ Remember, one new HC03 was made for each H+ added to phosphate. The added H+ can easily come off if urine pH is raised to 7.4 (in the lab). Thus, phosphate is called a titratable acid. Phosphate is most important & abundant titratable acid in urine. There are other ones (urate, creatinine) but these are less important.

  10. Secreting Excess Acid ( H+ excretion via ammonium ) Ammonium (NH4+) is produce by H+ binding to ammonia (NH3). Proximal tubule produces ammonia for this purpose only “on demand” Very complicated process summarized only very simply here. When there is a need to get rid of acid, → NH3 & HCO3 are produced from the amino acid glutamine → The new HC03 is transported into the interstitium. → the NH3 diffused into tubular lumen and binds to a secreted H+ A General Concept: When ever a secreted H+ binds to something other than filtered HC03 it results in formation of new HC03.

  11. Ammonium (NH4+) is not a “Titratable Acid” Any H+ bound will not dissociate (you can not reverse titrate) by titrating the urine back to pH to 7.4. Once H+ binds it stays bound over the whole pH range of normal urine. Remember, one new HC03 was made for each H+ added to NH4+

  12. Some Typical HCO3 Gain/Loss Numbers: Note: During acidosis, NH4+ plays much larger role than Phosphate. • “Running the Numbers” • Maintaining acid/base balance is equivalent to maintaining HCO3 balance • Body’s net HC03 gain/loss = new HC03 gained in plasma - HC03 lost in urine • The HC03 gain comes from H+ binding to phosphate and ammonium • Normally, body needs to get rid of 60 mEq/day acid

  13. C02 + H20 HC03 + H+ Respiration Controls Kidney Controls Acid-Base Disturbances Important Reminder: General Categories: Respiratory Acidosis Respiratory Alkalosis Metabolic Acidosis Metabolic Alkalosis Plasma pH depends on both HC03 & C02

  14. Acid-Base Disturbances & Compensation

  15. Acid-Base Disturbances & Compensation Metabolic Disturbances may be of renal or non-renal in origin. Renal …. is when the problem is with kidney’s H+ or HC03 handling. Non-renal …. examples include vomiting, diarrhea, large acid consumption.

  16. The Diagnostic Table Simply a Summary of Previous Diagrams For Example Metabolic Acidosis:

  17. The Diagnostic Table Simply a Summary of Previous Diagrams For Example Metabolic Alkalosis:

  18. The Diagnostic Table but… you need more info in order to distinguish between these Simply a Summary of Previous Diagrams For Example Respiratory Alkalosis:

  19. high low low high Metabolic Acidosis: Renal … excreting to much HC03  [HC03]urine Non-Renal … HC03 lost in diarrhea  [HC03]urine Metabolic Alkalosis: Renal … reabsorbing too much HC03  [HC03]urine Non-Renal … acid lost by vomiting  [HC03]urine ( low H+ less HC03 reabsorbed … so more in urine) The Diagnostic Table [HC03]urine

  20. Renal Physiology Quiz for Lecture 7: 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.

  21. True/False Questions: • Metabolic production of acid is typically about 60 mEq/day. F • Bicarbonate (HC03) is the most important pH buffer in the plasma. T • Most hydrogen excreted in the urine is in its free ionic form (H+). F • NH4 is a titratable acid. F • Ammonium (NH3) enters the tubular lumen primarily in the collecting duct. F • The pH of urine is always less than 4.5. F 7. Most filtered bicarbonate is reabsorbed from the proximal tubule. T • New bicarbonate is formed when secreted H+ ions bind to something other than filtered bicarbonate. T

  22. Multiple Choice Questions: 9. Which of the following is true during an acidosis caused by a respiratory problem? a. higher than normal PCO2 b. lower than normal plasma concentration of HCO3 c. the patient could be hyperventilating d. a and b are both correct e. b and c are both correct 10. Which of the following statements does not accurately describe the HCO3 handling by intercalated cells of the collecting duct? a. during HCO3 reabsorption, apical antiporters transport H+ and Na+ b. during HCO3 reabsorption, the H+ ion is actively transported by an ATPase c. during HCO3 secretion, the H+ ion is actively transported by an ATPase d. during HCO3 secretion, the HCO3-Cl antiporters moveHCO3 across the apical membrane into the tubular lumen e. if secreted H+ binds to filtered HC03, then the filtered HCO3 disappears and a new HCO3 reforms inside the cell 11. Given the following values: NH4+ excretion: 40 mEq/day HCO3 excretion: 10 mEq/day Titratable acid excretion: 15 mEq/day Urine formation rate: 1 ml/min Calculate the daily amount of net bicarbonate added to the blood per day: a. 15 mEq b. 35 mEq c. 45 mEq d. 55 mEq e. 75 mEq 12. Vomiting (loss of gastic acid) may result in which of the following? a. immediate loss of HC03 from the body b. acidosis c. decreased plasma HCO3 level d. metabolic alkalosis of renal origin e. compensation by kidney and lung

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