1 / 34

H + secretion (proximal tubule/thick ascending Henle)

H + secretion (proximal tubule/thick ascending Henle). Proximal tubule (~80%), thick ascending limb (~15%) of H + secreted. Mechanisms of H + secretion (  intercalated cell).  intercalated cell (~5% of H + secreted). Bicarbonate reabsorption & synthesis.

kuper
Download Presentation

H + secretion (proximal tubule/thick ascending Henle)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. H+ secretion (proximal tubule/thick ascending Henle) Proximal tubule (~80%), thick ascending limb (~15%) of H+ secreted

  2. Mechanisms of H+ secretion ( intercalated cell)  intercalated cell (~5% of H+ secreted)

  3. Bicarbonate reabsorption & synthesis

  4. Bicarbonate reabsorption & synthesis if no HCO3- production or utilization: recycled HCO3- would ensure HCO3- balance if HCO3- used for buffering: new HCO3- replaces it

  5. Quantitation of secreted H+ & reabsorbed HCO3- “Titratable acidity” = excreted H2PO4-& other urinary buffers “Urinary ammonium” = excreted NH4+

  6. Important principles 1 H+ secreted = HCO3-reabsorbed H+ excreted = titratable acidity + urinary NH4+ Most of the H+ secreted is used to “reclaim” filtered HCO3- Filtered HCO3- is not reabsorbed as such; it is destroyed in tubule and resynthesized in tubular cell New HCO3-synthesized = H+ excreted = titratable acidity + urinary NH4+

  7. Important principles 2 Plasma [HCO3-] depends on the rate of renal H+secretion H+secretion plasma [HCO3-] (metabolic alkalosis) H+secretion plasma [HCO3-] (metabolic acidosis) Healthy kidney maintains the constancy of plasma [HCO3-] by maintaining constancy of H+secretion (irrespective of moderate acid or alkaline assaults)

  8. Henderson Hasselbalch equation H2O + CO2 H2CO3H+ + HCO3- Looking at 2nd half of equation: K (equilibrium constant) = [H+] x [HCO3-] [H2CO3] Rearranging and taking negative logs: pH = pK + log10 [HCO3-] [H2CO3] Assuming the 1st half of the equation is at equilibrium: [H2CO3] = 0.03 x Pa.CO2 Then, the Henderson Hasselbalch equation is: pH = pK + log10 [HCO3-] 0.03 x Pa.CO2

  9. Why use the bicarbonate buffer system? Not ideal because: pK 6.1, and buffers are most effective around their pKs However: the body can regulate Pa.CO2 & [HCO3-] independently and thus control pH lungs regulate Pa.CO2 & kidneys regulate [HCO3-] regulating pH will alter all buffer systems (isohydric principle) clinically, we can measure pH & Pa.CO2, & calculate [HCO3-]

  10. Davenport diagram

  11. Interpreting acid base data (DRW AIM) Normal values: pH 7.35 – 7.45, Pa.CO2 33 – 44 mm Hg, HCO3- 22 – 28 mEq/L 1. Acidosis or alkalosis? pH < 7.35 = acidosis, pH > 7.45 = alkalosis you may have to revise that later, but start with this “overcompensation” does not occur

  12. Metabolic or respiratory? 2a. Is it metabolic acidosis (alkalosis)? Look at [HCO3-];  metabolic alkalosis,  metabolic acidosis e.g. pH 7.25, [HCO3-] 14 mEq/L = Yes; metabolic acidosis e.g. pH 7.25, [HCO3-] 32 mEq/L = No; not metabolic acidosis 2b. Is it respiratory acidosis (alkalosis)? Look at Pa.CO2;  respiratory acidosis,  respiratory alkalosis e.g. pH 7.25, Pa.CO2 64 mm Hg = Yes; respiratory acidosis e.g. pH 7.25, Pa.CO2 26 mm Hg = No; not respiratory acidosis

  13. Respiratory compensation 3. Respiratory compensation (metabolic disorders) Mechanism: pH or pH detected by carotid body & aortic arch chemoreceptors, ventilation rate  Pa.CO2;  ventilation rate  Pa.CO2 Features: rapid response (minutes); no response suggests respiratory disorder relatively inadequate because  Pa.CO2 limits response i.e. metabolic acidosis AVR  Pa.CO2 AVR Pa.CO2 > 55 mm Hg is respiratory acidosis (too high for compensation)

  14. Metabolic compensation 3. Metabolic compensation (respiratory disorders) Mechanism:  Pa.CO2 or  Pa.CO2 causes  or  H+ secretion & HCO3- reabsorption Features: buffering is not compensation [HCO3-] will  by ~1 mEq/L for each 10 mm Hg Pa.CO2 (buffering) slow response ~ 24 hrs for [HCO3-] (excretion) days for [HCO3-] (induction of glutaminase II) very effective (eventually)

  15. Terminology (compensation vs. mixed condition) pH 7.30, [HCO3-] 14 mEq/L, Pa.CO2 29 mm Hg is compensated metabolic acidosis, not (mixed) metabolic acidosis and respiratory alkalosis pH 7.34, [HCO3-] 32 mEq/L, Pa.CO2 62 mm Hg is compensated respiratory acidosis, not (mixed) respiratory acidosis and metabolic alkalosis Compensation will disappear when the primary condition is treated; a mixed condition won’t

  16. 4. Anion gap; what is it?

  17. Anion gap; why does it change? The “gap” is [measured cations] - [measured anions]

  18. Significance of the anion gap Used for differential diagnosis of metabolic acidosis Hyperchloremic metabolic acidosis (normal anion gap) occurs when disorder is HCO3- loss, e.g. diarrhea, renal tubular acidosis, carbonic anhydrase inhibitors, Addison’s disease Normochloremic metabolic acidosis (increased anion gap) occurs when “non HCl” acids accumulate e.g. lactic acidosis, ketoacidosis, salicylate, methanol (formate), ethylene glycol (glycolate, oxalate), chronic renal failure (sulfate, phosphate, others)

  19. Causes of respiratory acid base disorders Respiratory acidosis: opiates, sleep apnea, administration of O2 to a “blue bloater” type of COPD, weakness of respiratory muscles, extreme obesity, pulmonary edema, asthma, pneumonia, pneumothorax Respiratory alkalosis: several respiratory diseases (pneumonia, interstitial fibrosis, pulmonary embolus), hyperventilation, liver failure, salicylate overdose, gram negative septicemia, mechanical ventilation

  20. Causes of metabolic acid base disorders Metabolic acidosis (hyperchloremic, normal anion gap): diarrhea, carbonic anhydrase inhibitors, aldosterone deficiency, types I & II renal tubular acidosis Metabolic acidosis (normochloremic, increased anion gap): diabetic ketoacidosis, lactic acidosis, chronic renal failure, various poisonings (salicylate, methanol, ethylene glycol) Metabolic alkalosis: antacid ingestion, vomiting, nasogastric suction, loop or thiazide diuretics, aldosterone excess, vascular volume depletion, potassium depletion

  21. Case F1: acid base condition pH 7.58; Pa.CO2 23 mm Hg; [HCO3-] 21 mEq/L 1. Look at pH (is it acidosis or alkalosis?) pH = 7.58  alkalosis 2. Look at HCO3- (is it metabolic alkalosis?) HCO3- = 21 mEq/L (normal 22-30)  not metabolic alkalosis 3. Look at Pa.CO2 (is it respiratory alkalosis?) Pa.CO2 = 23 mmHg (normal 35-45)  respiratory alkalosis • See if appropriate compensation has occurred: compensation for respiratory alkalosis is HCO3- excretion HCO3- = 21 mmHg (normal 22-30)  uncompensated i.e. acute respiratory alkalosis

  22. Case F1: questions Describe her acid base condition acute respiratory alkalosis Plausible causes for her acid base condition? hysterical hyperventilation Suggest causes of her dizziness  Pa.CO2 cerebral vasoconstriction Any evidence for ventilation/perfusion mismatch in pulmonary function? A-a O2 difference = 123-116 = 7 (i.e. OK) What is carpopedal spasm, and its possible cause? pH Ca++ binding to albumin  free [Ca++]  more negative threshold for muscle cell depolarization (Na+ channel sensitivity)  hypocalcemic tetany

  23. Case F2: acid base condition pH 7.29; Pa.CO2 26 mm Hg; [HCO3-] 12 mEq/L 1. Look at pH (is it acidosis or alkalosis?) pH = 7.29  acidosis 2. Look at HCO3- (is it metabolic acidosis?) HCO3- = 12 mEq/L (normal 22-30)  metabolic acidosis 3. Look at Pa.CO2 (is it respiratory acidosis?) Pa.CO2 = 26 mmHg (normal 35-45)  not resp. acidosis • See if appropriate compensation has occurred: compensation for metabolic acidosis is hyperventilation Pa.CO2 = 26 mmHg (normal 35-45); partial compensation 5. Anion gap = 142 - (100 + 12) = 30 (increased) i.e. partially compensated normochloremic metabolic acidosis

  24. Case F2: questions Total CO2 (CO2 content)? CO2 released when venous plasma is acidified equals [HCO3-] + 0.03 x P.CO2 (units mEq/L) Describe his acid base condition partially compensated normochloremic metabolic acidosis (increased anion gap) Plausible causes for his acid base condition? normochloremic metabolic acidosis diabetic ketoacidosis: [glucose] 650 mg/dL alcoholic ketoacidosis: starvation, GNG, lipolysis lactic acidosis:  bp  hypoperfusion Anion gap? ketoacids (diabetes, alcohol), lactate (shock, hypoxemia)

  25. Case F2: questions What precautions with his therapy? Aims:volume repletion, insulin, pH correction HCO3-, insulin &  osmolality causes K+ to enter cells (next slide) give supplemental intravenous K+

  26. Regulation of K+ distribution Normally, 98% of total body K+ is intracellular

  27. Case F3: acid base condition pH 7.05; Pa.CO2 45 mm Hg; [HCO3-] 12 mEq/L 1. Look at pH (is it acidosis or alkalosis?) pH = 7.05  acidosis 2. Look at HCO3- (is it metabolic acidosis?) HCO3- = 12 mEq/L (normal 22-30)  metabolic acidosis 3. Look at Pa.CO2 (is it respiratory acidosis?) Pa.CO2 = 45 mmHg (normal 35-45)  poss. resp. acidosis • See if appropriate compensation has occurred: compensation for metabolic acidosis is hyperventilation Pa.CO2 = 45 mmHg (normal 35-45) respiratory acidosis 5. Anion gap = 140 - (116 + 12) = 12 (unchanged) i.e. mixed hyperchloremic metabolic acidosis (normal anion gap) and respiratory acidosis

  28. Case F3: questions 1 Describe her original acid base condition mixed hyperchloremic metabolic acidosis and respiratory acidosis Plausible causes for her acid base conditions hyperchloremic metabolic acidosis possibilities include: diarrhea, carbonic anhydrase (CA) inhibitors, aldosterone deficiency, & renal tubular acidosis (types I & II) aldosterone deficiency would have  [K+], hers is 1.4 mEq/L; history rules out diarrhea, CA inhibitors,  RTA, urine pH 7.0  type 1 respiratory acidosis: hypokalemia (1.4 mEq/L) decreases excitability of diaphragm

  29. Renal tubular acidosis In general: proximal/thick ascending limb Na+/H+ exchager function is to destroy (& reabsorb) filtered HCO3-  intercalated H+ ATPase is to acidify urine  urinary NH4+ & titratable acidity thus synthesizing new HCO3- Proximal RTA (type 2)  activity of proximal/thick AL Na+/H+ exchanger  serum [HCO3-] proximal HCO3- load;  serum [HCO3-] stabilizes collecting duct H+ ATPase can acidify urine & synthesize “new” HCO3- urine pH within normal range Distal RTA (type 1)  activity of collecting duct H+ ATPase,or back diffusion of H+ inability of synthesize “new” HCO3- by acidifying urine progressive depletion of serum [HCO3-] urine pH at alkaline end of range although  body pH

  30. Case F3: questions 2 Urine pH towards alkaline end of range (pH 4.5-7.5)? type 1 RTA is failure of collecting duct H+ secretion (acidifying region; generating new HCO3-) Increased [HCO3-] in emergency room ( = +13 mEq/L)? buffering (1 mEq/L per 10 mm Hg Pa.CO2);  Pa.CO2 = +94 mm Hg, i.e. ~10 mEq/L  [HCO3-] Role of hypokalemia? hyperpolarization  muscle weakness (diaphragm)

  31. Case F3: questions 3 Cause of hypokalemia (1.4 mEq/L)? “Holy Grail” of collecting duct function (Na+ for K+ and/or H+) next slide Urinary NH4+ & titratable acidity? failure to acidify urine & synthesize “new” HCO3- Kroger’s chemical? daily NaHCO3 (baking soda) would work she was given polycitra-K (K citrate & citric acid) citrate metabolized as citric acid, removing H+ then, OH- + CO2 HCO3-

  32. The “Holy Grail” of collecting duct function

  33. Case F4: acid base condition pH 7.44; Pa.CO2 65 mm Hg: [HCO3-] 43 mEq/L 1. Look at pH (is it acidosis or alkalosis?) pH = 7.44 it’s close, but on alkalotic side of normal 2. Look at HCO3- (is it metabolic alkalosis?) HCO3- = 43 mEq/L (normal 22-30)  metabolic alkalosis 3. Look at Pa.CO2 (is it respiratory alkalosis?) Pa.CO2 = 65 mmHg (normal 35-45)  not resp. alkalosis • See if appropriate compensation has occurred: compensation for metabolic alkalosis would be hypoventilation  Pa.CO2 yes, but Pa.CO2 too high for compensation  respiratory acidosis i.e. mixed metabolic alkalosis and respiratory acidosis

  34. Case F4: questions Describe his acid base condition mixed metabolic alkalosis and respiratory acidosis Plausible causes for his acid base condition? metabolic alkalosis: diuretic excess, mild hypokalemia respiratory acidosis: COPD with hypoventilation (CO2 insensitivity; “blue bloater”) Ventilation perfusion mismatch? A-a O2 difference = 71-45 = 26 mm Hg (not bad for age 56 & COPD); hypoventilation & V/Q mismatch  hypoxemia Cause of mild hypokalemia (3.1 mEq/L)? furosemide is K+ wasting diuretic Treatment with 100% O2? hypercapnia; removal of O2 drive

More Related