Non-anion gap Metabolic Acidosis (NAGMA)

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  • Non-anion gap Metabolic Acidosis (NAGMA)

    1. 1. Interesting Electrolyte Cases Joel M. Topf, M.D. Nephrology 248.470.8163 http://PBFluids.blogspot.com
    2. 2. 58 y.o. female with weakness and muscle aches 7.34 / 87 / 33 / 17 139 115 3.1 17 16 1.0
    3. 3. Determine the primary acid-base disorder <ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul>7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3
    4. 4. Determine the primary acid-base disorder <ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul><ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul>7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3 7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3
    5. 5. Determine the primary acid-base disorder <ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul><ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul>7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3 7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3
    6. 6. Determine the primary disorder <ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul><ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul>Metabolic Acidosis 7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3 7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3
    7. 7. Predicting pCO 2 in metabolic acidosis: Winter’s Formula <ul><li>In metabolic acidosis the expected pCO 2 can be estimated from the HCO 3 </li></ul><ul><li>Expected pCO 2 = (1.5 x HCO 3 ) + 8 ± 2 </li></ul><ul><li>If the pCO 2 is higher than predicted then there is an addition respiratory acidosis </li></ul><ul><li>If the pCO 2 is lower than predicted there is an additional respiratory alkalosis </li></ul>
    8. 8. <ul><ul><li>Expected pCO 2 = (1.5 x HCO 3 ) + 8 ±2 </li></ul></ul>Predicting pCO 2 in metabolic acidosis: Winter’s Formula 7.33 / 87 / 33 / 17 pH / pO2 / pCO 2 / HCO 3
    9. 9. <ul><ul><li>Expected pCO 2 = (1.5 x HCO 3 ) + 8 ±2 </li></ul></ul><ul><ul><li>Expected pCO 2 = 31-35 </li></ul></ul>Predicting pCO 2 in metabolic acidosis: Winter’s Formula 7.33 / 87 / 33 / 17 pH / pO2 / pCO 2 / HCO 3
    10. 10. <ul><ul><li>Expected pCO 2 = (1.5 x HCO 3 ) + 8 ±2 </li></ul></ul><ul><ul><li>Expected pCO 2 = 31-35 </li></ul></ul><ul><ul><li>Actual pCO 2 is 33, which is within the predicted range, indicating a simple metabolic acidosis </li></ul></ul>Predicting pCO 2 in metabolic acidosis: Winter’s Formula 7.33 / 87 / 33 / 17 pH / pO2 / pCO 2 / HCO 3
    11. 11. <ul><ul><li>Expected pCO 2 = (1.5 x HCO 3 ) + 8 ±2 </li></ul></ul><ul><ul><li>Expected pCO 2 = 31-35 </li></ul></ul><ul><ul><li>Actual pCO 2 is 33, which is within the predicted range, indicating a simple metabolic acidosis </li></ul></ul>Predicting pCO 2 in metabolic acidosis: Winter’s Formula Appropriately compensated metabolic acidosis 7.33 / 87 / 33 / 17 pH / pO2 / pCO 2 / HCO 3
    12. 12. <ul><li>Metabolic acidosis is further evaluated by determining the anion associated with the increased H + cation </li></ul>
    13. 13. <ul><li>Metabolic acidosis is further evaluated by determining the anion associated with the increased H + cation </li></ul>It is either chloride Non-Anion Gap Metabolic Acidosis
    14. 14. <ul><li>Metabolic acidosis is further evaluated by determining the anion associated with the increased H + cation </li></ul>It is either chloride Non-Anion Gap Metabolic Acidosis Or it is not chloride Anion Gap Metabolic Acidosis
    15. 15. <ul><li>Metabolic acidosis is further evaluated by determining the anion associated with the increased H + cation </li></ul><ul><li>These can be differentiated by measuring the anion gap. </li></ul>It is either chloride Non-Anion Gap Metabolic Acidosis Or it is not chloride Anion Gap Metabolic Acidosis
    16. 16. Anion gap =
    17. 17. Anion gap =
    18. 18. Anion gap =
    19. 19. Anion gap =
    20. 20. Calculating the anion gap <ul><li>Anion gap = Na – (HCO 3 + Cl) </li></ul><ul><li>Normal is 12 </li></ul><ul><ul><li>Varies from lab to lab </li></ul></ul><ul><ul><li>Average anion gap in healthy controls is 6 ±3 </li></ul></ul><ul><li>Improving chloride assays have resulted in increased chloride levels and a decreased normal anion gap. </li></ul>139 115 3.1 17 16 1.0
    21. 21. Calculating the anion gap <ul><li>Anion gap = 139 – (17 + 115) </li></ul><ul><li>Anion gap = 7 </li></ul><ul><li>Anion gap = Na – (HCO 3 + Cl) </li></ul><ul><li>Normal is 12 </li></ul>139 115 3.1 17 16 1.0
    22. 22. Calculating the anion gap <ul><li>Anion gap = 139 – (17 + 115) </li></ul><ul><li>Anion gap = 7 </li></ul><ul><ul><li>Varies from lab to lab </li></ul></ul><ul><ul><li>Average anion gap in healthy controls is 6 ±3 </li></ul></ul><ul><li>Improving chloride assays have resulted in increased chloride levels and a decreased normal anion gap. </li></ul><ul><li>Anion gap = Na – (HCO 3 + Cl) </li></ul><ul><li>Normal is 12 </li></ul><ul><ul><li>Varies from lab to lab </li></ul></ul><ul><ul><li>Average anion gap in healthy controls is 6 ±3 </li></ul></ul><ul><li>Improving chloride assays have resulted in increased chloride levels and a decreased normal anion gap. </li></ul>Appropriately compensated non-anion gap metabolic acidosis 139 115 3.1 17 16 1.0
    23. 23. NAGMA: Loss of bicarbonate GI loss of HCO 3 Diarrhea Surgical drains Fistulas Ureterosigmoidostomy Obstructed ureteroileostomy Cholestyramine <ul><li>Renal loss of HCO 3 </li></ul><ul><li>Renal tubular acidosis </li></ul><ul><ul><li>Proximal </li></ul></ul><ul><ul><li>Distal </li></ul></ul><ul><ul><li>Hypoaldosteronism </li></ul></ul><ul><li>Saline infusions </li></ul><ul><ul><li>Dilutional acidosis </li></ul></ul><ul><li>HCl intoxication </li></ul><ul><li>Chloride gas intoxication </li></ul><ul><li>Early renal failure </li></ul>
    24. 24. NAGMA: Loss of bicarbonate GI loss of HCO 3 Diarrhea Surgical drains Fistulas Ureterosigmoidostomy Obstructed ureteroileostomy Cholestyramine <ul><li>Renal loss of HCO 3 </li></ul><ul><li>Renal tubular acidosis </li></ul><ul><ul><li>Proximal </li></ul></ul><ul><ul><li>Distal </li></ul></ul><ul><ul><li>Hypoaldosteronism </li></ul></ul>
    25. 25. NAGMA: Loss of bicarbonate GI loss of HCO 3 Diarrhea Surgical drains Fistulas Ureterosigmoidostomy Obstructed ureteroileostomy Cholestyramine <ul><li>Renal loss of HCO 3 </li></ul><ul><li>Renal tubular acidosis </li></ul><ul><ul><li>Proximal </li></ul></ul><ul><ul><li>Distal </li></ul></ul><ul><ul><li>Hypoaldosteronism </li></ul></ul>
    26. 27. Plasma Bile Pancreas Small intestines Large intestines 140 102 4.4 24 135 100 5.0 35 135 50 5.0 90 135 50 5.0 90 110 90 35 40
    27. 29. Urine pH=5.5 Serum pH=7.4 100 fold difference
    28. 30. Ureterosigmoidostomy Urine pH=5.5 Serum pH=7.4 100 fold difference
    29. 31. Ureterosigmoidostomy Ureteroileostomy Urine pH=5.5 Serum pH=7.4 100 fold difference
    30. 32. Renal causes of non-anion gap <ul><li>Renal tubular acidosis is a failure of the kidney to reabsorb all of the filtered bicarbonate or synthesize new bicarbonate to keep up with metabolic demands. </li></ul><ul><li>Daily acid load </li></ul><ul><ul><li>Protein metabolism consumes bicarbonate </li></ul></ul><ul><ul><li>This bicarbonate must be replaced </li></ul></ul><ul><ul><li>Generally equal to 1 mmol/kg </li></ul></ul>
    31. 33. Bicarbonate handling <ul><li>Normally 144 mmol of bicarbonate per hour are filtered at the glomerulus </li></ul><ul><ul><li>24 mmol/L x 100 mL/min x 60 min/hour </li></ul></ul><ul><ul><li>Equivalent to 3 amps of bicarb per hour or a bicarb drip running 1 liter per hour </li></ul></ul>3456 mmol/day 50-100 mmol/day
    32. 34. Bicarbonate handling <ul><li>Normally 144 mmol of bicarbonate per hour are filtered at the glomerulus </li></ul><ul><ul><li>24 mmol/L x 100 mL/min x 60 min/hour </li></ul></ul><ul><ul><li>Equivalent to 3 amps of bicarb per hour or a bicarb drip running 1 liter per hour </li></ul></ul><ul><li>The kidney must create 50-100 mmol per day of new bicarb-onate to replace bicarbonate lost buffering the daily acid load. </li></ul>3456 mmol/day 50-100 mmol/day
    33. 35. Proximal tubule: reabsorption of filtered bicarbonate
    34. 36. Proximal tubule: reabsorption of filtered bicarbonate
    35. 37. Proximal tubule: reabsorption of filtered bicarbonate
    36. 38. Distal tubule, completion of reabsorption and replacing bicarbonate lost to the daily acid load.
    37. 39. Distal tubule, completion of reabsorption and replacing bicarbonate lost to the daily acid load.
    38. 40. Distal tubule, completion of reabsorption and replacing bicarbonate lost to the daily acid load.
    39. 41. Fate of excreted hydrogen ion The minimal urine pH is 4.5. This is a H + concentration a 1000 times that of plasma.
    40. 42. Fate of excreted hydrogen ion The minimal urine pH is 4.5. This is a H + concentration a 1000 times that of plasma. But It still is only 0.04 mmol/L
    41. 43. Fate of excreted hydrogen ion The minimal urine pH is 4.5. This is a H + concentration a 1000 times that of plasma. But It still is only 0.04 mmol/L In order to excrete 50 mmol (to produce enough bicarb-onate to account for the daily acid load) one would need to produce 1250 liters of urine.
    42. 44. Fate of excreted hydrogen ion Ammonium Titratable acid
    43. 45. Proximal RTA (Type 2) <ul><li>The Tm is the maximum plasma concentration of any solute at which the proximal tubule is able to completely reabsorb the solute. </li></ul><ul><li>Beyond the Tm the substance will be incompletely reabsorbed and spill in the urine. </li></ul><ul><li>In Proximal RTA the Tm for bicarbonate is reduced from 26 to 15-20 mmol/L. </li></ul>Na + H 2 O HCO 3 Glucose Amino Acids
    44. 46. <ul><li>Proximal RTA </li></ul><ul><ul><li>Tm for bicarbonate at 15 </li></ul></ul><ul><li>Serum bicarbonate above the Tm </li></ul>Proximal RTA (Type 2) 24 mmol/L 15 mmol/L pH 8
    45. 47. <ul><li>Proximal RTA </li></ul><ul><ul><li>Tm for bicarbonate at 15 </li></ul></ul><ul><li>Serum bicarbonate at the Tm </li></ul>Proximal RTA (Type 2) 15 mmol/L 15 mmol/L pH 5
    46. 48. <ul><li>Proximal RTA </li></ul><ul><ul><li>Tm for bicarbonate at 15 </li></ul></ul><ul><li>Serum bicarbonate below the Tm </li></ul>Proximal RTA (Type 2) 12 mmol/L 12 mmol/L pH 5
    47. 49. Proximal RTA: etiologies <ul><li>Acquired </li></ul><ul><ul><li>Acetylzolamide </li></ul></ul><ul><ul><li>Ifosfamide </li></ul></ul><ul><ul><li>Chronic hypocalcemia </li></ul></ul><ul><ul><li>Multiple myeloma </li></ul></ul><ul><ul><li>Cisplatin </li></ul></ul><ul><ul><li>Lead toxicity </li></ul></ul><ul><ul><li>Mercury poisoning </li></ul></ul><ul><ul><li>Streptozocin </li></ul></ul><ul><ul><li>Expired tetracycline </li></ul></ul><ul><li>Genetic </li></ul><ul><ul><li>Cystinosis </li></ul></ul><ul><ul><li>Galactosemia </li></ul></ul><ul><ul><li>Hereditary fructose intolerance </li></ul></ul><ul><ul><li>Wilson’s disease </li></ul></ul><ul><li>Hyperparathyroidism </li></ul><ul><li>Chronic hypocapnia </li></ul><ul><ul><li>Intracellular alkalosis </li></ul></ul>
    48. 50. Proximal RTA: consequences <ul><li>Hypokalemia </li></ul><ul><li>Bone disease </li></ul><ul><ul><li>Bone buffering of the acidosis </li></ul></ul><ul><ul><li>Decreased 1,25 OH D leading to hypocalcemia and 2° HPTH </li></ul></ul><ul><li>Not typically complicated by stones </li></ul>
    49. 51. Distal RTA (Type 1) <ul><li>A failure to secrete the daily acid load at the distal tubule is distal rta. </li></ul><ul><li>A failure in any one of the three steps in urinary acidification can result in RTA </li></ul><ul><li>Each step has been demonstrated to fail and has independent etiologies </li></ul>
    50. 52. Distal RTA: Voltage dependent <ul><li>Only variety of distal RTA which is hyperkalemic </li></ul><ul><li>Differentiate from type 4 by failure to respond to fludrocortisone. </li></ul><ul><ul><li>Obstructive uropathy </li></ul></ul><ul><ul><li>Sickle cell anemia </li></ul></ul><ul><ul><li>Lupus </li></ul></ul><ul><ul><li>Triameterene </li></ul></ul><ul><ul><li>Amiloride </li></ul></ul>
    51. 53. Distal RTA: Voltage dependent <ul><li>Only variety of distal RTA which is hyperkalemic </li></ul><ul><li>Differentiate from type 4 by failure to respond to fludrocortisone. </li></ul><ul><ul><li>Obstructive uropathy </li></ul></ul><ul><ul><li>Sickle cell anemia </li></ul></ul><ul><ul><li>Lupus </li></ul></ul><ul><ul><li>Triameterene </li></ul></ul><ul><ul><li>Amiloride </li></ul></ul>
    52. 54. Distal RTA: Voltage dependent <ul><li>Only variety of distal RTA which is hyperkalemic </li></ul><ul><li>Differentiate from type 4 by failure to respond to fludrocortisone. </li></ul><ul><ul><li>Obstructive uropathy </li></ul></ul><ul><ul><li>Sickle cell anemia </li></ul></ul><ul><ul><li>Lupus </li></ul></ul><ul><ul><li>Triameterene </li></ul></ul><ul><ul><li>Amiloride </li></ul></ul>
    53. 55. Distal RTA: Voltage dependent <ul><li>Only variety of distal RTA which is hyperkalemic </li></ul><ul><li>Differentiate from type 4 by failure to respond to fludrocortisone. </li></ul><ul><ul><li>Obstructive uropathy </li></ul></ul><ul><ul><li>Sickle cell anemia </li></ul></ul><ul><ul><li>Lupus </li></ul></ul><ul><ul><li>Triameterene </li></ul></ul><ul><ul><li>Amiloride </li></ul></ul>
    54. 56. Distal RTA: H + Secretion <ul><li>Called classic distal RTA </li></ul><ul><li>Most common cause of distal RTA </li></ul><ul><ul><li>Congenital </li></ul></ul><ul><ul><li>Lithium </li></ul></ul><ul><ul><li>Multiple myeloma </li></ul></ul><ul><ul><li>Lupus </li></ul></ul><ul><ul><li>Pyelonephritis </li></ul></ul><ul><ul><li>Sickle cell anemia </li></ul></ul><ul><ul><li>Sjögren’s syndrome </li></ul></ul><ul><ul><li>Toluene (Glue sniffing) </li></ul></ul><ul><ul><li>Wilson’s disease </li></ul></ul>
    55. 57. Distal RTA: Gradient defect <ul><li>Amphotercin B </li></ul>
    56. 58. Distal RTA: consequences <ul><li>Bones </li></ul><ul><ul><li>Chronic metabolic acidosis results in bone buffering. </li></ul></ul><ul><ul><ul><li>Bicarbonate </li></ul></ul></ul><ul><ul><ul><li>Phosphate </li></ul></ul></ul><ul><ul><ul><li>Calcium </li></ul></ul></ul><ul><li>Kidney stones </li></ul><ul><ul><li>Calcium phosphate stones </li></ul></ul><ul><ul><ul><li>Due to hypercalciuria </li></ul></ul></ul><ul><ul><ul><li>Increased urine pH </li></ul></ul></ul><ul><ul><ul><li>Decreased urinary citrate </li></ul></ul></ul>Well Mr. Osborne, it may not be kidney stones after all.
    57. 59. Hypoaldosteronism <ul><li>Chronic hyperkalemia of any etiology decreases ammonia- genesis </li></ul><ul><li>Without ammonia to convert to ammonium total acid excretion is modest </li></ul><ul><li>Urinary acidification is intact </li></ul><ul><li>Acidosis is typically mild without significant bone or stone disease </li></ul><ul><li>Primary problem is with high potassium </li></ul>
    58. 60. Diagnosing the cause of: non-anion gap metabolic acidosis
    59. 61. To look for renal H + clearance look for urinary ammonium Ammonium Titratable acid
    60. 62. To look for renal H + clearance look for urinary ammonium Ammonium Titratable acid NH 4 +
    61. 63. Urinary anion gap: Urinary ammonium detector <ul><li>In the presence of ammonium the chloride will be larger than the sum of Na and K. </li></ul><ul><li>So a negative anion gap means ammonium in the urine. </li></ul><ul><li>Ammonium in the urine means effective renal acid secretion </li></ul><ul><li>Ammonium in the urine usually rules out RTA </li></ul>(Na + + K + ) – Cl –
    62. 64. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul>
    63. 65. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul>
    64. 66. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul>15 mmol/L 15 mmol/L pH 5
    65. 67. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul>15 mmol/L 15 mmol/L pH 5
    66. 68. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><ul><li>During treatment </li></ul></ul>24 mmol/L 15 mmol/L pH 8
    67. 69. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><ul><li>During treatment </li></ul></ul><ul><ul><ul><li>Positive </li></ul></ul></ul>24 mmol/L 15 mmol/L pH 8
    68. 70. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><ul><li>During treatment </li></ul></ul><ul><ul><ul><li>Positive </li></ul></ul></ul><ul><ul><li>During acid load </li></ul></ul>12 mmol/L 12 mmol/L pH 5
    69. 71. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><ul><li>During treatment </li></ul></ul><ul><ul><ul><li>Positive </li></ul></ul></ul><ul><ul><li>During acid load </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul>12 mmol/L 12 mmol/L pH 5
    70. 72. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><ul><li>During treatment </li></ul></ul><ul><ul><ul><li>Positive </li></ul></ul></ul><ul><ul><li>During acid load </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><li>Distal RTA </li></ul>
    71. 73. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><ul><li>During treatment </li></ul></ul><ul><ul><ul><li>Positive </li></ul></ul></ul><ul><ul><li>During acid load </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><li>Distal RTA: </li></ul><ul><ul><li>Positive </li></ul></ul>
    72. 74. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><ul><li>During treatment </li></ul></ul><ul><ul><ul><li>Positive </li></ul></ul></ul><ul><ul><li>During acid load </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><li>Distal RTA: </li></ul><ul><ul><li>Positive </li></ul></ul><ul><li>Type IV RTA </li></ul>
    73. 75. NAGMA and urinary anion gap <ul><li>Diarrhea </li></ul><ul><ul><li>Negative </li></ul></ul><ul><li>Proximal RTA </li></ul><ul><ul><li>At baseline </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><ul><li>During treatment </li></ul></ul><ul><ul><ul><li>Positive </li></ul></ul></ul><ul><ul><li>During acid load </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><li>Distal RTA: </li></ul><ul><ul><li>Positive </li></ul></ul><ul><li>Type IV RTA </li></ul><ul><ul><li>Positive </li></ul></ul>
    74. 76. 58 y.o. female with weakness and muscle aches 7.34 / 87 / 33 / 16 U/A pH 6.5 Urine electrolytes 139 115 3.1 17 16 1.0 80 115 45
    75. 77. 58 y.o. female with weakness and muscle aches 7.34 / 87 / 33 / 16 U/A pH 6.5 Urine electrolytes Appropriately compensated non-anion gap metabolic acidosis due to distal RTA 139 115 3.1 17 16 1.0 80 115 45
    76. 78. 74 y.o. female with 34 year history of DM c/o weakness 7.34 / 87 / 33 / 16 Albumin 1.8 139 123 6.6 17 21 1.2
    77. 79. Determine the primary disorder <ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul>7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3
    78. 80. Determine the primary disorder <ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul><ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul>7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3 7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3
    79. 81. Determine the primary disorder <ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul><ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul>7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3 7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3
    80. 82. Determine the primary disorder <ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul><ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul>7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3 7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3
    81. 83. Determine the primary disorder <ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul><ul><li>Acidosis or alkalosis </li></ul><ul><ul><li>If the pH is less than 7.4 it is acidosis </li></ul></ul><ul><ul><li>If the pH is greater than 7.4 it is alkalosis </li></ul></ul><ul><li>Determine if it is respiratory or metabolic </li></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 all move in the same direction (up or down) it is metabolic </li></ul></ul><ul><ul><li>If the pH, bicarbonate and pCO 2 move in discordant directions (up and down) it is respiratory </li></ul></ul>Metabolic Acidosis 7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3 7.34 / 87 / 33 / 16 pH / pO2 / pCO 2 / HCO 3
    82. 84. <ul><ul><li>Expected pCO 2 = (1.5 x HCO 3 ) + 8 ±2 </li></ul></ul><ul><ul><li>Expected pCO 2 = 31-35 </li></ul></ul><ul><ul><li>Actual pCO 2 is 33, which is within the predicted range, indicating a simple metabolic acidosis </li></ul></ul>Predicting pCO 2 in metabolic acidosis: Winter’s Formula 7.33 / 87 / 33 / 17 pH / pO2 / pCO 2 / HCO 3
    83. 85. <ul><ul><li>Expected pCO 2 = (1.5 x HCO 3 ) + 8 ±2 </li></ul></ul><ul><ul><li>Expected pCO 2 = 31-35 </li></ul></ul><ul><ul><li>Actual pCO 2 is 33, which is within the predicted range, indicating a simple metabolic acidosis </li></ul></ul>Predicting pCO 2 in metabolic acidosis: Winter’s Formula 7.33 / 87 / 33 / 17 pH / pO2 / pCO 2 / HCO 3
    84. 86. <ul><ul><li>Expected pCO 2 = (1.5 x HCO 3 ) + 8 ±2 </li></ul></ul><ul><ul><li>Expected pCO 2 = 31-35 </li></ul></ul><ul><ul><li>Actual pCO 2 is 33, which is within the predicted range, indicating a simple metabolic acidosis </li></ul></ul>Predicting pCO 2 in metabolic acidosis: Winter’s Formula 7.33 / 87 / 33 / 17 pH / pO2 / pCO 2 / HCO 3
    85. 87. <ul><ul><li>Expected pCO 2 = (1.5 x HCO 3 ) + 8 ±2 </li></ul></ul><ul><ul><li>Expected pCO 2 = 31-35 </li></ul></ul><ul><ul><li>Actual pCO 2 is 33, which is within the predicted range, indicating a simple metabolic acidosis </li></ul></ul>Predicting pCO 2 in metabolic acidosis: Winter’s Formula Appropriately compensated metabolic acidosis 7.33 / 87 / 33 / 17 pH / pO2 / pCO 2 / HCO 3
    86. 88. Calculating the anion gap <ul><li>Anion gap = Na – (HCO 3 + Cl) </li></ul>139 123 6.6 17 16 1.0
    87. 89. Calculating the anion gap <ul><li>Anion gap = Na – (HCO 3 + Cl) </li></ul><ul><li>Anion gap = 139 – (123 + 17) </li></ul><ul><li>Anion gap = -1 </li></ul>139 123 6.6 17 16 1.0
    88. 90. Calculating the anion gap <ul><li>Anion gap = Na – (HCO 3 + Cl) </li></ul><ul><li>Anion gap = 139 – (123 + 17) </li></ul><ul><li>Anion gap = -1 </li></ul>A negative anion gap! That’s got to mean something! 139 123 6.6 17 16 1.0
    89. 91. Hypoalbuminuria, hypophosphatemia <ul><li>The “other anions” includes phosphate and albumin </li></ul><ul><li>Hypoalbuminuria and hypophosphatemia lowers the anion gap </li></ul><ul><li>If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap </li></ul>
    90. 92. Hypoalbuminuria, hypophosphatemia <ul><li>The “other anions” includes phosphate and albumin </li></ul><ul><li>Hypoalbuminuria and hypophosphatemia lowers the anion gap </li></ul><ul><li>If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap </li></ul>
    91. 93. Hypoalbuminuria, hypophosphatemia <ul><li>The “other anions” includes phosphate and albumin </li></ul><ul><li>Hypoalbuminuria and hypophosphatemia lowers the anion gap </li></ul><ul><li>If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap </li></ul>Adjusted Normal Anion Gap
    92. 94. Hypoalbuminuria, hypophosphatemia <ul><li>The “other anions” includes phosphate and albumin </li></ul><ul><li>Hypoalbuminuria and hypophosphatemia lowers the anion gap </li></ul><ul><li>If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap </li></ul>Adjusted Normal Anion Gap
    93. 95. Hypoalbuminuria, hypophosphatemia <ul><li>The “other anions” includes phosphate and albumin </li></ul><ul><li>To estimate the normal anion gap for any individual multiply the albumin by 2.5 and add half the phosphorous </li></ul><ul><li>Hypoalbuminuria and hypophosphatemia lowers the anion gap </li></ul><ul><li>If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap </li></ul>Adjusted Normal Anion Gap
    94. 96. Other causes of a low anion gap <ul><li>Increased chloride </li></ul><ul><ul><li>Hypertriglyceridemia </li></ul></ul><ul><ul><li>Bromide </li></ul></ul><ul><ul><li>Iodide </li></ul></ul><ul><li>Decreased “ Unmeasured anions ” </li></ul><ul><ul><li>Albumin </li></ul></ul><ul><ul><li>Phosphorous </li></ul></ul><ul><ul><li>IgA </li></ul></ul><ul><li>Increased “ Unmeasured cations ” </li></ul><ul><ul><li>Hyperkalemia </li></ul></ul><ul><ul><li>Hypercalcemia </li></ul></ul><ul><ul><li>Hypermagnesemia </li></ul></ul><ul><ul><li>Lithium </li></ul></ul><ul><ul><li>Increased cationic paraproteins </li></ul></ul><ul><ul><ul><li>IgG </li></ul></ul></ul>Albumin Phos IgA Chloride Bicarb Sodium Potassium Calcium Magnesium IgG Normal anion gap
    95. 97. Recent lab history
    96. 98. Diagnose the cause of: non-anion gap metabolic acidosis with hyperkalemia
    97. 99. Diagnose the cause of: non-anion gap metabolic acidosis with hyperkalemia <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul>
    98. 100. Diagnose the cause of: non-anion gap metabolic acidosis with hyperkalemia <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA </li></ul>
    99. 101. A dipstick for aldosterone activity: The trans-tubular potassium gradient The TTKG
    100. 102. Trans-tubular Potassium Gradient (TTKG) <ul><li>The ratio of tubular to venous K indicates the level of aldosterone activity. </li></ul><ul><li>In the presence of hyperkalemia the ratio should be > 10. </li></ul><ul><li>In the presence of hypokalemia the ratio of < 4. </li></ul>
    101. 103. Trans-tubular Potassium Gradient (TTKG) <ul><li>The ratio of tubular to venous K indicates the level of aldosterone activity. </li></ul><ul><li>In the presence of hyperkalemia the ratio should be > 10. </li></ul><ul><li>In the presence of hypokalemia the ratio of < 4. </li></ul>
    102. 104. Trans-tubular Potassium Gradient (TTKG) <ul><li>The ratio of tubular to venous K indicates the level of aldosterone activity. </li></ul><ul><li>In the presence of hyperkalemia the ratio should be > 10. </li></ul><ul><li>In the presence of hypokalemia the ratio of < 4. </li></ul>
    103. 105. Trans-tubular Potassium Gradient (TTKG) <ul><li>The ratio of tubular to venous K indicates the level of aldosterone activity. </li></ul><ul><li>In the presence of hyperkalemia the ratio should be > 10. </li></ul><ul><li>In the presence of hypokalemia the ratio of < 4. </li></ul>
    104. 106. <ul><li>The trans-tubular potassium gradient adjusts the urine potassium for water loss in the collecting ducts. </li></ul><ul><li>This allows the use of urinary potassium to calculate the ratio of potassium from the tubule to the interstitium in the CCD. </li></ul>Trans-tubular Potassium Gradient (TTKG)
    105. 107. <ul><li>The trans-tubular potassium gradient adjusts the urine potassium for water loss in the collecting ducts. </li></ul><ul><li>This allows the use of urinary potassium to calculate the ratio of potassium from the tubule to the interstitium in the CCD. </li></ul>Trans-tubular Potassium Gradient (TTKG)
    106. 108. <ul><li>The trans-tubular potassium gradient adjusts the urine potassium for water loss in the collecting ducts. </li></ul><ul><li>This allows the use of urinary potassium to calculate the ratio of potassium from the tubule to the interstitium in the CCD. </li></ul>Trans-tubular Potassium Gradient (TTKG)
    107. 109. <ul><li>The trans-tubular potassium gradient adjusts the urine potassium for water loss in the collecting ducts. </li></ul><ul><li>This allows the use of urinary potassium to calculate the ratio of potassium from the tubule to the interstitium in the CCD. </li></ul>Trans-tubular Potassium Gradient (TTKG)
    108. 110. <ul><li>Pre-requisites to using the TTKG as a measure of aldosterone activity: </li></ul>Trans-tubular Potassium Gradient (TTKG) <ul><ul><li>Urine osmolality > serum osmolality </li></ul></ul>
    109. 111. <ul><li>Pre-requisites to using the TTKG as a measure of aldosterone activity: </li></ul>Trans-tubular Potassium Gradient (TTKG) <ul><ul><li>Urine osmolality > serum osmolality </li></ul></ul>Fluid leaving the LoH has an osmolality of 100 mOsm/Kg
    110. 112. <ul><li>Pre-requisites to using the TTKG as a measure of aldosterone activity: </li></ul>Trans-tubular Potassium Gradient (TTKG) <ul><ul><li>Urine osmolality > serum osmolality </li></ul></ul>Fluid leaving the LoH has an osmolality of 100 mOsm/Kg In the presence of ADH water leaves the DCT so that the tubular fluid becomes isosmotic
    111. 113. <ul><li>Pre-requisites to using the TTKG as a measure of aldosterone activity: </li></ul>Trans-tubular Potassium Gradient (TTKG) <ul><ul><li>Urine osmolality > serum osmolality </li></ul></ul><ul><ul><li>Urine Na > 20 mmol/L </li></ul></ul>Fluid leaving the LoH has an osmolality of 100 mOsm/Kg In the presence of ADH water leaves the DCT so that the tubular fluid becomes isosmotic
    112. 114. <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA </li></ul>Trans-tubular Potassium Gradient (TTKG) Lets play low normal or high! TTKG and Aldo level
    113. 115. <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA </li></ul>Trans-tubular Potassium Gradient (TTKG) <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><ul><li>Low TTKG </li></ul></ul><ul><ul><li>Low aldosterone </li></ul></ul>Lets play low normal or high! TTKG and Aldo level
    114. 116. <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA </li></ul>Trans-tubular Potassium Gradient (TTKG) <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><ul><li>Low TTKG </li></ul></ul><ul><ul><li>Low aldosterone </li></ul></ul><ul><li>Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA </li></ul><ul><ul><li>Low TTKG </li></ul></ul><ul><ul><li>High aldosterone </li></ul></ul>Lets play low normal or high! TTKG and Aldo level
    115. 117. 58 y.o. female with weakness and muscle aches
    116. 118. 58 y.o. female with weakness and muscle aches Both the bicarbonate and potassium were normal at admission. This is hospital acquired RTA (type 1 or 4)
    117. 119. <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1), voltage dependent distal RTA </li></ul>Hospital acquired RTA really means drug induced RTA
    118. 120. <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1), voltage dependent distal RTA </li></ul>Hospital acquired RTA really means drug induced RTA Lets play: Name that drug!
    119. 121. <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1), voltage dependent distal RTA </li></ul>Hospital acquired RTA really means drug induced RTA <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><ul><li>Spironolactone </li></ul></ul><ul><ul><li>ACEi/ARB </li></ul></ul><ul><ul><li>Heparin </li></ul></ul>Lets play: Name that drug!
    120. 122. <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1), voltage dependent distal RTA </li></ul>Hospital acquired RTA really means drug induced RTA <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><ul><li>Spironolactone </li></ul></ul><ul><ul><li>ACEi/ARB </li></ul></ul><ul><ul><li>Heparin </li></ul></ul><ul><li>Hyperkalemic Distal (Type 1), voltage dependent distal RTA </li></ul><ul><ul><li>Amiloride </li></ul></ul><ul><ul><li>Triamterene </li></ul></ul><ul><ul><li>Trimethoprim </li></ul></ul>Lets play: Name that drug!
    121. 123. <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1), voltage dependent distal RTA </li></ul>58 y.o. female with weakness and muscle aches
    122. 124. <ul><li>Type four RTA, hyporenin-hypoaldo </li></ul><ul><li>Hyperkalemic Distal (Type 1), voltage dependent distal RTA </li></ul>58 y.o. female with weakness and muscle aches Patient’s TTKG was 2.7 with a K of 5.7 Aldosterone was 22 The patient had been started on a high dose of TMP/SMX for a partially resistant urinary tract infection
    123. 125. <ul><li>Two women with non-anion gap metabolic acidosis </li></ul><ul><li>One with hypokalemia </li></ul><ul><li>One with hyperkalemia </li></ul><ul><li>Both with distal RTA </li></ul>
    124. 126. Fin

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