Presentation is loading. Please wait.

Presentation is loading. Please wait.

Normal Anion Gap Acidoses Renal Tubular Acidosis Jai Radhakrishnan, MD, MS, MRCP, FACC, FASN Associate Professor of Clinical Medicine Columbia University.

Similar presentations


Presentation on theme: "Normal Anion Gap Acidoses Renal Tubular Acidosis Jai Radhakrishnan, MD, MS, MRCP, FACC, FASN Associate Professor of Clinical Medicine Columbia University."— Presentation transcript:

1 Normal Anion Gap Acidoses Renal Tubular Acidosis Jai Radhakrishnan, MD, MS, MRCP, FACC, FASN Associate Professor of Clinical Medicine Columbia University

2 Disclosures None

3 Objective Physiology of renal acid handling Diagnostic approach to Metabolic Acidosis with normal anion gap. Case-based diagnostic workup of the RTA’s

4 Chemistry: Carbonic Acid Carbonic Acid. –[ H + ] x [ HCO 3 - ] = k1 x H 2 CO 3 = k2 x [ CO 2 ] x [ H 2 O ] Simplified –H 2 CO 3 is not of clinical interest –[H 2 O] is constant in-vivo –PCO 2 is more familiar than [CO 2 ]: [ H + ] x [ HCO 3 - ] = k x PCO 2 [ Modified Henderson Equation. ]Modified Henderson Equation. Hasselbalch ModificationHasselbalch 4

5 Metabolic Acidosis: The “Anion Gap” Na + Cl - HCO 3 - Alb -  [Na + ] - ([Cl - ] + [HCO 3 - ]) Na + Cl - HCO 3 - Alb - Nl Anion gap M acidosis ~ mM/L

6 1. GI bicarbonate loss (typically also with low K): diarrhea villous adenoma pancreatic, biliary, small bowel fistulae uretero-sigmoidostomy obstructed uretero-ileostomy Etiology of “normal anion gap” (A.K.A. “hyperchloremic”) metabolic acidosis

7 Pancreas Ileum Colon Pancreas Ileum Colon GI Loss of HCO 3 - HCO 3 - Cl - HCO 3 - Cl - K+K+ HCO 3 - NormalDiarrhea Cl -

8 Flooding the colon with HCO 3 - instead of Cl - drives K + secretion Na + K+K+ K+K+ Cl - HCO 3 - K+K+

9 Uretero-ileostomy Causes a Normal Anion Gap Acidosis ileal loop HCO 3 - Skin Cl -

10 2. Ingestions & infusions ammonium chloride hyperalimentation (arginine/lysine-rich) 3. Renal bicarbonate (or equivalent) loss proximal RTA distal RTA type IV RTA early renal failure acetazolamide hydrated DKA Causes of a “normal anion gap” (A.K.A. “hyperchloremic”) metabolic acidosis

11

12 Proximal RTA (“Type II”) HCO 3 - (1) Na + (3) HCO 3 - H+H+ CO 2 H2OH2O + H+H+ Na + HCO 3 - glucose amino acids urate phosphate Defective Na + - dependent resorption = Fanconi’s Syndrome

13 Distal RTA Na + K+K+ K+K+ Principal cell  IC cell  IC cell HCO 3 - Cl - HCO 3 - Cl - H+H+ ATP ADP + P i H+H+ ATP ADP + P i Cl - Aldosterone

14 Net acid excretion = urinary NH urinary “titratable acid” (H 2 PO 4 - ) - urinary HCO 3 - H+H+ NH 4 + NH 3 + HCO H 2 CO 3 HPO H 2 PO 4 - Not titratable; need to measure Present in Prox RTA Titratable acid

15 Hyperkalemic distal RTA: Na + K+K+ K+K+ Principal cell  IC cell  IC cell HCO 3 - Cl - HCO 3 - Cl - H+H+ ATP ADP + P i H+H+ ATP ADP + P i Cl - Aldosterone

16 ACIDOSIS IN HYPORENINEMIC HYPOALDOSTERONISM 2. Total body K+ excess K+K+ 3. K+ entry into proximal tubule cells HCO 3 - (1) Na + (3) HCO 3 - H+H+ CO 2 H2OH2O + H+H+ Na + H+H+ 4. Alkalinization of prox tubule cell by K + /H + exchange 1. Failed CCD K + secretion 5. Total Body K+ Excess Decreases Proximal Tubule Acidification and Ammoniagenesis via Intracellular Alkalosis

17 DIAGNOSTIC APPROACH Minimum Urine pH Urinary Anion Gap Plasma potassium Renal stones or Nephrocalcinosis Prox. Tubular dysfunction FE HCO3 Daily bicarbonate replacement needs

18 Urine pH Plasma [HCO 3 - ] mM Normal Proximal RTA Distal RTA (Oxford Textbook of Nephrology - Soriano et al, 1967) Urine pH vs. Plasma bicarbonate in RTA

19 19 Urinary Anion Gap Urine (Na+K) – Cl Proton is partially excreted as NH 4 (unmeasured cation) The gap is usually Zero or Negative In dRTA the anion gap will remain zero or positive In other acidoses, the gap will become more negative. Unmeasured anions-unmeasured cations

20 A positive urine anion gap ~ no NH 4 + Cl excretion (i.e. low renal tubule acidification) Normal acidotic: closed circles Diarrhea: closed triangles Type 1 or IV RTA: open circles Battle et al, NEJM 1988

21 Flooding the distal tubule with HCO 3 - instead of Cl - in Proximal RTA drives K + secretion Na + K+K+ K+K+ Cl - HCO 3 - K+K+ Proximal RTA: Hypokalemia

22 H + no longer shunts Na + current so K + must do so Na + K+K+ K+K+ Principal cell  IC cell  IC cell HCO 3 - Cl - HCO 3 - Cl - H+H+ ATP ADP + P i H+H+ ATP ADP + P i Cl - Aldosterone Distal RTA: Hypokalemia

23 Hyperkalemic Distal RTA Na + K+K+ K+K+ Principal cell  IC cell  IC cell HCO 3 - Cl - HCO 3 - Cl - H+H+ ATP ADP + P i H+H+ ATP ADP + P i Cl - Aldosterone Low Aldosterone Voltage defect

24 Nephrocalcinosis/Kidney Stones Distal RTA (High Incidence) –Alkaline urine: Calcium phosphate precipitation –Acidosis: Increased citrate reabsorption by proximal nephron Proximal RTA (Not Seen): –Urine pH not high –Citrate not absorbed

25 FANCONI’S SYNDROME only in Proximal RTA HCO 3 - (1) Na + (3) HCO 3 - H+H+ CO 2 H2OH2O + H+H+ Na + HCO 3 - glucose amino acids urate phosphate Defective Na + - dependent resorption = Fanconi’s Syndrome

26 Fractional excretion of HCO 3 -

27 Daily HCO3 Requirements Proximal –>4 meq/kg Distal –1-2 meq/kg Hyperkalemic –1-2 meq/kg

28 J Am Soc Nephrol 13: , 2002

29 Positive Urinary anion gap Urine pH & plasma [K + ] Urine pH < 5.5 & high[K + ] Hypo- aldosteronism RTA(type IV) Urine pH > 5.5 & low/nl[K + ] Distal RTA (“Type I”): secretory or gradient defect

30

31 Case 1 A 55-year-old woman presents with complaints of lethargy, thirst, muscle weakness and generalized body pains. Previous ED visits with hypokalemia. Her serum potassium level was 2.6 mmol/l. Other Electrolytes: –sodium 138 mmol/l –chloride 116 mmol/l –HCO 3 17 mmol/l –BUN/Creatinine normal –Glucose 75mg/dL Urine analysis: pH 5.4, 2+ glucose Urine anion gap: -20 Proximal RTA ABG: pH 7.25 pCO 2 28 pO total bicarbonate 15.1 mmol/l base excess –13.7 mmol/l

32 Case 1: Proximal RTA Minimum Urine pH <5.5 Plasma potassium Low-normal Renal stones/NC No Prox. Tubular dysfunction Glycosuria, Phosphate, AA, Urate FE HCO % Daily bicarbonate replacement needs >4 mmol/kg

33 FE HCO3 Intravenous infusion of sodium bicarbonate at a rate of 0.5 to 1.0 meq/kg per hoursodium bicarbonate U HCO3 x P Cr FE HCO3 = ——————————— x 100 P HCO3 x U Cr Proximal RTA: FE HCO3 >15-20%

34 Clinical Features of Proximal RTA Urine pH depends on plasma [HCO3-] Fractional HCO3- excretion high (15-20%) at nl plasma [HCO3-] Plasma [K+] reduced, worsens with HCO3- therapy Dose of daily HCO3- required: mEq/kg/d Non-renal: rickets or osteomalacia

35 Causes of Proximal RTA Primary isolated proximal RTA –hereditary (persistent) a. autosomal dominant b. autosomal recessive associated with mental retardation and ocular abnormalities –Sporadic (transient in infancy) Secondary proximal RTA –in the context of Fanconi syndrome (cystinosis, galactosemia, fructose intolerance, tyrosinemia, Wilson disease, Lowe syndrome, metachromatic leukodystrophy, multiple myeloma, light chain disease) –drugs and toxins (acetazolamide, outdated tetracycline, aminoglycoside antibiotics, valproate, 6-mercaptopurine, streptozotocin, iphosphamide, lead, cadmium, mercury) –other clinical entities (vitamin D deficiency, hyperparathyroidism, chronic hypocapnia, Leigh syndrome, cyanotic congenital heart disease, medullary cystic disease, Alport syndrome, corticoresistant nephrotic syndrome, renal transplantation, amyloidosis, recurrent nephrolithiasis) J Am Soc Nephrol 13: , 2002

36 Case 2 A 38-year-old woman was admitted with severe weakness (3 rd episode) PMH: artificial tears for dry eyes Laboratory –Urine pH 7.1 –sodium 141 mEq/L –potassium 3.0 mEq/L –carbon dioxide 14 mEq/L –chloride 114 mEq/L –S creatinine 0.8 mg/dL (70.7 µmol/L) –Albumin 4.3 –Urinary anion gap +4 Arch Intern Med. 2004;164: Distal RTA

37 Case 2: Distal RTA Arch Intern Med. 2004;164: Minimum Urine pH >5.5 Plasma potassium Low- normal Renal stones/NC YES Prox. Tubular dysfunction No FE HCO3 <3% Daily bicarbonate replacement needs <4 mmol/kg

38 Nephrocalcinosis/Recurrent Stones Consider Distal RTA

39 Furosemide/Fludrocortisone Test Baseline urine sample Oral administration of furosemide (40 mg) and fludrocortisone (1 mg). Fluid intake ad libitum. Urine q1h x 6 h after the baseline sample. Failed to acidify their urine to pH<5.3 Kidney International (2007) 71, 1310–1316

40 Schirmer’s test positive antibodies to the Ro/SSA and La/SSB + Cryocrit +

41 Causes of distal RTA J Am Soc Nephrol 13: , 2002

42 Case 3 50 year old male with NIDDMhas been prescribed a low Na diet for HTN. He presents to the ER with marked weakness. Labs: 130|98| |20|1.3 Urine pH 5.0, 1+ protein Urine Na130, K 15, Cl 120

43 Case 3 50 year old male with NIDDMhas been prescribed a low Na diet for HTN. He presents to the ER with marked weakness. Labs: 130|98| |20|1.3 Urine pH 5.0, 1+ protein Hyper- kalemic Minimum Urine pH <5.5 Plasma potassium High Renal stones/NC No Prox. Tubular dysfunction No FE HCO3 <3% Daily bicarbonate replacement needs <4 mmol/kg

44 Type IV RTA: Etiology Aldosterone –Hyporenin/hypoaldo (CKD) –Addison –Congenital :enzymes Voltage –PHA –Drugs: TMP, K-sparing, pentamidine CNI (Na-K ATPas) Multiple: Tubulointerstitial disease

45 RTA DistalProximal UAG neg Hyper- kalemic Minimum Urine pH >5.5+/- <5.5<5.5 Plasma potassium Low- normal High Renal stones/NC YESNo Prox. Tubular dysfunction NoGlycosuria, Phosphate, AA, Urate No FE HCO3 <3%15-20%<3% Daily bicarbonate replacement needs <4 mmol/kg >4 mmol/kg<4 mmol/kg


Download ppt "Normal Anion Gap Acidoses Renal Tubular Acidosis Jai Radhakrishnan, MD, MS, MRCP, FACC, FASN Associate Professor of Clinical Medicine Columbia University."

Similar presentations


Ads by Google