Metabolic Acidosis Anna Vinnikova, M.D. Division of Nephrology Virginia Commonwealth University Graphics by permission from The Fluid, Electrolyte and Acid-Base Companion, S. Faubel and J. Topf, http://www.pbfluids.com
Case 1 A 46 yo alcoholic comes to ED c/o abd pain/coffee grounds vomiting after a binge of Canadian Malt Whiskey. He is fully oriented but very tremulous BP is 80 s/40 s, HR 76
Case 1 VBG 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92
Case 1 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 AG 34
Case 1 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 AG 34 AGMA
Case 1 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 AG 34 What is his corrected bicarb?
Case 1 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 AG 34 Corrected bicarb is bicarb you would get after correction of AGMA
Case 1 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 AG 34 AG is elevated by:
Case 1 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 AG 34 AG is elevated by: 34-12=22
Case 1 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 AG 34, elevated by 22 If you corrected this AGMA, bicarb would be 4 + 22 = 26
Case 1 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 Corrected bicarb 26 Corrected bicarb is normal indicating simple AGMA
Case 1 VBG 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 Is respiratory compensation appropriate?
Case 1 VBG 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 Is respiratory compensation appropriate? You need ABG, not a VBG to answer this question
Case 1 6.79 / 25 / 82 / 3.9 / 81% 147 109 42 5.1 4 3.5 92 AG 34 Phos 20 Lactate 19 Urine ket 20 Alb 3
Case 1 Acetone 50 Ethanol 140 Isopropanol 30 Methanol 0 ASA <50 147 109 42 5.1 4 3.5 92
Case 1 Acetone 50 Ethanol 140 Isopropanol 30 147 109 42 5.1 4 3.5 92 What is his Osmolar Gap?
Ingestions: Osm gap Osmolar gap is present if measured osm > calculated osm by 10
Case 1 Acetone 50 Ethanol 140 Isopropanol 30 147 109 42 5.1 4 3.5 92 S Osm 345 Calc S Osm =
Case 1 Acetone 50 Ethanol 140 Isopropanol 30 147 109 42 5.1 4 3.5 92 S Osm 345 Calc S Osm = 147x2 +
Case 1 Acetone 50 Ethanol 140 Isopropanol 30 147 109 42 5.1 4 3.5 92 S Osm 345 Calc S Osm = 147x2 + 42/2.8 +
Case 1 Acetone 50 Ethanol 140 Isopropanol 30 147 109 42 5.1 4 3.5 92 S Osm 345 Calc S Osm = 147x2 + 42/2.8 + 92/18
Case 1 Acetone 50 mg/l Ethanol 140 mg/l Isopropanol 30 mg/l 147 109 42 5.1 4 3.5 92 S Osm 345 Calc S Osm = 147x2 + 42/2.8 + 92/18 + 14/4.6
Case 1 Acetone 50 mg/l Ethanol 140 mg/l Isopropanol 30 mg/l 147 109 42 5.1 4 3.5 92 S Osm 345 Calc S Osm = 147x2 + 42/2.8 + 92/18 + 14/3.8 + 5/5.8 + 3/6 = 318.6
Case 1 Acetone 50 Ethanol 140 Isopropanol 30 147 109 42 5.1 4 3.5 92 S Osm 345 Calc S Osm = 318.3 Osm Gap = 345 318 = 27
Case 1 Diagnosis: ethanol and isopropanol ingestion, suspected ethylene glycol ingestion
Case 1 Diagnosis: ethanol and isopropanol ingestion, suspected ethylene glycol ingestion Further testing: ethylene glycol not detected, UA no crystals
Case 1 Diagnosis: ethanol and isopropanol ingestion, suspected ethylene glycol ingestion Further testing: ethylene glycol not detected, UA no crystals Treatment:
Case 1 Diagnosis: ethanol and isopropanol ingestion, suspected ethylene glycol ingestion Further testing: ethylene glycol not detected, UA no crystals Treatment: fomepizole, bicarb drip, dialysis
Toxic alcohols Ethanol Metabolism: Ethanol
Toxic alcohols Ethanol Metabolism: Ethanol Acetaldehyde ALDH Acetic acid
Toxic alcohols Ethanol Metabolism: Ethanol Acetaldehyde ALDH Acetic acid Osm gap? Anion gap? Toxicity?
Toxic alcohols Ethanol Metabolism: Ethanol Acetaldehyde ALDH Acetic acid Osm gap? Yes Anion gap? Yes (lactate + ketones) Toxicity? Neuro, GI
Toxic alcohols Methanol Metabolism: Methanol ADH ALDH
Toxic alcohols Methanol Metabolism: Methanol ADH Formaldehyde ALDH Formic acid
Toxic alcohols Methanol Metabolism: Methanol ADH Formaldehyde ALDH Formic acid Osm gap? Anion gap? Toxicity?
Toxic alcohols Methanol Metabolism: Methanol ADH Formaldehyde ALDH Formic acid Osm gap? Yes Anion gap? Yes Toxicity? Eye, Neuro, GI, Renal
Toxic alcohols Ethylene glycol Metabolism: Ethylene glycol ADH ALDH
Toxic alcohols Ethylene glycol Metabolism: Ethylene glycol ADH Glycoaldehyde ALDH Glycolic acid Oxalic acid
Toxic alcohols Ethylene glycol Metabolism: Ethylene glycol ADH Glycoaldehyde ALDH Glycolic acid Oxalic acid Osm gap? Anion gap? Toxicity?
Toxic alcohols Ethylene glycol Metabolism: Ethylene glycol ADH Glycoaldehyde ALDH Glycolic acid Oxalic acid Osm gap? Yes Anion gap? Yes Toxicity? Neuro, Renal, GI
Calcium oxalate crystals in urine Monohydrate sigars Monohydrate dumbells Dihydrate envelopes
Calcium oxalate crystals in urine
Calcium oxalate crystals in urine
Toxic alcohols Isopropanol Metabolism: Isopropanol ADH
Toxic alcohols Isopropanol Metabolism: Isopropanol ADH Acetone
Toxic alcohols Isopropanol Metabolism: Isopropanol ADH Acetone Osm gap? Anion gap? Toxicity?
Toxic alcohols Isopropanol Metabolism: Isopropanol ADH Acetone Osm gap? Yes Anion gap? No! Toxicity? Neuro, GI
AG Metabolic Acidosis: causes M - methanol/metformin U - uremia D - diabetic ketoacidosis P - paraldehyde/propylene glycol I - isoniazid L - lactate E - ethylene glycol/ethanol S - salicylates/starvation
AG Metabolic Acidosis: causes G - glycoles O - oxoproline L - L -lactate D - D-lactate M - methanol A - aspirin R - renal failure K - ketones
AG Metabolic Acidosis K - ketones I - ingestions L - lactate U - uremia
Ketoacidosis
Aspirin overdose Treatment of Aspirin overdose IV sodium bicarbonate Dialysis HS H + + S -
Lactic acidosis: type A
Lactic acidosis: type B
Metabolic Acidosis of Renal Failure NAGMA AGMA: GFR < 15 cc/min: sulfate, phosphate and other anions retained
Case 2 Consult for metabolic acidosis and hypokalemia 147 122 14 3.3 15 1.2 166 A 58 yo female w h/o hematologic malignancy receiving chemo
Case 2 147 122 14 3.3 15 1.2 166 AG
Case 2 147 122 14 3.3 15 1.2 166 AG 10 NAGMA
Case 2 147 122 14 3.3 15 1.2 166 AG 10 UA: prot 100, glucose 500, ph 7
NAGMA: causes U - ureterosigmoidostomy S - small bowel fistula E - extra chloride D - diarrhea C - carbonic anhydrase inhibitors R RTA, renal failure A - adrenal insufficiency P - pancreatic fistula
NAGMA: Loss of bicarbonate GI loss of HCO 3 Renal loss of HCO 3
NAGMA: Loss of bicarbonate GI loss of HCO 3 Renal loss of HCO 3 Urine ph <5 Urine ph usually >6
Drains
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
NAG Metabolic Acidosis
Renal bicarbonate loss Type 1 Type 2 Type 4
Renal bicarbonate handling and urine acidification Proximal: reabsorption of filtered bicarb Distal: excretion of daily acid load Urine buffering
Renal bicarbonate handling and urine acidification 3000 mmol/day 100 mmol/day
Renal bicarbonate handling and urine acidification 3000 mmol/day 100 mmol/day
Proximal (type 2) RTA
Proximal (type 2 RTA Serum bicarb will fall until it reaches threshold
Proximal (type 2) RTA Once at threshold, there will be no further bicarb loss
Proximal (type 2) RTA Look for signs of generalized proximal tubular damage (Fanconi syndrome): hypophosphatemia, hypouricemia, glucosuria, proteinuria
Proximal RTA: ethiologies Think of what can damage nephron from above : Ifosfamide Cisplatin Tenofovir Multiple myeloma Amyloidosis Also congenital syndromes, heavy metals, Wilson s disease and acetazolamide
Proximal RTA: consequences Hypokalemia Bone disease Bone buffering of the acidosis Not typically complicated by stones
Case 2 147 122 14 3.3 15 1.2 166 AG 10 UA: prot 100, glucose 500, ph 7
Case 2 Day 0 138 109 11 3.7 23 0.6 147 UA prot 100, gluc neg, ph 6 Ifosfamide infusion Day 1 140 112 10 3.1 21 0.6 phos 1.9 Day 2 146 117 18 3.0 20 1.1 119 UA prot 30, gluc 100, ph 7 Day 3 147 122 14 3.3 15 1.2 166 UA prot 100, gluc 500, ph 7
Renal bicarbonate handling and urine acidification 3000 mmol/day 100 mmol/day
Distal nephron Hager at al, 2001
Distal nephron: H + Secretion
Distal RTA: H + Secretion
Distal RTA (Type 1) Inability to drain daily acid load in the urine. Blood is getting progressively more acidic
Distal RTA: ethiologies Think of what can damage nephron from below : Autoimmune diseases (Sjogren s, SLE) Obstructive uropathy Sickle cell disease Lithium Nephrocalcinosis Distal tubule drugs: amiloride, triamterene, bactrim
Distal RTA consequences There are hypokalemic and hyperkalemic forms
Distal RTA: nephrocalcinosis
Case 3 A 38 yo wf with recently diagnosed Graves disease Ever since this diagnosis, she repeatedly presents with muscle weakness and the following lab abnormalities: 138 119 17 1.9 10 0.7 UA ph 7 UAG positive
Type 4 RTA: very low ammonia excretion
Type IV RTA: unbuffered acidic urine!
Type IV RTA is a condition seen in hypoaldosterone states Aldosterone deficiency or insensitivity Diabetic nephropathy hyporeninemic hypoaldosteronism Aldosterone resistance Drugs: spironolactone
To look for renal H + clearance look for urinary ammonium Ammonium Titratable acid
To look for renal H + clearance look for urinary ammonium + NH 4 Ammonium Titratable acid
Urinary anion gap: (Na + + K + ) Cl Urinary ammonium detector
Urinary anion gap: (Na + + K + ) Cl Urinary ammonium detector Negative UAG is negative for RTA Positive UAG is positive for RTA
Renal Tubular Acidosis Recap Type 2 (proximal) RTA Defective bicarb reabsorption in proximal tubule Hypokalemia U ph alkaline when treated (acidic when untreated) Look for signs of proximal tubular dysfunction Type I (distal) RTA Defective distal acidification Hypokalemic and hyperkalemic variants U ph alkaline Look for nephrocalcinosis, kidney stones Type IV (hypoaldosteronism) Reduced ammonia generation and urine buffering Hyperkalemia U ph acidic Look for h/o diabetes or medullary interstitial disease Positive urine anion gap is positive for RTA
A 45 year old woman is admitted because of pathologic fracture of the right femur with evidence of severe osteopenia. She has h/o kidney stone 10 years previously. H/o profound LE weakness associated with hypokalemia in the past, was not compliant with potassium supplementation. Serum: cr 1.5, Na 138, K 2.3, Cl 115, bicarb 14, ph 7.29 Urine ph 6.5, Na 40, K 30, Cl 50 The patient has metabolic acidosis that is consistent with: A. Type I RTA B. Type II RTA C. Type III RTA D. Type IV RTA E. Extra-renal source of bicarbonate loss
A 45 year old woman is admitted because of pathologic fracture of the right femur with evidence of severe osteopenia. She has h/o kidney stone 10 years previously. H/o profound LE weakness associated with hypokalemia in the past, was not compliant with potassium supplementation. Serum: cr 1.5, Na 138, K 2.3, Cl 115, bicarb 14, ph 7.29 Urine ph 6.5, Na 40, K 30, Cl 50 The patient has metabolic acidosis that is consistent with: A. Type I RTA B. Type II RTA C. Type III RTA D. Type IV RTA E. Extra-renal source of bicarbonate loss
A 63 year old factory worker presents with muscle cramps and weakness over the past 2 weeks. For the past 6 months, he has had low back pain that caused him to miss work. Aspirin relieved the pain somewhat. Na 135, K 2.6, Cl 117, bicarb 15, glucose 88, Ca 11, phos 2.0, Hgb 9, plts 106, serum osm 277, ph 7.30, PCO 2 31 UA ph 6, protein neg, glucose 100, sulfosalicylic acid test positive What disease process best explains the patient s acidbase status? A. Proximal RTA B. Distal RTA C. Salicylate toxicity D. Ethylene glycol toxicity
A 63 year old factory worker presents with muscle cramps and weakness over the past 2 weeks. For the past 6 months, he has had low back pain that caused him to miss work. Aspirin relieved the pain somewhat. Na 135, K 2.6, Cl 117, bicarb 15, glucose 88, Ca 11, phos 2.0, Hgb 9, plts 106, serum osm 277, ph 7.30, PCO 2 31 UA ph 6, protein neg, glucose 100, sulfosalicylic acid test positive What disease process best explains the patient s acidbase status? A. Proximal RTA B. Distal RTA C. Salicylate toxicity D. Ethylene glycol toxicity
A 25-year-old African-American female with DMI, maintained on insulin and losartan, presents for a routine clinic visit. On exam, BP is 145/93, and there is mild dependent edema. Serum sodium 140 meq/l, Serum potassium 6.4 meq/l, Serum chloride 107 meq/l, Serum bicarbonate 18 meq/l, Blood urea nitrogen 21 mg/dl, Serum creatinine 1.9 mg/dl. Urine ph is 5.0 The patient has metabolic acidosis that is consistent with: A. Type I RTA B. Type II RTA C. Type IV RTA D. Hyperkalemic distal RTA
A 25-year-old African-American female with DMI, maintained on insulin and losartan, presents for a routine clinic visit. On exam, BP is 145/93, and there is mild dependent edema. Serum sodium 140 meq/l, Serum potassium 6.4 meq/l, Serum chloride 107 meq/l, Serum bicarbonate 18 meq/l, Blood urea nitrogen 21 mg/dl, Serum creatinine 1.9 mg/dl. Urine ph is 5.0 The patient has metabolic acidosis that is consistent with: A. Type I RTA B. Type II RTA C. Type IV RTA D. Hyperkalemic distal RTA