Anna Vinnikova, M.D. Division of Nephrology Virginia Commonwealth University

Transcription

1 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,

2 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

3 Case 1 VBG 6.79 / 25 / 82 / 3.9 / 81%

4 Case / 25 / 82 / 3.9 / 81% AG 34

5 Case / 25 / 82 / 3.9 / 81% AG 34 AGMA

6 Case / 25 / 82 / 3.9 / 81% AG 34 What is his corrected bicarb?

7 Case / 25 / 82 / 3.9 / 81% AG 34 Corrected bicarb is bicarb you would get after correction of AGMA

8 Case / 25 / 82 / 3.9 / 81% AG 34 AG is elevated by:

9 Case / 25 / 82 / 3.9 / 81% AG 34 AG is elevated by: 34-12=22

10 Case / 25 / 82 / 3.9 / 81% AG 34, elevated by 22 If you corrected this AGMA, bicarb would be = 26

11 Case / 25 / 82 / 3.9 / 81% Corrected bicarb 26 Corrected bicarb is normal indicating simple AGMA

12 Case 1 VBG 6.79 / 25 / 82 / 3.9 / 81% Is respiratory compensation appropriate?

13 Case 1 VBG 6.79 / 25 / 82 / 3.9 / 81% Is respiratory compensation appropriate? You need ABG, not a VBG to answer this question

14 Case / 25 / 82 / 3.9 / 81% AG 34 Phos 20 Lactate 19 Urine ket 20 Alb 3

15

16 Case 1 Acetone 50 Ethanol 140 Isopropanol 30 Methanol 0 ASA <

17 Case 1 Acetone 50 Ethanol 140 Isopropanol What is his Osmolar Gap?

18 Ingestions: Osm gap Osmolar gap is present if measured osm > calculated osm by 10

19 Case 1 Acetone 50 Ethanol 140 Isopropanol S Osm 345 Calc S Osm =

20 Case 1 Acetone 50 Ethanol 140 Isopropanol S Osm 345 Calc S Osm = 147x2 +

21 Case 1 Acetone 50 Ethanol 140 Isopropanol S Osm 345 Calc S Osm = 147x2 + 42/2.8 +

22 Case 1 Acetone 50 Ethanol 140 Isopropanol S Osm 345 Calc S Osm = 147x2 + 42/ /18

23 Case 1 Acetone 50 mg/l Ethanol 140 mg/l Isopropanol 30 mg/l S Osm 345 Calc S Osm = 147x2 + 42/ / /4.6

24 Case 1 Acetone 50 mg/l Ethanol 140 mg/l Isopropanol 30 mg/l S Osm 345 Calc S Osm = 147x2 + 42/ / / / /6 = 318.6

25 Case 1 Acetone 50 Ethanol 140 Isopropanol S Osm 345 Calc S Osm = Osm Gap = = 27

26 Case 1 Diagnosis: ethanol and isopropanol ingestion, suspected ethylene glycol ingestion

27 Case 1 Diagnosis: ethanol and isopropanol ingestion, suspected ethylene glycol ingestion Further testing: ethylene glycol not detected, UA no crystals

28 Case 1 Diagnosis: ethanol and isopropanol ingestion, suspected ethylene glycol ingestion Further testing: ethylene glycol not detected, UA no crystals Treatment:

29 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

30 Toxic alcohols Ethanol Metabolism: Ethanol

31 Toxic alcohols Ethanol Metabolism: Ethanol Acetaldehyde ALDH Acetic acid

32 Toxic alcohols Ethanol Metabolism: Ethanol Acetaldehyde ALDH Acetic acid Osm gap? Anion gap? Toxicity?

33 Toxic alcohols Ethanol Metabolism: Ethanol Acetaldehyde ALDH Acetic acid Osm gap? Yes Anion gap? Yes (lactate + ketones) Toxicity? Neuro, GI

34 Toxic alcohols Methanol Metabolism: Methanol ADH ALDH

35 Toxic alcohols Methanol Metabolism: Methanol ADH Formaldehyde ALDH Formic acid

36 Toxic alcohols Methanol Metabolism: Methanol ADH Formaldehyde ALDH Formic acid Osm gap? Anion gap? Toxicity?

37 Toxic alcohols Methanol Metabolism: Methanol ADH Formaldehyde ALDH Formic acid Osm gap? Yes Anion gap? Yes Toxicity? Eye, Neuro, GI, Renal

38 Toxic alcohols Ethylene glycol Metabolism: Ethylene glycol ADH ALDH

39 Toxic alcohols Ethylene glycol Metabolism: Ethylene glycol ADH Glycoaldehyde ALDH Glycolic acid Oxalic acid

40 Toxic alcohols Ethylene glycol Metabolism: Ethylene glycol ADH Glycoaldehyde ALDH Glycolic acid Oxalic acid Osm gap? Anion gap? Toxicity?

41 Toxic alcohols Ethylene glycol Metabolism: Ethylene glycol ADH Glycoaldehyde ALDH Glycolic acid Oxalic acid Osm gap? Yes Anion gap? Yes Toxicity? Neuro, Renal, GI

42 Calcium oxalate crystals in urine Monohydrate sigars Monohydrate dumbells Dihydrate envelopes

43 Calcium oxalate crystals in urine

44 Calcium oxalate crystals in urine

45 Toxic alcohols Isopropanol Metabolism: Isopropanol ADH

46 Toxic alcohols Isopropanol Metabolism: Isopropanol ADH Acetone

47 Toxic alcohols Isopropanol Metabolism: Isopropanol ADH Acetone Osm gap? Anion gap? Toxicity?

48 Toxic alcohols Isopropanol Metabolism: Isopropanol ADH Acetone Osm gap? Yes Anion gap? No! Toxicity? Neuro, GI

49 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

50 AG Metabolic Acidosis: causes G - glycoles O - oxoproline L - L -lactate D - D-lactate M - methanol A - aspirin R - renal failure K - ketones

51 AG Metabolic Acidosis K - ketones I - ingestions L - lactate U - uremia

52 Ketoacidosis

53 Aspirin overdose Treatment of Aspirin overdose IV sodium bicarbonate Dialysis HS H + + S -

54 Lactic acidosis: type A

55 Lactic acidosis: type B

56 Metabolic Acidosis of Renal Failure NAGMA AGMA: GFR < 15 cc/min: sulfate, phosphate and other anions retained

57 Case 2 Consult for metabolic acidosis and hypokalemia A 58 yo female w h/o hematologic malignancy receiving chemo

58 Case AG

59 Case AG 10 NAGMA

60 Case AG 10 UA: prot 100, glucose 500, ph 7

61 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

62 NAGMA: Loss of bicarbonate GI loss of HCO 3 Renal loss of HCO 3

63 NAGMA: Loss of bicarbonate GI loss of HCO 3 Renal loss of HCO 3 Urine ph <5 Urine ph usually >6

64

65 Drains

66 Plasma Bile Pancreas Small intestines Large intestines

67 NAG Metabolic Acidosis

68 Renal bicarbonate loss Type 1 Type 2 Type 4

69 Renal bicarbonate handling and urine acidification Proximal: reabsorption of filtered bicarb Distal: excretion of daily acid load Urine buffering

70 Renal bicarbonate handling and urine acidification 3000 mmol/day 100 mmol/day

71 Renal bicarbonate handling and urine acidification 3000 mmol/day 100 mmol/day

72 Proximal (type 2) RTA

73 Proximal (type 2 RTA Serum bicarb will fall until it reaches threshold

74 Proximal (type 2) RTA Once at threshold, there will be no further bicarb loss

75 Proximal (type 2) RTA Look for signs of generalized proximal tubular damage (Fanconi syndrome): hypophosphatemia, hypouricemia, glucosuria, proteinuria

76 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

77 Proximal RTA: consequences Hypokalemia Bone disease Bone buffering of the acidosis Not typically complicated by stones

78 Case AG 10 UA: prot 100, glucose 500, ph 7

79 Case 2 Day UA prot 100, gluc neg, ph 6 Ifosfamide infusion Day phos 1.9 Day UA prot 30, gluc 100, ph 7 Day UA prot 100, gluc 500, ph 7

80 Renal bicarbonate handling and urine acidification 3000 mmol/day 100 mmol/day

81 Distal nephron Hager at al, 2001

82 Distal nephron: H + Secretion

83 Distal RTA: H + Secretion

84 Distal RTA (Type 1) Inability to drain daily acid load in the urine. Blood is getting progressively more acidic

85 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

86 Distal RTA consequences There are hypokalemic and hyperkalemic forms

87 Distal RTA: nephrocalcinosis

88 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: UA ph 7 UAG positive

89 Type 4 RTA: very low ammonia excretion

90 Type IV RTA: unbuffered acidic urine!

91 Type IV RTA is a condition seen in hypoaldosterone states Aldosterone deficiency or insensitivity Diabetic nephropathy hyporeninemic hypoaldosteronism Aldosterone resistance Drugs: spironolactone

92 To look for renal H + clearance look for urinary ammonium Ammonium Titratable acid

93 To look for renal H + clearance look for urinary ammonium + NH 4 Ammonium Titratable acid

94 Urinary anion gap: (Na + + K + ) Cl Urinary ammonium detector

95 Urinary anion gap: (Na + + K + ) Cl Urinary ammonium detector Negative UAG is negative for RTA Positive UAG is positive for RTA

96 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

97 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

98 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

99 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

100 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

101 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

102 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