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Acid-Base Disorders

Acid-Base Disorders. Sharon Anderson, M.D. Division of Nephrology and Hypertension May 2003. General Acid-Base Relationships. Henderson-Hasselbach equation: pH = pK + log HCO 3 _ /pCO 2 H + = 24 x pCO 2 /HCO 3 _  0.1  pH unit =  10 nm/L H +. Approach to Acid-Base Disorders.

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Acid-Base Disorders

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  1. Acid-Base Disorders Sharon Anderson, M.D. Division of Nephrology and Hypertension May 2003

  2. General Acid-Base Relationships Henderson-Hasselbach equation: pH = pK + log HCO3_/pCO2 H+= 24 x pCO2/HCO3_ 0.1pH unit =10 nm/L H+

  3. Approach to Acid-Base Disorders • 1. Consider the clinical setting! • 2. Is the patient acidemic or alkalemic? • 3. Is the primary process metabolic or respiratory? • 4. If metabolic acidosis, gap or non-gap? • 5. Is compensation appropriate? • 6. Is more than one disorder present?

  4. Simple Acid-Base Disorders Primary Compensatory DisorderpHH+DisorderResponse Metabolic acidosis  HCO3_  pCO2 Metabolic alkalosis HCO3_  pCO2 Respiratory acidosis pCO2 HCO3_ Respiratory alkalosis pCO2 HCO3_

  5. Metabolic Acidosis • Etiology: Inability of the kidney to excrete the dietary H+ load, or increase in the generation of H+ (due to addition of H+ or loss of HCO3-)

  6. Metabolic Acidosis: Elevated Anion Gap AG = Na+ - (Cl- + HCO3-) = 12 ± 2 [Note: Diagnostic utility is best when AG > 25] Causes: Ketoacidosis Lactic acidosis Intoxications Renal failure Rhabdomyolysis

  7. Anion Gap in Hypoalbuminemia • The true anion gap is underestimated in hypoalbuminemia (= fall in unmeasured anions); AG must be adjusted • Formulas for adjusted AG: • For every 1.0 fall in albumin, increase AG by 2.5 • Consider the patient’s “normal” AG to be (2 x alb) + (0.5 x phosphate) • Adjusted AG = Observed AG + (2.5 x [normal alb - adjusted alb]

  8. Ketosis Diabetes Starvation Alcoholic Isopropyl alcohol* * Ketosis with normal AG and HCO3_

  9. Ketosis: Points to Remember -- Normal AG and HCO3_ = isopropyl alcohol -- Beta-hydroxbutyrate not seen by ketotest -- Acetoacetate spuriously  Cr -- False positive ketotest: paraldehyde, disulfiram, captopril

  10. Lactic Acidosis Type A: Hypoxic Lactate:pyruvate > 10:1 Type B: Glycolytic Lactate:pyruvate = 10:1

  11. Intoxications Causing High AG Acidosis • Aspirin - [high salicylate level; also primary respiratory alkalosis] • Methanol - [optic papillitis] • Ethylene Glycol - [calcium oxalate crystals] • Paraldehyde

  12. Use of venous vs. arterial pH As compared with arterial blood gasses: pH  0.03-0.04 pCO2 7-8 mmHg HCO3 2 mEq/L

  13. The Delta/Delta:  AG/  HC03 • Rationale: For each unit INCREASE in AG (above normal), HC03should DECREASE one unit (below normal) • “Normal” values: AG = 12, HC03 = 24

  14. Use of the Delta/Delta: Examples AG HCO3Diagnosis 18 ( 6) 18 ( 6) Appropriate; pure AG acidosis 18 ( 6) 22 ( 2) HCO3 has  less than predicted, so HCO3 is too high; mixed AG acidosis AND met alk 18 ( 6) 12 ( 12) HCO3 has  more than predicted, so HCO3 is too low; mixed AG AND non-AG acidosis

  15. Causes of Low Anion Gap • Etiology: Fall in unmeasured anions or rise in unmeasured cations Hyperkalemia Lithium intoxication Hypercalcemia Multiple myeloma Hypermagnesemia • Artefactual: hypernatremia, bromide, hyperlipidemia

  16. Osmolar Gap Measured serum osmolality > calculated serum osmolality by > 10 mOsm Calc Sosm = (2 x Na) + BUN/2.8 + Glu/18

  17. Causes of High Osmolar Gap Isotonic hyponatremia Hyperlipidemia Hyperproteinemia Mannitol Glycine infusion Chronic renal failure Ingestions Ethanol, isopropyl alcohol, ethylene glycol, mannitol Contrast Media

  18. Relationship between AG and Osmolar Gap AGOsm gapComments Ethylene glycol ++ * Double gap Methanol ++ * Double gap Renal failure ++ * Double gap Isopropyl alcohol -+ Ethanol -+ Lipids, proteins -+

  19. Causes of Normal AG (Hyperchloremic) Metabolic Acidosis High K+Low K+ Adrenal insufficiency Diarrhea Interstitial nephritis RTA NH4Cl, Arg HCl Ureteral diversion

  20. Use of the Urine Anion Gap (UAG) in Normal AG AcidosisBatlle et al. NEJM 318:594, 1988 • Urine AG = (Na + K) - Cl • Negative UAG = Normal, or GI loss of HCO3 • Positive UAG = altered distal renal acidification • Caveats: Less accurate in patients with volume depletion (low urinary Na); and in patients with increased excretion of unmeasured anions (e.g. ketoacidosis), where there is increased excretion of Na and K to maintain electroneutrality)

  21. Use of the Urinary AG in Normal Gap AcidosisBatlle et al. NEJM 318:594, 1988 Plasma KUAG U pHDiagnosis Normal - < 5.5 Normal Normal-low - > 5.5 GI HCO3 loss High + < 5.5 Aldo deficiency High + > 5.5 Distal RTA Normal-low + > 5.5 Proximal RTA

  22. Use of the Urine Osmolal Gap • When UAG is positive, and it is unclear if increased cation excretion is responsible, urine NH4 concentration can be estimated from urine osmolal gap • Calc Uosm = (2 x [Na+K]) + urea nitrogen/2.8 + glu/18 • The gap between the calculated and measured Uosm = mostly ammonium • In patients with metabolic acidosis, urine ammonium should be > 20 mEq/L. Lower value = impaired acidification

  23. Renal Tubular Acidosis Type 1 (distal)Type 2 (proximal) Type 4 Defect distal acid. prox HCO3 reab aldo HCO3 May be < 10 12-20 > 17 Urine pH > 5.3 Variable < 5.3 Plasma K Usually low Usually low High Response Good Poor Fair to HCO3 Rx

  24. Calculation of Bicarbonate Deficit • Bicarb deficit = HCO3- space x HCO3- deficit/liter • HCO3- space = 0.4 x lean body wt (kg) • HCO3- deficit/liter = [desired HCO3-] - [measured HCO3-]

  25. Approach to Metabolic Acidosis Anion Gap Normal High Osmolar Gap GI Fluid Loss? No Yes Normal Increased Diarrhea Ileostomy Enteric fistula Urine pH Uremia Lactate Ketoacids Salicylate Ethylene glycol Methanol < 5.5 > 5.5 Serum K Distal RTA (Type 1) High Low Type 4 RTA Proximal RTA (Type 2)

  26. Metabolic Alkalosis • Etiology: Requires both generation of metabolic alkalosis (loss of H+ through GI tract or kidneys) and maintenance of alkalosis (impairment in renal HCO3 excretion) • Causes of metabolic alkalosis Loss of hydrogen Retention of bicarbonate Contraction alkalosis • Maintenance factors: Decrease in GFR, increase in HCO3 reabsorption

  27. Use of Spot Urine Cl and K Very Low (< 10 mEq/L) Vomiting, NG suction Postdiuretic, posthypercapneic Villous adenoma, congenital chloridorrhea, post- alkali Urine Chloride > 20 mEq/L Low (< 20 mEq/L) Urine Potassium Laxative abuse Other profound K depletion > 30 mEq/L Diuretic phase of diuretic Rx, Bartter’s, Gitelman’s, primary aldo, Cushings, Liddle’s, secondary aldosteronism

  28. Treatment of Metabolic Alkalosis 1. Remove offending culprits. 2. Chloride (saline) responsive alkalosis: Replete volume with NaCl. 3. Chloride non-responsive (saline resistant) alkalosis: Acetazolamide (CA inhibitor) Hydrochloric acid infusion Correct hypokalemia if present

  29. Calculation of Bicarbonate Excess Bicarb excess = HCO3- space x HCO3- excess/liter HCO3- space = 0.5 x lean body wt (kg) HCO3- excess/liter = [measured HCO3-] - [desired HCO3-]

  30. Respiratory Acidosis Causes of Respiratory Acidosis Inhibition of medullary respiratory center Disorders of respiratory muscles and chest wall Upper airway obstruction Disorders affecting gas exchange across pulmonary capillaries Mechanical ventilation

  31. Respiratory Alkalosis Causes of Respiratory Alkalosis Hypoxemia Pulmonary disease Stimulation of medullary respiratory center Mechanical ventilation

  32. Mixed Acid-Base Disorders: Clues -- Degree of compensation for primary disorder is inappropriate -- Delta AG/delta HCO3_ = too high or too low -- Clinical history

  33. Problem 1 A 30-yo man with DM presents with a week of polyuria, polydipsia, fever to 102, nausea, and abdominal pain. He is orthostatic on admission. 130 I 94 I 75 I 906 pH 7.14 6.1 I 6 I 2.3 pCO2 18 pO2 102

  34. Problem 1, cont. 130 I 94 I 75 I 906 7.14/18/102 6.1 I 6 I 2.3 1. Anticipate the disorder DKA (with anion gap acidosis) 2. Acidemic or alkalemic? 3. Metabolic or respiratory? pH = acidemic; must be metabolic (low HCO3, low pCO2) 4. If metabolic acidosis: gap or non-gap? AG = 30; + anion gap metabolic acidosis 5. Is compensation appropriate? pCO2 should = last 2 digits of pH [18] or (1.5 x HCO3) + 8 [17] 6. Mixed disorder? AG = 30 (­18); HCO3 = 6 (¯18); thus simple AG met acidosis

  35. Problem 2 A 30-yo man with DM presents with a week of polyuria, polydipsia, fever to 102, and vomiting for four days. 135 I 89 I 50 I 1181 pH 7.26 6.1 I 10 I 2.3 pCO2 23 pO2 88

  36. Problem 2, cont. 135 I 89 I 50 I 1181 7.26/23/88 6.1 I 10 I 2.3 1. Anticipate the disorder DKA (AG acidosis); met alk from vomiting 2. Acidemic or alkalemic? 3. Metabolic or respiratory? pH = acidemic; must be metabolic (low HCO3, low pCO2) 4. If metabolic acidosis: gap or non-gap? AG = 36; + anion gap metabolic acidosis 5. Is compensation appropriate? pCO2 should = last 2 digits of pH [26] or (1.5 x HCO3) + 8 [23] 6. Mixed disorder? AG = 36 (­24); HCO3 = 10 (¯14); HCO3 is too high; mixed AG metabolic acidosis and metabolic alkalosis

  37. Problem 3 A 30-yo man with DM presents with a week of polyuria, polydipsia, fever to 102, and diarrhea. 138 I 111I 49 I 650 pH 7.26 5.5 I 8I 1.4 pCO2 23 pO2 88

  38. Problem 3, cont. 138 I 111 I 49 I 650 7.26/23/88 5.51 I 8 I 1.4 1. Anticipate the disorder DKA (AG acidosis); nongap met acidosis from diarrhea 2. Acidemic or alkalemic? 3. Metabolic or respiratory? pH = acidemic; must be metabolic (low HCO3, low pCO2) 4. If metabolic acidosis: gap or non-gap? AG = 19; + anion gap metabolic acidosis 5. Is compensation appropriate? pCO2 should = last 2 digits of pH [26] or (1.5 x HCO3) + 8 [23] 6. Mixed disorder? AG = 19 (­7); HCO3 = 8 (¯16); HCO3 is too low; mixed AG metabolic acidosis and metabolic acidosis (nongap)

  39. Problem 4 A 30-yo man with DM presents with a week of polyuria, polydipsia, fever, cough, and prurulent sputum. 140 I 104 I 75 I 1008 pH 6.95 7.0 I 7 I 2.6 pCO2 33 pO2 60

  40. Problem 4, cont. 140 I 104 I 75 I 1008 6.95/33/60 7.0 I 7 I 2.6 1. Anticipate the disorder DKA (AG acidosis); resp alk or resp acidosis from hypoxemia/pneumonia 2. Acidemic or alkalemic? 3. Metabolic or respiratory? pH = acidemic; must be metabolic (low HCO3, low pCO2) 4. If metabolic acidosis: gap or non-gap? AG = 29; + anion gap metabolic acidosis

  41. Problem 4, cont. 140 I 104 I 75 I 1008 6.95/33/60 7.0 I 7 I 2.6 5. Is compensation appropriate? pCO2 should = last 2 digits of pH [95!!] or (1.5 x HCO3) + 8 [18]; pCO2 is too high so he has a superimposed respiratory acidosis 6. Mixed disorder? AG = 29 (­17); HCO3 = 7 (¯17); so metabolic acidosis is pure AG acidosis. Thus, mixed AG metabolic acidosis and respiratory acidosis

  42. Problem 5 A 31-yo woman who is 33 weeks pregnant presents with a 2-day history of vomiting. 140 I 104 I 8 I 85 pH 7.64 3.0 I 26 I 0.6 pCO2 25 pO2 93

  43. Problem 5, cont. 140 I 104 I 8 I 85 7.64/25/93 3.0 I 26 I 0.6 1. Anticipate the disorder Pregnancy: resp alk Vomiting: met alk 2. Acidemic or alkalemic? pH = alkalemic 3. Metabolic or respiratory? If resp, HCO3 should be low; if metabolic, then pCO2 should be high; must have both 4. If metabolic acidosis: gap or non-gap? N/A; no acidosis; no AG

  44. Problem 5, cont. 140 I 104 I 8 I 85 7.64/25/93 3.0 I 26 I 0.6 5. Is compensation appropriate? NO (by eyeball, for reasons listed above) 6. Mixed disorder? Yes, mixed metabolic and respiratory alkalosis. No acidosis component.

  45. Problem 6 A 60-yo man has crushing chest pain, SOB and diaphoresis. He has HTN, for which he takes HCTZ. Exam shows BP 88/60, bilateral crackles, S3. EKG shows ischemia; CXR = pulmonary edema. 140 I 94 I 45 I 300 pH 7.14 5.9 I 20 I 1.9 pCO2 60 pO2 52

  46. Problem 6, cont. 140 I 94 I 45 I 300 7.14/60/52 5.9 I 20 I 1.9 1. Anticipate the disorder Pulm edema -> resp alk or resp acidosis; shock -> metabolic acidosis; HCTZ -> metabolic alkalosis 2. Acidemic or alkalemic? pH = acidemic 3. Metabolic or respiratory? If resp, HCO3 should be > 24 in compensation; if metabolic, then pCO2 should < 40; must have both respiratory and metabolic acidoses 4. If metabolic acidosis: gap or non-gap? AG = 26; + anion gap metabolic acidosis

  47. Problem 6, cont. 140 I 94 I 45 I 300 7.14/60/52 5.9 I 20 I 1.9 5. Is compensation appropriate? NO (by eyeball, for reasons listed above) 6. Mixed disorder? Anything else? AG = 26 (­14); HCO3 = 20 (¯ 4); so HCO3 is too high; must have a superimposed metabolic alkalosis. Thus, triple disorder: respiratory acidosis, anion gap metabolic acidosis, and metabolic alkalosis

  48. Problem 7 A 55-yo woman with a history of a CVA presents to clinic complaining of shortness of breath. 140 I 100 I 30 I 115 pH 7.36 3.9 I 30 I 1.5 pCO2 38 pO2 91

  49. Problem 7, cont. 140 I 100 I 30 I 115 7.36/38/91 3.9 I 30 I 1.5 1. Anticipate the disorder Resp alk due to CNS disorder or acute pulmonary process 2. Acidemic or alkalemic? pH = acidemic 3. Metabolic or respiratory? 4. If metabolic acidosis: AG? HCO3 is high (not metabolic acidosis); pCO2 is < 40 (not respiratory acidosis); AG is normal (10), so what’s going on??

  50. Problem 7, cont. 140 I 100 I 30 I 115 7.36/38/91 3.9 I 30 I 1.5 LAB ERROR! By Henderson-Hasselbach H+ = 24 x pCO2/HCO3 = 24 x (38/30) = 30 pH should be 7.50

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