Objectives Diagnostic approach to acid base disorders Common clinical examples of acidoses and alkaloses Acid-Base Disorders Jai Radhakrishnan 1 2 Diagnostic Considerations Data points required: ABG: ph, pco 2, Chem-7 panel: anion gap Step 1: Acidemia/alkalemia (Primary disorder) Step 2: Compensation Step 3: Anion gap / delta AG-delta Step 1: Primary Disorder Alkalemia Metabolic alkalosis ( high ) Respiratory alkalosis ( low pco 2 ) Acidemia Metabolic acidosis ( low ) Respiratory acidosis ( high PCO 2 ) ph pco 2 7.45 46 31 7.46 22 15 ph pco 2 7.34 28 15 7.34 56 30 3 4 Step 2: Compensation LIMITS Met. alkalosis PCO 2 <55 Resp. alkalosis >12 Resp. acidosis <45 Met. acidosis PCO 2 >10 mmhg Acute/Chronic phase only with respiratory disorders. Formulae Metabolic acidosis Change in PaCO2 = 1.2 x change in HCO3- Metabolic alkalosis Change in PaCO2 = 0.6 x change in HCO3 Acute respiratory acidosis Change in HCO3- = 0.1 x change in PaCO2 Chronic respiratory acidosis Change in HCO3- = 0.35 x change in PaCO2 Acute respiratory alkalosis Change in HCO3- = 0.2 x change in PaCO2 Chronic respiratory alkalosis Change in HCO3- = 0.5 x change in PaCO2 *A positive or negative change represents an increase or decrease, respectively, from the normal value of 40 mm Hg for PaCO2 or 24 meq/l for HCO3-. 5 6
Step 3: Anion Gap - (- + ) Unmeasured anions-unmeasured cations Normal: 8-12 Albumin contributes 2-4 to the A.G. A.G. >20 implies the presence of a wide anion-gap metabolic acidosis 7 8 Watch that delta! Question An 80 year male patient with osteoarthritis was found comatose. Physical exam: ecchymoses + Labs: 140 105 20 Glucose=80 Ketones=1+ 4.8 15 1.5 ABG (RA)=7.45/15/85 What is the acid-base disorder? 1.Respiratory alkalosis 2.Metabolic acidosis 3.Both respiratory alkalosis and metabolic acidosis An 80 year male patient with osteoarthritis was found comatose: Physical exam: ecchymoses + Labs: 140 105 20 Glucose=80 Ketones=1+ 4.8 15 1.5 ABG (RA)=7.45/15/85 Step 1: Acidemia/alkalemia (Primary disorder) Step 2: Compensation Step 3: Anion gap Differential Diagnoses Sepsis Salicylate Cirrhosis All 10 9 METABOLIC ACIDOSIS WIDE ANION GAP (OTHER ACIDS) Lactic acid Ketoacids Sulfuric acid (Renal failure) Ingestions Methanol Ethylene glycol NORMAL ANION GAP (HCL) Renal loss GI loss HCl consumption TPN Question 24-year-old female with a history of ileal conduit presented to the ED with severe weakness. ABG: ph = 7.21; PCO2 = 26 mmhg; [HCO3-] = 10 meq/l; K+ = 2.2 meq/l with anion gap 13. What is the diagnosis? 1 Mixed metabolic and respiratory acidosis 2 Metabolic acidosis with respiratory compensation 3 Respiratory acidosis with renal compensation 4 Shift of protons due to hypokalemia 11 12
GI Loss of - Question Pancreas - - Ileum Colon Pancreas HCO - 3 - Ileum Colon A 38-year-old woman was admitted with severe weakness (3 rd episode). She has a history of recurrent Ca Phosphate stones Laboratory sodium 141 meq/l potassium 3.0 meq/l carbon dioxide 14 meq/l chloride 114 meq/l Albumin 4.3 ph= 7.18, P CO2, =23 mmhg, P O2 =100 mmhg Normal Diarrhea Should you suspect RTA in this person? Yes No 14 Arch Intern Med. 2004;164:905-909 Is this RTA? Proximal RTA NORMAL ANION GAP (HCL) Renal loss Proximal Distal Hyporenin/Hypoaldosteronism GI loss HCl consumption TPN 15 16 J Am Soc Nephrol 13:2160-2170, 2002 Proximal tubule also absorbs glucose (glycosuria without hyperglycemia) Amino acids, phosphate, uric acid Distal RTA 17 18 J Am Soc Nephrol 13:2160-2170, 2002
Ammonia Recycling Urine Hypoaldosteronism/Type IV RTA Medullary Collecting Tubule Reabsorption of Na, Cl, HCO3 Loss of Proton and K K channel Na channel Aldo R Na-K ATPase Aldosterone Blood Proton Pump C.A. Annu. Rev. Physiol. 2007. 69:317 40 19 Hyporeninism=Hyperkalemia + Mild NAG acidosis 20 Urinary Anion Gap Urine (Na+K) Cl Unmeasured anions-unmeasured cations 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. A positive urine anion gap = no NH 4+ Cl excretion (less distal tubule acidification) Normal acidotic: closed circles Diarrhea: closed triangles Type 1/IV RTA: open circles Battle et al, NEJM 1988 21 Urine Urine ph 6.5 Urinary anion gap +4 Which type of RTA does she have? Comparison of Normal Anion-Gap Acidoses Finding Type 1 RTA Type 2 RTA Type 4 RTA GI Bicarbonate Loss Minimum urine ph >5.5 <5.5 <5.5 5 to 6 % Filtered bicarbonate excreted <10 >15 <10 <10 Serum potassium Low Low High Low Fanconi syndrome No Yes No No Stones/nephrocalcinosis Yes No No No Low Normal Low High Urine anion gap Positive Negative Positive Negative Daily bicarbonate replacement needs <4 mmol/kg >4 mmol/kg <4 mmol/kg Variable 23 24
Metabolic Acidosis Workup Anion Gap If wide: DKA, lactate, renal failure, poison If normal: GI or Renal Loss Urinary Anion Gap If negative: GI or Proximal RTA If positive: Distal RTA or Type IV RTA METABOLIC ALKALOSIS 25 26 loss across epithelia: Generation of Met Alkalosis Step 1:GENERATION Vomiting Renal loss Diuretics Aldosterone Addition of Post-CPR Multi transfusion Metabolic Alkalosis-Maintenance Step 2: MAINTENANCE (prevention of kidneys getting rid of ) Decrease GFR Aldosterone Hypokalemia 27 28 Urine Maintenance of Met Alkalosis Medullary Collecting Tubule Reabsorption of Na, Cl, HCO3 Loss of Proton and K K channel Na channel Aldo R Na-K ATPase Aldosterone Blood Metabolic Alkalosis:Case 1 A 60 year old woman with COPD and CHF is admitted with respiratory failure. After being intubated: ph=7.55 pco 2 =50 =40 AG=14 Proton Pump C.A. How would you treat her alkalosis? 1.IV SALINE 2.Oral spironolactone 29 30
Classification of Metabolic Alkalosis by Treatment SALINE RESPONSIVE Volume depletion SALINE RESISTANT Primary hyperaldosteronism Effective volume depletion Cirrhosis/ascites COPD/RHF Treatment of Saline-Resistant Metabolic Alkalosis Spironolactone Acetazolamide HCl IV 31 32