Metabolic alkalosis. ICU Fellowship Training Radboudumc

Metabolic alkalosis ICU Fellowship Training Radboudumc

Case History 28-year-old male Discovered by roommate at home in bewildering state During transport by EMS possible tonicclonic seizure Arrival in ER at 16.30 with GCS E1-M5-V2

Case History Medication Venlafaxin (Effexor ) - SNRI Methylphenidate (Ritalin ) Disulfiram (Refusal )

Case History Temperature 37. 2 0 C Airway - accepts oral airway Breathing - SpO2 100% on 12 L O2 Circulation - BP 170/100 mm Hg Disability - E1-M5-V2

Laboratory results 16.30 Na K ph Lactate 95 mmol/l 1.4 mmol/l 7.54 mmol/l 8.9 mmol/l 7.54 / 19.1 / 6.1 / 37.8 / 13.3

Things always get worse 17.00 Lactate 2.9 mmol/l 7.61 / 17.2 / 5.7 / 40.0 / 16.5 Is the respiratory response appropriate? What are the immediate life-threatening dangers?

Respiratory response Expected PaCO2 (mm Hg) = 0.7 [HCO3-] + 20 ± 5 0.7 [40] + 20 ± 5 = 43-53 mm Hg = (5.7-7.1 kpa) Actual PaCO2 5.7 kpa = appropriate

Metabolic alkalosis Decrease in cardiac output Depression of central ventilation Leftward shift of the oxyhemoglobin saturation curve Worsening of hypokalemia and hypophosphatemia

Why K + shift with metabolic alkalosis? Na + H + Na + -K + - ATPase 3 Na + 2 K + K + Insulin β-mimetics Potassium enters the cell because of a negative transmembrane gradient

Stewart-Figge theory Body water is inexhaustible source of H + ions Three independent components influence the dissociation of water PCO2 Total concentration of weak acids (ATOT) Strong Ion Difference

Strong Ion Difference Electrical neutrality Apparent SID Effective SID Na + Cl - Na + Cl - Lact - - Lact - Total negative charges of K + HCO3 - K + HCO3 - Ca 2+ Mg 2+ Alb - P - Ca 2+ Mg 2+ Normal SIDa 40-42 meq/l Alb - P - Strong Ion Gap = SIDa - SIDe

Pathophysiology Acidosis Alkalosis Respiratory PaCO2 PaCO2 Metabolic 1 Changes in SID a) H20 or b) Change in strong anions - chloride or - unmeasured anions 2 Changes in weak acids a) Albumin b)anorganic phosphate SID [H2O ] SID [Cl - ] SID [Xa - ] [Alb] [P] SID [H2O ] SID [Cl - ] [Alb] [P] Unmeasured cations?

What about our patient? Na + 96 K + 1.9 Ca 2+ 2.02 Mg 2+ 1.64 Cl - 44 Lact - 2.9 Apparent SID 54.66 (normal 40-42 meq/l) Albumen 44 Phosphate 0.78 Total negative charges of HCO3-40 Alb - 13.3 P - 1.46 No strong ion gap Effective SID 54.76

Metabolic alkalosis solely explained by Cl - Why does hypokalemia due to an intracellular shift not result in an acid-base disturbance?

If you believe in Stewart

If you believe in HH Bicarbonate 15L 25 mmol from 375 to 345 mmol (23 mmol/l) 30 mmol H + 30 mmol Na + -K + - ATPase K + 15 L 2 mmol

Where do we loose chloride? HCl loss - vomiting NH4Cl loss - diuretics / specific disorders KCl loss (GI tract) NaCl loss Urinary chloride is low in all cases except 2

Case record History compatible with extensive vomiting Urinary chloride excretion 44 mmol/l, ph 7 Patient does not use diuretics Differential diagnosis of high urinary chloride loss?

Differential diagnosis with high Cl - excretion Bartter syndrome Gitelman syndrome Other causes of excess aldosterone Severe potassium deficiency

Upregulated by Inhibited or blocked by Thiazides Gitelman syndrome K + depletion Cotransporter Cl - depletion alkalosis Cl - HCO3 - Early distal nephron Na + Cl - Connecting tubule PENDRIN Distal tubule Flow and alkali stimulation Thiazides Loop diuretics Gitelman Bartter GI Cl - loss Inhibited or blocked by Loop diuretics Bartter syndrome K + depletion Loop of Henle Na + K + 2Cl - Cotransporter Secondary to ENaC activity K + H + Secondary to K + depletion ROMK Maxi K H + - ATP-ase Collecting duct ENaC Na + Direct stimulation Conn GRA Cushing Liddle Congenital adrenal disease 11 β HS dehydrogenase Proximal tubule 80% HCO3 - reabsorption K + H + /K + - H + ATP-ase

Treatment Correct volume depletion Correct chloride depletion Correct potassium depletion

Additional therapy Hydrochloric acid Acetazolamide How does acetazolamide decrease ph?

Metabolic alkalosis Moviat M. Crit Care 2006;10:R14

Metabolic alkalosis Moviat M. Crit Care 2006;10:R14

Conclusion Severe metabolic alkalosis due to gastric chloride loss (vomiting) and inappropriate urinary chloride loss due to hypokalemia Correction with chloride and potassium suppletion

Gennari FJ. AJKD 2011;58:626-636