1. Eric Niederhoffer, Ph.D. SIU-SOM Biochemical basis of acidosis and alkalosis: evaluating acid base disorders

2. Outline Approach history physical examination differentials clinical and laboratory studies compensation Respiratory acidosis alkalosis Metabolic acidosis alkalosis Special cases pregnancy children

3. Approach History - subjective information concerning events, environment, trauma, medications, poisons, toxins Physical examination - objective information assessing organ system status and function Differentials - potential reasons for presentation Clinical and laboratory studies - degree of changes from normal Compensation - assessment of response to initial problem

4. Reference ranges and points ParameterReference rangeReference point pH7.35-7.457.40 P CO 2 33-44 mm Hg40 mm Hg P O 2 75-105 mm Hg HCO 3 - 22-28 mEq/L24mEq/L Anion gap8-16 mEq/L12 mEq/L Osmolar gap<10 mOsm/L

5. Delta ratio Assessment <0.4Hyperchloraemic normal anion gap acidosis 0.4 – 0.8 Combined high AG and normal AG acidosis Note that the ratio is often <1 in acidosis associated with renal failure 1 - 2 Uncomplicated high-AG acidosis Lactic acidosis: average value 1.6 DKA more likely to have a ratio closer to 1 due to urine ketone loss (if patient not dehydrated) >2 Pre-existing increased [HCO 3 - ]: concurrent metabolic alkalosis pre-existing compensated respiratory acidosis ratio = Anion gap/[HCO 3 - ] = (AG – 12)/(24 - [HCO 3 - ])

6. Compensation Primary Disturbance pHHCO 3 - P CO 2 Compensation Respiratory acidosis<7.35Compensatory increase Primary increase Acute: 1-2 mEq/L increase in HCO 3 - for every 10 mm Hg increase in P CO 2 Chronic: 3-4 mEq/L increase in HCO 3 - for every 10 mm Hg increase in P CO 2 Respiratory alkalosis>7.45Compensatory decrease Primary decrease Acute: 1-2 mEq/L decrease in HCO 3 - for every 10 mm Hg decrease in P CO 2 Chronic: 4-5 mEq/L decrease in HCO 3 - for every 10 mm Hg decrease in P CO 2 Metabolic acidosis<7.35Primary decrease Compensatory decrease 1.2 mm Hg decrease in P CO 2 for every 1 mEq/L decrease in HCO 3 - Metabolic alkalosis>7.45Primary increase Compensatory increase 0.6-0.75 mm Hg increase in P CO 2 for every 1 mEq/L increase in HCO 3 -, P CO 2 should not rise above 55 mm Hg in compensation

7. Respiratory acidosis P CO 2 greater than expected Acute or chronic Causes excess CO 2 in inspired air (rebreathing of CO 2 -containing expired air, addition of CO 2 to inspired air, insufflation of CO 2 into body cavity) decreased alveolar ventilation (central respiratory depression & other CNS problems, nerve or muscle disorders, lung or chest wall defects, airway disorders, external factors) increased production of CO 2 (hypercatabolic disorders)

8. R acid acute A 65-year-old man with a history of emphysema comes to the physician with a 3-hour history of shortness of breath. pH7.18 P O 2 61 mm Hg P CO 2 58 mm Hg HCO 3 - 26 mEq/L History suggests hypoventilation, supported by increased P CO 2 and lower than anticipated P O 2. Respiratory acidosis (acute) due to no renal compensation.

9. Description pH7.18 P O 2 61 mm Hg P CO 2 58 mm Hg HCO 3 - 26 mEq/L 1-2 mEq/L increase in HCO 3 - for every 10 mm Hg increase in P CO 2. P CO 2 increase = 58-40 = 18 mm Hg. HCO 3 - increase predicted = (1-2) x (18/10) = 2-4 mEq/L add to 24 mEq/L (reference point) = 26-28 mEq/L

10. R acid chronic A 56-year-old woman with COPD is brought to the physician with a 3-hour history of severe epigastric pain. pH7.39 P O 2 62 mm Hg P CO 2 52 mm Hg HCO 3 - 29 mEq/L History suggests hypoventilation, supported by increased P CO 2. Respiratory acidosis (chronic) with renal compensation.

11. Description pH7.39 P O 2 62 mm Hg P CO 2 52 mm Hg HCO 3 - 29 mEq/L 3-4 mEq/L increase in HCO 3 - for every 10 mm Hg increase in P CO 2. P CO 2 increase = 52-40 = 12 mm Hg. HCO 3 - increase predicted = (3-4) x (12/10) = 4-5 mEq/L add to 24 mEq/L (reference point) = 28-29 mEq/L

12. Respiratory alkalosis P CO 2 less than expected Acute or chronic Causes increased alveolar ventilation (central causes, direct action via respiratory center; hypoxaemia, act via peripheral chemoreceptors; pulmonary causes, act via intrapulmonary receptors; iatrogenic, act directly on ventilation)

13. R alk acute A 17-year-old woman is brought to the physician with a 3- hour history of epigastric pain and nausea. She admits taking a large dose of aspirin. Her respirations are full and rapid. pH7.57 P O 2 104 mm Hg P CO 2 25 mm Hg HCO 3 - 23 mEq/L History suggests hyperventilation, supported by decreased P CO 2. Respiratory alkalosis (acute) due to no renal compensation.

14. Description pH7.57 P O 2 104 mm Hg P CO 2 25 mm Hg HCO 3 - 23 mEq/L 1-2 mEq/L decrease in HCO 3 - for every 10 mm Hg decrease in P CO 2. P CO 2 decrease = 40-25 = 15 mm Hg. HCO 3 - decrease predicted = (1-2) x (15/10) = 2-3 mEq/L subtract from 24 mEq/L (reference point) = 21-22 mEq/L

15. R alk chronic A 81-year-old woman with a history of anxiety is brought to the physician with a 2-hour history of shortness of breath. She has been living at 9,000 ft elevation for the past 1 month. Her respirations are full at 20/min. pH7.44 P O 2 69 mm Hg P CO 2 24 mm Hg HCO 3 - 16 mEq/L History suggests hyperventilation, supported by decreased P CO 2. Respiratory alkalosis (chronic) with renal compensation.

16. Description pH7.44 P O 2 69 mm Hg P CO 2 24 mm Hg HCO 3 - 16 mEq/L 4-5 mEq/L decrease in HCO 3 - for every 10 mm Hg decrease in P CO 2. P CO 2 decrease = 40-24 = 16 mm Hg. HCO 3 - decrease predicted = (4-5) x (16/10) = 6-8 mEq/L subtract from 24 mEq/L (reference point) = 16-18 mEq/L

17. Metabolic acidosis Plasma HCO 3 - less than expected Gain of strong acid or loss of base Alternatively, high anion gap or normal anion gap metabolic acidosis Causes high anion-gap acidosis (normochloremic) (ketoacidosis, lactic acidosis, renal failure, toxins) normal anion-gap acidosis (hyperchloremic) (renal, gastrointestinal tract, other)

18. M acid high AG A 20-year-old man with a history of diabetes is brought to the emergency department with a 3-day history of feeling ill. He is non-adherent with his insulin. Urine ketones are 2+ and glucose is 4+. pH7.26Na + 136 mEq/L P O 2 110 mm HgK + 4.8 mEq/L P CO 2 19 mm HgCl - 101 mEq/L HCO 3 - 8 mEq/LCO 2, total10 mEq/L Glucose343 mg/dLUrea49 mg/dL Creatinine1 mg/dL History suggests diabetic ketoacidosis. Metabolic acidosis with appropriate respiratory compensation.

19. Description pH7.26Na + 136 mEq/L P O 2 110 mm HgK + 4.8 mEq/L P CO 2 19 mm HgCl - 101 mEq/L HCO 3 - 8 mEq/LGlucose343 mg/dL Urea49 mg/dL AG = 136-101-8=27 mEq/LCreatinine1 mg/dL 1.2 mm Hg decrease in P CO 2 for every 1 mEq/L decrease in HCO 3 -. HCO 3 - decrease = 24-8 = 16 mEq/L P CO 2 decrease predicted = 1.2 x 16 = 19 mm Hg. subtract from 40 mm Hg (reference point) = 21 mm Hg

20. M acid normal AG A 43-year-old man comes to the physician with a 3-day history of diarrhea. He has decreased skin turgor. pH7.31Na + 134 mEq/L P O 2 -- mm HgK + 2.9 mEq/L P CO 2 31 mm HgCl - 113 mEq/L HCO 3 - 16 mEq/LUrea74 mgl/dL Creatinine3.4 mmol/L History is limited. Metabolic acidosis with respiratory compensation.

21. Description pH7.31Na + 134 mEq/L P O 2 -- mm HgK + 2.9 mEq/L P CO 2 31 mm HgCl - 113 mEq/L HCO 3 - 16 mEq/LUrea74 mg/dL Creatinine3.4 mg/dL AG = 134-113-16=5 mEq/L 1.2 mm Hg decrease in P CO 2 for every 1 mEq/L decrease in HCO 3 -. HCO 3 - decrease = 24-16 = 8 mEq/L P CO 2 decrease predicted = 1.2 x 8 = 10 mm Hg. subtract from 40 mm Hg (reference point) = 30 mm Hg

22. Metabolic alkalosis Plasma HCO 3 - greater than expected Loss of strong acid or gain of base Causes (2 ways to organize) loss of H + from ECF via kidneys (diuretics) or gut (vomiting) gain of alkali in ECF from exogenous source (IV NaHCO 3 infusion) or endogenous source (metabolism of ketoanions) or addition of base to ECF (milk-alkali syndrome) Cl - depletion (loss of acid gastric juice) K + depletion (primary/secondary hyperaldosteronism) Other disorders (laxative abuse, severe hypoalbuminaemia)

23. Urinary Chloride Spot urine Cl - less than 10 mEq/L often associated with volume depletion respond to saline infusion common causes - previous thiazide diuretic therapy, vomiting (90% of cases) Spot urine Cl - greater than 20 mEq/L often associated with volume expansion and hypokalemia resistant to therapy with saline infusion causes: excess aldosterone, severe K + deficiency, current diuretic therapy, Bartter syndrome

24. M alk high Urine Cl - An 83-year-old woman is brought to the physician with a 1- week history of weakness and poor appetite. pH7.58Na + 145 mEq/L P O 2 60 mm HgK + 1.9 mEq/L P CO 2 56 mm HgCl - 86 mEq/L HCO 3 - 52 mEq/LUrine Cl - 74 mEq/L History is limited. Metabolic alkalosis with respiratory compensation. The cause is unknown, most likely excess adrenocortical activity, current diuretic therapy, or idiopathic.

25. Description pH7.58Na + 145 mEq/L P O 2 60 mm HgK + 1.9 mEq/L P CO 2 56 mm HgCl - 86 mEq/L HCO 3 - 52 mEq/LUrine Cl - 74 mEq/L 0.6-0.75 mm Hg increase in P CO 2 for every 1 mEq/L increase in HCO 3 -. HCO 3 - increase = 52-24 = 28 mEq/L P CO 2 increase predicted = 0.6-0.75 x 28 = 17-21 mm Hg. add to 40 mm Hg (reference point) = 57-61 mm Hg

26. M alk low Urine Cl - An 24-year-old woman is brought to the physician with a 3- month history of weakness and fatigue. Blood pressure is 90/60 mm Hg. pH7.52Na + 137 mEq/L P O 2 78 mm HgK + 2.6 mEq/L P CO 2 49 mm HgCl - 90 mEq/L HCO 3 - 39 mEq/LUrine Cl - 5 mEq/L History and physical examination suggests bulimia. Metabolic alkalosis with respiratory compensation. The cause is most likely bulimia.

27. Description pH7.52Na + 137 mEq/L P O 2 78 mm HgK + 2.6 mEq/L P CO 2 49 mm HgCl - 90 mEq/L HCO 3 - 39 mEq/LUrine Cl - 5 mEq/L 0.6-0.75 mm Hg increase in P CO 2 for every 1 mEq/L increase in HCO 3 -. HCO 3 - increase = 39-24 = 15 mEq/L P CO 2 increase predicted = 0.6-0.75 x 15 = 9-12 mm Hg. add to 40 mm Hg (reference point) = 49-52 mm Hg

28. Special Cases Pregnancy – hyperventilation (respiratory alkalosis), hyperemesis (metabolic alkalosis or acidosis), maternal ketosis (metabolic acidosis) Children – low bicarbonate reserve (N=12-16 mEq/L), low acid excretion reserve, inborn errors in metabolism, diabetes, and poisoning (all metabolic acidosis)

29. Review Questions What is an effective approach to acid base problems? What are the normal ranges and reference points? What are the anion and osmolar gap? What is compensation? What are the characteristics of respiratory acidosis and alkalosis? What are the characteristics of metabolic acidosis and alkalosis? What is the utility of spot urine Cl - ? What kinds of acid base conditions present during pregnancy and infancy?