Biochemical basis of acidosis and alkalosis evaluating acid

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

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

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

Reference ranges and points Parameter Reference range Reference point p. H 7. 35 -7. 45 7. 40 PCO 2 33 -44 mm Hg 40 mm Hg P O 2 75 -105 mm Hg HCO 3 - 22 -28 m. Eq/L 24 m. Eq/L Anion gap 8 -16 m. Eq/L 12 m. Eq/L Osmolar gap <10 m. Osm/L

Delta ratio �� ratio = �� Anion gap/�� [HCO 3 -] = (AG – 12)/(24 - [HCO 3 -]) Delta ratio Assessment <0. 4 Hyperchloraemic normal anion gap acidosis 0. 4 – 0. 8 1 -2 >2 Combined high AG and normal AG acidosis Note that the ratio is often <1 in acidosis associated with renal failure 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) Pre-existing increased [HCO 3 -]: concurrent metabolic alkalosis pre-existing compensated respiratory acidosis

Compensation Primary Disturbance p. H HCO 3 - PCO 2 Compensation Respiratory acidosis <7. 35 Compensatory increase Primary increase Acute: 1 -2 m. Eq/L increase in HCO 3 - for every 10 mm Hg increase in PCO 2 Chronic: 3 -4 m. Eq/L increase in HCO 3 - for every 10 mm Hg increase in PCO 2 Respiratory alkalosis >7. 45 Compensatory decrease Primary decrease Acute: 1 -2 m. Eq/L decrease in HCO 3 - for every 10 mm Hg decrease in PCO 2 Chronic: 4 -5 m. Eq/L decrease in HCO 3 - for every 10 mm Hg decrease in PCO 2 Metabolic acidosis <7. 35 Primary decrease Compensatory decrease 1. 2 mm Hg decrease in PCO 2 for every 1 m. Eq/L decrease in HCO 3 - Metabolic alkalosis >7. 45 Primary increase Compensatory increase 0. 6 -0. 75 mm Hg increase in PCO 2 for every 1 m. Eq/L increase in HCO 3, PCO 2 should not rise above 55 mm Hg in compensation

Respiratory acidosis PCO 2 greater than expected Acute or chronic Causes ü 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) ü decreased alveolar ventilation (central respiratory depression & other CNS problems, nerve or muscle disorders, lung or chest wall defects, airway disorders, external factors) ü increased production of CO 2 (hypercatabolic disorders)

Racid acute A 65 -year-old man with a history of emphysema comes to the physician with a 3 -hour history of shortness of breath. p. H 7. 18 P O 2 61 mm Hg PCO 2 58 mm Hg HCO 3 - 26 m. Eq/L History suggests hypoventilation, supported by increased PCO 2 and lower than anticipated PO 2. Respiratory acidosis (acute) due to no renal compensation.

Description p. H 7. 18 P O 2 61 mm Hg PCO 2 58 mm Hg HCO 3 - 26 m. Eq/L 1 -2 m. Eq/L increase in HCO 3 - for every 10 mm Hg increase in PCO 2 increase = 58 -40 = 18 mm Hg. HCO 3 - increase predicted = (1 -2) x (18/10) = 2 -4 m. Eq/L add to 24 m. Eq/L (reference point) = 26 -28 m. Eq/L

Racid chronic A 56 -year-old woman with COPD is brought to the physician with a 3 -hour history of severe epigastric pain. p. H 7. 39 P O 2 62 mm Hg PCO 2 52 mm Hg HCO 3 - 29 m. Eq/L History suggests hypoventilation, supported by increased PCO 2. Respiratory acidosis (chronic) with renal compensation.

Description p. H 7. 39 P O 2 62 mm Hg PCO 2 52 mm Hg HCO 3 - 29 m. Eq/L 3 -4 m. Eq/L increase in HCO 3 - for every 10 mm Hg increase in PCO 2 increase = 52 -40 = 12 mm Hg. HCO 3 - increase predicted = (3 -4) x (12/10) = 4 -5 m. Eq/L add to 24 m. Eq/L (reference point) = 28 -29 m. Eq/L

Respiratory alkalosis PCO 2 less than expected Acute or chronic Causes ü 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)

Ralk 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. p. H 7. 57 P O 2 104 mm Hg PCO 2 25 mm Hg HCO 3 - 23 m. Eq/L History suggests hyperventilation, supported by decreased PCO 2. Respiratory alkalosis (acute) due to no renal compensation.

Description p. H 7. 57 P O 2 104 mm Hg PCO 2 25 mm Hg HCO 3 - 23 m. Eq/L 1 -2 m. Eq/L decrease in HCO 3 - for every 10 mm Hg decrease in PCO 2 decrease = 40 -25 = 15 mm Hg. HCO 3 - decrease predicted = (1 -2) x (15/10) = 2 -3 m. Eq/L subtract from 24 m. Eq/L (reference point) = 21 -22 m. Eq/L

Ralk 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. p. H 7. 44 P O 2 69 mm Hg PCO 2 24 mm Hg HCO 3 - 16 m. Eq/L History suggests hyperventilation, supported by decreased PCO 2. Respiratory alkalosis (chronic) with renal compensation.

Description p. H 7. 44 P O 2 69 mm Hg PCO 2 24 mm Hg HCO 3 - 16 m. Eq/L 4 -5 m. Eq/L decrease in HCO 3 - for every 10 mm Hg decrease in PCO 2 decrease = 40 -24 = 16 mm Hg. HCO 3 - decrease predicted = (4 -5) x (16/10) = 6 -8 m. Eq/L subtract from 24 m. Eq/L (reference point) = 16 -18 m. Eq/L

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 ü high anion-gap acidosis (normochloremic) (ketoacidosis, lactic acidosis, renal failure, toxins) ü normal anion-gap acidosis (hyperchloremic) (renal, gastrointestinal tract, other)

Macid 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+. p. H 7. 26 Na+ 136 m. Eq/L P O 2 110 mm Hg K+ 4. 8 m. Eq/L PCO 2 19 mm Hg Cl 101 m. Eq/L HCO 38 m. Eq/L CO 2, total 10 m. Eq/L Glucose 343 mg/d. L Urea 49 mg/d. L Creatinine 1 mg/d. L History suggests diabetic ketoacidosis. Metabolic acidosis with appropriate respiratory compensation.

Description p. H P O 2 PCO 2 HCO 3 - 7. 26 110 mm Hg 19 mm Hg 8 m. Eq/L Urea AG = 136 -101 -8=27 m. Eq/L Na+ K+ Cl. Glucose 49 mg/d. L Creatinine 136 m. Eq/L 4. 8 m. Eq/L 101 m. Eq/L 343 mg/d. L 1. 2 mm Hg decrease in PCO 2 for every 1 m. Eq/L decrease in HCO 3 - decrease = 24 -8 = 16 m. Eq/L PCO 2 decrease predicted = 1. 2 x 16 = 19 mm Hg. subtract from 40 mm Hg (reference point) = 21 mm Hg

Macid normal AG A 43 -year-old man comes to the physician with a 3 -day history of diarrhea. He has decreased skin turgor. p. H 7. 31 Na+ 134 m. Eq/L P O 2 -- mm Hg K+ 2. 9 m. Eq/L PCO 2 31 mm Hg Cl 113 m. Eq/L HCO 316 m. Eq/L Urea 74 mgl/d. L Creatinine 3. 4 mmol/L History is limited. Metabolic acidosis with respiratory compensation.

Description p. H P O 2 PCO 2 HCO 3 - 7. 31 -- mm Hg 31 mm Hg 16 m. Eq/L Creatinine AG = 134 -113 -16=5 m. Eq/L Na+ K+ Cl. Urea 3. 4 mg/d. L 134 m. Eq/L 2. 9 m. Eq/L 113 m. Eq/L 74 mg/d. L 1. 2 mm Hg decrease in PCO 2 for every 1 m. Eq/L decrease in HCO 3 - decrease = 24 -16 = 8 m. Eq/L PCO 2 decrease predicted = 1. 2 x 8 = 10 mm Hg. subtract from 40 mm Hg (reference point) = 30 mm Hg

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

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

Malk high Urine Cl. An 83 -year-old woman is brought to the physician with a 1 week history of weakness and poor appetite. p. H 7. 58 Na+ 145 m. Eq/L P O 2 60 mm Hg K+ 1. 9 m. Eq/L PCO 2 56 mm Hg Cl 86 m. Eq/L HCO 352 m. Eq/L Urine Cl 74 m. Eq/L History is limited. Metabolic alkalosis with respiratory compensation. The cause is unknown, most likely excess adrenocortical activity, current diuretic therapy, or idiopathic.

Description p. H P O 2 PCO 2 HCO 3 - 7. 58 60 mm Hg 56 mm Hg 52 m. Eq/L Na+ K+ Cl. Urine Cl- 145 m. Eq/L 1. 9 m. Eq/L 86 m. Eq/L 74 m. Eq/L 0. 6 -0. 75 mm Hg increase in PCO 2 for every 1 m. Eq/L increase in HCO 3 - increase = 52 -24 = 28 m. Eq/L PCO 2 increase predicted = 0. 6 -0. 75 x 28 = 17 -21 mm Hg. add to 40 mm Hg (reference point) = 57 -61 mm Hg

Malk 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. p. H 7. 52 Na+ 137 m. Eq/L P O 2 78 mm Hg K+ 2. 6 m. Eq/L PCO 2 49 mm Hg Cl 90 m. Eq/L HCO 339 m. Eq/L Urine Cl 5 m. Eq/L History and physical examination suggests bulimia. Metabolic alkalosis with respiratory compensation. The cause is most likely bulimia.

Description p. H P O 2 PCO 2 HCO 3 - 7. 52 78 mm Hg 49 mm Hg 39 m. Eq/L Na+ K+ Cl. Urine Cl- 137 m. Eq/L 2. 6 m. Eq/L 90 m. Eq/L 5 m. Eq/L 0. 6 -0. 75 mm Hg increase in PCO 2 for every 1 m. Eq/L increase in HCO 3 - increase = 39 -24 = 15 m. Eq/L PCO 2 increase predicted = 0. 6 -0. 75 x 15 = 9 -12 mm Hg. add to 40 mm Hg (reference point) = 49 -52 mm Hg

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

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?