Eric NiederhofferMedical Biochemistry

Biochemical basis of acidosis and alkalosis: evaluating acid base disorders

Outline

• Approachhistoryphysical examinationdifferentialsclinical and laboratory studiescompensation

• Respiratoryacidosisalkalosis

• Metabolicacidosisalkalosis

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

Evaluation of Acid-Base Conditions• Examine serum electrolytes (increased or decreased

total CO2, increased or decreased AG, increased or

decreased HCO3- gap) and ABGs (directional changes

in pH, HCO3-, and PCO2).

• Examine ABG data for mixed acid-base conditions.• Complete clinical assessment of history, physical

examination, previous ABGs and serum electrolytes, along with other laboratory data.

• Identify underlying clinical cause(s) for each acid-base disorder.

• Treat the clinical conditions.

Reference ranges and pointsParameter Reference range Reference

pointNa+ 135-147 mEq/LK+ 3.5-5.0 mEq/LCl- 95-105 mEq/L

CO2, total 24-30 mEq/L

pH 7.35-7.45 7.40

PCO2 33-44 mm Hg 40 mm Hg

PO2 75-105 mm Hg

HCO3- 22-28 mEq/L 24 (27) mEq/L

Anion gap 8-16 mEq/L 12 mEq/LBicarbonate gap -6-6 mEq/L

Osmolar gap <10 mOsm/L

Evaluation of Serum ElectrolytesTotal CO2

Increased, >30 mEq/L metabolic alkalosis HCO3

- retention for respiratory acidosis

Decreased, <24 mEq/L metabolic acidosis (AG or HCA) HCO3

- excretion for respiratory alkalosis

Normal

Anion Gap

NormalIncreased, >20 mEq/L consider potential cause

Decreased, <8 mEq/L consider hypoproteinemia,

abnormal proteins or cations

Negative, < -6 mEq/L hyperchloremic acidosis (HCA) and/or HCO3

- excretion for respiratory alkalosis

Bicarbonate Gap

Positive, > 6 mEq/L metabolic alkalosis and/or HCO3

- retention for respiratory acidosis

Evaluation of Arterial Blood Gas

Metabolic acidosis

Metabolic alkalosis

Respiratory acidosis

Respiratory alkalosis

Primary process Compensatory response

Delta ratioDelta ratio Assessment

<0.4 Hyperchloraemic normal anion gap acidosis

0.4 – 0.8 Combined high AG and normal AG acidosisNote that the ratio is often <1 in acidosis associated with renal failure

1 - 2

Uncomplicated high-AG acidosisLactic 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 [HCO3

-]:concurrent metabolic alkalosispre-existing compensated respiratory acidosis

𝛥 ratio = Anion gap/ [HCO𝛥 𝛥 3-] = (AG – 12)/(24 -

[HCO3-])

CompensationPrimary

DisturbancepH HCO3

- PCO2 Compensation

Respiratory acidosis <7.35 Compensatory increase

Primary increase

Acute: 1-2 mEq/L increase in HCO3

- for every 10 mm Hg increase in PCO2Chronic: 3-4 mEq/L increase in HCO3

- for every 10 mm Hg increase in PCO2

Respiratory alkalosis >7.45 Compensatory decrease

Primary decrease

Acute: 1-2 mEq/L decrease in HCO3

- for every 10 mm Hg decrease in PCO2

Chronic: 4-5 mEq/L decrease in HCO3

- for every 10 mm Hg decrease in PCO2

Metabolic acidosis <7.35 Primary decrease

Compensatory decrease

1.2 mm Hg decrease in PCO2 for every 1 mEq/L decrease in HCO3

-

Metabolic alkalosis >7.45 Primary increase

Compensatory increase

0.6-0.75 mm Hg increase in PCO2 for every 1 mEq/L increase in HCO3

-

, PCO2 should not rise above 55 mm Hg in compensation

Respiratory acidosisPCO2 greater than expectedAcute or chronicCauses

excess CO2 in inspired air(rebreathing of CO2-containing expired air, addition of CO2 to inspired air, insufflation of CO2 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 CO2

(hypercatabolic disorders)

Racid acuteA 65-year-old man comes to the physician with a 3-hour history of shortness of breath after feeling ill for the past week. His BMI is 30 kg/m2. His temperature is 38.3°C (101°F), pulse is 96/min, respirations are 20/min and shallow, and blood pressure is 145/90 mm Hg.

Na+ 138 mEq/L pH 7.33K+ 4.2 mEq/L PCO2 50 mm HgCl- 101 mEq/L PO2 67 mm HgCO2, total 28 mEq/L HCO3

- 26 mEq/LHistory/PE suggest hypoventilation, supported by increased PCO2 and (A-a)PO2 difference. Reference range AG and BG.

Respiratory acidosis (acute) due to no renal compensation.

DescriptionNa+ 138 mEq/L pH 7.33K+ 4.2 mEq/L PCO2 50 mm HgCl- 101 mEq/L PO2 67 mm HgCO2, total 28 mEq/L HCO3

- 26 mEq/LAG = 11 mEq/L BG = 1 mEq/L

1-2 mEq/L increase in HCO3- for every 10 mm Hg increase

in PCO2.PCO2 increase = 50-40 = 10 mm Hg.HCO3

- increase predicted = (1-2) x (10/10) = 1-2 mEq/Ladd to 24 mEq/L (reference point) = 25-26 mEq/L

Racid chronicA 56-year-old woman with COPD is brought to the physician with a 3-hour history of shortness of breath. Her temperature is 37°C (98.6°F), pulse is 90/min, respirations are 22/min and shallow, and blood pressure is 135/80 mm Hg.

Na+ 145 mEq/L pH 7.33K+ 4.5 mEq/L PCO2 62 mm HgCl- 99 mEq/L PO2 32 mm HgCO2, total 34 mEq/L HCO3

- 32 mEq/LHistory/PE suggest V/Q imbalance, supported by increased PCO2 and (A-a)PO2 difference. Reference range AG with increased BG.

Respiratory acidosis (chronic) with renal compensation.

DescriptionNa+ 145 mEq/L pH 7.33K+ 4.5 mEq/L PCO2 62 mm HgCl- 99 mEq/L PO2 32 mm HgCO2, total 34 mEq/L HCO3

- 32 mEq/LAG = 14 mEq/L BG = 10 mEq/L

3-4 mEq/L increase in HCO3- for every 10 mm Hg increase

in PCO2.PCO2 increase = 62-40 = 22 mm Hg.HCO3

- increase predicted = (3-4) x (22/10) = 7-9 mEq/Ladd to 24 mEq/L (reference point) = 31-33 mEq/L

Respiratory alkalosis

PCO2 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)

Ralk acuteA 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 20/min and full.

Na+ 136 mEq/L pH 7.55K+ 3.7 mEq/L PCO2 25 mm HgCl- 101 mEq/L PO2 104 mm HgCO2, total 23 mEq/L HCO3

- 22 mEq/LHistory/PE suggest hyperventilation, supported by decreased PCO2. Reference range AG and BG.Respiratory alkalosis (acute) due to no renal compensation.

DescriptionNa+ 136 mEq/L pH 7.55K+ 3.7 mEq/L PCO2 25 mm HgCl- 101 mEq/L PO2 104 mm HgCO2, total 23 mEq/L HCO3

- 22 mEq/LAG = 12 mEq/L BG = -1 mEq/L

1-2 mEq/L decrease in HCO3- for every 10 mm Hg decrease

in PCO2.PCO2 decrease = 40-25 = 15 mm Hg.HCO3

- decrease predicted = (1-2) x (15/10) = 2-3 mEq/Lsubtract from 24 mEq/L (reference point) = 21-22 mEq/L

Ralk chronicA 81-year-old woman with a history of anxiety is brought to the physician with a 2-day 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.

Na+ 133 mEq/L pH 7.48K+ 4.9 mEq/L PCO2 22 mm HgCl- 105 mEq/L PO2 69 mm HgCO2, total 17 mEq/L HCO3

- 16 mEq/LHistory/PE suggest hyperventilation, supported by decreased PCO2. Reference range AG with decreased BG.Respiratory alkalosis (chronic) with renal compensation.

DescriptionNa+ 133 mEq/L pH 7.48K+ 4.9 mEq/L PCO2 22 mm HgCl- 105 mEq/L PO2 69 mm HgCO2, total 17 mEq/L HCO3

- 16 mEq/LAG = 12 mEq/L BG = -8 mEq/L

4-5 mEq/L decrease in HCO3- for every 10 mm Hg decrease

in PCO2.PCO2 decrease = 40-22 = 18 mm Hg.HCO3

- decrease predicted = (4-5) x (18/10) = 7-9 mEq/Lsubtract from 24 mEq/L (reference point) = 15-17 mEq/L

Metabolic acidosis

Plasma HCO3- 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)

Macid increased AGA 75-year-old man with severe congestive heart failure is brought to the emergency department. He takes none of his prescribed medications. His respirations are 24/min and blood pressure is 80/50 mm Hg. He has decreased urine output; his baseline creatinine concentration has been 1.6 mg/dL.

Na+ 135 mEq/L pH 7.19K+ 4.0 mEq/L PCO2 21 mm HgCl- 97 mEq/L PO2 80 mm HgCO2, total 8 mEq/L HCO3

- 8 mEq/LLactate 20 mEq/LUrea 54 mg/dLCreatinine 2.5 mg/dL

History/PE suggest congestive heart failure (poor perfusion). Increased AG with reference range BG.Metabolic acidosis with appropriate respiratory compensation.

DescriptionNa+ 135 mEq/L pH 7.19K+ 4.0 mEq/L PCO2 21 mm HgCl- 97 mEq/L PO2 80 mm HgCO2, total 8 mEq/L HCO3

- 8 mEq/LLactate 20 mEq/LUrea 54 mg/dL AG = 30 mEq/LCreatinine 2.5 mg/dL BG = 2 mEq/L

1.2 mm Hg decrease in PCO2 for every 1 mEq/L decrease in HCO3

-.HCO3

- decrease = 24-8 = 16 mEq/L PCO2 decrease predicted = 1.2 x 16 = 19 mm Hg.subtract from 40 mm Hg (reference point) = 21 mm Hg

Macid reference range AGA 2-year-old girl is brought to the physician because of a 1-week history of diarrhea. She is at the 30th centile for height and weight. Physical examination shows no abnormalities. Laboratory studies show a fractional excretion of HCO3

- of 2.5%.

Na+ 139 mEq/L pH 7.34K+ 4.3 mEq/L PCO2 29 mm HgCl- 112 mEq/L PO2 96 mm HgCO2, total 16 mEq/L HCO3

- 15 mEq/LUrine pH 5.0

History/PE suggest intestinal electrolyte loss. Reference range AG (hyperchloremic) with decreased BG.Metabolic acidosis with respiratory compensation.

DescriptionNa+ 139 mEq/L pH 7.34K+ 4.3 mEq/L PCO2 29 mm HgCl- 112 mEq/L PO2 96 mm HgCO2, total 16 mEq/L HCO3

- 15 mEq/LUrine pH 5.0FEHCO3

- 2.5%AG = 12 mEq/L BG = -9 mEq/L

1.2 mm Hg decrease in PCO2 for every 1 mEq/L decrease in HCO3

-.HCO3

- decrease = 24-15 = 9 mEq/L PCO2 decrease predicted = 1.2 x 9 = 11 mm Hg.subtract from 40 mm Hg (reference point) = 29 mm Hg

Metabolic alkalosis

Plasma HCO3- 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 NaHCO3

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)

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

Malk low Urine Cl-An 24-year-old woman is brought to the physician with a 3-month history of weakness and fatigue. She has binges of eating followed by self-induced vomiting. Blood pressure is 90/60 mm Hg. Physical examination shows erosions of the lingual surface of the teeth.

Na+ 137 mEq/L pH 7.52K+ 2.6 mEq/L PCO2 49 mm HgCl- 90 mEq/L PO2 78 mm HgCO2, total 41 mEq/L HCO3

- 39 mEq/LUrine Cl- 5 mEq/L

History/PE suggest bulimia nervosa. Reference range AG with increased BG.Metabolic alkalosis with respiratory compensation.The cause is most likely bulimia nervosa.

DescriptionNa+ 137 mEq/L pH 7.52K+ 2.6 mEq/L PCO2 49 mm HgCl- 90 mEq/L PO2 78 mm HgCO2, total 41 mEq/L HCO3

- 39 mEq/LUrine Cl- 5 mEq/LAG = 8 mEq/L BG = 11 mEq/L

0.6-0.75 mm Hg increase in PCO2 for every 1 mEq/L increase in HCO3

-.HCO3

- increase = 39-24 = 15 mEq/L PCO2 increase predicted = 0.6-0.75 x 15 = 9-12 mm Hg.add to 40 mm Hg (reference point) = 49-52 mm Hg

Malk high Urine Cl-An 83-year-old woman is brought to the physician with a 1-week history of weakness, nausea, and poor appetite. Her current medications are aspirin and hydrochlorothiazide. Her blood pressure is 110/70 mm Hg.

Na+ 130 mEq/L pH 7.48K+ 1.9 mEq/L PCO2 49 mm HgCl- 77 mEq/L PO2 66 mm HgCO2, total 38 mEq/L HCO3

- 36 mEq/LUrine Cl- 74 mEq/L

History/PE suggest electrolyte imbalance. Reference range AG with increased BG.Metabolic alkalosis with respiratory compensation.The cause most likely is current diuretic therapy.

DescriptionNa+ 130 mEq/L pH 7.48K+ 1.9 mEq/L PCO2 49 mm HgCl- 77 mEq/L PO2 66 mm HgCO2, total 38 mEq/L HCO3

- 36 mEq/LUrine Cl- 74 mEq/LAG = 17 mEq/L BG = 17 mEq/L

0.6-0.75 mm Hg increase in PCO2 for every 1 mEq/L increase in HCO3

-.HCO3

- increase = 36-24 = 12 mEq/L PCO2 increase predicted = 0.6-0.75 x 12 = 7-9 mm Hg.add to 40 mm Hg (reference point) = 47-49 mm Hg

Multiple Acid-Base DisordersA 65-year-old man with a history of multiple myocardial infarctions is brought to the emergency department after being found unconscious in his nursing home room. His blood pressure is 80/50 mm Hg. His skin turgor is decreased.

Na+ 165 mEq/L pH 7.72K+ 4.0 mEq/L PCO2 32 mm HgCl- 105 mEq/L PO2 86 mm HgCO2, total 34 mEq/L HCO3

- 32 mEq/L[Albumin] 2 g/dL

What is the best description of his acid-base status?Dr. Anderson and I will announce the best response from those submitted to D2L.

A 36-year-old woman with a 30-year history of diabetes and a recent history of acute kidney injury is brought to the emergency department after being found unconscious in the street.

Na+ 144 mEq/L pH 6.85K+ 4.0 mEq/L PCO2 60 mm HgCl- 115 mEq/L PO2 70 mm HgCO2, total 10 mEq/L HCO3

- 10 mEq/L[Albumin] 1.5 g/dL

What is the best description of her acid-base status?Dr. Anderson and I will announce the best response from those submitted to D2L.

Multiple Acid-Base Disorders

Review Questions

• What is an effective approach to acid base problems?• What are the reference ranges and reference points?• What are the anion, bicarbonate, and osmolar gap?• How does serum albumin impact the anion gap?• What is the delta ratio?• 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-?