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
 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 points
Parameter Reference range Reference point
Na+ 135-147 mEq/L
K+ 3.5-5.0 mEq/L
Cl- 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/L
Bicarbonate gap -6-6 mEq/L
Osmolar gap <10 mOsm/L
 Evaluation of Serum Electrolytes
Total CO2

Increased, >30 mEq/L Normal Decreased, <24 mEq/L

 metabolic alkalosis  metabolic acidosis (AG or HCA)
 HCO3- retention for respiratory acidosis  HCO3- excretion for respiratory alkalosis

Anion Gap
Increased, >20 mEq/L Normal Decreased, <8 mEq/L
 consider potential cause  consider hypoproteinemia,
abnormal proteins or cations

Bicarbonate Gap
Positive, > 6 mEq/L Negative, < -6 mEq/L
 metabolic alkalosis and/or  hyperchloremic acidosis (HCA) and/or
 HCO3- retention for respiratory acidosis  HCO3- excretion for respiratory alkalosis
 Evaluation of Arterial Blood Gas
Primary process Compensatory response

[HCO-3 ] -[HCO-3 ]
¯pH @ Respiratory acidosis -pH @
-PCO 2 -PCO2

[HCO-3 ] ¯[HCO-3 ]
-pH @ Respiratory alkalosis ¯pH @
¯PCO 2 ¯PCO2

¯[HCO-3 ] ¯[HCO-3 ]
¯pH @ Metabolic acidosis -pH @
PCO2 ¯PCO2

-[HCO-3 ] -[HCO-3 ]
-pH @ Metabolic alkalosis ¯pH @
PCO2 -PCO2
 Delta ratio
𝛥 ratio = 𝛥Anion gap/𝛥[HCO3-] = (AG – 12)/(24 - [HCO3-])

Delta ratio Assessment

<0.4 Hyperchloraemic normal anion gap acidosis

Combined high AG and normal AG acidosis
0.4 – 0.8 Note that the ratio is often <1 in acidosis associated
with renal failure
Uncomplicated high-AG acidosis
Lactic acidosis: average value 1.6
1-2
DKA more likely to have a ratio closer to 1 due to urine
ketone loss (if patient not dehydrated)
Pre-existing increased [HCO3-]:
>2 concurrent metabolic alkalosis
pre-existing compensated respiratory acidosis
 Compensation
Primary pH HCO3- PCO2 Compensation
Disturbance
Respiratory acidosis <7.35 Compensatory Primary Acute: 1-2 mEq/L increase in
increase increase HCO3- for every 10 mm Hg increase
in PCO2
Chronic: 3-4 mEq/L increase in
HCO3- for every 10 mm Hg increase
in PCO2
Respiratory alkalosis >7.45 Compensatory Primary Acute: 1-2 mEq/L decrease in
decrease decrease 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 Compensatory 1.2 mm Hg decrease in PCO2 for
decrease decrease every 1 mEq/L decrease in HCO3-
Metabolic alkalosis >7.45 Primary Compensatory 0.6-0.75 mm Hg increase in PCO2
increase increase for every 1 mEq/L increase in HCO3-
, PCO2 should not rise above 55 mm
Hg in compensation
 Respiratory acidosis

PCO2 greater than expected

Acute or chronic
Causes
 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 acute
A 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 7.33
K+ 4.2 mEq/L PO2 61 mm Hg
Cl- 101 mEq/L PCO2 50 mm Hg
CO2, total 28 mEq/L HCO3- 26 mEq/L
History suggests hypoventilation, supported by increased PCO2 and
lower than anticipated PO2. Reference range AG and BG.
Respiratory acidosis (acute) due to no renal compensation.
 Description
Na+ 138 mEq/L pH 7.33
K+ 4.2 mEq/L PO2 61 mm Hg
Cl- 101 mEq/L PCO2 50 mm Hg
CO2, total 28 mEq/L HCO3- 26 mEq/L
AG = 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/L
add to 24 mEq/L (reference point) = 25-26 mEq/L
 Racid chronic
A 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 7.33
K+ 4.5 mEq/L PO2 52 mm Hg
Cl- 99 mEq/L PCO2 62 mm Hg
CO2, total 34 mEq/L HCO3- 32 mEq/L
History suggests hypoventilation, supported by increased PCO2.
Reference range AG with increased BG.
Respiratory acidosis (chronic) with renal compensation.
 Description
Na+ 145 mEq/L pH 7.33
K+ 4.5 mEq/L PO2 52 mm Hg
Cl- 99 mEq/L PCO2 62 mm Hg
CO2, total 34 mEq/L HCO3- 32 mEq/L
AG = 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/L
add 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 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 20/min
and full.
Na+ 136 mEq/L pH 7.55
K+ 3.7 mEq/L PO2 104 mm Hg
Cl- 101 mEq/L PCO2 25 mm Hg
CO2, total 23 mEq/L HCO3- 22 mEq/L
History suggests hyperventilation, supported by decreased
PCO2. Reference range AG and BG.
Respiratory alkalosis (acute) due to no renal compensation.
 Description
Na+ 136 mEq/L pH 7.55
K+ 3.7 mEq/L PO2 104 mm Hg
Cl- 101 mEq/L PCO2 25 mm Hg
CO2, total 23 mEq/L HCO3- 22 mEq/L
AG = 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/L
subtract from 24 mEq/L (reference point) = 21-22 mEq/L
 Ralk chronic
A 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 7.48
K+ 4.9 mEq/L PO2 69 mm Hg
Cl- 105 mEq/L PCO2 22 mm Hg
CO2, total 17 mEq/L HCO3- 16 mEq/L
History suggests hyperventilation, supported by decreased
PCO2. Reference range AG with decreased BG.
Respiratory alkalosis (chronic) with renal compensation.
 Description
Na+ 133 mEq/L pH 7.48
K+ 4.9 mEq/L PO2 69 mm Hg
Cl- 105 mEq/L PCO2 22 mm Hg
CO2, total 17 mEq/L HCO3- 16 mEq/L
AG = 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/L
subtract 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 AG
A 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 7.19
K+ 4.0 mEq/L PO2 80 mm Hg
Cl- 97 mEq/L PCO2 21 mm Hg
CO2, total 8 mEq/L HCO3- 8 mEq/L
Lactate 20 mEq/L
Urea 54 mg/dL
Creatinine 2.5 mg/dL
History suggests congestive heart failure (poor perfusion). Increased AG
with reference range BG.
Metabolic acidosis with appropriate respiratory compensation.
 Description
Na+ 135 mEq/L pH 7.19
K+ 4.0 mEq/L PO2 80 mm Hg
Cl- 97 mEq/L PCO2 21 mm Hg
CO2, total 8 mEq/L HCO3- 8 mEq/L
Lactate 20 mEq/L
Urea 54 mg/dL AG = 30 mEq/L
Creatinine 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 AG
A 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 7.34
K+ 4.3 mEq/L PO2 96 mm Hg
Cl- 112 mEq/L PCO2 29 mm Hg
CO2, total 16 mEq/L HCO3- 15 mEq/L
Urine pH 5.0
History suggests intestinal electrolyte loss. Reference
range AG (hyperchloremic) with decreased BG.
Metabolic acidosis with respiratory compensation.
 Description
Na+ 139 mEq/L pH 7.34
K+ 4.3 mEq/L PO2 96 mm Hg
Cl- 112 mEq/L PCO2 29 mm Hg
CO2, total 16 mEq/L HCO3- 15 mEq/L
Urine pH 5.0
FEHCO3- 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 7.52
K+ 2.6 mEq/L PO2 78 mm Hg
Cl- 90 mEq/L PCO2 49 mm Hg
CO2, total 41 mEq/L HCO3- 39 mEq/L
Urine Cl- 5 mEq/L
History and physical examination suggests bulimia nervosa.
Reference range AG with increased BG.
Metabolic alkalosis with respiratory compensation.
The cause is most likely bulimia nervosa.
 Description
Na+ 137 mEq/L pH 7.52
K+ 2.6 mEq/L PO2 78 mm Hg
Cl- 90 mEq/L PCO2 49 mm Hg
CO2, total 41 mEq/L HCO3- 39 mEq/L
Urine Cl- 5 mEq/L
AG = 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 7.48
K+ 1.9 mEq/L PO2 66 mm Hg
Cl- 77 mEq/L PCO2 49 mm Hg
CO2, total 38 mEq/L HCO3- 36 mEq/L
Urine Cl- 74 mEq/L
History and physical examination suggest electrolyte
imbalance. Reference range AG with increased BG.
Metabolic alkalosis with respiratory compensation.
The cause most likely is current diuretic therapy.
 Description
Na+ 130 mEq/L pH 7.48
K+ 1.9 mEq/L PO2 66 mm Hg
Cl- 77 mEq/L PCO2 49 mm Hg
CO2, total 38 mEq/L HCO3- 36 mEq/L
Urine Cl- 74 mEq/L
AG = 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
 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-?