DOI: 10.1002/ncp.

10881

INVITED REVIEW

Acid‐base
Acid‐base disorders:
disorders: A primer
A primer for for clinicians
clinicians

Anne M. Tucker PharmD1 | Tami N. Johnson PharmD2

1
Division of Pharmacy, Clinical Pharmacy
Specialist—Critical Care/Nutrition Abstract
Support, University of Texas MD An understanding of acid‐base physiology is necessary for clinicians to
Anderson Cancer Center, Houston,
Texas, USA
recognize and correct problems that may negatively affect provision of nutrition
2
Division of Pharmacy, Clinical Pharmacy support and drug therapy. An overview of acid‐base physiology, the different
Specialist—Emergency Medicine, acid‐base disorders encountered in practice, a stepwise approach to evaluate
University of Texas MD Anderson Cancer
arterial blood gases, and other key diagnostic tools helpful in formulating a safe
Center, Houston, Texas, USA
and effective medical and nutrition plan are covered in this acid‐base primer.
Correspondence Case scenarios are also provided for the application of principles and the
Anne M. Tucker, PharmD, Division of
development of clinical skills.
Pharmacy, Clinical Pharmacy Specialist—
Critical Care/Nutrition Support,
University of Texas MD Anderson Cancer KEYWORDS
Center, 1515 Holcombe Boulevard, Unit acid‐base disorder, acidosis, alkalosis, blood gas analysis, nutrition support, pH
90, Houston, TX 77030, USA.
Email: amtucker@[Link]

For this and other NCP continuing

education articles, Please see [Link]
[Link]/aspen/publications/13/view

A C I D‐ BASE PHYSIOLOGY Acid‐base balance is tightly regulated with an extracellular

pH between 7.35 and 7.45.3 The terms acidemia and
A coordinated effort of internal buffer systems that alkalemia refer to the actual pH of the blood. Acidemia
includes the lungs and kidneys work to maintain occurs when the pH is <7.35 and alkalemia occurs when
homeostasis and resist changes in acid‐base balance for the pH is >7.45.4 Acidosis and alkalosis refer to the
normal cell function. Acid‐base physiology involves the processes that change the pH. There are four primary
maintenance of normal hydrogen ion (H+) concentration acid‐base processes: metabolic acidosis, metabolic alkalo-
in the body. Most of the H+ ions originate from by‐ sis, respiratory acidosis, and respiratory alkalosis.
products or end products of cellular metabolism and must Buffer systems help maintain the pH around 7.4 and
be excreted to maintain acid‐base balance.1 The degree of are the first line of defense when acid‐base alterations are
acidity or the H+ in the blood, is referred to as the pH and detected. The most abundant extracellular buffer is the
can be determined using the Henderson‐Hasselbalch carbonic acid (H2CO3) and bicarbonate (HCO3−) system
equation1,2: pH = 6.1 + log ([HCO3−]/(0.03 x PCO2)). (Figure 1).3 Other buffers include plasma protein,

[Correction added on 29 June 2022, after first online publication: Reference citation numbers in the text were corrected.]

© 2022 American Society for Parenteral and Enteral Nutrition.

980 | [Link]/journal/ncp Nutr. Clin. Pract. 2022;37:980–989.

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NUTRITION IN CLINICAL PRACTICE | 981

TABLE 1 Normal adult blood gas values2

Measurement Arterial Venous
pH 7.40 (7.35–7.45) 7.36 (7.33–7.43)
PCO2, mm Hg 40 (35–45) (PaCO2) 41–51 (PvCO2)
PO2, mm Hg 100 (80–100) (PaO2) 35–40 (PvO2)
F I G U R E 1 Carbonic acid and bicarbonate buffer system.3
HCO−
3,
(lung's ability
bicarbonate; H2CO3, carbonic acid; H+, hydrogen ion; H2O, water to oxygenate)
HCO3−, mEq/L 24 (22–26) 24–28
Base excess 0 (−2 to +2) −2.4 to 2.3
hemoglobin, phosphates, ammonium/ammonia, and
SO2, % >93 70–75
lactic acid/lactate. These buffer systems are limited,
(hemoglobin
and, once exhausted, acid‐base imbalances can occur. capacity)
The main function of the lungs in acid‐base balance is
Abbreviations: HCO3−, bicarbonate; SO2, oxygen saturation.
regulation of the PCO2 in the blood. The normal PCO2
value is ~40 mm Hg (range, 35–45 mm Hg).3 The lungs
regulate PCO2 through adjustments in the rate and depth
of respirations. As seen in the H2CO3 and HCO3− buffer PaCO2 and PaO2. The addition of “v” designates venous
system equation (Figure 1), H2CO3 concentration is in blood samples (eg, PvCO2 and PvO2). The HCO3− value
equilibrium with CO2 gas plus water in the presence of on a blood gas is a calculated number and should be
carbonic anhydrase. Because H2CO3 is directly propor- compared with the serum total CO2. These two values
tional to PCO2 in the blood, PCO2 is considered an acid.2 should be within 1‐ to 2‐mEq/L agreement, with the
Increases in PCO2, as seen with hypoventilation, produce serum total CO2 slightly higher than the calculated
a decrease in pH. Decreases in PCO2 as a result of HCO3−.2,3 If a difference >2 mEq/L is noted, interpreta-
increased respiratory rate produce an increase in pH. tion should be with caution, as there may be an error in
When metabolic acid‐base disorders are present, the sample collection, improper sample storage prior to
lungs will adjust the depth and rate of respirations to analysis, nonsimultaneous measurements, or analyzer
compensate. This occurs within minutes.5 miscalibration.2,3 In this situation, the clinician should
The kidneys regulate the HCO3− concentration in the consider repeat simultaneous serum total CO2 and blood
blood through alterations in renal H+ excretion, HCO3− gas HCO3− collections, recalibration of the blood gas
reabsorption, and titratable acid formation.1,3 Bicarbonate analyzer, or performing an independent calculation of
is considered a base. The normal HCO3− value is the HCO3− from the blood gas results.2,6 A base excess
~24 mEq/L (range, 22–26 mEq/L).2 Increases in HCO3− value may also be found on a blood gas analysis and is a
lead to an increase in pH. Decreases in HCO3− lead to a calculated number that represents an estimate of the
decrease in pH. When respiratory acid‐base disorders metabolic component status in whole blood.4,7 A normal
occur, the kidneys will adjust the HCO3− concentration base excess value for arterial blood is ~0 (range of −2 to
through the methods stated above to attempt to normalize +2).2 An elevated base excess (>+2) indicates there is a
pH. Unlike the lungs, the kidneys respond slower and may higher than normal amount of HCO3− in the blood
take days for full compensation efforts.2 consistent with a metabolic alkalosis.4,7 A negative base
excess (<−2) is commonly referred to as a base deficit
and reflects an insufficient amount of buffer in the blood
BL OO D GAS AN AL YSIS leading to metabolic acidosis.4,7

Arterial blood gases (ABGs) and venous blood gases

(VBGs) reflect the pH and the amount of gas exchange STEPWISE APPROACH OF BLOOD
between oxygen and CO2 in the blood. Normal values GAS AN AL YSES
can be found in Table 1.2 ABG measurements help
determine the gas exchange of the lungs or oxygen into A systematic process for evaluating ABG values is
the blood. VBG measurements determine the tissue important for the diagnosis of acid‐base imbalances or
oxygenation or the heart and circulation function. The disorders. These steps are not precise and are strongly
pH, PCO2, PO2, and oxygen saturation are measured recommended to be used in conjunction with a thorough
values. The PCO2 and PO2 from arterial blood samples history and physical to accurately diagnose the acid‐base
are designed by the addition of the letter “a”, as seen with disorder and underlying cause.
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982 | TUCKER AND JOHNSON

Step 1. Obtain an ABG and evaluate the pH TABLE 2 Acid‐base disorders and compensation2,3
Acid‐base
The reference range for pH is 7.35–7.45, with an average disorder pH Primary disorder Compensation
of 7.4. A pH < 7.35 indicates acidemia and a pH > 7.45 Respiratory
indicates alkalemia.2,3 Many practitioners use a pH of
Acidosis <7.4 ↑PCO2 > 40 mm Hg ↑HCO3−
7.4 as a target pH to help identify the primary acid‐base
disorder. Alkalosis >7.4 ↓PCO2 < 40 mm Hg ↓HCO3−
Metabolic
Acidosis <7.4 ↓HCO3− < 24 mEq/L ↓PCO2
Step 2. Evaluate the PCO2
Alkalosis >7.4 ↑HCO3− > 24 mEq/L ↑PCO2

The respiratory component in acid‐base regulation is Abbreviations: ↑, increased; ↓, decreased; HCO3−, bicarbonate.
PCO2. The PCO2 value is the acid component in the
H2CO3/HCO3− buffer system. The reference range for level is the largest source. The following formula can be
PCO2 is 35–45 mm Hg, with an average of 40 mm Hg. A used to correct AG during hypoalbuminemia: corrected
PCO2 > 40 mm Hg indicates a respiratory acidosis, and a AG = observed AG + 2.5 × (4.5 – measured serum albu-
PCO2 < 40 mm Hg indicates a respiratory alkalosis.2,3 min level [g/dl]).8

Step 3. Evaluate the HCO3− Step 5. Determine if the acid‐base disorder

is acute vs chronic
The metabolic component in acid‐base regulation is
HCO3−. The HCO3− value is the base component in the Respiratory processes can be further categorized as
H2CO3/HCO3− buffer system. The reference range for acute and chronic disorders. Acute disorders are
HCO3− is 22–26 mEq/L, with an average of 24 mEq/L. considered to occur within minutes to hours. Chronic
Compare the HCO3− value on the blood gas to the serum disorders are considered to occur in days.3 Identification
total CO2 and question blood gas sample validity if there of the appropriate category is important for determining
is more than a 2‐mEq/L difference between the two the degree and appropriateness of any compensatory
values. If the difference is >2 mEq/L, sample recollec- response to an acid‐base disorder.
tion, recalibration of the analyzer, or independent
calculation of the HCO3− should be considered.4,6 A
HCO3− > 24 mEq/L indicates metabolic alkalosis, and a Step 6. Determine the primary acid‐base
HCO3− < 24 mEq/L indicates metabolic acidosis.2 disorder

Use steps 1–5 to establish the primary acid‐base disorder

Step 4. Calculate the anion gap and compensation (Table 2). Evaluate the PCO2 and
HCO3− to determine which component is driving the pH
The anion gap (AG) is calculated to help determine the (respiratory or metabolic).
etiology of metabolic acidosis. This calculation estimates
the difference between measured and unmeasured
major extracellular fluid cations and anions. The AG Step 7. Determine if appropriate
equation is as follows: AG = Na+ – (Cl− + HCO3−).3,8 The compensation or if a mixed disorder exists
reference range for AG is ~10 mEq/L (range, 8–12 mEq/L).2
An elevated AG metabolic acidosis signifies the Table 3 lists equations that will help predict the body's ability
presence of increased unmeasured anions as seen with to compensate when an acid‐base disturbance occurs.3 These
organic acidosis. In hyperchloremic metabolic acidosis, equations are not precise. Appropriate compensation is
HCO3− losses from the extracellular fluid are equally considered when the calculated and actual values are within
replaced by chloride maintaining a normal AG. Hy- 10% of each other.4 Therefore, the smaller the difference is
poalbuminemia can cause a falsely decreased AG. For between the actual and calculated numbers, the more likely
every 1 g/dl change in serum albumin level, a similar there is a simple acid‐base disorder. Large differences
change in AG by 2.5 mEq/L occurs.3,8 This is because of are more indicative of the presence of a mixed acid‐base
most of the AG being based on the sum of anionic disorder. Mixed processes are when two or more primary
changes on circulating protein, of which serum albumin acid‐base disorders occur simultaneously.3
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NUTRITION IN CLINICAL PRACTICE | 983

TABLE 3 Equations to determine appropriate compensation2,3

Acidosis Compensation
Metabolic PaCO2 (in mm Hg) should decrease by 1.25 times the fall in plasma HCO3– (in mEq/L or mmol/L)
Decrease in PaCO2 = 1.25 × (normal HCO3− – measured HCO3−)
Acute respiratory The plasma HCO3− (in mEq/L or mmol/L) should rise by 0.1 times the increase in PaCO2 (in mm Hg)
HCO3− = 0.1 × (measured PaCO2 – normal PaCO2)
Chronic respiratory The plasma HCO3− (in mEq/L or mmol/L) should rise by 0.4 times the increase in PaCO2 (in mm Hg)
HCO3− = 0.4 × (measured PaCO2 – normal PaCO2)
Alkalosis Compensation
Metabolic PaCO2 (in mm Hg) should increase by 0.6 times the rise in plasma HCO3− (in mEq/L or mmol/L)
PaCO2 = 0.6 × (measured HCO3− – normal HCO3−)
Acute respiratory The plasma HCO3− (in mEq/L or mmol/L) should fall by 0.2 times the decrease in PaCO2 (in mm Hg),
but usually not to <18 mEq/L (mmol/L)
HCO3− = 0.2 × (normal PaCO2 – measured PaCO2)
Chronic respiratory The plasma HCO3− (in mEq/L or mmol/L) should fall by 0.4 times the decrease in PaCO2 (in mm Hg),
but usually not to <14 mEq/L (mmol/L)
HCO3− = 0.4 × (normal PaCO2 – measured PaCO2)
Note: Normal HCO3− = 24 mEq/L; normal PaCO2 = 40 mm Hg.
Abbreviation: HCO3−, bicarbonate.

Step 8. Make a conclusion a loss of bicarbonate‐rich fluids, excessive administration of

non–alkali‐based fluids, or the consumption or accumulation
Assessing the results of steps 1–7 is the last step to final of acids. Causes of metabolic acidosis are further classified as
diagnosis. Determine the primary disturbance, appropriate having an elevated or normal AG. Respiratory compensation
compensation, and if a mixed disorder is present. See in metabolic acidosis is through increased respiratory rate to
Figure 2 for a helpful algorithm. In elevated AG metabolic decrease PCO2. See Table 4 for the specific causes of
acidosis, the delta ratio may also help determine if another metabolic acidosis.2–4,7 Mnemonics can help clinicians
acid‐base disorder exists. The delta ratio provides the ratio remember major causes of metabolic acidosis. The com-
of the change in AG to the change in HCO3−. Delta ratio = monly used mnemonic for elevated AG metabolic acidosis
(Measured AG – 12)/(24 – measured HCO3−), using 12 as is GOLD MARK, in which G = glycols (ethylene and
the normal AG value and 24 as the normal HCO3− value.10 propylene), O = oxoproline, L = lactate, D = D‐lactate, M =
See Figure 2 for guidance on delta ratio interpretation. The methanol, A = aspirin (salicylates), R = renal failure, and
delta ratio should not be the only analysis used to detect K = ketoacidosis.12 The mnemonic used for normal AG
mixed acid‐base disorders, but it can point the clinician in metabolic acidosis is ACCRUED, in which A = ammonium
the right direction for accurate diagnosis.10 chloride, C = chronic renal failure, C = carbonic anhydrase
inhibitors, R = renal tubular acidosis, U = ureteroenterost-
omy (eg, ileal conduit), E = extra‐alimentation (eg, excessive
METABOLIC DISORDERS chloride ion [Cl−] supplementation in parenteral nutrition
formulation) or endocrine disorders (eg, aldosterone defi-
Metabolic acid‐base disorders result from an excess or ciency), and D = diarrhea/gastrointestinal (GI) losses due to
deficit of HCO3− in the blood. Compensation occurs high output ostomies or GI fistula.
by the lungs through altering the depth and rate of Clinical presentation may include hyperventilation (a
respirations leading to an increase or decrease in PCO2. compensatory response), headache, anxiety, lethargy,
Respiratory compensation occurs rapidly. If there is altered mental status, nausea, vomiting, sweating, hypo-
concomitant pulmonary disease, full compensation may tension, electrocardiographic (ECG) changes, arrhyth-
not allow for restoration of serum pH to a normal value.5 mias, and cyanosis.2,3 Symptoms are largely based on
the onset and degree of abnormality, underlying status of
the patient, and presence of comorbid conditions. A
Metabolic acidosis thorough history and physical including medication
review should be undertaken to guide empiric therapy.
Metabolic acidosis is defined as a pH < 7.4 primarily due to a Serum and urine chemistries, toxicology panel (for
decrease in HCO3− below 24 mEq/L.3 This can be because of elevated AG with suspected toxic alcohol ingestion),
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984 | TUCKER AND JOHNSON

F I G U R E 2 Algorithm for determining acid‐base disorders.2,3,7 Cl−, chloride; HCO3−, bicarbonate; Na+, sodium; K+, potassium.
Adapted with permission from Reference 9

serum lactate and ketones levels, ECG, microbiological dietary restriction of refined carbohydrate (in patients with
analysis, and radiographic imaging are useful when short‐bowel syndrome and D‐lactic acidosis).2–4 Oral alkali
determining the etiology.3 Management depends on the agents (eg, sodium bicarbonate and sodium citrate) can be
severity of the patient's symptoms and the specific under- used for acute and chronic metabolic acidosis. Sodium
lying cause.2 Cause‐directed and supportive care measures bicarbonate infusion and hemodialysis are reserved for
may include discontinuation of offending medications or profound acidosis (pH < 7.2) refractory to other treatment
toxin removal, fluid replacement (eg, isotonic formulations measures.2
containing bicarbonate or a bicarbonate‐precursor such as
lactate or acetate), use of a higher acetate to chloride salt
ratio for parenteral nutrition formulations, antidiarrheal Metabolic alkalosis
and antisecretory agents, insulin infusion for diabetic
ketoacidosis, antimicrobial therapy (sepsis), thiamin sup- Metabolic alkalosis is defined as a pH >7.4 primarily
plementation (if deficiency or malnutrition is present), and due to an increase in HCO 3 − above 24 mEq/L.3
 TABLE 4 Causes of acid‐base disorders2–4,7,11
Metabolic acidosis:
Respiratory acidosis Elevated AG Normal/non‐AG Respiratory alkalosis Metabolic alkalosis
• Respiratory depression • 5‐Oxoprolinemia • GI loss
HCO3− • CNS/respiratory stimulation • GI H+ loss
∘ Anesthetics ∘ Acetaminophen use ∘ Cholestyramine ∘ Anxiety ∘ Vomiting
∘ Benzodiazepines and sedatives • Lactic acidosis ∘ Diarrhea ∘ Asthma ∘ Nasogastric losses
∘ Neuromuscular blocking agents ∘ Carbon monoxide poisoning ∘ Fistula (biliary, pancreatic, ∘ Brain injury or tumor ∘ Congenital chloride diarrhea
∘ Opioids (overdose) ∘ Isoniazid small bowel) ∘ Caffeine and theophylline • Renal H+ loss
∘ Ventilator underuse ∘ Linezolid ∘ High output ostomy ∘ Catecholamines ∘ Diuretics (loop and thiazides)
NUTRITION IN CLINICAL PRACTICE

• Neuromuscular disorders/ ∘ Liver disease ∘ Laxative overuse ∘ Fever/sepsis ∘ Mineralocorticoid excess (primary:
abnormalities ∘ Metformin (use in renal failure) ∘ Urinary diversion (ileal conduit) ∘ Head trauma Cushing syndrome)
∘ Amyotrophic lateral sclerosis ∘ Nitroprusside • Renal HCO3− loss ∘ Meningitis ∘ 11‐β‐hydroxylase deficiency
∘ Brain injury or tumor ∘ NRTIs ∘ Carbonic anhydrase inhibitors ∘ Nicotine ∘ Licorice intake
∘ Guillain‐Barre ∘ Propofol (high doses) (acetazolamide) ∘ Pain ∘ Liddle syndrome
∘ Multiple sclerosis ∘ Rhabdomyolysis ∘ Renal failure (tubular acidosis) ∘ Pregnancy ∘ Mineralocorticoid therapy (fludro-
∘ Myasthenia gravis ∘ Severe anemia • Hyperkalemia (electrolyte shift) ∘ Salicylate overdose cortisone, hydrocortisone)
∘ Stroke ∘ Seizures ∘ Hypoaldosteronism ∘ Ventilator overuse ∘ Bartter or Gitelman syndrome
• Pulmonary/airway abnormalities ∘ Short‐bowel syndrome (D‐lactic ∘ K+ sparing diuretics ∘ Rapid correction of chronic hypo-
∘ Airway obstruction acidosis) ∘ Trimethoprim • Hypoxia capnia
∘ Asthma (includes exacerbation) ∘ Thiamin deficiency ∘ (Bactrim) ∘ Anemia • HCO3− addition
∘ ARDS ∘ Tissue hypoxia (shock, sepsis) ∘ ACE‐I and ARBs ∘ High altitude ∘ Antacids
∘ COPD/emphysema • Ketoacidosis ∘ NSAIDs ∘ Hyperventilation ∘ Citrate (blood products)
(includes exacerbation) ∘ Diabetic ketoacidosis ∘ Heparin ∘ Hypoxemia ∘ Excessive acetate salt use
∘ Hemothorax ∘ Starvation ketosis ∘ Cyclosporine ∘ Interstitial fibrosis ∘ Sodium bicarbonate
∘ Pulmonary embolism ∘ Alcohol ketoacidosis • H+ or Cl− addition ∘ Pneumonia • Others causes
∘ Obesity • Renal failure ∘ Pulmonary edema ∘ Contraction alkalosis (loop diuretic)
∘ Ammonium chloride
hyperventilation syndrome • Toxins/overdoses ∘ Pulmonary embolism ∘ Profound hypokalemia
∘ Calcium chloride
∘ Pulmonary edema ∘ Ethylene glycol ∘ Excessive Cl− salt use • Other causes ∘ Cystic fibrosis (Cl− loss from the
∘ Thyrotoxicosis
∘ Pulmonary fibrosis ∘ Methanol ∘ Rapid saline administration skin)
∘ Pneumonia ∘ Propyl alcohol ∘ Cirrhosis
∘ Pneumothorax ∘ Propylene glycol
∘ Smoke inhalation ∘ Salicylates
∘ Sleep apnea
• Metabolic
∘ Overfeeding

Abbreviations: ACE‐I, angiotensin converting enzyme inhibitor; AG, anion gap; ARB, angiotensin receptor blocker; ARDS, adult respiratory distress syndrome; Cl−, chloride; CNS, central nervous system; COPD,
chronic obstructive pulmonary disorder; GI, gastrointestinal; H+, hydrogen ion; HCO3−, bicarbonate; K+, potassium; Na+, sodium; NRTI, nucleoside‐analog reverse transcriptase inhibitor; NSAID, nonsteroidal
anti‐inflammatory drug.
[Correction added on 12 July 2022, after first publication: The heading of Table 4 was corrected and in column “Metabolic alkalosis” in the section “Others Causes” the second point was revised to “Profound
hypokalemia”.]
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986 | TUCKER AND JOHNSON

This can be due to loss of chloride‐rich or acidic R E S P I R A T O R Y DI S O R D E R S

fluids, volume depletion leading to contraction
alkalosis, excessive administration of alkali‐based Respiratory acid‐base disorders occur owing to an
fluids in patients with reduced renal function, or alteration or abnormality in respiratory rate or
severe hypokalemia leading to both an intracellular pulmonary gas exchange leading to either an excess
H+ shift and renal H + excretion. Causes of metabolic or deficit of PCO 2 in the blood. They are classified as
alkalosis are further classified as saline‐responsive either acute or chronic disorders. For both, the
(urine chloride < 10 mEq/L) or saline‐resistant (urine kidneys will attempt to compensate through altera-
chloride > 10 mEq/L). Respiratory compensation in tions in the HCO 3− concentration. Full compensation
metabolic alkalosis is through decreased respiratory does not occur rapidly, and typically requires days.
rate to increase PCO2 . See Table 4 for the specific Concomitant renal dysfunction may not allow for full
causes of metabolic alkalosis. 2–4,7 Like metabolic compensation and restoration of serum pH to a
acidosis, mnemonics can help clinicians remember normal value. 2
major causes of metabolic alkalosis. The commonly
used mnemonic for saline‐responsive metabolic alka-
losis is DAMPEN, in which D = diuretics, A = ade- Respiratory acidosis
noma of the colon, M = miscellaneous (eg, bulimia),
P = posthypercapnia, E = emesis, and N = nasogastric Respiratory acidosis is defined as a pH < 7.4 primarily
tube output. The mnemonic used for saline‐resistant due to an increase in PCO2 above 40 mm Hg.3 This
metabolic alkalosis is A BELCH, in which A = alkali occurs when a disease, condition, or situation leads to
ingestion with reduced glomerular filtration rate, respiratory depression or weakness, inadequate exhala-
B = 11‐β‐hydroxylase deficiency, E = exogenous ste- tion of CO2, or an increased production of CO2 as seen
roids, L = licorice ingestion, C = Cushing syndrome, in chronic overfeeding. Excess carbohydrate and total
and H = hyperaldosteronism. calories lead to increased CO2 production and may
Clinical presentation may include signs and symp- decrease the ability to wean patients off oxygen support
toms associated with volume depletion, muscle weak- and mechanical ventilation. See Table 4 for the specific
ness, ECG changes, altered mental status, neuro- causes of respiratory acidosis.2–4,7 Clinical presentation
muscular excitement, and vasoconstriction.2,3 may include confusion, fatigue, altered mentation,
Symptoms are largely based on the degree of abnor- decreased respiratory rate, tachycardia, diaphoresis,
mality, subtype, underlying status of the patient, and and cyanosis.2,3 Management of respiratory acidosis
presence of comorbid conditions. A thorough history should focus on identifying and treating the underlying
and physical including medication review should be cause to restore acid‐base homeostasis. Assessment
undertaken to guide empiric therapy. Other helpful should begin with a thorough history and physical
assessments include serum chemistries, urine chloride, including medication review. Other useful assessments
ECG, plasma renin and aldosterone to identify hyper- include a toxicology screen (if suspected drug use or
aldosteronism, and cortisol level if Cushing syndrome overdose), serum chemistry panel, pulmonary assess-
is suspected.3 Cause‐directed therapies for saline‐ ment, microbiological analysis, and radiographic imag-
responsive metabolic alkalosis include discontinuation ing.3 If the patient is in acute respiratory distress,
of offending medications, isotonic fluid replacement supportive care, including oxygen therapy, broncho-
(eg, 0.9% sodium chloride), use of a higher chloride to dilators, and invasive ventilation, may be required.11
acetate salt ratio in parenteral nutrition formulations, Cause‐directed therapy may include antimicrobial
potassium supplements, antiemetic medications, acid therapy, discontinuation of offending medications, use
suppressant agents, and carbonic anhydrase inhibitors of overdose medications (eg, naloxone or flumazenil),
to increase renal HCO3− excretion.2–4 For saline‐ corticosteroids, or centrally acting stimulants.2–4 In
resistant metabolic alkalosis, potassium‐sparing diure- cases of overfeeding, a reduction in caloric provision is
tics (eg, spironolactone), potassium supplements, corti- indicated.3,7 Sodium bicarbonate infusion is reserved
costeroids, and antihypertensive agents are indi- for profound acidosis (pH < 7.2) refractory to other
cated.2–4 Hemodialysis with a low HCO3− bath may treatment measures; however, its use in respiratory
be required in cases of severe metabolic alkalemia acidosis remains controversial because of the possibility
(pH > 7.55).2 of inducing acute respiratory failure.2,11
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NUTRITION IN CLINICAL PRACTICE | 987

Respiratory alkalosis ABG values were as follows: pH, 7.50 (7.35–7.45);

PaCO2, 45 mm Hg (35–45 mm Hg); PaO2, 100 mm Hg
Respiratory alkalosis is defined as a pH > 7.4 primarily (80–100 mm Hg); HCO3−, 35 mEq/L (22–26 mEq/L).
due to a decrease in PCO2 below 40 mm Hg.3 This occurs What is the acid‐base disorder?
when a disease, condition, or situation is present leading
to increased respiratory drive, hyperventilation, or • Step 1. Obtain an ABG and evaluate the pH
hypoxia. See Table 4 for the specific causes of respiratory ∘ pH is >7.4—alkalosis.
alkalosis.2–4,7 Clinical presentation may include nausea, • Step 2. Evaluate the PCO2
vomiting, dizziness, paresthesia, tachypnea, tachycardia, ∘ PaCO2 is >40 mm Hg.
chest pain, palpitations, and tetany.2,3 Respiratory alkalo- • Step 3. Evaluate the HCO3−
sis is not generally life‐threatening but may occur prior to ∘ HCO3− is >24 mEq/L; ABG HCO3− is within
respiratory or cardiac decompensation. Like the other 1 mEq/L of the serum HCO3− (resulted as serum
acid‐base disorders, identification of the underlying cause CO2), so ABG sample appears valid.
is key to management. A thorough history and physical, • Step 4. Calculate the AG
medication review, toxicology screen (if suspected salicy- ∘ AG = 137 – (97 + 34) = 6, normal (nonelevated) AG.
late overdose), laboratory analysis (eg, serum chemistries, • Step 5. Determine if the acid‐base disorder is acute vs
complete blood count, hepatic panel, and thyroid studies), chronic
microbiological analysis, and radiographic imaging can be ∘ Chronic disorder as the symptoms have been going
helpful for determining etiology.3 Treatment should on for 3 days.
be directed at the underlying cause with appropriate • Step 6. Determine the primary acid‐base disorder
supportive care measures to restore acid‐base homeostasis. ∘ Using steps 1–5 and Table 2, the primary acid‐base
This may include supportive counseling during an anxiety disorder is saline‐responsive metabolic alkalosis.
or panic attack, anxiolytics, pain management strategies, It is saline‐responsive because urine chloride is
discontinuation of offending medications, and the use of <10 mEq/L.
respiratory depressants. Antimicrobial therapy is indicated • Step 7. Determine if appropriate compensation or if a
in cases of sepsis or suspected infection.2–4 mixed disorder exists
∘ For metabolic alkalosis, the PCO2 should increase
by 0.6 times the rise in plasma HCO3.
CASE SCENARIOS • Calculation is as follows:
∘ Expected increase in PaCO2 = 0.6 × (measured
Application of knowledge to case scenarios can help HCO3− – normal HCO3−) = 0.6 × (34 – 24) = 6 mm Hg.
strengthen clinical practice skills. Three cases will be ∘ Add 6 mm Hg to the normal PaCO2 of 40 mm Hg to
presented below. Using the stepwise analysis of get the expected PaCO2 on the ABG of 46 mm Hg.
blood gas analyses presented in this primer, diagnosis This is within 10% of the actual PaCO2 on the ABG of
will be determined with cause‐directed therapy 45, so there is low suspicion of a concomitant or
recommendations. mixed acid‐base disorder present. No need to calculate
a delta ratio.
• Step 8. Make a conclusion
Case 1 ∘ Primary metabolic alkalosis and appropriate respi-
ratory compensation.
A female aged 68 years presents to the emergency ∘ Etiology is refractory vomiting, so treatment should
department because of fatigue, weakness, and refractory include supportive care measures of antiemetics, fluid
vomiting for 3 days. Abdominal x‐ray suggests small‐ resuscitation, nasogastric suctioning, and further work-
bowel obstruction. up/treatment of bowel obstruction.
Past medical history is as follows: colon cancer status
postsurgical resection 2 years ago, hypertension, and
hypothyroidism. Case 2
Laboratory values were as follows: sodium, 137 mEq/L
(135–145 mEq/L); potassium, 3.4 mEq/L (3.5–5 mEq/L); A patient aged 60 years is brought to the emergency
chloride, 97 mEq/L (98–107 mEq/L); CO2, 34 mEq/L department by a family member after he was found
(22–28 mEq/L); blood urea nitrogen, 32 mg/dl (7–20 drowsy, breathing slow, and moaning. He is arousable
mg/dl); creatinine, 1.5 mg/dl (0.7–1.5 mg/dl); and urinary but unable to follow all commands. The family member
chloride, <10 mEq/L. states he has recently had his pain medications adjusted
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988 | TUCKER AND JOHNSON

and was acting normal about 30 min before bringing him Case 3
in for evaluation.
Past medical history: anxiety, chronic back pain after A male aged 52 years is brought to the emergency
motor vehicle accident 6 weeks ago (treated with opioids department with fever, hypotension, altered mental status,
and acetaminophen), and seasonal allergies. and difficulty breathing. Symptoms started ~2 h ago. Septic
Laboratory values were as follows: sodium, 139 mEq/L shock with impending respiratory failure is suspected.
(135–145 mEq/L); potassium, 3.9 mEq/L (3.5–5 mEq/L); Past medical history includes: hypertension.
chloride, 101 mEq/L (98–107 mEq/L); CO2, 27 mEq/L Laboratory values were as follows: sodium, 144 mEq/L
(22–28 mEq/L); blood urea nitrogen, 9 mg/dl (7–20 mg/ (135–145 mEq/L); potassium, 4.2 mEq/L (3.5–5 mEq/L);
dl); creatinine, 0.5 mg/dl (0.7–1.5 mg/dl). chloride, 108 mEq/L (98–107 mEq/L); CO2, 15 mEq/L
ABG values were as follows: pH, 7.28 (7.35–7.45); (22–28 mEq/L); blood urea nitrogen, 30 mg/dl (7–20 mg/
PaCO2, 60 mm, Hg (35–45 mm Hg); PaO2, 86 mm Hg dl); creatinine, 1.3 mg/dl (0.7–1.5 mg/dl).
(80–100 mm Hg); HCO3−, 27 mEq/L (22–26 mEq/L). ABG values were as follows: pH, 7.26 (7.35–7.45);
What is the acid‐base disorder? PaCO2, 34 mm Hg (35–45 mm Hg); PaO2, 88 mm Hg
(80–100 mm Hg); HCO3−, 15 mm Hg (22–26 mEq/L).
• Step 1. Obtain an ABG and evaluate the pH What is the acid‐base disorder?
∘ pH is <7.4—acidosis.
• Step 2. Evaluate the PCO2 • Step 1. Obtain an ABG and evaluate the pH
∘ PaCO2 is >40 mm Hg. ∘ pH is <7.4—acidosis
• Step 3. Evaluate the HCO3− • Step 2. Evaluate the PCO2
∘ HCO3− is >24 mEq/L; ABG HCO3− is within ∘ PaCO2 is <40 mm Hg
1 mEq/L of the serum HCO3− (resulted as serum • Step 3. Evaluate the HCO3−
CO2), so ABG sample appears valid. ∘ HCO3− is <24; ABG HCO3− is the same as the
• Step 4. Calculate the AG serum HCO3− (resulted as serum CO2), so ABG
∘ AG = 139 – (101 + 29) = 9, normal (nonelevated) AG. sample appears valid.
• Step 5. Determine if the acid‐base disorder is acute vs • Step 4. Calculate the AG
chronic ∘ AG = 144 – (108 + 15) = 21, elevated AG.
∘ Acute disorder as the symptoms are recent • Step 5. Determine if the acid‐base disorder is acute vs
onset. chronic
• Step 6. Determine the primary acid‐base disorder ∘ Acute disorder as the symptoms started ~2 h ago.
∘ Using steps 1–5 and Table 2, primary acid‐base • Step 6. Determine the primary acid‐base disorder
disorder is acute respiratory acidosis. ∘ Using steps 1–5, Table 2 and AG calculation, primary
• Step 7. Determine if appropriate compensation or if a disorder is elevated AG metabolic acidosis. Decreased
mixed disorder exists PaCO2 suggests respiratory compensation.
∘ For acute respiratory acidosis, the plasma HCO3− • Step 7. Determine if appropriate compensation or if a
should rise by 0.1 times the increase in PaCO2. mixed disorder exists
• Calculation is as follows: ∘ For metabolic acidosis, the PaCO2 should decrease
∘ Expected increase in HCO3− = 0.1 × (measured by 1.25 times the fall in plasma HCO3−.
PaCO2 – normal PaCO2) = 0.1 × (60 – 40) = 2 mEq/L. • Calculation is as follows:
∘ Add 2 mEq/L to the normal HCO3 − of 24 mEq/L ∘ Expected decrease in PaCO2 = 1.25 × (normal HCO3− –
to get the expected measured HCO 3− of 26 mEq/ measured HCO3−) = 1.25 × (24 – 15) = 11.25 mm Hg.
L. This is within 10% of the actual HCO 3 − on the ∘ Subtract 11.25 mm Hg from the normal PaCO2 of
ABG and serum of 27, so there is low suspicion of 40 mm Hg to get the expected PaCO2 on the ABG,
a concomitant or mixed acid‐base disorder which is 28.75 mm Hg.
present. ∘ His actual PaCO2 on the ABG is 34, which is greater
• Step 8. Make a conclusion than a 10% difference from the expected PaCO2
∘ Primary acute respiratory acidosis with appropriate calculation. This is indicative of a mixed acid‐base
renal compensation. disorder. Because of altered mental status and
∘ Etiology is opioid overdose likely due to recent difficulty breathing, he is not able to blow off enough
dose titration or overdose. Treatment may PaCO2 to adequately compensate; thus, his actual
include use of naloxone and supportive care PaCO2 is higher than expected. This suggests a
measures. concomitant acute respiratory acidosis.
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NUTRITION IN CLINICAL PRACTICE | 989

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AUTHOR CONTRIBUTIONS 9. Bruno J, Canada N, Canada T, Tucker AM, Ybarra JV, eds.
Anne M. Tucker and Tami N. Johnson equally con- Acid‐base homeostasis and disorders. ASPEN fluids, electro-
tributed to the design of the work; Anne M. Tucker and lytes, and acid‐base disorders handbook, 2nd ed. Silver Spring,
Tami N. Johnson contributed to the drafting of the work. MD: American Society for Parenteral and Enteral Nutri-
Both authors critically revised the manuscript, read and tion; 2020.
gave final approval of the version to be published, and 10. Seifter JL. Anion‐gap metabolic acidemia: case‐based analyses.
agree to be accountable for all aspects of the work Eur J Clin Nutr. 2020;74(suppl 1):83‐86.
11. Al‐Jaghbeer M, Kellum JA. Acid‐base disturbances in
ensuring integrity and accuracy.
intensive care patients: etiology, pathophysiology and
treatment. Nephrol Dial Transplant. 2015;30(7):1104‐1111.
CONFLI CT OF I NTER EST
12. Mehta AN, Emmett JB, Emmett M. GOLD MARK: an
The authors declare no conflict of interest. anion gap mnemonic for the 21st century. Lancet.
2008;372(9642):892.
ORCID
Anne M. Tucker [Link]
Tami N. Johnson [Link]
1773-1315 How to cite this article: Tucker AM, Johnson
TN. Acid‐base disorders: A primer for clinicians.
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