Lesson 3

Acid-Base Disorders
(metabolic acidosis)
• Understanding the aetiology of a clinically important acid–base
disturbance is important because therapy generally should be
directed at the underlying cause of the disturbance rather than
merely the change in pH.
• Severe acid–base disorders can affect multiple organ systems,
• Cardiovascular (impaired contractility, arrhythmias)
• Pulmonary (impaired O2 delivery, respiratory muscle fatigue,
dyspnoea)
• Renal (hypokalaemia, nephrolithiasis)
• Neurologic (decreased cerebral blood flow, seizures, coma)
 Definitions
• Acid-base imbalance -abnormality of the human body's
normal balance of acid & bases that may result when renal or
respiratory function is abnormal or when an acid or base load
overwhelms excretory capacity
• Hence a deviation out of the normal pH range (7.35 - 7.45)
✓ Acidemia- an arterial blood pH < 7.35
✓ Alkalemia - an arterial blood pH > 7.45
✓ Acidosis refers to physiologic processes that cause acid accumulation
or alkali loss.
✓ Alkalosis refers to physiologic processes that cause alkali
accumulation or acid loss.
5
 pH control
• Great need to regulate acid-base balance for normal body
functions.

• Therefore pH is controlled by the following mechanisms:

• Respiratory mechanisms- control CO2
• Renal mechanisms (metabolic system) - control serum HCO3-
• Buffering systems within ECF & ICF, e.g. carbonic acid-
bicarbonate system

6
 pH control
• Respiratory centre & lungs-rate of CO2 elimination controlled by
chemo receptors in the respiratory centre.
• Kidneys – HCO3- reclamation & generation.
• Buffer systems include:–
• Bicarbonate
• Haemoglobin
• Phosphate
• Proteins

7
Buffer System

8
 Buffer System
• Bicarbonate is produced through the carbonate dehydratase system
H2O + CO2 ↔ H2CO3 ↔ HCO3- + H+
• The reaction is catalysed by the enzyme carbonate dehydratase
(carbonic anhydrase) found in erythrocytes & in renal tubular cells
• Other buffers in both the ECF & ICF
• Phosphate buffer pair
• Proteins (ammonia)
• They are urinary buffers & allow excess H+ to be eliminated
from the body.
• This makes the renal route very important in compensation of
chronic acidosis. 9
 Buffer System
• To maintain acid–base balance, the kidney must reclaim &
regenerate all the filtered HCO3−
• Daily reabsorbed 180 L/day GFR × 24 mEq/L HCO3− = 4,320
mEq/day)
• Proximal tubule reabsorbs about 85% of the filtered HCO3−
• Loop of Henle & the distal tubule reabsorb about 10%.
• NB
1. Acid salts, e.g. HPO4− (pKa of 6.8), that have a pKa > the pH of
the urine (titratable acids) can accept a proton & be excreted as
the acid, thus regenerating an HCO3− anion.
HCO3− Regeneration
 Not titratable acids
• Sulphuric acid + other acids with a pKa < 4.5 are not titratable
• Protons from these acids must be combined with another buffer to
be secreted
• Glutamine deamination in proximal tubular cells forms NH3,
which accepts these protons
• In the collecting tubule, the NH4+ produced is lipid insoluble,
trapping it in the lumen & causing its excretion, eliminating the
proton, & allowing for regeneration of HCO3−
Acid-Base Physiology
 Acid-Base Physiology
• Daily metabolism of carbohydrates & fats generates about 15,000
mmol of CO2

• Although CO2 not an acid, it combines reversibly with H2O to

form carbonic acid (i.e., H2CO3).

• Respiration prevents the accumulation of volatile acid thro’ the

exhalation of CO2

• Metabolism of proteins & fats results in several fixed acids & bases

• Lysine & arginine have a net positive charge (serve as acids)

• Glutamate, aspartate & citrate have a negative charge (bases)

 Acid-Base Physiology
• In general, animal proteins contain more sulphur & phosphates,
producing an acidic diet

• Vegetarian diets consist of more organic anions, resulting in a more

alkaline diet

• Normally, fatty acids are metabolized to HCO3−

• However, during starvation or diabetic ketoacidosis, they may be

incompletely oxidized to acetoacetate & β- hydroxybutyric acid.
 Acid-Base Physiology
• Typical diet generates a net nonvolatile acid load of about 70 to 100
mEq of H+ (1.0–1.5 mEq/kg)/day

• Renal excretion of 70 mEq in 2 L of urine each day would require a

pH of 1.5

• Because the kidney cannot produce a pH less than 4.5, most of this
fixed acid load must be buffered

• Primary buffers for renal net acid excretion are NH3−/NH4 + and
titratable buffers, e.g. HPO4−/H 2PO42−
 Arterial Blood Gases
Parameter Arterial blood Mixed venous blood

pH 7.4 (7.35 - 7.45) 7.38 (7.33 - 7.43)

PaO2 80 - 100 mm Hg 35 - 40 mm Hg

PaCO2 35 - 45 mm Hg 45 - 51 mm Hg

HCO3− 22 - 26 mmol/L 24 - 28 mmol/L

17
 Classification
• Process that causes the imbalance is classified based on:-
A. Aetiology of the disturbance (respiratory or metabolic)
B. Direction of change in pH (acidosis or alkalosis)
• This yields the following four basic processes:
1. Metabolic acidosis
2. Respiratory acidosis
3. Metabolic alkalosis
4. Respiratory alkalosis

18
 Classification
• The four basic processes can be broadly classified as:
1. Simple acid-base disorders;
✓ One basic acid-base disorder occurring at a time
2. Mixed acid-base disorders;
✓ where two basic acid-base disorders occur at the same time.

19
 Classification
• Since PaCO2 is regulated by respiration, abnormalities that
primarily alter the PaCO2 are referred to as:-
• Respiratory acidosis (high PaCO2 )
• Respiratory alkalosis (low PaCO2 )
• In contrast, [HCO3−] is regulated primarily by renal processes.
Abnormalities that primarily alter the [HCO3−] are referred to as:-
• Metabolic acidosis (low [HCO3−])
• Metabolic alkalosis (high [HCO3−]).

20
 Laboratory Assessment
The correct assessment of acid–base disorders begins with an
evaluation of appropriate laboratory data & an
understanding of the physiologic mechanisms responsible for
maintaining a normal pH
 Arterial blood gas (ABG) determination
• Abnormalities occur when the concentration of PaCO2(an acid) or
HCO3−(a base) is altered.

• Parameters obtained are

1. Arterial pH

2. Arterial carbon dioxide tension (PaCO2)

3. Serum bicarbonate (HCO3−)

4. Arterial oxygen tension (PaO2) (does not directly influence

decisions regarding acid–base abnormalities)
 Arterial Blood Gas (ABG) Determination
• Arterial pH < 7.35; patient is considered acidemic & causative
process acidosis

• Arterial pH > 7.35; patient is considered alkalemic & causative

process alkalosis
• Process is further defined as respiratory in cases of an
inappropriate elevation or depression of PaCO2 or metabolic with
an inappropriate rise or fall in serum HCO3−
• Acid–base balance is normally maintained by the primary
extracellular buffer system of HCO3−/CO2
Arterial Blood Gas (ABG) Determination
• Other extracellular buffers (e.g., serum proteins, inorganic
phosphates) & intracellular buffers (e.g., hemoglobin, proteins,
phosphates), however, also contribute significant buffering activity
• Serum electrolytes are obtained to calculate the anion gap, an
estimate of the unmeasured cations & anions in serum
• The anion gap helps determine the probable cause of a metabolic
acidosis
• Urine pH, electrolytes, & osmolality help to further differentiate
among the possible causes of metabolic acidosis.
 Acid–Base Balance, CO2 Tension, &
Respiratory Regulation
• NB
• Virtually, all the H2CO3 in body fluids is in the form of CO2
• PaCO2, a measure of CO2 gas, is therefore directly proportional to
the amount of carbonic acid in the HCO3− / H2CO3 buffer

• Lungs can rapidly exhale large quantities of CO2 & thereby contribute
significantly to the maintenance of a normal pH
 Acid–Base Balance, CO2 Tension, &
Respiratory Regulation
• In clinical practice, the serum [HCO3−] usually is
1. estimated from the total CO2 content when the serum concentration of
electrolytes are ordered on an electrolyte panel
2. calculated from the pH & PaCO2 on an ABG determination

• Estimations of the serum [HCO3−] are more convenient than directly

measuring serum bicarbonate, that is;

✓Total CO2 content that is reported on serum electrolyte panels is

determined by acidifying serum to convert all the HCO3− to CO2 &
measuring the PaCO2
Acid–Base Balance, Carbon Dioxide Tension, &
Respiratory Regulation
 Stepwise approach in Evaluation of Acid-
Base disorder
1. Obtain a detailed patient history & clinical assessment

2. Check the arterial blood gas, sodium, chloride, & HCO3−

3. Identify all abnormalities in pH, PaCO2 , & HCO3−

4. Determine which abnormalities are primary & which are

compensatory based on pH
 Stepwise approach in Evaluation of Acid-
Base disorder

• If the pH < 7.40, then a respiratory or metabolic acidosis is

primary
• If the pH > 7.40, then a respiratory or metabolic alkalosis is
primary
Stepwise approach in Evaluation of
Acid-Base disorder
 Stepwise approach in Evaluation of Acid-
Base disorder
• Consider other laboratory tests to further differentiate the cause of
the disorder

• If the anion gap is normal, consider calculating the urine anion gap.
If the anion gap is high and a toxic ingestion is expected, calculate
an osmolal gap.
If the anion gap is high, measure serum ketones & lactate

• Compare the identified disorders to the patient history and begin

patient-specific therapy
 Metabolic Acidosis
• Characterized by loss of HCO3− from the body, decreased
acid excretion by the kidney, or increased endogenous acid production

• 2 categories; normal & elevated AP

 Metabolic Acidosis
• Anion gap (AG) represents the concentration of unmeasured
negatively charged substances (anions) in excess of the
concentration of unmeasured positively charged substances
(cations) in the ECF

• The concentrations of total anions & cations in the body are equal
because the body must remain electrically neutral
• Most clinical laboratories, however, measure only a portion of
these ions (i.e., Na+, Cl−, & HCO3− )
 Metabolic Acidosis
• The concentrations of other negatively & positively charged
substances, e.g. K+, Mg+, Ca2+, 2PO42−, & albumin, are measured less
often

• The [unmeasured anions] normally exceeds the [unmeasured cations]

by 6 to 12 mEq/L, & the anion gap can be calculated as follows;

• Of the unmeasured anions, albumin is perhaps the most important

 Increased AG in hypoalbuminemia
• In critically ill patients with hypoalbuminemia, the calculated AG
should be adjusted using the following formula:

Adjusted AG = AG + 2.5 × (normal albumin − measured albumin

in g/dL),

• where a normal albumin concentration is assumed to be 4.4

g/dL
 Metabolic Acidosis (with normal AG)
• Metabolic acidosis with a normal AG (e.g., hyperchloremic
metabolic acidosis) usually is caused by loss of bicarbonate & can
be further characterized as hypokalemic or hyperkalemic
✓Increased production of organic acids (e.g., formic, lactic acids)
is buffered by extracellular bicarbonate with resultant
consumption of bicarbonate & appearance of an unmeasured
anion (e.g., formate, lactate).
 Metabolic Acidosis (with Increased AG
• Decrease in serum HCO3− approximates the increment in the AG, the
latter being a good estimate of the circulating anion level
i. Prolonged hypoxia results in lactic acidosis
ii. Uncontrolled diabetes mellitus or excessive alcohol intake with
starvation can cause ketoacidosis
iii. In the case of renal failure, the capacity for H+ secretion
diminishes, resulting in metabolic acidosis

• The accompanying increased AG results from decreased excretion of

unmeasured anions, e.g. sulphate & phosphate
 Case 1
• J.D., a 21-year-old, 75-kg woman, is hospitalized for evaluation of weakness. She has
a history of bipolar affective disorder and reports recent ingestion of paint from the
walls of her house. J.D.’s only current medication is lithium carbonate 300 mg 3
times a day (TID). On admission, she appears weak and apathetic and complains of
anorexia. Laboratory tests reveal the following:

• Serum Na, 143 mEq/L

• K, 3.0 mEq/L

• Cl, 121 mEq/L

• Albumin, 4.4 g/dL

• pH, 7.28

• Paco2, 26 mm Hg

• HCO3−, 12 mEq/L
 Case 1
• J.D.’s urine pH after an ammonium chloride (NH4Cl) 0.1 g/kg IV load is
less than 5.1. A bicarbonate load of 1 mEq/kg infused intravenously (IV)
for 1 hour induces bicarbonaturia (urinary pH, 7.0) and lowers the serum
potassium to 2.0 mEq/L. Her blood pH only increased to 7.31. What type
of acid–base disorder is present?
 What type of acid-Base disorder?
• Using a stepwise approach, we see that J.D.’s history gives a clue to the cause for

her acidosis

• The low pH is consistent with a metabolic acidosis because her CO2 & HCO3− are

both reduced.

• Alterations in pH resulting from a primary change in serum bicarbonate are

metabolic acid–base disorders.

• Specifically, metabolic acidosis is associated with a decrease in serum HCO3− and decreased

pH, whereas metabolic alkalosis is associated with an increase in serum HCO3− & increased

pH. In respiratory disorders, the primary change occurs in the PaCO2

• If J.D. had a decrease in pH and increase in Paco2, a respiratory acidosis

would be present.
 What type of acid-Base disorder?
• Because J.D. has a low PaCO2 & decreased serum HCO3−, she has a metabolic acidosis

• In most cases of metabolic acidosis or alkalosis, the lungs compensate for the primary change in serum

[HCO3− ] by increasing or decreasing ventilation.

• Most stepwise approaches would next suggest the evaluation of whether the decrease in PaCO2 of 14

mm Hg for J.D. is consistent with respiratory compensation

A primary decrease in the

serum bicarbonate to a level

of 12 mEq/L should result

in a compensatory decrease

in the PaCO2 concentration

by 12 to 14 mm Hg
 What type of acid-Base disorder?
• . J.D.’s PaCO2 has fallen by 14 mm Hg (normal, 40 mm Hg; current, 26 mm Hg),

confirming that normal respiratory compensation has occurred.

• When values for PaCO2 or serum HCO3− fall outside of normal compensatory ranges,

either a mixed acid–base disorder, inadequate extent of compensation, or inadequate

time for compensation should be suspected.

• Nomograms, especially ones that are different for acute & chronic disorders, are

inherently difficult to memorize, however, and are often not available to the clinician at

the point of care.

• Following the stepwise approach advocated herein will enable clinicians to identify

most clinically important disorders without needing to depend on tables or formulas

 Potential Causes of J.D. Metabolic acidosis?
• Steps 4 to 7 of the stepwise approach in the evaluation of acid–base disorders

are used to further determine the cause of the disorder

• In patients with metabolic acidosis, calculation of the AG serves as a 1st step in

classifying the metabolic acidosis & provides additional information about

conditions that might be responsible

• J.D.’s calculated AG is 10 mEq/L

• Thus, J.D. has hyperchloremic metabolic acidosis with a normal AG.

• Normal AG metabolic acidosis usually is caused by gastrointestinal loss of bicarbonate (diarrhea, fistulous

disease, ureteral diversions); exogenous sources of chloride (normal saline infusions); or altered excretion of

hydrogen ions (renal tubular acidosis). J.D. reports a history of both, pica resulting in paint ingestion

(perhaps lead-based paint) and chronic use of lithium. Both lead and lithium have been associated with the

development of renal tubular acidosis.

 Renal tubular necrosis
• How do the results of NH4Cl and sodium bicarbonate (NaHCO3) loading help

identify the type of renal tubular acidosis in J.D.?

• Master level????
 Metabolic Acidosis with Elevated Anion Gap
EVALUATION AND OSMOLAL GAP
• A 64-year-old, 60-kg man, is brought to the emergency department
(ED) by his family in a semi-comatose state. He was found lying on
the floor of his garage near a partially empty bottle of windshield
wiper fluid 30 minutes ago. He has a long history of alcohol abuse
and recently diagnosed dementia. In the ED, supine blood pressure
(BP) is 120/60 mm Hg, pulse is 100 beats/minute, and respiratory
rate is 40 breaths/minute. His pupils are reactive, and mild
papilledema is noted.

• Laboratory tests reveal the following:

 Metabolic Acidosis with Elevated Anion Gap
EVALUATION AND OSMOLAL GAP
• Serum Na, 139 mEq/L, K, 5.8 mEq/L, Cl, 103 mEq/L, Blood urea
nitrogen (BUN), 25 mg/dL, Creatinine, 1.4 mg/dL, Fasting glucose,
150 mg/dL

• ABG include pH, 7.16; Paco2, 23 mm Hg; and HCO3−, 8 mEq/L. His
toxicology screen is negative for alcohol, and his serum osmolality is
332 mOsm/kg.

• What acid–base disturbance is present in this patient?

• What are possible causes of the disorder?

 What acid–base disturbance is present in
this patient?
• Acidosis (pH, 7.16; HCO3−, 8 mEq/L) with a large AG (28 mEq/L).

• Subtracting 10 from the anion gap of 28 and adding this value to his
serum [HCO3−] (see Step 5 in the section Evaluation of Acid–Base
Disorders) yields a value of 26, suggesting no other metabolic
abnormality is present.

• An elevated AG metabolic acidosis often indicates lactic acidosis

resulting from intoxications (e.g., salicylates, acetaminophen,
methanol, ethylene glycol, paraldehyde, metformin) or ketoacidosis
induced by diabetes mellitus, starvation, or alcohol
 What acid–base disturbance is present in
this patient?
• Step 6 in the stepwise approach leads to the consideration of
additional laboratory tests that may be helpful in the differential
diagnosis of an elevated AG.
• Include :serum ketones, glucose, lactate, BUN, creatinine, &
plasma osmolal gap

• Osmolal gap is defined as the difference between measured serum

osmolality (SO) & calculated SO
 What acid–base disturbance is present in
this patient?
• When the difference between measured & calculated SO is greater
than 10 mOsm/kg, the presence of an unmeasured osmotically active
substance, such as ethanol, methanol, or ethylene glycol, should be
considered
• The calculated SO is 295 mOsm/kg, compared with the measured
value of 332; therefore, his osmolal gap is 37 mOsm/kg
• An increase in the anion gap & osmolal gap, without diabetic
ketoacidosis or chronic renal failure, suggests the possibility of
metabolic acidosis resulting from a toxic ingestion
 What acid–base disturbance is present in
this patient?
• Based on his presentation (papilledema, history of alcohol abuse, increased
osmolal gap, increased AG metabolic acidosis), history of dementia, &
partially empty bottle of windshield wiper fluid found at the scene, methanol
intoxication should be considered

• Methanol intoxication results in the formation of two organic acids, formic &
lactic acids, which consume HCO3− with production of an AG metabolic
acidosis

• Alcohol dehydrogenase in the liver metabolizes methanol to formaldehyde

& then to formic acid
• Formic acid contributes to the metabolic acidosis & also is responsible for the retinal
oedema & blindness associated with methanol intoxication
 What acid–base disturbance is present in
this patient?
• Serum lactic acid concentrations also are increased in patients with
methanol intoxication

• Lactic acidosis classically has been divided into 2 types

• A, which is associated with inadequate delivery of oxygen to the
tissue
• B, which is associated with defective O2 utilization at the
mitochondrial level ( lactic acidosis caused by methanol
intoxication is most consistent with the type B variety)
 Treatment: antidote
• Mental status is impaired and his respiratory rate is 40 breaths/minute, his airway
was secured via endotracheal intubation and he was placed on mechanical
ventilatory support

• Antidotes: Ethanol & fomepizole compete with methanol for alcohol

dehydrogenase binding sites (educe the conversion of methanol to its toxic
metabolite)

• Fomepizole is easier to dose & does not need serum-level monitoring to ensure
efficacy like ethanol
• Dose: IV, 15 mg/kg loading dose for 30 minutes, followed by bolus doses
of 10 mg/kg every 12 hours

• Folinic acid or folic acid at a dosage of 50 mg IV every 6 hours should be given

to enhance the elimination of formate.

• + IV thiamine
 Treatment : Antidote
• Fomepizole is costly & thus infrequently used

• Ethanol Dose:
• IV-loading dose of 0.6 g/kg ethanol solution over the course of
30 minutes, followed by a continuous infusion of about 150
mg/kg/hour if the patient has been drinking,
• 70 mg/kg/hour for non-drinkers if the patient was not drinking.
 Treatment :Bicarbonate
• Severe acidosis causes reduced myocardial contractility, impaired
response to catecholamines, & impaired oxygen delivery to tissues (2,3-
diphosphoglycerate depletion )

• Amount administered to raise the arterial pH using is calculated following

equation (distributes to ≈ 50% of total body weight (thus, the factor
of 0.5 L/kg

• To prevent overtreating, bicarbonate doses should only attempt to increase

the bicarbonate concentration by 4 to 8 mEq/L
 Treatment :Bicarbonate
• For this patient;
• the dose required to raise serum bicarbonate from 8 to 12 mEq/L amounts to 120
mEq of bicarbonate (0.5 L/kg × 60 kg × 4 mEq/L
 Metabolic alkalosis

• Metabolic alkalosis is associated with an increase in serum [HCO3−]

& a compensatory increase in PaCO2 (caused by hypoventilation).

• 2 general classifications of metabolic alkalosis, saline-responsive &

saline-resistant (Table next page), are usually distinguishable based
on an assessment of the patient’s volume status, BP, & urinary
chloride concentration
 Saline-responsive metabolic alkalosis
• Associated with disorders that result in the loss of chloride-rich,
bicarbonate-poor fluid from the body (e.g., vomiting, nasogastric
suction, diuretic therapy, cystic fibrosis)

• Physical examination may reveal

• Volume depletion (e.g., orthostatic hypotension, tachycardia, poor
skin turgor),
• Urinary [Cl-] often will be less than 10 to 20 mEq/L (although
urine chloride levels may be >20 mEq/L in patients with recent
diuretic use)
 Saline-resistant metabolic alkalosis
• Result from severe hypokalaemia or excessive mineralocorticoid
activity

• Rare in comparison with saline responsive metabolic alkalosis

• Should be suspected in alkalemic patients with evidence of increased

ECF volume, hypertension, or high urinary chloride values (>20
mEq/L) without recent diuretic use
 Case
• A 75-year-old, 60-kg woman, was admitted to the hospital 4 days ago with
peripheral oedema & pulmonary congestion consistent with a congestive
heart failure exacerbation. Since admission, she has been treated
aggressively with furosemide 80 to 120 mg IV daily, which has generated
approximately 3 L
of urine output each day. Today her lung sounds are clear and peripheral
oedema shows considerable improvement with diuresis; however, she now
complains of dizziness when she gets out of bed to go to the
bathroom. Physical examination reveals a tachycardic (heart rate [HR], 100
beats/minute), thin elderly woman with poor skin turgor and slight muscle
weakness. S.J.’s electrocardiogram shows flattened T waves and U
waves.
 Case
• Laboratory tests reveal the following:

• Serum Na, 138 mEq/L, K, 2.5 mEq/L, Cl, 92 mEq/L, Creatinine,

0.9 mg/dL, BUN, 28 mg/dL, pH, 7.49, PaCO2, 46 mm Hg, HCO3−,
34 mEq/L, Urine Cl concentration is 60 mEq/L.

• What acid–base disorder is present?

 Mechanisms
of Drug induced metabolic alkalosis (contraction
alkalosis”)
• Enhances Na+, Cl- & H2O, resulting in EC volume contraction
• Volume contraction alone will cause only a modest increase in plasma
bicarbonate

• However, volume contraction also stimulates aldosterone release → increases

distal tubular Na+ reabsorption & induces H+ ion and K+ secretion → in
alkalosis & hypokalemia

• Additionally, hypokalemia induced by diuretics will stimulate IC movement of H+

to replace cellular K → extracellular alkalosis

• Hypochloremia also is important in sustaining metabolic alkalosis

• In a hypochloremic state, sodium will be reabsorbed, accompanied by bicarbonate

generated by secreted H+
 Rx
• Removal of the cause

• Volume status and electrolytes can be restored (replace Cl- & K by infusing
NaCl & KCl)

• As long as hypochloremia exists, renal bicarbonate excretion will not occur

and the alkalosis will not be corrected

• Severity of alkalosis dictates how rapidly fluid and electrolytes

should be administered

• Amount of potassium required to replace total body stores is difficult to

determine accurately because 98% of the potassium in the body is
intracellular
 Rx
• Unresponsive to NaCl & KCl therapy or those at risk for
complications with these agents can be treated with acetazolamide,
hydrochloric acid, or a hydrochloric acid precursor

• acetazolamide is the most commonly used

• A solution of 0.1 N HCl may be administered to patients who require rapid

correction of alkalemia
• Dose of HCl is based on the bicarbonate excess using below, where the factor
0.5 × body weight (kg) represents the estimated bicarbonate space