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Acid-Base Disorders
PCCSU Article | 10.01.11
By Deepa Bangalore, MD; and Janice L. Zimmerman, MD, FCCP
Dr. Bangalore is Intensivist and Dr. Zimmerman is Professor of Clinical Medicine and Head, Critical Care Division,
Department of Medicine, The Methodist Hospital, Weill Cornell Medical College, Houston, Texas.
Dr. Bangalore and Dr. Zimmerman have disclosed no significant relationships with the companies/organizations whose
products or services may be discussed within this chapter.
Objectives

1. Describe different approaches to acid-base analysis and their limitations.

2. Review the diagnosis, manifestations, and management of metabolic acidosis.
3. Discuss less common causes of metabolic acidosis and their management.
4. Review the diagnosis, manifestations and management of metabolic alkalosis and respiratory acid-base disorders.
Key words: anion gap; base deficit; lactic acidosis; metabolic acidosis; metabolic alkalosis; respiratory acidosis;
respiratory alkalosis; strong ion difference; strong ion gap
Abbreviations: AG = anion gap; Atot = Total weak acid concentration; BE = base excess; SBE = standard base
excess; SID = strong ion difference; SIDapp = apparent strong ion difference; SIDeff = effective strong ion
difference; SIG = strong ion gap
Acid-base disturbances are common in critically ill and chronically ill patients and result from a variety of underlying
clinical disorders. Although the contribution of acid-base disturbances to morbidity and mortality is not always clear,
the appropriate analysis of the abnormalities can offer insight into underlying etiologies and potentially influence
therapeutic interventions.

Acid-Base Analysis
Three methods of analysis have been used to describe the acid-base status of patients: the traditional approach, base
excess (BE) approach, and the physicochemical approach. All of these methods describe the respiratory component of
acid-base changes based on change in PCO2 but differ in how the metabolic component of acid-base disorders is
analyzed (Table 1).
Table 1Comparison of Components of Acid-Base Analysis Methods

Acid-Base Disorder

Traditional

Base Excess

Physicochemical

Respiratory acidosis

PCO2

PCO2

PCO2

Respiratory alkalosis

PCO2

PCO2

PCO2

Metabolic acidosis

HCO3-, anion gap

Base excess

SID, Atot

Base excess

SID

Metabolic alkalosis

HCO3

The traditional method relies on analysis of changes in bicarbonate concentration and the anion gap to assess the
metabolic component. In general, an increased bicarbonate concentration indicates a metabolic alkalosis and a
decreased bicarbonate concentration indicates a metabolic acidosis. The relation of pH and bicarbonate concentration
is described by the Henderson-Hasselbalch equation: pH = pK + log HCO3-/H2CO3 = 6.1 + log HCO3-/0.03 PCO2.
The Henderson equation shows the interrelation between pH, HCO3- and pCO2: H+ = 24 PCO2/HCO3-. The anion gap
(AG) is used to classify metabolic acidoses into high AG or normal AG type.
Siggaard and Anderson developed nomograms and algorithms that form the methodology for analyzing acid-base
status based on BE. Base excess quantifies the degree of metabolic acidosis or alkalosis as the amount of acid or base
that must be added to a sample of whole blood in vitro to restore the pH of the sample to 7.40 while the PCO2 is held
constant at 40 mm Hg. To correct for inaccuracies when applied in vivo, BE has been modified to standardize the
effect of hemoglobin and PCO2.The standard base excess (SBE) formula is written as follows:
SBE = 0.9287 (HCO3- 24.4 + 14.83 [pH 7.4]),
where SBE is given in mEq/L.
The SBE changes with any change in weak acid concentrations. A change in base excess describes a change in the
metabolic component of acid-base status, with positive BE indicating metabolic alkalosis and negative BE indicating
metabolic acidosis.
The physicochemical approach, sometimes referred to as Stewarts approach, identifies three independent variables
that determine acid-base status: PCO2, strong ion difference (SID), and total nonvolatile weak acids (Atot).1,2 These
variables also determine changes in dependent variables, such as pH, HCO3-, CO32-, OH- and H+. The SID is the

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difference between the sum of all strong cation concentrations and the sum of all strong anion concentrations. All
concentrations must be expressed in mEq/L. The formula for calculating SID (in mEq/L) is as follows:
SID = [Na+ + K+ + Ca2 + Mg2+] [Cl- + Lactate].
This calculation is also referred to as the apparent SID (SIDapp), taking into account that there are other unmeasured
ions in the plasma. Under normal circumstances, the cationic concentration exceeds the anionic concentration so that
plasma SIDapp is approximately +40 to 42 mEq/L. In pathologic conditions, strong anions, such as lactate, formate,
sulfates, ketoacids, and fatty acids, may be present in higher concentrations. Plasma proteins, such as albumin (which
carries a negative charge at physiologic pH), and inorganic phosphates are the main components of Atot, but also
contribute to SID. According to the physicochemical approach, metabolic acid-base changes result only from changes
in SID and/or Atot. SID changes with deficits or excess of water in plasma (associated with changes in Na+
concentrations) and changes in the concentrations of strong anions (such as Cl-). Changes in Atot are primarily
attributable to changes in the concentration of phosphates and albumin.
Effective SID (SIDeff) is an estimate of the anions that balance the excess cations in order to maintain
electroneutrality. SIDeff is derived from PCO2 (from which HCO3- and CO32- can be estimated) and the concentration
of weak acids (albumin and phosphate), with the following formula, in which albumin is measured in g/L and PO4 in
mmol/L:
SIDeff = (12.2 PCO2/10-pH) + 10 [Albumin (0.123 pH 0.631)] + [PO4 (0.309 pH 0.469)].
A simplified formula for bedside use has been suggested to approximate SIDeff,1 again with albumin in g/L and PO4 in
mmol/L:
SIDeff = HCO3- + 0.28 Albumin + 1.8 PO4.
Strong ion gap (SIG) is the difference between the apparent and effective SID (SIG = SIDapp SIDeff).3 It is a
measure of the balance of anions and cations, similar to the AG. SIG is positive in situations where unmeasured
anions are in excess (acidosis) and negative when unmeasured cations are in excess (alkalosis). Strong ion gap is a
misnomer as both strong and weak ions may produce a gap. In healthy people, the SIG has a mean value of
approximately 0 mEq/L.
Attempts to identify which method of acid-base analysis is most correct or most clinically useful have resulted in
numerous debates and studies.4-6 Support for each of these methods can be found in the literature. Studies have also
found that the traditional approach using the AG corrected for albumin concentration was equivalent to the
physicochemical approach for diagnosis of acid-base disorders in ICU patients. In a retrospective study, the SIG was
found to correlate with the anion gap corrected for all known anions, such as albumin and phosphates.3 Several
studies have also found high correlations between the SID, BE, and AG. Although the physicochemical approach is
comprehensive in identifying acid-base imbalances, it is cumbersome to use at the bedside. It does allow identification
of the components contributing to metabolic disorders (strong ions, weak acids, or changes in albumin). However, it is
not clear whether identification of subtle acid-base abnormalities by the physiochemical method is of clinical
significance. The traditional approach, in which AG corrected for albumin concentration is used, is easy to apply at the
bedside but fails to account for the influence of other nonbicarbonate buffers and electrolytes on acid-base status. The
traditional approach allows diagnosis of the acid-base disorder but does not always identify the mechanism. The BE
approach has the advantage of readily available results from arterial blood gas analysis. However, it cannot be used to
identify coexisting metabolic acidoses and alkaloses, nor does it aid in identifying the etiology of an acid-base
abnormality.
The clinician must be aware of the limitations and advantages of each acid-base approach. The clinician should
integrate the analysis of the acid-base status with the patients clinical history and additional testing results when
determining the most appropriate interventions. Analysis of acid-base status in a critically ill patient at a single point
in time provides only a snapshot of a complex and rapidly changing environment.

Metabolic Acidosis
Metabolic acidosis is a common acid-base disorder in critically ill patients that may contribute to acute ventilatory and
circulatory deterioration. Comorbid conditions and therapeutic interventions (eg, fluid resuscitation, diuretics,
mechanical ventilation) may both lead to mixed acid-base disorders in these patients. Although metabolic acidosis is
suggested by a low bicarbonate level, diagnosis requires a careful analysis of additional factors, such as albumin
concentration, unmeasured anions, and coexisting acid-base disorders.
The traditional method of analysis focuses on the AG to suggest etiologies of metabolic acidoses (see Tables 2 and 3).
The AG is usually calculated as [Na+ (Cl- + HCO3-)], although calculation including potassium[(Na+ + K+) (Cl- +
HCO3-)]is also used. The normal AG is usually 8 to 12 4 to 6 mEq/L, but the normal range varies with the
laboratory and whether potassium is included in the calculation. The majority of unmeasured anions contributing to
the AG in normal individuals are albumin and phosphate. Decreases in either of these components will decrease the
AG and could mask an increase in organic acids, such as lactate. Correcting the AG for changes in albumin
concentration increases the utility of the traditional method in detecting metabolic acidoses.7,8 For every decrease of 1
g/dL in albumin, a decrease of 2.5 to 3 mEq in AG occurs. The corrected AG can be calculated as follows, with albumin
given in g/dL:
Corrected AG = Observed AG + 2.5 (Normal Albumin Measured Albumin).
Table 2Causes of Normal Anion Gap (Hyperchloremic) Metabolic Acidosis

GI Loss of HCO3Diarrhea
Ileostomy
Ureterosigmoidostomy
Renal Loss of HCO3Proximal renal tubular acidosis
Isolated

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Fanconi syndrome
Familial
Cystinosis
Tyrosinemia
Multiple myeloma
Wilson disease
Ifosfamide
Osteopetrosis
Carbonic anhydrase inhibitors
Ileal bladder
Reduced Renal H+ Secretion
Distal renal tubular acidosis (classic type I)
Familial
Hypercalcemic/hypercalciuric states
Sjgren syndrome
Autoimmune disease
Amphotericin
Renal transplant
Type 4 renal tubular acidosis
Hyporeninemic hypoaldosteronism
Tubulointerstitial disease
Nonsteroidal antiinflammatory drugs
Defective mineralocorticoid synthesis/secretion
Addison disease
Acquired adrenal enzymatic defects (chronic heparin therapy)
Congenital adrenal enzymatic defects
Inadequate renal response to mineralocorticoid
Sickle cell disease
Systemic lupus
Potassium-sparing diuretic
Pseudohypoaldosteronism (type 1 and 2)
Early uremia
HCl/HCl Precursor Ingestion/Infusion
HCl
NH4Cl
Arginine Cl
Other
Recovery from sustained hypocapnia
Treatment of diabetic ketoacidosis
Toluene inhalation with good renal function

Table 3Causes of an Increased Anion Gap and Strong Ion Gap

Renal failure
Ketoacidoses
Diabetic ketoacidosis
Alcoholic ketoacidosis
Starvation
Metabolic errors
Lactic acidoses
L-lactic

acidosis

D-lactic

acidosis

Toxins
Acetaminophen
Cyanide
Ethylene glycol

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Iron
Isoniazid
Metformin
Methanol
Paraldehyde
Propofol
Propylene glycol
Salicylates
Toluene
Valproic acid
Dehydration
Sodium salts
Sodium lactate*
Sodium citrate
Sodium acetate
Sodium penicillin ( >50 mU/d)
Decreased unmeasured cations
Hypomagnesemia*
Hypocalcemia*
Alkalemia
*Already

accounted for in SIG.

Corrections for changes in phosphate concentration have less impact on the AG. Every decrease of 1 mg/dL in
phosphate leads to a decrease of 0.5 mEq in AG. Pathologic paraproteinemias also decrease the AG because
immunoglobulins (IgG) are largely cationic. Conversely, an elevated AG does not always reflect an underlying
acidosis. In patients with significant alkalemia (usually pH >7.5), albumin is more negatively charged, which increases
unmeasured anions in the absence of an acidosis. The respiratory compensation for metabolic acidosis (an increase in
minute ventilation) can be estimated by either of the following formulas, both with PCO2 expressed in mm Hg: PCO2 =
1.5 HCO3- + 8 2 or PCO2 = 1.2 HCO3-.
The delta gap (gap) is a concept used to identify additional acid-base disorders when a metabolic acidosis is present.
It is based on the assumption that every increase of 1 mEq/L in the AG will result in a similar decrease in the HCO3concentration. The calculation is expressed as follows: gap = (deviation of the AG from normal) (deviation of
HCO3- concentration from normal). Although the expected normal value is zero, small deviations may not be
significant and must always be interpreted along with clinical information. A positive gap suggests the concomitant
presence of a metabolic alkalosis and a negative value suggests the presence of a hyperchloremic normal AG acidosis.
The physicochemical approach suggests a different approach to classifying metabolic acidoses (Table 4): free water
excess, increase in strong anions (hyperchloremia), and increase in weak acids. When a change in extracellular fluid
volume is accompanied by an alteration in the proportional water content of the plasma, there is a reduction in SID
that leads to acidosis. Hyperchloremia leads to a reduction in the SID and a consequent decrease in pH. The
physicochemical approach to acid-base analysis suggests that the acidosis seen in fluid-resuscitated patients is a
result of the chloride concentration changes rather than dilution of the bicarbonate concentration. Following normal
saline infusion, the plasma Cl- concentration increases to a greater extent than Na+ concentration. Aggressive fluid
infusion can also result in dilution of total weak acids (Atot), and this could give rise to a concomitant metabolic
alkalosis.
Table 4Primary Metabolic Acid-Base Disturbances Described by the Physicochemical Approach

Acidosis

Alkalosis

Water deficit/excess

Na+,SID (dilution acidosis)

Na+, SID (concentration alkalosis)

Change in strong anions

Cl-, SID

Cl-, SID

Unmeasured acid, SID

Albumin, phosphate, Atot, SID

Albumin, phosphate, Atot, SID

Change in weak acids

Crystalloids with a SID of zero, such as saline solution, cause an acidosis by lowering extracellular SID enough to
overwhelm the metabolic alkalosis of Atot dilution.
When infusions containing organic anions such as L-lactate are administered, L-lactate can be regarded as a weak ion
that does not contribute to fluid SID, provided it is readily metabolized. The presence of weak acids contributing to
Atot must be considered with administration of colloids. Albumin and gelatin preparations contain weak acids, whereas
starch preparations do not. The SID and presence of weak acids in fluid options may affect the choice of fluid
replacement therapy for specific acid-base effects.
Specific Acidoses
Lactic Acidosis: Two types of lactic acidosis exist: type A and type B. Type A lactic acidosis is usually present in
critically ill patients and results from overproduction of L-lactate through anaerobic glucose metabolism as a result of
inadequate tissue oxygen delivery.9 L-lactate often accounts for the unmeasured anion detected by an increased anion
gap. Type B lactic acidosis is associated with adequate oxygen delivery and is being recognized more frequently. Type

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B lactic acidosis results from altered cell metabolism (usually mitochondrial function), increased aerobic metabolism or
glucose production with enhanced pyruvate production, or inhibition of cytochrome oxidase. -Agonists, including
epinephrine and dobutamine, stimulate glycolysis with production of excess pyruvic acid that may not be cleared
owing to inhibition of pyruvate dehydrogenase. Excess pyruvic acid is converted to lactate. Several drugs can also
result in elevated lactate levels without evidence of hypoperfusion (Table 5). In addition, type B lactic acidosis can be
associated with certain malignancies, such as lymphomas and leukemias. It is important to recognize the presence
and etiology of type B lactic acidoses in order to distinguish them from the more clinically ominous type A lactic
acidosis. In some cases, specific medications may need to be discontinued because the lactate level suggests toxicity.
Table 5Drugs and Conditions Associated With Type B Lactic Acidosis

Dobutamine
Epinephrine
Etomidate
Linezolid
Lorazepam
Metformin
Nucleoside reverse transcriptase inhibitors
Pentobarbital
Propofol
Tetracyclines
Thiamine deficiency
Valproic acid

D-lactic

Acidosis: D-lactic acidosis can result from overgrowth of D-lactate-producing bacteria, such as Lactobacillus
species, Streptococcus bovis, Bifidobacterium species, and Eubacterium species in patients with anatomic
(ileojejunal bypass) or functional short bowel syndrome (malabsorption).10 D-lactate is not measured by laboratory
assays but does contribute to the AG as an unmeasured anion. Symptoms can be precipitated after ingestion of
carbohydrates with absorption of D-lactate from the affected intestinal segment, but can also occur after consumption
of dairy products or lactobacillus tablets. Symptoms of D-lactic acidosis include transient neurologic findings, such as
headache, weakness, delirium, visual disturbances, dysarthria, ataxia, cranial nerve palsies, and changes in affect.
Pyroglutamic Acidosis: Pyroglutamic acid is recognized as another etiology of anion gap metabolic acidosis, especially
in association with acetaminophen use.11,12 Pyroglutamic acid (5-oxoproline) can be overproduced when glutathione
is depleted (associated with acetaminophen use, sepsis, liver dysfunction, and malnutrition) through effects on the glutamyl cycle, resulting in increased production of -glutamylcysteine, which is converted to pyroglutamic acid.
Additionally, inhibition of 5-oxoprolinase (associated with penicillins and vigabatrin) can lead to pyroglutamic acidosis.
The dose of acetaminophen associated with pyroglutamic acidosis has been variable but acidosis resolves with
discontinuation of acetaminophen. Repletion of glutathione stores with N -acetylcysteine has been suggested despite
the lack of evidence.
Hospital-Acquired Acidoses: Some drugs used in critically ill patients can lead to anion gap metabolic acidoses that
are important to recognize. Propylene glycol is a solvent found in IV formulations of lorazepam, diazepam, etomidate,
phenytoin, nitroglycerin, esmolol, phenobarbital, pentobarbital, and other drugs. The greatest risk for causing acidosis
occurs with the use of high-dose lorazepam for more than 3 days.13 However, toxicity has also been reported with
short-term high-dose use. Lorazepam contains 830 mg/mL of propylene glycol and accumulation occurs with doses
>0.1 mg/kg/h or in the presence of hepatic or renal dysfunction. Signs and symptoms correlate with an increased
osmolar gap. The clinical manifestations of propylene glycol toxicity can mimic sepsis and other inflammatory
disorders. These manifestations include CNS depression or agitation, renal dysfunction, seizures, arrhythmias, and
hemolysis. Management includes discontinuation of lorazepam and substitution of another sedating drug.
Propofol infusion syndrome is typically seen in pediatric patients but is being reported more frequently in the adult
population.14 Acidosis results from lactate production. The exact etiology is unknown but may be related to
mitochondrial utilization of free fatty acids or a genetic predisposition. Reported risk factors include dose, duration of
use, age, sepsis, head injury, steroid use and catecholamine infusion. Experience is variable but the syndrome is
usually associated with doses >4 g/kg/h and durations longer than 48 h. Manifestations can include arrhythmias,
heart failure, rhabdomyolysis, hyperkalemia, acute renal failure, bradycardia, and hyperlipemia. An increased need for
inotropic support in a patient receiving propofol with no other clear etiology can be a clue to propofol infusion
syndrome.
Clinical Manifestations and Management of Metabolic Acidosis
The predominant clinical manifestations of metabolic acidosis may be difficult to distinguish from manifestations of the
underlying disorder. Metabolic acidosis results in increased cerebral blood flow but mental status is often decreased.
Pulmonary effects include an increase in minute ventilation, respiratory failure, pulmonary edema, and increased
pulmonary vascular resistance. Cardiovascular effects may include arrhythmias and a decrease in myocardial function
or response to catecholamines. Acute acidemia enhances oxygen unloading from hemoglobin by shifting the
oxyhemoglobin dissociation curve to the right. However, if acidosis persists, it causes the red blood cell concentration
of 2,3-diphosphoglycerate to fall and restores the oxyhemoglobin dissociation curve to baseline. Other metabolic
effects of metabolic acidosis include hyperkalemia, hypercalcemia, insulin resistance, and increased protein
catabolism. Chronic metabolic acidosis can lead to development of osteoporosis, osteomalacia, renal osteodystrophy,
renal hypertrophy, nephrocalcinosis, and nephrolithiasis.
Treatment of metabolic acidosis requires identification of the underlying etiology. Treatment of normal AG metabolic
acidoses (hyperchloremic) involves replacing volume with a low-chloride, bicarbonate-containing fluid. Other
interventions may include insulin for diabetic ketoacidosis, antidote for poisonings, renal replacement therapy for
acute kidney injury, and restoration of oxygen delivery in hypoperfusion states. Administration of bicarbonate does
not improve outcome in metabolic acidosis. Some studies suggest that bicarbonate may improve myocardial
responsiveness when the pH is <7.1 and the patient has severe hemodynamic instability. However, myocardial
performance is often normal in metabolic acidosis.

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Metabolic Alkalosis
Metabolic alkalosis is diagnosed by findings of increased pH with an increased bicarbonate concentration using the
traditional method. In the physicochemical approach, the bicarbonate change is seen as the effect rather than the
cause. An increase in the SID resulting from a decrease in Cl- or water deficit with increase in Na+ can result in a
metabolic alkalosis (Table 4). Hypoalbuminemia is another cause of metabolic alkalosis detected by physicochemical
analysis that may be missed by other approaches. Hypophosphatemia alone does not cause enough change in Atot to
result in metabolic alkalosis because the normal value of phosphate is only about 1 mmol/L.
Etiologies of metabolic alkalosis can be characterized as chloride depleted (hypovolemic) or chloride expanded
(hypervolemic; Table 6). Urine chloride <20 mEq/L can be used to distinguish chloride-depleted causes of metabolic
alkalosis. Hypokalemia is common to all causes of metabolic alkalosis.
Table 6Etiologies of Metabolic Alkalosis

Hypovolemic, chloride depleted

GI loss of H+
Vomiting
Gastric suction
Cl rich diarrhea
Villous adenoma
Renal loss of H+
Diuretics
Posthypercapnia
Hypervolemic, chloride expanded
Renal loss of H+
Primary hyperaldosteronism
Primary hypercortisolism
Adrenocorticotropic hormone excess
Pharmacologic hydrocortisone/mineralocorticoid excess
Renal artery stenosis with right ventricular hypertension
Renin-secreting tumor
Hypokalemia
Bicarbonate overdose
Pharmacologic overdose of NaHCO3
Milk-alkali syndrome
Massive blood transfusion
Reprinted with permission from Zimmerman.15
Clinical Manifestations and Management of Metabolic Alkalosis
Clinical manifestations of metabolic alkalosis include tachycardia, arteriolar constriction including the coronary
arteries, supraventricular and ventricular arrhythmias, hypoventilation, decreased cerebral blood flow, altered mental
status, and seizures. Metabolic effects include stimulation of anaerobic glycolysis, hypokalemia, hypomagnesemia,
hypophosphatemia, and decreased ionized calcium concentrations. Oxygen release at the tissue level may be impaired
in metabolic alkalosis because a leftward shift in the oxyhemoglobin dissociation curve decreases hemoglobins oxygen
affinity.
Treatment involves identifying the cause and correcting it, if possible. Volume replacement with chloride-containing
fluid is indicated for etiologies associated with chloride depletion. It is important to correct metabolic alkalosis before
ventilator weaning in an intubated patient as this acid-base disorder causes compensatory hypoventilation. Potassium
deficiencies should be corrected. It is rarely necessary to administer hydrochloric acid to correct severe metabolic
alkalosis. Deliberate hypoventilation with sedation in intubated patients may be an option for severe conditions.
Although acetazolamide will increase excretion of bicarbonate, efficacy is limited and administration can result in
metabolic acidosis and exacerbate potassium losses.

Respiratory Disorders
Increases and decreases of PaCO2 indicate respiratory acidosis and respiratory alkalosis, respectively. The clinical
manifestations of respiratory disorders depend on the absolute change and the rate of change in PaCO2, the underlying
etiology (Tables 7 and 8), and the presence of hypoxemia. Evaluation of the respiratory component of acid-base
abnormalities is the same for all three methods of acid-base analysis. Formulas for changes in PaCO2 arising from
acute and chronic respiratory disorders allow prediction of pH and bicarbonate concentration. These formulas are less
helpful when chronic and acute respiratory conditions are present simultaneously.
Table 7Etiologies of Respiratory Acidosis

Airway obstruction
Foreign body
Tongue displacement
Laryngospasm
Obstructed endotracheal tube

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Severe bronchospasm
Obstructive sleep apnea
Respiratory center depression
General anesthesia
Sedative or narcotic drugs
Cerebral injury, ischemia
Increased CO2 production
Malignant hyperthermia
Shivering
Hypermetabolism
High-carbohydrate diet
Neuromuscular disorders
Drugs or toxins
Electrolyte disorders
Spinal cord injury
Guillain-Barr syndrome
Myasthenia gravis
Polymyositis
Lung conditions
Restrictive disease
Obstructive disease
Hemothorax or pneumothorax
Flail chest
Acute lung injury
Obesity-hypoventilation syndrome
Inappropriate ventilator settings
Reprinted with permission from Zimmerman.15

Table 8Etiologies of Respiratory Alkalosis

Hypoxemic drive
Pulmonary disease with arterial-alveolar gradient
Cardiac disease with right-to-left shunt
Cardiac disease with pulmonary edema
High altitude
Acute and chronic pulmonary disease
Emphysema
Pulmonary embolism
Pulmonary edema
Mechanical overventilation
Stimulation of respiratory center
Neurologic disorders
Pain
Psychogenic
Liver failure with encephalopathy
Sepsis/infection
Salicylates
Progesterone
Pregnancy
Fever
Reprinted with permission from Zimmerman.15
In acute respiratory acidosis, the following formulas apply:
Decrease in pH = 0.08 (PaCO2 40)/10, and
Increase in [HCO3-] = PaCO2/10 3.

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The formulas for chronic respiratory acidosis are as follows:

Decrease in pH = 0.03 (PaCO2 40)/10, and
Increase in [HCO3-] = 3.5 PaCO2/10.
For acute respiratory alkalosis, use the following formulas:
Increase in pH = 0.08 (40 PaCO2)/10, and
Decrease in [HCO3-] = 2 PaCO2/10.
For chronic respiratory alkalosis, these are the formulas:
Increase in pH = 0.03 (40 PaCO2)/10, and
Decrease in [HCO3-] = (5 to 7) PaCO2/10.
Clinical Manifestations and Management of Respiratory Acidosis
Respiratory acidosis can result in somnolence, confusion, combativeness, delusions, stupor, and coma. Cerebral
vasodilation can also increase cerebral blood flow and intracranial pressures. Cardiovascular manifestations include
tachycardia, hypertension, depressed myocardial contractility, peripheral vasodilation, and arrhythmias. Severe
hypercapnia causes renovascular constriction and hypoperfusion via the renin-angiotensin axis. Hypercapnia also
stimulates antidiuretic hormone secretion, resulting in increased salt and water retention. There is a complex interplay
of PaCO2 and pH on the oxyhemoglobin dissociation curve as CO2 shifts it to the right (Bohr effect) and acidemia shifts
the curve to the left. This effect is further complicated by increased 2,3-diphosphoglycerate concentrations in chronic
respiratory acidosis.
The treatment of respiratory acidosis is to provide ventilation, which may necessitate intubation and mechanical
ventilation in some patients. Bicarbonate administration offers no benefit and generates additional CO2 for elimination.
Clinical Manifestations and Management of Respiratory Alkalosis
Acute respiratory alkalosis (hyperventilation) can cause circumoral numbness, paresthesias, muscle cramps,
carpopedal spasms, and seizures. Low PaCO2 causes cerebral vasoconstriction with the potential for hypoperfusion, an
increase in plasma catecholamines, tachycardia, and arrhythmias (especially with pH >7.6). Metabolic changes include
hypokalemia, hypophosphatemia, and ionized hypocalcemia.
Management of significant respiratory alkalosis involves treating the underlying condition (ie, supplying oxygen,
analgesic administration, adjusting ventilator settings). In some circumstances, sedation may be needed to control
severe respiratory alkalosis.

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Related Terms: Critical Care Non-pulmonary Critical Care CME PCCSU
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