Review Article

Diagnosing Acid-Base Disorders

AK Ghosh
Abstract
Diagnosis and management of acid-base disorders ranks high among the medical problems that intimidate
many physicians. In practice, acidbase disorders can be approached very systematically as they can be
easily diagnosed when certain rules are applied. Using a four step process including, 1) determination the
serum pH, 2) calculation of the serum anion gap, 3) estimating the degree of compensation, 4) calculation of
the excess anion gap, the reader will be able solve any complex acid-base problem. In this review we describe
a practical stepwise approach to identify and resolve issues involving acidbase disorders.

espite the continuous production of acid in the body,

perfect homeostasis is maintained by the interplay
of various intracellular and extracellular buffers working
continuously in perfect harmony with a normal
functioning renal and respiratory regulatory system. The
normal pH of body is maintained within a narrow range
of 7.40 0.05 and any diversion of this range results in
an array of serious medical symptoms that bring the
patient emergently to the physicians attention.
Approaching a patient presenting with acid-base
disorder might intimidate many physicians.1 In this
review we would describe the practical approach to solve
any acidbase disorder. Physicians should be able to
interpret acid base disorders problems by following a
systematic four step approach. I will describe clues to
identify conditions presenting with primary acid base
disorders and outline strategies to solve complex
disorders by using a systematic approach. In the current
review I will discuss the technique to solve simple and
complex acid-base problems. For advanced perusal of
the topics on the mechanisms of acid base disorders and
details of individual acid-base disorders readers are
recommended to consult the following reviews.2-6
Initial approach to a patient suspected to have an
acid base disorder
Approach to an acid-base disorders starts with a good
history and physical examination of a patient. Very often
the presenting symptoms and signs give us a clue
regarding the underlying acid-base disorder. Later in
the review I will describe the approach to diagnose the
acid-base disorder in a comatose patient. The list of acid
base disorders associated with common medical
conditions is described in Table 1. For example the
primary acid-base disorder in case of vomiting is
Associate Professor, Department of Internal Medicine, Mayo
Clinic Rochester, Minnesota, USA.
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metabolic alkalosis (due to loss of hydrochloric acid in

vomiting), while the primary disorder in a patient with
diarrhoea is metabolic acidosis (due to loss of
bicarbonate in the stool).
Physicians need to recognize that very often it is the
underlying disorders responsible for the acidbase
disorder and not just the pH of the blood that determines
the patients status and prognosis.5,6 For example a pH
of 7.2 measured in a patient immediately after a seizure
could be ignored, however the same pH could suggest a
much more worrisome situation in a patient suspected
to have ingested ethylene glycol. Additionally, the effects
of an acidbase disorder could vary depending on the
underlying medical condition of the patient. Effect of
alkalosis could have an ominous outcome in a patient
with an underlying pulmonary or cardiac disease, as
opposed to a patient with panic attack and
hyperventilation.
The arterial blood gas and common errors in
interpretation of patients laboratory data
Assessment of the patients acidbase status begins
with the measurement of an arterial blood gas (ABG). A
common error performed in clinical practice is to
comment on the patients acid-base state just from
observing the bicarbonate and anion gap in the
electrolyte panel. For example once could err in
diagnosing normal anion gap acidosis in a patient
presenting with low bicarbonate and normal anion gap.
However, the most common situation that causes a low
bicarbonate in clinical practice is respiratory alkalosis
and not normal anion gap metabolic acidosis. Thus one
should always look at the ABG first before commenting
on the acid-base status of the patient. Corollary while
reading ABGs, the reader needs to know that the pH
and the PaCO2, is measured directly by the blood gas
analyzer, while the bicarbonate value is calculated using
the Henderson-Hasselbalch equation. Hence direct

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JAPI VOL. 54 SEPTEMBER 2006

in the review

Table 1 : Acid -base disorders of common medical

conditions
Metabolic Acidosis
High anion gap
Methanol intoxication
MUDPILERS
Uremia
Diabetic ketoacidosis
Paraldehyde
Isoniazide
Lactic acidosis
Ethanol
Rhabdomyolysis
Salicylates
Non anion gap
GI bicarbonate loss
acidosis
Diarrhoea
Ureteral diversion
Renal bicarbonate loss
Renal tubular acidosis
Aldosterone inhibitors
Carbonic anhydrase inhibitors
Posthypocapnia
Early renal failure
Metabolic Alkalosis
Urinary chloride low
Vomiting, nasogastric suction
(chloride sensitive)
Diuretic use
Posthypercapnia
Urinary chloride high
Excess mineralocorticoid activity
or normal
Primary hyperaldosteronism
(chloride resistant)
Licorice exogenous steroids
Cushings disease
Bartters syndrome
Current or recent diuretic use
Excessive alkali administration
Refeeding alkalosis
Respiratory Acidosis
Acute
Central nervous system depressiondrugs, CVA, Neuromuscular disease
Myasthenia gravis
Acute airway obstruction
Severe pneumonia
Lung injury- flail chest
Ventilator malfunction
Chronic
Chronic obstructive lung disease
Chronic respiratory center
depression-Pickwician
Chronic neuromuscular disorders
Respiratory Alkalosis
Acute
Anxiety
Drug use-salicylate, catecholamines,
progesterone
Hypoxia
Pregnancy
Sepsis
Mechanical ventilation
Hepatic encephalopathy
CNS system disease

Serum Anion Gap: clinical uses and reciprocal

relation with change in serum bicarbonate
After confirmation of the presence of metabolic
acidosis, calculation of the serum anion gap is most
useful in differential diagnosis of metabolic acidosis
disorders (Fig. 1) and differentiating mixed acid-base
disorders. The serum anion gap is defined as Na- (Cl- +
HCO3-); a normal value is 12 2 meq/L. It measures the
unmeasured anion in plasma and includes negatively
charged proteins (albumin), phosphates, sulfate and
organic anions (such as citrate). The list of the causes for
abnormal serum anion gap is outlined in Table 4.
Table 2 : Normal range of pH and alterations in primary
acid-base disorders
Disorder

pH

HCO 3 mEq/L

paCO 2
mm Hg

Normal
Metabolic acidosis
Metabolic alkalosis
Respiratory acidosis
Respiratory alkalosis

7.40
decreased
increased
decreased
increased

24
decreased
increased
increased
decreased

40
decreased
increased
increased
decreased

Table 3 : Compensatory responses in simple acid-base

disorders

measurement of the serum bicarbonate level in the

electrolyte panel may be more accurate, though in
practical terms the difference between the two measures
(i.e., bicarbonate measure in ABG and electrolyte panel
respectively) is often minimal. I will also discuss the use
of mixed venous blood gas in few clinical situations later
JAPI VOL. 54 SEPTEMBER 2006

The arterial blood gas (ABG): common trends and

compensation pattern in different acid-base states
The normal range of pH is 7.35- 7.45, the normal pCO2
is 40 mm of mercury and the normal bicarbonate level is
22-26 mmol/L. Table 2 depicts the expected change in
pH, bicarbonate and pCO 2 in primary acid-base
disorders. Notice that the expected change occurs in the same
direction in primary metabolic disorders and in the opposite
direction in primary respiratory disorders. The degree of
compensation for simple acid base disorder is described
on Table 3. It is important to realize that respiratory
compensation for metabolic disorders occur rapidly,
however metabolic compensation for respiratory
disorders take three to five days.1 Please remember that
the primary abnormality lies in the direction of pH
disorder. The body does not fully compensate the primary
acid-base disorder

Disorder

Degree of compensation

Metabolic acidosis
Metabolic alkalosis

PaCO 2= (1.5 X HCO3- ) +8 2

PaCO 2 will increase 6 mm Hg for each
10 mEq /L increase in HCO3-

Respiratory acidosis
A cu t e
HCO3- will increase 1 meq /L
Hg increase in PaCO 2
Chronic
HCO3- will increase 4 meq /L
Hg increase in PaCO 2
Respiratory alkalosis
A cu t e
HCO 3- will decrease 2 meq/L
Hg increase in PaCO2
Chronic
HCO 3- will decrease 4 meq/L
Hg increase in PaCO2

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per 10 mm
per 10 mm

per 10 mm
per 10 mm

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Decrease of serum bicarbonate concentration >

increase in serum anion gap
Hyperchloremic and anion gap acidosis co-exists
Decrease of serum bicarbonate concentration <
increase in serum anion gap
Complex acid-base disorder
An important clinical pearl to differentiate between simple
and mixed acid-base disorder is : in contrast to simple
disorders, an abnormal value of PaCO2 and bicarbonate in the
face of near-normal values of pH should always raise the
suspicion of mixed-acid base disorders.
Fig. 1 : Approach to metabolic acidosis with low serum pH.

Table 4 : Causes of abnormal serum anion gap

Increased Anion Gap
Frequent *

Infrequent
Decreased Anion Gap

Methanol intoxication
Uremia
Diabetic ketoacidosis
Paraldehyde
Isoniazide
Lactic acidosis A and B
Ethanol
Rhabdomyolysis
Salicylates
Hyperalbuminemia
Administered anions
Hypoalbuminemia
Paraproteinemia (multiple myeloma)
Spurious hypercholeremia
(Bromide intoxication)
Spurious hyponatremia
Hypermagnesemia

*remember MUDPILERS

Increase of anion gap may result from other

miscellaneous situations like hyperalbuminemia and
addition of anions (penicillins). Conversely a decreased
anion gap is seen in patients with hypoalbuminemia,
paraproteinemia, hypermagnesemia, spurious
hypercholeremia (in bromide intoxication) and spurious
hyponatremia.
In primary acid-base disorders and in a case of simple
metabolic acidosis the anion gap will increase by one
mEq/L for every 1 mEq/L decrease in serum bicarbonate
level (one for one ratio). However this relationship is
altered in mixed acid-based disorders due to partial
compensatory mechanisms by the kidney and lungs in
their effort to maintain homeostais. A comparison in the
increment change in anion gap relative to the change
in bicarbonate concentration can aid in identifying acidbase disorders. This concept is utilized in the calculation
of excess anion gap and diagnose mixed acid-base
disorders.
Decrease in serum bicarbonate concentration =
increase in serum anion gap
Primary anion gap metabolic acidosis
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Urinary Anion Gap

Urinary anion gap is used to differentiate between
renal and extra-renal cause of normal anion gap (NAG)
metabolic acidosis. The urinary anion gap is defined as
(UNa + UK)-UCl and is an indirect estimation of urinary
ammonium excretion. The normal range is 10 to +10,
and represents the amount of unmeasured anions in the
urine including sulfates, phosphates, bicarbonates and
organic anions like lactate and citrate. These
unmeasured anions are accompanied by acid excreted
as ammonium. In extra-renal causes of NAG acidosis
the kidney produces large amount of ammonium chloride
and the urinary anion gap is largely negative ( > -10), in
renal causes of NAG metabolic acidosis the kidney is
not able to generate ammonium and unable to excrete
acid; therefore the urinary anion gap is largely positive
(> + 10). Urinary anion gap is useful in patient presenting
with normal anion gap acidosis where the patient is not
forthcoming with a history of eating disorder or
ingestion of laxatives that could cause an extrarenal
cause of normal anion gap acidosis (Fig. 1).
Osmolar Gap
The plasma osmolality can be calculated by the
formula 2 X sodium [meq/L] + glucose [ mg/dl] divided
by 18 + urea [ mg/dl] divided by 2.8. If the calculated
osmolality differ from the measured osmolality by 15
mosm/kg H2O, this is called as osmolar gap and further
investigations need to be done. Table 5 gives a list of the
causes of osmolar gap.
In case of unexplained excess anion gap metabolic
acidosis, osmolar gap should be calculated. Excess anion
gap acidosis associated with high osmolar gap include
ingestion of ethyl gycol, isopropyl alcohol or methanol
Table 5 : Causes of increased osmolar gap
Ethanol
Isopropyl alcohol
Methanol
Glycine
Mannitol
Ethylene glycol
Glycerol
Chronic renal failure

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JAPI VOL. 54 SEPTEMBER 2006

ingestion, and uremia. Hence in a comatose patient

presenting in the emergency room, evaluation should
include measurement of ABG, serum osmolality, osmolar
gap and a toxicology screen to evaluate for drug and
alcohol ingestion.
Four steps to solve acid-base disorders
Having gone over the basic rules of acid-base
compensation and pattern of change of PaCO2 and
bicarbonate in metabolic (same direction) and respiratory
disorders (opposite direction), we are now ready to go
over the four steps of solving any acidbase problem.
Using a four step process including, 1) determination
the serum pH, 2) calculation of the serum anion gap, 3)
estimating the degree of compensation, 4) calculation of
the excess anion gap, the reader will be able solve any
complex acid-base problem (Table 6). I will use a case to
demonstrate the use of these 4 steps to solve a acid base
question.
Case : A 48-year-old male was brought to the emergency
room with a history recent obtundation. He has a history
of alcoholism and a witnessed grand mal seizure just
prior to his arrival. His blood pressure is 128/70 mm
Hg, and heart rate was 114/mt. There was no
improvement in mental status despite thiamine and
dextrose infusion. His electrolyte panel revealed a serum
sodium 137 meq/L, potassium 5.0 meq/L, chloride was
100 meq/L, HCO3- was 12 meq/L , creatinine was 4.2
mg/dl. His ABG revealed a pH 7.12, and PaCO2 was 40
mm Hg. Was is the acid-base disorder? And what could
be the potential causes for the patients condition?
Answer : From the history you suspect possible
alcohol related problems, withdrawal or intoxication?
Could he have ingested something else? You probably
will get a toxic screen and get a serum osmolality to
calculate the osmolar gap.
You proceed to stabilize the patient and solve the acid
base disorders following the 4 steps ( Table 6).
Step 1. pH is 7.12 patient has acidosis
Step 2. Anion gap was 137- (12+100) = 25, high anion
gap acidosis, remember any AG > 20 indicates that the
primary defect is metabolic acidosis (are you thinking of
MUDPILERS?). Please note that you could use the serum
HCO-3 level here to calculate anion gap.
Step 3. Compensation step:
Primary acid-base disorder was metabolic acidosis
you apply the formula : calculated PaCO2 = (1.5X12) + 8
2 = 26 2 = 24 to 28 mm Hg; however patient measured
PaCO2 was 40 mm Hg hence patient also has associated
respiratory acidosis
Step 4. Calculate excess anion gap
Calculated HCO3 -= (patient anion gap- normal anion
gap) + patients HCO3= (25-12) + 12 = 25 meq/L
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Answer : Metabolic with respiratory acidosis with acute

renal failure, possible cause pending results methanol
intoxication, or ethylene glycol ingestion and uremia.
The patient was urgently administered 5 ampoules
of sodium bicarbonate, 50 mEq/L per 50 ml
intravenously and the following laboratory test was
obtained :
Serum sodium 150 meq/L, potassium 5.0 meq/L,
chloride was 99 meq/L, HCO3- was 26 meq/L, pH 7.47,
paCO2 was 40 mm Hg was is the acid-base disorder
now ?
Using the steps outlined in Table 6, we do the
calculations again:
Step 1 : pH is 7.47 patient has alkalosis
Step 2 : Anion gap was 150 - (26 + 99) = 25, high
anion gap acidosis, AG > 20 primary defect is still
Table 6 : Four steps to solve acid-base problems
Step 1. Determine the pH status
Acidic
pH < 7.35
Alkalemia pH > 7.45
The primary abnormality lies in the direction of
pH disorder
The body does not fully compensate the primary
acid-base disorder
Step 2. What is the Anion gap?
Calculate the Anion gap. If anion gap > 20 mmol/L
there is a primary metabolic acidosis regardless of the
bicarbonate level
Step 3. What is the degree of compensation?
Metabolic acidosis
Calculated PaCO 2 = (1.5X
HCO3 -) + 8 2 mm Hg
If calculated PaCO2 is lower
than measured PaCO2 then
there is associated Respiratory
acidosis
If calculated PaCO2 is higher
than measured PaCO2 then
there is associated Respiratory
alkalosis
Metabolic alkalosis Increase in paCO2= 0.6 X
increase in HCO3Respiratory Acidosis
Acute For every 10mm Hg increase in paCO 2, there is
1 meq/L increase in HCO3Chronic For every 10mm Hg increase in paCO2, there is
4 meq/L increase in HCO3Respiratory Alkalosis
Acute For every 10mm Hg decrease in paCO2, there is
2 meq/L decrease in HCO3Chronic For every 10mm Hg decrease in paCO2, there
is 4 meq/L decrease in HCO3 Step 4. What is the excess anion gap?
Calculate the excess anion gap(total anion gap
normal anion gap [12 mmol/L]) and add this value
to the measured bicarbonate concentration.
If the calculated HCO 3- > 30 mmol/L there is
associated metabolic alkalosis
If the calculated HCO 3- < 23 mmol/L there is
associated nonanion gap acidosis
In primary acid base disorders; change in anion gap=
change in bicarbonate level

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723

metabolic acidosis.
Step 3 : Primary acid-base disorder was metabolic
acidosis regardless of pH or serum bicarbonate you
apply the formula : calculated PaCO2= ( 1.5 X 26) + 8 2
= 47 2 = 45 to 49 mm Hg; however patient PaCO2 was
40 mm Hg, patient respiration has not changed, i.e.
patient is not hyperventilating, has not been intubated;
you cannot discount that the patient still has respiratory
acidosis
Step 4. Calculate excess anion gap
Calculated HCO3- = (patient anion gap- normal anion
gap) + patients HCO3= (25 -12) + 26 = 39 meq/L
Calculated HCO3- is greater that 30 meq/L, patient
now also has metabolic alkalosis from the bicarbonate
infusion.
Answer: You just discovered a triple disorder!
Metabolic with respiratory acidosis and metabolic alkalosis
(beware of bicarbonate infusion as patients respiration
could be compromised further)
Indication of obtaining mixed venous gas
In patients with profound depression of cardiac and
pulmonary circulation, but with preservation of alveolar
ventilation, for example patient undergoing
cardiopulmonary resuscitation, arterial blood gas could
reveal arterial hypocapnia, due to increased ventilation:
perfusion ratio causing larger than normal removal of
carbon dioxide per unit of blood in the pulmonary
circulation, thereby falsely indicating arterial
hypocapnia, when in reality there is an absolute increase
in carbon dioxide. This form of arterial hypocapnia is
called pseudorespiratory alkalosis when in reality it is

respiratory acidosis.7 Sampling of mixed venous (central

blood) can help in establishing the correct diagnosis of
respiratory acidosis in this kind of situation. Accurate
diagnosis of this condition is indicated as treatment lies
in optimizing the systemic hemodynamic condition.

CONCLUSION
Acid base disorders are commonly encountered by
physicians. Taking a good history and physical
examination along with a step-wise approach to solving
primary and complex acid-base disorders, physicians
would be able to identify acid-base disorders associated
with serum and urinary anion gap, osmolar gap and
identify indications for obtaining a mixed venous blood
gas.

REFERENCES
1.

Haber RJ. A practical approach to acid-base disorders. West

J Med 1991;155:146-51.

2.

Madias NE, Perrone RD. Acid-base disorders in association

with renal disease. In: Schrier RW, Gottschalk CW, eds.
Diseases of the Kidney. 5 th ed. Boston:Little Brown,
1993;3:2669-99.

3.

Madias NE, Androgue HJ. Respiratory alkalosis and acidosis.

In: Seldin DW, Giebisch G, eds. The Kidney : Physiology and
Pathophysiology. 3 rd Ed. New York: Raven Press, 2000:
2131-66.

4.

Gluck SL. Acid-base. Lancet 1998;352;474-79.

5.

Androgue HJ, Madias NE. Management of life-threatening

acid-base disorders. N Engl J Med 1998;338:26-34.

6.

Androgue HJ, Madias NE. Management of life-threatening

acid-base disorders: second of two parts. N Engl J Med
1998;338:107-11.

7.

Androgue HJ, Rashad MN, Gorin AB, Yacoub J, Madias NE.

Assessing acid-base status in circulatory failure : differences
between arterial and central venous blood. N Engl J Med
1989;320:1312-16.

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