1. health and fitness
2. disease

a guide to the
interpretation and understanding
of
Arterial
Blood
Gases
Dr John L Holmes
Director Emergency Medicine , Mater Adult Hospital, Brisbane, Australia
ABG’s 2
CONTENTS
SUBJECT
PAGE
What's it all about?
3
Ventilatory and Pulmonary Function
3
Alvelar Gas Equation
3
Using the Alveolar Gas Equation
4
The A-a Gradient
5
Predicting the “normal” A-a Gradient
6
The Alveolar Gas Equation in Pulmonary Disease
9
Approximation to the Alveolar Gas Equation
11
Acid – Base Disturbances
12
Physiology of Acid – Base Homeostasis
13
Henderson – Hasselbach Equation
13
ABG’s in Acid – Base Disturbances
14
Scheme for Interpretation of ABG results
15
Acid – Base Nomogram
16
Metabolic Acidosis
17
The Anion Gap
17
Increased Anion Gap Acidosis
18
Normal Anion Gap Acidosis
19
Metabolic Alkalosis
20
Respiratory Acidosis
21
Rspiratory Alkalosis
23
Mixed Acid – Base Disorders
24
Clinical Examples of Acid – Base Disorders
25
Summary
28
Formulae and Rules of Thumb
29
ABG’s 3
ARTERIAL BLOOD GASES
In medicine many laboratory tests may be ordered as a matter of "routine" or on the off
chance that something just might turn up to help explain a patient's condition. One of
the frequently performed laboratory tests in the Emergency Department is the analysis
of arterial blood gases (ABG's). It is often not realised that the ABG's have the
potential to reveal far more information than may initially be suspected from a casual
perusal of the numberers on the computer screen or print out.
The following is the hitchhiker's guide to arterial blood gases. Hopefully after reading
these notes you may be persuaded to take a little extra time to sit down and analyse
ABG results and to think about what they imply. You might learn more about your
patient than you suspected!
WHAT'S IT ALL ABOUT?
There are two main reasons for performing ABG’s:
1. To assess ventilatory and pulmonary function
2. To assess acid base disturbance
1. VENTILATORY AND PULMONARY FUNCTION
The PaCO2 gives an indication of VENTILATION ie: a measure of the adequacy of the
movement of gas in and out of the alveoli.
The PaO2, (when related to the FiO2 and PaCO2) gives an indication of PULMONARY
FUNCTION ie: the efficacy of gas exchange between the alveoli and the blood.
The key to all this is the ALVEOLAR GAS EQUATION but before discussing this we
first have to understand some basic terminology.
A lower case "a" stands for "arterial" thus PaO2 = the partial pressure of oxygen in
arterial blood.
An upper case "A" stands for "alveolar" thus PAO2 = the partial pressure of oxygen in
alveolar gas.
"F" stands for "fractional concentration" and "i" for "inspired". Thus FiO2 = "Fractional
concentration of inspired oxygen" and is usually expressed as a decimal fraction. We
breathe atmospheric air at an Fi O2 of 0.21.
OK, here's the ALVEOLAR GAS EQUATION:
PAO2
=
P iO 2
- PaCO2 + F
R
where R is the Respiratory Quotient and usually = 0.8
and F is a negligible correction factor.
This equation states that:
ABG’s 4
The partial pressure of oxygen in the alveolar gas
is equal to
the partial pressure of oxygen in the inspired gas
minus
the partial pressure of carbon dioxide present in the alveolar gas.
In other words, there is a reciprocal balance between the amount of oxygen and
carbon dioxide in the alveoli.
Because carbon dioxide diffuses readily across biological membranes, the alveolar
partial pressure of CO2 is equal to its partial pressure in arterial blood. Hence the
PACO2 term can be replaced with the more useful PaCO2. (which we can measure).
And because dividing by O.8 is the same as multiplying by 5/4, the equation becomes:
PAO2
=
P iO 2
-
5 . PaCO2
4
IMPRINT THIS EQUATION ON YOUR BRAIN - it will prove to be of inestimable value
whenever you need to interpret ABG's. You'll also be surprised to find out that ABG’s
which initially may seem to imply that all is well with a patient, may actually reveal a
more sinister degree of pulmonary dysfunction (and sometimes vice versa).
USING THE ALVEOLAR GAS EQUATION
It is necessary to first determine the partial pressure of inspired oxygen (ie: PiO2).
The partial pressure of an individual gas is proportional to its fractional concentration in
the gas mixture, thus:
P i O2
=
Patmos
-
PH2O
X
FiO2
where PH2O = the Saturated Vapour Pressure of Water ( = 47 mmHg at 37oC). In
the respiratory tract, the inspired air becomes fully saturated with water vapour and this
must be corrected for.
Atmospheric pressure at sea level = 760 mmHg, thus for a person breathing room air
at sea level (where FiO2 = 0.21)
P i O2 =
(760 - 47) x 0.21
= 150 mmHg
If the patient was breathing 35% oxygen
P i O2 =
(760 - 47) x 0.35
= 250 mmHg
What does the alveolar gas equation predict in the "normal" situation for a person
breathing room air?
ABG’s 5
The normal value of PaCO2 = 40 mmHg and PiO2 O2 = 150 mmHg
Substituting these values into the alveolar gas equation, we get:
PAO2
=
P iO 2
-
5 . PaCO2
4
=
150
-
5 . 40
4
50
=
150
-
=
100
mmHg
In a healthy young adult, the alveolar oxygen tension approximates the arterial oxygen
tension ( ie: PAO2 = PaO2 ) and hence our "normal" subject should have a PaO2 of
approximately 100 mmHg.
THE A - a GRADIENT
Nothing in life, however, is perfect, and gas exchange between the alveoli and the
blood is not 100% efficient. Usually the arterial partial pressure of oxygen is somewhat
less than the alveolar oxygen tension.
The difference between the calculated PAO2 and the measured PaO2 is the A - a
gradient. It is written in a variety of ways including P(A-a)O2 or (A -a)DO2.
Factors Influencing the A - a gradient
1. Age
2. Inspired oxygen partial pressure of oxygen & PAO2
3. Pulmonary disease
1. Age
For young people it's OK to have an A - a gradient of up to 15 mmHg on air and it
tends to get bigger with advancing age.
A useful rule of thumb is that the maximum A - a gradient (breathing air) should equal
approximately one third the age.
ABG’s 6
2. Inspired partial pressure of Oxygen
On supplemental oxygen, the A - a gradient is widened, but the extent of this is
influenced by a number of factors including the shape of the oxygen dissociation curve
and the degree of intrapulmonary shunting (V/Q mismatch).
In normal lungs there is relatively little widening of the A -a gradient with increasing
FiO2. However, when there is a significant degree of V/Q mismatching, the A - a
gradient does widen markedly with increasing FiO2 (see fig:4).
Predicting the “Normal” A-a Gradient
This formula relates “normal” A-a gradients to the effects of both AGE and PAO2 :
A - a gradient
=
Age
+
PAO2
3
-
23
5
Consider a 60 year old man breathing 50% oxygen and with a PaCO2 of 40 mm Hg.
From the alveolar gas equation, the PAO2 = (713 X 0.5) – 5 X 40/4 = 307 mmHg.
He may thus be expected to have an A - a gradient of 60/3 + 307/5 - 23 = 58 mmHg
and his PaO2 should be around 307 - 58 = 249 mmHg.
If his measured PaO2 was significantly less than this, then there would be a strong
possibility of pulmonary disease.
150
Age (years)
A - a gradient
140
mmHg
130
80
60
40
20
120
110
100
90
80
70
60
50
40
30
20
10
0
0
100
200
300
400
500
600
700
PAO2
800
mmHg
Fig. 1. A - a gradient as a function of Age and PAO2
ABG’s 7
PaO2 mmHg
600
FiO2
550
1.0
500
450
400
350
300
0.60
250
0.50
200
150
0.35
100
0.21
50
0
0
20
40
60
80
100
age (years)
Fig. 2. PaO2 as a function of Age and FiO2 (assuming a PaCO2 of 40 mmHg)
PaO2 mmHg
120
PaCO2
mmHg
110
20
100
30
90
40
80
50
70
60
60
70
50
80
40
90
30
100
20
10
0
0
20
40
60
80
100
age (years)
A -ag idar tne
Fig. 3 PaO2 as a function of Age and PaCO2 (breathing room air)
ABG’s 8
3. The A - a Gradient in Pulmonary Disease
In pulmonary disease, the A - a gradient is increased.
NOTE: The A -a gradient is NOT affected by just alveolar hypoventilation alone.
There are three pathological causes of increased A - a gradient in pulmonary disease:
1. Ventilation / perfusion inequality (most important)
2. Barriers to gas diffusion from the alveolus into the blood.
3. Arterio - venous "shunts"
A - a gradient
mmHg
500
50%
20%
400
300
15%
200
100
5%
1%
0
0
100
200
300
400
500
600
700
P AO 2
800
mmHg
Fig. 4 Effect on A-a gradient of increasing PAO2 at differing degrees of V/Q mismatch
ABG’s 9
THE ALVEOLAR GAS EQUATION IN PULMONARY DISEASE
To give an idea of how to apply the alveolar gas equation in practice, we'll consider
some clinical scenarios.
Case 1
A 54 year old man presents with dyspnoea and fever. He has pleuritic chest pain and
cough and on examination he has an area of bronchial breathing at the left base. CXR
is suggestive of left lower lobe pneumonia.
You have taken ABG's with the patient breathing oxygen at 35% (FiO2 = 0.35).
The results are:
pH
PaO2
PaCO2
HCO3
BE
SpO2
=
=
=
=
=
=
7.35
92
46
26
-2
97%
We shall ignore the acid/base parameters in this case and concentrate on the
respiratory function. The question to be answered is: Is there a significant degree of
pulmonary impairment?
At first glance, these gas results seem reasonable - the PaO2 = 92 which is OK and
the PaCO2 is only minimally elevated (46 mmHg – normal range 35 – 45).
But let's now plug these numbers into the alveolar gas equation:
PAO2
=
P i O2
-
5 . PaCO2
4
=
(760-47) X 0.35
-
5 X 46
4
=
249.6 -
=
192
57.5
mmHg
The MEASURED PaO2
= 92 mmHg
Thus the A - a gradient
= 192 - 92 = 100 mmHg
The predicted normal A -a gradient for this man is:
“Normal” A - a
=
AGE / 3 + PAO2 / 5 - 23
=
54 / 3
=
33 mmHg
+ 192 / 5
-
23
The patient thus has a significantly increased A - a gradient which implies that there is
a large degree of pulmonary dysfunction, even though he is maintaining an adequate
PaO2 on supplemental oxygen therapy.
Looking at it from another angle, if we apply the normal A-a gradient for his age we
would expect his measured PaO2 to be at least 192 – 33 = 159 mmHg on this FiO2
ABG’s 10
Case 2
A 21 year old female is found comatose in the street, possibly as the result of a drug
overdose. She is somewhat cyanosed and you are concerned that she may have
aspirated vomitus. Her arterial blood gases on room air are:
pH
PaO2
PaCO2
HCO3
BE
SpO2
=
=
=
=
=
=
7.29
71
58
25
-1
82%
Using the alveolar gas equation:
PAO2
=
P i O2
-
5 . PaCO2
4
=
(760-47) X 0.21
-
5 X 58
4
=
=
The MEASURED PaO2 =
149.7 77
72.5
mmHg
71 mmHg
Thus the A - a gradient = 77 – 71 = 6
This is a low A -a gradient and tells us that the patient's hypoxaemia is due solely to
hypoventilation and not due to pulmonary disease (including aspiration).
The correct initial management of this patient is to assist her ventilation using bag &
mask. However, note that she still needs supplemental oxygen until she is breathing
up more adequately as she will undoubtedly, after she is given naloxone.
Case 3
A 45 year old woman is brought into the Emergency Department following a motor
vehicle accident in which she sustained multiple injuries including blunt trauma to the
chest. She is conscious but distressed.
She is administered high flow oxygen at an estimated concentration of 60% and has
the following arterial blood gases:
pH
PaO2
PaCO2
HCO3
BE
SpO2
=
=
=
=
=
=
7.29
151
52
22
-3
97%
ABG’s 11
Initial assessment of thses results suggests that oxygenation appears to be adequate,
though there is an elevated PaCO2 of 52 suggesting underventilation.
Using the alveolar gas equation:
PAO2
=
P i O2
-
5 . PaCO2
4
=
(760-47) X 0.60
-
5 X 52
4
=
427.8 -
=
The MEASURED PaO2 =
363
65.0
mmHg
151 mmHg
Thus the A - a gradient = 363 - 151 = 212
The estimated “normal” A -a gradient for this lady breathing 60% oxygen is be
approximately:
= AGE / 3 + PAO2 / 5 - 23
= 45/3 + 363/5 - 23
= 65
The significantly widened A -a gradient in this case tells us that, despite maintaining an
adequate PaO2 of 151 mmHg on supplemental oxygen, this patient nevertheless has
a significant degree of pulmonary dysfunction IN ADDITION to her hypoventilation.
She should have a PaO2 = 363 – 65 = 298 mmHg. Her ABG’s are consistent with
pulmonary contusion or haemothorax etc.
The above cases illustrate that the careful assessment of ABG's using the alveolar gas
equation can give us a lot more information about a patient's pulmonary status than
initial reading of the results might suggest.
In some cases, as in patients 1 and 3 above, an adequate PaO2 on supplemental
oxygen may be obscuring underlying pulmonary pathology. Conversely, patient 2 is an
example of where hypoventilation gives the impression of pulmonary pathology but
where in fact lung function per se is adequate.
Approximation to the Alveolar Gas Equation
For most circumstances the alveolar gas equation can be approximated to :
PAO2
=
7 X %O2 - PaCO2 - 10
Applying this formula to the first example above (54 y.o. man on 35 % oxygen):
PaO2
=
92
ABG’s 12
PaCO2
=
46
PAO2
≈
≈
≈
7 X 35 - 46
245
- 46
199 mmHg
When calculated using the original formula:
PAO2
=
=
=
(760-47) X 0.35 - 46 X 5/4
250 - 58
192 mmHg
2. ACID - BASE DISTURBANCES
Acid/base physiology can be fairly daunting but unfortunately we do have to know a
smattering of this subject, so the following is a primer. Luckily, when it comes to
working out what is going on from the ABG's, there are a few rules of thumb which can
aid in interpretation. We shall come to these later.
BASIC PHYSIOLOGY OF ACID/BASE HOMEOSTASIS
The pH of body fluids is maintained within a narrow range by homeostatic mechanisms
of which there are three major players:
1. Kidneys
2. Lungs / Respiratory centre
3. Buffer systems
Of the various buffering systems in the body, by far the most important is the
BICARBONATE - CARBONIC ACID system.
Importantly, the variables in this system (bicarbonate and PaCO2) are independently
regulated by the kidneys and central respiratory centre respectively.
We thus talk about the metabolic and respiratory components of acid/base
homeostasis and by measuring the plasma bicarbonate and PaCO2 in arterial blood,
we get an indication of the aetiology of any underlying acid/base disturbance.
Either the bicarbonate or PaCO2 may be primarily disturbed depending on whether the
fundamental problem is metabolic or respiratory in origin. In addition, both may be
secondarily altered in compensation for other acid/base abnormalities.
The important chemical relationship representing the bicarbonate buffer system is:
CO2 + H2O
H2CO3
H + + H2CO3
ABG’s 13
Derivation of the Henderson - Hasselbalch Equation
-
+
[H ] . [HCO3 ]
Ka
=
(by definition)
[H2CO3]
-
and
log Ka
=
+
log [H ]
[HCO3 ]
+
log
[H2CO3]
-
- log Ka
=
+
- log [H ]
[HCO3 ]
-
log
[H2CO3]
-
[HCO3 ]
Thus
pKa
=
pH
-
log
[H2CO3]
-
[HCO3 ]
And
pH
=
pKa
+
log
[H2CO3]
Now the plasma concentration of carbonic acid is directly proportional to the partial
pressure of CO2 in the plasma, the solubility coefficient being 0.03 mmol/litre/mmHg.
-
[HCO3 ]
Thus
pH
=
pKa
+
log
0.03 PaCO2
This is the famous Henderson - Hasselbalch equation.
The important thing to realise is that the RATIO of plasma bicarbonate concentration to
the PaCO2 needs to be kept constant in order to maintain a constant plasma pH. Thus
if bicarbonate concentrations fall, then in order to maintain pH, PaCO2 must also fall.
Conversely, if bicarbonate concentrations rise, then PaCO2 must also rise.
Irrespective of whether PaCO2 or bicarbonate is primarily disturbed, the other follows in
compensation to maintain the ratio and thus maintain pH.
The pKa of carbonic acid is 6.1. Normal serum bicarbonate = 24 mmol/L and normal
PCO2 is ~ 40 mmHg. Thus the Henderson - Hasselbalch equation can be used to
predict normal plasma pH:
-
[HCO3 ]
pH
=
pKa
+
log
0.03 PaCO2
24
=
6.1
+
log
0.03 X 40
=
=
=
6.1
6.1
7.4
+
+
log
1.3
20
ABG’s 14
Other buffer systems also have effect on acid/base homeostasis though they are not
as quantifiably important as the bicarbonate system. In addition there are other renal
responses to pH disturbance.
ARTERIAL BLOOD GASES IN ACID/BASE DISTURBANCES
When confronted with a possible acid/base disturbance, it is important to determine if
the disturbance is predominantly metabolic or respiratory in origin, and to recognise the
appropriate type and degree of homeostatic compensation.
A metabolic disturbance invokes a respiratory compensation which is fairly rapid in
onset. A respiratory acid/base disturbance invokes a metabolic compensatory
response which takes a few days to become maximal.
Scheme fo the Interpretation of Arterial Blood Gases
1.
Look at the pH
Decide if acidosis or alkalosis is present. Normal range 7.35 - 7.45. Note that
compensations for acid/base disturbances are rarely complete.
2.
Look at the BICARBONATE
If ↑ then either a primary metabolic alkalosis or compensated respiratory
acidosis is present.
If ↓ then either a primary metabolic acidosis or
compensated respiratory alkalosis is present.
3.
Look at the PaCO2
If ↑ then either a primary respiratory acidosis or compensated metabolic
alkalosis is present.
If ↓ then either a primary respiratory alkalosis
orcompensated metabolic acidosis is present.
Note that underlying respiratory pathology may make interpretation difficult.
Aide memoire
Note that both the PaCO2 and the bicarbonate tend to move in the same direction.
If the PaCO2 and the bicarbonate move in the SAME direction as the pH change, then
the problem is METABOLIC in origin.
If the PaCO2 and the bicarbonate move in the REVERSE direction to the pH change,
then the problem is RESPIRATORY in origin.
ABG’s 15
-
-
pH
PCO2
Metabolic
↓
↓
↓
Respiratory
↓
↑
↑
Metabolic
↑
↑
↑
Respiratory
↑
↓
↓
HCO3
-
ACIDOSIS
ALKALOSIS
Figure 4: Summary Acid – Base Disturbances
You will note that we have completely ignored the so-called BASE EXCESS. This
parameter is a derived value and can sometimes be misleading. It should not be
necessary for you to look at the BE (especially now that you have a good
understanding of what's going on with the PaCO2 and bicarbonate).
Figure 5 is an acid - base nomogram and plots the relationship between plasma
bicarbonate and arterial PCO2 at different pH levels. The shaded areas show the
approximate ranges of HCO3 and PaCO2 which occur with pure acid-base
disturbances.
ABG’s 16
pH
7.7 7.6
7.5
7.4
50
-
chronic
resp
acidosis
metabolic
alkalosis
HCO 3
mmol/L
7.3
40
7.2
acute
resp
acidosis
30
24
7.0
acute
resp
alkalosis chronic
resp
alkalosis
20
6.9
6.8
metabolic
acidosis
10
0
7.1
0
20
Figure 5.
40
60
P CO2
80
mmHg
ACID - BASE NOMOGRAM
100
ABG’s 17
Rules of thumb formulae which can be used to predict bicarbonate and PaCO2 levels
in various acid-base disturbances are based on this and similar nonograms.
METABOLIC ACIDOSIS
Metabolic acidosis is characterised by a primary fall in the plasma bicarbonate to less
than 24 mmol/L.
There are three main causes:
1. Increased production or gain of non-volatile acids
2. Decreased acid excretion by the kidney
3. Loss of alkali from the body
-
H+ ions react with HCO3 to form carbonic acid (H2CO3) which dissociates to form CO2
and H2O. Increased H+ ion concentration (ie: lowered pH) stimulates ventilation and
PaCO2 is reduced (despite the increased production of CO2).
Metabolic acidosis may be divided into two major groups depending on whether the
ANION GAP is widened or not.
METABOLIC ACIDOSIS
INCREASED ANION GAP
NORMAL ANION GAP
(↑
↑ non-volatile acids)
(hyperchloraemic acidosis)
1. ↑ acid production
Ketoacidosis
1. Loss of Alkali
Diarrhoea
Ostomies
Carbonic anhydrase inhibition
Renal tubular acidosis (proximal)
diabetic
alcoholic
starvation
Lactic acidosis
2. Exogenous acid ingestion
Salicylates
Methanol
Ethylene glycol
3. ↓ acid excretion
Renal failure
Methanol
Ethylene glycol
2. ↓ excretion of H+ ions
Hypoaldosteronism
Renal tubular acidosis (distal)
1. Cationic acids
TPN
NH4Cl
figure 6: Causes of metabolic acidosis
ABG’s 18
The Anion Gap is the difference between the measured anions and cations in plasma.
+
+
( Na + K )
-
-
-
(Cl + HCO3 )
Although there is electrical neutrality, there is normally an anion gap of up to 15 mmol/L
due to the presence of negatively charged moieties (especially proteins) which are not
usually measured in standard laboratory testing.
An increase in the anion gap is found when there is an accumulation of anionic forms
23of non-volatile acids (eg: acetoacetate, lactate, SO4 , PO4 etc).
Thus acidosis due to the accumulation of non-volatile acids is known as increased
anion gap metabolic acidosis.
In non-anion gap acidosis there is no change in the levels of non-volatile acids.
However, there is usually loss of bicarbonate (which is compensated for by a rise in
chloride ion) or decreased excretion of hydrogen ions by the renal tubules.
Non-anion gap acidosis can also be caused when there is the administration of cationic
acids (as in TPN). These forms of acidosis are also known as hyperchloraemic
acidosis.
INCREASED ANION GAP ACIDOSIS
There is an accumulation of non-volatile acids either through increased production,
ingestion or decreased excretion.
1. Increased Acid Production
1.1 Ketoacidosis:
Diabetes: There is accumulation of acetoacetate and beta-hydroxybutyrate.
Alcoholism: Often middle aged females following a period of starvation. Betahydroxybutyrate is the predominant ketone and this may lead to ketosis being
missed as routine testing usually only detects acetoacetate.
Starvation: Mild ketosis is due to increased fat metabolism.
1.2 Lactic Acidosis:
•
Tissue hypoxia and subsequent anaerobic glycolysis usually secondary to shock
(including sepsis) or respiratory failure.
•
May be associated with liver necrosis, leukaemia, solid tumours or diabetic
ketoacidosis.
•
Drugs and Toxins: biguanides, alcohol, cyanide, salicylates etc.
•
TPN. - Fructose metabolism
•
Congenital enzyme defects
ABG’s 19
2
Exogenous acid ingestion or administration
2.1 Poisoning:
Ethylene glycol: Metabolised to aldehydes and oxalic acid.
Salicylates: Produce build up of endogenous organic acids (acetoacetate,
lactate, pyruvate) due to impairment of carbohydrate metabolism.
Methanol: Oxidised by alcohol dehydrogenase to formaldehyde and formic
acid. Formic acid is buffered to formate but also blocks carbohydrate
metabolism leading to accumulation of organic acids.
3. Decreased Excretion of Non-volatile Acid
3.1 Chronic Renal Failure:
Principal defect is decreased excretion of NH4+ and other non-volatile acids such as
sulphate and phosphate.
There may also be some renal wasting of bicarbonate.
NORMAL ANION GAP ACIDOSIS
The loss of bicarbonate is balanced by an increase in chloride ion thereby maintaining
electrical neutrality.
1. Loss of Alkali
1.1 Gastrointestinal Losses:
From diarrhoea, pancreatic fistulae, "ostomies".
1.2 Carbonic Anhydrase Inhibition:
Carbonic anhydrase is required for tubular conservation of bicarbonate which is thus
lost in the urine when the enzyme is inhibited. At the same time HCl is reabsorbed.
1.3 Proximal Renal Tubular Acidosis
A defect in the proximal renal tubule leads to decreased reabsorption of bicarbonate
and large losses of bicarbonate in the urine.
2. Dilution of Bicarbonate Concentration
Extracellular fluid
concentration.
volume
expansion
by
normal
saline
dilutes
bicarbonate
ABG’s 20
+
3. Decreased Excretion of H Ion
3.1 Hypoaldosteronism
Aldosterone promotes Na+ conservation and H+ and K+ excretion. Inhibition of
aldosterone thus causes H+ ion retention (and hyperkalaemia) which also decreases
NH3 production.
3.2 Potassium sparing diuretics
These inhibit the distal tubular secretion of acid and potassium.
RULES OF THUMB IN METABOLIC ACIDOSIS
If pH = 7.XY, then PaCO2 ≈ XY
(eg: pH = 7.29, PaCO2 ≈ 29)
C = 1¼ B + 10
(C = PaCO2 and B = Bicarbonate)
eg: If Bicarbonate = 16 mmol/L, PCO2 should be approx. 16 X 5/4 +10 = 30 mmHg
METABOLIC ALKALOSIS
Characterised by a primary increase in the plasma bicarbonate (> 28 mmol/L)
Pathophysiology
There is either a net gain of bicarbonate or a net loss of hydrogen ion.
Normally there is very efficient renal excretion of excess bicarbonate, so for alkalosis to
be maintained, an additional mechanism is required whereby bicarbonate is
significantly reabsorbed or regenerated.
Clinically the maintenance of metabolic alkalosis is most often associated with
extracellular fluid volume deficit. During ECF contraction, the renal conservation of
sodium under the influence of aldosterone takes precedence over acid/base
homeostasis. In these circumstances there is NaCl depletion and most Na+ ions are
paired with HCO3-. The reabsorption of Na+ from the renal tubules therefore also
results in the reabsorption of HCO3- into the plasma, thereby maintaining alkalosis.
This can be treated by the administration of Normal Saline which provides Cl- ions in
place of HCO3- ions.
Similarly primary hyperaldosteronism may initiate and maintain metabolic alkalosis
due to excess excretion of H+ ions (in preference to sodium which is conserved).
ABG’s 21
Severe hypokalaemia may also be a cause of metabolic alkalosis and also contributes
to its maintenance. When serum potassium levels fall, there is exchange of
+
+
+
intracellular K for extracellular H ions. This movement of H ions into cells raises the
pH of the ECF. Also in the kidney, H+ ions are excreted in preference to K+ ions.
METABOLIC ALKALOSIS
CAUSES
MAINTAINANCE
+
1. Loss of H ions
Vomiting
Gastric drainage
Renal losses
Primary hyperaldosteronism
Secondary hyperaldosteronism
Cushing’s syndrome
Bartter’s syndrome
Drugs: steroids, diuretics, carbenoxolone
↑ extracellular fluid volume
Hyperaldosteronism
Hypokalaemia (severe)
2. Gain of Bicarbonate
NaHCO3 administration
Metabolic conversion of lactate, citrate, acetate
Figure 7: Causes of metabolic alkalosis
ARTERIAL BLOOD GASES IN METABOLIC ALKALOSIS
pH and HCO3- are elevated. There is a highly variable respiratory compensation.
Increased pH leads to hypoventilation and subsequent increased PaCO2.
Thus pH, bicarbonate and PaCO2 are all elevated in metabolic alkalosis.
RULE OF THUMB:
C = B / 2 + 30
(C = PaCO2 and B = Bicarbonate)
eg: If Bicarbonate = 37 mmol/L, PCO2 should be approx. 37 / 2 +30 = 49 mmHg
ABG’s 22
RESPIRATORY ACIDOSIS
Ventilatory failure leads to CO2 retention and an increased PaCO2 due to ongoing
metabolic production of carbon dioxide.
The increased CO2 forms carbonic acid which dissociates to bicarbonate and water.
Metabolic compensation occurs in chronic respiratory acidosis with the renal
conservation of bicarbonate and increased secretion of acid.
RESPIRATORY ACIDOSIS
ACUTE
CHRONIC
Thoracic trauma
Acute respiratory disease
Chronic respiratory disease
asthma
acute pulmonary oedama
pneumonia / pneumonitis
Neuromuscular disease
Drugs (opiates & other CNS depressants)
↑ intracerebral pressure
COPD , emphysema
chronic asthma
fibrosing alveolitis
Morbid obesity (Pickwickian)
meningitis, encephalitis
head trauma
cerebral haemorrhage
expanding space occupying lesion
Brainstem stroke
Cardiac arrest
Figure 8: Causes of respiratory acidosis
The underlying causes of acute or chronic ventilatory or circulatory failure should be
corrected clinically. The administration of bicarbonate to "correct" a pure respiratory
acidosis is counterproductive as it is converted to CO2, compounding the underlying
problem. 100 mmol of bicarbonate is the equivalent of giving 2.5 litres of CO2 !
RULES OF THUMB IN RESPIRATORY ACIDOSIS
In acute respiratory acidosis, the HCO3- ↑ by 0.1 mmol per 1 mmHg ↑ in the PaCO2
(due to the equation CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+ being driven to the right).
In chronic respiratory acidosis, the HCO3- ↑ by 0.3 – 0.4 mmol per 1 mmHg ↑ in the
PaCO2 (due to compensatory renal reabsorption of bicarbonate).
These trends are represented in the following two formulae: (again B = Bicarbonate and
C = PaCO2)
B = C / 10 + 20
B = C/2
+ 2
(Acute Respiratory Acidosis)
(Chronic Respiratory Acidosis)
ABG’s 23
Example : If the PaCO2 = 60 mmHg
•
•
-
If this were acute respiratory acidosis (eg: acute asthma), the HCO3 should be
60/10 + 20 = 26 mmol/L.
If this were chronic respiratory acidosis (eg: COPD – “blue bloater”), the HCO3
should be 60/2 + 2 = 32 mmol/L.
RESPIRATORY ALKALOSIS
Essentially due to hyperventilation and ↑loss of CO2.
RESPIRATORY ALKALOSIS
RESPIRATORY CENTRE STIMULATION
Acute hypoxia
asthma
acute pulmonary oedama
pneumonia
OTHER
Anxiety – hyperventilation syndrome
Exercise
Artifical ventilation
Pregnancy
Chronic hypoxia
pulmonary fibrosis
cyanotic heart disease
altitude
Fever
Drugs (salicylates, amphetamines etc)
Cerebral disease / head injury
Figure 9: Causes of Respiratory Alkalosis
The loss of CO2 in hyperventilation leads to a reduction in plasma HCO3- The degree
of compensation depends on whether the process is acute or chronic. In fully
compensated respiratory alkalosis the pH may actually return to normal (the only acid /
base disturbance where compensation may be completely effective).
RULES OF THUMB IN RESPIRATORY ALKALOSIS
In acute respiratory alkalosis, the HCO3- ↓ by 0.25 mmol per 1 mmHg ↓ in the PaCO2
(due to the equation CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+ being driven to the left).
In chronic respiratory acidosis, the HCO3- ↓ by 0.50 mmol per 1 mmHg ↓ in the
PaCO2 (due to compensatory renal excretion of bicarbonate).
These trends are represented in the following two formulae:
B = C / 4 + 14
(Acute Respiratory Alkalosis
ABG’s 24
B = C/2
again -
(Chronic Respiratory Alkalosis)
+ 4
B = Bicarbonate and C = PaCO2
Example : If the PaCO2 = 28 mmHg
•
•
-
If this were acute respiratory alkalosis (eg: hyperventilation syndrome), the HCO3
should be 28/4 + 14 = 21 mmol/L.
If this were chronic respiratory acidosis (eg: adaptation to high altitude), the HCO3should be 28/2 + 4 = 18 mmol/L.
MIXED ACID - BASE DISORDERS
It has been said that life wasn't meant to be easy. It is not unusual for patients to be
suffering from multiple pathology. In such cases acid/base disturbances may also be
multifactorial in origin.
For example, in salicylate poisoning, direct stimulation of the respiratory centre initially
leads to a respiratory alkalosis. However, after a few hours, the salicylates cause an
uncoupling of oxidative phosphorylation resulting in an additional co-existent lactic
metabolic acidosis. Another example would be a patient with sepsis due to pneumonia
who may have both a metabolic and respiratory acidosis.
In cases such as these, interpretation of ABG's on first reading may not lead to an
obvious conclusion. However, with a bit of inspired perspicacity the primary disorder
can usually be identified (usually on the basis of the history) and coexistent pathology
can be surmised. By application of the appropriate rule of thumb formulae, the clinical
impressions can be verified. Let's illustrate the process using a clinical example:
Case 4
A 4 year old child is brought to the Emergency Department and the parents tell you he
may have taken some pills about 4 hours ago. The child’s temperature is 38.5o and
the respiratory rate is 40 per minute. The rest of the clinical examination is normal.
The ABG's (on air) are as follows:
pH
PaO2
PaCO2
HCO3BE
=
=
=
=
=
7.50
119
21
14
3
There is obviously an alkalosis (pH=7.50) and because the pH is ↑ whilst the PaCO2
and HCO3- are both ↓ , the primary disorder must be respiratory in origin.
However, is this the whole story? Because from the history this is likely to be an acute
process, let's plug the figures into our formula for acute respiratory alkalosis:
ABG’s 25
Predicted
B
=
1/4 C + 14
=
21/4 + 14
=
19 mmol/L
The measured bicarbonate (14) is actually significantly less than this. So what’s going
on? The discrepancy can be explained by postulating that in addition to the major
problem of respiratory alkalosis, there is an additional process causing a metabolic
acidosis which is driving the bicarbonate even further down. This is exactly the picture
seen in acute salicylate intoxication where salicylates initially directly stimulate the
respiratory centre causing hyperventilation (acute respiratory alkalosis) but later poison
aerobic glycolysis leading to lactic acidoisis.
CLINICAL EXAMPLES OF ACID - BASE DISTURBANCES
Case 5
A 68 year old man with a history of "bronchitis" presents in respiratory distress with
wheeze. He is placed on low flow oxygen (estimated FiO2 = 0.25). His ABG's are:
pH
PaO2
PaCO2
HCO3
BE
SpO2
=
=
=
=
=
=
7.34
86
49
26
0
87%
The primary acid/base disturbance appears to be respiratory acidosis as the pH is low
but the PaCO2 and HCO3 are both elevated. However, can we be sure that this is a
pure respiratory acidosis and if so is it likely to be acute or chronic?
Using the formula for acute respiratory acidosis:
Predicted Bicarbonate
=
=
=
PCO2 / 10 + 20
49/10 + 20
25
This accords well with the measured result and thus these results are consistent with a
pure acute respiratory acidosis.
It is instructive to analyse the respiratory function also in this case. Uing the alveolar
gas equation as previously:
PAO2
=
P i O2
-
5 . PaCO2
4
=
(760-47) X 0.25
-
5 X 49
4
=
178
-
61
ABG’s 26
=
117
mmHg
The PaO2 = 86 and the A - a gradient = 117 - 86 = 31 mmHg.
The predicted normal A -a gradient for this man is:
“Normal” A - a
=
AGE / 3 + PAO2 / 5 - 23
=
68 / 3
=
23 mmHg
+ 117 / 5
-
23
The widened A - a gradient implies pulmonary disease and corroborates a diagnosis
of respiratory acidosis in this case.
Case 6
A 66 year old lady with septicaemia of unknown cause. The ABG's on 30% O2 are:
pH
PaO2
PaCO2
HCO3
BE
SpO2
=
=
=
=
=
=
7.15
96
29
10
-1
96%
The primary acid/base disturbance is a metabolic acidosis (low pH and low
bicarbonate). The PaCO2 is also low implying respiratory compensation for the
metabolic acidosis. Let's try to confirm this using the equation for acute metabolic
acidosis:
Predicted
C
=
=
=
1.25 B + 10
13 + 10
23 mmHg
The measured PaCO2 (29 mmHg) is higher than that predicted. The patient has not
been able to mount a full repiratory response to her metabolic acidosis. This is
suggestive of an underlying respiratory problem and she in fact has a mixed metabolic
and respiratory acidosis and is consistent with pneumonia complicated by sespsi.
Again, we can confirm that this is a respiratory proboem by analysing her pulmonary
function. This time we’ll use the approximation to the alveolar gas equation :
≈
≈
PAO2
7 X 30 - 29 -10
171 mmHg
The predicted normal A -a gradient for this woman is:
“Normal” A - a
=
AGE / 3 + PAO2 / 5 - 23
=
66 / 3
=
33 mmHg
+ 171 / 5
-
23
ABG’s 27
The actual A-a gradient is 171 – 96 =
75 mmHg so there is confirmation of
respiratory disase consistent with pneumonia.
Case 7
A 16 y.o. boy with a history of cystic fibrosis presents with yet another chest infection.
The ABG's (on 35% oxygen) are:
pH
PaO2
PaCO2
HCO3
BE
SpO2
=
=
=
=
=
=
7.40
116
51
29
2
99%
At fiirst glance there appears to be no acid/base disturbance as the pH is "normal"
(7.40). However, the PaCO2 and the HCO3- are both elevated. This occurs in both
respiratory acidosis and in metabolic alkalosis.
So what's going on?
It helps to know that cystic fibrosis is associated with metabolic alkalosis, so we'll start
by applying the formula for metabolic alkalosis and seeing what we come up with:
Predicted
C
=
=
=
B / 2 + 30
29 / 2 + 30
45 mmHg
Now the PaCO2 = 51 mmHg which is higher than predicted. However, this would be
consistent with an acute respiratory acidosis superimposed on an underlying metabolic
alkalosis. This may well happen if this patient was having an acute pulmonary
infection. The combination of a chronically compensated metabolic alkalosis plus an
acute respiratory acidosis just happens to result in a "normal" pH in this case.
However . . . . . . . . . could there be another explanation? What about the possibility of
chronic respiratory acidosis in this patient? After all, CF is characterised by chronic
lung disease.
OK, this time we’ll analyse the ABG results using the formula for chronic respiratory
acidosis:
Predicted
B
=
=
=
C/2 + 2
51 / 2 + 2
28 mmol/L
This in fact is very close to the measured bicarbonate of 29 mmol/L.
So, where do we go from here? Do these ABG's represent a mixed metabolic alkalosis
and acute respiratory acidosis OR a pure chronic respiratory acidosis? Perhaps a
small clue can be gleaned from the "normal" pH which makes a pure acid/base
disturbance unlikely. But as with all laboratory tests, ABG's need to be interpreted in
light of the complete clinical picture and it is at this point that clinical judgement needs
to be exercised.
ABG’s 28
The clinical picture would be most consistent with the first explanation. However, there
may be elements of all three processes involved in this case!
SUMMARY
Arterial blood gases can reveal a great deal of information, far more than is usually
realised. The principles and rules presented in these notes will help you to rationally
and usefully interpret the data you receive back from the blood gas lab. You should be
able to tell a lot about your patients' respiratory function and acid/base status from one
simple blood test. But to make the most of this you must be prepared to sit down,
often with pen and paper, and spend a couple of minutes analysing the data. Do not
merely glance at the result slip and be satisfied with a superficial interpretation of the
results even though with experience you should be able to rapidly recognise obvious
patterns of pathology.
The last clinical case example (case 7) illustrates the principle that laboratory tests are
an aid to diagnosis only. To a large extent, lab tests, including ABG's, should be used
to confirm and quantify a clinical diagnosis. And remember above all. . . . . . . . . .
ALWAYS TREAT THE PATIENT
AND NOT THE MACHINE!
 John L Holmes Revised June 2008
ABG’s 29
Summary – FORMULAE & RULES of THUMB
Alveolar Gas Equation
PAO2
=
713 X FiO2
-
5 . PaCO2
4
Approximation to Alveolar Gas Equation
PAO2
≈
7 X %O2
-
PaCO2
- 10
Estimation of “normal” A-a gradient
A-a
=
age
3
+
PAO2
5
-
23
RULES OF THUMB IN ACID – BASE DISTURBANCES
METABOLIC ACID - BASE DISORDERS
C = 11/4 B + 10
C=
1
/2 B + 30
(acidosis)
(alkalosis)
RESPIRATORY ACID - BASE DISORDERS
B=
B=
1
B=
B=
1
/10 C + 20
1
/2 C + 2
/4 C + 14
1
/2 C + 4
(acute acidosis)
(chronic acidosis)
(acute alkalosis)
(chronic alkalosis)
ABG’s 30
FORMULAE & RULES OF THUMB USING SI UNITS (kPa)
Many hospitals in Europe use SI units when reporting ABG results. There is no
compelling reason for this other than to conform to standards in other disciplines.
The conversion factor between mmHg and kPa is 0.133 and the conversion factor
between kPa and mm Hg is 7.5
Thus 1 atmosphere = 760 mm Hg = 101 kPa
PaO2 “normal range “ = 90 - 100 mmHg = 12 .0 - 13.3 kPa
PaCO2 “normal range” = 35 – 45 mm Hg = 4.7 – 6.0 kPa
The formuale given above can be converted for use with SI units as follows:
Alveolar Gas Equation
PAO2
=
95 X FiO2
-
5 . PaCO2
4
Estimation of “normal” A-a gradient
A-a
=
0.04age
+
0.2PAO2
METABOLIC ACID - BASE DISORDERS
C = B/6 + 11/3
C = B/15 + 4
(acidosis)
(alkalosis)
RESPIRATORY ACID - BASE DISORDERS
B=
B=
B=
B=
3
/4 C + 20
4C
2C + 14
4C + 3
(acute acidosis)
(chronic acidosis)
(acute alkalosis)
(chronic alkalosis)
-
3