Arterial Blood Gases: Purpose and Indication

The purpose of arterial blood gas sampling is to assess patients respiratory status as well as acid base balance or rarely for laboratory testing, when venous blood is unavailable, and is frequently requested for seriously ill patients.
So, an arterial blood gas (ABG) will help in the assessment of oxygenation, ventilation, and acid-base homeostasis. It can also aid in the determination of poisonings (carboxyhemaglobinemia or methemaglobinemia) and in the measurement of lactate concentration.

Note: Pulse oximetry gives a reasonable estimate of the adequacy of oxygenation in many circumstances but does not assess acid-base status or ventilation and should not be used alone in cases where these measurements are important. However, most of the time if pulse oximetry gives normal readings, there is no need for arterial blood gas.

A. Basic Conditions Diagnosed by ABG’s

• Respiratory acidosis
Any condition making organism unable to decrease concentration of CO2, which increases acidity (decreases pH).
• Respiratory alkalosis
Any condition, causing hyperventilation when CO2 will be “washed” out leading to decrease acidity (increase pH).
• Metabolic alkalosis
Any condition, which increases base content and increases pH.
• Metabolic acidosisAny condition which decreases base content and decreases pH.
Blood gases helping to establish a diagnosis, to monitor severity, progression, and prognosis as well as guide therapy of:
• respiratory failure;
• cardiac failure;
• renal failure
• hepatic failure;
• diabetic ketoacidosis;
• poisoning;
• sepsis.
B. Acid-Base Balance; Compensatory Mechanisms; Respiratory and Metabolic Abnormalities

1. Acid-Base Balance: pH of the Blood

The acidity or alkalinity of a solution is measured using the pH scale. pH is a logarithmic measure of hydrogen ion concentration.

pH = -log[H+] , where log is a base-10 logarithm and [H+] is the concentration of hydrogen ions in moles per liter of solution.
pH has been more accurately defined accounting an activity factor. This represents the tendency of hydrogen ions to interact with other components of the solution, which affects among other things the electrical potential read using a pH meter.

Hydrogen ion activity coefficients cannot be measured directly and they are based on theoretical calculations. So, the pH scale is defined in practice as traceable to a set of standard solutions whose pH is established by international agreement.

For example, the hydrogen ion concentration in pure water at 25 °C  (77 °F) is about 1.0 × 10-7 M (pH 7) which is considered “neutral”, because the concentration of hydrogen ions is exactly equal to the concentration of hydroxide (OH-) ions produced by dissociation of the water. Increasing the concentration of hydrogen ions above 1.0 × 10-7 M produces a solution with a pH of less than 7, and the solution is considered “acidic”. Decreasing the concentration below 1.0 × 10-7  M produces a solution with a pH above 7, and the solution is considered “alkaline” or “basic”.

2. Respiratory and Renal Compensation in Acid-Base Imbalance

The pH of the blood is maintained within a normal range by a number of compensatory mechanisms, the mostly by the body buffer mechanisms (extracellular, and intracellular buffers) and the renal and respiratory systems. Buffers prevent a change in pH when H+ ions are added or removed.

The major extracellular buffer is HCO3-. HCO3- produced from the following chemical reaction:
CO2 + H2O ↔ H2CO3 ↔ H+  +  HCO3-
Minor extracellular buffer is Phosphate. Phosphate is most important as a urinary buffer. (H2PO4-/HPO4-2 – Phosphate buffer pair).

Intracellular buffers are organic phosphates (AMP, ADP, ATP, 2,3-DPG), proteins (Hemoglobin; Deoxyhemoglobin is a better buffer than Oxyhemoglobin in the physiologic pH range).

The degree of compensation varies between individuals and depends on the severity and duration of the primary problem and associated medical comorbidities.
Respiratory compensation for metabolic problems is usually rapid and almost complete. The lungs respond quickly by hyperventilation (Kussmaul Breathing) to blow off excessive CO2 (Carbon Dioxide) in metabolic acidosis or hypoventilation to retain Carbon Dioxide (in metabolic alkalosis).

The latter compensation is less complete than the former for obvious reasons.

The renal compensation for respiratory imbalances is slow and incomplete. The kidneys regulate extracellular fluid H+ ion concentration by:
• secretion of H+ ions;
• reabsorption of filtered HCO3- ions; and
• the production of new HCO3- ions.

Excess HCO3- is filtered into the renal tubules and eliminated in the urine. Depending on the need to excrete either an acid or a base load, the kidneys can excrete urine with a pH ranging from 4.5 to 8.0.

3. Abnormalities of Gas Exchange

a. Hypoxia

The first step is to detect the presence of hypoxia (i.e., less than 60 mm Hg on room air). Patients with clinically evident respiratory problems who have been given oxygen supplementation before blood gas analysis must be assumed to be hypoxic at this stage. If a patient is being given oxygen supplementation, then the ratio of the  pO2 (in mm Hg) to FiO2(in %) is used to detect hypoxia. Usually, the oxygen saturation of the blood is also noted which correlates with the pO2 of the arterial blood and helps in establishing the diagnosis of hypoxia. The saturation as obtained by a blood gas analysis is more accurate than that obtained by a pulse oximetry, as it is not influenced by shock states and skin pigmentation.

b. Hypercapnia

The pCO2 level must then be noted, which will help in differentiating between type I and type II respiratory failure.

Note: In type I respiratory failure, the pCO2 will be normal or low (</=45) and in type II respiratory failure, the pCO2 will be high (>45).
Differentiation between types I and II failure is essential to determine the etiology and institute further treatment. It may also rarely be used to restrict O2 supplementation in patients with type II failure because such patients are dependent on hypoxia for the respiratory drive and abolishing hypoxia might further suppress the CNS (Central Nervous System) stimulation for respiration.

Note: Patients with persistent hypoxia, rising CO2 levels and respiratory acidosis require mechanical ventilation and are usually seen by the anesthetist at this stage.

In patients on a ventilator, hypoxia might indicate one of several things, including:

1.  Disconnection of the breathing circuit ( which should be evident by the alarms, fall in O2, fall in saturation on pulse oximetry, clinical evidence of respiratory distress, etc.);
2. Development of pneumothorax which could be detected clinically and need confirmation by X-ray before intercostal tube drainage;
3. Development or worsening of pre-existing chest problems:
• Bronchopneumonia
• Acute Respiratory Distress Syndrome (ARDS)
• Pulmonary contusion

These conditions almost always require changes in settings of the ventilator like increasing FiO2 levels, ventilatory rate or tidal volume, adding or increasing Positive End-Expiratory pressure (PEEP), or changing to other modes of ventilation.

A high CO2 level is always associated with hypoxia unless the patient is on oxygen supplementation. However, hypercapnia associated with a normal oxygen level should also be approached with the same urgency as the patient might deteriorate rapidly. In patients on a ventilator, moderate rise in CO2 levels are currently considered acceptable and interventions to correct these might be associated with significant side effects including barotraumas and hypotension (permissive hypercapnia). Similarly, patients with Chronic Obstructive Pulmonary Disease (COPD) have adapted to higher levels of carbon-dioxide and might not require correction to normal levels.

Acute changes in pCO2 result in predictable changes in pH:

• Increase in pCO2 of 20 mm Hg (2.6 kPa) above normal, the pH falls approximately by 0.1
• Decrease in pCO2 of 10 mm Hg (1.3 kPa) below normal, the pH rises by 0.1.

Any change in pH outside these parameters is metabolic in origin. The kidneys take time to compensate for the change in pH the amount of renal compensation indicates the need for urgent correction. Correction will usually involve a combination of treatment of the cause, initiation of mechanical ventilation or modification of the settings and reduction of CO2 production.

Alveolar-arterial oxygen gradient (A-A) pO2: This is the difference in the oxygen partial pressures between the alveolar and arterial sides. In patients with type II respiratory failure, it may help to determine whether the patient has associated lung disease or just reduced respiratory effort.

The A-A gradient increases a little with age, but should be less than 2.6kPa (20mmHg). A normal gradient would imply conditions like CNS depression and neuromuscular disorders as the cause and a high gradient would imply some lung disease.

4. Abnormalities of Acid-Base Balance

The pH is usually maintained within a narrow range by a number of buffer systems in the body. A normal pH value may still be due to a well-compensated imbalance or a mixed acid base disorder and an abnormal value is definitely due to a poorly compensated acid base problem or due to both metabolic and respiratory decompensation causing an imbalance.

a. Serum bicarbonate

The actual bicarbonate is the value calculated from the blood gas sample. The standard/corrected bicarbonate is the value obtained after correction of CO2 levels to 40mm Hg and at 25 °C  (77 °F) (room temperature). It gives a better estimate of the metabolic problem causing acid base imbalance. The base deficit/excess is the amount of deviation of the standard bicarbonate from the normal. The metabolic problem could either be a low (base deficit or metabolic acidosis) or high (base excess or metabolic alkalosis) standard bicarbonate.

b. Compensation

A primary metabolic derangement will be accompanied by some degree of respiratory compensation. The ability to detect the primary abnormality and the amount of compensation is covered by other co-existing conditions causing respiratory acidosis and/or alkalosis. Co-existing medical problems can cause both metabolic acidosis and alkalosis.

c. Metabolic acidosis

Metabolic acidosis can be due to a number of conditions. Treatment of metabolic acidosis is treatment of the cause. Direct administration of sodium bicarbonate is last choice and reserved for severe cases. A variety of conditions can result in metabolic acidosis, the most important among them being the under perfusion of tissues resulting in accumulation of lactic acid. Differentiation of the causes of metabolic acidosis requires the estimate of an entity called the “anion gap”.

d. Serum Anion Gap

Serum anion gap = [Na+] – [Cl-] – [HCO3-]
Body fluids including blood may contain a variable number of ions, but the total number of anions (negative ions) and cations (positive ions) are approximately the same. The ions that are usually measured in blood are cations like sodium (Na+) and potassium (K+) and anions including chloride (Cl-) and bicarbonate (HCO3-). There are unmeasured ions in both groups (cations and anions), which also contribute to the ionic constitution of blood. The measured cations are usually greater than the measured anions by about 8-16mmol/L. This is because the unmeasured anions constitute a significant proportion of the total number of anions in blood. Proteins make this up predominantly, but also included are sulphates, phosphates, lactate and ketones.
Decreased anion gap can be caused by:
• hypoalbuminemia;
• severe hemodilution;
• increase cation concentrations (calcium and magnesium).

Increased anion gap can be caused by:
• dehydration;
• raised unmeasurable anions (lactate, ketones and renal acids);
• treatment with drugs which are an organic acids (penicillin, salicylates); 
• poisoning with methanol, ethanol and paraldehyde;
• decreased cation concentrations (calcium and magnesium).

Raised anion gap metabolic acidosis
Accumulation of a number of acids can result in raised anion gap metabolic acidosis. In such cases, the reduction in serum HCO3- matches the anion gap. If not, possible a second acid base disorder, should be kept in mind. When metabolic acidosis and alkalosis coexist, as in vomiting and ketoacidosis, the plasma HCO3- may be normal, and a raised anion gap may be the initial evidence of an underlying acid-base disturbances.

To differentiate between the causes of increased anion gap metabolic acidosis the best way to
measure the osmolar gap (difference between the measured osmolarity and the calculated osmolarity).
Normal anion gap (hyperchloremic) metabolic acidosis
Normal anion gap metabolic acidosis results from conditions wherein there is a loss of alkali (i.e.HCO3-) or metabolic equivalent (eg, excretion of salts of organic anions in proportionate excess of chloride) or an accumulation of HCl or metabolic equivalent (eg, NH4Cl and chloride salts of amino acids).
Loss of HCO3- can occur due to:
• Extrarenal causes (for example: excessive diarrhea or drainage of gastrointestinal secretions, NH4Cl administration, parenteral nutrition, rapid saline infusion and congestive cardiac failure).
• Renal causes (renal excretion or insufficient generation, for example: various types of renal tubular acidosis- RTA type I, RTA type II and RTA type IV).
• Some surgical conditions.

Some causes of Metabolic Acidosis include:
1. Ketoacidosis (accumulation of β-OH-butyric acid and aceto-acetic acid; ↑anion gap )
2. Lactic acidosis (accumulation of lactic acid during hypoxia ; ↑anion gap)
3. Chronic renal failure (failure to excrete H+ as titratable acid and NH4+ ; ↑anion gap)
4. Salicylate intoxication (also can cause repsiratory alkalosis ; ↑anion gap)
5. Methanol/formaldehyde intoxication (produces formic acid ; ↑anion gap)
6. Ethylene glycol intoxication (produces glycolic and oxalic acids ; ↑anion gap)
7. Diarrhea (GI loss of HCO3-; normal anion gap)
8. Type 2 renal tubular acidosis (renal loss of HCO3-; normal anion gap)
9. Type 1 distal RTA (failure to excrete titratable acid and NH4+ and failure to acidify urine; normal anion gap)
10. Type 4 RTA (hypoaldosteronism with hyperkalemia and failure to excrete NH4+; normal anion gap)
e. Metabolic Alkalosis

Metabolic alkalosis can result from the loss of acid, addition of alkali or both in the kidneys or elsewhere. Extrarenal sites include stomach (loss of acid), redistribution of alkali from the intracellular stores to the ECF (as in potassium or chloride depletion), oral administration (antacids, ion-exchange resins, milk alkali syndrome, oral HCO3-) and parenteral administration of alkali (citrate in blood transfusions, bicarbonate in severe metabolic acidosis).
Renal causes of alkali excess include mineralocorticoid excess, response to long-standing hypercapnia (persists even after correction of respiratory acidosis), hypokalemia (promotes H+ secretion in the distal nephron) and ECF volume depletion (impaired HCO3- excretion). Certain conditions can cause metabolic alkalosis by a number of mechanisms (e.g. diuretic use causes both ECF depletion and hypokalemia).

Some causes of Metabolic Alkalosis include

1. Vomiting (loss of gastric H+; leaves HCO3- behind in blood; worsened by volume contraction;hypovolemia; may have ↑anion gap due to production of ketoacids)
2. Hyperaldosteronism (increased H+ secretion by distal tubule)
3. Loop or thiazide diuretics (volume contraction alkalosis)

f. Respiratory Acidosis
Respiratory acidosis is caused primarily by decrease in respiratory rate and retention of CO2.

Note: There is no respiratory compensation for respiratory acidosis.

Respiratory acidosis  is compensated by renal system. Compensation consists of increased excretion of H+ and NH4+, and increased reabsorption of HCO3-.

Some causes of Respiratory Acidosis include:
1. Some drugs: Opiates, sedatives; anesthetics (inhibiion of medullary respiratory center)
2. Guillain-Barré syndrome (weekening of respiratory muscles)
Note: Guillain–Barré syndrome is an acute inflammatory demyelinating polyneuropathy (AIDP), an autoimmune disorder affecting the peripheral nervous system, usually triggered by an acute infectious process.
3. Polio (weekening of respiratory muscles)
Note: Polio (Poliomyelitis) is a viral disease that can affect nerves and can lead
to partial or full paralysis.
4. ALS (weekening of respiratory muscles)
Note: Amyotrophic lateral sclerosis (abbreviated ALS, also referred to as Lou Gehrig’s disease) is a form of motor neuron disease. ALS is a progressive, fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement.
5. Multiple sclerosis (weekening of respiratory muscles)
Note: Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms.
6. Airway obstruction
7. ARDS (adult respiratory distress syndrome) (decrease CO2 exchange in pulmonary capillaries)
8. COPD (chronic onstructive pulmonary disease) (decrease CO2 exchange in pulmonary capillaries)

f. Respiratory Alkalosis

Respiratory alkalosis is caused by a primary increase in respiratory rate and loss of CO2,  so hypocapnia caused by  hypoxia and its causes (type I respiratory failure).

Note: There is no respiratory compensation for respiratory alkalosis.

Respiratory alkalosis can be compensated by renal system. Compensation consists of decreased excretion of H+ and NH4+, and decreased reabsorption of HCO3-.

Some Causes of Acute Respiratory Alkalosis include:
1. Anxiety
2. Fever
3. Pain
4. Sepsis
5. Acute liver failure
6. CNS disorders (stroke, infections)

7. Pulmonary disorders without hypoxia (infections and interstitial lung disease)
8. Delirium tremens
Note: DT (Delirium tremens) is a severe form of alcohol withdrawal that involves sudden and severe mental or neurological changes.
9. Salicylate intoxication (direct stimulation of medullary respiratory center; also causes metabolic acidosis).

Some Causes of Chronic Respiratory Alkalosis include:
1. High altitude (hypoxemia causes increase of ventilation rate)
2. Chronic liver failure
3. Chronic pulmonary disease
4. CNS trauma
5. Anemia
6. Hyperthyroidism
7. Beriberi
Note: Beriberi is a nervous system ailment caused by a deficiency of thiamine- vitamin B1.
8. Pregnancy

Treatment should be directed towards the cause.

Note: There is possibilities to use Venous Blood Gas instead of ABG.
Normal Range for Venous Blood Gas:
pH – 7.32-7.42 (little bit lower than arterial pH but almost the same).
pO2 – 40-50 mm/Hg
pCO2 – 46 mm/Hg

So, in many situation, pulse oximetry, as well as VBG are quiet reliable. Of course pulse oximetry is not enough, especially in carbon monoxide poisoning, and in significant drop of oxygen saturation, however in these cases VBG may be useful.

Ramaz Mitaishvili, MD

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