According to electrochemical law, equal number of anions balance equal number of cations giving electrical neutrality. A small amount of anion that cannot be measured by biochemical investigations is named as anion gap:

(Na+ + K+) = (Cl– + HCO3–) +

(Unmeasured anions) (Anion gap)

(135 + 04) = (100 + 24) + 8 to 16

In some type of metabolic acidosis, addition of acids results in fall of HCO3 . In this condition to maintain the anionic charge, unmeasured anions increase without any alterations of chloride level, known as metabolic acidosis with increased anion gap also known as "normochloremic acidosis". In metabolic acidosis with normal anion gap, basic pathology is loss of bicarbonate ions where chloride level is increased, this is designated as "hyperchloremic acidosis" (Table II).

Since the management of each type of metabolic acidosis grossly differs, anion gap calculation may be useful apart from the detailed clinical history and evaluation. These children should be subjected to investigations like serum electrolytes, urea, creatinine, sugar, ketone bodies, etc.

If increased anion gap acidosis (normochloremic acidosis) is evident, the etiology should be identified and corrected, where administration of HCO3– may be hazardous. In children with normal anion gap acidosis (hyperchloremic acidosis) bicarbo-nate correction should be done judiciously.

Since acidosis is beneficial to the body homeostasis, correction should be attempted only when HCO3– goes below 15 mEq/L (pH 7.2 or base deficit reaches 10 mmol/L). Overzealous correction of acidosis with HCO3 (hypertonic solution) leads to many adverse effects like shifting of the oxygen-hemoglobin dissociation curve to the left resulting in poor release of O2 at tissue level, precipitation of hypokalemia, intraventricular hemorrhage, hypernatremia and hypocal-cemic tetany. So the correction of acidosis is advised only when HCO3– falls below 15 mEq/L.

(15 – measured HCO3–) × 0.6 × Body weight                               (in kg)

Half of the HCO3– correction can be done immediately by slow intravenous administra-tion after diluting with 5% dextrose, the rest can be added in the maintenance fluid over 24 hours.

Metabolic alkalosis results due to loss of acids (H+ ions) from the gastrointestinal tract, through renal mechanisms, due to alkali gain or due to disproportionate loss of extracellular fluid. (Table III).

In metabolic alkalosis the child may present with shallow respiration (hypo-ventilation) in an attempt to conserve CO2 . However the compensation cannot extend beyond physiological limits (PaCO2 may not rise above 55 mm of Hg). When the alkalosis increases, altered sensorium, muscle cramps, dysarrhythmias and features of tetany due to low ionized calcium and acetyl choline release, may occur.

Many children with metabolic alkalosis may present with volume loss and or associated hypokalemia. The correction of these derangements will automatically restore functional derangements. When glomerular filtration rate (GFR) is maintained with adequate ECF volume, the normally functioning kidney will eliminate excessive HCO3– (alkali loss), reduce the production of NH3 (acid gain) thereby normalizing the basic pathology. Contrary to this, if ECF volume is not adequately maintained, low GFR results in HCO3– retention (alkali gain) and increased aldosterone production resulting in further loss of H+ ion (acid loss) in exchange of Na+ at the distal convoluted tubule. However, in hypokalemic state, body loses H+ in exchange offer while retaining sodium resulting in paradoxical aciduria. Thus, the presence of associated hypokalemia aggravates the basic pathology. The best way to manage metabolic alkalosis (saline responsive) is to maintain adequate ECF volume and serum potassium.

Metabolic alkalosis resulting from in-creased aldosterone activity (saline resistant) will respond to aldosterone antagonists (spironolactone), ACE inhibitors, or at times to amiloride and indomethacin. Estimation of urinary chloride may help to differentiate saline responsive (urine chloride-level <10 mEq/L) from saline resistant (urine chloride >10 mEq/L) type of metabolic alkalosis(6).

Mild respiratory disorders causes hypoxemia (oxygenation failure or Type I respiratory failure) resulting in respiratory alkalosis as the hypoxic drive causes hyperventilation and wasting out of carbon-di-oxide. Other than lung diseases, heart disease, sepsis, central nervous system infection, and hysterical overbreathing may result in respiratory alkalosis (Table IV).

Children with respiratory alkalosis need prompt oxygen supplementation apart from correcting the basic pathological condition. Oxygen is a drug, which should be used judiciously. Since the PaO2 of 60 mm of Hg saturates 90% of the hemoglobin (SaO2) majority of children with mild lung condi-tions may not require supplemental oxygen therapy. However, when PaO2 falls below 60 mm of Hg, SaO2 falls steeply hence oxygen supplementation should be done imme-diately. Majority of the clinical situations can be managed with nasal catheter or face mask alone with oxygen flow rate of 6-8 litres /minute. Respiratory alkalosis induced by hysterical breathing is common in adolescent girls and is best managed by rebreathing in paper bag.

Ventilation is a process, which needs the co-ordinated activity of central nervous system and thoracic cage (pump) and lungs. Advanced respiratory disease, thoracic cage and neuromuscular dysfunction leads to carbon-di-oxide retention (PaCO2 >45 mm of Hg) resulting in respiratory acidosis also known as ventilatory (Type II) failure (Table V).

In ventilatory failure CO2 should be eliminated from the body at the earliest, which can be done by mechanical ventilatory support. Oxygen supplementation is essential, as oxygenation failure is invariably present. When respiratory support is not feasible, bag and mask ventilation should be continued till adequate ventilatory support is made available to eliminate CO2.

In metabolic dysfunction the body buffers take an important role to normalize the pH. In metabolic acidosis, the buffer base becomes negative which is referred to as "base deficit" or negative base excess. Buffer base will remain unaffected in respiratory problem. Since there is a constant relationship between PaCO2 and pH the respiratory pH can be predicted. By finding the difference between respiratory pH (predicted) and measured pH (laboratory value), base excess and base deficit can be calculated. Though the calculation of base excess and deficit is not mandatory in all the cases, such calculation is important in the management of metabolic problems to quantify the contribution of the body buffer base system especially when administration of HCO3– is desired.

The most important interpretation in ABG is to look for the adequacy of oxygenation status. The normal partial pressure of O2 in the artrial blood (PaO2 ) is 80-100 mm of Hg in adults on breathing at atmospheric oxygen (which contains 21% of oxygen = FiO2 21%). When fraction of the inspired O2 (FiO2) concentration increases, the arterial PaO2 increases by five times (PaO2 = FiO2 × 5). When PaO2 falls below 80 mm of Hg, hypoxemia results which can be classified as either mild (PaO2 of 60-80 mm), moderate (PaO2 of 40-60 mm) or severe (PaO2 <40 mm).

The tolerance of hypoxemia is better at extremes of ages. Thus in newborn baby, the normal PaO2 is 40-70 mm of Hg and in older age (> 60 years) PaO2 falls by 1 mm of Hg frm the lower limit of normal PaO2 (80 mm Hg) for every year increase of age (e.g., at 90 years of age, PaO2 of 60 mm Hg is normal). Arterial oxygen tension (PaO2 ) depends upon atmospheric oxygen content and adequacy of ventilation.

Though PaO2 reflects oxygen level in arterial blood, the adequacy of tissue oxygenation ultimately decides cellular metabolism. Reduction of oxygen at tissue level is called hypoxia. In addition to PaO2, other parameters like hemoglobin content, circulatory efficiency and mitochondrial function (cytochrome oxidase) decide ultimate delivery of oxygen to tissues. In ahypoxic child maintenance of the above parameters are important to ensure normal aerobic metabolism.

Further, the delivery of oxygen at the tissue level is decided by the shift of Oxygen hemoglobin dissociation curve. Shift to the right is advantageous to the body as the liberation of oxygen at the tissue level is more. This occurs in acidosis, pyrexia, hypercarbia and increased DPG level.

Though estimation of PaO2 through ABG is the best investigation to identify oxygena-tion status and acid base disturbances, it requires arterial puncture every time. Since a constant relationship exists between PaO2 and oxygen saturation of hemoglobin (PaO2 40 mm of Hg = SaO2 70%; PaO2 50 mm of Hg = SaO2 80%; PaO2 60 mm of Hg = SaO2 90%) real time monitoring of oxygen status by estimating SaO2 with pulse oximetry is (a non-invasive technique) popularly practiced though it has its own limitations. By placing the sensor in the arterial catheter, continuous arterial gas monitoring is possible(8). Pulse oxymetry is useful to assess the oxygenation status in minor cardiopulmonary diseases and procedures; however, at higher oxygen tension, poor perfusion status and in meth-haemoglobinemia, pulse oximetry fails.

Memorizing the normal values of arterial blood gas analysis is an important pre-liminary exercise before going for actual ABG interpretation (Table VI).

The radial artery at the wrist is the most preferred site of ABG specimen collection as it has adequate collaterals where inadvertent puncture of veins is unlikely. When this is not feasible, popliteal, brachial or femoral arteries can be chosen. The injection site is cleansed with iodine or alcohol. The index and middle finger of the other hand can be used to palplate the artery. Heparinized syringe with 22 gauge needle should be held like a pen with 45º angle (with beveled edge of the tip facing downwards) and the artery should be punctured just 2 cm above the wrist crease.

ABG syringes are the most advantageous where the arterial blood gets filled on its own without any application of suction force and ensure anaerobic collection. Presence of air bubbles may increase oxygen values and lower CO2 values. If ordinary syringes are used, the nozzle should be stoppered immediately and transported to the laboratory by placing on an ice slush or refrigerated to reduce metabolism of red blood cells(9). Estimation should be done immediately otherwise values of oxygen and CO2 may be altered due to cellular metabolism. Though 0.05 ml of heparin is enough for 1 ml of blood, upto 0.1 ml of heparin may not interfere with blood gas values. Excess of heparin should be avoided as it may increase the acidity because of its high hydrogen ion concentration. After arterial puncture, the site should be compressed tightly for 3 to 5 minutes to prevent hematoma formation.

ABG Interpretation - Step by Step Approach(9)

I. pH: Acidosis/alkalosis
II. Respiratory/Metabolic
III. Stages of compensation
IV. Oxygenation status
V. Simple disorder/Mixed disorder
VI. Acute/chronic
VII. Laboratory error

By looking at the pH we will be able to differentiate normal pH from acidemia and alkalemia. Normal pH ranges between 7.36 to 7.44; pH less than 7.36 denotes acidemia and above 7.44 alkalemia.

Acidemia would be either due to increase of PaCO2 or fall of HCO3–. Alkalemia would be either due to decrease of PaCO2 or increase of HCO3–.

In respiratory acidosis kidney regenerates HCO3– and increase the HCO3– level as a compensatory response in addition to hyper-ventilation. Similarly, in respiratory alkalosis loss of HCO3– occurs through kidney as a compensatory event.

Metabolic acidosis is compensated by hyperventilation (Kussmaul’s breathing), when elimination of CO2 increases the pH to alkaline side. Metabolic alkalosis occurs when HCO3– level exceeds the normal limit, which is compensated by hypoventilation to increase CO2 level.

During initial stage of acid-base disturbance there is no time for compensa-tion this phase is known as acute or uncompensated stage where pH and one of the parameters PaCO2 or HCO3– is abnormal. To normalize the pH, compensation occurs where body buffers come first (within minutes) followed by respiratory (within hours) and renal system buffering (within days). The initial compensation is not complete and is known as subacute or partially compensated stage where both the parameters (CO2 and HCO3–) change in the same direction. In fully compensated stage (chronic state), pH becomes near normal with abnormally altered PCO2 or HCO3–. Accord-ingly the ABG disorder may either be acute (uncompensated), subacute (partially com-pensated) or chronic (fully compen-sated).

While assessing the oxygentation status, knowledge regarding age of child and the inspired oxygen concentaration (FiO2) are very important. The normal value of PaO2 is 80-100 mm of Hg in children and adults whereas in a normal newborn it ranges from 40-70 mm of Hg. In older age, the normal PaO2 comes down from the adult level. In children with supplemental oxygen therapy the PaO2 will be high (PaO2 = FiO2 × 5).

Irrespective of the oxygen status, if the child is critically ill with cardiopulmonary problem, the child should be benefited with 100% oxygen. It is advisable to keep the oxygen supplementation below 60% to avoid oxygen toxicity (bronchopulmonary dysplasia, retrolental fibroplasia). Another important factor that should be borne in mind is the hemoglobin status. Even if PaO2 and SaO2 is normal, where the hemoglobin is inadequate the final delivery of O2 to the tissues will be compromised.

In simple acid base disorder, both PaCO2 and HCO3– change in the same direction. If they do not follow this trend, the possibility of mixed disorder is likely. The expected compensation for simple acid base disorder is predetermined and if they deviate from the norms there is the possibility of mixed disorder. If the difference between total carbon dioxide (TCO2) and HCO3– is more than 1.2 in addition to metabolic problem, the underlying respiratory disturbance should be thought of. When both actual bicarbonate and standard bicarbonate are not the same, in addition to respiratory added metabolic component should be thought off. Gross deviation of buffer base reflects the under-lying metabolic problem.

Common problems leading on to mixed disturbance are acute severe asthma, shock, cardiopulmonary arrest, respiratory distress syndrome in newborn, diarrhea with vomit-ing, decompensated liver disease, diuretic therapy and salicylate poisoning (10).

By knowing the duration of illness, we can easily adjudge whether it is an acute or chronic problem. This knowledge is important because the compensation that occurs during acute and chronic stage especially in respiratory disorders grossly differs due to delayed renal compensation that occurs in addition to buffer base adjustment (Table VII).

According to the Henderson Hasselbach equation, out of the three measured values (pH, PaCO2, HCO3–) if two are known, the third can be calculated provided the pH is presented as H+ ion concentration. If there is discrepancy between the measured value and calculated values one should suspect laboratory error by applying the following formula: H (nmol/L) = 24 ´ (PCO2 / HCO– ).

Application of ABG in day to day clinical practice on a sick child is the secret behind the proficiency of this complex subject. Examples may illustrate. Let us work out the ABG status in following clinical situations (Table VIII).