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Analysis of blood gases and acidebase balance
James Day Jaideep J Pandit

ðPCO2 Þ. This yields the familiar HendersoneHasselbalch equation (HeH equation): Â Ã pH ¼ pK þ log10 HCOÀ =PCO2 Â 0:23 3 where 0.23 is the solubility coefficient for CO2. In this negative logarithmic scale a small change in pH reflects a relatively large change in [Hþ] in the opposite direction. A change of 0.3 pH units is equivalent to doubling or halving the [Hþ]. The range of [Hþ] compatible with life is 20e160 nmol/l (pH 7.70e6.80). See Table 1 for pH values against hydrogen ion concentrations. The start of clinical acidebase measurement was the poliomyelitis epidemic in the 1950s. Large numbers of patients needed artificial ventilation for extended periods. This was really the birth of intensive care as a speciality. To titrate ventilation, measurements of carbon dioxide partial pressure ðPCO2 Þ were needed; this was initially achieved by measuring pH and HCOÀ and using the 3 HeH equation to derive PCO2 .

Analysis of blood gases is widely used for patients with many different conditions from surgical, medical and intensive care fields. Knowledge of the basic science behind the subject is essential to gain a full understanding of what the results mean on a typical blood gas result. Understanding the history of acidebase physiology and why certain analytical tools were developed can make interpretation easier. The scope of this article is to explain some of the background to this area and show how it relates to clinical medicine.

Keywords Acidebase balance; acidosis; alkalosis; blood gas analysis

Chemistry of water
The human body is composed mostly of water. Water is a simple triatomic molecule with strong ionic bonds between O and H with unequal charge distribution. This gives rise to the physical characteristics of water. Water has a large dielectric constant so molecules with strong ionic bonds dissociate when in water. Water itself dissociates only slightly.  à  à K  ½H2 OŠ ¼ Hþ  OHÀ The concentration of water is altered only slightly by dissociation so the left hand of the equation can be taken as a constant. This is termed K0 w (the ion product of water). Therefore: à  à  K0 w ¼ Hþ  OHÀ For electroneutrality, [Hþ] must equal [OHÀ]. At 25  C, pure water has a K0 w of 1.008  10À14 mol2/litre3. Thus we can say that [Hþ] ¼ [OHÀ] ¼ 1  10À7 Eq/litre. Using Sorensen’s pH scale this gives a pH of 7. However, as temperature changes, so does molecular activity and at 37  C, for solutions in the body, K0 w ¼ 4.4  10À14 mol2/litre3. Thus [Hþ] and [OHÀ] are both increased in proportion. In other words, a ‘neutral’ pH of 7 is only true for a temperature of 25  C. At body temperature, acidebase ‘neutral’ pH is 6.8. At 0  C ‘neutral’ pH is 7.5 and at 100  C ‘neutral’ pH is 6.1. pH is therefore simply a measure of

Background to acids and bases
In 1909, Sorensen introduced the pH terminology to measure hydrogen ion concentration:  à pH ¼ Àlog10 Hþ pH is thus a compressed, non-linear and dimensionless scale. This is useful for chemists who work with a large range of concentrations but clinicians only deal with a clinical range of 20e160 nmol/litre. In 1909, Henderson rearranged the equilibrium reaction for carbonic acid: CO2 þ H2 O/H2 CO3 /H To give the ‘Henderson equation’:  à à  Hþ ¼ K1  ½H2 CO3 Š= HCOÀ 3


where K1 ¼ dissociation constant. Substituting [CO2] for [H2CO3] gives:  à  þà H ¼ K1  ½CO2 Š= HCOÀ 3 Hasselbalch (1916) further changed the equation to fit in with Sorensen’s (1909) pH terminology by taking logarithms and substituting [CO2] for the partial pressure of carbon dioxide

pH and [HD] concentration
pH HD concentration (nmol/litre) 1 10 40 50 100 mol/litre 10À9 10À8 10À7.4 10À7.3 10À7

James Day BSc MRCS MRCP is a Specialist Registrar in Anaesthesia at the John Radcliffe Hospital, Oxford, UK. Conflicts of interest: none declared. Jaideep J Pandit MA BM DPhil FRCA is a Consultant Anaesthetist and Senior Clinical Lecturer at the John Radcliffe Hospital, Oxford, UK. Conflicts of interest: none declared.

9.0 8.0 7.4 7.3 7.0 Table 1



Ó 2010 Elsevier Ltd. All rights reserved.

The effects of respiratory acidosis/alkalosis are eliminated.g. Note that these are bases and not actually acidic. The most common in use is the Radiometer developed in Denmark. These are usually referred to by their anion (lactate. Some of these variables are measured directly by the machine and some are derived. Around 13. An acidic buffer consists of a weak acid and a salt of the acid. 3. and with haemoglobin fully saturated with O2. The buffering systems present are either:  blood (carbonic acid/bicarbonate. plasma proteins. phosphate). There are a number of ‘defence’ mechanisms to try to resist changes in [Hþ] which is important for homeostasis: 1. The pH electrode separates a buffered solution and the sample with a pH sensitive glass membrane.4 at PCO2 5. A stable reference electrode is connected to the pH electrode. Organs such as the heart and brain are sensitive to changes in [Hþ]. Derived variables include:  Actual bicarbonate: is usually 24 mmol/litre and is derived from the HeH equation. This is important given the high buffering capacity of Hb. sulphate.000 mEq/day of acid are excreted by the lungs as CO2 compared with 100 mEq/day as metabolic acids. Over time a number of analytical methods have been developed to try to identify the causes of the acidebase disturbance that are measured. haemoglobin. and is the actual concentration in the sample. phosphate. This terminology is common place because they have been formed by the liberation of an Hþ from their parent acid. None of the following methods are fully accurate and each has their own groups of followers.  Base excess: the quantity of strong acid (or base) required to titrate 1 litre of blood back to pH 7. All rights reserved. [Hþ] is measured using a modified pH electrode. Renal: alteration in HCOÀ excretion. the induced voltage being proportional to the [Hþ]. This comprises a silver/silver chloride anode and platinum cathode in an electrolyte bath.BASIC SCIENCE hydrogen concentration and does not necessarily reflect acide base neutrality.  PaO2: measured using a polarographic (Clark) electrode.3 kPa (40 mmHg) at 20  C and actual HCOÀ calculated from the volume of PCO2 3 evolved when acid (HCl) is added to the sample. Plasma is equilibrated with PCO2 5. A buffer is a solution that resists changes in pH when acid or alkalis are added. A small potential difference is applied across the electrodes and the current measured. The induced current is directly related to the PO2. Removal of carbon dioxide is useful as it will reduce intracellular pH as carbon dioxide can cross membranes very easily. The lungs have a huge capacity to increase ventilation and remove carbon dioxide from the body.  PaCO2: measured using a Severinghaus electrode.3 kPa (40 mm Hg) and 37  C. Directly measured variables are:  pH: measured using a pH electrode. Respiratory: alteration in arterial carbon dioxide pressure ðPCO2 Þ. The body has a huge buffering capacity which is virtually immediate in effect. 2. The acid load produced by the body each day is substantial. . but not the cause.3 kPa (40 mmHg) at 37  C. 108 Other variables also routinely included Oximetry status C Alveolar arterial oxygen gradient C Oximetry values C Haemoglobin concentration C Oxygen saturation C % of oxyhaemoglobin C % of carbaminohaemoglobin C % of methaemoglobin C Haematocrit Electrolyte values Potassium C Sodium C Calcium C Chloride Metabolic values C Glucose C Lactate Oxygen status C Oxygen content C Oxygen p50 C Table 2 SURGERY 29:3 Ó 2010 Elsevier Ltd. If temperature correction is performed then the reference ranges are not applicable as these are for 37  C only. Normal range is 24e33 mmol/litre. These non-volatile acids are also termed ‘fixed’ acids. The kidneys are 3 responsible for adjustment of bicarbonate excretion but the process is much slower taking several days to reach maximal capacity. Current practice is to not temperature correct. The acid produced is either volatile (CO2) or non-volatile acids. b-hydroxybutyrate). if the patient is hypothermic).  Standard base excess: is the base excess when the [Hb] is set at 5 g/dl which is an approximation for all extracellular fluid (ECF) not just blood. The variables above reflect the effect. CO2 diffuses across a membrane where a chemical reaction releases Hþ ions. Acidebase physiology Hydrogen ion concentration has important effects on body proteins. phosphate)  intracellular fluid (proteins. It measures PCO2 directly. Buffering: is a rapid physico-chemical response. of acidebase disorders. Analytical approaches to acidebase disorders Although blood gas analysis is widely used it provides incomplete information about acidebase chemistry.  Standard bicarbonate: is the concentration of bicarbonate when the sample is equilibrated with PCO2 5. The potential difference across this membrane is measured. It consists of two half cells.  See Table 2 for other variables that are also routinely included. An increase in ventilation will reduce the level of carbon dioxide. Measurement of blood gases: arterial blood gas analysis A standard blood gas analyser gives us the figures for many variables. There is a function to temperature correct the sample (e. acetoacetate. Temperature correction The blood gas machine analyses the samples at 37  C.

If the hyperventilation is persistent 3 e. In plasma. Respiratory acidebase disturbances Respiratory acidosis is a process caused by a rise in PaCO2. Chloride deficiency causes the kidney to reabsorb more HCOÀ than normal: an adequate 3 anion level is required for electroneutrality with the cations Naþ and Kþ. We will discuss the common changes under the broad headings ‘respiratory’ and ‘metabolic’. generated or destroyed. since it assumed that PCO2 and HCOÀ are independent variables. CO2 and weak acids) c.g. etc  a loss of acid from ECF. Strong ions (fully dissociated e. vomiting or nasogastric suction. Weak ions (partially dissociate e.e. Stewart identified three principal mathematically independent variables which.35). The drawback with this concept was the alteration of buffering capacity associated with changes in haemoglobin concentrations. Increased CO2 production occurs in exercise and in malignant hyperthermia. They developed the concept of the ‘buffer base’. interdependent. As SID decreases (i. SURGERY 29:3 . If alkalosis supervenes. Dissociation: body fluids can be considered as aqueous solutions that contain: a. In plasma. Arterial hypoxaemia can be corrected by supplemental oxygen although this does nothing to correct the level of CO2. This was the sum of all the buffering agents in the blood. a Canadian physiologist. the rise in plasma ½HCOÀ Š is only brief. HCOÀ 3 3 3 is excreted by the kidney. e. The PaCO2 rises and causes an increase in hydrogen ion concentration depressing the pH. e. This can occur by excessive minute ventilation if the patient’s lungs are mechanically ventilated or as a physiological response to hypoxia. Electroneutrality: in aqueous solution. Whenever plasma ½HCOÀ Š rises >24 mmol/litre. and hence on [Hþ]. but in fact they are in 3 dynamic equilibrium i. NaCl) b. In healthy humans. diuretics.45. Mass conservation: the amount of any substance remains constant unless it is added. removed.g.BASIC SCIENCE The initial approach was termed the ‘Boston’ approach. All rights reserved. These variables are:  carbon dioxide  total weak acid concentration e mainly plasma proteins (principally albumin) and phosphates  strong ion difference (SID) given by the total concentration (in mequiv/litre) of fully dissociated cations in solution minus the total concentration of fully dissociated anions in solution. iii. infusion of NaHCO3. If 100 ml 8.g. developed by researchers from that city. The kidney’s response is quick and effective. plasma SID is 40e44 mmol/ litre. His model is based on the following properties of water-based solutions: i. PaCO2 is proportional to VCO2/VA (where VCO2 is CO2 production by the body and VA is alveolar ventilation). Metabolic acidebase disturbances Metabolic alkalosis is a process caused by a rise in plasma ½HCOÀ Š. water dissociates more to maintain electrical neutrality. Other approaches are the anion gap (which we describe later) and Stewart’s theory.g. becomes less positive). when changed. It is deemed to be inaccurate to refer to a compensatory process as either an acidosis or alkalosis. A rise in PaCO2 can therefore only be caused by presence of CO2 in inspired gas. Non-electrolytes (non charged species) ii. which acts to inhibit or overcome this rapid excretion of excess bicarbonate. Processes for maintaining an alkalosis include:  chloride depletion  potassium depletion. Metabolic acidosis is produced by a decrease in SID. hyperventilating in response to an acidosis should be referred to as respiratory compensation and not a respiratory alkalosis.35 whereas an alkalaemia refers to a pH > 7. Likewise an alkalosis refers to the process rather than the state. dictate the acide base balance.g. They used acidebase maps in chronic patients to calculate how serum bicarbonate is related to carbon dioxide tension using the HendersoneHasselbalch equation. They concentrated on the metabolic component of acidebase disturbances. e. citrate from stored blood. This approach was refined by the base deficit/excess concept as a measure of metabolic acid/base activity. Most causes are due to alveolar hypoventilation. The SID has a powerful electrochemical effect on water dissociation. strong cations (mainly Naþ) outnumber strong anions (mainly ClÀ): the difference between them is as follows: à  à  SID ¼ Naþ þ Kþ þ Ca2þ þ Mg2þ À ClÀ þ lactateÀ Of note bicarbonate is not a strong ion. which also usually causes a decrease in oxygen uptake. elevating the pH. the sum of all the positive charged ions must equal the sum of all the negative charged ions. 3 there must therefore be a process at work. This is prompted 3 by an increase in CO2 in the renal tubular cells. In 1983. Chloride and HCOÀ are the only anions in significant 3 109 Ó 2010 Elsevier Ltd. The main drawback is that it assumes that bicarbonate and carbon dioxide are independent rather than interdependent variables. This then becomes a ‘compensated respiratory acidosis’. Initiating causes of an alkalosis include:  an increase in alkali in the ECF.g. An acidosis refers to a process that will produce acid (the pH does not strictly have to be <7. Respiratory alkalosis is a process caused by a fall in PaCO2 which causes a decrease in [Hþ]. A respiratory alkalosis is always due to alveolar hyperventilation. argued that the HendersoneHasselbalch concept of acid/base balance was an oversimplification.e. Explaining common acidebase disturbances Acidebase disturbances can be acute or chronic or have a degree of compensation. These last need a little explanation. An acidaemia refers to a pH < 7. If this persists then renal compensation may occur by reabsorbing HCOÀ . To overcome the change in haemoglobin concentration and its effect the approach was modified to use serum and calculate the standard base excess. at altitude then compensation may be complete. Researchers in Copenhagen developed another approach moving away from the HendersoneHasselbalch equation. Renal compensation then occurs by increasing the amount of HCOÀ excreted. It also runs into trouble when trying to explain critically ill patients who may have a number of acidifying and alkalinizing processes coexisting. Stewart.4% NaHCO3 is infused in a healthy subject. alveolar hypoventilation or increased production by the body.

Summary guide to interpreting blood gas measurements Look at pH to classify primary acid—base disorder Low pH (acidosis) Raised pH (alkalosis) High PCO2 Low SBC/–ve BE Low PCO2 High SBC/–ve BE Respiratory acidosis Metabolic acidosis Respiratory alkalosis Metabolic alkalosis Is SBC raised? Is PCO2 low? Is SBC low? Is PCO2 raised? Yes No Yes No Yes No Yes No Compensation No compensation Compensation No compensation Compensation No compensation Compensation No compensation SBC. The 3 unmeasured anions include serum proteins. A metabolic 3 alkalosis is most likely in pyloric stenosis where only acidic gastric secretions are lost. If there is concurrent use of proton pump inhibitors then metabolic acidosis may occur paradoxically. Therefore as albumin falls it tends to reduce the size of the anion gap.g. particularly albumin: AG ¼ ÃÁ À þ à  þ ÃÁ À À à  À Cl þ HCOÀ Na þ K 3 The normal range is 3e11 mmol/litre. standard bicarbonate. Liþ. The gastric secretion of Hþ produces HCOÀ . This is rarely seen in clinical practice but can happen in hypermagnesaemia or lithium toxicity. sulphate and organic anions (e. Kþ).e. Mg2þ. from the bowel in diarrhoea or from kidney in as a result of carbonic anhydrase inhibitors). The ‘unmeasured’ cations include Ca2þ. lactate and ketoacids). .g. so a deficiency in one (e. ClÀ and HCOÀ ) vs the commonly measured cations (Naþ. being an anion itself. A correction can be used. base excess Figure 1 SURGERY 29:3 110 Ó 2010 Elsevier Ltd. A common way to classify a metabolic acidosis is to refer to whether the ‘anion gap’ is raised or normal. there is no true gap in anions) but simply an artefact of measurement in the commonly measured anions (i. HCOÀ ) to maintain electroneutrality. The anion gap can be underestimated in hypoalbuminaemia. mitigating the degree of acidebase disturbance. alkaline duodenal secretions may be lost too. either through nasogastric drainage or vomiting. a range with an error of Æ2 mmol/litre should be used. In other causes of vomiting. Metabolic acidosis is caused by a reduction in plasma ½HCOÀ Š. for example normal saline infusion. chloride) will lead to rise in the other (e. BE. endogenous ketoacids in diabetes)  a loss of base (e. Proper correction of these abnormalities is therefore with volume and chloride replacement. The 3 patients that develop metabolic alkalosis the most are those that are volume depleted and salt restricted. which is returned to the blood. Hypokalaemia also occurs. assuming a normal albumin correction of 40 g/litre. 3 by two mechanisms:  a gain of strong acid (e.e. All rights reserved. as the Hþ load of the gastric secretions is reduced. which is retained in blood to cause alkalosis. This concept was developed to try to address limitations in the Boston and Copenhagen approaches (referred to above) to acidebase analysis. but several terms in the equation each with inherent measurement errors.g. and diuretic use. Urinary losses of ClÀ then exceed those of HCOÀ .g. Albumin gap ¼ 40 À apparent albumin AGcorr ¼ AG þ ð0:25  Albumin gapÞ The anion gap can be reduced by addition of unmeasured cations. The 3 commonest causes of metabolic alkalosis are those causing chloride depletion: loss of gastric acid. or have an alkalinizing effect. Albumin is a potent and plentiful contributor towards the normal anion gap.g. phosphate. Thus the ‘gap’ is mainly due to the negative charge of the plasma proteins. It can also occur with excess immunoglobulin such as myeloma. Metabolic acidosis tends to be the most common acute surgical acidebase disturbance.BASIC SCIENCE concentrations. The anion gap (AG) is not a physiological reality (i. 3 Some can predominantly secrete ClÀ in which case a hypochloraemic metabolic alkalosis would result. Another rarer cause is a villous adenoma which typically secretes HCOÀ leading to a hyperchloraemic metabolic acidosis. Diuretics such as frusemide and thiazides reduce ClÀ and Naþ reabsorption in the renal tubules.

It is the ratio of the change in the anion gap to the change in bicarbonate concentration: D AG=D HCOÀ 3 The measurement is restricted clinically by the large error associated with its calculation. above).anaesthesiamcq. Renal acidosis is treated with dialysis or filtration. Renal failure a Uraemic acidosis b Acidosis with acute renal failure 4. A FURTHER READING http://www. 2009. Renal causes such as a Renal tubular acidosis b Carbonic anhydrase inhibitors 2.acid-base. Elbers PWG. However.BASIC SCIENCE Acidoses with a high anion gap include: 1.php. The contribution of the various acidebase abnormalities may be difficult to interpret. Some aspects of treatment are selfevident. The delta ratio is a bedside technique that to identify mixed disorders. Gastrointestinal causes a Severe diarrhoea b Uretero-enterostomy or blockage of ileal conduit c Drainage of biliary or pancreatic secretions d Small bowel fistula Patients who are critically ill often have a number of processes occurring at once. Treatment of acidebase disorders The mainstay is to diagnose the underlying abnormality and the process driving it and aim to treat Diabetic ketoacidosis is treated with volume resuscitation and insulin therapy. Most acidoses will resolve with physiological stabilization and multiorgan support. Lactic acidosis a Type A (impaired perfusion) b Type B (impaired carbohydrate metabolism) 2. Toxins a Ethylene glycol b Methanol c Salicylates Acidoses with a normal anion gap include: 1. it is felt that buffer therapy may 3 worsen intracellular acidosis. (b) increased SID due to Naþ loading without an accompanying strong anion (see Stewart hypothesis. Lactic acidosis is treated with volume resuscitation and source control. All rights reserved. Investigations and laboratory work should complement the clinical assessment and not vice versa (see Figure 1). http://www. Buffer therapy can be achieved by the use of parenteral NaHCO3 which has three effects: (a) volume expansion. USA: Lulu. (c) Increased CO2 from the HCOÀ . Ketoacidosis a Starvation b Diabetes mellitus c Alcoholism Kellum JA. Stewart’s textbook of acidebase. . SURGERY 29:3 111 Ó 2010 Elsevier Ltd.