09

Acid base balance and blood gases

09

Acid base balance and blood gases

09

Acid base balance and blood gases

09

Acid base balance and blood gases

  9 Acid-base balance and blood gases

Oswald Müller-Plathe, Lothar Thomas

9.1 Acid-base homeostasis

The acid-base homeostasis is the homeostatic regulation of the pH of the extracellular fluid of the body. Normally systemic acid-base balance is regulated with arterial pH between 7.36 and 7.44. The proper balance between acids and bases is maintained by the integrated function of kidneys, lungs and liver. The liver is the principal organ responsible for hydrogen ion (H+ ) metabolism from the body’s daily protein intake and a resulting acid loading on the body. The H+ must be buffered and cleared to maintain acid-base homeostasis /12/.

Intracellular and extracellular buffers are the optimal mechanisms of defense against changes in the pH. The HCO3/CO2 buffer system is the clinically most significant extracellular buffer system. Buffering of H+ leads to the formation of CO2 that is expired by the lung:

H+ + HCO3  H2CO3 ═ H2O + CO2

The HCO3/CO2 buffer system is physiologically most important because of its quantitative capacity to buffer acid or alkali loads and because of the capacity for independent regulation of HCO3 and PCO2 by the kidneys and lungs, respectively /2/. The HCO3 consumed in this process must be regenerated by the kidneys. In this way, 20–30 mVal of acids from food and the same amount from the endogenous metabolism as well as HCO3 losses are compensated via excretion.

Arterial CO2 is predominantly regulated by alveolar ventilation after production in peripheral tissues.

Disorders of HCO3or non-volatile acids (fixed acids) are usually referred to as metabolic disorders. Disorders of CO2 are referred to as respiratory disorders /2/. Fixed acids are lactic acid, phosphoric acid and sulfuric acid.

Under physiological conditions, the acid-base balance is kept constant within a tight range. Normal H+ concentration is 40 nmol/L; expressed as negative logarithm, this corresponds to pH 7.4. The reference intervals of the acid-base parameters in arterial blood are pH 7.36–7.44, PCO2 36–44 mmHg and HCO3 21–26 mmol/L. However, the critical parameter ensuring normal physiology and cell metabolism of the organism is the intracellular pH that does not change until the extracellular pH undergoes significant changes. A decrease in pH is referred to as acidemia and an increase as alkalemia. In contrast, the terms “acidosis” and “alkalosis” designate the conditions that cause a decrease (acidosis) or increase (alkalosis) in pH.

9.2 Blood gases

Blood gases are the gases dissolved in the blood. They comprise the main constituents of atmospheric air such as nitrogen (N2), oxygen (O2), as well as carbon dioxide produced in metabolic processes (CO2). The partial pressure (P) of a mixture of gases is defined as the pressure exerted by a gas as an individual component of the gas mixture /3/.

Arterial blood gas analysis is an essential part of diagnosing and managing a patient’s oxygenation status and acid-base balance. Blood gas analysis is performed in patients with acid-base disorders to detect concurrently existing pulmonary changes /4/.

The widely used investigations to acid-base disorders are /4/:

  • The HCO3- (in the context of PCO2)
  • The standard base excess
  • The strong ion difference (refer to Section 8.3.5.1).

9.2.1 CO2 transport in blood

The arterial blood supplying the tissues contains much O2 bound to hemoglobin (HbO2) and little CO2. Due to the partial pressure gradient between tissue and plasma, CO2 diffuses from the tissue into the plasma and from there the majority shifts into the red blood cells. In the red blood cells:

  • 20% of the CO2 bind to the amino groups of the Hb as carbamino CO2
  • 70% of the CO2 are hydrated to H2CO3 by carbonic anhydrase. The H2CO3 dissociates into HCO3 and H+. The HCO3 are released to the plasma in exchange for Cl and the H+ bind to hemoglobin
  • 10% of the CO2 remain physically dissolved.

Hypercapnia refers to an increase in PCO2 and occurs in cases of respiratory insufficiency with hypo ventilation.

9.2.2 O2 transport in blood

The oxygen in the blood is transported bound to hemoglobin (Hb). The transport capacity is dependent on the O2 partial pressure (PO2) and the Hb level, and the Hb saturation with O2 is dependent on the PO2. The relation between PO2 and HbO2 is expressed by the HbO2 dissociation curve. The curve is not linear but S-shaped. The affinity of O2 to Hb and, thus, the course of the dissociation curve is dependent on the temperature, H+ concentration and PCO2 (Fig. 9-1 – HbO2 dissociation curve and effects of temperature, H+ and PCO2).

The following applies:

  • An increase in the above-mentioned parameters causes the HbO2 dissociation curve to shift to the right (lower affinity of O2 to Hb)
  • A decrease in the above-mentioned parameters causes the curve to shift to the left (higher affinity of O2 to Hb).

Within the PO2 range in the pulmonary alveoli (about 100 mmHg), the Hb saturation changes little even at greater partial pressure gradients. In the other tissues with a PO2 of about 40 mmHg, the steep course of the HbO2 dissociation curve maintains the necessary pressure gradient even at lower Hb saturation. Parameters to be measured for analyzing the acid-base homeostasis and oxygen supply are shown in Tab. 9-1 – Parameters to be measured for analyzing the acid-base homeostasis and oxygen supply.

9.3 Indication

  • Obstructive and restrictive ventilation disorders
  • Disease of lung parenchyma and bronchi
  • Disorders of lung perfusion (e.g., right-to-left shunt)
  • Circulatory insufficiency, hypovolemia, shock
  • Renal insufficiency, renal tubular dysfunction
  • Decompensated diabetes mellitus
  • Coma, intoxication
  • Gastroenterological disorders (vomiting, diarrhea)
  • Gallbladder and pancreatic fistula
  • Hypokalemia and hyperkalemia
  • Hypochloremia and hyperchloremia
  • Dysfunction of the adrenal cortex
  • Therapy monitoring, such as infusion treatment, artificial respiration, parenteral feeding, hemodialysis, hemofiltration, massive transfusion, treatment with diuretics, corticosteroids.

9.4 Method of determination

The pH, PCO2 and PO2 are determined in anaerobically sampled, heparin anticoagulated whole blood in a single measuring chamber at 37 °C /5/.

9.4.1 pH measurement

The pH value is measured with a glass electrode chain. The outer glass membrane is placed in direct contact with the blood, whilst the inner membrane is in contact with a solution of constant H+ activity. A conductive electrode is placed within this solution. At 37 °C a potential difference between the electrodes arises, that changes in 61.5 mV per increase or decrease of one pH unit. For the measurement of voltage change a conductive reference electrode in contact with the blood sample is required. Calibration is performed with two buffer solutions traceable to the primary standards of the National Institute of Standards and Technology.

9.4.2 PCO2 measurement

The PCO2 is measured with the CO2 electrode. This glass electrode is placed in a sodium bicarbonate solution together with the reference electrode. The solution is separated from the blood by a CO2-permeable membrane. The pH of the solution changes in proportion to the PCO2 of the blood sample according to the following equation:

–Δ pH = 1 Δ log PCO 2

9.4.3 PO2 measurement

The PO2 is measured amperometrically with a platinum electrode covered with an O2 permeable membrane. Molecular O2 diffuses across the membrane to the surface of the platinum cathode where it is reduced according to the following equation:

O2 + 2 H2O + 4e 4 HO

A reductive current of minimal intensity is created due to the charge transfer to the reference electrode. The intensity of the current is dependent upon the pO2 of the blood sample.

9.4.4 Bicarbonate in serum/plasma

The determination of the bicarbonate (HCO3) concentration is important for the determination of the acid-base status and the electrolyte balance /6/. HCO3 is calculated using the following transformation of the Henderson-Hasselbalch equation:

cHCO3 (mmol/L) = 0.0307 PCO2 (mmHg) × 10(pH – 6.1)

PCO2 is the partial pressure of arterial CO2, and 0.037 describes the solubility of CO2 in blood.

9.4.5 Base excess

The base excess /67/:

  • Is used as an indicator of the degree of metabolic disturbances
  • Is the dose of acid or alkali to return the extracellular fluid to normal pH (7.40) under standard conditions (at 37 °C at a PCO2 of 40 mmHg)
  • Is defined as equal to zero (–3 to +3 mmol/l) when pH = 7.40, PCO2 = 40 mmHg (5.33 kPa) at 37 °C (98.6 °F)
  • Is often assessed in association with the anion gap and the PCO2 to make reliable statements of either metabolic or respiratory components of acid-base disturbance, because it can be affected by both
  • Is calculated by arterial blood gas analyzers according to the van Slike equation

BE(ECF) (mmol/L) = (HCO3 – 24.4) + (2.3 × Hb + 7.7) × (pH – 7.4) × (1 – 0.023 × Hb)

For further information refer to Tab. 9-1 – Parameters to be measured for analyzing the acid-base homeostasis and oxygen supply.

9.4.6 Total carbon dioxide (tCO2) in blood serum/plasma

The CO2 is present in blood as dissolved carbonic acid (H2CO3), bicarbonate (HCO3), carbonate (CO32–), carbamate (CO2 bound to free amino groups of proteins, mainly hemoglobin; RNHCOO) and complex bound ion pairs. The concentration is 16–25 mmol/L. Lower levels are measured in acidosis and higher ones in alkalosis. HCO3 account for up to 95% of tCO2. The selected reference measurement procedure for tCO2 is an extraction method. In this procedure, the CO2 set free from the sample by the acid reagent (lactic acid; pH 2) shifts to a vessel for titration.

9.4.7 Oxygen saturation (SO2) and oxyhemoglobin fraction

The SO2 is calculated by approximation from PO2 and pH. The calculation for the range in venous blood (PO2 below 55 mmHg) is not accurate enough in many cases. In this range, the SO2 should be measured by oximetry. In oximetry, the spectrophotometric absorption of the blood sample is measured in a cuvette of approximately 0.1 mm path length at 6–7 wavelengths after gentle erythrocytolysis such that the total Hb, oxy-Hb, deoxy-Hb, COHb and metHb are measured individually. Appropriate calculation procedures either yield the free oxy-Hb fraction (fHbO2) related to the total Hb /4/:

fHbO 2 = HbO 2 = 1 Hb (tot)

or the oxygen saturation based on Hb capable of binding (SO2):

sO 2 = HbO 2 × 100 HHb + HbO 2

9.4.8 Oxygen concentration

The total oxygen concentration (tO2) is calculated as follows:

tO2 (mL/L) = 1.39 HbO2 (g/L) + 0.03 PO2 (mmHg)

All calculations described above are performed automatically by the analyzers.

9.5 Specimen

Arterial blood

The blood is usually collected with a specially prepared plastic syringe containing a dry heparin salt /9/. Immediately after removing the syringe from the puncture site, air bubbles should be expelled and the tip of the syringe sealed with a cap. The analysis must be performed within 15 min. at the most because plastic syringes are not gas-tight /6/.

If the period until analysis is expected to exceed 15 min., a glass syringe is required. Its dead space must be filled with liquid heparin to a final concentration below 50 IU/mL blood. The liquid must be free of air bubbles. The syringe is filled with blood to its nominal volume, and sealed promptly and stored on ice slush until analyzed. This procedure provides stability for 1 hour.

Arterialized capillary blood

After hyperemization of the relevant skin area, tap the blood from the earlobe or the finger tip or, in infants, from the side of the heel into a heparinized glass capillary /8/. Fill the capillary completely. Insert a flee for mixing. Seal the capillary with caps on both ends and perform the analysis immediately; if the sample is stored between cooling elements, the analysis should be performed within 1 hour.

Venous blood

The only diagnostically relevant venous specimen for the analysis of PCO2, PO2, and SO2 is mixed venous blood (pulmonary artery catheder) /8/. Venous blood collected from a peripheral vein can only be used explicitly for determination of the base parameters: in this case, collection is done without application of a tourniquet. The arm from which the sample is collected must be at complete rest (no muscular activity).

Venous plasma or serum

In order to determine bicarbonate or total CO2 in plasma or serum the collecting tubes are completely filled and immediately sealed with a cap /8/. Furthermore they must be centrifuged while the tube is still closed. Serum or plasma must be analyzed without delay with as little exposure to atmospheric air as possible.

9.6 Reference intervals

Refer to Ref. /91011/ and Tab. 9-2 – Reference intervals for acid-base markers.

9.7 Clinical significance

Disorders of acid-base homeostasis may be suspected based on the medical and medication history and clinical examinations. In many cases, however, acid-base disorders are not associated with any clinical symptoms, and laboratory findings provide initial evidence. Basic assays include /1213/:

  • Blood gas analysis, pH, PCO2, PO2 and bicarbonate
  • In plasma: Na+, K+, Cl and calculation of the anion gap.

9.7.1 Acid-base parameters

9.7.1.1 Interpretive approach

After history and clinical examination of the patient the second step is to determine the primary acid-base disorder and the secondary response /1/. The diagnosis of acid-base disorders is done in two phases.

Phase one

Determination of pH, PCO2 and bicarbonate. The four acid-base disturbances are defined as primary acid-base disorders.

Metabolic acidosis

Respiratory acidosis

Metabolic alkalosis

Respiratory alkalosis

Determination of the degree of compensation of the disorder. The assumed duration of the acid-base disorder is to be considered in this context. Respiratory compensation of metabolic disorders starts almost immediately and is fully developed after approximately 12 hours. Renal compensation of respiratory disorders does not become manifested until the second day and is complete after about six days. Fig. 9-2 – The principal constellation of values in acid-base disorders and Fig. 9-3 – Nomogram for diagnosing acid-base disorders considering the degree of compensation refer to this first phase of the diagnostic approach.

Phase two

The cause of the acid-base disorder is to be determined based on the following findings:

  • A general overview of the patient’s clinical situation, especially his history, state of consciousness, state of hydration, and current medication
  • The electrolyte status, especially the levels of Na+, K+, Cl and the anion gap in plasma
  • The oxygen parameters PO2 and SO2
  • Urine pH, ketone bodies, blood glucose, serum creatinine, blood lactate and more clinical laboratory measurements if needed.

9.7.1.2 Mixed acid-base disorders

Empirical observations suggest that the homeostatic response to acid-base disorders is predictable and can be calculated. They are diagnosed when the secondary response differs from that which would be expected. Primary disorder and secondary response can either combine to impede pH compensation; or if they are of opposing influence, they can lead to an overcompensation. The clarification of mixed disorders can be achieved by taking into account the clinical context, current medication and further laboratory findings. An increased anion gap, for example, suggests a primary decrease in bicarbonate. At atmospheric pressure a greatly decreased PO2 implies the primary character of an increased PCO2.. Nomograms alone are not sufficient to clarify mixed disorders, but from the location of the status point one can detect an under compensation or overcompensation which raises the possibility that a combined disorder is present.

The following combinations are possible:

  • Respiratory and metabolic acidosis
  • Respiratory acidosis and metabolic alkalosis
  • Respiratory and metabolic alkalosis
  • Respiratory alkalosis and metabolic acidosis.

An example is provided for each of the combined disorders (Case 1, Case 2, Case 3, and Case 4). The respective status points can be plotted in Fig. 9-2 – The principal constellation of values in acid-base disorders.

9.7.1.3 Quantitative assessment of measurement results

pH

Deviations from normal behavior within the range 7.3–7.5 are to be considered as mild, but should be clarified. pH values of 7.1–7.3 and 7.5–7.6 characterize severe decompensated acidosis and/or alkalosis, respectively. Values below 7.1 and above 7.6 are critical, especially if they are of acute respiratory origin. The range of pH that is compatible with life is 7.80 to 6.80 /3/.

PCO2

Primarily induced deviations from the reference interval within the limits of 30–50 mmHg are to be considered as mild, but should be diagnostically clarified. An uncompensated acute primary change of PCO2 is considered life threatening if it is below 25 mmHg or above 60 mmHg.

Significantly higher PCO2 values (80 mmHg and higher) are relatively well tolerated in many cases of chronic hypercapnia developed over weeks or months. Compensatory increases in PCO2 in cases of metabolic alkalosis rarely exceed 50 mmHg. In contrast, PCO2 can for a short period of time be reduced to values around 15 mmHg and lower to compensate metabolic acidosis with intact lung function: for example, Kussmaul respiration.

Bicarbonate

Values below 10 or above 40 mmol/L are rarely found. The extreme limits are around 5 and 55 mmol/L. The degree of risk from pathological bicarbonate concentrations is indicated by the resulting pH shift. The same applies by analogy to the other base parameters.

9.7.1.4 Metabolic acidosis

The H+ concentration of the organism is tightly regulated because changes in the H+ alter protein and membrane functions. Metabolic acidosis is a disorder that reduces the HCO3 concentration and occurs if the H+ production exceeds the body’s capacity for adequate compensation by buffering or increased respiration.

Metabolic acidosis /8/ may be attributed to Tab. 9-3 – Metabolic acidosis due to acid addition or bicarbonate subtraction:

  • The addition of H+ with the consumption of HCO3 as the reaction shifts to the left: increased production or supply of acids such as keto acids, lactic acid, chloride, various intoxications
  • Removal of HCO3 from the body resulting in increased H+ concentration as the reaction shifts to the right: enteral or renal loss of HCO3
  • Acid retention: reduced renal clearance of H+ and/or reduced HCO3 production in the kidney in renal insufficiency, tubular dysfunction or hormonal disorder. For causes, see Tab. 9-4 – Metabolic acidosis due to renal acid retention or base subtraction. See also chloride in urine (Section 8.8.4 – Disturbances of chloride excretion).

Calculation of the anion gap is useful in the initial evaluation for the presence of mixed metabolic acid-base disturbances /1/.

9.7.1.5 Metabolic alkalosis

Metabolic alkalosis develops if a net loss of acids or a net increase in bases cannot be compensated by increased renal clearance of bicarbonate. Clinical laboratory results are a pH higher than 7.4 and an HCO3 concentration higher than 26 mmol/L.

The main causes are /14/:

  • Gastrointestinal acid loss due to vomiting. The gastric juice contains up to 100 mmol/L of H+ and the secretory volume is 1–2 liters per day. Since the loss of H+ is stoichiometrically associated with an increase in HCO3 in the blood, it undergoes glomerular filtration together with Na+ as NaHCO3. The clearance of NaHCO3 theoretically leads to a loss of Na+. Due to the loss of volume as a result of vomiting, however, the Na+ are replaced by H+ and K+ in the distal nephron; this additionally results in a loss of K+.
  • Renal acid loss due to primary or secondary hyperaldosteronism. In the distal nephron, the H+ are increasingly secreted in exchange for Na+. This situation also occurs in the Liddle syndrome (activated epithelial Na+ channels, ENaC). Renal-induced alkalosis can also occur due to compensation of respiratory acidosis. During hypercapnia, renal acid secretion generates new HCO3 to attenuate the decrease in pH in the blood. However, the increase in renal acid clearance is also associated with a loss of NH4Cl. If, after the correction of hypercapnia, the replenishment of Cl is impaired by insufficient NaCl uptake or diuretics medication, renal clearance of HCO3 is not possible and metabolic alkalosis occurs as a result.
  • Exogenous supply of bases through the administration of large quantities of HCO3 during cardiopulmonary resuscitation or treatment of ketoacidosis or lactic acidosis. However, HCO3 loading alone does not result in metabolic alkalosis unless renal HCO3 clearance is impaired by hypochloremia or renal failure at the same time.

For further causes, see Tab. 9-5 – Metabolic alkalosis.

9.7.1.6 Respiratory acidosis, respiratory alkalosis

These are conditions characterized by the retention and/or increased release of CO2. Accordingly, any such case is associated with a corresponding change in PCO2. The deviation of the pH value characteristic of acidemia (pH decrease) and/or alkalemia (pH increase) can be significantly reduced by compensation processes. Please refer to:

Chronic respiratory acidosis

In this condition, the kidney gradually increases H+ clearance and bicarbonate reabsorption. As a result, increasing amounts of bicarbonate are produced from the back-diffusing CO2 and are shifted to the extracellular space or the plasma. Thus, contrary to acute respiratory acidosis, chronic respiratory acidosis is characterized by an increase in bicarbonate concentration and base excess. This adaptation process starts on the first day and reaches its peak after 5–6 days.

9.7.1.7 Respiratory compensation of metabolic disorders

Metabolic disorders are always associated with a primary decrease in HCO3 and are compensated by respiration. In this process, alveolar ventilation is increased (PCO2 decreased) or reduced (PCO2 increased) to approach the HCO3/H2CO3 ratio of 20 : 1.

To achieve this, the respiratory center is stimulated centrally by chemoreceptors on the anterior surface of the medulla oblongata and peripherally by chemoreceptors in the aorta and carotid arteries.

Adaptation of respiration starts immediately and is completed after 12–24 hours due to the slow diffusion of ions across the blood-brain barrier into the plasma. Normalization of respiration is delayed by several hours compared to therapeutic normalization of the bicarbonate concentration for the same reasons.

9.7.1.8 Renal compensation of respiratory disorders

Acute respiratory acidosis

In this situation, the buffering effect of Hb immediately results in a pronounced increase in bicarbonate in the plasma. As this occurs at the expense of the Hb buffer, the concentration of the buffer bases and, as a result, the extracellular base excess remain unchanged. Nevertheless, the blood base excess is slightly decreased because the newly produced bicarbonate is distributed to the entire extracellular compartment and thereby in part removed as a base equivalent from the blood. This could appear to be an accompanying metabolic acidosis. To prevent misdiagnosis only the extracellular base excess (in-vivo base excess) should be used.

Respiratory alkalosis

As in all alkaloses, the kidney is capable to compensate reduced CO2 expiration by increased excretion of bicarbonate.

9.7.2 Oxygen parameters

Besides specific aspects in pulmonology and cardiology, the O2 parameters are mainly analyzed to assess the degree of arterialization of the blood in the lungs /5/. Arterialization depends on the following factors:

  • Pulmonary function
  • O2 content of inspired air
  • Atmospheric pressure.

Reduced arterialization

Reduced arterialization is most sensitively detected by arterial PO2. If the PO2 decreases from 90 to 60 mmHg in cases of pneumonia, the SO2 only decreases from 97 to 91%. On the other hand, the SO2 reflects the situation regarding the O2 supply in a quantitatively adequate manner. In the example above, the oxygen available to the organs is only reduced by 6% and not by a third because, at the same Hb content, the oxygen concentration is much more strongly influenced by saturation than by partial pressure (Tab. 9-8 – Arterial hypoxemia; decreased PO2 and SO2).

Oxygen supply to the organs

The oxygen supply to the organs depends not only on arterialization of the blood, but also on cardiac output and Hb content. Thus, a normal arterial PO2 or even an elevated one observed under mechanical ventilation does not, in any way, exclude a situation of poor supply with oxygen. Hypoxemia can only be detected by determining the oxygen difference (mL/L) between arterial and mixed venous blood (avDO2). If the threshold value of 50–60 mL/L is exceeded while the arterial PO2 is normal, this indicates hypoxia caused by reduced cardiac output, anemia or dyshemoglobinemia. Lactate determination can provide initial evidence of hypoxia.

The arterial O2 parameters must, of course, always be evaluated together with the PCO2.

In most cases, pulmonary and/or respiratory diseases that mainly impair the ventilation/blood flow relationship, diffusion or perfusion (right-to-left shunt) lead to a decrease in arterial PO2 without a concomitant increase in PCO2. This pattern is referred to as partial pulmonary insufficiency. Arterial PCO2 can even be low in this case due to hypoxic stimulation of the respiratory center.

If the decrease in PO2 is associated with an increase in PCO2, this is referred to as generalized pulmonary insufficiency. It occurs in all diseases with alveolar hypo ventilation, is common in obstructive ventilation disorders and manifests in advanced stages of restrictive ventilation disorders. Illnesses normally accompanied by partial insufficiency, such as pneumonia or tumors, may also be observed with generalized insufficiency when these diseases are more extensive or advanced.

9.7.2.1 Assessment of PO2

The arterial PO2 in healthy individuals is 75–95 mmHg and the values can range from 65–105 mmHg depending on the age of the individual. Values of 50–65 mmHg are considered to be potentially dangerous, because PO2 changes very rapidly. Precautionary measures and diagnostic clarification are necessary. Values below 50 mmHg, corresponding to less than 85% oxygen saturation, are to be considered as critical and may require immediate intervention.

Elevated arterial PO2 is only found in spontaneous or mechanical ventilation with oxygen-enriched air and/or gas mixtures. In theory, a maximal PO2 of about 670 mmHg can be reached with pure oxygen respiration at normal atmospheric pressure. Since pure oxygen may only be administered for a short period of time, values above 500 mmHg are rarely measured. In such cases, the O2 saturation reaches approximately 100%.

Patients with chronic obstructive pulmonary disease (COPD) have tissue hypoxia due to arterial hypoxemia, which is largely the result of a ventilation-perfusion imbalance in the lung. Hypoxia-inducible factors constitute the master switch in the human response to hypoxia /18/.

Environmental hypoxia leads to hypoxemia as well as tissue hypoxia. For every 1% increase in the inspired oxygen concentration, the physiological altitude is reduced by approximately 300 meters.

9.8 Comments and problems

Pre analytical factors are of great significance in blood gas analysis /26/.

Specimen

Syringe: the lack of pulsation during blood collection indicates inadvertent venipuncture if a syringe with an easily moving plunger is used. This affects the acid-base parameters slightly; however, the oxygen quantities are altered to the point of being useless.

Capillary: practically pure arteriolar blood emerges if the skin in the hyperemized region is tapped in a professional manner. Any squeezing, however, leads to contamination with venous blood.

Contact with air

Syringe: any air bubbles in the syringe must be expelled at once and the syringe itself must be immediately capped once the specimen has been obtained. Plastic syringes are only to be considered sufficiently gas-tight for 10–15 min. at the most.

Capillary: if the puncture in the appropriate region is sufficiently deep, the emerging drop of blood is large enough to quickly fill a capillary immersed into the middle of the drop. Seal the capillary immediately at both ends.

Acidification and dilution by heparin

In excess, both factors result in imitation of metabolic acidosis. The heparin concentration per mL of blood should be below 50 IU in syringes and below 80 IU in capillaries. The volume of the heparin solution in syringes should not be more than 6% of the total volume of the blood sample.

Metabolic processes in the sample

If the analysis is not performed within 15 min., the sample must be cooled to minimize glycolysis and O2 consumption. Syringes are stored in ice water and capillaries are stored horizontally between cooling elements.

Incomplete resuspension

Before the sample is analyzed it is warmed to 37 °C in the blood gas analyzer, because its original composition with its plasma and erythrocyte buffer systems must be restored. Resuspension of the erythrocytes is especially important if Hb determination is performed simultaneously within the scope of the blood gas analysis.

Syringe: slowly move and turn the syringe vertically up and down ten times and then roll it back and forth horizontally for 10 sec.

Capillary: move the wire flea inserted after sampling back and forth from the outside with a magnet.

Clotting

Insufficient heparin content or (more commonly) inadequate mixing of the specimen after sampling leads to clot formation, either already in the syringe or capillary or during warming in the blood gas analyzer. Clots can render an analyzer useless for an extended period of time.

Body temperature of the patient

The body temperature of the patient is still subject of debate whether or not the results found in hypothermic patients should be converted to those of normothermic conditions. The debate centers around whether the reference values applying to normothermia are still valid under hypothermic conditions. Conversion is available in blood gas analyzers but can also be performed with nomograms /16/.

Determination of tCO2

Principle: in order to measure tCO2, HCO3 is determined enzymatically using phosphoenolpyruvate carboxylase. Catalyzed by malate dehydrogenase, the oxalo acetate formed is converted into malate and NAD in the presence of NADH /17/.

High LD activity in the sample results in elevated values of tCO2. This is the case in samples with an LD activity > 845 U/L, because the pyruvate present in the sample is converted into lactate and NAD under NADH consumption. The decrease in NADH falsely indicates the concentration of tCO2 as too high. In a case report, instead of a HCO3 concentration of 6 mmol/L, a tCO2 concentration of 16 mmol/L at an LD activity of 4490 U/L was determined.

9.9 Pathophysiology

9.9.1 Acid-base elimination of the body

Normally the equivalent of 40–60 mmol of acid is ingested daily in the diet, metabolized and eliminated by the kidneys. About 24 moles of CO2 are generated and pulmonally eliminated within the same period. Despite these turnovers, the body is capable of keeping the H+ concentration stable at 40 nmol/L, corresponding to pH 7.4.

Even under stress conditions acting on the acid-base system that may ultimately lead to acidosis or alkalosis, the pH deviation can be kept within relatively tight limits for a long time.

This is achieved by the following organs:

  • The lungs can increase CO2 expiration to more than ten-fold for a short period of time
  • The clearance capacity of healthy kidneys for acids is 400–500 mmol/24 h.

Metabolic acidosis cannot occur until metabolic acid formation has reached this magnitude or the acid clearance capacity of the kidneys is reduced.

9.9.2 Renal acid-base regulation

Bicarbonate reabsorption

The cells of the proximal tubule reabsorb 80% of the glomerularly filtered bicarbonate. The membrane-bound and cytoplasmic carbonic anhydrases catalyze the formation of CO2 as follows:

H+ + HCO3  H2CO3  H2O + CO2

By transmembrane diffusion, the CO2 passes from the lumen into the tubule cell (see also Fig. 8.8-3 – Maintaining the acid-base homeostasis in the proximal tubulus). Usually balanced at an extracellular HCO3 concentration of 26 mmol/L, this process is stimulated by hypercapnia (see compensation of respiratory acidosis). The capacity is approximately 4500 mmol/24 h.

Adaptive H+ elimination

This process takes place in the distal tubule and the cortical part of the collecting ducts. At the luminal side, the cells involved have H+-transporting ATPase that is capable of secreting H+ against a gradient of three pH units (see also Fig. 8.8-4 – H+ secretion into the cortical collecting ducts). This process is stimulated by hypercapnia and aldosterone. The capacity is 70–100 mmol/24 h.

Elimination of ammonium

Acid loading leads to the increased formation of glutamine in the hepatocyte at the expense of urea synthesis /19/; from the glutamine, NH3 is formed in the proximal tubule cells. H+ secreted into the lumen of the collecting ducts are bound as NH4+ and excreted (see also Fig. 8.8.4). The capacity is 300–400 mmol/24 h.

9.9.3 Urinary buffer system

The H+ are buffered by NH3 and hydrogen phosphate:

NH3 + H+ NH4+
HPO42- + H+ H2PO4

The H2PO4 are determined by measuring the titratable acidity of the urine; the NH4+ are measured directly.

9.9.4 Blood buffer system

At pH 7.4, the blood contains approximately 48 mmol/L of buffer bases. Two buffer systems are significant:

  • The HCO3/H2CO3 system that accounts for about 75% of the buffering of fixed acids
  • The Hb buffer system that accounts for about 20% of the buffering of fixed acids but is primarily responsible for H+ transport and buffering.

H2CO3 + Hb HCO3 + HHb

Bicarbonate produced by the H2CO3 buffering process is released from the erythrocyte into the plasma in exchange for chloride. The components of the HCO3/H2CO3 system are used for the quantitative assessment of the acid-base status. Their relationship is described by the Henderson-Hasselbalch equation.

pH = 6.1 + log HCO 3 H 2 CO 3

or

pH = 6.1 + log HCO 3 0.0307 × PCO 2

When the ratio between HCO3 and H2CO3 is 20 : 1 or the numeric ratio between bicabonate concentration (mmol/L) and PCO2 (mmHg) is 0.6, the result in a pH of 7.4.

Buffering within the cells is based on the bicarbonate and hydrogen phosphate systems and the plasma proteins. The buffering function of these systems is not available for routine analysis.

References

1. Berend K, de Vries APJ, Gans ROB. Physiological approach to assessment of acid-base disturbances. N Engl J Med 2014; 371: 1434–45.

2. Hamm LL, Nakhoul N, Hering-Smith KS. Cin J Am Soc Nephrol 2015; 10: 2232–42.

3. Moran RF. The laboratory assessment of oxygenation. JIFCC 1994; 5: 170–82.

4. Sood P, Paul G, Puri S. Interpretation of arterial blood gas. Indian J Crit Care Med 2010; 14: 57–64.

5. Wimberley PD, Burnett RW, Covington AK, Fogh-Andersen N, Müller-Plathe O, Zijlstra WG, et al. Guidelines for routine measurement of blood hemoglobin oxygen affinity. JIFCC 1991; 3: 81–6.

6. Kofstad J. Base excess- a historical review. Has the calculation of base excess been more standardised the last 20 years? Clin Chim Acta 2001; 307: 193–5.

7. Siggard-Andersen O. The oxygen status of the arterial blood revised: relevant oxygen parameters for monitoring the arterial oxygen availability. Scand J Clin Lab Invest 1990; Suppl 203: 17–28.

8. Seifter JL. Integration of acid-base and electrolyte disorders. N Engl J Med 2014; 371: 1281–31.

9. Burnett RW, Covington AK, Fogh-Andersen N, Külp­mann WR, Maas AHJ, Müller-Plathe O, et al. Approved IFCC-Recommendations on whole blood sampling, transport and storage for simultaneous determination of pH, blood gases and electrolytes. Eur J Clin Chem Clin Biochem 1995; 33: 247–53.

10. Müller-Plathe O. Säure-Basen-Haushalt und Blutgase, 2nd ed. Stuttgart: Thieme, 1982.

11. Marshall BE, Wyche MQ. Hypoxemia during and after anesthesia. Anethesiology 1972; 37: 178–209.

12. Gunnerson KJ. Clinical review: the meaning of acid-base abnormalities in the intensive care unit – epidemiology. Critical Care 2005; 9: 508–16.

13. Adrogue HJ, Gennari FJ, Galla JH, Madias NE. Assessing acid-base disorders. Kidney Int 2009; 76: 1239–47.

14. Pochet JM, Laterre PF, Jadoul M, Devuyst O. Metabolic alkalosis in the intensive care unit. Acta Clinica Belgica 2001; 56: 1–9.

15. Müller-Plathe O. A nomogram for the interpretation of acid-base data. J Clin Chem Clin Biochem 1987; 25: 795–8.

16. Bacher A. Effects of body temperature on blood gases. Intensive Care Med 2005; 31: 24–7.

17. Saleem M, Dimenski C, Bourne L, Coates P. Artifactually elevated serum bicarbonate results caused by elevated serum lactate dehydrogenase concentrations. Ann Clin Biochem 2013; 50: 365–7.

18. West JB. Physiological effects of chronic hypoxia. N Engl J Med 2017; 376: 1965–71.

19. Guder WG, Häussinger D, Gerok W. Renal and hepatic nitrogen metabolism in systemic acid-base regulation. J Clin Chem Clin Biochem 1987; 25: 457–66.

20. Berend K. Diagnostic use of base excess in acd-base disorders. N Engl J Med 2018; 378: 1419–27.

Table 9-1 Parameters to be measured for analyzing the acid-base homeostasis and oxygen supply /123, 4, 56/

Laboratory tests of the acid-base homeostasis

pH

The pH is the negative logarithm of the hydrogen ion (H+) activity. The cellular metabolism needs a pH that remains constant within tight limits. The pH is controlled by the lungs through CO2 release and by the kidneys through H+ buffering by means of HCO3.

Partial pressure of carbon dioxide (PCO2)

The CO2 is a metabolite released from the cells into the blood where it is transported as CO2, HCO3 and H2CO3. The relevant form depends on the net supply or net loss of acid equivalents and the resulting adaptive changes in the bicarbonate buffer system. PCO2 represents the respiratory component of acid-base homeostasis. The base parameters plasma bicarbonate and base excess represent the metabolic component. HCO3 is greatly influenced by PCO2. The base excess of the extracellular fluid, however, describes the metabolic component independently of changes in pCO2 and Hb concentration. This advantage makes the parameter superior to older ones such as the base excess concentration of the whole blood or standard bicarbonate. Diagnostic use of standard bicarbonate is becomimg less common.

Bicarbonate (HCO3)

Based on the Henderson-Hasselbalch equation, the pH and PCO2 are used to calculate HCO3 in the following transformation: cHCO3 (mmol/L) = 0.0307 PCO2 (mmHg) × 10(pH – 6.1).

Standard bicarbonate: this is the bicarbonate content of the plasma that would be present in blood equilibrated to 40 mmHg PCO2. As a result of this standardization, the bicarbonate is independent of the PCO2, but still dependent on the Hb of the specimen.

Problems with bicarbonate are:

  • Bicarbonate levels are affected by metabolic and respiratory components of the acid-base disturbance and are not an ideal indicator of either metabolic or respiratory acid-base disturbances
  • The relationship between metabolic acidosis and bicarbonate is neither consistent nor linear
  • The concentration of the bicarbonate ion (HCO3) is not measured, it is calculated from the pH and PCO2

Base excess /20/

The terms base excess or base deficit are often used interchangeably. The terms are used as an indicator of the degree of metabolic disturbance. Since blood gas analyzers do not provide base deficit, the term base excess is used.

Base excess and standard base excess

The base excess is the dose of acid or alkali to return in vitro blood to normal pH 7.40 under standard conditions (37 °C, PCO2 40 mmHg).

The standard base excess is the dose of acid or alkali to return the extracellular fluid (ECF) to normal (pH 7.40) under standard conditions (37 °C , PCO2 40 mmHg). This is the base excess calculated for anemic blood (Hb 50 g/L) based on the principle that this closely represents the behavior of the whole body, as Hb effectively buffers the plasma as well as the ECF.

In clinical routines commercially available arterial blood gas analyzers determine standard base excess.

Use of base excess:

  • In the first step standard base excess is evaluated in relation to pH and PCO2.
  • The next step is to determine the secondary response of the four primary acid-base disorders (respiratory alkalosis, respiratory acidosis, metabolic alkalosis, metabolic acidosis). In the acid-base disorders physiologic mechanisms (compensatory mechanisms) occur that restore pH to normal.
  • In mixed acid-base disorders the secondary response differs from that which would be expected.
  • The third step is to differentiate standard base excess or evaluate the anion gap. The anion gap is important to rule out mixed metabolic acid-base disturbances if the anion gap is increased.

Example normal anion gap metabolic acidosis: hyperchloremia, gastrointestinal loss of bicarbonate, renal tubular acidosis, acetazolamide.

Example base excess with abnormal anion gap: lactic acidosis with preexisting metabolic alkalosis; High anion gap metabolic acidosis masked by hypoalbuminemia (if anion gap is uncorrected; salicylate toxicity – respiratory alkalosis plus increased anion gap metabolic acidosis

Anion gap

The anion gap is calculated according to the equation: anion gap (mmol/L) = Na+ – Cl + HCO3. It is mainly used in the differential diagnosis of metabolic acidosis. It can suggest a cause of unmeasured anions. There is an equilibrium between cations and anions in the blood. However, not all cations and anions are measured by routine laboratory analysis. Consequently, a gap of 7–16 mmol/L exists on the anion side. This gap results from anions such as proteins, sulfate, phosphate, lactate, keto acids and various acid radicals that are not measured.

A normal anion gap acidosis occurs when the decrease in HCO3 that usually occurs in metabolic acidosis corresponds with an increase in Cl to retain electroneutrality (hyperchloremic metabolic acidosis). This type of acidosis results from gastrointestinal loss of HCO3 (diarrhea) or by the renal tubules (renal tubular acidosis).

If the deficit of HCO3 is not compensated by Cl , this suggests an accumulation of unmeasured anions. Possible causes include lactic acidosis, ketoacidosis, uremic acidosis, ingestion of salicylate, methanol and ethylene glycol; and many inborn errors of metabolism. See also Section 8.4 – Anion gap.

CO2 and/or bicarbonate in plasma/serum

The following methodologies are available for this purpose:

  • Addition of strong acid and subsequent measurement of the preformed and driven-out CO2 through photometric recording of the color reaction with an indicator, with a PCO2 electrode or through infrared spectrometry.
  • Addition of alkali and subsequent enzymatic measurement of the carbonic acid system components converted into carbonate and bicarbonate in a UV assay.

Partial pressure of oxygen (PO2)

The oxygen partial pressure is an indicator of oxygen uptake by the lungs. The following can be calculated from the PO2 and pH based on the simplifying assumption of a generally valid O2 binding curve of Hb: SO2, the oxygen saturation of Hb in % (can be determined more accurately by direct measurement with an oximeter). The CO2 (oxygen concentration of the blood in mL/dL) can be calculated if PO2, SO2 and the Hb concentration are known.

Arteriovenous oxygen difference (avDO2)

The avDO2 is the difference between the O2 concentration of the arterial and the mixed venous blood (right heart catheter) and is usually 50 mL/L. Elevated levels indicate increased oxygen exhaustion due to inadequate cardiovascular output. For further oxygen parameters such as half-saturation pressure of Hb (P50) and the parameters for the assessment of O2 availability in tissue, see Ref. /7/.

Blood gas analysis

Usually, routine blood gas analysis only determines the pH, PCO2 and PO2 and in some cases also the hemoglobin value and SO2. The base parameters and as necessary the O2 concentration are usually calculated.

If the focus is only on the non-respiratory (metabolic) component of acid-base homeostasis, the bicarbonate and chloride in serum can be determined in the course of electrolyte measurement. For analytical reasons the parameter referred to as total CO2 (tCO2) is often preferred as a close equivalent of HCO3.

Table 9-2 Reference intervals for acid-base markers

Adults /910/

Unit

Whole blood arterial

Whole blood mixed-venous

Plasma/serum

pH

 

7.37–7.45

7.35–7.43

PCO2

mmHg

35–46

32–43

37–50

kPa

4.7–6.1

4.3–5.7

4.9–6.7

 

PO2

mmHg

71–104

36–44

kPa

9.5–13.9

4.8–5.9

 

Actual HCO3

mmol/L

21–26

21–26

21–28

Base excess (BE)

mmol/L

–3 to +3

–3 to +3

Standard bicarbonate

mmol/L

21–26

21–26

Total CO2 (tCO2)

mmol/L

23–28

22–29

22–29

Oxygen saturation (SO2)

%

95.0–98.5

70.0–80.0

HbO2 fraction (fHbO2)

%

94.0–98.0

70.0–80.0

 

Total oxygen content (tO2)

mL/L

180–230

130–180

Anion gap

mmol/L

7–16

Children and neonates

pH

PCO2

PO2

Standard bicarbonate mmol/L

mmHg

kPa

mmHg

kPa

Umbilical artery

7.09–7.40

35–80

4.7–10.7

0–22

0–2.9

Umbilical vein

7.15–7.45

30–57

4.0–7.6

16–35

2.2–4.7

11.8–21.4

Neonates, day 1

7.20–7.41

29.4–60.6

4.0–8.0

18.6–22.6

10–90 days

7.34–7.45

26.5–42.5

3.5–5.7

70–85

9.3–11.4

18.5–24.5

4–12 months

7.38–7.45

27.0–39.8

3.6–5.3

19.8–24.2

Relationship between arterial PO2 and age /11/

PO2 arterial (mmHg) = 102 – 0.33 × years of age

95% range: ± 10 mmHg

PO2 arterial (kPa) = 13.6–0.044 × years of age

95% range: ± 1.33 kPa

Acid-base status in urine /10/

pH value (mean)

5.5–7.0 (≈ 6.0)

Titratable acid

10–40 mmol/24 h

Ammonium

20–50 mmol/24 h

Bicarbonate

Only detectable in relevant concentrations at alkaline pH

Ammonium + titratable acid – bicarbonate = Net acid 40–80 mmol/24 h

Case 1:

Acid-base status

Additional parameters

pH

7.14

PO2

35 mmHg

PCO2

57 mmHg

Anion gap

25 mmol/L

HCO3

19 mmol/L

Lactate

11.5 mmol/L

Diagnosis: cardiac and respiratory arrest with hypercapnia and lactic acidosis due to hypoxemia. Status point lies in between the areas of respiratory and metabolic acidosis and indicates a combined acidosis (see Fig. 9-3 – Nomogram for diagnosing acid-base disorders considering the degree of compensation)

Case 2:

Acid-base status

Additional parameters

pH

7.46

PO2

48 mmHg

PCO2

63 mmHg

Anion gap

normal

HCO3

44 mmol/L

Serum K+

2.8 mmol/L

Diagnosis: chronic hypercapnia due to obstructive pulmonary emphysema. The accompanying decompensated right ventricular failure requires therapy with diuretics, which itself leads to metabolic alkalosis and hypokalemia. Even in a state of full compensation, a pH of over 7.40 is not to be expected with a PCO2 of 63 mmHg. Looking at the status point a combination of metabolic alkalosis and respiratory acidosis is indicated (see Fig. 9-3 – Nomogram for diagnosing acid-base disorders considering the degree of compensation).

Case 3:

Acid-base status

Additional parameters

pH

7.62

Serum Cl-

82 mmol/L

PCO2

31 mmHg

Serum K+

2.6 mmol/L

HCO3

31 mmol/L

Serum Na+

124 mmol/L

 

PO2

93 mmHg

Diagnosis: chronic vomiting (hypochloremic alkalosis with its typical hypokalemia) with contemporaneous hyperventilation due to decompensated liver cirrhosis. The status point is located between the areas of respiratory and metabolic alkalosis, indicating a combined alkalosis (see Fig. 9-3 – Nomogram for diagnosing acid-base disorders considering the degree of compensation).

Case 4:

Acid-base status

Additional parameters

pH

7.36 mmHg

PO2

47 mmHg

PCO2

21 mmol/L

Anion gap

24 mmol/L

HCO3

11.6 mmol/L

Blood glucose

467 mg/dL

 

Ketone bodies in urine: positive

Diagnosis: multiple pulmonary infarctions with pneumonic infiltrations, resulting in hypoxic reflectory hyperventilation and in simultaneous keto-acidotic decompensation of diabetes mellitus. The status point shows the combination of respiratory alkalosis and metabolic acidosis (see Fig. 9-3 – Nomogram for diagnosing acid-base disorders considering the degree of compensation).

Table 9-3 Metabolic acidosis due to acid addition or bicarbonate subtraction

Disturbances

Anion
gap

Cl

Ketoacidosis (Lactate in plasma > 45 mg/dL; 5.0 mmol/L)

Decompensated diabetes mellitus, hunger, thyrotoxicosis, high fever; ketonuria

N to

Lactic acidosis

Hypoxia [shock of any origin, respiratory failure (PO2 below 40 mmHg), anemia (Hb below 70 g/L), methemoglobinemia, carbon oxide poisoning, cyanide poisoning, extreme muscular activity, generalized seizures, massive transfusion, leukemia, lymphomas, extensive malignancies, burns, hepatic failure, diabetes mellitus]

Congenital metabolic disorders (glycogenosis type I), methylmalonic acidemia,

Fructose intolerance, fructose-1,6-bisphosphatase deficiency, chronic congenital lactic acidosis, pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency, D-lactate reabsorption (condition following extensive intestinal resection)

Chronic respiratory alkalosis, ethanol poisoning, fructose infusions, sorbitol and xylitol infusions, isoniazid medication

N to

Various intoxications

Salicylates, methanol, paraldehyde, ethylene glycol. Toxicological analysis positive

N to

Increased chloride absorption (ammonium chloride medication, arginine or lysine hydrochloride medication, ureteroenterostomy, infusions with 0.9% NaCl solution, potassium substitution with neutral salts (KCl). NH3

N

Bicarbonate loss

  • Pancreatic fistula, biliary fistula, K

N

  • Diarrhea, K

N

N to

  • Condition following chronic hyperventilation (posthypocapnic)

N

Abbreviations: N, normal; Cl, serum chloride

Table 9-4 Metabolic acidosis due to renal acid retention or base subtraction

Disorders

Clinical and laboratory findings

Global renal acidosis

Acute renal failure

Chronic renal insufficiency,

GFR below 30 [mL × min–1 × (1.73 m2)–1]

Anion gap: increased

Serum chloride: normal

Serum potassium: increased

Serum phosphate: increased

Serum creatinine: > 4 mg/dL (354 μmol/L)

Proximal renal tubular acidosis (RTA type 2)

Primary isolated forms

Irreversible hereditary

RTA (from 2–11 years of age) Fanconi syndrome (RTA, variably combined with diabetes renalis, phosphaturia, aminoaciduria)

Symptomatic forms:

Hereditary diseases: tyrosinosis, Wilson’s disease, Lowe syndrome, cystinosis, fructose intolerance, galactosemia, pyruvate carboxylase deficiency, glycogenosis type I, metachromatic leukodystrophy

Protein metabolism disorders: myeloma, amyloidosis, nephrotic syndrome

Immunological diseases: disseminate lupus erythematosus, Sjögren’s syndrome, after renal transplantation

Calcium metabolism disorders: secondary hyperparathyroidism, vitamin D deficiency

Drug-induced or toxic: tetracycline (out of date), streptozotocin, acetazolamide, 6-mercaptopurine, lead, cadmium, mercury

Anion gap: normal

Serum chloride: increased

1. Concrements or nephrocalcinosis are rare

2. In many cases associated with diabetes renalis and phosphate diabetes

3. Potassium in serum: decreased

4. HCO3 in serum ≥ 15 mmol/L

5. Serum creatinine is initially normal

6. Random urine sample pH below 6

7. After exposure to NH4Cl (0.1 g per kg of BW) urine pH below 5.5

8. Acidosis is generally bicarbonate resistant.

See also Section 8.8.7.1 – Renal-tubular acidoses (RTA)

Distal renal tubular acidosis (RTA type 1)

Primary isolated forms; sporadic or

familial occurrence

Symptomatic forms:

Hereditary diseases: Marfan syndrome, Ehlers-Danlos syndrome, Wilson’s disease, sickle-cell anemia, Fabry’s disease, congenital elliptocytosis

Protein metabolism disorders: myeloma, amyloidosis, hypergammaglobulinemia

Immunological diseases: lupus erythematosus, Sjögren’s syndrome, condition following renal transplantation, chronic active hepatitis, sarcoidosis

Nephrocalcinosis-inducing diseases: hyperparathyroid disorder, vitamin D intoxication, idiopathic hypercalciuria, hyperthyreosis

Specific renal diseases: medullary sponge kidney, obstructive uropathy, hyperoxaluria

Drug-induced or toxic: amphotericin B, lithium, analgesics, cyclamate, toluol, lead, acute

drug-induced allergic interstitial nephritis

Anion gap: normal

Serum chloride: increased

1. Often renal stones or nephrocalcinosis

2. Phosphate diabetes and renal diabetes are rare

3. Potassium normal or decreased

4. HCO3 in serum below 15 mmol/L

5. Serum creatinine is initially normal

6. Random urine pH above (beware: urinary tract infection!)

7. After exposure to NH4Cl (0.1 g per kg of BW) urine pH above 5.5

8. Acidosis can be influenced with bicarbonate.

See also Section 8.8.7.1 – Renal-tubular acidoses (RTA)

Hyperkalemic renal tubular acidosis (RTA type 4) 11β-hydroxylase deficiency, familial and idiopathic aldosterone deficiency

Secondary aldosterone deficiency: hyporeninemia in cases of diabetic nephropathy, obstructive nephropathy, interstitial nephropathy, nephrosclerosis, extracellular volume expansion

Aldosterone resistance: tubular dysfunctions

Drug-induced: amiloride, spironolactone, triamterene, analgesics

Anion gap: normal

Serum chloride: increased/normal

Potassium in serum: increased

See also Section 8.8.7.1 – Renal-tubular acidoses (RTA)

Table 9-5 Metabolic alkalosis

Disorder

Clinical and laboratory findings

Gastrointestinal hydrochloric acid and/or chloride losses

Loss of gastric juice due to continued vomiting or gastric drainage (gastric alkalosis)

Congenital chloride diarrhea

The following findings apply to gastric alkalosis:

  • Cl in serum ↓↓ (50–85 mmol/L)
  • K+ in serum
  • Cl in urine ↓↓ (below 5 mmol/24 h)
  • K+ in urine ≈ 20–50 mmol/24 h
  • Mildly acidic urine pH

Increased alkali intake: sodium bicarbonate (natron), antacids, citrate, lactate, gluconate, acetate, milk-alkali syndrome

Diuretics: thiazides, ethacrynic acid, furosemide, bumetanide

The conditions in this group tend to yield the same constellation of findings as in gastric alkalosis; however, the tendencies regarding Cl in serum and especially Cl in urine are not as pronounced.

Condition following alveolar hypo ventilation (post hypercapnic)

Volume contraction (without shock)

Pronounced potassium depletion

The diseases in this group show a tendency of volume contraction. Alkalosis (except for kaliopenic alkalosis) can be corrected by NaCl administration.

Excessive mineralocorticoid effect

Primary hyperaldosteronism (Conn syndrome)

The following findings apply to this group of diseases:

  • Serum Cl
  • Serum K+
  • Cl in urine above 10 mmol/L

Cushing’s syndrome, para neoplastic hypercortisolism, corticoid medication, Bartter syndrome, 17α-hydroxylase deficiency, 11α-hydroxylase deficiency, Liddle syndrome

Secondary hyperaldosteronism (e.g., renal artery stenosis, renin-producing tumors, decompensated heart failure, liver cirrhosis)

Except for the Bartter syndrome, these diseases show a tendency toward volume expansion in most cases and arterial hypertension in some cases.

Alkalosis cannot be influenced by NaCl administration.

Table 9-6 Respiratory acidosis

Point of attack

Clinical and laboratory findings

Respiratory center

Drug-induced: opiates, sedatives, narcotics

Lesion-induced: tumor, hemorrhage, trauma, ischemia, encephalitis, meningitis

Function-induced: primary central hypo ventilation, Pickwickian syndrome, obesity

Peripheral nerves

High paraplegic lesion, bilateral phrenic paresis, poliomyelitis, polyneuropathy, Guillain-Barré syndrome

Neuro-muscular

Myasthenia gravis, botulism, drugs such as succinylcholine, d-tubocurarine, aminoglycosides

Muscles

Myositis, muscular dystrophy, hypokalemic palsy

Thorax

Kyphoscoliosis, pneumothorax, serial rib fracture

Respiratory tract

Foreign body, tumor, bronchostenotic emphysema, asthmatic status (fatigue stage), bronchial mucoid hypersecretion

Lung parenchyma

Extensive pneumonia, severe pulmonary edema, advanced interstitial processes, tumor sequelae, cystic lung fibrosis, ARDS grade III

Mechanical ventilation

Insufficient ventilatory minute volume, excessive dead space fraction

Table 9-7 Respiratory alkalosis

Affected area

Clinical and laborarory findings

Direct stimulation of the respiratory center

Hyperventilation syndrome (anxiety, excitement, hysteria)

Lesions of the CNS: encephalitis, meningitis, subarachnoidal hemorrhage, tumor, trauma

Hormone-induced: elevated progesterone, pregnancy, thyrotoxicosis

Drug-induced: salicylates, analgesics, theophylline, catecholamines

Miscellaneous: septic shock (gram-negative pathogens), fever, liver cirrhosis

Reflex stimulation

Pulmonary disease* with disturbed ventilation/perfusion ratio or disturbed diffusion for oxygen such as pulmonary fibrosis, pneumonia, pulmonary vascular congestion, pulmonary edema, atelectasis, tumor conditions, ARDS-stages I and II

Right-to-left shunt in congenital heart defects, high-altitude respiration, pneumothorax

Different reflex stimulation

Pulmonary embolism, cold stimuli

Mechanical ventilation

Artificial hyperventilation

* Advanced degrees of these diseases (i.e., in case of both impaired O2 uptake and impaired CO2release ) may result in respiratory acidosis.

Table 9-8 Arterial hypoxemia; decreased PO2 and SO2

Pulmonary causes

Predominantly restrictive ventilation disorder (PCO2 normal in most cases):

  • Condition after lung resection
  • Lung compression due to pleural effusion or tumor
  • Pneumothorax

Predominantly diffusion disorder (PCO2 normal or low in most cases):

  • Carcinomatous lymphangiosis, sarcoidosis, Hamman-Rich syndrome, pulmonary hemosiderosis (in cases of mitral stenosis), ARDS stages I and II

Predominantly distribution disorder (PCO2 normal or low in most cases):

  • Bronchial asthma, emphysema, pneumonia, atelectasis, pulmonary infarction, pneumoconiosis, tumor, bronchial mucoid hypersecretion, thorax deformity

Predominantly perfusion disorder (PCO2 normal or low in most cases):

  • Right-to-left shunt, lung edema

Predominantly alveolar hypoventilation (PCO2 always elevated): See Tab. 9-5 – Metabolic alkalosis

Other causes

Air pressure reduction (PCO2 decreased):

  • High-altitude respiration

Mechanical ventilation:

  • Insufficient O2 fraction (PCO2 unchanged)
  • Insufficient ventilatory minute volume (PCO2 elevated)
  • Too much dead space (PCO2 elevated)

Figure 9-1 HbO2 dissociation curve and effects of temperature, H+ and PCO2. B: normal affinity. A: increased O2 affinity due to decrease in H+, PCO2 and temperature. C: decreased O2 affinity due to increase in H+, PCO2 or temperature.

20 80 100 HbO 2 A B C 60 40 20 40 60 80 100 (mmHg) 120 PO 2

Figure 9-2 The principal constellation of values in acid-base disorders. Primarily changed values are indicated by bold arrows. Compensatory changes and the direction of change in pH are indicated by thin arrows sloped diagnostically upwards or downwards. The curved, dotted arrows indicate the direction the values change with increasing compensation. The curved arrow for pH is directed to the reference interval, which is represented by the horizontal dotted line /8/.

Interference Base excess Bicarbonate pH pCO 2 Metabolicacidosis Metabolicalkalosis Respiratoryacidosis Respiratoryalkalosis

Figure 9-3 Nomogram for diagnosing acid-base disorders considering the degree of compensation /15/. PCO2 is represented logarithmically on the abscissa. Bicarbonate concentration is reported on the ordinate. The resulting status point allows an acid-base disorder to be classified as an exclusive acute and/or chronic disorder or as a combined disorder. If the disorder appears with a normal degree of compensation, the status point is found in one of the corresponding shaded fields. If the status point doesn’t fall in one this fields, it must be decided which of the following situations is present:

– The disorder just appeared, compensation could not yet occur

– The function of the compensating organ (e.g., lung in metabolic disorders and kidney in respiratory disorders) is impaired

– A second acid-base disorder is present concurrently. For example, respiratory acidosis in ventilatory failure and lactic acidosis might be present simultaneously.

60 50 45 40 35 32 30 28 26 24 22 20 18 16 14 12 6 7 8 9 10 60 50 45 40 35 32 30 28 26 24 22 20 18 16 14 12 7 8 9 10 6 10 12 14 16 18 20 1.3 1.6 1.9 2.1 2.4 2.7 mm Hg kP a 30 4.0 40 50 60 70 80 90 100 5.3 6.7 8.0 9.3 10.7 12.0 13.0 10 12 14 16 18 20 mm Hg 30 40 50 60 70 80 90 100 1.3 1.6 1.9 2.1 2.4 2.7 kPa 4.0 5.3 6.7 8.0 9.3 10.7 12.0 13.0 cHCO 3 mmol/l 7.6 7.0 6.8 7.1 7.3 7.4 7.5 7.7 7.8 6.8 7.2 7.1 7.0 6.9 7.3 pH mm Hg kPa PCO 2 Comb. Alkal. Comb. Acid. Resp. Alk. + Met. Acid. 7.6 7.5 7.7 7.4 Metabol. Acid. Chron. Resp. Alkal. Acute Resp. Alkal. Acute Resp. Acid. Chron. Resp. Acid. Metab. Alk. + Resp. Acid. Metabol. Alkal. 6.9 7.2 7.8
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