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Physiological role and pathophysiology, reference intervals and the most likely causes of abnormalities


Reference interval pH – examples
Why measure pH ?
When should pH (pCO2 and HCO3) be measured ?
Causes of acid-base disturbances
Symptoms of acid-base disturbances
Clinical interpretation
Fetal scalp pH and umbilical-cord pH
pH in pleural fluid

The degree of acidity or alkalinity of any liquid (including blood) is a function of its hydrogen ion concentration [H+], and pH is simply a way of expressing hydrogen ion activity. The relationship between pH and hydrogen ion concentration is described thus [24]:

where aH+ is hydrogen ion activity

Low pH is associated with acidosis and high pH with alkalosis.

Reference interval pH – examples

Why measure pH?

Normal metabolism is associated with continuous production of H+ and CO2 that both tend to decrease pH. Despite this normal tendency towards acidosis, pH remains tightly controlled within very narrow limits (7.35 – 7.45). Even a small deviation outside this normal range can have numerous detrimental effects on cellular metabolism that translates to tissue/organ dysfunction; and pH lower than 6.8 or higher than 7.8 is usually incompatible with life. Therefore, it is essential that abnormal pH is detected and the cause identified, to be able to make the necessary medical intervention. The maintenance of normal pH (acid-base homeostasis) is a complex synergy of actions involving lungs, kidneys, brain and chemical buffers present in blood (Fig. 9) [6]. pH provides evidence that these homeostatic mechanisms are either working normally or are disturbed in some way. Although measurement of pH is essential for the assessment of patient acid-base status (see acid-base), it is not sufficient of itself; two other parameters, pCO2 and bicarbonate (HCO3) are equally necessary (see pCO2 and HCO3) to accurately identify an acid-base disturbance and formulate effective therapy.

When should pH (pCO2 and HCO3) be measured?

pH (along with pCO2 and HCO3) is used both to diagnose and to monitor acid-base disturbance [73]. Given the complexity of acid-base homeostasis, involving as it does the function of several organ systems, measurement of pH (pCO2 and HCO3) has clinical value in the context of many severe acute or critical illnesses as well as significant injury (trauma). pH measurements are thus usually made in hospital settings, e.g. emergency room, operation room, critical care/intensive care setting, etc. In broad terms all acid-base disturbances can be attributed to one of three main causes:

  • Disease of, or damage to, any one of the three organs, (lungs, kidneys, brain) whose function is necessary for keeping pH within normal healthy limits
  • Disease or condition that results in increased production of metabolic acids (e.g. lactic acid, keto acids) such that the homeostatic mechanisms for the maintenance of normal pH are overwhelmed
  • Medical intervention (mechanical ventilation as well as a number of drugs can cause or contribute to acid-base disturbance)


Causes of acid-base disturbances

A non-exhaustive list of diseases or conditions in which acid-base may be disturbed and pH (pCO2 and HCO3) measurement may be useful for diagnosis and/or monitoring includes [74]:

  • Respiratory failure/distress (e.g. COPD, pneumonia, pulmonary edema, pulmonary embolism, asthma, acute respiratory distress syndrome, Guillain-Barré syndrome and traumatic chest injury)
  • Acute/chronic renal failure
  • Diabetic ketoacidosis
  • Circulatory failure/shock (e.g. hemorrhage, burns, sepsis, cardiac arrest and other conditions with increased production of lactic acid)
  • Liver failure (associated with decreased elimination of lactic acid)
  • Traumatic brain injury, cerebral edema, brain tumor
  • Fetal distress
  • Drug overdose/toxic poisoning (e.g. salicylate, antacids, opiates, barbiturates, diuretics, methanol, ethanol and ethylene glycol)


Symptoms of acid-base disturbances

Symptoms that might indicate acid-base disturbance and prompt measurement of pH, pCO2 and HCO3:

  • Reduced consciousness, drowsiness, confusion
  • Convulsions/seizures
  • Reduced blood pressure
  • Reduced or increased respiratory rate
  • Cardiac arrhythmia
  • Anuria/polyuria
  • Muscle spasm/tetany
  • Electrolyte disturbance
  • Hyperglycemia
  • Anemia/hemorrhage
  • Hypoxemia


Clinical interpretation

Although measurement of pH can identify an acid-base disorder, either acidosis or alkalosis, and provides an indication of its severity, it provides no indication of its cause. This depends on two further parameters: pCO2 and HCO3, which are related to pH thus:

This relationship allows distinction between acid-base disturbance caused by respiratory disease, in which pCO2 is the primary abnormality, and acid-base disturbance caused by metabolic (non-respiratory) disease, in which HCO3 is the primary abnormality.

With these two additional parameters it is possible to classify the acid-base disturbance as one of four types [6]:

Respiratory acidosis:    
Characterized by decreased pH, increased pCO2 and normal HCO3

Respiratory alkalosis:    
Characterized by increased pH, decreased pCO2 and normal HCO3

Metabolic acidosis:    
Characterized by decreased pH, decreased HCO3 and normal pCO2

Metabolic alkalosis:    
Characterized by increased pH, increased HCO3 and normal pCO2

Because of the prime physiological importance of maintaining pH within normal limits, acid-base disturbances are associated with a compensatory response that aims to normalize pH (Fig. 11).

Metabolic disturbance, in which the primary determinant of abnormal pH is abnormal HCO3 concentration, is associated with a respiratory compensatory response that changes pCO2, so that the ratio of HCO3 to pCO2 and thereby pH is getting closer to normal. In a similar way respiratory disturbance provokes a compensatory response that changes HCO3. In practice these compensatory responses move pH towards normality but do not usually achieve normality, although this can occur. It is important to be aware that pH within the reference intervals does not exclude an acid-base disturbance; it may simply reflect this compensatory response. Mixed acid-base disturbance (alkalosis and acidosis) is a common reason for a patient with acid-base disturbance to have a normal pH. In such cases the abnormally high pH associated with alkalosis is covered by the abnormally low pH associated with acidosis.

Fetal scalp pH and umbilical-cord pH

In obstetric/perinatal care fetal scalp pH is often used as a stand-alone parameter to make clinical decisions during labor in high-risk pregnancies, when electronic fetal monitoring (EFM) indicates risk of fetal hypoxia. Reduction in fetal pH (acidosis) is indicative of hypoxia, a condition that may significantly affect the function of various fetal organ systems, such as the central nervous system and the cardiovascular system [75]. Since low pH (acidosis) is associated with risk of birth asphyxia and consequent neurologic injury [76], it is an indication for urgent delivery by cesarean section. This is reflected in the guidance from NICE (National Institute for Clinical Excellence) [77] which states that fetal scalp pH should be used whenever possible to confirm fetal distress suggested by EFM, before undertaking cesarean section. A fetal pH equal to or higher than 7.25 is considered normal and reassuring of no fetal distress but a fetal pH lower than 7.20 is usually considered unequivocal evidence of acidosis and a distressed fetus that needs urgent delivery [78]. However, fetal scalp pH results need to be interpreted in the context of each individual labor.

Just as fetal scalp pH is used to detect fetal acidosis and associated hypoxia risk during labor, umbilical-cord arterial pH provides the same evidence in relation to babies at the time of birth. Severe acidemia at birth is indicative of hypoxia and risk of hypoxia-mediated serious long-term neurological deficit, up to and including that associated with cerebral palsy. Umbilical-cord pH is measured at birth if the baby is considered at risk of hypoxia either because of complications during labor, or there is evidence of fetal distress (e.g. decreased scalp pH) during labor. NICE recommends umbilical-cord pH measurement for all babies delivered by cesarean section because of fetal distress, to identify birth asphyxia and neurologic injury [77]. The use of cord blood testing on all neonates is discussed in a review article [332].

pH in pleural fluid

Measuring the pH of pleural fluid is sometimes of value in the assessment of patients with pleural effusion. Normal pleural fluid has a pH of 7.60 – 7.66. Probably the most common use is in the management of patients whose pleural effusion is the result of pneumonia. For these patients, a pleural fluid pH <7.2 is indicative of advanced disease and need for urgent drainage of the pleural cavity. Clinical utility of pleural fluid pH, which is not confined to this patient group, is fully discussed in a review article [79].



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Ref.: Acute care testing handbook. Radiometer Medical ApS, 2700 Brønshøj, Denmark, 2014.

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