The human body maintains and regulates acid-base balance mainly through four major buffering mechanisms: the body fluid buffering system, pulmonary regulation, renal regulation, and ionic exchange compensation. Among these, the body fluid buffering system is the most sensitive, including the bicarbonate system, phosphate system, hemoglobin system, and plasma protein system, with the bicarbonate system being the most critical. Under normal conditions, the bicarbonate [HCO3-]/carbonic acid [H2CO3] ratio is 20:1. Pulmonary regulation usually functions within 10 to 30 minutes by releasing volatile acids in the form of CO3. Ionic exchange regulation becomes effective after approximately 2 to 4 hours. Renal regulation occurs most slowly, typically taking several hours to initiate, but it is the most potent and sustained mechanism, serving as the only pathway for the excretion of non-volatile acids and alkaline substances. The body fluid buffering system and ionic exchange mechanisms are temporary, and excess acidic or alkaline substances ultimately depend on the clearance by the lungs and kidneys. If the body produces or retains excessive acid and/or insufficient base (or vice versa), altering the hydrogen ion concentration in the blood, acid-base imbalance may occur.
Acid-Base Balance Indicators
Clinically, acid-base balance is assessed primarily by three factors: pH, respiratory-related parameters, and metabolic-related parameters.
pH
pH represents the negative logarithm of the H+ concentration. The normal arterial blood pH ranges from 7.35 to 7.45, approximately 0.03 higher than venous blood due to dual effects from respiratory and metabolic factors. A pH > 7.45 indicates alkalosis, while < 7.35 indicates acidosis. A pH between 7.35 and 7.45 can indicate three possibilities:
- Normal acid-base balance.
- Compensated acid-base imbalance.
- Mixed acid-base imbalance.
pH alone cannot distinguish between metabolic or respiratory, as well as primary or mixed acid-base disorders. The tolerable pH range for humans is 6.8 to 7.8. Non-respiratory pH (pHNR), determined after equilibrating the blood sample with 40 mmHg of CO2, reflects metabolic acid-base balance since it is not affected by respiratory factors. The normal arterial pHNR is 7.40.
H+ Concentration
The normal arterial H+ concentration is (40 ± 5) nmol/L. H+ concentration and pH are inversely related logarithmically.
Partial Pressure of Carbon Dioxide (PaCO2)
PaCO2 measures the pressure generated by CO2 dissolved in arterial blood. Normal values range from 35 to 45 mmHg and reflect the CO2 concentration in alveoli. It serves as an essential indicator of respiratory acid-base balance:
- Increased PaCO2 indicates hypoventilation, leading to respiratory acidosis.
- Decreased PaCO2 indicates hyperventilation, leading to respiratory alkalosis.
Metabolic factors can cause compensatory changes in PaCO2: decreased in metabolic acidosis or increased in metabolic alkalosis.
Standard Bicarbonate (SB)
SB refers to the HCO3- content measured under standardized conditions (i.e., 37°C, PaCO2 = 40 mmHg, full hemoglobin oxygenation). The normal range is 22 to 26 mmol/L. SB is unaffected by respiratory factors and reflects HCO3- reserves, making it an important indicator of metabolic acid-base balance:
- Increased SB suggests metabolic alkalosis.
- Decreased SB suggests metabolic acidosis.
Actual Bicarbonate (AB)
AB indicates the HCO3- content measured under actual physiological conditions, reflecting the actual HCO3- concentration in the body and being influenced by respiratory factors.
Normally, SB = AB = 22–26 mmol/L.
- AB > SB often suggests CO2 retention, indicating respiratory acidosis.
- AB < SB suggests excessive CO2 excretion, indicating respiratory alkalosis.
The difference between AB and SB reflects the impact of respiratory factors on HCO3- concentration. For example, both AB < SB and AB = SB can suggest uncompensated metabolic acidosis, while AB > SB may indicate compensated metabolic alkalosis or respiratory acidosis.
Buffer Base (BB)
BB represents the total amount of base available for buffering, including both open buffering anions (bicarbonate) and non-open buffering anions (hemoglobin, plasma proteins, phosphates, etc.). BB is only affected by hemoglobin concentration and serves as another indicator of metabolic acid-base balance. Reduced BB suggests acidosis, while elevated BB suggests alkalosis.
Base Excess (BE) or Base Deficit (BD)
BE or BD refers to the amount of acid or base required to titrate blood under standardized conditions (37–38°C, CO₂ pressure = 40 mmHg, and pH = 7.40). Normal values are (0 ± 2.3) mmol/L.
- Positive BE indicates increased BB and metabolic alkalosis.
- Negative BE (i.e., BD) indicates reduced BB and metabolic acidosis.
BE is independent of respiratory factors and can be divided into whole blood BE (BEb) and extracellular BE (BEecf or BEHb5). Hemoglobin variation can influence BEb, and it must be corrected to match the actual hemoglobin concentration during measurement.
Carbon Dioxide Combining Power (CO2CP)
CO2CP represents the total CO2 content in HCO3- and H2CO3 combined. The normal range is 22–29 mmol/L. CO2CP reflects the combined effects of metabolic and respiratory factors:
- Reduced CO2CP may indicate metabolic acidosis or compensated respiratory alkalosis.
- Increased CO2CP may indicate metabolic alkalosis or compensated respiratory acidosis.
Anion Gap (AG)
AG is the difference between commonly measurable cations and anions in the blood. It is calculated as:
AG (mmol/L) = (Na+ + K+) - (HCO3- + Cl-), or
AG = Na+ - (HCO3- + Cl-).
The normal AG ranges from 8 to 16 mmol/L.
- AG > 16 mmol/L typically indicates organic acid accumulation in metabolic acidosis.
- AG < 8 mmol/L may suggest hypoalbuminemia.
Acid-Base Imbalance
Acid-base imbalance occurs when the production or intake of acidic or alkaline substances overwhelms the buffering, neutralizing, and excretion capacity of the body, causing their accumulation. In the early stages, compensatory mechanisms such as the HCO3-/H2CO3 buffer system may maintain the ratio at 20:1, keeping the pH and H+ concentrations within the normal range, which is known as compensated acidosis or alkalosis. In severe cases, when compensation fails, resulting in an altered HCO3-/H2CO3 ratio and pH or H+ concentration outside the normal range, decompensated acidosis or alkalosis develops.
Metabolic Acidosis is commonly observed in conditions like chronic renal failure.
Respiratory Acidosis is often associated with respiratory failure.
To be continued