Acid Pathways	Cause	Measure
Cells produce acid (acid production increases).	Hypermetabolic states, such as pain, hyperthermia, or inflammation. The respiratory and heart rates increase, and bicarbonate is initially consumed by buffering.	HCO₃ ↓
	Tissues are hypoxic; anaerobic metabolism ensues resulting in lactic acidosis.	Lactate level ↑
	Absolute insulin deficiency results in failure of glucose to be transported into cells.	Blood glucose level ↑ Ketoacids ↑
Cells regulate acids.	When acid production (H⁺) increases, pH decreases, bicarbonate is initially consumed by buffering, and CO₂ is exhaled in larger amounts, and H⁺ exchanges for K⁺ as cells buffer acid.	pH ↓ HCO₃ ↓ K⁺ ↑ Total serum CO₂ ↓
Lungs regulate acid.	When acid increases due to hypermetabolic states such as pain, hyperthermia, or inflammation, carbonic acid (H₂CO₃) increases and rapidly converts to CO₂ and H₂O. The respiratory rate increases to blow off CO₂.	Paco₂ ↓
Kidneys regulate acid.	When acid increases, tubules are affected by low blood pH, and work to neutralize increased carbonic acid (H₂CO₃) by separating it into H⁺ and bicarbonate HCO₃. Kidneys excrete what is necessary to sustain normal pH if renal function is normal. If abnormal, kidneys may not perform this task.	HCO₃ ↑ Kidney function is assessed by serum BUN and creatinine; elevated BUN and creatinine indicate abnormal kidney function.

The most important component identified is the H₂CO₃, or carbonic acid. As carbonic acid increases (“goes up”), the pH decreases (“goes down”), reflecting the presence of acid. If the carbonic acid decreases (“goes down”), the pH increases (“goes up”), reflecting the absence of acid. The equation is constantly shifting from left to right and right to left to maintain a normal H₂CO₃ and therefore a normal pH. Whatever causes the change of carbonic acid concentration (may be related to a regulation failure by either the lungs or kidneys or a metabolic acid production state) is the “primary culprit.” Identifying the origin or cause of the change in pH direction identifies the problem. Therefore, if the problem is too much acid (either increased CO₂ or H⁺ ), the carbonic acid goes up and the pH goes down. The primary problem is acidosis. Further evaluation is needed to determine whether failure to regulate the acid was ineffective regulation by the lungs, the kidneys or an increase in cellular acid production (ketoacidosis or lactic acidosis).

Changes in pH are associated with changes in the potassium level. As the plasma level of nonvolatile or metabolic acid (H⁺) increases, H⁺ moves into the cells in order to buffer the acid effect. In this case H⁺ “exchanges places” with the intracellular potassium (K⁺), resulting in a measured serum hyperkalemia but is actually an intracellular hypokalemia. The positively charged intracellular potassium ions are replaced by positively charged hydrogen ions. During an alkalotic state, K⁺ may shift into cells as H⁺ is released into the serum, creating a transient hypokalemia. As pH changes, it is imperative for the care providers to observe the corresponding changes in the K⁺ level, and manage K⁺ carefully. When the pH normalizes, the K1 will shift back to its original location. If a transient K⁺ change is managed too aggressively, the patient may experience dangerous hypokalemia or hyperkalemia when pH normalizes.

Understanding the arterial blood gas

The ABG is the most commonly used measurement to help assess the origins of problems with acid-base imbalance and to guide treatment designed to restore pH balance and effective oxygenation. “Perfect” values for each reflects chemical neutrality. There are normal variations or a range for each value.

Abg values

Blood gas analysis is usually based on sampling of arterial blood. Mixed venous blood sampling from a pulmonary artery (PA) catheter (SvO₂) and central venous sampling from a central intravenous (IV) line (ScVO₂) may also be performed for very critically ill patients. Venous values are given for reference only.

Normal Arterial Values	Normal Venous Values
pH: 7.35–7.45	pH: 7.32–7.38
PaCO₂: 35–45 mm Hg	PvCO₂: 42–50 mm Hg
PaO₂: 80–100 mm Hg	PvO₂: 40 mm Hg
SaO₂: 95%–100%	SvO₂: 60%–80%
Base excess (BE): −2 to +2	BE: −2 to +2 (only calculated on ABG analyzer)
HCO₃⁻: 22–26 mEq/L	total Serum CO₂⁻: 23–27 mEq/L

pH (perfect 7.40, range of normal 7.35 to 7.45): This reflects the level of respiratory and metabolic acids found in the blood during the continuous “balancing act” that regulates the acid environment. If this balance is altered, derangements in pH occur. Any alteration in pH should be evaluated. If the pH has changed from perfect, it can only be one of two reasons: normal variation, or abnormality with compensation. When pH is less than 7.35 or greater than 7.45, it is considered an acute change that is uncompensated. When full compensation is attained for an acid-base imbalance, the pH normalizes. Failure to bring pH to range of normal means that there is failure to compensate, even if there is an attempt. Traditionally this was known as partial compensation. That term is no longer advocated.

Paco₂ (perfect 40, range of normal 35 to 45 mm Hg): This is a measure of pressure (partial pressure which is designated by the P) that the dissolved CO₂ exerts in the arterial blood. The dissolved gas exerts the pressure of CO₂, enabling it to diffuse across the capillary and alveolar cell wall.

CO₂ is released during aerobic metabolism and is the main contributor to serum acid. CO₂ is controlled through ventilation. In the normal lung, CO₂ is regulated by changes in the rate and depth of alveolar ventilation. CO₂ is carried both bound to hemoglobin and dissolved in the blood. The measured CO₂ is termed PaCO₂. PaCO₂ is directly measured (not calculated) and is a reliable indicator of respiratory acid-base regulation. The correlation between PaCO₂ and respiratory-based pH changes is direct, consistent, and linear. In other words if PaCO₂ is up and pH is down, the cause is respiratory deregulation. If the issue is metabolic, and respiratory compensation has occurred, the PaCO₂ will decrease in order to bring pH back to normal levels. Respiratory compensation typically occurs rapidly in metabolic acid-base disturbances as long as respiratory function is not impaired. When a patient hyperventilates, PaCO₂ decreases as it is “blown off” by rapid exhalations. During hypoventilation (slow and/or shallow breathing), PaCO2 increases. Although the only way to evaluate true lung function is by the gas exchange, the capacity of the lungs (CO₂ regulation response) is measured via the minute ventilation (VE or MV). This measures the amount of volume exhaled per minute (V_E) calculated as respiratory rate (RR) × V_T. Normal MV is about 8 to 10 L/min. B

Pao₂ (perfect 95 to 100 mm Hg, normal range 80 to 100 mm Hg): The partial pressure of oxygen (O₂), or PaO₂, is a measure of the dissolved (usable) gas in the arteries. The dissolved gas exerts the pressure of O₂, enabling it to diffuse across the capillary and cell wall to oxygenate cells. PaO₂ normally declines in the older adult.

• Hypoxemia (PaO₂ less than 80 mm Hg): Low partial pressure of O₂ affects the cellular levels of oxygen available and may result in cellular metabolic dysfunction reflected by lactic acid production and metabolic acidosis.

• Fio₂: Fraction of inspired O₂ or the percentage of the atmospheric pressure which is oxygenated. Room air is 21% or 0.21 O₂. O₂ delivery devices can increase the FIO₂ to 100% or 1.00.

P/F ratio (greater than 300): PaO₂ is evaluated in relationship to FIO₂; that is, the higher the percent O₂ pressure that is delivered to the lungs, the higher the O₂ in the blood should be.

Sao₂ (perfect 100% or 1.0, normal range 95% to 100% or 0.95 to 1.0): O₂ saturation (SaO₂) reflects the loading of O₂ onto hemoglobin (Hgb) in the lungs. When Hgb is loaded with O₂, it is termed oxyhemoglobin. Hgb is the primary transporter of O₂ and supplies a reservoir (reserve) of O₂ for cellular use. Each Hgb molecule carries 1.34 to 1.36 ml of O₂. O₂ must be released from the Hgb, dissolve in blood (PaO₂), and exert pressure to diffuse across the cell wall. The uptake/use of O₂ by the tissues is measured by SvO₂ and/or ScVO₂ (mixed venous and/or central venous saturation of Hgb, respectively). Cellular metabolism and O₂ utilization are affected by changes in stress level, temperature, pH, blood flow, and PaCO₂. When the PaO₂ falls to less than 60 mm Hg, there is a large drop in saturation, reflected in the oxyhemoglobin dissociation curve.

• Pulse oximetry (SpO₂): This can be used to noninvasively trend the arterial O₂ saturation and determine ventilation status using a probe fastened to the patient’s finger, earlobe, or forehead. This monitoring technique is frequently used in critical care areas for patients at high risk of ventilation problems, in operating rooms, and in emergency departments. SpO₂ should be correlated with SaO₂ (or oxyhemoglobin) via blood gas analysis when pulse oximetry is initiated, to assess accuracy of SpO₂ readings. Pulse oximetry is a close correlate to SaO₂ under normal physiologic conditions, but if perfusion decreases, the pulse needed for accurate measurement by the SpO₂ probe is decreased, prompting inaccurate readings. Anemic patients should have consistently high readings, so what is usually considered a normal SpO₂ reading may be too low in an anemic patient. The measure of true oxyhemoglobin (Hgb saturated with O₂) requires an ABG analysis. Many centers do not perform a correlation analysis when oximetry is initiated.

BE (perfect 0, normal range −2 to +2): Base excess or base deficit uses a calculation to reflect the presence (excess) or absence (deficit) of buffers. The calculation reflects the tissue and renal tubular presence (or absence) of acid. As the proportion of acid rises, the relative amount of base decreases (and vice versa). Abnormally high values (greater than +2) reflect alkalosis, or an excess of base; low values (less than −2) reflect acidosis, or a deficit of base (base deficit).

• All buffers: Absorb acids (H⁺), but do so with a varying affinity. Buffers are present in all body fluids and cells and act within 1 second after acid accumulation begins. They combine with excess acid to form substances that may not greatly affect pH. Some buffers have a strong affinity to acid; others are weak. The three primary plasma buffers are bicarbonate (HCO3−), intracellular proteins, and chloride (Cl⁻). All are negatively charged to facilitate attraction to positively charged hydrogen ions (H⁺). Combining positively charged with negatively charged ions yields a neutral substance.

• Proteins: Serum and intracellular proteins offer a significant contribution to buffering acids. Hgb not only transports O₂ but also provides a very strong buffer for hydrogen ions (H⁺). Albumin is also a significant buffer, and hypoalbuminemia must be considered when performing anion gap calculations.

• HCO₃⁻ (perfect 24, normal range 22 to 26 mEq/L): Serum bicarbonate (HCO₃⁻) is one of the major components of acid-base regulation by the kidney. Bicarbonate is generated and/or excreted by normally functioning kidneys in direct proportion to the amount of circulating acid to maintain acid-base balance. Because bicarbonate is affected by both the respiratory and metabolic components of the acid-base system, the relationship between metabolic acidosis and bicarbonate is not particularly linear or predictable. When the bicarbonate level changes, the acid level changes in the opposite direction. To determine the cause of bicarbonate changes (as the source of a pH problem versus compensation), the relationship to pH must be evaluated. The pH changes in the presence or absence of acid, and the directional relationship reflects what caused the pH alteration. The kidney is responsible for the regeneration of bicarbonate ions, as well as excretion of the hydrogen ions. Although serum bicarbonate is a buffer, it is usually reported in the standard electrolyte panel from a venous blood sample as “CO₂ content” or “total CO₂” rather than as bicarbonate (HCO₃⁻). The serum HCO₃⁻ concentration is usually calculated and reported separately with ABG analysis. Either value may be used as part of the assessment of acid-base balance (Table 1-2).

• Chloride (Cl−): The number of positive and negative ions in the plasma must balance at all times. Aside from the plasma proteins, bicarbonate and chloride are the two most abundant negative ions (anions) in the plasma. To maintain electrical neutrality, any change in chloride must be accompanied by the opposite change in bicarbonate concentration. If chloride increases, bicarbonate decreases (hyperchloremic acidosis) and vice versa. However the combination of H⁺ and chloride actually exerts an acid effect (HCl). Chloride concentration may influence acid-base balance (see anion gap). Chloride concentration should be observed closely when large amounts of normal saline are administered to patients.

• Other buffers: Other buffers, including phosphate and ammonium, are present in very limited quantities and have a lesser impact on the regulation of acid.

• Cellular electrolytes: The cells also offer protection in the metabolic acid environment. H⁺ may exchange across the cell wall, attracted by negatively charged intracellular proteins in a cellular buffering process. When this happens, K⁺ is released from the proteins and shifts out of the cell, causing an excess of K⁺ in the blood.

• Anion gap: Anion gap is an estimate of the differences between measured and unmeasured cations (positively charged particles, such as Na and H⁺ respectively) and measured and unmeasured anions (negatively charged particles such as HCO₃⁻ and Cl⁻. Normally, cations and anions are equally balanced in live humans (in vivo), but when measured in the laboratory (in vitro), the difference may be between 10 to 12 mmol/L. This difference is termed a normal gap (between + and – ions). Particles that possess charges tend to have high affinity to bind to other particles that possess charges that are opposite their own (hence the term, “opposites attract”). Anion gap is used to determine if a metabolic acidosis is due to an accumulation of nonvolatile acids such as lactic acid or ketoacids. Both contribute a positive charge due to excess H⁺ or from net loss of bicarbonate (e.g., diarrhea). The gap is not affected when a patient has metabolic acidosis purely from kidney failure. The formula for calculation of anion gap is

Table 1-2 DIAGNOSTIC TESTS FOR ACID-BASE BALANCE

Role of the ABG	Measures	Normals
Evaluation of arterial oxygen (dissolved oxygen and oxygen bound to hemoglobin)	Arterial oxygen saturation (oxygen bound to hemoglobin)	Sao₂: 0.95–1.0 or 95%–100%
	Partial pressure of arterial oxygen (dissolved oxygen)	Pao₂: 80–100 mm Hg (decreased over the age of 70)
Calculation of alveolar-arterial (A-a) oxygen gradient	Alveolar-arterial gradient	A-a Do₂: <20 mm Hg
Calculation of alveolar-arterial (A-a) oxygen gradient	Pao₂/Fio₂ ratio	PF ratio: .300
Evaluation of cellular environment	pH (reflects H₂CO₃) i.e., ↑↑ H₂CO₃ then pH ↓↓	pH Perfect: 7.40 Normal range: 7.35–7.45
Evaluation of ventilation	Paco₂	Paco₂ Normal range: 35–45 mm Hg
Evaluation of tissue metabolism	H⁺ inversely (indirectly) reflected by buffers: Bicarbonate (HCO₃⁻) Base measures (+ or −) Total CO₂ i.e., ↑↑ H⁺ then buffers ↓↓	pH Perfect: 7.40 Normal range: 7.35–7.45
		HCO₃⁻: 22–26 mEq/L
		Total CO₂: 20–26
		Base Normal range: −2 to +2
		Anion gap: 12 + or −2
Additional measures of tissue metabolism	Both contribute H⁺ to blood lactic acid Ketoacids	Lactic acid: 1–2 mmol/L
Additional measures of tissue metabolism	Both contribute H⁺ to blood lactic acid Ketoacids	Ketoacids Blood: 0.27–0.5 mmol/L Urine levels Small: <20 mg/dl Moderate: 30–40 mg/dl Large: >80 mg/dl
Evaluation of renal clearance	Appropriate clearance of excessive components: H⁺ or HCO₃⁻ Appropriate clearance of excessive components: BUN and creatinine	pH Perfect: 7.40 Range: 7.35–7.45 BUN: 0–20 mg/dl Creatinine: <2.0 mEq/L