Tools to Use to Diagnose Acid–Base Disorders

Introduction

There are four primary acid–base disturbances, two metabolic and two respiratory. Each of these disorders has an expected compensatory response, which is aimed at minimizing the change in H ⁺ ion concentration. These expected responses, unfortunately, must be memorized. Knowing these expected responses helps identify mixed acid–base disorders.

As was emphasized in Chapter 1 , the role of buffering in patients with metabolic acidosis is not simply to lower the concentration of H ⁺ ions but, of even greater importance, to minimize the binding of H ⁺ ions to proteins in cells of vital organs (e.g., the brain and the heart). This “safe” removal of H ⁺ ions occurs via the bicarbonate buffer system (BBS), the bulk of which is in the intracellular fluid and the interstitial space of skeletal muscle. Free-flowing brachial venous partial pressure of carbon dioxide (PCO ₂ ), which reflects the capillary blood PCO ₂ in skeletal muscles, should be measured in patients with metabolic acidosis to assess the effectiveness of BBS in removing the H ⁺ ion load.

The role of the kidney in chronic metabolic acidosis is to generate new bicarbonate ions $({HCO}_{3}^{-})$ $({HCO}_{3}^{-})$ by increasing the rate of excretion of ammonium ( ${NH}_{4}^{+}$ ${NH}_{4}^{+}$ ) ions.

Metabolic alkalosis is an electrolyte disorder accompanied by an elevated concentration of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions in plasma ( $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ ) and a rise in plasma pH. Most patients with metabolic alkalosis have a deficit of NaCl, KCl, and/or HCl, each of which leads to a higher $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ . The expected physiologic response in patients with metabolic alkalosis is hypoventilation and hence an increase in the arterial PCO ₂ .

In patients with respiratory acid–base disorders, the expected change in $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ differs depending on whether the disorder is acute or chronic.

We emphasize that one must integrate all the information from the medical history and the physical examination together with the laboratory data to make an acid–base diagnosis.

Abbreviations

BBS, bicarbonate buffer system
${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ , bicarbonate ions
$P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ , concentration of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions in plasma
ECF, extracellular fluid
P _{Anion gap} , anion gap in plasma
P _Albumin , concentration of albumin in plasma
[H ⁺ ], concentration of hydrogen ions
ICF, intracellular fluid
EABV, effective arterial blood volume
PCT, proximal convoluted tubule
P _K , concentration of potassium (K ⁺ ) ions in plasma
P _Na , concentration of sodium (Na ⁺ ) ions in plasma
P _Cl , concentration of chloride (Cl ⁻ ) ions in plasma

Objectives

▪
To illustrate the tools needed to identify whether there is an acid–base disorder and why it is present. Our emphasis will be on metabolic acidosis.
▪
To illustrate how to obtain a quantitative estimate of the extracellular fluid (ECF) volume to assess the content of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions in the ECF compartment to determine if metabolic acidosis is present in a patient with significantly contracted ECF volume.
▪
To illustrate how to determine whether metabolic acidosis is due to the overproduction of acids or the loss of sodium bicarbonate (NaHCO ₃ ).
▪
To illustrate how to assess whether H ⁺ ions were removed appropriately by the BBS in a patient with metabolic acidosis.
▪
To illustrate how to assess the rate of excretion of ${NH}_{4}^{+}$ ${NH}_{4}^{+}$ ions in the urine in a patient with metabolic acidosis, and to illustrate the urine tests that may help to identify the cause of a low rate of excretion of ${NH}_{4}^{+}$ ${NH}_{4}^{+}$ ions.

Case 2-1: Does This Man Really Have Metabolic Acidosis?

A 25-year-old man was perfectly healthy until 24 hours ago, when he developed severe, watery diarrhea. He had no intake of food or water. He noted that he had very little urine output over the last several hours. His blood pressure is 90/60 mm Hg, pulse rate is 110 beats per minute, and his jugular venous pressure is low. Acid–base measurements in arterial blood reveal a pH 7.39, $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ 24 mmol/L, and PCO ₂ 39 mm Hg. His P _{Anion gap} is 24 mEq/L. His diarrhea volume is estimated to be ∼5 L, and the concentration of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions in a sample of his diarrhea fluid is 40 mmol/L. His hematocrit on admission is 0.60, and his P _Albumin is 8.0 g/dL (80 g/L).

Normal Acid–Base Values in Plasma

pH: 7.40 ± 0.02
[H ⁺ ]: 40 ± 2 nmol/L
$P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ : 25 ± 2 mmol/L
Arterial PCO ₂ : 40 ± 2 mm Hg
Venous PCO ₂ : At usual rates of blood flow and metabolic work at rest, brachial venous PCO ₂ is about 46 mm Hg (∼6 mm Hg greater than the arterial PCO ₂ )

Questions

Does this patient have a significant degree of metabolic acidosis?
What is the basis for the high P _{Anion gap} ?

Case 2-2: Lola Kaye Needs Your Help

Lola Kaye, an 18-year-old woman, is brought to the emergency department because of severe weakness. Her blood pressure is low (80/50 mm Hg), and her pulse rate is high (124 beats per minute). Her respiratory rate is not low (20 breaths per minute). Her jugular venous pressure is low. The only laboratory values available at this time are from arterial blood gas measurements: pH 6.90 ([H ⁺ ] = 125 nmol/L), PCO ₂ = 30 mm Hg. She does not have a history of diabetes mellitus and denies ingestion of methanol or ethylene glycol.

Question

What is/are the major acid–base diagnosis/diagnoses in this patient?

Part A

Diagnostic Issues

Disorders of Acid–Base Balance

Before the discussion of each of the acid–base disorders, there are two points that are not included in the traditional approach to acid–base disorders and require emphasis.

The $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ Is Influenced by Changes in the ECF Volume

Concentration terms can be altered by changes in their numerator and/or their denominator. The concentration of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ in the ECF compartment can be influenced by changes in the amount of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ in the ECF compartment and/or changes in the ECF volume. Therefore, a patient may have metabolic acidosis with a near normal $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ and hence no appreciable acidemia, if the ECF volume is very contracted. Hence, a quantitative assessment of ECF volume is required to estimate the amount of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions in the ECF compartment and determine if metabolic acidosis is present (see the discussion of Case 2-1 ).

Measurement of Brachial Venous PCO ₂ to Assess Buffering of an H ⁺ Ion Load by BBS

In Chapter 1 , we emphasized that H ⁺ ions must be removed by the BBS to minimize their binding to proteins in cells of vital organs (e.g., the brain and the heart). A low PCO ₂ in the interstitial fluid compartment of the ECF of muscles and in muscle cells, where the bulk of the BBS exists, is a prerequisite to achieve this safe removal of H ⁺ ions. The traditional approach to acid–base disorders focuses only on the arterial PCO ₂ , which is influenced predominantly by regulation of ventilation. Having a low arterial PCO ₂ does not ensure that the PCO ₂ is low in the interstitial fluid compartment of the ECF of muscles and in muscle cells, because that PCO ₂ is also influenced by both the rate of production of CO ₂ and the blood flow rate to muscles. Patients with metabolic acidosis and a contracted effective arterial blood volume (EABV) have a high PCO ₂ in the interstitial fluid of skeletal muscles and skeletal muscle cells (reflected by a high PCO ₂ in their venous blood), and therefore may fail to titrate an H ⁺ ion load with the BBS in their skeletal muscle. As a result, the degree of acidemia may become more pronounced, and more H ⁺ ions may bind to proteins in the extracellular and intracellular fluids in other organs, including the brain. Notwithstanding, because of autoregulation of cerebral blood flow, it is likely that there will be only minimal changes in the PCO ₂ in brain capillary blood unless there is a severe degree of contraction of the EABV with failure of autoregulation of cerebral blood flow. Therefore, the BBS in the brain will continue to titrate much of this large H ⁺ ion load. Considering the limited content of HCO ₃ ⁻ ions in the brain and that the brain receives a relatively larger proportion of the cardiac output, there is a risk that more H ⁺ ions will bind to proteins in brain cells, further compromising their functions. At usual rates of blood flow and metabolic work at rest, brachial venous PCO ₂ is about 46 mm Hg, which is ∼6 mm Hg greater than the arterial PCO ₂ . If the blood flow rate to the skeletal muscles declines owing to a low EABV, the brachial venous PCO ₂ will be more than 6 mm Hg higher than the arterial PCO ₂ . Based on this analysis, and although experimental evidence to support this view is lacking, we recommend that in patients with metabolic acidosis, enough saline should be administered to increase the blood flow rate to muscle to restore the difference between the brachial venous PCO ₂ and the arterial PCO ₂ to its usual value of ∼6 mm Hg.

Definitions

Acidemia is a low pH or a high concentration of H ⁺ ions in plasma.
Acidosis is a process that adds H ⁺ ions to or removes ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions from the body.

pH versus [H ⁺ ]

The authors prefer to think in terms of the [H ⁺ ] rather than the pH, but the principles are the same: a low [H ⁺ ] is a high pH, and vice versa.

Disorders With a High Concentration of H ⁺ Ionsin Plasma

There are two types of acid–base disorders ( Flow Chart 2-1 ):
- Metabolic acid–base disorders: the primary change is in the $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$
- Respiratory acid–base disorders: the primary change is in the arterial PCO ₂

If the concentration of H ⁺ ions in plasma is higher (pH is lower) than normal values, the patient has acidemia. There are two potential primary disorders: metabolic acidosis or respiratory acidosis.

Metabolic acidosis

Metabolic acidosis is a process that adds H ⁺ ions to or removes ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions from the body, which will lead to a decrease in the content of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions in the ECF compartment. An expected physiologic response to acidemia of metabolic origin is hyperventilation, which leads to a lower arterial PCO ₂ . The $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ may be close to normal if there is a very contracted ECF volume, and hence there may be no changes in the arterial pH and PCO ₂ . Free-flowing brachial venous PCO ₂ , which best reflects the capillary blood PCO ₂ in skeletal muscles, should be measured in patients with metabolic acidosis to assess the effectiveness of the BBS in removing the H ⁺ ion load.

Respiratory acidosis

Respiratory acidosis is caused by impaired ventilation, and is characterized by a high arterial blood PCO ₂ and [H ⁺ ]. The expected physiologic response is an increase in $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ . The increase in $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ is tiny in patients with acute respiratory acidosis, because it reflects a shift to the left in the bicarbonate buffer reaction (see Eqn 1 ). In patients with chronic respiratory acidosis, there is a much larger increase in $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ due to the effect of associated intracellular acidosis in cells of the proximal convoluted tubule (PCT) to stimulate ammoniagenesis, which adds more ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions to the body, and the effect of the high peritubular PCO ₂ to enhance ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ion reabsorption by the PCT.

H^{+} + {HCO}_{3}^{-} ⇌ {CO}_{2} + H_{2} O

$H^{+} + {HCO}_{3}^{-} ⇌ {CO}_{2} + H_{2} O$

Disorders with a Low Concentration of H ⁺ Ions in Plasma

If the concentration of H ⁺ in plasma is lower (pH is higher) than normal, the patient has alkalemia. Again, there are two potential primary disorders: metabolic alkalosis or respiratory alkalosis.

Metabolic alkalosis

This is a process that raises the $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ and lowers the concentration of H ⁺ ions in the ECF compartment. The expected physiologic response is hypoventilation and hence an increase in the arterial PCO ₂ ; the rise in PCO ₂ , however, is usually modest because of the effect of the resultant hypoxemia to stimulate ventilation.

Respiratory alkalosis

Respiratory alkalosis is due to hyperventilation and is characterized by low arterial PCO ₂ and plasma [H ⁺ ]. The expected physiologic response is a reduction in the $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ . As in respiratory acidosis, this response is modest in patients with acute respiratory alkalosis; it reflects the effect of the low PCO ₂ to shift the bicarbonate buffer reaction to the right (see Eqn 1 ). In patients with chronic respiratory alkalosis, there is a more appreciable decrease in $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ because of the effect of the low peritubular PCO ₂ to decrease the reabsorption of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions by the PCT. However, the concentration of H ⁺ ions in plasma may not change appreciably if the patients has an acid-base disorder that tends to increase the concentration of H ⁺ ions in plasma, and a concomitant acid-base disorder, but one that tends to decrease the concentration of H ⁺ ions in plasma (e.g., chronic respiratory acidosis due to chronic obstructive airway disease and metabolic alkalosis due to the administration of diuretics).

Making an Acid–Base Diagnosis

One must integrate the clinical picture and the laboratory data to make a proper acid–base diagnosis. For example, the finding of acidemia, a high arterial PCO ₂ , and an elevated $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ does not indicate that chronic respiratory acidosis is present if that patient does not have a chronic problem with ventilation; rather, the patient may have a metabolic alkalosis with an acute respiratory acidosis.

In addition to the parameters mentioned above commonly used in making an acid–base diagnosis, we use the hematocrit and/or total protein concentration in plasma to obtain a quantitative estimate of the ECF volume and calculate its content of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions, and the brachial venous PCO ₂ to assess the effectiveness of the BBS in a patient with metabolic acidosis.

Laboratory Tests Used in a Patient with Metabolic Acidosis

In this section we provide the rationale for some of the laboratory tests that are used in the clinical approach to the patient with metabolic acidosis ( Table 2-1 ). The specific questions to be addressed are shown in the table; the importance of each will become clear when the specific disorders are discussed in the following chapters.

TABLE 2-1

Tools Used in the Clinical Approach to Patients with Metabolic Acidosis

Question	Parameter Assessed	Tools to Use
Is the content of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions low in the ECF?	ECF volume	Hematocrit or total plasma proteins
Is metabolic acidosis due to overproduction of acids?	Appearance of new anions in the body or the urine	P _{Anion gap} Urine anion gap
Is metabolic acidosis due to ingestion of alcohol?	Detect alcohols as unmeasured osmoles	P _{Osmolal gap}
Is buffering of H ⁺ ions by BBS in skeletal muscle?	Buffering of H ⁺ ions by ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions in muscle interstitial fluid and in its intracellular fluid compartment	Brachial venous PCO ₂
Is the renal response to chronic acidemia adequate?	Examine the rate of excretion of ${NH}_{4}^{+}$ ${NH}_{4}^{+}$ ions in the urine	U _{Osmolal gap}
If ${NH}_{4}^{+}$ ${NH}_{4}^{+}$ ion excretion is high, which anion is excreted with ${NH}_{4}^{+}$ ${NH}_{4}^{+}$ ions?	Gastrointestinal loss of NaHCO ₃ Acid added, but the anions are excreted in the urine with NH ₄ ⁺ ions	Urine Cl ⁻ Urine anion gap
What is the basis for a low excretion of ${NH}_{4}^{+}$ ${NH}_{4}^{+}$ ions?	Low distal H ⁺ ion secretion Low NH ₃ availability Both defects	Urine pH > 7.0 Urine pH ~ 5.0 Urine pH ~ 6.0
Where is the defect in H ⁺ ionsecretion?	Distal H ⁺ ion secretion Proximal H ⁺ ion secretion	PCO ₂ in alkaline urine ${FE}_{{HCO}_{3}}$ ${FE}_{{HCO}_{3}}$ , U _Citrate

Questions to ask in the clinical approach to the patient with metabolic acidosis

Is the Content of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ Ions in the ECF Compartment Low?

Calculate the content of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions in the ECF compartment ( $P_{{HCO}_{3}}$ $P_{{HCO}_{3}}$ × ECF volume) if the ECF volume is appreciably low. The hematocrit or the concentration of total proteins in plasma are useful to obtain a quantitative estimate of the ECF volume (see margin note).

Use of the Hematocrit to Estimate the ECF Volume

Blood volume in an adult subject is ~70 mL/kg body weight. Therefore, in a 70 kg subject, blood volume is close to 5 L, with a RBC volume of 2 L and a plasma volume of 3 L. The hematocrit (the ratio of RBC volume to blood volume) is 0.40. When the hematocrit is 0.50, and assuming no change in RBC volume, the new plasma volume can be calculated as follows:

0.50 = RBC (2 L)/ blood volume (X L)

X = 4 L

∴ Plasma volume = blood volume − RBC volume (2 L) = 2 L
Therefore, the plasma volume is reduced by one-third. Ignoring changes in Starling forces for simplicity ( see following margin note ), the ECF volume has decreased to approximately two-thirds of its normal volume.

Starling Forces

Starling forces determine the distribution of volume between the intravascular and the extravascular or interstitial compartment of the ECF volume. The higher colloid osmotic pressure in plasma helps defend the plasma volume at the expense of the interstitial fluid volume. Hence, the degree of ECF volume contraction is even higher than that estimated from the calculated reduction in plasma volume.

Is There an Overproduction of Acids?

Overproduction of acids is detected by the appearance of new anions. The presence of new anions in plasma can be detected by a rise in the P _{Anion gap} . The presence of new anions in the urine can be detected by calculating the anion gap in the urine (see margin note); for this calculation, the concentration of ${NH}_{4}^{+}$ ${NH}_{4}^{+}$ ions in the urine ( $U_{{NH}_{4}}$ $U_{{NH}_{4}}$ ) should be estimated using the calculations of the urine osmolal gap (U _{Osmolal gap} ).

Urine Anion Gap

To detect new anions in the urine, we use the formula: U _Na + U _K + $U_{{NH}_{4}}$ $U_{{NH}_{4}}$ − U _Cl

Is the Metabolic Acidosis due to the Ingestion of Alcohols?

This is detected by calculation of the osmolal gap in plasma (P _{Osmolal gap} ). A high P _{Osmolal gap} indicates the presence of an unmeasured, uncharged compound in plasma. In clinical practice, this calculation is helpful to detect the presence of alcohols (e.g., ethanol, ethylene glycol, methanol, isopropyl alcohol) in plasma.

Abbreviations

HCMA, hyperchloremic metabolic acidosis
${FE}_{{HCO}_{3}},$ ${FE}_{{HCO}_{3}},$ fractional excretion of ${HCO}_{3}^{-}$ ${HCO}_{3}^{-}$ ions
U _Citrate , concentration of citrate in the urine
P _{Osmolal gap} , osmolal gap in plasma
P _Osm , plasma osmolality
U _NH4 , concentration of NH ₄ ⁺ ions in the urine
U _Na , concentration of sodium ions in the urine
U _K , concentration of potassium ions in the urine
U _Cl , concentration of chloride ions in the urine
U _Osm , urine osmolality
U _{Osmolal gap} , osmolal gap in the urine
U _Creatinine , concentration of creatinine in the urine

Is Buffering of the H ⁺ Ion Load by BBS in Skeletal Muscle?

To make this assessment, we measure the brachial venous PCO ₂ . A value that is more than 6 mm Hg higher than the arterial PCO ₂ indicates that the PCO ₂ in the interstitial space and cells of skeletal muscle is high, and therefore the BBS in skeletal muscle is ineffective in removing the H ⁺ ion load.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here

Introduction

Objectives

Case 2-1: Does This Man Really Have Metabolic Acidosis?

Questions

Case 2-2: Lola Kaye Needs Your Help

Question

Part A

Diagnostic Issues

Disorders of Acid–Base Balance

The PHCO3 P HCO 3 <math> <mrow> <msub> <mtext> P </mtext> <msub> <mtext> HCO </mtext> <mn> 3 </mn> </msub> </msub> </mrow> </math> Is Influenced by Changes in the ECF Volume

Measurement of Brachial Venous PCO 2 to Assess Buffering of an H + Ion Load by BBS

Disorders With a High Concentration of H + Ionsin Plasma

Metabolic acidosis

Respiratory acidosis

Disorders with a Low Concentration of H + Ions in Plasma

Metabolic alkalosis

Respiratory alkalosis

Making an Acid–Base Diagnosis

Laboratory Tests Used in a Patient with Metabolic Acidosis

Questions to ask in the clinical approach to the patient with metabolic acidosis

Is the Content of HCO3− HCO 3 − <math> <mrow> <msup> <msub> <mtext> HCO </mtext> <mn> 3 </mn> </msub> <mo> − </mo> </msup> </mrow> </math> Ions in the ECF Compartment Low?

Is There an Overproduction of Acids?

Is the Metabolic Acidosis due to the Ingestion of Alcohols?

Is Buffering of the H + Ion Load by BBS in Skeletal Muscle?

You're Reading a Preview

Related Posts

Hyperglycemia

Hyperkalemia

Hypokalemia

Potassium Physiology