Endocrine and Metabolic 6: Acid-Base Portal
Concepts and Clinical Considerations
Concepts: Definitions, Components, Values, and Calculations
Thebody strives to maintain tight regulation of hydrogen ions for optimal
cellular function with 3 complex interlocking processes:
intra/extracellular buffers (weak acids and bases), alveolar
ventilation of carbon dioxide, and renal hydrogen excretion. Clinical
acid-base management is derived from 2 lab tests drawn simultaneously:
(the arterial blood gas [ABG] and venous electrolytes) and a complete
clinical assessment of the patient. (Venous pH and PCO2
may be used for
calculations, except in profound shock states.1
For that reason and the
usefulness of the PO2 information, ABGs became
the preferred source for
obtaining the pH and PCO2.)
The pH, pCO2,
and HCO3- are the acid-base components of the
ABG:
pH:
The pH expresses the hydrogen ion (H+ Ion) concentration in the blood
as a negative logarithm via the Henderson-Hasselbalch equation:
pH = 6.1 + log of the base (bicarbonate, HCO3-)/acid
(bicarbonic acid,
H2CO3).
There
are no units to pH. The normal arterial value is 7.40 (normal range
from about 7.38 to 7.42). Due to the nature of this mathematical
relationship, a (small) linear change in pH reflects a (large) inverse
logarithmic change in hydrogen ion concentration. For example, a change
in pH of only 0.3 reflects a 100% change in hydrogen ion concentration
in the opposite direction.
Table 1. Relationship of pH values and nmol/L of H+ ion
| Acidosis | pH | H+ nmol/L |
| 6.8 | 160 | |
| 7.0 | 100 | |
| 7.1 | 80 | |
| 7.2 | 64 | |
| 7.3 | 50 | |
| Normal | 7.4 | 40 |
| Alkalosis | 7.5 | 32 |
| 7.6 | 25 | |
| 7.7 | 20 | |
| 7.8 | 16 | |
| 8.0 | 10 |
Acidemia refers to blood being in an acidic pH range; alkalemia refers to blood in a basic pH range. Primary metabolic and respiratory disorders cause these pH alterations and are referred to as metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Combinations of the primary disorders are referred to as mixed disorders. When these disorders happen, the body strives to adjust the pH back to an acceptable functional range for cellular metabolism by mobilizing compensatory mechanisms, which can also contribute to a ‘mixed’ state of acid-base affairs. See Clinical Considerations.
PaCO2 , usually written as PCO2, is the arterial CO2 pressure with units in mm of Hg. It is basically equivalent to alveolar CO2 pressure, as there is generally no gradient of CO2 between the alveoli and the circulation. Normal value of PCO2 is 40 plus or minus 2 to 5 mm Hg. It varies inversely with ventilation: as ventilation increases, the PCO2 decreases; as ventilation decreases, the PCO2 increases. Note that CO2 has a reciprocal relationship with O2: impaired ventilation and CO2 accumulation will displace O2 (and lower PO2 ).
HCO3- is bicarbonate, the weak base component of bicarbonic acid, H2CO3. It is a major anion in the serum, and part of the buffering system to maintain the body’s pH in a livable range. It is measured in units of mEq/liter, with a normal value of 25 plus or minus 2 mEq/L. The ABG reports out a calculated value for HCO3-, whereas the measured serum value actually consists of total carbon dioxide which is composed largely of HCO3- along with a little bit of dissolved carbon dioxide (0.03 X PCO2 ). (Therefore, true HCO3- = total serum carbon dioxide – [0.03 X PCO2 ]). Often, this bit is ignored, and the total carbon dioxide value is equated with the HCO3- value.
The components of serum electrolytes are sodium, potassium, chloride, and bicarbonate (total carbon dioxide). They are part of a group of chemicals that have either a positive valence (called cations) or a negative valence (called anions). Other cations and anions exist in the plasma; however, not all are routinely measured or can be.
Major Serum Cation:
- Sodium, Na+: normal value = 140 mEq/L +/- 4 mEq/L
Major Serum Anions:
- Chloride, Cl- : normal value is equal to approximately a normal value
of 100 if the sodium is 140 (roughly Na+ divided by 1.4). An abnormal
Cl- level is a red flag for some form of an acid/base
abnormality, even if HCO3- is normal.
- Hyperchloremia is an increase in serum Cl- above the NA+ linked expected value and may reflect a decrease in the anion gap.
- Hypochloremia is a decrease in serum Cl- below the NA+ linked expected value, and may reflect an increase in the anion gap.
- Bicarbonate, HCO3- : normal value = 25 plus or minus 2 mEq/L.
- Base deficit is of the bicarbonate in mEq/L contained in the extracellular fluid of the body (the intravascular volume plus interstitial fluid).
- Base excess is the excess amount of bicarbonate in the extracellular fluid of the body.
Serum Anion Gap
Subtracting
the values of the measured major anions from the value of the sodium
cation, we see that a normal ‘gap’ exists, which represents the
dominance of the unmeasured anions over the unmeasured cations. The
normal anion gap value is 12 ± 2-4 mEq/L.
- Anion gap =
NA+ - [Cl- + HCO3-] =
unmeasured anions - unmeasured
cations.
An increased anion gap reflects either an increase of unmeasured cations minus unmeasured anions. The presence of an increased anion gap signifies a base deficit and a metabolic acidosis. The utility of measuring the anion gap is that those things that cause an anion gap acidosis (anion gap > 12 ± 2-4) are different from those causing a non-anion gap acidosis (anion gap < or = to 12 ± 2-4). - Note the somewhat confusing terminology: An anion gap acidosis means that the value is above the normal gap whereas a non-anion gap acidosis means that the value is < than or = to the normal gap.
- Protein disorders change the normal anion gap values. The anion gap decreases by 2.5 for each gram that the albumin decreases below 4 g/L (ie, if the albumin level is 2.0, the normal anion gap is 7.0).
Urinary Anion Gap
One
can also calculate a urinary anion gap that can sometimes be useful in
evaluating whether or not renal tubular acidosis is the cause of a
patient’s serum non-anion gap metabolic acidosis.
- Major measured urinary cations are NA+ and K+; major measured urinary anion is Cl-.
- Major unmeasured cation is NH+ and the major unmeasured anion is HCO3-.
- Urinary anion gap = (NA+ + K+) - Cl- (This is usually positive or near zero in the normal state of acid-base balance.)
- Note: Ketonuria and severe volume depletion (from extrarenal sodium bicarbonate loss) make this calculation unreliable.
Utility: in patients with metabolic acidosis, the normally functioning kidney excretes the acid NH4Cl to help compensate for the abnormal acidosis. This increases the amount of measured Cl in the urine, resulting in a negative urinary anion gap (ie, the Cl value is greater that the sum of Na and K so the value has a negative value)—the response of a normal kidney getting rid of acid in the face of metabolic acidosis. Therefore, a positive urinary anion gap (positive value to the calculation of [Na + K]-Cl) in a patient with a serum non-anion metabolic acidosis suggests renal tubular acidosis as the cause.
Clinical Considerations
Primary
Acid-Base Disorders and Some Guiding Rules
As
the body’s pH equilibrium (vital for cellular function) is disturbed by
acute or chronic clinical insults, its systems interact to compensate
for changes. The respiratory system reacts much faster (in minutes)
than the renal system does (in hours to days). Disease states
underlying these primary disorders are listed following this section.
Respiratory Acidosis
is manifested as increased PCO2 due to
hypoventilation. Increased
CO2 increases H+ ion concentration with the
result that pH decreases.
(In compensation, HCO3- will increase in order
to bring the pH back
toward normal.)
- Rule 1
An increase in PCO2 by 10 mm Hg causes the pH to decrease by 0.08 in the absence of metabolic compensation. - Rule 2
In acute respiratory acidosis, an increase of PCO2 by 10 mm Hg results in an HCO3- increase of 1 mEq/L. - Rule 3
In chronic respiratory acidosis (or compensated respiratory acidosis), a 10 mm Hg increase in PCO2 results in a compensatory 5 mEq/L increase in HCO3- .
Respiratory
Alkalosis is manifested as decreased PCO2
due to hyperventilation. Less CO2
leads to a lower H+ ion concentration
and therefore pH increases. (In compensation, HCO3-
will decrease in
order to bring the pH back toward normal.)
- Rule 4
A decrease in PCO2 by 10 mm Hg causes a pH increase of 0.08 in the absence of metabolic compensation. - Rule 5
In acute respiratory alkalosis, a 10 mm Hg decrease in PCO2 results in a 2.5 mEq/L decrease in HCO3-. - Rule 6
In chronic respiratory alkalosis (or compensated respiratory alkalosis), a 10 mm Hg decrease in PCO2 results in a compensatory 5 mEq/L decrease in HCO3- .
Metabolic Acidosis is a primary decrease in HCO3- concentration, and manifests as an acidemia (the H+ ion concentration increases and the pH decreases). (In compensation, ventilation is increased, blowing off CO2 in order to bring the pH back toward normal.) Two categories of metabolic acidosis are discussed below.
- Rule 7
A 10 mEq/L decrease in HCO3- results in a 0.15 unit pH decrease if there is no respiratory compensation. - Rule 8
Winter's Rule for normal respiratory compensation of metabolic acidosis is: expected PCO2 = (1.5 x HCO3-) + (8 ± 2). This means that the PCO2 should decrease by 1.5 mm Hg for each one mEq decrease in HCO3- if the respiratory system can adequately respond to help normalize the pH.
Metabolic Alkalosis is manifested as an increase in HCO3- concentration and a decrease in H+ ion concentration. The pH increases. (In compensation, breathing is slowed, and CO2 rises in order to increase H+ to bring the pH back toward normal.
- Rule 9
A 10 mEq increase in HCO3- results in a pH increase of 0.15 units if there is no respiratory compensation.
Causes of
Respiratory Acidosis
Conditions that depress ventilation, such as:
- CNS dysfunction (CNS disease, drug overdoses, anesthetic agents, etc.)
- Musculoskeletal disorders (Guillain-Barre, kyphoscoliosis, myasthenia gravis, polio, massive obesity, diaphragmatic paralysis)
- Pulmonary disease (pneumothorax, COPD, pneumonia, asthma, obstruction)
Causes of
Respiratory Alkalosis
Conditions that increase ventilation, such as:
- Any acute pulmonary problem
- Anxiety
- Cirrhosis
- CNS events (hemorrhage)
- Decreased lung compliance
- Drugs (salicylates, others)
- Hypoxemia
- Sepsis
Causes of Metabolic Alkalosis
- Chloride-responsive alkalosis (responds to NaCl or KCl treatment)
- Alkali ingestion (large amounts of non-absorbable antacids)
- Loss of gastric secretions (vomiting, NG suction)
- Diuresis
- Volume contraction
- Corticosteroids
- Miscellaneous: cystic fibrosis, villous adenoma, post-hypercapnic state
- Chloride-resistant alkalosis (urine chloride >20 mEq/L)
- Hypokalemia
- Renal failure; renal artery stenosis
- Bartter’s syndrome and other familial disorders
- Any hyperaldosterone state
Causes of
Metabolic Acidosis with Increased Anion Gap
Metabolic
acidosis with an increased anion gap results from accumulated acidic
metabolites and is manifested by a decreased pH and a decreased HCO3-.
When respiratory compensation has reached the limit of its ability to
compensate further (PCO2 maximally lowered), any
continued acid
accumulation/decrease in HCO3- is unopposed and
the pH is dangerously
lowered. Be aware of the potentially fatal combination of low PCO2
and
low HCO3- . Furthermore, if the person tires
from breathing maximally
and starts to fail, the now increasing PCO2 adds
fuel to the fire.
Therefore, find the cause for the increased anion gap metabolic
acidosis and treat as appropriately and quickly as possible.
The mnemonic MUD PILES summarizes the causes for anion gap acidosis:
M—Methanol
U—Uremia (advanced renal failure)
D—Diabetic ketoacidosis
P—Paraldehyde
I—Iron, ison— Iron, isoniazide, inhalants (CO, CN, H2S)
L—Lactic acidosis (sepsis, prolonged seizures, LV failure, others)
E—Ethanol ketoacidosis, ethylene glycol
S—Salicylates, solvents (toluene), starvation (ketoacidosis)
Causes of
Metabolic Acidosis without an Anion Gap
(Non-anion Gap Metabolic
Acidosis, also called hyperchloremic metabolic
acidosis)
This group of diseases are rarely immediately life threatening. These
can be summarized with the mnemonic USED CARP.
| U | Ureteroenterostomy/ureteral diversion |
| S | Small bowel fistula |
| E | Extra chloride (when volume loading with too much NS, the extracellular fluid pool’s HCO3- is diluted while its Cl- concentration increases |
| D | Diarrhea (HCO3- excreted) |
| C | Carbonic anhydrase inhibitors (eg, Diamox) |
| A | Adrenal insufficiency; Acid infusion (HCL, NH4Cl) or inhalation (Cl gas) |
| R | Renal tubular acidosis; Renal compensation for respiratory alkalosis; (early) Renal failure |
| P | Pancreatic fistula; Parental nutrition (inadequately matched hyperal solutions) |
Eight-Step Clinical Approach* to Acid-Base Problems2-4
| Step 1 | What is the pH? Does the patient
have an acidosis or an alkalosis? If so, what type? Low pH (acidosis) is < 7.38
|
| Step 2 | If it is a respiratory problem,
is
it acute or chronic? Acute changes signify a new/dynamic process suggesting a need for more acute intervention.
|
| Step 3 | If the patient has a metabolic
acidosis, is the anion gap normal or increased?
|
| Step 4 | If the patient has an anion gap
metabolic acidosis, are there any co-existing metabolic disturbances?
|
| Step 5 | Is
there an appropriate
respiratory response to the metabolic acidosis?
|
| Step 6 |
Is there an appropriate
respiratory response to metabolic alkalosis? The body can slow down breathing only so much to help compensate for metabolic alkalosis; there is no linear relationship between PCO2 and HCO3- in this condition, and the response isn’t easily predictable. The PCO2 can increase up to 50 to 55 mm Hg; the pH will remain somewhat alkalotic. If the patient is acidemic in the face of metabolic alkalosis and increased PCO2, suspect a concurrent respiratory acidosis. |
| Step 7 |
What is the appropriate treatment
for the underlying disease causing the acid-base disorder? Addressing the disease process underlying each primary acid-base disorder is critical in re-establishing acid-base homeostasis. In many of these underlying diseases, fluid, electrolyte, and ventilation management play critical roles: the ABCs of resuscitation go a long way. Several tips can further clarify the underlying disease:
|
| Step 8 |
When and how does one give
specific acid-base replacement therapy? 5,6 Severe metabolic alkalosis (pH> 7.55 to 7.60) is a life-threatening emergency, which may require HCl infusion or dialysis. Obtain a stat consult with a nephrologist while addressing coexisting fluid and electrolyte concerns. Consider bicarbonate therapy IV with severe metabolic acidosis (pH< 7.2), especially with cardiac dysfunction or in the situations described previously under AG metabolic acidosis. (pH values >7.2 are generally well tolerated.) The goal is to raise the pH to 7.2 or a bit more without causing ‘overshoot’ alkalosis, hypernatremia, hyperosmolality, or fluid overload. If the patient needs to be given HCO3-, calculate the total body HCO3 deficit:
|
Viewpoint of Acid-Base Interpretation
The Henderson-Hasselbalch formula can be plotted to form the Davenport
Diagram as shown because PCO2 is proportional to H2CO3 (carbonic acid)
concentration. Understanding the relationships of PCO2, pH, the normal
buffer line, and HCO3 level is the key to being comfortable with blood
gas interpretation. The Davenport Diagram allows you to plot a
patient’s lab values and visualize these relationships.
The Davenport Diagram, © 1977 by the Upjohn Company
The normal buffer line is determined by the normal concentration of weak acids and bases found in the plasma. When abnormal concentrations of these weak acids, bases, or abnormal substances (such as ketones) exist, there is a base excess or base deficit.
References
- Abram S. Acid-base disturbances: metabolic acidosis. Practical Reviews in Emergency Medicine. Oct 1999; 24-3 (1).
- Narins RG. Simple and mixed acid-base disorders: a practical approach. Medicine. 1980;59:161-187.
- Morganroth ML. Six steps to acid-base analysis: clinical applications. J Crit Ill. 1990;5:460-469.
- Morganroth ML. An analytic approach to diagnosing acid-base disorders. J Crit Ill. 1990; 5:138-150.
- Adrogue H, Madias N. Management of life-threatening acid-base disorders. N Engl J Med. 1998;338:26-34.
- Adrogue H, Madias N. Management of life-threatening acid-base disorders. N Engl J Med. 1998;338:107-11.
References for Concepts, Rules, Formulas, Values
- Martin, L. All you really need to know to interpret arterial blood gases. 2nd Edition. 1999. Lippincott Williams Wilkins.
- Rose BD. Clinical physiology of acid-base and electrolyte disorders. 5th Edition. 2000. McGraw Hill.