WARNING: It has been longer since freshman chemistry than you realize. We strongly advise reading Chapter 10, Introduction to Acid-Base before advancing beyond this point.
Metabolic acidosis is characterized by a low bicarbonate, a low pH and,
after respiratory compensation, a low PCO2.
Metabolic acidosis occurs by one of two mechanisms: • loss of bicarbonate
• addition of acid
Metabolic acidosis is characterized by a fall in the
arterial concentration of bicarbonate.
This chapter is an introduction to the pathophysiology and differential diagnosis of the two types of metabolic acidosis. Additionally, the formulas used to uncover other acid-base dis-orders are reviewed. This chapter should be read prior to Chapters 12 and 13.
Metabolic acidosis is characterized by a _____ (low/high) pH and a _____ (low/high) bicarbonate concentration.
After compensation for metabolic acidosis, the PCO2 is _____ (low/high).
Metabolic acidosis is due to either the ________ (loss/gain) of bicarbon-ate or the addition of ________.
low low low loss acid pH ∝ HCO3 – CO2 pH ∝ HCO3 – CO2 pH ∝ HCO3 – CO2 pH ∝ HCO3 – CO2
Metabolic acidosis can be caused by the loss of
One type of metabolic acidosis is due to the loss of bicarbonate. By this mechanism, direct loss of bicarbonate lowers the plasma bicarbonate con-centration. The decrease in bicarbonate causes the concentrations of both hydrogen and chloride to increase.
Increased hydrogen (decreased pH). Hydrogen and bicarbonate are in equilibrium with water and carbon dioxide as shown in the bicarbonate buffer equation above. Loss of bicarbonate drives this equation toward the produc-tion of bicarbonate and hydrogen. The increase in bicarbonate producproduc-tion is not sufficient to replace the lost bicarbonate and its concentration remains low. However, the increase in hydrogen production does raise the hydrogen concentration, decreasing pH.
Increased chloride. Bicarbonate is one of the primary anions in the body. If this anion decreases, another anion must increase in order to tain electroneutrality. When bicarbonate is lost, chloride increases, main-taining electroneutrality.
Both mechanisms of metabolic acidosis result in a decreased bicarbonate and a(n) __________ (decreased/increased) pH.
If bicarbonate is lost, then the chloride concentration ___________ (decreases/increases).
Loss of bicarbonate shifts the bicarbonate buffer equation to-ward the production of hydrogen ion. HCO3 H+ HCO3 H+ C HCO3 H+ HCO3 H+ C cations = anions = HCO3
Na+ K+ cations anions HCO3
Na+ K+ A- other
anions A- otheranions
Loss of bicarbonate causes the chloride concentration to in-crease, maintaining electroneutrality.
HCO3– cations = anions =
Na+ K+ anions cations
Na+ K+ HCO3
Cl– A- other anions HCO3
Cl– A- other anions
Addition of an acid shifts the bicarbonate buffer equation toward the pro-duction of water and car-bon dioxide. The reaction consumes bicarbonate, de-creasing its concentration.
Addition of an acid is the addition of an H+
and its ac-companying anion. When an acid is added, its anion accumulates in the plas-ma; the Cl– concentration does not change.
Metabolic acidosis can be caused by the addition
The other type of metabolic acidosis is due to the addition of acid. For the purpose of understanding metabolic acidosis, an acid is defined as a hydro-gen cation and its accompanying anion. In this type of metabolic acidosis, the addition of acid directly raises the hydrogen ion concentration (lowers pH). The increase in hydrogen causes the bicarbonate concentration to de-crease. Due to the presence of increased anions, the chloride concentration does not change.
Decreased bicarbonate. Hydrogen and bicarbonate are in equilibrium with water and carbon dioxide as shown in the bicarbonate buffer equation above. The addition of acid (hydrogen ion), shifts the reaction toward the production of water and carbon dioxide. Bicarbonate decreases as it is con-sumed buffering hydrogen.
Increased anions. As acid is added, the accompanying anions accumu-late in the plasma. Even though the bicarbonate concentration is low, the chloride concentration does not change because the accompanying anions maintain electroneutrality.
An acid consists of two components: a(n) ___________ ion and an accompanying ________.
In metabolic acidosis due to the addition of acid, the bicarbonate concentration ____________ (decreases/increases) as it is con-sumed buffering hydrogen.
hydrogen anion decreases HCO3 H+ HCO3 H+ C HCO3 H+ HCO3 H+ C
= anions cations Na+ K+ HCO3 Cl– A- other anions .
The anion gap is a tool used in the evaluation of
Metabolic acidosis due to the loss of bicarbonate or the addition of acid can be distinguished by the anion gap.
The anion gap is a clinical tool based on the principle of electroneutrality
which is used to detect an increase in plasma anions other than Cl– and
HCO3– . The formula is shown above. Normally, the anion gap is between 5
and 12 mEq/L.
In metabolic acidosis due to the loss of bicarbonate, the anion gap re-mains within the normal range. The anion gap is normal because a rise in chloride compensates for the fall in bicarbonate. This type of acidosis is known as non-anion gap metabolic acidosis or hyperchloremic acidosis.
In metabolic acidosis due to the addition of acid, the anion gap increases because the addition of acid includes the addition of anions. The increased anion gap indicates the presence of these additional anions in the plasma. This type of acidosis is known as anion gap metabolic acidosis.
Because it so effectively narrows the differential diagnosis, calculating
the anion gap is the first step in the evaluation of metabolic acidosis.
Anion gap = Na+
The formula for anion gap is _____________________. Calculate the anion gap: Na+ = 140 mEq/L, Cl– = 118 mEq/L and HCO3– = 15 mEq/L. This is a(n) ________ gap metabolic acidosis. Calculate the anion gap: Na+ = 140 mEq/L, Cl– = 101 mEq/L and HCO3– = 12 mEq/L. This is a(n) ________ gap metabolic acidosis.
Na+ – (Cl– + HCO3–) anion gap = 7 non-anion anion gap = 27 anion
The concept of anion gap was introduced in Chapter 1, Moles and Water page 21.
= cations anions HCO3 Cl– Na + K+ A- other anions HCO3 A -H+ A -H+
= cations anions HCO3
Na+ K+ A- other anions
Non-anion gap metabolic acidosis is caused by the
loss of bicarbonate.
GI LOSS OF HCO3– RENAL LOSS OF HCO3–
Renal tubular acidosis (RTA)
proximal (type 2 RTA) distal (type 1 RTA)
hypoaldosteronism (type 4 RTA)
GI loss diarrhea surgical drains fistulas ureterosigmoidostomy obstructed ureteroileostomy cholestyramine
Non-anion gap metabolic acidosis is due to the loss of bicarbonate from either the GI tract or kidney. The differential diagnosis of non-anion gap metabolic acidosis is listed above.
In non-anion gap metabolic acidosis, the anion gap is less than 12 mEq/L.
Non-anion gap metabolic acidosis is due to the ________ of bicar-bonate from either the ____ tract or the ________.
In non-anion gap metabolic acidosis, the chloride concentration is __________.
loss GI; kidney
All of the causes of non-anion gap metabolic acidosis are reviewed in detail in Chapter 12,
= anions cations
Na+ K+ HCO3
Cl– A- other anions
Anion gap metabolic acidosis is caused by the
addi-tion of acid.
Anion gap metabolic acidosis is due to the addition of acid. The additional acid is either endogenous (produced by the body) or exogenous (ingested). In anion gap metabolic acidosis, the anion gap is greater than 12 mEq/L.
There are four fundamental processes that cause anion gap metabolic acidosis: lactic acidosis, ketoacidosis, renal failure and ingestions. A handy mnemonic for the differential diagnosis of anion gap metabolic acidosis is PLUM SEEDS.
Paraldehyde ... Ingestion Lactic Acidosis ... Lactic acidosis Uremia ... Renal Failure Methanol ... Ingestion Salicylate poisoning ... Ingestion Ethanol ... Ketoacidosis Ethylene glycol ... Ingestion DKA ... Ketoacidosis Starvation ... Ketoacidosis C C O O CH3 CH2 O O C C HO CH3 CH2 O O H CH3 CH3 CH2 KETOACIDOSIS RENAL FAILURE Oxygen LACTICACIDOSIS INGESTIONS lactic; ketoacidosis, renal failure; ingestions PLUM SEEDS Anion gap metabolic acidosis is caused by one of four
funda-mental processes: _________ acidosis, _____________, _______ ______ and _____________.
A good mnemonic is _________________.
All of the causes of anion gap metabolic acidosis are reviewed in detail in Chapter 13,
The compensation for metabolic acidosis is an
increase in ventilation which decreases PCO2
Regardless of the anion gap, compensation for the low bicarbonate found in both types of metabolic acidosis is a decrease in PCO2. PCO2 decreases through
an increase in ventilation. The expected fall in PCO2 in metabolic acidosis is
predicted by the following equation.
In metabolic acidosis, if the PCO2 is ________ than the expected
value, a concurrent respiratory alkalosis is present.
If the HCO3– is 12 mEq/L, what is the expected PCO2? If the PCO2
is 19 mmHg, what other disorder is also present?
24 to 28 mmHg respiratory alkalosis
If the PCO2 falls within the expected range, appropriate compensation has
If the PCO2 is above or below the PCO2 predicted by the formula, a
concur-rent respiratory acid-base disorder is present. If the PCO2 is lower than
pre-dicted, a respiratory alkalosis is also present; if the PCO2 is higher than
expected, a respiratory acidosis is also present.
16 18 20 22 14 10 12 40 38 36 34 32 30 28 26 24 22 20 18 16 14 8 6 24 26 44 42 RESPIRAT ORY ALKALOSIS RESPIRAT ORY ACIDOSIS Bicarbonate (mEq/L) PCO 2 (mmHg) Normal
Metabolic acidosisMETABOLICACIDOSIS Expected PCO2 = (1.5 × HCO3–) + 8 ± 2 C C C
Just as assessing compensation can uncover a concomitant respira-tory acid-base disorder, determining the corrected bicarbonate can un-cover a concomitant metabolic acid-base disorder (i.e., non-anion gap metabolic acidosis or metabolic alkalosis). The formula is shown above. The corrected bicarbonate is the bicarbonate before the anion gap acidosis began. If the corrected bicarbonate is above the normal range of bicarbonate concentration (22 to 28 mEq/L), a concurrent metabolic alkalosis is present; if the corrected bicarbonate is below the normal bicarbonate range, a concurrent non-anion gap metabolic acidosis is present. The following case illustrates how two metabolic acid-base disorders can be present at the same time:
MJ is an 18-year-old diabetic who develops infectious diarrhea which causes a non-anion gap metabolic acidosis. Because she is not feeling well, she stops taking her insulin. She then develops diabetic ketoaci-dosis (DKA), causing an anion gap metabolic aciketoaci-dosis. When she pre-sents to the hospital, her bicarbonate is 10 and the anion gap is 22. The corrected bicarbonate is 10 + (22-12) or 20 mEq/L. This means that before she developed DKA, the bicarbonate was 20 mEq/L. 20 mEq/L is below the normal range for bicarbonate indicating that a non-anion gap metabolic acidosis is also present. In this patient, it is from diarrhea.
Another equation that can be used to assess the presence of an addi-tional metabolic acid-base disorder in anion gap metabolic acidosis is the delta-delta. The formula is shown above. If the ratio is less than one, a concurrent non-anion gap metabolic acidosis is present. If the ratio is greater than two, a concurrent metabolic alkalosis is present.
Using the example above, the delta-delta is (22 – 12) ⁄ (24 – 10) = 10 ⁄ 14 = 0.7. Since 0.7 is less than one, a non-anion gap metabolic acido-sis is also present, as determined by the corrected bicarbonate above.
Clinical correlation: In anion gap metabolic acidosis, the
correct-ed bicarbonate or delta-delta can be uscorrect-ed to uncover an additional
metabolic acid-base disorder.
• if > 28, then a metabolic alkalosis is present
• if < 22, then a non-anion gap metabolic acidosis is present measured HCO3– + (anion gap – 12)
measured anion gap – ideal anion gap ideal HCO3– – measured HCO3–
= ∆ gap
• if > 2, then a metabolic alkalosis is present
Metabolic acidosis: the overview.
Metabolic acidosis is one of the four primary acid-base disorders. It is recognized by a low pH and a low plasma bicarbonate.
In metabolic acidosis, the decreased bicarbonate concentration can be due to either the loss of bicarbonate or the addition of an acid.
The anion gap is a tool that can distinguish between the two fundamental processes which cause metabolic acidosis.
Compensation for metabolic acidosis from any etiology is increased
venti-lation to lower the PCO2 and raise the pH. In metabolic acidosis, the carbon
dioxide falls by a predictable amount depending on the plasma bicarbonate
concentration. If the PCO2 is not within the predicted range, a respiratory
acid-base disorder is present in addition to metabolic acidosis. In anion gap metabolic acidosis, the corrected bicarbonate can be used to uncover a con-current metabolic alkalosis or non-anion gap metabolic acidosis.
= anions cations
Na+ K+ HCO3
Cl– A- other anions = cations anions HCO3
Na+ K+ A- other anions
orLOSSOFBICARBONATE NON-ANION GAP ADDITIONOFACID ANION GAP cations = anions
Na+ K+ HCO3
Cl– A- other anions
Renal tubular acidosis
proximal distal hypoaldosteronism GI loss of bicarbonate diarrhea fistulas ureterosigmoidostomy obstructed ureteroileostomy cholestyramine
NON-ANION GAPMETABOLIC ACIDOSIS
Paraldehyde Lactic Acidosis Uremia Methanol Starvation Ethanol Ethylene glycol DKA Salicylate poisoning
ANION GAP METABOLIC ACIDOSIS
pH ∝ HCO3– CO2 pH ∝ HCO3– CO2 pH ∝ HCO3– CO2 pH ∝ HCO3– CO2 metabolic acidosis metabolic alkalosis respiratory acidosis respiratory alkalosis
Expected PCO2 = (1.5 × HCO3–) + 8 ± 2
CORRECTED BICARBONATE Measured HCO3– + (Anion gap – 12)
The causes of both non-anion gap and anion gap metabolic acidosis are listed below. The next two chapters will look at the individual disorders in detail.