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S. Faubel and J.

Topf 11 Metabolic Acidosis: The Overview

11
Metabolic Acidosis:
11 The Overview

WARNING: It has been longer since freshman chemistry than you realize.e strongly
W
advise reading Chapter 10,Introduction toAcid-Basebefore advancing beyond this point.

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The Fluid, Electrolyte and Acid-Base Companion

IntroductionMetabolic acidosis is characterized by a fall in the


arterial concentration of bicarbonate.

METABOLIC ACIDOSIS METABOLIC ALKALOSIS

– –
HCO3 HCO3
pH ∝ pH ∝
CO2 CO2

RESPIRATORY ACIDOSIS RESPIRATORY ALKALOSIS


– –
HCO 3
HCO3
pH ∝ pH ∝
CO2 CO2

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

This chapter is an introduction to the pathophysiology andferential


dif 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


(low/high) bicarbonate concentration. low

After compensation for metabolic acidosis, the PCO2 is _____ (low/high). low

Metabolic acidosis is due to either the ________ (loss/gain) of bicarbon- loss


ate or the addition of ________. acid

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S. Faubel and J. Topf 11 Metabolic Acidosis: The Overview

MechanismMetabolic acidosis can be caused by the loss of


bicarbonate.

H+ H+ HCO3 HCO3 H+ C
Loss of bicarbonate
shifts the bicarbonate
buffer equation to-
ward the production
of hydrogen ion.
H+ HCO3 HCO3 H+ C

Cl– Na+ – – Na+


Cl Cl
Loss of bicarbonate
causes the chloride
concentration to in-
crease, maintaining HCO3
HCO3
electroneutrality.
+
K A-
other
anions
A-
other
anions
K+

cations = anions anions = cations

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 production 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 main-
tain electroneutrality. When bicarbonate is lost, chloride increases, main-
taining electroneutrality.

Both mechanisms of metabolic acidosis result in a decreased bicarbonate aaa


and a(n) __________ (decreased/increased) pH. decreased

If bicarbonate is lost, then the chloride concentration ___________ increases


(decreases/increases).

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The Fluid, Electrolyte and Acid-Base Companion

MechanismMetabolic acidosis can be caused by the addition


of acid.

HCO3
Addition of an acid shifts H+ HCO3 HCO3 H+ C
the bicarbonate buffer
equation toward the pro-
duction of water and car-
bon dioxide. The reaction
consumes bicarbonate, de- H+ HCO3 HCO3 H+ C
creasing its concentration.

Na+ Na+
Anions Cl –
Cl –
Addition of an acid is the
addition of an H+ and its ac- HCO3
companying anion. When HCO3
an acid is added, its anion
accumulates in the plas-
– K+ A-
other A-
other K+
ma; the Cl concentration anions anions
does not change. cations = anions anions = cations

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 hydrogen


an accompanying ________. anion

In metabolic acidosis due to the addition of acid, the bicarbonate


concentration ____________ (decreases/increases) as it is con- decreases
sumed buffering hydrogen.

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S. Faubel and J. Topf 11 Metabolic Acidosis: The Overview

DiagnosisThe anion gap is a tool used in the evaluation of


metabolic acidosis.
Anion gap = Na+ – (Cl– + HCO3– )

LOSS OF BICARBONATE NORMAL ANION GAP ADDITION OF ACID INCREASED ANION GAP

– Na+ Na+
Cl
A- H +
Cl–

HCO3
H+ A-
HCO3
HCO3 A-
other
anions
K+ A-
other K+
anions
anions = cations anions = cations

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.
The concept of anion gap was introduced in ChapterMoles
1, and Water page 21.

The formula for anion gap is _____________________. Na+ – (Cl– + HCO3–)

Calculate the anion gap: Na+ = 140 mEq/L, Cl– = 118 mEq/L and anion gap = 7
HCO3– = 15 mEq/L. This is a(n) ________ gap metabolic acidosis. non-anion

Calculate the anion gap: Na+ = 140 mEq/L, Cl– = 101 mEq/L and anion gap = 27
HCO3– = 12 mEq/L. This is a(n) ________ gap metabolic acidosis. anion

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The Fluid, Electrolyte and Acid-Base Companion

EtiologiesNon-anion gap metabolic acidosis is caused by the


loss of bicarbonate.

GI LOSS OF HCO – RENAL LOSS OF HCO –


3
– Na+ 3

Cl

HCO3
A-
other
anions
K+

anions = cations

GI loss Renal tubular acidosis (RTA)


diarrhea proximal (type 2 RTA)
surgical drains distal (type 1 RTA)
fistulas hypoaldosteronism (type 4 RTA)
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.

All of the causes of non-anion gap metabolic acidosis are reviewed in detail in Chapter 12,
MetabolicAcidosis: Non-Anion Gap .

Non-anion gap metabolic acidosis is due to the ________ of bicar- loss


bonate from either the ____ tract or the ________. GI; kidney

In non-anion gap metabolic acidosis, the chloride concentration is


__________. increased

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S. Faubel and J. Topf 11 Metabolic Acidosis: The Overview

EtiologiesAnion gap metabolic acidosis is caused by the addi-


tion of acid.

O O O O
C C CH3
Oxygen +
Na CH2 CH2 O CH2

Cl– HO C
H
CH3
O
C
CH3
CH3

LACTIC ACIDOSIS KETOACIDOSIS


HCO3

A-
other
anions
K+

anions = cations

RENAL FAILURE INGESTIONS

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
All of the causes of anion gap metabolic acidosis are reviewed in detail in Chapter 13,
MetabolicAcidosis:Anion Gap.

Anion gap metabolic acidosis is caused by one of four funda-


mental processes: _________ acidosis, _____________, lactic; ketoacidosis,
_______ ______ and _____________. renal failure; ingestions

A good mnemonic is _________________. PLUM SEEDS

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The Fluid, Electrolyte and Acid-Base Companion

CompensationThe compensation for metabolic acidosis is an


increase in ventilation which decreases P CO2.
44
42
40 Normal
38
36 s
RESPIRAT ORY i
34 ACIDOSIS
d os
PCO2 (mmHg)

32 i
30 ac
28 l ic
26 a bo
24 et
M
22 RESPIRAT ORY
20 ALKALOSIS

18
16
14
6 8 10 12 14 16 18 20 22 24 26
Bicarbonate (mEq/L)
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.

METABOLIC ACIDOSIS
C
C Expected PCO2 = (1.5 × HCO3–) + 8 ± 2
C

If the PCO2 falls within the expected range, appropriate compensation has
occurred.
If the PCO2 is above or below the P CO2 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.

In metabolic acidosis, if the PCO2 is ________ than the expected lower


value, a concurrent respiratory alkalosis is present.

If the HCO3– is 12 mEq/L, what is the expected PCO2? If the PCO2 24 to 28 mmHg
is 19 mmHg, what other disorder is also present? respiratory alkalosis

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S. Faubel and J. Topf 11 Metabolic Acidosis: The Overview

Clinical correlation: In anion gap metabolic acidosis, the correct-


ed bicarbonate or delta-delta can be used to uncover an additional
metabolic acid-base disorder.
CORRECTED BICARBONATE

measured HCO3– + (anion gap – 12)


• if > 28, then a metabolic alkalosis is present
• if < 22, then a non-anion gap metabolic acidosis is present

DELTA - DELTA

∆ gap measured anion gap – ideal anion gap



=
∆ HCO 3
ideal HCO3– – measured HCO3–
• if > 2, then a metabolic alkalosis is present
• if < 1, then a non-anion gap metabolic acidosis is present

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 acidosis. 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.

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The Fluid, Electrolyte and Acid-Base Companion

SummaryMetabolic 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.

metabolic acidosis metabolic alkalosis respiratory acidosis respiratory alkalosis


HCO –
HCO – HCO3– HCO3–
pH ∝
3
pH ∝
3 pH ∝ pH ∝
CO2 CO2 CO2 CO2

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.
LOSS OF BICARBONATE ADDITION OF ACID
NON-ANION GAP ANION GAP
+
Na+ – – Na – Na+
Cl Cl Cl
or HCO3
HCO3 HCO3
K+ A-
other A-
other K+ A-
other
anions
K+
anions anions

cations = anions anions = cations anions = cations

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.
NON - ANION GAP METABOLIC ACIDOSIS ANION GAP METABOLIC ACIDOSIS
GI loss of bicarbonate Renal tubular acidosis Paraldehyde Starvation
diarrhea proximal Lactic Acidosis Ethanol
fistulas distal Uremia Ethylene glycol
ureterosigmoidostomy hypoaldosteronism Methanol DKA
obstructed ureteroileostomy Salicylate poisoning
cholestyramine

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.

METABOLIC ACIDOSIS CORRECTED BICARBONATE



Expected PCO2 = (1.5 × HCO ) + 8 ± 2
3
Measured HCO3– + (Anion gap – 12)

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