11 introduction to metabolic acidosis

277

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

11

WARNING: It has been longer since freshman chemistry than you realize. We stronglyadvise reading Chapter 10, Introduction to Acid-Base before advancing beyond this point.

Metabolic Acidosis:11 The Overview

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The Fluid, Electrolyte and Acid-Base Companion

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

Introduction�Metabolic acidosis is characterized by a fall in thearterial concentration of bicarbonate.

METABOLIC ALKALOSIS

RESPIRATORY ALKALOSISRESPIRATORY ACIDOSIS

METABOLIC ACIDOSIS

This chapter is an introduction to the pathophysiology and differential diagnosis of the twotypes 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 ________.

lowlow

low

lossacid

pH ∝ HCO3

–

CO2

pH ∝ HCO3

–

CO2

pH ∝ HCO3

–

CO2

pH ∝ HCO3

–

CO2

279


Mechanism�Metabolic acidosis can be caused by the loss ofbicarbonate.

One type of metabolic acidosis is due to the loss of bicarbonate. By thismechanism, direct loss of bicarbonate lowers the plasma bicarbonate con-centration. The decrease in bicarbonate causes the concentrations of bothhydrogen and chloride to increase.

Increased hydrogen (decreased pH). Hydrogen and bicarbonate are inequilibrium with water and carbon dioxide as shown in the bicarbonate bufferequation above. Loss of bicarbonate drives this equation toward the produc-tion of bicarbonate and hydrogen. The increase in bicarbonate production isnot sufficient to replace the lost bicarbonate and its concentration remainslow. However, the increase in hydrogen production does raise the hydrogenconcentration, decreasing pH.

Increased chloride. Bicarbonate is one of the primary anions in thebody. 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 bicarbonateand a(n) __________ (decreased/increased) pH.

If bicarbonate is lost, then the chloride concentration ___________(decreases/increases).

aaadecreased

increases

Loss of bicarbonateshifts the bicarbonatebuffer equation to-ward the productionof hydrogen ion.

HCO3 H+HCO3H+ C

HCO3 H+HCO3H+ C

cations = =anions

HCO3

Cl–Na+

K+

cationsanions

HCO3

Cl–Na+

K+A- other�

anions A- other�anions

H+

Loss of bicarbonatecauses the chlorideconcentration to in-crease, maintainingelectroneutrality.

Cl–

280


HCO3–

cations = =anions

Na+

K+

anions cations

Na+

K+

HCO3

Cl–

A- other�anions

HCO3

Cl–

A- other�anions

Addition of an acid shiftsthe bicarbonate bufferequation toward the pro-duction of water and car-bon dioxide. The reactionconsumes bicarbonate, de-creasing its concentration.

Addition of an acid is theaddition of an H+ and its ac-companying anion. Whenan acid is added, its anionaccumulates in the plas-ma; the Cl– concentrationdoes not change.

Mechanism�Metabolic acidosis can be caused by the additionof acid.

The other type of metabolic acidosis is due to the addition of acid. For thepurpose 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 (lowerspH). The increase in hydrogen causes the bicarbonate concentration to de-crease. Due to the presence of increased anions, the chloride concentrationdoes not change.

Decreased bicarbonate. Hydrogen and bicarbonate are in equilibriumwith water and carbon dioxide as shown in the bicarbonate buffer equationabove. The addition of acid (hydrogen ion), shifts the reaction toward theproduction 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, thechloride concentration does not change because the accompanying anionsmaintain electroneutrality.

An acid consists of two components: a(n) ___________ ion andan accompanying ________.

In metabolic acidosis due to the addition of acid, the bicarbonateconcentration ____________ (decreases/increases) as it is con-sumed buffering hydrogen.

hydrogenanion

decreases

HCO3 H+HCO3H+ C

HCO3 H+HCO3H+ C

Anions

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=anions cations

Na+

K+

HCO3

Cl–

A- other�anions

.

Diagnosis�The anion gap is a tool used in the evaluation ofmetabolic acidosis.

NORMAL ANION GAP INCREASED ANION GAP

Metabolic acidosis due to the loss of bicarbonate or the addition of acidcan be distinguished by the anion gap.

The anion gap is a clinical tool based on the principle of electroneutralitywhich is used to detect an increase in plasma anions other than Cl– andHCO3

– . The formula is shown above. Normally, the anion gap is between 5and 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 inchloride compensates for the fall in bicarbonate. This type of acidosis isknown as non-anion gap metabolic acidosis or hyperchloremic acidosis.

In metabolic acidosis due to the addition of acid, the anion gap increasesbecause the addition of acid includes the addition of anions. The increasedanion gap indicates the presence of these additional anions in the plasma. Thistype of acidosis is known as anion gap metabolic acidosis.

Because it so effectively narrows the differential diagnosis, calculatingthe anion gap is the first step in the evaluation of metabolic acidosis.

Anion gap = Na+ – (Cl– + HCO3– )

LOSS OF BICARBONATE ADDITION OF ACID

The formula for anion gap is _____________________.

Calculate the anion gap: Na+ = 140 mEq/L, Cl– = 118 mEq/L andHCO3

– = 15 mEq/L. This is a(n) ________ gap metabolic acidosis.

Calculate the anion gap: Na+ = 140 mEq/L, Cl– = 101 mEq/L andHCO3

– = 12 mEq/L. This is a(n) ________ gap metabolic acidosis.

Na+ – (Cl– + HCO3–)

anion gap = 7non-anion

anion gap = 27anion

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

= cationsanions

HCO3

Cl–Na+

K+A- other�

anionsHCO3

A-H+

A- H+

282


= cationsanions

HCO3

Cl–Na+

K+A- other�

anions

Etiologies�Non-anion gap metabolic acidosis is caused by theloss of bicarbonate.

GI LOSS OF HCO3– RENAL LOSS OF HCO

3–

Renal tubular acidosis (RTA)proximal (type 2 RTA)distal (type 1 RTA)hypoaldosteronism (type 4 RTA)

GI lossdiarrheasurgical drainsfistulasureterosigmoidostomyobstructed ureteroileostomycholestyramine

Non-anion gap metabolic acidosis is due to the loss of bicarbonate fromeither the GI tract or kidney. The differential diagnosis of non-anion gapmetabolic 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__________.

lossGI; kidney

increased

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

283


=anions cations

Na+

K+

HCO3

Cl–

A- other�anions

Etiologies�Anion gap metabolic acidosis is caused by the addi-tion of acid.

Anion gap metabolic acidosis is due to the addition of acid. The additionalacid is either endogenous (produced by the body) or exogenous (ingested). Inanion gap metabolic acidosis, the anion gap is greater than 12 mEq/L.

There are four fundamental processes that cause anion gap metabolicacidosis: lactic acidosis, ketoacidosis, renal failure and ingestions. A handymnemonic for the differential diagnosis of anion gap metabolic acidosis isPLUM SEEDS.

Paraldehyde ............................................... Ingestion

Lactic Acidosis ............................................ Lactic acidosis

Uremia ........................................................ Renal Failure

Methanol ..................................................... Ingestion

Salicylate poisoning ................................... IngestionEthanol ....................................................... Ketoacidosis

Ethylene glycol ........................................... Ingestion

DKA ............................................................ Ketoacidosis

Starvation ................................................... Ketoacidosis

C

CO

O

CH3

CH2

O O

C

CHO CH3

CH2

O O

H

CH3

CH3

CH2

KETOACIDOSIS

RENAL FAILURE

Oxygen

LACTIC ACIDOSIS

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,Metabolic Acidosis: Anion Gap.

284


Compensation�The compensation for metabolic acidosis is anincrease in ventilation which decreases PCO2.

Regardless of the anion gap, compensation for the low bicarbonate found inboth types of metabolic acidosis is a decrease in PCO2. PCO2 decreases throughan increase in ventilation. The expected fall in PCO2 in metabolic acidosis ispredicted by the following equation.

In metabolic acidosis, if the PCO2 is ________ than the expectedvalue, 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?

lower

24 to 28 mmHgrespiratory alkalosis

If the PCO2 falls within the expected range, appropriate compensation hasoccurred.

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 thanexpected, a respiratory acidosis is also present.

16 2218 201410 12

4038363432302826242220181614

86 24 26

4442

RESPIRATORY

ALKALOSIS

RESPIRATORY

ACIDOSIS

Bicarbonate (mEq/L)

PC

O2 (m

mH

g)

Normal

Metabolic

acid

osis

METABOLIC ACIDOSIS

Expected PCO2 = (1.5 × HCO3

–) + 8 ± 2CCC

285


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 gapmetabolic acidosis or metabolic alkalosis). The formula is shown above.

The corrected bicarbonate is the bicarbonate before the anion gapacidosis began. If the corrected bicarbonate is above the normal rangeof bicarbonate concentration (22 to 28 mEq/L), a concurrent metabolicalkalosis is present; if the corrected bicarbonate is below the normalbicarbonate range, a concurrent non-anion gap metabolic acidosis is present.

The following case illustrates how two metabolic acid-base disorderscan be present at the same time:

MJ is an 18-year-old diabetic who develops infectious diarrhea whichcauses a non-anion gap metabolic acidosis. Because she is not feelingwell, 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. Thecorrected bicarbonate is 10 + (22-12) or 20 mEq/L. This means thatbefore she developed DKA, the bicarbonate was 20 mEq/L. 20 mEq/L isbelow the normal range for bicarbonate indicating that a non-anion gapmetabolic 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 isthe delta-delta. The formula is shown above. If the ratio is less thanone, a concurrent non-anion gap metabolic acidosis is present. If theratio 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 used to uncover an additionalmetabolic acid-base disorder.

CORRECTED BICARBONATE

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

measured HCO3– + (anion gap – 12)

DELTA-DELTA

measured anion gap – ideal anion gap

ideal HCO3– – measured HCO3

–=∆ gap

∆ HCO3–

• if > 2, then a metabolic alkalosis is present• if < 1, then a non-anion gap metabolic acidosis is present

286


Summary�Metabolic acidosis: the overview.

Metabolic acidosis is one of the four primary acid-base disorders. It isrecognized by a low pH and a low plasma bicarbonate.

In metabolic acidosis, the decreased bicarbonate concentration can be dueto either the loss of bicarbonate or the addition of an acid.

The anion gap is a tool that can distinguish between the two fundamentalprocesses 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 carbondioxide falls by a predictable amount depending on the plasma bicarbonateconcentration. If the PCO2 is not within the predicted range, a respiratoryacid-base disorder is present in addition to metabolic acidosis. In anion gapmetabolic 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

= cationsanions

HCO3

Cl–Na+

K+A- other�

anions

or

LOSS OF BICARBONATE

NON-ANION GAPADDITION OF ACID

ANION GAP

cations = anions

Na+

K+

HCO3

Cl–

A- other�anions

Renal tubular acidosisproximaldistalhypoaldosteronism

GI loss of bicarbonatediarrheafistulasureterosigmoidostomyobstructed ureteroileostomycholestyramine

NON-ANION GAP METABOLIC ACIDOSIS

ParaldehydeLactic AcidosisUremiaMethanol

StarvationEthanolEthylene glycolDKASalicylate 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

METABOLIC ACIDOSIS

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 listedbelow. The next two chapters will look at the individual disorders in detail.

11 introduction to metabolic acidosis

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