11 Introduction to Metabolic Acidosis

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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Introduction
Metabolic acidosis is characterized by a fall in the arterial concentration of bicarbonate.

METABOLIC ACIDOSIS

METABOLIC ALKALOSIS –

–

pH ∝

HCO3 CO2

RESPIRATORY ACIDOSIS

pH ∝

HCO CO2

– 3

pH ∝

HCO3 CO2

RESPIRATORY ALKALOSIS –

pH ∝

HCO3 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 and ferential dif diagnosis of the two types of metabolic acidosis. Additionally , the formulas used to uncover other acid-base disorders 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.

low low

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

low

Metabolic acidosis is due to either the ________ (loss/gain) of bicarbonate or the addition of ________.

loss acid

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11 Metabolic Acidosis: The Overview

Mechanism
Metabolic acidosis can be caused by the loss of bicarbonate.

H+ Loss of bicarbonate shifts the bicarbonate buffer equation toward the production of hydrogen ion.

Cl– Loss of bicarbonate causes the chloride concentration to increase, maintaining electroneutrality.

H+

HCO3

HCO3 H+

C

H+

HCO3

HCO3 H+

C

Na+

–

–

Cl

Cl

HCO3 +

K

A-

other anions

cations = anions

Na+

HCO3 A-

other anions

anions

K+

= cations

One type of metabolic acidosis is due to the loss of bicarbonate. By this mechanism, direct loss of bicarbonate lowers the plasma bicarbonate concentration. 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 production 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 maintain electroneutrality. When bicarbonate is lost, chloride increases, maintaining 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).

aaa decreased increases

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Mechanism
Metabolic acidosis can be caused by the addition of acid. –

HCO3

Addition of an acid shifts the bicarbonate buffer equation toward the production of water and carbon dioxide. The reaction consumes bicarbonate, decreasing its concentration.

Anions Addition of an acid is the addition of an H+ and its accompanying anion. When an acid is added, its anion accumulates in the plas– ma; the Cl concentration does not change.

H+

HCO3

HCO3 H+

C

H+

HCO3

HCO3 H+

C

Na+

–

–

Cl

Cl

Na+

HCO3 HCO3 K+

A-

other anions

cations = anions

A-

other anions

K+

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 hydrogen 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 decrease. 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 consumed buffering hydrogen. Increased anions. As acid is added, the accompanying anions accumulate 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 ________.

hydrogen anion

In metabolic acidosis due to the addition of acid, the bicarbonate concentration ____________ (decreases/increases) as it is consumed buffering hydrogen.

decreases

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11 Metabolic Acidosis: The Overview

Diagnosis
The anion gap is a tool used in the evaluation of metabolic acidosis. Anion gap = Na+ – (Cl– + HCO3– ) LOSS OF BICARBONATE

NORMAL ANION GAP

–

Cl

INCREASED ANION GAP

ADDITION OF ACID

Na+

Na+

Cl–

A- H +

HCO3 H+

HCO3 HCO3

A-

other anions

anions

K+

= cations

A-

A-

other anions

K+

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 remains 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 HCO3– = 15 mEq/L. This is a(n) ________ gap metabolic acidosis.

anion gap = 7 non-anion

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

anion gap = 27 anion

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Etiologies
Non-anion gap metabolic acidosis is caused by the loss of bicarbonate. GI LOSS OF HCO – 3

–

Cl

RENAL LOSS OF HCO –

Na+

3

HCO3 A-

other anions

anions GI loss diarrhea surgical drains fistulas ureterosigmoidostomy obstructed ureteroileostomy cholestyramine

K+

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

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 bicarbonate from either the ____ tract or the ________.

loss GI; kidney

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

increased

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11 Metabolic Acidosis: The Overview

Etiologies
Anion gap metabolic acidosis is caused by the addition of acid. O

Oxygen

+

Cl–

Na

HO

O

O

O

C

C

CH2

CH2

C

CH3

C

CH3 O

H

O

CH2 CH3

CH3

KETOACIDOSIS

LACTIC ACIDOSIS

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 fundamental processes: _________ acidosis, _____________, _______ ______ and _____________. A good mnemonic is _________________.

lactic; ketoacidosis, renal failure; ingestions PLUM SEEDS

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PCO2 (mmHg)

Compensation
The compensation for metabolic acidosis is an increase in ventilation which decreases P CO2. 44 42 40 38 36 34 32 30 28 26 24 22 20 18 16 14

Normal

RESPIRAT ORY ACIDOSIS

M

et

a

l bo

ic

i ac

d

i os

s

RESPIRAT ORY ALKALOSIS

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. C C C

METABOLIC ACIDOSIS

Expected PCO2 = (1.5 × HCO3–) + 8 ± 2

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 concurrent respiratory acid-base disorder is present. If the PCO2 is lower than predicted, 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 value, a concurrent respiratory alkalosis is present.

lower

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

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11 Metabolic Acidosis: The Overview

Clinical correlation: In anion gap metabolic acidosis, the corrected 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 – 3

∆ HCO

=

measured anion gap – ideal anion gap 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 respiratory acid-base disorder, determining the corrected bicarbonate can uncover 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 ketoacidosis (DKA), causing an anion gap metabolic acidosis. When she presents 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 additional 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 acidosis is also present, as determined by the corrected bicarbonate above.

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Summary
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. metabolic acidosis HCO pH ∝

– 3

CO2

metabolic alkalosis – 3

HCO pH ∝

CO2

respiratory acidosis HCO3– pH ∝ CO2

respiratory alkalosis HCO3– pH ∝ 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

–

–

Cl

Cl

–

Cl

or HCO3 K+

A-

Na+

HCO3

HCO3

other anions

A-

anions

cations = anions

K+

other anions

other anions

A-

= cations

K+

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

GI loss of bicarbonate Renal tubular acidosis diarrhea proximal fistulas distal ureterosigmoidostomy hypoaldosteronism obstructed ureteroileostomy cholestyramine

ANION GAP METABOLIC ACIDOSIS

Paraldehyde Lactic Acidosis Uremia Methanol

Starvation Ethanol Ethylene glycol DKA Salicylate poisoning

Compensation for metabolic acidosis from any etiology is increased ventilation 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 concurrent metabolic alkalosis or non-anion gap metabolic acidosis. METABOLIC ACIDOSIS – 3

Expected PCO2 = (1.5 × HCO ) + 8 ± 2

286

CORRECTED BICARBONATE

Measured HCO3– + (Anion gap – 12)