2.1: Acid-Base Balance

Each day there is always a production of acid by the body's metabolic processes and to maintain balance, these acids need to be excreted or metabolised. The various acids produced by the body are classified as respiratory (or volatile) acids and as metabolic (or fixed) acids. The body normally can respond very effectively to perturbations in acid or base production.

Respiratory Acid

The acid is more correctly carbonic acid (H₂CO₃) but the term 'respiratory acid' is usually used to mean carbon dioxide. But CO₂ itself is not an acid in the Bronsted-Lowry system as it does not contain a hydrogen so cannot be a proton donor. However, CO₂ can instead be thought of as representing a potential to create an equivalent amount of carbonic acid. Carbon dioxide is the end-product of complete oxidation of carbohydrates and fatty acids. It is called a volatile acid meaning in this context it can be excreted via the lungs. Of necessity, considering the amounts involved there must be an efficient system to rapidly excrete CO₂.

The amount of CO₂ produced each day is huge compared to the amount of production of fixed acids. Basal CO₂ production is typically quoted at 12,000 to 13,000 mmols/day.

Basal Carbon Dioxide Production Consider a resting adult with an oxygen consumption of 250 mls/min and a CO2 production of 200 mls/min (Respiratory quotient 0.8): Daily CO2 production \( = \frac {0.2 \times 60 \times 24 \text {litres/day}} {22.4 \text {litres/mole}} \) \(= 12,857 \text {mmoles/day} \)

Increased levels of activity will increase oxygen consumption and carbon dioxide production so that actual daily CO₂production is usually significantly more than the oft-quoted basal level. [Different texts quote different figures usually in the range of 12,000 to 24,000 mmoles/day but the actual figure simply depends on the level of metabolic activity and whether you quote basal or typical figures.]

Daily CO₂ production can also be calculated from the daily metabolic water production. The complete oxidation of glucose produces equal amounts of CO₂ and H₂0. The complete oxidation of fat produces approximately equal amounts of CO₂and H₂O also. These two processes account for all the body's CO₂ production. Typically, this metabolic water is about 400 mls per day which is 22.2 moles (ie 400/18) of water. The daily typical CO₂ production must also be about 22,200 mmoles.

Metabolic Acids

This term covers all the acids the body produces which are non-volatile. Because they are not excreted by the lungs they are said to be fixed in the body and hence the alternative term fixed acids. All acids other then H₂CO₃ are fixed acids.

These acids are usually referred to by their anion (eg lactate, phosphate, sulphate, acetoacetate or b-hydroxybutyrate). This seems strange at first because the anion is, after all, the base and not itself the acid. This useage is acceptable in most circumstances because the dissociation of the acid must have produced one hydrogen ion for every anion so the amount of anions present accurately reflects the number of H⁺ that must have been produced in the original dissociation.

Another potentially confusing aspect is that carbon dioxide is produced as an end-product of metabolism but is not a metabolic acid according to the usual definition. This inconsistency causes some confusion: it is simplest to be aware of this and accept the established convention.

Net production of fixed acids is about 1 to 1.5 mmoles of H⁺ per kilogram per day: about 70 to 100 mmoles of H⁺ per day in an adult. This non-volatile acid load is excreted by the kidney. Fixed acids are produced due to incomplete metabolism of carbohydrates (eg lactate), fats (eg ketones) and protein (eg sulphate, phosphate).

The above total for net fixed acid production excludes the lactate produced by the body each day as the majority of the lactate produced is metabolised and is not excreted so there is no net lactate requiring excretion from the body.

For acid-base balance, the amount of acid excreted per day must equal the amount produced per day.

The routes of excretion are the lungs (for CO₂) and the kidneys (for the fixed acids). Each molecule of CO₂ excreted via the lungs results from the reaction of one molecule of bicarbonate with one molecule of H⁺. The H⁺ remains in the body as H₂O.

Response to an Acid-Base Perturbation

The body's response¹ to a change in acid-base status has three components:

• First defence: Buffering
• Second defence: Respiratory : alteration in arterial pCO₂
• Third defence: Renal : alteration in HCO₃^- excretion

The word 'defence' is used because these are the three ways that the body 'defends' itself against acid-base disturbances. This is not the complete picture as it neglects some metabolic responses (eg changes in metabolic pathways) that occur.

This response can be considered by looking at how the components affect the \( \frac {[HCO_{3}^{-}} {pCO_{2}} \) ratio in the Henderson-Hasselbalch equation. The 3 components of the response are summarised below.

The Immediate Response : Buffering

Buffering is a rapid physico-chemical phenomenon. The body has a large buffer capacity. The buffering of fixed acids by bicarbonate changes the [HCO₃^-] numerator in the ratio (in the Henderson-Hasselbalch equation).

The Respiratory Response : Alteration in Ventilation

Adjustment of the denominator pCO₂ (in the Henderson-Hasselbalch equation) by alterations in ventilation is relatively rapid (minutes to hours). An increased CO₂ excretion due to hyperventilation will result in one of three acid-base outcomes:

• correction of a respiratory acidosis
• production of a respiratory alkalosis
• compensation for a metabolic acidosis.

Which of these three circumstances is present cannot be deduced merely from the observation of the presence of hyperventilation in a patient.

This respiratory response is particularly useful physiologically because of its effect on intracellular pH as well as extracellular pH. Carbon dioxide crosses cell membranes easily so changes in pCO2 affect intracellular pH rapidly and in a predictable direction.

The system has to be able to respond quickly and to have a high capacity because of the huge amounts of respiratory acid to be excreted.

The Renal Response : Alteration in Bicarbonate Excretion

This much slower process (several days to reach maximum capacity) involves adjustment of bicarbonate excretion by the kidney. This system is responsible for the excretion of the fixed acids and for compensatory changes in plasma [HCO₃^-] in the presence of respiratory acid-base disorders.

Balance: Internal versus External

This refers to the difference between Hydrogen Ion Turnover in the body (or Internal Balance) versus Net H⁺ Production & Excretion requiring excretion from the body (ie External Balance)

Most discussions of hydrogen ion balance refers to net production (which requires excretion from the body to maintain a stable body pH) rather than to turnover of hydrogen ions (where H⁺ are produced and consumed in chemical reactions without any net production). Net production under basal conditions gives 12 moles of CO₂ and 0.1 moles of fixed acids.

The majority of the fixed acids are produced from proteins (sulphate from the three sulphur containing amino acids; phosphate from phosphoproteins) with a smaller contribution from metabolism of other phosphate compounds (eg phospholipids).

Key Fact: Turnover of hydrogen ions in the body is HUGE & very much larger then net acid excretion.

Turnover² includes:

• 1.5 moles/day from lactic acid turnover
• 80 moles/day from adenine dinucleotide turnover
• 120 moles/day from ATP turnover
• At least another 360 moles/day involved in mitochondrial membrane H+ movements (Johnston & Alberti).

Compared to the total of these huge turnover figures, the 12 moles/day of CO₂ produced looks small and the 0.1 mole/day of net fixed acid production looks positively puny. (Appearances of course can be deceptive). Because with turnover, these H⁺ are produced and consumed without any net production requiring excretion, they are less relevant to this discussion where the emphasis is on external acid-base balance.

By definition, for acid-base equilibrium, the net acid production by the body must be excreted. This discussion of external acid-base balance also includes any acids or bases ingested or infused into the body. Acid-base balance means that the net production of acid is excreted from the body each day (ie 'external balance'). The internal turnover of H⁺ is largely ignored (except for lactic acid) in the rest of this book.

References

1. Adrogue HE and Adrogue HJ. Acid-base physiology. Respir Care 2001 Apr; 46(4) 328-41. PubMed
2. Johnston DG and Alberti KG. Acid-base balance in metabolic acidoses. Clin Endocrinol Metab 1983 Jul; 12(2) 267-85.PubMed