Acid–base homeostasis

Acid–base homeostasis is that part of biologic homeostasis which is concerned with the proper balance between acids and bases in the extracellular fluids, and therefore determines the body's extracellular fluids' pH. Many of the body's extracellular components (including the proteins on the exterior surfaces of its cells) are very sensitive for their 3D configurations (or "tertiary structures") on the extracellular pH. Sringent mechanisms therefore exist to maintain the pH within very narrow limits. Outside the acceptable range of pH, proteins are denatured, causing enzymes and cellular transmembrane ion channels (among others) to malfunction. In the worst cases death may occur if the situation remains unremedied.

In various animals, including humans, acid–base homeostasis is maintained by means of three interconnected systems. The first are the various chemical buffers which minimize pH changes that would otherwise occur in their absence. They do not correct pH deviations, but only serve to limit the extent of the change that would otherwise occur. These buffers include the bicarbonate buffer system, the phosphate buffer system, and the protein buffer system. Physiological corrective measures make use of, primarily, the bicarbonate buffer system. This is because abnormalities in the carbonic acid (H2CO3, or dissolved carbon dioxide) concentration in the blood plasma can rapidly be corrected by variations in the rate and depth of breathing (i.e. by hyperventilation or hypoventilation). Abnormally low or high plasma bicarbonate (HCO
3
) ion concentrations can be corrected by the excretion of H+ or HCO
3
ions in the urine, in instances where the plasma pH is abnormal. Plasma pH abnormalities are known as acidemia or alkalemia depending on which way the pH has deviated from normal.

Acid–base balance

The pH of the body's extracellular fluids is normally tightly regulated by buffering agents, the respiratory system, and the renal system, keeping the pH of the arterial blood plasma between 7.36 and 7.42.[1][2]

Buffers are simple watery solutions that will react with strong acids or strong bases by absorbing excess H+ or OH
ions replacing the strong acids and bases with weak ones.[3] This has the effect of damping the effect of pH changes, or reducing the pH change that would otherwise have occurred. But buffers cannot correct abnormal pH levels in a solution, be that solution in a test tube or in the extracellular fluids of a living organism. Buffers typically consist of a pair of compounds in solution, one of which is a weak acid and the other a weak base.[3] The most abundant buffer in the extracellular fluids of many living organisms consist of a solution of carbonic acid (H2CO3), and the bicarbonate (HCO
3
) salt of, usually, sodium (Na+). Thus, when there is an excess of OH
ions in the solution carbonic acid partially neutralizes them by forming H2O and bicarbonate (HCO
3
) ions.[4] An excess of H+ ions is partially neutralized by the bicarbonate component of the buffer solution to form carbonic acid (H2CO3), which, because it is a weak acid, remains largely in the undissociated form, releasing very few H+ ions into the solution.

The pH of a buffer solution depends solely on the ratio of the molar concentrations of the weak acid to the weak base. The higher the concentration of the weak acid in the solution (compared to the weak base) the lower the resulting pH of the solution. Similarly, if the weak base predominates the higher the resulting pH.

In the living body this principle is exploited to regulate the pH of the extracellular fluids (rather than just buffering the pH). For the carbonic acid-bicarbonate buffer, a molar ratio of weak acid to weak base of 1:20 produces a pH of 7.4; and vice versa: when the pH of the extracellular fluids is 7.4 then the ratio of carbonic acid to bicarbonate ions in that fluid is 1:20.[5]

This relationship is described mathematically by the Henderson–Hasselbalch equation, which, when applied to the carbonic acid-bicarbonate buffer system in the extracellular fluids, states that:[5]

${\displaystyle \mathrm {pH} =\mathrm {p} K_{\mathrm {a} ~\mathrm {H} _{2}\mathrm {CO} _{3}}+\log _{10}\left({\frac {[\mathrm {HCO} _{3}^{-}]}{[\mathrm {H} _{2}\mathrm {CO} _{3}]}}\right),}$
where:

However, since the carbonic acid concentration is directly proportional to the partial pressure of carbon dioxide (${\displaystyle P_{{\mathrm {CO} }_{2}}}$) in the extracellular fluid, the Henderson–Hasselbalch equation can be rewritten as follows:[5]

${\displaystyle \mathrm {pH} =6.1+\log _{10}\left({\frac {[\mathrm {HCO} _{3}^{-}]}{0.0307\times P_{\mathrm {CO} _{2}}}}\right),}$
where:
• pH is the acidity in the plasma
• [HCO
3
]
is the molar concentration of bicarbonate in the plasma
• PCO2 is the partial pressure of carbon dioxide in the blood plasma.

The pH of the extracellular fluids can thus be controlled by separately regulating the partial pressure of carbon dioxide (which determines the carbonic acid concentration) and bicarbonate ion concentration in the extracellular fluids.

There are therefore at least two homeostats (or, negative feed-back systems) responsible for the regulation of the plasma pH. The first is the plasma partial pressure of carbon dioxide homeostat, which determines the carbonic acid concentration in the plasma, and can change the pH of the arterial plasma within a few seconds. The partial pressure of carbon dioxide in the arterial blood is measured by the "central blood gas chemoreceptor" on the anterior surface of the medulla oblongata of the brainstem.[6] This chemoreceptor is particularly sensitive to the pH of the cerebrospinal fluid, which is directly influenced by the partial pressure of carbon dioxide in the arterial blood.[5][6] But it is also sensitive to the carbon dioxide concentration itself in the cerebrospinal fluid.[6]

Information from the blood gas chemoreceptors (which include the partial pressure of oxygen chemoreceptors) is relayed to a series of interconnected nuclei which comprise the respiratory centers in the medulla oblongata and the pons of the brainstem.[6] This information determines the average rate of ventilation of the alveoli of the lungs, to keep the partial pressure carbon dioxide in the arterial blood constant. The respiratory center does so via motor neurons which activate the muscles of respiration (in particular the diaphragm).[7] A rise in the partial pressure of carbon dioxide in the arterial blood plasma above 5.3 kPa (40 mmHg) reflexly causes an increase in the rate and depth of breathing. Normal breathing is resumed when the partial pressure of carbon dioxide has returned to 5.3 kPa.[8] The converse happens if the partial pressure of carbon dioxide falls below the normal range. Breathing may be temporally halted, or slowed down to allow carbon dioxide to accumulate once more in the lungs and arterial blood.

The sensor for the plasma HCO
3
concentration is not known for certain. It is very probable that the renal tubular cells of the distal convoluted tubules are themselves sensitive to the pH of the plasma. The metabolism of these cells produces CO2, which is rapidly converted to H+ and HCO
3
through the action of carbonic anhydrase.[9][10] When the extracellular fluids tend towards acidity, the renal tubular cells secrete the H+ ions into the tubular fluid from where they exit the body via the urine. The HCO
3
ions are simultaneously secreted into the blood plasma, thus raising the bicarbonate ion concentration in the plasma, lowering the carbonic acid:bicarbonate ion ratio, and consequently raising the pH of the plasma.[6] The converse happens when the plasma pH rises above normal: bicarbonate ions are excreted into the urine, and hydrogen ions into the plasma. These combine with the bicarbonate ions in the plasma to form carbonic acid, thus raising the carbonic acid:bicarbonate ratio in the extracellular fluids, and returning its pH to normal.

In general metabolism produces more waste acids than bases. The urine is therefore generally acid. This urinary acidity is, to a certain extent, neutralized by the ammonia (NH3) which is excreted into the urine when glutamate and glutamine (carriers of excess, no longer needed, amino groups) are deaminated by the distal renal tubular epithelial cells.[10] Thus some of the "acid content" of the urine resides in the resulting ammonium ion (NH4+) content of the urine, though this has no effect on pH homeostasis of the extracellular fluids.[6][11]

Imbalance

An acid base nomogram for human plasma, showing the effects on the plasma pH when carbonic acid (partial pressure of carbondioxide) or bicarbonate occur in excess or are deficient in the plasma

Acid–base imbalance occurs when a significant insult causes the blood pH to shift out of the normal range (7.35 to 7.45). In the fetus, the normal range differs based on which umbilical vessel is sampled (umbilical vein pH is normally 7.25 to 7.45; umbilical artery pH is normally 7.18 to 7.38).[12] An excess of acid in the blood is called acidemia and an excess of base is called alkalemia. The imbalance is classified based on the cause of the disturbance (respiratory or metabolic) and the direction of change in pH (acidosis or alkalosis). There are four basic processes: metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. One or a combination may occur at any given time.

References

1. ^
2. ^ Caroline, Nancy (2013). Nancy Caroline's Emergency care in the streets (7th ed.). Buffer systems: Jones & Bartlett Learning. pp. 347–349. ISBN 978-1449645861.
3. ^ a b Tortora, Gerard J.; Anagnostakos, Nicholas P. (1987). Principles of anatomy and physiology (Fifth ed.). New York: Harper & Row, Publishers. pp. 35–37, 697–700. ISBN 0-06-350729-3.
4. ^ Garrett, Reginald H.; Grisham, Charles M (2010). Biochemistry. Cengage Learning. p. 43. ISBN 978-0-495-10935-8.
5. ^ a b c d Bray, John J. (1999). Lecture notes on human physiology. Malden, Mass.: Blackwell Science. p. 556. ISBN 978-0-86542-775-4.
6. Tortora, Gerard J.; Anagnostakos, Nicholas P. (1987). Principles of anatomy and physiology (Fifth ed.). New York: Harper & Row, Publishers. pp. 494, 556–582. ISBN 0-06-350729-3.
7. ^ Levitzky, Michael G. (2013). Pulmonary physiology (Eighth ed.). New York: McGraw-Hill Medical. p. Chapter 9. Control of Breathing. ISBN 978-0-07-179313-1.
8. ^
9. ^ Tortora, Gerard J.; Anagnostakos, Nicholas P. (1987). Principles of anatomy and physiology (Fifth ed.). New York: Harper & Row, Publishers. pp. 581–582, 675–676. ISBN 0-06-350729-3.
10. ^ a b Stryer, Lubert (1995). Biochemistry. (Fourth ed.). New York: W.H. Freeman and Company. pp. 39, 164, 630–631, 716–717. ISBN 0 7167 2009 4.
11. ^ Rose, Burton; Helmut Rennke (1994). Renal Pathophysiology. Baltimore: Williams & Wilkins. ISBN 0-683-07354-0.
12. ^ Yeomans, ER; Hauth, JC; Gilstrap, LC III; Strickland DM (1985). "Umbilical cord pH, PCO2, and bicarbonate following uncomplicated term vaginal deliveries (146 infants)". Am J Obstet Gynecol. 151: 798–800. PMID 3919587. doi:10.1016/0002-9378(85)90523-x.