Acid–base homeostasis is thehomeostatic regulation of thepH of thebody'sextracellular fluid (ECF).[1] The properbalance between theacids andbases (i.e. the pH) in the ECF is crucial for the normalphysiology of the body—and forcellularmetabolism.[1] The pH of theintracellular fluid and the extracellular fluid need to be maintained at a constant level.[2]
Thethree dimensional structures of many extracellular proteins, such as theplasma proteins andmembrane proteins of the body'scells, are very sensitive to the extracellular pH.[3][4] Stringent mechanisms therefore exist to maintain the pH within very narrow limits. Outside the acceptable range of pH,proteins aredenatured (i.e. their 3D structure is disrupted), causingenzymes andion channels (among others) to malfunction.
Anacid–base imbalance is known as acidemia when the pH is acidic, or alkalemia when the pH is alkaline.
In humans and many other animals, acid–base homeostasis is maintained by multiple mechanisms involved in three lines of defense:[5][6]
The second and third lines of defense operate by making changes to the buffers, each of which consists of two components: a weak acid and itsconjugate base.[5][13] It is the ratio concentration of the weak acid to its conjugate base that determines the pH of the solution.[14] Thus, by manipulating firstly the concentration of the weak acid, and secondly that of its conjugate base, the pH of theextracellular fluid (ECF) can be adjusted very accurately to the correct value. The bicarbonate buffer, consisting of a mixture of carbonic acid (H2CO3) and a bicarbonate (HCO−
3) salt in solution, is the most abundant buffer in the extracellular fluid, and it is also the buffer whose acid-to-base ratio can be changed very easily and rapidly.[15]
ThepH of the extracellular fluid, including theblood plasma, is normally tightly regulated between 7.32 and 7.42 by thechemical buffers, therespiratory system, and therenal system.[13][16][17][18][1] The normal pH in thefetus differs from that in the adult. In the fetus, the pH in theumbilical vein pH is normally 7.25 to 7.45 and that in theumbilical artery is normally 7.18 to 7.38.[19]
Aqueousbuffer solutions will react withstrong acids orstrong bases by absorbing excessH+
ions, orOH−
ions, replacing the strong acids and bases withweak acids andweak bases.[13] 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 fluid. Buffers typically consist of a pair of compounds in solution, one of which is a weak acid and the other a weak base.[13] The most abundant buffer in the ECF consists of a solution of carbonic acid (H2CO3), and the bicarbonate (HCO−
3) salt of, usually, sodium (Na+).[5] Thus, when there is an excess ofOH−
ions in the solution carbonic acidpartially neutralizes them by forming H2O and bicarbonate (HCO−
3) ions.[5][15] Similarly an excess of H+ ions ispartially 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 far fewer H+ ions into the solution than the original strong acid would have done.[5]
The pH of a buffer solution depends solely on theratio of themolar 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.[citation needed]
This principle is exploited toregulate the pH of the extracellular fluids (rather than justbuffering the pH). For thecarbonic 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.[14]
TheHenderson–Hasselbalch equation, when applied to thecarbonic acid-bicarbonate buffer system in the extracellular fluids, states that:[14]
where:
However, since the carbonic acid concentration is directly proportional to thepartial pressure of carbon dioxide () in the extracellular fluid, the equation can berewritten as follows:[5][14]
where:
The pH of the extracellular fluids can thus be controlled by the regulation of and the other metabolic acids.
Homeostatic control can change thePCO2 and hence the pH of the arterial plasma within a few seconds.[5] The partial pressure of carbon dioxide in the arterial blood is monitored by thecentral chemoreceptors of themedulla oblongata.[5][20] These chemoreceptors are sensitive to the levels of carbon dioxide and pH in thecerebrospinal fluid.[14][12][20]
The central chemoreceptors send their information to therespiratory centers in the medulla oblongata andpons of thebrainstem.[12] The respiratory centres then determine the average rate of ventilation of thealveoli of thelungs, to keep thePCO2 in the arterial blood constant. The respiratory center does so viamotor neurons which activate themuscles of respiration (in particular, thediaphragm).[5][21] A rise in thePCO2 in the arterial blood plasma above 5.3 kPa (40 mmHg) reflexly causes an increase in the rate and depth ofbreathing. 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.[citation needed]
The sensor for the plasma HCO−
3 concentration is not known for certain. It is very probable that therenal tubular cells of thedistal 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 ofcarbonic anhydrase.[5][10][11] 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.[5][12] 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 (H+ + HCO−
3 H2CO3), thus raising the carbonic acid:bicarbonate ratio in the extracellular fluids, and returning its pH to normal.[5]
In general, metabolism produces more waste acids than bases.[5] Urine produced is generally acidic and is partially neutralized by the ammonia (NH3) that is excreted into the urine whenglutamate andglutamine (carriers of excess, no longer needed, amino groups) aredeaminated by thedistal renal tubular epithelial cells.[5][11] 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.[5][22]
Acid–base imbalance occurs when a significant insult causes the blood pH to shift out of the normal range (7.32 to 7.42[16]). An abnormally low pH in the extracellular fluid is called anacidemia and an abnormally high pH is called analkalemia.[citation needed]
Acidemia andalkalemia unambiguously refer to the actual change in the pH of the extracellular fluid (ECF).[24] Two other similar sounding terms areacidosis andalkalosis. They refer to the customary effect of a component, respiratory or metabolic.Acidosis would cause anacidemia on its own (i.e. if left "uncompensated" by an alkalosis).[24] Similarly, analkalosis would cause analkalemia on its own.[24] In medical terminology, the termsacidosis andalkalosis should always be qualified by an adjective to indicate theetiology of the disturbance:respiratory (indicating a change in the partial pressure of carbon dioxide),[25] ormetabolic (indicating a change in the Base Excess of the ECF).[9] There are therefore four different acid-base problems:metabolic acidosis,respiratory acidosis,metabolic alkalosis, andrespiratory alkalosis.[5] One or a combination of these conditions may occur simultaneously. For instance, ametabolic acidosis (as in uncontrolleddiabetes mellitus) is almost always partially compensated by arespiratory alkalosis (hyperventilation). Similarly, arespiratory acidosis can be completely or partially corrected by ametabolic alkalosis.[citation needed]
Respiratory acidosis: definition.
