# Acid-base balance

The term acid-base balance summarizes the physiological control mechanisms that serve to keep the proton concentration constant ( homeostasis ) and thus the pH value . In arterial blood this should be 7.40 ± 0.05 (corresponding to an H⁺ concentration around 40 nmol / l), deviations from this are called acidosis (over-acidification, i.e. too high H⁺ concentration / too low pH value) or Alkalosis (acidosis, i.e. too low H⁺ concentration / too high pH value). The permissible fluctuations in the pH value are very small because changes affect the degree of protonation of proteins , thereby changing their conformation and thus affecting almost all functions in the body.

Strictly keeping the proton concentration constant in the nanomolar range appears extremely difficult when you consider that the acids produced in the metabolism can easily reach millimolar concentrations. In fact, the rapid compensation of an H excess or deficiency takes place completely automatically through the buffer properties of the blood and tissue. Disorders of acid-base balance can in the short term on the respiratory drive are compensated, since the deeper breathing CO 2 - partial pressure , and thus the carbon dioxide concentration in the blood decreases. In the long term, however, all protons that are effectively produced in the metabolism must be excreted via the kidneys .

## Metabolic processes

CO 2 as the end product of cellular respiration occurs in large quantities, particularly during physical work. In the blood it reacts with water to form carbonic acid, which immediately dissociates into hydrogen carbonate and protons in the body. The reaction is catalyzed by the enzyme carbonic anhydratase , so that most of the CO 2 in the blood is not physically dissolved, but transported as hydrogen carbonate:

${\ displaystyle \ mathrm {CO_ {2} + H_ {2} O \ \ rightleftharpoons \ H_ {2} CO_ {3} \ \ rightleftharpoons \ H ^ {+} + HCO_ {3} ^ {-}}}$

The protons produced in this way are largely buffered by the fact that deoxygenated hemoglobin ( tense conformation) has a higher affinity for protons than oxygenated hemoglobin ( relaxed conformation); in other words increases the pK S value of hemoglobin for delivery of oxygen (see Bohr effect and Haldane effect ).

The protons produced by carbonic acid do not have to be excreted renally, as the processes described are reversed in the lungs, where all of the CO 2 formed in the metabolism is exhaled. H⁺ is mainly obtained when sulfur-containing amino acids are broken down into sulfuric acid , which means that up to 100 mmol of urinary protons are produced every day. Otherwise, carbohydrates , fatty acids and amino acids can be completely broken down into water, CO 2 and urea . No protons are produced in the overall balance. In some metabolic situations, however, organic acids increasingly appear as intermediate products of energy metabolism, such as lactic acid in the case of oxygen deficiency or 3-hydroxybutanoic acid and acetoacetic acid in starvation metabolism.

## Buffer systems

A mixture of acid and corresponding base in approximately the same concentration forms a buffer , since the addition or withdrawal of protons in such a system almost exclusively results in the conversion of acid and base into one another and hardly affects the proton concentration. That pH value at which a given acid / base pair is present in exactly the same concentrations and buffers optimally, is called pK S value . The Henderson-Hasselbalch equation

${\ displaystyle \ mathrm {pH} = \ mathrm {p} K _ {\ mathrm {S}} + \ log _ {10} {\ frac {[\ mathrm {A ^ {-}}]} {[\ mathrm { HA}]}}}$

establishes the connection between the current pH value and the current acid / base concentration ratio; it is simply a logarithmic and rearranged variant of the law of mass action of deprotonation.

For the blood buffer So acid / base pairs with a pK S required value close to 7.4. For a large buffer capacity, these must also be present in large concentrations .

### Protein buffer

The protein buffer is made up of the hemoglobin in the erythrocytes and the plasma proteins . It makes up about 24% of the buffering effect of the blood. Play especially histidine residues of proteins play a role whose pK S value is about 6.0.

### Carbonic acid / hydrogen carbonate buffer

The carbonic acid / hydrogen carbonate buffer makes up 75% of the total buffer capacity of the blood. Because the CO 2 in the lungs can switch freely between blood and air, it is an open buffer system . This gives an advantage of the great importance of this buffer despite suboptimal pK S declared value from 6.1: The CO 2 partial pressure can be quickly reduced by deeper breathing and also be increased to a limited extent due to decreased breathing. The depth of breath is regulated by the pH value: a drop represents a strong breath stimulus , which deepens breathing and thus lowers CO 2 partial pressure and carbon dioxide concentration. As can be seen from the Henderson-Hasselbalch equation, lowering the carbon dioxide concentration in the denominator increases the pH value, resulting in a negative feedback control loop . At normal hydrogen carbonate concentration, an arterial CO 2 partial pressure of 40 mmHg is established, which corresponds to a carbonic acid concentration of 1.2 mmol / l.

The cells of the proximal tubule in the kidney release one molecule of hydrogen carbonate into the blood for every H⁺ they secrete in the urine. In the Henderson-Hasselbalch equation, hydrogen carbonate is in the numerator, so an increase in concentration increases the pH value. Renal H⁺ secretion is also dependent on the pH value, but short-term effects cannot be achieved. At normal CO 2 partial pressure, a concentration of 24 mmol / l is established.

The regulations of CO 2 partial pressure and hydrogen carbonate concentration that have so far been shown separately are in truth not possible independently of one another, since they are equilibrium reactions - also with other buffers. To increase the hydrogen carbonate concentration by 1 mmol / l, for example, it is not enough for the kidney to release one millimole of hydrogen carbonate to every liter of blood: every addition of hydrogen carbonate drives the reaction of hydrogen carbonate with H⁺ to water and CO 2 , so that part of the hydrogen carbonate is generated immediately used up to neutralize protons and exhaled as CO 2 . In the same way, the CO 2 partial pressure cannot be increased without increasing the hydrogen carbonate concentration at the same time.

### More buffers

The other partial buffer systems are often summarized as non-bicarbonate buffers , NBP, because of their minor importance . They are closed systems, the total concentration of the buffer substances cannot change quickly:

Both buffer systems play a role primarily in the urine ; they ensure that its pH value does not get too low even when large amounts of protons are excreted. The amount of protons secreted depends heavily on diet; Under certain metabolic conditions, acidic urine is an expression of intact kidney function and does not mean over- acidification of the body , as is often claimed in alternative medicine.

Acidosis inhibits urea synthesis in the liver, which instead sends the excreted nitrogen to the kidneys in the form of glutamine . The cells of the proximal tubule deaminate the glutamine and use the carbon structure for gluconeogenesis , while the released ammonia diffuses through the apical membrane into the urine, where it binds a proton and at the same time is fixed in the lumen because ammonium cannot cross the membrane.

## Disruptions

To assess the severity, cause and compensation of acid-base disorders, two parameters are initially sufficient.
• An acidosis is present value of blood pH <7.35 at one.
• An alkalosis is present if the blood pH value is> 7.45.

Depending on whether the cause of acidosis or alkalosis in breathing (= respiration ). is to be sought, one speaks of

• a respiratory or
• a non-respiratory (synonym: metabolic ) disorder.

### Respiratory

From the reaction equation given above, it can be seen that an increase in the concentration (of the partial pressure) of CO 2 on the left leads to an increase in the concentrations of hydrogen carbonate (HCO 3 - ) and H + on the right (acidosis, for example due to a ventilatory disturbance). "Increased" exhalation of CO 2 (more precisely: exhaling the same amount with reduced partial pressure in the blood), conversely, reduces the concentrations of hydrogen carbonate (HCO 3 - ) and H + (alkalosis, for example when breathing excessively due to a gas exchange disorder or inadequate as hyperventilation ).

The respiratory altitude alkalosis is not based on an organic disorder. If you climb a mountain, the air pressure drops: The air becomes “thinner” (see barometer formula ), in particular the partial pressures of oxygen and CO 2 drop . In order for enough oxygen to pass through the alveolar membrane anyway , the breathing frequency and breathing depth must be increased. The partial pressures in the alveoli approach the partial pressures in the outside air, which means an increase in the oxygen partial pressure and a decrease in the CO 2 partial pressure. Thus, on the one hand, the oxygen uptake is improved, on the other hand, however, a problematically low CO 2 partial pressure arises in the blood.

### Non-respiratory

Non-respiratory disorders arise from

• increased or decreased excretion of H⁺ or hydrogen carbonate (via the kidneys, but also through vomiting and diarrhea),
• excessive intake of acids or bases,
• increased accumulation of acids in the metabolism.

Metabolic acidosis without disease value occurs during heavy physical work, since the muscles release lactic acid (lactate and protons) during anaerobic glycolysis ; the increased CO 2 production, on the other hand, is only of local importance, since physical work also increases breathing, so that the increased CO 2 that occurs can be exhaled at normal partial pressure.

### compensation

Non-respiratory disturbances are immediately compensated for by the respiratory system (by adjusting the CO 2 partial pressure), respiratory disturbances are slowly compensated renally (by adjusting the hydrogen carbonate concentration). Compensation is usually incomplete. Inadequate or excessive compensation can indicate the presence of another disease. Combinations of respiratory and non-respiratory disorders also occur.

## Interaction with other electrolyte homeostasis

Hydrogen carbonate, together with chloride, provides most of the negative charge in the plasma. In order to maintain electroneutrality, a deficiency in hydrogen carbonate is therefore accompanied by an excess of chloride and vice versa, unless there is also a disturbance on the part of the positive charge. An exception to this rule is metabolic acidosis with an enlarged anion gap , which is caused by the accumulation of acids such as lactic acid, ketone bodies and some toxins that bring their own anion in the form of the acid residue.

In manifold switching cells exist that secrete H + exchange with potassium. Acidosis and hyperkalemia can therefore be mutually exclusive, as can alkalosis and hypokalaemia (which in turn can result from a sodium deficiency ). Most body cells also exchange potassium for protons with the extracellular fluid (indirectly via Na⁺ / H⁺ exchangers and Na⁺ / K⁺-ATPase ); this is used in the acute therapy of hyperkalaemia by administering sodium hydrogen carbonate.

## Assessment parameters

The following parameters are used in the clinic to classify acidosis or alkalosis in terms of its origin and to find out to what extent the body (partially) compensates for it.

### Bicarbonate

Clinical significance The HCO 3 concentration is significant when determining the “non-respiratory components” in the event of a disturbance in the acid-base balance. Changes in this concentration will aid the clinician in identifying the origin of an acidosis or alkalosis. In the clinic -Alltag two versions are used.

Current bicarbonate The Henderson-Hasselbalch equation relates the pH value, the CO 2 partial pressure and the current bicarbonate concentration in the blood. If pH and pCO 2 are measured, the current bicarbonate can be calculated from them.

• The current bicarbonate shows the HCO 3 concentration as it is actually present at known pH and pCO 2 values.
• changes with metabolic and respiratory disorders

Standard bicarbonate In order to determine the HCO 3 hours , the sample blood originally had to be examined at 37 ° C, 100% oxygen saturation and a CO 2 partial pressure of 40 mmHg . However, all modern analyzers are now able to calculate this parameter from the current sample blood. ( Van Slyke and Cullen )

• The HCO 3 std represents the bicarbonate content of the plasma that would be present at a pCO 2 of 40 mmHg
• changes with non-respiratory disorders
• remains unchanged in respiratory disorders

### Base deviation and total buffer bases

Base excess ( base excess ):

• indicates the deviation from the reference value of the total buffer bases. “+1” means a value of the total buffer base of 49 mmol / l.
• positive values: metabolic alkalosis (or metabolically compensated respiratory acidosis)
• negative values: metabolic acidosis (or metabolically compensated respiratory alkalosis)

Total buffer bases:

• Sum of standard bicarbonate and all other basic buffers in the blood. Reference value for blood 100% saturated with oxygen: 48 mmol / l
• does not change in respiratory disorders, but does in non-respiratory disorders.

### Anion gap

The anion gap is a calculated quantity that is used for the differential diagnosis of metabolic acidosis .

## Normal values

 pH 7.35-7.45 p CO 2 35 - 45 mmHg current HCO 3 - 20 - 27 m mol / l Standard HCO 3 - 21-26 mmol / l Base Excess BE (−3) - (+3) mmol / l Total buffer bases BB 42 - 54 mmol / l Anion gap 3-11 mmol / l

## Individual evidence

1. ^ Robert Franz Schmidt , Florian Lang, Manfred Heckmann (eds.): Physiology of humans . 31st edition. Springer Medizin Verlag, Heidelberg 2010, ISBN 978-3-642-01650-9 , p. 754 .

## literature

• Peter Deetjen, Erwin-Joseph Speckmann, Jürgen Heschler: Physiology. 4th, completely revised Edition. Urban & Fischer at Elsevier, 2005, ISBN 3-437-41317-1 .
• Friedrich F. Sander: The acid-base balance of the human organism. 3. Edition. Hippokrates Verlag, Stuttgart 1999, ISBN 3-7773-1428-5 .
• S. Silbernagl, A. Despopoulos: Pocket Atlas of Physiology. 7th edition. Thieme, 2007, ISBN 978-3-13-567707-1 .