Jörg Thomas and Werner Klingler

pH regulation and influence on fascial tissue

Intra- and extracellular pH is one of the main determinants of all biochemical reactions in the body. The name relates to the Latin expression potentia Hydrogenii and is a measure for the strength of acidity, i.e., concentration, of protons (H⁺). The organs, the immune system, coagulation, and all other systems of the body need to work in a specific microenvironment with a pH-optimum. In blood, the normal range of pH is very tight and has to be between 7.36 and 7.44 for ideal conditions. Under pathophysiological conditions, with a blood pH lower than 7.0 and higher than 7.7, there is a high probability for the individual to die due to organ dysfunction.

The kidney and the lungs work together to help maintain a blood pH of 7.4 by affecting the components of the buffers in the blood. To a lesser extent, acids are egested by skin, liver, and bowels. In the body there are at least three buffer systems: first, the most important is the carbonic acid–bicarbonate buffer; second, the phosphate buffer, which plays a minor role; and third, the hemoglobin protein, which can reversibly bind either H⁺ or O₂. During exercise, hemoglobin helps to control the pH of the blood by binding some of the excess protons that are generated in the muscle.

How does the most important buffer system, the carbonic acid–bicarbonate buffer work, and what are the influences of lungs and kidney on this buffer system?

Acid–base buffers in the blood keep the pH constant when hydrogen ions or hydroxide ions are added or removed. An acid–base buffer typically consists of a weak acid, and its conjugate base. When protons are added to the solution, some of the base components are converted to the weak acid; and when hydroxide ions are added, protons are dissociated from the weak acid molecule. As mentioned above, the most important buffer is the carbonic acid–bicarbonate buffer in the blood. The simultaneous equilibrium reactions of interest in the blood are as follows:

Furthermore, the Henderson–Hasselbach equation gives an idea how this buffer system works:

The pH of the buffer solution is dependent on the ratio of the amount of the partial pressure of CO₂ and the in the blood. This ratio is relatively constant, because the concentrations of both buffer components are very large, compared with the amount of H⁺ added or removed in the body during normal circumstances. Under heavy exercise or pathophysiological situation, the added H⁺ protons may be too great for the buffer alone to control the blood pH. When this happens, another organ must help to maintain a constant pH in the blood.

Figure 4.4.1 gives an idea how the most important organs, the kidney and lungs influence the bicarbonate–acid buffer. Physical exercise, for example, leads to a significant increase of acidic metabolites such as lactate and CO₂ due to glycolysis and the cellular respiratory chain. An increase of the partial CO₂ pressure in the blood, measured in the brain stem and in peripheral chemoreceptors located in the aortic arch and carotid arteries, is the most dominant breathing stimulator for the breathing center located in the brain stem. Activation of the breathing center leads to deeper and faster breathing, thereby increasing ventilation. Thereby CO₂ can be eliminated, which helps to keep the blood pH constant. Furthermore, under pathophysiological conditions – like in septic patients with a metabolic acidosis (pH < 7.3, and low buffer base) – breathing is often enormously activated to counteract the metabolic acidosis. Instead, patients with a metabolic alkalosis (pH > 7.5, and high buffer base), for example due to excessive vomiting, may show a depression of respiration with an increase of partial CO₂ pressure in the blood to keep the pH in the physiological range. However, this compensation mechanism is limited, because hypoventilation is only tolerated in narrow ranges. The kidneys provide a mechanism of saving basic metabolites by regeneration of the bicarbonate () and secretion of H⁺. Moreover, the kidney is important in respiratory diseases, like chronic obstructive pulmonary disease, where the patients suffer from a chronic high partial CO₂ in the blood, which induces a so-called respiratory acidosis (high CO₂, normal bicarbonate at the beginning). The kidney has the ability to counteract this acidosis by regeneration of more bicarbonate and an increase of acid secretion with the urine. In contrast to the lung, the counteraction of the kidney to keep the pH constant is slower.

Taken together, the carbonic acid–bicarbonate buffer is the most important buffer for maintaining acid–base balance in the blood and is mainly influenced by the kidney and lungs. This means, on the other hand, that in patients with lung and/or kidney disease it is important to control pH levels.

Chronic hyperventilation – also called “breathing pattern disorder” – tends to lead to a state of reduced CO₂ in the blood, known as hypocapnia. Hypocapnia goes along with increased alkalosis and leads to vasoconstriction as well as to increased nerve and muscle excitability. Hypocapnic alkalosis has been observed in anxiety as well as in other negative affective states and traits (Chaitow et al. 2002). Reversing sustained or spontaneous hyperventilation with therapeutic capnometry has proven beneficial effects in the treatment of panic disorder as well as asthma (Meuret & Ritz 2010). Interestingly, patients with psychogenic hyperventilation frequently show elevated lactate levels. While high lactates are usually associated with acidosis, it has recently been shown that in patients with psychogenic hyperventilation this correlation is not valid, due to adaptation processes (Ter Avest et al. 2011).

In this connection, it is very interesting that psychiatric disorders like panic disorders (PD) with chronic or acute hyperventilation may have an influence on fascial function. For example, it has been shown that patients with PD have a significantly, higher incidence of joint hypermobility syndrome (Martin-Santos et al. 1998). In another study, patients with PD suffered significantly more often with prolapse of the mitral valve, also indicating more lax connective tissue (Tamam et al. 2000). However, there are other studies that could not detect any significant relationship between PD and joint hypermobility syndrome or mitral valve prolapse (Gulpek et al. 2004). Furthermore, the exact pathomechanism behind these findings is still unknown. Genetic studies, for example, have looked at elastin polymorphism and could not find any association with PD (Philibert et al. 2003). It is known that patients with PD often have electrolyte disturbances, like hypophosphatemia (indicator of chronic hyperventilation), elevated lactate levels, and increased CO₂ sensitivity (Sikter et al. 2007). Whether these electrolyte disturbances may be explanations for the higher incidence of lax connective tissue in patients with PD has to be proven in the future.

Acid–base status is strongly linked with the electrolyte balance in the cells. Protons (H⁺) and potassium (K⁺) are the cations to which resting cellular membranes are permeable. This is the reason why H⁺ and K⁺ supersede each other in order to hold an electrochemical equilibrium across the membranes. However, the effect of acid–base status on the serum potassium is very complicated and depends on the nature of the disorder. In general, extracellular K⁺ concentration rises in acidic conditions and falls in alkalosis. This is important because K⁺ is stabilizing the resting membrane potential and K⁺ deviations can lead to heart arrhythmia, for example, and muscle fatigue. However, exercise can lead to a significant increase of extracellular K⁺ in the muscle. Indeed, K⁺ levels rise significantly after extensive physical exertion. Emergency medics need to treat cardiac arrhythmias in almost every marathon event, where of course factors other than high K⁺ contribute to heart instability. The K⁺ accumulation in the muscular microenvironment (i.e., within the transverse tubular system) has also been linked to muscle fatigue, which is counteracted by simultaneous elevation of muscle temperature, lactic acidosis, and the presence of endogenous catecholamine (Pedersen et al. 2003).

Not only global pH maintenance can be disturbed, but also a specific region in the body can be affected by local accumulation of acids. This is the case in inflammations, and for local acidosis it is not relevant if the cause is traumatic, infectious, or autoimmune.