The cellular pH

Hydrogen ions are produced in the body as a result of metabolism, particularly from the oxidation of the “Sulphur-containing amino acids” of protein ingestion. In normal conditions, the concentration of hydrogen protons (H+) in a “Neutral” solution is close to (0.1 μMole), which equal to (10-7). By taking the logarithmic number of (10-7), we get 7. The pH is simply defined as the “logarithmic representation of strength of acidity”, i.e., concentration, of protons (H+) within a medium

The pH scale is extended from (0 to 14), where 0 is very acidic, and 14 is very alkaline. The higher the pH of a solution, the more “Electrical resistant” it becomes (e.g., electricity travel slower with higher pH). As the blood pH becomes acidic, the following scenarios start to appear:

a) Microbes start to thrive and grow, with some shows pathologic pleomorphism (e.g., candidiasis)

b) Oxygen start to be dissociated from the RBCs since the hemoglobin will be used partially to buffer the blood acidity, causing tissue hypoxia (e.g., degenerative disorders & cancer start to appear). Hypoxia due to acidity is what is called “Rotting

c) Enzymes will start to show abnormal structural folding due to change in the functional group charge by the blood acidity, and their function is disturbed (e.g., slower metabolism & slower detoxification)  

The blood pH level is kept within a very narrow spectrum (pH 7.34-7.44), which equals (-20 to -25 mV) in physical terms, according to Dr. Jerry Tennant. Intra- and extracellular pH is one of the main determinants of all biochemical reactions in the body such as immune system function, coagulation, and organ functions. No microenvironment can work optimally in a disturbed interstitial fluid pH. Under pathophysiological conditions, such as a blood pH < 7.0 or > 7.7, there is a high probability for the individual to die due to organ dysfunction

Normal intracellular pH is (6.0-7.4) and the extracellular / interstitial pH is (7.34-7.44).The body cannot survive with pH (< 6.8) or pH (> 8.0). The interstitial pH in inflammation can reach (pH = 5.4)!!! Acidic interstitial environment causes decreased proteoglycans synthesis (e.g., causes cartilage and disc degeneration)

The body normally is "Acid production machine"; acidic chemicals are produced from: (a) bacterial metabolism intermediates; and (b) metabolism of glucose, fatty acids, and nucleoproteins. The main buffering systems in the body are: (a) Interstitial bicarbonate level (HCO3-); (b) Respiratory CO2 expiration; (c) organic phosphates (bone); and (d) excretion of ammonium (NH+4) in the kidney by combining (H+) with (NH3)

The body’s buffering system

A “Buffer” is a solution of a weak acid and its salt (or a weak base and its salt) that is able to bind hydrogen protons (H+) and therefore resist changes in pH. Buffering does NOT remove hydrogen protons (H+) from the body. Rather, buffers “Temporarily mop-up” any excess hydrogen protons (H+) that are produced (The same way that a sponge soaks up water). Buffering is only a short-term solution to the problem of excess hydrogen protons (H+). Ultimately, the body must get rid of the hydrogen protons (H+) by renal excretion. The buffers in the body include:

A. In extracellular fluid: Bicarbonate (Normal H2CO3 = 24 mmol/L)

B. In blood: Hemoglobin + Plasma proteins

C. In urine: Phosphate + Ammonia

In the body, an acid–base buffer typically consists of a weak acid, and its conjugate base. The blood pH is dependent on the ratio of the amount of the partial pressure of CO2 and the HCO3- in the blood. Under heavy exercise or pathophysiological situation (e.g., uncoping stress), the blood H+ protons may be too great for the buffer alone to control the blood pH. Under these situations, another organ must help to maintain a constant pH in the blood. The main buffers of the blood pH come from 2 organs: the kidneys and the lungs:

Kidneys: the kidneys provide the main buffering mechanism by regeneration of the bicarbonate (HCO3-) and secretion of (H+) through urination (Urine is acidic mostly)

One of the by-products of food metabolism is carbon dioxide (CO2), which is eliminated mostly via respiration. In order to eliminate all of the carbon dioxide that is generated from normal metabolism, the lungs would need a respiration rate far above normal breathing, which would indeed be very difficult. In order to get rid of the remaining CO2 in the blood, the liver combines CO2 with ammonia (produced from the oxidation of glutamine) and converts it to “Urea”, which is excreted by the kidneys

Lungs: an increase in the partial CO2 pressure in the blood is measured in the brain-stem and in peripheral chemoreceptors located in the aortic arch and carotid arteries; these chemoreceptors will trigger the breathing center located in the medulla oblongata, causing deeper and faster breathing, thereby increasing ventilation (CO2 washout). Thereby CO2 can be eliminated, which helps to keep the blood pH constant. This compensation mechanism is limited, because hypoventilation is only tolerated in narrow ranges

The body’s ability to keep the pH constant can be achieved by 3 systems:

1. Carbonic acid–bicarbonate buffer: H+ + HCO3-   H2CO3   H2O + CO2

(H+: hydrogen ion, HCO3- : bicarbonate ion, H2CO3: carbonic acid, H2O: water, CO2: carbon dioxide)

(The enzyme that catalyzed this reaction require Zinc as a cofactor to work)

2. The phosphate buffer (minor role)

3. Hemoglobin: it can reversibly bind either H+ or O2. During exercise, hemoglobin helps to control the pH of the blood by binding some of the excess H+ protons that are generated in the muscle


Selected references

1. Satyanarayana U et al. Biochemistry. 2013; Elsevier; 4th edition

2. Vasudevan DM et al. Textbook of biochemistry for medical students with revision exercises. 2013; JPB; 7th edition

3. Gupta RC. Essentials of medical biochemistry. 2013; CBS Publishers & Distributors; 2nd edition