pH control

Within the body, normal pH is 7.35-7.45.

The pH refers to the acidity or alkalinity of the blood. Tight control of pH is needed for normal metabolic function.

Within the body, normal arterial pH is 7.35-7.45. This is determined by the concentration of hydrogen ions. Precise regulation of pH requires alteration of the free hydrogen ion concentration within bodily fluids. The actual concentration of hydrogen ions is extremely small (~40 nano moles per litre). Therefore, pH is an easier way to express the concentration of hydrogen ions. pH is a logarithmic scale.

Inverse relationship

The numerical value of pH is inversely proportional to the hydrogen ion concentration.

• Acidosis (pH <7.35): increase in hydrogen ion concentration
• Alkalosis (pH >7.45): decrease in hydrogen ion concentration

Within the body, pH is tightly regulated by chemical buffers, the respiratory system and renal system.

The pH is tightly controlled to enable normal metabolic function.

A pH <6.8 or >8.0 will invariably lead to death. Deviation from the normal pH range results in:

• Altered excitability of nerves and muscles
• Abnormal enzyme activity
• Altered electrolyte concentrations (e.g. potassium)

Each day, we produce a large quantity of hydrogen ions through metabolism and production of carbon dioxide. 

Carbon dioxide

Carbon dioxide is converted to carbonic acid, which is catalysed by the enzyme carbonic anhydrase. Carbonic acid subsequently dissociates into hydrogen ions and bicarbonate ions. 

This enables the transfer of carbon dioxide to the lungs where the reaction is reversed and it is excreted. Carbon dioxide acts as an acid. Any increase in PaCO2 (partial pressure of carbon dioxide in arterial blood), leads to the formation of hydrogen ions. The increase in bicarbonate is negligible compared to the overall concentration in the blood, so has little effect.

Metabolism

Inorganic and organic acids are created from the breakdown of nutrients and as part of normal metabolism. 

Proteins in the diet contain large amounts of sulphur and phosphorus. Breakdown of protein leads to generation of sulphuric acid and phosphoric acid. Both are strong acids, which dissociate in the blood and add to the hydrogen ion concentration. Additionally, organic acids may be formed during normal metabolism (e.g. lipid metabolism to fatty acids) that also contributes to the hydrogen ion concentration. 

Control systems

To counteract the increase in hydrogen ion load, the body has three processes to control pH:

• Chemical buffers
• Respiratory system
• Renal system

Chemical buffers can yield, or bind, free hydrogen ions.

Chemical buffers essentially alter the distribution of hydrogen ions so they do not add to the acidity of fluids. They are immediate acting, but temporary (can become exhausted). Depending on the pH, they can yield free hydrogen ions if the concentration falls, or bind free hydrogen ions if the concentration increases

There are four main buffers:

• Carbonic acid/carbonate ion buffer system (extracellular)
• Protein buffer system (intracellular & extracellular)
• Haemoglobin buffer system (intracellular)
• Phosphate buffer system (intracellular)

When these chemical buffers are exhausted, the respiratory and renal systems are able to actively remove hydrogen ions.

The lungs are able to adjust pH through its regulation of carbon dioxide (CO2).

The respiratory system can control hydrogen ion concentration, and thus pH, through its control on carbon dioxide levels. 

• If acidosis is present (<7.35): increased ventilation, which reduces carbon dioxide levels and increases pH
• If alkalosis is present (>7.45): decreased ventilation, which increases carbon dioxide levels and decreases pH

Ventilation refers to the exchange of gas within the alveoli of the lungs. Ventilation can be adjusted through altering work of breathing (i.e. increases or decreases in respiratory rate) and volume of air (i.e. increase or decrease amount of air entering the lungs). 

Acidosis and alkalosis trigger the respiratory centre within the brainstem to alter ventilation. Respiratory mechanisms can restore pH around 50-75% towards normal. The respiratory mechanism is quick acting, but cannot adjust respiratory causes of altered pH (i.e. if the primary cause of acidosis is hypoventilation from respiratory disease, it will not be able to self-correct).

The kidneys can adjust pH through its regulation of hydrogen and bicarbonate ions.

The kidneys control hydrogen ion concentration through three mechanisms:

• Hydrogen ion removal: secreted from tubular cells within the nephrons. Occurs in proximal convoluted tubules. Also occurs in distal convoluted tubules and collecting ducts via intercalated cells.
• Bicarbonate ion regulation: can reabsorb or secrete bicarbonate ions. Reabsorption coupled with hydrogen ion secretion or it can add ‘new’ bicarbonate ions to plasma.
• Ammonia ion secretion: ammonia and phosphate are needed to buffer hydrogen ions with tubular fluid of nephrons. This allows more to be secreted by the tubular cells against its concentration gradient.

When the hydrogen ion concentration increases and blood becomes acidotic, the kidneys work to secrete more hydrogen ions and reabsorb bicarbonate. If the hydrogen ion concentration decreases and blood becomes alkalotic, the kidney work to reduce both secretion of hydrogen ions and reabsorption of bicarbonate ions.

Bicarbonate and hydrogen ions can ‘neutralise’ the other through the formation of carbonic acid (see diagram above). The renal system has a more delayed response taking hours to days to alter the pH, but the mechanism is powerful.