Acid-Base Homeostasis

Overview

The arterial blood pH is normally regulated between 7.35 and 7.45. This is crucial for the normal functioning of the body, as processes such as metabolic pathways involving enzymes depend on a controlled pH environment.

There are 3 main homeostatic mechanisms involved in controlling blood pH:

• Chemical blood pH buffer systems (responds within seconds to minutes) – this includes:
  • The bicarbonate buffer system
  • The phosphate buffer system
  • The protein buffer system
• The respiratory system (responds within minutes)
• The kidneys (respond over hours to days)

pH

The pH scale is logarithmic, meaning one pH unit is equal to a 10 times increase or decrease in the hydrogen ion (H⁺) concentration. It is also inversely proportional to the H⁺ concentration, therefore:

• A lower pH means more H⁺ ions and the solution is more acidic
• A higher pH means fewer H⁺ ions and the solution is more basic

Adding more H⁺ makes a solution more acidic, and decreases the pH.

Chemical Blood pH Buffer Systems

The bicarbonate buffer system

Carbonic anhydrase is an enzyme that catalyses the reaction between carbon dioxide (CO₂) and water (H₂O) to form carbonic acid (H₂CO₃), which dissociates to form a bicarbonate ion (HCO₃^–) and (H⁺). The following equilibrium is set up:

CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO₃^– + H⁺

Le Chatelier’s principle explains how the bicarbonate buffer system works. It states that if a system in equilibrium is disturbed by changing conditions, the equilibrium will shift in such a way as to counteract the change.

If more H⁺ is present in the blood, the above equilibrium shifts to the left, and HCO₃^– and H⁺ combine to give H₂CO₃, which is converted back into CO₂ and H₂O by carbonic anhydrase. This decreases the H⁺ concentration back to normal levels.

CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO₃^– + H⁺

If the CO₂ concentration increases (e.g. due to decreased ventilation), the equilibrium shifts to the right, and more CO₂­ and H₂O are combined using carbonic anhydrase to form H₂CO₃, which gives more HCO₃^– and H₂O. This decreases the concentration of CO₂ back to normal.

If a base is added (e.g. OH^–), this reacts with H⁺ and decreases its concentration. The equilibrium, therefore, shifts to the right, and more CO₂ and H₂O are combined using carbonic anhydrase to form H₂CO₃, which gives more HCO₃^– and H₂O. This restores H⁺ to normal.

As with most buffers similar to this one, they can resist small changes in pH. If too much acid or base is added, this system may fail.

The Respiratory System and Acid-Base Balance

Overview

Metabolism generates CO₂ which dissolves in water in the plasma and forms carbonic acid (H₂CO₃), which dissociates into bicarbonate ions (HCO₃^–) and hydrogen ions (H⁺) as mentioned above. Since there is an increase in H⁺ concentration, the pH decreases and these changes are detected by the central chemoreceptors in the medulla oblongata. These chemoreceptors send impulses to the respiratory centres in the medulla oblongata and pons and change the rate and depth of breathing accordingly.

The effects of ventilation on pH

HCO₃^– returns to the lungs where it is converted back into CO₂ and released during exhalation. The rate of CO₂ removal influences which way the bicarbonate system of the blood shifts due to Le Chatelier’s principle:

CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO₃^– + H⁺

Increased ventilation (hyperventilation) increases the removal of CO₂. Therefore, the bicarbonate buffer equilibrium shifts to the left (to restore CO₂ to normal by bringing it back up). This combines HCO₃^– and H⁺ to form H₂CO₃, which is converted into CO₂ and H₂O. This returns CO₂ to normal but decreases H⁺. Therefore, hyperventilation can make the blood less acidic and have a higher pH.

Decreased ventilation (hypoventilation) decreases the removal of CO₂. Therefore, the bicarbonate buffer equilibrium shifts to the right (to restore CO₂ to normal by bringing its levels down). This combines CO₂ and H₂O to form H₂CO₃, which dissociates into HCO₃^– and H⁺. This returns CO₂ to normal but increases H⁺. Therefore, hypoventilation can make the blood more acidic and have a lower pH.

The Kidneys and Acid-Base Balance

Overview

The kidneys are considered the third line of defence when maintaining the acid-base balance and work through removing excess acid or base in the urine and reabsorbing and/or producing HCO₃^–. To reabsorb HCO₃^–, it must react with H⁺ to form H₂CO₃, which is converted into H₂O and CO₂ by carbonic anhydrase. This happens because H₂O and CO₂ move into the renal tubule cells more readily. Once inside the nephron tubules, H₂O and CO₂ are converted back into H₂CO₃ which dissociates into HCO₃^– and H⁺. Most HCO₃^– is reabsorbed from the nephron tubules, and H⁺ is secreted into them, increasing the H⁺ ion concentration in the urine, lowering its pH, and acidifying it.

The ammonia buffer

The urine can only contain so many H⁺ ions and cannot go below a pH of around 4.5. Therefore, to increase the amount of H⁺ excretion in the urine, an ammonia buffer is present in the urine. Renal tubular cells break down amino acids into ammonia which enters the nephron tubule and combines with H⁺ to form ammonium ions (NH₄⁺). This combines with chloride (Cl^–) ions in the urine, which forms ammonium chloride (NH₄Cl), which leads to a less acidic pH.

When there is more H⁺ in the blood, the renal tubular cells secrete more H⁺ into the nephron tubule, which as mentioned above, combines with HCO₃^– to form H₂CO₃, which is then converted to H₂O and CO₂ and moves back into the renal tubular cells. HCO₃^– is then reabsorbed and H⁺ is released into the urine.

When there is less H⁺ in the blood, the renal tubular cells secrete less H⁺ into the nephron tubule. This means less HCO₃^– combines with H⁺ within the nephron tubule to form H₂CO₃, so less is converted into H₂O and CO₂ and less moves back into renal tubular cells. Therefore, less HCO₃^– is reabsorbed. This causes the bicarbonate buffer system in the blood to shift to the right, leading to CO₂ and H₂O in the blood combining to form H₂CO₃, which dissociates into HCO₃^– and H⁺, which restores H⁺ to normal.

The phosphate buffer

This is another buffer in the urine that can help with replenishing HCO₃^–. As mentioned above, the renal tubular cells secrete H⁺ into the nephron tubules, which combines with HCO₃^– to form H₂CO₃, which is converted to H₂O and CO₂ to readily move into the renal tubular cells. If HCO₃^– is low, the H⁺ can instead combine with hydrogen phosphate (HPO₄^2–) and sodium ions (Na⁺) to form NaH₂PO₄, which is excreted in the urine. This causes the bicarbonate buffer system in the blood to shift to the right, leading to CO₂ and H₂O in the blood combining to form H₂CO₃, which dissociates into HCO₃^– and H⁺, restoring HCO₃^–.