Renal System 5: Hormones and pH

Hormones

Antidiuretic hormone (vasopressin) controls fluid concentration and is important in preventing changes in cell volume. ADH reacts rapidly to changes in the extracellular fluid concentrations and regulates water reabsorption in the collecting duct (meaning it also causes sodium reabsorption). ADH is released in response to increased plasma/ECF concentration. It stimulates the incorporation of aquaporins in the distal convoluted tubule and collecting ducts, and allows for water to be reabsorbed. ADH is produced in the hypothalamus and is released from the posterior pituitary gland.

Aldosterone controls sodium reabsorption, and because water moves with sodium, aldosterone therefore controls fluid volume. This is important in regulation of blood pressure. It is slower acting than antidiuretic hormone. Aldosterone acts by incorporating Na+ and K+ pumps in the distal convoluted tubule and cortical region of the collecting duct.

pH

The extracellular fluid pH is narrowly controlled between 7.35 and 7.45. Acidosis occurs when the pH is less than 7.35 and alkalosis occurs when the pH is greater than 7.45. Overall, the movement of H+ ions (protons) maintains pH.

Why is maintaining pH of such high importance? Well, protein structure and function are completely pH sensitive. Too high or too low pH can result in protein deformation and as their function is shape-dependent, changes to their shape results in an inability to function. Nerve and muscle excitability are also pH sensitive. pH affects membrane structure and also determines enzyme activity.

On average, people gain 40mmol of H+ ions per day and excrete this same amount per day.

How are changes in pH handled?

Changes in pH are 'dealt' with using chemical buffers and a respiratory response. Chemical buffers act quickly to provide a barrier against pH changes. They are a short term measure and have limits to their buffering capacity. Chemical buffers include:

• Proteins
• Carbonic acid-bicarbonate (in equilibrium with bound and free H+ ions)
• Haemoglobin
• Phosphate
• Ammonia

The equilibrium reaction critical to understanding blood pH is:

H₂O + CO₂ ↔ H⁺ + HCO₃⁻

In terms of a respiratory response, normal arterial carbon dioxide concentration is 40mmHg. When acidosis occurs, the increased H+ concentration stimulates chemical buffering. This pushes the equilibrium reaction to the left, resulting in decreased HCO3- but increased carbon dioxide. The increased carbon dioxide stimulates the respiratory response, i.e. increased ventilation. The removal of carbon dioxide further shifts the equation to the left, resulting again in fewer H+ ions. The pH returns to a normal range. To assist in returning plasma pH to normal, the kidney secretes and excretes H+.

However, all these processes means HCO3- is at a low level, meaning it must be replaced. Thus, we reabsorb HCO3- which is freely filtered and generate new HCO3- through the filtration of H+. 

When alkalosis occurs, plasma H+ concentration is high and the kidney secretes less H+. Some HCO3- is filtered and not reabsorbed, meaning HCO3- concentrations in the plasma decrease. The equation shifts to the right to increase both HCO3- and H+.

Two systems also occur in what is known as the urinary buffer system, a division of the chemical buffers when it comes to maintaining pH. Urine pH cannot fall below 4.4, limiting the amount of H+ that can be excreted. If acidosis occurs, we over come the inability to increase urine pH by binding it to either ammonium (NH4+) or phosphate (HPO⁴₂₋) (bound H+ ions do not contribute to pH).

Acid-Base Disorders

Respiratory acid-base disorders are an imbalance between CO₂ generation in peripheral tissues and CO₂ excretion at the lungs. This causes abnormal CO₂ levels in the extracellular fluid:

• Respiratory acidosis (e.g. emphysema)
• Sustained alkalosis (e.g. sustained hyperventilation)

Metabolic acid-base disorders are the production of organic or fixed acids. They are conditions affecting H+ or HCO3- concentrations in the extracellular fluid:

• Metabolic acidosis (e.g. ketoacidosis from uncontrolled diabetes)
• Metabolic alkalosis (e.g. vomiting)