ADH

The role of the hypothalamus and pituitary in secreting ADH

There are specialised cells in the hypothalamus called osmoreceptors. These osmoreceptors are situated outside the blood-brain barrier and are very sensitive to blood water potential and osmolarity changes.

Correlation between water potential and osmolarity

Water potential and osmolarity are negatively correlated. Therefore, a fall in water potential means that the osmolarity in the blood is too high. Water moves from an area of low osmolarity (high water potential) to an area of high osmolarity (low water potential).

When the blood water potential drops:

1. Water moves out of the osmoreceptor cells, causing them to shrink.
2. This action triggers a neuronal response to the hypothalamus control centre to increase ADH release.
3. This raises the blood water potential

In the case of a rise in blood water potential:

1. Water moves down its osmotic gradient into the osmoreceptors.
2. This action causes osmoreceptors to swell and increase in size.
3. This change in cell shape also triggers neuronal responses to decrease ADH release.
4. This lowers blood water potential.

Hypovolaemia

A drop in blood volume (hypovolaemia) also stimulates ADH secretion. Hypovolaemia causes low blood pressure detected by baroreceptors in the heart, aorta, and the carotid artery. The neuronal signal is then relayed to the posterior pituitary to release more ADH.

The synthesis and release of ADH are controlled by negative feedback. When the blood water potential and blood pressure are restored, the amount of ADH released returns to its normal level.

The action of ADH

The main target of the ADH is the kidney. It acts on the distal convoluted tubule and the collecting duct to regulate the volume and osmolarity of the urine by controlling how much water is reabsorbed back into the blood.

ADH can also act on peripheral blood vessels to regulate blood pressure.

In response to high plasma osmolarity

Low water potential corresponds with high osmolarity in the blood. This result can arise from various causes such as:

• Not drinking a sufficient amount of water
• Losing more water than consumed, such as heavy sweating or diarrhoea.
• Eating salty food that is high in sodium and chloride ions.

A fall in water potential is detected by the osmoreceptors in the hypothalamus, triggering ADH secretion. ADH then targets the kidney and acts on the distal convoluted tubule and the collecting duct.

The process:

1. ADH binds to specific cell surface receptors on the basolateral side of the epithelial cells in these two regions.
2. The receptor then changes its shape and initiates a cascade of events leading to the activation of an intracellular phosphorylase.
3. This enzyme causes the fusion of specific intracellular vesicles with the apical membrane.
4. The vesicles contain particular types of water channels called aquaporins.
5. An increased number of aquaporins on the distal convoluted tubule and the collecting duct increases the permeability of these tubules for water leading to more water being reabsorbed.

ADH also increases the permeability of the collecting duct to urea. As more water is being reabsorbed, urea becomes highly concentrated, generating a high gradient for passive movement of urea out of the filtrate. Reabsorption of urea with water ensures that the water potential at the interstitial space is kept lower than the filtrate, so water continues to be reabsorbed.

Fig. 1 - Fusion of aquaporin containing vesicle with the apical membrane in the epithelial cells lining the collecting duct in response to ADH

High concentrations of ADH also causes vasoconstriction of peripheral blood vessels, ensuring that blood pressure does not drop too low.

The action of ADH on the kidney merely prevents further lowering of the blood water potential. Restoring the blood osmolarity is only fully achieved by drinking more water. The hypothalamus also activates the thirst centre in response to low blood water potential, increasing the urge to drink water. Following the restoration of the blood water potential, osmoreceptors send fewer impulses to the hypothalamus and secretion of ADH is reduced. This is an example of negative feedback.

In response to low plasma osmolarity

Low plasma osmolarity means the blood water potential is high. There is either too little salt and electrolytes in the blood or too much water in the blood. This may be caused by:

• Drinking too much water
• Not having sufficient salt and electrolytes in the diet to replace those lost in metabolism and excretions.
• Fluid overload due to excessive infusion of too much fluid in fluid replacement therapy (this usually happens to patients in hospitals)

The process:

1. A drop in low plasma osmolarity causes the osmoreceptors to increase in size since water enters those cells by osmosis.
2. The osmoreceptors then send fewer impulses to the hypothalamus causing less ADH to be released.
3. Less water is reabsorbed in the kidney to lower the blood water potential. This results in the production of very dilute urine.

Upon restoration of the blood osmolarity, impulses sent by the hypothalamus osmoreceptors return to normal and so does the ADH secretion.

Fig. 2 - The overall homeostatic process of osmoregulation is coordinated by the hypothalamus