Antidiuretic hormone (ADH) is produced in the hypothalamus and secreted by the posterior pituitary gland. The hypothalamus and pituitary are found towards the middle of the brain. ADH is also known as vasopressin. ADH acts on the collecting ducts of the nephrons in the kidneys to stimulate water reabsorption from the urine to the blood. Diuresis refers to increased urine volume, with increased fluid loss from the body into the urine. The overall effect of antidiuretic hormone is to reduce diuresis, causing less urine volume and more fluid retained in the body.
Control of Antidiuretic Hormone
The hypothalamus and pituitary gland are located in the middle of the brain. Inside the hypothalamus are the supraoptic nucleus (SON) and paraventricular nucleus (PVN), which contain specialised neurosecretory cells that produce antidiuretic hormone. These cells stretch down into the posterior pituitary, where they release antidiuretic hormone into the general circulation.
The release of antidiuretic hormone by the neurosecretory cells is primarily controlled by two specialised cells:
- Osmoreceptors in the hypothalamus
- Baroreceptors in the artery walls, particularly in the carotid sinus (neck) and aortic arch (chest)
The hypothalamus contains specialised cells called osmoreceptors. Osmoreceptors detect the blood osmolarity. Osmolarity refers to the concentration of solutes, such as sodium, in a fluid. When there is a high osmolarity, meaning that the blood is more concentrated, usually due to dehydration, water moves out of the osmoreceptors by osmosis, causing them to shrink. Shrinkage of the osmoreceptors triggers a signal to the neurosecretory cells to release antidiuretic hormone.
Baroreceptors in the artery walls can sense the stretch in the artery wall. When there is higher blood pressure or blood volume, the arteries expand, and the walls are stretched. Baroreceptors detect this stretch in the artery walls and signal the hypothalamus. The signal from the baroreceptors has a negative effect on the release of ADH. The higher the blood volume and pressure, the greater the baroreceptor signal, and the less ADH is released. When the person is dehydrated and has reduced blood volume, there is less stretch in the arteries and less signal from the baroreceptors, resulting in more ADH release.
Action of Antidiuretic Hormone
Inside the kidneys, many tiny structures called nephrons filter the blood and produce urine. The basic structures of the nephron are the glomerulus, proximal tubule, loop of Henle, distal tubule and collecting duct. At the start of the nephron is the glomerulus. The afferent arterioles bring blood into the glomerulus, and the efferent arterioles drain blood out of the glomerulus. Fluid filters from the blood in the glomerulus into Bowman’s capsule, the first part of the nephron. The filtered fluid is called filtrate. This fluid travels along the nephron, where various chemicals are secreted and reabsorbed before draining into the collecting ducts and out of the kidneys as urine.
Antidiuretic hormone targets the epithelial cells that line the distal convoluted tubule and collecting duct. ADH stimulates V2 receptors (vasopressin receptor 2) on the basolateral membrane of these cells (the side facing the blood). This sets off a signalling cascade inside the cell, resulting in aquaporin-2 channels (proteins that allow water to pass through the membrane) being inserted into the apical membrane (the side facing the filtrate). The aquaporin-2 channels allow water to pass from the filtrate (urine) into the cell.
Water exits the other side of the cells through aquaporin-3 and aquaporin-4 channels on the basolateral membrane, into the interstitial fluid and then the blood.
The result is that antidiuretic hormone causes more water reabsorption from the urine, helping to dilute the blood and retain fluid within the body. This helps prevent dehydration and maintain the blood volume and blood pressure.
Diabetes Insipidus
Diabetes insipidus occurs when the effects of antidiuretic hormone are absent. There are two types:
- Cranial diabetes insipidus involves a lack of antidiuretic hormone from the hypothalamus and pituitary
- Nephrogenic diabetes insipidus involves a lack of response to antidiuretic hormone by the kidneys
With diabetes insipidus, the kidneys are unable to reabsorb water and concentrate the urine, leading to features of:
- Polyuria (excessive urine production)
- Polydipsia (excessive thirst)
- Dehydration (due to excessive water loss in the urine)
- Postural hypotension (a drop in blood pressure on standing due to a low blood volume)
Nephrogenic diabetes insipidus is when the collecting ducts of the kidneys do not respond to ADH. It can be idiopathic, without a clear cause, or it can be caused by:
- Medications, particularly lithium (used in bipolar affective disorder)
- Genetic mutations in the ADH receptor gene (X-linked recessive inheritance)
- Hypercalcaemia (high calcium)
- Hypokalaemia (low potassium)
- Kidney diseases (e.g., polycystic kidney disease)
Cranial diabetes insipidus is when the hypothalamus does not produce ADH for the pituitary gland to secrete. It can be idiopathic, without a clear cause, or it can be caused by:
- Brain tumours
- Brain injury
- Brain surgery
- Brain infections (e.g., meningitis or encephalitis)
- Genetic mutations in the ADH gene (autosomal dominant inheritance)
- Wolfram syndrome (a genetic condition also causing optic atrophy, deafness and diabetes mellitus)
Water Deprivation Test
The water deprivation test, also known as the desmopressin stimulation test, is used to diagnose diabetes insipidus.
Initially, the patient avoids consuming fluids for a period of “water deprivation” (e.g., 8 hours). After this period, the urine osmolality is measured.
In individuals without diabetes insipidus, antidiuretic hormone acts on the kidneys to increase water reabsorption, concentrate urine, and prevent dehydration during water deprivation. A normal result following water deprivation is a high urine osmolality.
In diabetes insipidus, the effects of antidiuretic hormone are absent, the kidneys cannot concentrate the urine, and the urine osmolality will be low after water deprivation.
When the urine osmolality is low after water deprivation, indicating diabetes insipidus, desmopressin (synthetic ADH) is given. The urine osmolality is measured over the following 2-4 hours.
In cranial diabetes insipidus, the patient lacks ADH. However, the kidneys are still capable of responding to ADH. The kidneys respond to desmopressin by reabsorbing water and concentrating the urine, which raises the urine osmolality.
In nephrogenic diabetes insipidus, the patient is unable to respond to ADH. The kidneys will not respond to the desmopressin, and the urine osmolality will remain low.
|
Urine Osmolality After Water Deprivation |
Urine Osmolality After Desmopressin |
|
|
Cranial Diabetes Insipidus |
Low |
High |
|
Nephrogenic Diabetes Insipidus |
Low |
Low |
Syndrome of Inappropriate Antidiuretic Hormone
Syndrome of inappropriate antidiuretic hormone (SIADH) involves excessive antidiuretic hormone (ADH).
There are two potential sources of too much ADH:
- Increased secretion by the hypothalamus and posterior pituitary
- Ectopic ADH from elsewhere, most commonly by small-cell lung cancer
Excessive ADH causes increased water reabsorption in the collecting ducts, diluting the blood. This excess water reduces the sodium concentration (hyponatraemia). The extra water is not usually significant enough to cause fluid overload. SIADH results in euvolaemic hyponatraemia. Euvolaemic refers to a normal volume of fluid in the body.
The urine becomes more concentrated as the kidneys excrete less water. Patients with SIADH have high urine osmolality and high urine sodium.
There is a long list of causes of SIADH:
- Post-operative after major surgery
- Lung infection, particularly atypical pneumonia and lung abscesses
- Brain pathologies, such as a head injury, stroke, intracranial haemorrhage or meningitis
- Medications (e.g., SSRIs and carbamazepine)
- Malignancy, particularly small-cell lung cancer
- Human immunodeficiency virus (HIV)
The symptoms of SIADH relate to low sodium (hyponatraemia). Depending on the sodium level and how rapidly it occurs, they may be asymptomatic or present with non-specific symptoms:
- Headache
- Fatigue
- Muscle aches and cramps
- Confusion
Severe hyponatraemia can cause seizures and reduced consciousness.
Medications
Vasopressin (antidiuretic hormone) can be given by intramuscular or subcutaneous injection to replace the missing antidiuretic hormone in the treatment of cranial diabetes insipidus.
Desmopressin is a medication that has a similar action to antidiuretic hormone (it is a vasopressin analogue). The options for administering desmopressin are oral, intranasal (nasal spray), sublingual (under the tongue) or injection. It is used to treat diabetes insipidus and nocturnal enuresis (bedwetting) in children.
Vasopressin receptor antagonists, such as tolvaptan, work by blocking ADH receptors. They can cause a rapid rise in sodium and require close monitoring of sodium levels. Vasopressin receptor antagonists are used to treat SIADH. They are also used to slow the progression of autosomal dominant polycystic kidney disease.
Last updated August 2024
Now, head over to members.zerotofinals.com and test your knowledge of this content. Testing yourself helps identify what you missed and strengthens your understanding and retention.
