Role Of Antidiuretic Hormone In Nocturia

Introduction

Understanding Nocturia

Definition

Nocturia is defined as the condition wherein there is a regular urgent need to urinate in the middle of the night.¹ It is a highly prevalent urinary symptom and can often add burden on patients quality of life and productivity.² Nocturia can disrupt your sleep routine and affect your quality of life including productivity and energy. There are several causes of nocturia which can include increased fluid intake, reduced bladder capacity and underlying health conditions, which will be discussed in more detail in this article. 

Introduction to Antidiuretic Hormone (ADH)

Definition & Function

ADH (also known as vasopressin) is one of the body’s hormones responsible for controlling water and blood pressure.³ It is produced in the hypothalamus and released by the pituitary gland. ADH works inside the kidneys and is a vital hormone to ensure that you are hydrated and that your blood pressure and volume is normal.

Basics of Antidiuretic Hormone (ADH)

Production and Secretion

ADH is stored in the hypothalamus (a gland in the brain) and is stored and released from the pituitary gland (also a gland in the brain).⁴ ADH is secreted in response to the water content of the blood, known as osmolarity. A high osmolarity indicates reduced water content in the blood and a low osmolarity indicates increased water content in the blood. 

The hypothalamus contains receptors, known as osmoreceptors, that detect changes in the blood osmolarity and send signals to cause the release of ADH from the pituitary gland into the blood. Therefore when osmoreceptors detect an increase in osmolarity (decreasing water content in the blood) it causes the release of ADH from the pituitary gland into the systemic circulation. The blood then carries ADH to the kidneys where their effects take place.

ADH release is also controlled by the volume status of the blood. Blood volume is detected by baroreceptors in the left atrium, carotid artery and aortic arch, which are specifically known as the cardiopulmonary receptors.⁵ In times of reduced blood volume, known as hypovolaemia, these baroreceptors send signals to the pituitary gland to release ADH.

Function of ADH

Once ADH has reached the kidneys, its main functions are to control water reabsorption from the kidneys to control osmolarity of the blood. ADH increases water reabsorption by increasing aquaporin-2 channels in the distal convoluted tubules and collecting ducts which increases permeability for water to be reabsorbed into the blood⁶. Increasing water reabsorption helps to reduce and stabilise osmolarity and increase blood volume in cases of hypovolaemia.

ADH plays a role in urine production as well. More ADH means that more water will be reabsorbed and retained. This causes less urine volume which is more concentrated, which helps the body retain water in times of dehydration and low blood volume. Constrastingly, if the body is overhydrated, ADH levels fall, resulting in more water to be passed out through urine which increases urine volume and concentration.

Nocturia

What is Nocturia?

As mentioned before, nocturia is the need to wake up one or more times in the middle of the night to urinate, and is considered to be the most irritating symptom of urinary tract dysfunction.⁷ Nocturia is slightly more common in women but is more common in men for 70+ year olds.⁸

Nocturia can significantly impact your quality of life, specifically sleep quality, daytime wellbeing, productivity, and can affect chronic diseases.⁹

Common causes of Nocturia

There can be many causes of Nocturia, which can be associated with your lifestyle, medical conditions, or whether you are taking any medications. Nocturia can simply be caused by increasing your fluid intake.² This can occur at bedtime in the evening or even throughout the day. Fluids can include caffeinated drinks or alcohol and not just water.

Another potential cause of Nocturia is a reduced bladder capacity or detrusor overactivity, which is the increased contraction of the muscles that control the bladder. A reduced bladder capacity can make you need to use the toilet more often and detrusor overactivity can make you need to urinate even with a partially full bladder. Detrusor overactivity may have neurological or iatrogenic causes (caused by a medical examination or treatment).

Global polyuria is another cause of nocturia. Global polyuria is the daily excretion of over 40mL/kg body weight. This is commonly found in people with uncontrolled diabetes mellitus, central or nephrogenic diabetes insipidus, or primary polydipsia (meaning drinking too much fluids).¹⁰

Nocturia can also be caused by Obstructive Sleep Apnoea (OSA). OSA is when your upper airway becomes completely or partially blocked causing reduced oxygen saturation.¹¹ OSA leads to increased levels of ANP which is a hormone that leads to increased urine production.¹⁰

Connection between ADH and Nocturia

Normal ADH function in urine production

When everything is functioning as it should, ADH is released to reduce urine production by increasing water reabsorption in the kidneys, and by doing this it maintains adequate levels of hydration and maintains plasma osmolarity. When osmoreceptors detect an increase in osmolarity, a signal is sent to the hypothalamus to produce ADH which is released from the pituitary gland. ADH in the blood then travels to the kidneys where they act by binding to V2 receptors in the collecting duct which increases the number of aquaporin 2 channels. This increases the amount of water that can be reabsorbed and therefore reduces urine production.

ADH levels are typically higher at night to reduce urine production while you sleep and reduce dehydration. Melatonin, which is secreted at night and in darkness can increase levels of ADH. ADH levels are typically lower during the day to help increase urine production and maintain fluid balance as you go about your daily activities.

ADH dysfunction and nocturia

In some cases, ADH production may be reduced at night or undetectable, which can cause nocturnal polyuria syndrome.¹² This can cause increased urine production during the night and cause nocturia. In addition, ageing can cause a decrease in the natural secretion of ADH and reduced sensitisation of the kidneys to ADH.

Disrupting your circadian rhythm can also affect your body’s natural release of ADH. This can include working regular night shifts, travelling across time zones causing jet lag, or sleep disorders such as insomnia, OSA or irregular and inconsistent sleeping patterns.

Treatment Options

Lifestyle Changes

Initial management of nocturia typically involved making changes to your routine, especially before bedtime. This can include but is not limited to:

• Meditation before bedtime
• Limiting fluid intake in the late afternoon
• Avoiding fluids 2 hours before bedtime
• Reducing dietary salt and protein, particularly in the evening

Medication

Your physician may offer a medication called Desmopressin to treat your nocturia. Desmopressin is a synthetic analog of ADH, and therefore works the same as ADH by causing the kidneys to produce less urine. This is typically taken at bedtime.

Addressing underlying conditions

Nocturia can be caused due to an underlying condition. As mentioned before this can include diabetes mellitus, obstructive sleep apnoea, and others. Therefore, it is important to ensure that you manage your condition and health as advised by your doctor and keep on top of any treatments that they have provided you with. 

Summary 

Nocturia can be a very bothersome symptom where you wake up in the middle of the night one or more times to urinate which can negatively affect your quality of life. Normal urine production is controlled by the appropriate release of the hormone ADH which is released at greater levels at night to reduce urine production. Nocturia is caused by the insufficient release of ADH at night causing increased urine production. Nocturia can have several causes such as increased fluid intake, especially towards the end of the day, reduced bladder capacity, which can diminish with age,¹³ and other health conditions such as diabetes mellitus. It is therefore important to ensure you regularly attend health checks and follow your doctor's treatment plan for any conditions you may have. Making lifestyle changes may also help with nocturia such as limiting fluid intake and reducing dietary salt and protein.