What Are the Phrenic Nerves?

Your two phrenic nerves are the only nerves that control the diaphragm, the dome-shaped muscle that sits between your chest and abdomen. They play a critical role in breathing and are responsible for the hiccup reflex.

The phrenic nerves also have sensory and sympathetic functions. In addition, they are often responsible for the referred pain to the shoulder that can accompany abdominal disorders.

Originating in the cervical spine (C3 to C5), the phrenic nerves are vulnerable to injury as they travel down the neck and through the chest into the diaphragm.

This article looks at the anatomy and function of the phrenic nerves. It also discusses conditions that might involve the phrenic nerves, and how they are diagnosed and treated.

Phrenic Nerve Anatomy

Understanding the anatomy of the phrenic nerves is essential for surgeons and others who perform procedures in the neck or chest.

Structure

Nerves such as the phrenic nerves are made up of axon fibers, which convey information to and from the brain. Nervous tissue is one of the four types of tissue and is made up of neurons (nerve cells) and supporting cells called neuroglia.

The neuroglia secrete a substance called myelin that lines the nerves and increases the rate of conduction (speed of nervous signal).

The phrenic nerves run from the cervical spine to the diaphragm. They do so on both sides of the body, but the left phrenic nerve is longer due to the course it takes as it descends.

Both phrenic nerves are supplied by the pericardiophrenic artery, which is a branch of the internal thoracic artery, and the superior phrenic vein.

Location

The phrenic nerves begin in the neck (cervical spine) and travel to the right and left diaphragm to control contraction and inspiration.

The phrenic nerves originate primarily from the fourth cranial nerve but include contributions from both the third and fifth cranial nerve (C3-C5). As the nerves leave the spine, they both travel along the internal jugular vein and along the anterior scalene muscle deep to the subclavian vein.

As the nerves enter the chest, they take somewhat different paths as they run through the posterior mediastinum (the area between the lungs):

• The left phrenic nerve passes just anterior to the pericardium (the lining of the heart) near the left ventricle.
• The right phrenic nerve descends along the inner aspect of the lung and passes just lateral to the right atrium and right ventricle of the heart.

It then passes through the vena cava hiatus on its way to the diaphragm. The phrenic nerves then insert into the left dome and right dome of the diaphragm, respectively.

Known Anatomic Variations

In some people, an accessory phrenic nerve is present and may supply the subclavius muscle. This variant may also receive branches from the brachial and cervical plexus.

Function

The phrenic nerve has sensory, motor, and sympathetic functions.

Motor Function

As the only nerves that control the diaphragm, the phrenic nerves have a vital role in respiration.

Signals from the nerve (which can be voluntary or involuntary) cause the diaphragm to contract and flatten during inspiration, drawing air into the lungs. When the diaphragm relaxes, air is expelled.

Sensory Function

The phrenic nerves also transmit sensory information to the brain from the region of the central tendon of the diaphragm, the pericardium (the membrane lining the heart), and the outer lining (parietal pleura) that lies on the medial region of the lungs.

For example, irritation of the diaphragm (such as by carbon dioxide injected into the abdomen during laparoscopic surgery) may be felt as pain in the right shoulder. Similarly, some tumors near the top of the lungs, Pancoast tumors, may irritate the nerve as it travels nearby and cause pain that is sensed in the shoulder.

The referred pain due to irritation of the diaphragm and other regions the left phrenic nerve is usually felt on the tip of the left shoulder and referred to as the Kehr's sign.

Sympathetic Function

The phrenic nerves also appear to communicate with the sympathetic nervous system, but the significance of this is largely unknown. It has been noted that phrenic nerve stimulation for central sleep apnea can cause sympathetic activity (release of catecholamines) that can lead to worsening or even an increased risk of death.

A 2018 study found that there are communicating fibers between the phrenic nerve and the sympathetic trunk, and that the phrenicoabdominal branch of the right phrenic nerve is a branch of the celiac plexus. This finding could have important implications with regard to nerve stimulation practices.

Associated Conditions

Conditions associated with phrenic nerve function or dysfunction can range from benign hiccups to paralysis of both sides of the diaphragm and severe respiratory distress.

Damage to the nerves due to trauma, compression, some infections, and neuromuscular diseases can lead to partial or total paralysis of one or both sides of the diaphragm. The phrenic nerves are also the nerves responsible for a very common symptom related to contraction and spasm of the diaphragm—hiccups.

Hiccups

The phrenic nerve is responsible for the hiccup reflex. Stimulation by the nerve causes spasm of the diaphragm, and the sound that is heard occurs when the diaphragm contracts and pulls air against the closed larynx.

While primarily a nuisance for most people, chronic hiccups, which are hiccups that last for over 48 hours, or "intractable hiccups," hiccups lasting more than 30 days, can result in loss of sleep, weight loss, and extreme fatigue.

Understanding the anatomy of the phrenic nerve can be helpful in looking for potential causes. For example, chronic hiccups can be related to conditions such as hepatitis, Crohn's disease, and ulcers via sensory input to the phrenic nerve.

Chronic hiccups could also be potentially related to pressure on the phrenic nerve anywhere in its course from the neck to the diaphragm, such as a tumor in the mediastinum pressing on the nerve. Central nervous system causes are possible as well.

The importance of chronic hiccups, medically known as "persistent singuitis," has gained renewed attention both for the severe quality of life issues they create and the importance of a thorough workup for potential causes.

Paralysis of the Diaphragm

When one or both phrenic nerves are damaged or severed, the diaphragm can no longer contract, resulting in paresis (partial paralysis) or paralysis. This can be temporary or permanent depending on whether the nerve is only injured or if it is disrupted.

When the nerve is disrupted, it does not recover.

Causes

There are a number of possible causes of phrenic nerve injury leading to paralysis of the diaphragm. These can be broken down by mechanism.

Trauma

The phrenic nerve(s) may be injured with spinal cord injuries, but this depends on the level of injury. Spinal cord injuries, especially above C5, often lead to paralysis of the diaphragm.

Surgery to the neck, chest, or liver can damage the nerve, and cardiac surgery is the most common cause of trauma to the phrenic nerve. It is also very common during surgery for congenital heart disease in infants. When the inferior vena cava is clamped during liver transplantation, the nearby right phrenic nerve is often damaged.

In addition, trauma from motor vehicle accidents or falls and chiropractic manipulation can result in injury to the phrenic nerve.

Ablation for arrhythmias, or radio-frequency ablation for conditions such as atrial fibrillation, carries a risk for phrenic nerve injury. Repeated trauma to the neck (chronic cervical radiculopathy), anesthetic injury (the phrenic nerve may be damaged during an interscalene block for shoulder surgery), and birth trauma can all result in phrenic nerve injury.

Compression of the Nerve

Tumors or other structures that press on the phrenic nerve may lead to damage, including:

• Lung cancer
• Enlarged mediastinal lymph nodes
• Aortic aneurysms

Neuromuscular Diseases

Paralysis of the diaphragm may occur with conditions such as:

• Amyotrophic lateral sclerosis (ALS)
• Muscular dystrophy
• Multiple sclerosis (MS)

Neuropathic, Autoimmune, and Infectious Processes

Conditions may include:

• Guillain-Barré syndrome
• Congenital Zika virus infection
• Herpes zoster
• Lyme disease
• Thyroid disease
• Post-polio syndrome
• Parsonage-Turner syndrome (neuropathy of the brachial plexus)

Idiopathic

It's thought that in roughly 20% of cases, the cause of phrenic nerve palsy is unknown.

Symptoms

The symptoms of phrenic nerve injury depend on whether one or both nerves are damaged as well as the age of the person and other health conditions.

When only one nerve is damaged in an adult, there may be no symptoms, or there may be shortness of breath that is more apparent with exercise and problems with sleep-disordered breathing.

When both nerves are damaged symptoms often include severe shortness of breath that is worse with lying down or when submerged in water up to the chest. Other symptoms may include chest wall pain, cough, fatigue, anxiety, and morning headache.

A significant decrease in lung capacity is noted whether a single or both nerves are damaged, with a decrease of roughly 50% due to one-sided injury and a decrease of 70% to 80% when both nerves are involved.

Diagnosis

The diagnosis is sometimes challenging as symptoms can mimic those of a number of heart and lung conditions. Since a paralyzed diaphragm results in a paradoxical motion of he diaphragm (the diaphragm moves up in the chest during inspiration and down during expiration), a person's abdomen may be noted to move inward rather than outward with inspiration.

Elevation of the diaphragm on one side is often seen on a chest X-ray when one phrenic nerve is injured. The diagnosis is often made by visualizing the abnormal motion of the diaphragm on ultrasound or fluoroscopically. Pulmonary function tests will show a restrictive pattern (restrictive lung disease in contrast to obstructive).

Treatment

The treatment of a phrenic nerve injury and paresis or paralysis of the diaphragm will depend on whether one or both nerves are involved, as well as whether the nerve is severed (as when it is disrupted during surgery) or remains functional (such as with ALS or a spinal cord injury).

With some injuries causing only partial paralysis, function may return in time. When both sides are involved or if one phrenic nerve is involved but a person is symptomatic, options include:

• Noninvasive ventilation (such as CPAP or BiPAP), especially at night
• Diaphragmatic placation: a surgery in which the diaphragm is "tacked down" with sutures to aid inspiration
• Diaphragm pacemakers (if the phrenic nerves are still functional a pacemaker may work well)
• Mechanical ventilation (oftentimes, a tracheostomy and mechanical ventilation is required)
• Phrenic nerve reconstruction (a relatively new and very specialized procedure, reconstruction may be effective)

It's also important to treat the underlying cause of the phrenic nerve injury.

Prognosis

The prognosis of a phrenic nerve injury leading to paresis or paralysis of the diaphragm depends on the cause. With some infectious or autoimmune conditions, or when the nerve is only injured and not destroyed such as with radiofrequency ablation, function may be restored in several months.

Since nerves such as the phrenic nerve do not regenerate, complete disruption of the nerve will lead to permanent paralysis of the diaphragm.

Summary

The phrenic nerves play an important role in breathing. These nerves are vulnerable to injury and can cause serious problems when damaged.

Paralysis of the diaphragm is caused by damage to both phrenic nerves. This can happen during certain kinds of surgery or trauma. Some kinds of infectious and neuromuscular diseases can also affect the phrenic nerves.

Damaged phrenic nerves can be treated with ventilation, diaphragm pacemakers, or surgery.