What causes hiccups?

The particular mechanism that provokes the occurrence of hiccups is still unknown. It is also not yet known if hiccups have any specific purpose.

A hiccup involves a unilateral contraction of the left half of the diaphragm, also known as the left hemidiaphragm in roughly 80 percent of reported cases³. However, it is not simply a sudden movement of the diaphram that causes hiccups, but rather a complex motor action within the body.

Medically speaking, it is believed that a hiccup involves a reflex arc (i.e. a neural pathway that is involved in a reflex action) which consists of the following components:

1. An afferent limb (i.e. a neural (nerve) pathway that conducts impulses from the periphery (nerves and ganglia located outside of the brain and spinal cord) to the central nervous system  (which is made up of the brain and spinal cord) – this includes the phrenic and vagus nerves and sympathetic chain. The phrenic nerves (there are two, left and right) originate in the neck and run down between the lung and heart to reach the diaphragm. The vagus nerve is the longest cranial nerve, it runs from the brain down the neck and thorax and to the abdomen. It is comprised of motor and sensory fibers, and can send and receive information to and from the brain. The sympathetic chain is a paired bundle of nerve fibers that extend from the base of the skull to the coccyx.
2. A central mediator (this is thought to include the phrenic nerve nuclei, hypothalamus, respiratory centres and the reticular area of the brainstem).
3. An efferent limb (i.e. a neural pathway that conducts impulses away or outwards from the central nervous system) that includes the phrenic nerve with accessory efferent (outward) nerve connections to the intercostal muscles and glottis.

Whether hiccups play a physiological role in the human body is still unclear, although some experts believe that in utero, hiccups may form a part of programmed exercise to develop the inspiratory muscles necessary for breathing in the unborn baby.

Causes of hiccup bouts

These are the most common form of hiccups and are usually a result of one or more of the below causes:

• Gastric distention – This refers to bloating of the stomach as a result of drinking carbonated beverages and overeating.
• Aerophagia – This refers to swallowing air when eating or chewing gum.
• Sudden changes in gastrointestinal temperature or ambient temperature
• Drinking excessive quantities of alcohol
• Emotional stress or sudden excitement
• Gastric insufflation – This refers to air being blown into the stomach in order to inflate it for a better view during endoscopic procedures.

Persistent and intractable (uncontrollable) hiccups

There is very little known about the prevalence and incidence of persistent, uncontrollable hiccups, however, uncontrollable hiccups may be caused by a severe underlying health condition such as a structural lesion (for example, a tumour or build-up of fluid) or infection of the brain.

The majority of studies conducted on these types of hiccups involve limited case reports. There is no geographic, socioeconomic or racial variation observed in the cases of hiccups documented. However, one study ⁴ involving the review of 220 cases wherein patients suffered intractable hiccups (hiccups that last for longer than one month), found that the majority of the patients (roughly 80 percent) were older men (with an average age of 57 years old). A large number of the patients in this study also suffered from comorbid conditions (i.e. the presence of one or more conditions or diseases occurring simultaneously or one after the other), including 20 percent with vascular disease, 18 percent suffering from postoperative states, 17 percent with central nervous system disease and five percent with duodenal ulcers.

Another case study found that reflux oesophagitis, also known as GERD (gastroesophageal reflux disease) was identified as the most common comorbidity⁵. While other research has shown that persistent or intractable hiccups are experienced by between one and nine percent of patients suffering from advanced cancer⁶.

Chronic hiccups may have significantly adverse effects on the sufferer’s quality of life, leading to insomnia, dehydration, mental stress, weight loss and malnutrition as a result.

Some of the potential causes linked to persistent, as well as intractable hiccups, are described below:

• CNS (central nervous system) disorders –Damage to the vascular (blood vessels including the veins and arteries) and structural portions of the brain and/or spinal cord as well as infections of these, are believed to interfere with the inhibition of the sufferer’s hiccup reflex, simply put, the conditions described below prevent the hiccup reflex from naturally disappearing, resulting in chronic hiccups.                                    

• Vascular lesions – Chronic hiccups as a result of vascular lesions generally occur due to the presence of arteriovenous malformations (AVMs). An AVM is a tangle of poorly formed, abnormal blood vessels connecting the veins and arteries. Arteries carry oxygen-rich blood to the heart and brain, while veins carry deoxygenated blood back to the heart and lungs. AVMs disrupt this important process. They also have a higher bleeding rate in comparison to normal vessels. AVMs may occur anywhere in the body but are most commonly observed in the brain and spine.
• Infectious causes – Infections of the central nervous system (CNS) that can result in chronic hiccups include meningitis (inflammation of the membranes known as meninges surrounding the brain and spinal cord) and encephalitis (inflammation of the brain).
• Structural lesions – These forms of lesions include brainstem tumours and intracranial lesions (areas of injury or disease within the brain), hydrocephalus (this is a disorder also known as ‘water on the brain’ which describes an excessive accumulation of cerebrospinal fluid around the brain and spinal cord), syringomyelia (this is a chronic condition associated with the development of a cyst in the spinal cord) and multiple sclerosis (also known as MS, this is a chronic disorder of the central nervous system wherein the immune system attacks myelin, the protective sheath that covers nerve fibres, and eventually the nerves themselves, causing communication issues between the brain and the rest of the body that results in a host of complications).
• Phrenic and vagus nerve irritation – The phrenic nerve originates in the neck and passes between the heart and lungs to reach the diaphragm. The vagus nerve is the longest cranial nerve and connects the brain to the body. The irritation of these major nerves is often a common cause of chronic hiccups. Some causes of irritation in these nerves include:
  • Laryngitis (inflammation of the voice box), pharyngitis (inflammation of the back of the throat), or tumours in the neck that result in the stimulation of a branch of the vagus nerve known as the laryngeal nerve.
  • Cysts, tumours, goitres (swelling in the neck as a result of an enlarged thyroid gland), diaphragm abnormalities, and mediastinal masses (growths forming in the mediastinum, which is the area of the chest that separates the lungs) may result in the irritation of the phrenic nerve.
  • The auricular branch of the vagus nerve may become irritated by foreign bodies that come into contact with the cone-shaped membrane, known as the tympanic membrane, that separates the external ear and middle ear.

A number of the below disorders may also irritate the phrenic and vagus nerves, leading to hiccups:

• Gastrointestinal disorders – Conditions that affect the intestines and stomach, and may lead to chronic hiccups include:
  • Gastric distention – Bloating of the stomach that occurs when substances such as fluid or air accumulate in the abdomen.
  • Gastritis – This refers to the irritation, inflammation or erosion of the stomach lining which may be the result of a number of different conditions.
  • Gastroesophageal reflux disease (GERD) – Also known as chronic acid reflux, this is a digestive condition that involves bile or stomach acid irritating the lining of the oesophagus.

• Diaphragmatic eventration (protrusion) – This refers to a disorder wherein the diaphragm muscle has an abnormal shape and structure, causing this usually dome shaped structure to be elevated and displaced into the thorax. Diaphragmatic hernia refers to an irregular displacement of the abdominal wall, interfering with the diaphragmatic muscle and resulting in the herniation (i.e. the abnormal protrusion) of the abdominal contents through it.
• Peptic ulcer disease – Wherein a stomach ulcer or sore forms in the abdominal lining.
• Pancreatitis – Inflammation of the pancreas which is often caused by gallstones.
• Pancreatic cancer – Cancer of the pancreas.
• Gastric carcinoma – A type of malignant (cancerous) tumour of the stomach.
• Abdominal abscesses – A collection or pocket of pus and fluid that forms inside the abdominal cavity.
• Gallbladder disease – This encompasses a range is disorders that cause inflammation and irritation of the gallbladder such as cancer, gallstones, and cholestasis (this slows or stops the flow of bile from the liver).
• Inflammatory bowel disease (IBD) – IBD is the term that describes a number of disorders that are linked to the inflammation of the digestive tract.
• Hepatitis – A viral infection resulting in inflammation of the liver.
• Aerophagia – A condition wherein air is swallowed, leading to bloating and excessive belching.
• Oesophageal distention – Distention refers to the state of being enlarged or swollen as a result of internal When the oesophagus becomes distended this may be as a result of inflammation or an infection.
• Oesophagitis – Inflammation or irritation of the oesophagus as a result of infection, medication use, allergies or stomach acid.
• AIDS – Intractable hiccups may also be caused by uncommon complications resulting from AIDS, particularly when these are linked to diseases affecting the oesophagus such as oesophageal candidiasis.

• Thoracic disorders – These conditions include those that are related to the lungs, heart, oesophagus and chest, some of which are mentioned below:
  • Enlargement of the lymph nodes – This occurs as a result of infection or abnormal tissue growth (neoplasm), often caused by Lymph nodes form a vital part of the body’s lymphatic system, which, as part of the immune system, helps to fight off infections.
  • Pneumonia – A lung infection caused by viruses or bacteria that results in the inflammation of the small air sacs (alveoli) of the lungs.
  • Empyema – This condition often occurs secondary to a respiratory infection such as pneumonia and refers to a purulent (i.e. collection of pus) infection in a pleural space. Pleural describes the two membranes surrounding the lungs.
  • Bronchitis – Inflammation of the lining of the bronchial tubes which are responsible for carrying air to and from the lungs.
  • Asthma – This chronic condition affects the airways of the lungs. Asthma results in inflammation of the bronchial tubes which causes them to swell and produce excess mucus, making it difficult to breathe.
  • Pleuritis – Also known as pleurisy, is associated with sharp chest pain when breathing as a result of inflammation of the lining of the lungs, known as the pleura. The most common cause of this condition is a viral infection that spreads to the pleural cavity.
  • Aortic aneurysm – The body’s largest blood vessel is known as the aorta. An aortic aneurysm refers to a bulge or abnormal enlargement of this vessel which is responsible for carrying oxygen-rich blood from the heart to the rest of the body.
  • Mediastinal tumours – These growths form in the part of the chest that separates the lungs from one another (i.e. mid chest or mediastinum).
  • Mediastinitis – This is a life-threatening condition that often occurs as a complication of chest surgery or as a result of a tear in the oesophagus. It has an extremely high mortality rate if it is not timeously diagnosed or treated adequately. It involves the inflammation of the tissues of the chest cavity, also known as the mediastinum, which contains the heart, lymph nodes, thymus gland as well as sections of the aorta, oesophagus, thyroid and parathyroid glands.
  • Chest trauma – A chest injury or trauma is often the result of physical injury or impact to the chest which includes the lungs, heart and ribs. Chest injuries are typically the result of blunt force trauma sustained during motor vehicle accidents or due to a stabbing.
  • Pulmonary embolism – This condition refers to when one or more of the arteries in the lungs becomes blocked as a result of a blood clot, resulting in restricted blood flow, decreased oxygen levels in the blood and fatality. While this is rarely associated with chronic hiccups, it is still considered a possible cause.

• Cardiac disorders – These conditions include a variety of disorders that affect the heart. Cardiac disorders that may cause chronic hiccups include pericarditis, which is the irritation or swelling of the thin, sac-like membrane that surrounds the heart known as the pericardium and myocardial infarction (MI), which is commonly known as a heart attack, and occurs when blood flow to the heart is compromised (i.e. decreased or stopped).
• Toxic-metabolic diseases or drug-related disorders - Toxic-metabolic diseases refer to a collection of conditions that result in chronic or acute CNS (central nervous system) functional disorders. There are a number of factors that can affect the way in which the CNS functions, the use of recreational substances and drugs are among these. Drug-induced states may result in hiccups by affecting the CNS, specifically the vagus or phrenic nerves. Chronic or intractable hiccups may also occur with hyponatremia (a disorder that occurs due to low levels of sodium in the blood) and uraemia (a condition that involves abnormally high amounts of waste products in the blood).
• Postoperative – Chronic hiccups may occur postoperatively, some of the common postoperative causes for hiccups include:
• General anaesthesia (GA) – This refers to the reversible state of unconsciousness that is induced when you receive sedative medications prior to surgical procedures.
• Intubation – Intubation refers to a procedure wherein a flexible plastic tube is inserted through the mouth into the trachea, this allows for the patient to breathe freely during an emergency situation wherein the airway closes or during and/or post-operation. Intubation with glottic stimulation may result in chronic hiccups. The glottis is the natural space that occurs between the vocal folds and the structures surrounding it within the larynx.
• Visceral irritation – The word ‘visceral’ refers to the viscera, which are the internal organs of the body, particularly those found in the chest and abdomen. Visceral irritation or pain is considered a serious medical problem, and describes pain originating from the internal organs. This pain can also stimulate the vagal or phrenic nerves and trigger the hiccup reflex in the brain.
• Drug-related – Certain medications may lead to chronic hiccups, some of these include:
  • Diazepam (Valium) – Part of the benzodiazepine group typically prescribed to induce a calming effect.
  • Barbiturates – Central nervous system depressants that are prescribed as sedatives and sleeping pills, but some are used to induce sedation and anaesthesia.
  • Dexamethasone – A type of corticosteroid medication used in the treatment of a variety of inflammatory conditions.
  • Certain chemotherapeutic agents – Some patients receiving chemotherapy medications for the treatment of cancer may suffer from chronic hiccups as a result. Examples of these drugs include - Oxaliplatin, 5-fluorouracil, leucovorin⁷.
  • Alpha-methyldopa – Medication used to treat high blood pressure

• Psychogenic factors – There are some psychogenic factors (i.e. of a psychological origin as opposed to a physical one) that are associated with chronic hiccups. Psychogenic causes will, however, only be taken into consideration after a thorough medical examination has been conducted. Some of these conditions include:
  • Anxiety – An uncomfortable feeling of worry or nervousness
  • Stress – A state of tension or mental strain
  • Excitement – Feeling great eagerness or enthusiasm
  • Malingering – To exaggerate or pretend to be sick or incapable

 

^References:

^{3. NCBI. 1952. Hiccup; a ten-year review of anatomy, etiology, and treatment. Available: https://www.ncbi.nlm.nih.gov/pubmed?term=13009550 [Accessed 08. 02. 2017]}

^{4. NCBI. 1968. Intractable hiccup. Etiologic factors in 220 cases. Available: https://www.ncbi.nlm.nih.gov/pubmed?term=5638775 [Accessed 08. 02. 2017]}

^{5. NCBI. 1992. Chronic hiccups. Available: https://www.ncbi.nlm.nih.gov/pubmed?term=1344930 [Accessed 08. 02. 2017]}

^{6. NCBI. 2012. Treatment of chronic hiccups in cancer patients: a systematic review. Available: https://www.ncbi.nlm.nih.gov/pubmed?term=22891647 [Accessed 08. 02. 2017]}

^{7. NCBI. 2009. Severe hiccups during chemotherapy: corticosteroids the likely culprit. Available: https://www.ncbi.nlm.nih.gov/pubmed/19276142 [Accessed 27. 02. 2017]}