What causes Hiccups?

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Definition and Causes
Hiccup is a reflex and involuntary contraction of the diaphragm which causes closure of the vocal chords after 0.25 seconds after the diaphragmatic contraction. The sudden closure of the glottis produces the characteristic ‘œhic’ sound. Hence, a sudden spasmodic diaphragm contraction which causes its lowering from a relaxed state causes the inspiratory cough or hiccup. Hiccups may occur rhythmically or as a single episode. The symptoms and features include a series of uncontrolled diaphragm spasms or myoclonic jerks, tremor in shoulders, abdomen or throat, audible sound (uncontrolled) or inhaling gasp (controlled) and sometimes pain may occur. The common causes of hiccup include excess coughing, sudden swallowing, rapid eating, intense emotions, drinking carbonated drinks, pneumonia, renal disorders, abdominal surgery, and consumption of opiate drugs and inhalation of noxious fumes.

Pathophysiology of Hiccups
The pathophysiological of hiccups have been suggested through various pathways. In one explanation, it is claimed that a lesion in the medulla that affects the respiratory centres lying ventral and lateral areas of nucleus of tractus solitarius. The diaphragm is innervated by the phrenic nerve which originates in the ventral horns of the spinal cord in cervical segments (C3-C5). The stimulus from the respiratory centres reaches the phrenic nucleus, which modulates diaphragmatic movements during inspiration and expiration. Lesion in medulla causes a reflex hyper-stimulation of phrenic nuclei causing sudden contractions of diaphragm.

In another explanation put forward by Howes (2012), it is suggested that hiccups originate as reflex process of suckling and to maintain homeostasis of suckling mechanism. During suckling, milk is taken inside the stomach, which causes flatulence, thereby irritating the abdominal viscera and the overlying diaphragm.

The sudden stimulation of the diaphragm results in hiccups which allows, the air trapped inside the stomach to flow out, paving way for further milk intake. It has been postulated that such reflexes in the later stages becomes a part of unconditional learning that leads to hiccups. Air bubbles in the stomach excites sensory reflex by stimulating receptors of stomach, oesophagus and diaphragm that causes hiccups. Suction is created in the chest, which pulls air out from the stomach through the mouth. The development of hiccups in foetus is due to myelination of the phrenic nerves. Such myelination occurs in the intrauterine life of a foetus.

Various Central nervous system disorders like stroke, multiple sclerosis and meningitis are responsible for hiccups, and gastrointestinal disorders like gastrointestinal reflux disease (GERD) may also cause hiccups. The CNS disorders are mainly related to damage of the phrenic nerves or impaired stimulation of the phrenic nerves that causes hiccups. On the other hand in GERD, due to the incomplete closure of lower oesophageal sphincter, there is continuous gasping to force food or contents re-enter into the stomach, this causes reflex and sudden closure of the glottis leading to closure.

From a phylogenetic point of view, hiccups have been attributed to remnants of amphibian respiration. Amphibians gulp air and water through the gills by a motor reflex similar to hiccupping in humans. Hiccups are also inhibited by excess carbon dioxide and release of GABA receptor agonists. Excess carbon dioxide, inhibits the respiratory chemo receptors, which inhibits the episodes of hiccups. On the other hand, GABA receptor agonists like Gabapentin and Pregabalin, reduces neurotransmitter release and hence blocking the overstimulation of phrenic nerves, inhibiting hiccup.

Management of Hiccups
Hiccups are managed by various home treatments and medication administration. The objective of treatment is to treat the underlying cause that elicits the involuntary reflex. The phrenic nerve may be blocked by 0.5% procaine or the phrenic nerve may be ablated as treatment options for hiccups. Similarly administration of lidocaine 3% into ear canal may act to inhibit hiccups. Lidocaine causes stimulation of the vagus nerve that which inhibits sudden spasms of diaphragm. As earlier stated GABA receptor agonists reduces neurotransmitter release and blocks overstimulation of phrenic nerves, inhibiting hiccups. Drugs like Haloperidol and chlorpromazine which are anti-psychotic and sedative are effectively used to treat hiccups. As hiccup treatment is associated with treatment of the underlying cause, proton pump inhibitors like omeprazole may be used to inhibit underlying GERD.

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