Nausea and Vomiting pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Vishnu Vardhan Serla M.B.B.S. [2]

Vomiting is coordinated in the vomiting center in the lateral medullary reticular formation in the pons. Receptors on the floor of the fourth ventricle of the brain represent a chemoreceptor trigger zone, stimulation of which can lead to vomiting. The chemoreceptor zone lies outside the blood-brain barrier, and can therefore be stimulated by blood-borne drugs that can stimulate vomiting, or inhibit it.

There are various sources of input to the vomiting center:

• The chemoreceptor trigger zone at the base of the fourth ventricle has numerous dopamine D₂ receptors, serotonin 5-HT₃ receptors, opioid receptors, Acetylcholine receptors, and receptors for substance P. Stimulation of different receptors are involved in different pathways leading to emesis, in the final common pathway substance P appears to be involved.^[1]
• The vestibular system which sends information to the brain via cranial nerve VIII (vestibulocochlear nerve). It plays a major role in motion sickness and is rich in muscarinic receptors and histamine H₁ receptors.
• Cranial nerve X (vagus nerve), which is activated when the pharynx is irritated, leading to a gag reflex.
• Vagal and enteric nervous system inputs that transmit information regarding the state of the gastrointestinal system. Irritation of the GI mucosa by chemotherapy, radiation, distention or acute infectious gastroenteritis activates the 5-HT₃ receptors of these inputs.
• The CNS mediates vomiting arising from psychiatric disorders and stress.

The vomiting act encompasses three types of outputs initiated by the medulla: Motor, parasympathetic nervous system (PNS) and sympathetic nervous system (SNS). Collectively, they are as follows:

• Increased salivation to protect the enamel of teeth from stomach acids (excessive vomiting leads to caries). This is part of the PNS output.
• Retroperistalsis, starting from the middle of the small intestine, sweeping up the contents of the digestive tract into the stomach, through the relaxed pyloric sphincter.
• A lowering of intrathoracic pressure (by inspiration against a closed glottis), coupled with an increase in abdominal pressure as the abdominal muscles contract, propels stomach contents into the esophagus without involvement of retroperistalsis. The lower esophageal sphincter relaxes. This is part of the motor output, and it is also important to note that the stomach itself does not contract in the process of vomiting.
• Vomiting is ordinarily preceded by retching.
• Vomiting also initiates a SNS response causing both sweating and increased heart rate.

The neurotransmitters that regulate vomiting are poorly understood, but inhibitors of dopamine, histamine and serotonin are all used to suppress vomiting, suggesting that these play a role in the initiation or maintenance of a vomiting cycle. Vasopressin and neurokinin may also participate.

Since the stomach secretes acid, vomit contains a high concentration of hydronium ions and is thus strongly acidic. Recent food intake will be reflected in the gastric vomit.

The content of the vomitus (vomit) may be of medical interest. Fresh blood in the vomit is termed hematemesis ("blood vomiting"). Old blood bears resemblance to coffee grounds (as the iron in the blood is oxidized), and when this matter is identified the term "coffee ground vomiting" is used. Bile can enter the vomit during subsequent heaves due to duodenal contraction if the vomiting is severe. Fecal vomiting is often a consequence of intestinal obstruction, and is treated as a warning sign of this potentially serious problem ("signum mali ominis"); such vomiting is sometimes called "miserere". If food has recently been consumed, then partly digested food may show up in the vomit.

If the vomiting reflex continues for an extended period of time with no appreciable vomitus, the condition is known as non-productive emesis or dry heaves, which can become both extremely painful and debilitating.

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