Vomiting - Pathophysiology

Pathophysiology

Receptors on the floor of the fourth ventricle of the brain represent a chemoreceptor trigger zone, known as the area postrema, stimulation of which can lead to vomiting. The area postrema is a circumventricular organ and as such lies outside the blood–brain barrier; it 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 involved.
• The vestibular system, which sends information to the brain via cranial nerve VIII (vestibulocochlear nerve), plays a major role in motion sickness, and is rich in muscarinic receptors and histamine H₁ receptors.
• The Cranial nerve X (vagus nerve) is activated when the pharynx is irritated, leading to a gag reflex.
• The Vagal and enteric nervous system inputs 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 that arises from psychiatric disorders and stress from higher brain centers.

The vomiting act encompasses three types of outputs initiated by the chemoreceptor trigger zone: Motor, parasympathetic nervous system (PNS), and sympathetic nervous system (SNS). They are as follows:

• Increased salivation to protect tooth enamel from stomach acids. (Excessive vomiting leads to dental erosion). This is part of the PNS output.
• The body takes a deep breath to avoid aspirating vomit.
• Retroperistalsis, starts from the middle of the small intestine and sweeps up digestive tract contents into the stomach, through the relaxed pyloric sphincter.
• Intrathoracic pressure lowers (by inspiration against a closed glottis), coupled with an increase in abdominal pressure as the abdominal muscles contract, propels stomach contents into the esophagus as the lower esophageal sphincter relaxes. The stomach itself does not contract in the process of vomiting except for at the angular notch, nor is there any retroperistalsis in the esophagus.
• Vomiting is ordinarily preceded by retching.
• Vomiting also initiates an 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.