The Pathophysiology of Vomiting

Vomiting is the process by which gastric contents come out of the mouth due to reverse peristalsis in the small intestine and an organized sequence of muscular activity secondary to a well-coordinated nervous circuit both of which eventually result in expulsion of the vomitus.How does vomiting occur?Vomiting occurs when the vomiting centres (present in the lateral reticular formation of the medulla) are stimulated. The following areas can stimulate the vomiting centre:

The Chemoreceptor Trigger Zone: This area is located in the floor of the 4th ventricle of the brain and constitutes the area postrema, a circumventricular organ which is devoid of the blood brain barrier due to which substances such as drugs and toxins carried in the blood can directly reach it. This explains why some drugs cause or stop vomiting. This zone contains dopamine D2, serotonin 5-HT3, opioid, acetylcholine and substance P receptors whose activations results in different pathways, the end result of all of which includes substance P.

The Vagus Nerve: This is the 10th cranial nerve and gets activated whenever the pharynx is activated and the gag reflex results.

The Vestibular System: This system controls balance and sends its input to the CNS via the vestibular nerve, playing a role in any disturbance of balance (such as motion sickness), eventually resulting in vomiting. This system has a rich supply of muscarinic receptors.

Vagal and Enteric Nervous System: The nervous system of the gut, when stimulated, can induce vomiting via the vagal afferents or its rich sympathetic nervous supply. The gastrointestinal tract can be irritated by chemotherapy, radiation, certain drugs, severe distension and infection.

The CNS: When the higher brain centres such as the cerebrum are affected by stress or certain psychiatric conditions, this can also result in vomiting.

So to sum up, whatever stimulates these five components will stimulate the vomiting centre, thus causing vomiting.

The Phases of Vomiting:Vomiting consists of three phases;

1. Nausea, sweating and salivation2. Retching3. Expulsion of gastric contents through the mouth4.

The physiology behind vomiting:Vomiting is mediated by the parasympathetic & sympathetic nervous system along with the motor system, as described below:

The parasympathetic nervous system causes excessive salivation to protect the tooth enamel from the acid contents of the stomach when are vomited out.

The sympathetic nervous system causes sweating as well as increase in heart rate.

The motor system causes a deep breath so that the vomitus is not aspirated. In addition, reverse peristalsis begins from the middle of the small intestine so that its contents are brought up to the stomach, passing the pyloric sphincter, which lies relaxed at this point due to the parasympathetic activity. Contrary to popular belief, the oesophagus or stomach do not contract and there is not negative peristalsis in these organs. Then how is the vomitus expelled? That happens due to two processes: inspiration against a closed glottis and contraction of the abdominal musculature. The former lowers the pressure inside the thoracic cavity and the latter increases abdominal pressure, thus propelling the contents of the small intestine to move easily from a region of high pressure to a region of low pressure. The stomach is contracted only at the angular notch whereas the lower oesophageal sphincter relaxes when the stomach contents have to be propelled out. To put this in to order, inspiration lowers the thoracic pressure while the lower oesophageal sphincter is contracted and the abdominal muscles are contracting forcefully, thus building up pressure within the abdominal cavity. The intestines are undergoing negative peristalsis and as soon as their contents reach the lower oesophageal sphincter, it opens and pressure is suddenly released, propelling the gastric contents out of the mouth through the relaxed oesophagus.

Vomiting: The molecular level:  Vomiting is mediated by neurotransmitters such as histamine, dopamine, serotin, neurokinin and vasopressin, with the former three

being the main controllers. That is why dopamine, serotonin and histamine antagonists are given for the suppression of vomiting.

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Vomiting is a forceful expulsion of the contents of the stomach and sometimes the gut. The whole mechanism is guided and controlled by the brain and its vomiting centre.

The vomiting centre of the brain

The fourth ventricle of the brain hosts the vomiting centre. The floor of the fourth ventricle contains an area called the chemoreceptor trigger zone (CTZ). It is also called the area postrema. When the CTZ is stimulated, vomiting may occur.

The CTZ contains receptors for dopamine, serotonin, opioids, acetylcholine and the neurotransmitter substance P. When stimulated, each of these receptors gives rise to pathways leading to vomiting and nausea. Present in high concentrations in the vomiting centre, Substance P seems to be involved in the final common pathways that give rise to vomiting.

The CTZ lies outside the blood-brain barrier (BBB). Normally, the BBB controls substances that affect the brain. Medications and chemicals in the blood have selective access to the brain when protected by the BBB. As the CTZ, however, lies outside the BBB, drugs and medications are capable of stimulating this area to trigger vomiting. Medications that control or are used to treat vomiting may inhibit this area to prevent vomiting.

Inputs to the vomiting centre in the brain

The CTZ in the brain is stimulated by various inputs from different parts of the body and this leads to vomiting. Some of the inputs to the CTZ include:

Inputs from the vestibular system of the inner ear. These travel via the eighth cranial nerve or the vestibulocochlear nerve and are involved in motion sickness causing nausea and vomiting. There is an abundance of the H1 type of histamine receptors in this system that can be suppressed by the H1 type of antihistaminics to control vomiting induced by motion sickness.

The tenth cranial nerve or the vagus nerve carries signals to the CTZ when the back of the throat or pharynx is irritated or stimulated. This is called the gag reflex.

The nervous system around the gut or the enteric nervous system also transmits signals to the brain via the vagus nerve. It is via this system that radiation therapy, chemotherapy and gastroenteritis activate the 5-HT3 receptors leading to vomiting.

Dopamine receptors are activated by stress and several psychiatric conditions, leading to vomiting.

The process of vomiting

The process of vomiting involves several phases and steps. These include:

Stimulation of the CTZ leading to activation of the motor, parasympathetic and sympathetic nervous system

Stimulation of the parasympathetic nervous system leading to increased salivation Deep breathing preceding the actual vomiting to protect the lungs from aspiration Heaving or retching before the actual vomiting Relaxation of the pyloric sphincter that guards the lower end of the stomach to bring

up content from the gut The pressure within the abdomen rises and the pressure within the chest or thorax is

lowered. The abdominal muscles contract to expel the contents of the stomach Activation of the sympathetic nervous system leads to sweating, palpitation and rapid

heart rate

Vomiting is the forceful expulsion of contents of the stomach and often, the proximal small intestine. It is a manifestation of a large number of conditions, many of which are not primary disorders of the gastrointestinal tract. Regardless of cause, vomiting can have serious consequences, including acid-base derangments, volume and electrolyte depletion, malnutrition and aspiration pneumonia.

The Act of Vomiting

Vomiting is usually experienced as the finale in a series of three events, which everyone reading this has experienced:

Nausea is an unpleasant and difficult to describe psychic experience in humans and probably animals. Physiologically, nausea is typically associated with decreased gastric motility and increased tone in the small intestine. Additionally, there is often reverse peristalsis in the proximal small intestine.

Retching ("dry heaves") refers to spasmodic respiratory movements conducted with a closed glottis. While this is occurring, the antrum of the stomach contracts and the fundus and cardia relax. Studies with cats have shown that during retching there is repeated herniation of the abdominal esophagus and cardia into the thoracic cavity due to the negative pressure engendered by inspiratory efforts with a closed glottis.

Emesis or vomition is when gastric and often small intestinal contents are propelled up to and out of the mouth. It results from a highly coordinated series of events that could be described as the following series of steps (don't practice these in public):

o A deep breath is taken, the glottis is closed and the larynx is raised to open the upper esophageal sphincter. Also, the soft palate is elevated to close off the posterior nares.

o The diaphragm is contracted sharply downward to create negative pressure in the thorax, which facilitates opening of the esophagus and distal esophageal sphincter.

o Simultaneously with downward movement of the diaphragm, the muscles of the abdominal walls are vigorously contracted, squeezing the stomach and thus elevating intragastric pressure. With the pylorus closed and the esophagus relatively open, the route of exit is clear.

The series of events described seems to be typical for humans and many animals, but is not inevitable. Vomition occasionally occurs abruptly and in the absense of premonitory signs - this

situation is often referred to as projectile vomiting. A common cause of projectile vomiting is gastric outlet obstruction, often a result of the ingestion of foreign bodies.

An activity related to but clearly distinct from vomiting is regurgitation, which is the passive expulsion of ingested material out of the mouth - this often occurs even before the ingesta has reached the stomach and is usually a result of esophageal disease. Regurgitation also is a normal component of digestion in ruminants.

There is also considerable variability among species in the propensity for vomition. Rats reportedly do not vomit. Cattle and horses vomit rarely - this is usually an ominous sign and most frequently a result of acute gastric distension. Carnivores such as dogs and cats vomit frequently, often in response to such trivial stimuli as finding themselves on a clean carpet. Humans fall between these extremes, and interestingly, rare individuals have been identified that seem to be incapable of vomiting due to congenital abnormalities in the vomition centers of the brainstem.

Control of Vomition

The complex, almost sterotypical set of activities that culminate in vomiting suggest that control is central, which indeed has been shown to be true. Within the brainstem are two anatomically and functionally distinct units that control vomiting:

Bilateral vomition centers in the reticular formation of the medulla integrate signals from a large number of outlying sources and their excitement is ultimately what triggers vomition. Electric stimulation of these centers induces vomiting, while destruction of the vomition centers renders animals very resistant to emetic drugs. The vomition centers receive afferent signals from at least four major sources:

The chemoreceptor trigger zone (see below) Visceral afferents from the gastrointestinal tract (vagus or sympathetic nerves) - these

signals inform the brain of such conditions as gastrointestinal distention (a very potent stimulus for vomition) and mucosal irritation.

Visceral afferents from outside the gastrointestinal tract - this includes signals from bile ducts, peritoneum, heart and a variety of other organs. These inputs to the vomition center help explain how, for example, a stone in the common bile duct can result in vomiting.

Afferents from extramedullary centers in the brain - it is clear that certain psychic stimuli (odors, fear), vestibular disturbances (motion sickness) and cerebral trauma can result in vomition.

The chemoreceptor trigger zone is a bilateral set of centers in the brainstem lying under the floor of the fourth ventricle. Electrical stimulation of these centers does not induce vomiting, but application of emetic drugs does - if and only if the vomition centers are intact. The chemoreceptor trigger zones function as emetic chemoreceptors for the vomition centers - chemical abnormalities in the body (e.g. emetic drugs, uremia, hypoxia and diabetic ketoacidosis) are sensed by these centers, which then send excitatory signs to the vomition centers. Many of the antiemetic drugs act at the level of the chemoreceptor trigger zone.

To summarize, two basic sets of pathways - one neural and one humoral - lead to activation of centers in the brain that initiate and control vomition. Think of the vomition centers as commander in chief of vomition, who makes the ultimate decision. This decision is based on input from a battery of advisors, among whom the chemoreceptor trigger zone has considerable influence. This straighforward picture is almost certainly oversimplified and flawed in some details, but helps to explain much of the physiology and pharmacology of vomition.

Causes and Consequences of Vomiting

The myriad causes of vomiting are left as an exercise - come up with a list based on personal experience and your understanding of the control of vomition. An important point, however, is that many cases of vomiting are due to diseases outside of the gastrointestinal tract.

Simple vomiting rarely causes problems, but on occasion, can lead to such serious consequences as aspiration pneumonia. Additionally, severe or repetitive vomition results in disturbances in acid-base balance, dehydration and electrolyte depletion. In such cases, the goal is to rapidly establish a definitive diagnosis of the underlying disease so that specific therapy can be instituted. This is often not easy and in many cases, it is advantageous to administer antiemetic drugs in order to suppress vomition and reduce its sequelae.

The circumventricular organs (CVO) are structures that permit polypeptide hypothalamic hormones to leave the brain without disrupting the blood-brain barrier (BBB) and permit substances that do not cross the BBB to trigger changes in brain function. 2. In mammals, CVO include only the median eminence and adjacent neurohypophysis, organum vasculosum lamina terminalis, subfornical organ and the

area postrema. 3. The CVO are characterized by their small size, high permeability and fenestrated capillaries. The subcommissural organ is not highly permeable and does not have fenestrated capillaries, but new evidence indicates that it may be involved in the hypertension produced by aldosterone acting on the brain. 4. Feedback control of corticotropin-releasing hormone (CRH) secretion is exerted by free steroids diffusing into the brain, but substances such as cytokines and angiotensin II act on CVO to produce increases in CRH secretion. Gonadal steroids also diffuse into the brain to regulate gonadotrophin-releasing hormone secretion. Thyrotropin-releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion.

Dapus

Ganong’s review of medical physiology

Sherwood

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