Vomiting

VOMITING 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): ◦ 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. ◦ The diaphragm is contracted sharply downward to create negative pressure in the thorax, which facilitates opening of the esophagus and distal esophageal sphincter. ◦ 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. Vomiting 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 to be involved. • 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 from higher brain centers. Act 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 the enamel of teeth from stomach acids (excessive vomiting leads to dental erosion). This is part of the PNS output. • A deep breath is taken to avoid aspiration of vomit. • 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 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.

Phases The vomiting act has two phases. In the retching phase, the abdominal muscles undergo a few rounds of coordinated contractions together with the diaphragm and the muscles used in respiratory inspiration. For this reason, an individual may confuse this phase with an episode of violent hiccups. In this retching phase nothing has yet been expelled. In the next phase, also termed the expulsive phase, intense pressure is formed in the stomach brought about by enormous shifts in both the diaphragm and the abdomen. These shifts are, in essence, vigorous contractions of these muscles that last for extended periods of time - much longer than a normal period of muscular contraction. The pressure is then suddenly released when the upper esophageal sphincter relaxes resulting in the expulsion of gastric contents. For people not in the habit of exercising the abdominal muscles, they may be painful for the next few days. The relief of pressure and the release of endorphins into the bloodstream after the expulsion causes the vomiter to feel better B. Pupillary Light Reflex The pupillary light reflex involves adjustments in pupil size with changes in light levels. • The reflex is consensual: Normally light that is directed in one eye produces pupil constriction in both eyes. • The direct response is the change in pupil size in the eye to which the light is directed (e.g., if the light is shone in the right eye, the right pupil constricts). • The consensual response is the change in pupil size in the eye opposite to the eye to which the light is directed (e.g., if the light is shone in the right eye, the left pupil also constricts consensually). The pupillary light reflex allows the eye to adjust the amount of light reaching the retina and protects the photoreceptors from bright lights. The iris contains two sets of smooth muscles that control the size of the pupil (Figure 7.2). • The sphincter muscle fibers form a ring at the pupil margin so that when the sphincter contracts, it decreases (constricts) pupil size. • The dilator muscle fibers radiate from the pupil aperture so that when the dilator contracts, it increases (dilates) pupil size. Both muscles act to control the amount of light entering the eye and the depth of field of the eye1. • The iris sphincter is controlled by the parasympathetic system, whereas the iris dilator is controlled by the sympathetic system. • The action of the dilator is antagonistic to that of the sphincter and the dilator must relax to allow the sphincter to decrease pupil size. Normally the sphincter action dominates during the pupillary light reflex. The pupillary light reflex neural circuit: The pathway controlling pupillary light reflex (Figure 7.3) involves the • retina, optic nerve, optic chiasm, and the optic tract fibers that join the • brachium of the superior colliculus, which terminate in the • pretectal area of the midbrain, which sends most of its axons bilaterally in the posterior commissure to terminate in the • Edinger-Westphal nucleus of the oculomotor complex, which contains parasympathetic preganglionic neurons and sends its axons in the oculomotor nerve to terminate in the

• ciliary ganglion, which sends its parasympathetic postganglionic axons in the • short ciliary nerve, which ends on the • iris sphincter Recall that the optic tract carries visual information from both eyes and the pretectal area projects bilaterally to both Edinger-Westphal nuclei: Consequently, the normal pupillary response to light is consensual. That is, a light directed in one eye results in constriction of the pupils of both eyes. C. Pupillary Dark Response The pupils normally dilate (increase in size) when it is dark (i.e., when light is removed). This response involves the relaxation of the iris sphincter and contraction of the iris dilator. The iris dilator is controlled by the sympathetic nervous system. The pupillary dark reflex neural circuit: The pathway controlling pupil dilation involves the • retina and the optic tract fibers terminating on neurons in the hypothalamus and the • axons of the hypothalamic neurons that descend to the spinal cord to end on the • sympathetic preganglionic neurons in the lateral horn of spinal cord segments T1 to T3, which send their axons out the spinal cord to end on the • sympathetic neurons in the superior cervical ganglion, which send their • sympathetic postganglionic axons in the long ciliary nerve to the • iris dilator. Axons from the superior cervical ganglion also innervate the face vasculature, sweat and lachrymal glands and the eyelid tarsal muscles. When the superior cervical ganglion or its axons are damaged, a constellation of symptoms, known as Horner's syndrome, result. This syndrome is characterized by miosis (pupil constriction), anhidrosis (loss of sweating), pseudoptosis (mild eyelid droop), enopthalmosis (sunken eye) and flushing of the face. D. The Accommodation Response The accommodation response is elicited when the viewer directs his eyes from a distant (greater than 30 ft. away) object to a nearby object (Nolte, Figure 17-40, Pg. 447). The stimulus is an “out-of-focus” image. The accommodation (near point) response is consensual (i.e., it involves the actions of the muscles of both eyes). The accommodation response involves three actions: Pupil accommodation: The action of the iris sphincter was covered in the section on the pupillary light reflex. During accommodation, pupil constriction utilizes the "pin-hole" effect and increases the depth of focus of the eye by blocking the light scattered by the periphery of the cornea (Nolte, Figure 17-39, Pg. 447). The iris sphincter is innervated by the postganglionic parasympathetic axons (short ciliary nerve fibers) of the ciliary ganglion (Figure 7.3). Lens accommodation: Lens accommodation increases the curvature of the lens, which increases its refractive (focusing) power. The ciliary muscles are responsible for the lens accommodation response. They control the tension on the zonules, which are attached to the elastic lens capsule at one end and anchored to the ciliary body at the other end (Figure 7.4). Convergence in accommodation: When shifting one's view from a distant object to a nearby object, the eyes converge (are directed nasally) to keep the object's image focused on the

foveae of the two eyes. This action involves the contraction of the medial rectus muscles of the two eyes and relaxation of the lateral rectus muscles. The medial rectus attaches to the medial aspect of the eye and its contraction directs the eye nasally (adducts the eye). The medial rectus is innervated by motor neurons in the oculomotor nucleus and nerve. The accommodation neural circuit: The circuitry of the accommodation response is more complex than that of the pupillary light reflex (Figure 7.6). The afferent limb of the circuit includes the • retina (with the retinal ganglion axons in the optic nerve, chiasm and tract), • lateral geniculate body (with axons in the optic radiations), and • visual cortex. Ocular motor control neurons are interposed between the afferent and efferent limbs of this circuit and include the • visual association cortex, which 0 determines the image is "out-of-focus" 1 sends corrective signals via the internal capsule and crus cerebri to the • supraoculomotor nuclei, which 0 is located immediately superior to the oculomotor nuclei 1 generates motor control signals that initiate the accommodation response 2 sends these control signals bilaterally to the oculomotor complex. The efferent limb of this system has two components: the • Edinger-Westphal nucleus, which 0 sends its axons in the oculomotor nerve to 1 control the ciliary ganglion, which 0 sends it axons in the short ciliary nerve to 1 control the iris sphincter and the ciliary muscle/zonules/lens of the eye • oculomotor neurons, which 0 sends its axons in the oculomotor nerve to 1 control the medial rectus 2 converge the two eyes.