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inquisitive girlsby: Gene Smith

Introduction

Welcome back, friends and loyal readers, to another installment of my Behind the Scenes series. My previous article ran several years ago, so if you have no idea what I’m talking about, that’s quite alright. First, I’m happy to report that my first year of medical school is moving closer to a victorious conclusion.

But for now, at the time of this writing at least, spring break is in full swing. I didn’t make the crunch for the previous issue; so if it’s no longer springtime, indulge me anyway. To many college students, spring break is a symbol for wild partying and excessive drinking. In celebration of the debauchery, this article will look closely at the art and science of vomiting. Yes, the art and the science.

The Boring Basics

Vomiting is the expulsion of gastric contents resulting from contraction of the gut and abdominal musculature. Regurgitation, unlike vomiting, is an effortless (from your body’s point of view) return of said contents. Nausea is the subjective sensation of the need to vomit, a vague and unpleasant feeling that tends to immediately precede the act of vomiting. Hiccups are involuntary spasms of the diaphragm caused by irritation of the phrenic or vagus nerve pathways. The diaphragm muscles contract against a closed glottis creating the ‘hic’ sound. There is no well-defined hiccup center.

In the MRI image outlined below, the only medullary structure that I have labeled is an unspecific vomiting center. Not labeled are the visceral and cranial nerve nuclei that also send and receive connections to the vomiting reflex. They aren’t labeled because they are in such close proximity they are indistinguishable on a gross anatomical image (microscopically they can all be identified). The larger point is that the proximity of participating nuclei makes a complex effort more efficient – and they are all located in the medulla. Vomiting is efficient. Get it? Tickle the back of your throat if you don’t believe me.

da brain

The Barf Zones

Vomiting is caused by the stimulation of one or more of the following sites: (1) Gastrointestinal tract, (2) vestibular system (3) higher CNS centers, and (4) chemoreceptor trigger zone (CTZ) in the area postrema of the floor of the fourth ventricle.

This last one is a mouthful (pun intended), so let me explain. The blood brain barrier (BBB) is a protective network of vessels separating the central nervous system (CNS) from the rest of the body. As a result, one would assume that the area postrema, contained within the CNS, would be well protected by the BBB. It is not, because it is a circumventricular organ. Circumventricular organs are a set of anatomical structures in the CNS, most of them bordering the third and fourth ventricles, that lack a BBB. They’re the “exceptions to the rule,” if you will. Area postrema is one such barrier-deficient structure; others include the pineal gland and the posterior pituitary. The take home point here is that, since unprotected, the vomiting center is easily accessible.

 

Neurotransmitters

The medullary vomiting centers contain receptors for histamine, dopamine, acetylcholine, serotonin, and opioids. The myenteric plexus in the GI tract is loaded with serotonin receptors, so it’s no surprise that serotonin enhancers may wander off into the intestines and precipitate nausea and vomiting.

The Sarin Gas attack on the Tokyo Subway in 1995 showed us how organophosphate nerve agents overload the acetylcholine receptors to produce vomiting and – if not immediately treated with antidotes atropine/2-PAM – an inevitably painful death.

Opioid receptors can be stimulated by morphine or an overdose of Imodium (opioids cause constipation and are used to treat diarrhea). Nausea and vomiting is notoriously associated with chemotherapy. Chemo irritates GI enterochromaffin cells, which release serotonin to stimulate 5-HT-type-3 receptors on “vagal afferents” (a linkage pathway between the gut and brain).

The vestibular system is rich in histamine and acetylcholine receptors; overstimulated, it forms the neurochemical basis for vomiting associated with motion sickness. In short, neurotransmitter centers in the chemoreceptor trigger zone, situated over in the medulla of the brainstem, are fundamental to the vomiting reflex. Efficient, easily accessible, and stimulated by neurotransmitters.

Physiological Response

Let’s go back to the act of vomiting itself for just a moment. A wave of reverse peristalsis first begins in the proximal small intestine. Remember, the enteric neural circuits can be programmed to produce contractions in either direction along the intestine. This retroperistalsis propels gastric contents in the oral direction, eventually into the esophagus. If the sphincter is closed, retching (‘dry heaves’) occurs against a closed glottis. If the pressure is high enough to open the sphincter, you vomit.

vomit

Suppose that you do. Water and electrolytes are lost from the body. Loss of H+ by vomiting acidic gastric juice means that the H+ never arrives in the small intestine. The arterial blood becomes alkaline with a metabolic alkalosis. Breathing rate slows as compensation, in order to restore the blood pH and CO2 to normal levels. You know, that spent feeling you get when you’re down puking.

The Ipecac Challenge

Syrup of ipecac is a plant-derived compound containing two alkaloids – emetine and cephaeline. Ipecac works locally by irritating the gastric mucosa (similar mechanism to chemotherapy), and centrally by stimulating chemoreceptor trigger zone directly. In season 4 episode 8 of Family Guy, Peter, Brian, Stewie, and Chris each drink sizeable portions of Ipecac to see who would go the longest in resisting the drug’s effects. The prize? The last piece of pie. Peter cracked first, mid-sentence. Stewie and Brian followed suit almost immediately. Chris won, by a few seconds. It was a brilliant 2-minute comedic performance. In reality, the drug would need 30-60 minutes to take effect and the alkaloids can still found in the urine months later.

Babies

Vomiting is not uncommon during the neonatal period. It can result from GI irritation by material the baby swallows during delivery, or from acute withdrawal secondary to the mother’s drug addiction. For some historical perspective on drug-addicted babies, one may appreciate William Hogarth’s well-known engraving Gin Lane (1751). Gin Lane depicts the slum ruins around St. Giles church in the city of London, home to class dangereuse – thieves, prostitutes, impoverished alcoholics. The most prominent figure of this painting is a mother in drunken stupor, so wasted that her child falls from her lap. In the far right, a woman feeds her baby some gin. Vomit is poorly represented, but not inconceivable given the atmosphere.

Blood-Vomiting Game

This unfortunately-named ‘game’ actually refers to a famous ‘Go’ match. ‘Go’, for the uninitiated, is a strategic one-on-one Chinese board game. The game rewards subtle and deeply intellectual tactics, in which players use their black or white stones to compete for territory. In 1835, Honinbo Jowa (“Honinbo” house) and Gennan Inseki (“Inoue” house) were two bitter rivals from two of the four major houses of Go. Both were vying for the most prestigious Go title of Meijin (meaning ‘master’ or ‘expert’). Inseki, lacking confidence, sent his pupil Akaboshi Intetsu to face Jowa.

Intetsu took an early advantage, unleashing the secret taisha variation developed by the Inoue house. As the week-long game progressed, Jowa assertively grabbed the lead with three famous moves known as ‘Ghost Moves’” so called because they were supposedly told to him by ghosts. At the end of the game, the defeated Intetsu coughed up and vomited blood, only to die a month later at the age of 25.

Competitive Eaters

The International Federation of Competitive Eating (IFOCE) is the world body that governs this intense, demanding sport. The contests feature an important rule: you may be disqualified for an “urge contrary to swallowing.” They don’t use the ‘V’ word. Whatever they call it, if you lose your food you lose the contest.

How these athletes build resistance to the vomiting reflex is a mystery. Current hypotheses have to do with satiety signals: training the body to redefine its interpretation of the normal and the dangerous. Soon, competitive eaters will earn more money than competitive bodybuilders, and will be able to fund their own scientific inquiry. For now, we’ll let the mystery intensify.

References

1. Abel EL. Gin Lane: did Hogarth know about fetal alcohol syndrome? Alcohol Alcohol. 2001 Mar-Apr;36(2):131-4.
2. Kasper D, Isselbacher K, Braunwald E, Wilson J, Martin J, Fauci A, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005
3. Krakauer EL, Zhu AX, Bounds BC, Sahani D, McDonald KR, Brachtel EF. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 6-2005. A 58-year-old man with esophageal cancer and nausea, vomiting, and intractable hiccups. N Engl J Med. 2005 Feb 24;352(8):817-25.
4. Kumar V, Fausto M, Abbas A, eds. Robbins Pathological Basis of Disease. 7th ed. New York, NY: WB Saunders; 2004.
5. Marx J. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 5th ed. St. Louis, Mo: Mosby, Inc.; 2002
6. Wang SC, Borison HL. A new concept of organization of the central emetic mechanism: recent studies on the sites of action of apomorphine, copper sulfate and cardiac glycosides. Gastroenterology. 1952 Sep;22(1):1-12.
7. Yamashita M, Yamashita M, Azuma J. Urinary excretion of ipecac alkaloids in human volunteers. Vet Human Toxicol 2002;44:257—9.

 

Behind the Scenes: Vomiting!

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