Mechanism of Nausea and Vomiting

Mechanism of Nausea and Vomiting

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Table of Contents Background ................................................................................................................................................. 2

Etiology ........................................................................................................................................................ 2

Pathophysiology ...................................................................................................................................... 2-5

Management ........................................................................................................................................... 5-6

Conclusion .................................................................................................................................................. 6

Refernces .................................................................................................................................................... 6


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Background

Nausea and vomiting are basic human protective reflexes against the absorption of toxins, as

well as responses to certain stimuli.9 Vomiting is the means by which the upper gastrointestinal

tract rids itself of its contents when almost any part of the upper tract becomes excessively

irritated, overdistended, or even overexcitable. Nausea which is often a prodrome of vomiting,

and is the conscious recognition of subconscious excitation in an area of the medulla closely

associated with or part of the vomiting center.1 And the aim of this paper, is to understand what

nausea and vomiting is? And how does it occur? Which is based on several references, both

medical books and articles.

Etiology

The main etiologies for nausea and vomiting include iatrogenic, that is almost any

medication that can cause nausea and vomiting, such as, chemotherapeutic agents. Toxic

infectious causes, which is mainly caused by ingestion of a toxin. The other causes contain

gastrointestinal disorders, central nervous system or psychiatric conditions, and some conditions

caused by metabolism such as Pregnancy, which is the most common endocrinologic cause of

nausea and vomiting. 2

Pathophysiology

There are many conditions out there that cause nausea and vomiting, but we know that there

are at least three kinds of nausea and vomiting, the first of which has been attributed to

anaesthetics such as ether, the second to reflex responses, the last to opioids. 8

Nausea and vomiting occurs via different mechanisms and pathways. The afferent and

efferent reflexes involved in nausea and vomiting are integrated with two distinct centers at

brainstem level, which are the vomiting center, where it is proposed that, it is multiple distributed

nuclei located in the medulla, that contain histamine (H1), acetylcholine (ACh) and

5hydroxytryptamine2 (5HT2) receptors, however, it is now thought that an anatomically discrete

vomiting center is unlikely to exist, as proposed nearly 60 years ago by Wang and Borison.

Rather, a number of loosely organized neuronal areas within the medulla probably interact to

coordinate the emetic reflex, and the neurons coordinating the complex series of events that

occur during emesis have been termed the “central pattern generator”.6 And the second center is

chemoreceptor trigger zone (CTZ), which is located bilaterally on the floor of the fourth

ventricle in area postrema near the obex, where this part has no blood-brain barrier and may be

accessible to humoral stimuli in either blood or cerebrospinal fluid, so various drugs, toxins and

metabolites can access it, and has dopamine (D2), 5HT3 and Neurokinin-1 receptors. The

vomiting center receives afferent stimulation via the CTZ, the cerebral cortex, and the vestibular

system, and peripheral stimulation via the vagal and sympathetic nerves which, in turn, leads to

emesis.


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Once the vomiting center stimulated, the vomiting reflex occurs which is divided into two

phases: (1) Pre-ejection phase, which is characterized by a sensation of nausea associated with

cold, sweating, pupil dilatation, salivation and tachycardia mediated by sympathetic and

parasympathetic nerves, (2) Ejection phase, where it comprises of retching and vomiting with

expulsion of gastric contents.

Nausea Which is the prodrome of vomiting, is excitation of part of the medulla that is

closely associated with vomiting center, which can be caused by (1) irritative impulses coming

from the gastrointestinal tract, (2) impulses that originate in the lower brain associated with

motion sickness, or (3) impulses from the cerebral cortex to initiate vomiting. But it doesn’t

mean that Nausea and Vomiting are coupled together, because vomiting can occasionally occur

without the prodromal sensation of nausea, indicating that only certain portions of the vomiting

center area associated with the sensation of nausea. Vomiting usually starts with salivation and

the sensation of nausea, and the vomiting reflex occurs only when through stimulation of the

vomiting center.

There are several ways that vomiting center is stimulated, the First way is when the stomach

and the upper portions of the small intestine faces irritation, excessive distention or

overexcitation, it causes antiperistalisis -the prelude of vomiting-, often appears many minutes

before vomiting, which is peristalsis up the digestive tract rather than downward. This may begin

as far down in the intestinal tract as the ileum, and the antiperistaltic wave travels backward up

the intestine at a rate of 2 to 3 cm/sec; this process can actually push a large share of the lower

small intestine contents all the way back to the duodenum and stomach within 3 to 5 minutes.

Then, as these upper portions of the gastrointestinal tract, especially the duodenum, become

overly distended, this distention becomes the

exciting factor and an impulse is formed by

stimulation of H1 and ACh receptors, leading to an

afferent stimulus that terminates in the brain stem by

both vagal and sympathetic afferent nerve fibers,

primarily in the nucleus tractus solitarius, and

subsequently activates the vomiting center, which is

shown in figure (1).

The emetic stimuli in gut are detected by two types

of vagal afferent fibres, mechanoreceptors and

chemoreceptors, and the abdominal vagal afferents

appear to have the greatest relevance for

chemotherapy-induced nausea and vomiting, and

post-operative nausea and vomiting.

Second way is arising nervous signals in

chemoreceptor trigger zone. Electrical stimulation

and administration of certain drugs, including

apomorphine, morphine, and some digitalis

derivatives, can directly stimulate this

chemoreceptor trigger zone and in return stimulating

Vomiting center, as shown in figure(1). Destruction

of this area blocks this type of vomiting but does not

block vomiting resulting from irritative stimuli in the

gastrointestinal tract itself.


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Third way, is through stimulation of Ach or H1 receptors in the vestibular labyrinth of the

inner ear, when direction or rhythm of motion of the body is changed, which then transmitted to

vestibular nuclei that mediates the nausea and vomiting of motion sickness, from there, it is

transmitted into the cerebellum, then to the chemoreceptor trigger zone, and finally to the

vomiting center to cause vomiting.

Fourth way is stimulation of the Vomiting

Center from higher centers of the brain. When a

stimulation is formed from the diencephalon,

limbic system and cerebral cortex, then

transmitted to the cortical center, after that to

vomiting center to cause vomiting. Because

emetic responses to emotionally charged

stimuli such as nauseating smells, sickening

sights and pain occur. In addition to the

pathways already described, when there is

raised intracranial pressure cerebral histamine

receptors may be stimulated and meningeal

mechanoreceptors stimulate the vomiting

center. Also vestibular cardiac afferent induce

nausea and vomiting as in MI, and pharyngeal

stimulation may induce nausea and vomiting,

too. Figure (2) demonstrates the most of the

pathways for the stimulation of the vomiting

center, which we talked about before.9

Once the vomiting center has been

sufficiently stimulated and the vomiting act

instituted, the vomiting act takes place, where

motor impulses that cause the actual vomiting

are transmitted from the vomiting center by

way of the 5th, 7th, 9th, 10th, and 12th cranial nerves to the upper gastrointestinal tract, through

vagal and sympathetic nerves to the lower tract, and through spinal nerves to the diaphragm and

abdominal muscles, which cause the following effects that are (1) a deep breath, (2) raising of

the hyoid bone and larynx to pull the upper esophageal sphincter open, (3) closing of the glottis

to prevent vomitus flow into the lungs, and (4) lifting of the soft palate to close the posterior

nares. Also Serotonin (5-HT) released from enterochromaffin cells in the small intestine that

initiate impulses via 5-HT 3 receptors trigger vomiting, where reverse peristalsis empties

material from the upper part of the small intestine into the stomach, and it causes distention of

the stomach, which means further stimulation of the vomiting center. Next comes a strong

downward contraction of the diaphragm along with simultaneous contraction of all the

abdominal wall muscles, along with partial relaxation of the esophageal-stomach sphincter, thus

allowing vomitus to begin moving from the stomach into the esophagus. This squeezes the

stomach between the diaphragm and the abdominal muscles, building the intragastric pressure to

a high level. Finally, the lower esophageal sphincter relaxes completely, allowing expulsion of

the gastric contents upward through the esophagus, then the vomitus is expelled to the exterior

easily. 1, 4,6,8 The vomiting act is simply shown in Figure (3). 7


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Management

A wide variety of antiemetic agents are available for the prevention and treatment of nausea and

vomiting. These agents can be classified according to the therapeutic index of their usefulness as

high index, such as, 5-HT3 antagonists or low index, such as, cannabinoids. The table below

shows some common antiemetic agents.

Class of medication Example Common uses

Antihistamines cyclizine Possible adjunct for cytotoxic

chemotherapy, prophylaxis

and treatment of motion

sickness

Butyrophenones droperidol Anticipatory and acute

chemotherapeutic nausea and

vomiting, postoperative

nausea and vomiting

Cannabinoids dronabinol Refractory chemotherapy-

related nausea and vomiting

Corticosteroids dexamethasone Adjunct for chemotherapy

related symptoms

5-HT3 Antagonists dolasetron Post chemotherapy nausea and

vomiting, severe nausea and

vomiting


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There are also alternative treatments such as, Acupuncture, Acupressue, Ginger (powdered root),

and Pyridoxine for conditions like, chemotherapy-induced nausea and vomiting, post-operative

nausea and vomiting and early pregnancy nausea and vomiting.2,7

Conclusion

After over 150 years of research, still the mechanism of nausea and vomiting is not very clear?.

there are four factors that help us answer this ‘million’ dollar question: the First factor is

complexity of the problem, due to the variables which are so many that it becomes difficult to

identify the mechanism to assess the effects of an intervention, as it requires a considerable

number of patients in well controlled trials. Second is lack of animal model to study the

physiology and pharmacology of the mechanism of nausea and vomiting. Many species, such as,

rat and rabbit do not vomit irrespective of stimulus. Though, monkeys and dogs respond to the

same range of emetic stimuli as man with cytotoxic drugs and radiation, they do not suffer from

pregnancy and motion sickness and post-operative and post-anaesthetic emesis. The last factor is

inadequate quantification of the phenomena, irrespective of the huge number of clinical trials,

the phenomena have been poorly quantified. 8

References

1. Guyton AC, Hall JE. Gastrointestinal Physiology. Textbook of Medical Physiology 11th

ed. P823.

2. Scorza K, Williams K, Phillips JD, Shaw J. Evaluation of Nausea and Vomiting.

American Family Physician, 2007. V76, N1, P76-7.

3. Einarson TR, Piwko C, Koren G. Prevalence of Nausea and Vomiting of pregnancy in the USA.

University of Toronto.

4. Barrett KE, Boitano S, Barman SM, Brooks HL. Gastrointestinal Physiology. Ganong’s

Review of Medical Physiology 24ed .P502.

5. Chand S. Nausea and vomiting in palliative care, 2014. The Pharmaceutical Journal.

P2,3.

6. Hesketh PJ. Chemotherapy-Induced Nausea and Vomiting. N Engl J Med

2008.358,2482-94.

7. Paulev PE, Calleja GZ. New Human Physiology 2nd ed. Gastrointestinal Function and

Disorders, Chap22.

8. Islam S, Jain PN. post-operative nausea and vomiting (PONV) : a review article. Indian J.

Anaesth, 2004.48(4):253-258.

9. Garrett K, Tsuruta K, Walker S, Jackson S, Sweat M. Managing Nausea and Vomiting.

Critical Care Nurse, 2003. V23, N1.

Health & Medicine

Mechanism of Nausea and Vomiting