Nausea and vomiting Flashcards
What are some of the input pathways triggering vomiting?
- Stimulation of the back of the throat, triggering the gag reflex
- Noxious chemicals, stimulating the CTZ
- Distension/irritation of the stomach or duodenum due to activation of mechanoreceptors or chemoreceptors
- Rotation or acceleration of the head
This involves the vestibular apparatus within the inner ear feeding into the vestibular nuclei causing dizziness/motion sickness - Elevated intracranial pressure
Brain tumours, haemorrhage - Emotional factors
Unpleasant sites and smells - learned pathways
How do noxious chemicals pass the BBB in order to stimulate the CTZ?
The CTZ is actually located adjacent to the base of the fourth ventricle and is surrounded by fenestrated capillaries. These are capillaries in which the endothelial cells have holes in them - essential they are leaky and noxious chemicals can pass through the blood vessels to stimulate the CTZ without the need to cross the BBB. The area samples the blood to detect noxious chemicals.
Where do all the input vomit pathways feed into?
They feed into the vomiting centre within the medulla - nucleus of the solitary tract known as the NTS. This then co-ordinates the downstream signalling pathway and outcomes.
What are some examples of noxious chemicals which could potentially stimulate the CTZ?
Bacterial alkaloids
Poisonous alkaloids
Drugs e.g. chemotherapies
Where is the nucleus of the solitary tract found?
Adjacent to the area postrema/CTZ at the base of the fourth ventricle. These two areas work closely together with dendrites from the NTS projecting into the AP/CTZ.
What is the purpose of the NTS?
It is a major relay centre and is responsible for the integration of all the signal inputs it receives and then co-ordinates an appropriate response for the motor side of the vomiting reflex.
Explain the pro-emetic effects associated with dopamine agonists.
Dopamine agonists stimulate D2 receptors found within the CTZ such as apomorphine which results in nausea and vomiting side effect profile e.g. Levodopa
Describe how GI input can cause nausea and vomiting.
The cells that are responsible for the GI input are the enterochromaffin cells which are a type of enteroendocrine cells within the gastric epithelium. They have both chemoreceptors which are able to detect noxious stimuli and mechanoreceptors which detect stretch for example eating too much.
Upon activation of these cells, 5-HT is released which then acts upon adjacent 5-HT3 receptors within the gut causing an action potential and stimulation of the nerve endings of vagal afferent fibres which then transmit the information to the NTS.
Additionally released 5-HT into systemic circulation can then get into the CTZ causing activation there.
What are the two main output pathways associated with the vomiting reflex?
Autonomic pathway stimulated by both the sympathetic and parasympathetic nervous system
Somatomotor response which involves skeletal muscle
What are does the autonomic pathway response involve?
Sweating
Cutaneous vasoconstriction within the skin causing us to go pale
Tachycardia
Contraction (retrograde) of the small intestine which moves contents upwards which opposes the action of peristalsis
Relaxation of the stomach, oesophagus and sphincter to allow the outflow of vomit
What does the somatomotor pathway response involve?
Contraction of the diaphragm which pushes downwards on the stomach
Closure of the glottis (respiratory pathway)
Closure of nasal cavities
Strong contraction of the diaphragm and abdominal muscles
Pressure forces stomach contents to move upwards and ejected via the mouth
Describe how the sensation of nausea occurs.
In comparison to vomiting, less input is required to generate nausea. This is important in the role of learned behaviour, something that has made us vomit in the past - the sight or smell of that again causes nausea making us reluctant to eat it again.
What is the mechanism of nausea?
Not much is known about the mechanism of nausea, however it is known that vasopressin also known as antidiuretic hormone is released and therefore this could be a potential drug target in the future for medications to reduce vomiting.
What are some of the neurotransmitters known to be involved in the vomiting reflex?
Acetylcholine
Histamine
5-HT
Dopamine
Substance P
Endocannabinoids
Enkephalins
How is acetylcholine involved in the vomiting reflex?
Acetylcholine is particularly involved in reflexes involving the vestibular system as muscarinic receptors are involved in this pathway - specifically within the vestibular nuclei.
This is known as antimuscarinics are particularly helpful in the treatment of motion sickness which is associated with this pathway.
