Symptoms of GI disease: nausea, vomiting and pain Flashcards
what is nausea?
a sensation
- personal, self reported
- associated with physiological changes
- unpleasant
- triggers aversion
what is vomiting/emesis?
a physical act, usually follows nausea
- expels contents of upper GI tract via mouth
- forceful (diff to regurgitation, reflux)
- associated with a sensation of relief
what is nausea produced by?
the same stimuli as vomiting
nausea is generally a prodrome of vomiting - what does this mean?
premonitory symptom
are nausea and vomiting always linked?
no
-nausea may clear up without triggering vomiting
-vomiting can occur without prior nausea
list some emetic stimuli
- Drugs – trigger anti-poisoning defences that pick up toxins in the blood
- GI disease and infections will cause inflammation mediators and trigger the anti-poisoning defences
- Metabolic disturbances – strange thing in the blood will make you nauseous
- Raised intracranial pressure – will press down on the NTS and the brainstem and produce abnormal activity there, triggers nausea and maybe vomiting
how does taste and smell provide protection against ingested toxins?
- can potentially prevent ingestion
- we have a built-in dislike of bitter flavours, and any toxins have a bitter flavour
where is the next layer of defence located (after taste and smell)?
in the stomach and the upper part of the small intestine - here we have receptors that will respond to a range of poisons
gastric & upper GI afferents
they can can potentially expel harmful agents before they have a chance to be absorbed
associated with chemoreceptive cells that respond to:
irritants
inflammatory mediators
bacterial (and some other) toxins
chemoreceptors will set off nausea – and can therefore remove the toxic substance before it is broken down
why do IV chemo drugs cause nausea/vomiting even though they didn’t come through the GI tract?
because the receptors in the gut wall need a blood supply, so they need to be in contact with the circulation
as a result, they will also respond to poisons in the circulation
what is the next line of defence if the toxin starts to be absorbed and gets into the blood stream?
- Chemoreceptor trigger zone (in the medulla)
2. Vestibular system
chemoreceptor trigger zone
the area postrema in the brainstem
Blood-brain barrier is “leaky” (everywhere else in the brain there is a barrier between the bloodstream and the brain tissue)
Leaky barrier means that chemoreceptors that can detect and respond to circulating toxins in the blood, and trigger nausea and vomiting
why would chemoreceptors in brain trigger vomiting if the toxin has made it through the GI tract already?
triggers nausea and vomiting as a precaution in case there is still material in the stomach that hasn’t gone round the body yet
Vestibular system
- system in the ear that detects the movement of the head and the direction of gravity, but also a trigger for emesis
- can be overstimulated with an unnatural form of motion
-system has very delicate apparatus that can be damaged by toxins presence, which explains why any diseases that affect the vestibular system are nausea inducing
(travelling in boats/cars are all unnatural motions – the cause of motion sickness)
what are receptors within the vestibule system like?
very sensitive to chemical insult- will start to produce aberrant activity if there are toxins in their environment, vomiting will occur
Prevention of ingestion – learning and aversion
if we survive a mistake we avoid repeating it (unpleasantness reinforces learning)
aversion may hard-wire avoidance
give an example of an incorrect association that can be created though this learning and aversion process
eating food before chemo, patient gets sick from chemo and the next time they see that food they feel sick even though it was the chemo that made them ill
the body’s anti-poison defenses are co-ordinated by which part of the brain?
the Nucleus Tractus Solitarius (NTS), found in the medulla of the brainstem
It also integrates cardiac, respiratory and gastrointestinal functions
“vomiting centre”
what are the 4 different types of “warning inputs” the NTS receives
- Visceral afferents (that trigger N & V)
- Area postrema
- Vestibular system
- Higher centres
Visceral afferents (that trigger N & V)
Afferents are associated with receptors
Afferents from the GI – respond to toxins, irritants and distention. These have axons that run through the vagus nerve to the brainstem, and will trigger nausea and vomiting if activated
Area postrema
Chemoreceptive zone (no blood-brain barrier) in medulla
sits very close the the foramen magnum (hole in the base of the skull that the spinal cord goes out through
respond to toxins in the blood in the brainstem
Vestibular system
(inner ear)– respond to toxins in blood - disrupting vestibular receptors
Higher centres
things that have made you sick in the past
other people in your group being sick
Limbic areas that are feeding down info about things that made you sick in the past (emotional stimuli)
what does the NTS do when it receives any of these 4 warnings?
integrates the info and produces the outputs: nausea and vomiting
NTS and nausea
- NTS triggers hypothalamus to increase ADH release, this is because you want to start conserving fluid given you might lose a large portion of it when you vomit
- sympathetic activity goes up which in combination with reduced parasympathetic activity to the upper GI tract leads to a decrease in food processing - you don’t want process this food that could potentially be poisonous
- pale, start to sweat
NTS and vomiting
If the stimulus continues and you prepare to vomit, the NTS will coordinate muscles that increase the pressure on the abdomen and decrease the anti-reflux barriers so stuff can go back up the oesophagus- coordinates expulsion of stomach contents
Mechanism of Nausea
- Reduced mixing and peristalsis
- prevents toxins from being carried further through the system - Proximal stomach relaxes
- prepares stomach to receive additional contents - Giant retrograde contraction
- sweeps up from mid-small intestine
- returns upper intestinal contents to stomach
Mechanism of vomiting
- Retching (dry heaves)
- co-ordinated contractions of abdominal muscles and diaphragm
- waves of high pressure in abdomen
- compresses stomach but anti-reflux barriers intact so no expulsion
- happens in waves - Vomiting (emesis)
- oesophageal sphincters and crural diaphragm relax
- further waves of contraction expel stomach contents
how do the fast coordinated contractions of the diaphragm and abdominal cavity come about?
because the NTS triggers the phrenic and somatic nerves
Nociceptors
“Pain” receptors
They respond to:
- Abnormal levels of distension
- inflammation
- muscle spasm
found at all levels of the gut – different from the afferent that produce nausea and vomiting
run with the sympathetic nerves and into the spinal cord via the splanchnic nerves
do nociceptors respond to pain?
no, the pain is what the brain produced to tell you something bad has happened
gut distention and visceral pain
Low levels of distention will produce low frequency of action potential firing - brain iterates this as normal
Then you have levels of distention that you only see under pathological conditions, which will stretch the walls of the gut to a potentially damaging degree
The more stretched the gut wall is, the more AP’s will be sent to the nocioreceptors
When the AP frequency of firing gets to a high level, the brain will interpret that as a noxious event and produce visceral pain
when the nociceptors depolarised, what can they release?
proinflammatory mediators from their sensitive endings
what do nociceptors respond to other than stretching of the gut wall?
inflammatory mediators
- injury
- irritants
- toxins
- infection
- autoimmunity
these will depolarise the nociceptors and make them fire a higher frequency of AP’s, sensitise them
so, gut distention + inflammation just makes frequency of AP firing increase
why is sunburnt skin painful?
sensitisation of nociceptors by inflammatory mediators has made them respond at a high frequency of firing even with normal stimulation
nociceptors - positive feedback loop
Nociceptors respond to inflammatory mediators but also release pro-inflammatory chemicals (like substance P) when depolarised
this which makes inflammation worse, which makes them respond even more strongly
this loop can contribute to IBS
what is the consequence of the feedback loop and the signals?
the signals can become self-sustaining, leading to chronic pain with no obvious cause
combination of positive feedback loop and the plasticity of the synapses that makes them easily potentiatable means what?
even when the inflammation has died down the nociceptor can continue to fire at a higher frequency than normal, meaning normal gut activity will continue to feel painful
Somatic pain is…
precisely localised
Visceral pain is…
diffuse & variable
viscero-somatic convergence
the oesophageal nociceptor has a similar structure to
the somatic nociceptor
synapses in the dorsal horn and onto the somatic pathway, since it doesn’t have its own pathway
so, both nociceptors have activation in the cortex in the same location
what do the oesophageal nociceptors have?
broad spreading axons which make sloppy connections
how can the nociceptor can project the pain as coming from anywhere between the C2-T4 dermatomes?
The somatic pathways in between are projecting into a broad area of the somatosensory cortex
explain how each organ has a characteristic pattern of referral
initially to dermatomes matching the embryonic origin of the organ
but may evolve as other tissues are affected
Each of the visceral organs sends input to the spinal cord segment that correlate to the somite they developed from during embryonic development
why can visceral pain from the abdomen can move around a lot?
because everything is packed in very tightly
so inflammation of the gall bladder can produce inflammation of the overlying diaphragm, so you get pain in the right shoulder because the afferents from the diaphragm are piggybacking onto the pathways from the shoulder
