Symptoms of GI disease: nausea, vomiting and pain

Question 1

what is nausea?

Answer 1

a sensation

• personal, self reported
• associated with physiological changes
• unpleasant
• triggers aversion

Question 2

what is vomiting/emesis?

Answer 2

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

Question 3

what is nausea produced by?

Answer 3

the same stimuli as vomiting

Question 4

nausea is generally a prodrome of vomiting - what does this mean?

Answer 4

premonitory symptom

Question 5

are nausea and vomiting always linked?

Answer 5

no
-nausea may clear up without triggering vomiting

-vomiting can occur without prior nausea

Question 6

list some emetic stimuli

Answer 6

• 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

Question 7

how does taste and smell provide protection against ingested toxins?

Answer 7

• can potentially prevent ingestion

- we have a built-in dislike of bitter flavours, and any toxins have a bitter flavour

Question 8

where is the next layer of defence located (after taste and smell)?

Answer 8

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

Question 9

why do IV chemo drugs cause nausea/vomiting even though they didn’t come through the GI tract?

Answer 9

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

Question 10

what is the next line of defence if the toxin starts to be absorbed and gets into the blood stream?

Answer 10

1. Chemoreceptor trigger zone (in the medulla)

2. Vestibular system

Question 11

chemoreceptor trigger zone

Answer 11

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

Question 12

why would chemoreceptors in brain trigger vomiting if the toxin has made it through the GI tract already?

Answer 12

triggers nausea and vomiting as a precaution in case there is still material in the stomach that hasn’t gone round the body yet

Question 13

Vestibular system

Answer 13

• 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)

Question 14

what are receptors within the vestibule system like?

Answer 14

very sensitive to chemical insult- will start to produce aberrant activity if there are toxins in their environment, vomiting will occur

Question 15

Prevention of ingestion – learning and aversion

Answer 15

if we survive a mistake we avoid repeating it (unpleasantness reinforces learning)
aversion may hard-wire avoidance

Question 16

give an example of an incorrect association that can be created though this learning and aversion process

Answer 16

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

Question 17

the body’s anti-poison defenses are co-ordinated by which part of the brain?

Answer 17

the Nucleus Tractus Solitarius (NTS), found in the medulla of the brainstem

It also integrates cardiac, respiratory and gastrointestinal functions

“vomiting centre”

Question 18

what are the 4 different types of “warning inputs” the NTS receives

Answer 18

1. Visceral afferents (that trigger N & V)
2. Area postrema
3. Vestibular system
4. Higher centres

Question 19

Visceral afferents (that trigger N & V)

Answer 19

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

Question 20

Area postrema

Answer 20

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

Question 21

Vestibular system

Answer 21

(inner ear)– respond to toxins in blood - disrupting vestibular receptors

Question 22

Higher centres

Answer 22

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)

Question 23

what does the NTS do when it receives any of these 4 warnings?

Answer 23

integrates the info and produces the outputs: nausea and vomiting

Question 24

NTS and nausea

Answer 24

• 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

Question 25

NTS and vomiting

Answer 25

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

Question 26

Mechanism of Nausea

Answer 26

1. Reduced mixing and peristalsis
   - prevents toxins from being carried further through the system
2. Proximal stomach relaxes
   - prepares stomach to receive additional contents
3. Giant retrograde contraction
   - sweeps up from mid-small intestine
   - returns upper intestinal contents to stomach

Question 27

Mechanism of vomiting

Answer 27

4. 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
5. Vomiting (emesis)
   - oesophageal sphincters and crural diaphragm relax
   - further waves of contraction expel stomach contents

Question 28

how do the fast coordinated contractions of the diaphragm and abdominal cavity come about?

Answer 28

because the NTS triggers the phrenic and somatic nerves

Question 29

Nociceptors

Answer 29

“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

Question 30

do nociceptors respond to pain?

Answer 30

no, the pain is what the brain produced to tell you something bad has happened

Question 31

gut distention and visceral pain

Answer 31

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

Question 32

when the nociceptors depolarised, what can they release?

Answer 32

proinflammatory mediators from their sensitive endings

Question 33

what do nociceptors respond to other than stretching of the gut wall?

Answer 33

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

Question 34

why is sunburnt skin painful?

Answer 34

sensitisation of nociceptors by inflammatory mediators has made them respond at a high frequency of firing even with normal stimulation

Question 35

nociceptors - positive feedback loop

Answer 35

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

Question 36

what is the consequence of the feedback loop and the signals?

Answer 36

the signals can become self-sustaining, leading to chronic pain with no obvious cause

Question 37

combination of positive feedback loop and the plasticity of the synapses that makes them easily potentiatable means what?

Answer 37

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

Question 38

Somatic pain is…

Answer 38

precisely localised

Question 39

Visceral pain is…

Answer 39

diffuse & variable

Question 40

viscero-somatic convergence

Answer 40

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

Question 41

what do the oesophageal nociceptors have?

Answer 41

broad spreading axons which make sloppy connections

Question 42

how can the nociceptor can project the pain as coming from anywhere between the C2-T4 dermatomes?

Answer 42

The somatic pathways in between are projecting into a broad area of the somatosensory cortex

Question 43

explain how each organ has a characteristic pattern of referral

Answer 43

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

Question 44

why can visceral pain from the abdomen can move around a lot?

Answer 44

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