Visceral afferents in GI Flashcards
What is sensation?
Activation of sensory/afferent neurones
Bidirectional cross-talk between these neurones and the surrounding cells and the CNS
What kinds of cells are involved in the cross-talk that mediates sensation?
enteroendocrine cells
immune cells
fibroblasts, glia, enterocytes
interstitial cells of Cajal
Do all sensory inputs from the gut mediate sensation?
No, sensory inputs are tightly modulated by the brain and spinal cord before sensation precipitates
What kind of sensations can be felt from the gut?
oesophageal distension gastric distension i.e. fullness nutrient density in stomach, duodenum toxins or excess nutrients causing nausea gas pain urgency awareness of rectal content
What are the 5 types of sensory neurones?
serosal mesenteric mucosal muscular musculo-mucosal
What are the 6 types of visceral afferents in the gut?
intraganglionic (vagal and pelvic) enteric viscerofugal intramuscular (vagal and pelvic) vascular muscular-mucosal mucosal (vagal and pelvic)
What are the 3 main pathways involved in visceral pain sensation from the gut?
PRIMARY SENSITISATION: of primary sensory afferents innervating the viscera
CENTRAL SENSITISATION: hyper-excitability of spinal afferents reacting to sensory input from gut viscera
DYSREGULATION: of descending pathways that modulate spinal nociceptive transmission
Describe the nature of the 6 visceral afferents in the gut?
intraganglionic: low threshold mechanoreceptor (pelvic and vagal)
enteric viscerofugal: interneurons with mechanosensitivity
intramuscular: mechanosensitive (pelvic and vagal)
vascular: extramural and intramural blood vessels, mechano-nociceptive (splanchnic and pelvic)
muscular-mucosal: mucosal stroking and distension/contraction (pelvic and vagal)
mucosal: mucosal distortion and entero-endocrine cell mediators (pelvic and vagal)
What are 5 entero-endocrine mediators of mucosal afferents?
CCK PYY 5-HT (serotonin) ghrelin secretin
What are the different types of pain?
somatic
visceral
neuropathic
phantom
What is visceral pain?
Activation of nociceptors in the thoracic, pelvic and abdominal organs
Usually most sensitive to distension (stretch), ischaemia and inflammation
usually referred pain
What is somatic pain?
activation of pain receptors in tissues (e.g. skin, muscle, connective tissue)
Usually activated by pressure, temperature, vibration or swelling
often describes as cramping sort of pain
usually well localised
What is dysesthesia?
abnormal sensation
often as a result of neuropathic pain
What is allodynia?
Pain presenting from normally non-painful stimuli
often as a result of neuropathic pain
What is neuropathic pain?
Damage or disease to the somatosensory nervous system
Can result in either dysesthesia or allodynia
What is phantom pain?
Pain from a body part that is no longer there
Some evidence to suggest this is not entirely psychological, pain sensations do original from the spinal cord and brain
Why are not all internal organs sensitive to pain?
Many organs e.g. liver, lungs, kidneys do not contain nociceptors (pain receptors) and so cannot ‘feel’ direct pain in the same way as somatic pain is felt
Also, several visceral converge onto the same spinal cord neurones and so localised pain is not felt
Severe visceral discomfort may be referred onto cutaneous structures e.g. within a dermatome
What stimuli can result in visceral pain?
inflammation ischaemia traction hollow organ distension acids/irritant chemical electrical stimulation 'pinching' only causes pain when hyperalgesia is present
What is hyperalgesia?
Increased sensitivity to pain receptors etc
Can be caused by neuropathic damage
Also caused by consumption of opiods
How can visceral pain be caused by ‘structural’ conditions?
Inflammatory: gastric-acid/peptic disease
Neoplastic: tumours
How can visceral pain be caused by ‘functional’ conditions?
IBS (inc. bloating) functional dyspepsia (nausea)
What is dyspepsia?
Simply indigestion
Can be caused by pathology in oesophagus, stomach, duodenum or intestine
What is ‘somatic’ abdominal pain?
Pain from abdominal wall or inguinal ligaments
Often well localised, reproduces pain
Can present asymmetrically
Affected by position, movement, straining
Unaffected by defecation, or food
e.g. painful rib syndrome, spinal pain
How can appendicitis migrate from visceral to somatic pain?
Early phase: visceral pain presenting as peri-umbilical, centralised and colicky
Later phase: parietal peritoneal inflammation pushes pain towards right iliac fossa (RIF)
worse with movement or straining
Tenderness at McBurney’s point
What can be used to treat visceral pain?
Treat underlying cause/disease
Use anti-spasmodics e.g. mebeverine for IBS
Use tricyclics e.g. amitryptiline for visceral hypersensitivity (hyperalgesia)
[latter is effective when used at sub anti-depressant doses, with main side effect being sedation]
How does hyper-vigilance relate to visceral pain?
Mild pain is often exacerbated by awareness of pain, which causes anxiety or panic. This anxiety can also result in hyper vigilance which causes a vicious cycle of pain etc
e.g. painful rib syndrome - patients exhibit pain reduction when they are told it is not serious
What is achalasia?
Oesophageal motility disorder
Results in aperistalsis and incomplete lower sphincter relaxation
Causes dysphagia
Can be treated by botulinum toxin, myotomy, pneumatic dilatation
What is myotomy?
Heller’s myotomy for achalasia
surgical procedure in which muscles of the cardia (gastric) aka the lower oesophageal sphincter are cut to allow for food to pass more easily
What is pneumatic dilation?
Endoscopic therapy for achalasia
Placement of a balloon over the lower oesophageal sphincter to loosen the muscles and therefore allow food to pass
How can botulinum toxin be used to treat achalasia?
Injection of the lower oesophageal sphincter with botulinum toxin causes temporary paralysis of the muscles
This causes them to relax and therefore allows food to pass through into the stomach cardia
What are the main features of gastric oesophageal reflux disease (GORD)?
incompetent lower oesophageal sphincter, but normal resting pressure
Normal gastric acid secretion
Oseophagitis observed by endoscopy but usually non-erosive lesion seen
What are the 3 types of hypersensitivity evoked by gastric acid exposure?
Hyperalgesia: primary, local focal point of hypersensitivity
Allodynia: to non-painful stimuli
Secondary hyperalgesia: generalised hypersensitivity
What are the clinical subdivisions of GORD?
Erosive reflux disease (20-30%)
Non-erosive reflux disease, NERD (60-70%)
Barrett’s Oesophagus (5-10%)
What are the 2 main ion channels in the oesophagus?
TRPV1: transient receptor potential vanilloid 1
ASIC: acid sensing ion channel
What happens when (gastric) acid is exposed to the TRPV1 channels?
neurogenic inflammation
release of pro-inflammatory mediators
What stimuli are the ion channels in the oesophagus sensitive to?
Mechanical
Electrical
Thermal
What are the clinical subtypes of NERD?
pH positive vs pH negative
pH neg: if symptoms are associated with pH changes then its hypersensitive oesophagus (40%)
pH neg: if symptoms are not associated with pH changes then its functional heartburn - reflux negative (60%)
How do the vagus, gastrin and Ach affect gastric motility?
They promote acid secretion
Delayed gastric emptying can be present in dysmotility conditions. What are examples where this may be exacerbated?
gastroparesis (weakened muscular contractions in stomach)
post-infective diabetes
How is delayed gastric emptying monitored or identified?
Isotope gastric emptying study
How can delayed gastric emptying be treated?
pro-kinetic drugs
e.g. domperidone, metocloperaminde
These also function as anti-emetics
What are the demographics for GORD?
10-15% prevalence greater anxiety, lower QoL F > M No excess mortality Assessed using Rome and Manning Criteria
What are the Rome and Manning criteria?
2x algorithm used to assess IBS Dx
Consists of a series of questions asked by the doctor to the patient
How does the Rome IV criterial describe IBS?
disorders of the gut-brain interaction Motility disturbance visceral hypersensitivity altered mucosal and immune function altered gut microbiota Altered CNS processing
What are the 3 types of IBS relating to stool consistency?
IBS with constipation
>25% hard stools, <25% loose stools
IBS-mixed
both hard and loose stools
IBS with diarrhoea
>25% loose stools, <25% hard stools
What are common causes of constipation?
low fibre diet
medications e.g. opiates
hypercalcaemia
hypothyroidism
What are the functional types of constipation?
colonic inertia (slow transit, assessed by marker studies) Pelvic floor dysyngergia (pelvic floor muscles do not relax with defecation) management is similar between both types
Which dietary fibre types have been shown to more effective to combat constipation in RCTS?
Sorbitol (prunes)
Kiwifruit
Vegetable and wholegrain powder
Fruit and fibre to porridge
Why are osmotic laxatives such as macrogol considered to be more effective and better tolerated than lactulose?
Proven efficacy in long term treatment improved stool frequency improved pain less need for other top-up laxatives side effects: diarrhoea and bloating
What are the first line laxative used to treat IBS with constipation?
Osmotic (e.g. macrogol)
Stimulant (Sodium picosulphate, Bisacodyl, Senna)
Stool softeners (sodium docusate)
Side effects:
Osmotic: bloating
Stimulant: cramps
What is the mechanism of action for secretagogues used to treat IBS?
Increases water-Cl- secretion into intestinal lumen
Therefore softens stools correcting constipation
Name two examples of secretagogues used to treat IBS with constipation?
Lubiprostone (Cl channel activator)
SE nausea, diarrhoea, cramps
Linaclotide (guanylate cyclase C agonist)
IBS-C (improves abdo pain)
SE diarrhoea
What diet advice could be given to patients with IBS?
should be individualised to patient Regular, small meals Fat reduction Caffeine Reduce lactose and fructose Reduce gas-producing foods Modify soluble/insoluble fibre Reduce wheat Low FODMAP diet (reduces bifidobacteria)
How would you treat a patient with opiod-induced constipation?
Use a Peripherally Acting Mu Opioid Antagonist (PAMORA)
e.g. Naloxegol (pegylated naloxone)
What embryological structuer is Meckel’s diverticulum derived from?
the vitello-intestinal duct
it is a congenital diverticulum of the small intestine, containing exotic ileal, gastric or pancreatic mucosa
What is the “rule of 2’s” for Meckel’s diverticulum?
affects 2% of population 2 inches (5cm) long 2 feet (60cm) from the ileocaecal valve 2x more common in men 2 types of tissue involved
