Symptoms of GI disease: Nausea, Vomiting and Pain

• What is the physiological function of nausea?

  • Nausea serves as a warning signal of potential ingestion of harmful or irritant substances.
  • It encourages avoidance behaviour, often preceding vomiting, and reduces the desire to eat or drink, preventing further intake of toxins.
• What is the purpose of vomiting (emesis) in GI disease?

  • Vomiting is a defensive reflex that helps to expel harmful substances from the stomach or upper GI tract.
  • It protects the body from ingested toxins, infections, or irritants by forcibly removing them before absorption.
• What role does retching play in the vomiting process?

  • Retching is a preparatory phase of vomiting involving rhythmic contraction of respiratory and abdominal muscles without expulsion of gastric contents.
  • It builds up pressure needed for forceful expulsion and helps align the oesophagus and stomach to facilitate vomiting.
• Which areas of the brain coordinate nausea and vomiting?

  The vomiting centre in the medulla oblongata coordinates the emetic response, receiving input from:

  • Chemoreceptor Trigger Zone (CTZ): detects toxins in the blood
  • Vestibular system: motion-related nausea
  • Higher brain centers: sensory/emotional input
  • GI tract: vagal afferents detecting irritants
• Why are nausea and vomiting considered protective reflexes in the context of GI disease?

  They prevent absorption of potentially dangerous substances and help eliminate irritants or pathogens, thereby minimising damage and maintaining homeostasis.
• How does the body detect the need to vomit?

  • CTZ (area postrema) sensing toxins or drugs in blood
  • Vagal afferents from GI tract sensing stretch, inflammation, or irritants
  • Sensory input (smell, taste, sight) and emotions processed by higher brain centers
• What is the role of the chemoreceptor trigger zone (CTZ) in vomiting, and how can it cause vomiting without benefit?

  • The CTZ, located in the area postrema of the medulla, detects toxins, drugs, and metabolic disturbances in the blood/CSF.
  • It can trigger vomiting reflexes even when no GI threat is present.
  • This explains vomiting in chemotherapy, uraemia, or opioid use, where the body reacts to perceived harm despite no direct GI benefit.
• How can cortical inputs contribute to vomiting without gastrointestinal benefit?

  • Cortical inputs from the limbic system and higher brain centres can activate the vomiting centre in response to emotions (fear, disgust, anxiety) or anticipatory cues (e.g., in chemotherapy patients).
  • This results in psychogenic vomiting, where there is no actual GI irritant or physiological need to expel contents.
• What is anticipatory vomiting and why is it considered vomiting without benefit?

  • Anticipatory vomiting occurs in patients who have learned to associate a stimulus (like a hospital environment) with previous vomiting (e.g., from chemotherapy).
  • It is a conditioned response involving the cerebral cortex, not a GI insult. There's no protective benefit—it's driven by psychological conditioning.
• How does vomiting without benefit differ from protective vomiting?

  • Protective vomiting removes toxins or irritants from the stomach (e.g., spoiled food, alcohol). 
  • Vomiting without benefit, such as in migraine, anxiety, chemotherapy, or anticipatory stress, occurs without a noxious GI stimulus and provides no survival advantage—often contributing to malnutrition, dehydration, or distress.
• Why might pain or GI discomfort trigger vomiting in the absence of a clear benefit?

  • Severe visceral pain, distension, or inflammation (e.g., pancreatitis, bowel obstruction) can stimulate vagal afferents that signal the vomiting centre.
  • Even if vomiting does not relieve the cause, the body misinterprets pain as a sign of toxic ingestion, triggering a reflexive response that is not beneficial.
• Which neurotransmitters are involved in non-beneficial vomiting?

  • Dopamine (D2)
  • Serotonin (5-HT3)
  • Histamine (H1)
  • Acetylcholine (M1)
  • Substance P (NK1)Overactivity or dysregulation of these can lead to inappropriate activation of the vomiting centre (e.g., in motion sickness, drugs, migraines), causing vomiting without clear GI cause or benefit.
• What brainstem structure is considered the primary coordinating centre for vomiting?

  The vomiting centre in the medulla oblongata, specifically in the reticular formation, coordinates the vomiting reflex by integrating inputs from multiple sources.
• What are the four main afferent inputs to the vomiting center in the brainstem?

  1. Chemoreceptor trigger zone (CTZ) in the area postrema
  2. Vestibular system (inner ear)
  3. Vagal and spinal visceral afferents from the GI tract
  4. Higher brain centers (e.g., cortex and limbic system)
• Where is the chemoreceptor trigger zone (CTZ) located and what is its role in vomiting?

  The CTZ is located in the area postrema of the medulla, outside the blood-brain barrier. It detects toxins in the blood and cerebrospinal fluid and sends signals to the vomiting centre.
• How do vagal afferents from the GI tract contribute to nausea and vomiting?

  Vagal afferents detect irritation, distension, or inflammation in the GI tract and send signals to the nucleus tractus solitarius (NTS) and vomiting center, triggering nausea and emesis.
•  How does the vestibular system contribute to nausea and vomiting (e.g., motion sickness)?

  The vestibular nuclei send signals via cranial nerve VIII to the vomiting center using histamine (H1) and acetylcholine (muscarinic) pathways.
• What brain areas are responsible for the emotional and psychological aspects of nausea (e.g., anxiety-induced nausea)?

  The cerebral cortex and limbic system, including the amygdala, can influence the vomiting centre, especially under stress, fear, or strong emotions.
• What is the role of the nucleus tractus solitarius (NTS) in nausea and vomiting?

  The NTS receives afferent input from the vagus nerve, CTZ, and other sources, and integrates these signals to coordinate the emetic response.
• What type of nerve fibres mediate GI pain and how do they reach the CNS?

  Visceral afferent fibres, mainly C fibres, travel with sympathetic nerves to the spinal cord via dorsal root ganglia, contributing to dull, poorly localized pain.
• What spinal segments typically receive visceral pain signals from the GI tract?

  T5 to L2 spinal segments, depending on the GI region. For example:

  • Foregut → T5–T9
  • Midgut → T10–T12
  • Hindgut → L1–L2
• Why is visceral pain often referred to somatic regions (e.g., shoulder tip in gallbladder pain)?

  Due to convergence of visceral and somatic afferents onto the same second-order neurons in the spinal cord, leading the brain to misinterpret the origin of pain.
•  How does GI inflammation (e.g., gastritis or enteritis) cause nausea?

  Inflammation stimulates mucosal serotonin release, activating 5-HT3 receptors on vagal afferents, which send signals to the NTS and vomiting centre.
• What are the two main types of sensory afferent fibres involved in GI visceral pain transmission?

  1. Vagal afferents – carry non-painful sensory information (e.g. stretch, chemical changes) from upper GI to brainstem (NTS).
  2. Spinal afferents (splanchnic + pelvic) – carry pain signals from GI organs to the spinal cord (T1–L2, S2–S4).
• Which cranial nerve carries afferent signals from the upper GI tract to the brainstem?

  The vagus nerve (cranial nerve X) carries afferent signals (mostly non-nociceptive) from the oesophagus, stomach, and upper small intestine to the nucleus tractus solitarius (NTS) in the medulla.
• Where do visceral pain afferents from the lower GI tract (colon and rectum) primarily project to in the spinal cord?

  They project to the sacral spinal cord segments (S2–S4) via pelvic splanchnic nerves, and to thoracolumbar segments (T9–L2) via lumbar splanchnic nerves.
• Which spinal tract do visceral pain signals from the GI tract ascend in to reach the brain?

  Visceral pain signals ascend in the spinothalamic tract after synapsing in the dorsal horn of the spinal cord.
• What central brain structures are involved in processing GI visceral pain?

  • Thalamus – relays pain to higher cortical areas
  • Somatosensory cortex – conscious perception of pain
  • Anterior cingulate cortex – emotional response to pain
  • Insula – interoceptive awareness of GI discomfort
• What is referred pain in the context of GI disease and why does it occur?

  Referred pain is pain perceived at a location other than the site of origin (e.g., shoulder pain in gallbladder disease).It occurs because visceral and somatic afferents converge on the same spinal neurons, leading to misinterpretation of the pain's origin by the brain.
•  How does GI visceral pain contribute to the sensation of nausea and vomiting?

  • Visceral pain can activate the area postrema and nucleus tractus solitarius (NTS), both part of the vomiting centre in the medulla.
  • This stimulation, especially via vagal afferents, can trigger nausea and vomiting reflexes.
• Which neurotransmitters are involved in the neural pathways of GI visceral pain?

  • Substance P
  • Calcitonin Gene-Related Peptide (CGRP)
  • GlutamateThese mediate nociceptive signalling from the GI tract through primary afferent neurons.
•  Why does inflammation in the GI tract cause pain?

  • Inflammation leads to the release of chemical mediators (e.g. prostaglandins, bradykinin, histamine) which sensitise or directly stimulate nociceptors in the gut wall.
  • This activation of pain receptors contributes to the visceral pain felt in GI diseases such as appendicitis or Crohn’s disease.
•  How does visceral pain differ from somatic pain in GI disease?

  • Visceral pain is dull, poorly localised, and often referred to midline areas due to low density of visceral nociceptors.
  • Somatic pain, often felt later in disease progression (e.g., appendicitis), is sharp and well-localised due to involvement of the parietal peritoneum.
• What is the mechanism behind vomiting in GI disease?

  • Vomiting is triggered by irritation, inflammation, or distension of the GI tract, which stimulates the vomiting centre (medulla).
  • Input comes from vagal afferents, the chemoreceptor trigger zone (CTZ), and higher CNS centers.
  • Inflammatory cytokines can also contribute to the emetic response.
• What is visceral hypersensitivity and how does it contribute to GI pain?

  • Visceral hypersensitivity is an increased responsiveness of gut nociceptors to stimuli, often seen in IBS and IBD.
  • Chronic inflammation or prior sensitization can lower pain thresholds, causing pain with normal gut activity like peristalsis or gas.
• How can inflammation contribute to referred pain patterns in GI disease?

  • Inflammation increases visceral afferent activity, which converges with somatic afferents at the spinal cord. This convergence can lead to referred pain.
  • For example, gastric ulcer pain may be referred to the epigastrium, while pancreatic pain may radiate to the back.
• How does the body interpret GI pain in relation to dermatomes?

  • Visceral afferents from GI organs enter the spinal cord at specific levels that correspond to dermatomes.
  • The brain may misattribute visceral pain to these dermatomal skin areas (referred pain).
  • Example: appendicitis may initially present with pain in the T10 dermatome (umbilicus).