Week 9

• Regulation of gastric phase

  1. Cephalic phase

  2. Gastric phase

  3. Intestinal phase
• Bariatric surgery


  • Acts as an obesity treatment
  • Non-pharmacological intervention
  • Metabolic disease is reversed by decreasing the percentage of body mass
  • Other non-pharmacological intervention is diet and exercise
  • Sustained weight loss is hard to achieve with diet and exercise
  • If sustained weight loss is achieved metabolic disease can go into remission
  • Non-pharmacological interventions can be successful
  • Reduction in excess body mass is critical
  • Sufficient excess body mass reduction can result in remission of metabolic disease
  • Roux-en-y is the most complex surgery and involves a substantial change to the gastro-intestinal tract, but provides the most durable outcomes
• Enteric nervous system (ENS)

  • The gastrointestinal tract has its own nervous system that is capable of operating independently of the central nervous system
  • It is referred to as the mini brain
  • It can act independently of the CNS, it is the intermediary between the GIT and the two other branches of the autonomic nervous system (the sympathetic and parasympathetic) and the CNS
• Gastrointestinal tract pathways


  1. Pathways from the gastrointestinal tract project outwards, via intestinofugal neurons, to the CNS, sympathetic ganglia, gallbladder, pancreas and trachea

  2. Some neurons in sympathetic prevertebral ganglia receive both CNS and ENS inputs
• Vagal pathways


  Sensory information goes both to the ENS via intrinsic primary afferent (sensory) neurons and to the CNS via extrinsic primary afferent neurons that follow spinal and vagal nerve connections
• Small and large intestines

  The small and large intestines contain full ENS reflex circuits (motor neurons and interneurons, sensory neurons)
• Types of neurons in the ENS

  • Sensory neurons (intrinsic primary afferent neurons)
  • Interneurons
  • Motor neurons
  • Secretomotor neurons
• Parasympathetic nervous system


  Increases activity in the gastrointestinal tract
• Sympathetic nervous system


  Reduces GI tract activity
• Hormonal regulation of the gastrointestinal tract

  Typically divided into endocrine, paracrine and neurocrine
• The pancreas


  • Dual functional organ
  • Important exocrine role in secreting pancreatic enzymes into the duodenum
  • Indispensable endocrine role in regulating nutrient levels (in particular glucose) in the blood
  • Exocrine pancreatic secretion is regulated by vagal pathways and hormonal control
  • Pancreatic exocrine secretions are made by acinar cells that release pancreatic enzymes into the ductal system of the pancreas
  • These pancreatic secretions enter the duodenum via these collecting ducts which merge with the common bile duct
  • About 25% of pancreatic exocrine secretions into the duodenum occur during the cephalic phase of digestion, about 10% during the gastric phase and the remainder in the intestinal phase
  • Endocrine pancreatic function comes from the pancreatic islets, which are distributed throughout the pancreas and are most closely opposed to the vasculature
  • Islets contain three major cells types: alpha-cells, beta-cells and delta-cells
• The liver


  • Connected to the gallbladder and has a somewhat complex circulatory system
  • Inflow of blood to the liver occurs from both hepatic artery and the hepatic portal vein
  • Outflow occurs through the hepatic vein, which joins the inferior vena cava
  • Outflow from gastro-intestinal tract, pancreas and spleen all pass through the liver before this venous supply reaches the heart in order to pass through pulmonary circulation
• Liver functions


  • Detoxification
  • Bile production
  • Major glucoregulatory organ
  • Breakdown of red blood cells
• Barrier and immune function in the gastrointestinal tract

  • Every person is a portable habitat for micro-organisms
  • Having a vast ecosystem of micro-organisms in our gastrointestinal tract is vital to normal health
  • The natural propensity of these organisms is to activate the immune system, and this must be tightly controlled
  • At the same time the gastro-intestinal tract must allow for uptake of all nutrients from our diet
• Mucous layer


  1. The intestinal barrier is made up of a mucous layer, which is the primary barrier to prevent micro-organisms from coming into contact with the epithelial cells

  2. The mucus layer is made up of highly glycosylated proteins (mucins), which are produced by goblet cells and form the basis of the mucus gel layer that protects the epithelial cells

  3. Into the gel are secreted anti-microbial peptides and IgA molecules that help to modulate immune function
• Stirred mucus layer


  Unlike the small intestine, in the large intestine there is the additional "stirred" layer which provides a niche for commensal micro-biota
• Unstirred mucus layer


  In the small intestine there is only one mucus layer
• Epithelial cells


  1. Below the mucus layer is a single layer of epithelial cells that provide an additional barrier to micro-organisms as well as large molecules

  2. These cells form a continuous barrier due to the presence of tight junction structures between the cells and provide the physical support for the overall barrier
• Lamina propria


  Below the epithelial layer is the lamina propria, which is packed with connective tissue that hosts a variety of immune cells
• Gastroparesis


  Disorder of delayed gastric emptying in the absence of a physical obstruction
• Gastroparesis


  • Clinically manifests through primarily non-specific symptoms such as nausea, abdominal pain, early satiety, vomiting, postcibal (post meal) fullness, anorexia and weight loss
• Causes of gastroparesis


  • Idiopathic (30-50% associated with recent viral gastroenteritis)
  • Post-operative (gastric surgery, vagotomy, Roux-en-Y surgery)
  • Other surgeries (gastroesophageal reflux disease, oesophageal cancer, Whipple procedure, chronic pancreatitis, heart-lung transplantation)
  • Malignancies (non-obstructive pancreatic cancer, small cell lung carcinoma)
• Diagnostic process for gastroparesis

  1. Identification of any underlying disease

  2. Initial differential diagnosis to rule out mechanical obstruction

  3. Assessment of gastric emptying by scintigraphy
• The role of viral gastroenteritis in the aetiology of gastroparesis is debated
• In about 5% of patients who undergo gastric surgery, gastroparesis develops
• It is unclear whether gastroparesis in patients who undergo surgery for gastroesophageal reflux disease antedates or is a result of the surgery
• Gastroparesis is common in patients who have recently undergone heart-lung transplantation, and increases the risk for micro-aspirations in the transplanted lung
• Gastroparesis from malignancy has a poor response to medical therapy, and often requires surgical drainage
• Dyspepsia


  Widely referred to as functional dyspepsia to differentiate it from peptic ulcer disease; the clinical definition of dyspepsia is recurring indigestion with no obvious cause
• Dyspepsia


  • It is a common gastrointestinal disease and is associated with irritable bowel syndrome, the consumption of alcohol, smoking and NSAID use, and is more common in women
  • Dyspepsia presents as a variety of stomach related discomforts which may typically be described as indigestion, including postcibal (postprandial) bloating, pain, excessive belching, nausea and early fullness and can also be accompanied by stomach pains that are unrelated to meals
• Diagnosis of dyspepsia


  1. Endoscopy, to rule out inflammatory causes

  2. Tests for H.Pylori, the causative agent of peptic ulcers and some instances of gastritis

  3. Blood tests, to eliminate other diseases
• Causes of dyspepsia


  • It is not clear what the cause(s) are for functional dyspepsia
  • Since the causes are not known, the treatment is aimed at symptomatic relief
  • In cases where this is associated with irritable bowel syndrome treatment may overlap
• Gastritis


  Refers to a group of conditions that are characterised by inflammation of the stomach lining
• Gastritis


  • Gastritis is less common than dyspepsia and can present either acutely or chronically
  • It is associated with H.Pylori infection, alcohol consumption, NSAID use, smoking and is more common as we get older
  • Gastritis can occur as an auto-immune condition, where one's own immune system attacks the lining of the stomach and this can be more common in individuals with Crohn's, celiac and Hashimotos diseases
  • Gastritis can often present as indigestion, with similar symptoms to dyspepsia and can also feature comiting but in some instances it is without symptoms
• Diagnosis of gastritis


  1. Endoscopy, to identify any areas of inflammation

  2. Tests for H.Pylori

  3. Imaging of the upper gastro-intestinal tract
• Causes of gastritis


  Gastritis is commonly caused by infection of H.Pylori but can also be cause by other inflammatory conditiond, either brought about by excess alcohol or NSAID consumption or due to auto-inflammatory diseases
• Gastroesophageal reflux disease (GORD)


  GORD is characterised by repeated acid reflux, where contents of the stomach (including acid) flow back up the oesophagus
• GORD


  • While it is quite common that people experience acid reflux from time to time, persistent or chronic acid reflux, that would meet the clinical definition of GORD is not common
  • The causes of GORD are not clear, however obesity is a risk factor and GORD can occur during pregnancy, presumably due to increased pressure on the stomach
  • Herniation of the stomach above the diaphragm can lead to GORD
• Diagnosis of GORD


  1. Endoscopy, to identify any areas of inflammation

  2. Oesophageal pH test, involving inserting a probe into the oesophagus and monitoring pH over 1 to 3 days

  3. Imaging of the upper gastro-intestinal tract
• Cause of GORD


  Technically the cause of GORD is loss of resting tine in the lower oesophageal sphincter