Gastrointestinal Endocrinology Flashcards
1
Q
Where is secretin synthesised and released?
What is the target organ?
What is the target effect?
A
- Secretin is produced by the S cells located principally in the duodenum
- Secretin is released in response to H+ ions in the gastric secretions
Target Organs:
- Secretin targets the biliary tract epithelium and pancreatic ductal cells
- Secretin also targets the gastric epithelium
Effects:
- Increased bicarbonate synthesis from the pancreas
- Increased bile production within the biliary tree
- Decreased/inhibition of gastric acid secretion
- Inhibition of gastric motility
2
Q
Where is glucagon synthesised and released?
What is the target organ?
What is the target effect?
A
- Glucagon is secreted by the pancreatic alpha islet cells
- Transcription of the same gene that leads to glucagon release, produces GIP and GLP from the gastrointestinal L cells
Target Organ:
- Glucagon primarily acts within the liver
Effect:
- Glucagon is the primary hormone stimulus for gluconeogenesis and glycogenolysis
- Overall effect is to counter the actions of insulin
3
Q
Where is glucagon-like peptide (GLP) synthesised and released?
What is the target organ?
What is the target effect?
A
- GLP (GLP-1 and GLP-2) are produced within the L cells in the small intestine and colon
- GLP may also be secreted by neurons in the solitary tract of the brain stem
- The peptide is released into the portal system
Target Organ:
- Pancreas and gastrointestinal tract
- Also has effects widely throughout the body
- Liver - decreased gluconeogenesis
- Adipose - increased glucose uptake and lipogenesis
- Heart - increased glucose uptake and function
- Muscle - increased glucose uptake
- Brain - increase satiety and decrease appetite
Effects:
- GLP primary acts to promote insulin secretion in a glucose dependent manner
- Increased glucose sensitivity
- Increased b-cell proliferation
- Decreased glucose sensitivity of the b-cells (reduces negative feedback)
- Reduced gastric motility and emptying
- Other as noted above
4
Q
Where is gastric inhibitory peptide synthesised and released?
What is the target organ?
What is the target effect?
A
- Gastric Inhibitory Peptide or Glucose dependent Insulinotropic Polypeptide (GIP) is produced by K cells within the duodenum and jejunum
Target Organs:
Similar to GLP, GIP is an incretin with the major physiological effect exerted via stimulation of the pancreatic b-cells to release insulin
Effect:
The effects of the incretins are numerous and include:
- Increased insulin production, increased b-cell proliferation, decreased b-cell apoptosis
- Increased glucose utilisation in the muscle and heart
- Satiety and hunger regulation in the brain with influences on hippocampal memory formation
- Positive effect on bone remodelling and improved bone quality and density
5
Q
Where is gastrin synthesised and released?
What is the target organ?
What is the target effect?
A
- Gastrin is secreted by the neuroendocrine G cells in the gastric antrum and duodenum and pancreas
- Secreted in response to gastric stretch and the presence of ingested protein
Target Organ:
- Gastrin targets the parietal cells in the gastric fundus and body
Effect:
- Gastrin stimulates histamine release from enterochromaffin-like cells
- Stimulate the insertion of the K+/H+ pump in the apical surface of the parietal cell
- Release of H+ ions into the gastric lumen
6
Q
Where is cholecystokinin synthesised and released?
What is the target organ?
What is the target effect?
A
- Synthesized in I cells located in the duodenum and jejunum
- Released in response to various substances entering the duodenal lumen, namely fatty acids, H+ and amino acids
Target Organ:
- Peptide neurotransmitter in the enteric nervous system
- stimulates pre-synaptic cholinergic neurons
- Effects on the gallbladder and pancreas are mediated by acetylcholine release from these enteric neurons
- Gallbladder
- Pancreas
Effect:
- Gallbladder contraction
- Release of pancreatic enzymes
- Overall co-ordination of digestion
- regulation of fluid secretion
- inhibition of gastric emptying
- Sphincter of Oddi relaxation
- Stimulation of pancreatic growth
7
Q
Where is somatostatin synthesised and released?
What is the target organ?
What is the target effect?
A
- Somatostatin is produced within the:
- Hypothalamus
- Delta cells within the
- Pancreatic islet cells
- Subsets of neurons in the CNS and enteric nervous system
- Instestinal D cells release somatostatin in response to fats, protein and bile within the gut lumen
Target Organs / effect: Overall inhibition of the following:
- Gastric acid production
- Pepsinogen
- Gallbladder contraction
- Insulin secretion
- Exocrine pancreatic function
- GIT motility
- Nutrient absorption
- Also inhibits the release of growth hormone, TSH and prolactin in the hypothalamus and pituitary.
The overall effect of somatostatin is to slow the digestive process and reduce growth / metabolism
8
Q
Where is motilin synthesed and released?
What is the target organ?
What is the target effect?
A
- Synthesised in GI cells and structurally related to ghrelin
- Secretion is dependent on the fasted or fed state, with the majority of action occuring during the fasted state
- Release due to gastric acid or lipd entering the small intestine
Target:
- Gastrointestinal tract
- Pancreas
- Biliary tract
Effect:
- Initiates and coordinates migrating motility complexes
- Help to clear the GIT in the interdigestive state
- Regulates gastric, pancreatic and biliary secretions during the fed state
9
Q
Where is ghrelin synthesised and released?
What is the target organ?
What is the target effect?
A
- Ghrelin is synthesised and secreted by enteroendocrine cells within the stomach and pancreas
- Ghrelin concentration is at its highest with an empty stomach and prior to a meal
Target:
- The primary action is within the gastrointestinal tract
- Also has a direct effect on the pituitary gland and hypothalamus
Effect:
- Binds to L cells and augments the secretion of GLP-1
- enhanced GLP-1 secretion and similar effects
- Simulates growth hormone synthesis and release
- Activates the central cholinergic-dopaminergic reward system for food and addictive drugs/alcohol
10
Q
Where is serotonin synthesed and released?
What is the target organ?
What is the target effect?
A
- Released from the enteric neurons and enterochromaffin cells (90%) within the gastrointestinal tract
- 8% is found within platelets
- 1-2% within the CNS
Target / effect:
- Acts with an endocrine and paracrine function to stimulate smooth muscle contraction and intestinal secretion
- In the brain, serotonin helps to regulate mood, appetite and sleep
- Released from platelets, contributes to either vasoconstriction or vasodilation (via mediation of nitric oxide release)
11
Q
Describe the clinical syndrome caused by a gastrin-producing tumour
A
- The syndrome caused by gastrin hypersecretion in humans is called Zollinger-Ellison syndrome
- Gastrin stimulates hypertrophy of the gastric / pyloric antrum
- Gastric hyperacidity can lead to gastric ulceration and if associated with vomiting / reflux, oesophagitis may also be seen
- When severe, oesophagitis may lead to regurgitation in combination with the vomiting
- Diarrhoea may results due to gastrin’s inhibitory effect on intestinal water absorption
12
Q
Describe the clinical findings of dogs with gastrinoma
A
- Clinical signs largely depend on the stage of disease
- Vomiting, diarrhoea and weight loss are the most common owner observations
- Abdominal pain, regurgitation, GI bleeding and polydipsia may also be seen
- Signs could be as for any dog with chronic vomiting, but may manifest as more severe
13
Q
Describe the potential clinicopathological findings in dogs with gastrinoma
A
- There are no specific changes on routine CBC and biochemistry testing
- Leukocytosis, neutrophilia, left shift, anaemia and low protein may be seen with gastric ulceration and inflammation
- Hypokalaemia, hypochloraemia and hyponatraemia may be seen with chronic vomiting
- Metabolic alkalosis may be present due to loss of H+ in gastric secretions and vomit
- Elevated liver enzymes - non-specific
- Elevated bilirubin if the pancreatic mass causes biliary obstruction
14
Q
Discuss the utility of imaging, endoscopy and specific lab tests for the diagnosis of gastrinoma in dogs
A
- Radiographs - unhelpful
- Ultrasound:
- May identify pancreatic tumour
- May identify metastasis to local lymph nodes, liver or mesentery
- Gastric antral hypertrophy may be visualised
- Endoscopy: can identify the secondary changes due to hypergastrinemia. Even with biopsy, the changes are not specific for gastrinoma diagnosis
- Antral hypertrophy
- Ulceration
- Oesophagitis
- Duodenal inflammation
- Increased gastric luminal fluid
- Gastrin levels (often paired with gastric fluid pH)
- Not extensively investigated and no cut-off has been identified
- Should be several-fold above the upper reference range
- Finding of high gastrin, low gastric pH with clinical suspicion should be diagnostic
- Gastrin can be elevated with renal disease, gastropathies, hepatopathies and with the use of acid blocking drugs
- Provocative testing with secretin, calcium or both.
- Either or both should lead to a two-fold increase in gastrin levels with gastrinoma
15
Q
Provide a brief overview of the clinical findings and diagnostic tests that could confirm a diagnosis of glucagonoma
Note the important differentials or diseases that need to be excluded when investigating for possible glucagonoma
A
- Dogs with glucagonoma may present with insulin-resistant diabetes mellitus, lethargy, decreased appetite. Necrolytic migratory erythema is commonly reported and often considered diagnostic in people with glucagonoma.
- NME is more often seen with liver disease in dogs
- Increased glucagon –> increased gluconeogenesis and amino acid utilisation –> amino acid deficiency
- Both metabolic liver disease responsible for so-called hepatocutaneous syndrome and glucagonoma cause amino acid deficiency, likely to contribute to NME
- Ultrasound - the primary pancreatic tumour has only rarely been identified. Hepatic changes as seen in hepatocutaneous syndrome may be identified/excluded
- Glucagon should be elevated, but there is no commercially available canine assay.
- Amino acids have been uniformly decreased - arginine, histidine, lysine
