Gastrointestinal endocrinology Flashcards

Question

What are the gut-brain axis regulators (7)

Answer 1

1. Diet 2. Delivery method 3. Medication 4. Environment 5. Social interaction 6. Genetics 7. Sex differences

Answer 2

1. Lipogenesis - energy intake (carbohydrates, lipids, proteins) 2. Lipolysis - energy expenditure (BMR, physical activity, thermogenesis)

Answer 3

1. The release of GI hormones is in response to input from G-protein-coupled receptors that detect changes in luminal contents. 2. Some of these receptors only respond to selective luminal substances and subsequently release GI hormones from their respective enteroendocrine cells through unknown mechanisms.

Answer 4

1. Contraction and relaxation of smooth muscle wall and sphincters 2. Secretion of enzymes for digestion 3. Secretion of fluid and electrolytes 4. Trophic (growth) effects on tissues of GI tract 5. Regulating secretion of other GI peptides (i.e., somatostatin inhibits secretion of all GI hormones)

Answer 5

Gastrointestinal hormones are composed of polypeptides that can divide into two structurally homologous families that include the hormones responsible for a majority of regulation of GI function.

Answer 6

1. The first hormone family consists of gastrin and CCK because both hormones share an identical 5 C-terminal amino acid sequence, also known as “pentagastrin.” 2. The pentagastrin sequence includes the tetrapeptide that is minimally required for gastrin activity but is only about one-sixth as potent as the entire 17-amino acid gastrin peptide.

Answer 7

1. 5 C-terminal amino acid sequence, also known as “pentagastrin.” 2. The pentagastrin sequence includes the tetrapeptide that is minimally required for gastrin activity but is only about one-sixth as potent as the entire 17-amino acid gastrin peptide. 3. Gastrin also exists in a 34-amino acid form called “big” gastrin which gets secreted during the inter-digestive period. During meal ingestion, the 17-amino acid form of gastrin, also called “little” gastrin, is secreted. 4. Although each form of gastrin has its own distinct biosynthetic pathway, the mediation of the action of both gastrin peptides is via binding of cholecystokinin (CCK-2) receptors.

Answer 8

1. The second hormone family consists of secretin, glucagon, GLP-1, and GIP. 2. In contrast with the gastrin-CCK family, all amino acids in the polypeptide are necessary for biological activity, and these two polypeptides only share 14 common amino acids.

Answer 9

1. Secretin has 27 amino acids 2. structurally similar to glucagon, which has 29 amino acids.

Answer 10

1. Glucagon derives from a 180-amino acid precursor peptide called proglucagon 2. proglucagon undergoes tissue-specific post-translation processing to produce different peptides in different cell types. 3. Proglucagon is cleaved to form glucagon in the pancreas 4. in the intestines, proglucagon undergoes processing to produce a 30-amino acid peptide called GLP-1.

Answer 11

1. GIP is 42 amino acids long 2. shares 9 amino acids with secretin 3. shares 16 amino acids with glucagon.

Answer 12

1. Gastrin controls acid release within the stomach. 2. The main site of gastrin production is within G cells (via exocytosis) of the gastric antrum. 3. Exocytosis is positively regulated by gastrin-releasing peptide which is expressed within neuronal fibres in the stomach, whilst somatostatin, produced by D cells in response to luminal acid, inhibits gastrin release from G cells 4. Following release into the circulation, gastrin acts on enterochromaffin-like (ECL) cells in the gastric corpus/fundus stimulating release of histamine which in turn binds to H2 receptors and stimulates acid secretion by parietal cells.

Answer 13

1. The presence of certain foodstuffs 2. Especially peptides, certain amino acids and calcium, in the gastric lumen. 3. Compounds in coffee, wine and beer are potent stimulants for gastrin secretion.

Answer 14

when the lumenal pH of the stomach becomes very low less than about 3.

Answer 15

1. Nutrients entering the small intestine stimulate hormones: 2. CCK triggers bile secretion to emulsify fats and pancreatic enzymes to digest macronutrients. 3. Secretin neutralises stomach acid by stimulating bicarbonate secretion from the pancreas

Answer 16

Hormones like GLP-1 and PYY help slow gastric emptying and reduce appetite to ensure efficient nutrient absorption.

Answer 17

1. pancreas - induces secretions 2. intestine - facilitates the transport of food, Trophic (growth) effects on the mucosa 3. stomach - stimulates HCl acid secretion by parietal cells, Trophic (growth) effects on the mucosa 4. liver - aids in bile production 5. gall bladder - emptying 6. Inhibits the actions of Secretin and GIP

Answer 18

1. Protein in meals stimulates the G-cells to release gastrin into the blood. 2. Gastrin stimulates the enterochromaffin-like (ECL) cells to release histamine. The histamine then stimulates acid-producing parietal cells. 3. This is the gastrin–ECL axis, the main stimulatory pathway of gastric acid secretion. 4. The over-production of acid is prevented by negative feedback inhibition by intragastric acidity as low antral pH inhibits gastrin release via somatostatin from D-cells.

Answer 19

1. Stomach gastric emptying 2. Activation of hormones: GLP, CCK, 5-HT 3. Feedback control/pancreatic secretion control

Answer 20

1. The other member of the gastrin family, CCK, is a 33-amino acid peptide that includes the pentagastrin sequence and the C-terminal tetrapeptide sequence necessary for minimal gastrin activity; 2. This enables CCK to demonstrate activity on gastrin (CCK-2) receptors, although it mediates a very weak stimulation of gastric acid secretion. 3. The minimally active fragment for CCK activity is its C-terminal heptapeptide, which acts on CCK-1 receptors to mediate gallbladder contraction. 4. Gastrin can also act on the CCK-1 receptor, but each hormone is more potent at its own receptor than those of its homolog.

Answer 21

1. The gut communicates with the brain via hormones and the vagus nerve to regulate hunger and satiety: 2. Ghrelin (hunger hormone): Levels increase before meals, signaling the brain to initiate food intake. 3. PYY and GLP-1: Released after meals, signalling satiety to the hypothalamus.

Answer 22

1. the nutrient composition of the meal. 2. Oral lipid intake markedly stimulates motilin secretion, for up to 60 min after consumption. 3. Gastric acid and bile are both secreted into the duodenum and are considered the two major physiological regulators for motilin release.

Answer 23

stomach G cells

Answer 24

duodenum, jejunum I cells

Answer 25

duodenum S cells

Answer 26

small intestine M cells

Answer 27

stomach (fundus)

Answer 28

ileum, colon L cells

Answer 29

ileum, colon L cells

Answer 30

stomach, pancreas D cells

Answer 31

1. Pharmacists play a key role in managing disorders related to GI hormones. Some therapeutic approaches include: 2. Proton Pump Inhibitors (PPIs): Reduce acid secretion in hypergastrinemia. 3. GLP-1 Receptor Agonists: Used in Type 2 diabetes and obesity to enhance insulin secretion and reduce appetite. 4. Somatostatin Analogues: Manage hormone-secreting tumors, such as in Zollinger-Ellison syndrome.

Answer 32

Excess gastrin secretion by gastrinomas → hyperacidity → peptic ulcers

Answer 33

1. Severe GERD 2. abdominal pain 3. chronic diarrhoea

Answer 34

Proton Pump Inhibitors (PPIs) (e.g., omeprazole, lansoprazole):

Answer 35

Irreversibly inhibit H+/K+-ATPase in parietal cells to reduce acid secretion.

Answer 36

1. Headache 2. diarrhoea 3. risk of long-term hypocalcemia

Answer 37

1. Inhibits gastrin secretion from tumours. 2. Used in severe cases or metastatic disease.

Answer 38

Reduced GLP-1 activity → impaired insulin secretion, hyperglycemia.

Answer 39

GLP-1 Receptor Agonists (e.g., liraglutide, semaglutide):

Answer 40

Mimic GLP-1 to enhance glucose-dependent insulin secretion

Answer 41

1. Weight loss 2. reduced HbA1c

Answer 42

1. Nausea 2. risk of pancreatitis

Answer 43

1. Systemic gastrin, arising from G-cell secretion may play a role in carcinogenesis in an endocrine manner (pre-clinical studies), 2. or gastrin may be locally produced as a result of constitutive expression and secretion by cancer cells leading to paracrine or autocrine activity.

Answer 44

1. Systemic hypergastrinaemia may occur through the administration of proton pump inhibitors or infection with Helicobacter pylori. 2. Hypergastrinaemia resulting from H. pylori infection is associated with the occurrence of gastric and colorectal adenocarcinoma. 3. Administration of proton pump inhibitors has not been clearly linked to adenocarcinoma incidence in patients, in spite of the fact that they accelerate tumour progression in animal models 4. This suggests that gastrin can promote adenocarcinoma formation but only in conjunction with other co-factors, such as a mutant cell phenotype or bacterial pathogenicity factors, or through synergising with inflammatory events associated with H. pylori infection.

Answer 45

1. Hypergastrinemia: Excess gastrin secretion, often seen in Zollinger-Ellison syndrome, causes increased gastric acid and peptic ulcers. 2. Malabsorption Syndromes: Disruption in secretin or CCK secretion can impair digestion. 3. Obesity and Diabetes: Dysregulation of hormones like ghrelin, GLP-1, and PYY contributes to abnormal appetite and glucose metabolism.

Answer 46

1. The parietal cells contain the H+/K+ ATPase or “proton pumps” located in the canaliculus of the parietal cell and are responsible for the transport of acid (H+) into the stomach lumen. 2. The main stimulants of acid secretion at the level of parietal cells are histamine, acetylcholine and, to a lesser extent, gastrin.

Answer 47

1. PPIs are a class of medications that selectively and irreversibly inhibit the proton pump that accomplishes the final step in acid secretion. 2. PPIs are weak bases and therefore accumulate in the acidic space, the secretory canaliculus, of parietal cells. 3. After acid-induced activation PPIs covalently bind to the active proton pump (H+/K+-ATPase); the binding is achieved through the disulphide bond between the activated PPI and cysteines of the pump enzyme. 4. This covalent binding enables the prolonged inhibition of acid secretion, even after the drug concentration in the blood has waned. 5. The duration of the inhibitory activity is variable and affected by pump turnover and the loss of covalently bound PPIs.

Answer 48

1. While PPIs are effective and have a relatively desirable safety profile there is still uncertainty in regards to the safety of long-term, and often life-long, PPI therapy. 2. increasing number of reports about adverse events due to long-term use and the implementation of PPI deprescribing to address these issues. 3. PPIs are commonly continued long-term although the most common indications such as GERD and mild esophagitis are recommended for short-term use (e.g., eight weeks) to heal inflammation and resolute symptoms in management guidelines. 4. Concerns about the appropriateness of their use and potential adverse effects that might stem from continuous PPI therapy have been growing 5. There is also inappropriate prescribing of PPIs and in cross-sectional studies only approximately 30% of people were prescribed PPIs with appropriate indication concordant with guideline recommendations. 6. PPIs’ clinical efficacy and that they are generally well tolerated is likely the reason for their overutilisation and inappropriate use but concerns regarding their long-term safety are increasing. 7. PPI overuse (e.g., poor indication, excessive dose, excessive duration) contributes to polypharmacy and potential risk of drug interactions and side effects.

Answer 49

1. The aim of deprescribing PPIs in most cases is to reduce medication burden and potential adverse effects while maintaining quality of life. 2. PPI deprescribing algorithms have been proposed and published in UK, Canada and Australia. 3. Both recommend deprescribing of PPIs in adults who are symptom free after a minimum of four-week PPI therapy for GERD or upper GI-symptoms. 4. However, deprescribing can be difficult, and there is no evidence-based method of stopping or reducing PPIs. 5. Various different approaches to deprescribing have been outlined in prior trials and guidelines 6. Long-term PPI therapy can be appropriate and where there is a clear indication the benefit outweighs potential risk. 7. Patients with Barrett's oesophagus (BE), severe esophagitis grade C or D, and a history of bleeding GI ulcer or bleeding risk with chronic NSAID use are recommended to continue PPIs or consult a gastroenterologist before discontinuation

Answer 50

1. Some studies have shown an association between PPIs and the risk of fracture — particularly hip fracture — while others have not. 2. Calcium is absorbed in the small intestine, not the stomach. 3. But low stomach acid levels can have downstream effects, especially in the duodenum, and some research shows that one of them could be reduced absorption of calcium, which could lead to osteoporosis, weaker bones, and, consequently, a greater chance of breaking a bone.

Answer 51

1. People typically develop Clostridium difficile infections in the hospital after taking antibiotics that have disrupted the natural bacterial ecology of the large intestine. 2. The infections cause diarrhoea but can also become a lot more serious, even life-threatening. Studies have shown a fairly strong statistical correlation between PPI use and C. difficile infection (correlation and not proof of direct cause and effect). 3. Some experimental evidence suggests that PPIs may change conditions in the gut to be more favourable to C. difficile bacteria.