4. Pathophysiology of GIT-peptides

From greek.doctor

Gastrointestinal hormones or peptides regulate the secretion of digestive juices and the function of the Langerhans islets. They have some common features:

  • They are all peptides
  • They are produced in cells of the wall of hollow organs
  • They participate in the “gut-brain axis”
  • Several of them may derive from the same gene
  • They may act via endocrine, paracrine, autocrine or neurocrine transmission

Gastrin is produced by G-cells in the gastric antrum and stimulates gastric motility and the HCl secretion by the parietal cells. This transmission is endocrine. HCL secretion can also be enhanced by the vagus nerve and histamine relase. It’s inhibited by negative feedback when too much HCl is secreted.

Secretin is produced in the intestinal mucosa and increases the quantity and bicarbonate content of pancreatic juice. It inhibits HCl secretion.

Cholecystokinin (CCK) stimulates bile secretion and pancreatic enzyme production. It also inhibits HCl secretion.

Vasoactive intestinal peptide (VIP) stimulates intestinal and pancreatic secretions. It also inhibits HCl secretion.

Somatostatin (SST) inhibits the production of secretin and HCl.

Gastric inhibitory peptide (GIP) inhibits the secretion of only HCl.

Motilin increases intestinal motility.

GLP-1 and GIP together form a group called the incretins. They increase the secretion of insulin.

Serotonin is a neurotransmitter and not a peptide, however it’s present in the GI tract where it regulates intestinal motility.

Pathophysiology

The decreased function or secretion of GI peptides is rarely seen as the remaining working hormones usually make up for the deficient peptide. However, there are some cases:

  • In untreated coeliac disease will there by atrophy of the intestinal mucosa, which results in decreased CCK production.
  • In cholelithiasis is the CCK level decreased
  • In atrophic gastritis is the gastric mucosa atrophic due to autoimmunity. No HCl, pepsin or intrinsic factor is produced, the latter of which leads to pernicious anaemia. Also, no HCl means that the G-cells won’t be subjected to negative feedback, so gastrin secretion increases.

We usually see hypersecretion of these peptides due to a tumor.

Zollinger-Ellison syndrome is a disease where an ectopic gastrinoma (gastrin-producing tumor often located in the pancreas) stimulates HCl release uncontrollably. The tumor obviously isn’t affected by the negative feedback that usually prevents oversecretion so hyperacidity of the stomach occurs. This causes small and deep ulcers to form in the stomach. The duodenal pH also decreases, which impairs the function of pancreatic enzymes, causing malabsorption.

Hypersecretion of gastrin also occurs in G-cell hyperplasia, gastric ulcer or pernicious anaemia. In pernicious anaemia will the B12 deficiency limit the cell division of the gastric mucosa, causing it to atrophy. Now that there are fewer parietal cells secreting HCl will the negative feedback of the G-cells be reduced, which stimulates them to produce more gastrin. This increases the gastric motility.

WDHA syndrome (Watery diarrhoea – hypokalaemia – achlorhydria) is a condition that occurs due to a VIPoma, a VIP-producing tumor. The excess VIP stimulates production of intestinal juice and motility, while inhibiting gastrin and HCl production (achlorhydria). K+ and bicarbonate are lost from the intestines causing hypokalaemia and metabolic acidosis. Secondary hyperaldosteronism occurs due to fluid loss, which worsens the hypokalaemia.

Multiple endocrine neoplasia type 1 is a syndrome that occurs due to the presence of endocrine tumors that produce gastrointestinal peptides. The symptoms depend on which peptides are produced.

Carcinoid syndrome is a paraneoplastic syndrome that occurs secondary to carcinoid tumors, tumors that originate from neuroendocrine cells. The tumors produce lots of serotonin which causes hypermotility.

Insulinomas, glucagonomas and somatostatinomas are all subtypes of pancreatic neuroendocrine tumors. The symptoms differ depending on the hormone that is secreted and simply correspond to the hyperfunction of that hormone.

Pharmacology

Some GI peptides have some uses pharmacologically or therapeutically.

Glucagon can be given to decrease the motility during gastrointestinal imaging.

Secretin can be given to increase pancreatic blood flow during angiography.

CCK can be given to increase bile flow and as a diagnostic aid for evaluation of gallbladder disorders.

Somatostatin analogues are used for their growth hormone-inhibiting effect. They can treat growth-hormone producing tumors and acromegaly.