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Gastrointestinal Hormones (Enteric Hormones)
They are biogenic amines and polypeptide hormones (neurohormones) secreted by
gastrointestinal epithelial cells called endocrinocytes, which are found in the lining of the
stomach, small intestine, colon and other body organs, These cells do not form a gland;
instead, these cells are found distributed in many parts of the of body forming what is known
as the neuroendocrine system.
1‐ Gastrin
Secreted by G cells, which are located primarily in the antrum of the stomach.
It stimulates gastric acid secretion through histamine release from enterochromaffin
cells, which binds to H2 receptors on parietal cells.
It also has a trophic effect on the gastric mucosa.
The primary stimulus for secretion of gastrin is presence of peptides, and calcium, others
are coffee, wine, beer, etc….. .
Excessive secretion of gastrin, is a well recognized feature of Zollinger‐Ellison syndrome,
Most commonly, hypergastrinemia is the result of gastrin‐secreting tumors
(gastrinomas), which develop in the pancreas or duodenum.
2‐ Cholecystokinin
It is secreted from mucosal epithelial cells in the duodenum, and it is also produced by
neurons in the nervous system.
The most potent stimuli for secretion of cholecystokinin are the presence of triglycerides
then proteins then polysaccharides respectively in the lumen of the duodenum.
Cholecystokinin stimulates secretion of pancreatic enzymes, contraction and emptying
of the gall bladder.
Cholecystokinin is a key peptide involved in generating the satiety signal via the vagus
nerve.
3‐ Secretin:
Secreted from mucosal epithelial cells in the duodenum in response to acid (acidification
of the duodenum), and Stimulates secretion of water and bicarbonate from the pancreas
and the bile ducts to neutralizes the acid.
4‐ Gastric inhibitory polypeptide (GIP)
Is a member of the secretin family. it is produced by enteroendocrine K‐cells, mainly in
the duodenal and jejunal epithelia.
It is released in response to presence of fat and glucose in the small intestine.
It Inhibits gastric motility and potentiates release of insulin from beta cells.
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5‐ Ghrelin
Primarily it is secreted from the stomach, hypothalamus and smaller amounts are
secreted from the intestine.
It play role in the control and secretion of growth hormone in the anterior pituitary in
coordination with that of growth hormone releasing hormone and somatostatin.
It is also a strong stimulant for appetite and feeding; It increase hunger through
receptors in the hypothalamus.
In Prader‐Willi syndrome, affected patients develop extreme obesity associated with
uncontrollable and voracious appetite. Their plasma ghrelin levels are exceptionally
high.
6‐ Motilin
Controls the pattern of smooth muscle contractions in the upper gastrointestinal tract
(stomach and small intestine). Motilin secretion sweeps the stomach and small intestine
clear of undigested material.
Erythromycin and related antibiotics act as nonpeptide motilin agonists, and are
sometimes used for their ability to stimulate gastrointestinal motility.
7‐ Glucagon is best known as a peptide hormone secreted within alpha cells of the pancreatic.
It participates in control of glucose metabolism, and it action was discussed in DM
lectures.
8‐ Glucagon‐like peptide‐1 (GLP‐1), and Other types of "Glucagon‐like peptide" with less
activity, are
Glucagon‐like peptide‐2 (GLP‐2),
Oxyntomodulin,
Glicentin.
All are secreted into blood after ingestion of a meal containing carbohydrates or lipids.
Has a major effect of enhancing the release of insulin in response to a glucose stimulus, and
suppress secretion of glucagon so lower blood glucose levels.
Also GLP‐1 has been shown to inhibit gastric emptying, gastric secretion and pancreatic
secretion.
8‐ Vasoactive Intestinal Peptide (VIP)
GASTROINTESTINAL NEUROENDOCRINE TUMORS
Are tumors derived from the neuroendocrine system, and are divided to pancreatic
endocrine tumors (PETs) and carcinoid tumors.
Recent pathologic classifications have proposed that they are all to be classified as
gastrointestinal neuroendocrine tumors (NETs), but the terms carcinoid tumor and PETs
are still widely used.
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I‐ Pancreatic endocrine tumor
a‐ Zollinger‐Ellison Syndrome. b‐ Insulinoma.
c‐ Glucagonoma. d‐ Somatostatinoma.
e‐ GRFoma. f‐ ACTHoma
g‐ VIPoma (Verner‐Morrison syndrome, pancreatic cholera)
VIPoma (Verner‐Morrison syndrome, pancreatic cholera)
Rare, (incidence/1 per 10,000,000 per year),
VIPomas are usually large and solitary;
50 to 75% of these tumors occur in the pancreatic tail,
Of these 90% originating from non‐β islet cell of the pancreas
40 to 70% of them are malignant at diagnosis.
Action of (VIP)
a‐ Stimulates contractility of the heart,
b‐ Increases glycogenolysis leading to hyperglycemia
c‐ Vasodilatation and Lowering of arterial blood pressure
d‐ Relaxes the smooth muscle of trachea, stomach and gall bladder that lead to: Dilated
loops of bowel as well as a dilated, atonic gallbladder.
e‐ Stimulate secretion of water into pancreatic juice and bile.
f‐ Inhibition of gastric acid secretion.
g‐ Potent stimulant of secretion in both the small and large intestine.
h‐ Hypercalcaemia (mechanism remains unclear). could be part of (MEN1 (Pituitary,
parathyroid and pancreatic tumors))
Clinical Features VIP cause
• Profound and chronic watery diarrhea (>1 L/day);
Diarrhea is secretory in nature, occurs even during fasting and lead to dehydration,
hypokalemia and non–anion gap acidosis. due to excretion of large amounts of
potassium and bicarbonate in the stool.
Flushing and hypotension due to vasodilatation that occur in 20% of patients.
• Symptoms of hypercalcaemia in 41 to 50% of cases, and of hyperglycemia in 25 to 50%
of cases.
• Lethargy, muscle weakness, nausea, vomiting and crampy abdominal pain are frequent
symptoms.
• Achlorhydria.
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Diagnosis
Typical history of profound diarrhea and the diagnosis is excluded if the fasting stool
volume is less than 700 mL/day.
Fasting plasma VIP levels to differentiate VIPomas from other causes of large‐volume,
fasting diarrhea, including
ZES, surreptitious use of laxatives, the pseudopancreatic cholera syndrome and human
immunodeficiency virus (HIV).
Treatment
Correct dehydration is the first goal of treatment.
Octreotide by daily doses of (50 to 400 μg once to three times daily) or by monthly
injections of the depot form.
Surgical resection if possible to remove all visible tumor; many have liver metastases at
diagnosis.
Chemotherapy For patients with advanced cases and refractory symptoms.
II‐ Carcinoid tumors
Slow‐growing tumor that arise from the enterochromaffin cells throughout the body;
most commonly from GI tract (70%) and the lung (15%).
Most common site of GI tract is the appendix,
95–100% of carcinoid tumors are malignant.
Carcinoid tumors produce vasoactive substances, mainly serotonin, possibly tachykinins,
motilin, prostaglandins, and histamine.
Clinical Manifestations
1‐ Intestinal obstruction and other complications associated with tumor growth.
2‐ Carcinoid syndrome Only 8 to 10% of all carcinoid tumors lead to
carcinoid syndrome. The carcinoid syndrome occurs when mediators
produced by the tumor
a‐ Escape into the systemic circulation bypassing the liver.
b‐ Or if the primary tumor is from the GI tract and is so advanced (large) that it overwhelms
the liver's ability to metabolize the released mediators, leading to the following symptoms.
1‐ Flushing (63–80%) due to tachykinins or histamine and may be prostaglandin, is a common
clinical feature. The typical flush is dark red to violaceous, involves the head, neck, and upper
trunk that usually lasts for 30 seconds to 3 minutes, associated with lacrimation and periorbital
edema, tachycardia,
Low or normal blood pressure.
2 ‐ Diarrhea (32–84%) due to Serotonin and may be prostaglandin, Chronic diarrhea with a
secretory component
3‐ Cramping abdominal Pain (10–34%)
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4‐ Heart disease (11–41%) Plaque like thickening of the endocardium of the valvular cusps and
cardiac chambers occurs primarily on the right side of the heart, the left side may be minimally
involved, leading to , heart failure, palpitation and peripheral edema.
5‐ Asthma (4–18%) Bronchoconstriction, usually most pronounced during flushing attacks, is a
less common feature of the syndrome, but it may be severe, both histamine and serotonin
may be responsible
Other features of the tumor
1. Telangiectasia primarily on the face and neck.
2‐ Pellagra (3%): Serotonin overproduction shunts dietary tryptophan into the
hydroxylation pathway, thus leaving less tryptophan available for the formation of
niacin
Carcinoid crisis
Attacks of severe and sustained flushing with life‐threatening hemodynamic
compromise and bronchoconstriction may occur. Precipitating factors include anesthesia
or surgery, tumor necrosis, and catecholamine infusion.
Death usually is caused by cardiac or hepatic failure due to metastasis.
Diagnoses
Recurrent abdominal symptoms in a healthy appearing individual,
Hepatic metastases or the discovery of hepatomegaly associated with minimal
symptoms.
Bowel obstruction with abdominal pain, flushing, or diarrhea.
Lab
Increased 5‐hydroxyindoles and increased excretion of urinary 5‐Hydroxyindoleacetic
acid (5‐HIAA).
CT scan to assess the extent and localization of both primary and metastatic tumor of
the abdomen and chest.
Treatment
(1) Pharmacologic
Somatostatin analogues Octreotide Somatostatin can prevent the flushing and other
endocrine symptoms of the carcinoid syndrome.
(2) The reduction of tumor mass.
Surgery Given the slow progression of this neoplasm, effective reduction in tumor mass can
ameliorate morbidity and improve the quality of life even after metastases.