Dr. Omar Al- Azzawy
Lec. 9
GASTROINTESTINAL
(ENTERIC) HORMONES
Thur. 14 / 4 / 2016
Done By: Ibraheem Kais
2015 – 2016
ﻣﻜﺘﺐ ﺁ
ﺷﻮﺭ ﻟﻼﺳﺘﻨﺴﺎﺥ
Gastrointestinal (enteric) Dr. Omar Al- Azzawy
hormones
14-4-2016
1
Gastrointestinal (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.
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.
Gastrointestinal (enteric) Dr. Omar Al- Azzawy
hormones
14-4-2016
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.
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.
Gastric inhibitory polypeptide (GIP)
It 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.
Gastrointestinal (enteric) Dr. Omar Al- Azzawy
hormones
14-4-2016
3
Ghrelin
o Primarily it is secreted from the stomach, hypothalamus and smaller amounts
are secreted from the intestine.
o 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.
o It is also a strong stimulant for appetite and feeding; It increase hunger through
receptors in the hypothalamus.
o In Prader
‐
Willi syndrome, affected patients develop extreme obesity associated
with uncontrollable and voracious appetite. Their plasma ghrelin levels are
exceptionally high.
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.
Glucagon
It is best known as a peptide hormone secreted within alpha cells of the
pancreas
It participates in control of glucose metabolism, and it action was discussed in
DM lectures.
Gastrointestinal (enteric) Dr. Omar Al- Azzawy
hormones
14-4-2016
4
Glucagon‐like peptide‐1 (GLP‐1), and other types of
"Glucagon‐like peptide" with less activity, are
1. Glucagon
‐
like peptide
‐
2 (GLP
‐
2),
2. Oxyntomodulin,
3. 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.
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.
I‐ Pancreatic endocrine tumors
a. Zollinger
‐
Ellison Syndrome.
b. Insulinoma.
c. Glucagonoma.
d. Somatostatinoma.
e. GRFoma.
f. ACTHoma.
g. VIPoma (Verner
‐
Morrison
syndrome, pancreatic cholera).
Gastrointestinal (enteric) Dr. Omar Al- Azzawy
hormones
14-4-2016
5
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)
Stimulates contractility of the heart.
Increases glycogenolysis leading to hyperglycemia.
Vasodilatation and Lowering of arterial blood pressure.
Relaxes the smooth muscle of trachea, stomach and gall bladder that lead to:
dilated loops of bowel as well as a dilated, atonic gallbladder.
Stimulate secretion of water into pancreatic juice and bile.
Inhibition of gastric acid secretion.
Potent stimulant of secretion in both the small and large intestine.
Hypercalcaemia (mechanism remains unclear), and could be part of (MEN1
(pituitary, parathyroid and pancreatic tumors).
Gastrointestinal (enteric) Dr. Omar Al- Azzawy
hormones
14-4-2016
6
Clinical features VIP cause
o Profound and chronic watery diarrhea (>1 L/
day);
o Diarrhea is secretory in nature, occurs even during fasting and leads to
dehydration, hypokalemia and non–anion gap acidosis. due to excretion of
large amounts of potassium and bicarbonate in the stool.
o Flushing and hypotension due to vasodilatation that occur in 20% of patients.
o Symptoms of hypercalcaemia in 41 to 50% of cases, and of hyperglycemia in
25 to 50% of cases.
o Lethargy, muscle weakness, nausea, vomiting and crampy abdominal pain
are frequent symptoms.
o Achlorhydria.
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.
Gastrointestinal (enteric) Dr. Omar Al- Azzawy
hormones
14-4-2016
7
II‐ Carcinoid tumors
Slow
‐
growing tumors 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:
- 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.
- Diarrhea (32–84%) due to serotonin and may be prostaglandin. Chronic
diarrhea with a secretory component
- Cramping abdominal Pain (10–34%).
Gastrointestinal (enteric) Dr. Omar Al- Azzawy
hormones
14-4-2016
8
- 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.
- 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. 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.
Diagnosis
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.
Gastrointestinal (enteric) Dr. Omar Al- Azzawy
hormones
14-4-2016
9
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.
… END …