Exploring Life through Clinical Chemistry!

Gastric Acid, Gastrin, and 

Zollinger-Ellison Syndrome

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It happened about 3 years ago. Mom and I were having lunch together at our place. She was reminiscing about my childhood. Suddenly, mom stopped eating and felt something painful on her chest. “It’s like my chest is burning! It’s awfully painful!” she said. I panicked. I didn't know what to do. We rushed her to her doctor and after a few tests he said its heartburn. It’s a painful sensation on the chest which resulted from gastric acid reflux. From that moment on, I would never forget about heartburn anymore.

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I know you are familiar with the gastric juice in your stomach. I also know that it’s not uncommon to you that it is the gastric juice that aids in the digestion of every food you take. But let me ask this question, have you ever thought of how it is produced and secreted so the food you take in will be digested?

The major hormonal regulator of gastric acid secretion is referred to as the Gastrin. According to Michael Bishop’s book, “Clinical Chemistry Techniques, Principles, Correlations”, it is also defined as the most powerful stimulus to gastric secretion. During the gastric phase of digestion, hormone gastrin regulates the gastric secretion.

It was John Sydney Edkins, a British physiologist, who first noted the discovery of gastrin. Later on, Roderic Alfred Gregory of the University of Liverpool was the one responsible for its isolation in 1964.

(Photo credits: Grossman, M. I. (Ed), University of

California Press, Los Angeles, 1966)

“What are the situations in which gastrin production is stimulated?”

These incidents may be:

·         distension or swelling of the stomach,

·         vagal stimulation,

·         partially digested proteins and caffeine in stomach,

·         the increased pH of chyme due to the presence of food in the stomach, and

·         acetylcholine released from parasympathetic neurons.

I'm pretty sure that you started formulating questions in your mind. How is it released? Well, as said by Tortora and Derrickson in their book “Principles of Anatomy and Physiology Maintenance and Continuity of the Human Body”, it is the works of the G cells which is situated on the antral gastric glands that the hormone gastrin is produced. G cells belong to the larger family of Amine Precursor Uptake and Decarboxylation (APUD) cells. Gastrin-secreting cells can also be found on the pituitary gland, brain and nerves, and the fetal pancreatic islets.

As the food you eat enters your stomach, release of gastrin in the blood stream is stimulated by the G cells. This process will now initiate gastrin level to increase which will eventually lead to gastric acid release. Breaking down of your proteins and absorption of vitamins will now take place. Another major effect of gastrin is to promote gastric mucosal growth. Treatment with gastrin stimulates DNA, RNA and protein synthesis in gastric mucosa and increases the number of parietal cells. When bacteria enter the stomach together with food, hormone gastrin serves as the disinfectant and will kill most of the bacteria. This circumstance helps to minimize the infection within the gut.

(Please click and check these videos for further information)

The Journey of Food ... Inside Your Body !

The Digestion Song !

(I do not own the videos. Credits to Mr. Travis Finlay and nesvikk, both YouTube account owner)

“Are there any other effects or functions of gastrin that will help my body?”

Here are some of the minor actions of gastrin include that you would want to know…

·    strengthening of the contraction of the lower esophageal sphincter to prevent reflux of acid chyme into the esophagus,

·         increase stomach motility, and

·         gastric emptying through the relaxation of the pyloric sphincter.

Stimulation of insulin and glucagon secretion is also done by gastrin. After introduction of a protein meal into the body, gastrin is secreted in adequate amount to elevate the insulin secretion.

Aside from the stomach, this hormone also plays a role with your other organs inside your body. It has also a minor effect in aiding the intestines, liver, and pancreas as well. It functions to activate the production of digestive enzymes in the pancreas, it aids in bile production in the liver, and its role in the intestines is to assist the food movement through the lower part of the digestive tract.

Inhibition of gastrin secretion happens when the pH off the gastric juice drops below 2.0. High gastric acidity decreases gastrin release by the gastric G cells. The K cells in the proximal jejunum, in the middle and distal duodenum produces gastric inhibitory polypeptide in response to variants of food such as fats, glucose, and amino acids. On the other hand, H cells in the intestinal mucosa releases vasoactive intestinal polypeptide which will now inhibit the gastric secretion, gastric motility, and gastrin release directly. This negative feedback mechanism helps provide an optimal low pH for the functioning of pepsin, the killing of microbes, and the denaturation of proteins in your stomach.

“What will happen if my gastrin level is decreased?”

Because gastrin helps protect your stomach by serving as a disinfectant that will kill the bacteria, risk of having or acquiring an infection within the gut is increased. Digestion and absorption of nutrients and vitamins too is affected as the decrease of gastrin may limit your stomach’s ability to do so. However, It is not usual for you and for an individual to have little amount of gastrin.

“What will happen if my gastrin level is elevated?”

About the above mentioned information, most probably you might ask me this question. I found a very nice yet simple explanation about that…

The cause of increased levels of gastrin can be grouped into either an underlying disease or condition which causes the body to produce extra gastrin, and/or a neoplasm is producing abnormal amount of gastrin such as gastrinoma. A gastrinoma is a relatively rare type of tumor which can occur in single large or multiple small tumors. It is frequently found in the duodenum and less often in the pancreas. Due to the excessive gastrin release of these tumors, an abnormal production of gastric acid takes place. The condition is also known as hypergastrinemia or more specifically, the Zollinger-Ellison Syndrome or ZES.

High levels of gastrin can lead to stomach and/or small intestinal ulcers, which may be a cause of abdominal pain. Because the lining of small intestine becomes damaged, diarrhea can also occur. 

(Photo credits: http://gastriculcer.blogspot.com/2011/08/difference-between-duodenal-ulcer-and.html)

In treating the causes I have mentioned above, whichever may be your case, clinicians will not focus more on decreasing your gastrin level but instead, the underlying cause will be corrected.

“What exactly this Zollinger-Ellison Syndrome is?”

(Photo credits: http://medaddicts.blogspot.com/2012/12/zollinger-ellison-syndrome.html)

The cells of your stomach control the production of gastrin under normal conditions. This hormone travels through your bloodstream. To release the gastric acid, your hormone sends signals to other cells of your stomach. The release of abnormally high amount of gastrin by the G cells is caused by tumors also known as gastrinoma. In turn, it leads to excess acid production that causes peptic ulcers on your duodenum and stomach. The exact cause of ZES is unknown. Those who suffer from the inherited disorder Multiple Endocrine Neoplasia Type 1 (MEN1) have tumors of the pituitary gland, parathyroid gland as well as the pancreas, thus, making the experts believe that it may be the cause of the aforementioned syndrome. It often affects men who are in the age group of thirty to fifty years. Twenty-five to sixty percent who have MEN1 are more to be expected to develop Zollinger-Ellison syndrome.

“How would I know if I already have ZES? Are there symptoms of this condition?”

“If symptoms persist, consult your doctor!” --- A statement which is always said after commercials and TV ads of some medications.

Symptoms of the said syndrome are not all the time evident. They are often confused with peptic ulcer symptoms. That is why the above quotation has to be followed.

Here are some symptoms of ZES but are not only specific to it:

• extreme pain in the upper abdomen,
• severe burning sensations in the stomach,
• nausea,
• vomiting with blood,
• loss of appetite affected by pain,
• diarrhea or evidence of black bowel movements, and
• weight loss.

Chronic diarrhea, which is often experienced between or after meals, and esophageal pain, which takes place due to gastroesophageal reflux, is just one of the specific symptoms observed on patients with ZES. Gastroesophageal reflux, also known as heartburn, is a condition in which gastric juice in the stomach has a backflow into the esophagus, which will, in the end, causes burning and irritation.

“How is ZES diagnosed and the different tests done in its diagnosis?”

Symptoms are not always the basis of diagnosing ZES. It is necessary that you talk to your doctor and he/she will also ask about your medical history and then do a complete physical examination. Follow up procedure include blood tests, to determine the level of gastrin into the bloodstream, and endoscopy, wherein a small tube is inserted passing through the mouth, into the abdomen to look for the presence of ulcers and multiple tumors. To locate the site of tumors or ulcers, ultrasound may also be used.

Some other tests done also include:

·         Octreotide scan,

·         Computerized Tomography (CT) scan,

·         Abdominal Angiography,

·         Secretin Stimulation Test, and

·         Calcium Infusion Test.

“Is ZES treatable? If yes, how is it?”

Yes. Zollinger-Ellison Syndrome can be treated. The ulcers and tumors are often positioned in places where they are difficult to remove. But still, to prevent cancer, removal of tumors is of utmost importance. After the tumors and ulcers are removed, medication to prevent acid from forming will follow. However, with ZES, reappearance of tumors frequently occurs. Experience of pain again in the upper abdomen may signify potential surgery.

According to Michael Bishop, “the normal value of gastrin level in the plasma ranges from 50-150 picograms/mL”. He also stated in his book that in simple peptic ulcer disease, gastrin level is not usually elevated. On the other hand, elevated gastrin levels takes place in most patients with pernicious anemia and decreased to normal when hydrochloric acid (HCl) is artificially implanted into the stomach.

Nowadays, medications such as omeprazole and lansoprazole, collectively known as proton pump inhibitors, are the drug of choice for treating ZES. These medications help in reducing the production of acid in the stomach. These also help promote healing of ulcers, and ease abdominal pain and diarrhea. Since ZES is caused by tumors that are often treatable, the ulcer it causes is also cured. With the help of surgery or by using chemotherapy, the tumor can be treated. In some ZES patients, exploratory surgery is performed. Careful search for, and resection of all pancreatic and extrapancreatic gastrinomas should be incorporated with it. In line with this, Wolfe and Jensen stated in their journal that “it is least likely twenty percent of ZES patients can be cured”. However, gastrinomas grow slowly. This allows patients to live for many years after the discovery of the tumor. To control the symptoms of excessive gastric acid production, acid-supressing medications are often effective.

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Thank you for spending your time with my page. I hope you now know a bit about the gastric acid secretion in your body, gastrin and ZES. I also hope these things can help you with your research. Have a great day in looking for other sources for you to have more than enough knowledge about it. Good Luck in your research and God Bless!

References:

Berg, CL, and Wolfe, MM., Zollinger-Ellison syndrome, 1991

Bishop, Michael L., et. Al., Clinical Chemistry Techniques, Principles, Correlations 6th Edition,2010

Grossman, M. I. (Ed), Gastrin. UCLA Forum Med. Sci. No. 5, University of California Press, Los Angeles, 1966

Liddle, Rodger A. MD., et. Al., Physiology of gastrin, 2012

Sircar, Sabyasachi, Principles of Medical Physiology, 2008

Tortora, Gerard J., and Derrickson, Bryan H., Principles of Anatomy and Physiology Maintenance and Continuity of the Human Body 12th Edition Vol.1&Vol.2, 2009

Wolfe MM, and Jensen RT., Zollinger-Ellison syndrome. Current concepts in diagnosis and Management., 1987

URL:

http://www.healthplus24.com/diseases/zollinger-ellison-syndrome.aspx

http://www.nlm.nih.gov/medlineplus/ency/article/000325.htm