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GIT tutorial 1

Case History

A 25-year old woman enters the hospital with persistent diarrhoea and abdominal pain.

An upper GIT endoscopy shows the presence of multiple duodenal ulcers and enlarged

gastric mucosal folds. The patient’s basal rate of gastric HCl secretion is 12 mmole/hr

(normal range 1-5 mmole/hr). The patient’s serum gastrin is 1145 pg/ml (normal range

50-150 pg/ml).

The patient also has moderate steatorrhoea. Histologic examination of the gastric mucosal

specimen reveals that the gastric glands are more numerous than normal and have a

higher density of parietal cells than normal.

After a test meal, the patient’s serum gastrin level does not increase significantly (double

in normal subject). The patient’s rate of HCl secretion can be brought to below normal

levels by treatment with a proton pump inhibitor like omeprazole.

Questions for Discussion

1. Why might the patient have an elevated basal rate of gastric secretion?

Overactive parietal cells which may be stimulated by an overactive vagal nerve or excessive

gastrin secretions which may be due to Gastrinoma.

2. How would you expect the patient’s rate of pepsinogen secretion compare with normal?

Pepsinogen secretion is stimulated by the vagal nerve in the cephalic phase and by low pH andACh in the gastric phase and finally by secretin in the intestinal phase. Thus as she has an elevated

basal rate of gastric secretion, there is a lower pH and rate of pepsionogen secretion is elevated.

3. Why does the patient have duodenal ulcers?

Excessive low pH gastric juice (HCl) flows into the duodenum and damages the duodenal mucosa,

resulting in ulcers.

Due to higher basal gastric levels

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4. Why doesn’t the patient have gastric ulcers?

The stomach has many mucous cells which secrets a thick layer of mucous over the epithelium

and thus the HCl and hydrolytic enzymes do not come into direct contact with the epithelium. In

addition the enzymes secreted are in their inactive form. HCO3- is also secreted and the unstirred

layer slows inward diffusion of H+ and outward diffusion of HCO3-.

Feedback loop to ensure acid secretion is reduced. Hence due to this inhibitory mechanism,

patients with gastric ulcer have lower basal acid secretion

5. What abnormalities might lead to elevated serum gastrin levels?

Gastrinoma- Tumor secreting gastrin.

6. Why does the patient have steatorrhoea?

Excessive highly acidic gastric juices flow into the Jejunum and damages the epithelial cells as theJejunal environment is slightly alkaline. This results in malabsorption of lipids, leading to

steatorrhoea. In addition, the low pH due to the presence of excessive HCl does not allow

alkalinic enzymes such as pancreatic lipase to work properly and thus there is also poor digestion

of lipids, leading to further reductions in lipid absorption.

7. Why does a normal person have an increase in serum gastrin after a test meal? What is the

significance for this patient?

After a test meal, gastrin levels increase to stimulate HCl and pancreatic secretion to increase

rate of digestion of food. In the case of this patient, this shows that gastrin secretion is no longer

stimulated by food and thus there may be neuropathy of the Entero Nervous system in which the

G cells are perpetually stimulated, resulting in excessive HCl secretions.

8. Why is a proton pump inhibitor like omeprazole effective?

Parietal cells have H+/K+ ATPase to pump HCl out for secretion. Hence by inhibiting the ATPase,

HCl secretions will be inhibited and thus reduced. Close control of concentration of inhibitors

allow for HCl levels to be brought back down to normal.

Or antihistamines can also attain the same effect (blocks histamine but have to see cause)

9. What, if any, are the long term consequences of taking a proton pump inhibitor over a prolonged

period of time in a normal person (say for chronic gastro-oesophageal reflux)?

Mitochondria and other proton pump systems such as absorption, renal function, etc affected.

Insensitisation

Increasing cells to counteract effect of omeprezole – rapid proliferation – high tendency for cancer...