Ans. b (Pernicious anemia) (Ref: Ganong's 22nd edition, p. 485; Harrison's 18th/ch. 105; 17th edition, p. 1869).# Parietal cell-containing gland is preferentially targeted in pernicious anemia, and achlorhydria results.# Achlorhydria, coupled with relative sparing of antral mucosa (site of G cells), leads to hypergastrinemia.# Gastrin levels can be markedly elevated (>500 pg/mL) in patients with pernicious anemia.# Fasting gastrin levels are usually <150 pg/mL. All gastrinoma patients have gastrin level >150-200 pg/mL.PERNICIOUS ANEMIA# Antibodies to parietal cells have been detected in >90% of patients with pernicious anemia and in up to 50% of patients with type A gastritis. The parietal cell antibody is directed against H+,K+-ATPase# These antibodies are observed in patients with vitiligo, Addison's disease and thyroid disease.# Anti-IF antibodies are more specific than parietal cell antibodies for type A gastritis, being present in -40% of patients with pernicious anemia.# Parietal cells are the source of IF, lack of which will lead to vitamin Bp deficiency.# HLA-B8 and -DR3 positive.Pernicious AnemiaPernicious anemia (PA) may be defined as a severe lack of IF due to gastric atrophy. The ratio of incidence in men and women among whites is 1:1.6, and the peak age of onset is 60 years, with only 10% of patients being <40 years of age. The disease occurs more commonly than by chance in close relatives and in persons with other organ-specific autoimmune diseases, e.g., thyroid diseases, vitiligo, hypoparathyroidism, and Addison's disease.It is also associated with hypogammaglobulinemia, with premature graying or blue eyes, and persons of blood group A. An association with human leukocyte antigen (HLA) 3 has been reported in some but not all series and, in those with endocrine disease, with HLA-B8, -B12, and -BW15. Life expectancy is normal in women once regular treatment has begun. Men have a slightly subnormal life expectancy as a result of a higher incidence of carcinoma of the stomach than in control subjects. Gastric output of hydrochloric acid, pepsin, and IF is severely reduced. The serum gastrin level is raised, and serum pepsinogen I levels are low.Gastric BiopsyThis usually shows atrophy of all layers of the body and fundus, with loss of glandular elements, an absence of parietal and chief cells and replacement by mucous cells, a mixed inflammatory cell infiltrate, and perhaps intestinal metaplasia. The infiltrate of plasma cells and lymphocytes contains an excess of CD4 cells. The antral mucosa is usually well preserved. Helicobacter pylori infection occurs infrequently in PA, but it has been suggested that H. pylori gastritis occurs at an early phase of atrophic gastritis and presents in younger patients as iron-deficiency anemia but in older patients as PA. H. pylori is suggested to stimulate an autoimmune process directed against parietal cells, with the H. pylori infection then being gradually replaced, in some individuals, by an autoimmune process.Serum AntibodiesTwo types of IF immunoglobulin G antibody may be found in the sera of patients with PA. One, the "blocking," or type I, antibody, prevents the combination of IF and cobalamin, whereas the "binding," or type II, antibody prevents attachment of IF to ileal mucosa. Type I occurs in the sera of 55% of patients, and type II in 35%. IF antibodies cross the placenta and may cause temporary IF deficiency in a newborn infant. Patients with PA also show cell-mediated immunity to IF. Type I antibody has been detected rarely in the sera of patients without PA but with thyrotoxicosis, myxedema, Hashimoto's disease, or diabetes mellitus and in relatives of PA patients. IF antibodies also have been detected in gastric juice in 80% of PA patients. These gastric antibodies may reduce absorption of dietary cobalamin by combining with small amounts of remaining IF.Parietal cell antibody is present in the sera of almost 90% of adult patients with PA but is frequently present in other subjects. Thus, it occurs in as many as 16% of randomly selected female subjects age >60 years. The parietal cell antibody is directed against the end subunits of the gastric proton pump (HK+-ATPase).JUVENILE PERNICIOUS ANEMIAThis usually occurs in older children and resembles PA of adults. Gastric atrophy, achlorhydria, and serum IF antibodies are all present, although parietal cell antibodies are usually absent. About one-half of these patients show an associated endocrinopathy such as autoimmune thyroiditis, Addison's disease, or hypoparathyroidism; in some, mucocutaneous candidiasis occurs.# Multiple processes can lead to an elevated fasting gastrin level: gastric hypochlorhydria or achlorhydria (the most frequent), with or without pernicious anemia; retained gastric antrum; G cell hyperplasia; gastric outlet obstruction; renal insufficiency; massive small-bowel obstruction; and conditions such as rheumatoid arthritis, vitiligo, diabetes mellitus, and pheochromocytoma. Although a fasting gastrin >10 times normal is highly sugg. of ZE, two-thirds of patients will have fasting gastrin levels that overlap with levels found in the more common disorders outlined above.# The next step in establishing a biochemical diagnosis of gastrinoma is to assess acid secretion. Nothing further needs to be done if decreased acid output is observed. In contrast, normal or elevated gastric acid output suggests a need for additional tests. Up to 12% of patients with common PUD may have comparable levels of acid secretion. A BAO/MAO ratio >0.6 is highly suggestive of ZES, but a ratio <0.6 does not exclude the diagnosis. Pentagastrin is no longer available in the United States, making measurement of MAO virtually impossible. An endoscopic method for measuring gastric acid output has been developed but requires further validation. If the technology for measuring gastric acid secretion is not available, a basal gastric pH =3 virtually excludes a gastrinoma.# Gastrin provocative tests are the secretin stimulation test and the calcium infusion study. The most sensitive and specific gastrin provocative test for the diagnosis of gastrinoma is the secretin study. An increase in gastrin of =200 pg within 15 min of secretin injection has a sensitivity and specificity of >90% for ZES.# The calcium infusion study is less sensitive and specific than the secretin test, with a rise of >400 pg/mL observed in -80% of gastrinoma patients. The lower accuracy, coupled with it being a more cumbersome study with greater potential for adverse effects, makes calcium infusion less useful. It is used in the rare cases where the patient's clinical characteristics are highly suggestive of ZES. but the secretin stimulation is inconclusive.