Investigations
1st investigations to order
haemoglobin
Test
About 25% of achlorhydric patients develop iron-deficiency anaemia.[63][64][65][66][76]
As intrinsic factor, secreted from parietal cells, is essential for cobalamin absorption, atrophic gastritis is the most common cause of cobalamin deficiency.[74][78]
Result
decreased due to cobalamin (vitamin B12) and/or iron deficiency
biopsy of corpus and/or fundus of stomach
Test
This test, which is the diagnostic standard, may be performed when a differential diagnosis of achlorhydria is entertained based on history, physical exam, and/or laboratory findings.[5][6][7][10]
Gastric atrophy is characterised by loss of glands and parietal cells with a decreased ratio of the area occupied by glands to the total mucosa area.[85]
Autoimmune atrophic gastritis is characterised by lymphocytic infiltration into the epithelium (98%), muscularis mucosa thickening (93%), gland shortening and branching (87%), basal lymphoid aggregates (83%), eosinophil infiltration (46%), and neutrophil infiltration (44%).[86]
Result
absence of parietal cell-containing oxyntic glands
intragastric pH
Test
This test may be performed using a pH electrode or by using pH paper. It is more useful in ruling, by showing low gastric pH, out achlorhydria than in establishing the diagnosis (since reflux of alkaline duodenal contents, in the absence of achlorhydria, can increase the pH of gastric juice to >6).
A spot pH test using pH paper is a pragmatic, easy method of ruling out achlorhydria during routine endoscopy, especially when performed off acid suppressive therapy. Intragastric pH can be measured using a pH catheter over a 24-hour period, and is a more accurate method of quantifying gastric pH. Gastric acid analysis, either basal or stimulated, is often used in hypergastrinaemic patients.
Result
a fasting gastric juice pH <6 rules out achlorhydria
Investigations to consider
serum gastrin
Test
Hypergastrinaemia is the physiological response to achlorhydria or hypochlorhydria.
This test should be performed during fasting, and if markedly elevated a gastric pH should be obtained to rule out Zollinger-Ellison syndrome (gastrinoma) as the aetiology of the hypergastrinaemia.[70]
A secretin stimulation test is only indicated if serum gastrin is high, and gastric pH is acidic. This test is performed to diagnose or rule out Zollinger-Ellison syndrome when gastric pH is <2 with a high serum gastrin.
Other causes of hypergastrinaemia include antisecretory drugs, retained gastric antrum in duodenal limb after antrectomy, renal insufficiency, massive small bowel resection, and gastric outlet obstruction with marked distension.[71]
Result
elevated, usually >400 picograms/mL and frequently >1000 picograms/mL
gastric acid secretory test (gastric analysis)
Test
Definitive test for the diagnosis of achlorhydria, but is not widely available or performed.[82][83] May be considered (in specialised centres) when the diagnosis remains in doubt after less invasive testing. The test requires aspiration of gastric juice in the fasting state, and calculating gastric acid concentration using titration to pH 7.0 with an alkaline medium.
Maximal acid output, which measures the acid secretory response to an exogenous secretagogue (usually pentagastrin), is an indirect measure of parietal cell mass.
Achlorhydric patients produce no acid, even when stimulated.
Result
no acid is produced during fasting as well as during stimulation; it is usually performed by injecting pentagastrin (6 micrograms/kg) subcutaneously, intramuscularly, or intravenously
parietal cell antibodies
Test
Antibodies directed against hydrogen-potassium-stimulated adenosine triphosphatase (H+/K+ ATPase) are found in 90% of patients with pernicious anaemia.
The incidence of these antibodies may decrease to about 55% to 80% with progression of autoimmune gastritis, presumably because of the loss of antigenic drive.[27][28][33][34][35]
Result
present in about 90% of patients with gastric atrophy
intrinsic factor antibodies
Test
Over 70% of patients with gastric atrophy and/or autoimmune gastritis have antibodies directed against the parietal cell hydrogen-potassium-stimulated adenosine triphosphatase (H+/K+ ATPase) and/or intrinsic factor (IF).[28][33][34][35]
IF antibodies block the attachment of cobalamin to IF, or the attachment of the cobalamin-IF complex to cubilin.
IF antibodies are >95% specific and 50% to 85% sensitive for pernicious anaemia.[74][78][79][80]
Result
anti-IF antibodies are detectable in the serum in about 30% of patients with gastric atrophy and up to 80% to 90% with pernicious anaemia
diagnostic tests for Helicobacter pylori infection
Test
Infection with H pylori is probably the most important contributory factor for the development of achlorhydria, even though most patients harbouring the organism are not achlorhydric.
Diagnostic tests for H pylori infection, each with >90% sensitivity and >90% specificity, include histology with immunohistochemical stain, urea breath test, rapid urease test on biopsy samples, polymerase chain reaction (PCR), fluorescence in situ hybridisation, and stool antigen test.[92][93][94][95][96][97]
Use of proton-pump inhibitors may decrease the sensitivity of some tests by decreasing the number of organisms.[98]
Serology, although >90% sensitive, is <80% specific for active infection, since antibodies may remain detectable years after the organism is eradicated.[10][95][96] Consequently, serology should not be used to document eradication of infection.
Result
detection of active infection with H pylori; detection of active or prior infection with H pylori (serology); positive (PCR, fluorescence in situ hybridisation)
serum pepsinogen I and II (PGI and PGII)
Test
A PGI <25 nanograms/mL or PGI/PGII ratio of 2.5 to 3.0 or less has been used as a non-invasive screening test to detect mucosal atrophy with about 80% sensitivity and 85% specificity.[108][109][110][111][112][113][114][115][116][117]
However, some studies have reported lower sensitivities, or even no significant differences in the PGI and PGI/PGII ratio between those with and without chronic atrophic gastritis.[114][115][118]
Measurement of pepsinogen is used in Asia and the Scandinavian countries, but not routinely in the US.
Further studies are needed to validate serum pepsinogen measurements as biomarkers for gastric atrophy with achlorhydria.
Result
PGI/PGII ratio <2.5 to 3
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