PEPSINOGEN 1, in Visit Clinic

Pepsinogen 1 is an inactive zymogen secreted by chief and mucous neck cells in the gastric fundus and body. Acid converts it to pepsin, which initiates protein digestion in the stomach. Levels reflect gastric mucosal health—reduced in atrophic gastritis—and secretion is stimulated by vagal activity and gastrin. Measurement of pepsinogen 1 and its ratio to pepsinogen 2 helps assess gastric atrophy and cancer risk.

Low pepsinogen I indicates reduced chief-cell function in the stomach’s corpus, often reflecting chronic atrophic gastritis or long-standing Helicobacter pylori infection. It signals decreased acid and enzyme production and may indicate higher risk of intestinal metaplasia and gastric cancer. Clinicians usually recommend further evaluation—H. pylori testing and eradication if positive, and endoscopy with biopsy as clinically indicated.

Pepsinogen II is an inactive precursor (zymogen) of pepsin produced mainly by gastric chief and mucous neck cells and by Brunner’s glands in the proximal duodenum. It becomes active pepsin in acidic stomach conditions. Blood pepsinogen II levels serve as noninvasive biomarkers of gastric mucosal status and H. pylori–related inflammation, helping assess atrophic gastritis and gastric disease risk.

High pepsinogen levels (elevated pepsinogen I and/or II) usually indicate increased gastric mucosal activity or injury — for example active gastritis, Helicobacter pylori infection, peptic or duodenal ulcers, or acid hypersecretion. Patterns matter: a raised absolute pepsinogen suggests inflammation, while a low PG I/PG II ratio points to atrophic gastritis. Clinical context and further testing are needed for diagnosis.

Not all gastritis is autoimmune. Gastritis means stomach-lining inflammation caused most often by H. pylori infection, NSAIDs, alcohol or stress. Autoimmune (type A) gastritis is a less common form in which immune attack on parietal cells causes chronic atrophic gastritis, loss of intrinsic factor, vitamin B12 deficiency and sometimes pernicious anemia. Diagnosis and treatment differ from other causes.

Pepsinogen, secreted by gastric chief cells, is activated primarily by stomach acid (HCl) released from parietal cells; low pH converts pepsinogen to active pepsin. Once formed, pepsin catalyzes further activation of pepsinogen (autocatalysis). Parietal cells secrete HCl via the H+/K+ ATPase pump. Acid secretion is stimulated by gastrin, vagal acetylcholine, and histamine, promoting activation.