In mouse models, pre-existing chronic metabolic acidosis exacerbates pancreatic damage during both mild and severe acute pancreatitis by increasing edema, necrosis, and leukocyte infiltration, and severe acute pancreatitis further reduces blood pH in mice with chronic metabolic acidosis, indicating a bidirectional, mutually reinforcing relationship between the two conditions.

When the blood is too acidic for a long time, it makes pancreatic cells more sensitive to damage, causing digestive enzymes to activate inside the pancreas instead of in the gut. This triggers inflammation, cell death, and swelling. The damaged pancreas then releases toxins that shut down blood flow to organs and impair kidney function, which prevents the body from removing acid. This makes the blood even more acidic, which in turn worsens the pancreatic damage in a continuous loop.