The most proximal and widest part of the small intestine is the duodenum. Starting at the pylorus of the stomach, the duodenum ends at the duodenojejunal junction and measures about 25 cm long. It receives partly digested food (chyme) from the stomach and bile and pancreatic fluids from the pancreaticobiliary duct. After entering the duodenum the acidic contents from the stomach is neutralized by secretion from the intestine and pancreas. Enzymes secreted from the pancreas starts the digestion of lipids, carbohydrates and proteins to enable absorption.

As in other parts of the small intestine, the mucosa forms fingerlike projections called villi that extend into the intestinal lumen. These are epithelial folds lined by two types of cells, enterocytes and goblet cells. Enterocytes are simple columnar cells with basal elongated nuclei and an apical brush border. The brush border is the microscopic representation of small protrusions of the cell membrane, microvilli, which greatly increase the surface area of the cell enhancing absorptive capacity. The other cell type is mucus secreting goblet cells that can be recognized by the presence of an apical mucous cup. The core of the villus is part of the lamina propria. The most numerous cells in the lamina propria are immune cells, most of which are lymphocytes. Because villi are the site of absorption of nutrition they have a rich blood supply, each villus is supplied by central arterioles and drained by central venules and a central lymph vessel.

Underlying the villi are the intestinal glands, also called the crypts of Lieberkühn. These glands are lined with numerous relatively undifferentiated columnar cells that usually undergo two rounds of mitosis before differentiating into either absorptive cells or goblet cells. Enterocytes, goblet cells, paneth cells that secrete antibacterial enzymes (recognized by eosinophilic granules in their apical cytoplasm) and enteroendocrine cells also line the crypt. A thin layer of smooth muscle marks the end of the mucosa, the muscularis mucosae.

In the submucosa numerous pale stained glands are present, namely the Brunner’s glands. These are branched tubular or alveo-tubular glands lined with columnar secretory epithelium. Brunner’s glands secrete large amounts of alkaline mucous that neutralize the acidic contents from the stomach.