LIEBERKÜHN CRYPTS: HISTOLOGY, LOCATION, FUNCTION - ANATOMY AND PHYSIOLOGY - 2025

The crypts of Lieberkühn, also called intestinal crypts, are considered simple tubular glands, because their cells synthesize substances with enzymatic, hormonal and defense functions. Hence, some authors call it the Lieberkühn glands.

This structure is part of the intestinal tissue, positioning itself at the level of the mucosa, between the villi and immersed in the lamina propria. The crypts are named after the German anatomist JN Lieberkühn (1711-1756).

Crypts of Lieberkühn. Source: Nephron

They are made up of various types of cells, the most important being Paneth cells and pluripotent stem cells, among others. Each cell has a specific function within the epithelium of the intestinal mucosa.

The former fulfill a regulatory function of the intestinal microbiota, by secreting enzymes that lyse certain bacteria.

While the latter are responsible for renewing the cells that make up the epithelium of the crypt itself and the villi, that is, stem cells, Paneth cells, goblet cells, enterocytes and enteroendocrine cells.

The crypts of Lieberkühn are present throughout the intestinal mucosa, that is, in the duodenum, jejunum, ileum and even in the colon.

In biopsies of patients with stage 2 celiac disease, the presence of inflammation of the lamina propria can be seen, with hyperplastic crypts of Lieberkühn.

Histology

A characteristic of intestinal tissue is that it uses the formation of folds to expand the area of ​​absorption of nutrients.

These extensions are tiered, starting from highest to lowest. The first level is made up of the circular folds or Kerckring valves, then the villi, then the microvilli, and finally the glycocalyx.

On the other hand, it should be noted that the intestinal tissue is made up of several layers that are the mucous layer, the submucosa, the muscular layer and the serosa. The mucous layer in turn is made up of the epithelium, the lamina propria and the muscular layer of the mucosa (muscularis mucosae).

The epithelium superficially mimics the shape of circular folds but on a smaller scale, that is, it projects outward in the shape of fingers and is inserted again. These micro-folds are known as villi, which are made up of various types of epithelial cells and the Lieberkühn glands or crypts are located below the depression of each villi.

The Lieberkühn crypts are between 320 to 450 microns in length. These start from the villi, maintaining continuity with it and penetrate towards the lamina propria, almost until reaching the muscular layer of the mucosa.

Graphic representation of the structures of the intestinal tissue. Source: taken from Ferrufino J, Taxa L, Ángeles G. Normal histology of the small intestine. Rev Med Hered 1996; 7: 46-57. Available at: scielo.org. Edited image

The lamina propria that contains the crypts of Lieberkühn consists of a loose connective tissue, rich in elastic and collagen fibers, plasma cells, lymphocytes, among other cells.

To complete the system of expansion of the absorption area are the microvilli and the glycocalyx. The microvilli are located on the enterocyte (apical portion) of the villi and on the microvilli is the glycocalyx.

- Cells present in the crypts of Lieberkühn

In the epithelium, two areas to be mentioned are distinguished: the epithelium of the villi and the epithelium of the crypts.

The crypt epithelium has pluripotent stem cells that will give rise to at least four main cell types. These are goblet cells, absorption cells or enterocytes, Paneth cells and enteroendocrine cells or also called M cells.

Each stem cell goes through a process of proliferation and later differentiation, until it reaches each of the named cells.

From proliferation of the stem cell to differentiation into a mature cell, 5 to 6 days may elapse and 1 to 12 mitoses occur. 5 or 6 days is also the time it takes for cells to migrate from the crypt to the most apical part of the villi.

Each stem cell gives rise to two daughter cells, but only one of them will continue the maturation process, as the other will remain as a replacement stem cell. The one that advances in the maturation process can become one of the different cell types, for example: an enterocyte, a goblet cell, an enteroendocrine cell or a Paneth cell.

The stem cell is located deep in the Lieberkühn gland or crypt and, as they mature, they rise to the surface, passing towards the villi, where they continue on their way to the outermost layer. Those that are reaching the surface are detached into the lumen and others remain in the crypt, such as Paneth cells.

Enterocytes die in two days, they are shed into the intestinal lumen to be eliminated, which is why they must be renewed each time.

-Location and function of cells

Paneth cells

They represent 1% of the cells of the intestinal epithelium and are located at the bottom of the crypt. They have a pyramidal shape and their rounded nucleus is displaced towards the base.

The cytoplasm contains abundant supranuclear granules. The main function is the secretion of bacteriolytic substances, such as: lysozymes, phospholipase A and defensins.

These substances are enzymes that digest the cell wall of many bacteria and therefore regulate the intestinal microbiota, protecting the epithelium from the presence of pathogenic bacteria.

These cells are present in the crypts throughout the intestine, except for those located in the colon.

The crypts present in the colon are dominated by goblet cells, enteroendocrine cells, cells in the process of differentiation, and stem cells.

Pluripotent stem cells

They are responsible for renewing the cell stand present in the villi. These are located at a higher level than Paneth cells, that is, in the neck of the crypt and from there they differentiate into the different cell types, until they reach the villi.

Each cell type will have an approximate half-life of 5 days, with the exception of the enterocyte that lives approximately 2 days and Paneth cells that have a half-life of approximately 30 days.

Thus, crypts are composed of a mixture of undifferentiated cells of all cell types. These cells, as they mature, migrate towards the villi, until they are eliminated by desquamation towards the lumen.

Stem cells are also renewed at each mitotic division, as one daughter cell will be a stem cell, while the other will differentiate into a specific cell type. These processes are regulated by the expression of the following genes: MATH1, Cdx1 or Cdx2.

Function of the Lieberkühn crypts

It plays a very important role in the renewal of the epithelium of the intestinal mucosa, since it has the pluripotent cells that give rise to the various types of cells present in the crypt itself and in the villi.

In addition, it is also highly relevant in the process of digestion and absorption of nutrients, due to the functions performed by each of the differentiated cells in the crypt.

References

1. Villi, crypts, and the life cycle of enterocytes. Available at: saber.ula.ve/
2. "Lieberkühn Crypts". Wikipedia, the free encyclopedia. Apr 8 2019, 02:24 UTC. Apr 8 2019, 02:24
3. Herrería E. Small intestine and pathologies associated with intestinal malabsorption. Valdecillas Health House, University of Cantabria. 2013.Available at: repositorio.unican.es
4. Ferrufino J, Taxa L, Ángeles G. Normal histology of the small intestine. Rev Med Hered 1996; 7: 46-57. Available at: scielo.org.
5. López P. (2014). Usefulness of histopathology in intestinal transplantation in adults: macroscopic, microscopic and immunocystic study of biopsies and resection pieces of intestinal grafts: HU Transplant Program October 12. Thesis to Opt for the Degree of Doctor. Complutense University of Madrid. Available at: eprints.ucm.es/