Intestinal epithelium
The intestinal epithelium is the single cell layer that forms the luminal surface of both the small and large intestine of the gastrointestinal tract. Composed of simple columnar epithelium its main functions are absorption, and secretion. Useful substances are absorbed into the body, and the entry of harmful substances is restricted. Secretions include mucins, and peptides.
Absorptive cells in the small intestine are known as enterocytes, and in the colon they are known as colonocytes. The other cell types are the secretory cells – goblet cells, Paneth cells, enteroendocrine cells, and Tuft cells. Paneth cells are absent in the colon.
As part of its protective role, the intestinal epithelium forms an important component of the intestinal mucosal barrier. Certain diseases and conditions are caused by functional defects in the intestinal epithelium. On the other hand, various diseases and conditions can lead to its dysfunction which, in turn, can lead to further complications.
Structure
The intestinal epithelium is part of the mucosal lining. The epithelium is simple cuboidal epithelium composed of a single layer of cells, while the other two layers of the mucosa, the lamina propria and the muscularis mucosae, support and communicate with the epithelial layer. To securely contain the contents of the intestinal lumen, the cells of the epithelial layer are joined together by tight junctions, thus forming a contiguous and relatively impermeable membrane.Epithelial cells are continuously renewed every 4–5 days through a process of cell division, maturation, and migration. Renewal relies on proliferative cells that reside at the crypt of the intestinal glands. After being formed at the base, the new cells migrate upwards and out of the crypt, maturing along the way. Eventually, they undergo apoptosis and are shed off into the intestinal lumen. In this way, the lining of the intestine is constantly renewed while the number of cells making up the epithelial layer remains constant.
In the small intestine, the mucosal layer is specially adapted to provide a large surface area in order to maximize the absorption of nutrients. The expansion of the absorptive surface, 600 times beyond that of a simple cylindrical tube, is achieved by three anatomical features:
- Circular folds are transverse folds that slow the passage of the luminal contents and serve to expand the total surface area threefold.
- Villi and intestinal glands serve to increase the mucosal surface area tenfold.
- Microvilli covering the apical surface of the enterocytes increase the absorptive surface twentyfold. These numerous microscopic finger-like projections form an undulated brush border.
Cell types
Different cell types are produced by the stem cells that reside at the base of the crypts. Each type matures according to its specific differentiation program as it migrates up and out of the crypt. Many of the genes necessary for differentiation into the different epithelial cell types have been identified and characterized.The cell types produced are: enterocytes , Goblet cells, enteroendocrine cells, Paneth cells, microfold cells, cup cells and tuft cells. Their functions are listed here:
- Enterocytes known as colonocytes in the colon, are the most numerous and function primarily for nutrient absorption. Enterocytes express many catabolic enzymes on their exterior luminal surface to break down molecules to sizes appropriate for uptake into the cell. Examples of molecules taken up by enterocytes are: ions, water, simple sugars, vitamins, lipids, peptides and amino acids.
- Goblet cells secrete the mucus layer which protects the epithelium from the luminal contents.
- Enteroendocrine cells secrete various gastrointestinal hormones including secretin, pancreozymin, enteroglucagon among others. Subsets of sensory intestinal epithelial cells synapse with nerves, and are known as neuropod cells.
- Paneth cells produce antimicrobial peptides such as human alpha-defensin.
- Microfold cells sample antigens from the lumen and deliver them to the lymphoid tissue associated with the mucosa. In the small intestine, M cells are associated with Peyer's patches.
- Cup cells are a distinct cell type that produces vimentin.
- Tuft cells play a part in the immune response.
Structural components of cellular junctions
Important for the barrier function of intestinal epithelium, its cells are joined securely together by four types of cell junction which can be identified at the ultrastructural level:- Gap junctions
- Desmosomes
- Adherens junctions
- Tight junctions
Gap junctions
Desmosomes
These complexes, consisting of transmembrane adhesion proteins of the cadherin family, link adjacent cells together through their cytoskeletons. Desmosomes leave a gap of 30 nanometers between cells.Adherens junctions
Adherens junctions, also called zonula adherens, are multiprotein complexes formed by proteins of the catenin and cadherin families. They are located in the membrane at the contact points between the cells. They are formed by interactions between intracellular adapter proteins, transmembrane proteins and the actin cytoskeletons of the cells. Besides their role in linking adjacent cells, these complexes are important for regulating epithelial migration, cell polarity, and the formation of other cell junction complexes.Tight junctions
Tight junctions, also called zonula occludens, are the most important components of the intestinal epithelium for its barrier function. These complexes, formed primarily of members of the claudin and the occludin families, consist of about 35 different proteins, form a ring shaped continuous ribbon around the cells, and are located near the borders of the lateral and apical membranes.The extracellular domains of the transmembrane proteins in adjacent cells cross connect to form a tight seal. These interactions include those between proteins in the same membrane and proteins in adjacent cells. In addition, interactions can be homophilic or heterophilic.
Similar to adherens junctions, the intracellular domains of tight junctions interact with different scaffold proteins, adapter proteins and signaling complexes to regulate cytoskeletal linking, cell polarity, cell signaling and vesical trafficking.
Tight junctions provide a narrow but modifiable seal between adjacent cells in the epithelial layer and thereby provide selective paracellular transport of solutes. While previously thought to be static structures, tight junctions are now known to be dynamic and can change the size of the opening between cells and thereby adapt to the different states of development, physiologies and pathologies. They function as a selective and semipermeable paracellular barrier between apical and basolateral compartments of the epithelial layer. They function to facilitate the passage of small ions and water-soluble solutes through the paracellular space while preventing the passage of luminal antigens, microorganisms and their toxins.
Physiology
The intestinal epithelium has a complex anatomical structure which facilitates motility and coordinated digestive, absorptive, immunological and neuroendocrine functions.The mucus secreted by goblet cells acts as a lubricant and protects the epithelial cell layer against irritation from mucosal contents.
Traditionally, crypt cells were considered primarily as secretory cells while enterocytes are considered principally absorptive. However, recent studies have challenged this classical functional partitioning and have shown that both the surface and crypt cells can perform both secretory and absorptive functions and that, in fact, these functions can occur simultaneously.
Nutrient uptake
Overlaying the brush border of the apical surface of the enterocytes is the glycocalyx, which is a loose network composed of the oligosaccharide side chains of integral membrane hydrolases and other enzymes essential for the digestion of proteins and carbohydrates. These glycoproteins, glycolipids, and enzymes catalyze the final digestive stages of luminal carbohydrates and proteins. The monosaccharides and amino acids thus produced are subsequently transported across the intestinal epithelium and eventually into the bloodstream.The absorption of electrolytes and water is one of the most important functions of the digestive tract. Water absorption is passive and isotonic - depending on the speed and direction of solute flow. Other factors influencing fluid absorption are osmolarity and the specific intestinal region. Regulated selective permeability is performed through two major routes: the transcellular route and the paracellular route.