Introductory Chapter: Structure and Functions of the Small Intestine

1. Introduction

The small intestine is a tubular structure that connects the stomach to the colon.  The intestinal mucosa is the innermost layer that is in contact with the intestinal lumen.

It is constituted by a glandular epithelium supported on the lamina propria, below which, the muscular layer is located. The folds on its surface, called conniving valves or Kerckring folds, that are formed by mucosa and submucosa, while the villi that project on its surface, are covered only by the mucosal layer, being its height greater in the proximal sections of the duodenum and jejunum to decrease progressively toward the ileum. This design of the intestinal mucosa, forming folds alternating with villi, is aimed at obtaining the maximum possible nutrient absorption surface. At the base of the villi lie the crypts of Lieberkühn, which form glandular structures that extend to the muscularis mucosa [1].

2. Microscopic structure

In the intestinal epithelium, both at the level of the villi and in the crypts, five types of cells are identified, which are the following:

1. Enterocytes: These are the epithelial cells responsible for absorbing nutrients. Their surface is covered with microvilli, which further increase the absorption surface, containing numerous enzymes for their functions.

2. Goblet cells: They are responsible for the secretion of mucus that acts as a lubricant and protector.

3. Paneth cells: They have phagocytic and lysozyme elimination capacity, playing an important role in the regulation of the microbiota and in the immune defense mechanisms.

4. Entero-endocrine cells: They secrete different hormones with important functions on intestinal motility and secretion, such as cholecystokinin (CCK), secretin, neurotensin, peptide YY, ghrelin, and gastric inhibitory peptide (GIP).

5. M cells: They are located in the domes of the lymphoid aggregates and have a relevant function, which consists of transporting various tumors, both food and bacteria, toward the underlying lymphoid tissue.

The lamina propria on which the epithelial cells are located is made up of a connective component and gut-associated lymphoid tissue. Its main function is to participate in the defense against microorganisms and other pathogens.

3. Intestinal absorption

There are three main mechanisms that are carried out mainly through the apical membrane of the enterocytes.

1. Passive diffusion: It does not need carrier molecules and does not consume energy. It is produced by a concentration gradient from the intestinal lumen.

2. Facilitated diffusion: There is also a concentration gradient, but a specific carrier protein is also involved, which facilitates the passage of the nutrient through the membrane of the enterocyte.

3. Active transport: A carrier protein intervenes, which requires a cellular energy supply. In this way, the substance can be absorbed although there is no greater intraluminal gradient.

Prior to intestinal absorption, a process of chemical and mechanical digestion of foods takes place, which begins in the mouth, through chewing and salivary secretion, and continues in the stomach, by mixing food with gastric juice rich in pepsin. In this way, food is converted into substances capable of crossing the epithelial barrier and passing into the blood and lymphatic circulation [2].

At the level of the brush border formed by the intestinal microvilli of the enterocytes, some enzymes are located, which are not released into the intestinal lumen, carrying out there, various specific hydrolytic functions against disaccharides, peptides, and other nutrients.

4. Microbiota

The organization of the small intestine is in the form of a model of strata formed through the creation of the intestinal barrier in which two layers are located, one “external” (consisting of the microbiota, the mucous layer, and the intestinal epithelium) that acts as an anatomical and, therefore, physical barrier, preventing their adhesion and other more “internal,” mainly formed by the GALT (gut-associated lymphoid tissue), responsible for the production of the immune response and tolerance mechanisms. The correct interrelation between both layers contributes to maintaining proper functioning of the small intestine, actively ensuring its intestinal permeability.

The microbiota contributes to the digestion and recovery of energy from dietary waste and the production of vitamins and hormones. It prevents the growth of pathogenic bacteria, increasing its protection and local defense. It also contributes to trophism, favoring the production of mucin, as well as the proliferation and differentiation of the intestinal epithelium. It also exerts immunological functions, participating in the development and maturation of the immune system [3].

5. Mucosal immune system

Peyer’s patches located at the level of the submucosa are sites of controlled uptake of antigens and activation of naive T and B lymphocytes. They are made up of several aggregates of B cells (lymphoid follicles) surrounded by rings of T cells, and also by antigen-presenting cells (APC), usually macrophages.

The epithelium that covers the dome of the lymphoid aggregates contains M cells, with the capacity to transport antigens from the intestinal lumen to the underlying lymphoid tissue, together with dendritic cells located in the lamina propria, whose formation is induced by various factors produced by the epithelial cells through stimulation of Toll-like receptors (TLR).

The products captured and processed by the APCs are presented to the naive T lymphocytes, initiating clonal expansion to collaborator or helper lymphocytes (Th1 or Th2) or regulatory T lymphocytes (Th3, Tr1, or CD25+/CD4+).

Following the process of antigenic stimulation, lymphocytes migrate into the mesenteric lymph nodes where further antigenic exposure and clonal expansion occur, then passing into the systemic circulation, returning to other mucosal surfaces, forming the so-called associated lymphoid tissue to the mucous membranes [4].

The humoral response occurs with the binding of the antigen to the IgM membrane of the B lymphocyte. The action signal generated by this binding stimulates a clonal expansion and as a consequence. The induction by antigen-specific T lymphocytes, or mediated by various factors, an additional differentiation takes place, which includes several processes of reorganization of the immunoglobulin chains, mainly of the IgA type. Activated B lymphocytes undergo a terminal differentiation process and become as plasma cells [5].

Secretory IgA (sIgA) is a powerful protector of the intestinal mucosa against bacterial invasions, constituting the first line of defense against multiple external infections including various viruses and other pathogens.