Intestinal epithelium

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Intestinal epithelium

Simple columnar epithelial cells

Identifiers

FMA 17229

Anatomical terminology

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Epithelia

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The intestinal epithelium is the single cell layer that form the luminal surface

(lining) of both the small and large intestine (colon) of the gastrointestinal tract.
Composed of simple columnar epithelial cells, it serves two main functions:
absorbing useful substances into the body and restricting the entry of harmful
substances. 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.

Contents

 1Structure
o 1.1Cell types
o 1.2Structural components of cellular junctions
 1.2.1Gap junctions
 1.2.2Desmosomes
 1.2.3Adherens junctions
 1.2.4Tight junctions
 2Physiology
o 2.1Nutrient uptake
o 2.2Transcellular permeability
o 2.3Paracellular permeability
 3Functions
 4Importance for human health
 5See also
 6References

Structure[edit]
The intestinal epithelium is part of the intestinal mucosa layer. The epithelium is
composed of a single layer of cells. The other two layers of the mucosa,
the lamina propria and the muscularis mucosae, support and articulate the
epithelial layer. To securely contain of 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.
Proliferative stem cells residing at the base of the intestinal glands produce new epithelial cells which
migrate upwards and out of the crypt. Eventually, they are shed into the intestinal lumen

Drawing showing the relationship between villi and microvilli of the small intestine. The luminal surface
of the enterocytes have microvilli (1 micrometer long) while the cell layer itself is folded to form villi
(0.5-1.6 millimeters long) and crypts. Both serve to increase the total absorption surface of the
intestine.

Epithelial cells are continuously renewed every 4–5 days through a process of
cell division, maturation, and migration. Renewal relies on proliferative cells
(stem cells) that reside at the crypt (base) of the intestinal glands (epithelial
invaginations into the underlying connective tissue). [1] 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.[2] In this way, the lining of the intestine is constantly renewed while the
number of cells making up the epithelial layer remains constant. [3]
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: [4]
 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. (Intestinal villus)
 Microvilli covering the apical surface of the enterocytes increase the
absorptive surface twentyfold. These numerous microscopic (100
nanometers in diameter) finger-like projections form an undulated brush
border.

The brush border on the apical surface of the epithelial cells is covered
with glycocalyx, which is composed of oligosaccharides attached to membrane
glycoproteins and glycolipids.[5]

Transmission electron microscope image of a thin section cut through an epithelial cell. This image
shows that the luminal surface (apical end) of the cell is packed with microvilli that make up the
absorbing surface. Each microvillus is approximately 1 micrometers long and 0.1 micrometer in
diameter.

Cell types[edit]
Seven different cell types are produced by the stem cells that reside at the base
of the crypts.[6] 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 (see this table). The cell types produced are: enterocytes, Goblet
cells, enteroendocrine cells, Paneth cells, microfold cells, cup cells and tuft cells.
Their functions are listed here:[7]

Enterocytes 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 that protects the epithelium from the
lumenal contents.

Enteroendocrine cells secrete various gastrointestinal
hormones including secretin, pancreozymin, enteroglucagon among others.
Subsets of sensory intestinal epithelial cells synapse with nerves, [8] and are
known as neuropod cells.[9]

Paneth cells produce antimicrobial peptides such as human beta-
defensin.[10][11]

Microfold cells (commonly referred to as M cells) sample antigens from
the lumen and deliver them to the lymphoid tissue associated with the
mucosa (MALT). In the small intestine, M cells are associated with Peyer's
patches.

Cup cells are a distinct cell type but with no known function.

Tuft cells play a part in the immune response.[12]

Throughout the digestive tract, the distribution of the different types of epithelial
cells varies according to the function of that region. [3]
Structural components of cellular junctions[edit]

Types of cell junctions (click to enlarge).

Important for the barrier function of intestinal epithelium, its cells are joined
securely together by four types of junctions (cell junctions),[13] which can be
identified at the ultrastructural level:[14]

 Gap junctions
 Desmosomes
 Adherens junctions
 Tight junctions

Gap junctions[edit]
Gap junctions bring the adjacent cells within 2 nanometers of each other. They
are formed by several homologous proteins encoded by the connexin gene
family coming together to form a multiprotein complex. The molecular structure of
this complex is in the form of a hexamer. The complex, which is embedded in the
cell walls of the two joined cells, forms a gap or channel in the middle of the six
proteins. This channel allows various molecules, ions and electrical impulses to
pass between the two cells.[15]
Desmosomes[edit]
These complexes, consisting of transmembrane adhesion proteins of
the cadherin family, link adjacent cells together through their cytoskeletons.
[16]
 Desmosomes leave a gap of 30 nanometers between cells. [15]
Adherens junctions[edit]
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. [14]
Tight junctions[edit]
Tight junctions, also called zonula occludens, are the most important
components of the intestinal epithelium for its barrier function. [17] These
complexes, formed primarily of members of the claudin and the occludin families,
consist of about 35 different proteins,[13] form a ring shaped continuous ribbon
around the cells, and are located near the borders of the lateral and apical
membranes.[14]
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 ("cis") and proteins in adjacent cells ("trans"). In addition,
interactions can be homophilic (between identical proteins) or heterophilic
(between different proteins).[14]
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. [14]
Tight junctions provide a narrow but modifiable seal between adjacent cells in the
epithelial layer and thereby provide selective paracellular transport of solutes.
[14]
 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.
[17]
 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.[14]

Physiology[edit]
Further information: Intestinal permeability
The intestinal epithelium has a complex anatomical structure which
facilitates motility and coordinated digestive, absorptive, immunological and
neuroendocrine functions.[18]
The mucus secreted by goblet cells acts as a lubricant and protects the epithelial
cell layer against irritation from mucosal contents.[19]
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. [20][21]
Nutrient uptake[edit]
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.[5]
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.[18] Regulated selective
permeability is performed through two major routes: the transcellular
(transepithelial) route and the paracellular route. [14]
Transcellular permeability[edit]
Scheme of selective permeability routes of epithelial cells (red arrows). The transcellular (through the
cells) and paracellular (between the cells) routes control the passage of substances between the
intestinal lumen and blood.

This consists of specific transport of solutes across the epithelial cells. It is

predominantly regulated by the activities of specialised transporters that
translocate specific electrolytes, amino acids, sugars, short chain fatty acids and
other molecules into or out of the cell.[14]
Paracellular permeability[edit]
Paracellular permeability depends on transport through the spaces that exist
between epithelial cells. It is regulated by cellular junctions that are localized in
the laminal membranes of the cells.[14] This is the main route of passive flow of
water and solutes across the intestinal epithelium. Regulation depends on the
intercellular tight junctions which have the most influence on paracellular
transport.[22] Studies using the electron microscope showed that the electrical
resistance of epithelial layers depends on the complexity and number of
filaments within the tight junction transmembrane protein complexes. [18] Also,
the plasma membrane resistance and variable transmembrane conductance of
the epithelial cells can also modulate paracellular pathway function. [18]

Functions[edit]
The barrier formed by the intestinal epithelium separates the external
environment (the contents of the intestinal lumen) from the body[14] and is the
most extensive and important mucosal surface of body.[17]
The intestinal epithelium serves several crucial functions, exhibiting both innate
and adaptive immune features. It closely monitors its intracellular and
extracellular environment, communicates messages to neighbouring cells and
rapidly initiates active defensive and repair measures, if necessary. [23] On the one
hand, it acts as a barrier, preventing the entry of harmful substances such as
foreign antigens, toxins and microorganisms.[13][14] On the other hand, it acts as a
selective filter which facilitates the uptake of dietary nutrients, electrolytes, water
and various other beneficial substances from the intestinal lumen. [14]
When barrier integrity is lost, intestinal permeability increases and uncontrolled
passage of harmful substances can occur. This can lead to, depending on the
genetic predisposition of the individual, the development
of inflammation, infection, allergies, autoimmune diseases or cancer - within the
intestine itself or other organs.[18]
Although they primarily function as part of the digestive system, enterocytes of
the intestinal epithelium also express toll-like receptors and nucleotide
oligomerization domain proteins that recognize diverse types of microbes and
contribute to immune system function.[24][25] Thus the intestinal epithelium not only
serves as a physical barrier separating the intestinal lumen from the body proper
but also carries out pathogen recognition functions as part of the intrinsic immune
system.

Importance for human health[edit]

Loss of integrity of the intestinal epithelium plays a key pathogenic role
in inflammatory bowel disease (IBD).[26] Changes in the composition of
the intestinal microbiota are an important environmental factor in the
development of IBD. Detrimental changes in the intestinal microbiota induce an
inappropriate (uncontrolled) immune response that results in damage to the
intestinal epithelium. Breaches in this critical barrier (the intestinal epithelium)
allow further infiltration of microbiota that, in turn, elicit further immune
responses. IBD is a multifactorial disease that is nonetheless driven in part by an
exaggerated immune response to gut microbiota that causes defects in epithelial
barrier function.[27]

See also[edit]
 Intestinal mucosal barrier
 Intestinal permeability

References[edit]
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