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SMALL INTESTINE
The small intestine is the site of terminal food digestion, metabolite absorption, and
endocrine secretion.
The small intestine consists of 3 segments: duodenum, jejunum, and ileum, which have
many characteristics in common.
I. MUCOUSA
The lining of the small intestine shows a series of permanent folds, plicae circulares
(Kerckring’s valves), consisting of mucosa and submucosa and having a semilunar, circular, or
spiral form. The plicae are most developed in, and consequently a characteristic of, the jejunum.
Intestinal villi, 0.5-1.5 mm long, are outgrowths of the mucosa (epithelium plus lamina propria)
projecting into the lumen of the small intestine. In the duodenum they are leaf-shaped, gradually
assuming the form of a finger as the ileum is reached (fig.1).
Between the villi are small openings of simple tubular glands called intestinal glands
(crypts, or glands of Lieberkun) that extend from the intervillous spaces to the muscularis
mucosae [Fig.1].
1. Epithelium
The epithelium of the small intestine is a simple columnar type. The epithelium of the
villi is composed of absorptive, goblet and some endocrine cells. The epithelium of the villi is
continuous with that of the glands. In the intestinal glands one finds mainly undifferentiated
cells, some absorptive cells, goblet cells, Paneth cells, and enteroendocrine cells.
Absorptive cells are tall columnar cells, each with an oval nucleus in the basal half of the
cell. At the apex of each cell is a layer of densely packed microvilli. Each microvillus is a
cylindrical extension of the apical cytoplasm and consists of a cell membrane enclosing a core of
20-30 actin-containing microfilaments that are cross-linked to each other and to the surrounding
plasma membrane by several other proteins. The basal ends of these microfilaments intermingle
with microfilaments of the terminal web found just beneath the microvilli. Each microvillus is
approximately 1 μm tall x 0.1 μm in diameter. It is estimated that each absorptive cell has an
average of about 3000 microvilli and that 1 mm 2 of mucosa contains about 200 million of these
structures. Covering the microvillus is a filamentous coat, the glycocalyx, which contains
glycoproteins. The complex of microvilli and glycocalyx is called striated (brush) border.
Microvilli have the important physiologic function of considerably increasing the area of contact
between the intestinal surface and food. The striated border of these cells is the site of activity of
the disaccharides and dipeptides into monosaccharides and amino acids that are easily absorbed.
Another important function of the columnar intestinal cells is to absorb the metabolites that
result from the digestive process. So, the brush border is the site of very high concentration of
various digestive and transporting enzymes. The cytoplasm of the absorptive cells has numerous
mitochondria, smooth and rough reticulum, and Golgi complex.
Goblet cells are interspersed between the absorption cells (Fig.1). They are less abundant
in the duodenum and increase in number as the ileum is approached. These cells produce acid
glycoproteins whose main function is to protect and lubricate the lining of the intestine.
Mucinogen appears in membrane-bounded granules in the apical region of the cell. Mucinogen
accumulation distends the apical region of the cell, which is known as the theca. When released,
mucinogen is converted to mucus. The region of the cell that houses the nucleus and other
organelles is the stem.
Paneth cells are found at the basal portion of the intestinal glands. They are exocrine
serous cells with large acidophilic secretory granules, containing protein-polysaccharide
complex, Zn, and lysozyme. Lysozyme possesses antibacterial activity and may play a role in
controlling the intestinal flora.
M (membranous) cells are specialized epithelial cells overlying the lymphoid follicles of
Peyer’s patches. These cells are characterized by the presence of numerous membrane
invaginations forming pits at their apical and lateral surfaces that contain intraepithelial
lymphocytes. M cells can endocytose antigens and transport them to the underlying lymphoid
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cells that then migrate to the lymphoid nodes, where immune responses to foreign antigens are
initiated. The basement membrane is discontinuous under M cells, facilitating transit between the
lamina propria and M cells.
Endocrine cells are especially numerous in the crypts. The most common cells of the
small intestine are EC-, G-, I-, S-, K- and D-cells (Table 1).
The stem cells and proliferating cell-precursors are situated at the lower half of the
crypts. From this proliferative zone most of differentiating cells migrate upward and differentiate
into absorptive or goblet cells of the villus epithelium. Replacement of these cell types occurs
every 1-4 days. Others stay at the site and become Paneth cells or enteroendocrine cells. These
cells turn over much more slowly, living about several weeks.
The high replacement rate explains why the intestine is promptly affected by the
administration of antimitotic drugs, as in cancer chemotherapy. The epithelial cells continue to
be lost at the tips of villi, but the drugs inhibit cell proliferation. This promotes atrophy of the
epithelium, which results in defective absorption of nutrients, excessive fluid loss, and diarrhea.
2. Lamina propria
The lamina propria of the small intestine is a loose connective tissue forming not only the
core of the villus but also the interstices between the crypts of the mucosa. It is infiltrated by
lymphoid cells, plasma cells, and macrophages, forming an immunologic barrier at this region. It
also possesses lymphatic nodules, blood and lymphatic vessels, smooth muscle cells, mast cells,
and neural elements.
The lamina propria penetrates the core of the intestinal villi, taking along blood and
lymph vessels, nerves, and smooth muscle cells. The smooth muscle cells are responsible for the
rhythmic movements of the villi, which are important for absorption.
3. The muscularis mucosae
The muscularis mucosae does not present any peculiarities in this organ and is composed
of an inner circular and an outer longitudinal layer of smooth muscle.
II. SUBMUCOSA
The submucosa is composed of fibroelastic connective tissue that contains blood and
lymphatic vessels, and the submucosal nerve plexus. In the duodenum, it also contains clusters of
compound, coiled tubular glands that open into the intestinal glands. These are the duodenal (or
Brunner’s) glands (fig.3). Their cells are of the mucous type. The product of secretion of the
glands is distinctly alkaline (pH 8.1-9.3). It acts to protect the duodenal mucous membrane
against the effects of the acid gastric juice and to bring the intestinal contents to the optimum pH
for pancreatic enzyme action. It also produce and release urogastrone, a polypeptide that
enhances epithelial cell division and inhibits HCl production.
The lamina propria and the submucosa of the small intestine contain diffuse lymphoid
tissue, solitary lymphoid nodules, and aggregates of lympoid nodules known as Peyer’s patches
(there are 50- 200 patches in the human, especially numerous in the ileum). All these elements
make up IALT – intestinal-associated lymphoid tissue. It is the largest part of the immune
system, containing about 40% of immune effector cells of the body, and composing about 25%
of the gut mass. Each Peyer’s patch consists of 10-400 secondary nodules (B-depending zones),
their crown is directed toward the epithelium. Internodular aggregations of lymphoid tissue
represent T-depending zones. When viewed from the luminal surface, each Peyer’s patch
appears as a dome-shaped area devoid of villi. Instead its covering epithelium consists of M
cells.
Vessels
The blood vessels that nourish the intestine and remove absorbed products of digestion
penetrate the muscularis and form a large plexus in the submucosa (Fig.4). From the submucosa,
branches extend through the muscularis mucosae and lamina propria and into the villi. Each
villus receives, according to its size, one or more branches that form a capillary network just
below its epithelium. At the tips of the villi, one or more venules arise from these capillaries and
run in the opposite direction, reaching the veins of the submucosal plexus. The lymph vessels of
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the intestine begin as blind tubes in the core of the villi. These vessels (lacteals) run to the region
of lamina propria above the muscularis mucosae, where they form a plexus. From there they are
directed to the submucosa, where they surround lymphoid nodules. These vessels anastomose
repeatedly and leave the intestine along with the blood vessels.
III. MUSCULARIS EXTERNA
The muscularis externa is composed of two layers of smooth muscle cells, an inner
circular layer and an outer longitudinal layer. Auerbach’s myenteric plexus is located between
these two layers.
IY. SEROSA
Adventitia and serosa cover the external aspect of the duodenum. Serosa covers the
jejunum and ileum.
HISTOPHYSIOLOGY
The presence of plicae, villi, and microvilli greatly increases the surface of the intestinal
lining – an important characteristic in an organ where absorption occurs so intensely. It has been
calculated that the presence of plicae increases the intestinal surface 3-fold, the villi increase it
10-fold, and the microvilli increase it 20-fold.
The digestive process is completed and its products are absorbed in the small intestine.
Lipid digestion occurs mainly as a result of the action of pancreatic lipase and bile. In humans,
most of the lipid absorption occurs in the duodenum and upper jejunum (Fig.5).
The amino acids and monosaccharides derived from digestion of proteins and
carbohydrates are absorbed by active transport. In newborns transfer of undigested proteins from
colostrums can be clearly observed as a result of pinocytotic processes in the cell apex. In this
way, antibodies secreted into the colostrums can be transferred. This capacity to transfer proteins
is almost completely lost after a few days.
Another process that is important for intestinal function is the rhythmic movement of the
villi. This is the result of the contraction of smooth muscle cells running vertically between the
muscularis mucosae and the tip of the villi. These movements occur at the rate of several strokes
per minute. During digestion, their rate increases. These contractions also tend to empty the
lymph vessels and propel the lymph and absorbed metabolites to the mesenteric lymphatics.
LARGE INTESTINE
The main functions of the large intestine are: 1) the absorption of water and electrolytes;
the absorption of water is passive, following active transport of sodium out of the basal surfaces
of the absorptive epithelial cells; 2) the absorption of products of the intestinal bacterial flora
activities: vitamins K (a cofactor of coagulation) and B12, as well as products of cellulose
hydrolysis; 3) formation of fecal mass (compacted dead bacteria and the indigestible remnants of
the ingested material).
I. MUCOSA
The large intestine consists of a mucosal membrane with no folds except in its distal
(rectal) portion. No villi are present in this portion of the intestine.
1. The epithelium is a simple, columnar epithelium.
The intestinal crypts are long and characterized by a great abundance of goblet and
absorptive cells and a small number of enteroendocrine cells (Fig.6). The numerous goblet
cells produce mucus, a highly hydrated gel that not only lubricates the intestinal surface but also
facilitates the passage and elimination of the feces. The absorptive cells are columnar and have
short, irregular microvilli. Dilated intercellular spaces filled by interdigitating membrane leaflets,
a sign of active water transport, are characteristic for the absorptive epithelium.
Stem and proliferating cells are disposed at the lower third of the crypts of the large
intestine. Epithelial cells of the large intestine are replaced about every 6 days.
2.The lamina propria is rich in lymphoid cells and nodules. The nodules frequently
extend into the submucosa. This richness in lymphoid tissue is probably the result of the
extremely abundant bacterial population present in the large intestine.
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3.The muscularis mucosae consists of an inner circular and an outer longitudinal layer
of smooth muscle cells.
II. SUBMUCOSA
Submucosa is composed of fibroelastic connective tissue. It contains blood and lymphatic
vessels, as well as the submucosal plexus. Glands are not present in the submucosa of this
region.
III. MUSCULARIS EXTERNA
This layer differs from that of the small intestine since fibers of the outer longitudinal
layer congregate in 3 thick longitudinal bands called teniae coli (Fig.7). Teniae coli when
continuously contracted form sacculations of the cecum and colon, known as the haustra coli.
IY. SEROSA
In the intraperitoneal portions of the colon, the serous layer is characterized by small,
pendulous protuberances composed of adipose tissue – the appendices epiploicae. Adventitia
covers the ascending and descending portions of the colon.
In the anal region, the mucous membrane forms a series of longitudinal folds, the rectal
columns of Morgagni. About 2 cm above the anal opening, the intestinal mucosa is replaced by
stratified squamous epithelium. In this region, the lamina propria contains a plexus of large veins
that, when excessively dilated and varicose, produce hemorrhoids.
APPENDIX
The appendix is an evagination of the cecum; it is characterized by a relatively small,
narrow, and irregular lumen that is caused by the presence of abundant lymphoid follicles in its
wall. Although its general structure is similar to that of the large intestine, it contains fewer and
shorter crypts and has no teniae coli. The crypts possess some goblet cells, surface columnar
cells, M-cells, regenerative cells, occasional Paneth cells, and numerous (especially deep in the
crypts) endocrine cells. Serosa completely surrounds the appendix.