In histology, an intestinal gland (also crypt of Lieberkühn and intestinal crypt) is a

gland In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormones) for release into the bloodstream (endocrine gland) or into cavities inside the body or its outer surface (exocrine gland). Structure De ...

found in between villi in the intestinal epithelium lining of the

small intestine The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...

and large intestine (or colon). The glands and intestinal villi are covered by

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

, which contains multiple types of cells: enterocytes (absorbing water and electrolytes),

goblet cells Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their secre ...

(secreting mucus),

enteroendocrine cells Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic ef ...

(secreting hormones), cup cells, tuft cells, and at the base of the gland,

Paneth cells Paneth cells are cells in the small intestine epithelium, alongside goblet cells, enterocytes, and enteroendocrine cells. Some can also be found in the cecum and vermiform appendix, appendix. They are below the intestinal stem cells in the intest ...

(secreting anti-microbial peptides) and

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

Structure

Intestinal glands are found in the epithelia of the

, namely the

duodenum The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...

, jejunum, and ileum, and in the large intestine (colon), where they are sometimes called ''colonic crypts''. Intestinal glands of the small intestine contain a base of replicating

s, Paneth cells of the

innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...

, and

goblet cell Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their secre ...

s, which produce mucus. In the colon, crypts do not have Paneth cells.

Function

The

enterocyte Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its ...

s in the small intestinal

mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...

contain digestive enzymes that digest specific foods while they are being absorbed through the epithelium. These enzymes include peptidase,

sucrase Sucrase is a digestive enzyme that catalyzes the hydrolysis of sucrose to its subunits fructose and glucose. One form, sucrase-isomaltase, is secreted in the small intestine on the brush border. The sucrase enzyme invertase, which occurs more commo ...

, maltase, lactase and intestinal

lipase Lipase ( ) is a family of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; however, these are usually tr ...

. This is in contrast to the gastric glands of the stomach where chief cells secrete

pepsinogen Pepsin is an endopeptidase that breaks down proteins into smaller peptides. It is produced in the gastric chief cells of the stomach lining and is one of the main digestive enzymes in the digestive systems of humans and many other animals, whe ...

. Also, new epithelium is formed here, which is important because the cells at this site are continuously worn away by the passing food. The basal (further from the intestinal lumen) portion of the crypt contains multipotent stem cells. During each

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...

, one of the two daughter cells remains in the crypt as a stem cell, while the other differentiates and migrates up the side of the crypt and eventually into the

villus Villus ( la, "shaggy hair", plural villi) may refer to: * Intestinal villus, refers to any one of the small, finger-shaped outgrowths of the epithelial lining of the wall of the intestine. Clusters of projections are referred as intestinal villi. ...

. These stem cells can differentiate into either an absorptive ( enterocytes) or secretory (

Goblet cells Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their secre ...

) lineages. Both Wnt and Notch signaling pathways play a large role in regulating cell proliferation and in intestinal morphogenesis and homeostasis. Loss of proliferation control in the crypts is thought to lead to

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

Intestinal juice

''Intestinal juice (''also called ''succus entericus'') refers to the clear to pale yellow watery secretions from the glands lining the

walls. The Brunner's glands secrete large amounts of alkaline mucus in response to (1) tactile or irritating stimuli on the duodenal mucosa; (2) vagal stimulation, which increases Brunner's glands secretion concurrently with increase in stomach secretion; and (3) gastrointestinal hormones, especially

secretin Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duode ...

.''Guyton and Hall Textbook of Medical Physiology'', 11th edition, p. 805 Its function is to complete the process begun by pancreatic juice; the enzyme trypsin exists in pancreatic juice in the inactive form trypsinogen, it is activated by the intestinal enterokinase in intestinal juice. Trypsin can then activate other protease enzymes and catalyze the reaction pro-colipase → colipase.

Colipase Colipase, abbreviated CLPS, is a protein co-enzyme required for optimal enzyme activity of pancreatic lipase. It is secreted by the pancreas in an inactive form, procolipase, which is activated in the intestinal lumen by trypsin. Its function i ...

is necessary, along with bile salts, to enable

function. Intestinal juice also contains hormones, digestive enzymes, mucus, substances to neutralize hydrochloric acid coming from the stomach. Various exopeptidase which further digests

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

s into amino acids complete the digestion of proteins.

Colonic crypts

The intestinal glands in the colon are often referred to as colonic crypts. The epithelial inner surface of the colon is punctuated by invaginations, the colonic crypts. The colon crypts are shaped like microscopic thick-walled test tubes with a central hole down the length of the tube (the crypt lumen). Four tissue sections are shown here, two (A and B) cut across the long axes of the crypts and two (C and D) cut parallel to the long axes. In these images the cells have been

stained A stain is a discoloration that can be clearly distinguished from the surface, material, or medium it is found upon. They are caused by the chemical or physical interaction of two dissimilar materials. Accidental staining may make materials app ...

to show a brown-orange color if the cells produce a

mitochondrial A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...

protein called cytochrome c oxidase subunit I (CCOI or COX-1). The nuclei of the cells (located at the outer edges of the cells lining the walls of the crypts) are stained blue-gray with haematoxylin. As seen in panels C and D, crypts are about 75 to about 110 cells long. The average crypt circumference is 23 cells. From the images, an average is shown to be about 1,725 to 2530 cells per colonic crypt. Another measure was attained giving a range of 1500 to 4900 cells per colonic crypt. Cells are produced at the crypt base and migrate upward along the crypt axis before being shed into the colonic lumen days later. There are 5 to 6 stem cells at the bases of the crypts. As estimated from the image in panel A, there are about 100 colonic crypts per square millimeter of the colonic epithelium. The length of the human colon is, on average 160.5 cm (measured from the bottom of the cecum to the colorectal junction) with a range of 80 cm to 313 cm. The average inner circumference of the colon is 6.2 cm. Thus, the inner surface epithelial area of the human colon has an area, on average, of about 995 cm², which includes 9,950,000 (close to 10 million) crypts. In the four tissue sections shown here, many of the intestinal glands have cells with a

mitochondrial DNA Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, such as adenosine triphosphate (ATP). Mitochondrial D ...

mutation in the CCOI gene and appear mostly white, with their main color being the blue-gray staining of the nuclei. As seen in panel B, a portion of the stem cells of three crypts appear to have a mutation in CCOI, so that 40% to 50% of the cells arising from those stem cells form a white segment in the cross cut area. Overall, the percentage of crypts deficient for CCOI is less than 1% before age 40, but then increases linearly with age. Colonic crypts deficient for CCOI reaches, on average, 18% in women and 23% in men, by 80–84 years of age. Crypts of the colon can reproduce by fission, as seen in panel C, where a crypt is dividing to form two crypts, and in panel B where at least one crypt appears to be fissioning. Most crypts deficient in CCOI are in clusters of crypts (clones of crypts) with two or more CCOI-deficient crypts adjacent to each other (see panel D).

Clinical significance

Crypt inflammation is known as '' cryptitis'' and characterized by the presence of neutrophils between the

s. A severe cryptitis may lead to a crypt

abscess An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...

. Pathologic processes that lead to Crohn's disease, i.e. progressive intestinal crypt destruction, are associated with branching of the crypts. Causes of crypt branching include: *

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...

(e.g. ulcerative colitis,

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...

), * persistent infectious colitides, and *

ischemic colitis Ischemic colitis (also spelled ischaemic colitis) is a medical condition in which inflammation and injury of the large intestine result from inadequate blood supply. Although uncommon in the general population, ischemic colitis occurs with greater ...

. File:Crypt branching high mag.jpg, Micrograph showing intestinal crypt branching, a histopathological finding of chronic

colitides Colitis is swelling or inflammation of the large intestine ( colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label ''colitis'' (without qualification) ...

. H&E stain. File:Cryptitis high mag.jpg, Micrograph showing crypt inflammation. H&E stain. File:Histopathology of a crypt abscess.jpg, Crypt abscess. H&E stain.

Research

Intestinal glands contain adult stem cells referred to as intestinal stem cells. These cells have been used in the field of stem biology to further understand

stem cell niche Stem-cell niche refers to a microenvironment, within the specific anatomic location where stem cells are found, which interacts with stem cells to regulate cell fate. The word 'niche' can be in reference to the ''in vivo'' or ''in vitro'' stem-cell ...

s, and to generate intestinal organoids.

History

The crypts of Lieberkühn are named after the eighteenth-century German anatomist

Johann Nathanael Lieberkühn Johann Nathanael Lieberkühn (5 September 1711, in Berlin – 7 October 1756, in Berlin) was a German physician. His middle name is sometimes misspelled ''Nathaniel''. Lieberkühn studied theology initially, and then moved to physics, in particu ...

References

External links

Illustration at trinity.edu

Illustration at uokhsc.edu
* {{Authority control Digestive system