histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

, an intestinal gland (also

crypt A crypt (from Greek κρύπτη (kryptē) ''wikt:crypta#Latin, crypta'' "Burial vault (tomb), vault") is a stone chamber beneath the floor of a church or other building. It typically contains coffins, Sarcophagus, sarcophagi, or Relic, religiou ...

of Lieberkühn and intestinal crypt) is a

gland A gland is a Cell (biology), cell or an Organ (biology), organ in an animal's body that produces and secretes different substances that the organism needs, either into the bloodstream or into a body cavity or outer surface. A gland may also funct ...

found in between villi in the intestinal epithelial lining of the

small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...

and

large intestine The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the Digestion, digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces befor ...

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

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

, which contains multiple types of cells:

enterocytes 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 i ...

(absorbing water and electrolytes),

goblet cells Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 2 in the lower gastrointestinal tract, and mucin 5AC in the respiratory tract. The goblet cells mainly use the merocrine method of secretion, secreting ...

(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 ...

(secreting hormones), cup cells,

myofibroblast A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell. Structure Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-s ...

tuft cell Tuft cells are chemosensory cells in the epithelial lining of the intestines. Similar tufted cells are found in the respiratory epithelium where they are known as brush cells. The name "tuft" refers to the brush-like microvilli projecting from ...

s, and at the base of the gland, Paneth cells (secreting anti-microbial peptides) and

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

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 vertebrates, including mammals, reptiles, and birds. In mammals, it may be the principal site for iron absorption. The duodenum precedes the jejunum and ileum and is the shortest p ...

jejunum The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialized for the absorption by enterocytes of small nutrient molecules which have been pr ...

, and

ileum The ileum () is the final 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 posterior intestine or distal intestine may ...

, and in the

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

Paneth cell 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 located below the intestinal stem cells in th ...

s of the

innate immune system The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...

, and

goblet cell Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 2 in the lower gastrointestinal tract, and mucin 5AC in the respiratory tract. The goblet cells mainly use the merocrine method of secretion, 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 ...

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 ...

contain

digestive enzyme Digestive enzymes take part in the chemical process of digestion, which follows the mechanical process of digestion. Food consists of macromolecules of proteins, carbohydrates, and fats that need to be broken down chemically by digestive enzymes ...

s that digest specific foods while they are being absorbed through the epithelium. These enzymes include

peptidase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do ...

sucrase Sucrases are digestive enzymes that catalyze the hydrolysis of sucrose to its component monosaccharides, fructose and glucose. One form, sucrase-isomaltase, is secreted in the small intestine on the brush border. The enzyme invertase, which occurs ...

maltase Maltase is an informal name for a family of enzymes that catalyze the hydrolysis of disaccharide maltose into two simple sugars of glucose. Maltases are found in plants, bacteria, yeast, humans, and other vertebrates. Digestion of starch requi ...

lactase Lactase () is an enzyme produced by many organisms and is essential to the complete digestion of whole milk. It breaks down the sugar lactose into its component parts, galactose and glucose. Lactase is found in the brush border of the small ...

and intestinal

lipase In biochemistry, lipase ( ) refers to a class 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; howe ...

. This is in contrast to the gastric glands of the

stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...

where chief cells secrete

pepsinogen Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids. It is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pe ...

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

. During each

mitosis Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...

, 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. These stem cells can differentiate into either an absorptive (

) or secretory (

Goblet cells Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 2 in the lower gastrointestinal tract, and mucin 5AC in the respiratory tract. The goblet cells mainly use the merocrine method of secretion, secreting ...

, Paneth cells,

) lineages. Both Wnt and Notch signaling pathways play a large role in regulating cell proliferation and in intestinal

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...

and

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

. 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 (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

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 Brunner's glands (or duodenal glands) are compound tubuloalveolar submucosal glands found in that portion of the duodenum proximal to the hepatopancreatic sphincter (i.e sphincter of Oddi). For decades, it was believed that the main function of ...

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 duodenum ...

.''Guyton and Hall Textbook of Medical Physiology'', 11th edition, p. 805 Its function is to complete the process begun by

pancreatic juice Pancreatic juice is a liquid secreted by the pancreas, which contains a number of digestive enzymes, including trypsinogen, chymotrypsinogen, elastase, carboxypeptidase, pancreatic lipase, nucleases and amylase. The pancreas is located in th ...

; the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

trypsin Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the dig ...

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 that counteracts the inhibitory effect of intestinal bile acid on the enzymatic activity of pancreatic lipase. It is secreted by the pancreas in an Zymogen, inactive form, procolipase, which is a ...

is necessary, along with

bile salts Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...

, to enable

function. Intestinal juice also contains

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

mucus Mucus (, ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both Serous fluid, serous and muc ...

, substances to neutralize

hydrochloric acid Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...

coming from the

. Various

exopeptidase An exopeptidase is any peptidase that catalyzes the cleavage of the terminal (or the penultimate) peptide bond; the process releases a single amino acid, dipeptide or a tripeptide from the peptide chain. Depending on whether the amino acid is r ...

which further digests

polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

s into

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s complete the digestion of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

Colonic crypts

The intestinal glands in the colon are often referred to as colonic crypts. The

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

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 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 used ...

protein called

cytochrome c oxidase subunit I Cytochrome c oxidase I (COX1) also known as mitochondrially encoded cytochrome c oxidase I (MT-CO1) is a protein that is encoded by the ''MT-CO1'' gene in eukaryotes. The gene is also called ''COX1'', ''CO1'', or ''COI''. Cytochrome c oxidase ...

(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 Haematoxylin American and British English spelling differences#ae and oe, or hematoxylin (), also called natural black 1 or Colour Index International, C.I. 75290, is a chemical compound, compound extracted from wood#Heartwood and sapwood, heart ...

. 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 and mDNA) is the DNA located in the mitochondrion, mitochondria organelles in a eukaryotic cell that converts chemical energy from food into adenosine triphosphate (ATP). Mitochondrial DNA is a small portion of the 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 Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

is known as '' cryptitis'' and characterized by the presence of

neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...

s 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, usually caused by bacterial infection. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pre ...

. 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 inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...

(e.g.

ulcerative colitis Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...

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, fever, abdominal distension, and weight loss. Complications outside of the ...

), * 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 (ischemia). Although uncommon in the general population, ischemic colitis occurs ...

. File:Crypt branching high mag.jpg,

Micrograph A micrograph is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnify, magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken ...

showing intestinal crypt branching, a

histopathological Histopathology (compound of three Greek language, Greek words: 'tissue', 'suffering', and ''-logy, -logia'' 'study of') is the light microscope, microscopic examination of Tissue (biology), tissue in order to study the manifestations of dis ...

finding of chronic colitides.

H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin–eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diag ...

. File:Cryptitis high mag.jpg,

showing crypt inflammation.

. 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 niches, and to generate intestinal organoids.

History

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

References

External links

Illustration at trinity.edu

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