Crypt (anatomy)

A crypt is a narrow but deep invagination of an epithelial surface into the tissue beneath it, and it is one of the commonest ways by which an epithelium increases its surface area.

Crypts occur in the intestine, tonsils, cervix, anus and several other organs, and each type has its own cellular content and clinical behaviour.

The word comes from the Greek kryptē, meaning hidden place, and it was applied to glands and recesses long before their microscopic structure was known.

Definition

• A crypt is defined by depth greater than width, which distinguishes it from a simple pit or fossa.
• Most crypts are lined by epithelium that continues from the surface, so the crypt lumen is continuous with the lumen of the organ.
• Crypts may be simple tubular invaginations or branching structures with secondary outpouchings, and the branching pattern differs between organs.
• The term is not synonymous with gland, because a crypt may contain several cell types and may serve immune or stem-cell functions rather than secretion alone.
• Crypts are usually surrounded by a specialised lamina propria that carries capillaries, immune cells and fibroblasts.

Types

• The intestinal crypts of Lieberkühn are tubular invaginations between villi or between colonic surface cells, and they open onto the mucosal surface.^[1]
• Each intestinal crypt contains stem cells at its base, Paneth cells, goblet cells, enterocytes and enteroendocrine cells at different levels.
• Tonsillar crypts are deep branching clefts that extend into the lymphoid tissue of the palatine, lingual and pharyngeal tonsils.
• Because tonsillar crypts open to the pharynx, they expose deep lymphoid tissue to antigens and also to infection.
• The anal crypts and anal sinuses lie at the dentate line and are the origin of most cryptoglandular anal fistulas.
• Cervical crypts are the glandular invaginations of the endocervical mucosa, and their mucus secretion changes with the menstrual cycle.
• Gastric pits are sometimes called gastric crypts, although they are shallow surface invaginations rather than deep tubular glands.
• Urethral lacunae, also called crypts of Morgagni, are small recesses of the urethral mucosa that can harbour infection.

Structure

• An intestinal crypt is a test-tube-shaped structure with a base, a proliferative zone and a neck that opens between villi.
• The crypt base columnar cells are slender cycling stem cells that sit between Paneth cells and give rise to the whole epithelial lineage.
• Paneth cells occupy the crypt base in the small intestine and secrete antimicrobial peptides such as lysozyme and defensins.
• The crypt lumen is normally tight, and the paracellular space is sealed by junctional complexes between neighbouring epithelial cells.
• Tonsillar crypts have a non-keratinised stratified squamous lining that is infiltrated by lymphocytes and antigen-presenting cells.
• The lamina propria around a crypt contains a vascular plexus and a network of myofibroblasts that support epithelial renewal.

Function

• Intestinal crypts house the stem-cell niche that replaces the epithelium every few days, making them central to gut homeostasis.
• Paneth cells at the crypt base shape the microbial community by secreting antimicrobial peptides and by regulating stem-cell signalling.
• Crypt cells also secrete fluid and electrolytes, and this secretion contributes to the watery environment of the gut lumen.
• Tonsillar crypts increase the surface area available for sampling inhaled and ingested antigens, which supports local immune surveillance.
• Anal crypts allow small amounts of glandular secretion into the anal canal and serve as a route for cryptoglandular infection.
• Cervical crypts produce mucus that changes viscosity across the cycle and influences sperm transport and cervical barrier function.

Development

• Intestinal crypts form after birth in humans, when the flat neonatal mucosa is remodelled into villi and crypts.
• Crypt formation depends on Wnt signalling, and loss of Wnt activity prevents the epithelial invagination that creates a crypt.
• The crypt-villus axis is a classic model of a stem-cell compartment and a differentiated compartment separated in space.
• Tonsillar crypts develop as the lymphoid tissue expands and the surface epithelium is pushed inward during fetal and early postnatal life.
• Anal crypts are remnants of the embryonic anal membrane and the proctodeal invagination, and their position marks the dentate line.

Clinical significance

• Crypt abscesses in the colon are collections of neutrophils within crypt lumina and are a hallmark of active ulcerative colitis.
• Crypt distortion and branching are chronic histological features of inflammatory bowel disease and help distinguish it from acute infection.
• Tonsillar crypt infection can lead to recurrent tonsillitis, crypt abscesses and peritonsillar abscess.
• Cryptoglandular anal fistula begins with infection of an anal crypt and tracks through the intersphincteric or transsphincteric plane.
• Cervical crypt obstruction can produce Nabothian cysts, which are benign retention cysts of the cervix.
• Crypt cells are the target of enteric pathogens such as Salmonella and Cryptosporidium, which exploit the stem-cell niche.
• Radiation and chemotherapy preferentially damage the proliferative crypt compartment, producing mucositis and diarrhoea.

Comparative anatomy

• Crypts are widespread among vertebrates, and the intestinal crypt-villus unit is most elaborate in mammals and birds.
• Fish and amphibians have simpler intestinal folds and fewer true crypts, and their epithelial renewal relies more on scattered proliferating cells.
• Tonsillar crypts vary greatly among mammals, and species with extensively crypted tonsils are more prone to chronic tonsillar infection.
• The anal crypts of mammals are homologous in position but differ in depth, which influences the prevalence of perianal fistula across species.

History

• The intestinal crypts were described by Johann Nathanael Lieberkühn in the eighteenth century, and his name remains attached to them.
• Nineteenth-century histologists recognised that crypts are lined by continuously renewing epithelium, but the stem-cell model was only established in the twentieth century.
• The crypt-villus axis became a model system for adult stem cells after lineage-tracing experiments in the 2000s.
• Terminologia Histologica distinguishes cryptae from glandulae, although clinical usage often treats the two loosely.

Research and controversies

• Whether the intestinal crypt base contains one homogeneous stem-cell population or several competing populations is still debated.
• Organoid culture has shown that a single crypt stem cell can regenerate a full epithelial organoid, which supports the stem-cell model.
• The origin of crypt abscesses in ulcerative colitis, whether from crypt epithelium or from invading neutrophils, remains incompletely understood.
• Three-dimensional imaging has revealed that crypt branching is more complex than two-dimensional sections suggest, which complicates counts used in pathology.