Ductal cells

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Ductal cells refer to the epithelial cell lining of the pancreatic duct that deliver enzymes from the acinar cells to the duodenum. They have the essential function of producing bicarbonate-rich (HCO3-) secretion to neutralize stomach acidity. The hormone secretin stimulates ductal cells and is responsible for maintaining the duodenal pH and preventing duodenal injury from acidic chyme. Ductal cells mix their production with acinar cells to make up the pancreatic juice. [1]

Contents

A diagram of the acinar cells in the pancreas, and will deliver enzymes from the acinar cells to the duodenum. 2424 Exocrine and Endocrine Pancreas.jpg
A diagram of the acinar cells in the pancreas, and will deliver enzymes from the acinar cells to the duodenum.

Ductal cells comprise about 10% of the pancreas by number and about 4% in volume. Its function is to secrete bicarbonate and mucins and to form the tubule network that transfers enzymes made by acinar cells to the duodenum. Ductal cells have a proliferation rate of about 0.5% in normal adults, but mitotic activity goes up when the pancreas is damaged. [3]

Ductal network

The ductal pancreas network originates from the central pancreatic duct—this main duct with the bile duct opens into the duodenum. The ductal cells of the main pancreatic duct are bound by connective tissue and produce a columnar epithelium. [3] Interlobular ducts originate from the main pancreatic duct and connect the various pancreatic lobes. In these lobes, the intercalated ducts expel acini. Meanwhile, the ductal cells of these intercalated ducts create a simple squamous epithelium that rapidly converts into simple cuboidal, and connective tissue also surrounds them. [3] As the ducts grow larger, the epithelium becomes cuboidal or columnar (when large in diameter, the ducts become stratified cuboidal), and connective tissue surrounds them. Pancreatic ductal cells are very similar to ductal cells of other exocrine glands (liver, bile duct, salivary glands). [3] Because of this, a common diagnosis affects these cells: cystic fibrosis.

Ductal cell physiology

While ductal cells are a minor type of cell in the adult pancreas, they have a critical function besides making the network that transfers enzymes from acini to the digestive tract. The primary function of pancreas ductal cells is to secrete a bicarbonate-rich, isotonic fluid. This fluid washes away the inactive form of digestive enzymes in the ductal system, neutralizes stomach acidity and mucins, and creates a pH environment necessary for the pancreas's normal function. [4]

Multiple factors affect the rate of bicarbonate secretion: species, cell location in the ductal system, secretory rate, etc. When stimulated, bicarbonate levels can get to 140mM. Due to this, there is a contrast in concentration between the outside and inside environment of ductal cells. The channels and ion transporters on ductal cells vary on the luminal and basolateral membrane, meaning there is functional polarization of the ductal cell. [4]  

The largest network branches in this system contain goblet cells that interact with ductal cells, making up about 2% of this structure—these cells aid mucin assembly. Furthermore, unlike other exocrine glands, the pancreas does not have myoepithelial cells around the ducts. [3] Ductal cells have a single cilium that is made up of nine peripheral doublets but does not have a central microtubule. This cilium is considered vital for perceiving flow in ducts. [3]

Ductal System of the Exocrine Pancreas by Phase Contrast Ductal System of the Exocrine Pancreas by Phase Contrast (40759036833).jpg
Ductal System of the Exocrine Pancreas by Phase Contrast

Exocrine cell type

Morphology is what identifies ductal cells. However, there is barely anything to differentiate pancreatic ductal cells from other bodily ductal cells. [6] There is still a lot unknown about these ductal cells. Their molecular identity still needs to be improved; more knowledge is necessary regarding stage-specific markers and the regulators of ductal cell development. It recently was discovered that the ducts start as separate microlumens in a stratified epithelium that expand, attach, and resolve to form the pancreatic ducts. These cells work with intercalating ducts that link to distinct acini and are within the larger ducts in the two core pancreatic ducts (dorsal and ventral duct) that drain into the intestine. [6]

Ductal cells are exocrine, but they are more like endocrine cells when developing. A recent lineage analysis showed that ductal cells came directly from bipotent precursor cells and have the possibility of creating either ductal or endocrine cells. Meanwhile, mature ducts have a restricted ability to transdifferentiate to other types of cells, even when the pancreas is injured. [6]

Ductal cell plasticity

There is disagreement about the plasticity potential of ductal cells in the adult pancreas. In the embryonic pancreas, the endocrine and exocrine cells originate in the pancreatic ducts as progenitor cells. [7] In adult ductal cells, there are observations that these cells take on the identity of progenitor cells when stressed. This proposes the idea that there might be a subgroup of ductal cells that have the ability to dedifferentiate and generate endocrine cells when there is an injury to the pancreas. [7] Essentially, ductal cells function in retaining the adult pancreas β cell mass when injured. However, there is a possibility that this capability is limited to a subtype of ductal cells only, meaning this cannot be a main pathway for pancreas regeneration. [7]

Associated pathologies

Cystic fibrosis

Human cystic fibrosis transmembrane conductance regulator (CFTR) Human cystic fibrosis transmembrane conductance regulator (CFTR).png
Human cystic fibrosis transmembrane conductance regulator (CFTR)

Cystic fibrosis affects pancreatic ducts as well as many other secretory epithelia. Cystic fibrosis transmembrane conductance regulator (CFTR) is the mutated gene and is essential to chloride and bicarbonate secretion. [3] The abnormal amount of anion secretion causes a reduced amount of ductal water flow. Because of this, the duct's protein concentration increases and causes the duct lumina to get plugged. The onset of cystic fibrosis affects the pancreas more than any other organ (even before birth). [3]

Pancreatitis

The incorrect activation of proteolytic enzymes leads to edema, inflammation, and possible pancreas necrosis, causing acute pancreatitis. The most prominent cause of acute pancreatitis is gallstones. [3] Permanent damage is possible from chronic pancreatitis due to progressive inflammation and the reoccurrence of acute pancreatitis. Acute pancreatitis is caused by mutations in a trypsinogen inhibitor, while a mutation in CFTR causes chronic pancreatitis. In fact, chronic pancreatitis often causes pancreatic adenocarcinoma. [3]

Pancreatic ductal adenocarcinoma

Tissue necrosis in chronic pancreatitis Tryptic fat tissue necrosis in severe pancreatitis, HE 2.JPG
Tissue necrosis in chronic pancreatitis
A breast duct with ductal carcinoma in situ (DCIS) Nci-vol-4353-300 ductal carcinoma in situ.jpg
A breast duct with ductal carcinoma in situ (DCIS)

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal cancers and has an expected survival of five years. [11] Pancreatic adenocarcinoma cells resemble pancreatic ductal cells. Both cell groups show tubule formation, cuboidal shape, and ductal markers. Additionally, acinar and endocrine cells have often been found in many of these cancers, demonstrating plasticity and the possibility that the initial target cells are pancreas progenitor cells. [3] Moreover, human tumors usually go with lower-grade lesions that are called pancreatic intraepithelial neoplasias (PanINs) and are in ducts. Because these lesions are in ducts, this means that it is possible that the beginning target cells are ductal cells.

Breast ductal carcinoma

Ductal carcinoma in situ (DCIS) is the proliferation of malignant ductal cells without penetrating the stromal tissue around them. [12] In other words, DCIS is the presence of abnormal cells in a breast's milk duct. It is thought to be the earliest form of breast cancer and is noninvasive (it has not spread from the milk duct and has a low risk of becoming invasive). [13] DCIS can be differentiated into groups based on low, intermediate, and high grade. When comparing the growth potential of normal epithelial cells to DCIS, it is 10 times larger, and the apoptosis rate was also 15 times greater. Furthermore, comedo-type DCIS usually causes necrosis in the duct center and has a more significant threat of reappearance. [12]

The majority of ductal carcinomas are positive for luminal cell markers (CK8, CK18, CK19) but negative for basal cellmarkers (CK5/6 and CK14). In 30% of cases, DCIS is multifocal and usually is in the same breast. There is axillary lymph node invasion in 2-6% of DCIS cases. DCIS is frequently found during mammograms and makes up 25% of screen-detected breast cancers. [12]

The degree of the disease in the breast determines DCIS treatment. In widespread or multifocal DCIS patients, a mastectomy is the recommended choice with the chance of reconstruction. [13] Further clinical trials are being worked on to find an alternative to surgery.

There is not a clear cause for DCIS. This type of cancer comes from genetic mutations in the breast duct cells' DNA. The mutations make the cells look abnormal, but these cells are still not able to leave the breast duct. It is unknown what the exact cause is of this abnormal cell growth that causes DCIS. However, factors that potentially have a role are lifestyle, environment, and passed-down genes. [13]

Related Research Articles

<span class="mw-page-title-main">Pancreas</span> Organ of the digestive system and endocrine system of vertebrates

The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e., it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins and fats in food entering the duodenum from the stomach.

<span class="mw-page-title-main">Exocrine gland</span> Gland that secretes substances onto an epithelial surface by way of a duct

Exocrine glands are glands that secrete substances onto an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous, lacrimal, sebaceous, prostate and mucous. Exocrine glands are one of two types of glands in the human body, the other being endocrine glands, which secrete their products directly into the bloodstream. The liver and pancreas are both exocrine and endocrine glands; they are exocrine glands because they secrete products—bile and pancreatic juice—into the gastrointestinal tract through a series of ducts, and endocrine because they secrete other substances directly into the bloodstream. Exocrine sweat glands are part of the integumentary system; they have eccrine and apocrine types.

<span class="mw-page-title-main">Chronic pancreatitis</span> Medical condition

Chronic pancreatitis is a long-standing inflammation of the pancreas that alters the organ's normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption. It is a disease process characterized by irreversible damage to the pancreas as distinct from reversible changes in acute pancreatitis. Tobacco smoke and alcohol misuse are two of the most frequently implicated causes, and the two risk factors are thought to have a synergistic effect with regards to the development of chronic pancreatitis. Chronic pancreatitis is a risk factor for the development of pancreatic cancer.

<span class="mw-page-title-main">Digestive enzyme</span> Class of enzymes

Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption into the cells of the body. Digestive enzymes are found in the digestive tracts of animals and in the tracts of carnivorous plants, where they aid in the digestion of food, as well as inside cells, especially in their lysosomes, where they function to maintain cellular survival. Digestive enzymes of diverse specificities are found in the saliva secreted by the salivary glands, in the secretions of cells lining the stomach, in the pancreatic juice secreted by pancreatic exocrine cells, and in the secretions of cells lining the small and large intestines.

<span class="mw-page-title-main">Cystic fibrosis transmembrane conductance regulator</span> Mammalian protein found in humans

Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the CFTR gene.

<span class="mw-page-title-main">Pancreatectomy</span> Surgical removal of the pancreas

In medicine, a pancreatectomy is the surgical removal of all or part of the pancreas. Several types of pancreatectomy exist, including pancreaticoduodenectomy, distal pancreatectomy, segmental pancreatectomy, and total pancreatectomy. In recent years, the TP-IAT has also gained respectable traction within the medical community. These procedures are used in the management of several conditions involving the pancreas, such as benign pancreatic tumors, pancreatic cancer, and pancreatitis.

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 the visceral region, and is a major part of the digestive system required for proper digestion and subsequent assimilation of macronutrient substances required for living.

<span class="mw-page-title-main">Exocrine pancreatic insufficiency</span> Human disease

Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack or reduction of digestive enzymes made by the pancreas. EPI can occur in humans and is prevalent in many conditions such as cystic fibrosis, Shwachman–Diamond syndrome, different types of pancreatitis, multiple types of diabetes mellitus, advanced renal disease, older adults, celiac disease, IBS-D, IBD, HIV, alcohol-related liver disease, Sjogren syndrome, tobacco use, and use of somatostatin analogues.

Pancreatic diseases are diseases that affect the pancreas, an organ in most vertebrates and in humans and other mammals located in the abdomen. The pancreas plays a role in the digestive and endocrine system, producing enzymes which aid the digestion process and the hormone insulin, which regulates blood sugar levels. The most common pancreatic disease is pancreatitis, an inflammation of the pancreas which could come in acute or chronic form. Other pancreatic diseases include diabetes mellitus, exocrine pancreatic insufficiency, cystic fibrosis, pseudocysts, cysts, congenital malformations, tumors including pancreatic cancer, and hemosuccus pancreaticus.

Pancreatic elastase is a form of elastase that is produced in the acinar cells of the pancreas, initially produced as an inactive zymogen and later activated in the duodenum by trypsin. Elastases form a subfamily of serine proteases, characterized by a distinctive structure consisting of two beta barrel domains converging at the active site that hydrolyze amides and esters amongst many proteins in addition to elastin, a type of connective tissue that holds organs together. Pancreatic elastase 1 is a serine endopeptidase, a specific type of protease that has the amino acid serine at its active site. Although the recommended name is pancreatic elastase, it can also be referred to as elastase-1, pancreatopeptidase, PE, or serine elastase.

<span class="mw-page-title-main">Acinus</span> Multi-lobed biological cell structure

An acinus refers to any cluster of cells that resembles a many-lobed "berry," such as a raspberry. The berry-shaped termination of an exocrine gland, where the secretion is produced, is acinar in form, as is the alveolar sac containing multiple alveoli in the lungs.

The secretin-cholecystokinin test is a combination of the secretin test and the cholecystokinin test and is used to assess the function of both the pancreas and gall bladder.

Pancreatic stellate cells (PaSCs) are classified as myofibroblast-like cells that are located in exocrine regions of the pancreas. PaSCs are mediated by paracrine and autocrine stimuli and share similarities with the hepatic stellate cell. Pancreatic stellate cell activation and expression of matrix molecules constitute the complex process that induces pancreatic fibrosis. Synthesis, deposition, maturation and remodelling of the fibrous connective tissue can be protective, however when persistent it impedes regular pancreatic function.

<span class="mw-page-title-main">Neurogenin-3</span> Mammalian protein found in Homo sapiens

Neurogenin-3 (NGN3) is a protein that in humans is encoded by the Neurog3 gene.

<span class="mw-page-title-main">Canine pancreatitis</span>

Canine pancreatitis is inflammation of the pancreas that can occur in two very different forms. Acute pancreatitis is sudden, while chronic pancreatitis is characterized by recurring or persistent form of pancreatic inflammation. Cases of both can be considered mild or severe.

Cystic fibrosis–related diabetes (CFRD) is diabetes specifically caused by cystic fibrosis, a genetic condition. Cystic fibrosis related diabetes mellitus (CFRD) develops with age, and the median age at diagnosis is 21 years. It is an example of type 3c diabetes – diabetes that is caused by damage to the pancreas from another disease or condition.

<span class="mw-page-title-main">Pancreatic tumor</span> Medical condition

A pancreatic tumor is an abnormal growth in the pancreas. In adults, almost 90% are pancreatic cancer and a few are benign. Pancreatic tumors are rare in children.

<span class="mw-page-title-main">Human digestive system</span> Digestive system in humans

The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion. Digestion involves the breakdown of food into smaller and smaller components, until they can be absorbed and assimilated into the body. The process of digestion has three stages: the cephalic phase, the gastric phase, and the intestinal phase.

<span class="mw-page-title-main">Pancreatic progenitor cell</span>

Pancreatic progenitor cells are multipotent stem cells originating from the developing fore-gut endoderm which have the ability to differentiate into the lineage specific progenitors responsible for the developing pancreas.

Heterocrine glands are the glands which function as both exocrine gland and endocrine gland. These glands exhibit a unique and diverse secretory function encompassing the release of proteins and non-proteinaceous compounds, endocrine and exocrine secretions into both the bloodstream and ducts respectively, thereby bridging the realms of internal and external communication within the body. This duality allows them to serve crucial roles in regulating various physiological processes and maintaining homeostasis. These include the gonads, pancreas and salivary glands.

References

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