Introduction

A gland is a functional unit of cells that works together to create and release a product into a duct or directly to the bloodstream. Two principal types of glands exist: exocrine and endocrine. The key difference between the two types is that, whereas exocrine glands secrete substances into a ductal system to an epithelial surface, endocrine glands secrete products directly into the bloodstream [1]. Exocrine secretions form in the acinus, a small cluster of cells at the origination of glandular ducts. Exocrine glands subclassify into subtypes based on the method of secretion, the compound produced, or the shape of the gland.

Issues of Concern

This article will discuss:

• Various cell types found within the exocrine gland, and their functions
• Embryologic development of exocrine glands
• Organ systems impacted by exocrine physiology
• Functions of exocrine glands
• Related clinical testing
• Pathophysiology of exocrine glands
• Significant clinical aspects

Cellular Level

Exocrine glands are comprised of an acinus and a duct with different cell types, respectively. These glands are found in many organs within the body and demonstrate a large variety in the function of their secretions.  As such, a wide range of cell types exists in exocrine glands.

While the duct functions primarily to transport glandular secretions, the acinus is responsible for the production of glandular secretions, and as such, shows more variety in cellular composition. Typical cell types within the acinus include serous, mucinous, or sebaceous.

• Serous cells secrete an isotonic fluid that contains proteins such as enzymes. Salivary glands are made up of serous cells to a large extent [2].
• Mucinous glands secrete mucus, a typical example being Brunner glands in the duodenum.
• Sebaceous glands secrete sebum, an oily compound. Sebaceous glands are most prevalent in the face, scalp, groin, and armpits. Cell types can be differentiated histologically as well.  Mucous cells typically stain lighter than their serous counterparts when stained with hematoxylin and eosin.

As ducts move from the acinus toward the final target, secretions initially enter the intralobular duct. Intralobular ducts have a simple cuboidal epithelium commonly surrounded by parenchyma. Intralobular ducts drain into interlobular ducts, which are a simple columnar epithelium. The final ductal unit is the interlobar duct recognized by a stratified columnar epithelium. Connective tissue surrounds both interlobular and interlobar ducts.

Development

The initial manifestation of exocrine gland formation is epithelial budding resulting from a complex interaction between mesenchymal and epithelial cell populations [3]. This initial period of ingrowth is influenced by fibroblast growth factors, most notably FGF10 and cadherin-2 [4]. Other transcription factors that have been shown to contribute to epithelial budding include HlxB9, Isl1, LEF-1, Msx1/2, Pbx1, Pdx1, and Tbx3 [5].

Following the initial formation of the epithelial bud, ductal elongation occurs. This process undergoes mediation by a large group of molecular signals such as Netrin-1, TIMP1, amphiregulin, IGF1, and leukemia inhibitory factor [5]. Several matrix metalloproteinases (MMPs) contribute assistance with basement membrane renewal and facilitate ductal elongation [6][7]. After an initial period of ductal elongation, the exocrine gland begins to form ductal branches. NF-kappa-B is thought to play a role [8], as well as sonic hedgehog and Wnts [3]. As the duct begins to elongate, the acinus undergoes a period of cell proliferation and differentiation. Due to the large variety in exocrine gland function, the exact number of cellular signals and interactions is immense. In general, however, a large role exists for cell adhesion molecules such as laminin and cadherins [9].

Exocrine morphogenesis is a rapid process. Ductal elongation and branching typically occur in less than a week, with acini formation occurring 5 to 9 days later [10][11]. In a relatively short developmental period, exocrine glands form and can begin secreting a functional product.

Organ Systems Involved

Due to the diverse number and function of epithelial surfaces in the body, many organ systems utilize exocrine glands to carry out their respective actions. Several examples will be included here, including skin, mouth, stomach, pancreas, duodenum, and breasts. 

Skin

The skin has a variety of exocrine glands, including the eccrine sweat glands and sebaceous glands. Eccrine sweat glands are the most widespread sweat gland in the body and are present on nearly every external body surface. The sweat produced is clear with little to no oil, in contrast to sebaceous glands, also found on the skin, which secretes the more oily substance sebum.  

Salivary Glands

The salivary glands in the mouth are another example of exocrine glands and include the parotid glands, submandibular glands, and sublingual glands. While each gland has a unique mixture of serous and mucous cells, together, the salivary glands act to begin the process of food digestion while also lubricating and protecting the mucosal surfaces.

Stomach

The stomach holds multiple types of exocrine glands that include pyloric glands, cardiac glands, and fundic glands. These glands incorporate many different cell types, including parietal cells, chief cells, and G cells. Together they regulate the gastric pH, release enzymes to breakdown food products to a digestible form, and assist with the absorption of necessary vitamins and minerals.  

Pancreas

The pancreas has both an endocrine and an exocrine function. The exocrine pancreas assists in food digestion by releasing a secretion rich in bicarbonate, which helps to neutralize the acidic environment created in the stomach. The secretion also includes digestive enzymes.

Duodenum

Brunner glands are present in the duodenum of the small intestine. These exocrine glands are submucosal and produce a mucous product that protects the duodenum from acid released from the stomach. The alkaline nature of the secretion also activates intestinal enzymes to assist with food breakdown and absorption.

Breast

The mammary gland is one of the most well-known examples of an exocrine gland found in the breast. Mammary glands produce milk rich in nutrients that also provides passive immunity to a baby’s immune system.

Function

The specific function of exocrine glands within the body varies by location and organ system. However, the primary role is to create a secretion which subsequently gets released through a ductal system onto an epithelial surface. Examples include secretions that assist in food digestion, mucosal protection, thermoregulation, lubrication, and nutrition.

Mechanism

The three mechanisms by which exocrine glands release their secretions include merocrine, apocrine, and holocrine.

• Merocrine glands are the most common subtype. By definition, merocrine gland secretions exit the cell via exocytosis. In this method of secretion, there is no cell damage. An example of merocrine secretion is the eccrine sweat gland. 
• Apocrine glands, in contrast, form buds of the membrane which break off into the duct, losing part of the cellular membrane in the process. A well-known apocrine gland is the breastmilk-producing mammary gland. 
• The final subtype of excretion is holocrine, in which the cellular membrane ruptures to release its product into the duct. Sebaceous glands are a representation of holocrine secretion.

Related Testing

In general, testing for an individual exocrine gland function is not performed. However, dysfunction of exocrine glands can create a wide range of clinical manifestations.

Imaging may be performed to confirm a diagnosis of blocked glands. Sialolithiasis refers to instances where a stone becomes lodged within the salivary gland or duct, and sialoadenitis refers to inflammation of the gland. CT and ultrasound are effective methods of identifying and localizing stones [12].

The liver itself acts as an exocrine gland when creating and excreting bile to be stored in the gallbladder, awaiting expulsion and release through the pancreatic duct into the duodenum. Obstruction, at any point in this pathway, can cause cholecystitis due to inflammation and dysfunction of the gallbladder. Ultrasound is the initial diagnostic test to diagnose cholecystitis [13].

In cystic fibrosis, sodium and chloride are not reabsorbed within the sweat duct due to a dysfunctional CFTR protein, resulting in abnormally salty skin. The sweat chloride test is the primary test for the diagnosis of cystic fibrosis [14].

Pancreatic insufficiency occurs when the exocrine glands of the pancreas are no longer able to produce the digestive enzymes necessary for food breakdown in the small intestine. Common etiologies include chronic pancreatitis, cystic fibrosis, and hereditary hemochromatosis. Several methods can be used to evaluate the function of the exocrine pancreas. Fat malabsorption can lead to deficiencies in fat-soluble vitamins A, D, E, and K. Thus, vitamin levels can be used to estimate pancreatic function [15]. Fecal elastase-1 testing is another method with relatively high specificity and sensitivity. Low levels of fecal elastase-1 indicate a poorly functioning exocrine pancreas [16]. The most sensitive diagnostic method for exocrine pancreatic insufficiency, however, is utilizing direct pancreatic function tests such as the cholecystokinin (CCK) or secretin stimulation test [17].

Pathophysiology

Sjogren Syndrome

Sjogren’s syndrome is commonly associated with rheumatoid arthritis and other rheumatic diseases. The syndrome is an autoimmune disorder that demonstrates decreased lacrimal and salivary gland function that can also have associated systemic symptoms [18][19]. The disease is characterized by eye and mouth dryness due to the gland dysfunction.  Due to mouth dryness, patients with Sjogren syndrome show increased rates of oral candidiasis and dental caries [18][20]. 

Cystic Fibrosis

Cystic fibrosis is an autosomal recessive disease that causes impaired chloride transport due to a mutation of the CFTR protein.  Because CFTR is involved in the production of sweat, mucus, and digestive fluids, the mutation causes a direct effect on exocrine gland secretions.  Indeed, approximately 90% of infants born with cystic fibrosis will develop pancreatic insufficiency by one year of age [21].

Acne vulgaris

The prevalence of acne is an estimated 35 to 90% in adolescents [22]. The disorder affects the pilosebaceous unit, of which sebaceous glands are an example. The pathogenesis is multifactorial and often involves hyperkeratinization of the follicle, increased sebum production, and proliferation of Propionibacterium acnes with associated inflammation. As sebum accumulates, an open comedo forms, also known as a white head. Hyperkeratinization and increased sebum production lead to clogging of the pores of the pilosebaceous unit. As the lipids within sebum oxidize, the follicular orifice opens, forming an open comedo, or blackhead.

Treatment for acne largely depends on the severity of inflammatory symptoms, but topical retinoids are usually the first-line treatment, although antimicrobial agents are an additional option for refractory cases [23]. For severe cases of nodulocystic acne or for patients who have failed treatment with systemic antibiotics, oral isotretinoin the therapeutic choice [24].

Clinical Significance

The exocrine gland can be found in many organs and serves a wide variety of functions within the body. Due to this fact, an understanding of the physiology of exocrine glands is essential for healthcare workers. Exocrine glands play a key role in the physiology of many organ systems from the skin to the pancreas, providing the body with a method to release secretions containing proteins, mucus, and other products to epithelial surfaces around the body. Owing to their varied and essential roles, the dysfunction of exocrine glands is associated with diseases as wide-ranging as acne vulgaris to Sjogren syndrome.