Eccrine and apocrine sweat glands

 

Salient features

 

·       Eccrine sweat glands are activated by emotional and thermal stimuli and are necessary for thermoregulation; they have a generalized distribution, with the highest density on the palms and soles

 

·       The eccrine secretory unit consists of a coiled secretory portion that drains into a long thin duct whose apical portion (acrosyringium) opens to the skin surface

·       Up to 10 L/day of sweat is produced by acclimatized individuals.

·       Hypothalamic temperature is the strongest stimulus for sweating.

 

·       Innervation of eccrine glands consists of postganglionic sympathetic fibers that have acetylcholine as the principal neurotransmitter

 

·       Apocrine sweat glands are androgen-dependent for their development and have an unclear function in humans; primary locations are the axillae, anogenital region, periumbilical region and nipples

 

·       Apocrine glands, whose apical portion (acrosyringium) drains into terminal hair follicles, continuously secrete a sterile odorless viscous fluid that is rich in precursors of odoriferous substances

 

·       Bacteria are necessary for apocrine  odor

 

Introduction

 

The major sweat glands in humans are eccrine and apocrine glands. They vary in type and density, depending on anatomic location. In addition to their well-established role in thermoregulation, eccrine sweat glands have immunomodulatory, antimicrobial and excretory functions. Apocrine sweat is an odorless viscous fluid that contains precursors of odoriferous substances.

 

 

CHARACTERISTICS OF SWEAT GLANDS
	Eccrine	Apocrine
Localization	Entire body skin, highest density on palms and soles	Axillae, anogenital, periumbilical, nipples and areolae
Morphology	Long, thin duct opens to skin surface	Short, thick duct opens into upper part of follicular canal
	Secretory coil with narrow lumen	Secretory coil with wide lumen
Cell types in secretory coil	Large secretory clear cells, dark cells, and myoepithelial cells	Epithelial (typically cuboidal) and myoepithelial cells
Main innervation/neurotransmitter	Sympathetic fibers/acetylcholine	Unclear/possible humoral effects of β-adrenergic receptor agonists
Development	Present at birth	Present at birth
	No relationship to pilosebaceous follicle	Associated with terminal hair follicle
Function/pathogenic role	Thermoregulation/role in hyperhidrosis and hypohidrosis	Unclear/some role in olfactory communication; role in follicular apocrine Fox–Fordyce disease

 

 

In humans, there are two main types of sweat glands: eccrine and apocrine. They are distinct from one another structurally, developmentally and functionally

 

Eccrine Sweat Glands

 

Structure

 

Approximately 1.5 to 4 million eccrine sweat glands are distributed over the entire cutaneous surface, with the exception of the external auditory canals, vermilion lips, clitoris, and labia minora. The highest density is found on the palms and soles. The eccrine secretory unit consists of a proximal coiled secretory portion in the lower dermis and subcutaneous tissue. This drains into a long thin duct with an apical portion (acrosyringium) that opens directly onto the skin surface. The secretory coils contain two cell types interspersed within a single cell layer: (1) large clear cells responsible for the gland’s secretion of electrolytes and water; and (2) dark cells, of unknown function, with basophilic granules that are thought to produce sialomucin. Both cell types are surrounded by myoepithelial cells, which probably function to enhance the delivery of sweat to the skin surface. The ductal epithelium is composed of two or more layers of cuboidal cells without surrounding myoepithelium. The intraepidermal portion of the duct, the acrosyringium, is twisted like a corkscrew with similar coils in the stratum corneum. Stem cell markers (e.g. prominin-1/CD133) are expressed in the secretory and ductal portions of eccrine glands.

 

Innervation of the eccrine glands is provided by postganglionic sympathetic fibers that have acetylcholine (not norepinephrine) as their principal terminal neurotransmitter. These sympathetic fibers are controlled by the hypothalamic sweat center. The sweat center responds to its own temperature (as a reflection of core body temperature) as well as neural stimuli from the periphery.

 

 

INNERVATION AND RECEPTOR PROFILES OF SWEAT GLANDS
	Eccrine	Apocrine
Nerve fibers near gland	+	±
Cholinergic muscarinic (M3) receptors	++	±
α1-adrenergic receptors	+	−
β2- > β3-adrenergic receptors	+	+
Purinergic receptors	+	+

 

Development

 

During embryogenesis, at 3 months’ gestation, sweat glands begin to develop as cords of epithelial cells that bud from the epidermal ridges on the palms and soles. By 5 months’ gestation, similar structures have appeared over the remainder of the body. Functional eccrine glands are present at birth and react to thermal and emotional stimuli. Unlike apocrine glands, they have no developmental relationship with the pilosebaceous follicle.

 

Function

 

Eccrine sweat is a sterile, dilute electrolyte solution that contains primarily sodium chloride (NaCl), potassium and bicarbonate. Other components include antimicrobial peptides (e.g. dermcidin), proteolytic enzymes, glucose, pyruvate, lactate, urea, ammonia, calcium, amino acids, epidermal growth factor, cytokines and immunoglobulins. In addition, other organic compounds and heavy metals such as arsenic, cadmium, lead, and mercury are excreted in sweat. A recent study demonstrated that sweat activates NF-κB, ERK and JNK pathways in keratinocytes, resulting in the upregulation of interleukin (IL)-8 and IL-1β production. Keratinocyte outgrowths from eccrine sweat glands also have a role in re-epithelialization of human wounds.

 

The quantity and quality of eccrine sweat secretion varies greatly, depending on emotional and environmental stimuli. Under maximal stimulation, the body can produce 3 liters in 1 hour. Sweat is formed in two steps: (1) release of nearly isotonic primary sweat by the secretory coil; and (2) partial reabsorption of NaCl by duct cells, resulting in the delivery of a hypotonic fluid to the skin surface. The final concentration of NaCl may be higher when sweat is produced at a more rapid rate. The neuropeptide galanin and its receptors were recently shown to regulate transepithelial ion transport and fluid secretion from human eccrine sweat glands.

 

Continuous secretion of sweat provides a mechanism for thermoregulation via evaporative heat loss, maintenance of electrolyte balance, and keeping the stratum corneum moist to ensure fine tactile skills and pliability of the palms and soles. The excretory function of the sweat gland can be instrumental in the delivery of systemically administered drugs to the stratum corneum (e.g. ketoconazole, griseofulvin), and it provides an explanation for cutaneous side effects of certain chemotherapeutic drugs. Botulinum toxin can be used to treat eccrine hyperhidrosis. After dermal injection, botulinum toxin taken up by the nerve terminal interferes with proteins required to release acetylcholine at the neuroglandular junction

 

Apocrine Sweat Glands

Structure

 

Apocrine sweat glands are confined to certain anatomic locations (axillae, anogenital region, periumbilical area, areolae, nipples, vermilion border of the lip) and are larger than eccrine glands. Modified forms of apocrine glands are found in the external auditory canals (ceruminous glands) and on the eyelid margins (glands of Moll). Apocrine glands consist of a secretory portion, which is located in the deep dermis and subcutaneous fat, and a stretched duct that opens into the upper portion of the follicular canal, i.e., the apocrine acrosyringium. The secretory unit is a convoluted tube with a single layer of epithelial cells (typically columnar) surrounded by myoepithelial cells. The duct consists of a double layer of cuboidal cells, as well as myoepithelial cells that support the movement of secretions to the skin surface.  immunohistochemical staining may help to differentiate between apocrine and eccrine sweat glands (e.g. CD15 staining of apocrine but not eccrine secretory cells).

 

Apocrine gland secretion increases in response to local or systemic administration of catecholamines and cholinergic agonists, but the mechanisms controlling physiologic secretion are poorly understood. In normal axillary skin, secretory coils of apocrine glands have β-adrenergic and purinergic, but not cholinergic, receptors. Nerve fibers are found near eccrine glands but not apocrine glands, suggesting that catecholamines stimulate the latter through humoral mechanisms.

 

Development

 

Embryologically, the apocrine sweat gland is derived from the primary epithelial germ layer, which also gives rise to the sebaceous gland and hair follicle. In the embryo, apocrine sweat glands are present over the entire skin surface, but most of them subsequently disappear, resulting in the characteristic distribution found in adults. Enlargement of the glands occurs with the approach of puberty due to hormonal stimulation, primarily by androgens.

 

Function

 

Apocrine glands continuously secrete very small quantities of an oily fluid. This sweat is sterile, odorless and viscous, with a pH between 5.0 and 6.5. It is rich in precursors of odoriferous substances such as cholesterol, triglycerides, fatty acids, cholesterol esters, and squalene. It also contains androgens, carbohydrates, ammonia, and ferric iron. Apocrine or “decapitation” secretion refers to the “pinching off” and release of the luminal portion of secretory cells; apocrine glands also employ merocrine (exocytosis of vesicles) and holocrine (rupture of the plasma membrane) secretion.

In humans, apocrine glands do not have a clear function but may play some role in olfactory communication.

 

Pathophysiology

 

Although apocrine sweat is initially sterile and odorless, bacteria on the skin surface modify and degrade the secreted substances, resulting in rancid (Corynebacterium spp.) or sweaty (Micrococcus spp.) body odor termed bromhidrosis. When biopsies from bromhidrosis patients have been compared with controls, the apocrine glands were more abundant and larger with active decapitation. These histologic differences may reflect increased production of apocrine sweat and thus may help explain bromhidrosis. Insufficient body and textile hygiene will worsen the condition. Of note, some androgenic steroids have an odor similar to natural axillary odor.

 

Apocrine chromhidrosis refers to the secretion of pigmented (yellow, green, or black) sweat. It is a reflection of the rich lipofuscin content of apocrine sweat. Pseudo- or extrinsic apocrine chromhidrosis results from staining of the sweat by chromogenic bacteria, especially Corynebacterium spp., or colored garments.