Medical Physiology, 3rd Edition


Eccrine, but not apocrine, sweat glands contribute to temperature regulation

Sweat glands are exocrine glands of the skin, formed by specialized infoldings of the epidermis into the underlying dermis. Sweat glands are of two types, apocrine and eccrine (Fig. 60-9A). The apocrine sweat glands, located in the axillary and anogenital regions of the body, are relatively few in number (~100,000) and large in diameter (2 to 3 mm). Their ducts empty into hair follicles. These glands, which often become active during puberty, produce a turbid and viscous secretion that is rich in lipids and carbohydrates and carries a characteristic body odor that has spawned an entire industry to conceal. Apocrine sweat glands have no role in temperature regulation in humans, although they may act as a source of pheromones.


FIGURE 60-9 Sweat glands. The sebaceous gland—the duct of which empties into the hair follicle independently of the duct of the apocrine sweat gland—secretes sebum, a mixture of fat and the remnants of the cells that secrete the fat.

Eccrine sweat glands are distributed over the majority of the body surface, are numerous (several million), and are small in diameter (50 to 100 µm). The palms of the hands and soles of the feet tend to have both larger and more densely distributed eccrine glands than elsewhere. The full complement of eccrine sweat glands is present at birth, they become functional within a few months, and their density decreases as the skin enlarges during normal growth. The essential role of eccrine sweating is temperature regulation (see p. 1197), although stimuli such as food, emotion, and pain can evoke secretory activity. Regionally, the trunk, head, and neck show more profuse sweating than the extremities. Sweat production is quantitatively lower in women than in men, which reflects less output per gland rather than fewer eccrine sweat glands.

Eccrine sweat glands are tubules comprising a secretory coiled gland and a reabsorptive duct

An eccrine sweat gland is a simple tubular epithelium composed of a coiled gland and a duct (see Fig. 60-9B). A rich microvascular network surrounds the entire sweat gland. The coiled gland, located deep in the dermis, begins at a single blind acinus innervated by postganglionic sympathetic fibers that are cholinergic. imageN14-4 The release of acetylcholine stimulates muscarinic receptors on the acinar cells, causing them to secrete into the lumen a clear, odorless solution, similar in composition to protein-free plasma. This primary secretion flows through a long, wavy duct that passes outward through the dermis and epidermis. Along the way, duct cells reabsorb salt and water until the fluid reaches the skin surface through an opening, the sweat pore. Although these pores are too small to be seen with the naked eye, their location is readily identified as sweat droplets form on the skin surface. Both the secretory cells in the coil and reabsorptive cells in the duct are rich in mitochondria, which are essential for providing sustained energy for the high rates of ion transport that are necessary for prolonged periods of intense sweating—for example, during exercise in hot environments.

Surrounding the secretory cells in the coil is a layer of myoepithelial cells that resemble smooth muscle and may contract, thereby expressing sweat to the skin surface in a pulsatile fashion. However, this action is not essential because the hydrostatic pressures generated within the gland can exceed 500 mm Hg.

Secretion by Coil Cells

The release of acetylcholine onto the secretory coil cells activates muscarinic G protein–coupled receptors (see p. 341), which leads to the activation of phospholipase C; phospholipase C activation in turn stimulates protein kinase C and raises [Ca2+]i. These signals trigger the primary secretion, which follows the general mechanism for Cl secretion (see p. 139). An Na/K/Cl cotransporter (see p. 122) mediates the uptake of Cl across the basolateral membrane, and the Cl exits across the apical membrane via a Cl channel (see Fig. 60-9B, lower inset). As Cl diffuses into the lumen, the resulting lumen-negative voltage drives Na+ secretion through the paracellular pathway.

The secretion of NaCl, as well as of urea and lactate, into the lumen sets up an osmotic gradient that drives the secretion of water, so the secreted fluid is nearly isotonic with plasma. This secretion of fluid into the lumen increases hydrostatic pressure at the base of the gland and thereby provides the driving force for moving the fluid along the duct to reach the skin surface.

Reabsorption by Duct Cells

As the secreted solution flows along the sweat gland duct, the duct cells reabsorb Na+ and Cl (see Fig. 60-9B, upper inset). Na+ enters the duct cells across the apical membrane via epithelial Na+ channels (ENaCs; see p. 126), and Cl enters through the cystic fibrosis transmembrane conductance regulator (CFTR; see p. 120). The Na-K pump is responsible for the extrusion of Na+ across the basolateral membrane, and Clexits via a Cl channel. Because the water permeability of the epithelium lining the sweat duct is low, water reabsorption is limited, so that the final secretory fluid is always hypotonic to plasma.

Because sweat is hypotonic, sweating leads to the loss of solute-free water (see pp. 806–807), that is, the loss of more water than salt. As a result, the ECF contracts and becomes hyperosmolar, which causes water to exit from cells. Thus, intracellular fluid volume decreases and intracellular osmolality increases (see pp. 132–133). This water movement out of cells helps to correct the fall in ECF volume. The solute-free water lost in perspiration therefore is ultimately derived from all body fluid compartments.

The NaCl content of sweat increases with the rate of secretion but decreases with acclimatization to heat

Flow Dependence

With mild stimulation of acinar cells, the small volume of primary secretion travels slowly along the duct, and the ducts reabsorb nearly all of the Na+ and Cl, which can fall to final concentrations as low as ~10 to 20 mM (Fig. 60-10). In contrast, with strong cholinergic stimulation, large volume of primary secretion travels rapidly along the duct, so the load exceeds the capacity of the ductal epithelium to reabsorb Na+and Cl. Thus, a greater fraction of the secreted Na+ and Cl remains within the lumen, which results in levels of 60 to 70 mM. In contrast, [K+] in the sweat remains nearly independent of flow at 5 to 10 mM.


FIGURE 60-10 Flow dependence of sweat composition. CF, cystic fibrosis.

Cystic Fibrosis

In patients with cystic fibrosis (see Box 43-1), abnormal sweat gland function is attributable to a defect in the CFTR, a cAMP-regulated Cl channel (see p. 120) that is normally present in the apical membrane of sweat gland duct cells. These individuals secrete normal volumes of sweat into the acinus but have a defect in absorption of Cl (and, therefore, Na+) as the fluid travels along the duct. As a result, the sweat is relatively rich in NaCl (see Fig. 60-10).


During a thermoregulatory response in a healthy individual, the rate of sweat production can commonly reach 1 to 2 L/hr, which, after a sufficient time, can represent a substantial fraction of total-body water. Such a loss of water and salt requires adequate repletion to preserve fluid and electrolyte balance. Restoration of body fluid volume following dehydration is often delayed in humans despite the consumption of fluids. The reason for this delay is that dehydrated persons drink free water, which reduces the osmolality of the ECF and thus reduces the osmotic drive for drinking (see pp. 845–846). This consumed free water distributes into the cells as well as the extracellular space, diluting the solutes. In addition, the reduced plasma osmolality leads to decreased secretion of arginine vasopressin (i.e., antidiuretic hormone), so that free-water excretion by the kidney is increased (see p. 844).

A more effective means of restoring body fluid volume is to ingest NaCl with water. When Na+ is taken with water (as in many exercise drinks), plasma [Na+] remains elevated throughout a longer duration of the rehydration period and is significantly higher than with the ingestion of water alone. In such conditions, the salt-dependent thirst drive is maintained and the stimulation of urine production is delayed, which leads to more complete restoration of body water content.


With ample, continuing hydration, a heat-acclimatized individual can sweat up to 4 L/hr during maximal sweating. Over several weeks, as the body acclimates to high rates of eccrine sweat production, the ability to reabsorb NaCl increases, which results in a more hypotonic sweat. This adaptation is mediated by aldosterone (see p. 766) in response to the net loss of Na+ from the body during the early stages of acclimatization. For example, an individual who is not acclimatized and who sweats profusely can lose >30 g of salt per day for the first few days. In contrast, after several weeks of acclimatization, salt loss falls to several grams per day. Thus, an important benefit of physical training and heat acclimatization is the development of more dilute perspiration, which promotes evaporative cooling while conserving NaCl content and thus effective circulating volume (see pp. 554–555) during dehydration.

The hyperthermia of exercise stimulates eccrine sweat glands

As discussed on p. 1193, the rate of perspiration increases with body Tcore, which in turn increases during exercise (see p. 1202). The major drive for increased perspiration is the sensing by the hypothalamic centers of increased Tcore. Physical training increases the sensitivity of the hypothalamic drive to higher Tcore. Indeed, the hyperthermia of exercise causes sweating to begin at a lower skin temperature than does sweating elicited by external heating. The efferent limb of the sweating reflex is mediated by postganglionic sympathetic cholinergic fibers (see p. 543). imageN14-4

Sweating is especially important for thermoregulation under hot ambient conditions and with exercise-induced increases in body temperature. Indeed, as ambient temperature rises to >30°C, heat loss through radiation, convection, and conduction (see pp. 1196–1197) becomes progressively ineffective, and evaporative cooling becomes by far the most important mechanism of regulating body temperature. Compounding the problem in hot humid environments, evaporative cooling becomes progressively less effective as ambient humidity rises (see Equation 59-5).