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THE SWEAT GLAND, HOW DOES IT WORK, AND WHAT
FACTORS AFFECT SWEAT RATE AND COMPOSITION?

Introduction 1
Types of Exocrine Sweat Glands
Sympathetic Nervous System Control of Sweating Substances Used To Determine Sweat Gland Function In Vitro 3 Formation of Primary Sweat Effect of Increased Intracellular Calcium on Sweat Secretion Other Biochemical Requirements for Sweat Secretion Evidence for Calcium Oscillations in RSD Cells Effect of Cardiovascular and Thermoregulatory Systems Effect of Local Skin Temperature (Tsk) 9 Effect of Sweat Gland Morphology Measurement of Sweat Electrolyte Composition Influence of Sweat Rate on Sweat Electrolyte Composition Hidromeiosis 13 Other Mineral Losses in Sweat Introduction
Humans are second only to camels in their ability to remain moderately active during
the day, in the hottest regions of the world, due largely to their capacity to sweat. In
humans, the eccrine sweat gland is probably the most active exocrine gland in terms of
fluid and electrolyte secretion.
Humans have one of the most efficient evaporative cooling systems, which is evidenced
by the efficiency of the thermoregulatory system, for three reasons: 1) the thermal
sweat is produced by eccrine sweat glands, 2) there are two to three million eccrine
sweat glands which are distributed over the skin surface, and their secretions cover the
whole body, and, 3) the relative lack of body hair. These factors allow maximal sweat
evaporation and, therefore, heat loss. Due to the importance of sweating for
evaporative heat loss, however, the major limiting factor for the human animal in
maintaining thermal homeostasis is the availability of sufficient water intake to
compensate for sweat fluid losses.
Types of Exocrine Sweat Glands
There are three types of sweat gland in the human: the eccrine, apocrine and
apoeccrine, but it is the eccrine sweat glands that are involved in thermoregulation.
The eccrine glands secrete a hypotonic solution to plasma, with variable obligatory
amounts of electrolytes, mainly sodium, chloride and potassium together with other
compounds in very small amounts, namely: lactate, urea, ammonia, proteins and
peptides. Apocrine and apoeccrine glands, in contrast, generally produce secretions
which are richer in fats, proteins and salts, and which evaporate at a slower rate than
eccrine secretions, and thus reduce the rate of heat loss. In humans, apocrine glands are
mainly restricted to the face and hands, but are also located with apoeccrine glands in
the mammary, axillary, anal and genital areas, whereas eccrine glands are distributed
widely over the body surface.
Structure of the Eccrine Sweat Gland
The eccrine sweat gland consists of a simple tubular epithelium, and is comprised of the
reabsorptive sweat duct (RSD) and the secretory coil. The coiled portion of the gland
consists of the secretory coil and the proximal portion of the RSD, which are located in
the dermis of the skin. The RSD of the sweat gland consists of the proximal coiled
segment, a distal straight segment that traverses the dermis, and the intraepidermal
sweat duct unit which opens directly onto the skin surface.
Secretory Coil
The secretory coil is comprised of three types of cells: dark, clear (secretory) and
myoepithelial cells. The clear cell of the secretory coil is characterised by the presence
of basal membrane infoldings (the reported site of Na - K ATPase), membrane villi,
intercellular canaliculi which open into the lumen, and abundant mitochondria located
near the basolateral membrane (BLM), which indicates that the clear cell is involved in
the active secretion of electrolytes and water. The clear cell also reportedly has
receptor sites for cholinergic and adrenergic neurotransmitters.
The myoepithelial cells are located near the BLM of the secretory coil, and are filled
with dense myofilaments, which contract in response to cholinergic, but not adrenergic,
stimulation. The function of the myoepithelial cells is believed to be structural in
providing mechanical support for the secretory coil wall against the increase in luminal
hydrostatic pressure during sweating, rather than the pumping out of preformed sweat.
The dark cells are located near the lumen of the secretory coil, but their function is as
yet unknown.
Reabsorptive Sweat Duct
The RSD is composed of two layers of cells - the basal ductal (peripheral) cells and the
luminal cells. The basal ductal cells are rich in mitochondria, and the entire
circumference of the cell membrane shows evidence of Na+-K+ATPase activity,
suggesting that the entire cell membrane is involved in sodium pumping for ductal
sodium reabsorption. In addition, it appears that the basal ductal cells also have
receptor sites for sympathetic nervous system neurotransmitters. In contrast, the
luminal cells of the duct have fewer mitochondria and only a small number of Na+-
K+ATPase pumps, but a dense layer of tonofilaments near the luminal membrane,
which appear to function to provide structural resilience to the tubular lumen. In addition, the luminal cells contain channels for both sodium and chloride, and appear to act as the absorptive surface for passive diffusion of sodium, for ultimate active reabsorption by the basal ductal cells. Sympathetic Nervous System Control of Sweating
Sweat gland activation occurs as a result of the discharge of cholinergic fibres, whose
activity is controlled by the thermoregulatory centre located in the hypothalamus.
Efferent nerves, originating from the sweat centre, presumably in the preoptic region of
the hypothalamus, descend through the ipsilateral brain stem and medulla, and synapse
in the intermediolateral cell columns of the spinal cord. The myelinated axons arising
from the intermediolateral horn of the spinal cord (preganglionic fibres), pass out in the
anterior roots to reach (through white rami communicantes) and synapse with
postganglionic fibres, in the sympathetic chain ganglia. These sympathetic post
ganglionic fibres are the nerves which innervate the sweat glands and consist of
unmyelinated C class fibres, and which terminate, with other peripheral nerves,
surrounding the sweat glands. Efferent nervous innervation to all sweat glands of the
body leaves the spinal column at the thoracic and lumbar regions of T1 - L2. The term
'sudomotor' pertains to the efferent nerves that control the activity of the eccrine sweat
glands.
In contrast to ordinary sympathetic innervation, acetylcholine is the principle
neurotransmitter of the sudomotor system, although it also has an adrenergic
component. Sweat cells exhibit cholinergic and alpha and beta adrenergic receptors on
the BLM. Vasoactive intestinal peptide (VIP), atrial natriuretic peptide, ATP, and other
substances, have also been located in the periglandular nerves of the sweat gland.
However, the role and function of most of these peptides and neurotransmitters on
sweat gland function is not fully understood.
Substances Used To Determine Sweat Gland Function In Vitro
Cultured sweat gland cells retain the ability to respond to a variety of secretagogues by
receptor mediated processes, including the adrenergic agonists isoproterenol (ISO),
prostaglandin E2, phenylephrine, and the cholinergic agonists methacholine (MCh) and
pilocarpine. Cultured human sweat cells also respond to acetylcholine and adrenaline.
In vitro, the addition of ISO to cultured sweat cells results in sweat secretion, reportedly
via the beta adrenergic receptor. Phenylephrine, an alpha adrenergic agonist also
results in sweat secretion, but significantly less than beta adrenergic sweat stimulation
by ISO. Sweat secretion induced by the beta adrenergic agonist ISO, may be due in
large part to accumulated cAMP because this substance collects in the sweat gland
during stimulation with ISO, but not with acetylcholine. External calcium is not
required for the ISO induced cAMP response. Furthermore, sweat secretion can be
induced by theophylline which enhances cAMP. It is believed that a minimum level of
intracellular calcium may be required for beta adrenergic sweating.
Acetylcholine and adrenaline stimulate sweat secretion in isolated human sweat glands,
but adrenaline appears to activate calcium influx without mobilising intracellular
calcium, in contrast to acetylcholine. Adrenaline reportedly acts via alpha adrenergic
receptors.
Formation of Primary Sweat
The secretory portion of the eccrine sweat gland secretes isotonic fluid into the lumen.
The primary fluid is rendered hypotonic during its passage to the skin surface by
reabsorption of sodium chloride in excess of water, a process performed by the
epithelial cells lining the duct.
The series of events leading to the secretion of an isotonic fluid into the sweat duct are
as follows: acetylcholine is released from periglandular cholinergic nerve endings in
response to nerve impulses from the CNS, and binds to cholinergic receptors located in
the BLM of the clear cell of the secretory coil. Activation of cholinergic receptors
results in the mobilisation of intracellular calcium, and influx of extracellular calcium
into the clear cells' cytoplasm, which results in the commencement of sweat secretion.
Sweat secretion is sustained by acetylcholine in two phases: a transient extracellular
calcium independent stage, and a sustained extracellular calcium dependent stage. The
transient component is attributed to the release of calcium from bound intracellular
stores, and therefore acetylcholine can increase intracellular calcium in the absence of
extracellular calcium, but only for a short period. The sustained phase, however,
appears to result from calcium influx, and occurs only in the presence of extracellular
calcium.
Calcium Mobilisation Mediators
Calcium ions are ubiquitous regulators of many cellular processes, and eukaryotic cells
have evolved a complex system of channels, pumps and exchangers, and
transmembrane molecules, which maintain intracellular calcium concentrations at very
low levels 10-100nM. This allows for rapid metabolic responses to calcium fluxes.
Inositol polyphosphates (IPP's) are important mediators of intracellular calcium
mobilisation and calcium influx, and are rapidly generated following cholinergic
stimulation.
The signal transduction pathway for calcium's rapid agonist responses in many tissues
involves the activation of the enzyme phospholipase C, which acts on the substrate
phosphatidylinositol 4,5 biphosphate, and which results in the formation of inositol
1,4,5 triphosphate (IP3) and diacylglycerol. The second messenger of this reaction -
IP3, generated at the cell membrane, causes the rapid release of calcium from
intracellular stores by activating specific receptors and directly opening calcium
channels, on the membranes of these stores in specific organelles, such as the
endoplasmic reticulum.
Cytoplasmic calcium is significantly reduced when extracellular calcium is removed,
and thus the formation of IP3 may be of limited importance in the sustained elevation of
cytoplasmic calcium during sweat gland stimulation. However, it has been speculated
that IPP's could also mediate calcium entry from the ECF, and not just from
intracellular stores. It has recently been reported that depletion of internal stores of
calcium triggers a capacitative influx of extracellular calcium across the plasma
membrane. Because internal calcium stores are finite, prolonged bouts of signalling
depend on the influx of external calcium through store operated channels (SOC's) in the
plasma membrane. The influx of calcium can be recorded as SOC in the plasma membrane, or as a current known as the calcium release activated current (Icrac) An as yet unanswered question in cell signalling is how SOC and Icrac sense and respond to intracellular calcium store depletion. It is postulated that IP3 receptors in intracellular stores are coupled to SOC and Icrac by a tight functional interaction with Htrp3 protein channels. Effect of Increased Intracellular Calcium on Sweat Secretion
The increased cytoplasmic calcium, due to the transient and sustained acetylcholine
phases through the activation of IPP's, stimulates chloride channels in the apical
(luminal) membrane, and potassium channels in the BLM of the secretory clear cell,
resulting in the efflux of both ions. The rise in cytoplasmic calcium is reportedly the
key factor in the activation of the potassium channels, although not fully elucidated it
may shift the voltage threshold for potassium channel opening. It has recently been
reported that calcium activated potassium channels, which are gated by intracellular
calcium, result in the coupling of intracellular calcium levels and membrane potential.
Chloride enters the secretory cell via either a Na- 2Cl -K or Na - Cl cotransport system,
and leaves the cells by diffusion into the lumen of the sweat duct.
The cholinergic stimulation of eccrine sweat secretory cells, and the associated rise in
intracellular calcium concentration, is also associated with an influx into the cells of
sodium, along with the efflux of potassium and chloride. Mch induces potassium and
chloride efflux through their respective channels, activated in a calcium dependent
fashion, and a sodium influx which can increase threefold the intracellular sodium
concentration. During steady state Mch stimulation, the potassium concentration of
clear cells reportedly decreases by approximately 45%, whereas sodium concentration
increases in such a way as to maintain the constancy of the sum of sodium and
potassium concentrations. In the secretory cells, blockade of the BLM potassium
conductance inhibits sweat secretion, and a fall in cytoplasmic potassium accompanies
secretion, showing the importance of potassium efflux in sweat secretion.
The movement of chloride across the apical membrane depolarises the apical membrane
and generates a negative luminal potential. This negative lumen charge then attracts
sodium into the lumen across the intercellular junction (ie., paracellular pathway), and
therefore, osmotically water, for the formation of sweat, which is reportedly isotonic to
plasma.
Other Biochemical Requirements for Sweat Secretion
The acetylcholine responses could not be obtained for either the transient or sustained
phase in a bicarbonate free medium, and the human sweat gland in vitro appears to have
a strict requirement for bicarbonate. Potassium efflux is drastically reduced in the
absence of bicarbonate. Removal of extracellular bicarbonate influences intracellular
pH, and reduces cytoplasmic hydrogen ion buffering capacity which may affect sweat
gland secretion. In addition, secretagogues which mobilise calcium are known to effect
cytoplasmic pH by stimulating proton extrusion via Na - H counter-transport. It is
possible that in the human sweat gland, the cytoplasmic calcium store is pH sensitive
and becomes depleted during periods of acidosis, thereby inhibiting secretagogue-
evoked calcium mobilisation.
In addition, the transient phase of acetylcholine stimulation was abolished when external sodium was replaced with a similar compound, suggesting that the mobilisation of cytoplasmic calcium is dependent, in some way, on external sodium. In contrast, the sustained phase of the response was not affected by the removal of external sodium, suggesting that calcium influx does not occur via a sodium dependent system. Sodium Chloride Reabsorptive Process
Although the biochemical reactions which result in primary sweat formation are
essentially the same as those for sodium reabsorption in the sweat duct, ie. an
intracellular rise in calcium concentrations following acetylcholine stimulation, there is
differing selective permeability for certain ions in the ductal cells, as sodium is actively
transported back into the blood.
The RSD is a unique tissue compared with many sodium chloride absorbing epithelia,
in that it has low cell membrane electrical potential (BLM potential is approximately
-7.0mV, and the apical membrane -19.0mV), and an extremely high transepithelial
chloride conductance. The sodium absorbing tissue has a poor BLM potassium
permselectivity, a relatively large BLM chloride conductance, and the transepithelial
potential in vivo human sweat ducts is measured as -40Mv (lumen negative), that is due
to sodium reabsorption. Other authors have recorded the transepithelial potential as
-30mV at the opening of the duct.
The capacity of in vivo human sweat ducts to absorb sodium was estimated at
400pmmol/mm.min, which corresponds to 20nmol/cm.second, assuming a diameter of
10um for the duct lumen. The cholinergic agonist, Mch, stimulates sodium transport in
cultured epithelia, and with a few minute delay, evokes oscillations in the
transepithelial potential difference and short circuit current (>5um concentrations).
Sodium transport, in cultured sweat gland epithelia, is thought to result from an
increase in intracellular calcium, which in turn activates calcium-sensitive potassium
channels in the BLM, as with sweat formation. As a result of activation of these
potassium channels in the BLM, the apical membrane hyperpolarizes, thereby
increasing the electrochemical gradient for sodium entry. The results of studies
indicate that Na+-K+ATPase pump activity in the BLM of the basal ductal cells is
mainly responsible for the high intracellular potassium activity (above equilibrium)
evidenced in the RSD cells. However, the role of other transport carriers such as Na -
2Cl - K or K - Cl cotransporters, which in turn depend on the Na - K pump activity, to
maintain the higher potassium activity, is also possible. The apical membrane of the
reabsorptive sweat duct does not seem to possess a potassium conductance. The
intracellular potassium activity may also be modulated by the sodium transport status in
the apical membrane.
As aforementioned, the apical membrane of the reabsorptive sweat duct does not seem
to possess a potassium conductance. Regarding the serosal membrane, the potassium
conductance of differentiated cells is localised in this membrane, but under selective
conditions. The basal ductal cells show high activity of Na+-K+ATPase, with potassium
conductance on the BLM, but not on the luminal membrane, and amiloride sensitive
sodium channels on the luminal membrane. The duct is highly permeable to chloride,
and it appears that sodium enters passively from the lumen through amiloride sensitive channels, and is pumped out through the BLM in exchange for potassium. At the new steady state, the large influx of sodium across the apical membrane is equal to the flux of sodium carried by the pump in the BLM. Amiloride, or specific antagonists (atropine after carbachol, mepyramine after histamine), prevent sodium entry into the sweat gland epithelial cells. Exposure to mucosal amiloride, or sodium free solution, caused the cells to hyperpolarise, the fractional resistance of the apical membrane to increase, and the short circuit current to decrease to zero, i.e., sodium transport has ceased. Evidence for Calcium Oscillations in RSD Cells
Cytosolic calcium oscillations are a nearly universal mode of signalling in excitable and
non excitable cells. Although calcium is known to mediate a diverse array of cell
functions, it is not known whether oscillations contribute to the efficiency or specificity
of signalling or are merely a consequence of the feedback control of intracellular
calcium.
Calcium signals can either activate highly localized cellular processes in the immediate
vicinity of the channels, or by recruiting channels throughout the cell, can activate
processes at a 'global' level. In many cells, IP3 is a global signalling molecule that
liberates calcium throughout the cytoplasm. For sites of elementary calcium release to
produce global responses, the individual channels must communicate with each other to
set up calcium waves. If cells are connected, such intracellular waves can spread into
neighbouring cells and become intercellular waves to coordinate cellular responses
within a tissue.
It is believed that the increase in intracellular calcium is the primary event for sodium
reabsorption, and with many cells behaving in synchrony. The spread of intracellular
calcium waves is dependent on the presence of gap junctions, and although the presence
of gap junctions in ductal cells has not been reported, electrophysiological studies
indicate that the basal ductal cells are electrically coupled. In contrast, other studies
unequivocally state that cultured sweat glands have prominent gap junctions, and are
electrically coupled. The luminal and basal ductal cells appear to behave like a
syncytium, presumably through intercellular communication, i.e. gap junctions. It is
also reported that gap junctions are calcium controlled.
Sweat stimulation also reportedly results in oscillatory changes in membrane potential,
and which is believed to be due to the potassium activated channels which appear
synchronous in their opening and closing following cholinergic stimulation. It is
postulated that the oscillations in cytoplasmic calcium are responsible for the cyclic
changes in potassium channel activity. However, it is not understood how this
specialized coupling between cytoplasmic calcium and potassium channels is achieved,
but preliminary data indicate an absolute segregation of coupling between channels, and
illustrates the functional importance of submembrane calcium microdomains.
Transient increases, or oscillatory behaviour, in intracellular calcium levels may be
important to protect cells from injury which would occur upon prolonged elevation of
intracellular calcium. The best way to achieve this, however, is if cells behave
asynchronously so that intracellular calcium can be dissipated through gap junctions to
quiescent cells. In sweat glands, however, whose function is to reabsorb salts from
small luminal volumes, asynchronous behaviour would mean that cells downstream would perform the absorptive task from an already depleted fluid. Synchronous behaviour results in intermittent waves of absorption, followed by periods of rest during which the luminal fluid is renewed, as appropriate flow rates are needed to ensure maximal efficiency. However, data shows that in the monkey palm sweat gland, the proximal duct contains approximately 10 times higher Na+-K+ATPase activity than the distal segments, indicating possibly greater sodium reabsorption in this area. (This is contradicted by other authors who suggest that the RSD acts in syncytium, i.e. constant reabsorption throughout duct, otherwise cells upstream would have a depleted fluid) Recent results have shown that calcium oscillations increase both the efficacy and information content of calcium signals that lead to gene expression and cell differentiation. IP3 releases calcium from intracellular stores and triggers complex waves and oscillations in the levels of cytosolic free calcium. The physiological functions of oscillations in cytosolic free calcium levels and the existence of IP3 oscillations remain controversial. It is reported that IP3 pulses mimic the natural cycle of calcium release from internal stores. Oscillations in IP3 levels may be due to the fact that cells may only be able to generate a limited total amount of IP3, because it's biosynthesis uses many ATP molecules and depletes stores of the scarce lipid, phosphatidylinositol 4,5 biphosphate. Repetitive pulses are more effective than a continuous supply of the same total amount of IP3 for producing large and reliable calcium spikes, which in turn results in optimal signalling. Three isoforms of the IP3 receptor have been identified - I, II and III. Although the isoform of the receptor within the eccrine sweat gland has not been identified, the presence of calcium oscillations may be determined by elucidating the isoform. The Type III IP3 receptor is restricted to the trigger zone from which calcium waves originate, and has distinctive IP3 binding properties. Activation of type III isoform, in cells that express only this isoform, results in a single transient, but global, increase in intracellular calcium concentration. The bell shaped calcium dependence curve of type I IP3 receptor indicates that it is ideal for supporting calcium oscillations, as it provides amplification of the initial IP3 signal, and negative feedback inhibition of further IP3 stimulated calcium release. The feedback inhibition is important because it provides autoregulation, and is essential for calcium oscillations and for the propagation of regenerative intracellular calcium waves. The properties of type III IP3 are better suited to signal initiation as calcium dependent inhibition is lacking in this isoform, i.e., there is positive feedback as calcium is released. As far as cell function is concerned, oscillations proved to be more efficient than stable increases in calcium - but only when the average concentration of cytosolic calcium remains below ~300nM. In addition, the oscillations appear to be generated at the cell surface, without any involvement of intracellular receptors. Factors Effecting Sweat Gland Function
As aforementioned, the preoptic/anterior region of the hypothalamus has an essential
role in the control of thermoregulation. However, sweating does not commence until a
specific temperature setpoint, Ts, has been exceeded, at which point there is a linear
increase in sweat rate with Tcor. For a given person, sweat rate is dependent on
environmental conditions (Ta, dew point temperature, radiant load and air velocity),
clothing (insulation and moisture permeability), degree of acclimatisation and physical activity level. The rate of local sweat output can be mathematically represented as the sum of afferent inputs from internal and mean skin temperatures, and modified by local Tsk. In addition, it has been suggested that sweat output is also influenced by non thermal factors, such as changes in blood osmotic pressure. Effect of Cardiovascular and Thermoregulatory Systems
Isotonic hypovolemia reportedly reduces the sensitivity of the sweating response and
increases the Tcor threshold for sweating and cutaneous vasodilatation. This indicates
that blood volume may also have an effect on sweat gland function, however this is also
inconclusive. The effect of skin blood flow on sweat rate is also inconclusive, but some
authors report that a decrease in skin blood flow is associated with reduction in
sweating rates. The altered function of sweat glands, occasionally reported in the
literature, during hypovolemia has been attributed to the lack of oxygen for sweat gland
function.
Recent studies have indicated that the Ts or core temperature threshold for sweating can
be changed by altering the homeostasis of the body. The infusion of a hypertonic
sodium chloride solution reportedly results in an increase in Tcor of 1°C, which alters
the threshold for sweating in defence of Tcor. In addition, it has been reported that
during exercise, the increase in plasma sodium concentration, results in a slowing of the
onset of sweating, and also raises the plateau for steady state Tcor. The effect of
plasma osmolality, however, on sweat gland function is inconclusive.
Effect of Local Skin Temperature (Tsk)
Local Tsk also reportedly modifies the effect of Tcor on sweating rate in a cumulative
fashion. An increase in local Tsk is associated with a decrease in the Tcor threshold for
sweating. However, this response is not universal, and there is a wide variability in
responses between individuals. For some individuals, an increase in local Tsk results in
increased sensitivity of the sweat gland to periglandular neurotransmitters. It has been
observed, however, that an increase in Tcor is nine times more efficient in stimulating
the sweat centre, and therefore sweat rate, than an increase in mean Tsk. The
mechanism(s) for the effects of local Tsk on sweat gland function is unknown, but the
periglandular temperature on glandular metabolism, neurotransmitter release and
metabolism, membrane transport and/or receptor affinity has been postulated.
Effect of Sweat Gland Morphology
The quantity of sweat secreted from glands depends on the size, sensitivity and overall
activity of the glands. The maximum sweat rate per gland is directly proportional to the
sensitivity of the gland, and linearly related to the size of the gland. The size of the
sweat gland varies almost fivefold between individuals, and this largely correlates with
the individual (and perhaps regional) differences in sweat rates. As the size of the
sweat gland increases, there is: 1) a higher sweat rate per gland, 2) a higher sweat rate
per unit tubular length of the secretory coil, 3) a higher sweat rate per unit volume of
the secretory coil, and 4) an increase in cholinergic sensitivity of the sweat gland. Maximal sweat rate per gland ranges between 2-20nL/min. There is reportedly no difference in the ability of males and females to sweat as the total number of sweat glands is fixed and does not change throughout life, in both sexes. There is, however, a significant regional difference in gland number, with the highest number on the palms and soles, followed by the forehead, forearms and the back. It has been reported that sweat glands use glucose as their primary energy source, but they also may utilise mannose, lactate and pyruvate. The total sweating rate does not seem to differ as a function of adiposity, and this seems to be true in both men and women. Effect of Training and Acclimatisation
As sweat rate and blood volume are strongly correlated with VO2max and degree of
acclimatisation, physical training and acclimatisation results in improvement in
glandular function. It has been reported that the enhancement of sweating can occur
with physical training and heat acclimatisation. Acclimatisation is usually associated
with an increased sweat rate by an increased sweating response to a given increase in
Tcor. However, it is not clear whether the improved ability to sweat after
acclimatisation is achieved at the central level, at the peripheral level (i.e., the level of
the sweat gland and the periglandular nerves and vascularity), or both levels. Although
the mechanisms for improved glandular function during acclimatisation remains
unresolved, the maximal sweat rate increases after a number of days with heat
exposure, and the rate of sweating is inversely proportional to the degree of
acclimatisation. After approximately five days of initial heat exposure, however, there
is no further increase in sweat rate.
The higher sweat rates observed in trained subjects is reportedly to be largely due to an
increased sensitivity to the central sweating drive, at the peripheral level.
Consequently, a relatively unfit person requires a higher central thermoregulatory drive to dissipate a given thermal load than a fitter person. It is speculated that this increased sweat gland response is mediated by 1) increased periglandular concentrations of acetylcholine, 2) increased cholinergic sensitivity of the sweat gland, 3) glandular hypertrophy, and 4) a combination of these factors. As the sweat rates increase with training and acclimatisation, the sweat electrolyte concentration decreases. Effect of Maturation
Maximum sweat rate is not affected until at least the '60's, but gland function does
decline during the 70's and 80's. This may be attributed, in part, to skin changes
associated with many years in the sun, as the density of glands is unchanged throughout
life. Maximal sweat rate per gland, which is an indicator of the functional capacity of
the sweat gland, does not appreciably decrease until age 70.
Subjects of varying ages, from prepubescent (9 years), pubescent (12 years) and adult
(21 years), males and females cycled at 50% VO2max in 42°C; 18% RH for 40
minutes. Sweat was collected from a plastic bag attached to the back. Sweat sodium
and chloride losses tended to increase with maturation (children ~40mmol/L and adults
~60mmol/L), while sweat potassium was lower in adults compared to the
prepubescents. Children have a lower sweating rate than adults, even when corrected for BSA, and per active gland. As a result, the amount of sodium chloride lost in the sweat of children is lower than that of adults, in absolute and per kg of body weight, with no maturational difference found in potassium loss. Within the same maturational group, there were no gender differences in sweat electrolyte loss or sweat rate when matched for aerobic power. Local sweat rate is a product of sweat rate per gland and the number of activated sweat glands. Sweat rate per gland correlates with BSA. Both BSA and sweat gland size increase with age and these changes may contribute to the increased sweat rate per gland as a person matures. Data suggest that in children there is a lower population density of sweat glands in those with a higher surface area for older than for younger children. The changes in sweat rate and sweat gland population density with physical maturation may be attributed to geometric changes i.e., increase in body size and SA. However, the differences in sweat electrolyte composition between children and adults suggest that there are qualitative differences occurring in the sweat response during puberty. The maturational differences in sweat sodium loss may be related to differences in sensitivity of the duct cells to plasma aldosterone levels, or that sodium loss in the sweat is a function of sweat rate, and occurs in the reabsorptive duct rather than in the acinus of the gland. However, there are reportedly no significant differences in plasma aldosterone levels between young and adult individuals, suggesting that difference in sweat sodium is probably not related to aldosterone, unless the sensitivity of the receptor to aldosterone is altered by maturation. It has been reported, however, that hormones do not affect the eccrine sweat cells in many of the ways that they affect the kidney. Measurement of Sweat Electrolyte Composition
The sweat, which is secreted onto the skin, contains a wide variety of organic and
inorganic solutes, with variable quantities of electrolytes. The amount of electrolytes
lost depends on a number of factors, including the concentration of individual
electrolytes, as well as the total sweat volume. The sweat composition undoubtedly
varies between individuals, but may also vary within the same individual depending on
the rate of secretion, the state of acclimatisation and the degree of physical fitness i.e.
state of training. Well trained people, and those who are heat acclimatised, have
attained the ability to minimise the excretion of electrolytes by the sweat glands, and
have generally lower sweat electrolyte concentrations than unacclimatised and less fit
individuals. The quantity of electrolytes excreted from different regions of the body is
not uniform, and there are also differences in sweat electrolyte concentrations with
maturation, with prepubescent individuals having lower sweat sodium concentrations.
Apocrine apoeccrine sweat also differs in composition to eccrine sweat. For these
reasons, it seems impossible to determine the one and only electrolyte composition of
human sweat.

The knowledge of sweat electrolyte composition has been derived from a variety of
studies, and there is wide variability in the results. There are a number of factors
responsible for the variability in the composition of sweat: a large biological variability,
variable electrolyte losses from different body sites, and methodological problems in
the collection procedure including evaporative loss, incomplete collection and
contamination with sloughed skin cells. Some studies use a washdown technique for
the collection of sweat, others use bags or capsules for sweat collection.

In order to determine the accuracy and reproducibility of different sweat collection
procedures, collections of sweat were made in six subjects, utilising a total body
washdown technique, and collections from one arm in an occlusive arm bag. Arm
occlusive bags gave higher readings of sweat electrolyte losses than other measures,
possibly due to the change in local Tsk and humidity at the sweat collection site.
However, given that there are regional variations in sweat sodium loss, and that whole
body sweat collection includes eccrine, apoeccrine and apocrine secretions, whereas
arm sweat consists only of eccrine sweat, differences in results between the methods are
to be expected. Pore occlusion, by sweat collection methods, influences excretion rate
and the electrolyte concentrations in sweat.
Influence of Sweat Rate on Sweat Electrolyte Composition
Some authors report that sweat sodium concentrations are influenced by the flow rate of
sweat, whereas other authors have found that sweat sodium concentrations are not
related to the sweat flow rate. It has been suggested that sodium loss in the sweat
increases with increasing sweat rates, with the explanation that a high sweat rate
decreases the time available for sodium reabsorption in the duct of the sweat gland.
However, the correlation between sweat sodium loss and sweat rate is low. In addition,
within the same individual, there are also significant regional differences in sweat rate
and sweat composition, which makes the relationship between sweat rates and sweat
electrolyte composition difficult to quantify.
Source of Potassium in Sweat
The potassium concentration in human sweat is much higher than in blood. Results
indicate that there is no potassium conductance or potassium - dependent carrier system
to account for any potassium secretion across the apical membrane of the RSD. In
addition, there are tight junctions between the cells of the RSD so it is unlikely that
potassium could leak into the lumen as a consequence of luminal negativity. Since
potassium concentration in the sweat reportedly increases with decreasing sweat rates,
water reabsorption across the potassium impermeable luminal membrane may result, to
some extent in an increase in luminal potassium concentration, but it is not the sole
cause of potassium accumulation in the lumen of the RSD. However, it is more likely
that primary sweat from the secretory coil is the source of the higher potassium
concentration in human sweat. Although the concentration of potassium in the sweat is
high compared to the plasma values of potassium, the plasma content represents only a
fraction of the whole body stores.
Values for Sweat Electrolytes
Mean sweat sodium concentration has been reported as 33mmol/L with a range of 20-
80mmol/L. However, other authors report the upper limit for sodium in the sweat as
60mmol/L with a range of 10-50mmol/L. The sweat from these studies was obtained
using a whole body washdown technique or arm occlusive bags, and it is unclear in
some studies as to the training or acclimatisation status of the subjects and the
environmental conditions. Sweat sodium losses for 233 children, aged from 1-15 years of age, have been reported as 5-46mmol/L. Sweat potassium losses range between 4-8 mmol/L. The mean value of potassium in the RSD was measured at 4.1mmol/L. In contrast, it is also reported that mean potassium loss in the sweat varies between 8-10mmol/L (range 2.5-21.0mmol/L). Sweat Rates
Depending on the exercise intensity, level of training and state of heat acclimatisation,
sweat rates have been reported to rise as high as 2-3L/hr. For athletes, the highest
sweat rates occur during prolonged, high intensity activity in the heat.

Sweat rates of 1L/hr are very common
In a study the average sweat loss of marathon runners 1.325L/hr.
Hidromeiosis
Hidromeiosis is the decline in sweat rate during repeated or prolonged sweating. The
reason for hidromeiosis has yet to be ascertained but it may represent a decrease in the
sweat rate due to poral occlusion or sweat gland fatigue. However, there is evidence
that hidromeiosis is not associated with a decrease in sweat gland density or poral
occlusion, and appears only to occur in acclimatised individuals. The sweat gland
fatigue hypothesis has also been disputed. If an individual is put in a heat chamber, the
hidromeiotic phenomenon can be observed as the sweating rate decreases over time.
However, if the subject is removed and the skin dried, the sweat rate begins to increase
again which indicates that the hidromeiotic phenomenon has little to do with sweat
gland fatigue. In addition, in those subjects that exhibit a reduction in sweating over
time, after prolonged heat exposure, there is no increase in Tcor. Consequently,
hidromeiosis is believed to represent a physiological adaptation to acclimatisation that
is apparently designed to minimise the loss of sweat water from the skin by dripping,
without resulting in a rise in Tcor.
Other Mineral Losses in Sweat
It has been reported that copper lost in the sweat can vary from negligible to 4.9mg/L,
and therefore, the nutritional significance of this loss is questionable, although there is
some evidence that indicates copper excretion may take place in the sweat, as well as in
the bile. There is also extremely variable sweat losses reported for zinc, from
negligible to substantial. Some authors suggest that there are excessive losses of iron in
sweat, with one author suggesting a loss of 2.5mg of iron per litre of sweat during a
marathon race. However, this has not been supported by other authors, and results also
range from negligible to substantial. Iron excretion in the sweat, from the whole body
washdown technique (filtered for cellular material), is significantly lower than that
reported from other methods where the sweat may be contaminated with sloughed cells.
However it is generally agreed that there is not a significant amount of minerals lost in
sweat and there is no need for rehydration drinks to add these minerals. This is
especially so when maximal absorption is required, as any additional molecules will
alter the tonicity of the drink and slow down absorption.

Source: http://www.pointhealth.com.au/pdf/THE%20SWEAT%20GLAND,%20HOW%20DOES%20IT%20WORK,%20AND%20WHAT%20FACTORS%20AFFECT%20SWEAT%20RATE%20AND%20COMPOSITION.pdf