Sweat test
Encyclopedia
The sweat test measures the concentration
of chloride
that is excreted in sweat. It is used to screen for cystic fibrosis
(CF).
is caused by defects in a protein found in many tissues, including the airways and the sweat gland
s. As a result, these tissues do not work properly. Sweat testing takes advantage of the fact that cystic fibrosis patients have defective sweat glands.
Sweat glands produce sweat through a well understood process of secretion and reabsorption of sodium chloride (salt). Secretion entails the movement of salt and water from sweat gland cells into the sweat duct. Reabsorption occurs in the duct with the movement of salt from the sweat back into sweat duct cells. What remains is sweat, a salt solution with a relatively finely tuned concentration of sodium and chloride.
For normal salt reabsorption to occur, individual ions of sodium and chloride must be taken from the sweat and moved back into cells of the sweat duct. These ions are moved by transporters called ion channel
s. In the case of sodium, there is a sodium channel; for chloride, there is a chloride channel
called CFTR
. For sweat to be produced with the proper concentrations of sodium and chloride, sodium channels and chloride channels (CFTRs) must work properly.
In cystic fibrosis, the CFTR chloride channel is defective, and does not allow chloride to be reabsorbed into sweat duct cells. Consequently, more chloride stays in the duct, and more sodium remains in the sweat. The concentration of chloride in sweat is therefore elevated in individuals with cystic fibrosis.
The concentration of sodium in sweat is also elevated in cystic fibrosis. Unlike CFTR chloride channels, sodium channels behave perfectly normally in cystic fibrosis. The elevation in sodium concentration comes from the electrical charge of retained chloride trapping sodium in the sweat duct, preventing its reabsorption. Chloride carries a negative charge, while sodium's charge is positive; the opposing charges ensure that sodium and chloride attract one another. The extra chloride ions retained in the sweat duct produce a negative charge inside the duct and therefore attract sodium ions. The final result is that both sodium and chloride concentrations are elevated in individuals with cystic fibrosis.
iontophoresis
. At the test site, an electrode is placed over gauze containing pilocarpine and electrolyte
solution that will not interfere with the sodium and chloride measurement. A second electrode (without pilocarpine) will be placed at another site and a mild electrical current will draw the pilocarpine into the skin where it stimulates the sweat glands.
The test site is carefully cleaned and dried, then a piece of preweighed filter paper is placed over the test site and covered with parafilm to prevent evaporation. Specialized collection devices may also be used. Sweat is collected for 30 minutes. The filter paper is retrieved and weighed to determine the weight of sweat collected. Several laboratory methods are then used to determine the sodium and chloride concentrations.
Before this method of inducing sweat was developed, the method was to place the entire person to be tested in a hemispherical chamber and slowly raise the humidity and temperature of the air inside.
For people older than 6 months of age, a chloride level of the:
, mineralocorticoid
hormone therapy, and skin rash
on the tested area may produce incorrect results.
Positive test results may also be caused by malnutrition, adrenal insufficiency, glycogen storage diseases, hypothyroidism, hypoparathyroidism, nephrogenic diabetes insipidus, G6PD deficiency or ectodermal dysplasia (source: http://www.eMRCP.com)
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
of chloride
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...
that is excreted in sweat. It is used to screen for cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
(CF).
Background
Cystic fibrosisCystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
is caused by defects in a protein found in many tissues, including the airways and the sweat gland
Sweat gland
Sweat glands, or sudoriferous glands, are small tubular structures of the skin that produce sweat. There are two kinds of sweat glands:...
s. As a result, these tissues do not work properly. Sweat testing takes advantage of the fact that cystic fibrosis patients have defective sweat glands.
Sweat glands produce sweat through a well understood process of secretion and reabsorption of sodium chloride (salt). Secretion entails the movement of salt and water from sweat gland cells into the sweat duct. Reabsorption occurs in the duct with the movement of salt from the sweat back into sweat duct cells. What remains is sweat, a salt solution with a relatively finely tuned concentration of sodium and chloride.
For normal salt reabsorption to occur, individual ions of sodium and chloride must be taken from the sweat and moved back into cells of the sweat duct. These ions are moved by transporters called ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s. In the case of sodium, there is a sodium channel; for chloride, there is a chloride channel
Chloride channel
Chloride channels are a superfamily of poorly understood ion channels consisting of approximately 13 members.Chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell...
called CFTR
Cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator is a protein that in humans is encoded by the CFTR gene.CFTR is a ABC transporter-class ion channel that transports chloride and thiocyanate ions across epithelial cell membranes...
. For sweat to be produced with the proper concentrations of sodium and chloride, sodium channels and chloride channels (CFTRs) must work properly.
In cystic fibrosis, the CFTR chloride channel is defective, and does not allow chloride to be reabsorbed into sweat duct cells. Consequently, more chloride stays in the duct, and more sodium remains in the sweat. The concentration of chloride in sweat is therefore elevated in individuals with cystic fibrosis.
The concentration of sodium in sweat is also elevated in cystic fibrosis. Unlike CFTR chloride channels, sodium channels behave perfectly normally in cystic fibrosis. The elevation in sodium concentration comes from the electrical charge of retained chloride trapping sodium in the sweat duct, preventing its reabsorption. Chloride carries a negative charge, while sodium's charge is positive; the opposing charges ensure that sodium and chloride attract one another. The extra chloride ions retained in the sweat duct produce a negative charge inside the duct and therefore attract sodium ions. The final result is that both sodium and chloride concentrations are elevated in individuals with cystic fibrosis.
Method
Sweating is induced by pilocarpinePilocarpine
Pilocarpine is a parasympathomimetic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its...
iontophoresis
Iontophoresis
Iontophoresis is a technique using a small electric charge to deliver a medicine or other chemical through the skin. It is basically an injection without the needle...
. At the test site, an electrode is placed over gauze containing pilocarpine and electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
solution that will not interfere with the sodium and chloride measurement. A second electrode (without pilocarpine) will be placed at another site and a mild electrical current will draw the pilocarpine into the skin where it stimulates the sweat glands.
The test site is carefully cleaned and dried, then a piece of preweighed filter paper is placed over the test site and covered with parafilm to prevent evaporation. Specialized collection devices may also be used. Sweat is collected for 30 minutes. The filter paper is retrieved and weighed to determine the weight of sweat collected. Several laboratory methods are then used to determine the sodium and chloride concentrations.
Before this method of inducing sweat was developed, the method was to place the entire person to be tested in a hemispherical chamber and slowly raise the humidity and temperature of the air inside.
Reference ranges
For infants up to and including 6 months of age, a chloride level of:- Equal to or less than 29 mmol/L = CF is very unlikely
- 30 - 59 mmol/L = intermediate means that CF is possible
- Greater than or equal to 60 mmol/L = CF is likely to be diagnosed
For people older than 6 months of age, a chloride level of the:
- Equal to or less than 39 mmol/L = CF is very unlikely
- 40 - 59 mmol/L = intermediate means that CF is possible
- Greater than or equal to 60 mmol/L = CF is likely to be diagnosed
Interpretation
Two reliable positive results on two separate days is diagnostic for CF. Because of the existence of milder variants, borderline or even near-borderline negative results may be used to diagnose CF. Clinical presentation, family history and patient age must be considered to interpret the results. Highly discordant sodium and chloride values may indicate technical errors.Sources of error
Technical errors, insufficient sample, evaporation, contamination, dehydrationDehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
hormone therapy, and skin rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
on the tested area may produce incorrect results.
Positive test results may also be caused by malnutrition, adrenal insufficiency, glycogen storage diseases, hypothyroidism, hypoparathyroidism, nephrogenic diabetes insipidus, G6PD deficiency or ectodermal dysplasia (source: http://www.eMRCP.com)