Sweat test | |
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Purpose | measures concentration of chloride |
The sweat test measures the concentration of chloride that is excreted in sweat. It is used to screen for cystic fibrosis (CF). [1] Due to defective chloride channels (CFTR), the concentration of chloride in sweat is elevated in individuals with CF.
Cystic fibrosis is caused by defects in a protein found in many tissues, including the airways and the sweat glands. [1] As a result, these tissues do not work properly. Sweat testing makes use of the fact that cystic fibrosis patients have defective sweat glands. [2]
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 channels. 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 sodium stays in the duct, and more chloride 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. However, in order for the secretion to be electrically neutral, positively charged sodium cations remain in the sweat along with the negatively charged chloride anions. In this way, the chloride anions are said to "trap" the sodium cations.[ citation needed ]
Sweating is induced by pilocarpine iontophoresis. [3] 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 electric 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. [4]
For infants up to and including 6 months of age, a chloride level of:
For people older than 6 months of age, a chloride level of:
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.
Technical errors, insufficient sample, evaporation, contamination, dehydration, 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.
Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.
Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals.
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a central role in the homeostatic regulation of blood pressure, plasma sodium (Na+), and potassium (K+) levels. It does so primarily by acting on the mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron. It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of the kidney, thereby indirectly influencing water retention or loss, blood pressure, and blood volume. When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and kidney disease. Aldosterone has exactly the opposite function of the atrial natriuretic hormone secreted by the heart.
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in electrolyte and fluid balance through reabsorption and excretion, processes regulated by the hormones aldosterone and vasopressin.
Renal physiology is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death.
Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable coupled or cotransport and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters.
Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.
Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the CFTR gene.
Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations. The condition typically cannot last long if the kidneys are functioning properly.
Bartter syndrome (BS) is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels (hypokalemia), increased blood pH (alkalosis), and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome, is milder than both subtypes of Bartter syndrome.
The epithelial sodium channel(ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (Na+). It is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. The ENaC is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons. In addition to being implicated in diseases where fluid balance across epithelial membranes is perturbed, including pulmonary edema, cystic fibrosis, COPD and COVID-19, proteolyzed forms of ENaC function as the human salt taste receptor.
Eccrine sweat glands (; from Greek ek +krinein 'out /external+secrete'; sometimes called merocrine glands as their type of secretion is merocrine, are the major sweat glands of the human body. Eccrine sweat glands are found in virtually all skin, with the highest density in the palms of the hands, and soles of the feet, and on the head, but much less on the torso and the extremities. In other mammals, they are relatively sparse, being found mainly on hairless areas such as foot pads. They reach their peak of development in humans, where they may number 200–400/cm2 of skin surface. They produce sweat, a clear, odorless substance, consisting primarily of water. These are present from birth. Their secretory part is present deep inside the dermis.
The salt gland is an organ for excreting excess salts. It is found in the cartilaginous fishes subclass elasmobranchii, seabirds, and some reptiles. Salt glands can be found in the rectum of sharks. Birds and reptiles have salt glands located in or on the skull, usually in the eyes, nose, or mouth. These glands are lobed containing many secretory tubules which radiate outward from the excretory canal at the center. Secretory tubules are lined with a single layer of epithelial cells. The diameter and length of these glands vary depending on the salt uptake of the species.
Carbonic anhydrase 12 is an enzyme that in humans is encoded by the CA12 gene.
A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, such as cations, anions, amino acids, and other chemicals. These blockers act as ion channel antagonists, preventing the response that is normally provided by the opening of the channel.
Transepithelial potential difference (TEPD) is the voltage across an epithelium, and is the sum of the membrane potentials for the outer and inner cell membranes.
Denufosol (INN) is an inhaled drug for the treatment of cystic fibrosis, being developed by Inspire Pharmaceuticals and sponsored by the Cystic Fibrosis Foundation. It was tested in two Phase III clinical trials, TIGER-1 and TIGER-2. Initially, in the first Phase III trial, TIGER-1, the compound showed significant results as compared with placebo. In the second Phase III trial, TIGER-2, the compound did not meet the primary endpoint, a significant change in baseline FEV1 at the week 48 endpoint as compared to placebo. As of 2011, no additional clinical studies are being conducted with the compound.
Elexacaftor/tezacaftor/ivacaftor, sold under the brand names Trikafta (US) and Kaftrio (EU), is a fixed-dose combination medication used to treat cystic fibrosis. Elexacaftor/tezacaftor/ivacaftor is composed of a combination of ivacaftor, a chloride channel opener, and elexacaftor and tezacaftor, CFTR modulators.
Underrepresented populations, especially black and hispanic populations with cystic fibrosis are often not successfully diagnosed. This is in part due to the minimal dissemination of existing data on patients from these underrepresented groups. While white populations do appear to experience a higher frequency of cystic fibrosis, other ethnicities are also affected and not always by the same biological mechanisms. Thus, many healthcare and treatment options are less reliable or unavailable to underrepresented populations. This issue affects the level at which public health needs are being met across the world.