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Oral rehydration therapy (ORT) is a type of
fluid replacement Fluid replacement or fluid resuscitation is the medical practice of replenishing bodily fluid lost through sweating, bleeding, fluid shifts or other pathologic processes. Fluids can be replaced with oral rehydration therapy (drinking), intravenous ...
used to prevent and treat
dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
, especially due to
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
. It involves drinking water with modest amounts of sugar and salts, specifically
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
and
potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
. Oral rehydration therapy can also be given by a
nasogastric tube Nasogastric intubation is a medical process involving the insertion of a plastic tube (nasogastric tube or NG tube) through the nose, down the oesophagus, and down into the stomach. Orogastric intubation is a similar process involving the inserti ...
. Therapy should routinely include the use of
zinc supplements Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic ta ...
. Use of oral rehydration therapy has been estimated to decrease the risk of death from diarrhea by up to 93%. Side effects may include
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...
,
high blood sodium Hypernatremia, also spelled hypernatraemia, is a high concentration of sodium in the blood. Early symptoms may include a strong feeling of thirst, weakness, nausea, and loss of appetite. Severe symptoms include confusion, muscle twitching, and ...
, or
high blood potassium Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...
. If vomiting occurs, it is recommended that use be paused for 10 minutes and then gradually restarted. The recommended formulation includes
sodium chloride Sodium chloride , commonly known as salt (although sea salt also contains other chemical salts), is an ionic compound with the chemical formula NaCl, representing a 1:1 ratio of sodium and chloride ions. With molar masses of 22.99 and 35.45 g ...
,
sodium citrate Sodium citrate may refer to any of the sodium salts of citric acid (though most commonly the third): * Monosodium citrate * Disodium citrate * Trisodium citrate The three forms of salt are collectively known by the E number E331. Applications F ...
,
potassium chloride Potassium chloride (KCl, or potassium salt) is a metal halide salt composed of potassium and chlorine. It is odorless and has a white or colorless vitreous crystal appearance. The solid dissolves readily in water, and its solutions have a salt ...
, and
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
. Glucose may be replaced by
sucrose Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula . For human consumption, sucrose is extracted and refined ...
and sodium citrate may be replaced by
sodium bicarbonate Sodium bicarbonate (IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda, is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cation ( Na+) and a bicarbonate anion ( HCO3−) ...
, if not available. It works as glucose increases the uptake of sodium and thus water by the
intestines The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
. A number of other formulations are also available including versions that can be made at home. However, the use of homemade solutions has not been well studied. Oral therapy was developed in the 1940s using electrolyte solutions with or without glucose on an empirical basis chiefly for mild or convalescent patients, but did not come into common use for rehydration and maintenance therapy until after the discovery that glucose promoted sodium and water absorption during cholera in the 1960s. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
. Globally, , oral rehydration therapy is used by 41% of children with diarrhea. This use has played an important role in reducing the number of deaths in children under the age of five.


Medical uses

ORT is less invasive than the other strategies for fluid replacement, specifically
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
(IV) fluid replacement. Mild to moderate dehydration in children seen in an
emergency department An emergency department (ED), also known as an accident and emergency department (A&E), emergency room (ER), emergency ward (EW) or casualty department, is a medical treatment facility specializing in emergency medicine, the acute care of pati ...
is best treated with ORT. Persons taking ORT should eat within six hours and return to their full diet within 24–48 hours. Oral rehydration therapy may also be used as a treatment for the symptoms of
dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
and rehydration in
burn A burn is an injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or ultraviolet radiation (like sunburn). Most burns are due to heat from hot liquids (called scalding), solids, or fire. Burns occur mainl ...
s in resource-limited settings.


Efficacy

ORT may lower the mortality rate of diarrhea by as much as 93%. Case studies in four developing countries also have demonstrated an association between increased use of ORS and reduction in mortality. ORT has no effect on the duration of the diarrheic episode or the volume of fluid loss.


Treatment algorithm

The degree of dehydration should be assessed before initiating ORT. ORT is suitable for people who are not dehydrated and those who show signs and symptoms of mild to moderate dehydration. People who have severe dehydration should seek professional medical help immediately and receive intravenous rehydration as soon as possible to rapidly replenish fluid volume in the body.


Contraindications

ORT should be discontinued and fluids replaced intravenously when vomiting is protracted despite proper administration of ORT; or signs of dehydration worsen despite giving ORT; or the person is unable to drink due to a decreased level of consciousness; or there is evidence of intestinal blockage or
ileus Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction. The word 'ileus' is from Ancient Greek ''eileós'' (, "intestinal obstruction"). The term 'subileus' re ...
. ORT might also be contraindicated in people who are in hemodynamic shock due to impaired airway protective reflexes. Short-term vomiting is not a contraindication to receiving oral rehydration therapy. In persons who are vomiting, drinking oral rehydration solution at a slow and continuous pace will help resolve vomiting.


Preparation

WHO Who or WHO may refer to: * Who (pronoun), an interrogative or relative pronoun * Who?, one of the Five Ws in journalism * World Health Organization Arts and entertainment Fictional characters * Who, a creature in the Dr. Seuss book '' Horton He ...
and
UNICEF UNICEF (), originally called the United Nations International Children's Emergency Fund in full, now officially United Nations Children's Fund, is an agency of the United Nations responsible for providing Humanitarianism, humanitarian and Devel ...
have jointly developed official guidelines for the manufacture of oral rehydration solution and the oral rehydration salts used to make it (both often abbreviated as ORS). They also describe acceptable alternative preparations, depending on material availability. Commercial preparations are available as either prepared fluids or packets of oral rehydration salts ready for mixing with water. A basic oral rehydration therapy solution can also be prepared when packets of oral rehydration salts are not available.Rehydration Project, Homemade Oral Rehydration Solution Recipe. The molar
ratio In mathematics, a ratio shows how many times one number contains another. For example, if there are eight oranges and six lemons in a bowl of fruit, then the ratio of oranges to lemons is eight to six (that is, 8:6, which is equivalent to the ...
of sugar to salt should be 1:1 and the solution should not be hyperosmolar. The Rehydration Project states, "Making the mixture a little diluted (with more than 1 litre of clean water) is not harmful." The optimal fluid for preparing oral rehydration solution is clean water. However, if this is not available, the usually available water should be used. Oral rehydration solution should ''not'' be withheld simply because the available water is potentially unsafe; rehydration takes precedence. When oral rehydration salts packets and suitable teaspoons for measuring sugar and salt are not available, the WHO has recommended that homemade gruels, soups, etc., may be considered to help maintain hydration. A Lancet review in 2013 emphasized the need for more research on appropriate home made fluids to prevent dehydration.
Sports drink Sports drinks, also known as electrolyte drinks, are functional beverages whose stated purpose is to help Sportsperson, athletes replace water, electrolytes, and energy before, during and especially after training or competition. There are many ...
s are not optimal oral rehydration solutions, but they can be used if optimal choices are not available. They should not be withheld for lack of better options; again, rehydration takes precedence. But they are not replacements for oral rehydration solutions in nonemergency situations.


Reduced-osmolarity

In 2003, WHO and UNICEF recommended that the
osmolarity Osmotic concentration, formerly known as osmolarity, is the measure of solute concentration, defined as the number of osmoles (Osm) of solute per litre (L) of solution (osmol/L or Osm/L). The osmolarity of a solution is usually expressed as Osm/L ...
of oral rehydration solution be reduced from 311 to 245 mOsm/L. These guidelines were also updated in 2006. This recommendation was based on multiple clinical trials showing that the reduced osmolarity solution reduces stool volume in children with diarrhea by about twenty-five percent and the need for IV therapy by about thirty percent when compared to standard oral rehydration solution. The incidence of vomiting is also reduced. The reduced osmolarity oral rehydration solution has lower concentrations of glucose and sodium chloride than the original solution, but the concentrations of potassium and
citrate Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in t ...
are unchanged."New ORS."
UNICEF. Accessed 16 February 2009.
The reduced osmolarity solution has been criticized by some for not providing enough sodium for adults with cholera. Clinical trials have, however, shown reduced osmolarity solution to be effective for adults and children with cholera. They seem to be safe but some caution is warranted according to the
Cochrane review Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...
.


Administration

ORT is based on evidence that water continues to be absorbed from the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
even while fluid is lost through diarrhea or vomiting. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
specify indications, preparations and procedures for ORT. WHO/UNICEF guidelines suggest ORT should begin at the first sign of diarrhea in order to prevent dehydration. Babies may be given ORS with a dropper or a syringe. Infants under two may be given a teaspoon of ORS fluid every one to two minutes. Older children and adults should take frequent sips from a cup, with a recommended intake of 200–400 mL of solution after every loose movement. The WHO recommends giving children under two a quarter- to a half-cup of fluid following each loose
bowel movement Defecation (or defaecation) follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus. The act has a variety of names ranging fro ...
and older children a half- to a full cup. If the person vomits, the caregiver should wait 5–10 minutes and then resume giving ORS."The treatment of diarrhea, a manual for physicians and other senior health workers."
World Health Organization, 2005.
ORS may be given by
aid worker Humanitarian aid is material and logistic assistance to people who need help. It is usually short-term help until the long-term help by the government and other institutions replaces it. Among the people in need are the homeless, refugees, and v ...
s or health care workers in
refugee A refugee, conventionally speaking, is a displaced person who has crossed national borders and who cannot or is unwilling to return home due to well-founded fear of persecution.
camps, health clinics and hospital settings."WHO position paper on oral rehydration salts to reduce mortality from cholera."
WHO 2014. Accessed 1 January 2014.
Mothers should remain with their children and be taught how to give ORS. This will help to prepare them to give ORT at home in the future. Breastfeeding should be continued throughout ORT.


Associated therapies


Zinc

As part of oral rehydration therapy, the WHO recommends supplemental zinc (10 to 20 mg daily) for ten to fourteen days, to reduce the severity and duration of the illness and make recurrent illness in the following two to three months less likely. Preparations are available as a
zinc sulfate Zinc sulfate is an inorganic compound. It is used as a dietary supplement to treat zinc deficiency and to prevent the condition in those at high risk. Side effects of excess supplementation may include abdominal pain, vomiting, headache, and ti ...
solution for adults, a modified solution for children and in tablet form.


Feeding

After severe dehydration is corrected and appetite returns, feeding the person speeds the recovery of normal intestinal function, minimizes weight loss and supports continued growth in children. Small frequent meals are best tolerated (offering the child food every three to four hours). Mothers should continue to
breastfeed Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that brea ...
."Community health worker training materials for cholera prevention and control."
CDC.
A child with watery diarrhea typically regains their appetite as soon as dehydration is corrected, whereas a child with bloody diarrhea often eats poorly until the illness resolves. Such children should be encouraged to resume normal feeding as soon as possible. Once diarrhea is corrected, the WHO recommends giving the child an extra meal each day for two weeks, and longer if the child is malnourished.


Children with malnutrition

Dehydration may be overestimated in
wasted Wasted may refer to: Arts, entertainment, and media Literature *'' Wasted: Tales of a GenX Drunk'', a 1997 memoir by Mark Judge *'' Wasted: A Memoir of Anorexia and Bulimia'', a 1998 autobiography by Marya Hornbacher *'' Wasted: A Childhood Sto ...
children and underestimated in
edematous Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
children.National Guidelines for the Management of Severely Malnourished Children in Bangladesh
, Institute of Public Health Nutrition, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of the People's Republic of Bangladesh, May 2008, "Step 3. Treat/prevent dehydration" and "Step 4. Correct electrolyte imbalance," pages 21–23 (22-24 in PDF).
Care of these children must also include careful management of their
malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues a ...
and treatment of other infections. Useful signs of dehydration include an eagerness to drink, lethargy, cool and moist extremities, weak or absent
radial pulse In human anatomy, the radial artery is the main artery of the lateral aspect of the forearm. Structure The radial artery arises from the bifurcation of the brachial artery in the antecubital fossa. It runs distally on the anterior part of the ...
(wrist), and reduced or absent
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...
flow. In children with severe malnutrition, it is often impossible to reliably distinguish between moderate and severe dehydration. A severely malnourished child who has signs of severe dehydration but who does not have a history of watery diarrhea should be treated for
septic shock Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Con ...
. The original ORS (90 mmol sodium/L) and the current standard reduced-osmolarity ORS (75 mmol sodium/L) both contain too much sodium and too little potassium for severely malnourished children with dehydration due to diarrhea. ReSoMal (Rehydration Solution for Malnutrition) is recommended for such children. It contains less sodium (45 mmol/L) and more potassium (40 mmol/L) than reduced osmolarity ORS. It can be obtained in packets produced by UNICEF or other manufacturers. An exception is if the severely malnourished child also has severe diarrhea (in which case ReSoMal may not provide enough sodium), in which case standard reduced-osmolarity ORS (75 mmol sodium/L) is recommended. Malnourished children should be rehydrated slowly. The WHO recommends 10 milliliters of ReSoMal per kilogram body weight for each of the first two hours (for example, a 9-kilogram child should be given 90 mL of ReSoMal over the course of the first hour, and another 90 mL for the second hour) and then continuing at this same rate or slower based on the child's thirst and ongoing stool losses, keeping in mind that a severely dehydrated child may be lethargic. If the child drinks poorly, a nasogastric tube should be used. The IV route should not be used for rehydration except in cases of shock and then only with care, infusing slowly to avoid flooding the circulation and overloading the heart. Feeding should usually resume within 2–3 hours after starting rehydration and should continue every 2–3 hours, day and night. For an initial cereal diet before a child regains his or her full appetite, the WHO recommends combining 25 grams skimmed milk powder, 20 grams vegetable oil, 60 grams sugar, and 60 grams rice powder or other cereal into 1,000 milliliters water and boiling gently for five minutes. Give 130 mL per kilogram of body weight during per 24 hours. A child who cannot or will not eat this minimum amount should be given the diet by nasogastric tube divided into six equal feedings. Later on, the child should be given cereal made with a greater amount of skimmed milk product and vegetable oil and slightly less sugar. As appetite fully returns, the child should be eating 200 mL per kilogram of body weight per day. Zinc, potassium, vitamin A, and other vitamins and minerals should be added to both recommended cereal products, or to the oral rehydration solution itself. Children who are breastfed should continue breastfeeding.


Antibiotics

The WHO recommends that all severely malnourished children admitted to hospital should receive
broad-spectrum antibiotic A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial inf ...
s (for example,
gentamicin Gentamicin is an antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. It is not e ...
and
ampicillin Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B strepto ...
). In addition, hospitalized children should be checked daily for other specific infections. If cholera is suspected give an antibiotic to which ''V. cholera''e are susceptible. This reduces the volume loss due to diarrhea by 50% and shortens the duration of diarrhea to about 48 hours.


Physiological basis

Fluid from the body enters the
intestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
lumen during
digestion Digestion is the breakdown of large insoluble food molecules into small water-soluble food molecules so that they can be absorbed into the watery blood plasma. In certain organisms, these smaller substances are absorbed through the small intest ...
. This fluid is
isosmotic Osmotic concentration, formerly known as osmolarity, is the measure of solute concentration, defined as the number of osmoles (Osm) of solute per litre (L) of solution (osmol/L or Osm/L). The osmolarity of a solution is usually expressed as Osm/L ...
with the blood and contains a high quantity, about 142 mEq/L, of
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
. A healthy individual secretes 2000–3000 milligrams of sodium per day into the intestinal lumen. Nearly all of this is reabsorbed so that sodium levels in the body remain constant. In a diarrheal illness, sodium-rich intestinal secretions are lost before they can be reabsorbed. This can lead to life-threatening
dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
or
electrolyte imbalance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...
s within hours when fluid loss is severe. The objective of therapy is the replenishment of sodium and water losses by ORT or intravenous infusion. Sodium absorption occurs in two stages. The first is via intestinal
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
cells (
enterocyte Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its ...
s). Sodium passes into these cells by
co-transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...
with glucose, via the
SGLT1 Sodium/glucose cotransporter 1 (SGLT1) also known as solute carrier family 5 member 1 is a protein in humans that is encoded by the gene which encodes the production of the SGLT1 protein to line the absorptive cells in the small intestine and th ...
protein. From the intestinal epithelial cells, sodium is pumped by
active transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...
via the sodium-potassium pump through the basolateral cell membrane into the
extracellular space Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells. The compositi ...
. The sodium–potassium ATPase pump at the basolateral
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
moves three sodium ions into the extracellular space, while pulling into the enterocyte two
potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
ions. This creates a "downhill" sodium
gradient In vector calculus, the gradient of a scalar-valued differentiable function of several variables is the vector field (or vector-valued function) \nabla f whose value at a point p is the "direction and rate of fastest increase". If the gradi ...
within the cell. SGLT proteins use energy from this downhill sodium gradient to transport
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
across the
apical membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
of the cell against the glucose gradient. The co-transporters are examples of
secondary active transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...
. The GLUT
uniporters Facilitated diffusion (also known as facilitated transport or passive-mediated transport) is the process of spontaneous passive transport (as opposed to active transport) of molecules or ions across a biological membrane via specific transmembr ...
then transport glucose across the basolateral membrane. Both SGLT1 and SGLT2 are known as
symporter A symporter is an integral membrane protein that is involved in the transport of two (or more) different molecules across the cell membrane in the same direction. The symporter works in the plasma membrane and molecules are transported across the ...
s, since both sodium and glucose are transported in the same direction across the membrane. The co-transport of glucose into epithelial cells via the
SGLT1 Sodium/glucose cotransporter 1 (SGLT1) also known as solute carrier family 5 member 1 is a protein in humans that is encoded by the gene which encodes the production of the SGLT1 protein to line the absorptive cells in the small intestine and th ...
protein requires sodium. Two sodium ions and one molecule of glucose (or
galactose Galactose (, '' galacto-'' + '' -ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molec ...
) are transported together across the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
via the SGLT1 protein. Without glucose, intestinal sodium is not absorbed. This is why oral rehydration salts include both sodium and glucose. For each cycle of the transport, hundreds of water molecules move into the epithelial cell to maintain osmotic equilibrium. The resultant absorption of sodium and water can achieve rehydration even while diarrhea continues.


History


Definition

In the early 1980s, "oral rehydration therapy" referred only to the preparation prescribed by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) and
UNICEF UNICEF (), originally called the United Nations International Children's Emergency Fund in full, now officially United Nations Children's Fund, is an agency of the United Nations responsible for providing Humanitarianism, humanitarian and Devel ...
. In 1988, the definition changed to encompass recommended home-made solutions, because the official preparation was not always readily available. The definition was again amended in 1988 to include continued feeding as an appropriate associated therapy. In 1991, the definition became, "an increase in administered
hydrational fluid Oral rehydration therapy (ORT) is a type of fluid replacement used to prevent and treat dehydration, especially due to diarrhea. It involves drinking water with modest amounts of sugar and salts, specifically sodium and potassium. Oral rehydrati ...
s" and in 1993, "an increase in administered fluids and continued feeding".


Development

Dehydration was a major cause of death during the 1829
cholera Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...
pandemic in Russia and Western Europe. In 1831,
William Brooke O'Shaughnessy Sir William Brooke O'Shaughnessy (from 1861 as William O'Shaughnessy Brooke) MD FRS (October 1809, in Limerick, Ireland – 8 January 1889, in Southsea, England) was an Irish physician famous for his wide-ranging scientific work in pharmacology, ...
noted the changes in blood composition and loss of water and salt in the stool of people with cholera and prescribed intravenous fluid therapy (IV fluids), first administered by Latta. The prescribing of
hypertonic In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective membrane- ...
IV therapy by Rogers decreased the mortality rate of cholera from 70 to 40 percent. In the West, IV therapy became the "gold standard" for the treatment of moderate and severe dehydration. In 1953, Indian physician
Hemendra Nath Chatterjee Hemendra Nath Chatterjee was an Indian scientist from West Bengal, who gave a dilute salt and glucose solutions both rectally and orally to a small percentage of pre-selected mildly ill cholera patients. He did not measure intake and output and pr ...
published his results in
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...
of treating people with mild cholera with ORT. He gave the solution orally and rectally along with Coleus extract, antihistimines and antiemetics without controls. The formulation of the fluid replacement solution was 4 g of
sodium chloride Sodium chloride , commonly known as salt (although sea salt also contains other chemical salts), is an ionic compound with the chemical formula NaCl, representing a 1:1 ratio of sodium and chloride ions. With molar masses of 22.99 and 35.45 g ...
, 25 g of
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
and 1000 mL of
water Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as a ...
. He did not publish any balance data and his exclusion of patients with severe dehydration did not lead to any confirmatory study; his report remained anecdotal.
Robert Allan Phillips Robert Allan Phillips MD (July 16, 1906 in Clear Lake, Iowa&nbsPaperity Retrieved 2014-11-19. – September 20, 1976) was a research scientist whose research contributed to a transformation in the treatment of cholera. Education Dr. Phi ...
attempted to create an effective ORT solution based on his discovery that, in the presence of glucose, sodium and chloride could be absorbed in patients with cholera. However, Phillips' efforts failed because the solution he used was excessively hypertonic, and he used to try to stop the diarrhea rather than to rehydrate patients. In the early 1960s, biochemist
Robert K. Crane Robert Kellogg Crane (December 20, 1919 – October 31, 2010) was an American biochemist best known for his discovery of sodium–glucose cotransport. Biography Crane was born on December 20, 1919 in Palmyra, New Jersey, to Wilbur Fiske Crane, J ...
described the sodium-glucose co-transport mechanism and its role in intestinal glucose absorption. This, combined with evidence that the intestinal
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
appears undamaged in cholera, suggested that intestinal absorption of glucose and sodium might continue during the illness. This supported the notion that oral rehydration might be possible even during severe diarrhea due to cholera. In 1967–1968,
Norbert Hirschhorn Norbert Hirschhorn (born 1938) is an Austrian-born American public health physician. He was one of the inventors and developers of the life-saving method called oral rehydration therapy Oral rehydration therapy (ORT) is a type of fluid replace ...
and Nathaniel F. Pierce, working in Dhaka, Bangladesh and Calcutta, India, respectively, showed that people with severe cholera can absorb glucose, salt and water and that this can occur in sufficient amounts to maintain hydration. In 1968, David R. Nalin and
Richard A. Cash Richard Alan Cash (born June 9, 1941) is an American global health researcher, public health physician, and internist. He is a Senior Lecturer in International Health at the Harvard T.H. Chan School of Public Health in Boston. He is an alumnus ...
, assisted by Rafiqul Islam and Majid Molla, reported that in adults with cholera, given an oral glucose-electrolyte solution in volumes equal to that of the diarrhea losses, reduced the need for IV fluid therapy by eighty percent. 6 In 1971, fighting during the
Bangladesh Liberation War The Bangladesh Liberation War ( bn, মুক্তিযুদ্ধ, , also known as the Bangladesh War of Independence, or simply the Liberation War in Bangladesh) was a revolution and War, armed conflict sparked by the rise of the Benga ...
displaced millions and an epidemic of cholera ensued among the refugees. When IV fluid ran out in the
refugee camp A refugee camp is a temporary settlement built to receive refugees and people in refugee-like situations. Refugee camps usually accommodate displaced people who have fled their home country, but camps are also made for internally displaced peo ...
s,
Dilip Mahalanabis Dilip Mahalanabis (12 November 1934 – 16 October 2022) was an Indian paediatrician known for pioneering the use of oral rehydration therapy to treat diarrhoeal diseases. Mahalanabis had begun researching oral rehydration therapy in 1966 as a r ...
, a physician working with the Johns Hopkins International Center for Medical Research and Training in Calcutta, instructed to prepare and distribute an oral rehydration solution prepared from individual ingredients to family members and caregivers. Over 3,000 people with cholera received ORT in this way. The
mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of de ...
was 3.6 percent among those given ORT compared with 30 percent in those given IV fluid therapy. After the independence of Bangladesh, a wide circulation campaign was conducted on the use of saline in the treatment of diarrhea. In the year 1980, the World Health Organization recognized ORT and began a global program for its dissemination. In the 1970s,
Norbert Hirschhorn Norbert Hirschhorn (born 1938) is an Austrian-born American public health physician. He was one of the inventors and developers of the life-saving method called oral rehydration therapy Oral rehydration therapy (ORT) is a type of fluid replace ...
used oral rehydration therapy on the White River Apache Indian Reservation with a grant from the National Institute of Allergy and Infectious Diseases. He made the important observation that children would voluntarily drink as much of the solution as needed to restore hydration, and that rehydration and early re-feeding would protect their nutrition. This led to increased use of ORT for children with diarrhea, especially in developing countries. In 1980, the Bangladeshi nonprofit BRAC created a door-to-door and person-to-person sales force to teach ORT for use by mothers at home. A task force of fourteen women, one cook and one male supervisor traveled from village to village. After visiting with women in several villages, they hit upon the idea of encouraging the women in the village to make their own oral rehydration fluid. They used available household equipment, starting with a "half a seer" (half a quart) of water and adding a fistful of sugar and a three-finger pinch of salt. Later on, the approach was broadcast over television and radio and a market for oral rehydration salts packets developed. Three decades later, national surveys have found that almost 90% of children with severe diarrhea in Bangladesh are given oral rehydration fluids at home or in a health facility. ORT is known in Bangladesh as Orosaline or Orsaline. From 2006 to 2011, UNICEF estimated that worldwide about a third of children under 5 who had diarrhea received an oral rehydration solution, with estimates ranging from 30% to 41% depending on the region. ORT is one of the principal elements of the UNICEF "GOBI FFF" program (growth monitoring; ORT; breast feeding; immunization; female education; family spacing and
food supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
ation). The program aims to increase child survival in developing nations through proven low-cost interventions.


Mozambique civil war refugees, 1990

People had fled from civil war in Mozambique to southern Malawi. In November 1990, cholera broke out in a refugee camp in southern Malawi where approximately 74,000 persons were temporarily living. David Swerdlow of the U.S.'s CDC
Epidemic Intelligence Service The Epidemic Intelligence Service (EIS) is a program of the U.S. Centers for Disease Control and Prevention (CDC). The modern EIS is a two-year, hands-on post-doctoral training program in epidemiology, with a focus on field work. History Creation ...
(EIS) wrote about the situation. He recommended setting up a tent just for children who would be assisted by some of the best nurses. He recommended against over-reliance on IV tubes, which often were left attached to persons for a week or more and which could lead to infections and septic shock. And he noticed that sick persons were not drinking enough rehydration solution. He assigned so-called "ORS officers" whose job was to encourage persons to drink more solution.Inside the Outbreaks: The Elite Medical Detectives of the Epidemic Intelligence Service
Mark Pendergrast, Boston, New York: Houghton Mifflin Harcourt, 2010, Section III: Complex Challenges (1982 – Present), pages 269–70. "Cholera continued its inexorable spread during the drawn-out seventh world pandemic that had begun in 1961 . . "
It was a minor mystery how persons were getting sick since deep-bore wells provided clean water and refugees were encouraged to wash their hands. It was then discovered that the only place for persons to wash hands were in the same buckets in which water was transported and stored. Swerdlow wrote in his report, "Use of narrow mouthed water containers would probably decrease the likelihood of contamination."


Awards

* Centre for Health and Population Research,
Dhaka Dhaka ( or ; bn, ঢাকা, Ḍhākā, ), formerly known as Dacca, is the capital and largest city of Bangladesh, as well as the world's largest Bengali-speaking city. It is the eighth largest and sixth most densely populated city ...
,
Bangladesh Bangladesh (}, ), officially the People's Republic of Bangladesh, is a country in South Asia. It is the eighth-most populous country in the world, with a population exceeding 165 million people in an area of . Bangladesh is among the mos ...
, 2001 Gates award for global health. *
Norbert Hirschhorn Norbert Hirschhorn (born 1938) is an Austrian-born American public health physician. He was one of the inventors and developers of the life-saving method called oral rehydration therapy Oral rehydration therapy (ORT) is a type of fluid replace ...
,
Dilip Mahalanabis Dilip Mahalanabis (12 November 1934 – 16 October 2022) was an Indian paediatrician known for pioneering the use of oral rehydration therapy to treat diarrhoeal diseases. Mahalanabis had begun researching oral rehydration therapy in 1966 as a r ...
,
David Nalin David R. Nalin (born April 21, 1941) is an American physiologist, and Pollin Prize for Pediatric Research and Prince Mahidol Award, a.k.a. Mahidol Medal winner. Nalin had the key insight that oral rehydration therapy (ORT) would work if the vo ...
, and Nathaniel Pierce, 2002 inaugural
Pollin Prize for Pediatric Research The Pollin Prize for Pediatric Research was an annual award given to physicians who contributed important advances to the field of pediatrics, and was the only existing international pediatric award. The prize was created in 2002 by Irene and Abe ...
. *
Richard A. Cash Richard Alan Cash (born June 9, 1941) is an American global health researcher, public health physician, and internist. He is a Senior Lecturer in International Health at the Harvard T.H. Chan School of Public Health in Boston. He is an alumnus ...
,
David Nalin David R. Nalin (born April 21, 1941) is an American physiologist, and Pollin Prize for Pediatric Research and Prince Mahidol Award, a.k.a. Mahidol Medal winner. Nalin had the key insight that oral rehydration therapy (ORT) would work if the vo ...
,
Dilip Mahalanabis Dilip Mahalanabis (12 November 1934 – 16 October 2022) was an Indian paediatrician known for pioneering the use of oral rehydration therapy to treat diarrhoeal diseases. Mahalanabis had begun researching oral rehydration therapy in 1966 as a r ...
and
Stanley Schultz Stanley G. Schultz (October 26, 1931 – October 23, 2014) was an American physician and scientist whose work led to the development of oral rehydration therapy. He held the Fondren Family Chair in Cellular Signaling and the H. Wayne Hightower Di ...
, 2006
Prince Mahidol Award The Prince Mahidol Award ( th, รางวัลสมเด็จเจ้าฟ้ามหิดล) is an annual award for outstanding achievements in medicine and public health worldwide. The award is given by the Prince Mahidol Award Found ...
."Prince Mahidol Award 2006."
Prince Mahidol Award Foundation. Accessed 22 February 2009.


References

Sources *


Further reading

*


External links


Rehydration Project
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