Unit 2 - Pathopysiology of Watery Diarrhoea: Dehydration and Rehydration
Medical Education: Teaching Medical Students about Diarrhoeal Diseases

World Health Organization 1992
http://apps.who.int/iris/handle/10665/40343

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INTESTINAL PHYSIOLOGY Normal intestinal fluid balance Intestinal absorption of water and electrolytes Intestinal secretion of water and electrolytes MECHANISMS OF WATERY DIARRHOEA Secretory diarrhoea Osmotic diarrhoea CONSEQUENCES OF WATERY DIARRHOEA Isotonic dehydration Hypertonic (hypernatraemic) dehydration Hypotonic (hyponatraemic) dehydration Base-deficit acidosis (metabolic acidosis) Potassium depletion REHYDRATION THERAPY Oral rehydration therapy (ORT) Oral rehydration salts (ORS) Composition of ORS Sodium concentration Home fluids Limitations of ORT Intravenous therapy Preferred solution Acceptable solutions Unacceptable solution EXERCISES

UNIT 2 - PATHOPHYSIOLOGY OF WATERY DIARRHOEA: DEHYDRATION AND REHYDRATION

INTESTINAL PHYSIOLOGY

Watery diarrhoea results from disordered water and electrolyte transport in the small intestine. Intestinal transport mechanisms are also the basis for the management of diarrhoea, through oral fluid therapy and feeding. It is therefore important to understand some of the normal mechanisms of intestinal transport and how they are altered during diarrhoea.

Normal intestinal fluid balance

Normally, absorption and secretion of water and electrolytes occur throughout the intestine. For example, a healthy adult takes in less than two litres of fluid each day. Saliva and secretions from the stomach, pancreas, and liver add about seven litres, making a total of about nine litres that enter the small intestine every day. There, water and electrolytes are simultaneously absorbed by the villi and secreted by the crypts of the bowel epithelium. This causes a two-directional flow of water and electrolytes between the intestinal lumen and the blood. Since fluid absorption normally is greater than fluid secretion, the net result is fluid absorption.

Usually, more than 90% of the fluid entering the small intestine is absorbed, so that about one litre reaches the large intestine. There, further absorption occurs, only 100 to 200 millilitres of water being excreted each day in formed stools. Any change in the two-directional flow of water and electrolytes in the small intestine (i.e., increased secretion, decreased absorption, or both) results in either reduced net absorption or net secretion and causes an increased volume of fluid to enter the large intestine. When this exceeds its limited absorptive capacity, diarrhoea occurs.

Intestinal absorption of water and electrolytes

Absorption of water from the small intestine is caused by osmotic gradients that are created when solutes (particularly sodium) are actively absorbed from the bowel lumen by the villous epithelial cells. There are several mechanisms whereby sodium is absorbed in the small intestine. To enter the epithelial cells, sodium is linked to the absorption of chloride, or absorbed directly as sodium ion, or exchanged for hydrogen ion, or linked to the absorption of organic materials such as glucose or certain amino acids. The addition of glucose to an electrolyte solution can increase sodium absorption in the intestine as much as threefold.

After being absorbed, sodium is transported out of the epithelial cells by an ion pump referred to as Na+K+ ATPase. This transfers sodium into the extracellular fluid (ECF), which elevates its osmolality and causes water and other electrolytes to flow passively from the bowel lumen through intercellular channels and into the ECF (see Figure 2.2, part 1). This process maintains an osmotic balance between fluid in the bowel and ECF in the intestinal tissue.

Intestinal secretion of water and electrolytes

Secretion of water and electrolytes normally occurs in the crypts of the small bowel epithelium where NaCl is transported from ECF into the epithelial cell across its basolateral membrane (see Figure 2.2, example E). The sodium is then pumped back into the ECF by Na+K+ ATPase. At the same time, secretory stimuli increase the ability of chloride to pass through the luminal membrane of the crypt cells, allowing that ion to enter the bowel lumen. This movement of chloride ion creates an osmotic gradient that causes water and other electrolytes to flow passively from the ECF into the bowel lumen through the intercellular channels.

MECHANISMS OF WATERY DIARRHOEA

There are two principal mechanisms by which watery diarrhoea occurs: (i) secretion, and (ii) osmotic imbalance. Intestinal infections can cause diarrhoea by both mechanisms, secretory diarrhoea being more common, and both may occur in a single individual.

Secretory diarrhoea

Secretory diarrhoea is caused by the abnormal secretion of fluid (water and salts) into the small bowel. This occurs when the absorption of sodium by the villi is impaired while the secretion of chloride in the crypts continues or is increased (see Figure 2.1, part 2). Net fluid secretion results and leads to the loss of water and salts from the body as watery stools; this causes dehydration. In infectious diarrhoea, these changes may result from the action on the bowel mucosa of bacterial toxins, such as those of Escherichia coli and Vibrio cholerae 01, or of viruses, such as rotavirus; other mechanisms may also be important.

Osmotic diarrhoea

The small bowel mucosa is a porous epithelium; water and salts move across it rapidly to maintain osmotic balance between the bowel contents and the blood. Under these conditions, diarrhoea can occur when a poorly absorbed, osmotically active substance is ingested. If the substance is taken as an isotonic solution, the water and solute will simply pass through the gut unabsorbed, causing diarrhoea. Purgatives, such as magnesium sulfate, work by this principle. The same process may occur when the solute is lactose (in children with lactase deficiency) or glucose (in children with glucose malabsorption); both conditions are occasional complications of enteric infections. If the poorly absorbed substance is taken as a hypertonic solution, water (and some electrolytes) will move from the ECF into the gut lumen, until the osmolality of the intestinal contents equals that of ECF and blood. This increases the volume of the stool and, more importantly, causes dehydration owing to the loss of body water. Because the loss of body water is greater than the loss of sodium chloride, hypernatraemia also develops (see below).

CONSEQUENCES OF WATERY DIARRHOEA

Diarrhoea stool contains large amounts of sodium, chloride, potassium, and bicarbonate (see Table 2.1).

All the acute effects of watery diarrhoea result from the loss of water and electrolytes from the body in liquid stool. Additional amounts of water and electrolytes are lost when there is vomiting, and water losses are also increased by fever. These losses cause dehydration (due to the loss of water and sodium chloride), metabolic acidosis (due to the loss of bicarbonate), and potassium depletion. Among these, dehydration is the most dangerous because it can cause decreased blood volume (hypovolaemia), cardiovascular collapse, and death if not treated promptly. Three types of dehydration are considered below.

Isotonic dehydration

This is the type of dehydration most frequently caused by diarrhoea. It occurs when the net losses of water and sodium are in the same proportion as normally found in the ECF. The principal features of isotonic dehydration are:

• there is a balanced deficit of water and sodium;
  
• serum sodium concentration is normal (130-150 mmol/l);
  
• serum osmolality is normal (275-295 mOsmol/l);
  
• hypovolaemia occurs as a result of a substantial loss of extracellular fluid.

Isotonic dehydration is manifested first by thirst, and subsequently by decreased skin turgor, tachycardia, dry mucous membranes, sunken eyes, lack of tears, a sunken anterior fontanelle in infants, and oliguria. The physical signs of isotonic dehydration begin to appear when the fluid deficit approaches 5% of body weight and worsen as the deficit increases. As the fluid deficit approaches 10% of body weight, dehydration becomes severe and anuria, hypotension, a feeble and very rapid radial pulse, cool and moist extremities, diminished consciousness, and other signs of hypovolaemic shock appear. A fluid deficit that exceeds 10% of body weight leads rapidly to death from circulatory collapse.

Hypertonic (hypernatraemic) dehydration

Some children with diarrhoea, especially young infants, develop hypernatraemic dehydration. This reflects a net loss of water in excess of sodium, when compared with the proportion normally found in ECF and blood. It usually results from the ingestion during diarrhoea of fluids that are hypertonic (owing to their content of sodium, sugar, or other osmotically active solutes, such as lactose in whole cow's milk) and not efficiently absorbed, and an insufficient intake of water or other low-solute drinks. The hypertonic fluids create an osmotic gradient that causes a flow of water from ECF into the intestine, leading to a decrease in the ECF volume and an increase in sodium concentration within the ECF (see Figure 2.3, B). The principal features of hypernatraemic dehydration are:

• there is a deficit of water and sodium, but the deficit of water is greater;
• serum sodium concentration is elevated (>150 mmol/l);
• serum osmolality is elevated (>295 mOsmol/l);
• thirst is severe and out of proportion to the apparent degree of dehydration; the child is very irritable;
• seizures may occur, especially when the serum sodium concentration exceeds 165 mmol/l.

Hypotonic (hyponatraemic) dehydration

Children with diarrhoea who drink large amounts of water or other hypotonic fluids containing very low concentrations of salt and other solutes, or who receive intravenous infusions of 50% glucose in water, may develop hyponatraemia. This occurs because water is absorbed from the gut while the loss of salt (NaCl) continues, causing net losses of sodium in excess of water. The principal features of hyponatraemic dehydration are:

• there is a deficit of water and sodium, but the deficit of sodium is greater;
  
• serum sodium concentration is low (<130 mmol/l);
  
• serum osmolality is low (<275 mOsmol/l);
  
• the child is lethargic; infrequently, there are seizures.

Base-deficit acidosis (metabolic acidosis)

During diarrhoea, a large amount of bicarbonate may be lost in the stool. If the kidneys continue to function normally, much of the lost bicarbonate is replaced by the kidneys and a serious base deficit does not develop. However, this compensating mechanism fails when renal function deteriorates, as happens when there is poor renal blood flow due to hypovolaemia. Then, base deficit and acidosis develop rapidly. Acidosis also results from excessive production of lactic acid when patients have hypovolaemic shock. The features of base-deficit acidosis include:

• the serum bicarbonate concentration is reduced - it may be less than 10 mmol/l;
  
• arterial pH is reduced - it may be less than 7.10;
  
• breathing becomes deep and rapid, which helps to raise arterial pH by causing a compensating respiratory alkalosis;
  
• there is increased vomiting.

Potassium depletion

Patients with diarrhoea often develop potassium depletion owing to large faecal losses of this ion; these losses are greatest in infants and can be especially dangerous in malnourished children, who are frequently potassium-deficient before diarrhoea starts. When potassium and bicarbonate are lost together, hypokalaemia does not usually develop. This is because the metabolic acidosis that results from the loss of bicarbonate causes potassium to move from ICF to ECF in exchange for hydrogen ion, thus keeping the serum potassium level in a normal or even elevated range. However, when metabolic acidosis is corrected by giving bicarbonate, this shift is rapidly reversed, and serious hypokalaemia can develop. This can be prevented by replacing potassium and correcting the base deficit at the same time. The signs of hypokalaemia may include:

• general muscular weakness;
  
• cardiac arrhythmias;
  
• paralytic ileus, especially when drugs are taken that also affect peristalsis (such as opiates).

REHYDRATION THERAPY

The goal in managing diarrhoeal dehydration is rapidly to correct fluid and electrolyte deficits (termed "rehydration therapy") and then to replace further fluid and electrolyte losses as they occur until diarrhoea stops (termed "maintenance therapy"). Fluid losses can be replaced either orally or intravenously; the latter route is usually needed only for initial rehydration of patients with severe dehydration.

Oral rehydration therapy (ORT)

ORT is based on the principle that intestinal absorption of sodium (and thus of other electrolytes and water) is enhanced by the active absorption of certain food molecules such as glucose (which is derived from the breakdown of sucrose or cooked starches) or l-amino acids (which are derived from the breakdown of proteins and peptides). Fortunately, this process continues to function during secretory diarrhoea, whereas most other pathways of intestinal absorption of sodium are impaired. Thus, if patients with secretory diarrhoea drink an isotonic salt solution that contains no source of glucose or amino acids, sodium is not absorbed and the fluid remains in the gut, ultimately adding to the volume of stool passed by the patient. However, when an isotonic solution of glucose and salt is given, glucose-linked sodium absorption occurs and this is accompanied by the absorption of water and other electrolytes. This process can correct existing deficits of water and electrolytes and replace further faecal losses in most patients with secretory diarrhoea, irrespective of the cause of diarrhoea or the age of the patient.

Oral rehydration salts (ORS)

Composition of ORS. The principles underlying ORT have been applied to the development of a balanced mixture of glucose and electrolytes for use in treating and preventing dehydration, potassium depletion, and base deficit due to diarrhoea. To attain the latter two objectives, salts of potassium and citrate (or bicarbonate) have been included, in addition to sodium chloride. This mixture of salts and glucose is termed oral rehydration salts (ORS); when ORS is dissolved in water, the mixture is called ORS solution. The following guidelines were used in developing the WHO/UNICEF-recommended ORS solution:

• the solution should have an osmolarity similar to, or less than that of plasma, i.e., about 300 mOsmol/l or less;
  
• the concentration of sodium should be sufficient to replace efficiently the sodium deficit in children or adults with clinically significant dehydration;
  
• the ratio of glucose to sodium (in mmol/l) should be at least 1:1 to achieve maximum sodium absorption;
  
• the concentration of potassium should be about 20 mmol/l in order adequately to replace potassium losses;
  
• the concentration of base should be 10 mmol/l for citrate or 30 mmol/l for bicarbonate, which is satisfactory for correcting base-deficit acidosis due to diarrhoea. The use of trisodium citrate, dihydrate, is preferred, since this gives ORS packets a longer shelf life.

Sodium concentration: ORS solution has been used to treat millions of diarrhoea cases of different etiologies in all ages, and has proved to be remarkably safe and effective. Nevertheless, because stool electrolyte concentrations vary in different types of diarrhoea and in patients of different ages, doctors are sometimes concerned about using a single ORS solution in all clinical situations. In this regard, Table 2.1 compares the composition of ORS solution with the average electrolyte composition of stool in different kinds of acute watery diarrhoea. The stools of patients with cholera contain relatively large amounts of bicarbonate and potassium. In children with acute non-cholera diarrhoea, the concentrations of sodium, bicarbonate, and chloride in the stool are lower, although they vary considerably. A child with dehydration due to diarrhoea has deficits of sodium and water. In cases of severe dehydration, the sodium deficit has been estimated to be 70-110 mmol for each 1000 ml of water. The sodium concentration of 90 mmol/l in ORS solution is within this range and hence it is suitable for the treatment of dehydration. During the maintenance phase, however, when ORS is used to replace continuing stool losses, the concentration of sodium excreted in the stool averages 50 mmol/l. Although this could be replaced with a separate solution containing 50 mmol of sodium, the same result can be obtained by giving the standard ORS with water or breast milk. This approach reduces the average concentration of sodium ingested to a range that is both safe and effective, and any modest excess of sodium or water can be excreted in the urine; this is especially important in young infants, in whom renal function is not fully developed. A major advantage of this approach is that it avoids confusing mothers, nurses, and even doctors, who might otherwise have to use different ORS solutions for the rehydration and maintenance phases of treatment.

Home fluids

Although their composition is not as appropriate as that of ORS solution for treating dehydration, other fluids such as soups, cereal gruels, cereal-salt solutions, or home-made sugar-and-salt solutions may be more practical and nearly as effective for preventing dehydration. Home fluids should be given to children to drink as soon as diarrhoea starts and feeding should be continued. Such early home therapy can prevent many cases from becoming dehydrated and it also facilitates continued feeding by restoring appetite.

Table 2.3 gives the WHO recommended composition of home therapy fluids. Home fluids should have an osmolality below that of blood plasma (i.e., less than 300 mOsm/l) and the concentration of sodium should preferably be in the range of 30-80 mmol/l. This concentration is obtained by dissolving 2.0 - 4.5 g of common salt in one litre of water; solutions that contain little or no salt may be effective if salt is present in the child's food. The source of glucose may be a food starch, such as a cooked cereal, or sucrose.

Table 2.3: WHO-recommended composition of home therapy fluids

1. Osmolality less than 300 mOsm/l

2. Sodium 30-80 mmol/l

3. Starch* usually 50-80 g/l OR Sucrose** 30-140 mmol/l

^* Usually a cooked cereal, e.g., rice gruel, or a starchy vegetable. ^** The molar ratio of sucrose to sodium should be at least 1:1.

When the fluid contains starch, as in a cooked cereal, it will have a lower osmolality than a fluid containing an equal amount of sucrose, in grams/litre. Moreover, within the intestine, starch breaks down gradually into glucose, which is rapidly absorbed. Thus, the osmolality of the fluid in the intestine remains at a safe level. As a practical guide, the amount of starch used should be such that the fluid is thick, but can still be drunk easily (usually not more than 80 g/litre). A similar situation exists when a fluid contains proteins, e.g., soups containing legumes. The proteins break down slowly into amino acids, which are absorbed quickly, so that the osmolality of the fluid in the intestine remains within a safe range. For optimal absorption of sodium, the molar ratio of sucrose:sodium in a sugar-and-salt solution should be at least 1:1 - e.g., 50 mmol/l of sodium requires a sucrose concentration of at least 50 mmol/l. The ratio may exceed 1:1, but should not cause total osmolality to exceed 300 mOsm/l, and the total sucrose should not be greater than 50 g/l. If solutions containing salt and carbohydrate are not available, or cannot be accurately prepared, salt-free fluids such as water should be given in their place. However, these are less effective in preventing dehydration when diarrhoea is severe; if given in large amounts, they might also cause hyponatraemia. Infants with diarrhoea should always continue to breast-feed. Breast-feeding during diarrhoea is an important source of water and nutrients, and can actually decrease stool volume and the duration of illness. Young infants who are not breast-fed should be given occasional drinks of water. There are also some fluids that may be available in the home which should not be given to children with diarrhoea. These include commercial soups, which may contain dangerously high concentrations of salt, and sweetened commercial fruit drinks or soft drinks, which are usually hyperosmolar owing to their high concentrations of sucrose. These fluids can cause hypernatraemia as a result of an excessive salt intake, osmotic diarrhoea, or both.

Limitations of ORT

In at least 95% of episodes of secretory diarrhoea dehydration can be corrected or prevented using only ORS solution (or ORT). However, ORT is either inappropriate or unsuccessful in the following situations:

ORT is inappropriate for:

initial treatment of severe (life-threatening) dehydration, because fluid must be replaced very rapidly (this requires intravenous infusion of water and electrolytes);

patients with paralytic ileus or marked abdominal distension;

patients who are unable to drink (however, ORS solution can be given to such patients through a nasogastric tube if intravenous treatment is not possible).

ORT is unsuccessful in:

patients with very rapid stool loss, i.e., greater than 15 ml/kg body weight per hour; such patients may be unable to drink fluid at a sufficient rate to replace their losses;

patients with severe, repeated vomiting (this is unusual); generally, most of the oral fluid is absorbed despite vomiting, and vomiting stops as dehydration and electrolyte imbalance are corrected;

patients with glucose malabsorption (also unusual); in such cases ORS solution causes stool volume to increase markedly and the stool contains large amounts of glucose; dehydration may also worsen.

Intravenous therapy

Intravenous fluids are required only for patients with severe dehydration, and then only to restore rapidly their blood volume and correct shock. Although a number of intravenous solutions are available, they are all deficient in at least some of the electrolytes required to correct the deficits found in patients dehydrated by acute diarrhoea. To ensure adequate electrolyte replacement, some ORS solution should be given as soon as the patient is able to drink, even while the initial fluid requirement is being provided by intravenous therapy. The following is a brief discussion of the relative merits of the most widely available solutions. The composition of each is shown in Table 2.4.

Preferred solution

Ringer's Lactate Solution (also called Hartmann's Solution for Injection) is the best commercially available solution. It supplies an adequate concentration of sodium and sufficient lactate, which is metabolised to bicarbonate, for the correction of acidosis; the concentratation of potassium, however, is low, and the solution provides no glucose to prevent hypoglycaemia. Ringer's Lactate Solution can be used in all age groups to correct dehydration due to acute diarrhoea of any cause. Early provision of ORS solution and early resumption of feeding will provide the required amounts of potassium and glucose.

Acceptable solutions

When Ringer's Lactate Solution is not available, normal saline, half-strength Darrow's Solution, or half normal saline solution may be used; however, these are less appropriate as regards content of sodium, potassium, or a base precursor (see Table 2.4).

Normal saline (also called isotonic or physiological saline) is often available. It does not contain a base to correct acidosis and does not replace potassium losses. Sodium bicarbonate or sodium lactate (20-30 mmol/l) and potassium chloride (5-15 mmol/l) can be added to the solution, but this requires a supply of the appropriate sterile solutions.

Half-strength Darrow's Solution (also called lactated potassic saline) contains less sodium chloride than is needed to correct efficiently the sodium deficit in cases with severe dehydration. This is prepared by diluting full strength Darrow's Solution with an equal volume of 5% or 10% glucose solution.

Half normal saline with 5% or 10% glucose, like normal saline, does not correct acidosis, nor does it replace potassium losses. It also contains less sodium chloride than is needed for optimal correction of dehydration.

Unacceptable solution

Plain glucose (dextrose) solution should not be used because it provides only water and glucose. It does not contain electrolytes and thus does not replace the electrolyte losses or correct acidosis. It does not effectively correct hypovolaemia.

EXERCISES

1. Indicate whether the following features are most characteristic of secretory or osmotic diarrhoea. Place an S (for secretory) or an O (for osmotic) against each, as appropriate.

1. Hypernatraemic dehydration
   
2. Isotonic dehydration
   
3. Non-absorbed solute
   
4. Impaired sodium absorption
   
5. E. Successfully treated with ORT

2. Which of the following can increase the efficacy of sodium absorption in the intestine? (There may be more than one correct answer.)

1. Cooked rice starch
   
2. Palm oil
   
3. Plain sugar
   
4. Some amino acids
   
5. Glucose

3. Which one of the following effects of severe diarrhoea is most dangerous?

1. Potassium depletion
   
2. Anorexia
   
3. Metabolic acidosis
   
4. Fever
   
5. Hypovolaemia

4. Which of the following are features of hypertonic dehydration? (There may be more than one correct answer.)

1. Extreme thirst
   
2. Serum sodium concentration: 140 mmol/l
   
3. Very irritable child
   
4. Serum potassium concentration: 3.8 mmol/l
   
5. Lethargic child

5. For which of the following situations is ORT using ORS solution not satisfactory? (There may be more than one correct answer.)

1. Maintenance therapy for an infant with rotavirus diarrhoea
   
2. Rehydration of a child with non-severe dehydration due to cholera
   
3. Rehydration of a child with non-severe dehydration due to enterotoxigenic E. coli
   
4. Rehydration of a comatose child with severe dehydration and shock due to rotavirus diarrhoea
   
5. Maintenance therapy of a child with cholera

6. Which of the following might happen if ORS was mixed with only half of the required amount of water and used to treat a child with rotavirus diarrhoea and dehydration? (There may be more than one correct answer.)

1. The solution would be an "improved ORS" and cause the stool volume to be reduced and the duration of diarrhoea to be shortened
   
2. The child would develop hypernatraemia
   
3. The child would refuse to drink the solution
   
4. The child would develop paralytic ileus and abdominal distension
   
5. The child would become extremely thirsty

7. Which of the following "home fluids" can be safely used to prevent dehydration in children with diarrhoea? (There may be more than one correct answer.)

1. Rice water
   
2. Cereal gruel with a small amount of salt added
   
3. Cola drink
   
4. Soup made from cooked legumes
   
5. Commercial fruit drink

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Answers

1. A. - 0

B. - S

C. - 0

D. - S

E. - S

2. A, C, D, E.

3. E. Hypovolaemia causes shock and cardiovascular collapse. This is the cause of death from severe dehydration due to diarrhoea.

4. A, C.

5. D. Patients with severe hypovolaemia require very rapid replacement of water and salt to restore the blood volume and prevent death. ORT is not sufficiently rapid. Such patients need intravenous fluid replacement, if it is available.

6. B, E. The child would probably become hypernatraemic because of the high concentrations of salt and glucose in the solution. Extreme thirst is a sign of hypernatraemia.

7. A, B, D. Soft drinks and commercial fruit drinks are often very hypertonic owing to a high sugar content. Such fluids can cause osmotic diarrhoea and hypernatraemic dehydration. They also contain very little sodium to replace what has been lost.

updated: 7 June, 2017