Ashish Chogle, MD MPH

Abha Kaistha, MD;

SUNY-Downstate Medical Center

Brooklyn, NY

Pretest

Q1. [T or F] Rotavirus is the most common cause of gastroenteritis in children and accounts for half of all hospital admissions for severe acute infectious diarrhea.

Q2. [T or F] 98% of water that we ingest is absorbed in small and large intestine.

Q3. [T or F] In mild - moderate dehydration IV hydration is the preferred method.

Q4. [T or F] Gatorade is the best oral rehydration solution available for use at home.

Q5. [T or F] All children with gastroenteritis should be treated with antibiotics

Q6. [T or F] Antidiarrheals have no place in treatment of acute diarrhea in children.

Q7. [T or F] One should wait for atleast 6 hours after rehydration to start age appropriate diet in a child with AGE.

Objectives

On completion of this module, residents and physicians will be able to

1. Define and diagnose diarrheal disease

2. Recognize the etiology and consequences of the most common forms of diarrheal disease in the united States.

3. Appreciate the physiology of fluid absorption and pathogenesis of diarrhea

4. Use nutritional principles in treatment based on the most current and best scientific information.

Facilitator Preparation

1. American Academy of Pediatrics: Practice parameter: the management of acute gastroenteritis in young children. American Academy of Pediatrics, Provisional Committee on Quality Improvement, Subcommittee on Acute Gastroenteritis. Pediatrics 1996 Mar; 97(3): 424-35

2. Sellin JH. Intestinal electrolyte absorption and secretion. In: Feldman M, et al, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia, WB Saunders, 1998:1451-1471.

3. Snyder JD. Use and misuse of oral therapy for diarrhea: comparison of US practices with American Academy of Pediatrics recommendations. Pediatrics 1991; 87(1):28-33.

4. Weizman Z, Ghaleb Asli, and Ahmed Alsheikh. Effect of a Probiotic Infant Formula on Infections in Child Care Centers: Comparison of Two Probiotic Agents Pediatrics. 2005; 115: 5 - 9. This recent paper demonstrated that probiotics were effective in preventing episodes of acute diarrhea in a pediatric population at high risk, namely in a daycare setting.

5. See also the modules on chronic diarrhea and probiotic use in the Teacher's Guide written by Dr. Weizman

Introduction

Diarrhea in children refers to stool output >10 ml/kg or decreased stool consistency. Acute diarrhea lasts less than 2 week. Persistent diarrhea lasts greater than 14 days and chronic diarrhea more than 30 days.

Gastroenteritis in children is still a common reason for ER visits and for hospital admissions. Rotavirus is the most common cause of gastroenteritis in children and accounts for half of all hospital admissions for severe acute infectious diarrhea. Most children with gastroenteritis do not develop dehydration and can be treated at home. Children with mild to moderate dehydration should be treated with low osmolarity oral rehydration solutions, and those with severe dehydration or shock need to be admitted for administration of intravenous fluids. Antidiarrheal drugs have no place in pediatrics and antibiotics have very limited indications.

Case Study

Mary Ann, a 20-month-old girl, is brought to the emergency department by her mother. She has had ten watery stools and five vomits in the previous 12 hours. She is eating poorly but drinks eagerly, has no fever and is bright and alert. Her eyes look sunken, but capillary return is normal. There is no blood in the stool and the vomitus is clear yellow in color. Her mother has been giving her ginger ale with a teaspoon of sugar in every cup.

The child attends day-care, and has previously been well, with normal growth and development. The patient health record indicates she has lost 6% of body weight. Her mother is concerned that she might be dehydrated and asks, "Will Mary Ann need to be admitted for a drip?"

Q1. What happens to the water we drink?

The Physiology of Water absorption: The small intestine absorbs vast majority of body fluids. Small intestine is presented with 8 lts of fluid daily in healthy adults. This amount includes ingested liquid and salivary, gastric and duodenal secretions. By the time this fluid reaches ileo-cecal valve only 600 cc remains. By the time this fluid reaches the anus, only 100cc of fluid remains [2]. This represents about 98% efficiency of water absorption in small and large intestine. It is assumed that children have similar efficiency in water absorption. Insensible water losses are greater in infants due to increased body surface area; therefore children can become ill and dehydrated more rapidly than adults.

What has happened to may Ann is that her drinking was unable to keep up with her stools loss because of the vomiting. The weakness may reflect tjhis water loss as well as the loss of sodium ion and a intravascular fluid depletion

Na Transport & Water absorption are the critical factors in acute diarrheal disease. The mechanism are as follows:

1) Neutral sodium chloride absorption occurs throughout the small intestine but predominantly in the ileum. This transport is mediated via Na+/H+ cation exchanger & Cl-/HCO3- anion exchanger.

2) Active Na+/K+ ATPase dependent transport occurs both in large and small intestine, but predominates in colon. Na+ enters the cell via electrochemical gradient. It is this mechanism that is damaged during enteric infection resulting in diarrhea.

3) Sodium co-transport operates throughout the small intestine but not in the colon. Na+ absorption is completed with organic solutes e.g. glucose, amino acids and peptides. This co-transport remains intact during acute diarrhea, thus rehydration is possible using ORS.

Q2. What are the possible mechanisms of diarrhea in our patient?

Pathogenesis

Diarrhea results when secretory process for water and electrolytes predominates over absorption.

There is much overlap in the following mechanisms which cause diarrhea.

" Osmotic

" Secretory

" Increased motility

" Inflammatory

Osmotic Diarrhea

When there is an absorbable solute in the lumen e.g. lactose, there is water retention instead of the normal absorption, resulting in diarrhea. Some enteric infections can cause damage to epithelial cells leading to brush border villi destruction and malabsorption, hence osmotic diarrhea.

Secretory Diarrhea

When there is active secretion of water into the gut lumen e.g. in infections such as cholera. Noninfectious causes can be VIP and gastrin mediated diarrhea; Bile acids & fatty acids in the lumen; Laxatives; Congenital chloride diarrhea.

Combined Osmotic and Secretory Diarrhea

Can occur due to: Clostridium difficile endotoxin; Shigella (Shiga toxin); E. coli; Rotavirus gastroenteritis, wherein the virus causes disruption of the brush border resulting in osmotic diarrhea and also Non-Structural Protein (NSP4) causes Ca++ dependant transepithelial Cl- secretions from crypt cell with resultant secretory diarrhea.

Diarrhea due to Increased Motility

As in IBS, can cause stasis, inflammation, bacterial overgrowth and secondary bile acid deconjugation and malabsorption.

Inflammatory Diarrhea

Exudation of mucus, proteins and blood in the gut lumen cause water and electrolyte loss resulting in diarrhea. Most common cause is infections which can cause mucosal damage directly and via enterotoxins. Intestinal inflammation due to Inflammatory Bowel Disease and Celiac disease can also cause diarrhea. The etiology is multifactorial, but mostly secondary to malabsorption.

It is most ikely that Mary Ann is showing the effects of a Combined Osmotic and Secretory Diarrhea. The most common form of infdectious diarrhea, likely in a day-care child - is rota virus. This is associated with a stool sodium concentration of 70 milliEquivilents/liter (mEq/L). Note that the mother is giving her a sugar beverage without sodium. This will be discussed below.

Teaching Caption: Rotavirus is the most common cause for acute gastroenteritis in infants and young children in the United States. In developing countries one must always consider cholera.

Q3. How do we evaluate our patient?

Clinical Features and Evaluations

Most causes of acute diarrhea in infants and children are infections. The clinical features depend on the age of the child and offending organisms.

History:

One must consider:

Travel history to endemic areas
Day care (Rotavirus, Cryptosporidiosis)
Family illness (Food poisoning by Salmonella, Clostridium, S. aureus)
Recent antibiotic use (C. difficile)

Our child was in day-care. Rotavirus should be suspected in a one year old presenting in winter months with 3-4 day history of vomiting and watery diarrhea with mild dehydration. Laboratory evaluation is not necessary for evaluation, but Rotazyme test is helpful in diagnosis.

Bacterial gastroenteritis is suspected in a one year old presenting with fever and bloody diarrhea with mucus. In this case stool culture, stool for occult blood and leukocytes are helpful laboratory evaluations. Testing stool for ova and parasites is helpful in children with history of travel to endemic areas. Complete blood count is helpful in looking for bandemia found in invasive bacterial infections. Electrolytes are generally not indicated.

Q4. What is the severity of dehydration and options for management of our patient?

Treatment:

As a rule, younger the child, higher the risk for sever dehydration. This occurs secondary to increased body surface area, limited renal compensatory capacity and fever. Dehydration rather than diarrhea itself is the usual cause of morbidity.

Treatment goals are:

Rehydration
Maintenance fluids
Replacement of ongoing losses
Early feedings

Rehydration

First determine degree of dehydration.

Table 2: Assessment of dehydration [4]

Teaching point:Estimation of degree of dehydration is of utmost importance in management of patients with AGE.

In mild dehydration oral rehydration solution is the preferred method. The choice of ORS depends on the local environment and the most likely agent. For e.g. in the US, Rotavirus is a common etiology, so Pedialyte and Infalyte are appropriate choices. In regions where cholera is common, a solution with higher Na+ concentration, e.g. WHO ORS is the best choice.

ORS can be given in a small amount, a teaspoon (5 ml) every 1-2 minutes. Using this technique around 150-300 ml can be given in an hour, faster than IV therapy. Liquids with high osmolarity, e.g. Apple juice and colas can aggravate the diarrhea

Table 3: Solutions appropriate for Oral rehydration therapy[8]

Teaching point: Maximal water uptake occurs with a sodium concentration from 40 to 90 mmol/L, a glucose concentration from 110 to 140 mmol/L (2.0 to 2.5 g/100 mL) and an osmolality of about 290 mOsm/L, the osmolality of body fluids.

Rehydration Guidelines

BRAT diet is no longer recommended because it is hypocaloric, low in protein, also bananas and apple sauce can add to much sugar and contribute to diarrhea [6].

Table 4: Rehydration guidelines [6]

Teaching point: According to AAP guidelines, patients with mild to moderate dehydration should be give a trial of oral rehydration before IV infusion is started.

The case continues

There is a s little more discussion and then the mother asks, "Doctor, let's give the child some antibiotics for the infection and medicine to stop the diarrhea

Q5. Are antibiotics and anti-diarrhea medications indicated for our patient?

Antibiotics and Antidiarrheals

1. Most episodes of diarrhea do not require treatment with these agents.

2. Only a few indications for antibiotic treatment:

Cholera
Systemic Shigella
C.difficile
Salmonella
Enterotoxigenic E.coli
E.histolytica

3. Medications that alter motility have NO use in children. Potential problems include prolongation of illness, paralytic ileus, etc.

Residents practice.
Take turns trying to explain to Mary Ann's mothert than neither antibiotics nor anti-diarrheal medicines are approate in childhood.

Potential Therapies

Probiotics: These are live microbes that later the intestinal flora and improve barrier function. Their role in acute diarrheal illness is controversial as it is mostly self limiting.

Zinc: It is a micronutrient that is important for growth of intestinal mucosa. It constitutes more than 100 metallo-enzymes and is essential for growth; protein, RNA, & DNA synthesis; & epithelial repair. It improves transport of water and electrolytes across the intestinal mucosa in experimental zinc deficiency [7]. Acute diarrhea can cause significant Zinc loss and Zinc supplementation may be an effective and affordable method in management of acute diarrhea [8] .

Acetorphan: This is an enkephalinase inhibitor with antisecretory and antidiarrheal actions. It decreases hypersecretion but has no effect on motility. It appears to decrease duration of diarrhea and stool output in children and adults [9] . It routine use still needs further studies.

Conclude the case study

REFERENCES

1. Cicirello HG, Glass RI. Current concepts of the epidemiology of diarrheal diseases. Semin Pediatr Infect Dis. 1994;5:163-167

3. Behrman RE, Kliegman RM, Jenson HB. Gastroenteritis. Nelson Textbook of Pediatrics, 17th ed., 2004;321:1272-1276

4. Duggan C, Santosham M, Glass RI. The management of acute diarrhea in children: oral rehydration, maintenance, and nutritional therapy. MMWR. 1992;41(RR-16):1-20

5. Snyder JD. Use and misuse of oral therapy for diarrhea: comparison of US practices with American Academy of Pediatrics recommendations. Pediatrics 1991; 87(1):28-33.

6. American Academy of Pediatrics: Practice parameter: the management of acute gastroenteritis in young children. American Academy of Pediatrics, Provisional Committee on Quality Improvement, Subcommittee on Acute Gastroenteritis. Pediatrics 1996 Mar; 97(3): 424-35

7. Ghishan FK. Transport of electrolytes, water, and glucose in zinc deficiency. J Pediatr Gastroenterol Nutr. 1984 Sep;3(4):608-12.

8. Roy SK, Tomkins AM, et al. Randomized controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhea. Arch. Dis. Child., Sept, 1997; 77(3): 196

9. Baumer P, Danquechin Dorval E, et al. Effects of acetorphan, an enkephalinase nhibitor, on experimental and acute diarrhea. Gut 1992; 33:753-758.

Postest

1. [T or F] Rotavirus is the most common cause of gastroenteritis in children and accounts for half of all hospital admissions for severe acute infectious diarrhea.

2. [T or F] 98% of water that we ingest is absorbed in small and large intestine.

3. [T or F] In mild - moderate dehydration IV hydration is the preferred method.

4. [T or F] Gatorade is the best oral rehydration solution available for use at home.

5. [T or F] All children with gastroenteritis should be treated with antibiotics

6. [T or F] Antidiarrheals have no place in treatment of acute diarrhea in children.

7. [T or F] One should wait for atleast 6 hours after rehydration to start age appropriate diet in a child with AGE.

Annotated Pre-test Answers

A1. Answer = True. Rotavirus accounts for about 3.5 million cases per year and as many as 110,000 hospital admissions for diarrhea. It produces severe diarrhea, accounting for most episodes in children younger than 2 years who require hospitalization for diarrhea and dehydration.

A2. Answer = True. On an average 8 liters of water is consumed by a healthy adult, most of it is absorbed by the small intestine and the rest by the large intestine. Only about 100 cc of water reaches the anus. Thus any disturbance or alteration of intestinal mucosa will interfere with this absorptive mechanism resulting in diarrhea.

A3. Answer = False. According to AAP guidelines, preferred management of mild to moderate dehydration is Oral Rehydration Therapy.

A4. Answer = False. The amount of fluid absorbed depends on three factors: the concentration of sodium, the concentration of glucose and the osmolality of the luminal fluid. Maximal water uptake occurs with a sodium concentration from 40 to 90 mmol/L, a glucose concentration from 110 to 140 mmol/L (2.0 to 2.5 g/100 mL) and an osmolality of about 290 mOsm/L (osmolality of body fluids). Gatorade has a sodium concentration of 20 mmol/L, a glucose concentration of 255 mmol/L, & an osmolality of 330 mmol/L. This makes Gatorade a wrong choice for ORS.

A5. Answer = False. Although treatment may shorten the course of some diarrheal illnesses (e.g., Shigella or traveler's diarrhea), most bacterial diarrheas are self-limited and will be resolving before the causative organism is identified. Incase of noninvasive Salmonella species, treatment may prolong the carrier period after the symptoms have resolved. Antimicrobial therapies are recommended only for selected children with AGE who present with special risks or evidence of a serious bacterial infection (SBI)

A6. Answer = True. Antidiarrheals are generally not indicated in children with acute gastroenteritis because of lack of convincing evidence that they are effective and because of concerns that adverse effects may outweigh any benefits. Opiate-anticholinergic combinations or opiates other than loperamide have a high potential for toxic side effects. Antidiarrheal medications also have the potential to worsen the course of inflammatory bacterial enteritis, leading to toxic megacolon and colonic hemorrhage.

A7. Answer = False. According to AAP guidelines, age appropriate diet should be given as soon as dehydration is corrected. Bowel rest and BRAT diet is no longer recommended.