Gastroenterology- Diarrhea Jan 2007

Diarrheal Disorders Rebecca Abiog-Castro, M.D. Pediatric Gastroenterology UST Hospital

Diarrhea • It is passage of stool at least twice the normal bowel movement wherein the stools follow the shape of the container. • It is also defined in infants and children as a stool output of greater than 10 g/kg/day (normal=5-10 g/kg/day) and more than the adult limit of 200 g/24 hour.

Definition of Terms Acute Diarrhea • It is the passage of loose and watery stool of less than two weeks duration. Chronic/Persistent Diarrhea • It is the passage of loose and watery stool of two weeks or longer duration.

Epidemiology: • One of the leading cause of morbidity and mortality in children • One billion episodes of illness • 3-5 million deaths annually

• Global Impact of Diarrhea: – 1970 (late): ORT & ORS adopted by WHO & UNICEF succeeded in managing diarrheal disorder – 1979:

4.5 M of children under FIVE die of diarrhea

– 1990:

More than 1 M deaths / year were prevented attributable to these therapeutic management

– 2002:

Deaths due to diarrhea has been reduced to 1.6 M

– At present: Knowledge on ORT in some countries have been declining

The Goals: • Reduce by one half deaths due to diarrhea among children under five by 2010 compared to 2000. • Reduce by two thirds the mortality rate among children under five by 2015 compared to 2000

Pathophysiology of Diarrhea = Diarrhea results from altered intestinal water and electrolyte transport.

= GIT of infant handles approximately 285 ml/kg/24 hour of fluid (intake + intestinal secretion) with a stool output of 5-10 g/kg/24 hour.

Pathophysiologic Mechanisms of Diarrhea

•

Osmotic diarrhea

•

Secretory Diarrhea

•

Reduction in anatomic surface area

•

Alteration in Intestinal motility

Osmotic diarrhea • Due to presence of non-absorbable solutes in the GIT • Classic example: Lactose Intolerance which is caused by lactase deficiency  lactose in colon • Colon  bacteria  lactic acids & short-chain organic acids  osmotic load  water secreted into the lumen

Important Features of Osmotic Diarrhea • • • • • •

stops with fasting ph <5 positive for reducing substance volume of stool <200 ml/day stool Na+: <70 meq/L Na+ + K+ x 2 = < stool osmolarity suggestive of presence of other osmols in the stool

Features of Secretory Diarrhea • • • • •

high volume output > 200 ml/24 hr diarrhea persists even with fasting stool Na+ >70 mEq/L reducing substances: (-) stool ph: >6

Mechanisms of Secretory Diarrhea 1) Activation of the intracellular mediators such as cyclic AMP, cyclic GMP, and intracellular Ca2+ A) Activation of cyclic adenosine monophosphate B) Activation of cyclic guanosine monophosphate C) Calcium-dependent

A) Activation of cyclic adenosine monophosphate – Bacterial toxins: • • • • •

Enterotoxins of Cholera E. Coli (heat labile) Shigella Salmonella Campylobacter jejuni

– Hormones: • vasoactive intestinal peptide • Gastrin • secretin

– Anion surfactants: • bile acids • ricinoleic acid

B) Activation of cyclic guanosine monophosphate • Bacterial toxins: – E. Coli (heat stable) – Yersinia Enterocolitica toxin

C) Calcium-dependent • Bacterial toxins: – Cl. Dificile enterotoxin

• Neurotransmitters: – acetylcholine, serotonin

• Paracrine agents: – bradykinin

Mechanisms of Secretory Diarrhea 2) Reduction in Anatomic Surface Area • Short bowel syndrome: • Flattening of the proximal intestinal surface with marked – Celiac disease, Cow milk allergy, Postenteritis enteropathy

3) Alteration in Intestinal Motility – Hypomotility as in malnutrition  bacterial overgrowth  bile salt deconjugation 

intracellular mediator 

secretory diarrhea – diabetes mellitus, scleroderma and intestinal pseudoobstruction.

Acute Diarrhea: 1) Inflammatory diarrhea 2) Non-inflammatory Diarrhea

Acute Diarrhea 1) Inflammatory Diarrhea: – caused by organisms that invade the intestine directly or produce cytotoxin – Etiologic Agents: Shigella, Salmonella, Enteroinvasive E.Coli, Shiga toxin-producing E.Coli, Campylobacter jejuni, Clostridium Dificile – Presents as bloody mucoid stool – Stool Examination: (+) fecal leucocytes

Acute Diarrhea 2) Non-inflammatory Diarrhea: – Caused by organisms that: • produce enterotoxin by some bacteria (Cholera), • destruction of villi (viruses), • adherence by parasites and adherence or translocation by bacteria

Chronic Diarrhea • Causes of chronic Diarrhea: – Pancreatic Disorders: • Cystic fibrosis • malnutrition – Bile acid disorders: • chronic cholestasis • terminal ileum resection • bacterial overgrowth • chronic use of bile acid sequestrants

Causes of Chronic Diarrhea – Intestinal disorders: • • • • • • • • •

Infections: bacterial, viral, fungal infestations: parasitic cow’s and soy protein intolerance IBD autoimmune enteropathy eosinophilic enteropathy carbohydrate malabsorption excessive carbonated fluid intake excessive intake of sorbitol, magnesium hydroxide, lactulose

- Mucosal Factors: • • • • • • •

enterokinase deficiency glucoamylase deficiency postenteritis syndrome short bowel syndrome Hirschsprung disease Partial bowel obstruction malrotation

Bloody Stool 1) Infectious: Enteroinvasive organism: Shigella, EIEC, E. Histolytica 2) Non-infectious: a) Medical Condition: Protein Intolerance (Cow’s milk & Soya protein) b) Surgical Conditions: Intussusception, Meckel’s Diverticulum

Bloody Stool 1) Infectious: - Shigella Dysentery: - Acute course with high fever, vomiting, seizure - Laboratory Tests: Leucocytosis; Stool analysis: numerous pus cells and rbc - Intestinal Amebiasis: - Chronic course at least two wks - Clinical course: no fever & vomiting

Bloody Stool 2) Non-infectious: a) Food Allergy (Food Hypersensitivity): 1) Ig-E mediated : 2) Non-IG-E mediated:

Bloody Stool A. Ig-E mediated Food Hypersensitivity: - Gastrointestinal Anaphylaxis: B. Non-Ig-E Mediated Disorders: • Allergic Proctocolitis:

Bloody Stool Diagnosis • Food-induced Enterocolitis: – Protracted vomiting & diarrhea begin between 1 week and 3 mo of age – Stools contain occult blood, neutrophils, eosinophils – Diagnosis: • Gold standard is elimination of diet and Double Blind, placebo controlled food challenge (DBPCFC) • Skin prick test or radioallergosorbent (RAST)

Food-induced Enterocolitis: Treatment: – Elimination of diet: the only proven treatment for food allergy 30% of infants with cow’s milk allergy is allergy to soy protein – Most infants improve with Protein hydrolysate ; 5% don’t respond and maybe given amino-acid-based formulas – 85% of infants with non-IG-E mediated food allergy are no longer allergy by 3 years of age – Allergy to cow’s milk and soy protein resolve by one year of age

Food-induced Enterocolitis: • Prevention: – Breastfeeding

Bloody Stool 2) Non-infectious: b) Surgical Causes: 1) Intussusception - Barium Enema, Ultrasound 2) Meckel’s Diverticulum: - Pertechnetate technetium Scan

Diagnostic Work-ups for Diarrhea 1. Acute Diarrhea: • Stool examination: look for mucus, blood, leucocytes •

fecal leucocytes indicates the presence of an invasive or cyto-toxin-producing organism such as Shigella, salmonella, C. Jejuni, invasive E. Coli, C. Dificile

• Stool culture:

• Chronic Diarrhea: Pls refer to page 1280 Fig 322-3

Complications of Diarrhea • • •

Fluid & electrolyte losses: sodium, potassium, bicarbonate Malabsorption and malnutrition Lactose Intolerance

Fluid & Electrolyte Losses Assessment of Hydration Status • Look: • Feel: • Ask

Classification of Dehydration • Group A : No Signs of Dehydration (<5% of body weight fluid loss)

• Group B: Some Signs of Dehydration = Mild Dehydration (5-6% of Body weight fluid loss)

= Moderate Dehydration (7-10% of BW fluid loss)

• Group C: Severe Signs of Dehydration (>10% BW fluid loss)

• Group A: – No evidences of dehydration

Additional Clinical Parameters of Dehydration Some signs of Dehydration: (Group B) • Mild dehydration (5-6%): – Volume loss: 50-60 ml / kg • Average:

50 ml / kg

• Clinical Manifestations: – – – –

Normal pulse decreased urine output thirsty normal physical examination

Additional Clinical Parameters of Dehydration Some signs of Dehydration: (Group B) • Moderate dehydration (7-10%): – Volume Loss: 70-100 ml / kg • Average:

80 ml / kg

– Clinical Manifestations: • • • • •

Tachycardia irritable / lethargic sunken eyes and fontanel decreased tears Mottled skin

- dry mucous membranes - little or no urine output - mild tenting of the skin - delayed capillary refill

Laboratory Tests • • • • • •

Serum sodium: determines the type of dehydration Serum potassium Blood gases: determines the presence of metabolic acidosis Blood urea nitrogen and serum creatinine concentration Urinalysis Complete blood count

Types of dehydration based on the serum sodium concentration

Isotonic Dehydration: • Proportional loss of water and sodium • Serum sodium= 135 - 155 meq/l

Types of dehydration based on the serum sodium concentration Hyponatremic Dehydration: • Serum sodium: <135 meq/l • Excessive sodium loss or decrease sodium intake • ↓ ECF osmolality  ICF higher osmolality  water from ECF space  ICF space  maintain osmotic equilibrium  cellular swelling  cerebral edema

Types of dehydration based on the serum sodium concentration • Hyponatremic Dehydration – Cerebral edema  increased intracranial pressure  herniation, seizures – Increased risk of Central Pontine Myelinolysis CPM) – More manifestations of intravascular volume depletion – ICF movement of sodium  depletes the ECF space with Na & plasma volume

Fluid Management of Specific Fluid & Electrolytes Disturbance Hyponatremia: • Initial goal: Correction of intravascular volume depletion with isotonic fluid (NSS or Ringer lactate) • Increase sodium level to 135 meq / L • Avoid ‘overly rapid correction’ i.e. >12 meq / L/day  central pontine myelinosis (CPM). • D5 ½ NS + 20 meq / L KCl is effective half of the fluid can be administered over the first 8 hours.

Types of dehydration based on the serum sodium concentration Hypernatremic Dehydration: • Serum sodium: >145 meq/l • Excessive intake of sodium or excessive water loss  ECF osm  ICF fluid depletion  brain cell shrinkage  brain movement away from skull  tearing of the Intracerebral & bridging blood vessels subdural, subarachnoid, parenchymal hemorrhage  seizure.

Types of dehydration based on the serum sodium concentration

Hypernatremic Dehydration: • Most dangerous type of dehydration due to complications of hypernatremia and during therapy • Thrombotic complications (stroke) due to hemoconcentration  hypercoagulability / stasis • CPM & extrapontine myelinolysis

Hypernatremic Dehydration: • Patients are lethargic but irritable when touched; it may cause fever, hypertonicity, hyperreflexia • Patients appear less ill / dehydrated • Because of the ICF loss, the skin has “doughy” feel • Intravascular volume is protected Blood pressure is maintained, less tachycardia and urine output preserved longer

Management of Specific Fluid & Electrolytes Disturbance

Hypernatremia: • Sodium concentration decrease: not > 12 meq / L/24 hour at the rate of 0.5 mEq/l / hour • Severe hypernatremia should be corrected over 2-4 days • Guide in the fluid treatment: – Determine the time for correction based on the initial sodium concentration • • • •

Na+: Na+: Na+: Na+:

145-157 meq / L = 24 hours 158-170 meq / L = 48 hours 171-183 meq / L = 72 hours 184-196 meq / L = 84 hours

New Developments on ORT (Oral Rehydration Treatment):

– Based on recent scientific advances: • Improved ORS formulation • Zinc supplementation • Protective effects of zinc supplementation

Composition of Standard & New Improved ORS Standard WHO-ORS (meq or mmol/l

Glucose Sodium Chloride Potassium Citrate Osmolarity

111 90 80 20 10 311

New Improved ORS (meq /l or mmol/l

75 75 65 20 10 245

Composition of Intravenous solutions Fluid Normal saline (0.09%NaCl) ½ Normal Saline (0.45% NaCl) ¼ Normal Saline (0.225% NaCl) Ringer lactate

Na+ Cl+ K+ Ca++ Lactate 154 154 77

77

38.5 3 8.5 130 109 4

3

28

Maintenance fluid • Replaces the obligatory fluid losses both measurable (urine and stool) and not measurable (insensible losses from the skin and lungs) •

Goals: – – – –

Prevent dehydration Prevent electrolyte disorders Prevent ketoacidosis Prevent protein degradation

• It is composed in general of a solution consisting of water, glucose, sodium and potassium;

Maintenance fluid • It provides approximately 20% of the normal caloric needs of the patient enough to prevent ketoacidosis from starvation and protein degradation • It does not provide adequate calories, protein, fat, minerals ( calcium, phosphorus, magnesium or bicarbonate) and vitamins. • Calculation of maintenance fluid

Components of Maintenance water Urine

60%

Insensible (skin and lungs)

35%

Stool

05%

Computation of Maintenance Fluid 10 kg: 11-20 kg >20 kg

100 ml/kg/day 1000 ml + 50 ml/kg > 10 kg 1500 ml + 20 ml/kg > 20 kg

Adjustments in maintenance Water Source

Causes of Increased Water needs

Causes of Decreased water needs

Skin

•radiant warmer •Fever •Sweat •Burns

mist tent

Lungs

Tachypnea

Humidified ventilator

Gastrointestinal Tract

•Diarrhea •Emesis •Nasogastric suction

Renal

Polyuria

Oliguria / anuria

Miscellaneous

•Surgical drain •Third spacing

Hypothyroidism

Replacement Fluid • Losses should then be replaced as they occur using a solution with the same approximate electrolyte concentration as the GI fluid; • the losses are replaced every 1-6 hour depending on the rate of loss

Replacement Fluid • GI tract is potentially a source of considerable water loss; •

GI losses are often associated with loss of potassium, leading to hypokalemia and bicarbonate, causing metabolic acidosis which maybe aggravated when there is hypoperfusion causing a concurrent lactic acidosis;

• emesis or losses from NG tube cause a metabolic alkalosis.

Other Metabolic complications Hypokalemia: • It is common among children, with most cases related to gastroenteritis • Clinical manifestations: – Heart and skeletal muscles are vulnerable to hypokalemia – ECG changes include a flattened wave, depressed ST segment and appearance of a U wave and a P wave – Ventricular fibrillation and torsades de pointes (ventricular arrhythmia / tachycardia) may occur

Other Metabolic complications Hypokalemia: •

Effects on skeletal muscles: muscle weakness and cramps; possible paralysis with levels < than 2.5 meq / L

•

It slows gastrointestinal motility: manifests as constipation, or with levels <2.5 meq / l  ileus.

•

It may also slow bladder function  urinary retention

•

Diagnosis: History: child’s diet, gastrointestinal losses and medications

•

Treatment: Oral potassium is the choice because of the risk of hyperkalemia when given by IV (Dose 0.5-1 meq / L give over an hour.

Metabolic Acidosis • Most common etiology is diarrhea due excessive losses of bicarbonate from the body; • Clinical manifestations: – Hyperventilation – At ph < 7.2, there is impaired cardiac contractility and an increased arrythmias • Treatment: – Most effective therapeutic approach: repair of the underlying disorder

Lactose Intolerance • It’s a condition wherein lactases are reduced as a result of gut injury as in diarrheal infection; • Reasons why Lactose Intolerance is common: – infant diet is high in lactose; lactose hydrolysis is the rate-limiting step in its absorption – Lactase has the lowest activity among the brush borders disaccharidases

Lactose Intolerance Reasons why lactose intolerance is common: •

Lactases are superficially located and preferentially degraded by proteolytic enzymes

•

IF lactose is not digested and absorbed in the intestine  degradation  lactic acids and short chain fatty acids ( butyrate, acetate and propionate) and production of methane, carbon dioxide and hydrogen gases.

Lactose Intolerance Clinical manifestations: • Acidic stools  perineal chemical burn • Flatulence  abdominal distention, discomfort • Intake of lactose containing food  aggravates diarrhea; while fasting  resolves diarrhea.

Lactose Intolerance Diagnosis: • Stool ph of <5 is suggestive of carbohydrate / lactose malabsorption • Stool clinitest for the determination of reducing sugars (all carbohydrates are reducing sugars except sucrose); 2+ or higher (blue-green to brickred) indicative of the presence of reducing sugars such as lactose.

Lactose Intolerance • Hydrogen Breath Test: – Mechanics: The gas produced by bacterial degradation of lactose is absorbed in the colon , enters the portal and systemic venous return, goes to the lungs, and is then released in the breath. • A release of > 20 ppm from baseline is consistent with lactose intolerance.

Lactose Intolerance Treatment: • Small frequent feeding to decrease lactose load • If ineffective: Partial removal of milk from diet or use of yoghurt

Protein Intolerance (Cow’s Milk Allergy) • Food allergy is a group of disorders in which symptoms result from immunologic responses to specific food antigens

• Food allergy occurs in as many as 6% of children during the first year of life, including the 2-3% of infants and toddlers with cow’s milk allergy

Protein Intolerance (Cow’s Milk Allergy)

Clinical Manifestations: A. Ig-E mediated Food hypersensitivity: Gastrointestinal Anaphylaxis: • Rapid

onset of nausea, cramping abdominal pain, vomiting or diarrhea or a combination of these conditions

• Occurs after ingestion of peanuts, nuts, fish and shellfish.

Protein Intolerance (Cow’s Milk Allergy)

B. Non-Ig-E Mediated Disorders: – Allergic Proctocolitis: • Infants may present between 1 day to 3 mo of age with spots or streaks of blood and mucus in stool and occasional mild diarrhea

• Increased white blood cells in stool and peripheral eosinophilia • Patchy mild colitis is present; (+) nodular hyperplasia in 25% • Often results from hypersensitivity to cow’s milk; soy sensitivity is less common

Protein Intolerance (Cow’s Milk Allergy) B. Non-Ig-E Mediated Disorders: – Allergic Proctocolitis: – Breast-fed infants may suffer this disorder but usually abates with maternal diet modification and elimination of milk products – Non-breastfed infants can be treated with protein hydrolysate formulas

Protein Intolerance (Cow’s Milk Allergy) Food-induced Enterocolitis: • Protracted vomiting & diarrhea begin between 1 week and 3 mo of age • Stools contain occult blood, neutrophils, eosinophils, • Jejunal biopsy shows flattened villi, edema and inflammatory cells • Symptons resolve within 72 hour of removal of the offending food and recur within 1-6 hour of reintroduction

Protein Intolerance (Cow’s Milk Allergy)

Food-induced Enteropathy: • Malabsorption, protracted diarrhea, vomiting

and failure to thrive occur most often during the first month of life

•

Protein Intolerance (Cow’s Milk Allergy) Food-induced Enterocolitis: • Older infants may develop poorly characterized syndrome of anemia, hypoproteinemia or failure to thrive. • Eosinophilia is common

Protein Intolerance (Cow’s Milk Allergy) Diagnosis: • Gold standard: – Elimination of diet – Double Blind, placebo controlled food challenge (DBPCFC)

•

Open food challenge: less reliable

•

Skin prick test

•

Radioallergosorbent (RAST): determines whether an Ig-E allergic reaction is the cause of a food allergy

•

Small bowel biopsy: Patchy villus atrophy with mononuclear cell inflammatory response

Treatment: • Elimination of diet: the only proven treatment for food allergy • 30% of infants with cow’s milk allergy is allergy to soy protein • Most infants improve with Protein hydrolysate ; 5% don’t respond and maybe given amino-acidbased formulas

Prognosis – 85% of infants with non-IG-E mediated food allergy are no longer allergy by 3 years of age – Allergy to cow’s milk and soy protein resolve by one year of age – Symptons to Ig-E mediated allergy to peanut, nuts, fish, or shellfish DO NOT resolve

Malabsorption • May present as watery diarrhea, acidic diarrhea, or steatorrhea

Generalized Malabsorptive States in Childhood Site

More Common

Exocrine pancreas

Protein – Energy Malnutrition Biliary Atresia

Liver, Biliary Tree Intestine – Anatomic Defects – Chronic Infection – Others

Massive resection Stagnant Loop Syndrome Giardiasis Chronic Diarrhea Protein Intolerance (Cow’s milk or Soya Protein Hypersensitivity)

Malabsorption Clinical manifestations: • Abdominal distention, pale foul smelling, bulky stools • Muscle wasting • Poor weight gain or weight loss • Growth retardation

Malabsorption Diagnosis: • Stool examination for fat globulesfollowed by Sudan staining III • 72-hour quantitative fecal fat test: gold standard for assessing steatorrhea – Premature Infant: absorbs about 65-75% of ingested fats – Term infants: absorbs about 90% – Older children and adults: absorbs 95% of ingested fats; with vegetable fats absorbed better.

Treatment: Treat the main problem

Drug Therapy For dysentery: • Cotrimoxazole ( Trimethoprim + sulfamethoxazole): Trimethoprim: 7 mg/kg/day Sulfamethoxazole: 50 mg/kg/day Given 2x a day for 5 days • Nalidixic Acid For cholera: • Tetracycline (only for 6 years old and >) • Co-Trimoxazole • Erythromycin • Furazolidone