1. Diarrhoea Dr. Mohamed Haseen Basha Assistant professor ( Paediatrics)
Faculty of Medicine
Al Maarefa College of Science and Technology

2. Diarrhea Is defined as an increase in frequency and fluidity of stools over and above the normal for that particular age. Types Acute Watery Diarrhea It refers to diarrhea that begins acutely, lasts for less than 14 days, with passage of frequent loose or watery stools without visible blood. Dysentery It is the term used for diarrhea with visible blood and mucus. It is often associated with fever and tenesmus. Persistent Diarrhea It represents diarrhea, presumed to be caused by infectious agents that begins acutely, but is of usually long duration (more than 14 days).

3. Etiology
Infective
Commonest infective cause is viral infection - Rota virus.
Bacteria like E coli, Shigella and Salmonella.
Protozoa like amoeba and giardia
Fungus like cryptosporidium.
Food Poisoning – Staphylococcus aureus, Clostridium Perfringens, Bacillus Cereus
Parenteral diarrhea is diarrhea due to infection elsewhere in the body, apart
from the gut,like otitis media and urinary tract infection.
Infection in immunocompromised host, e.g. cryptosporidiosis.

4. Non-Infective
Diet – Food Allergy, Food intolerance
Anatomic Defects – Malrotation, Hirschprung disease, Short bowel Syndrome, Microvillus Atrophy
Food Poisoning – Heavy Metals, Mushrooms
Endocrinopathies – Thyrotoxicosis, Addison’s disease
Malabsorption – Disaccharidase deficiencies, Pancreatic insufficiency, Celiac disease
Neoplasm – Neuroblastomas, Ganglioneuromas, Zollinger- Ellison Syndrome
Miscellaneous – Crohns disease, Ulcerative colitis, Laxative abuse

5. Etiology of Acute Dysentery
The common pathogens causing acute dysentery are Shigella—S. dysenteriae, E. coli, enterohemmorhagic, enteroinvasive, Campylobacter jejuni, Salmonella, Yersinia enterocolitica, HIV, Cytomegalovirus (CMV) and E. histolytica.
The other causes are Pseudomembranous colitis, inflammatory bowel disease, radiation induced colitis and segmental enteritis.

6. PATHOPHYSIOLOGY
Acute watery diarrhea results due to an imbalance between the absorption and secretion of water by the intestinal villi. The important pathophysiological mechanisms are osmotic, secretory, motility, invasive and mixed.

7. Approach to acute diarrhea
Assessment of the hydration status.
Assessment of the Nutritional status.
Accompanying Symptoms
Associated Infections

8. Symptoms associated with Dehydration

9. Assess the nutritional status:
This is very important as it predicts the progression to persistent diarrhea (PD) and also the fluid therapy differs in children with severe malnutrition.
Accompanying Symptoms
History of fever, vomiting, abdominal distension and seizures
help in identifying children with complications or the presence
of coinfections.
Associated Infections
Sepsis, bronchopneumonia, UTI, acute Suppurative otitis
media are the associated infections which predispose children
with AD progressing to persistent diarrhea (PD).

10. Investigations in Acute Diarrhoea
Serum biochemistry (e.g. Na, K, HCO3 , urea, pH)
Full blood counts
Blood culture
Stool bacterial culture
Stool lactoferrin, occult blood and leucocytes
Stool viral antigens, viral EM, viral culture
Stool parasites
Stool biochemistry for carbohydrate intolerance (pH, reducing substance and osmotic gap)

11. Principles of Treatment
• General assessment of the child. • Assessment of hydration status. • Correction of electrolyte and acid-base imbalance. • Proper feeding to provide normal nutritional requirements. • Treatment of associated problems like dysentery and persistent diarrhea.

12. Correction of dehydration
Severe dehydration - PLAN C:
In infancy, a bolus of 30 ml/kg fluid over 1hour followed by 70 ml/kg over 5 hours is given, followed by reassessment.
Severe dehydration beyond infancy, a bolus of 30 ml/kg fluid over ½ hour followed by 70 ml/kg over 2 ½ hours is given.
Some dehydration - PLAN B:
Give 75 ml/kg over 4 hours.
No dehydration - PLAN A:
Give daily fluid requirements.

14. Oral rehydration salts or solutions (ORS)
Oral rehydration salts or solutions (ORS), is a simple, cheap, and effective treatment for diarrhea-related dehydration. It consists of a solution of salts and other substances such as glucose, sucrose, citrates. Super ORS contain some amino acids essential for salt and water absorption. Natural ORS – examples are rice water and coconut water. Killer ORS are sweet due to high sugar content and more palatable but cause severe osmotic diarrhea and even death hence only WHO ORS is recommended. Low salt ORS is mainly used to reduce stool frequency in malnourished children.

15. In WHO ORS the high Na+ and glucose were drawbacks

16. The rationale for the administration of ORS containing Na+ and glucose is based on the fact that Na+ glucose coupled transport stimulates water absorption by solvent drug . Maximal uptake of Na+ and H2O occurs when the molar ratio of glucose to Na+ is close to 1. This mechanism is intact in patients with cholera and also sufficiently intact in Rota viral infection.
The dose of ORS for no dehydration is 10 mL/kg/stool and some dehydration is 50–75 mL/kg in first 4 hours (Plan B).
After correction of dehydration, ORS is given 50–100 mL/kg in 24 hours in between feeds. The ongoing losses can be corrected by giving 10 mL/kg for every stool.

17. Advantages of ORT Use of normal physiologic mechanisms
Early re-feeding
90-95% effective
Effective for all types of dehydration
No need for laboratory tests
Low economic and social cost
Availability
No infectious, metabolic, or electrolytic complications

18. Contraindications Shock Patient younger than 1 month of age Ileus
Significantly altered sensorium
Severe difficulty breathing
Painful abdominal distension

19. Correction of Electrolyte Imbalance
Hypokalemia should be undertaken only after the child passes urine to rule out presence of acute renal shut down following diarrhea. It should be given at 20meq/l initially and the titrated according to serum potassium reports. Correction of dehydration itself usually corrects sodium and bicarbonate deficits but if very severe, they may be slowly corrected by using a simple formula, i.e. the amount of bicarbonate or sodium to be given in meq /l = Wt (in kg) × HCO3 deficit in meq /l (Na deficit as the case may be)× 0.6 Never give a bolus of any of the electrolytes. They should always be given in IV fluids.

20. Nutrition Therapy
Breastfeeding should continue through rehydration and maintenance phases of treatment.
Children should continue to be fed age-appropriate diets.
Gradual reintroduction of milk-based formulas or cow's milk is not routinely required.
Lactose free or lactose-reduced formulas are not routinely required. These formulas may be considered if there is no improvement in the stool consistency after several days or if reducing substances are identified in the stool.
Complex carbohydrates (e.g. rice, wheat, potatoes, bread and cereals), lean meat, yoghurt, fruits, and vegetables are better tolerated and more preferred than foods which are sugary (e.g. tea, juices and soft drinks) or fatty.

21. Drugs Antibiotics There is no role for routine antibiotics in AWD.
Specific antibiotics are prescribed if there is blood or mucous in stool, infants less than 3 months of age, giardiasis, cholera, immunocompromised child and when associated infections such as UTI, bronchopneumonia, sepsis or ASOM are present.
Zinc
Zinc improves the cell mediated and humoral immunity, increases the synthesis of brush border enzymes, increases the absorption of fluid and electrolytes from the gut, and accelerates the villous repair.
Zinc supplementation is recommended at 20 mg/day for children more than 6 months and 10 mg/day for those younger than 6 months for 14 days from the onset.

22. Probiotics
Probiotics are live microbial food supplements that have beneficial effect on humans by improving the endogenous microbial flora.
Probiotics may be of bacterial (Lactobacillus,Bifidobacter) or yeast (Saccharomyces) origin.
Ant secretory Drugs
There is presently not enough evidence on either safety or efficacy of ant secretory drugs like racecadotril for its routine use in the treatment of diarrhea.
Adsorbents such as pectin, kaolin, loperamide, opioids, steroids are banned as therapeutic agents.

23. COMPLICATIONS Electrolyte Imbalance
Hypernatremia, Hyponatremia, Hypokalemia
Hypoglycemia
severely malnourished, Sick young infants (less than 2 months) who are not able to breastfed.
Metabolic Acidosis
Loss of large amounts of bicarbonate lost in the stool, Hypovolemic shock in severe diarrhea results in excessive production of lactic acid, which may further contribute to metabolic acidosis.
Acute Renal Failure
Severe dehydration and shock lead to decrease in renal blood flow resulting in prerenal type of acute renal failure.
Hemolytic Uremic Syndrome
Invasive diarrhea due to S. Dysenteriae or enteroinvasive E. coli may have HUS due to nephrotoxin liberated by these organisms.

24. PREVENTION OF DIARRHEA
Promotion of exclusive breastfeeding up to 6 months of Age and Improved complementary feeding practices.
Use of clean drinking water and sufficient water for personal hygiene
Hand washing and Use of sanitary toilets
Make availability of ORS sachets.
Vaccinations- Rota, Measles, Cholera, Typhoid..
Treating and preventing malnutrition
Zinc supplementation.
Avoid using iron during diarrhea episodes as the fimbriae or pili of E. coli easily bind to them.

25. Signs of dehydration

26. Persistent diarrhea
Persistent diarrhea (PD) is defined by WHO as a diarrheal illness of presumed infectious etiology with an acute onset lasting for more than 14 days which does not include conditions such as celiac disease or other hereditary disorders.
Since the main disturbing feature of PD is growth faltering or undernutrition it is preferable to express PD as “with or without weight loss”.
Causes:
Re-infection or protracted course of the initial infection Adenovirus, EPEC, Salmonella, Shigella, C. difficile
Small-intestinal bacterial overgrowth Malabsorption particularly of carbohydrates due to enteric infections
Milk or other dietary protein intolerance

27. Pathophysiology of persistent diarrhea

28. Treatment for persistent diarrhea

29. Chronic Diarrhoea
Diarrhea which lasts for more than 14 days, is usually non infectious and associated with malabsorption is labeled as chronic diarrhea.

30. Etiology of chronic diarrhea
Intestinal
Intraluminal or mucosal
Pancreatic
Cystic fibrosis, chronic pancreatitis, Shwachman
Bile acid
Chronic cholestasis, ileal surgery
Endocrine
Hyperthyroid, diabetes mellitus, VIPoma, Zollinger-Ellison syndrome
Factitious
Junk foods, laxatives
Functional
Part of irritable bowel syndrome

31. Etiological diagnosis based on age of onset
Common disorders
New born
Microvillus inclusion disease, congenital chloridorrhea
2 weeks–6 months
Autoimmune enteropathy, CMPA
6 months–2 years
CMPA, lactose intolerance
> 2–5 years
Celiac disease, parasitic infestation, immune deficiencies
> 5 years
IBD, tuberculosis, spurious diarrhea

32. Symptoms of Chronic Diarrhoea
Cramping
Abdominal pain
Nausea or vomiting
Fever
Chills
Bloody stools
Children with chronic diarrhea who have malabsorption can experience
Bloating and swelling, also called distention, of the abdomen
Changes in appetite
Weight loss or poor weight gain

33. Approach to a patient with chronic diarrhea
Dietary History
Etiological diagnosis based on dietary history
Dietary history
Diagnosis
Onset after starting of animal milk
CMPA
Starting wheat cereal
Celiac
Following every milk feed
Lactose intolerance
Following intake of sugars/fruit
Sucrase / Isomaltase deficiency
Diarrhea decreases on withholding food
Osmotic diarrhea
Increased appetite
Pancreatic insufficiency

34. Etiological diagnosis based on associated symptoms
Fever
TB, IBD, lymphoma, HIV
Wheeze
Cystic fibrosis, immunoglobulin deficiency, food allergy
Recurrent infections
Immune deficiencies
Vomiting
Protein intolerance, Koch’s, IBD
Increased appetite
Pancreatic insufficiency
Abdominal pain
TB, IBD, lactose intolerance
Arthralgia
IBD
Jaundice
Bile acid diarrhea
Thirst
Disaccharide intolerance
Anorexia
Malabsorption

35. Underlying Disease Chronic liver disease, diabetes mellitus, thyroid disorders. Growth and Development Failure to thrive, birth weight, growth chart, marked recent loss of weight and whether child is well nourished or not are some of the features to be noted. Family History Cystic fibrosis, celiac disease, lactose intolerance, IBD. Treatment History Drugs: Laxatives, antacids, antibiotics, immunosuppressives. Surgery: Short bowel syndrome.

36. Complete Examination
General
Anthropometry, features of apathy, lethargy, hypoproteinemia, alopecia, acrodermatitis enteropathica, features of malabsorption, ascites, jaundice may be clues to etiological diagnosis.
Abdomen
Presence of organomegaly, ascites and rectal examination.
Respiratory: Wheeze, rales (cystic fibrosis).
CVS: Murmur (anemia).
CNS: Weakness, neuropathy, B12 deficiency.

37. Step 1—Confirm that there is chronic diarrhea
Step 2—Is it of small bowel or large bowel origin?

38. Step 3—Is it mainly due to impaired digestion or due to impaired absorption? Malabsorption syndromes - celiac disease Maldigestion - pancreatic exocrine insufficiency or inadequate duodenal bile acid concentration

40. Investigations
Hematologic—anemia and its type i.e. microcytic or macrocytic.
Acanthocytosis suggests abetalipoproteinemia.
Raised platelets are often seen in IBD
Raised ESR suggests an inflammatory pathology.
Lymphopenia points towards lymphangiectasia
Deranged INR suggests vitamin K deficiency secondary to fat malabsorption or liver disease.
Biochemistry—Serum protein, albumin, electrolytes, calcium, phosphorus and alkaline phosphatase.
Complete liver function tests.

41. Stool examination: occult blood; microscopy for ova and parasites, fat globules and fatty acid crystals and culture sensitivity.
Fat malabsorption: microscopic examination of random stool sample for fat globules gives clue to the presence of steatorrhea. Excretion of >4.5 g/day of fat in stools is taken as abnormal.
Chymotrypsin or elastase concentration in stool : is reduced in exocrine pancreatic insufficiency.
D-xylose test : used to asses abnormal intestinal absorption.
Hydrogen breath test: Used to asses lactose malabsorption.
Fecal pH lower than 5.5 or presence of reducing substances >0.5% also suggests carbohydrate malabsorption.

42. B12 and folate malabsorption
Bacterial overgrowth: Quantitative culture of a small intestinal aspirate is the gold standard.
Endoscopic inspection of the duodenal mucosa provides clues to some causes of malabsorption like aphthae (Crohn’s disease), white punctate lesions (lymphangiectasia) or scalloping of duodenal folds and reduction in number of duodenal folds (celiac disease).
Colonoscopy when large bowel diarrhea is suspected. Biopsies confirm the diagnosis of IBD, tuberculosis and parasitic/viral infections like cryptosporidium/CMV.
Small bowel barium study: diverticulum, intestinal hypo motility, dilatation and intestinal fistulas. Ulcerations and strictures may be seen in Crohn’s disease, radiation enteritis, intestinal lymphoma and tuberculosis.

43. CT scan: good modality for pancreatic diseases
CT scan: good modality for pancreatic diseases. It is a sensitive test to detect enlarged abdominal lymph nodes, commonly present in tuberculosis, small bowel lymphoma, or small intestinal Crohn’s disease.
Special scan and endoscopic ultrasound: neuroendocrine tumor (e.g., gastrinoma, somatostatinoma), an indium-111 octreotide scintigraphic scan or an endoscopic ultrasound examination of the pancreas is useful.
Special tests: Antiendomysial and tissue transglutaminase antibodies are used for screening of celiac disease. Ant enterocyte antibodies are present in autoimmune enteropathy. Immunoglobulin levels, T cell functions, HIV serology, thyroid function, gastrin and other enteric hormone levels and sweat chloride test are required in specific situations.

44. Management Supportive
Correction of fluid and electrolyte disturbances.
Correction of vitamin and mineral deficiencies.
Nutritional support is the pillar of treatment
Albumin infusion is needed only for severe symptomatic hypoalbuminemia.

45. Diet
Cow’s Milk Protein Allergy : All animal milk and milk products are avoided till the age of 1 year.
Lactose intolerance: Milk is restricted or load of lactose is reduced.
Celiac disease: Lifelong gluten free diet.
Intestinal lymphangiectasia, pancreatic, cholestatic liver disorders: Medium chain triglycerides based diet.
Adequate calories are provided for all children. Supplement folic acid, zinc and vitamin A.
Enteral nutrition is given in severe malnutrition. Parenteral nutrition is provided only if GUT cannot be utilized.

46. Specific Therapy
Acrodermatitis enteropathica: Zinc 5–10 mg/kg/day
Pancreatitis: Pancreatic enzyme replacement
Parasitic infestations: Antiparasitic therapy
Tuberculosis: Antituberculous drugs
Crohn’s disease: 5ASA, steroids, azathiopurine
Congenital chloridorrhea: Lifelong replacement—Na and K chloride, PPIs
Congenital villi disorders: Intestinal transplant.

47. Celiac disease

48. Celiac disease
Celiac disease (CD) is an enteropathy caused by permanent sensitivity to gluten in genetically susceptible subjects.
The prevalence in children in the West is about %.
CD is the most common cause of chronic diarrhea in children over 2 years of age. Disease may also remain asymptomatic for prolonged periods despite the intestinal damage.
Symptoms usually appear around 6-24 months of age, after weaning with wheat products. Age of introduction and amount of wheat eaten and duration of breast feeding account for variability in age of onset of symptoms.

49. Barley
Rye
Oats

50. The common presenting symptoms are:
Gastro Intestinal- diarrhea, FTT, abdominal distension, vomiting and mild abdominal pain.
Non Gastro Intestinal- anemia, short stature, delayed puberty, osteopenia/osteoporosis, dental enamel hypoplasia and dermatitis herpetiformis
Stunting (100%), anemia (90-100%) and chronic diarrhea (88-94%) are the most common symptoms.

51. The lag period between symptom onset and diagnosis runs into years mainly due to lack of awareness and often leads to severe growth failure and malnutrition.
Screening for celiac disease:
Children with type I diabetes
Autoimmune thyroiditis
Down’s syndrome
Turner’s syndrome
William’s syndrome
Selective IgA deficiency
First degree relatives of celiac subjects are at an increased risk.

52. Investigations: Serology:
IgA antibody to tissue transglutaminase (tTG) is a simple, accurate, ELISA based test for initial testing of CD. It has a high sensitivity (92-100%) and specificity (91-100%).
IgA antiendomysial antibody (EMA) is an equally accurate test (sensitivity %; specificity ).
Both these tests are IgA dependent so if they are negative and still there is a very high clinical suspicion of CD, one should get a total IgA estimation. In IgA deficient individuals, IgG tTG estimation should be done.
Antigliadin (IgA and IgG) and antireticulin antibodies have high false positivity and thus are not recommended as a test of choice now.

53. Upper GI endoscopy & intestinal biopsy :
may be normal or show absence of folds, scalloped folds, visible submucosal vessels and mosaic pattern between folds.
For a diagnosis of CD, intestinal biopsy is a must and multiple endoscopic biopsies from second/third part of duodenum are taken.
HLA (DQ2/DQ8) positivity: is seen in majority (>99%) of subjects with CD and suggests the genetic association.

54. Histology:
The characteristic histological changes in CD are increased intraepithelial lymphocytes (>30/100 enterocytes), increased crypt length, partial to total villous atrophy, decreased villous to crypt ratio and infiltration of plasma cells and lymphocytes in lamina propria.

55. The histological changes are graded according to Marsh criteria as follows:
Grade 0 —normal
Grade 1 —infiltrative (increased intraepithelial lymphocytes)
Grade 2 —hyperplastic (grade 1 + hyperplastic crypts)
Grade 3 —destructive (grade 2 + villous atrophy)
Grade 4 —hypoplastic (total villous atrophy + hypoplastic crypts)
Marsh grade 3/4 changes are characteristic of CD.
Marsh grade 2 is compatible with CD but needs serological positivity for definite diagnosis
Marsh grade 1 changes are not specific for CD in children.

56. The modified ESPGHAN criteria for diagnosis of CD are:
Suggestive clinical picture
Positive biopsy
Unequivocal response to gluten free diet (GFD).
Positive serology (EMA/ tTG)

57. Treatment:
It is indicated in symptomatic children with CD and asymptomatic children from high risk groups with histological findings detected after screening.
The treatment is life long Gluten Free Diet
Correction of iron and folate deficiency
Avoidance of lactose in the initial period
for children with total villous atrophy.
Repeated counselling to parents by dieticians regarding both food items to be consumed and not to be eaten is very helpful in sustaining compliance after the child is asymptomatic.

58. Growth monitoring
The celiac disease guideline committee recommends tTG estimation after 6 months of GFD to show a decrease in titres as an indicator of dietary compliance and also if there is recurrence of symptoms at any time after GFD initiation.
Ideally an annual assessment should be done as part of the long term follow up.

59. Repeat biopsy with gluten challenge may be required in
Children who were diagnosed before two years of age
Who had either atypical changes on first biopsy or no previous biopsy
Adolescents who are unlikely to continue with GFD.
Increased risk of lymphoma, cancers, various autoimmune conditions and osteoporosis in celiacs.

60. Thank You