PERSISTENT DIARRHEA

Prof. dr. Yati Soenarto, Ph.D., Sp.A (K)

Why is diarrhea dangerous?

DIARRHEA  DEATH due to LOST (& LACK)

of:

WATER & ELECTROLYTE

FOOD
 CAUSES OF DEATHS IN CHILDREN U5

GLOBAL ASIA – WHO SEAR

Other YR 2002
10%

Neonatal
36%

Diarrhea
Pneumo
17%
nia INDONESIA
19% YR 2000 - 2003
Others
Bryce J, et.al., 2005 22%

Neonatal www.who.int.org
38%

P neumonia
14%

D iarrhea
18%
“DIARRHEA”
WHO,2006
Bhutta, 2006
• Chronic diarrhea = persistent diarrhea?
 overlap in definition
 Chronic diarrhea :
episode of diarrhea lasts for >2 weeks (Ghishan, 2007)

 Persistent diarrhea :
The passage of watery stools > 3 times per day for >2
weeks in a child who either fails to gain or loses weight.

(Working Group Report of the First World Congress of Pediatric

Gastroenterology, Hepatology, and Nutrition. Bhutta et al.,2002)
Indonesian Gastrohepatology peer group
 Persistent diarrhea :
diarrhea, with or without blood, which begins acutely and lasts for 14
days or longer (WHO,2006)

• Chronic diarrhea : episode diarrhea lasts for > 4 wks, associated with
non-infectious agent. (American Gastroenterological Association,1999)

persistent diarrhea : prolonged acute diarrhea, due

to infection.
 chronic diarrhea : episode of diarrhea lasts for >than
several weeks, caused by non-
infectious etiology.
 Persistent/chronic
Acute diarrhea
continuous diarrhea diarrhea
0 7 14 (days)

• WHO 2006  acute diarrhea : lasts for several days

(<14 days)
(1) Intraluminal factor :
 pancreatic & liver disorder, brush border membrane

(2) Mucosal factor :

 alteration of mucosal membrane integrity, due to infection
(virus, bacteria, parasite, fungi)
 Cow’s milk allergy & lactose intolerance  villous atrophy.

Ghishan,2007
Bhutta, 2006
Concept of Pathogenesis of Persistent and Chronic Diarrhea , taken from : Studies
of the Small Intestine in Persistent Diarrhea and Malnutrition : The Gambian
Experience, Sullivan, 2002.
Bhutta, 2006
1. Osmotic diarrhea
 Caused by presence of non-absorbable substance in the GI tract
 Ex : lactose intolerance.
 Stop with avoidance of substance causing diarrhea.
 Lab investigation : low pH, reducing substance (+)

2. Secretory diarrhea
 endogenous substances induce fluid secretion.
 Activation of intracellular mediators (cAMP, cGMP, intracellular
Calcium)
 Ex : diarrhea due to V. cholera, E. coli enterotoxin

Ghishan, 2007
3.Congenital defects of ion transport protein
 Defects in Na-H exchange or Cl-/HCO3- exchange (congenital
chloride-losing diarrhea) or Sodium-Bile acid transport protein.
 Symptom occurs in early age of life  secretory diarrhea & failure to
thrive since neonatal period.

4. Reduction in Anatomic Surface Area

 Results from the resection of the bowel  short bowel syndrome
 Characterized of loss of fluids, electrolyte, micro & macronutrient.

Ghishan, 2007
5. Alteration in Intestinal Motility
 Various etiology (malnutrition, scleroderma, intestinal obstruction,
and DM).

Malnutrition  reduce intestinal motility 

overgrowth bacteria  bile salt deconjugated  intracellular
cAMP   secretory diarrhea

Ghishan, 2007
 Watery diarrhea > bloody stools.
 Generally : malnutrition
 Loss of appetite
 Vomiting
 Fever
 Mucous in stools
 Cold syndrome
(Roy, et al, 2006; Vernacchio, et al, 2006)
1. Host (child) factors
 < 12 months of age

 Low birth weight (<2500 gram)

 Malnourished children/infants

 Impaired cell-mediated immunity

 In association with respiratory tract infection

2. Maternal factors
 Young age and limited mothering experience
 Maternal educational status, knowledge, attitude & behaviour about
hygiene, health, and nutrition

(cit. Gracey,2007)
 Risk factors :

3. Feeding practices
 Recent introduction of animal milks

 Use of feeding bottles and teats or dummies (pacifiers)

4. Microbial isolates during episodes

 Enteroadherent Escherichia coli (EAEC), Enteroaggregative E. coli
(EaggEC), Enteropathogenic E. coli (EPEC)
 Shigella

 Cryptosporidium

 Multiple enteric pathogens

(cit. Gracey,2007)
5. Previous episodes of infections
 Recent episode(s) of acute diarrhea

 Previous episode(s) of persistent diarrhea

6. Use of drugs at previous time

 Antimotility  reduce motility of gastrointestinal

 Antimicrobial

(cit. Gracey, 2007)

1. History Taking

• Age at onset
• Diet history
• Nutritional assessment
• Assessment of diarrhea : frequency, volume,
character of diarrhea (watery, blood, undigested
food particles)
• Family history : inherited conditions
• Review of systems
2.Physical Examination

• Dehydration status
• Signs of malnutrition
• Measurement of nutritional status
• Abdominal distention, bowel sounds  obstruction?
Motility disorder?
3.Laboratory Investigation

• Blood & stool examination See table

• Hydrogen breath test
• Sweat test  cystic fibrosis ?
 Tests Indication Interpretation
Qualitative fecal fat Fat malabsorption detects >90% of significant steatorrhea
(Sudan stain)
Quantitative fecal fat Fat malabsorption Gold standard;
(48- or 72-hour) normal fecal fat value is <6 g/24 hr, values >10–
24 g/24 hr indicate fat malabsorption.
Fecal leukocytes/ Inflammation Limited usefulness because of variable
lactoferrin sensitivity and specificity
Stool osmolarity Verification of <250 mosm/kg = factitious diarrhea (e.g.,
diarrhea addition of water or hypotonic urine to stool
sample).
Stool electrolytes Differentiation of Osmotic gap >125 mosm/kg = osmotic diarrhea
secretory from osmotic gap <50 mosm/kg = secretory diarrhea.
osmotic diarrhea

American College of Physicians, 2006

 Tests Indication Interpretation
Stool pH Osmotic diarrhea pH <6.0 = carbohydrate malabsorption.

hydrogen breath test Carbohydrate Increased hydrogen excretion after

malabsorption carbohydrate challenge; often replaced by an
empiric trial of dietary exclusion.
Small bowel biopsy Malabsorption, Loss of villi (e.g., celiac sprue) - inflammatory
inflammation infiltrates
Duodenal aspirates Small bowel Quantitative bacterial culture >105 is positive;
bacterial mixed flora

American College of Physicians, 2006

 SUSPECT CLINICAL SCREENING SPECIAL DIAGNOSTIC
ETIOLOGY MANIFESTATION TEST
I. MALABSORPTION SYNDROME
1. Carbohydrate Stool : watery, foam Stool : •Stool : glucose
Intolerance appearance - pH chromatography, fat
Abdomen : Flatulence - reducing determination
Anorectal: Erythema substance •“Breath”: hydrogen breath
- Age test
- History of introducing •Intestinal mucous :
some foods disaccharidase
•Urine: lipid absorption test
2. Fat Stool : fatty, sticky Stool : fat globule
maldigestion- (72-hour stool ;
Malabsorption gold standard)
3. Protein Microscopic stool : Stool
Maldigestion- “Striated Muscle Fibres” - Nitrogen stool
Malabsorption - 1, Antitrypsin
clearance
- Duodenal aspirate :
Trypsine activity test
II. ALLERGY
4.Cow’s milk - ”Non-breast feed”, - Eliminating Cow’s milk - “Re-challenge”
- Introduction of - Stool : blood & - Biopsy
cow’s milk leukocyte
- Family history - Blood : fosfatase lindi
xylose
5. Other protein - introduction some - Eliminating particular - “Re-challange”
protein food
- Diarrhea
III. INFECTION
6. Enteropathogen - Specific cause - stool : Microscopic stool : culture, ELISA
infection - Spesific clinical investigation - Aspirasi duodenum
manifestation - Toxin Assay
- Stool
7. Extraintestinal - depend on the - Blood smear : - blood : culture
infection cause leucocyte count - other screening
5 LANGKAH TUNTASKAN
5 STEPS DIARE FOR DIARRHEA
OF MANAGEMENT

CASE MANAGEMENT
1. NEW REDUCED
1. DEHYDRATION:  Rehydration: IV  oralit  OSMOLARITY ORALIT

2. CONTINUED SEVERITY
2.NUTRITION:   3.ZINC  & INCIDENCE
FEEDING

4. RATIONAL
ANTIMICROBIAL
3. ETIOLOGY  PHARMACOLOGIC
(commonly infection)
NO ANTIMICROBIAL &
ANTIVOMITING
4. SUCCES OF 5. PATIENT-DOCTOR
PRACTICE: COMMUNICATION
Algorithm of Management of Persistent Diarrhea

Bhutta, 2006
 MANAGEMENT OF PERSISTENT
DIARRHEA

 Assessing dehydration status & nutritional status

 Manage electrolyte imbalance

2. Dietary management (1)

Daily energy requirement : 100 kcal/kg/day
Daily protein requirement : 2-3 g/kg/day

(Bhutta,2006)
 MANAGEMENT OF PERSISTENT
DIARRHEA

2. Dietary management (2)

 Give daily supplementary multivitamins and minerals for two
weeks  at least two RDAs of folate, vit A, zinc, magnesium and
copper.
 One RDA for a child aged 1 year :
- folate 50 micrograms - zinc 10 mg
- Vit. A 400 micrograms - Fe 10 mg
- Cu 1 mg - Mg 80 mg.

WHO, 2006
 MANAGEMENT OF PERSISTENT
DIARRHEA

3. Follow-up
Dietary management failure :
• increase in stool frequency (>10 watery stools/day),
often with a return of signs of dehydration, OR
• failure to establish daily weight gain within 7 days.

Re-investigate : exclude intractable diarrhea

Bhutta, 2006; WHO, 2006

 MANAGEMENT OF PERSISTENT
DIARRHEA

 Routine treatment with antibiotics  not recommended

 Extraintestinal infections Treat with antibiotics following the
guidelines.
 Intestinal infections  give oral antibiotic which is effective for
Shigella if blood present in the stool.
 ciprofloxacine, cefixime, nalidixic acid
trofozoit of E. histolytica (+)  oral metronidazole (50 mg/kg BW,
divided in 3 doses)
 Give antibiotic treatment based on sensitivity culture.

WHO, 2006
 Probiotics & Persistent Diarrhea

 Probiotics are defined as living organisms that when administered in

adequate amounts confer a health benefit on the host

 Widely used for various indications because of their widespread acceptance

and general lack of adverse effects

 Probiotics commonly used include three genera of lactic acid bacteria,

namely, Lactobacillus, Bifidobacterium, and Streptococcus

 Acute infectious diarrhoea is the most investigated field in the area of

probiotic use in children

 However, the effects of probiotics in acute diarrhoea are not generalizable

to persistent diarrhoea

The Cochrain Collaberation, 2009

Pineiro, M. & Stanton, C., 2007
Rationale For Use of Probiotics in
Persistent Diarrhea

 the assumption that probiotics modify the

composition of intestinal microflora and act against
enteric pathogens

 the beneficial effects of probiotics in acute diarrhoea

in children seem to be strain-dependent, dose-
dependent (greater for doses of > 1010 colony
forming units), significant in people with viral
gastroenteritis, and more evident when treatment
with probiotics is initiated early in the course of
disease

The Cochrain Collaberation, 2009

Rationale For Use of Probiotics in
Persistent Diarrhea (cont.)

De Vrese, M. & Marteau, P.R., 2007

Future Application of Probiotics

 Future studies on the therapeutic potential of

probiotics are necessary

 Efforts should be made to standardize doses,

duration of treatment

 Direct comparisons of probiotics versus placebo are

indicated

 Adverse reaction data and cost-effectiveness

analyses would be helpful

(McFarland, L.V.; et.al.; 2005)

1. HIV
 Persistent diarrhea  common symptoms in HIV.
 Incidence : 5 times higher in HIV
 Risk factors of persistent diarrhea in HIV :
- Number of prior acute diarrheal episode (3-4 episode of
acute diarrhea increases risk of persistent diarrhea
- Severity disease of HIV in mother
Thea et al, 1993

 Parthasaraty (2006)  screening of children with chronic

diarrhea in New Delhi revealed 4,1% HIV seropositive.
 HIV Binding to cell-surface CD4
infection molecule (receptor-mediated)

Depletion CD4-T cells

Reduction of T CD4/CD8 ratio

Decrease IgA secretion (in B cells,

plasma & intestinal)

Bacterial overgrowth

Increase absorption of bacterial

products (endotoxin)
(Winter, 1996)
 Viruses Bacteria & Parasites Fungi
mycobacteria
• CMV Salmonella Giardia lamblia Histoplasma
•Astrovirus Shigella E. histolytica C. albicans
•Picornavirus Campylobacter Microsporidia
•Coronavirus Clostridium difficile -Enterocytozoon
•Rotavirus Treponema pallidum bieneusi
•Herpesvirus Spirochaetes -Encephalocytozoon
•Adenovirus Neisseria gonorrheae intestinalis
•Small round virus Vibrio cholerae Cyclospora
•HIV Pseudomonas ? Cryptosporidium
S.aureus Isospora belli
M. avium-complex Blastocystis hominis?
M.tuberculosis
2. MALIGNANCY
1. Pancreatic cholera  neoplasm of endocrine-cell produces
neurotransmitter, leading to intestinal over-secretion.

2. Carcinoid tumor secrete Serotonin,bradikynin, prostaglandin,

P-substance

Stimulating intestinal secretion

3. Thyroid medullar calcitonin Intestinal secretion diarrhea
carcinoma

4. Zollinger-Elison gastrin  gastric gastric

(gastrinoma acid  acidity 

diarrhea malabsorption Bile salt inactivate pancreatic

precipitate enzyme
Field, 2003
2. MALIGNANCY
Persistent diarrhea in malignancy is not only caused by its
disease, but also adverse effect of chemotherapy
Chemotherapy-induced diarrhea :

morphologic changes of the intestinal epithelium :

• Epithelial flattening
• Villous atrophy
• Down-regulation of enterocyte-specific gene
expression
 Grade 0 1 2 3 4

No. of Normal 2-3 4-6 7-9 >10

stools/day

Symptom - - Nocturnal Incontinence Bloody

stools stool
- - Moderate Severe Need for
cramping cramping parenteral fluid
support
THANK YOU FOR YOUR ATTENTION