Diarrhea

Question 1

Diarrhea: the basics

Answer 1

Diarrhea is a small bowel problem.
Absorption: movement from luminal side to blood and lymphatics.
Secretion: movement from mucosa to intraluminal space.
Net absorption = net ion flux = net difference absorption: secretion

Question 2

Diarrhea the players

Answer 2

Receptors:
- Na+/H+ exchangers (NHEs)
- Na+/K+ pump
-Cl- and K+ channels
- organic solute carriers.
Water, ions (Na+, H+, Cl-, and K+) and solute transport (Na+ coupled glucose).
Salt absorption creates an osmotic gradient for water absorption (80% of water absorption occurs via paracellular pathway).

Question 3

Osmotic vs Secretory Diarrhea

Answer 3

Question 4

Osmotic Diarrhea

Answer 4

Osmotic Diarrhea
- Electrolytes: Na <70mEq/L
- Osmolarity: >(Na +K) x2
- pH <5
- Volume: <200 ml/day (10gm/kg/day)

Question 5

Secretory Diarrhea

Answer 5

Secretory Diarrhea
- Electrolytes: Na >70 mEq/L
- Osmolarity = (Na +K) x2
- pH >6
- Volume: >200 ml/day (10gram/kg/day)

Question 6

Toddler’s Diarrhea

Answer 6

• chronic diarrhea despite normal growth and exam.
• usually 6 months to 5 years.
• Diarrhea becomes more watery as the day progresses.
• Etiology is dietary: low fat diet leads to decreased intestinal transit time.
  high carb diet, especially fructose and sorbitol leads to increased osmotic load.

Question 7

Congenital Diarrhea

Answer 7

• Rare
• Vast majority are inherited
• Diarrhea starts within first few days of life.
• Disorders of selective nutrient/electrolyte assimilation versus
• Disorders of intestinal fialure: immune dysfunction/enterocyte cytoskeleton/brush border/ autoimmune.

Question 8

Diagnosis of Congenital Diarrhea

Answer 8

Dietary challenges = key diagnostic test
-accurate assessment of stool volume, pH, reducing substances and electrolytes (during fasting and feeding states)
Secretory vs osmotic/malabsorptive.
If you stop feeding them and the diarrhea stops, it is an osmotic diarrhea.
If osmotic/malabsorptive: selective versus generalized (range of nutrients affected)
Upper GI SBFT to rule out malrotation with intermittent volvulus, and to also rule out congenital short bowel syndrome

Question 9

Tufting Enteropathy

Answer 9

• Moderate to severe watery diarrhea in neonatal period (4 days to 4 weeks).
• Tufts of extruded epithelial cells, tear drop shaped, appear to shed into lumen.
• Total or partial villous atrophy and crypt hyperplasia.

Question 10

Microvillous inclusion disease

Answer 10

100-500 ml/kg/day if taking PO
- High Na+ content of 100mmol/L
- light microscopy: villous atrophy without IELs, absence of marked crypt hypertrophy, Periodic acid-Schiff + material in upper crypt and villous epithelium.
- Diagnosis with transmission EM: intracellular inclusions and secretory granules. Microvilli depletion on apical epithelial surface. Microvilli present in intracellular inclusion bodies. Crypt epithelium shows secretory granules.

Question 11

Evaluation of Congenital Diarrhea

Answer 11

Electrolytes, albumin, immunoglobulins, T and B cell subsets

Question 12

Congenial Chloride Diarrhea

Answer 12

• Only diarrhea that leads to metabolic ALKALOSIS due to Cl/HCO3 exchange.
• Most common severe congenital secretory diarrhea
• Severe exacerbation of diarrhea a/w most febrile illnesses.
• Life long enteral KCL and NaCl supplementation, PPI, cholyestyramine.
  -SLC26A3

Question 13

Congenital Sodium Diarrhea

Answer 13

High volume, secretory diarrhea with high concentration of Na.
Tx: Lifelong use of PO fluids and slat supplements

Question 14

Prebiotics

Answer 14

• Nondigestible food that promotes intestinal growth of beneficial bacterial
• Dietary oligosaccharides
• Risks: gas, GI upset, neonatal sepsis

Question 15

Probiotics

Answer 15

• microorganisms introduced into the body for beneficial qualities
• possible risk of translocation in immune compromised patients
• possible indications: rotavirus, pouchitis

Question 16

Pharmacology: absorbents and bulking agents

Answer 16

• Pectin, fiber, methylcellulose
• can affect absorption of other medications (MTX, warfarin)

Question 17

Pharmacology “slowers”

Answer 17

• anti-cholinergics (belladonna alkaloids)
• opiates (loperamide)

Question 18

Pharmacology: anti-inflammatories

Answer 18

Bismuth subsalicylate

Question 19

Protein Losing Enteropathy

Answer 19

PLE is a syndrome and NOT a diagnosis.
Key: low albumin and lymphopenic.

Management: diuretics, high protein diet, low fat diet, MCT and fat soluble vitamin supplementation, and fix underlying problem.

Question 20

PLE Mechanisms:

Answer 20

• Ulceration (IBD/peptic ulcer)
• Decreased capillary glycocalyx (sepsis, CDG Ib)
• Increased hydrostatic pressure (Fontan)
• Increased lymphatic pressure (lymphatic obstruction)
• Increased tight junction permeability (celiac disease, IBD)
• Disrupted epithelial glycosaminoglycans (GAG) CDGIb and Ic, IBD.

Question 21

Autoimmune Enteropathy

Answer 21

Associated: thyroiditis, hematologic abnormalities (Coombs + anemia, neutropenia and thrombocytopenia), liver, kidney and pulmonary disease, splenomegaly.
Histology: villous atrophy. Massive mononuclear infiltrate in lamina propria (versus celiac disease which has intraepithelial lymphocytes).
Antienterocyte/anticolonocyte antibodies (Anti-75-AIE) are highly sensitive.
Supportive therapy: TPN, steroids, tacrolimus or sirolimus. Stem Cell Transplantation

Question 22

IPEX Syndrome

Answer 22

• Immune dysregulation, polyendocrinopathy, enteropathy, X-linked.
• FOXP3 gene mutation results in compromised suppressor function of T regulatory cells.
• Clinical presentation: typical trial of AIE, autoimmune endocrinopathy, and eczema.
  markedly increased IgE, peripheral eosinophilia, food allergies.
  can have diabetes 2/2 islet cell destruction
  severe secretory diarrhea
  hypoalbuminemia and electrolyte disturbance requiring bowel rest and TPN