Malabsorption

Question 1

Main Intestinal Absorptive Functions

Answer 1

SI: Duodenum and Proximal Jejunum: Iron, Folic Acid
SI: Protein digestion (peptides, AA), Carbs, Fat, Ca, Mg, Trace elements, Vitamins, Water and Electrolytes.
Terminal Ileum: Bile salts and Vitamin B12
Colon: absorbs water, electrolytes, SCFA

Question 2

Monosaccharides:

Answer 2

• Glucose
• Fructose
• Galactose

Question 3

Monosaccharide digestion: Glucose

Answer 3

Glucose is absorbed by carrier protein SGLT1 (Na coupled absorption), both apical and basolateral location

Question 4

Disaccharidase Digestion: Lactose

Answer 4

Lactose: Glucose + Galactose.
enzyme lactase in brush border splits lactose into glucose and galactose, both glucose and galactose complete for absorption via SGLT1. GLUT2 on basolateral side

Question 5

Disaccharides

Answer 5

Lactose: Glucose +Galactose
Sucrose: Glucose + Fructose
Maltose: Glucose + Glucose

Question 6

Disaccharide digestion: Sucrose

Answer 6

Sucrose is divided by Sucrase-Isomaltase into Glucose and Fructose. Glucose is absorbed by SGLT1. Fructose is absorbed via passive diffusion and also by GLUT 5

Question 7

Carbohydrate digestion (starch)

Answer 7

Starch: polysaccharide contained in plants. Amylase is enzyme which cleaves starch into Maltose (disaccharide). Maltase then splits Maltose into two glucose molecules

Question 8

Carbohydrate malabsorption consequences

Answer 8

Carbohydrates reach the colon: fermentation occurs: production of CO2, SCFA, H2: leading to watery, acidic stools

Question 9

Tests for CHO malabsorption

Answer 9

• Fecal pH, reducing substances
• H2 breath test: 2g/kg PO of carbohydrate to be tested. Malabsorbed CHO metabolized by colonic microbiotica –> organic acids, H2 and CH4. Absorbed H2 measured in the expired air.
  Interpretation: above 20ppm diagnostic for malabsorption

Question 10

SIBO diagnosis can also be made using breath test.

Answer 10

early peak in graph

Question 11

Protein digestion

Answer 11

First phase: Gastric: HCl and Pepsinogens.
Second phase: Duodenum: Enterokinase (brush border enzyme: which activates pancreatic proteases). Leads to free AA and di and tri peptides.
Di- and Tri- Peptide Carriers: PEPT-1- and PEPT-2. H+/peptide cotransporters (Not sodium linked);

Question 12

Tests for protein malabsorption

Answer 12

Fecal alpha-1- antitrypsin: a test of protein losing enteropathy

Question 13

Lipid digestion

Answer 13

Triglyceride: composed of glycerol +fatty acids. Lipase separates glycerol from fatty acids.
Lingual lipase and FT babies.
Pancreatic lipase: develops very slowly.
Breast milk lipase: highly efficient.
Daily fat loss in stool (Steatorrhea): high in newborn. decreases to <3g/day (Coefficient of absorption: more than 90%)

Question 14

Tests for lipid malabsorption

Answer 14

Fecal fat: partially reliable:
If “neutral fat” is increased: disorder of digestion.
If “split fat” is increased: disorder of absorption.
Best way to assess lipid malabsorption: 72 hour quantitative fecal fat.

Question 15

Bile Acid Malabsorption

Answer 15

SeHCAT test: 75 Selenium-homocholic acid taurine test.

Question 16

Malabsorption of Electrolytes

Answer 16

Chloride Diarrhea:
Absorption of chloride is result of double antiport on apical membrane: Na+/H+ and Cl-/HCO3-.
Defect: Cl cannot be absorbed and HCO3- cannot be excreted. This leads to H+ being retained: Metabolic Acidosis.
This leads to Cl- being lost: Secretory diarrhea.
Stool values: Cl >Na + K.

Question 17

Sodium losing diarrhea

Answer 17

Absorption of sodium is result of double antiport on apical membrane: Na+/H+ and Cl-/HCO3-.
Dysfunction of Na+/H+ transport: Na cannot be absorbed, which means H+ cannot be excreted. This leads to retention of HCO3- which causes metabolic alkalosis. Loss of Sodium leads to secretory diarrhea.
Stool values: Na very high: 90-140mMol.

Question 18

Malabsorption Syndromes with NORMAL Duodenal biopsies

Answer 18

Glu-Gal Malabsorption
Lactase Deficiency
Enterokinase Deficiency
Primary bile acid malabsorption
Congenital Cl diarrhea
Congenital Na diarrhea

Question 19

Malabsorption Syndromes with Abnormal (atrophic) duodenal biopsies

Answer 19

Microvillus inclusion disease
Tufting enteropathy
Short Gut Syndrome

Question 20

Microvillus Inclusion Disease

Answer 20

• Lethal if untreated
• Autosomal recessive
• MYO5B gene mutation
• Profuse watery diarrhea (both secretory and osmolar)-usually starts a few days after birth.
• Characteristic defect: mucosal surface enterocytes complete lack the brush border.
• Total and permanent inability to digest/absorb any nutrients and a marked secretory state

Question 21

Approach to the newborn with profuse watery diarrhea:

Answer 21

Stool tests: volume, reducing substances, Na, K, Cl and Osmolality.
If mixed: Osmolar and Secretory Diarrhea, consider Microvillus Inclusion Disease. Duodenal biopsy with EM

Question 22

Secretory Diarrhea DDX

Answer 22

Na >120: Congenital Na-losing diarrhea
Cl >90mMol: Congential Chloride Diarrhea: SLC26A3 Mutation

Question 23

Osmolar Diarrhea: DDX

Answer 23

Step 1: remove carbohydrates.
Diagnostic oral challenge for Glu-Gala Malabsorption: SLC5A1 Mutation

Question 24

Malabsorption Syndromes with Onset in Infancy with ABNORMAL Duodenal biopsies

Answer 24

• FPIES
• Celiac disease
• Eosinophilic Gastroenteropathy
• Post-enteritis Protracted Diarrhea
• Primary Lymphangiectasia
• CVID
• Autoimmune Enteropathy

Question 25

Malabsorption Syndromes with Onset in Infancy with NORMAL Duodenal biopsies

Answer 25

- Acrodermatitis Enteropathica - SB Bacterial Overgrowth - Sucrase-Isomaltase Deficiency - Cystic Fibrosis - Shwachman-Diamond Syndrome - Isolated Lipase/Coliapse Deficiency