Malabsorption

1
Malabsorption
2
Case

• 32 year old man previously well
• 3 months loose, soft foul-smelling bowel movement
• 6 kg weight loss
• Tired, weak
• Abdominal distension
• Bleeding tendency
• Back pain

3
Case

• Thin, pale, bruises on skin
• Ankle edema
• Hemoglobin 11.2 g/dL, MCV 105
• Albumin 3.1 g/dL (N gt3.4)
• PT-INR 1.9 (N lt1.2)
• Serum calcium 6.9 (N 8.5-10.2 mg/dL)
• Stool fecal fat excretion 19 g/day

4
Malabsorption

• Clinical syndrome
• Due to defects occurring during the digestion
  and absorption of food nutrients by the
  gastrointestinal tract
• Result of many different disease processes
• Luminal
• Absorptive
• Post-abortive phases

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Symptoms

• 3 months loose, soft foul-smelling bowel
  movement
• Diarrhea
• Most common symptomatic complaint
• Frequently watery
• Cause
• Osmotic load received by the intestine
• Bacteria produce hydroxy fatty acids from
  undigested fat increases net fluid secretion
  from the intestine

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Symptoms

• 3 months loose, soft foul-smelling bowel
  movement - Stool fecal fat excretion 19 g/day
• Steatorrhea gt7g fat/day
• Steatorrhea - fat malabsorption
• Pale, bulky, and malodorous stools
• Float on top of the toilet water
• Difficult to flush
• Oil droplets in the toilet following defecation

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Symptoms

• 6 kg weight loss Tired
• Weight loss and fatigue
• Weight loss is common
• Compensate by increasing caloric consumption,
• Most noticeable in diffuse diseases
• Celiac disease and Whipple disease

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Symptoms

• Abdominal distension
• Flatulence and abdominal distention
• Bacterial fermentation of unabsorbed food
  hydrogen and methane
• Causes abdominal distention and cramps

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Symptoms

• Bleeding tendency, bruises on skin, PT-INR 1.9
  (N lt1.2)
• Bleeding disorders
• Vitamin K malabsorption and subsequent
  hypoprothrombinemia.
• Easy bruising
• Rarely melena and hematuria

10
Symptoms

• Ankle edema, albumin 3.1 g/dL (N gt3.4)
• Edema (also ascites)
• Hypoalbuminemia
• Protein malabsorption
• Loss of protein into lumen
• Intestinal lymphangiectasia
• Obstruction of the lymphatic system,
• Lymphoma

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Symptoms

• Back pain, serum calcium 6.9 (N 8.5-10.2 mg/dL)
• Metabolic defects of bones
• Vitamin D deficiency
• Osteopenia or osteomalacia.
• Bone pain and pathological fractures
• Malabsorption of calcium can lead to secondary
  hyperparathyroidism.

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Symptoms

• Weakness
• Neurological manifestations
• Vitamin malabsorption
• Generalized motor weakness
• Peripheral neuropathy

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Digestion and Absorption

• Carbohydrate (CHO)
• Protein
• Fat
• Vitamins and minerals
• Water and electrolytes

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Malabsoption - Mechanisms

• Luminal phase
• Impaired nutrient hydrolysis
• Impaired micelle formation
• Luminal processing
• Mucosal phase
• Impaired brush-border hydrolase activity
• Impaired nutrient absorption
• Post absorptive phase

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Malabsorption

• Luminal Phase

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Luminal PhasePancreas

• Exocrine
• Enzymes (acini)
• Bicarbonate (ducts)

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Luminal Malabsortion or Maldigestion Impaired
Nutrient Hydrolysis

• Pancreatic insufficiency
• Chronic pancreatitis, pancreatic resection,
  pancreatic cancer, or cystic fibrosis
• Lipase, protease, carbhydrase deficiency leads to
  lipid,protein, carbohydrate malabsorption,
  respectively

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Malabsorption - Pancreas

• Methods to assess dysfunction
• Anatomic - damage
• Physiology - assessement of function

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Anatomical Chronic PancreatitisCalcified
Pancreas
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Anatomical ERCP Chronic Pancreatitis and
Carcinoma
Carcinoma
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Anatomical Chronic Pancreatitis - EUS
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Malabsorption Pancreatic Function

• Secretory Function
• Non-invasive
• Low fecal Chymotrypsin and Elastase 1
• Bentiromide Test
• Invasive
• Collect pancreatic juice
• Before and after hormonal stimulation
• Secretin, CCK
• Analyze volume, enzyme activity and bicarbonate

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Function - Bentiromide Test

• PABA is cleaved off by pancreatic chymotrypsin
• Free PABA is absorbed, conjugated by the liver,
  and excreted in urine and measured
• Decreased PABA excretion pancreatic insufficiency
• Highly sensitive and specific for advanced
  pancreatic failure
• Not very sensitive in mild pancreatic
  insufficiency

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Luminal Malabsortion or Maldigestion Impaired
Micelle Formation Bacterial Overgrowth

• Bile salt deconjugation
• Stasis of intestinal content caused by a motor
  abnormality (eg, scleroderma, diabetic
  neuropathy, intestinal obstruction),
• Anatomic abnormality (eg, small bowel
  diverticula, stricture, blind loops
• Small bowel contamination from enterocolonic
  fistulas

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Malabsorption - Bacterial OvergrowthSmall Bowel
Series
Diverticulosis
Scleroderma
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Malabsorption Bacterial OvergrowthBreath Tests

• Hydrogen breath test
• Glucose
• Bile acid breath test
• C13-glycocholate breath test
• Xylose breath test
• C13-xylose

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Malabsorption - Bacterial OvergrowthCulture

• Quantitative culture of an aspirate of luminal
  fluid
• The gold standard
• Positive culture gt 106 organisms/mL
• Aerobic or anaerobic culture

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Luminal Malabsortion or Maldigestion Impaired
Micelle Formation

• Impaired fat solubilization
• Decreased bile salt synthesis from severe
  parenchymal liver disease
• impaired bile secretion from biliary obstruction
  or cholestatic jaundice

X
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Luminal Malabsortion or Maldigestion Impaired
Micelle Formation

• Impaired enterohepatic bile circulation
• small bowel resection or regional enteritis

X
30
Luminal Malabsortion or Maldigestion Impaired
Nutrient Hydrolysis

• Inadequate mixing of nutrients, bile, and
  pancreatic enzymes
• Rapid transit
• Gastrojejunostomy

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Malabsorption

• Mucosal phase

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Malabsorption Mucosal phase

• Reduced brush-border hydrolase
• Primary lactase deficiency
• Genetic factors
• Secondary lactase deficiency
• Acute gastroenteritis, chronic alcoholism, celiac
  sprue, radiation enteritis, regional enteritis,
  or AIDS enteropathy.

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Malabsorption - Mucosal phase

• Impaired nutrient absorption
• Acquired disorders
• Damaged absorbing surface
• Celiac sprue, tropical sprue, giardiasis, Crohn
  disease, AIDS enteropathy, chemotherapy, or
  radiation therapy
• Decreased absorptive surface area
• intestinal resection or intestinal bypass
• Infiltrating disease of the intestinal wall
  
• lymphoma and amyloidosis.

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Malabsorption

• Postabsorptive Phase

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Malabsorption Postabsorptive Phase

• Obstruction of the lymphatic system
• Congenital
• Intestinal lymphangiectasia
• Acquired
• Whipple disease, neoplasm ie.g. lymphoma,
  tuberculosis
• Impaired absorption of chylomicrons and
  lipoproteins
• fat malabsorption and/or protein-losing
  enteropathy

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Investigation of Malabsorption
Jungle
Confusion
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Malabsorption - Investigation

• Does the patient have malabsorption?
• History
• Physical
• Initial blood tests
• Deficiencies of vitamins and minerals
• Stool examination
• 3-Day Fecal Fat gt6g/day or gt 7 of fat intake

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Suspected malabsorption
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Malabsorption Major Categories and Causes

• Intraluminal - maldigestion
• Pancreatic insufficiency
• Bacterial overgrowth
• Defective bile secretion

• Mucosal - malabsorption
• Celiac disease
• Tropical sprue
• Infection bacteria, parasites
• Whipples disease
• Intestinal resection short gut
• Abetalipoproteinemia
• Crohns disease

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Malabsorption Luminal, Mucosal or Postabsorptive?
Diabetes mellitus Liver disease (20 of cirrhosis
patients, chronical hepatitis, fat
liver) Hypoglycemia Malnutrition Overdose
antidiabetic drug Pancreas cancer Chronical
alcohol abuse Hyperglycemia Reference range for
OGTT Fasting 60 min 120 min normal lt100 mg/dL
160 mg/dL 120 mg/dL impaired 100-130 mg/dL
160-220 mg/dL 120-150 mg/dL Assessment of
Malabsorption Carbohydrate I oral dose 25 g
D-xylose in 250 500 mL water over 10 min to
fasting subject D-xylose measurement in blood
hourly upto 5 h Normal blood D-xylose rises
upto 30 35 mg/dL at least 25 of the dose
should be excreated in 5 h-urine D-Xylose test in
patient with bowel resection after treatment with
TPN and EN

• D-Xylose test
• Oral dose 25 g D-xylose in 250 500 mL water
  over 10 min to fasting subject
• D-xylose measurement in blood hourly upto 5 h and
  in 5 h-urine
• Normal blood D-xylose rises upto 30 35 mg/dL
• at least 25 of the dose should be excreted in 5
  h-urine

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Malabsorption - Investigation

• Xylose Normal
• Suspect pancreatic disease

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Malabsorption- Pancreatic FailureTrial of
Treatment

• Pancreatic enzyme replacement
• Provides sufficient lipase, trypsin, and amylase
  to abolish maldigestion of fat, protein, and
  carbohydrate
•  Arrives intact in appropriate amounts in the
  duodenum  
• Liberates active enzyme in the duodenum
• Has a long shelf life.
• Palatable, cheap and reliable.

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Malabsorption - Bacterial Overgrowth

• Trial of treatment
• Antibiotics

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Malabsorption Mucosal/Postmucosal Disease
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Mucosal Malabsorption Small Bowel Series

• Small bowel barium studies
• An abnormal small bowel pattern
• The mucosa pattern associated with celiac disease
  often becomes obliterated or coarsened
• Flocculation of the barium occurs in the gut
  lumen
• Regional enteritis of the small intestine can
  lead to stricture, ulceration, and fistula
  formation

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Mucosal MalabsorptionBiopsy

• Endoscopically obtained
• Definitive diagnosis of malabsorption of the
  mucosal/post absorptive phase
• Examples
• Celiac sprue, giardiasis, Crohn disease, Whipple
  disease, amyloidosis, abetalipoproteinemia, and
  lymphoma.

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Jejunal biopsy-Whipple's disease
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Eosinophilic Gastroenteritis
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LymphangiectasiaDilated Submucosal Lacteals
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Celiac disease
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Celiac Disease

• Genetically-determined
• Chronic inflammatory intestinal disease
• Environmental precipitant- gluten.
• Mainly non-gastrointestinal symptoms
• Patients present to various medical practitioners

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Celiac Disease - Genetics

• Multigenic disorder
• Associated with HLA-DQ2 (DQA105/DQB102) or
  HLA-DQ8 (DQA10301/DQB10302).
• HLA-DQ2 gt90 of people with coeliac disease.
• HLA-DQ2 or HLA-DQ8 necessary, but not sufficient,
  to develop the disease.
• Identical twins 70 concordance

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Epidemiological studies

• 1/100 people
• Any age
• Mortality excess - 1938
• Reduction in excess mortality after 15 years on
  gluten free diet

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Celiac Disease The Old Picture
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Celiac disease The Usual Picture
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What we see is the tip of the iceberg
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Celiac Disease
Most cases undiagnosed
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Celiac Disease - Clinical Classification

• Symptomatic, active, or classic celiac disease
• diarrhoea, with or without malabsorption
• Asymptomatic
• Gastrointestinal symptoms are absent or not
  prominent
• Latent celiac disease
• May develop celiac disease in the future
• At time of investigation has normal mucosa while
  ingesting gluten

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Celiac Spectrum of Disease
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Celiac Disease Toxic Proteins

• Gliadin - most studied
• All gluten containing proteins
• Barley - hordeins
• Rye - secalins
• Dose-dependent response

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Celiac Disease - Clinical

• Symptomatic
• weight loss, metabolic bone disease, anaemia, and
  general weakness
• Trigger
• Pregnancy
• Traveler's diarrhea
• Gastroenteritis
• Gastrointestinal surgery

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Celiac Disease Atypical Presentations

• Osteoporosis
• Infertility
• Autoimmune diseases
• Malignant disease, especially lymphomas

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Celiac Disease Atypical Presentations

• Aphthous stomatitis
• Arthritis
• Dental enamel defects
• Abnormal liver transminases

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Celiac Disease Atypical Presentations

• Villous atrophy in patients undergoing endoscopy
• Assessment of iron concentrations and bone
  density
• Dermatitis herpetiformis
• Neurological symptoms
• peripheral neuropathy
• ataxia
• epilepsy

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Celiac Disease - Screening

• First-degree relatives
• Type 1 diabetes
• Down's syndrome
• Chronic liver disease
• primary biliary cirrhosis

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Celiac Disease - Diagnosis

• Small intestinal biopsy gold standard
• Improvements in clinical symptoms or histological
  tests on a gluten-free diet
• Positive serological tests

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Celiac Disease - Endoscopy
Normal
Celiac Disease
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Celiac Disease - Biopsies

• Loss of crypts
• Increased mitotic activity
• Loss of brush border
• Infiltration with lymphocytes and plasma cells
  (B-cells sensitized to gliaden)
• Lesion more severe in proximal small intestine
  than distal

Normal
Celiac Disease
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Celiac Disease - Serological Testing

• Anti-gliadin antibodies
• Anti-endomysium almost 100
• Anti- tissue transglutaminase (Anti-tTG)

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Celiac Disease Pitfalls in Diagnosis

• Serological tests
• Selective IgA deficiency 1726
• 10 to 16-fold higher - general population
• Check total serum IgA
• Test for IgG endomysial antibodies, IgG anti-tTG

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Celiac Disease Serological Testing

• Titres of anti-endomysial antibodies correlate
  with
• Degree of villous atrophy
• Presentation with symptoms
• Patients with partial villous atrophy
• May not have antibodies against endomysium or tTG
• Usually have antibodies against gliadin
• Anti endomysium only miss 20
• Up to 33 - one antibody absent
• Titres of endomysial antibodies are usually
  undetectable after 612 months on diet

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Celic Disease Role of Serological Testing

• Screening patients or populations at risk
• Confirming diagnosis when biopsy questionable
• Follow-up for compliance
• Diagnosis? biopsy still required

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Celiac Disease - Treatment

• Dietician - gluten-free diet for life
• Avoid trial of gluten restriction without a
  biopsy
• Avoid wheat, barley, and rye
• Oats are not toxic
• Support groups
• Correct deficiencies
• Active follow-up - compliance

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Celiac Disease - Response

• Rapid most patients
• Extremely ill admission
• repletion of fluids and electrolytes,
• intravenous alimentation
• steroids.
• Iron or folate supplements if deficiency
  documented

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Celiac Disease
Before treatment
3 months treatment
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Poorly or Non-responsive Celiac Disease

• Review original biopsy,
• Continued gluten ingestion
• Lactose or fructose intolerance
• Intolerance to other foods is rare

• Microscopic colitis
• Collagenous colitis
• Inflammatory bowel disease
• Lymphoma,
• Ulcerative jejunitis,
• Collagenous sprue

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Refractory Sprue.

• Intractable diarrhoea
• Severe villous atrophy
• Failure to respond to a gluten-free diet.
• Response to steroids, azathioprine or cyclosporin

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Celiac Disease Special Considerations

• Malignant disease increased
• Small bowel adenocarcinoma,
• Esophageal and oropharyngeal squamous carcinoma
• non-Hodgkin lymphoma
• A gluten-free diet is protective

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Celiac Disease - Autoimmune Disorders

• Autoimmune disorders RR x10arise
• Insulin dependent diabetes
• Thyroid disease
• Sjögren's syndrome
• Addison's disease
• Autoimmune liver disease
• Cardiomyopathy
• Neurological disorders.
• Can improve on diet

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Celiac Disease Other Complications

• Osteoporosis
• Measurement of bone mineral density
• Fertility
• Delayed menarche,
• Premature menopause,
• Amenorrhoea,
• Recurrent abortions
• Postnatal
• Low birthweight
• Increased perinatal mortality
• shorter duration of breast feeding
• Gluten-free diet improves

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Digestion and Absorption

• GENERAL PRINCIPLES
• Breakdown of complex molecules
• Enzymes (pH)
• Absorption into gut cells
• Intestinal epithelium
• Lymphatics

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SECRETIONS OF THE GUT
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Bulk flow of liquid in gut

• Input
• Ingestion 2 litres per day
• Secretion (gut) 7 litres/day
• Output
• Faeces 100 ml/day
• Conclude 9 litres/day absorbed

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Carbohydrate Digestion
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Carbohydrate Absorption
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Protein Digestion

• Proteins to peptides
• Gastric pepsinogen
• Activated by HCl AND pepsin
• Pancreatic proteases (trypsin, chymotrypsin etc.)

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Protein Absorption

• Peptides to amino acids (brush border)
• Absorbed by secondary active transport
• Depends on Na transport

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Fat Digestion

• Fat to triglycerides (pancreatic lipase)
• Bile salts emulsify (surface area)
• Bile salts micelles containing monoglycerides
  and free fatty acids (FFA)
• Enter passively
• Triglyceride synthesis chylomicrons
• Exocytosis and thence to lacteals

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Fat Absorption

• Monoglycerides and FFA enter cells by diffusion
• Triglyceride synthesis
• Add protein
• Chylomicrons
• To lacteal (lymph)