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Malabsorption

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Malabsorption Case 32 year old man previously well: 3 months loose, soft foul-smelling bowel movement 6 kg weight loss Tired, weak Abdominal distension Bleeding ... – PowerPoint PPT presentation

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Title: 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

5
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

6
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

7
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

8
Symptoms
  • Abdominal distension
  • Flatulence and abdominal distention
  • Bacterial fermentation of unabsorbed food
    hydrogen and methane
  • Causes abdominal distention and cramps

9
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

11
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.

12
Symptoms
  • Weakness
  • Neurological manifestations
  • Vitamin malabsorption
  • Generalized motor weakness
  • Peripheral neuropathy

13
Digestion and Absorption
  • Carbohydrate (CHO)
  • Protein
  • Fat
  • Vitamins and minerals
  • Water and electrolytes

14
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

15
Malabsorption
  • Luminal Phase

16
Luminal PhasePancreas
  • Exocrine
  • Enzymes (acini)
  • Bicarbonate (ducts)

17
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

18
Malabsorption - Pancreas
  • Methods to assess dysfunction
  • Anatomic - damage
  • Physiology - assessement of function

19
Anatomical Chronic PancreatitisCalcified
Pancreas
20
Anatomical ERCP Chronic Pancreatitis and
Carcinoma
Carcinoma
21
Anatomical Chronic Pancreatitis - EUS
22
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

23
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

24
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

25
Malabsorption - Bacterial OvergrowthSmall Bowel
Series
Diverticulosis
Scleroderma
26
Malabsorption Bacterial OvergrowthBreath Tests
  • Hydrogen breath test
  • Glucose
  • Bile acid breath test
  • C13-glycocholate breath test
  • Xylose breath test
  • C13-xylose

27
Malabsorption - Bacterial OvergrowthCulture
  • Quantitative culture of an aspirate of luminal
    fluid
  • The gold standard
  • Positive culture gt 106 organisms/mL
  • Aerobic or anaerobic culture

28
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
29
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

31
Malabsorption
  • Mucosal phase

32
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.

33
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.

34
Malabsorption
  • Postabsorptive Phase

35
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

36
Investigation of Malabsorption
Jungle
Confusion
37
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

38
Suspected malabsorption
39
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

40
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

41
Malabsorption - Investigation
  • Xylose Normal
  • Suspect pancreatic disease

42
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.

43
Malabsorption - Bacterial Overgrowth
  • Trial of treatment
  • Antibiotics

44
Malabsorption Mucosal/Postmucosal Disease
45
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

46
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.

47
Jejunal biopsy-Whipple's disease
48
Eosinophilic Gastroenteritis
49
LymphangiectasiaDilated Submucosal Lacteals
50
Celiac disease
51
Celiac Disease
  • Genetically-determined
  • Chronic inflammatory intestinal disease
  • Environmental precipitant- gluten.
  • Mainly non-gastrointestinal symptoms
  • Patients present to various medical practitioners

52
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

53
Epidemiological studies
  • 1/100 people
  • Any age
  • Mortality excess - 1938
  • Reduction in excess mortality after 15 years on
    gluten free diet

54
Celiac Disease The Old Picture
55
Celiac disease The Usual Picture
56
What we see is the tip of the iceberg
57
Celiac Disease
Most cases undiagnosed
58
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

59
Celiac Spectrum of Disease
60
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61
Celiac Disease Toxic Proteins
  • Gliadin - most studied
  • All gluten containing proteins
  • Barley - hordeins
  • Rye - secalins
  • Dose-dependent response

62
Celiac Disease - Clinical
  • Symptomatic
  • weight loss, metabolic bone disease, anaemia, and
    general weakness
  • Trigger
  • Pregnancy
  • Traveler's diarrhea
  • Gastroenteritis
  • Gastrointestinal surgery

63
Celiac Disease Atypical Presentations
  • Osteoporosis
  • Infertility
  • Autoimmune diseases
  • Malignant disease, especially lymphomas

64
Celiac Disease Atypical Presentations
  • Aphthous stomatitis
  • Arthritis
  • Dental enamel defects
  • Abnormal liver transminases

65
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

66
Celiac Disease - Screening
  • First-degree relatives
  • Type 1 diabetes
  • Down's syndrome
  • Chronic liver disease
  • primary biliary cirrhosis

67
Celiac Disease - Diagnosis
  • Small intestinal biopsy gold standard
  • Improvements in clinical symptoms or histological
    tests on a gluten-free diet
  • Positive serological tests

68
Celiac Disease - Endoscopy
Normal
Celiac Disease
69
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
70
Celiac Disease - Serological Testing
  • Anti-gliadin antibodies
  • Anti-endomysium almost 100
  • Anti- tissue transglutaminase (Anti-tTG)

71
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

72
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

73
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

74
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

75
Celiac Disease - Response
  • Rapid most patients
  • Extremely ill admission
  • repletion of fluids and electrolytes,
  • intravenous alimentation
  • steroids.
  • Iron or folate supplements if deficiency
    documented

76
Celiac Disease
Before treatment
3 months treatment
77
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

78
Refractory Sprue.
  • Intractable diarrhoea
  • Severe villous atrophy
  • Failure to respond to a gluten-free diet.
  • Response to steroids, azathioprine or cyclosporin

79
Celiac Disease Special Considerations
  • Malignant disease increased
  • Small bowel adenocarcinoma,
  • Esophageal and oropharyngeal squamous carcinoma
  • non-Hodgkin lymphoma
  • A gluten-free diet is protective

80
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

81
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

82
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83
Digestion and Absorption
  • GENERAL PRINCIPLES
  • Breakdown of complex molecules
  • Enzymes (pH)
  • Absorption into gut cells
  • Intestinal epithelium
  • Lymphatics

84
SECRETIONS OF THE GUT
85
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

86
Carbohydrate Digestion
87
Carbohydrate Absorption
88
Protein Digestion
  • Proteins to peptides
  • Gastric pepsinogen
  • Activated by HCl AND pepsin
  • Pancreatic proteases (trypsin, chymotrypsin etc.)

89
Protein Absorption
  • Peptides to amino acids (brush border)
  • Absorbed by secondary active transport
  • Depends on Na transport

90
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

91
Fat Absorption
  • Monoglycerides and FFA enter cells by diffusion
  • Triglyceride synthesis
  • Add protein
  • Chylomicrons
  • To lacteal (lymph)
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