Diseases of the small intestine

Diseases of the small intestine

Objectives
1. Introduction to the intestine.
2. Classification of malabsorption syndrome:
3. How could a young patient present to you?
4. Investigations in malabsorption syndrome.

Malabsorption:-

Functions of the GIT is to digest and absorb nutrient and eliminate every thing else.

These nutrients include CHO, proteins, and fat, Vits and micronutrients, ex:
GIT may digest, solubilize, transport and resynthesize up to 80gm of fat per day.
Terminal ileum needs 1 microgram of Vit B12 \day.

Digestion begins with:

Fragmentation by the stomach.
Secretion of pancreatic juices, bile and water into the lumen of the intestine to allow digestion.
Terminal digestion of peptides and disaccharides by the brush border enzymes of the small intestine.
Absorption through enterocytes that lies on the brush border to form a surface area which widened by valvulae conniventes, intestinal villi and microvilli.
The food stays 1.5-2 hours in the intestine.









Some nutrients absorbed through out the intestine, while others absorbed in a specific area as ileum (terminal ileum) for vit.B12 and bile acid absorption.
Disorder at any of these sites may lead to maldigestion and malabsorption syndrome.

Classification of malabsorption syndrome:

inadequate digestion:

Pancreatic dis, ch. Pancreatitis, cystic fibrosis, &CA pancreas +gastrinoma.

Intraluminal bile salt deficiency.
Liver disease (biliary cirrhosis)
Disease of terminal ileum
Bacterial overgrowth

Specific causes as disaccharidase deficiency.

inadequate absorption

a. inadequate absorptive surface as

short bowel disease
bypass fistula
extensive Crohns disease
mucosal cell defect
genetic , abetalipoproteinemia ,cystinuria , monosaccharide absorptive defect
Acquired hypovitaminosis.

diffuse disease of small intestine
Immunological disease as celiac disease, eosinophilic enteritis & Crohns disease.
Infection: Whipples, giardiasis, tropical sprue, bacterial overgrowth.
Infiltrative disease as lymphoma, amyloidosis, mastocytosis.
Fibrosis and systemic sclerosis.


lymphatic obstruction :
Lymphangiectasia, Whipples and lymphoma
Drug induced:
Neomycin antacid, ethanol & laxative.
Multiple mechanisms:
DM, postgastrectomy, bacterial overgrowth, lymphoma, Whipples disease.
Hyper absorptive disease:
Hemochromatosis, hypervitaminosis D &hyperoxaluria.

Clinical picture of Malabsorption:

diarrhea , steatorrhea:
Bulky, light coloured stool, floating on water offensive odour, splitted, loose due to fat malabsorption with increase fecal water.
Picture of failure to thrive, growth retardation or short stature, the former occur during wearing the baby &put the pt on oral cereals, pubertal delay and absence of menses.
Weight loss, malnutrition (muscle wasting), weakness, fatigue, due to decrease caloric intake and electrolyte disturbances
abdominal distention and edema: due to bloating ,ascites ,decrease serum albumin and increase intestinal fluid
anemia :
- Iron deficiency anemia
Vit B12 deficiency anemia
Folate deficiency anemia
Anemia of chronic illness.


Paresthesia, tetany (+ve) Trousseau &chvostik signs) due to decrease Ca, Mg, K and Vit D.

Bone pain: pathological fracture and skeletal deformity due to osteoporosis on x- ray and osteomalacia on bone biopsy.
Bleeding tendency: ecchymosis melena and haematuria with prolonged PT, vitamin K deficiency.
Nocturia: reabsorption of intestinal fluid at night.
Milk intolerance. Pt has cramps, bloating and diarrhea after milk ingestion.
Clubbing of finger, pallor, fair skin, and fair hair.

Investigation:

fecal fat analysis:

Identification of fat in stool is a must (steatorrhea) by Sudan III stained stool smear .calculate the total fat in 3 days stool specimen while the pt on diet containing 80 100 gm of fat \day normal fat secretion should be less than 6 gm \day and is usually less than 2.5 gm \day. Value of more than 6 mg \day indicates steatorrhea.

tests of pancreatic excretion function:

bentiromide test:
orally administered synthetic peptide, split of this substances by pancreatic chemotropism, excretion in 6 hours of less than 50 % of a (500 mg of bentiromide )in the urine as (aryl amines) is diagnostic of pancreatic insufficiency
Abdominal x ray (calcified pancreas) and CT scan may be used also.

3. Xylose absorption excretion test:

Check the capacity of the mucosa to absorb xylose sugar .D-xylose is characterized by
Poorly metabolized 5-carbon sugar.
Absorbed well in the intestine.
Not degraded or concentrated in any tissue.
Largely excreted in the urine
The pt will ingest (25 gm) of d-xylose, then collect the urine for 5 days. Normal subject excretes more than 4.5 gm of D xylose in 5 hours, which may also decrease normally in aged, poor renal function, presence of oedema, ascites& bacterial over growth.
radiological studies:
They are non specific in Ba follow though:
thickening of the mucosal folds
Modest dilatation of intestinal lumen.
Clumping and segmentation of the Ba in a moulage pattern (thumb printing ).
Flocculation
Comb tooth appearance.
Incomplete lines in both sides of the lumen

small intestinal biopsy;

This is very important to identify the cause of malabsorption syndrome. Usually jujenal biopsy, although duodenal biopsy may be of benefit also.

Schilling test:

Vit.B12 malabsorption:
It is first conjugated with R-factor proteins, which are formed, by the saliva and stomach. this combination of R protein and cobalamine complex is formed in acid milieu of the stomach , are subsequently degraded in the duodenum by the effect of pancreatic enzyme trypsin and protease after release of R protein , Vit B12 will bind intrinsic factor released from the stomach which then travel and contact specific receptor in terminal ileum.

Disease may lie in the:-

pancreatic enzyme
Secretion of intrinsic factor. Or
Ileal absorption ofVit.B12.

Cobalamine absorption may be abnormal in the following:

pernicious anemia
chronic pancreatitis
achlorhydria
bacterial over growth syndrome
ileal dysfunction


this test is performed by administering radiolabled cobalamine Co58 orally and collecting urine for 24 hours. Before that we need to ensure to restore the hepatic storage of B12 by giving 1 mg of B12 injection intramuscularly.

DiseaseCo58-CoWith intrinsic factorWith pancreatic enzymesAfter 5 day of antibioticPernicious anemiaReducedNormalReducedReducedChronic pancreatitisReducedReducedNormalReducedBacterial over growthReducedReducedReducedNormalIleal diseaseReducedReducedReducedreduced
Antibiotic used is tetracycline capsule.

breath test:

the intra luminal space contain bacteria which are capable of degrading H and produce (CO2)14 that can be measured by breathing.
The 14(CO2)-xylose test measures 14 (CO2) produced in the breath at 30-60 min after ingestion of radioactive sugar, it is elevated in the presence of bacterial over growth in small intestine.

Breath H2 tends to increase early after ingestion.

Other specific sugars can also be detected as sucrose & lactose.
The most common causes of malabsorption:
coeliac dis
tropical sprue
giardiasis
primary intestinal lymphoma
other rare causes:
dermatitis herpetiformis
whipple disease
ileal resection
short bowel syndrome
abetalipoproteinaemia
radiation enteritis& proctocolitis


Coeliac disease:

It is an immunologically mediated inflammatory disorder of the small intestine occurring in genetically susceptible individuals and resulting from intolerance to wheat gluten and similar proteins found in rye, barley &oat, it can result in malabsorption and response to gluten free diet; it is commonly found in UK 1:200 although 50 % of those people are asymptomatic (silent) disease
Or latent coeliac dis which may develop later to clinical coeliac dis.

Pathogenesis:

Gluten peptides taken by epithelial cells.
Deamidation of gluten by tissue transglutaminase enzyme to give product, which can fit the antigen binding motif on HLA-DQ2 +ve antigen presenting cell.
the combination will be presented to the CD4+cells
Triggering of Th1 response to generate proinflammatory cytokines (IL-1, IFN-gamma, and TNF-alpha).
Infiltration of lamina properia by lymphocytes and increased intraepithelial lymphocytes.
Crypt hyperplasia.
Villous atrophy.

Clinical feature:

Coeliac dis. present at any age:

In infancy:

It starts after weaning on to cereals and typically present with diarrhea ,mal absorption and failure to thrive.


Older children:
Non specific features as
- delayed growth
features of malnutrition
mild abdominal distention
pubertal delay
short stature in adult hood

in adult hood:

peak onset fifth decay
female more than male
There may be non specific symptoms as tiredness, wt loss, folate deficiency or iron deficiency anemia.
Oral ulceration ,dyspepsia ,and bloating
Bleeding tendency (Vit. K Deficiency), night blindness (Vit A deficiency).

It may presented with other HLA-linked autoimmune dis as IDDM, thyroid dis , primary biliary cirrhosis ,pernicious anemia ,inflammatory bowel dis ,myasthenia gravis, T- cell lymphoma ,small bowel carcinoma ,squamous carcinoma of esophagus ,splenic atrophy.
etc.

Clinical manifestations and mechanisms:

Symptoms and signs: mechanisms


Nonspecific, malaise, anorexia-------------------iron, folate or Ca deficiency anemia
Diarrhea and steatorrhea---------------------------water, electrolytes fat malabsorption.
Wt loss------------------------------------------------fat&CHO mal absorption
Abdominal pain and bloating---------------------distended bowel loop.
Aphthus ulcers--------------------------------------gluten sensitivity and or Vit deficiency.
Nausea &vomiting
Itching spots on extensor surface (dermatitis herpetiformis).
Positive family history.
Oedema---------------------------------------------hypoproteinemia.
Pigmentation, tetany, bone pain and muscle weakness.Vit D& Ca deficiency
Bleeding tendency--------------------------------Vit K deficiency.
Night blindness------------------------------------Vit A deficiency
Anemia---------------------------------------------iron &folate deficiency (rarely Vit B)
Myopathy-------------------------------------------osteomalacia
(Proximal Myopathy)

Investigations:

duodenal (or jujenal biopsy):
The histopathology range from normal mucosa, only intraepithelial infiltration of lymphocytes to the usual characteristic total or subtotal villous atrophy.


Differential diagnosis of subtotal villous atrophy;
Coeliac dis 4. Giardiasis 7. radiation
Tropical sprue 5. Dermatitis herpetiformis 8. whipples
Lymphoma 6. AIDS enteropathy 9.Z-E syndrome

antibodies :

serum antigliadin antibodies IgA
anti endomysial antibodies IgA

They are:

not quantitative
sensitivity in 85 -95%
specificity 99%
not sensitive not specific in infants .

Antigliadin antibodies IgA & IgG presents in 90% but IgG is more sensitive &IgA is more specific.
Antiendomysial antibodies IgG used only for study purposes
TTG (tissue transglutaminase) assay.
Easier performed
semi quantitative
more accurate in IgA deficiency
All antibody detection test doesnt substitute for duodenal biopsy.
They are of benefit for follow up therapy, they are ve after good therapy.


blood test and biochemistry:
blood film for iron deficiency anemia or folate deficiency anemia.
Picture of hyposplenism
Decrease level of Ca ,Mg ,total protein ,Vit D
Barium follows through.
Dual energy x-ray absorptiometry (DEXA-scanning) to look for evidence of metabolic bone disease.

Management:

to correct all the deficit nutrients
life long gluten free diet (wheat ,rye ,barley and oats)
Regular monitory of symptoms, wt and nutrients is essentials.
Rarely, patients are refractory and require treatment with corticosteroids, or immunosuppressive drugs to induce remission.

Failure to response to therapy:

dietary compliance
other dis accompanying coeliac dis as pancreatic insufficiency , microscopic colitis
Complicated coeliac dis as ulcerative jujenitis or enteropathic associated T cell lymphoma .antiendomysial antibodies may becomes ve after 6 months post gluten free diet.

Dermatitis herpetiformis:picture of malabsorption(partial villous atrophy )skin rash intensely itching blisters over the extensor surfaces of elbow ,knee and buttocks.

Treatments:

gluten free diet
Dapsone 100-150 mg \day.