• Easily ingested, painless procedure
• Progresses naturally through the GI tract via peristalsis
• Ambulatory examination
• Disposable video capsule

Discuss the components of a capsule endoscope?
It contains an imaging device and light-source on one-side and transmits images at a rate of 2 images per second generating more than 50,000 pictures over an 8-hour period.

1. Optical dome
2. Lens holder
3. Lens
4. Illuminating LEDs
5. Imager
6. Battery
7. RF Transmitter
8. Antenna
9. Dimensions 27X11 mm and weighs 3.7gm

How is capsule endoscopy performed?

• A patient fasts starting at midnight the day before the procedure. Some physicians use bowel prep as for colonoscopy.
• A sensor array is attached to the patient’s abdomen and the data recorder to a belt around the patient’s waist. The capsule transmits data to the Sensor Array which is secured to the patient’s abdomen. The Sensor Array is connected to the Data Recorder (which stores the data), worn on the belt.
  
• The patient is then asked to swallow the capsule.  The patient can resume daily activities once he or she has successfully swallowed the video capsule.
• After 8-hours the patient returns to the physician’s office to return the data recorder and the pill passes naturally with a bowel movement usually within 24 hours.
• Images are downloaded from the data recorder to the workstation for review and diagnosis.
• Patients are allowed to drink clear liquids after two hours and eat a light meal after four hours following the capsule ingestion
• It takes 30 to 60 minute reading time per study

Discuss the effectiveness of WCE over other methods of investigating small bowel?
Summary of Incremental Yield (IY) of WCE over other modalities for suspected or diagnosed Crohn’s disease.

Ref: Triester SL, et al Am J Gastroenterol 2006
Discuss the indications of WCE?

• Obscure GI bleed:  WCE considerably shortens the time to diagnosis and lead to definitive treatment in a relevant proportion of patients. WCE also spare a number of alternative investigations with low diagnostic yield
• Suspected Crohn’s disease
• Assessment of coeliac disease
• Screening and surveillance for polyps in familial polyposis syndromes

Discuss capsule retention?
Capsule retention is defined as having a capsule remain in the digestive tract for more than two weeks.
Retention has been reported at ~ 0.75% overall or up to 13% in patients with known strictures (ref- Signorelli C, et al. Digestive and Liver Disease 2006 )
The published incidence of capsule retention varies with the risk being related to the indication: (Ref- Lewis B, Endoscopy 2005)

• OGIB ~ 1.5%
• Known Crohn’s disease (CD) ~ 5%
• Suspected CD ~ 1.4%
• In healthy volunteers, during clinical trial, no incident of capsule retention occurred in 773 individuals

What are the causes of capsule retention?
Causes of retention cited in the literature include:

• NSAID strictures
• Crohn’s disease
• Small bowel tumors
• Radiation enteritis
• Surgical anastomotic strictures

Capsule retention has not been reported in “normal” anatomy or anatomical variants (e.g., colon or small bowel diverticulosis and appendiceal orifices).
How do you treat capsule retention?
Capsule retention is managed by medical (steroid may improve strictures), surgical, or endoscopic intervention (using a balloon enteroscope)
Can capsule retention be prevented?

• Current methods for identifying intestinal strictures lack sensitivity and specificity to evaluate GI tract patency.
• The majority of capsule retentions have occurred in patients with normal small bowel radiological studies. Conversely, results have suggested that functional patency may be present in patients with radiologically-documented strictures.

However, capsule retention can be prevented by using a patency capsule
Discuss patency capsule?
The patency capsule is a simple and convenient accessory to video capsules that is intended to verify functional patency of the GI tract in patients with known or suspected strictures prior to administration of the video capsule.
A patency capsule stays intact for minimum 30 hours post-ingestion. It subsequently disintegrates and is excreted. It emits electromagnetic waves at 64 KHz when sensing electromagnetic waves at 128 KHz.
Procedure:
Day 1: Patient swallows the patency capsule
Day 2: The patient’s abdomen is scanned using a hand held patency scanner. Patency is proven if the capsule is not detected by the patency scanner.

What are the contraindications of WCE?

• Patients with known or suspected GI obstruction, strictures or fistulas based on clinical presentation or pre-procedure testing
• Patients with cardiac pacemakers or other implanted electro-medical devices
• Patients with swallowing disorders

(Ref- Gastrointestinal Endoscopy 2006 )

Double balloon enteroscopy (DBE) is a new diagnostic and therapeutic modality originally described by Yamamoto et al in 2001 that allows high resolution visualisation, diagnostic and therapeutic interventions in all segments of the small intestine. It came almost the same time as Video capsule endoscopy and at one point was thought to be each other competitors. However with more widespread use of VCE it is expected that roughly 10% of those patients will need enteroscopy for further evaluation or imparting therapy.

The double balloon enteroscope comprises a 145 cm overtube back loaded on a 200 cm enteroscope and a latex balloon attached to each end.

(courtesy-http://www.fujinonendoscopy.com)

Technical details

• Once the system is passed into the proximal small bowel, the balloon of the overtube is inflated to anchor the position, so that the endoscope can be advanced. When the endoscope is advanced to its most distal point, the endoscope balloon is inflated to hold the insertion point. The overtube can be advanced after deflating the overtube balloon.  This serial inflation and deflation of balloons allow pleating of bowel on the back of the overtube and forward advancement of the enteroscope into a new segment of bowel. This process is repeated until advancing the endoscope any further becomes difficult.
• DBE can be used both from the mouth (anterograde approach) and anus (retrograde approach). The insertion route can be chosen according to the estimated location of the suspected lesions. Stable advancement of the enteroscope into the ileum from the anal approach is particularly challenging and failures occur in about 20% of patients
• The procedure can generally be performed under conscious sedation ( with midazolam/fentanyl) but general anaesthesia is preferrable.The entire small bowel can be visualized in 80 to 90 percent of cases (but requires significant experience of over 150 cases), with lesser degrees of visualization in patients who are obese and in operators with less experience with DBE (1).
• Screening is helpful in initial stages of learning and nice concentric circle with three turns normally ensures the tip is in sight of the target.
• Panenteroscopy is generally achieved by a combination of both the antegrade (oral) and retrograde (rectal) approach. In rare situations, panenteroscopy can be achieved via a single (oral or rectal) approach. Panenteroscopy is demonstrated by India ink injection at the most distal site during antegrade (or retrograde) DBE and by successful advancement of the enteroscope to the tattooed area during the opposite approach.
• The mean duration of the procedure varies from 90-120 minutes depending on the operator experience.

Indications
The main indications are

• Investigation of gastrointestinal bleeding and inflammatory bowel disease.
• Evaluation of abnormal capsule endoscopy or abnormal radiographic studies

Other indications for DBE include an evaluation of suspected small-bowel diarrhoea, abdominal pain, the removal of small-bowel polyps, treatment for angiodysplasias (APC) or small intestinal bleeding ( Endoclip) ,the retrieval of tissue samples/ stuck capsule  and accessing ampulla for ERCP in Roux-en-Y anastomoses, post bariatric surgery, small intestinal stricture dilatation/ stenting, tattooing to assist laparoscopic small bowel resection. Difficult colonoscopy is another indication when rectal approach is used.

One important point is if APC is used to treat any telangiectasia in small bowel – Argon flow is to be reduced to 1.5 litres/minute (normally 2 litres/minute) and energy reduced to A30 (normally A65 for Stomach/duodenum). Also avoid physical contact of the small bowel wall with the tip of APC catheter as suddenly the wall can be blown up with the gas. Also to inflate CO2 should be preferentially used.

Limitations
The limitations of DBE include the long procedural time and the patient discomfort and increased need for sedation.

Complications
Diagnostic DBE has an overall complication rate of 1.7% (perforation 0.3%, bleeding 0.8%, pancreatitis 0.3%). The cause of pancreatitis is uncertain.  Therapeutic DBE has a relatively high complication rate of 4.3% (polypectomy bleeding 3.3%, argon plasma coagulation perforation 1.2%, dilation perforation 2.9%) (2).

Single balloon enteroscopy

Single balloon enteroscopy (SBE) is similar to DBE except that SBE utilizes a single balloon on the overtube and a hyper flexible endoscope tip. Rather than the balloon at the tip of the endoscope fixing the endoscope when overtube is advanced- the intestine is fixed by hooking the flexible distal tip (J manoeuvre).

1. Insert the scope as deep as possible into the small bowel and fix the angulation of the scope.



2. Advance the overtube.



3. Inflate the balloon.



4. Withdraw the overtube and if possible, try to push the endoscope simultaneously.

(courtesy-http://www.olympus.com)

This decreases set-up time and also no assistant is needed. The single balloon enteroscope is also stiffer that may facilitate one-to-one advancement in the small bowel and improve success rates for ileal intubation from the anal approach. In the initial clinical experience using SBE, average depth of insertion (270 cm) and diagnostic yield (54%) were similar to those with DBE (3).Procedure time was somewhat shorter. There are no comparison studies between DBE and SBE with regard to complete enteroscopy rates.

Previously Enteroscopy was done either by Push Enteroscopy or Sonde enteroscopy
Push Enteroscopy
Push enteroscopy is an endoscopic procedure whereby a longer endoscope is inserted into the jejunum through the mouth to evaluate a larger segment of the small bowel. The diagnostic yield of push enteroscopy is approximately 40% to 65%.
Push enteroscopy is normally done with a paediatric colonoscope +/- overtube. The main disadvantage is the fact that small bowel is too long and being supported on a mobile mesentery, the endoscope tends to accentuate the natural curvature and makes complete examination almost impossible.

Sonde enteroscopy
Sonde enteroscopy involves the use of a long, flexible, fiberoptic instrument propelled through the small bowel by peristalsis; this procedure may allow for viewing the remainder of the small bowel. Sonde instruments rely on a balloon placed at the instrument’s tip. Peristalsis then advances the long flexible endoscope to the distal small bowel, and the endoscopic examination is performed during withdrawal. In contrast to push enteroscopy, this instrument has no biopsy or therapeutic capability.

References

1. Gross SA, Stark ME. Initial experience with double-balloon enteroscopy at a U.S. center. Gastrointest Endosc 2008; 67:890-897.
2. Mensink PB, Haringsma J, Kucharzik T, et al. Complications of double balloon enteroscopy: a multicenter survey. Endoscopy 2007; 39:613-615.
3. Tsujikawa T, Saitoh Y, Andoh A, et al. Novel single-balloon enteroscopy for diagnosis and treatment of the small intestine: preliminary experiences. Endoscopy 2008; 40:11-15.

It is a chronic systemic infection by a gram positive bacterium, Tropheryma whippelli. The small intestine is most often affected, but other organs like joints, CVS and CNS may be involved too.

Discuss the epidemiology of WD?

Predominantly affects middle aged white males

Discuss the pathogenesis of WD?

Bacteria are most likely acquired by oral route. Bacteria are located in the intestinal mucosa. From here, the bacteria spread via lymphatics to mesenteric and mediastinal lymph nodes, the thoracic duct and the blood.

Discuss the clinical manifestations of WD?

• Intestines

Obstruction of mesenteric nodes leads to malabsorption with wt loss, diarrhoea and abdominal pain. Diarrhoea may be steatorrhea or watery. Occult GI bleed is common and in some cases gross GI bleeding occurs.
Abdominal and peripheral lymphadenopathy is common.

• CNS

Progressive dementia and cognitive changes, supranuclear ophthalmoplegia, altered level of consciousness and psychiatric symptoms

• CVS

Endocarditis, myocarditis and pericarditis

• Musculoskeletal

Oligo or polyarthralgias

Discuss the diagnosis of WD?

• Endoscopy- Whitish or yellow plagues are observed. Obtain 5 biopsies as distally as possible. A normal intestinal histology rules out the diagnosis
• Histology- Villi is distended by macrophage infiltrate that contain PAS positive particles and lipid droplets

Discuss the treatment of WD?
Antibiotics
Induction phase (10-14 days) – Ceftriaxone (2gm IV OD)
Maintenance phase (for at least 1 year) with an antibiotic that crosses the blood brain barrier- Trimethoprim-sulphamethoxazole

• The well-accepted definition of clinically important wt loss is 5% over a period of 6-12m.
• Up to 8% of all adult outpatients and 27% of people >65 years. Normal aging is ass with only very small decrements in wt (0.1-0.2 kg/year).
• It is associated with increased mortality, which can range from 9% to as high as 38% within 1 to 2.5 years after weight loss has occurred.

What are the possible causes of unexplained weight loss?

• Neoplasm- Cancer of the lung, colon, pancreas, breast, and prostate were the most common malignancies.
• Benign GI disease- peptic ulcer disease, motility disorders, cholelithiasis, IBD
• Psychiatric disorders
• Endocrine causes- Thyroid, diabetes mellitus, adrenal insufficiency (all pts have anorexia, nausea & wt loss)
• No cause (in upto 25%)

Chronic use of alcohol, nicotine, lead, opiates & CNS stimulants can cause decreased appetite and wt loss. Depression and malignancy are the commonest causes of isolated weight loss.

How do you approach pts with unexplained weight loss?

• It is imp to establish up front the presence of wt loss as up to half of people who claim to have lost weight have no documented evidence of wt loss.
• Careful history to elicit;
  • Appetite- key question
  • Think in terms of the fractional change in wt.
  • For how long has the patient been losing weight?
  • To what extent has the patient’s weight changed during adult life?
  • Localising symptoms
  • All elderly patients should be screened for dementia (MMSE) & depression.
  • Young pts consider eating disorder

What is the practical approach to investigations in the absence of diagnostic clues?

• FBC, LFT, U&E, Ca, TSH, ESR, iron profile, glucose, coeliac antibody, HIV tests (in pts at risk)
• There are no guidelines for how to proceed in the assessment of a patient with weight loss and negative initial findings. The diagnostic yield of a whole body CT examination to assess for occult or metastatic malignant disease has not been determined. We use whole body CT if the initial findings are negative.
• OGD is indicated for patients with early satiety. Colonoscopy is not indicated in the evaluation of weight loss, as colon cancer does not induce weight loss unless there is obstruction or extensive metastases.

How do you manage patients with unexplained weight loss?

• Treat any underlying illness
• Nutritional supplements lead to improvements in biochemical, anthropometric and QoL parameters in a number of trials. A systematic review showed a reduction in mortality among elderly patients who received protein-energy supplements, irrespective of whether they had weight loss.

Tropical sprue is a syndrome of intestinal malabsorption of two or more substances (Vit B12 and folic acid def is very common) which occurs among residents in or visitors to certain regions of the tropics. It often follows an acute diarrhoeal illness.
It is generally considered to be a disease primarily of the proximal small intestine.

Discuss the aetiology of TS?

The cause has not been clearly defined. While no single identifiable pathogen has been isolated, it is believed that persistent overgrowth in the small intestine of coliform bacteria leads to small bowel structural damage and chronic diarrhea.

Discuss the clinical features of TS?

• It should be suspected in patients with chronic diarrhea who have lived for more than one month in an area where tropical sprue exists. The diarrhea can first develop after a patient returns from the tropics.
• It is syndrome of chronic diarrhoea often with clinical features of steatorrhea, anorexia, abdominal cramps, bloating and prominent bowel sounds. Lactose intolerance is common.

Discuss the diagnosis of TS?

• Exclude infections with infection with Giardia lamblia, cryptosporidium parvum, and Cyclospora cayetanensis. (Stool tests X3)
• Once specific causes of diarrhoea and malabsorption have been excluded, fat, vitamin B12 and possibly D-xylose malabsorption are established, and a jejunal biopsy shows partial villus atrophy, the diagnosis can be assumed to be tropical sprue.

Discuss the treatment of TS?

• Restoration of water and electrolyte balance and replacement of nutritional deficiencies. There is dramatic response to oral folate therapy, so that it is almost considered to be diagnostic of the illness. Folate therapy leads to return of appetite, weight gain and general sense of well being.
• However, despite folate therapy, clinical and morphologic abnormalities of the intestine persist in 50 percent of patients who reside in an endemic area in the tropics. The administration of sulfa drugs or tetracycline for three to six months completely reverses the intestinal and hematologic abnormalities of tropical sprue in a majority of patients.

So, tetracycline (250 mg PO four times daily) plus folic acid  (5 mg/day) for three to six months is recommended as treatment for tropical sprue.

SBBO usually is defined as an overgrowth of more than 105 CFU/mL of bacteria in
the proximal small bowel.

Discuss the mechanism of malabsorption in SBBO?

Malabsorption is due to the intraluminal effects of proliferating bacteria (degrading CHO and protein, using up B12) combined with damage to mucosal enterocytes. This damage lead to diminished disaccharidase activity; decreased transport of monosaccharides, amino acids and fatty acids; and protein losing enteropathy.
Fat malabsorption results from bacterial deconjugation of bile salts to form bile acids. These are readily absorbed in the jejunum leading to insufficient concentrations for normal fat absorption.
Discuss the disorders associated with bacterial overgrowth?
Growth of bacteria in small bowel is normally controlled by the ability of gastric acid to kill swallowed microorganisms and the cleansing effects of normal intestinal motility. Immunoglobulins in intestinal secretions and an intact IC valve are also important.

• Small intestinal stasis-
  • Anatomic abnormalities- Small intestinal diverticulosis, surgically created blind loops (end-to-side anastomosis), Strictures (Crohn’s disease, radiation, surgery)
  • Abnormal small intestinal motility- Diabetes mellitus, Scleroderma, Idiopathic intestinal pseudo obstruction, Radiation enteritis, Crohn’s disease.
• Abnormal communication between the proximal and distal gastrointestinal tract- Gastrocolic or jejunocolic fistula, Resection of the ileocaecal valve.
• Associations usually with multifactorial causes- Hypochlorhydria due to atrophic gastritis or medications (These are usually not clinically significant unless there coexist concomitant motility disturbances of the small bowel, so malabsorption may be precipitated by the use of PPI in scleroderma), Immunodeficiency states (common variable immunodeficiency, AIDS, severe malnutrition), Chronic pancreatitis, Cirrhosis, Alcoholism, End stage renal disease, Advanced age (mechanisms not fully understood)

Some authorities think that SBBO is perhaps the most discernible cause of malabsorption in geriatric populations.
Discuss the clinical features of SBBO?
Abdominal discomfort, bloating, diarrhoea, flatulence, wt loss, weakness, neuropathy
Discuss the diagnosis of SBBO?
Patients should be tested and treated for SBBO in the presence of symptoms and a known predisposition to SBBO even in the absence of malabsorption.

• Small bowel (jejunal) aspiration and culture- ideal but cumbersome
• 14C glycocholate breadth test- small bowel bacteria would deconjugate this bile salt releasing 14CO2. Specificity is poor because of colonic bacterial deconjugation of unabsorbed bile slat when there is ileal damage or resection
• H2 breadth tests- Breath hydrogen testing is performed by administering a test dose of carbohydrate (usually lactulose or glucose). Excess bacteria in SBBO breakdown CHO to release H2. Breath hydrogen testing is safe, easy to perform, and can be used in women of child-bearing age and children as no radioisotope is involved.

In these breath tests, the diagnosis of SBBO is established when the exhaled breath H2 level increases by more than 10 parts per million greater than baseline on 2 consecutive samplings or if the fasting breath hydrogen level exceeds 20 parts per million. In patients with SIBO and an intact intestine, a peak occurs within 1 hour and is less prominent than the normal colonic peak.

The specificity is compromised when hydrogen is produced by colonic bacteria, especially when transit times are accelerated by the osmotic load of the substrate dose. Further upto 18% of persons are H2 non excretors. The test will false negative in these pts as H2 is metabolised by bacteria to methane.
Discuss the treatment of SBBO?

• Correct the underlying small intestinal abnormality, if possible
• Antibiotics- Effective antibiotic treatment should cover both aerobic and anaerobic enteric bacteria. A single course of therapy for 7 to 10 days may improve symptoms and have an effect lasting for months.
• Adequate antimicrobial coverage can be achieved with the following combinations: Amoxicillin-clavulanate (500mg tds), metronidazole (250 tds), ciprofloxacin (250 BD), rifaximin (1200mg/day), doxycycline (100 BD) etc
• In some symptoms promptly recur on stopping antibiotics.  Recurrent SBBO can be treated by cyclic (e.g. 1 week of 4) or continuous long-term antibiotics. Rotating antibiotic regimens may help to prevent the development of resistance.
• Prokinetics may help propel bacteria through the stagnant small bowel
• Nutritional support- replace deficient vitamins. Avoiding lactose- as lactase deficiency develops in many pts with SBBO.

In the literature, intestinal failure (IF) and short bowel (SB) are used interchangeably. Short bowel syndrome (SBS) is defined as <200cm of small intestine (normal length 3-8 m) However functional short bowel syndrome may also occur in cases of severe malabsorption in which the bowel length is often intact. The degree of intestinal function is better described in terms of energy absorption/loss rather than length of residual intestine.

What is IF?

IF may be defined as the inability to sustain adequate nutritional, electrolyte, or hydrational status in the absence of specialised nutrition support. IF is termed as severe when parenteral (Nutrition and or water/electrolytes) supplements are needed.

What are the common causes of IF/SB?

Crohn’s disease, mesenteric ischaemia, irradiation, small bowel volvulus etc

What are the main types of SBS?
There are 3 main types of patients with a SB:

• Jejunum-Colon: those who had a jejunoileal resection and a jejunocolic anastomosis
• Jejunum-ileum: those who had a predominant jejunal resection and have more then 10cm of terminal ileum and the colon remaining. These patients are uncommon and rarely have problems of undernutrition and thus do not often need nutrition support.
• Jejunostomy: those who had a jejunoileal resection, colectomy and formation of a stoma.

Can you predict long term fluid/nutritional support requirements based on the knowledge of residual small bowel length?
Yes

• Colon intact- No nutritional support required if > 100 cms of small bowel (jejunum) left. Only enteral support may be needed with 51-100cms of small bowel. Parenteral nutrition needed when less than 50 cms of small bowel left
• No colon- No nutritional support required if > 200 cms of small bowel (jejunum) left. Only enteral support may be needed with 101-200cms of small bowel. Parenteral support needed when less than 100 cms of small bowel left.

Discuss jejunum-colon patients?

Problems of undernutrition, diarrhoea (steatorrhoea which is malodorous and bulky) due to malabsorption, and vitamin/mineral deficiencies dominate the clinical picture. The colon has a large capacity to absorb sodium and water and thus these patients rarely need water or sodium supplements.

What are the principles of Management of jejunum-colon patients?

1. Undernutrition- 50% or more of the energy from the diet may be malabsorbed. Thus patients need to consume more energy either by eating more high energy food, having oral sip feeds or high energy enteral feeds given at night through a NG/PEG tube. However, increased energy intake leads to increased diarrhoea. Parenteral nutrition will need to be considered if the patient continues to lose weight or increasing oral/enteral intake causes a socially unacceptable amount of diarrhoea

2. Diarrhoea-

I. Causes of worsening

• Unabsorbed long chain fatty acids in the colon reduce transit time and reduce water and sodium absorption, thus making diarrhoea worse
• Ileal bile salt malabsorption occurs when >100cm TI is resected. This leads to impaired lipid digestion. Further bile salts affect colonocytes and impair water and salt absorption, thus worsening diarrhoea. In colon bile salts are also dehydroxylated to deoxy bile salts, which induce colonic water secretion. NB- Normally, the demand for bile salts for fat digestion cannot be met by synthesis alone. The demand is only met by ileal resorption of bile salts and the entero-hepatic circulation

II. Treatment of diarrhoea

• Loperamide 2-8mg given half an hour before food and occasionally codeine phosphate is also added (30-60mg 30 minutes before food)
• Limiting food intake- clearly not a feasible option. However if diarrhoea is unacceptable, parenteral nutrition will be needed.
• Low fat diet- it is hard to implement because fat is energy dense and makes food palatable. A low fat diet will involve eating large volume of food. MCT are an alternative source of energy and are absorbed from the small and large intestine. Some, but not all LCT can be replaced by MCT in the diet because the essential fatty acid linoleic acid is a constituent of LCT and is not found in MCT.
• Cholestyramine may help with bile salt diarrhoea. However, it will increase fat malabsorption by further reducing the bile salt pool and hence should not be used in patients with > 100 cm of ileal resection. Cholestyramine helps if < 100cms of ileum resected. (i.e. ileal resection of more than 100cms causes steatorrhoea. <100cm resection can cause diarrhoea without necessarily leading to steatorrhea)
• Bile salt replacement- Cholylsarcosine has been used with variable improvement in fat absorption. There is no evidence for its use.
• PPI-Small bowel resection is associated with transient gastric acid hypersecretion and hypergastrinemia, generally lasting for upto 6 months following resection.
• Thus PPI help reduce diarrhoea shortly after surgery, but may not be effective in the long term. PPI help reduce gastric acid secretion and thus prevent the bile acid deconjugation in the duodenum and decreased pancreatic lipase excretion (thus enhances fat digestion).

3. Vitamin and mineral deficiencies

• Long term B12 treatment is required is most cases.
• Water soluble vitamin deficiencies are unusual in SBS patients as these are absorbed in the proximal jejunum.
• Vitamins A, D, E and K and essential fatty acids may need to be replaced
• Selenium deficiency is common. Zinc deficiency is uncommon unless stool volumes are large. Measure zinc, copper and selenium at baseline and then further testing depending on the baseline results.

4. Confusion
Specific causes of confusion:

• Very low (<0.2 mmol/l) magnesium levels may cause mild confusion
• Thiamine deficiency can cause Wernicke/korsakoff psychosis
• D (-) lactic acidosis- Colonic bacteria degrade surplus fermentable carbohydrate to form D (-) lactate. This is absorbed but not easily metabolised causing a metabolic acidosis with a large anion gap. Treatment- a. restrict mono and oligosaccharides and encouraging the more slowly digestible polysaccharides (starch) b. thiamine supplements c. Broad spectrum antibiotics. Rarely the pt may need to fast with TPN
• Hyperammonaemia (also occurs in jejunostomy pts) – The small amount of intestine remaining cannot manufacture adequate citrulline to detoxify ammonia via the urea cycle. The increase in blood ammonia creates problem only if there is concomitant renal impairment, as the excess ammonia cannot be excreted. Hyperammonaemia can be corrected by giving arginine (an intermediary in the urea cycle)

5. Drug absorption
Many, but not all, medications are absorbed in the jejunum.

• Omeprazole can be absorbed in the duodenum/upper jejunum and only if less than 50 cms of jejunum remains are problems likely to occur.
• May drugs will be incompletely absorbed and thus may be needed in much higher amounts (like thyroxine, digoxin, warfarin) or intravenously
• Loperamide circulates in the enterohepatic circulation and hence need larger doses.

6. Gall stones
Gallstones are common (45%). Multiple therapies have been proposed including prophylactic cholecystectomy with massive small bowel resections.

7. Renal stones
In the presence of fat malabsorption, calcium preferentially binds to free fatty acids. This allows free oxalate to pass into the colon in which it is readily absorbed; dietary oxalate is absorbed only to a minimal extent in the small intestine. Oxalate can form discrete stones or less commonly a diffuse nephrocalcinosis leading to CRF. To prevent this, the pts should take a lox oxalate diet (avoiding food like spinach, rhubarb, beetroot, nuts, chocolate, tea, wheat bran, strawberries). Other measures include reducing dietary fat or replacing with MCT and increasing dietary calcium.

Discuss the management of jejunostomy patients?

1. Salt and water depletion
Jejunostomy patients lose large volume of salt and water from the stoma. This is greater after eating and drinking. The effluent from the stoma contains about 100mmol/l of sodium but relatively little potassium (15 mmol/l).
Potassium balance is usually not a problem unless less than 50 cm of jejunum remains. A low serum K is usually due to Na depletion with secondary hyperaldosteronism and thus greater than normal urinary losses of K. Low K can also be due to low Mg, which causes dysfunction of many of the K transport systems and increases urinary K losses. This hypokalemia is resistant to K treatment but responds to Mg replacement.

2. Hypomagnesemia
Causes
reduced absorption because of chelation with unabsorbed fatty acids
increased urinary losses due to secondary hyperaldosteronism
Low Mg reduces PTH secretion and function, so directly increasing urinary Mg losses and indirectly by reducing 1, 25, OH Vitamin D production, which normally increases jejunal Mg absorption

Treatment:
Correct water and salt depletion and thus hyperaldosteronism
Oral MgO (4mmol/capsule) – 12-24 mmol/day. MgO is usually given at night when intestinal transit is assumed to be slowest and hence there is more time for absorption. Mg salts may however worsen diarrhoea/stoma output.
If oral Mg salts do not normalise Mg levels- oral 1 alpha OH Cholecalciferol in a gradually increasing dose (q 2-4 weeks) of 0.25-900mcg daily may improve Mg balance. regular monitoring of serum calcium is necessary to avoid hypercalcemia.
IV Mg occasionally.

3. Undernutrition
These patients need a high energy diet in which osmolality is kept low using large molecules (polysaccharides, protein and triglycerides) and to which NaCL is added to give the feed a total Na conc. of 90-120 mmol/l and an osmolality of approx 300 mosm/kg
There is no advantage in giving a diet of small molecules, like elemental diet, which causes the feed to be hyperosmolar, thus increasing stomal losses
Jejunostomy pts absorb a constant proportion of the nitrogen, energy, and fat from their diet. Increasing fat in the diet increased energy density and keeps the diet osmolality low. It does increase fat excretion but does not usually increase stomal output, nor make output more offensive.

4. Many other problems like B12 def, confusion, drug absorption and gall stones are similar to jejunum colon patients.

Discuss the management of a high output jejunostomy/ileostomy?

Management principles are the same for management of high output enterocutaneous fistula and a high output jejunostomy/ileostomy.

• Exclude other causes of a high output like intraabdominal sepsis, partial/intermittent bowel obstruction, gastroenteritis, recurrent disease in the remaining bowel, suddenly stopping drugs (steroids/opioid) or using prokinetics.
• Correct dehydration with IV saline while the patient stays NPO for 24-48 hrs. This stops thirst and the desire to drink and will also demonstrate that output is driven by their oral intake. Over 2-3 days IV saline is gradually withdrawn while food and restricted fluids are introduced.
• Restrict hypotonic (water, tea, coffee, fruit juices, alcohol etc) and hypertonic (fruit juices, coca cola and most commercial sip feeds) fluids to less than 500 ml daily. To make up the rest of the fluid requirement, the patient is encouraged to drink a glucose-saline solution (WHO or St Marks).  The pt is encouraged to drink a litre or more throughout the day. It is a common mistake for pts to be encouraged to drink oral hypotonic solutions to quench their thirst but this causes large stomal losses
• Jejunostomy effluent is constant at 90 mmol/ and as fluid and glucose absorption improves with increasing Na concentration, pts are advised to sip glucose saline solution with a Na conc. of at least 90 mmol/l or take NaCL capsules. Pts with stomal losses of less than 1200 ml daily can maintain Na balance by adding extra salt to the limit of palatability at the table and when cooking. When stoma losses are 1200-2000 ml or more, Na balance may be maintained by taking a glucose-saline solution or salt capsules. NaCL capsules (500mg each) are effective when taken in large amounts (14/24 hrs) but can cause nausea and vomiting.
• Drug therapy- if above measures is not adequate the following drugs may be useful
  • Loperamide and codeine- reduce intestinal motility and thus decrease stoma output by 20-30%. Loperamide is more effective but the effects of the two together may be greater.
  • PPI reduce stoma output particularly if it is more than 2 litres
  • Octreotide (50 mcg SC BD) reduces stoma output possibly by slowing intestinal transit.
  • Mineralacorticoids (2mg fludrocortisone or 2 mg IV d-aldosterone) or high dose hydrocortisone may reduce stoma output in pts with a retained ileum.

Some patients will not maintain hydration with the above measures and IV/SC saline will be needed.

Ref

1. Based on British Society of Gastroenterology guidelines for Management of Patients with a Short Bowel

RCD can be defined as persisting or recurring villous atrophy with crypt hyperplasia and
increased intraepithelial lymphocytes (IEL’s) in spite of a strict GFD for more than 12 months or when severe persisting symptoms necessitate intervention independent of the duration of the GFD. RCD may not respond primarily or secondarily to GFD.

What are the Types of RCD?
2 immunologic categories
?

What are the clinical features of RCD?
Most of the patients (particularly Type II) develop severe malabsorption with weight loss, abdominal pain and diarrhoea.

What is the cause of RCD?

Unknown.

How do you approach a patient of RCD?

RCD is a diagnosis of exclusion.

• Reassess the initial diagnosis of CD
• Assessment of GFD
• Exclude other causes of diarrhoea
• Exclude malignant complications of CD

Discuss D2 biopsies in RCD?

• Multiple D2 (at least 10) are needed for histological, immunohistochemical and TCR gene rearrangement studies by flow cytometry.  The storage medium for immunohistochemical and flow cytometry should be checked with the lab.An abnormal clonal IEL population, characterized by a low ratio of CD8+/CD3+ and TCR-gamma gene rearrangement can be shown in 80% of RCD cases. This is associated with a high risk of ulcerative jejunitis and lymphomatous transformation.
• Clinically, a simple immunohistochemical method using 2 T-cell markers, CD3 and CD8, on paraffin sections is used to differentiate CD and RCD. An abnormal phenotype in the context of a flat biopsy is indicative of RCD, whereas a normal phenotype is more suggestive of continuing gluten ingestion as a cause of the villous atrophy. Those with an abnormal phenotype require TCR gene rearrangement studies because the presence of a clonal configuration indicates a poor prognosis in most with uncontrolled malabsorption and the development of lymphoma.

How do you treat RCD?
RCD Type I- These patients benefit from an immunosuppressive treatment. Induction is with corticosteroids (hydrocortisone 100mg IV qds or 40-60 mg of oral prednisolone). The dose can be tapered to the lowest dose needed after a few weeks in responding patients.  Azathioprine and 6-mercaptopurine appear to be effective steroid-sparing agent. Dose and duration of treatment with azathioprine are not established.
Cyclosporine A, infliximab, oral budesonide and tacrolimus have been reported to be effective in case reports. These agents should only be considered in cases of clinical deterioration despite corticosteroid therapy or intolerance to azathioprine.
RCD type II- is usually resistant to medical therapies.

• Some patients may benefit from steroids/azathioprine. However, response to corticosteroids treatment does not exclude underlying EATL. Caution is required when initiating immunosuppressive therapy, as this may induce a high risk of progression to an overt lymphoma.
• CHOP-like regimens
• Case reports of success with infliximab have been published.
• Cytotoxic chemotherapy with cladribine has been used on the assumption that some patients with RCD II may have a low-grade EATL.
• Autologous stem cell transplantation in RCD II seems to be promising.

When do you suspect Ulcerative jejunitis/intestinal lymphoma?

• RCD unresponsive to steroids.
• CD patients with symptoms of lassitude, anorexia, weight loss, abdominal pain, diarrhea, and fever.
• Clinical features like hepatomegaly, splenomegaly, duodenal mass, or ascites, are very suggestive of lymphoma. Lymphoma may also present with acute perforation, gastrointestinal obstruction, or GI bleed.

What is EATL?
Enteropathy-associated T-cell lymphoma (EATL) is a rare form of high-grade, T-cell non-Hodgkin lymphoma (NHL) of the upper small intestine that is specifically associated with CD. EATL commonly develops in the jejunum but may also be found in the ileum and lymph nodes and less frequently in the stomach and the colon. It is often multifocal with ulcerative lesions.
This NHL subtype arises in patients with either previously or concomitantly diagnosed CD. In a subgroup of patients, there is progressive deterioration of a RCD. EATL derives from a clonal proliferation of IEL’s and is often disseminated at diagnosis. Extra intestinal presentations are not uncommon in the liver/spleen, thyroid, skin, nasal sinus, and brain.
What is the lag period between CD diagnosis and EATL?
EATL occur in adults, with a peak in the sixth decade of life. Many years of latency is needed between the onset of CD and the development of EATL. If CD has been diagnosed first, lymphoma mostly develops in the following 5 to 10 years, although the time lag may occasionally be very long (up to 60 years).
How do you diagnose these conditions?

• Most patients present with malaise, anorexia, weight loss, and diarrhea often associated with abdominal pain. Physical signs include fever, lymphadenopathy, skin rash, and hepatomegaly and a palpable abdominal mass.
• The suspicion of EATL prompts an extensive diagnostic work-up that may include upper and lower intestinal endoscopy, CT scans, MR enteroclysis, video capsule endoscopy and double balloon enteroscopy. The final diagnosis is made on either endoscopic biopsies or full-thickness, laparoscopic, small bowel biopsies. PET scan can help identify suspicious lesions. Enlarged mesenteric lymph nodes often accompany RCD, without necessarily being specific for a T cell lymphoma.
• Ulcerative Jejuno-ileitis: This is an unusual complication in which unresponsive CD is associated with ulceration and stricturing.  Patients may become very unwell and are often unresponsive to medical therapy.  The discrimination between this and lymphoma can normally only be made at surgery, and in some instances lymphoma seems to have developed on a background of jejuno-ileitis.  Patients should be advised to continue with a gluten-free diet, but early surgery is indicated if there is no resolution of symptoms.
• It has an unfavorable prognosis. Up to one-third of patients die from complications. The prognosis can be improved if the ulcerated or strictured segment can be resected.

What is the prognosis?
These lymphomas are usually of high-grade histology and the prognosis is poor. Five-year survival is approximately 10 percent.
Multidrug therapy may be helpful in patients with minimal GI symptoms, who can tolerate therapy. Patients should also be maintained on a gluten-free diet.

Ref

1. Al-toma A et al. Update on the Management of Refractory Coeliac disease. J Gastrointestin Liver Dis 2007; 16(1): 57-63

PLE describes a diverse group of disorders characterised by an excessive loss of serum proteins into the gastrointestinal tract resulting in hypoproteinemia and edema. PLE should be suspected in pts with unexplained hypoproteinemia in the absence of renal disease, liver disease and malnutrition.

Hypoproteinemia occurs when the extent of net enteral protein loss is greater than the capacity of liver to synthesise particular proteins. Hepatic protein synthesis in PLE is usually normal or slightly increased. Thus proteins with slow catabolic rate (long half life) will be reduced mostly like albumin and immunoglobulins (IgG, IgA, IgM); whereas there is little change in the serum concentrations of proteins with a rapid turnover rate like insulin, clotting factors and IgE.

Discuss the pathogenesis/causes of PLE?

• Increased permeability due to mucosal disease without erosions/ulcerations E.g.-Coeliac disease, Giant hypertrophic gastritis (menetrier’s disease), Lymphocytic gastritis, amyloidosis, microscopic colitis, autoimmune diseases (RA, SLE, MCTD), infections (bacterial overgrowth, Whipple’s disease, viral/parasitic infections), eosinophilic gastroenteritis
• Inflammatory exudations due to mucosal erosions/ulcerations IBD, GI cancers, bacterial gastroenteritis, H. Pylori infection, NSAID enteropathy
• Lymphatic obstruction or increased lymphatic hydrostatic pressure, resulting in direct leakage of lymph containing plasma proteins. Intestinal lymphagiectasia (congenital or acquired), Rt sided heart failure (increased CVP causes increased lymphatic pressure), lymphoma, portal hypertension

What are the clinical manifestations of PLE?

• Symptoms and signs

Edema, diarrhoea,
Hypoproteinemia can also be associated with fat and carbohydrate malabsorption and fat soluble vitamin deficiencies due to small bowel involvement by the primary disease.
Laboratory abnormalities

• Hypoalbuminemia, decreased serum gamma globulins (IgG, IgA, IgM), decreased serum proteins (ceruloplasmin, AIAT, fibrinogen, transferrin, hormone binding proteins), decreased serum lipoproteins. Significant lymphocytopenia (due to loss of lymphocytes in the gut) can occur, leading to detectable alterations in cellular immunity. Increased susceptibility to infections is uncommon due to low immunoglobulins.

How do you confirm the diagnosis of PLE?

• Alpha-I antitrypsin (AIAT) is excreted intact in stool because it is resistant to degradation in the gut lumen. Further it is not secreted or absorbed. Faecal excretion of AIAT is thus used as an indirect measure of enteric albumin loss.
  Limitations:
  • There is poor correlation between random stool concentrations of AIAT and clearance measurements. A 24 hour stool specimen is thus preferred, since it produces a more reliable estimate of AIAT excretion than a spot sample. Alternatively a more reliable estimate of protein loss can be obtained by measuring the concentration in stool with simultaneous plasma measurement from which an estimate of intestinal protein loss can be derived.
  • Diarrhoea can increase AIAT clearance. A1AT clearance greater than 24ml/day (4.8mg/g of stool) in patients without diarrhoea and greater than 56ml/day (11.2mg/g of stool) in pts with diarrhoea is considered abnormal.
  • There is an inverse correlation between AIAT plasma clearance and the serum albumin concentration; as serum albumin levels fall below 3 g/dl, the clearance of AIAT exceeds 180 ml/day.
  • AIAT is degraded at a gastric pH below 3 and thus cannot be used to measure gastric protein loss. PPI can be used to avoid this.
  • Intestinal bleeding can also significantly increase the clearance rates. Thus positive OBT make the reading unreliable.
• Technetium 99m-labelled human serum albumin (Tc HSA) scintigraphy is a less sensitive test than AIAT to detect and monitor enteric protein loss. An additional advantage is that it can localise the specific site of gastric or enteric protein loss. It can also be used like AIAT to monitor response to therapy. Also it has a higher sensitivity in pts with low serum albumin, reflecting a higher degree of enteric protein leakage
• Technetium 99m-labelled dextran scintigraphy is another method to identify and monitor enteric protein loss.

How do you evaluate suspected PLE?

Step 1- Confirm by increase AIAT clearance, in the absence of confounding variables.
In addition Tc HAS scintigraphy can confirm and quantitate the extent of the disorder, directing the work up to a specific organ (stomach or small bowel)

Step 2- Check for steatorrhea

• If steatorrhea absent- Endoscopy/biopsy. Endoscopy may reveal scattered white spots in a snow flake like appearance. Histology may reveal markedly dilated lymphatics.
• Presence of steatorrhea indicate small bowel disease- barium meal follow through will help. If abnormal- consider biopsy. If however normal consider CT scan, cardiac evaluation, laparoscopy or lymphagiogram, if available.

How do you manage PLE?

• Treat the underlying disorder
• Pts should be given a diet low in saturated fat and high in protein. In PLE, the protein requirements may increase to 1.5-3.0g/kg/day. Protein supplements may be needed to achieve positive nitrogen balance. Low fat MCT enriched diet is useful in selected patients as they do not require lymphatic transport and therefore do not stimulate lymph flow.
• Supportive care- diuretic to reduce edema

Step 1

Suspecting Malabsorption

• The classical manifestation of malabsorption is steatorrhoea (pale, greasy, voluminous, foul smelling stools) and weight loss despite adequate food intake.
• There may be selective abnormality in the absorption of carbohydrates. This will lead to watery diarrhoea, cramping, bloating, flatulence and milk intolerance.
• May present with isolated nutrient deficiency like IDA, def of vitamins, calcium leading to anaemia, tetany, bruising, bone pain etc.
• The clinical features depend upon the cause and severity of the underlying disease.

Remember-

• All patients with suspected malabsorption of unknown cause should have the following tests-
• Haematology- FBC, B12, folate, ferritin, INR
• Biochemistry- Urea & electrolytes, LFT, albumin, TFT, Mg, PO4, Ca, glucose
• Inflammatory markers- CRP, ESR
• Immunology- coeliac antibody, autoantibody (systemic diseases), Immunoglobulins
• Check Zn, Cu, Selenium- if malabsorption for a long time

Step 2

Confirming Malabsorption

• Faecal fat excretion-
  • 14 C- triolein breadth test- measures 14CO2 in breadth after ingestion of a triglyceride that has been labeled with 14C. fat malabsorption results in decreased pulmonary excretion of 14CO2. It has been reported to have 100% sensitivity and 96% specificity however limitations such as the confounding effects of comorbidities altering fat metabolism or respiratory function have also been documented. Despite its limitations, it is usually the test of choice to detect fat malabsorption.
  • A qualitative assessment on a spot stool using Sudan III stain.  However, its use is not recommended due to its lack of sensitivity and poor reproducibility.
  • The acid steatocrit (a gravimetric assay performed on a spot stool sample) may provide an alternative accurate and simplified method for detecting steatorrhea on a spot stool specimen.
  • Quantitative assessment of a 72 hour stool collection on a 100 gram fat/day diet- if the qualitative tests above are negative. Normal fat excretion is < 6gm/day. Steatorrhea- if fat excretion >14 g/day. More than 6gm/day fat is pathologic; however fecal fat excretion can be increased upto 14g/day in diarrheal diseases even without fat malabsorption.
  • Faecal elastase- faecal elastase is more sensitive and specific than chymotrypsin determination. Among pancreatic function tests, faecal elastase measurement is the most sensitive and specific in the early phases of pancreatic insufficiency. In addition, its values are independent on pancreatic enzyme replacement therapy, thereby extending its utility. Faecal elastase decreases in pancreatitic insufficiency. Faecal elastase helps in differentiating between pancreatic and intestinal causes.
  • Low levels of serum beta-carotene, cholesterol, TG and calcium and a prolonged PT suggest malabsorption of fat and fat soluble vitamins. Beta carotene values less than 100 mcg/dl is suggestive and less than 47mcg/dl is strongly indicative of steatorrhea.
• Low levels of B12, folate, iron and albumin suggest malabsorption of water soluble substances and therefore indicate intestine disease rather than pancreatic or biliary disease.
  • Carbohydrate malabsorption
  • D-xylose test- Limited clinical value today
  • Hydrogen breadth (lactose tolerance) tests- H2 is produced by bacterial action on unabsorbed CH in the colon. Thus in CH malabsorption, a breadth H2 peak will occur 90 minutes after its ingestion when it first arrives in the colon and is broken down by the bacteria.  False positive results are possible particularly with small bowel bacterial overgrowth.  It can be used to diagnose specific forms of carbohydrate malabsorption (eg, lactose, fructose, sucrose isomaltase and others).
  • Concurrent antibiotic administration will alter the results of H2 breadth test as it relies on bacterial fermentation of carbohydrate.
  • Stool pH less than 5.5 is a qualitative indicator of CHO malabsorption. (SCFA and lactic acids are the products of CHO metabolism)
• Protein malabsorption- Not generally tested. The tests are technically difficult and intestinal protein loss is generally due to either bacterial overgrowth or protein losing gastroenteropathy. Enteral protein loss is demonstrable by measurement of the alpha-1 antitrypsin clearance. In massive enteral protein loss, the exact site of protein leakage may be localized by the infusion of 99mTc-albumin and gamma camera scintigraphy.
• d. Specific tests- SeHCAT, Schilling

Tests for Bile Acid Malabsorption
This can cause symptoms of chronic diarrhoea. Three types of bile acid malabsorption are recognised:
Type 1: following ileal disease or resection or bypass surgery.
Type 2: primary idiopathic malabsorption.
Type 3: associated with cholecystectomy, peptic ulcer surgery, chronic pancreatitis, coeliac disease and diabetes mellitus.
Bile acids are cathartic to colonic mucosa, and impair sodium and water absorption. A trial of cholestyramine may be appropriate in some patients with chronic diarrhoea for which other causes have been excluded; however, the Selenium-75 labeled Homotaurocholic Acid Test (75SeHCAT) is necessary in some.  The SeHCAT test involves the administration of a selenium75 labeled synthetic bile acid (selenium-homotaurocholic acid) orally, followed by measurement of retention of the bile acid by whole body scan or gamma camera at seven days (abnormal is less than 5 percent, normal is >12%, equivocal is between 5 and 12%).

Step 3

Finding the cause

History-

• Abdominal pain is unusual in malabsorption except in chronic pancreatitis, Crohns disease and pseudo obstruction (Scleroderma)
• Always ask about an h/o recurrent peptic ulcer disease (ZES)
• Always ask h/o previous surgery
• Take a careful alcohol history- it takes 10-20 years for pancreatic insufficiency to develop in alcoholics
• Some diseases associated with malabsorption are found more frequently in families- like coeliac, Crohns, lactase def- so take a careful family history.
• H/o travel to endemic areas of tropical sprue, giardiasis, or other GI infections
• Is there an increased likelihood of HIV infection?
• Does the patient have clinical features of thyrotoxicosis, Addison’s disease, Whipple’s disease or diabetic neuropathy?

If the case warrants further evaluation- Proceed stepwise as-

• H2-breath tests for carbohydrate malabsorption (lactose, fructose), coeliac antibodies, search for giardia lamblia, enteropathogenic bacteria, parasites and ova.
• Abdominal ultrasound (gallbladder; liver; pancreas; intestinal wall aspects; adenopathy; etc.)
• OGD including biopsies from stomach (autoimmune gastritis? H. pylori?) and duodenum
• Ileocolonoscopy including biopsies of colon and ileum
• If pancreatic disease with secretory insufficiency is suspected- check tests for secretory function like chymotrypsin or elastase in stool, CT/ERCP of pancreas
• If small bowel disease is still within the D/D- do small bowel x-rays (fistulae, diverticula, blind loops, short bowel, etc.), Schilling-test (Vit B12), Glucose-H2-test (bacterial overgrowth), Angiography of celiac and mesenteric arteries (ischemic bowel damage).

Practical approach to Malabsorption

Remember 3 major malabsorptive conditions- small bowel mucosal disease, small bowel bacterial overgrowth, and pancreatic insufficiency

Step A- Possible coeliac disease- D2 biopsies
Step B- If other diagnoses suspected- Do Triolein breadth test (TBT)
Step C- If TBT is abnormal- a. pancreatic insuff b. Small bowel bacterial overgrowth, c. diffuse enteropathy (radiology, endoscopy, biopsy, microbiology)
Step D- If TBT normal- a. CHO malabsorption b. Bile acid malabsorption c. segmental enteropathy (radiology, endoscopy, biopsy)

Discuss the mechanisms of malabsorption?

Mechanisms of fat malabsorption

• Pancreatic insufficiency
• Bile acid deficiency
• Small intestinal bacterial overgrowth
• Loss of absorptive surface area
• Defective enterocyte function
• Lymphatic disorders

Mechanisms of CHO malabsorption

• Selective disaccharidase deficiency
• Disruption of brush border/enterocyte function
• Loss of mucosal surface area
• Pancreatic insufficiency (loss of amylase)

Mechanisms of Protein malabsorption

• Pancreatic insufficiency (loss of pancreatic proteases)
• Disorders with impaired enterocyte function
• Disorders with decreased absorptive surface
• Protein-losing enteropathy