(This is part of Inflammatory Bowel Disease (IBD) along with Ulcerative Colitis and Whipples)

• Chron’s, or Iliocolitis are the aka’s

• Regional Enteritis starts at the distal ileum

• 40% involve cecum at the beginning; however it can be anywhere from mouth to anus.

• This is not the same as ulcerative colitis even though they are related

• Know Dif bet. UC, RE, and Whipples

• It is a full thickness IBD

• It involves very big holes

• Leads to perforations

• Can have long periods of remission

• Skip lesions seen on endoscopic exam and contrast.

• In remissive tissue lesions fill in with adhesion (scar tissue) that shrinks down over time

• Can decrease peristaltic wave through that region

• Can get low grade obstruction from narrowed lumen

• Can happen at any age though 2^nd and 3^rd decade is most common

• RE has no gender bias

• More Caucasians of Jewish descent get RE (chron’s)

• Chron’s is 2-3x more common in blood relatives.

• Diarrhea followed by constipation is a major sign of RE

• The lesion is dominated by immune globulins

• Milk and dairy are trigger foods, however they don’t cause the disease

• The cause seems to be genetic predisposition with viral trigger

• Once the skip lesions reach the capillary bed you will begin to see blood in the stool of RE patients (hemocult = positive)

• RE can cause anemia but so can menstruation so RE in women can be missed especially since it is prime in the 2^nd and 3^rd decade.

• If the SI isn’t absorbing appropriately RE people will see weight loss

• THE stool of RE patients will have stuff in it that should have been absorbed

• Retrograde endoscopy is the best way to diagnose it (contrast shows decrease peristaltic wave

• If it goes through one loop, it can go into another causing a fistula

• Additionally, it can also break through to surrounding organs (i.e. bladder) and urine will smell like caca (that means poop)

• TREATMENT of REGIONAL ENTERITES a.k.a. chron’s/iliocolitis

  • the most successful drugs claim 40% success rate, barely beating placebo

  • we (chiropractors) can help 40-50% without the side effects of drugs so we are better tx.

  • Cutting out/ avoiding trigger foods (i.e. dairy) is a good form of treatment

  • During inflammation consume highly absorbable foods

  • Avoid raw vegetables and fruits b/c the bulk of it will not get absorbed and will speed through the SI and not get absorbed.

  • Corticosteroids – are advised if the flare up is very bad

(NOT A FULL THICKNESS IBD)

• UC starts in the rectum and works its way backwards, skipping nothing in between

• It starts later than chron’s 3^rd, 4^th, and 5^th, decade

• Emotional stress is trigger for new round of inflammation.

• Since the first (most mature) lesion is at the rectum, the blood in the stool wil be painted on, unlike chron’s which will have blood mixed in.

• Alternating Diarrhea and constipation like Chron’s is present

• Weight loss is not a problem as it does not affect SI where nutrient absorption takes place

• 50%=mild 35%=moderate 15%=severe (bloody b.m.. daily, tachycardia w/ Low B.P. , inflammation involving JELS (joints,eyes, liver, skin), iron deficiency anemia is contracted due to bleeding, peripheral arthropathy, sacroilitis,

• Complications of UC

  • Toxic megacolon (septicemia) – 40%

  • Stricture

  • Massive Hemorrhage

  • Perforation is not as likely as Chron’s b/c UC is NOT A FULL THICKNESS DX LIKE CHRON’S

  • All the different ulcers in Ulcerative colitis are rare

  • UC AND CHRON’S ARE THE 2 MOST COMMON IBD’S

1. Volvulus – a twisting or folding over onto itself ( Small intestine) like a balloon artist with the long thing balloons.

• Closed Loop = High Grade

• Open Loop = Low Grade

• Volvulus is seen in premature infants.

• If there is an adhesion anchoring the bowels it causes a pivot point allowing for twisting.

2. Intusseception – is a telescoping or invagination

   • The most common cause of this in adults is a tumor!!!

3. Perforation – is the worst case scenario of obstruction as it leads to peritonitis.

4. Functional Obstruction (a.k.a. Adynamic Ileus, Paralytic Ileus)

• Whereas other obstructions maintain intact neurological tracts Functional Obstructions have inhibited motor function.

• Any “itis” in the abdomen can cause decreased motor function (i.e. Cholecystitis, Meckel’s diverticulitis, hepatitis, appendicitis, peritonitis.

• KUB is usually normal

• Bolus clears in a Functional Obstruction because of the work of more proximal parts of the Small Intestine.

• The area of functional obstruction just does not contract

• Functional obstruction can cause severe back pain

• Surgery can produce Functional Obstruction

• If an ITIS caused it take care of the IT IS!

• If back pain is decreased function is restored.

1. The most common obstruction of the GI is ABDOMINAL ADHESIONS which occur as a result of:

   • pancreatitis, surgery, etc.

   • old time migraine medications which lead to fibrosis in the abdomen.

2. The 2^nd most common GI obstruction is Hernia (it was the former #1 but now is #2)

High Grade vs. Low Grade GI Obstruction

High Grade (early vs. late)

Early

• In a high grade GI obstruction nothing gets past a certain portion of bowel.

• Parasympathetic driven persitalsis (due to stretch receptors) try to drive matter past the point of obstruction

• Multiple spinal levels get involved and as a result overlapping peristaltic waves that can be heard as increase peristaltic sounds (HYPERPERISTALSIS)

• Colicky pain – signifies an “unsatisfied contraction” meaning the neurological system is intact

• The colicky pain gets, bad, worse, worst, then goes way, only to return again and get even worse.

• The patient with a high grade obstruction will be normal for a while until it gets completely compacted up to that point; The individual may have a couple of Bowel movements after it happens b/c there was fecal matter distal to the site of obstruction.

• The obstruction may be palpable

Late

• At this phase of obstruction the area of involvement is very dilated. The muscular wall of the Small intestine is stretched so much that it is not very contractile.

• There is difficulty draining blood which causes obstruction, which then leads to no blood coming in

• No bowel sounds may be present for up to 5 minutes

• NO bowel movements will be present in Late High Grade Obstruction.

• Contrast is a contraindication in viewing a Late High Grade Obstruction as barium is in suspension when the patient drinks it. The patient will absorb the water and the Barium will be left behind forming a cement plug. A water soluble contrast agent is needed for a High Grade Obstruction so that the vascular tree can take it away.

• Upright KUB shows multiple air fluid levels due to the layering of feces

• Normal air fluid levels

• Stomach, cecum, hepatic flexure, splenic flexure will not be visible.

• 3 or more air fluid levels on a KUB is abnormal and is considered an obstruction unless proven otherwise.

KEY QUESTIONS

1. Is the Bowel movement schedule normal?

2. Is there a decrease in fecal bulk volume?

LOW GRADE

• The low grade GI Obstruction is like a toothpaste tube. It is a big tube with a small opening.

• Transient dilation (painful) occurs proximal to the partial obstruction.

• Low grade Obstruction is less severe than high grade obstruction

• The pain of a Low grade occurs a certain time after the meal.

• The pain occurs specifically when the area proximal to the obstruction dilates. The pain dissipates as some matter goes through the little hole, and the pain decreases as the stretch decreases.

• It is safe to perform a contrast study here

Chronic – Chronic Mesenteric Vascular lesion will progress over time as blood supply decreases

• These patients will present in the Chiropractic Office and can be treated as it is a vascular compromise.

• Chronic Mesenteric Vascular Lesion is a consequence of atherosclerotic disease.

• These individuals will eat and at a fixed time interval after the meal, they start to hurt.

• The blood supply can keep up with normal activity, but when you add a bolus of food and the activity of the Small Intestine increases with peristaltic waves, these individuals exceed the capacity of the vasculature and the muscles are demanded to contract without replacement energy .

• The muscles then become stressed because of the absence of oxygen necessary to do the work.

• The pain from Chronic Mesenteric Vascular Lesion will pass as the food passes.

• Usually as the patient decides they need a doctor, they start to feel better and don’t come in.

• An Arteriogram is the best way to observe the vasculature problems occurring in Chronic Mesenteric Vascular Lesion.

ACUTE MESENTERIC VASCULAR LESION

• AMVL presents with an abrupt vascular compromise.

• This is a patient that we as chiropractors will not treat

• The patient with AMVL will be sent directly to the Emergency Room

• Acute Mesenteric Vascular Lesion is a SURGICAL EMERGENCY!!!

• The bowels will die quickly due to vascular compromise.

• Ususally the scenario that a person with AMVL encounters is that they eat, pain emerges a fixed time after, and they describe the pain as “THE WORST PAIN I EVER FELT!!!!”

• Hopefully these patients live to make it to surgery.

Meckel’s Diverticulum– is not acquired, though others are. Formerly the umphalomesenteric duct (Vitelline Duct), but it did not close like it should. It is a blind sac with a single opening to the intestine.

• 2% have it

• There are two forms

1. Symptomatic – discovered before age 2

2. Asymptomatic

   • It is attached to the last 2 feet of the ileum

   • Meckel’s Diverticulum is the #1 cause for a bloody diaper (rectal bleeding).

   • It is a red flag for child abuse

   • Meckel’s diverticulum mimic appendicitis in its presentation of acute abdomen.

   • The appendix is also a blind sac

   • Both the appendix and Meckel’s Diverticulum can get obstructed

   • Because Meckel’s Diverticulum can be located anywhere in the last 2 feet of the ileum it is possible for it to present on the left or the right.

   • Infants with Meckel’s Diverticulum cannot afford the blood loss and as a result will not thrive.

   • Surgical repair is the treatment for Meckel’s Diverticulum

   • In adults meckel’s diverticulum is asymptomatic and because they have had it for so long the best thing to do is leave it alone and see if the individual can go the distance.

   • It is possible for these individuals to get an overlay of Zollinger-Ellison

1. Whipple’s is the 3^rd most common IBD

2. Whipple’s can associate itself with EA

3. Older white men mostly get this dx

4. Mr. Whipple from the Charmin commercial needed soft TP for his diarrhea

5. Bowel ds. And joint disease occur – treating 1 gets rid of the other

• Lots of problems come from sx of IBD,

• Chiropractic has 40% success rate w/ IBD, which is same as medical, but no side effects

• IBD - malabsorption, need smaller meals more often, supplement vit & minerals

• A variable combination of chronic or recurrent GI symptoms (attributed to pharynx, esophagus, stomach, SI, etc…) Not explained by structural or biomechanical abnormalities
• Chronic or recurrent
• Lower abdomin pain
• Disturbed defecation – diarrhea or constipation
• Bloating
• NOT EXPLAINED by structural (anatomical) or biomechanical abnormality
• Nervous system seems to be major playor
• So if IBS, that means that all anatomical biomechanical problems have been excluded

Testing showed that IBS pt. Was not just a person with decreased threshold for pain in general, but it is definitely a bowel problem that is neuro in origin

• We even know what neuro tracks are involved
• Genetics and environment play a role
• Bowel symptom improvement parallels psychological improvement
• Stress, anxiety

Treatment

• Adjustments / acupuncture help
• Education of pt - it is not cancer
• Focus on health, not illness
• Some may get antidepressants, but then that can cause more problems for pt
• Exercise can help mental health
• There is not usually a trigger food w/ IBS, but if there is something that bothers them, just avoid that

• Digestive ds that damages SI and decreases absorption
• Essentially have an allergy to gluten (protein in wheat, rye, barley)
• When they eat it, their immune system damages SI
• Starts in jejunum
• Immune system attaches villi (velvety) and leaves behind bowel wall that is flat with no villli - wall is featureless or moonfaced
• No villi = no absorption - malnourished, regardless of quanity of food eaten
• Gold standard for dx is endoscopy w/ biopsy
• Unlike crohn's , no hole developes through the mucosa
• They have eosinophelia (sign of hypersensitivity rxn)
• Signs and symptoms
• Recurring abdominal bloating and pain
• Tough to dx because symptoms look like other ds of GI
• Good test is blood test to see if they have antibodies to gluten - 3 of them
• Screening is not a bad idea
• They screen in Italy - dx comes 2-3 weeks after symptoms start
• In US dx comes > 10 yrs after symptoms
• Tx
• Gluten free diet - can be difficult

• Small bowel vs Large bowel
• Short bowel syndrome - not much bowel left to absorb
• Gall bladder removed - liver empties directly into duodenum, if you eat a huge fatty meal, the liver can’t keep up with enough bile and fat goes by unprepared for absorption….poop out fat
• Disacharidase insufficiency - ex is lactose intolerance
• Lymph obstruction
• Infection of cells of SI or LI - ex is Tropical Sprue
• Excess laxatives
• Some things are global malabsorption, some are just one (think lactose or fat)
• Steatorrhea - fatty stool, common in people w/ cholecystectomy that eats fatty meal, stool floats even after a few minutes
• Need to eat less fat at servings
• Lactose intolerance - eliminated lactose or take an enzyme or take in prepared lactose
  

3 M/c enteritis for malabsorption (if it is global malabsorption - - need lots of diff nutrients)

1. Celiac sprue - m/c

2. Crohn's

3. Chronic pancreatitis

4. Whipples could produce EA

5. Diverticulitis of SI

6. Tropical sprue - they have to have visited to tropics

7. Sx of stomach or SI

Any inflammatory ds that effects both stomach and intestine

• Cholera
  

So it is a group of diseases
It is basically a very broad , generic dx
Probably matching for this topic**



Cholera

• People lie and get sick from dehydration causing the electrolyte imbalance
• You must replace fluid and electrolytes to keep people healthy

E. Coli

• The E. coli strain that is in water in foreign place is new to your system and makes you sick
• Nursery diarrhea - epidemic at one time
• Changing diaper after diaper without washing hands gets organism transferred between infants - introduction of the next strain
• Travelers diarrhea

Staph food poisoning - m/c of food poisonings

• Custard is essentially a good culture media
• Pastries , processed meats, fish
• It produces a toxin that stimulates vomiting center,

Botulinum

• Neurotoxin that has broader effect then the toxin of staph
• Highest mortality rate of all these even with care
• Sustained heat is only way to kill it, microwave leaves pockets that survive

Salmonella

• Found in poultry
• Self limiting
• Can be carrier without being very sick
• Blood testing for antibodies is negative b/c it collects in the feces
• Montezuma's revenge - testing differentiates between the travelers diarrhea

Condition	Histological Characteristics
Normal	Villus to crypt ratio 3 to 4:1, columnar epithelial cells, scattered mononuclear cells in the lamina propria
Disorders in which small intestinal biopsy is diagnostic
Whipple’s disease Hypogammaglobulinemia Abetalipoproteinemia Amyloidosis	Blunting of villi, PAS-positive macrophages in the lamina propria; bacteria by electron microscopy Partial villus atrophy; lack of plasma cells and lymphocytic infiltrate in lamina propria; sometimes nodular lymphoid hyperplasia Enterocytes filled with lipid droplets Amyloid deposition in the mucosa and submucosa
Disorders in which small intestinal biopsy may be diagnostic
Celiac sprue Intestinal lymphangiectasia Intestinal lymphoma Crohn’s disease Parasitic infestations Radiation enteritis Eosinophilic gastroenteritis	Most common cause of total villus atrophy, crypt hyperplasia, lymphocytic infiltration of lamina propria Dilated lymphatics in the lamina propria Infiltration of laminal propria and displacement of crypts with malignant lymphocytes Fissuring, ulcerations, noncaseating granulomas Giardia or cryptosporidia trophozoites attached to epithelial cells; invasive isospora Partial villus atrophy, no crypt hyperplasia, decreased mitoses in crypts Blunting of villi or normal, eosinophils and neutrophils infiltrate mucosa

General Tests of Malabsorption	Comments
Qualitative stool fat Quantitative stool fat D-xylose test Lactose tolerance test (LTT) Hydrogen breath test	Sudan stain of stool; high sensitivity (90%) and specificity (90%) with fat malabsorption >10g/24º. Dependent on adequate fat intake (100g/day). Gold std for fat malabsorption; requires 3-day stool collection and 100g/day fat diet before and during the collection. Normal stool fat: 7.0g/day. Distinguishes mucosal malabsorption from that due to pancreatic disease; high false negative (30%) and false positive (20%) rates. Urine D-xylose (25g/500ml water). Blood levels at 1 and 2 hours improve sensitivity. A 50g oral dose of lactose is given and BS obtained 30 and 120 min. post dose; a rise of >25mg/dl glucose over fasting is normal. LTT has been replaced by the hydrogen breath test which is simpler and more sensitive. An oral dose of lactose (1g/kg BW) is given following basal breath hydrogen levels. A late peak (within 3-6hrs) of >20ppm of exhaled H2 following lactose ingestion is suggestive of lactose malabsorption.
Tests Indicating Deficiency State
CBC, Ca ++, Mg ++, Fe, folate, vitamins B12, A, D, E, albumin, B2, PT, zinc	Deficiency can be caused by other conditions but often indicates malabsorption.
Tests for Pancreatic Function
Secretin stimulation test Bentiromide test	Gold std for pancreatic function. Labor intensive, invasive, requires duodenal intubation and collection of pancreatic juice in response to IV secretin or a meal containing fat, CHO, protein (Lundh meal). A sensitive test of pancreatic fct. N-benzyl-L-tyrosyl-p-aminobenzoic acid (NBT-PABA) is given orally, cleaved in the SB by chymotrypsin to release PABA which is absorbed, conjugated by the liver and excreted in urine. Urine PABA is measured. An indirect measure of pancreatic function and positive only with extensive disease.

Tests for Bacterial Overgrowth
Quantitative cultures of small intestinal aspirate 14C-D-xylose breath test Hydrogen breath test	Gold std for SBBO. Greater than 105 CFU/ml suggests bacterial overgrowth. Requires rapid plating and care to avoid contamination. Diagnostic sensitivity, specificity comparable to that of quantitative culture for dx of SBBO. Nonabsorbable sugar lactulose (1g/kg BW) or glucose is given orally. When bacterial overgrowth present, increased H+ excreted in breath. An early peak (within 2 hrs) of >20ppm exhaled H+ suggestive of bacterial overgrowth.
Tests for Mucosal Disease
Small bowel biopsy Permeability studies	See Table 6 Test of mucosal integrity. Nonabsorbable markers, i.e. mannitol/lactulose or lactulose /51Cr-EDTA are given and urinary excretion measured.
Tests of Ileal Function
Schilling test Bile acid breath test	A test of B12 absorption. Performed as Part 1 then 2,3,4 as needed. Part I: A saturating dose (1mg im) of vitamin B12 is given followed by oral radioactive B12 (0.5-2.0 mcg). Urine collected for 24 hrs; abnormal in all people with B12 deficiency except those with dietary deficiency and food cobalamin malabsorption; Part II: Test repeated with intrinsic factor (IF). Part III: Test repeated with pancreatic enzymes Part IV: Test repeated with antibiotics 14C-labeled cholylglycine is given orally. Normally this BA is absorbed intact in the ileum. In patients with impaired ileal function, the labeled BAs pass into colon where deconjugation and metabolism of glycine to 14CO2 diffuses across tissue and is excreted in breath. Not specific; Abnormal in SBBO.
Tests for Protein Loss
51Cr-albumin test Alpha 1-antitrypsin test (alpha 1-AT)	51Cr-labeled albumin is given IV and 24 stool excretion is measured. Clearance is calculated similar to creatinine. Alpha 1-AT normally found in plasma but hardly in stool. Poorly absorbed once it enters the GI tract and resistant to proteolytic degradation; thus, can be used to measure stool protein loss. Clearance can be determined by measuring serum and stool alpha 1-AT.

A. Impaired Lymphatic Drainage

Intestinal lymphangiectasia can be congenital (malunion of intestinal lymphatics) or due to lymphatic obstruction (lymphoma, tuberculosis, sarcoidosis, retroperitoneal fibrosis, constrictive pericarditis, severe congestive heart failure). Increased pressure in lymphatics results in leak or rupture of lymph into the lumen with resulting loss of fat, protein (albumin, gammaglobulin) and lymphocytes.

Clinical sequelae include 1) fat and fat-soluble vitamin malabsorption, hypoproteinemia, lymphopenia and edema. Diagnosis can be made by intestinal biopsy and management includes a low fat diet supplemented with medium-chain triglycerides (MCTs) and fat-soluble vitamins as needed.

B. Protein-Losing Enteropathy

Individuals with malabsorption present often with hypoalbuminemia and edema. In many instances the low serum albumin is due to loss of protein into the gut lumen at the disease site. Protein loss in the gut may be due to many GI diseases with mechanisms as cited below.

ULCERATION	OBSTRUCTION	UNKNOWN MECHANISM
Inflammatory bowel disease	Lymphoma	Celiac diseases
Shigella	TB	Tropical sprue
Amebic colitis	Sarcoidosis	Whipple’s
Pseudo-membranous colitis	Retroperitoneal fibrosis	Menetriere’s disease
	Constrictive pericarditis	Eosinophilic gastroenteritis

Diagnosis is made by demonstrating increased amounts of alpha-1-antitrypsin in stool.

Factors influencing the efficiency of nutrient uptake:

1. Number of villus absorptive cells present

2. Presence of functional hydrolases and specific nutrient transport proteins on the brush border membrane

3. Transit time

A. Selective Brush Border Disaccharidase Deficiency

Acquired lactase deficiency

1. Most common cause of selective CHO malabsorption in adults

2. Prevalence: highest in Asians, African-Americans, Native Americans;

3. lowest in those of northern European descent

4. Quantity of lactose ingested to produce symptoms varies from individual to individual and depends on a) amount of enzyme present, and b) capacity to salvage wasted lactose in the colon by bacterial metabolism to short chain FAs (SCFAs)

5. Diagnosis depends on a) empiric treatment with lactose-free diet, b) lactose tolerance test, c) hydrogen breath test after oral administration of lactose.

Secondary lactase deficiency with reversible loss of lactase activity may follow injury to small bowel mucosa, e.g. viral gastroenteritis, giardiasis, bacterial overgrowth.

*Lactase is the disaccharidase of lowest abundance in the brush border membrane and thus is the first to be affected with diseases.

B. Congenital enteropeptidase (enterokinase) deficiency is a rare cause of severe

protein malabsorption. Affected infants present with diarrhea, growth retardation

and hypoproteinemic edema.

C. Abetalipoproteinemia is a rare autosomal recessive disease due to mutation of the microsomal triglyceride transfer protein (MTP) which is required for assembly and secretion of apoB-containing lipoproteins (chylomicrons) across the basolateral membrane of intestinal epithelial cells and into lymphatics. Affected children present with severe fat malabsorption and neurologic disorders (retinopathy and spinocerebellar degeneration due to vitamin E deficiency).

D. Diseases Associated with Mucosal Damage

Main mechanism of malabsorption in these disorders is a decrease in absorptive

surface area.

1. Mucosal inflammation and villus flattening

• celiac disease

• tropical sprue

• food allergies

• infections

• food allergies

• graft vs. host disease (GVHD)

• intestinal rejection

• early radiation enteritis

2. Mucosal ulceration

• ulcerative jejunitis

• NSAID-induced ulcer(s)

• ischemia (radiation enteritis, mesenteric ischemia)

3. Surgical resection or bypass

• short bowel syndrome (SBS)

Table 3. Impaired Mucosal Absorption

Clinical Condition/Drug	Mechanism	Biopsy Diagnosis	Malabsorb
Normal Mucosa
Lactase deficiency	 / absent lactase	No	CHO
Abetalipoproteinemia	Mutation MTP	Yes	FATS
Flat Mucosa Infections Giardia	Decreased Surface Area Giardia lamblia	Yes	All Nutrients
AIDS-related	Crypto, Iso, Micro, MAI	Yes
Whipple's	Tropheryma Whippleii	Yes
Celiac diseases	Gluten	No
Tropical sprue	Coliform bacteria?	No
Agammaglobulinemia	Lack of plasma cells	Yes
Drugs
Colchicine	Altered Membrane Traffic	No
Methotrexate	Villus blunting	No

E. Celiac Disease

1. Other terms: celiac sprue, non-tropical sprue, gluten-sensitive enteropathy

2. Etiology: an inflammatory disease of small bowel caused by ingestion of gluten (wheat protein).

3. Prevalence: US 1:4500 (based on GI Sx)

US 1:300

based on serology

Ireland 1:122

4. Associated with dermatitis herpetiformis (DH), a blistering, itching, burning rash on extensor surfaces, buttocks, and back; virtually all patients with DH have abnormal intestinal biopsies.

5. Two factors contribute to the development of celiac disease.
   Ingestion of gluten, a protein found in wheat and related grains, rye, barley, and oats. Toxic portion of protein is gliadin, the alcohol-soluble fraction which is rich in proline and glutamine.

Genetic background. Celiac disease runs in families; approximately 15% of first-degree relatives of affected individuals have celiac disease. There is 70-100% concordance rate in identical twins compared to 30% for nonidentical twins. The disease has been mapped to the HLA-D region on chromosome 6.

6. Onset most commonly at age 2 (after introduction of wheat into diet) and in early adult age but the disease can present any time.

7. Involves primarily the proximal small bowel but can involve ileum and colon.

8. Pathogenesis: Gluten triggers an inflammatory response resulting in villus flattening, which decreases the intestinal surface area available for fluid, electrolyte and nutrient absorption.

9. Clinical presentation is variable:

Diarrhea, weight loss, vitamin and mineral deficiencies

Anemia (iron and/or folate malabsorption)

Bone diseases (osteoporosis)

Neurologic disorders (myopathy, epilepsy, autism)

Gynecologic disorders (infertility, spontaneous abortion)

Psychiatric disorders (depression, schizophrenia)

10. Diagnosis

1. Intestinal biopsy is the “gold standard”.

• Characteristic findings of flat villi or subtotal villus atrophy which reverts to normal with gluten-free diet (GFD)

• A spectrum of mucosal abnormalities:

1. Increased intraepithelial lymphocytes (IEL) and normal villus/crypt architecture

2. Flat/atrophic mucosa

3. Hypoplastic mucosa

2. Serologic markers

Antigliadin antibodies (IgG, IgA) sensitive

Antireticulin antibodies not specific

Antiendomysial (EMA) antibodies (IgA)

Sensitivity 90%

Specificity 100%

* Tissue transglutaminase is the antigen which recognizes the anti-endomysial antibody

Disease or resection of terminal ileum or congenital absence of the ileal BA transporter results in BA malabsorption and wasting in the colon. Increased hepatic synthesis can compensate for BA losses of up to 3 g/day; however, when losses exceed 3 g/day, the enterohepatic BA pool shrinks, resulting in impaired micelle formation and fat malabsorption.

Daily fecal fat excretion remains normal until greater than 100cm of ileum is resected. With less extensive resections, fat absorption is preserved, but bile acid wasting in the colon results in a secretory diarrhea.

Long-term complications of chronic bile salt wasting and fat malabsorption:

1. Renal stones. Oxalate stones occur when unabsorbed FAs within the intestinal lumen bind Ca++ with generation of free oxalate anions which pass into the colon where they are absorbed.

2. Bone disease. Impaired micelle formation results in decreased absorption of vitamin D with resulting decreased calcium absorption.

3. Gallstones. Mechanism is unknown but both cholesterol and pigment (calcium bilirubinate) stones can form.

Impaired Mixing

Surgery altering normal intestinal flow e.g. partial gastric resection with gastrojejunostomy (Billroth II anastomosis) may result in malabsorption.

1. Release of bile and pancreatic secretions distal to the site of entry of gastric contents into jejunum results in poor mixing with resulting impaired lipolysis and micelle formation.

2. Rapid transit through the jejunum contributes to nutrient malabsorption.

3. Afferent loop of bowel not in continuity with intestinal flow predisposes to bacterial overgrowth.

Normally only small numbers (<10>3 organisms/ml) of bacteria (lactobacilli, enterococci gram-positive aerobes, facultative anaerobes), are found in the proximal small bowel, and motility, particularly phase 3 of the migrating motor complex (MMC), is most important in preventing bacterial overgrowth. Important in maintaining the relatively sterile environment of the proximal small bowel are gastric acid (HCl), pancreatic and biliary secretions, mucosal immunity and a competent ileocecal valve (ICV). Conditions which cause stasis or recirculation of colonic contents into the small bowel result in overgrowth of bacteria, mainly coliforms and anaerobes.

The pathophysiology of small bowel bacterial overgrowth (SBBO):

1. Overgrowth of anaerobic bacteria (bacteroides, clostridia) results in release of cholyl-amidases which deconjugate bile acids (BAs). Unconjugated BAs (UBAs) have a higher pKa than conjugated BAs (CBAs) and are predominantly protonated at the normal proximal small bowel pH of 6.0. Protonated UBAs are passively absorbed in the jejunum and are not available for micelle formation.

2. Bacteria release proteases that can damage brush border disaccharidases, in particular lactase, resulting in CHO malabsorption.

3. The effect of bacterial proteases on tight junctions or secondary intestinal inflammation may alter intestinal permeability.

4. Anaerobic bacteria ingest cobalamin (vitamin B₁₂) and synthesize folate.

Clinical manifestations of SBBO include watery diarrhea, steatorrhea, abdominal pain, bloating, and weight loss, and, over time, vitamin B₁₂ and fat-soluble vitamin deficiencies. Serum folate levels remain normal or are elevated, due to bacterial synthesis of folate, and serve to distinguish SBBO from tropical sprue, in which both folate and B₁₂ deficiencies are common. Diarrhea is due to stimulation of colonic secretion by unabsorbed FAs and the osmotic effect of unabsorbed CHOs and FAs.

Diagnosis of SBBO can be made by:

1. Quantitative culture of small bowel aspirate (>10⁵ colony-forming units (CFUs)/ml, the "gold standard."

2. Growth of strict anaerobes.

3. ¹⁴C-xylose breath test.

4. Schilling test pre- and post-antibiotic treatment.

Management includes:

1. Antibiotics, often cycled.

2. Screen for and treat nutritional deficiencies.

3. Lactose-free diet.

4. Medium-chain triglycerides (MCTs) which are not dependent upon micelles for absorption.

5. Supplementation with vitamin B₁₂, A, D, E, K when deficiencies are documented.

6. Prokinetic agents to stimulate motility (e.g. metoclopramide, erythromycin, low dose octreotide (for scleroderma)

diseases that cause malabsorption will be categorized as those that

1) impair intraluminal digestion,

2) impair mucosal absorption, or

3) impair nutrient delivery into the general circulation.

Impaired Intraluminal Digestion

Efficient intraluminal digestion requires regulated release of chyme into the duodenum to allow adequate mixing with pancreatic enzymes and BAs. Pancreatic enzyme activation and micelle formation is most efficient at pH 6.5. Fats are critically dependent on pancreatic enzymes and BAs for transport across the aqueous milieu in the intestinal lumen. Proteins and CHOs are mostly water-soluble and diffuse easily across the unstirred water layer to the brush border membrane of enterocytes. Within the brush border membrane are disaccharidases and proteases which allow adequate digestion of protein and CHO even when more than 90% of the pancreas is destroyed.

Impaired Lipolysis

A number of conditions and drugs impair lipolysis, most common of which is pancreatic insufficiency due to chronic pancreatitis. Fat malabsorption in chronic pancreatitis has two distinguishing features:

1. A high amount of fat in stool, usually greater than 30 g/day. Stools are bulky, greasy, and difficult to flush down the toilet. Watery diarrhea rarely occurs because triglycerides, unlike FAs, do not stimulate water and electrolyte secretion in the colon. Also, large fat droplets exert little osmotic effect.

2. Preservation of fat soluble-vitamin absorption. Gastric lipase (and residual pancreatic lipase) generate adequate FAs for micelle formation in most cases.

Table 1. Clinical Conditions and Drugs Which Impair Lipolysis

Clinical Condition/Drug	Mechanism	Manifestation
Chronic pancreatitis (alcohol, tropical, cystic fibrosis (CF)) Pancreatic Ca	 Enzyme secretion	Steatorrhea (bulky, fat-laden stool) Rarely, fat-soluble vitamin deficiency
Somatostatinoma
Zollinger-Ellison Syndrome (ZES)	Denatured lipase
Congenital	Absent pancreatic lipase, colipase
Drugs: orlistat octreotide	Lipase inhibitor  Enzyme secretion
Mucosal Diseases	CCK secretion

Impaired Micelle Formation

In general, fat malabsorption due to impaired micelle formation is less severe than that due to pancreatic lipase deficiency. This relates to the fact that fatty acids (FAs and monaglycerides (MGs), to some extent, can form lamellar structures which diffuse through the aqueous milieu of the lumen to the brush border membrane. Individuals with impaired micelle formation present with watery diarrhea and after prolonged illness, fat-soluble vitamin deficiencies. The diarrhea is watery due to the secretory effects of unabsorbed FAs on the colon.

Table 2. Clinical Conditions and Drugs Which Impair Micelle Formation

Clinical Condition/Drug	Mechanism	Manifestation
Primary Biliary Cirrhosis (PBC) Cirrhosis secondary to duct obstruction	 BA delivery  BA synthesis	Watery diarrhea, steatorrhea Fat-soluble vitamin deficiency
Bacterial overgrowth	BA deconjugation
Ileal disease/resection	BA malabsorption
Zollinger-Ellison Syndrome (ZES)	BA precipitation
Cholestyramine	BA binder

General Issues:

Malabsorption can be due to many diseases (intestinal or extraintestinal) and/or medications which impair nutrient digestion, absorption or delivery. Symptoms depend on

1) the nutrient(s) malabsorbed,
2) the location or site of disease, and
3) extent of diseases.

Clinical consequences of fluid, electrolyte and nutrient (FEN) malabsorption are listed in Table 1.

Malabsorption of fat and CHO will result in symptoms including abdominal cramping pain, bloating, diarrhea, and weight loss. A careful history is important and guides the physician to tests which will confirm the clinical suspicion of malabsorption and should lead to a correct diagnosis.

Goals in management include:

1) treatment of the disease, when possible,
2) repletion of nutritional deficiencies, and
3) repletion of fluid and electrolyte losses.