Disorders of the Small Bowel

Definition

• persistence or recurrence of signs, symptoms, and/or laboratory abnormalities consistent with active celiac disease despite treatment with gluten free diet for at least 6 mo

• Causes

  • SIBO

  • microscopic colitis 

  • refractory celiac disease (RCD) - persistent clinical symptoms and villous atrophy on histology despite strict adherence to gluten free diet for at least 12 mo

  • food intolerances

  • tropical sprue

  • IBD

  • malignancy

Definition

• persistent clinical symptoms and villous atrophy on histology despite strict adherence to gluten free diet for at least 12 mo

• Type 1 - normal intraepithelial T lymphocytes

• Type 2 - aberrant intraepithelial T lymphocytes (prevalence of abnormal cells >20%)

  • Differentiate between type 1 and 2 with flow cytometry

Risk Factors

• older age (particularly when diagnosed >50 yo)

Imaging Findings

• MR enterography and capsule endoscopy may be useful to evaluate the remainder of the small bowel for...

  1. additional etiologies if celiac disease otherwise well controlled

  2. suspicion of malignancy (ex. lymphoma)

  3. more distal small bowel lesions in RCD (ex. ulcerative jejunitis)

Pathology

• Type 1 - normal immunophenotype on flow cytometry without colonal T cell receptor 

• Type 2 - abrnormal immunophenotype on flow cytometry with increased CD3 positive cells and absent CD8

  • may progress to enteropathy-associated T cell lymphoma

Definition

• pathologic overgrowth of bacteria in the upper small intestine

Risk Factors

Signs and Symptoms

• watery, non-bloody diarrhea

• recurrent bacterial pneumonias

• iron deficiency anemia

• low 25-OH vitamin D

Diagnosis

Pathology Findings

• villous atrophy

• increased intraepithelial lymphocytes

• crypt hyperplasia

• absent plasma cells (versus increased in celiac disease)

Lab Findings

• negative celiac serologies

Treatment for GI symptoms

• Initial treatment - prednisone or budesonide

• Steroid dependent or refractory cases - infliximab or other anti-TNF agents

Definition

• rare disorder

Signs and Symptoms

• severe secretory diarrhea

• weight loss secondary to malabsorption

• associated with other autoimmune conditions

  • rheumatoid artritis

  • multiple sclerosis

Risk Factors

• associated with Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

Diagnosis

• rule out other causes of chronic diarrhea

• specific histology supportive of AIE

• presence of malabsorption and ruling out other causes of villous atrophy

• Supportive of diagnosis

  • anti-enterocyte antibodies (absence does NOT exclude diagnosis)

  • anti-goblet cell antibodies (absence does NOT exclude diagnosis)

Pathology Findings

• villous atrophy of the small intestinal mucosa

• decreased goblet and Paneth cells

• absence of surface intraepithelial lymphocytes

• increased crypt apoptosis

Treatment

• First line: oral steroids (systemic prednisone or topical budesonide)

• Second line: mycophenolate mofetil, azathioprine, cyclosporine

Definition

Signs and Symptoms

• diarrhea

• abdominal pain

• weight loss

Risk Factors

• Often results with progression from type 2 refractory celiac disease

Diagnosis

• abnormal immunophenotype on flow cytometry from duodenum biopsies

  • increased CD3 positive cells

  • absent CD8

  • similar findings in type 2 refractory celiac disease

Pathology Findings

• villous atrophy of the small intestinal mucosa

Signs and Symptoms

• diarrhea

Endoscopic Findings

• small bowel ulcerations, perforations

• diaphragm-like strictures

  • usually thin, concentric, diaphragm-like septa with a pinhole-sized lumen

  • considered pathognomonic for NSAID-induced enteropathy

  • risk of perforation is low with endoscopic dilation

Pathology Findings

• partial villous atrophy

• increased intraepithelial lymphocytes

• acute ileitis without architectural distortion

• diaphragm-like stricture biopsy

  • fibrosis of the submucosa with intact muscularis propria

Imaging Findings

• CT enterography - diaphragm-like stricture in the proximal ileum (specific to NSAID enteropathy)

Lab Findings

• negative celiac serologies

Definition

• can present in latent form >10 y from exposure with symptoms of chronic malabsorptive diarrhea

• Endemic to ...

  1. Caribbean

  2. southern and southeast Asia

  3. less commonly Middle east and Africa

Signs and Symptoms

• folic acid deficiency 

• similar symptoms to SIBO

• steatorrhea

• glossitis

• pitting pedal edema

• distended abdomen

Endoscopic Findings

• villous atrophy - similar to celiac disease but less severe

• increased plasma cells, eosinophils, and lymphocytes in lamina propria

Lab Findings

• decreased folate

• macrocytic anemia

• slightly decreased albumin

• positive fecal fat

Treatment

• 3-6 mo course of folic acid  + tetracycline 250 mg four times daily 

Versus

• SIBO - transient response to ciprofloxacin and metronidazole, elevated B12

Definition

• pathologic overgrowth of bacteria in the upper small intestine

Risk Factors

• altered anatomy (ex. gastric bypass, small bowel strictures, blind limbs)

• altered motility (ex. gastroparesis, small bowel dysmotility, prior radiation therapy)

• small bowel diverticulosis

• type 1 diabetes with autonomic neuropathy

• primary systemic scleroderma

• celiac disease

• immunodeficiency (ex. IgA deficiency)

• pancreatic insufficiency

• gastric hypochlorhydria from atrophic gastritis or from medications like PPIs

• can also be triggered after antibiotic use - leads to an imbalance of bacterial flora of the gut

Signs and Symptoms

• watery diarrhea

• bloating

• increased flatulence

• malabsorption (ex. fat soluble vitamins)

• protein losing enteropathy

Diagnosis

• Lactulose (first line) or glucose breath test

  • assess for hydrogen and methane after ingestion of a substrate

    • absolute increase of greater than or equal to 20 ppm hydrogen above baseline within 90 min

    • baseline hydrogen >20 ppm may indicate non-adherence to test protocol for fasting and restriction of specific complex carbohydrates and will require repeat testing

    • SIBO breath testing should be performed prior to lactose or fructose breath testing

  • variable accuracy can be affected by...

    • acid suppressing agents

    • promotility drugs

    • laxatives

    • antibiotics

    • probiotics

• Hydrogen breath test 

  • variable sensitivity and specificity with frequent false positive and false negative results

Lab Findings

• fat soluble vitamin deficiency (A, D, E)

• malabsorption of iron

• hypoalbuminemia

• increased or normal vitamin K due to synthesis by enteric bacteria

• increased or normal folate 

  • due to bacterial production of folate

• decreased vitamin B12

  • results from competitive uptake of B12 from bacteria

• slight anemia, macrocytosis

Treatment

• rifaximin for 10 days

• amoxicillin/clavulanate 

• Methane predominant SIBO

  • Rifaximin + neomycin

• reversal of altered anatomy if possible

• If underlying cause of SIBO is non-reversible - treat with cycling antibiotic

Definition

Signs and Symptoms

• chronic constipation

• bloating

• abdominal distension

Versus

• SIBO is seen with diarrhea

Diagnosis

• Lactulose (first line) or glucose breath test

Treatment

Risk Factors

• chronic inflammatory conditions (ex. Crohn's disease, ankylosing spondylitis)

Signs and Symptoms

• recurrent post-polypectomy bleed

  • consider senile amyloidosis

    1. found in 10-36% of those >80 yo

    2. typically affects heart and to a lesser extent the GI tract

    3. amyloid deposits in the sub-serosal veins in the small/large intestine

• malabsorption

• diarrhea

• abdominal pain

• weight loss

• ulceration resulting in gastrointestinal bleeding

• rarely perforation of the bowel

• restrictive cardiomyopathy

• CKD

• peripheral neuropathy

• periorbital edema

• Other symptoms of gastrointestinal amyloidosis

  • features of dysmotility 

    1. gastroparesis

    2. dysphgia

    3. GERD

    4. intestinal pseudo-obstruction

    5. SIBO

  • features of protein losing enteropathy 

    1. pleural/pericardial effusions

    2. malabsorptive diarrhea

    3. edema

    4. hypoalbuminemia 

Diagnosis

• Gold standard - biopsy

Endoscopic Findings

• granular mucosa with polypoid protrusions

Pathology Findings

• Congo Red staining with apple-green birefringence under polarized light

  • biopsy in rectum or duodenum

Lab Findings

• Positive stool alpha-1 antitrypsin - indicative of protein losing enteropathy

  • also seen in primary intestinal lymphagectasia, Crohn's disease of small intestine, SIBO

  • NOT seen in Celiac disease

  • not usually in ulcerative colitis

• elevated gamma globulins in AA amyloidosis - due to chronic inflammation due to chronic inflammation from associated conditions

Treatment

• supportive care

• anti-diarrheal therapy

• nutritional supplementation

• treatment of underlying disorder

Definition

• also known as Waldmann's disease

• rare condition characterized by dilation of the intestinal lymphatics which blocks effective fluid drainage leading to a subsequent loss of lymph fluid into the GI tract

Risk Factors

• associated with...

  1. Recklinghausean syndrome

  2. Turner syndrome

  3. Hennekam syndrome

Signs and Symptoms

• protein losing enteropathy which may result in...

  1. lymph edema

  2. peripheral edema

  3. serous effusion - particularly pleural and pericardial effusions

  4. hypoalbuminemia

  5. hypogammaglobinemia

  6. fat-soluble vitamin deficiencies 

Endoscopic Findings

• dilated lymphatics in the second part of the duodenum

• creamy yellow-white appearance of jejunal villi

Pathology Findings

• dilated lymphatics in the mucosal and submucosal layers

Lab Findings

• positive stool alpha-1 antitrypsin (present in protein losing enteropathy)

Treatment

• low-fat diet supplemented with medium chain triglycerides

• goal to minimize engorgement of lymphatics

  • medium chain triglycerides are directly absorbed so do not cause further lymphatic dilation

Versus

• Secondary intestinal lymphangiectasia - similar symptoms but is caused by impaired lymphatic flow from lymphoma, right sided heart failure, and thoracic duct outlet obstruction

Definition

• caused by impaired lymphatic flow, such as from lymphoma, right sided heart failure, and thoracic duct outlet obstruction

Signs and Symptoms

• protein losing enteropathy

• fat malabsorption

Risk Factors

• prior radiation therapy to lymph nodes in abdomen

Endoscopic Findings

• creamy yellow-white jejunal villi

  • indicates dilated lymphatic vessels

• WITHOUT duodenal scalloping, ulceration, friability, or angioectasias 

Lab Findings

• hypoalbuminemia

• elevated fecal alpha-1-antitrypsin (normal < 27 mg per 100 mL)

  • indicates luminal protein loss

Treatment

• First line: low fat diet with medium-chain triglycerides

• LeVeen shunt (peritoneovenous shunt) - alternative to decompress the blockage of lymphatic fluid - only after failing to improve with dietary changes

Definition

• acute occlusion of blood vessel with emboli, thrombi, or potentially vasoconstriction resulting in damage to the bowel

• mortality rate >50%

• intestinal viability decreases to nearly 18% after 24 hr from symptoms onset

Risk Factors

• older age

• hypercoagulable state (ex. Protein C deficiency)

• chronic heart failure

• sepsis

• recent myocardial infarction

Signs and Symptoms

• severe acute abdominal pain out of proportion to exam

Diagnosis

• CT angiography or MR angiography

Treatment

• emergent surgical revascularization

• exploratory laparotomy may be required if signs peritonitis are present on exam

Definition

• chronic blood vessel narrowing due to atherosclerosis

Signs and Symptoms

• sitophobia

Diagnosis

• Balloon tonometry

Treatment

• elective percutaneous transluminal mesenteric angioplasty 

Definition

• affects small and medium sized arteries

• associated with Hepatitis B

Signs and Symptoms

• often affects small intestine and gallbladder resulting in pneumatosis, infarction, or perforation

Versus

• Rheumatoid vasculitis also affects small and medium sized vessels, presents many years after onset of rheumatoid arthritis

Definition

• a necrotizing, systemic vasculitis

Risk Factor

• young males

Signs and Symptoms

• ulcerations of the oral mucosa and genitalia

• can also involve 

  1. joints

  2. CNS

  3. eyes

  4. GI tract - predominantly small bowel

Diagnosis

• positive pathergy test

  • 8.6% positivity in India

  • 70.7% positivity in China

Endoscopic Findings

• small bowel deep cratered ulcerations which may result in bleeding or perforation

Treatment

• corticosteroids, sulfasalazine, and azathioprine  can induce remission, avoiding surgery

  • limited clinical trials

• Resistant or complicated cases

  • TNF-alpha antagonists

  • thalidomide

Versus

• acute bleed from small bowel Crohn's disease - uncommon and usually characterized by punctate ulcerations 

• surreptitious NSAID use - common cause of GI bleed but would not have ulcers at genitalia

• mast cell disorder - may be associated with diffuse ulcerations but typically have maculopapular cutaneous lesions (not ulcerations of the oral mucosa)

• Takayasu arteritis - female predominant, common in Asian descent

Definition

• self-limited, systemic, non-granulomatous, autoimmune complex, small vessel vasculitis with multiorgan involvement

Signs and Symptoms

• Classic tetrad

  • nonthrombocytopenic palpable purpura

  • arthritis or arthralgias

  • gastrointestinal involvement

    • may mimic Crohn's disease

  • renal involvement

Treatment

• most cases self limited

• in cases with severe colicky abdominal pain treat with oral steroids

  • prednisone or methylprednisolone (1-2 mg/kg/day for 1-2 weeks) then taper over 1-2 wks

  • steroids may prevent complications (ex. GI bleed or intussusception)

• in cases without benefit from steroids alone

  • high-dose IV pulse steroids with immunosuppressive drugs (cyclophosphamide, azathioprine, cyclosporine A, and mycophenolate mofetil)

Defintion

• Systemic mastocytosis - systemic disorder characterized by expansion of mast cells into various organs

• mast cell activation results in excess release of vasoactive mediators leading to presentation similar to anaphylaxis

• bone marrow and GI tract are common extracutaneous sites for mast cell accumulation

Signs and Symptoms

• abdominal pain

• diarrhea, nausea, vomiting

  • may be related to increased gastric acid hypersecretion due to excess circulating histamine - can be associated with GI bleed

• itching

• flushing

• maculopapular rash

  • urticarial pigmentosa (diffuse macular or maculopapular rash beginning at the extremities progressing to involve the abdomen and chest

• worsening symptoms with alcohol

Diagnosis

• One major and one minor criterion 

• Three minor criterion

• Major criterion

  1. presence of >15 mast cells detected by tryptase staining in the bone marrow or extracutaneous organs

• Minor criterion

  1. atypical morphology in > 25% of mast cells

  2. codon 816 mutation of KIT (the gene for c-kit)

  3. mast cells expressing CD2 and/or CD25 in the bone marrow or extracutaneous organs

  4. serum tryptase levels >20 ng/mL

     • nonspecific - can also be elevated in AML, CML, MDS

• Skin biopsy alone is not sufficiency for diagnosis of systemic mastocytosis

Endoscopic Findings

• gastric and duodenal ulcers (multiple superficial ulcerations)

  • caused by increase in histamine from mast cell activation resulting in an activated parietal cell and increased acid production

• absence of esophageal findings

Pathology Findings

• biopsy showing KIT/CD117 leukocyte antigen and potentially increased tryptase

Treatment

• Anti IgE humanized monoclonal antibody (ex. omalizumab) and cromolyn sodium

  • used to control diarrhea associated with mast cell disorder

Versus

• gastric adenocarcinoma - typically a single discreet ulceration 

• gastrinoma - typically associated with esophagitis, duodenal ulcers, and diarrhea

Definition

Signs and Symptoms

• can present with esophageal, gastric, duodenal, and colonic disease

• dysphagia

• abdominal pain

• diarrhea

• malabsoprtion

• obstruction

Diagnosis

• Biopsy

  • eosinophilic infiltration can be patchy

  • multiple biopsies throughout suspected areas are required

Endoscopic Findings

• furrowed esophagus with concentric ring like appearance

• erythema in antrum

• erythematous duodenum

• ulcerated, inflamed mucosa in recto-sigmoid

Pathology Findings

• mucosal biopsy with eosinophil count >20-25% per HPF 

• antral biopsies negative for H pylori

• duodenal biopsies show villous blunting 

Lab Findings

• peripheral eosinophilia and elevated serum IgE

  • associated but not always present

Treatment

• corticosteroids

Versus

• other conditions may be associated with eosinophilic infiltrate on mucosal biopsy

  • parasite infection

  • medication related mucosal injury (ex. NSAIDs)

  • malignancy (ex. lymphoma and gastric cancer)

  • IBD

Definition

• most common  GI tumors of the mesenchymal origin

• believed to arise from interstitial cells of Cajal 

• predominantly found in stomach, small intestine, or rectum 

  • most commonly stomach > jejunum/ileum

  • can be found anywhere along the GI tract

• lymph node metastasis is rare

Risk factors

• often found in sixth decade of life

Signs and Symptoms

• usually presents with bleeding, intussusception, or abdominal pain

Diagnosis

• biopsy

Pathology Findings

• positive staining for KIT/CD117 leukocyte antigen on histology

• platelet derived growth factor receptor (PDG-FRA)

• non-mucosal mass

Treatment

• surgical resection

  • 50-60% cured with complete surgical resection alone

  • 40-50% relapse and require additional therapy (ex. imatinib)

• Metastatic, recurrent, or inoperable 

  • Imatinib (tyrosine kinase inhibitor)

• Progression despite treatment with imatinib

  • sunitinib maleate (multi-target inhibitor)

• Progression on sunitinib

  • regorafinib (multi-target inhibitor) 

  • or re-challenge with imatinib

Versus

• Melanoma of the GI tract - often found in small bowel or rectum, but positive for PS-100 and HMB-45

• Small bowel adenocarcinoma - mucosal, NOT submucosal

Risk Factors

• Crohn's disease or other chronic inflammatory states

Pathology Findings

• mucosal, NOT submucosal

Definition

Treatment

• dietary manipulation

• oral rehydration solutions

• Conservative management - loperaminde, atropine/diphenoxylate, tincture of opium

• glucagon-like peptide-2 agonist (ex. teduglutide)

  • indicated for short bowel syndrome with intestinal failure

  • Teduglutide is thought to stimulate mucosal growth and promote intestinal absorption

  • decreases stool output and improves quality of life

• somatostatin and its analog octreotide have been used to minimize refractory high-output stomal fluid losses

  • inhibits gastric, pancreatic, and intestinal secretions

  • however, affects enteral utilization of amino acids for splanchnic protein synthesis and interferes with physiologic postresection adaptation

Indication

• patients with intestinal failure with resulting nutritional and metabolic complications

• TPN failure for the following reasons

  1. impending or overt liver failure

  2. thrombosis of major central venous channels (two thromboses in subclavian, jugular, or femoral veins)

  3. frequent line infections (two episodes of systemic sepsis due to line infection OR one episode of line related fungemia OR septic shock or ARDS due to line infection)

  4. frequent severe dehydration

Exclusions

• metastatic malignancy

• chronic systemic infections

• HIV infection

Post-transplant course

• Immune suppression - often with tacrolimus and prednisone

• If no anastomotic leak on imaging, enteral feeding introduced about one week post-op

Post-operative Complications

• acute rejection (79%)

• chronic rejection (13%)

• CMV eneteritis

• post-transplant lymphoproliferative disorder (PTLD)

• Life expectancy at one year: 75-85%

• Long term survival at five to ten years: 60%

Defintion

• rare complication of cholecystectomy (occurs in 0.07-0.09% of cases)

Diagnosis

• upper GI series with gastrografin to localize the site of the leak

Imaging Findings

• CT - fluid collection around the duodenum within the retroperitoneal space 

Lab Findings

• Serum and fluid from percutaneous drain - elevated amylase and bilirubin

Treatment

• perforation is a relative contraindication to endoscopic evaluation 

Defintion

• congenital anomaly

• due to incomplete obliteration of the vitelline duct

• ectopic gastric mucosa with acid scretion that may lead to ulceration of the ileum

• ectopic pancreatic tissue may also be present

Diagnosis

• technicium-99m pertechnetate scan

Signs and symptoms

• Hematochezia, often self limited with unremarkable work up with EGD, colonoscopy, and VCE

Defintion

• Duodenum

  • Iron

  • Folate

  • Additional nutrients same as jejunum

• Jejunum

  • Water soluble vitamins

  • Fats

  • Sugars

  • Amino acids

  • Lactose

  • Calcium

• Distal ileum

  • Vitamin B12