1. Malabsorption Disorders – Overview

1.1 Epidemiology

• Malabsorption is a broad term encompassing a range of disorders involving impaired nutrient absorption.
• Precise incidence/prevalence varies with region and underlying cause (e.g. tropical sprue in endemic areas, coeliac disease in Western populations).
• Often under-diagnosed because of non-specific presentations, such as mild GI symptoms, mild weight loss, or vague fatigue.

1.2 Aetiology

Malabsorption typically arises from three main categories:

1. Structural or Mucosal Disorders
   • Pancreatic (e.g. chronic pancreatitis).
   • Small bowel (e.g. villous atrophy).
   • Biliary tree (e.g. cholestatic disease).
2. Abnormal Luminal Digestion
   • Metabolic defects (rare causes, e.g. congenital enzyme deficiencies).
   • Intraluminal factors (e.g. insufficient bile salts, bacterial overgrowth, or other disruptions).
3. Combined Deficiencies
   • Most disorders affect multiple nutrients (fats, proteins, carbohydrates) and possibly vitamins/minerals.
   • Isolated malabsorption of a single nutrient is relatively uncommon.

1.3 Pathophysiology

1. Normal Digestive Processes
   • Ingested nutrients require mechanical and chemical breakdown in the stomach and small intestine, involving pancreatic enzymes, bile salts, and mucosal absorption.
   • Small bowel epithelium (villi, microvilli) and normal mucosal blood flow are essential for effective absorption.
2. Mechanisms Leading to Malabsorption
   • Mucosal Abnormalities: Villous atrophy or damaged epithelium reduces the surface area (e.g. coeliac disease, infection).
   • Pancreatic Insufficiency: Deficient enzyme production (e.g. chronic pancreatitis), leading to incomplete luminal digestion, especially of fats.
   • Biliary Tree Dysfunction: Inadequate bile salts cause poor micelle formation and steatorrhoea.
   • Metabolic Defects: Rare inherited or acquired enzyme defects (e.g. carbohydrate intolerance) hamper specific nutrient assimilation.
3. Consequences
   • Fat malabsorption → steatorrhoea, deficiency of fat-soluble vitamins (A, D, E, K).
   • Protein malabsorption → hypoalbuminaemia, oedema, ascites.
   • Carbohydrate malabsorption → osmotic diarrhoea, bloating.
   • Micronutrient deficiencies → anaemia, neuropathy, bone disorders, etc.

1.4 Risk Factors

• Chronic GI diseases (e.g. coeliac, Crohn’s, chronic pancreatitis).
• Bacterial/parasitic infections (e.g. giardia, tropical sprue in endemic areas).
• Structural abnormalities (surgical resection, bypass).
• Genetic or congenital enzyme defects.

1.5 Clinical Features

1.5.1 General Symptoms

• Malaise and fatigue.
• Anorexia, abdominal bloating.
• Diarrhoea: Typically increased stool bulk rather than frequency (contrast with colonic disease).
• Weight loss (check body mass index, BMI).

1.5.2 Specific Indicators by Nutrient Deficiency

• Steatorrhoea = fat malabsorption (often severe in pancreatic vs. small bowel diseases).
• Oedema/ascites = protein deficiency.
• Paraesthesiae/tetany = Ca2+ or Mg2+ deficiency.
• Skin rash = Zn2+ or B-vitamin deficiency.
• Cheilitis/glossitis = B-vitamin deficiency.
• Neuropathy, psychological changes = B12 deficiency.
• Night blindness = vitamin A deficiency.
• Bruising = vitamins K or C deficiency.
• Bone pain, myopathy, osteoporosis = vitamin D deficiency.

1.6 Diagnostic Approach

Investigations focus on:

• Blood tests for consequences of malabsorption:
  • Anaemia profile (iron, B12, folate).
  • Calcium, magnesium, albumin, vitamins.
  • Coeliac serology or other disease-specific markers.
• Stool tests:
  • Faecal fat measurement (Sudan stain for fat globules).
  • Elastase (pancreatic function).
  • Microscopy (infection/parasites).
• Imaging / Endoscopy:
  • Small bowel imaging (e.g. MRI, CT enterography) to detect structural pathology.
  • Upper GI endoscopy ± small bowel biopsy if suspect coeliac or other mucosal disease.
  • Evaluate pancreas and biliary tree if exocrine insufficiency or cholestasis is suspected.
• Breath hydrogen test for bacterial overgrowth or carbohydrate malabsorption.

1.7 Management

• Identify and address the underlying cause (e.g. treat infection, correct structural lesion, manage coeliac disease with gluten-free diet, exocrine pancreatic insufficiency with enzyme supplementation).
• Nutritional support: Supplement missing macronutrients/micronutrients (e.g. vitamins, minerals) and consider high-protein, high-energy diet or enteral feeding in severe malnutrition.
• Symptomatic relief: Anti-diarrhoeal medication, acid suppression if indicated, and supportive therapies.

1.8 Prognosis / Complications

• Varies widely depending on cause and reversibility.
• Chronic malabsorption leads to recurrent deficiency states, e.g. osteopenia/osteoporosis, anaemia, and potential growth/neurological sequelae.
• Early identification and targeted treatment of the underlying pathology significantly improves outcomes and quality of life.

2. Coeliac Disease

2.1 Epidemiology

• Coeliac disease is a T-cell-mediated inflammatory disorder of the small bowel.
• Prevalence in the UK is about 1 in 200, with half the cases possibly ‘silent’.
• More frequent in females, less common in black and Oriental populations.
• Typically presents in childhood (as soon as weaning occurs), or in later adulthood (peak in 50s–60s).

2.2 Aetiology

• Immune response triggered by gluten, a protein found in wheat, barley, rye (but not in oats or rice).
• The pathogenic antigenic component is α‐gliadin.
• Chronic exposure leads to a T-cell‐mediated (type IV) reaction, causing villous atrophy that reverses on gluten withdrawal.
• Strong genetic association with HLA‐DQ2 (and to a lesser extent DQ8).
• Frequently coexists with other autoimmune disorders (e.g. dermatitis herpetiformis, type 1 diabetes, thyroid disease).

2.3 Pathophysiology

1. Gliadin Processing
   • Ingested α-gliadin is deamidated by tissue transglutaminase (tTG) in the intestinal mucosa.
   • The deamidated peptides are presented by antigen-presenting cells via HLA-DQ2/DQ8 molecules.
2. T-Cell Activation
   • Helper T-cells drive an inflammatory reaction in the small bowel mucosa (particularly duodenum).
   • This results in villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis (IEL).
   • The combined effect reduces the absorptive surface area, leading to malabsorption.
3. Autoimmune Features
   • The disease also generates IgA antibodies against endomysium, tissue transglutaminase, and gliadin.
   • However, the key pathogenic mechanism is T-cell driven rather than antibody mediated.

2.4 Risk Factors

• Genetic: HLA-DQ2 (95% of patients), also DQ8.
• Family history (first-degree relatives have ~6× relative risk).
• Other Autoimmune Diseases: Dermatitis herpetiformis, type 1 diabetes, autoimmune thyroid disease.
• Possible triggers: early wheat introduction in infancy or gut infections.

2.5 Clinical Features

2.5.1 Children

• Infants: Diarrhoea, malabsorption, failure to thrive upon weaning to cereal-based foods.
• Older children: Abdominal pain, anaemia, short stature, delayed puberty.

2.5.2 Adults

• Often more non-specific or mild:
  • Abdominal bloating, lethargy.
  • Diarrhoea or sometimes constipation.
  • Weight loss, or can be minimal.
  • Iron-deficiency anaemia is common.
  • Rare: aphthous mouth ulcers, psychiatric disturbances.
• May present with associated autoimmune conditions or dermatitis herpetiformis (itchy blistering rash on extensor surfaces).

2.6 Diagnostic Approach

1. Blood Tests
   • Haematinics: Check for iron, B12, folate deficiency.
   • Coeliac Serology: IgA antibodies to tissue transglutaminase (tTG), endomysium, and gliadin.
     • In IgA deficiency, rely on IgG tests.
   • HLA-DQ2 / DQ8 negativity essentially excludes coeliac but positivity is not diagnostic alone, as many unaffected people carry these haplotypes.
2. Duodenal Biopsy (Gold Standard)
   • On a gluten‐containing diet to demonstrate villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis.
   • Biopsy is essential if serology is positive or suspicion is high.
3. Assessing Consequences
   • FBC for anaemia type (micro- or macrocytic), blood film for hyposplenism (Howell–Jolly bodies).
   • Vitamin levels (A, D, E, K, B12, folate), coagulation (vit K), and bone density if osteopenia is suspected (DEXA scan).

2.7 Management

1. Lifelong Gluten‐Free Diet
   • Avoid wheat, barley, rye; note that oats are often tolerated but introduced cautiously.
   • Dietitian support is crucial.
   • Correct nutritional deficiencies (anaemia, vitamins/minerals).
2. Address Complications
   • Aggressive management of bone disease (calcium, vitamin D supplementation).
   • Vaccinate if hyposplenic (pneumococcal, influenza).
   • Monitor for GI T‐cell lymphoma (rare) if refractory to diet.
3. Refractory Cases
   • Ensure dietary compliance (some remain exposed to hidden gluten).
   • Exclude secondary conditions: lactase deficiency, microscopic colitis, IBS.
   • Rare: immunosuppressants if truly refractory due to suspected small bowel T‐cell lymphoma or ulcerative jejunitis.

2.8 Prognosis / Complications

• Excellent if compliant with diet: ~90% achieve lasting remission.
• ~10% persist with symptoms, mostly from ongoing gluten exposure or associated IBS/lactose intolerance.
• Rare progression to refractory coeliac or small intestinal T-cell lymphoma.
• Overall good life expectancy if properly treated, with improved quality of life and resolution of deficiency states.

3. Tropical Sprue

3.1 Epidemiology

• Tropical sprue is very rare in most parts of the world but seen in specific tropical regions (Far and Middle East, Caribbean).
• The condition mostly affects long-term residents rather than short-term travellers.
• Unclear incidence data, but considered uncommon even in endemic regions.

3.2 Aetiology

• Precise cause remains unknown; suspected bacterial infection in susceptible individuals.
• Occurs in tropical areas; frequently associated with chronic diarrhoea and malabsorption.

3.3 Pathophysiology

1. Post-Infectious Mechanism
   • Likely triggered by an unknown microbial factor leading to small bowel mucosal damage.
   • This results in villous atrophy (similar in appearance to coeliac disease), but the underlying inflammatory process is thought to be non-immune.
2. Malabsorption
   • Mucosal abnormality causes impaired absorption of multiple nutrients: folate, B12, fats, etc.
   • Bacterial overgrowth may exacerbate these malabsorptive changes, further compromising nutrient uptake.
3. Nutrient Deficiencies
   • Particularly folate and vitamin B12 deficiency, leading to megaloblastic anaemia if untreated.
   • General features of protein, fat, or vitamin malabsorption can also occur.

3.4 Risk Factors

• Residence (long-term) in endemic tropical regions (Far and Middle East, Caribbean).
• Possibly post-infectious context or bacterial overgrowth, though precise triggers are not definitively established.

3.5 Clinical Features

• Chronic diarrhoea (+/- steatorrhoea).
• Abdominal distension, bloating.
• Malabsorption symptoms: weight loss, fatigue.
• Deficiencies of folate, B12, or other micronutrients cause megaloblastic anaemia and related manifestations (e.g. glossitis, neuropathy).

3.6 Diagnostic Approach

1. Differential Diagnosis
   • Giardiasis must be excluded (common alternative cause of malabsorption in tropical settings).
   • Coeliac disease presents similarly but typically occurs outside tropical contexts.
2. Laboratory Tests
   • Evidence of folate and/or B12 deficiency (macrocytic anaemia).
   • General malabsorption tests (stool fat measurement if indicated).
   • Check stool microscopy to rule out parasitic causes.
3. Small Bowel Biopsy
   • Shows villous atrophy, but less severe than coeliac and not specifically associated with gliadin-driven immune changes.
   • Must consider local availability of endoscopic/biopsy procedures.

3.7 Management

• Long-term tetracycline (commonly suggested dosage: 250 mg every 6 hours) plus folic acid (5 mg daily) for 3–6 months is the traditional approach.
  • Folate supplementation often leads to rapid clinical improvement (especially in megaloblastic anaemia).
  • Vitamin B12 supplementation may be necessary if deficiency is present.
• Correct nutritional deficiencies (especially B12 and fat-soluble vitamins).
• Consider bacterial overgrowth management if suspected (antimicrobials).

3.8 Prognosis / Complications

• With appropriate antibiotic and folate supplementation, outcomes are usually good.
• Failure to respond should prompt reconsideration of diagnosis (e.g. persistent infection, coeliac disease, or another malabsorption aetiology).
• Potential complications revolve around persistent malabsorption (anaemia, vitamin deficiencies).

4. Small Intestine Bacterial Overgrowth

4.1 Epidemiology

• SIBO is rare in healthy individuals; prevalence depends on the incidence of underlying predisposing factors.
• More common in specific populations: post-GI surgery, motility disorders (e.g. systemic sclerosis), and certain immunodeficiencies.

4.2 Aetiology

SIBO arises from excessive colonisation of the small intestine by colonic-type bacteria (or abnormal bacterial flora). Key mechanisms include:

1. Gut Dysmotility
   • Impaired peristalsis or migrating motor complex (MMC) → bacterial stasis in the small bowel.
2. Structural Changes
   • Blind loops, diverticula, or surgical resection that disrupt normal flow → bacterial proliferation.
3. Altered GI Secretions
   • Reduced gastric acid (e.g. from PPIs) or pancreatic enzymes → less bacterial clearance.
   • Bile salt deficiency (cholestasis or biliary disease) can reduce antimicrobial properties.
4. Impaired Gut Immunity
   • Congenital or acquired (e.g. hypogammaglobulinaemia) → difficulty controlling bacterial overgrowth.

4.3 Pathophysiology

1. Colonisation of the Small Bowel
   • Bacteria typically found in the colon (anaerobes, some aerobes) proliferate in the small intestine.
   • They deconjugate bile salts, metabolise carbohydrate, and consume vitamin B12.
2. Malabsorption and Inflammation
   • Bile salt deconjugation → fat malabsorption and steatorrhoea.
   • Bacterial consumption of vitamin B12 → macrocytic anaemia (with normal folate).
   • Microbial fermentation of carbohydrates → osmotic diarrhoea, gas production, bloating.
3. Nutrient Deficiencies and Damage
   • Chronic bacterial overgrowth → mucosal inflammation, further impairing nutrient uptake.
   • Protein-energy malnutrition, deficiency states (e.g. B12, iron, fat-soluble vitamins) may ensue if prolonged.

4.4 Risk Factors

• Motility disorders: e.g. scleroderma, pseudo-obstruction, diabetes-related gastroparesis.
• Anatomical abnormalities: blind loops, strictures, diverticula, post-surgical bypass.
• Exocrine insufficiency: e.g. chronic pancreatitis, reduced bile production.
• Immunodeficiency: e.g. hypogammaglobulinaemia, common variable immunodeficiency.
• Medication: PPIs, opioids, anticholinergics.

4.5 Clinical Features

• Non-specific GI symptoms:
  • Chronic or recurrent diarrhoea, malodorous stools (steatorrhoea).
  • Abdominal bloating, discomfort, excess flatulence.
  • Weight loss, malnutrition.
• Nutrient deficiencies:
  • Vitamin B12 deficiency → macrocytic anaemia.
  • Other vitamins or minerals can also be depleted.
• Halitosis: from excess bacterial fermentation.

4.6 Diagnostic Approach

1. Suspect SIBO if:
   • Chronic diarrhoea/bloating + known risk factor (e.g. blind loop, motility disorder).
2. Hydrogen Breath Test (Preferred First-Line)
   • Glucose or lactulose ingestion → early rise in breath hydrogen or methane if bacterial overgrowth present in the small bowel.
   • Practical, non-invasive, though sensitivity/specificity vary.
3. Jejunal Aspirate and Culture (Gold Standard but rarely done)
   • 10^5 CFU/mL is diagnostic for SIBO.
   • Invasive, expensive, risk of contamination.
4. Assess Structural Causes
   • Small bowel imaging (CT, MRI) for strictures, loops, diverticula.
   • Evaluate for exocrine insufficiency, immunodeficiency, or motility problem if suspected.
5. Blood Tests
   • Vitamin B12 deficiency with normal folate is suggestive.
   • Check for other micronutrient levels depending on presentation.

4.7 Management

1. Treat Underlying Cause
   • Surgical correction of anatomical abnormalities (blind loop, strictures) if possible.
   • Improve motility (e.g. prokinetics).
   • Correct exocrine insufficiency or immunodeficiency.
2. Antibiotics (Mainstay)
   • Aim to reduce bacterial load rather than eradicate.
   • Rifaximin commonly used; other options include ciprofloxacin, metronidazole, trimethoprim, etc.
   • Duration and regimen vary; may need repeated or cyclical courses due to recurrence.
3. Nutritional Support
   • Replace vitamin B12, correct other deficiencies.
   • Adjust diet (reduce fermentable carbohydrates), possibly a low-FODMAP diet if indicated.
4. Monitoring and Follow-up
   • Symptom response often good, but recurrence is high if underlying predisposing factor persists.
   • Chronic management with periodic antibiotic courses or prophylaxis may be necessary in severe cases.

4.8 Prognosis / Complications

• Symptomatic response to antibiotics is generally good.
• However, relapse is common if the predisposing condition remains (e.g. irreversible surgical changes, severe motility disorders).
• Chronic or recurrent SIBO can lead to malnutrition, weight loss, and vitamin deficiencies (especially B12).
• Careful long-term follow-up is often required, especially in complex underlying diseases (e.g. scleroderma, Crohn’s).

5. Bile Acid Malabsorption

5.1 Epidemiology

• Bile acid malabsorption is relatively uncommon in the general population, though exact prevalence varies depending on the prevalence of underlying causes.
• It can be primary (idiopathic) or secondary, with common secondary causes being Crohn’s disease, ileal resection, or intestinal failure.

5.2 Aetiology

Two main categories:

1. Primary Bile Acid Malabsorption
   • Intrinsic defect in bile acid metabolism or regulation without obvious structural disease.
2. Secondary Bile Acid Malabsorption
   • Ileal disease (e.g. Crohn’s of the terminal ileum).
   • Ileal resection (bile acids not reabsorbed efficiently).
   • Intestinal failure scenarios (where normal absorption is disrupted).

5.3 Pathophysiology

1. Bile Acid Dynamics
   • Normally, bile acids are secreted into the duodenum and ~95% are reabsorbed in the ileum, returned to the liver (enterohepatic circulation).
   • When reabsorption is impaired (ileal disease/resection), more bile acids reach the colon.
2. Colonic Effects
   • Excessive bile salts in the colon induce an osmotic and irritant effect → postprandial diarrhoea.
   • Fat absorption can also be compromised (bile salts help emulsify fats), leading to steatorrhoea in some cases.
3. Vitamin Deficiencies
   • Malabsorption of fat-soluble vitamins (A, D, E, K) may also occur if bile acids are significantly depleted in the proximal gut.

5.4 Risk Factors

• Crohn’s disease involving the terminal ileum.
• Previous ileal resection (e.g. for tumour, Crohn’s, or other reasons).
• Other forms of intestinal failure (short bowel syndrome).

5.5 Clinical Features

• Postprandial diarrhoea (often chronic).
• Steatorrhoea (pale, malodorous stools).
• Potential deficiency of fat-soluble vitamins if bile acid pool is significantly reduced.
• Symptoms overlap with other malabsorptive or functional bowel disorders.

5.6 Diagnostic Approach

1. Se-HCAT Test
   • Patient ingests a synthetic radiolabelled bile acid analogue.
   • Reduced retention on scanning indicates bile acid malabsorption.
2. Assessment of Underlying Causes
   • Evaluate for Crohn’s (small bowel imaging, endoscopy).
   • History of ileal resection or other intestinal surgeries.
3. Steatorrhoea/Fat-soluble vitamins
   • Clinically or via stool tests (fat content) if indicated.

5.7 Management

• Bile Acid Sequestrants (e.g. cholestyramine) to bind excess bile acids in the colon and reduce diarrhoea.
• Treat underlying cause if possible (e.g. optimise Crohn’s therapy, surgical correction if feasible).
• Nutritional support: check for and supplement fat-soluble vitamins, correct any deficiencies.

5.8 Prognosis / Complications

• Symptoms generally respond well to cholestyramine or other sequestrants.
• Underlying diseases (e.g. Crohn’s, significant ileal resection) may be chronic or progressive, so patients often need long-term management strategies.
• Uncontrolled bile acid malabsorption leads to persistent diarrhoea, weight loss, and potential vitamin deficiencies.

6. Whipple’s Disease

6.1 Epidemiology

• Whipple’s disease is a rare malabsorptive disorder, predominantly affecting middle-aged men.
• Incidence is low worldwide and is associated with the pathogenic actinomycete Tropheryma whippelii(sometimes spelled Tropheryma whipplei).
• Untreated disease is typically fatal.

6.2 Aetiology

• Caused by the intracellular actinomycete Tropheryma whippelii in concert with defective cell-mediated immunity.
• Typically seen in white men, most commonly in Europe.
• The bacteria proliferate in macrophages, leading to systemic infiltration.

6.3 Pathophysiology

1. Bacterial Infection
   • Tropheryma whippelii invades the lamina propria and lymphatic channels of the small intestine.
   • Accumulates in macrophages, forming “foamy” periodic acid–Schiff (PAS)-positive inclusions.
2. Malabsorption Mechanism
   • Villous architecture is disrupted, resulting in malabsorption of fats, carbohydrates, proteins, and micronutrients.
   • Steatorrhoea may ensue because of improper digestion/absorption.
   • Lymphatic obstruction can further worsen malabsorption by impeding nutrient transport.
3. Systemic Involvement
   • Infection spreads beyond the intestine to joints (arthropathy), skin, brain (neurological symptoms), lymph nodes, and endocardium.
   • CNS involvement can range from dementia to ophthalmoplegia; endocarditis may be “culture-negative.”

6.4 Risk Factors

• Genetic predisposition is not well-defined but suspected.
• Immunodeficiency (especially defective T-cell immunity) may increase susceptibility.

6.5 Clinical Features

• Malabsorption: Diarrhoea, steatorrhoea, weight loss, abdominal pain.
• Arthropathy: Migratory, large-joint arthralgia; typically seronegative. Often an early presentation years before GI symptoms.
• Systemic: Intermittent fever, lymphadenopathy.
• Skin pigmentation: Hyperpigmentation is common.
• Finger clubbing.
• Neurological: Reversible dementia, ocular palsies, myoclonus.
• Cardiac: Potential involvement → “culture-negative” endocarditis.

6.6 Diagnostic Approach

1. Small Bowel Biopsy (Gold Standard)
   • Shows foamy macrophages in the lamina propria containing PAS-positive granules.
   • Villous atrophy is also noted.
2. Electron Microscopy
   • May visualise the Tropheryma whippelii organisms within macrophages.
3. Additional Tests
   • PCR of bacterial RNA on CSF, serum, or tissue can aid confirmation.
   • Check for macrocytic or microcytic anaemia due to malabsorption of vitamins and minerals.
   • Imaging (MRI) if CNS involvement is suspected.

6.7 Management

• Long-term Antibiotics: Must cross the blood–brain barrier to cover potential CNS involvement.
  • Current recommendation: 2 weeks of intravenous ceftriaxone, or IV penicillin + streptomycin, followed by co-trimoxazole (trimethoprim-sulfamethoxazole) orally for 1 year.
  • Tetracycline for 1 year is a classic alternative.
• Rapid symptomatic improvement often ensues, but full year of therapy is required to prevent relapse.

6.8 Prognosis / Complications

• Fatal if untreated.
• With proper antibiotic therapy, outcomes are significantly improved.
• Relapse occurs in ~33% (one-third) if therapy is insufficient or too short.
• Potential long-term neurological sequelae if CNS disease is not managed promptly.

7. Small Intestine Tumours

7.1 Epidemiology

• Small intestine tumours are rare, comprising <5% of all gastrointestinal (GI) tumours.
• The most significant types are carcinoid (neuroendocrine) tumours and lymphoma.
• Less common tumours include adenocarcinoma, immunoproliferative small intestinal disease (IPSID), and polyps (hamartomatous, adenomatous).

7.2 Carcinoid (Neuroendocrine) Tumours

7.2.1 Aetiology

• Carcinoid tumours (NETs) are slow-growing neoplasms arising from neuroendocrine cells in the GI tract.
• Common sites: appendix (45%), small intestine (30%), rectum (20%).
• Carcinoid syndrome occurs only when significant metastases (often hepatic) enable vasoactive substances (e.g. serotonin) to enter systemic circulation.

7.2.2 Pathophysiology

1. Neuroendocrine Origin
   • Tumour cells produce serotonin, prostaglandins, bradykinins, and other peptides.
   • Hormones usually metabolised in the liver if draining via the portal vein. Metastases in the liver or outside the portal system → hormones enter systemic circulation → carcinoid syndrome.
2. Carcinoid Syndrome
   • Provoked by release of serotonin, etc. → flushing, bronchospasm, diarrhoea, right-sided valvular lesions (carcinoid heart disease).
   • Typically occurs in ~2% of cases, especially if tumour >2 cm in size or metastasised.

7.2.3 Clinical Features

• Often asymptomatic if confined to small bowel; found incidentally (e.g. appendicectomy).
• Carcinoid syndrome: Flushing, diarrhoea, wheezing, palpitations. Right-sided heart valvular fibrosis can lead to tricuspid regurgitation, pulmonary stenosis.

7.2.4 Diagnostic Approach

• Urinary 5-HIAA (a serotonin metabolite) elevated in carcinoid syndrome.
• Incidental discovery sometimes at surgery (e.g. for appendicitis).
• Imaging (e.g. CT, MRI) or Octreotide scans may help localise metastases.

7.2.5 Management

1. Surgical Resection: Definitive treatment for localised disease.
2. Carcinoid Syndrome: Implies hepatic (or other) metastases.
   • Debulking procedures (hepatic resection, arterial embolisation) reduce tumour mass → symptom relief.
   • Octreotide (somatostatin analogue) palliates symptoms if debulking not possible. Also used for imaging (octreotide scans) and radiolabelled therapy.
3. Prognosis: Slowly progressive but often advanced at diagnosis if syndrome present.

7.3 Lymphoma

7.3.1 Aetiology

• Primary small bowel lymphoma is uncommon but can complicate:
  1. Coeliac disease (usually T-cell > B-cell).
  2. Immunodeficiency states (e.g. AIDS), typically B-cell lymphomas.
• May be sporadic or associated with chronic inflammation/autoimmune disorders.

7.3.2 Pathophysiology

1. Lymphoid Proliferation
   • In coeliac disease, ongoing immune stimulation leads to T-cell dysregulation → potential T-cell lymphoma.
   • In immunodeficiency, lack of immune surveillance → B-cell expansion.
   • Tumour typically involves mucosa/submucosa, can infiltrate mesenteric nodes.
2. Tumour Growth
   • Can present as obstruction, mass, ulceration, or infiltration.
   • Unlike gastric lymphoma, small bowel involvement may be more focal or segmental.

7.3.3 Clinical Features

• Obstructive symptoms: e.g. colicky pain, vomiting, intussusception.
• Haemorrhage or perforation possible.
• Weight loss common.
• Malabsorption is less typical, though it may happen, especially in coeliac-related T-cell lymphoma.

7.3.4 Diagnostic Approach

• Abdominal CT often identifies mass lesions in the small bowel; luminal imaging less frequently required.
• Staging laparotomy or endoscopy might be employed for biopsy/histology.

7.3.5 Management

• Surgical resection is first-line if resectable.
• Chemoradiotherapy may complement surgery in advanced or high-grade disease.
• Prognosis depends on histology, stage, and underlying condition (coeliac disease, AIDS).

7.4 Immunoproliferative Small Intestinal Disease (IPSID)

7.4.1 Aetiology

• Also called alpha heavy chain disease; predominantly in Mediterranean and Arab populations.
• Thought to stem from chronic bacterial antigen stimulation leading to proliferation of IgA-producing immunocytes.

7.4.2 Pathophysiology

1. Small Bowel Infiltration
   • Diffuse infiltration of the proximal small bowel by abnormal B-cells producing defective α-heavy chains (Fc portion of IgA).
2. Benign to Malignant Spectrum
   • Ranges from benign immunoproliferation to high-grade lymphoma transformation.

7.4.3 Clinical Features

• Typically young adults with chronic diarrhoea, malabsorption, clubbing, weight loss.
• Differential diagnosis includes Crohn’s, Whipple’s.

7.4.4 Diagnostic Approach

• Serum electrophoresis: α-heavy chains, hypo-γ-globulinaemia.
• Small bowel biopsy: Dense immunocyte infiltration of the proximal small bowel.

7.4.5 Management

• Long-term antibiotics to reduce antigenic drive.
• Chemotherapy if transformation to lymphoma occurs.
• Prognosis: variable; some respond well to antibiotics alone.

7.5 Polyps

7.5.1 Aetiology

• Single polyps: Rare, often malignant secondaries (e.g. from melanoma or lung).
• Multiple polyps:
  1. Nodular lymphoid hyperplasia in children with hypo-γ-globulinaemia.
  2. Hamartomas (Peutz–Jegher syndrome, with labial pigmentation, intussusception).
  3. Adenomatous (e.g. Cronkhite–Canada syndrome: alopecia, nail dystrophy).

7.5.2 Pathophysiology and Management

• Polyps can lead to intussusception, bleeding, or obstruction.
• Adenomatous lesions carry malignant potential → resection recommended.
• Syndromic polyp cases might need genetic counselling, surveillance endoscopy.

7.6 Adenocarcinoma

7.6.1 Aetiology

• Extremely rare in the small intestine.
• Associations: Coeliac disease, Crohn’s, Lynch syndrome, or familial adenomatous polyposis.
• Typically arises from dysplastic changes in the mucosa.

7.6.2 Pathophysiology

• Malignant glandular proliferation.
• Tends to occur in the duodenum or jejunum, can cause local invasion or metastases.

7.6.3 Clinical Features

• Obstruction (colicky pain, vomiting).
• Chronic blood loss → iron deficiency anaemia.
• Less commonly presents as an acute abdomen.

7.6.4 Management

• Surgical resection is definitive.
• Prognosis depends on stage at diagnosis; often advanced due to delayed detection.

8. Miscellaneous Intestinal Disorders

8.1 Chronic Intestinal Pseudo‐Obstruction

8.1.1 Aetiology

• Chronic intestinal pseudo‐obstruction (CIPO) refers to disorders mimicking mechanical obstruction withoutan actual blockage.
• Arises from pathology in gut smooth muscle (myopathy) or enteric nerves (neuropathy).
• Can be primary (familial) or secondary to other conditions (e.g. sarcoid, amyloid, endocrine, paraneoplastic), as in Table 14.4.

8.1.2 Pathophysiology

1. Impaired Motility
   • Damage to visceral smooth muscle or visceral autonomic innervation → defective peristalsis.
   • Bowel dilation occurs proximal to the affected segment, leading to obstructive-like symptoms.
2. Progressive Malabsorption / Distension
   • Initially episodic: vomiting, distension, constipation occur intermittently.
   • Over time, chronic stasis → weight loss, malnutrition, possibly bacterial overgrowth.

8.1.3 Clinical Features

• Early: Intermittent episodes of vomiting, abdominal distension, constipation.
• Later: Persistent symptoms, malnutrition, weight loss.
• Myopathic forms: Often accompanied by urinary tract dysfunction.

8.1.4 Diagnostic Approach

• Radiological evidence of dilated proximal small bowel in the absence of mechanical obstruction.
• Full-thickness biopsy (laparoscopic) to differentiate myopathy vs. neuropathy origin.

8.1.5 Management

• Symptomatic relief: Carefully manage acute episodes; limit opiate use to avoid dependence.
• Nutritional support: Parenteral nutrition often required due to poor motility.
• Surgery generally avoided (risk of further motility issues, no mechanical lesion to resect).

8.2 Meckel’s Diverticulum

8.2.1 Aetiology

• Commonest congenital gut anomaly, affecting ~2% of the population.
• Results from failure of vitelline duct (omphalomesenteric duct) to close.
• Located ~60 cm proximal to the ileocaecal valve, typically ~5 cm long.

8.2.2 Pathophysiology

1. Ectopic Mucosa
   • Diverticulum may contain gastric or pancreatic tissue.
   • Acid production by gastric mucosa can cause local ulceration → bleeding.
2. Potential Obstruction
   • Can act as a lead point for intussusception or volvulus, though less common.

8.2.3 Clinical Features

• Majority asymptomatic.
• If symptomatic, often presents before age 2: painless melaena is classic.
• Obstruction or intussusception is rare but possible.

8.2.4 Diagnostic Approach

• Meckel’s scan (technetium-labelled pertechnetate) → uptake by ectopic gastric parietal cells.
• Many discovered incidentally during surgery.

8.2.5 Management

• Surgical removal if symptomatic (bleeding, obstruction).
• Rarely resected if incidentally found and patient is asymptomatic.

8.3 Lactase Deficiency

8.3.1 Aetiology

• Lactase (brush border enzyme) breaks down lactose into glucose + galactose.
• Primary Hypolactasia: Very common in Africans, Asians (90% have reduced lactase). Rare in Caucasians.
• Secondary Deficiency: Post-infectious or mucosal injury (e.g. gastroenteritis).

8.3.2 Pathophysiology

1. Undigested Lactose in the small bowel travels to the colon.
2. Bacterial Fermentation → production of gas, short-chain fatty acids, osmotic diarrhoea.
3. Symptoms triggered by milk products ingestion.

8.3.3 Clinical Features

• Abdominal pain, bloating, flatulence, borborygmi.
• Osmotic diarrhoea after lactose intake.
• Usually mild–moderate severity.

8.3.4 Diagnostic Approach

• Hydrogen breath test with lactose substrate. Elevated breath hydrogen if lactose is malabsorbed.
• Dietary history pointing to milk-induced symptoms.

8.3.5 Management

• Reduce milk products; complete avoidance often not necessary.
• Commercial lactase enzyme supplements can help.
• Calcium/vitamin D supplementation if dairy is severely restricted.

8.4 Food Allergy

8.4.1 Aetiology

• Immune-mediated (type I hypersensitivity) response to specific food antigens.
• Common allergens: cow’s milk, soya in children; peanuts, shellfish in adults.

8.4.2 Pathophysiology

1. IgE Mediated Reaction
   • Immediate mast cell degranulation after ingestion.
   • Can be mild to severe (anaphylaxis).
2. Rare Life-Threatening Condition
   • Severe reactions → anaphylactic shock, airway compromise.

8.4.3 Clinical Features

• Immediate onset post ingestion: urticaria, angioedema, wheeze, GI upset.
• Mild forms self-limiting; severe forms can be life-threatening (anaphylaxis).

8.4.4 Diagnostic Approach

• Double-blind placebo-controlled food challenge = gold standard.
• Skin-prick tests or serum IgE levels often unhelpful alone.

8.4.5 Management

• Dietary avoidance of the allergen.
• Epinephrine autoinjector (adrenaline) for anaphylactic risk.
• Educate patient on allergen labelling, cross-contamination.

8.5 NSAID-Associated Enteropathy

8.5.1 Aetiology

• NSAIDs cause erosions, ulcers, webs, strictures throughout the GI tract, including the small bowel.
• Mechanism: Prostaglandin inhibition → less mucosal protection, leading to mucosal injury.

8.5.2 Pathophysiology

1. Mucosal Erosions or Ulcers
   • Similar to NSAID gastropathy, but can occur more frequently in the small bowel.
2. Bleeding, Protein Loss
   • Chronic ulcers can lead to protein-losing enteropathy, anaemia from occult or overt bleeding.

8.5.3 Clinical Features

• Often mild or asymptomatic.
• Potential for major haemorrhage, perforation, obstruction, or even sudden death similar to gastric complications.

8.5.4 Diagnostic Approach

• Capsule endoscopy is helpful to visualise small bowel lesions.
• Suspect in chronic NSAID users with unexplained iron deficiency, GI bleeding, or protein loss.

8.5.5 Management

• Discontinue or reduce NSAIDs if possible.
• Treat ulcers with supportive care, iron supplementation for anaemia, or surgery if severe complications.