1. Esophagus
   1. Infectious esophagitis
      1. Pathology
         1. Herpes: lateral margin of ulcer and intranuclear inclusion
         2. Candida: pseudohyphae
         3. CMV: Base of ulcer and large intranuc with granular cytoplasmic inclusions
   2. GERD
      1. Pathology
         1. Squamous proliferation
         2. Basal cell hyperplasia
         3. Increased lamina propria inflammation
         4. Papillae elongation
         5. Surface maturation decreases
   3. Barrett's esophagus
      1. Endoscopically: columnar metaplasia of esophageal mucosa
      2. Pathologically: intestinal metaplasia defined by goblet cells
      3. Development of adenocarcinoma: metaplasia-dysplasia*-carcinoma sequence
   4. Primary eosinophilic esophagitis
      1. Symptoms: dysphagia, food impaction. Many pts have allergic history
      2. Normal pH monitoring levels. Fail antireflux therapy
      3. >15 eoss/hpf from pts who lack postitive response to PPI or have normal pH
   5. Boerhaave's syndrome
      1. Mallory-Weiss laceration at GE junction
      2. Acute esophageal rupture
   6. Achalasia
      1. Clinical features
         1. Poorly relaxing LES
         2. Onset usually 30-50 years
         3. Dysphagia to both solid and liquid foods
         4. Retrosternal chest pain caused by eating
         5. Regurgitation of undigested foods
         6. Nocturnal cough, recurrent aspiration pneumonia
      2. Diagnosis
         1. Esophageal manometry is gold standard
            1. Complete aperistalsis and no LES relaxation
         2. Barium swallow: bird-beak appearance
         3. Upper endoscopy done in all cases to exclude other diseases and evaluate mucosa for treatment
      3. Can be confused with
         1. Secondary achalasia: Tumor of GE junction, Esophageal or pleural malignancies, Chagas
      4. Treatment
         1. Reduce LES pressure, improve esoph emptying
         2. Medications: nitrates and ca channel blockers
         3. Botox injection of toxin A to relax LES (1/2 life one year)
         4. Pneumatic dilatation
         5. Esophagomyotomy to reduce LES pressure
   7. Diffuse esophageal spasm
      1. Clinical features
         1. Mostly women
         2. Chest pain, intermittent dysphagia to liquids
      2. Diagnosis
         1. Clinical. EM shows increased wave amplitude and duration
         2. Barium swallow: rosary bead esophagus
         3. Upper endoscopy normal
      3. Can be confused with
         1. GERD, panic attack
      4. Treatment
         1. Medications: nitrates and ca blockers
         2. Botox if LES pressure is high
2. Stomach
   1. Congenital hypertrophic pyloric stenosis
      1. Concentric enlargement of pyloric sphincter and narrowing of pyloric canal that obstructs gastric outlet
      2. Projectile vomiting
   2. Gastritis
      1. Chronic
         1. Autoimmune
            1. Loss of parietal cells
            2. Clinical: Pernicious anemia (decrease vit B12)
            3. Labs: decreased B12, increased gastrin due to decreased acid
            4. Microscopically: limited to body/fundus, note intestinal metaplasia over time, patchy lymphocytic infiltrates in deep lamina propria
         2. H pylori
            1. Topic
            2. Characteristics
            3. Chronic, antral-predominant
            4. A/W peptic ulcer disease, gastric lymphoma, carcinoma, duodenal ulcers
            5. Microscopically: Antrum, lymphocytes in superficial mucosa
            6. Pathogenesis: Bacterial virulence factors
            7. Urease neutralizes acid in lumen
            8. Access to mucous layer and inflammation induction
            9. Direct effect on parietal cell secretion
            10. Hyperchlorhydria
            11. Hypergastrinemia: antral infection decreases somatostatin, lack of gastrin inhib delivers acid to duodenum
            12. Gastric metaplasia
            13. Decreased mucosal bicarbonate
      2. Acute
         1. Erosive/hemorrhagic
            1. Clinical features
            2. Associated with EtOH, NSAIDS, steroids, ASA or low hemodynamic state post-trauma
            3. Symptoms: abrupt onset, ab pain and bleeding
            4. Mechanism
            5. Breakdown of mucosal barrier via direct irritant, drug MOA or hypoperfusion
            6. Microscopic
            7. Limited to mucosa, superficial hemorrhage, mucosal sloughing/necrosis
            8. Treatment
            9. H2 blockers, PPIs
   3. Zollinger-Ellison Syndrome
      1. Mimics Menetrier's disease grossly
         1. Microscopic: has fundic expansion with increase in parietal cells (mucous cells in menetrier's)
      2. Hypergastrinemia due to gastrinoma
   4. Gastrinoma
      1. Sporadic or MEN-1
   5. Histamine
      1. Systemic mastocytosis
   6. Delayed gastric emptying
      1. Clinical features
         1. Bloating, nausea, vomiting
         2. Vomiting undigested food after one hour. No abdominal pain usually
      2. Diagnosis
         1. Nuclear medicine test - gastric emptying
      3. Differential
         1. Gastric outlet obstruction
            1. Pancreatic cancer causing extrinsic compression
            2. Pyloric stenosis due to peptic ulcer disease
            3. Test for these by upper endoscopy
            4. DO NOT use promotility agents for mechanical obstruction like these
         2. Gastroparesis
            1. Can be due to diabetes
            2. Idiopathic common in young females
            3. Treatment with prokinetic agents: metoclopramide, erythromicine, gastric pacemaker
3. Gallbladder
   1. Gallstones
      1. Types
         1. Black Pigment
            1. Calcium bilirubinate, <10% cholesterol
            2. Seen in pts with cirrhosis and chronic hemolytic conditions
            3. mostly a result of unconjugated billirubin
         2. Brown Pigment
            1. Calcium salts of unconjugated bilirubin
            2. Primary bile duct stones
            3. Result of stasis - above a stricture, foreign body or in setting of infection
            4. Assoc w biliary infection which leads to bacterial deconj of bilirubin
            5. Seen in Asians, secretory IgA deficiency
         3. Cholesterol stones
            1. 80% of gallstones in US
            2. 70% cholesterol by weight, radiolucent
            3. Stages
            4. Cholesterol supersaturation
            5. Most critical factor is cholesterol:bile acid ratio
            6. Excessive cholesterol synth (HmG-CoA stimulated by insulin, food intake and obesity), oversensitive feedback to turn off 7 hydroxylase
            7. Accelerated nucleation
            8. Vesicle and micelle formation cannot keep up with cholesterol formation, mucin glycoproteins promote precip
            9. Gallbladder hypomotility
      2. Diagnosis
         1. H&P
         2. Plain abdominal X-ray: only visualizes 20% of gallstones
         3. Abdominal ultrasonography
            1. Poor for intraductal stones, but no radiation and is portable
         4. HIDA
            1. Radiation but non-invasive and assess bile leak and focal obstruction
         5. Endoscopic ultrasound/MRI/MRCP
      3. Progress to
         1. Acute cholecystitis
            1. Clinical features
            2. RUQ pain >3 hours, parietal-type pain
            3. Bacterial infection
            4. Fever
            5. Murphy's sign, Boas' sign
            6. Leukocytosis, elevated LFTs
            7. Treatment
            8. 75% symptoms resolve in 72 hours, 25% symptoms persist with complications
         2. Gallbladder cancer
            1. 30-50% of gallstone related deaths
            2. 80% of pts with cancer have gallstones
            3. Risk factors
            4. Indians (Feathers not Dots)
            5. Porcelian Gallbladder
            6. Symptomatic gallstone
         3. Biliary colic
            1. Clinical features
            2. Steady pain, 1-3 hours
            3. Recurrent attacks in 50%
            4. Epigastric, postprandial, visceral-type pain
      4. Complications
         1. Choledocho-duodenal fistula
         2. Papillary stenosis
         3. Acute Pancreatsis
4. Small Intestine/Bowel
   1. Celiac Disease
      1. Gross pathology
         1. Scalloping and loss of folds
      2. Increased epithelia lymphocytes present, and loss of decrescendo pattern
      3. Marsh Classification
         1. Marsh 3: increased IEL and villous blunting
      4. Serologic tests: Anti-tTG IgA
      5. Gold-standard test
         1. response to gluten-free diet
      6. Conditions that can cause IEL/villous blunting
         1. CVID (histologically), HIV, infections, NSAID injury
      7. Diseases associated w CD: dermatitis herpetiforme (response to gluten-free diet)
   2. Microscopic colitis
      1. Clinical features
         1. Chronic watery diarrhea and normal endoscopy,
      2. Types
         1. Lymphocytic
            1. F:M 3:1. Increased IEL
         2. Collagenous
            1. Thickened subepithelial collagen band. F:M 8:1. Increased IEL.
      3. Treatment
         1. Budesonide
      4. Diagnosis
         1. Colon biopsy
   3. Inflammatory Bowel Disease
      1. Ulcerative Colitis
         1. Clinical features
            1. Hematochezia, bloody diarrhea, tenesmus, urgency, INCONTINENCE, nocturnal awakening
            2. Physical exam
            3. Gross: blood
            4. Pallor, abdominal tenderness
            5. Complications
            6. Toxic megacolon, hemorrhage, perforation, colon cancer
            7. Area of involvement
            8. Only involves colon
            9. Risk factors
            10. Cigarette smoking and appendectomy are protective
            11. Improved hygiene increases susceptibility
            12. Like CD, genetic, environmental and immunologic factors
            13. Radiography
            14. Lead pipe appearance in chronic disease
         2. Gross pathology: mucosal inflammation, ulcers and crypt abscesses, dysplasia may be present
         3. Treatment
            1. Medical
            2. 5-ASA
            3. Prophylactic against colon cancer
            4. Specific agents
            5. Sulfasalazine
            6. ADRs due to sulfa moiety
            7. Malaise, nausea, folic acid malabsorption, bone marrow suppression
            8. Mesalamine
            9. No sulfa moiety
            10. Olsalazine
            11. Diazo bond
            12. Immunomodulators
            13. Azathioprine/6-MP
            14. Maintain remission, be careful of ADRs and TPMT deficiency
            15. cyclosporine
            16. use
            17. Severe steroid-refrac UC
            18. ADRs
            19. nephro, neurotoxic, HTN
            20. Probiotics
            21. Glucocorticoids
            22. Use
            23. Only for severe disease, switch to 5-ASA and cytotoxic agents after induction remission
            24. Surgical
            25. Total proctocolectomy
      2. Crohn Disease
         1. Subtypes
            1. Inflammatory
            2. Fever, anorexia, weight loss, arhtralgias
            3. Fibrostenotic
            4. obstruction, diarrhea
            5. Fistulizing
            6. perianal, rectovaginal, enterocutaneous, enteroenteric
         2. Pathogenesis
            1. Genetic mutations assoc w IBD: NOD2 and CARD15
            2. Environmental: appendectomy, cigarette smoking, NSAIDS, antibiotics
            3. Immune dysregulation: See below in charac of both
         3. Endoscopic features
            1. severe: bear-claw ulcers, deep, linear
            2. mild: edema, hyperemic spots
         4. Radiography
            1. Strictures, fistulas
         5. Pathology
            1. Gross: TRANSMURAL inflammation, strictures, fissures, creeping fat
            2. Histo: non-caseating granulomas
         6. Physical exam
            1. Perianal fissure, fistua, abscess, tag
            2. Fever, orthostatic hypotension
            3. Tachycardia, pallor, RLQ tenderness
         7. Treatments
            1. Medical
            2. Antibiotics (for mild-moderate)
            3. Metronidazole
            4. ADRs
            5. metallic taste, peripheral neuropathy
            6. Ciprofloxacin
            7. ADR
            8. tendon rupture
            9. Glucocorticoids
            10. Systemic
            11. Use
            12. For induction of severe CD remission, NOT MAINTENANCE
            13. ADRs
            14. Cushing or 2 adrenal insuff
            15. Budesonide
            16. Use
            17. Mainenance of remission
            18. Immunomodulators
            19. Azathioprine
            20. Methotrexate
            21. Use
            22. Induction and maintenance of CD remission
            23. ADRs
            24. pneumonitis, hepatotoxicity, bone marrow suppression. DO NOT GIVE DURING PREGNANCY
            25. Natalizumab
            26. Use
            27. induction and maintenance remission
            28. MOA
            29. decreases WBC trafficking
            30. ADR
            31. PML - major so this is rarely used
            32. Anti-TNF alpha antibodies
            33. Use
            34. Induction and maintenance of severe CD
            35. ADRs
            36. Infusion reaction, infection, lymphoma, demyelination, SLE-like reaction, CHF
            37. Surgical
            38. ileocecectomy, stricturoplasty, perianal fistulotomy
            39. Not curative
      3. Characteristics of both CD and UC
         1. Chronicity: Paneth cell metaplasia of left colon
         2. Chronicity: Pyloric metaplasia of terminal ileum
         3. Activity: Cryptitis and crypt abscess
         4. Extraintestinal manifestations
            1. Uveitis
            2. Episcleritis
            3. Aklosing psondylitis
            4. Arthropathy
            5. Erythema nodosum, pyoderma gangernosum
            6. Nephrolitiasis
         5. Labs
            1. Iron deficiency in both, B12 in Crohn's
         6. Failure to downregulate mucosal immune system
            1. Secretion of cytokines
            2. increase in TNF alpha, decrease in antiinflammatory cytokines
            3. Leukocyte trafficking
            4. activation of T cells
            5. Increase in inflamm such as Th1 Th2 and Th17, decrease in regulatory T cells
            6. Defective intestinal barrier
            7. Decreased apoptosis of activated T cells
         7. Physical exam
            1. pallor, high HR/low BP, distended abdomen, tenderness, mass
      4. Diagnosis
         1. Endoscopy and histology
         2. Small bowel series of barium studies in CD
   4. Irritable Bowel Syndrome
      1. Clinical features
         1. Abdominal distension
         2. Pain relief with bowel action
         3. More frequent and looser stools with pain onset
         4. Mucus
         5. Negative for blood, weight loss or fever
      2. Check these to rule out IBS
         1. Sorbitol or lactase insufficiency
         2. Medications
         3. Depression or panic disorders or psychosocial factors
      3. Labs
         1. Complete blood count
         2. Sigmoidoscopy, colonoscopy if >50
         3. Thyroid function tests
         4. Latest: look for bacterial overgrowth using lactulose breath test
      4. Treatment
         1. Trial of fiber supplement, and/or variety of medications
   5. Chronic constipation
      1. Clinical features
         1. Significant change from stable bowel pattern, can be caused by colonic inertia, medications, obstruction lesions, hypothyrodisim, hirschsprung's disease
      2. Diagnosis
         1. Exclude osbtuction lesions with barium enema or colonoscopy
         2. Review meds
         3. Exclude hypothyroidism
         4. Marker study to demonstrate slow transit
         5. Defogram to evaluate pelvic floor dysfunction
         6. Rome II: 2 or more symptoms for at least three months
            1. <3 BM/week
            2. hard/lumpy stools
            3. straining
            4. sensation of incomplete evactuation
            5. sense of anorectal obstruction
            6. manual maneuvers
      3. Pathophysiology
         1. Slow-transit
            1. impaired contractile responses
            2. Reduced colonic propulsion of stool with slower transit
            3. fewer serotonin cells in colon
            4. abnormalities in serotonin receptor protein
            5. absent or decreased number of cells of Cajal
         2. dyssynergic
            1. Impaired coordination/sensation of muscles
         3. IBS with constipation
            1. primary complaint is abdominal pain, altered serotonin release/uptake