GI Flashcards
[Esophageal Disorders]
- Describe symptoms of esophageal disease
- Workup for dysphagia
- Symptoms:
A. heartburn (pyrosis) - intermittent burning sensation behind sternum; after eating, exercise, lying flat
B. chest pain - shared nerve plexus between heart and esophagus –> pressure in mid-chest, arm, jaw; have to rule out cardiac source
C. regurgitation - return of food without nausea or wretching
D. odynophagia - pain that comes with or is worsened by swallowing; more common with infectious esophagitis than GERD
E. Dysphagia - difficulty swallowing; ALARM symptom
2A. Timing:
- oropharyngeal dysphagia - difficulty initiating swallowing
- esophageal dysphasia - swallowing for several seconds after initial swallow as if food is stuck
B. Solids? Liquids? Both
- dysmotility - both liquids and solids at onset
- mechanical - solids progressing to liquids
[Esophageal Disorders]
Describe esophageal motility disorders incl causes, pathophys, presentation, and diagnosis
1. Zenker diverticulum
2. Achalasia
- Zenker diverticulum - uncommon
A. Cause - altered esophageal motility
B. Pathophys - false diverticulum (does not contain all the walls of the structure, as opposed to Meckel diverticulum in bowel) - just mucosa and not muscular layer
- herniation of esophageal mucosa at Killian triangle in inferior pharyngeal constrictor
C. Clinical - in elderly males; halitosis, regurgitation, nocturnal aspiration
D. Diagnosis - barium swallow
- other types of diverticulum are traction (associated with cancer or granuloma) and epiphrenic (associated with hypertensive LES) - Achalasia - uncommon
A. Cause - autoimmune, infection with T. cruzi (chagas causes secondary achalasia) –> damages ganglion cells of myenteric (Auerbach) plexus in muscularis propria
B. Pathophys - damage to ganglion cells –> inability to relax LES –> high resting lower esophageal sphincter (LES) pressure + absent peristalsis (esophageal dysmotility) –> esophageal body dilates (“bird beak” on barium swallow)
C. Clinical - dysphagia for solids and liquids, regurgitations (of undigested food), halitosis, nocturnal cough/aspiration, heartburn
D. Diagnosis - endoscopy, manometry (measuring pressures) –> all pressures low except LES which is high
[Esophageal Disorders]
Describe esophageal motility disorders incl causes, pathophys, presentation, and diagnosis
3. Diffuse esophageal spasm
4. Nutcracker esophagus
- Diffuse esophageal spasm - uncommon
A. Cause - unknown
B. Pathophys - impaired innervation of inhibitory neurons; problem with nitric oxide synthesis –> loss of coordination of peristaltic wave –> simultaneous contractions of normal pressure amplitude
C. Clinical - dysphagia for solids and liquids +/- retrosternal chest pain
D. Diagnosis - barium swallow “corkscrew” esophagus - Nutcracker esophagus - uncommon
A. Cause - unknown
B. Pathophys - overstimulation of excitatory cholinergic neurons –> sequential peristaltic contractions with very high amplitude
C. Clinical - dysphagia for solids and liquids, otherwise asymptomatic
[Esophageal Disorders] Describe esophageal inflammatory disorders incl causes, pathophys, presentation, and diagnosis 1. GERD A. Cause B. Pathophys C. Clinical D. Diagnosis E. Treatment F. Complications incl Barrett esophagus
- GERD - gastroesophageal reflux disease –> reflux of acid-containing gastric secretions and/or bile into esophagus
A. Cause - due to anatomic position (hiatus hernia), SMC relaxation - transient sphincter opening (food, drugs), LES length (gastric distension)
B. Pathophys - decreased LES pressure / tone –> reflux of acid from stomach to esophagus
- risk factors: obesity, pregnancy, gastric hypersecretory state, delayed gastric emptying, disruption of esophageal peristalsis
C. Clinical - fleeting sx that can resolve spontaneously
- heartburn and substernal chest pain, dysphagia, voice changes
- adult-onset asthma + cough (1 of 3 MCC of chronic cough, others are asthma and postnasal drip)
- must rule out CAD (angina and GERD present similarly)
D. Diagnosis - EGD (upper endoscopy) or 24 hr pH probes
E. Treatment - risk mgmt: avoid foods that reduce LES pressure (fatty, alcohol, mint, tomato, coffee/tea), weight reduction, PPIs
F. Complications
i. erosive esophagitis (necrosis of surface layers of esophageal mucosa) –> ulceration with strictures (fibrosis healing process of erosive esophagitis)
ii. Barrett esophagus (metaplasia from non-keratizinizing SSE to non-ciliated columnar with goblet cells) –> ↑ risk of esophageal adenocarcinoma
[Esophageal Disorders]
Describe esophageal inflammatory disorders incl causes, pathophys, presentation, and diagnosis
- Allergic (eosinophilic) esophagitis
- Infectious esophagitis
- Iatrogenic (Lye, Pill)
- Eosinophilic esophagitis
A. Cause - immunologic (Th2 cell mediated) induced by food allergens; intraepithelial eosinophils
B. Pathophys - Th2 –> IL-13 and IL-5 –> eosinophils
C. Clinical - intermittent dysphagia for solid foods, food impaction, central chest pain, GERD sx refractory to GERD treatment
D. Diagnosis - stacked circular rings on endoscopy (like a cat esophagus) - Infectious esophagitis
A. Cause - Candida albicans or CMV (in HIV patients with CD4 < 100), HSV1 (in organ transplant patients)
B. Pathophys -
C. Clinical - odynophagia (pain with swallowing)
- oral thrush in Candida
- distal esophagus in HSV
D. Diagnosis -
- white mucosal plaques in Candida esophagitis (can be scraped off, as opposed to leukoplakia)
- well-circumscribed “punched out” volcano ulcers in Herpes esophagitis
- linear ulcers in CMV esophagitis - Iatrogenic (Lye, Pill)
A. Pill - due to esophageal hypomotility or incorrect method of swallowing pill –> pill adheres to esophageal wall –> acute onset chest pain, heartburn, and severe odynophagia (even to sips of water)
most common - tetracyclines, bisphosphonates (esp alendronate), KCl, NSAIDs
B. Caustic ingestion
i. Alkali (e.g. lye) - causes liquefactive necrosis –> full thickness injury –> esophageal strictures
ii. Acid - causes coagulative necrosis –> superficial injury that damages stomach
[Esophageal Disorders] Esophageal cancer 1. Common clinical presentation 2. Esophageal adenocarcinoma 3. Squamous cell carcinoma
- Esophageal cancer - presents late in course
- dysphagia progressing from solids to liquids –> weight loss
- hematemesis –> iron deficiency anemia due to chronic blood loss
- tracheobronchial fistulas
- squamous cell –> hoarse voice (recurrent laryngeal nerve) or cough (Tracheal involvement) - Esophageal adenocarcinoma - most common in US
A. Cause - associated with GERD and Barrett esophagus, as well as smoking
- NOT associated with helicobacter (causes gastric cancer)
B. Pathophys - malignant proliferation of glands
- most commonly occurs at GE junction (distal third of esophagus) –> spreads to celiac and gastric lymph nodes - Squamous cell carcinoma - most common worldwide
A. Causes - associated irritation of mucosa –> smoking and alcohol, hot liquids, achalasia, esophageal webs (eg Plummer-Vinson syndrome), esophageal injury (Eg lye ingestion)
B. Pathophys - malignant proliferation of squamous cells
- most commonly arises in cervical and thoracic esophagus (upper or middle third) –> spreads to cervical or mediastinal/tracheobronchial lymph nodes
[Esophageal Disorders] Esophageal structural disorders 1. Webs 2. Rings 3. Hiatus hernia 4. Paraesophageal hernia
- Webs- proximal (cervical) esophagus; mucosal fold that protrudes into lumen
- associated with Plummer-Vinson syndrome (iron deficiency anemia, dysphagia, esophageal web) with spoon nails, atrophic glossitis - Rings - distal esophagus; Schatzki ring is most common; constant luminal size
- associated with hiatal hernia and GERD; causes intermittent solid food dysphagia - Hiatus hernia - type 1 (sliding) hernia; 50% of pts with GERD have hiatal hernia; GE junction rises above the diaphragm (supposed to be below)
- Paraesophageal hernia - type 2 hernia; GE junction in right position but fundus herniates into the chest
- gastric volvulus - whole stomach goes into the chest and rotates –> ischemia and perforation –> borchardt triad:
i. sudden severe pain in chest
ii. persistent retching but little vomit
iii. inability to pass nasogastric tube
- can hear bowel sounds in lower lung fields
[Esophageal Disorders] Describe esophageal mechanical injury incl causes, pathophys, presentation, and diagnosis 1. Mallory-Weiss tear 2. Boerhaave syndrome 3. Sclerodermal esophageal dysmotility
- Mallory-Weiss tear
A. Cause - longitudinal tear/laceration of mucosa of lower esophagus due to severe vomiting (alcoholism, bulimia)
B. Pathophys - self-limited cause of upper GI bleed
C. Clinical - retching and then vomiting red blood (hematemesis); usually painless, but there can be epigastric or back pain
- risk of boerhaave syndrome - Boerhaave syndrome
A. Cause - esophageal rupture associated with vomiting (Eg Mallory Weiss tear) –> spill esophageal contents into chest
B. Pathophys - most common in left distal esophagus
C. Clinical - excruciating retrosternal chest pain immediately following vomiting; air in mediastinum and neck –> subcutaneous emphysema (crackling noise)
- sepsis –> death high mortality - Sclerodermal esophageal dysmotility
A. Cause - Esophageal smooth muscle atrophy –> decreased LES pressure and dysmotility –> acid reflux and dysphagia
B. Clinical - stricture, Barrett esophagus, and aspiration
[Stomach Disorders]
- Describe pathophysiology of injury/inflammation to stomach
- Most common risk factors for ulcers
- Four layers of an ulcer
1A. Failure of mucosal defense barrier - mucous maintains physiologic pH around the cells (7) while outside is pH 2
B. Acid hypersecretion
2A. Helicobacter pylori- most common chronic bacterial infection in humans; MCC of gastritis in kids
B. NSAID use - one of most commonly used OTC drugs
- Four layers of an ulcer: debris, inflammation, granulation tissue, fibrosis
[Stomach Disorders] Risk factors for ulcers 1. H. Pylori A. Virulence B. Clinical i. Acute ii. Chronic C. Diagnosis
- H. Pylori
A. Virulence - Gram (-) curved rod with flagella that allow motility - penetrates mucous gel layer and epithelium
- urease, oxidase, catalase (+) –> urease converts NH3 into NH4+ CO2 –> creates alkaline environment to neutralize low pH in stomach
- adheres to epithelium through virulence factors (Type IV secretion system, exotoxins) –> mucosal and epithelial damage; does NOT invade
B. Clinical - causes 90% of all gastric ulcers and 80% of all duodenal ulcers
i. Acute infection - mild transient sx incl nausea, vomiting, intense neutrophilic infiltrate (pathologic diagnosis)
ii. Chronic infection -
- antral gastritis most common –> infection confined to antrum with decreased bicarbonate secretion –> duodenal ulcer
- gastritis of body and fundus –> reduced parietal cell mass and acid secretion –> intestinal metaplasia –> ↑ risk of gastric adenocarcinoma (intestinal type)
- non-atrophic pangastritis (inflammation of entire stomach lining) –> lymphoid aggregates with germinal centers –> ↑ risk of lymphoma (MALToma)
C. Diagnosis - urea breath test (↑ C02) or mucosal biopsy (patchy intestinal metaplasia) during endoscopy; NOT cultured
D. Treatment - triple therapy
- PPI
- clarithromycin (macrolide)
- amoxicillin (or metronidazole if penicillin allergy)
[Stomach Disorders] Risk factors for ulcers 2. NSAIDs A. MOA B. Risk factors C. NSAID-induced injury
- NSAIDs
A. MOA - inhibitors of COX1 (housekeeping) and COX2 (inflammation); aspirin is irreversible and ibuprofen, naproxen are reversible
- membrane phospholipids (PLA2) –> Arachidonic acid –> prostaglandins via COX1 or COX2
- COX1 –> TXA2, PGI2, PGE2–> platelet aggregation / vasoconstriction, GI mucosal integrity, renal function (dilates afferent arteriole)
- COX2 –> PGI2 and PGE2 –> inflammation, bone formation, mitogenesis –> fever, pain, increased vascular permeability
B. Risk factors - prior h/o peptic ulcer disease, high dose or multiple NSAIDs, H. pylori infection, smoking, alcohol, corticosteroid use (synergistic)
C. Injury - direct toxicity, perturbs epithelial mucous barrier (decreased mucous, HC03 secretion) –> acute hemorrhagic erosive gastropathy (GI bleeding)
- acute kidney injury, renal papillary necrosis, acute interstitial nephritis
- Type 4 RTA (hypoaldosteronism)
- respiratory alkalosis, tinnitus, aplastic anemia
- gastric inflammation, ulcers
- child with viral illness given NSAID –> Reye’s syndrome (hepatic encephalopathy)
[Stomach Disorders] Congenital disorders A. Cause B. Risk factors C. Clinical
- Pyloric stenosis
- Duodenal atresia
- Jejunoileal atresia
- Pyloric stenosis
A. Cause - congenital pyloric smooth muscle hypertrophy; MCC of gastric outlet obstruction in infants
B. Risk factors - more common in firstborn males, associated with exposure to macrolides
C. Clinical - develops 4-6 weeks after birth –> non-bilious projectile vomiting immediately after feeding
- physical: palpable olive-like mass in abdomen, dehydrated (dry mucous membranes, flat fontanelle)
- labs: hypochloremic, hypokalemic metabolic alkalosis and elevated bilirubin - Duodenal atresia
A. Cause - congenital failure of duodenum to recanalize –> complete obstruction of lumen
B. Risk factors - associated with Down syndrome, cardiac defects
C. Clinical - presents hours after birth
- prenatal- polyhydramnios in utero (baby cannot swallow amniotic fluid)
- bilious vomiting (emergency in newborn)
- blind loop of duodenum –> “double bubble” sign on X-ray - Jejunoileal atresia
A. Cause - associated with vascular accident eg disruption of mesenteric vessels –> ischemic necrosis
B. Risk factors - low association with chromosomal anomalies
C. Clinical - results in jejunal dilation with “apple peel” deformity of distal bowel
- also presents with bilious vomiting and abdominal distension
- multiple air-fluid levels and distended loops of small bowel on plain X-ray films
[Stomach Disorders] Inflammation disorders A. Cause B. Risk factors C. Clinical
- Acute gastritis
- Stress ulcer
Curling vs Cushing
- Acute gastritis
A. Cause - imbalance between mucosal defenses and acidic environment –> acid damage to stomach mucosa
- defenses: mucin layer of foveolar (surface mucous cells); HC03- secretion by surface epithelium; blood flow
- imbalance –> inflammation, erosion (loss of epithelium), or ulcers (loss of mucosal layer)
B. Risk factors - alcohol/smoking, NSAID use, bile reflux, stress ulcers
- Stress ulcer - shallow or deep erosions of gastric mucosa that cause acute gastritis
A. Cause - impaired mucosal protection (loss of mucous layer or ischemia) and hypersecretion of acid
B. Risk factors - patients in ICU setting with critical illness (usually have multiple ulcers)
C. Clinical
i. Curling - severe burn –> hypovolemia –> mucosal ischemia
ii. Cushing - brain injury –> increased intracranial pressure –> vagal stimulation –> ↑ ACh –> ↑ H+ production
[Stomach Disorders]
Inflammation disorders
3. Chronic gastritis A. Cause B. Location C. Clinical D. Sequelae
- Chronic gastritis - chronic inflammation of mucosa with patchy intestinal metaplasia
A. Cause
i. H. pylori (90%) - antibodies to H pylori
ii. autoimmune (10%) - mucosal atrophy of gastric parietal and chief cells via CD4+ T cell response (Type 4 HSN) –> loss of acid secretion (achlorhydria) –> hypergastrinemia (loss of negative feedback) –> ECL cell hyperplasia (gastrin stimulates ECL cells to release histamine)
- result is antibodies to IF (made by parietal cells)
B. Location
i. H. pylori - antrum involved
ii. Autoimmune - antrum spared - damage is in body and fundus (where gastric parietal cells are)
C. Clinical
i. H. pylori - epigastric abdominal pain + hyperplastic polyps
ii. Autoimmune - megaloblastic (pernicious) anemia
- (decreased B12 due to lack of IF) –> reversible glossitis, irreversible peripheral neuropathy, irreversible cerebral dysfunction (memory loss, personality change, psychosis)
D. Sequelae
i. H. pylori - peptic ulcer disease, MALToma, gastric adenocarcinoma
ii. Autoimmune - gastric adenocarcinoma, carcinoid tumor; associated with other autoimmune diseases (Hashimoto’s, DMI, Graves)
[Stomach Disorders]
Inflammation disorders
- Peptic Ulcer Disease - differentiate between duodenal and gastric ulcers
A. Cause B. Location C. Clinical D. Complications E. Treatment
- Peptic Ulcer Disease
A. Cause - break in the mucosal surface associated with chronic gastritis
i. Duodenal ulcer - H. pylori, in younger adults
ii. Gastric ulcer - H. pylori, NSAIDs, bile reflux, in adults >60 yo
B. Location - usually solitary (multiple - think ZE)
i. Duodenal (90%) - usually in first portion of duodenum
ii. Gastric (10%) - usually in lesser curvature of antrum
C. Clinical - benign ulcers - sharply “punched out” lesions with radiating folds of mucosa; most common cause of upper GI bleed
i. Duodenal - epigastric pain that improves with meals
- hypertrophy of Brunner’s glands
ii. Gastric - epigastric pain that worsens with meals
D. Complications - bleeding most common complication –> melana, hematemesis
i. Duodenal - if ulcer arises in posterior duodenum –> rupture –> bleeding from gastroduodenal artery, or acute pancreatitis
- 99% benign (don’t need to worry about cancer)
ii. Gastric - bleeding from left gastric artery
- DDx is gastric adenocarcinoma (large, irregular ulcers) - do biopsy
bleeding via coffee-ground emesis, melana, or occult bleeding
E. Treatment - treat H. pylori, avoid NSAIDs, acid suppressive therapy with PPIs (eg omeprazole)
- diagnose via upper endoscopy
[Stomach Disorders]
Gastric neoplasms
1. Gastric adenocarcinoma - differentiate between intestinal vs diffuse types A. Cause B. Risk factors C. Clinical D. Complications
- Gastric carcinoma - malignant proliferation of surface columnar epithelial cells –> adenocarcinoma
A. Cause -
i. Intestinal - chronic inflammation and continuous cycles of injury and repair –> atrophic gastritis –> metaplasia –> dysplasia –> carcinoma
ii. Diffuse - infiltrative cancer with invasion of “signet ring” cells (due to large mucin vacuoles) through gastric wall
B. Risk factors -
i. Intestinal - intestinal metaplasia (due to H pylori and autoimmune chronic gastritis), nitrosamines in smoked foods (Japan), blood type A
ii. Diffuse - not associated with any of above; in younger patients and has worse prognosis; cadherin mutations
C. Clinical - presents late with weight loss, epigastric abdominal pain, anemia, early satiety
- cutaneous paraneoplastic: (1) acanthosis nigricans (hyperpigmented plaques in axilla) and (2) Leser-Trelat sign (sudden onset of multiple keratoses)
i. Intestinal - large, irregular ulcer at lesser curvature of antrum
ii. Diffuse - “linitis plastica” stomach wall becomes thick and leathery; worse prognosis
D. Complications: 75% have spread to lymph nodes or distant metastases at time of diagnosis:
- Virchow’s node - swollen left supraclavicular node
- Sister Mary Joseph nodule (periumbilical region) –> intestinal
- Krukenberg tumor (bilateral ovarian metastasis) –> diffuse; mets have signet ring cells
[Stomach Disorders]
Gastric neoplasms
2. Gastric lymphoma A. Cause B. Risk factors C. Clinical D. Complications E. Treatment
- Gastric lymphoma
A. Cause - gastric MALToma is most common (mutation of “marginal zone” post germinal center memory B cell)
B. Risk factors - H. pylori (associated with chronic inflammation), most are gastric; associated with chromosomal translocations and constitutive activation of NF-kappaB
C. Clinical - peptic ulcer disease, abdominal symptoms, associated autoimmune disease
D. Complications - MALT associated with inflammation (thyroid MALT = Hashimoto’s, cutaneous = Borrelia, C. psittaci = Ocular, Sjogren’s = salivary)
E. Treatment - chemo and radiation; treat H pylori; can progress to DLBCL
[Stomach Disorders]
Gastric neoplasms
- Gastrointestinal stromal tumors
- Menetrier disease
- Diabetic gastroparesis
A. Cause
B. Clinical
- Gastrointestinal stromal tumors (GIST)
A. Cause - most common mesenchymal tumor of the abdomen (50% are gastric); arise from interstitial cells of Cajal (cells in gut muscle wall that are pacemakers for peristalsis, express c-KIT)
- associated with NF1
C. Clinical - overt or occult GI bleeding; tend not to metastasize
- solitary well-circumscribed masses with intact or ulcerated surface and spindle morphology
- treat with imatinib (Gleevec) tyrosine kinase inhibitor –> c-KIT positive tumors - Menetrier disease
A. Cause - diffuse hyperplasia of foveolar epithelium (Surface mucous cells) in gastric mucosa -> hypertrophied rugae (look like brain gyri)
B. Clinical - excess mucous production –> hypoproteinemia (mucous is a protein) and parietal cell atrophy –> malnutrition / weight loss, epigastric pain, diarrhea, peripheral edema
- can resolve spontaneously or regress - Diabetic gastroparesis
A. Cause - related to autonomic neuropathy –> loss of vagus nerve stimulation + loss of peristalsis
B. Clinical - epigastric pain, nausea, early satiety, vomiting
- will see retinopathy, peripheral neuropathy, and nephropathy
[Small intestine disorders]
1. Acute diarrheal illness
- Chronic diarrhea
A. Small bowel vs large bowel diarrhea
B. Malabsorption vs maldigestion - How do you measure osmolarity in stool in patient with watery diarrhea?
- Acute diarrheal illness - less than 2 weeks duration
- Causes - infectious, mostly viral –> Norovirus (single stranded RNA virus) and Rotovirus (dsRNA) - acute
- bacterial more likely with severe, fever, blood in stool, longer duration
- parasite most likely with travel, immunocompromised, culture negative, longer duration - Chronic diarrhea - more than 4 weeks duration
A. Small bowel diarrhea - bulky stools, infrequent and with less urgency
- Large bowel diarrhea - frequent small stools with urgency and tenesmus (cramping and spasm)
B.
i. Malabsorption - disease of intestinal mucous lining
- e.g. Celiac disease, environmental enteropathy, SIBO, Whipple disease, Giardia, Small bowel lymphoma
ii. Maldigestion - exocrine pancreatic dysfunction eg chronic pancreatitis (alcohol or cystic fibrosis) –> activation of trypsin in pancreas –> repeated insults –> calcifications on X-ray
- Both have weight loss, malnutrition, diarrhea, steatorrhea (mild in malabsorption, profound in maldigestion), muscle wasting, anemia, osteoporosis, and neurological issues
- Fecal osmotic gap = 290 - 2(Na + K)
<50 mOsm - secretory diarrhea
>125 mOsm - osmotic diarrhea due to agent eg colonoscopy prep
[Small intestine disorders] Describe the four categories of diarrhea including pathophys and causes: 1. Osmotic 2. Secretory 3. Inflammatory 4. Dysmotility
- Osmotic - driven by eating (and stops when oral intake stops) - excessive osmotic particles in gut lumen
- due to lactose intolerance, artificial sweeteners, mushrooms - Secretory - massive secretion of salt, sodium, and water irrespective of eating –> watery diarrhea
- due to infectious agents (cholera toxin, ETEC), neuroendocrine tumors (VIPoma), bile salts - Inflammatory - fever, dehydration, abdominal pain, bloody diarrhea with tenesmus, (cramping and spasm), urgency, nocturnal diarrhea
- due to ulcerative colitis, Crohn’s, invasive bacteria (EHEC, Shiga, Campylobacter) - Dysmotility - tissue transglutaminase negative (no Celiac) with normal IgA, no travel, HbA1C normal
- can be due to intestinal stasis (e.g. diabetic gastroparesis, scleroderma) –> SIBO (small intestine bacterial overgrowth) –> deconjugate bile salts and increased osmotic particles due to bacterial fermentation –> steatorrhea, diarrhea if severe
- confirm with early H2 breath peak on lactulose test
[Small intestine disorders]
Celiac disease A. Cause B. Pathophys C. Clinical D. Diagnosis E. Complications
Celiac disease eg Nontropical sprue
A. Cause - autoimmune; malabsorption type small bowel disease; associated with HLA-DQ2 and DQ8
B. Pathophys - gliadin (component of gluten) is deamidated by tissue transglutaminase (tTG) –> presented by APC via MHC II –> CD4+ T cells mediate tissue damage via inflammatory response –> villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes –> intestinal malabsorption and nutrient depletion
- affects mostly duodenum / proximal jejunum
C. Clinical- bloating/abdominal distension + chronic osmotic diarrhea (due to bile acid malabsorption), steatorrhea, megaloblastic anemia and secondary lactase deficiency
- Kids - failure to thrive (short stature, delayed puberty)
- Adults
i. Skin - dermatitis herpetiformis –> symmetric, pruritic herpes-like vesicles on extensor surfaces of extremities (elbows, knees); due to IgA anti-tTG deposition on tips of dermal papillae which form pustules/vesicles
ii. Bone - decreased bone density –> osteoporosis, arthritis
iii. CNS - ataxia, seizures
iv. Reproductive - infertility
D. Diagnosis - serology study to detect IgA antibodies against endomysium (connective tissue sheath around muscle fiber), tTG, or gliadin
- Sudan black stain for fecal fat
- D-xylose test - blood and urine levels of D-xylose (which is passively absorbed) are decreased –> malabsorption
E. Complications
- small intestinal carcinoma - v rare
- EATL (enteropathy-associated T cell lymphoma) - intestinal masses and lymphadenopathy
[Small intestine disorders]
- Environmental enteropathy i.e. Tropical sprue
- Short bowel syndrome
A. Cause B. Pathophys C. Clinical D. Diagnosis E. Treatment
- Environmental enteropathy i.e. Tropical sprue - malabsorption disorder
A. Cause - unknown infectious agent, seen in tropics e.g. Puerto Rico and India
B. Pathophys - unknown; occurs in jejunum and ileum (Celiac is in duodenum)
C. Clinical - same as celiac –> chronic diarrhea, steatorrhea, weight loss + megaloblastic anemia due to deficiencies (folate B9 absorbed in jejunum)
D. Diagnosis - small bowel biopsy shows flattened villi and mononuclear cell infiltrate in lamina propria, resembles celiac disease; returns to normal when they return to temperate area
E. Treatment - antibiotics (tetracycline), folic acid
*celiac does not respond to antibiotics - Short bowel syndrome - lack of adequate absorptive surface
A. Cause - surgical resection due to Crohn’s, malignancy, radiation, vascular insult
B. Pathophys + Clinical
i. jejunum - gastric hypersecretion (loss of GIP, VIP)
ii. ileum - B12 deficiency, bile salt malabsorption (>100cm resected) –> ADEK deficiency, steatorrhea, diarrhea (can be osmotic or secretory); SIBO (due to intestinal dysmotility)
Roux-en-Y gastric bypass –> leads to deficiency of thiamine B1 (encephalopathy, nystagmus, gait ataxia), B12 (megaloblastic anemia), + copper (neurological findings e.g. UMN spasticity, stocking glove neuropathy + anemia)
[Small intestine disorders]
3. Whipple disease
- Abetalipoproteinemia
A. Cause B. Pathophys C. Clinical D. Diagnosis E. Treatment
- Whipple disease
A. Cause - infectious agent Tropheryni whipplei (Gram + rods in Actinomycetes family)
- rare, predominately male
B. Pathophys - lamina propria of villi loaded with macrophages containing T. whippleii –> compress lacteals –> cannot transfer chylomicrons from enterocytes to lymphatics –> fat malabsorption
C. Clinical - more common in older men
- cardiac symptoms
- arthralgias (eg migratory arthritis)
- neuro sx (nystagmus, dementia, myoclonus)
- diarrhea, steatorrhea, weight loss occur later
D. Diagnosis - positive fecal Sudan stain, foamy macrophages that stain PAS (+) on small bowel biopsy; thickened small bowel with rapid transit time
E. Treatment - antibiotics - Abetalipoproteinemia
A. Cause - rare autosomal recessive deficiency of apolipoprotein B48 and B100; pediatric
B. Pathophys - cannot make chylomicron without B48; cannot make VLDL and LDL without B100
- acanthocytes - star-shaped RBCs
C. Clinical - presents in infancy as failure to thrive
- presents in childhood with steatorrhea, ataxia, retinitis pigmentosa, ADEK deficiency
Sketchies to review: Staphylococcus EHEC, ETEC Shigella Campylobacter Norovirus Salmonella Giardia Vibrio Entamoeba Schistosomiasis Cryptosporidium Ascaris Rotavirus
Staphylococcus X EHEC, ETEC X Shigella X Campylobacter X Norovirus X Salmonella X Giardia X Vibrio X Entamoeba X Schistosomiasis X Cryptosporidium X Ascaris X Rotavirus X
[GI Pharmacology]
I. Drugs that treat acid-peptic disease
- H2 receptor antagonists
A. MOA
B. Clinical indications
C. Adverse effects
I. Acid-peptic disease - peptic ulcers, GERD, stress-related mucosal injury due to imbalance between factors that are aggressive (acid, pepsin, bile) vs defensive (blood flow, mucous, HC03-, prostaglandins)
- H2 receptor antagonists - “-dines” eg ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid), cimetidine (Tagamet)
A. MOA - competitive inhibitors of histamine on H2 receptors - most effective at reducing nocturnal acid secretion
- famotidine is most potent and no drug interactions
B. Clinical indications - being replaced by PPIs but OTC versions heavily used
i. GERD - for <3x week
ii. Gastric and duodenal ulcers (Peptic ulcer disease) - bedtime administration
C. Adverse effects - generally safe, most side effects with cimetidine (anti-androgenic –> galactorrhea, impotence, gynecomastia)
- GI effects
- lipophilic - cross placenta and breast milk –> do not use in pregnancy
[GI Pharmacology]
I. Drugs that treat acid-peptic disease
- Proton Pump Inhibitors (PPIs)
A. MOA
B. Clinical indications
C. Adverse effects
- Proton Pump Inhibitors (PPIs) - “azoles” eg omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid)
* other -azoles are antifungals eg ketoconazole
A. MOA - prodrug that is activated via protonation in acid –> forms covalent disulfide bond with the proton pump –> noncompetitive, irreversible inhibitor
- suppress fasting and meal-stimulated acid secretion better than H2 antagonists
B. Clinical indications - once daily dosing
i. GERD - first line - most effective for tx of GERD
ii. peptic ulcer disease - heal duodenal (and to lesser extent gastric) ulcers, faster healing and symptom relief than H2 antagonists
iii. H. pylori associated ulcers - heal ulcer and eradicate organism (triple therapy with amoxicillin + clarithromycin; quadruple therapy with metronidazole)
iv. NSAID-associated ulcers eg ibuprofen (Advil), naproxen (Aleve)
C. Adverse effects - generally safe, some GI side effects
- low bioavailability when taken with food - eat on empty stomach
- suppresses gastric acid barrier –> ↑ gastric bacterial concentrations –> ↑ risk of enteric infections (eg C. difficile), respiratory infections
- decreased Ca2+ absorption (needs acidic environment) –> worsens osteoporosis and bone fractures
[GI Pharmacology]
I. Drugs that treat acid-peptic disease
- Antacids
A. MOA
B. Clinical indications
C. Adverse effects
- Antacids
A. MOA - weak bases - Mg(OH)2, Al(OH)3, CaC03 (Tums) - that react with gastric HCl –> salt + water
- reduce gastric acidity as well as pepsin, which is inactive in pH>4
- work fast but weak in neutralizing ability
B. Clinical indications
i. intermittent heartburn
ii. duodenal ulcers - but no gastric
iii. GERD - antacid + alginic acid (Gaviscon)
C. Adverse effects - gassy, bloated
[GI Pharmacology] I. Drugs that treat acid-peptic disease 4. Sucralfate 5. Colloidal bismuth compounds 6. Misoprostol
A. MOA
B. Clinical indications
C. Adverse effects
- Sucralfate - sucrose + Al(OH)3
A. MOA - viscous substance that is insoluble in water and has weak buffering action –> selectively binds necrotic ulcer tissue –> acts as a barrier to acid, pepsin, bile –> reestablish pH gradient in mucous layer
B. Clinical indications - duodenal ulcers - prevention and healing; traveler’s diarrhea
C. Adverse effects - requires acidic conditions –> cannot be taken with PPIs, H2 antagonists, or antacids - Colloidal bismuth compounds - Pepto-Bismol
A. MOA - same as sucralfate
B. Clinical indications - H. pylori ulcers -direct antimicrobial activity, esp when combined with tetracycline and metronidazole - Misoprostol
A. MOA - PGE1 analog –> ↑ production of mucous barrier and ↓ acid production
B. Clinical indications - NSAID-induced ulcers
- off label to induce labor
C. Adverse effects - don’t give to women of childbearing age (abortifacient), dose-dependent diarrhea
[GI Pharmacology]
II. Drugs that promote gastrointestinal motility (Prokinetic agents)
- Metoclopramide (Reglan)
A. MOA
B. Clinical indications
C. Adverse effects
- Metoclopramide (Reglan)
A. MOA - blocks dopamine D2 receptors in area postrema (chemoreceptor trigger zone) –> increases esophageal clearance, raises LES pressure, and accelerates gastric emptying
B. Clinical indications
i. antiemetic - main use
ii. prokinetic - symptomatic relief in pts with post-op gastric motor failure or diabetic gastroparesis
iii. treats refractory heartburn - in combo with antisecretory agents (H2 antagonist, PPI)
C. Adverse effects - many CNS effects –> extrapyramidal sx (Parkinsonism), anxiety, depression
[GI Pharmacology]
II. Drugs that promote gastrointestinal motility (Prokinetic agents)
- Lubiprostone
- Linaclotide
A. MOA
B. Clinical indications
C. Adverse effects
NOT ON STEP 1
- Lubiprostone (Amitiza)
A. MOA - fatty acid from PGE1 that activates Type 2 Cl- channels in GI epithelial cells –> chloride-rich fluid secretion –> softens stool, increases motility, promotes BMs
B. Clinical indication
i. chronic idiopathic constipation
ii. IBS with constipation
C. Adverse effects - not for use in children (under 16)
- nausea, diarrhea, headache - Linaclotide (Linzess)
A. MOA - peptide agonist of guanylate cyclase that activates CFTR Cl- channel in GI epithelial cell –> chloride-rich fluid secretion –> softens stool, increases motility, promotes BMs
- reduces pain by decreased activation of colonic sensory neurons
B. Clinical indications
i. chronic idiopathic constipation
ii. IBS with constipation
C. Adverse effects - not for use in children (under 16)
- most common is diarrhea
[Abdominal Pain] 1. Visceral pain A. Development B. Innervation C. Triggers D. Characteristics E. Clinical features (how is pain perceived) F. Describe how persistent visceral pain can become referred
- Visceral pain - arises from irritation of visceral peritoneum, hollow viscera, and mesentery
* visceral peritoneum - peritoneal covering over mesentery and solid organs
A. Development - derived from splanchnic layer of lateral plate mesoderm
B. Innervation - autonomic; visceral pain afferents travel with splanchnic SNS nerves and do not lateralize –> visceral pain perceived in midline
- nerves run along blood vessels in mesentery - can associate location of pain with blood supply e.g. foregut (celiac), midgut (SMA), hindgut (IMA)
C. Triggers - sense mechanical (tension, overdistension, mesenteric traction, visceral muscle spasm) and chemical (ischemia, inflammation)
D. Characteristics -midline
- poorly localized (low density of pain receptors, convergence onto same level of spinal cord)
- not evoked equally from all organs (hollow>solid)
E. Clinical - dull, deep-seated discomfort, crampy/colicky, aching
- accompanied by autonomic sx (pain afferents run with autonomic nerves) –> diaphoresis, changes in HR and BP, nausea, diarrhea
F. Referred pain - visceral pain perceived in superficial somatic structures due to convergence –> visceral afferents synapse onto same neurons in spinal cord as somatic afferents
- diffuse (midline) –> then referred
[Abdominal Pain] 2. Somatic (parietal) pain A. Development B. Anatomy C. Triggers D. Characteristics E. Clinical features (how is pain perceived) F. Describe rigidity associated with somatic pain
- Somatic pain - arises from irritation of parietal peritoneum (peritoneal lining of abdominal wall, pelvis, diaphragm)
A. Development - derived from somatic layer of lateral plate mesoderm
B. Anatomy - somatic; parietal pain afferents are spinal afferent nerves - skin, muscle and parietal peritoneum of abdominal wall innervated by the same T7-L1 spinal nerves –> pain lateralizes
C. Triggers - detects peritonitis - inflammation of peritoneum secondary to illness in viscera (e.g. perforation)
- fluid in abdomen common
D. Characteristics - lateralized to specific quadrant
- many sensory nerves with dense meshwork of free nerve endings
- precise mapping of spinal nerves to spinal cord and cortex (not multiple organs coming to same level like the viscera)
E. Clinical features - severe, sharp, knife-like pain
- constant (not colicky), well-localized, worsens with movement
F. Rigidity –> involuntary guarding due to reflex arc –> pain afferents come into spinal cord and synapse onto motor neurons going to abdominal wall musculature
- differentiate from voluntary guarding bc patient cannot maintain that on inspiration
[Abdominal Pain]
1. GI inflammation (e.g. peritonitis, appendicitis, diverticulitis, cholecystitis)
A. Pathophysiology
B. Clinical progression
- GI inflammation
A. Luminal obstruction (eg stone, lymph node) –> response is secretion of fluid into lumen (distension) and reflex contraction –> increased pressure –> venous congestion and thrombosis of capillaries –> barrier disrupted and bacteria invade –> ischemia and inflammation –> focal abscess –> gangrenous necrosis and perforation
B. Dull, periumbilical pain and nausea with luminal obstruction –> increasingly severe pain with venous congestion / ischemia –> constant, sharp, localized pain when inflamed organ perforates –> leads to parietal peritoneum inflammation “peritonitis”
- appendicitis - RLQ
- diverticulitis (usually in sigmoid colon) - LLQ
[Abdominal Pain] 1. Small bowel obstruction A. Causes B. Symptoms 2. Large bowel obstruction
Bowel obstruction - cessation of BM and passage of gas, high pitched tinkling bowel sounds, colicky/crampy abdominal pain + nausea/vomiting
- Small bowel obstruction
- Causes, in order of likelihood:
A- adhesions (from prior surgery), B- bulges (hernia), C- cancer
B. Symptoms - obstruction leads to secretion of fluid into lumen and reflex contraction of smooth muscle to overcome obstruction –> abdominal distension - Large bowel obstruction
- Cause - MCC is malignancy. most common benign cause is sigmoid volvulus (sigmoid colon twists on itself), more common in elderly
[Abdominal wall disorders]
Congenital defects
1. Gastroschisis
2. Omphalocele
Congenital defects
- Gastroschisis - full thickness abdominal wall defect that occurs to the right of umbilicus
- due to abnormal folding of anterior abdominal wall during development (closes by 4 wks) –> exposure of abdominal contents / viscera (not covered by peritoneal sac)
- emergency, needs immediate closure; higher survival rate (even with poorer GI function) bc not associated with other anomalies - Omphalocele - persistent herniation of bowel into umbilical cord –> covered by peritoneum and amnion lining, usually larger than gastroschisis
- physiological herniation during development at 6 wks that allows bowels to develop then rotate and go back into the gut at 10 wks
- worse prognosis bc of high risk of associated anomalies e.g. neuploidy, structural anomalies eg VACTERL –> Vertebral, Anal, Cardiac, TE fistula, Renal, Limb
[Abdominal wall disorders]
Congenital defects
3. Meckel diverticulum
4. Diaphragmatic hernia
- Meckel diverticulum - most common congenital anomaly of GI tract; true diverticulum - outpouching of all 3 layers of bowel wall due to incomplete obliteration of vitelline duct (connects umbilicus to terminal ileum in utero)
Rule of 2’s:
-2” long
- found in distal ileum, within 2 ft of ileocecal valve
- 2% of pop
- presents at 2 yrs of age
- 2 main presentations: A) acute appendicitis or B) hematochezia –> copious brick-red painless rectal bleeding
- 2 epithelial types (pancreatic + gastric) - Diaphragmatic hernia - due to congenital defect of pleuroperitoneal membrane, more commonly occurs on left side where pericardioperitoneal canal is larger and closes later
- hypoplastic lung on affected side with pulmonary HTN and hypoxemia
- diagnosed on prenatal US, present at birth with respiratory distress (tachypnea, grunting, nasal flaring), cyanosis, absent bowel sounds, and scaphoid abdomen
[Abdominal wall disorders] Abdominal wall hernia 1. Indirect inguinal 2. Direct inguinal 3. Femoral
- Indirect inguinal hernia - goes through deep inguinal ring, superficial inguinal ring, and into scrotum –> covered by all three layers of spermatic fascia
- lateral to inferior epigastric vessels
- more common in younger males, due to patent processus vaginalis - Direct inguinal - goes through superficial inguinal ring and bulges through abdominal wall at Hesselbach’s triangle (inferior epigastric vessels, rectus abdominus, inguinal ligament)
- medial to inferior epigastric vessels
- more common in older men, due to weakness in transversalis fascia - Femoral - protrudes through femoral canal inferior to inguinal ligament, and medial to femoral vein
- more common in women, but most common hernia overall in women are inguinal
- more likely to present with hernia or strangulation
* (NAVEL from lateral to medial - nerve, artery, vein, empty lymphatic space)
[Abdominal wall disorders]
- Derivatives of ventral mesentery
- Pringle Maneuver
- Ventral mesentery - suspensory ligaments of liver (falciform, coronary, and triangular)
+ lesser omentum (hepatogastric + hepatoduodenal ligaments)
- all others are dorsal - Pringle Maneuver - compress hepatoduodenal ligament (which contains portal triad - portal vein, common bile duct, and proper hepatic artery) to control bleeding
[Inflammatory Bowel Disease IBD] Crohn's disease 1. Epi 2. Pathology 3. Macro/Micro 4. Clinical 5. Complications 6. Extraintestinal 7. Treatment
Crohn’s
- Epi - peak incidence in 20s, higher risk in smokers, genetic predisposition
- linked to Th1 immune response (cell mediated immunity via IgG, IFNgamma, TNFalpha) - Pathology - transmural inflammatory disease that affects ANY part of GI tract from mouth to anus; terminal ileum most common site; rectum is spared
- Appearance
A. Macroscopic - skip lesions with cobblestone mucosa; creeping fat; strictures with “string sign” on imaging
- Aphthous ulcers in mouth (i.e. canker sores)
B. Microscopic - noncaseating granulomas throughout all three layers - Clinical - systemic symptoms, pain, abdominal mass, and large bowel obstruction more common than with UC
A. Ileocolitis - RLQ pain with non-bloody diarrhea
B. Jejunocolitis - malabsorption –> steatorrhea, nutritional deficiency eg B12 deficiency
C. Colonic - large bowel diarrhea (tenesmus, bleeding, frequent small stools)
D. Perianal - fistula, fissure, abscesses around anus - Complications - fistula (due to persistent inflammation), small bowel obstruction (due to strictures)
- Extraintestinal - calcium oxalate kidney stones
- normally oxalate in lumen combines with calcium to be excreted in stool
- in Crohn’s, unbound FFAs take up the Ca2+, so oxalate is reabsorbed in the colon –> hyperoxaluria –> kidney stones - Treatment - corticosteroids (e.g. prednisone, budesonide), antimetabolite (azathioprine), antibiotics (metronidazole, cipro), anti-TNF Abs (infliximab / Remicade, adalimumab / Humira)
[IBD] Ulcerative colitis 1. Epi 2. Pathology 3. Macro/Micro 4. Clinical 5. Complications 6. Extraintestinal 7. Treatment
Ulcerative colitis
- Epi - peak incidence in 20s, smoking is protective, genetic predisposition
- linked to Th2 (humoral immunity via IgE, IL-4,5,10,13) - Pathology - chronic inflammation of the mucosa (epithelium, lamina propria, and muscularis mucosa) and occasionally submucosa –> continuous and superficial
- starts in rectum and extends proximally throughout colon - Appearance
A. Macroscopic - continuous, symmetric lesions (NO skip lesions) ONLY in colon; pseudopolyps (regenerated mucosa); loss of haustra with “lead pipe” sign on X-ray
B. Microscopic - crypt abscesses with neutrophils - Clinical - bloody diarrhea more common than with Crohn’s
- exacerbations and remissions; LLQ pain with bloody diarrhea [Crohn’s is RLQ without blood in stool]
- large bowel diarrhea with frequent small stools, tenesmus, and urgency
- severe disease - diffuse abdominal tenderness + systemic symptoms - Complications
- toxic megacolon - sudden onset fever, abdominal distension, no bowel function + severe bloody diarrhea, low BP and increased HR
- colorectal cancer - increased risk with extent (entire colon) and duration (10+ years of disease) - Extraintestinal - primary sclerosing cholangitis (inflammation of bile ducts), associated with p-ANCA
Treatment - 5-aminosalicylates (mesalamine), antimetabolite (6-MP), anti-TNF Abs (infliximab / Remicade)
