Block 1 (Upper GI)

Question 1

Gut Development

Answer 1

splanchnic mesenchyme - muscle, tissue, walls of gut
Endoderm - epithelial components (foregut, midgut, hindgut)
neural crest - enteric nervous system
7weeks: stomach 90deg longitudinal clockwise (brings vagus nerve with it)
5weeks: midgut elongates, forms loop with cranial and caudal limb, grows, umbilical herniation, 90deg counterclockwise, then retracts back into abdomen, then 180deg more, for a total of 270deg rotation to form bowels

Question 2

Layers of the gut wall

Answer 2

lumen -
mucosa (epithelium, lamina propria-loose connective tissue and blood/lymph capillaries, muscularis musoca-local movements) -
submucosa-loose collagen, mucous secreting glands, Meissner’s plexus,
muscularis (inner circular, myenteric plexus, outer longitudinal),
adventitia (loose connective tissue, outside peritoneum) / serosa (simple squamous, within peritoneal cavity)

Question 3

Pancreas development

Answer 3

dorsal and ventral bud, ventral bud rotates around and fuses
dorsal bud: majority of pancreas
ventral bud: head and main duct

Question 4

Defects in GI devo

Answer 4

duodenal atresia or stenosis: vomiting, polyhydramnios
Gastroschesis: defect in abdominal wall, exposed abdominal viscera (not hernia)
Omphalocele: herniation of abdominal contents into umbilicus
Malrotation of gut
Meckel diverticulum: outpocketing of ileum
Hirschprung disease: megacolon due to aganglionosis, thus fails to relax

Question 5

Submucosal (Meissner’s) plexus vs Myenteric (Auerbach’s) plexus

Answer 5

Meissner’s: mucosal movement, secretory activity, blood flow

Auerbach’s: peristalsis

Question 6

Esophagus layers

Answer 6

Mucosa: stratified non-keratinized epithelium with Langerhans cells,, Lamina propria has cardiac glands that secrete mucous
Submucosa: glands (acini) similar to salivary, mucous cells (basal nucleus), serous cells (central nucleus, secrete pepsinogen and lysozyme)
Muscularis externa: upper 1/3 is skeletal, lower 2/3 is smooth
Adventitia:

Question 7

Gastroesophageal junction

Answer 7

stratified squamous epithelium transition to simple columnar

gastroesophageal sphincter

Question 8

Stomach layers

Answer 8

Epithelium: simple columnar, thick mucous, traps HCO3-, gastric pits
Lamina propria: gasric glands, Enterochromaffin-type cells secrete histamine which increases acid
Submucosa: wandering cells, lymphocytes, eosinophils, etc, vascular and lymphatics
Muscularis: circular and longitudinal as well as oblique fibers (controlled by Auerbachs)

Question 9

Gastric pits/glands

Answer 9

Pit: surface mucous cells
Isthmus: parietal cells
Neck: neck mucous cells, stem cells, parietal cells
Base: chief cells, parietal cells, mucous cells, neuroendocrine cells

[parietal=oxyntic,, chief=peptic/zymogenic]

Question 10

Enteroendocrine cells

Answer 10

small cells secrete specific proteins
G: gastrin (+ by GRP, - by somatostatin)
EC: serotonin
D: somatostatin (+ by HCl and gastrin, - by ACh)
A: enteroglucagon
ECL: histamine (+ by gastrin, - by somatostatin)

Question 11

Parietal cells

Answer 11

eosinophilic, pyramidal,, secretory canaliculus, microvilli, tubulovesicular network, rich in mitochondria
Secrete HCl and gastric Intrinsic Factor(B12)
HCl (+ by gastrin, ACh, Histamine, - by somatostatin)

Question 12

Chief cells

Answer 12

Secrete digestive enzymes (pepsinogen, gastric lipase)
zymogen secretory granules
have lots of rER, golgi
secretion stimulated by hormone secretin and vagus nerve
Pepsinogen (+ by ACh, HCl)

Question 13

Differences in mucosa in areas of stomach

Answer 13

fundus/body: straight tubular glands

pylorus: branched glands and more mucous cells
cardiac: shallower pits, highly coiled glands, more enteroendocrine cells

Question 14

Stomach response to a meal

Answer 14

Cephalic phase: parasympathetic - vagus - ACh - G cells - gastrin - HCl
Gastric phase: distention - G cells —
Intestinal phase: chyme released - gastric emptying slows - distention of intestine - enterogastric reflex - gastric-inhibition - cholecystokinin and secretin

Question 15

Esophagus anatomy

Answer 15

hollow muscular tube, GI layers as usual
UES (skeletal, fast) and LES (smooth, slow)
UES is right behind cricoid cartilage
LES is thickening of muscle at crural diaphram - Z-line

Question 16

Esophageal Peristalsis

Answer 16

Primary: triggered by swallow (pharyngeal contraction and UES relaxation)
Secondary: triggered by esophagus distention
Proximal (skeletal): sequence generated by central pattern generator in brinstem
Distal (smooth): latency gradient, dual peripheral innervation,, wave of inhibition followed by wave of excitation
Excitatory: ACh
Inhibitory: NO

Question 17

Dysphagia

Answer 17

difficulty swallowing
Mechanical: peptic stricture (chronic reflux), esophageal ring (intermittent), cancer (progressive),, solid>liquid
Neuromuscular: Achalasia (progressive, with reflux), spasm (intermittent), dysmotility,, liquid=solid
Eosinophilic esophagitis can be both
Diagnose: endoscopy, manometry, esophagram xray

Question 18

Achalasia

Answer 18

impaired relaxation of LES
loss of peristalsis (disorganized)
mega-esophagus
loss of inhibitory (NO) activity,, degeneration of ganglion cells in myenteric plexus, inflammatory lymphocytic infiltration
dysphagia of liquid and solid, heartburn, slow progression
can lead to squamous cell carcinoma, candida, or diverticulum
Diagnose: manometry, radiograph, endoscope (bird-beak early, sigmoid shape late)
Tx: drugs (NO donors), endoscopy (botox, dilation), surgery

Question 19

Esophageal spasm

Answer 19

discoordinated contraction of muscularis layer

dysphagia of food and fluid

Question 20

Complete Aperistalsis

Answer 20

usually from scleroderma

reflux symptoms

Question 21

Gastroesophageal Reflux Disease (GERD)

Answer 21

esophagus has some protection but not enough against acid,, most important barrier is LES
Incompetent LES - reflux - mucosal damage - esophagitis (IL-6, H2O2, PAF and PGE2) - decreased peristalsis - more damage - decreased LES pressure - worse reflux
elongation of lamina propria papillae, reactive epithelial changes
Probably usually due to transient LES relaxation
Tx: lifestyle mod (weight loss, avoid trigger, elevation), PPIs, surgery
Complications: ulcer, stricture, bleeding, Barrett’s

Question 22

Hiatal Hernia

Answer 22

part of stomach (LES) protrudes up past diaphram
sliding (common) or para-esophageal (rare)
Can cause GERD

Question 23

Reflux esophagitis

Answer 23

From GERD
basal zone hyperplasia,, eosinophils then neutrophils
hyperemia or erosions visible
sx: heartburn, regurgitation

Question 24

Eosinophilic Esophagitis

Answer 24

large numbers of eosinophils (more than 15/HPF), especially found higher up
sx: dysphagia in adults (food impaction), nausea and food intolerance in kids
allergic immune rxn to ingested allergens, T-cell mediated hypersensitivity
cytokine cascade, MBP, IL-5, IL-13
tissue remodeling and fibrosis
endoscope: corrugated or abscesses
Tx: elimination diet, steroids

Question 25

Other esophagitis

Answer 25

Chemical: acid, alcohol, hot, smoking Infectious: usually immnosupp, viral: HSV=punched out ulcers nuclear inclusions, CMV=shallow ulcers cytoplasmic and nuclear inclusions,, fungal: candida Iatrogenic: chemo and radiation Skin disorder: Bullous pemphigoid, epidermolysis bullosa

Question 26

Barrett's Esophagus

Answer 26

intestinal metaplasia of esophageal epithelium (goblet cells) near stomach junction complication of GERD,, pre-malignant if dysplastic Cdx gene involved,, cancers usually have p53, cyclinD1 probs Can lead to adenocarcinoma (invasion of lamina propria = carcinoma) Diagnose: endoscope and histologic metaplasia white adult male with chronic reflux

Question 27

Esophageal Adenocarcinoma

Answer 27

white middle age male, incidence increasing comes from Barrett's chromosomal and p53, cyclinD1 probs also TNF and NFkb (inflammation) distal esophagus,, produce mucin and form dense glands sx: dysphagia, weight loss, vomiting poor prognosis unless caught early

Question 28

Esophageal Squamous Cell Carcinoma

Answer 28

``` african american male older than 45 alcohol and tobacco risk factors middle or upper esophagus small, white plaques early, grow into and obstruct lumen mostly well differentiated sx: dysphagia, obstruction, weight loss poor prognosis ```

Question 29

Salivary glands

Answer 29

``` Parotid: CNXI Submaxillary: CNVII Sublingual: CNVII primary secretion: a-amylase, mucus, extracellular fluid,, also absorb Na, Cl,, secrete K, HCO3- 1L/day ```

Question 30

Saliva components

Answer 30

a-amylase, mucus, fluid, K, HCO3- (low NaCl) Lysozyme- kills G+ bacteria Other bacteria defense: Peroxidase, lactoferrin, IgA, Defensins, Mucins Mucins: lubricants, highly glycosylated, antimicrobial

Question 31

Sjogren's Syndrome

Answer 31

``` autoantibodies to salivary glands dry mouth (xerostomia), dry eyes, etc ```

Question 32

Stomach acid secretion

Answer 32

vagus nerve - ACh - stimulates parietal cell HCl and ECL cell histamine, inhibits D cell somatostatin gastric releasing peptide stimulates G cell gastrin D cell somatostatin is stimulated by HCl G cell gastrin inhibited by somatostatin Gastrin stimulates D cell somatostatin, ECl cell histamine, parietal cell HCl ECL cell histamine stimulated by ACh, inhibited by somatostatin Histamine stimulates parietal cell HCl Parietal cell HCl stim by ACh, histamine, gastrin,, inhibited by somatostatin Following a meal, pH goes up due to food buffering, then drops again as H is secreted and food empties

Question 33

Fat, carbohydrate, protein digestion in stomach

Answer 33

Fat: lingual lipase (saliva),, gastric lipase (chief cells) Carbohydrates: a-amylase (saliva) Protein: pepsinogens (chief cells) (activated by HCl or pepsin)

Question 34

Gastritis

Answer 34

``` inflammation and mucosal injury H. pylori metaplastic atrophic (autoimmune and environmental) Granulomatous Eosinophilic Lymphocytic ``` Acute: neutrophils, due to transient insult Chronic: lymphocytes, due to chronic inflammation - dysplasia and neoplasia

Question 35

Gastropathies

Answer 35

Epithelial cell damage with NO inflammation Acute hemorrhagic chronic chemical (NSAIDs, bile) Hyperplastic (Menetrier's and Zollinger-Ellison) Nonhyperplastic

Question 36

H pylori gastritis

Answer 36

Acute: epigastric pain, comiting, no fever prefers antrum, goes chronic unless treated Chronic: antrum and body, early-increased gastrin, late-loss of G cells and less acid lymphocytes present on histology

Question 37

H heilmannii gastritis

Answer 37

uncommon | treated similar to H pylori

Question 38

Metaplastic atrophic gastritis (MAG)

Answer 38

mucosal thinning, gland loss autoimmune or environmental metaplasia: pseudopyloric (replacement of parietal and chief with mucous cells) or intestinal (replacement o surface epithelium with goblet cells)

Question 39

Autoimmune MAG

Answer 39

Inherited immune response against parietal cells and intrinsic factor women,, pernicious anemia (B12 def), hypochloryhdria (low acid) metaplasia, glandular atrophy, inflammation body and fundus of stomach increased risk of malignancy less risk of H pylori

Question 40

Environmental MAG

Answer 40

dietary: nitroso compounds NO lack of acid, NO elevated gastrin, NO antibodies, no anemia increased risk of gastric ulcer and cancer multiple focally dist areas of atrophy, metaplasia, inflammation, in antrum

Question 41

Granulomatous gastritis

Answer 41

rare organized aggregate of infiltrate infectious or noninfectious Non-caseating (Crohns, sarcoidosis), caseating (infxn), or necrotizing (vasculitis)

Question 42

Eosinophilic gastritis

Answer 42

assoc with allergic disease Tx: prednisone distal antrum, nonspecific sx can get muscle layer or subserosal disease (ascites)

Question 43

Lymphocytic gastritis

Answer 43

Celiac disease assoc

Question 44

Acute hemorrhagic erosive gastropathy

Answer 44

damage to epithelium agents: alcohol, bile, NSAIDs, chemo, etc or hypoxia

Question 45

Chronic chemical gastropathy

Answer 45

long term exposure to substances NSAIDs or bile reflux foveolar hyperplasia, edema, more smooth muscle, vascular dilatation

Question 46

Hyperplastic gastropathy

Answer 46

enlarged gastric folds | Menetrier's or Zollinger-Ellison

Question 47

Menetrier's disease

Answer 47

``` hyperplastic gastropathy - protein loss overproduction of TGFa - EGFR - epithelial prolif CMV in pediatric cases Tx: CMV tx, gastrectomy, EGFR antibody increased risk of gastric adenocarcinoma ```

Question 48

Zollinger-Ellison syndrome

Answer 48

``` hyperplastic gastropathy caused by gastrinomas gastric acid hypersecretion (leads to ulcers) hyperplasia of parietal cell increase in histamine-secreing ECL cells gastric body and fundus ```

Question 49

Nonhyperplastic gastropathy

Answer 49

causes: infiltrative disease, malignancy

Question 50

Peptic ulcer disease (PUD)

Answer 50

defects extend through muscularis mucosa risks: H pylori, NSAIDs,, steroids too, smoking, diet, psychological Dyspepsia (upper abd pain),, or silent complications: penetrating, perforation, vomiting, bleeding, gastrocolic fistula Tx: PPIs (better than H2 blockers),, somatostatin and octreotide, endoscope

Question 51

Duodenal ulcers

Answer 51

H pylori increased gastric acid secretion gastric metaplasia,, inflammation

Question 52

Gastric ulcers

Answer 52

``` proximal ulcers: low acid distal ulcers: high acid Stress ulcers (many): Curling: proximal due to burns or trauma Cushing: due to intracranial injury ```

Question 53

Functional Dyspepsia

Answer 53

postprandial fullness, early satiety, epigastric pain no evidence of structural disease sx for 3mo over 6mo unclear, dysmotility, hypersensitivity, H pylori, microbiome, psychosocial eval: rule out bad stuff (EGD if alarms), treat H pylori, try PPI Tx: tricyclic antidep, metoclopramide, buspirone, painkillers

Question 54

Helicobacter pylori

Answer 54

spiral shaped, gram+ bacteria, with flagella, slow growing Catalase+, Oxidase+, urease+ exclusive to gastric epithelium, noninvasive, stim inflammatory IL-8 Bad kinds are VacA and CagA + Causes: gastric adenocarcinoma, MALT lymphoma, gastritis, Fe-def anemia, B12-def acid reflux (corpus: decreased acid, worse w treatment / antrum: increased gastrin, better with treatment), PUD Diagnose: urease testing, endoscope, urea breath test Tx: antibiotics, PPIs 10-14days

Question 55

NSAID gastric toxicity

Answer 55

COX1 produces prostaglandins PGs are good bc increase mucous secretions, blood flow, cell prolif, etc Also an effect from NO synthase Risk of PUD, esp with H pylori Slow release NSAIDs can get into distal small intestine and cause injury can cause strictures or diaphrams or erosions or ulcers

Question 56

Gastrointestinal Neuroendocrine tumors

Answer 56

well differentiated (G1, G2), glandular patterns, also called carcinoid tumors poorly diff (G3): resembles lung carcinoma increased mitotic index=worse prognosis (Ki67) Type 1: (most) derived from ECL cells, assoc with chronic atrophic gastritis and pernicious anemia, small and multiple, high gastrin and benign Type 2: assoc with gastrinomas and multiple endocrine neoplasia 1 (MEN1), high gastrin, indolent Type 3: most aggressive, normal gastrin level

Question 57

Multiple Endocrine Neoplasia type 1 (MEN1)

Answer 57

autosomal dominant PPP: pituitary, parathyroid, pancreatic type 2 gastrointestinal neuroendocrine tumors gastrinomas

Question 58

Gastrinoma

Answer 58

hypersecretion of acid from excess gastrin well diff neuroendocrine tumors located in triangle near duodenum/pancreas duodenal: small, multiple ,, pancreatic: solitary, malignant Zollinger-Ellison syndrome can be assoc with MEN1 (less metastasis) results in PUD usually, also diarrhea Diagnosis: fasting serum gastrin, secretin stim test Tx: PPI or surgery

Question 59

Gastric adenocarcinoma

Answer 59

intestinal or diffuse intestinal: related to risks, males, environmental factors,, Nitroso compounts, obesity, smoking, H pylori, Billroth surgery,, H pylori - NO synthase - b-catenin - wnt activation non-atrophic gastritis - atrophic gastritis - intestinal metaplasia - dysplasia - malignancy usually in antrum diffuse: worse prognosis, no risks,, loss of E-cadherin (16q22.1), no pre-cancer, signet ring, H pylori Tx: surgery

Question 60

Hereditary Diffuse Gastric Adenocarcinoma (HDGC)

Answer 60

autosomal dominant high risk for adenocarcinoma, also breast cancer Tx: prophylactic gastrectomy

Question 61

Gastric lymphoma

Answer 61

``` usually non-Hodgkin primary rare, secondary common marginal zone B-cell (MALT) or Diffuse large B-cell H pylori - MALT lymphoma Celiac - EATL and B-cell lymphoma ```

Question 62

Gastric Extrapulmonary Small Cell Carcinoma (ESCC)

Answer 62

rare, male usually advanced disseminated disease upper 1/3 of stomach tx: surgery, poor prognosis

Question 63

Esophageal webs

Answer 63

congenital or acquired from GERD upper esophagus, produce dysphagia Plummer-Vinson Syndrome: Fe-def anemia, atrophic glossitis, esophageal webs (pre-malignant)

Question 64

Esophageal rings

Answer 64

``` Schatzki rings A: above GE junction B: at GE junction dysphagia thicker and circumferential than web ```

Question 65

Pseudoacalasia

Answer 65

similar to achalasia | nerve damage due to T cruzi, metastatic tumor, amyloidosis, sarcoidosis

Question 66

Diverticula

Answer 66

out-pouching Zenker: just above UES - regurg of food, lump in neck Traction: midpoint of esophagus - asymptomatic Epiphrenic: just above LES - massive nocturnal regurg

Question 67

Mallory Weiss Syndrome

Answer 67

longitudinal tears at GE junction from severe wretching hemorrhage possible alcoholics

Question 68

Esophageal varices

Answer 68

secondary to portal HTN alcoholics massive hemorrhage

Question 69

Congenital hypertrophic pyloric stenosis

Answer 69

male predom progressive hypertrophy of pyloric sphincter presents at 2-4 weeks of age regurg and projectile vomit (w/o bile)

Question 70

Bezoars

Answer 70

bunches of stuff in digestive system Phytobezoar: plant Trichobezoar: hair

Question 71

Gastric polyps

Answer 71

``` uncommon in stomach usually inflammatory or hyperplastic (non-neoplastic) assoc with chronic gastritis Hyperplastic: inflammatory, multiple Adenoma: dysplastic, single ```