Ch. 17: The GI Tract Flashcards
fistula
connection of two tubes
-happens with trachea and esophagus
atresia
blind upper and lower esophagus with that little string thing in the middle
diaphragmatic hernia
abdominal viscera go into thoracic cavityy
-causes pulmonary hypoplasi= incompatible with life
omphalocele
when closure of abdominal musculature is incomplete and the abdominal viscera herniate into a ventral membranous sac
-gastroschisis is similar but it involves all of the layers
ectopia
most frequent: ectopic gastric mucosa in upper third of esophagus
ectopic pancreatic tissue
in esoph or stomach
-may mimic invasive cancer
gastric heterotopia
small patches of ectopic gastric mucosa in the small bowel or colon
-may present with occult blood loss due to peptic ulceration of adjacent mucosa
meckel diverticulum
true diverticulum
- outpouching of alimentary tract
- occurs at ILEUM
- failed involution of the vitelline duct
- 2’s
pyloric stenosis
more common in males
- turner syndrome and trisomy 18
- erythromycin and azithromycin exposure
- present between 3rd and 6th weeks of life NOT RIGHT AWAY
- firm ovoid abdominal mass
- obstructs the gastric outflow tract
hirschsprung disease
10% with down syndrome
- aganglionic megacolon
- distal instestinal segment that lacks both Meissner submucosal and the Auerbach myenteric plexus
- rectum is always affected
- failure to pass meconium
- bilious vomiting
- acquired version can come from Chagas disease (T. Cruzi)
nutcracker esophagus
high amplitude contractions at the distal esophagus
-loss of coordination of inner and outer muscle layers
diffuse esophageal spasm
contraction of the distal esophageal smooth muscle
hypertensive lower esophageal sphincter
abscence of altered patterns of osphageal contraciton
-achalasia is the same way but WITH perstaltic contractions…achalasia has no peristalsis
zenker diverticulum
above the upper esophageal sphincter
-regurgitation and halitosis
esophageal stenosis
atrophy of the uscularis propria
- benign: so they maintain their appetite and wiehgt
- malignant strictures are often associated with weight loss
esophageal mucosal webs
ledge-like protusions that may cause obstruction
- women older than 40
- iron deficiency anemia, glossitis, cheilosis= plummer vinson sndrome
- **dysphagia of incompletely chewed food
plummer-vinson syndrome
associated with esophageal webs
-iron deficiency anemia, glossitis, and cheilosis
esophageal rings
like webs but they’re circumferential
- A rings: squamous mucos
- B rings: in lower esophagus and may hae gastric cardia-type mucosa on their undersurface
Achalasia
triad of incomplete LES relaxation, increased LES tone, and aperistalsis of the esophagus
- primary: result of distal esophageal inhibitiory neuronal ganglion cell degeneration
- Secondary: from Chagas disease! T. cruzi gets the myenteric plexus
Esophagitis
- lacerations
- chemical and infectious
- reflux
- eosinophilic
- esophageal varices
- barrett esophagus
- esophageal tumors
- adenorcarcinoma
- SCC
Mallory-Weiss tears
longitudinal mucosal tears in esophagus
- 2ndard to acute alcohol intoxication
- hematemesis
- healing is rapid and complete
Boerhaave syndrome
much less common, but more serious
- transmural tearing and rupture of the distal esophagus
- requires surgical intervention
- myocardial infarction
odynophagia
pain on swallowing
pill-induced esophagitis
when they ledge and idssolve in the esophagus
esophageal infections
uncommon
- herpes simplex virus: punched out ulcers, nuclear viral inclusions*
- CMV: shallower ulcerations: nuclear AND cytoplasmic inclusions within capillary endothelium and stromal cells
- candidiasis is most common fungus: pseudomembranes
reflux esophagitis
stratified squamous epithelium to columnar epithelium with glands
- transient lower esophageal sphincter relaxation
- basal zone hyperplasia exceeding 20% of total epithelial thickness
- ppl older than 40
eosinophilic esophagitis
large numbers of intraeptihelial eosinophils, particularly superficially
- PPI’s don’t provide relief
- children in developed countries
esophageal varices
portal vein probs
- cirrhotic patients
- alcoholic liver disease
- hepatic schistosomiasis is the second most common cause of varices
- variceal hemorrhage is an emergency
- submucosa of the distal esophagus
barret esophagus
complication of chronic GERD
- increased risk of esophageal adenocarcinoma
- most do not develop tumors though
- goblet cells!
- stain bpale blue by H and E stain
- can only be ID’ed through endoscopy and biopsy…. prompted by GERD symptoms
esophageal tumors
either adenocarcinoma or SCC
-the benign ones are mesenchymal and arise within the esophageal wall… leiomyomas being most common
adenocarcinoma
- most arise from Barrett esophagus
- H. pylori is decreased risk becuase they cause gastric atrophy… reduced acid secretion and reflux
- metaplasia to dysplasia and invasive carcinoma
- TP53 and CKDN2A abnormalities detected early
- distal 3rd of esophagus
squamous cell carcinoma
males 4x more likely than females
- tobacco and alcohol use
- HPV
- middle 3rd of esophagus
- hot beverages too!
Gastritis
inflammatory process
-neutrophils will most likely be present
Gastropathy
when inflammatory cells are rare or absent
- surface epithelium is intact, but with goveolar cell hyperplasia… characteristic corkscrew profiles
- NSAID induced gastropathy responds to antacids or PPI’s
hypertrophic gastropathy
specific group of diseases
-menetrier disease and Zollinger-Ellison syndrome
stress ulcers
common in ppl with shock, sepsis, or sever trauma
curling ulcers
proximal duodenum
-associated with severe burns or trauma.
cushing ulcers
gastric, duodenal, and esophageal ulcers
- ppl with intracranial disease
- high incidence of perforation.
non-stress-related causes of gastric bleeding?
Dieulafoy lesion and gastric antral vascular ectasia (GAVE)
dieulafoy lesion
caused by submucosal A. that does not branch properly within the wall of the stomach
- lesser curvature, near GE junction
- bleeding associated with NSAID use
GAVE
longitudinal stripes on endoscopy
-antral mucosa shows reactive gastropathy with dilated capillaries containing fibrin thrombi
Chronic gastritis
infection with H. Pylori
- Autoimmune could happen too
- hematemesis is uncommon
H. Pylori Gastritis
present in 90% of people with chronic gastritis affecting the Antrum
- poverty
- antral gastritis
- flagella, rease, adhesins…
- attach onto foveolar cells
- toxin is CagA
- take an ANTRAL biopsy
- intraepithelial neutrophils and subepithelial plasma cells
- treat w. antibiotics and PPI’s
Autoimmune gastritis
- typically a patchy process
- spares the antrum
- hypergastrinemia
- Vit. B12 deficiency (because parietal cells secrete IF)
- decreased acid production(loss of parietal cells)
- increased GASTRIN
- CD4 T cells against parietal cell components including the H/K ATPase
- autoantibodies to H/K ATPase found, but not pathogenic
- peripheral neuropathy
Eosinophilic gastritis
esoinophils in the mucosa and muscularis
lymphocytic gastritis
affects entire stomach
- varioliform gastritis
- marked increase in the number of intraeptihelial T-lymphocytes
granulomatous gastritis
granulomas
-western populations: gastric involvement by Crohn disease is the most common specific cause of this
Peptic Ulcer Disease
Complication of chronic gastritis
- ulceration affecting the duodenum or stomach (antrum)
- H. pylori, NSAIDs, or cigarettes
- increased gastric acid secretion and decreased duodenal bicarbonate secretion
- most common in proximal duodenum
- ***sharply punched-out defect
- heaped up margins more characteristic of cancers
- perforation into peritoneal cavity is surgical emergency… free air under the diaphragm
- malgnant transformation of peptic ulcers is rare
- watch out for bleeding (life-threatening hemorrhage)
Mucosal atrophy and intestinal metaplasia
- loss of parietal cell mass
- increased risk for gastric adenocarcinoma (greatest in autoimmune gastritis)
Gastritis cystica
- trauma induced
- exuberant reactive epithelial proliferation associated with entrapment of epithelial-lined cysts
- may mimic invasive adenocarcinoma
Menetrier disease
rare disorder
- excessive secretion of TGF-a
- diffuse hyperplasia of the foveolar epithelium of the body and fundus
- pediatric disease is usually self-limited and often follows a respiratory infection
- enlarged rugae in the BODY and FUNDUS
- *HYPERPLASIA OF FOVEOLAR MUCOUS CELLS
- associated with adenocarcinoma
- hpoproteiniemia, weight loss, diarrhea
- no risk factors
- limited lymphocyte infiltrate
Zollinger-Ellison Syndrome
caused by gastrin-secreting tumors
- 2x of oxyntic mucosal thickness due to a five-fold increase in the number of parietal cells
- fundus
- neutrophilic infiltrate
- peptic ulcers
- MEN is a risk factor
- no adenocarcinoma…. but 60-90% are malignant so watch out
Inflammatory and hyperplastic polyps
most frequent kind
- H. pylori
- risk of dysplasia correlates with size
- larger than 1.5 cm…. resect it and examin histologically
fundic gland polyps
FAP
- PPI’s are a problem…. inhibit acid production… increased gastrin secretion…. oxyntic gland growth
- gastric body and fundus
- FAP associated can be cancerous (adenocarcinoma)
- sporadic fundic gland polyps carry no cancer risk
gastric adenoma
Antrum>body
- similar symptoms to chronic gastritis
- frequent association with adenocarcinoma*
- almost alway occur ona background of chronic gastritis with atrophy and intestinal metalasia
gastric adenocarcinoma
_the most common malignancy of the stomach
- intestinal (bulky masses) vs. diffuse type (signet ring cells)
- Japan, Chile, Costa Rica, Eastern Europe
- left axillary lymph node is the irish node
- loss of CDH1 gene (E-cadherin) in familial type
- Loss of E-cadherin is also a key stepin in the development of diffuse gastric cancer
- sporadic type: LOF in APC gene and GOF in B-catenin
- lesser curvature more involved
- depth of invasion and extent of nodal and distant metastases= prognosis
lymphoma
happens most commonly in the GI tract… stomach
- MALTOMA
- t11,18 translocation
- constitutive activation of NFkB… b cell growth
- dense lymphocytic infiltrate in the lamina propria
- express B-cell markers CD19 and CD20
carcinoid tumor
well differentiated neuroendocrine tumors
- has been linked to PPI therapy
- Chromogranin A
- most of these happen at the Jejunum and Ileum
- aggressive there
- *carcinoid syndrome only happens when the tumor has gone to the liver to get dumped intothe venous system
Gastrointestinal stromal tumor
GIST
- most common mesenchymal tumor of the abdomen
- arise from the interstial cells of Cajal… pacemaker cells
- GOF mutation in the RTK: “KIT”… most useful diagnostic marker
Intestinal obstruction
abdominal pain and istention, comiting, and constipation
- hernias
- adhesions
Hernias
most frequent cause of intestinal obstruction worldwide
Adhesions
like between bowel segments
- internal herniation
- most common cause of intestinal obstruction in the US
Volvulus
- twisted around
- rare
intussusception
proximal part telscopes into the immediately distal segment
- most common cuase of intestinal obstruction in chidren younger than 2 y/o
- air enema will fix kids, surgery for adults
Ischemic Bowel disease
vascular compromise…hypoxic injury
- MOST COMMON SITE IS THE SPLENIC FLEXURE!
- most common in older than 70 (colon)
- surface epithelial atrophy with normal or bigger crypts is morphologic signature of ischemic intestinal disease*
- Bloody diarrhea
- *mortality is doubled in pts with right sided colonic disease (right side is supplied by SMA)
angiodysplasia
malformed submucosal and mucosal blood vessels
- cecum or right colon (makes sense because cecum has largest diameter…. greatest wall tension
- after 60s
malabsorption
hallmark is steatorrhea
-results from one of 4 things: Intraluminal digestion, terminal digestion, transepithelial transport, and lymphatic transport
diarrhea
increase in stool mass, frequency, or fluidity >200gm per day
Cystic fibrosis
diarrhea du to intraluminal digestion problem
-problem with CFTR thing
Celiac disease
Problem with Terminal digestion (TD) and transepithelial transport (TET)
- immune-mediated enteropathy
- gluten problems
- gliadin causes most of the disease
- CD8 expressing NKG2D
- HLA-DQ2 or HLA-DQ8 allele
- end of duodenum or proximal jejunum
- increased number of intraepithelial lymphocytes in the VILLUS is key
- anti TTG will be there
- Dermatitis herpetiformis
environmental enteropathy
tropical sprue!
-we dont know what to do about it
Autoimmune enteropathy
X-linked
- young children… diarrhea persistent
- FOXP3 (treg cells
- tx with immunosuppressive drugs
abetalipoproteinemia
inability to secrete triglyceride rich lipoproteins
- intracellular lipid accumulation
- presents in infancy
- ***acanthocytic red cells (burr cells) in peripheral blood smears
- mutation in MTP (microsomal triglyceride transfer protein
lactase deficiency
Congenital…. auto recessive.. born with it… just give them formula
Acquired: down regulation of lactaste gene expression
-Native americans
cholera
comma-shaped, gram-negative bacteria that cause cholera,
- Ganges valley of india and bangladesh
- transmitted by contaminated drinking water
- noninvasive, remain in intestinal lumen
- Cholera toxin is encoded by a virulence phage
- binds CFTR and opens it… osmotic driving force… massive diarrhea (the A subunit causes it)
- rice water diarrhea
Campylobacter enterocolitis
- traveler’s diarrhea
- bloody diarrhea
- can result in reactive arthritis in patients with HLA-B27
- Erythema nodosum
- Guillain-Barre syndrome (flaccid paralysis caused by immuno mediated inflammation of peripheral nerves)
- comma shaped FLAGELLATED, gram negative in stool culture
- crypt architecture is preserved
- influenza-like prodrome
Guillain-Barre syndrome
flaccid paralysis cause by immunologically mediate inflammation of peripheral nerves… not HLA linked
shigellosis
- gram negative, unencapsulated, nonmotile, facultative anaerobes
- bloody diarrhea
- fecal-oral route or contaminated water
- resistant to harsh acidic stomach
- proliferate intracellularly
- carry virulence plasmids
- LEFT COLON
- M cells in dome epithelium over the peyer patches
- self limited disease: 1 wk of diarrhea, fever, and abdominal pain
- requires stool culture
- you just have to SHIT it out… antidiarrheal won’t help… get rid of it
salmonella
S. typhi or nontyphoid
- type 3 secretion
- again, it’s best to just shit it out
typhoid fever
S. Typhi
- but travellers usually get S. paratyphi because they have been vaccinated against typhi
- Gallbladder colonization… gallstones and chronic carrier state
- invade M cells… then go to lymphatics or blood
- terminal ileum… plateau-like elevations
- spleen is enlarged and soft
- parenchymal necrosis in which hepatocytes are replaces by macrophage aggregates…. TYPHOID NODULES
- give Abx!
- Rose spots on chest and abdomen
- pts with sickle cell disease susceptible to salmonella osteomyelitis
Yersinia
pumonic and bubonic plague
- pork, raw milk, water
- winter
- Y. enterocolitica more common
- invade M cells, have adhesins that bind to host B1 integrins
- *iron enhances virulence and stimulates systemic dissemination
- ileum, appendix, and RIGHT COLON
E. coli
gram negative bacilli in healthy GI tract
-ETEC, EPEC, EHEC, EIEC, EAEC
ETEC
Enterotoxogenic E. Coli -travelers diarrhea -LT and ST toxin -LT is like cholera, activates AC... increased cAMP -
EPEC
endemic diarrhea
- attaching and effacing A/E lesions
- Type 3 secretion like shigella… infects bacterial effector ptns into epithelial cytoplasm
EHEC
O157:H7 (more common) or non…
- cows are natural reservoir
- shiga-like toxins
- HUS is a big concern
- so DONT treat with Abx because that will result in increase shiga like toxins… enhancing the risk for hemolytic uremic syndrome
EIEC
no toxins
- invade epithelial cells
- acute self-limited colitis
- EAEC has adherence fibmriae, nonbloddy diarrhea, only visible by electron microscopy, minimal histologic damage
Pseudomembranous colitis
- C. difficile
- antibiotic associated colitis
- pseudomembranes
- lamina propria has dense infiltrate of neutophils and occasional fibrin thrombi within capillaries
- superficially damaged crypts… volcano… it erupts… pseudomembrane!
- hospitals
- ptn loss… hypoalbuminemia
- look for C dif toxin rather than culture
Whipple disease
- *the only malabsorptive thing caused by defective lymphocytic transport!**
- gram positive actinomycete: Tropheryma whippelii
- organism laden macrophages in mesenteric lymph nodes…. lymphatic obstruction
- foamy macs… like whipped cream
- acid fast stain to rule out mycobacteria
- presents with triad of diarrhea, weight loss, and arthlagia
Viral Gastroenteritis
- Norovirus: developed countries and IC pts, single stranded RNA genome
- Rotavirus: encapsulated segmented 2x stranded RNA genome… severe childhood diarrhea, destroys mature enterocytes
- Adenovirus: pediatric diarrhea and IC pts, symptoms resolve within 10 days
Ascaris
the one with the goofy life cycle
- ingested eggs, larve get into blood and go to lungs… grow in alveoli, coughed up and swallowed… mature into adult worms
- induce eosinophil -rich inflammatory reaction
- diagnosis is made by eggs in stool samples
strongyloides
- in ground soil
- can penetrate unbroken skin
- hatch in intestine and penetrate mucosa.. autoinfection… infection for life
- peripheral eosinophilia
necator duodenale
hookworms
- larval penetration through skin
- develop in lungs
- swallowed
- worms attach to mucosa, suck blood, and reproduce
- iron deficiency anemia
- diagnosis can be made by detection of eggs in fecal smears
enterobius vermicularis
pinworms
- rarely causes illness
- perirectal mucosa
- itchy butt
- tape!
trichuris trichiura
Whipworm
- young children
- usually fine
- heavy infections can cause bloody diarrhea and rectal prolapse
- like pin worms, doesn’t penetrate mucosa
schistosomiasis
trapping of eggs with in the mucosa nad submucosa
- granulomatous immune reaction
- can cause bleeding or obstruction
- adult worms residing in mesenteric veins
intestinal cestodes
Fish and pork tapeworms
-B12 deficiency and megaloblastic anemia
entamoeba histolytica
PROTOZOAN!
- India, mexico, colombia
- chitin wall
- cecum and ascending colon most often
- flask shaped ulcer
Giardia lamblia
resistant to chlorine
- flagellated protozoans
- 2 nuclei
- NO invasion
- villous blunting
- immunofluorescent cysts in stool samples
Cryptosporidium
- Chronic diarrhea in AIDS patients
- oocyte is ingested, releases sporozoites
- enterocyte engulfs the parasite… settles in an endocytic vacuole within the microvilli
- sodium malabsorption, chloride secretion, increased tight junction permeability
- non-bloody, watery diarrhea!
- Look for OOCYSTS IN THE STOOL
Irritable bowel syndrome
Characterized by chronic, relapsin abdominal pain, bloating, and changes in bowel habits
- fecal transplantation can work
- 20-40 y/o
- females
Inflammatory bowel disease
Ulcerative Colitis and Crohn disease
Ulcerative colitis
- limited to colon and rectum and extends only into the mucosa and submucosa
- toxic megacolon
- malignant potential
- pseudopolyps (mucosal bridges between them) and thin walls
- broad based ulcers
- no granulomas
- bloody diarrhea with stingy mucoid material
- pANCA
Crohn’s disease
-may involve any area of the GI tract and is typically transmural
-most commonly at ileum
-NOD2
NFkB pathway
-skip lesions
-stricture
-knife like lesions
-*perianal fistula
-recurs after surgery
-TH1 and 17(from IL 23)
-creeping fat
-cobblestoning
-crypt abscesses
-Noncaseating granulomas
-bloody diarrhea
-malabsorbtion of B12 and bile salts
-antibodies to saccharomyces cerevisiae
Sigmoid diverticular disease
- not invested by all three layers of the coonic wall
- flask-like outpouchings
- hypertrophy of the circular layer of muscularis propria
- there’s a shit ton of diverticula
- sensation of never being able to completely empty the rectum
- often resolves spontaneously
Hyperplastic polyps
- must rule out sessile serrated adenoma because they look the same*
- these things are benign though… above is malignant
- Left colon
inflammatory polyps
-rectal bleeding, mucus discharge, and inflammatory lesion of the anterior rectal wall
hamartomatous polyps
occur sporadically or as components of various genetically determined or acquired syndromes
- Juvenile polyps
- Peutz-Jehgers
Juvenile polyps
younger than 5 yrs
- rectal bleeding
- solitary if sporadic
- lots if auto dominant syndrome juvenile polyposis
- SMAD4 mutation
Peutz-Jeghers Syndrome
rare auto dominant syndrom
- 11 yrs old
- multiple GI hamartomatous polyps and mucocutaneous hyperpigmentation
- increased risk of several malignancies
- STK11 mutation
Neoplastic polyps
most common are colonic adenomas
- majority of adenomas do not progress to become adenocarcinomas
- sessile serrated adenomas are in the right colon (hyperplastic polyps are in the left colon)
- SIZE MATTERS IN THE COLON* more malignant-precursors to the majority of colorectal adenocarcinomas
Adenomatous Polyposis
FAP: numerous colorectal adenomas as teenagers
- APC gene
- at least 100 polyps
- *colorectal adenocarcinoma develops in 100% of untreated FAP patients
- hypertrophy of retinal pigment epithelium
- MYH lost as well
Hereditary Non-Polyposis Colorectal cancer
- Lynch syndrome
- caused by inherited mutations in genes that encode proteins responsible for the detection, excision, and repair of errors that occur during DNA replication (MSH2 or MLH1
- Right sided
Adenocarcinoma
the most common malignancy of the GI tract and is a major cause of morbidity and mortality worldwide
- small intestine is an uncommon site for benign and malignant tumors
- aspirin and NSAIDs hav e aprotective effect… inhibiting COX 2 solves probems
- APC to B-catenin to KRAS to TP53 to telomerase (the sequence)
- exophytic masses
- distal colon… napkin ring lesions
- abundant mucin=poor prognosis
- fatigue and weakness due to iron deficiency anemia
- the two most important prognostic factors are depth of invasion and the presence of lymph node metastases
- liver is most common metastatic site b/c of portal drainage of the colon
Tumors of the Anal Canal
- pure SCC of anal canal is associated with HPV infection
- basaloid
- upper zone is lined by columnar rectal epithelium
- middle third has transitional eptihelium
- lower third has stratified squamous epithelium
Hemorrhoids
anal varices…. they’ll be fine
- they relieve venous hypertension
- below anorectal line= external hemorrhoids
- above= internal hemorrhoids
Acute Appendicitis
diagnosis of this requires neutrophilic infiltration of the muscularis propria
- RLQ pain
- McBurney sign
Tumors of the Appendix
-most common is carcinoid tumor… it’s fucking yellow
-
Sclerosing retroperitonitis
Ormond disease= dense fibrosis that may extend to involve the mesentery
-IGg4 related
Tumors of the peritoneal cavity
- mesothelioma
- desmoplastic small round cell tumor
- t11,22
- fusion gene of EWS and WT1 genes
