GI Overview
I.
Esophagus
a.
b.
Congenital Abnormalities of Esophagus
i.
Agenesis
ii.
Atresia
iii.
Fistulas
c.
Acquired Abnormalities of Esophagus
i.
Mucosal webs
ii.
Schatzki’s ring
iii.
Stenosis
iv.
Varices
d.
Lesions ó Motor
Dysfunction
i.
Achalasia
ii.
Hiatal hernia
iii.
Diverticula
iv.
Lacerations
e.
Inflammatory conditions (Esophagitis)
i.
Acid reflux
ii.
Infections
iii.
Chemical Injury
iv.
Thermal Injury
v.
Metabolic
f.
Tumors
i.
Benign
ii.
Neoplasms
1.
SCC
2.
Adenocarcinoma
3.
Miscellaneous
II. Stomach
a.
b.
Gastritis
i.
Acute Gastritis
ii.
Chronic Gastritis
1.
Autoimmune Gastritis
c.
Chronic Peptic Ulcer Disease
i.
Duodenal Ulcers
ii.
Gastric Ulcers
d.
Acute (Stress) Ulcers
e.
Hypertrophic gastropathy
i.
Menetrier’s disease
ii.
Zollinger-Ellison syndrome
f.
Tumors
i.
Benign
ii.
Malignant
1.
Gastric Carcinoma
2.
Lymphoma
3.
Mesenchymal Tumors
III. Small
Intestine
a.
b.
Congenital Abnormalities
i.
Atresia
ii.
Meckel’s Diverticulum
c.
Malabsorption
i.
Defective Intraluminal Solubility
ii.
Mucosal Cell Abnormalities
iii.
Reduction in Intestine Surface
iv.
Lymphatic Obstruction
v.
Iatrogenic Causes
vi.
Drugs
vii.
Infection
1.
Giardiasis
2.
Viral gastroenteritis
viii.
Unexplained Causes
IV. Pancreas
a.
b.
Acute Pancreatitis
c.
Chronic Pancreatitis
i.
Chronic calcifying pancreatitis
ii.
Chronic obstructive pancreatitis
d.
Tumors
i.
Carcinoma of the Pancreas
ii.
Islet Cell Tumors
1.
Insulinoma
V.
Small Bowel and
a.
Congenital
i.
Duplications
ii.
Malrotations
iii.
Omphalocele
iv.
Gastroschisis
v.
Heterotopia
vi.
Atresia, Stenoses, Fistulas
vii.
Hirschsprung’s Disease
b.
Traveler’s diarrhea
c.
Infective enterocolitis
i.
Bacterial
ii.
Viral
iii.
Parasitic
iv.
GI + HIV
v.
Pseudomembranous colitis
1.
Clostridium difficile
d.
Inflammatory (idiopathic)
i.
Crohn’s Disease (= Regional enteritis)
ii.
Ulcerative Colitis
e.
Ischemic Bowel Disease
f.
Bowel Obstruction
g.
Diverticular Disease
h.
Tumors
i.
Benign
1.
Hyperplastic polyps
2.
Hamartomatous polyps
a.
Juvenile (Retention) polyps
b.
Peutz-Jeghers polyps
3.
Inflammatory polyps
ii.
Neoplastic
1.
Adenomatous polyps
a.
Tubular adenomas
b.
Villous adenomas
c.
Serrated adenomas
d.
Heredofamilial Polyposis
i.
Familial polpyposis
ii.
iii.
Turcot’s syndrome
2.
Carcinoma of the colon
3.
Lymphomas
4.
Mesenchymal tumors
5.
Carcinoid Tumors
6.
Metastatic tumors
VI. Appendix
a.
Appendicitis
b.
Tumors
I.
Esophagus
a.
Esophagus
= inferior extension of the pharynx
Conducts
food and prevents regurgitation
Upper
esophageal sphincter: level of cricopharyngeus muscle
Lower
esophageal sphincter: level of diaphragm (proximal to epithelial junction)
Layers
1. mucosa
a. non-keratinizing stratified squamous
epithelium
b. lamina propria: loose connective tissue
c. muscularis mucosa (often quite thick in esophagus)
2. submucosa
3. muscularis
propria: skeletal muscle proximally, smooth muscle lower 2/3
a. inner circular layer
b. outer longitudinal layer
b.
Congenital Abnormalities of Esophagus
i.
Agenesis
failure to form
ii.
Atresia
segment fails to form (usually adjacent to tracheal
bifurcation)
iii.
Fistulas
communication
between lumen to bronchus or trachea
c.
Acquired Abnormalities of Esophagus
i.
Mucosal webs
proximal, semicircular, middle aged-women
ii.
Schatzki’s ring
distal, circumferential
iii.
Stenosis
chemical injury related
iv.
Varices
etiology: portal hypertension (cirrhosis)
morphology: dilated veins (mucosal and submucosal)
40% mortality on
first bleed if ruptured
d.
Lesions ó Motor
Dysfunction
i.
Achalasia
failure to
relax, increased LES tone, bag-like esophagus
etiology: destruction of myenteric
ganglia, scleroderma
symptoms: dysphagia, regurgitation
can be primary or secondary to infection, neoplasm, etc.
ii.
Hiatal hernia
up to 20% of adults (stomach enters thoracic cavity)
iii.
Diverticula
proximal (Zenker’s), traction (mid), epiphrenic (distal)
iv.
Lacerations
Mallory-Weiss
tear
linear, retching-induced bleeding
if transmural rupture à Boerhaave
syndrome [mediastinitis (high mortality rate)]
e.
Inflammatory conditions (Esophagitis)
i.
Acid reflux
most common
cause of esophagitis
decreased LES tone
symptoms: dysphagia, pain, dyspepsia
hallmark: rich eosinophilic infiltrate
complications: bleeding, stricture, Barrett’s metaplasia (10%)
Barrett’s metaplasia
- squamous à metaplastic columnar
(glandular) epithelium
the longer the segment, the greater the chance of
complications (ulceration, bleeding, stricture, malignancy)
à dysplasia of metaplastic glandular mucosa (à screen every 6 months)
à adenocarcinoma (30-40X risk)
if Barrett’s is high-grade, 40% à invasive adenocarcinoma (therefore, resection)
ii.
Infections
- fungal (candida albicans: immunocompromise,
gray-white pseudomembranes)
- viral (HSV: punched out
ulcers, CMV: immunocompromise)
- bacterial (usually a
consequence of disease elsewhere)
iii.
Chemical Injury
acid, alkali, alcohol, drugs
iv.
Thermal Injury
hot liquid, radiation
v.
Metabolic
uremia
f.
Tumors
i.
Benign
usually of
mesenchymal origin (leiomyoma)
ii.
Neoplasms
1.
SCC
poor
prognosis
keratin pearls
4%
of all cancer deaths
males, black, (higher in
etiology: alcohol, smoking, nitrosamines (no hereditary role)
predisposing
factors: achalasia, stricture, esophageal webs
subforms:
- fungating exophytic
tumor
- flat diffuse neoplasm (infiltrates wall)
-
ulcerated, excavated
mass (grows deeply)
2.
Adenocarcinoma
poor
prognosis
middle-aged
white males
predisposing
factors: chronic reflux à Barrett’s
metaplasia
3.
Miscellaneous
leiomyosarcoma, melanoma, Kaposi sarcoma, metastatic SCC
II. Stomach
a.
Parietal
cells |
HCl |
digestive
acid |
fundus |
Chief cells |
pepsinogen |
à pepsin; digests protein |
fundus |
Mucous neck
cells |
mucous |
lubricant |
fundus,
cardia, antrum |
G
cells |
gastrin |
stimulates
HCl production |
antrum |
3 phases of
digestion
1.
cephalic phase (mediated by vagal activity; initiated
by food stimuli)
2.
gastric phase (stimulation of gastric juice; direct:
parietal; indirect: G cells
3.
intestinal phase (ends gastric secretion)
Gastric
defenses against autodigestion (pH 1.0-3.0)
1.
Mucous secretion (physical barrier to acid and pepsin)
2.
Bicarbonate secretion (creates alkaline environment immediately adjacent to
epithelium)
3.
Cellular barriers (tight junctions, rapid repair)
4.
Mucosal blood flow (removes excess H+ and supplies nutrients)
b.
Gastritis
inflammation of the gastric mucosa
i.
Acute Gastritis
neutrophilic infiltrate
very common
etiology: drugs (aspirin), alcohol, smoking, staphyolococcal
enterotoxin, helicobacter pylori, etc.
pathogenesis: gastric mucosal barrier breakdown, blood shunting
(injury)
complications: ulceration, bleeding
ii.
Chronic Gastritis
lymphocytic, plasmocytic infiltrate (neutrophils may be present)
association: gastric
carcinoma, helicobacter
pylori, pernicious anemia, bile reflux, etc.
pathology: swollen and boggy à
flat and thin
complications: gastric carcinoma, hypochlorhydria/achlorhydria (à pernicious anemia), ulceration (gastric or duodenal)
- chronic active gastritis = neutrophil component is
significant and H. pylori in superficial mucous layer
- chronic superficial gastritis = chronic inflammatory cells
predominate
- chronic atrophic gastritis = atrophy of gastric glands
is present
1.
Helicobacter pylori gastritis
gram negative spiral rod (produces urease à
direct damage)
clinical/histological picture resembles acute gastritis
antrum is more severely affected
does not invade (lives in mucous)
2.
Autoimmune gastritis
<10%
of cases of chronic gastritis
autoantibodies against parietal cells and intrinsic factor
fundus is
more severely affected
c.
Chronic Peptic Ulcer Disease
chronic, solitary ulcers occurring at any level of the GI
tract exposed to acid-pepsin
juices
etiology: increase in damaging forces or breakdown of
protective mechanisms, stress, aspirin, alcohol, coffee, smoking, increase in serum calcium levels, H. pylori, altered
gastric secretion
ulcers are deep and punched out
complications: bleeding, perforation, obstruction, pain (probably do
not lead to malignancy)
deep, single, large, scarred, sharp margins
i.
Duodenal Ulcers
associated with increased gastric acidity
ii.
Gastric Ulcers
not associated with increased gastric acidity
d.
Acute (Stress) Ulcers
multiple, small, shallow, ragged margins, not associated with
chronic gastritis
etiology: stress, severe illness (ICU setting: brain damage,
burns, shock, trauma, aspirin, NSAIDS)
granulation tissue, fibrinoid necrosis, no scarring
symptoms: bleeding, pain
e.
Hypertrophic gastropathy
i.
Menetrier’s disease
expansion
of stomach surface
epithelium
30-50
y.o. men
very rare
hypochlorhydria
ii.
Zollinger-Ellison syndrome
expansion
of parietal cell
compartment
caused by a
pancreatic or duodenal gastrinoma
causes enlarged gastric folds
and peptic ulcers
f.
Tumors
i.
Benign
polyps and adenomas of the stomach are rare and usually
benign
ii.
Malignant
1.
Gastric Carcinoma
Hypochlorhydria à increased risk for gastric carcinoma
exophytic, fungating tumor from mucosa (may be flat or excavated
= linitis plastica)
most common: pylorus or antrum
staging based on depth: early (mucosa and submucosal);
advanced (muscular wall)
5-year prognosis: early (95%) late (10%)
2.
Lymphoma
3.
Mesenchymal Tumors
spindle cell neoplasms (interstitial
cells of Cajal = GI pacemaker cells)
have smooth muscle and neural features
III. Small
Intestine
a.
lined by villi separated by pit-like crypts extending into
muscularis mucosa (normal villous:crypt height = 5:1)
villi (terminal digestion and absorption of food)
crypts (secrete ions, water, deliver IgA and antimicrobials)
mucus cells (mucus protects and facilitates uptake of
nutrients)
surface epithelial cells (uptake intrinsic factor-vitamin B12 complex)
Digestion, Absorption, Transport
1.
Intraluminal
breakdown of food (digestion)
a.
pancreatic phase:
proteins, fats, carbohydrates
b.
biliary phase: solubilize fats
2.
Intestinal absorption
a.
luminal surface of
brush border cells
b.
additional
digestion of carbohydrates and peptides
c.
intracellular
modification/mobilization of amino acids, fats
3.
Removal of
nutrients (transport)
a.
lymphatics,
capillaries
b.
Congenital Abnormalities
i.
Atresia
rare; most commonly: duodenum
ii.
Meckel’s Diverticulum
persistence of vitelline duct on antimesenteric side of bowel à diverticulum (within 30cm of ileocecal valve)
contains all three layers of normal bowel wall (true
diverticulum)
heterotopic (gastric or pancreatic) rests are possible (50%) à peptic ulceration of mucosa
complications: bleeding, intussusception, incarceration, perforation
c.
Malabsorption
abnormal secretion of fat (steatorrhea)
decreased absorption of fat, fat-soluble vitamins, proteins,
carbohydrates, minerals, water
i.
Defective Intraluminal Solubility
pancreatic insufficiency
bacterial overgrowth (reduces bile salt levels)
ii.
Mucosal Cell Abnormalities
disaccharidase deficiency (rare) = difficult to digest milk/dairy
(congenital or acquired)
iii.
Reduction in Intestinal Surface
Gluten sensitive
enteropathy = Celiac Disease (Celiac Sprue)
- Toxic effect of gluten (wheat, rye) on mucosal
epithelial cells
- hypersensitivity to gliadin (component of gluten)
- flattened mucosa
- treatment: remove gluten
from diet
- complications: T-cell
lymphoma, adenocarcinoma
iv.
Lymphatic Obstruction
interfering with transport of nutrients:
1.
tuberculosis
2.
lymphoma
3.
lymphangiectasia (dilated lacteals and lymphatics)
v.
Iatrogenic Causes
gastrectomy, radiation enteritis
vi.
Drugs
cholestyramine, colchicines, para-aminosalicylic
acid, cathartics, neomycin
vii.
Infection
1.
Giardiasis
Giardia Lamblia: parasitic
(usually coats, no invasion)
drinking contaminated water
2.
Viral gastroenteritis
rotavirus,
3.
Other Parasitic
strongyloidiasis
4.
Whipple’s Disease
multi-system, treatable (antibiotics)
morphology: foamy macrophages in lamina propria (PAS positive)
Actinomyces (gram+, PAS+, rod-shaped bacilli)
defective T-cell function (?)
villous architecture maintained
viii.
Unexplained Causes
mechanism unknown: DM, carcinoid syndrome, endocrine
abnormalities
IV. Pancreas
a.
main function: secretion (endocrine, exocrine)
duodenal enzymes
secretin:
controls electrolyte, water production by pancreas
choecystokinin: controls enzyme production by pancreas
pancreatic enzymes: exocrine
trypsin,
chymotrypsin, amylase, lipases, phospholipases, elastases, ribonucleases
released in
proenzymes form à pancreatic duct (activated in duodenum) à protects pancreas
pancreatic enzymes: endocrine (Islet of Langerhans)
A cells:
glucagons
B
cells: insulin (70% of Islet cells)
D
cells: somatostatin
PP
cells: pancreatic peptide
D1
cells: vasoactive intestinal polypeptide (VIP)
b.
Acute Pancreatitis
sudden destruction of pancreas (escape of activated pancreatic
enzymes into parenchyma)
common, life-threatening
etiology: Biliary tract disease (women), alcoholism (men), trauma,
iatrogenic, infections, hyperlipidemia,
AIDS
gross: necrosis, hemorrhage, chalky white fat necrosis
histology: acute inflammation, necrosis, mild to severe
hemorrhage
pathogenesis: premature activation.
Possible mechanisms:
1.
duct obstruction
(pressure build-up)
2.
acinar cell injury
(viruses, chemicals, trauma)
3.
proenzymes are
packaged (lysosomes) instead of secreted
complications:
1.
abscess, pseudocyst
(necrotic debris, enzymes)
2.
rupture of
abscess, pseudocyst
3.
hemorrhage (blood
vessel erosion)
4.
fat necrosis
(lipase release, pancreas and/or distal sites)
5.
duodenal
obstruction (secondary to pancreatic inflammation)
6.
systemic organ failure (ARDS, renal failure, shock, etc.)
c.
Chronic Pancreatitis
etiology: alcoholism,
biliary tract disease, pancreas
divisum (two parts of pancreas), CF, hyperlipidemia, hypercalcemia
pathogenesis: repeated flare ups of pancreatitis (not classic acute
pancreatitis)
repeated bouts of classic acute does not à chronic pancreatitis
40%: no identifiable cause
necrosisàfibrosis theory
relentless, progressive
steatorrhea
i.
Chronic calcifying pancreatitis
predominantly in alcoholics
atrophy of parenchymal cells, calcification of insterstitium
gross: hard, calcification and/or stones (diagnosed on x-ray)
ii.
Chronic obstructive pancreatitis
stenosis of sphincter
of Oddi
fibrosis, atrophy, no calcification
head of pancreas
d.
Tumors
i.
Carcinoma of the Pancreas
very poor prognosis (3%, 5 years)
painless jaundice
most are ductal adenocarcinomas
etiology: unclear (smoking, diet, benzidine, chronic
pancreatitis, DM)
morphology: 60% (head: may present earlier)
elevated CA 19-9
Trousseau’s sign
ii.
Islet Cell Tumors
glucagonoma, insulinoma, somatostatinoma,
Werner-Morrison (VIP), Zollinger-Ellison (gastrinoma: ectopic)
1.
Insulinoma
rare; most common islet cell tumor
most occur singly, encapsulated
good prognosis
Whipple’s triad
1.
insulin shock with
fasting (periodic hypoglycemia)
2.
low fasting blood
glucose
3.
relief of symptoms
with IV or oral glucose
V.
Small Bowel and
a.
Congenital
i.
Duplications
ii.
Malrotations
iii.
Omphalocele
iv.
Gastroschisis
v.
Heterotopia
vi.
Atresia, Stenoses, Fistulas
vii.
Hirschsprung’s Disease
congenital aganglionic megacolon
b.
Traveler’s diarrhea
symptoms: diarrhea, abdominal pain
may be enteroinvasive, or
enterotoxin-related
c.
Infective enterocolitis
i.
Bacterial
E-coli, salmonella, staphylococcal, vibrio cholera, shigella
ii.
Viral
iii.
Parasitic
strongyloides, entameba histolytica,
taenia, trichinella spiralis
iv.
GI + HIV
same as above, but with the addition of: mycobacterium avium-intracellulare (MAI), CMV, HSV, Adenovirus, etc.
v.
Pseudomembranous colitis
caused by bacterial
toxins
etiology: iatrogenic - long-term antibiotics (ampicillin,
etc.), nosocomial
morphology
gross: friable freckles, superficial ulceration, sparing of
adjacent mucosa
histology: pseudomembrane (fibrin, acute inflammatory
cells), “volcanic eruption”
1.
Clostridium
difficile
associated with pseudomembranous colitis
gram+, non-invasive, enterotoxin
d.
Inflammatory Bowel Disease (idiopathic) = IBD
overlap exists in symptoms and diagnosis
i.
Crohn’s Disease (= Regional enteritis)
hallmarks: granulomas,
transmural, skip lesions
may involve entire GI tract
epidemiology: females, whites, family history of IBD
etiology: unknown (autoimmune? infectious?)
morphology: linear, skip ulcers (abscesses are rare), cobblestone
mucosa, “creeping fat”,
non-caseating granulomas
complications
localized: fistulas, strictures,
hemorrhage
systemic: hepatic inflammation, arthritis, ocular
inflammation, erythema nodosum, nutritional deficiencies
ii.
Ulcerative Colitis
large bowel always
and only (begins in rectum)
hallmark: intermittent
cramping bloody diarrhea
may involve terminal ileum = backwash ileitis
diffuse, superficial mucosal ulceration (crypt abscesses); mucus secretion impairment
etiology: unknown
prone to remissions
complications
localized: toxic megacolon, hemorrhage, stricture, adenocarcinoma
systemic: hepatitis, hemolytic anemia, arthritis,
thromboembolism, erythema nodosum
e.
Ischemic Bowel Disease
resembles UC
lack of inflammatory response (blood supply is cut-off)
etiology: hypoperfusion (heart failure, shock, etc.)
f.
Diverticular Disease
mucosa herniations (through muscularis)
most common site: mesenteric side of sigmoid colon
associated: high fat, low fiber diet
complications: diverticulitis,
fistula, obstruction (secondary to inflammation), bleeding, bladder irritation,
mimics carcinoma
tend to be next to tenia coli
g.
Bowel Obstruction
hernias, adhesions, intussusception, volvulus
h. Tumors
polyp = protrusion of mucosa into gut lumen
- pedunculated polyp: stalk
(can be excised endoscopically)
- sessile polyp: no stalk
i.
Benign
1.
Hyperplastic polyps
increased proliferation of cells in colonic crypt (lower 1/3)
normal location,
normal cell differentiation (but expanded)
rectosigmoid in shape (“saw-tooth”)
not associated with
malignancy
2.
Hamartomatous polyps
a.
Juvenile (Retention) polyps
most common polyp in children
Juvenile Polyposis syndrome (autosomal dominant): multiple
adenomatous polyps (à carcinoma)
acute inflammation seen
b.
Peutz-Jeghers polyps
part of a clinical syndrome (autosomal dominant)
- melanin pigmentation of lips
- buccal
mucosa
- webs of fingers/toes
- harmartomatous polyps GI
tract (small bowel and stomach)
3.
Inflammatory polyps
occur in long-standing inflammatory bowel disease (not true polyps)
ii.
Neoplastic
1.
Adenomatous polyps
increased risk of cancer (villous > mixed > tubular)
increased size à increased cancer risk
10-15
years for polyp à cancer
a.
Tubular adenomas
most common adenomatous polyp
mutation in adenomatous polyposis coli (APC) gene
abnormal tissue involvement (whole crypt and surface of cells à proliferation)
dysplasia (may be pedunculated or sessile)
morphology: “test-tube”-like
b.
Villous adenomas
usually sessile
morphology: arranged in papillary fronds (finger-like)
complications: bleeding, water and electrolyte loss
c.
Tubulo-villous
adenomas
20-50% villous features
d.
Serrated adenomas
colon (right-side)
sessile or pedunculated
distribution similar to hyperplastic poly (but stratified and
dysplastic)
morphology: goblet cell immaturity, mitoses, prominent nucleoli
pre-malignant
e.
Heredofamilial Polyposis
i.
Familial polpyposis
autosomal dominant
polyps are adenomatous, but very numerous (fuzzy appearance)
cancer is inevitable
ii.
adenomatous polyps + soft
tissue tumors elsewhere in body
autosomal dominant
cancer is inevitable
iii.
Turcot’s syndrome
adenomatous polyps + brain
tumors (gliomas)
autosomal recessive
cancer is inevitable
2.
Carcinoma of the colon
second most common cause of death from cancer
etiology: diet (high fat, low-fiber diet with cholesterol);
bile salts à bacterial products
colon (left-side)
most common
left-side: napkin-ring (present earlier with obstruction)
right-side: fungating (clinically silent for a longer duration)
3.
Lymphomas
rare; MALT (B-cell origin); Burkitt’s
4.
Mesenchymal tumors
rare; smooth muscle, neural, vascular, fibrohistiocytic,
lipomatous
5.
Carcinoid Tumors
malignant neoplasms in slow motion
most carcinoid tumors (90%) occur in GI
neoplastic (serotonin, histamine, bradykinin, prostaglandins)
increased tryptophan metabolism àHIAA increase (diagnostic)
few mitoses
silver-stain
carcinoid syndrome
1. vasoactive disturbances
(flushing, sweating, hypotension)
2. intestinal hypermotility (diarrhea)
3. bronchoconstrictive
attacks (asthma)
4. cardiac involvement
(right-side plaques)
6.
Metastatic tumors
from lung, breast, melanoma
VI. Appendix
a.
Appendicitis
fecal stone obstruction à decreased blood flow à ischemia, bacteria overgrowth
acute (neutrophilic) inflammation of muscularis propria
complications: perforationàperitonitis, abscesses, pylephlebitis,
septicemia
b.
Tumors
1. carcinoid (most common)
2. benign hyperplastic polyps
3. mucocele
(neoplastic mucin-filled appendix)
- cystadenoma or cystadenocarcinoma
- pseudomyxoma peritonei (neoplastic
cells throughout peritoneal cavity)
4. invasive adenocarcinoma:
very unusual