Professional Documents
Culture Documents
Gastrointestinal
“A good set of bowels is worth more to a man than any quantity of brains.” ` Embryology 358
—Josh Billings
` Anatomy 360
“Man should strive to have his intestines relaxed all the days of his life.”
—Moses Maimonides ` Physiology 371
“All right, let’s not panic. I’ll make the money by selling one of my livers. I ` Pathology 376
can get by with one.”
—Homer Simpson ` Pharmacology 398
357
GASTROINTESTINAL—EMBRYOLOGY
``
Normal Foregut—esophagus to duodenum at level of pancreatic duct and common bile duct insertion
gastrointestinal (ampulla of Vater).
embryology Midgut—lower duodenum to proximal 2/3 of transverse colon.
Hindgut—distal 1/3 of transverse colon to anal canal above pectinate line.
Midgut development:
6th week—physiologic herniation of midgut through umbilical ring
10th week—returns to abdominal cavity + rotates around superior mesenteric artery (SMA),
total 270° counterclockwise
Ventral wall defects Developmental defects due to failure of rostral fold closure (eg, sternal defects [ectopia cordis]),
lateral fold closure (eg, omphalocele, gastroschisis), or caudal fold closure (eg, bladder exstrophy).
Gastroschisis Omphalocele
ETIOLOGY Extrusion of abdominal contents through Failure of lateral walls to migrate at umbilical
abdominal folds (typically right of umbilicus) ring persistent midline herniation of
abdominal contents into umbilical cord
COVERAGE Not covered by peritoneum or amnion A ; Surrounded by peritoneum B (light gray shiny
“the guts come out of the gap (schism) in the sac); “abdominal contents are sealed in the
letter G” letter O”
ASSOCIATIONS Not associated with chromosome abnormalities; Associated with congenital anomalies (eg,
favorable prognosis trisomies 13 and 18, Beckwith-Wiedemann
syndrome) and other structural abnormalities
(eg, cardiac, GU, neural tube)
A B
Congenital umbilical Failure of umbilical ring to close after physiologic herniation of the midgut. Small defects usually
hernia close spontaneously.
Tracheoesophageal Esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) is the most common (85%)
anomalies and often presents as polyhydramnios in utero (due to inability of fetus to swallow amniotic fluid).
Neonates drool, choke, and vomit with first feeding. TEFs allow air to enter stomach (visible on
CXR). Cyanosis is 2° to laryngospasm (to avoid reflux-related aspiration). Clinical test: failure to
pass nasogastric tube into stomach.
In H-type, the fistula resembles the letter H. In pure EA, CXR shows gasless abdomen.
Trachea Esophagus Tracheoesophageal
fistula
Esophageal
atresia
Gastric
bubble
Intestinal atresia Presents with bilious vomiting and abdominal distension within first 1–2 days of life.
A
Duodenal atresia—failure to recanalize. Abdominal x-ray A shows “double bubble” (dilated
stomach, proximal duodenum). Associated with Down syndrome.
Jejunal and ileal atresia—disruption of mesenteric vessels (typically SMA) ischemic necrosis of
fetal intestine segmental resorption: bowel becomes discontinuous. X-ray shows dilated loops of
small bowel with air-fluid levels.
Hypertrophic pyloric Most common cause of gastric outlet obstruction in infants (1:600). Palpable olive-shaped mass in
stenosis epigastric region, visible peristaltic waves, and nonbilious projectile vomiting at ∼ 2–6 weeks old.
A
More common in firstborn males; associated with exposure to macrolides.
Results in hypokalemic hypochloremic metabolic alkalosis (2° to vomiting of gastric acid and
stomach
pyloric wall subsequent volume contraction).
Ultrasound shows thickened and lengthened pylorus A .
ic
lor el
Treatment: surgical incision of pyloric muscles (pyloromyotomy).
py ann
c h
Pancreas and spleen Pancreas—derived from foregut. Ventral pancreatic bud contributes to uncinate process and main
embryology pancreatic duct. The dorsal pancreatic bud alone becomes the body, tail, isthmus, and accessory
A
pancreatic duct. Both the ventral and dorsal buds contribute to pancreatic head.
Annular pancreas—abnormal rotation of ventral pancreatic bud forms a ring of pancreatic tissue
encircles 2nd part of duodenum; may cause duodenal narrowing (arrows in A ) and vomiting.
Pancreas divisum—ventral and dorsal parts fail to fuse at 8 weeks. Common anomaly; mostly
stomach asymptomatic, but may cause chronic abdominal pain and/or pancreatitis.
Spleen—arises in mesentery of stomach (hence is mesodermal) but has foregut supply (celiac trunk
splenic artery).
Gallbladder
Accessory
pancreatic duct
Minor papilla
Major papilla
Dorsal
pancreatic bud
Uncinate process
Main pancreatic duct
Ventral
pancreatic bud
GASTROINTESTINAL—ANATOMY
``
Asc Desc
Liver Colon Colon
IVC Kidney
Aorta
IVC Ao
Kid Kid
Liver Stomach
Omental foramen
(epiploic foramen Spleen
of Winslow)
Gastrosplenic
Greater • ligament
sac Visceral
• peritoneum
Splenorenal
Right kidney ligament
Left adrenal gland
Left kidney
Inferior vena cava Lesser sac
T12 vertebra Aorta
LIGAMENT CONNECTS STRUCTURES CONTAINED NOTES
Falciform ligament Liver to anterior abdominal Ligamentum teres hepatis Derivative of ventral mesentery
wall (derivative of fetal umbilical
vein), patent paraumbilical
veins
Hepatoduodenal Liver to duodenum Portal triad: proper hepatic Derivative of ventral mesentery
ligament artery, portal vein, common Pringle maneuver—ligament is
bile duct compressed manually or with
a vascular clamp in omental
foramen to control bleeding
from hepatic inflow source
Borders the omental foramen,
which connects the greater
and lesser sacs
Part of lesser omentum
Gastrohepatic Liver to lesser curvature of Gastric vessels Derivative of ventral mesentery
ligament stomach Separates greater and lesser sacs
on the right
May be cut during surgery to
access lesser sac
Part of lesser omentum
Gastrocolic ligament Greater curvature and Gastroepiploic arteries Derivative of dorsal mesentery
(not shown) transverse colon Part of greater omentum
Gastrosplenic Greater curvature and spleen Short gastrics, left Derivative of dorsal mesentery
ligament gastroepiploic vessels Separates greater and lesser sacs
on the left
Part of greater omentum
Splenorenal ligament Spleen to left pararenal space Splenic artery and vein, tail of Derivative of dorsal mesentery
pancreas
Lumen
Submucosal nerve
plexus (Meissner)
Muscularis
Inner circular layer
Myenteric nerve plexus Tunica muscularis
(Auerbach)
Outer longitudinal layer Tunica serosa
Serosa (peritoneum)
co
ilia
on t
mm gh
mm
Le on il
ft iac
L5
weight/malnutrition).
Median sacral
Duodenum
Aorta
Right external Right internal Left internal Left external
iliac iliac iliac iliac
SMA
Celiac trunk Branches of celiac trunk: common hepatic, splenic, and left gastric. These constitute the main
blood supply of the foregut.
Strong anastomoses exist between:
Left and right gastroepiploics
Left and right gastrics
Abdominal aorta
Celiac trunk Esophageal branches
Left hepatic
Left gastric
Short gastric
Cystic
Left gastroepiploic
Proper hepatic
Common hepatic
“Anastamoses”
Gastroduodenal
Anterior superior pancreaticoduodenal Areas supplied by:
Posterior superior pancreaticoduodenal
Left gastric artery
Splenic artery
Right gastric
Right gastroepiploic Common hepatic artery
Portosystemic
anastomoses
Shunt
Systemic venous system
Left gastric vein
Portal venous system
Portal vein
Splenic vein
Paraumbilical vein
Superior mesenteric vein
Inferior mesenteric vein
R
Umbilicus
Colon
Pectinate line Also called dentate line. Formed where endoderm (hindgut) meets ectoderm.
Nerves Arteries Veins Lymphatics Above pectinate line: internal hemorrhoids,
Visceral innervation Superior rectal Superior rectal vein Drain to internal adenocarcinoma.
artery (branch → IMV → splenic iliac LN
of IMA) vein → portal vein Internal hemorrhoids receive visceral
innervation and are therefore not painful.
Pectinate line
Below pectinate line: external hemorrhoids,
anal fissures, squamous cell carcinoma.
External hemorrhoids receive somatic
innervation (inferior rectal branch of
pudendal nerve) and are therefore painful if
thrombosed.
Anal fissure—tear in anal mucosa below
Inferior rectal vein Pectinate line. Pain while Pooping; blood
Inferior rectal artery → internal pudendal
Somatic innervation (branch of internal vein → internal iliac
Drain to superficial on toilet Paper. Located Posteriorly because
inguinal LN
pudendal artery) vein → common iliac this area is Poorly Perfused. Innervated by
vein → IVC Pudendal nerve. Associated with low-fiber
diets and constipation.
Liver tissue The functional unit of the liver is made up of Zone I—periportal zone:
architecture hexagonally arranged lobules surrounding the Affected 1st by viral hepatitis
A
central vein with portal triads on the edges Best oxygenated, most resistant to circulatory
(consisting of a portal vein, hepatic artery, bile compromise
ducts, as well as lymphatics) A . Ingested toxins (eg, cocaine)
Apical surface of hepatocytes faces bile Zone II—intermediate zone:
canaliculi. Basolateral surface faces sinusoids. Yellow fever
Kupffer cells (specialized macrophages) located Zone III—pericentral vein (centrilobular) zone:
in sinusoids (black arrows in B ; yellow arrows Affected 1st by ischemia (least oxygenated)
show hepatic venule) clear bacteria and High concentration of cytochrome P-450
B damaged or senescent RBCs. Most sensitive to metabolic toxins (eg,
Hepatic stellate (Ito) cells in space of Disse ethanol, CCl4, halothane, rifampin,
store vitamin A (when quiescent) and produce acetaminophen)
extracellular matrix (when activated). Site of alcoholic hepatitis
Responsible for hepatic fibrosis.
Stellate cell
Zone 3
Zone 2
Space of Disse
Zone 1
Zone 1
Branch of
hepatic artery
Branch of
portal vein
Bile ductule
Portal triad
Biliary structures Gallstones that reach the confluence of the common bile and pancreatic ducts at the ampulla of
A
Vater can block both the common bile and pancreatic ducts (double duct sign), causing both
cholangitis and pancreatitis, respectively.
Tumors that arise in head of pancreas (usually ductal adenocarcinoma) can cause obstruction of
e
CHD common bile duct enlarged gallbladder with painless jaundice (Courvoisier sign).
op
sc
do
Cholangiography shows filling defects in gallbladder (blue arrow) and cystic duct (red arrow) A .
En
t
uc
cd
ati
n cre
Pa
Cystic duct
Liver
Gallbladder
Common hepatic duct
Tail
Accessory Neck Body
pancreatic duct
Pancreas
Head
Sphincter of Oddi
Ampulla of Vater
Main pancreatic duct
Duodenum
Femoral region
ORGANIZATION Lateral to medial: Nerve-Artery-Vein- You go from lateral to medial to find your
Lymphatics. NAVeL.
Femoral triangle Contains femoral nerve, artery, vein. Venous near the penis.
Femoral sheath Fascial tube 3–4 cm below inguinal ligament.
Contains femoral vein, artery, and canal (deep
inguinal lymph nodes) but not femoral nerve.
Femoral Nerve
Femoral Artery
Transversalis
fascia Femoral Vein
Inguinal
ligament
Lymphatics
Sartorius
muscle Femoral ring—site of
femoral hernia
Femoral
sheath
Adductor longus
muscle
Inguinal canal
Abdominal wall
Deep (internal)
Inferior epigastric site of protrusion of
inguinal ring
vessels direct hernia
site of protrusion of
Parietal peritoneum indirect hernia Medial umbilical ligament
Aponeurosis of external
oblique muscle
Superficial (external)
Inguinal ligament inguinal ring
Internal spermatic fascia Cremasteric muscle and fascia External spermatic fascia
(transversalis fascia) (internal oblique) (external oblique)
Abdominal wall
Anterior superior iliac spine
Posterior rectus sheath Transversus abdominis muscle
Transversalis fascia
Evagination of transversalis fascia Inferior epigastric vessels
Arcuate line Internal (deep) inguinal ring Rectus abdominis
Ductus (vas) deferens
Inferior epigastric vessels Genital branch of genitofemoral Inguinal ligament
Rectus abdominis nerve
Inguinal (Hesselbach) triangle
Internal spermatic vessels
Inguinal ligament
Iliacus muscle
Inguinal (Hesselbach) triangle Femoral nerve
External iliac vessels
Femoral vessels
Pubic tubercle Femoral triangle
Lacunar ligament
Hernias Protrusion of peritoneum through an opening, usually at a site of weakness. Contents may be at
risk for incarceration (not reducible back into abdomen/pelvis) and strangulation (ischemia and
necrosis). Complicated hernias can present with tenderness, erythema, fever.
Diaphragmatic hernia Abdominal structures enter the thorax A ; may occur due to congenital defect of pleuroperitoneal
A
membrane or from trauma. Commonly occurs on left side due to relative protection of right
hemidiaphragm by liver. Most commonly a hiatal hernia, in which stomach herniates upward
through the esophageal hiatus of the diaphragm.
Sliding hiatal hernia—gastroesophageal
junction is displaced upward as gastric cardia Herniated
gastric cardia Herniated
slides into hiatus; “hourglass stomach.” Most gastric fundus
common type. Associated with GERD.
Paraesophageal hiatal hernia—
gastroesophageal junction is usually normal
but gastric fundus protrudes into the thorax.
Sliding hiatal hernia Paraesophageal hiatal hernia
B
into the groin. Enters internal inguinal ring Deep
inguinal ring
lateral to inferior epigastric vessels. Caused Inguinal canal
by failure of processus vaginalis to close (can Superficial
form hydrocele). May be noticed in infants or inguinal ring
discovered in adulthood. Much more common Intestinal loop
within spermatic
in males B . cord
Follows the pathway of testicular descent.
Testis
Covered by all 3 layers of spermatic fascia.
GASTROINTESTINAL—PHYSIOLOGY
``
A
Gastric pit Surface epithelium
Vagus nerve
Fundus
Cardia
ACh
HCl Parietal
cells
Body
Intrinsic
factor
ACh
Pyloric D cells
sphincter ACh
Pepsinogen Histamine
CCK Antrum Chief
Somato- cells
I cells statin
Mucus
GRP ECL cells
S cells
Gastrin
Secretin Duodenum Mucous G cells (to circulation)
cells
GIP
K cells
Gastrin acid secretion primarily through its effects on enterochromaffin-like (ECL) cells (leading
to histamine release) rather than through its direct effect on parietal cells.
Pancreatic secretions Isotonic fluid; low flow high Cl−, high flow high HCO3−.
ENZYME ROLE NOTES
α-amylase Starch digestion Secreted in active form
Lipases Fat digestion
Proteases Protein digestion Includes trypsin, chymotrypsin, elastase,
carboxypeptidases
Secreted as proenzymes also called zymogens
Trypsinogen Converted to active enzyme trypsin Converted to trypsin by enterokinase/
activation of other proenzymes and cleaving enteropeptidase, a brush-border enzyme on
of additional trypsinogen molecules into active duodenal and jejunal mucosa
trypsin (positive feedback loop)
Food
iron
Hepcidin
Heme
iron
Non-heme
iron (Fe³+)
Ferroportin-1 Transferrin
Ferritin
Fe²+
Peyer patches Unencapsulated lymphoid tissue A found in Think of IgA, the Intra-gut Antibody
A
lamina propria and submucosa of ileum.
Contain specialized M cells that sample and
present antigens to immune cells.
B cells stimulated in germinal centers of Peyer
patches differentiate into IgA-secreting plasma
cells, which ultimately reside in lamina
propria. IgA receives protective secretory
component and is then transported across the
epithelium to the gut to deal with intraluminal
antigen.
Bile Composed of bile salts (bile acids conjugated to absorption of enteric bile salts at distal ileum
glycine or taurine, making them water soluble), (as in short bowel syndrome, Crohn disease)
phospholipids, cholesterol, bilirubin, water, prevents normal fat absorption
and ions. Cholesterol 7α-hydroxylase catalyzes Calcium, which normally binds oxalate, binds
rate-limiting step of bile acid synthesis. fat instead, so free oxalate is absorbed by gut
Functions: frequency of calcium oxalate kidney stones
Digestion and absorption of lipids and fat-
soluble vitamins
Cholesterol excretion (body’s 1° means of
eliminating cholesterol)
Antimicrobial activity (via membrane
disruption)
Bilirubin Heme is metabolized by heme oxygenase to biliverdin, which is subsequently reduced to bilirubin.
Unconjugated bilirubin is removed from blood by liver, conjugated with glucuronate, and excreted
in bile.
Direct bilirubin: conjugated with glucuronic acid; water soluble (dissolves in water).
Indirect bilirubin: unconjugated; water insoluble.
Excreted in urine as
urobilin (→ yellow color) Kidney
90% 10%
Enterohepatic
circulation
20%
Macrophages Bloodstream Liver Gut
Albumin
Unconjugated Unconjugated bilirubin- Conjugated
RBCs Heme Urobilinogen
bilirubin albumin complex bilirubin
UDP-
glucuronosyl-
Gut bacteria 80%
transferase
GASTROINTESTINAL—PATHOLOGY
``
Sialolithiasis Stone(s) in salivary gland duct A . Can occur in 3 Sialadenitis—inflammation of salivary gland due
A
major salivary glands (parotid, submandibular, to obstruction, infection, or immune-mediated
sublingual). Single stone more common in mechanisms.
submandibular gland (Wharton duct).
Presents as recurrent pre-/periprandial pain and
swelling in affected gland.
Caused by dehydration or trauma.
Treat conservatively with NSAIDs, gland
massage, warm compresses, sour candies (to
promote salivary flow).
Salivary gland tumors Most are benign and commonly affect parotid gland (80-85%). Nearly half of all submandibular
A
gland neoplasms and most sublingual and minor salivary gland tumors are malignant. Typically
present as painless mass/swelling. Facial paralysis or pain suggests malignant involvement.
Pleomorphic adenoma (benign mixed tumor)—most common salivary gland tumor A .
Composed of chondromyxoid stroma and epithelium and recurs if incompletely excised or
ruptured intraoperatively. May undergo malignant transformation.
Mucoepidermoid carcinoma—most common malignant tumor, has mucinous and squamous
components.
Warthin tumor (papillary cystadenoma lymphomatosum)—benign cystic tumor with germinal
centers. Typically found in smokers. Bilateral in 10%; multifocal in 10%. “Warriors from
Germany love smoking.”
Esophageal pathologies
Diffuse esophageal Spontaneous, nonperistaltic (uncoordinated) contractions of the esophagus with normal LES
spasm pressure. Presents with dysphagia and angina-like chest pain. Barium swallow reveals “corkscrew”
esophagus. Manometry is diagnostic. Treatment includes nitrates and CCBs.
Eosinophilic Infiltration of eosinophils in the esophagus often in atopic patients. Food allergens dysphagia,
esophagitis food impaction. Esophageal rings and linear furrows often seen on endoscopy. Typically
unresponsive to GERD therapy.
Esophageal Most commonly iatrogenic following esophageal instrumentation. Noniatrogenic causes include
perforation spontaneous rupture, foreign body ingestion, trauma, malignancy.
May present with pneumomediastinum (arrows in A ). Subcutaneous emphysema may be due to
dissecting air (signs include crepitus in the neck region or chest wall).
Boerhaave syndrome—transmural, usually distal esophageal rupture due to violent retching.
Esophageal strictures Associated with caustic ingestion, acid reflux, and esophagitis.
Esophageal varices Dilated submucosal veins (red arrows in B C ) in lower 1/3 of esophagus 2° to portal
hypertension. Common in cirrhotics, may be source of life-threatening hematemesis.
Esophagitis Associated with reflux, infection in immunocompromised (Candida: white pseudomembrane D ;
HSV-1: punched-out ulcers; CMV: linear ulcers), caustic ingestion, or pill-induced esophagitis
(eg, bisphosphonates, tetracycline, NSAIDs, iron, and potassium chloride).
Gastroesophageal Commonly presents as heartburn, regurgitation, dysphagia. May also present as chronic cough,
reflux disease hoarseness (laryngopharyngeal reflux). Associated with asthma. Transient decreases in LES tone.
Mallory-Weiss Partial thickness, longitudinal lacerations of gastroesophageal junction, confined to mucosa/
syndrome submucosa, due to severe vomiting. Often presents with hematemesis. Usually found in alcoholics
and bulimics.
Plummer-Vinson Triad of Dysphagia, Iron deficiency anemia, Esophageal webs. risk of esophageal Squamous cell
syndrome carcinoma ("Plumber DIES"). May be associated with glossitis.
Schatzki rings Rings formed at gastroesophageal junction, typically due to chronic acid reflux. Can present with
dysphagia.
Sclerodermal Esophageal smooth muscle atrophy LES pressure and dysmotility acid reflux and dysphagia
esophageal stricture, Barrett esophagus, and aspiration. Part of CREST syndrome.
dysmotility
A B C D
esophagus
Aortic
T arch Ao
E
Squamocolumnar
Esophagus
(epithelial) junction
(SCJ or Z line)
B
Lower
esophageal
sphincter
Stomach
Esophageal cancer Typically presents with progressive dysphagia (first solids, then liquids) and weight loss. Aggressive
course due to lack of serosa in esophageal wall, allowing rapid extension. Poor prognosis due to
advanced disease at presentation.
CANCER PART OF ESOPHAGUS AFFECTED RISK FACTORS PREVALENCE
Squamous cell Upper 2/3 Alcohol, hot liquids, caustic More common worldwide
carcinoma strictures, smoking, achalasia
Adenocarcinoma Lower 1/3 Chronic GERD, Barrett More common in America
esophagus, obesity, smoking,
achalasia
Gastritis
Acute gastritis Erosions can be caused by: Especially common among alcoholics and
NSAIDs— PGE2 gastric mucosa patients taking daily NSAIDs (eg, patients with
protection rheumatoid arthritis)
Burns (Curling ulcer)—hypovolemia Burned by the Curling iron
mucosal ischemia
Brain injury (Cushing ulcer)— vagal Always Cushion the brain
stimulation ACh H+ production
Chronic gastritis Mucosal inflammation, often leading to atrophy
(hypochlorhydria hypergastrinemia) and
intestinal metaplasia ( risk of gastric cancers)
H pylori Most common. risk of peptic ulcer disease, Affects antrum first and spreads to body of
MALT lymphoma stomach
Autoimmune Autoantibodies to the H+/K+ ATPase on parietal Affects body/fundus of stomach
cells and to intrinsic factor. risk of pernicious
anemia
Ménétrier disease Hyperplasia of gastric mucosa hypertrophied rugae (look like brain gyri A ). Causes excess
A mucus production with resultant protein loss and parietal cell atrophy with acid production.
Precancerous.
Presents with Weight loss, Anorexia, Vomiting, Epigastric pain, Edema (due to protein loss)
Stomach (WAVEE).
Ulcer complications
Hemorrhage Gastric, duodenal (posterior > anterior). Most common complication.
Ruptured gastric ulcer on the lesser curvature of stomach bleeding from left gastric artery.
An ulcer on the posterior wall of duodenum bleeding from gastroduodenal artery.
Obstruction Pyloric channel, duodenal.
Perforation Duodenal (anterior > posterior).
A
Anterior duodenal ulcers can perforate into the anterior abdominal cavity, potentially leading to
pneumoperitoneum.
May see free air under diaphragm (pneumoperitoneum) A with referred pain to the shoulder via
irritation of phrenic nerve.
Malabsorption Can cause diarrhea, steatorrhea, weight loss, weakness, vitamin and mineral deficiencies. Screen for
syndromes fecal fat (eg, Sudan stain).
Celiac disease Gluten-sensitive enteropathy, celiac sprue. mucosal absorption primarily affects distal
A
Autoimmune-mediated intolerance of duodenum and/or proximal jejunum.
gliadin (gluten protein found in wheat) d-xylose test: passively absorbed in proximal
malabsorption and steatorrhea. Associated small intestine; blood and urine levels with
with HLA-DQ2, HLA-DQ8, northern mucosa defects or bacterial overgrowth,
European descent, dermatitis herpetiformis, normal in pancreatic insufficiency.
bone density. Treatment: gluten-free diet.
Findings: IgA anti-tissue transglutaminase
(IgA tTG), anti-endomysial, anti-deamidated
gliadin peptide antibodies; villous atrophy,
crypt hyperplasia A , and intraepithelial
lymphocytosis. Moderately risk of
malignancy (eg, T-cell lymphoma).
Lactose intolerance Lactase deficiency. Normal-appearing villi, Lactose hydrogen breath test: ⊕ for lactose
except when 2° to injury at tips of villi (eg, viral malabsorption if post-lactose breath hydrogen
enteritis). Osmotic diarrhea with stool pH value rises > 20 ppm compared with baseline.
(colonic bacteria ferment lactose).
Pancreatic Due to chronic pancreatitis, cystic fibrosis, duodenal bicarbonate (and pH) and fecal
insufficiency obstructing cancer. Causes malabsorption of elastase.
fat and fat-soluble vitamins (A, D, E, K) as well
as vitamin B12.
Tropical sprue Similar findings as celiac sprue (affects small mucosal absorption affecting duodenum and
bowel), but responds to antibiotics. Cause is jejunum but can involve ileum with time.
unknown, but seen in residents of or recent Associated with megaloblastic anemia due to
visitors to tropics. folate deficiency and, later, B12 deficiency.
Whipple disease Infection with Tropheryma whipplei PAS the foamy Whipped cream in a CAN.
B
(intracellular gram ⊕); PAS ⊕ foamy
macrophages in intestinal lamina propria
B , mesenteric nodes. Cardiac symptoms,
Arthralgias, and Neurologic symptoms are
common. Diarrhea/steatorrhea occur later in
disease course. Most common in older men.
Appendicitis Acute inflammation of the appendix (yellow arrows in A ), can be due to obstruction by fecalith
A
(red arrow in A ) (in adults) or lymphoid hyperplasia (in children).
Proximal obstruction of appendiceal lumen produces closed-loop obstruction intraluminal
pressure stimulation of visceral afferent nerve fibers at T8-T10 initial diffuse periumbilical
pain inflammation extends to serosa and irritates parietal peritoneum. Pain localized to RLQ/
McBurney point (1/3 the distance from right anterior superior iliac spine to umbilicus). Nausea,
fever; may perforate peritonitis; may elicit psoas, obturator, and Rovsing signs, guarding and
rebound tenderness on exam.
Differential: diverticulitis (elderly), ectopic pregnancy (use hCG to rule out), pseudoappendicitis.
Treatment: appendectomy.
Meckel diverticulum True diverticulum. Persistence of the vitelline The rule of 2’s:
(omphalomesenteric) duct. May contain 2 times as likely in males.
ectopic acid–secreting gastric mucosa and/or 2 inches long.
pancreatic tissue. Most common congenital 2 feet from the ileocecal valve.
anomaly of GI tract. Can cause hematochezia/ 2% of population.
Umbilicus
melena (less common), RLQ pain, Commonly presents in first 2 years of life.
intussusception, volvulus, or obstruction near May have 2 types of epithelia (gastric/
terminal ileum. pancreatic).
Meckel
diverticulum Contrast with omphalomesenteric cyst = cystic
dilation of vitelline duct.
Diagnosis: 99mTc-pertechnetate scan (aka Meckel
scan) for uptake by heterotopic gastric mucosa.
Hirschsprung disease Congenital megacolon characterized by lack Risk with Down syndrome.
Nerve plexus
of ganglion cells/enteric nervous plexuses Explosive expulsion of feces (squirt sign)
(Auerbach and Meissner plexuses) in distal empty rectum on digital exam.
segment of colon. Due to failure of neural crest Diagnosed by absence of ganglionic cells on
Enlarged cell migration. Associated with loss of function rectal suction biopsy.
colon
mutations in RET. Treatment: resection.
Presents with bilious emesis, abdominal RET mutation in the REcTum.
No nerves
Collapsed distention, and failure to pass meconium
rectum within 48 hours chronic constipation.
Normal portion of the colon proximal to the
aganglionic segment is dilated, resulting in a
“transition zone.”
La
formation of fibrous bands (Ladd bands). ba
Stomach nd s
Can lead to volvulus, duodenal obstruction.
Small
Small bowel bowel
Colon
Intussusception Telescoping A of proximal bowel segment into May be associated with IgA vasculitis (HSP),
A a distal segment, commonly at the ileocecal recent viral infection (eg, adenovirus; Peyer patch
junction. Most commonly idiopathic, but may hypertrophy creates lead point).
be due to lead point.
Compromised blood supply intermittent,
severe, abdominal pain often with “currant
jelly” dark red stools.
Majority of cases in infants, unusual in adults.
Most common pathologic lead point:
Children—Meckel diverticulum
B
Adults—intraluminal mass/tumor
On physical exam, patient may draw their legs
to chest to ease pain, sausage shaped mass on
palpation.
Imaging—Ultrasound/CT may show “target
sign.” B
Colonic polyps Growths of tissue within the colon A . Grossly characterized as flat, sessile, or pedunculated on the
basis of protrusion into colonic lumen. Generally classified by histologic type.
HISTOLOGIC TYPE CHARACTERISTICS
Generally non-neoplastic
Hamartomatous Solitary lesions do not have significant risk of transformation. Growths of normal colonic tissue
polyps with distorted architecture. Associated with Peutz-Jeghers syndrome and juvenile polyposis.
Hyperplastic polyps Most common; generally smaller and predominantly located in rectosigmoid region. Occasionally
evolves into serrated polyps and more advanced lesions.
Inflammatory Due to mucosal erosion in inflammatory bowel disease.
pseudopolyps
Mucosal polyps Small, usually < 5 mm. Look similar to normal mucosa. Clinically insignificant.
Submucosal polyps May include lipomas, leiomyomas, fibromas, and other lesions.
Malignant potential
Adenomatous polyps Neoplastic, via chromosomal instability pathway with mutations in APC and KRAS. Tubular
B histology has less malignant potential than villous C (“villous histology is villainous”);
tubulovillous has intermediate malignant potential. Usually asymptomatic; may present with
occult bleeding.
Serrated polyps Neoplastic. Characterized by CpG island methylator phenotype (CIMP; cytosine base followed
by guanine, linked by a phosphodiester bond). Defect may silence MMR gene (DNA mismatch
repair) expression. Mutations lead to microsatellite instability and mutations in BRAF. “Saw-
tooth” pattern of crypts on biopsy. Up to 20% of cases of sporadic CRC.
A B C
Polyp
Polyp
Cancer
Sessile Pedunculated
Polyposis syndromes
Familial adenomatous Autosomal dominant mutation of APC tumor suppressor gene on chromosome 5q22. 2-hit
polyposis hypothesis. Thousands of polyps arise starting after puberty; pancolonic; always involves rectum.
Prophylactic colectomy or else 100% progress to CRC.
Gardner syndrome FAP + osseous and soft tissue tumors (eg, osteomas of skull or mandible), congenital hypertrophy of
retinal pigment epithelium, impacted/supernumerary teeth.
Turcot syndrome FAP or Lynch syndrome + malignant CNS tumor (eg, medulloblastoma, glioma). Turcot = Turban.
Peutz-Jeghers Autosomal dominant syndrome featuring numerous hamartomas throughout GI tract, along with
syndrome hyperpigmented macules on mouth, lips, hands, genitalia. Associated with risk of breast and GI
cancers (eg, colorectal, stomach, small bowel, pancreatic).
Juvenile polyposis Autosomal dominant syndrome in children (typically < 5 years old) featuring numerous
syndrome hamartomatous polyps in the colon, stomach, small bowel. Associated with risk of CRC.
Lynch syndrome Previously called hereditary nonpolyposis colorectal cancer (HNPCC). Autosomal dominant
mutation of mismatch repair genes (eg, MLH1, MSH2) with subsequent microsatellite instability.
∼ 80% progress to CRC. Proximal colon is always involved. Associated with endometrial, ovarian,
and skin cancers.
Colorectal cancer
DIAGNOSIS Iron deficiency anemia in males (especially > 50 years old) and postmenopausal females raises
A suspicion.
Screening:
Low risk: screen at age 50 with colonoscopy (polyp seen in A ); alternatives include flexible
sigmoidoscopy, fecal occult blood testing (FOBT), fecal immunochemical testing (FIT),
FIT-fecal DNA, CT colonography
Patients with a first-degree relative who has colon cancer: screen at age 40 with colonoscopy, or
10 years prior to the relative's presentation
Patients with IBD: distinct screening protocol
B
“Apple core” lesion seen on barium enema x-ray B .
CEA tumor marker: good for monitoring recurrence, should not be used for screening.
EPIDEMIOLOGY Most patients are > 50 years old. ~ 25% have a family history.
PRESENTATION Rectosigmoid > ascending > descending.
Right side (cecal, ascending) associated with occult bleeding; left side (rectosigmoid) associated
with hematochezia and obstruction (narrower lumen).
Ascending—exophytic mass, iron deficiency anemia, weight loss.
Descending—infiltrating mass, partial obstruction, colicky pain, hematochezia.
Can present with S bovis (gallolyticus) bacteremia/endocarditis or as an episode of diverticulitis.
RISK FACTORS Adenomatous and serrated polyps, familial cancer syndromes, IBD, tobacco use, diet of processed
meat with low fiber.
Molecular Chromosomal instability pathway: mutations in APC cause FAP and most sporadic cases of CRC
pathogenesis of via adenoma-carcinoma sequence; (firing order of events is “AK-53”).
colorectal cancer Microsatellite instability pathway: mutations or methylation of mismatch repair genes (eg, MLH1)
cause Lynch syndrome and some sporadic CRC (via serrated polyp pathway).
Overexpression of COX-2 has been linked to colorectal cancer, NSAIDs may be chemopreventive.
Chromosomal instability pathway
Loss of tumor suppressor
Loss of APC gene KRAS mutation gene(s) (TP53, DCC)
Normal colon Colon at risk Adenoma Carcinoma
Reproductive Metabolic
Testicular atrophy* Hyperbilirubinemia
Gynecomastia* Hyponatremia
Amenorrhea
Cardiovascular
Cardiomyopathy
Peripheral edema
*Due to estrogen
Spontaneous bacterial Also called 1° bacterial peritonitis. Common and potentially fatal bacterial infection in patients
peritonitis with cirrhosis and ascites. Often asymptomatic, but can cause fevers, chills, abdominal pain, ileus,
or worsening encephalopathy. Commonly caused by gram ⊝ organisms (eg, E coli, Klebsiella) or
less commonly gram ⊕ Streptococcus.
Diagnosis: paracentesis with ascitic fluid absolute neutrophil count (ANC) > 250 cells/mm3.
Empiric first-line treatment is 3rd generation cephalosporin (eg, cefotaxime).
Reye syndrome Rare, often fatal childhood hepatic Avoid aspirin in children, except in those with
encephalopathy. Kawasaki disease.
Associated with viral infection (especially VZV Salicylates aren’t a ray (Reye) of sunSHINE for
and influenza) that has been treated with kids:
aspirin. Aspirin metabolites β-oxidation Steatosis of liver/hepatocytes
by reversible inhibition of mitochondrial Hypoglycemia/Hepatomegaly
enzymes. Infection (VZV, influenza)
Findings: mitochondrial abnormalities, Not awake (coma)
fatty liver (microvesicular fatty changes), Encephalopathy
hypoglycemia, vomiting, hepatomegaly, coma.
Nonalcoholic fatty Metabolic syndrome (insulin resistance); ALT > AST (Lipids)
liver disease obesity fatty infiltration of hepatocytes A
A
cellular “ballooning” and eventual necrosis.
May cause cirrhosis and HCC. Independent of
alcohol use.
Hepatic adenoma Rare, benign liver tumor, often related to oral contraceptive or anabolic steroid use; may regress
spontaneously or rupture (abdominal pain and shock).
Metastases GI malignancies, breast and lung cancer. Most common overall; metastases are rarely solitary.
Budd-Chiari syndrome Thrombosis or compression of hepatic veins with centrilobular congestion and necrosis
congestive liver disease (hepatomegaly, ascites, varices, abdominal pain, liver failure). Absence
of JVD. Associated with hypercoagulable states, polycythemia vera, postpartum state, HCC. May
cause nutmeg liver (mottled appearance).
α1-antitrypsin Misfolded gene product protein aggregates in In lungs, α1-antitrypsin uninhibited elastase
deficiency hepatocellular ER cirrhosis with in alveoli elastic tissue panacinar
A
PAS ⊕ globules A in liver. Codominant trait. emphysema.
Often presents in young patients with liver
damage and dyspnea without a history of
smoking.
Conjugated (direct) Biliary tract obstruction: gallstones, cholangiocarcinoma, pancreatic or liver cancer, liver fluke.
hyperbilirubinemia Biliary tract disease:
1° sclerosing cholangitis
1° biliary cholangitis
Excretion defect: Dubin-Johnson syndrome, Rotor syndrome.
Unconjugated Hemolytic, physiologic (newborns), Crigler-Najjar, Gilbert syndrome.
(indirect)
hyperbilirubinemia
Mixed (direct Hepatitis, cirrhosis.
and indirect)
hyperbilirubinemia
BILIRUBIN UPTAKE Q
Unconjugated bilirubin
UDP-glucuronosyl-
transferase
Q
CONJUGATION
R
Conjugated bilirubin
(bilirubin diglucuronide, water soluble)
INTRACELLULAR S
TRANSPORT T
Obstructive jaundice
(downstream) Bile flow
Wilson disease Also called hepatolenticular degeneration. Autosomal recessive mutations in hepatocyte
A
copper-transporting ATPase (ATP7B gene; chromosome 13) copper incorporation into
apoceruloplasmin and excretion into bile serum ceruloplasmin. Copper accumulates,
especially in liver, brain, cornea, kidneys; urine copper.
Presents before age 40 with liver disease (eg, hepatitis, acute liver failure, cirrhosis), neurologic
disease (eg, dysarthria, dystonia, tremor, parkinsonism), psychiatric disease, Kayser-Fleischer rings
(deposits in Descemet membrane of cornea) A , hemolytic anemia, renal disease (eg, Fanconi
syndrome).
Treatment: chelation with penicillamine or trientine, oral zinc. Liver transplant in acute liver
failure related to Wilson disease.
Hemochromatosis Autosomal recessive. On HFE gene, located on chromosome 6; associated with HLA-A3. Leads
A
to abnormal iron sensing and intestinal absorption ( ferritin, iron, TIBC transferrin
saturation). Iron overload can also be 2° to chronic transfusion therapy (eg, β-thalassemia major).
Iron accumulates, especially in liver, pancreas, skin, heart, pituitary, joints. Hemosiderin (iron)
can be identified on liver MRI or biopsy with Prussian blue stain A .
Presents after age 40 when total body iron > 20 g; iron loss through menstruation slows progression
in women. Classic triad of cirrhosis, diabetes mellitus, skin pigmentation (“bronze diabetes”). Also
causes restrictive cardiomyopathy (classic) or dilated cardiomyopathy (reversible), hypogonadism,
arthropathy (calcium pyrophosphate deposition; especially metacarpophalangeal joints). HCC is
common cause of death.
Treatment: repeated phlebotomy, iron (Fe) chelation with deferasirox, deferoxamine, deferiprone.
Biliary tract disease May present with pruritus, jaundice, dark urine, light-colored stool, hepatosplenomegaly. Typically
with cholestatic pattern of LFTs ( conjugated bilirubin, cholesterol, ALP, GGT).
PATHOLOGY EPIDEMIOLOGY ADDITIONAL FEATURES
Primary sclerosing Unknown cause of concentric Classically in middle-aged men Associated with ulcerative
cholangitis “onion skin” bile duct with ulcerative colitis. colitis. p-ANCA ⊕. IgM.
fibrosis alternating Can lead to 2° biliary
strictures and dilation with cholangitis. risk of
“beading” of intra- and cholangiocarcinoma and
extrahepatic bile ducts on gallbladder cancer.
ERCP, magnetic resonance
cholangiopancreatography
(MRCP).
Primary biliary Autoimmune reaction Classically in middle-aged Anti-mitochondrial antibody ⊕,
cholangitis lymphocytic infiltrate women. IgM. Associated with other
+/– granulomas autoimmune conditions
destruction of lobular bile (eg, Hashimoto thyroiditis,
ducts. rheumatoid arthritis, celiac
disease).
Treatment: ursodiol.
Secondary biliary Extrahepatic biliary obstruction Patients with known May be complicated by
cirrhosis pressure in intrahepatic obstructive lesions (gallstones, ascending cholangitis.
ducts injury/ fibrosis and biliary strictures, pancreatic
bile stasis. carcinoma).
Cholelithiasis and cholesterol and/or bilirubin, bile salts, and Gender (female), Chronic hemolysis,
related pathologies gallbladder stasis all cause stones. age, obesity, genetics, biliary tract infection
↓cholesterol 7α hydroxylase
A 2 types of stones:
Cholesterol stones (radiolucent with 10–20%
opaque due to calcifications)—80% of stones. ↑Cholesterol, ↓bile ↑Unconjugated bilirubin,
Associated with obesity, Crohn disease, salts, gallbladder stasis gallbladder stasis
advanced age, estrogen therapy, multiparity, Supersaturation of bile
Supersaturation of
rapid weight loss, Native American origin. bile with cholesterol with calcium bilirubinate
Pigment stones A (black = radiopaque, Ca2+
Cholesterol stones Pigment stones
bilirubinate, hemolysis; brown = radiolucent,
infection). Associated with Crohn disease,
chronic hemolysis, alcoholic cirrhosis,
advanced age, biliary infections, total
parenteral nutrition (TPN).
Risk factors (4 F’s):
1. Female
2. Fat
3. Fertile (multiparity)
4. Forty
Most common complication is cholecystitis;
can also cause acute pancreatitis, ascending
cholangitis.
Diagnose with ultrasound. Treat with elective
cholecystectomy if symptomatic.
RELATED PATHOLOGIES CHARACTERISTICS
Biliary colic Associated with nausea/vomiting and dull RUQ pain. Neurohormonal activation (eg, by CCK after
a fatty meal) triggers contraction of gallbladder, forcing stone into cystic duct. Labs are normal,
ultrasound shows cholelithiasis.
Choledocholithiasis Presence of gallstone(s) in common bile duct, often leading to elevated ALP, GGT, direct bilirubin,
and/or AST/ALT.
Cholecystitis Acute or chronic inflammation of gallbladder.
B
Calculous cholecystitis—most common type; due to gallstone impaction in the cystic duct resulting
in inflammation and gallbladder wall thickening (arrows in B ); can produce 2° infection.
Acalculous cholecystitis—due to gallbladder stasis, hypoperfusion, or infection (CMV); seen in
critically ill patients.
Murphy sign: inspiratory arrest on RUQ palpation due to pain. Pain may radiate to right shoulder
(due to irritation of phrenic nerve). ALP if bile duct becomes involved (eg, ascending
cholangitis).
Diagnose with ultrasound or cholescintigraphy (HIDA scan). Failure to visualize gallbladder on
HIDA scan suggests obstruction.
Gallstone ileus—fistula between gallbladder and GI tract stone enters GI lumen obstructs
at ileocecal valve (narrowest point); can see air in biliary tree (pneumobilia). Rigler triad:
radiographic findings of pneumobilia, small bowel obstruction, gallstone (usually in iliac fossa).
Ascending cholangitis Infection of biliary tree usually due to obstruction that leads to stasis/bacterial overgrowth.
Charcot triad of cholangitis includes jaundice, fever, RUQ pain.
Reynolds pentad is Charcot triad plus altered mental status and shock (hypotension).
Acute pancreatitis Autodigestion of pancreas by pancreatic enzymes ( A shows pancreas [yellow arrows] surrounded by
A
edema [red arrows]).
Causes: Idiopathic, Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune disease,
Scorpion sting, Hypercalcemia/Hypertriglyceridemia (> 1000 mg/dL), ERCP, Drugs (eg, sulfa
drugs, NRTIs, protease inhibitors). I GET SMASHED.
Diagnosis by 2 of 3 criteria: acute epigastric pain often radiating to the back, serum amylase or
lipase (more specific) to 3× upper limit of normal, or characteristic imaging findings.
Complications: pseudocyst B (lined by granulation tissue, not epithelium), abscess, necrosis,
hemorrhage, infection, organ failure (ALI/ARDS, shock, renal failure), hypocalcemia
B (precipitation of Ca2+ soaps).
Chronic pancreatitis Chronic inflammation, atrophy, calcification of the pancreas A . Major causes include alcohol
A
abuse and genetic predisposition (ie, cystic fibrosis); can be idiopathic. Complications include
pancreatic insufficiency and pseudocysts.
Pancreatic insufficiency (typically when <10% pancreatic function) may manifest with steatorrhea,
fat-soluble vitamin deficiency, diabetes mellitus.
Amylase and lipase may or may not be elevated (almost always elevated in acute pancreatitis).
Pancreatic Very aggressive tumor arising from pancreatic ducts (disorganized glandular structure with cellular
adenocarcinoma infiltration A ); often metastatic at presentation, with average survival ~ 1 year after diagnosis.
A
Tumors more common in pancreatic head B (lead to obstructive jaundice). Associated with CA
19-9 tumor marker (also CEA, less specific).
Risk factors:
Tobacco use
Chronic pancreatitis (especially > 20 years)
Diabetes
Age > 50 years
Jewish and African-American males
B Often presents with:
Abdominal pain radiating to back
Weight loss (due to malabsorption and anorexia)
Migratory thrombophlebitis—redness and tenderness on palpation of extremities (Trousseau
syndrome)
Obstructive jaundice with palpable, nontender gallbladder (Courvoisier sign)
Treatment: Whipple procedure (pancreaticoduodenectomy), chemotherapy, radiation therapy.
GASTROINTESTINAL—PHARMACOLOGY
``
GRP
Vagus nerve
G cells ECL cells
H2 blockers
Atropine
CCKB H2 receptor
M3 receptor receptor
CI– Gq Gs Gi
Histamine-2 blockers Cimetidine, ranitidine, famotidine, nizatidine. Take H2 blockers before you dine. Think “table
for 2” to remember H2.
MECHANISM Reversible block of histamine H2-receptors H+ secretion by parietal cells.
CLINICAL USE Peptic ulcer, gastritis, mild esophageal reflux.
ADVERSE EFFECTS Cimetidine is a potent inhibitor of cytochrome P-450 (multiple drug interactions); it also has
antiandrogenic effects (prolactin release, gynecomastia, impotence, libido in males); can
cross blood-brain barrier (confusion, dizziness, headaches) and placenta. Both cimetidine and
ranitidine renal excretion of creatinine. Other H2 blockers are relatively free of these effects.
Antacids Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and
urinary pH or by delaying gastric emptying.
All can cause hypokalemia.
Overuse can also cause the following problems:
Aluminum hydroxide Constipation, Hypophosphatemia, Aluminimum amount of feces
Osteodystrophy, Proximal muscle weakness, CHOPS
Seizures
Calcium carbonate Hypercalcemia (milk-alkali syndrome), rebound Can chelate and effectiveness of other drugs
acid (eg, tetracycline)
Magnesium hydroxide Diarrhea, hyporeflexia, hypotension, cardiac Mg2+ = Must go 2 the bathroom
arrest
Bismuth, sucralfate
MECHANISM Bind to ulcer base, providing physical protection and allowing HCO3– secretion to reestablish pH
gradient in the mucous layer. Sucralfate requires acidic environment, not given with PPIs/H2
blockers.
CLINICAL USE ulcer healing, travelers’ diarrhea (bismuth). Bismuth also used in quadruple therapy for H pylori
gastritis.
Misoprostol
MECHANISM PGE1 analog. production and secretion of gastric mucous barrier, acid production.
CLINICAL USE Prevention of NSAID-induced peptic ulcers (NSAIDs block PGE1 production). Also used off-label
for induction of labor (ripens cervix).
ADVERSE EFFECTS Diarrhea. Contraindicated in women of childbearing potential (abortifacient).
Octreotide
MECHANISM Long-acting somatostatin analog; inhibits secretion of various splanchnic vasodilatory hormones.
CLINICAL USE Acute variceal bleeds, acromegaly, VIPoma, carcinoid tumors.
ADVERSE EFFECTS Nausea, cramps, steatorrhea. risk of cholelithiasis due to CCK inhibition.
Sulfasalazine
MECHANISM A combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory).
Activated by colonic bacteria.
CLINICAL USE Ulcerative colitis, Crohn disease (colitis component).
ADVERSE EFFECTS Malaise, nausea, sulfonamide toxicity, reversible oligospermia.
Loperamide
MECHANISM Agonist at μ-opioid receptors; slows gut motility. Poor CNS penetration (low addictive potential).
CLINICAL USE Diarrhea.
ADVERSE EFFECTS Constipation, nausea.
Ondansetron
MECHANISM 5-HT3 antagonist; vagal stimulation. Powerful central-acting antiemetic.
CLINICAL USE Control vomiting postoperatively and in patients undergoing cancer chemotherapy.
ADVERSE EFFECTS Headache, constipation, QT interval prolongation, serotonin syndrome.
Metoclopramide
MECHANISM D2 receptor antagonist. resting tone, contractility, LES tone, motility, promotes gastric emptying.
Does not influence colon transport time.
CLINICAL USE Diabetic and postoperative gastroparesis, antiemetic, persistent GERD.
ADVERSE EFFECTS parkinsonian effects, tardive dyskinesia. Restlessness, drowsiness, fatigue, depression, diarrhea.
Drug interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel
obstruction, Parkinson disease (due to D2-receptor blockade), seizure threshold.
Orlistat
MECHANISM Inhibits gastric and pancreatic lipase breakdown and absorption of dietary fats. Taken with
fat-containing meals.
CLINICAL USE Weight loss.
ADVERSE EFFECTS Abdominal pain, flatulence, bowel urgency/frequent bowel movements, steatorrhea; absorption of
fat-soluble vitamins.
Aprepitant
MECHANISM Substance P antagonist. Blocks NK1 (neurokinin-1) receptors in brain.
CLINICAL USE Antiemetic for chemotherapy-induced nausea and vomiting.