HIGH-YIELD SYSTEMS

Gastrointestinal

“A good set of bowels is worth more to a man than any quantity of brains.” ` Embryology 366
—Josh Billings
` Anatomy 369
“Man should strive to have his intestines relaxed all the days of his life.”
—Moses Maimonides ` Physiology 380
“All right, let’s not panic. I’ll make the money by selling one of my livers. I ` Pathology 385
can get by with one.”
—Homer Simpson, The Simpsons ` Pharmacology 407
“The truth does not change according to our ability to stomach it
emotionally.”
—Flannery O’Connor

When studying the gastrointestinal system, be sure to understand the

normal embryology, anatomy, and physiology and how the system is
affected by various pathologies. Study not only disease pathophysiology,
but also its specific findings, so that you can differentiate between
two similar diseases. For example, what specifically makes ulcerative
colitis different from Crohn disease? Also, be comfortable with basic
interpretation of abdominal x-rays, CT scans, and endoscopic images.

365

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` 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:
ƒ 6th week of development—physiologic herniation of midgut through umbilical ring
ƒ 10th week of development—returns to abdominal cavity + rotates around superior mesenteric
artery (SMA), total 270° counterclockwise

Pharyngeal origin
Foregut
Midgut
Hindgut

Celiac trunk

Aorta

Superior
mesenteric
artery
Inferior
mesenteric
artery

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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
PRESENTATION Extrusion of abdominal contents through Herniation of abdominal contents through
abdominal wall defect umbilicus
COVERAGE Not covered by peritoneum or amnion A ; Covered by peritoneum and amnion B (light
“the guts come out of the gap (schism) in the gray shiny sac); “abdominal contents are sealed
letter G” in the letter O”
ASSOCIATIONS Not associated with chromosome abnormalities; Associated with congenital anomalies (eg,
good 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 midgut. Covered by skin C .
hernia Protrudes with intra-abdominal pressure (eg, crying). May be associated with congenital
C disorders (eg, Down syndrome, congenital hypothyroidism). Small defects usually close
spontaneously.

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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

Normal anatomy Pure EA Pure TEF EA with distal TEF

(atresia or stenosis) (H-type) (most common)

Gastric
bubble

Normal Gasless stomach Prominent gastric bubble

Intestinal atresia Presents with bilious vomiting and abdominal distension within first 1–2 days of life.
A
Duodenal atresia—failure to recanalize. 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 may show “triple
bubble” (dilated stomach, duodenum, proximal jejunum) and gasless colon. Associated with
cystic fibrosis. May be caused by maternal cigarette smoking or use of vasoconstrictive drugs (eg,
cocaine) during pregnancy.

Hypertrophic pyloric Most common cause of gastric outlet obstruction in infants. Palpable olive-shaped mass in
stenosis epigastric region, visible peristaltic waves, and nonbilious projectile vomiting at ∼ 2–6 weeks old.
More common in firstborn males; associated with exposure to macrolides.
Results in hypokalemic hypochloremic metabolic alkalosis (2° to vomiting of gastric acid and
Narrow subsequent volume contraction).
pyloric
channel Ultrasound shows thickened and lengthened pylorus.
Treatment: surgical incision of pyloric muscles (pyloromyotomy).

Thickened and
lengthened
pylorus

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Pancreas and spleen Pancreas—derived from foregut. Ventral pancreatic bud contributes to uncinate process. Both
embryology ventral and dorsal buds contribute to pancreatic head and main pancreatic duct.
A 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.
Associated with Down syndrome.
stomach Pancreas divisum—ventral and dorsal parts fail to fuse at 7 weeks of development. Common
anomaly; mostly 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

Retroperitoneal Retroperitoneal structures A are posterior to SAD PUCKER:

structures (and outside of) the peritoneal cavity. Injuries Suprarenal (adrenal) glands [not shown]
to retroperitoneal structures can cause blood Aorta and IVC
or gas accumulation in retroperitoneal space. Duodenum (2nd through 4th parts)
Pancreas (except tail)
Ureters [not shown]
Colon (descending and ascending)
Kidneys
Esophagus (thoracic portion) [not shown]
Duodenum Duodenum/jejunum Rectum (partially) [not shown]
Ascending Peritoneum Descending
colon colon A
Right Left
Pancreas

Asc Desc
Liver Colon Colon
IVC Kidney
Aorta
IVC Ao

R. Kid L. Kid

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Important gastrointestinal ligaments

Falciform Diaphragm
ligament Liver
Liver
Hepatogastric
ligament Stomach
Stomach
Hepatoduodenal Spleen
Portal triad ligament

Spleen Gastrosplenic
ligament Transverse
colon
Kidney
Splenorenal
ligament
Gastrocolic
ligament

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
(portal vein, hepatic artery) vs
outflow (hepatic veins, IVC)
Borders the omental foramen,
which connects the greater
and lesser sacs
Part of lesser omentum
Hepatogastric 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
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

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Digestive tract Layers of gut wall A (inside to outside—MSMS):

anatomy ƒ Mucosa—epithelium, lamina propria, muscularis mucosa
ƒ Submucosa—includes submucosal nerve plexus (Meissner), secretes fluid
ƒ Muscularis externa—includes myenteric nerve plexus (Auerbach), motility
ƒ Serosa (when intraperitoneal), adventitia (when retroperitoneal)
Ulcers can extend into submucosa, inner or outer muscular layer. Erosions are in mucosa only.
Frequency of basal electric rhythm (slow waves), which originate in the interstitial cells of Cajal:
duodenum > ileum > stomach.
A
Mucosa
Epithelium
Lamina propria Tunica mucosa
Muscularis mucosa
Mesentery
Tunica submucosa
Submucosa
Vein Submucosal gland
Artery
Lymph vessel

Lumen
Submucosal nerve
plexus (Meissner)
Muscularis
Inner circular layer
Myenteric nerve plexus Tunica muscularis
(Auerbach)
Outer longitudinal layer Tunica serosa
Serosa (peritoneum)

Digestive tract histology

Esophagus Nonkeratinized stratified squamous epithelium. Upper 1/3, striated muscle; middle and lower 2/3
smooth muscle, with some overlap at the transition.
Stomach Gastric glands A . Parietal cells are eosinophilic (pink, red arrow in B ), chief cells are basophilic
(black arrow in B ).
Duodenum Villi C and microvilli absorptive surface. Brunner glands (bicarbonate-secreting cells of
submucosa), crypts of Lieberkühn (contain stem cells that replace enterocytes/goblet cells and
Paneth cells that secrete defensins, lysozyme, and TNF), and plicae circulares (distal duodenum).
Jejunum Villi, crypts of Lieberkühn, and plicae circulares (taller, more prominent, numerous [vs ileum])
feathered appearance with oral contrast and surface area.
Ileum Villi, Peyer patches (arrow in D ; lymphoid aggregates in lamina propria, submucosa), plicae
circulares (proximal ileum), crypts of Lieberkühn. Largest number of goblet cells in small
intestine.
Colon Crypts of Lieberkühn with abundant goblet cells, but no villi E .
A B C D E

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Abdominal aorta and branches

IVC AORTA Arteries supplying GI structures are single and
Right Left branch anteriorly.
Inferior phrenic Arteries supplying non-GI structures are paired
T12 Superior suprarenal and branch laterally and posteriorly.
Celiac
Two areas of the colon have dual blood supply
Middle suprarenal
from distal arterial branches (“watershed
regions”) susceptible in colonic ischemia:
SMA
ƒ Splenic flexure—SMA and IMA
L1
Inferior suprarenal ƒ Rectosigmoid junction—the last sigmoid
arterial branch from the IMA and superior
Renal
rectal artery
Gonadal
L2 Nutcracker syndrome—compression of left
renal vein between superior mesenteric artery
and aorta. May cause abdominal (flank) pain,
gross hematuria (from rupture of thin-walled
IM A
L3 renal varicosities), left-sided varicocele.
Superior mesenteric artery syndrome—
characterized by intermittent intestinal
obstruction symptoms (primarily postprandial
L4 pain) when SMA and aorta compress
transverse (third) portion of duodenum.
“Bifourcation” at L4
Typically occurs in conditions associated
Right
common iliac Left common iliac
with diminished mesenteric fat (eg, low body
L5
weight/malnutrition).

Median sacral
Duodenum
Aorta
Right external Right internal Left internal Left external
iliac iliac iliac iliac

SMA

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Gastrointestinal blood supply and innervation

EMBRYONIC PARASYMPATHETIC VERTEBRAL
GUT REGION ARTERY INNERVATION LEVEL STRUCTURES SUPPLIED
Foregut Celiac Vagus T12/L1 Pharynx (vagus nerve only) and lower esophagus
(celiac artery only) to proximal duodenum;
liver, gallbladder, pancreas, spleen (mesoderm)
Midgut SMA Vagus L1 Distal duodenum to proximal 2/3 of transverse
colon
Hindgut IMA Pelvic L3 Distal 1/3 of transverse colon to upper portion of
anal canal
Sympathetic innervation arises from abdominal prevertebral ganglia: celiac, superior mesenteric, and inferior mesenteric.

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:
ƒ Left and right gastroepiploics
ƒ Left and right gastrics

Celiac trunk
Abdominal aorta

Common hepatic
Left hepatic
Esophageal branches

Right hepatic
Left gastric
Splenic
Cystic Short gastric

Left gastroepiploic

Proper hepatic

Gastroduodenal

Posterior superior
pancreaticoduodenal Areas supplied by:

Anterior superior Left gastric artery

pancreaticoduodenal
Splenic artery
Common hepatic artery
Right gastric
Anastomosis
Right gastroepiploic

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Portosystemic
anastomoses

Azygos vein Pathologic blood in portal hypertension

Esophageal veins Flow through TIPS, reestablishing
IVC normal flow direction
Normal venous drainage
Hepatic vein Systemic venous system
Left gastric vein
Portosystemic Portal venous system
shunt

Portal vein

Splenic vein

Paraumbilical
vein
Inferior mesenteric
vein
Umbilicus

Epigastric Superior rectal

veins vein

Middle rectal veins

Inferior rectal veins

SITE OF ANASTOMOSIS CLINICAL SIGN PORTAL ↔ SYSTEMIC

Esophagus Esophageal varices Left gastric ↔ esophageal
(drains into azygos)
Umbilicus Caput medusae Paraumbilical ↔ small
epigastric veins (branches
of inferior and superficial
epigastric veins) of the
anterior abdominal wall
Rectum Anorectal varices Superior rectal ↔ middle and
inferior rectal
Varices of gut, butt, and caput (medusae) are commonly seen with portal hypertension.
Treatment with a Transjugular Intrahepatic Portosystemic Shunt (TIPS) between the portal
vein and hepatic vein relieves portal hypertension by shunting blood to the systemic circulation,
bypassing the liver. TIPS can precipitate hepatic encephalopathy due to clearance of ammonia
from shunting.

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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.
(inferior hypogastric artery (branch → IMV → splenic iliac LN
plexus [T12–L3]) of IMA) vein → portal vein Internal hemorrhoids—abnormal distention of
anal venous plexus. Risk factors include older
age and chronic constipation. 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 anoderm below
Inferior rectal vein
Somatic innervation Inferior rectal artery → internal pudendal pectinate line. Pain while pooping; blood
Drain to superficial
(pudendal nerve (branch of internal vein → internal iliac inguinal LN on toilet paper. Located in the posterior
[S2–S4]) pudendal artery) vein → common iliac
vein → IVC midline because this area is poorly
perfused. Associated with low-fiber diets and
constipation.

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Liver tissue The functional unit of the liver is made up of
architecture hexagonally arranged lobules surrounding the
A
central vein with portal triads on the edges
(consisting of a portal vein, hepatic artery, bile
ducts, as well as lymphatics) A .
Apical surface of hepatocytes faces bile
canaliculi. Basolateral surface faces sinusoids.
Kupffer cells (specialized macrophages) located
in sinusoids (black arrows in B ; yellow arrows
show central vein) clear bacteria and damaged
B or senescent RBCs.
Hepatic stellate (Ito) cells in space of Disse
store vitamin A (when quiescent) and produce
extracellular matrix (when activated).
Responsible for hepatic fibrosis.
Zone I—periportal zone:
ƒ Affected 1st by viral hepatitis
ƒ Best oxygenated, most resistant to circulatory
compromise
ƒ Ingested toxins (eg, cocaine)
Zone II—intermediate zone:
ƒ Yellow fever
Zone III—pericentral (centrilobular) zone:
ƒ Affected 1st by ischemia (least oxygenated)
ƒ High concentration of cytochrome P-450
ƒ Most sensitive to metabolic toxins (eg,
ethanol, CCl4, halothane, rifampin,
acetaminophen)
ƒ Site of alcoholic hepatitis

Central vein (drains

into hepatic vein)

Sinusoids

Stellate cell

Space of Disse

Kupffer cell

Blood flow

Zone 1 Branch of
hepatic artery Bile flow
Zone 2
Branch of
Zone 3 portal vein
Bile ductule

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Biliary structures Cholangiography shows filling defects in gallbladder (blue arrow in A ) and cystic duct (red arrow
A
in A ).
Gallstones that reach the confluence of the common bile and pancreatic ducts at the ampulla of
Vater can block both the common bile and pancreatic ducts (double duct sign), causing both
e
CHD sc
op cholangitis and pancreatitis, respectively.
do

Tumors that arise in head of pancreas (usually ductal adenocarcinoma) can cause obstruction of
En

t
uc
cd
ati
Pa
ncre
common bile duct enlarged gallbladder with painless jaundice (Courvoisier sign).

Cystic duct
Liver
Gallbladder
Common hepatic duct

Common bile 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-lymphatics. You go from lateral to medial to find your
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.

External iliac vessels Inferior epigastric

vessels
Iliopsoas
Anterior superior Rectus abdominis
iliac spine
Inguinal (Hesselbach)
Femoral nerve
triangle
Femoral artery
Inguinal ligament
Femoral vein

Fascia lata
Lymphatics

Femoral ring Femoral triangle

Satorius Femoral sheath

Adductor longus

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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

Extraperitoneal tissue Median umbilical ligament

Transversalis fascia Rectus abdominis muscle

Pyramidalis muscle
Transversus abdominis muscle
Conjoint tendon
Linea alba
Internal oblique muscle
Spermatic cord (ICE tie)

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)

Myopectineal orifice
Anterior superior iliac spine

Evagination of
transversalis fascia INGUINAL CANAL CONTENTS
Internal (deep) inguinal ring
Male: ductus (vas) deferens
Female: round ligament of uterus
Illioinguinal nerve
Internal spermatic vessels

INGUINAL (HESSELBACH) TRIANGLE Femoral nerve

Pubic tubercle External iliac vessels
Pubis symphysis

Anterior abdominal wall

(viewed from inside)

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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. Most common causes:
A
ƒ Infants—congenital defect of pleuroperitoneal membrane left-sided herniation (right
hemidiaphragm is relatively protected by liver) A .
ƒ Adults—laxity/defect of phrenoesophageal membrane hiatal hernia (herniation of stomach
through esophageal hiatus).
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

Indirect inguinal Goes through the internal (deep) inguinal

hernia ring, external (superficial) inguinal ring, and Peritoneum

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.

Direct inguinal hernia Protrudes through inguinal (Hesselbach) Peritoneum

triangle. Bulges directly through parietal Deep
Intestinal inguinal
peritoneum medial to the inferior epigastric loop ring
vessels but lateral to the rectus abdominis.
Superficial
Goes through external (superficial) inguinal inguinal ring
ring only. Covered by external spermatic
fascia. Usually occurs in older males due to Spermatic cord
acquired weakness of transversalis fascia.
MDs don’t lie:
Testis
Medial to inferior epigastric vessels =
Direct hernia.
Lateral to inferior epigastric vessels = indirect
hernia.
Femoral hernia Protrudes below inguinal ligament through
femoral canal below and lateral to pubic
tubercle. More common in females, but
overall inguinal hernias are the most common.
More likely to present with incarceration or
strangulation (vs inguinal hernia). Intestinal loop
beneath inguinal
ligament

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` GASTROINTESTINAL—PHYSIOLOGY

Gastrointestinal regulatory substances

REGULATORY SUBSTANCE SOURCE ACTION REGULATION NOTES
Gastrin G cells (antrum gastric H+ secretion by stomach by chronic PPI use
of stomach, growth of gastric mucosa distention/ in chronic atrophic gastritis
duodenum) gastric motility alkalinization, (eg, H pylori)
amino acids, in Zollinger-Ellison
peptides, vagal syndrome (gastrinoma)
stimulation via
gastrin-releasing
peptide (GRP)
by pH < 1.5
Somatostatin D cells gastric acid and by acid Inhibits secretion of various
(pancreatic islets, pepsinogen secretion by vagal hormones (encourages
GI mucosa) pancreatic and small stimulation somato-stasis)
intestine fluid secretion Octreotide is an analog used
gallbladder contraction to treat acromegaly, carcinoid
insulin and glucagon syndrome, VIPoma, and
release variceal bleeding
Cholecystokinin I cells (duodenum, pancreatic secretion by fatty acids, Acts on neural muscarinic
jejunum) gallbladder contraction amino acids pathways to cause pancreatic
gastric emptying secretion
sphincter of Oddi
relaxation
Secretin S cells pancreatic HCO3– by acid, fatty HCO3– neutralizes gastric
(duodenum) secretion acids in lumen acid in duodenum, allowing
gastric acid secretion of duodenum pancreatic enzymes to
bile secretion function
Glucose- K cells Exocrine: by fatty acids, Also called gastric inhibitory
dependent (duodenum, gastric H+ secretion amino acids, peptide (GIP)
insulinotropic jejunum) Endocrine: oral glucose Oral glucose load insulin
peptide insulin release compared to IV equivalent
due to GIP secretion
Motilin Small intestine Produces migrating motor in fasting state Motilin receptor agonists (eg,
complexes (MMCs) erythromycin) are used to
stimulate intestinal peristalsis.
Vasoactive Parasympathetic intestinal water and by distention VIPoma—non-α, non-β islet
intestinal ganglia in electrolyte secretion and vagal cell pancreatic tumor that
polypeptide sphincters, relaxation of intestinal stimulation secretes VIP; associated
gallbladder, smooth muscle and by adrenergic with Watery Diarrhea,
small intestine sphincters input Hypokalemia, Achlorhydria
(WDHA syndrome)
Nitric oxide smooth muscle Loss of NO secretion is
relaxation, including implicated in LES tone of
lower esophageal achalasia
sphincter (LES)
Ghrelin Stomach appetite (“ghrowlin’ in fasting state in Prader-Willi syndrome
stomach”) by food after gastric bypass surgery

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Gastrointestinal secretory products

PRODUCT SOURCE ACTION REGULATION NOTES
Gastric acid Parietal cells stomach pH by histamine,
(stomach A ) vagal
Intrinsic factor Parietal cells Vitamin B12–binding stimulation Autoimmune destruction
(stomach) protein (required for B12 (ACh), gastrin of parietal cells chronic
uptake in terminal ileum) by somatostatin, gastritis and pernicious
GIP, anemia
prostaglandin,
secretin
Pepsin Chief cells Protein digestion by vagal Pepsinogen (inactive) is
(stomach) stimulation converted to pepsin (active) in
(ACh), local the presence of H+
acid
Bicarbonate Mucosal cells Neutralizes acid by pancreatic Trapped in mucus that covers
(stomach, and biliary the gastric epithelium
duodenum, secretion with
salivary glands, secretin
pancreas) and
Brunner glands
(duodenum)

A
Gastric pit Surface epithelium

Upper glandular Mucous cell

layer Parietal cell
Deeper glandular Chief cell
layer Enterochromaffin-like
Muscularis mucosa cell
Submucosa

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Locations of gastrointestinal secretory cells

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
Duodenum Gastrin
Secretin 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) Dipeptides and tripeptides degraded within
intestinal mucosa

Carbohydrate Na+/K+- Only monosaccharides (glucose, galactose,

absorption SGLT-1 ATPase fructose) are absorbed by enterocytes. Glucose
Na+
3 Na+
and galactose are taken up by SGLT1 (Na+
dependent). Fructose is taken up via facilitated
Glucose or
galactose 2 K+ diffusion by GLUT5. All are transported to
GLUT-2
GLUT-5 blood by GLUT2.
Fructose d-xylose test: simple sugar that is passively
absorbed in proximal small intestine; blood
Apical Enterocyte Basolateral and urine levels with mucosal damage,
membrane membrane
normal in pancreatic insufficiency.

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 GASTROINTESTINAL ` GASTROINTESTINAL—PHYSIOLOGY SEC TION III 383

Vitamin and mineral Iron fist, Bro

absorption Vitamin and mineral deficiencies may develop
Salivary B12 P Animal
in patients with small bowel disease, bowel
R-protein R protein
resection, or bariatric surgery (eg, vitamin B12
deficiency after terminal ileum resection).
Iron absorbed as Fe2+ in duodenum.
HCI Intrinsic Folate absorbed in small bowel.
IF factor
Vitamin B12 absorbed in terminal ileum along
B12
with bile salts, requires intrinsic factor.
P
Pepsin

B12 R P
Pancreatic IF
IF
protease
B12
B12 IF
R

Small
bowel

IF B12 Terminal
ileum

Peyer patches Unencapsulated lymphoid tissue A found in Think of IgA, the Intra-gut Antibody
A
lamina propria and submucosa of ileum.
Contain specialized Microfold (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
glycine or taurine, making them water soluble),
phospholipids, cholesterol, bilirubin, water,
and ions. Cholesterol 7α-hydroxylase catalyzes
rate-limiting step of bile acid synthesis.
Functions:
ƒ Digestion and absorption of lipids and fat-
soluble vitamins
ƒ Bilirubin and cholesterol excretion (body’s 1°
means of elimination)
ƒ Antimicrobial activity (via membrane
disruption)
absorption of enteric bile salts at distal ileum
(as in short bowel syndrome, Crohn disease)
prevents normal fat absorption and may cause
bile acid diarrhea.
Calcium, which normally binds oxalate, binds
fat instead, so free oxalate is absorbed by gut
frequency of calcium oxalate kidney
stones.

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Bilirubin Heme is metabolized by heme oxygenase to biliverdin (green), which is subsequently reduced
to bilirubin (brown). 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.

Liver
Bloodstream Conjugated (direct)
bilirubin
Kidney
RBC
UDP-
glucuronosyl-
transferase 90%
Enterohepatic
Macrophage
circulation
Heme
10%

Unconjugated
(indirect) Gut
bilirubin

20%
Gut
Albumin bacteria

Unconjugated
bilirubin-albumin Urobilinogen 80%
Excreted in urine
Excreted in feces as as urobilin
stercobilin ( brown ( yellow color
color of stool) of urine)

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 GASTROINTESTINAL ` GASTROINTESTINAL—PATHOLOGY SEC TION III 385

` GASTROINTESTINAL—PATHOLOGY

Oral pathologies
Aphthous ulcers Also called canker sores. Common oral lesions that appear as painful, shallow, round to oval ulcers
covered by yellowish exudate A . Recurrent aphthous stomatitis is associated with celiac disease,
IBD, SLE, Behçet syndrome, HIV infection.
Squamous cell Most common malignancy of oral cavity. Usually affects the tongue. Associated with tobacco,
carcinoma alcohol, HPV-16. Presents as nonhealing ulcer with irregular margins and raised borders.
Leukoplakia (white patch B ) and erythroplakia (red patch) are precursor lesions.

Sialolithiasis Stone formation in ducts of major salivary glands (parotid C , submandibular, or sublingual).
Associated with salivary stasis (eg, dehydration) and trauma.
Presents as recurrent pre-/periprandial pain and swelling in affected gland.

Sialadenitis Inflammation of salivary gland due to obstruction, infection (eg, S aureus, mumps virus), or
immune-mediated mechanisms (eg, Sjögren syndrome).

Salivary gland tumors Usually benign and most commonly affect the parotid gland. Submandibular, sublingual, and
minor salivary gland tumors are more likely to be malignant. Typically present as painless mass/
swelling. Facial paralysis or pain suggests malignant involvement.
ƒ Pleomorphic adenoma (benign mixed tumor)—most common salivary gland tumor D .
Composed of chondromyxoid stroma and epithelium and recurs if incompletely excised or
ruptured intraoperatively. May undergo malignant transformation.
ƒ Warthin tumor (papillary cystadenoma lymphomatosum)—benign cystic tumor with germinal
centers. May be bilateral or multifocal. Typically found in people who smoke. “Warriors from
Germany love smoking.”
ƒ Mucoepidermoid carcinoma—most common malignant tumor. Mucinous and squamous
components.

A B C D

Achalasia Failure of LES to relax due to degeneration Manometry findings include uncoordinated or
A
of inhibitory neurons (containing NO and absent peristalsis with LES resting pressure.
Dilated VIP) in the myenteric (Auerbach) plexus of Barium swallow shows dilated esophagus with
esophagus esophageal wall. area of distal stenosis (“bird’s beak” A ).
1° achalasia is idiopathic. 2° achalasia may Treatment: surgery, endoscopic procedures (eg,
arise from Chagas disease (T cruzi infection) botulinum toxin injection).
or extraesophageal malignancies (mass effect
or paraneoplastic). Chagas disease can cause
achalasia.
Presents with progressive dysphagia to solids and
liquids (vs obstruction—primarily solids).
Associated with risk of esophageal cancer.

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Other esophageal pathologies

Gastroesophageal Transient decreases in LES tone. Commonly presents as heartburn, regurgitation, dysphagia. May
reflux disease also present as chronic cough, hoarseness (laryngopharyngeal reflux). Associated with asthma.
Complications include erosive esophagitis, strictures, and Barrett esophagus.
Esophagitis Associated with reflux, infection in immunocompromised (Candida: white pseudomembrane A ;
HSV-1: punched-out ulcers; CMV: linear ulcers), caustic ingestion, or pill-induced esophagitis
(eg, bisphosphonates, tetracycline, NSAIDs, iron, and potassium chloride).
Eosinophilic esophagitis—infiltration of eosinophils in the esophagus often in patients with atopy.
Etiology is multifactorial. Food allergens dysphagia, food impaction. Esophageal rings and
linear furrows often seen on endoscopy.
Esophageal strictures Associated with caustic ingestion, acid reflux, and esophagitis.
Plummer-Vinson Triad of dysphagia, iron deficiency anemia, esophageal webs. risk of esophageal squamous cell
syndrome carcinoma ("Plumber dies"). May be associated with glossitis.
Mallory-Weiss Partial thickness, longitudinal lacerations of gastroesophageal junction, confined to mucosa/
syndrome submucosa, due to severe vomiting. Often presents with hematemesis +/– abdominal/back pain.
Usually found in patients with alcohol use disorder, bulimia nervosa.
Esophageal varices Dilated submucosal veins (red arrows in B ) in lower 1/3 of esophagus 2° to portal
hypertension. Common in patients with cirrhosis, may be source of life-threatening hematemesis.
Distal esophageal Formerly called diffuse esophageal spasm. Spontaneous, nonperistaltic (uncoordinated)
spasm contractions of the esophagus with normal LES pressure. Presents with dysphagia and anginalike
chest pain. Barium swallow may reveal “corkscrew” esophagus. Manometry is diagnostic.
Treatment includes nitrates and CCBs.
Scleroderma Esophageal smooth muscle atrophy LES pressure and distal esophageal dysmotility acid
esophageal reflux and dysphagia stricture, Barrett esophagus, and aspiration. Part of CREST syndrome.
involvement
Esophageal Most commonly iatrogenic following esophageal instrumentation. Noniatrogenic causes include
perforation spontaneous rupture, foreign body ingestion, trauma, malignancy.
May present with pneumomediastinum (arrows in C ). 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.
A B C

Aortic
T arch

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