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Normal gastrointestinal embryology
UW: Case: newborn + bilious vomiting + Cecum is found in the RUQ, fixed with a fibrous band to the 2 nd part of
the duodenum?
 CAUSE  Intestinal malrotation:
o
Intestinal malrotation can cause 2 conditions both of them can cause intestinal obstruction
(bilious vomiting):
1. Cecum in the RUQ + adhesive bands compress the duodenum.
2. Midgut volvulus (intestinal ischaemia d2 twisting around blood vessel) d2 twisting of
the intestine around SMA  impaired perfusion  gangrene and perforation.
 NB: Bilious emesis in neonates is a sign of intestinal obstruction below the second part of the
duodenum.
 DD of bilious emesis in neonates:
1-midgut volvulus 2-adhesive bands d2 intestinal malrotation 3-intestinal stenosis or atresia.
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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).
Congenital umbilical hernia
Failure of umbilical ring to close after physiologic herniation of the intestines.
Small defects usually close spontaneously.
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Tracheoesophageal anomalies

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

Esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) is the most common (85%)
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 fstula resembles the letter H. In pure EA, CXR shows gasless abdomen.
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Intestinal atresia
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
Presents with bilious vomiting and abdominal distension within first 1–2 days of life.
Duodenal atresia—failure to recanalize. Associated with “double bubble” (dilated stomach,
proximal duodenum) on x-ray). Associated with Down syndrome.
Jejunal and ileal atresia—disruption of mesenteric vessels  ischemic necrosis  segmental
resorption (bowel discontinuity or “apple peel”).
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Hypertrophic pyloric stenosis
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

Most common cause of gastric outlet obstruction in infants
(1:600).
Palpable olive-shaped mass in 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 subsequent volume contraction).
Ultrasound shows thickened and lengthened pylorus.
Treatment is surgical incision (pyloromyotomy).
 UW: Case: 2 day neonate + bilious vomiting + Laparotomy shows absence of large segment of small
bowel & distal ileum winding around thin vascular stalk.
Dx: Apple peel atresia d2 vascular occlusion (SMA).
 NB: jejunal, ileal and colonic atresia ARE NOT caused by abnormal fatal development (they are not
congenital malformations). They are d2 vascular accident in utero.
↓perfusion  1-Ischemic segment absent  blind ended proximal jejunum.
2-Distal segment  spiral configuration around ileocolic vessel (mostly ileum) =
apple peel or Christmas tree deformity.
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Pancreas and spleen embryology


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



Pancreas: derived from foregut.
Ventral pancreatic buds contribute to uncinate process and main pancreatic duct.
The dorsal pancreatic bud alone becomes the body, tail, isthmus, and accessory 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
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).
 UW: annular pancreas  abnormal migration
of the ventral pancreatic bud.

Usually asymptomatic but may present
with intestinal obstruction or
pancreatitis.
 UW: ventral pancreatic bud is composed of

Main pancreatic duct.

Uncinate process.
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Pancreatic divisum:

Failure of fusion  the pancreatic ductal systems remain separate with accessory duct draining the
majority of the pancreas.
 UW: Case: distended air-filled stomach that narrows at the level of the proximal duodenum and then
dilate again  Double bubble sign
duodenal atresia  within hours after birth.
Annular pancreas  any time between infancy and adulthood or not at all.
 UW: the organ that has a blood supply from the foregut but it is not a foregut derivative (endoderm) 
spleen (mesoderm).

Spleen is the most common intra-abdominal organ to be injured by a blunt trauma.

Spleenmesoderm, *Liverendoderm, *Pancreasendoderm *kidneymesoderm.
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 UW: Abnormal omphalomesenteric duct obliteration results in:
 A persistent vitelline duct or vitelline fistula: occurs due to complete failure of the vitelline duct
to close. A small connection between the intestinal lumen and the outside of the body exists at
the umbilicus. Meconium discharge from the umbilicus is seen soon after birth.
 Meckel diverticulum is the most common vitelline duct anomaly. It results from a partial
closure of the vitelline duct. With the patent portion attached to the ileum, a fibrous band may
connect the tip of the Meckel diverticulum with the umbilicus
 Vitelline sinus results from a partial closure of the vitelline duct, with the patent portion open
at the umbilicus
 Vitelline duct cyst (enterocyst) forms if peripheral portions of the vitelline duct (connected to
the ileum and umbilicus) obliterate but the central part remains. This cyst is connected with the
ileum and abdominal wall by fibrous bands.
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 UW: Meckel’s diverticulum:
 Cause: failure of obliteration of omphalomesenteric duct.
 C/P: Lower gastrointestinal bleeding is one of the common presentations of Meckel
diverticulum. This diverticulum often contains ectopic gastic mucosa which produces acid
causing possible ulceration and bleeding.
 99mmTc-pertechnetate scan identifies ectopic gastric epithelium and helps to diagnose Meckel
diverticulum.
 When a Meckel diverticulum becomes inflamed clinical appearance is almost impossible to
differentiate from acute appendicitis.
 The diverticulum itself may also predispose the intestine to intussusception, which manifests as
a colicky abdominal y also pain and “currant jelly” stools. (If you’ve never seen currant jelly. It
looks a lot like Final strawberry Jam).
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 UW: Hirschsprung disease:
 Abnormal migration of neural crest cells into the intestinal wall.
 Characterized by absence of parasympathetic ganglion cells in a segment of the colon.
 The denervated area is narrowed, causing symptoms of intestinal obstruction and encouraging
compensatory dilatation of proximal segments of the bowel.
 Since neural crest cells migrate caudally, the rectum is always involved in Hirschsprung disease.
 The absence of ganglion cells in the colonic wall causes the affected segment to be narrowed
because it cannot relax.
 The passage of intestinal contents through this area is difficult, and compensatory dilatation of
proximal areas of the colon occurs.
 C/P:
1. Fail to pass meconium within 48 hours of birth.
2. Intestinal obstruction, such as bilious vomiting and abdominal distention.
3. The bowel is filled with stool, but the rectum is empty:
4. The tone of the anal sphincter is usually increased.
 Dx: Rectal biopsy reveals an aganglionic segment of bowel.
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RETROPERITONEAL STRUCTURES
NB: the primary retroperitoneal organ has 1ry
retroperitoneal blood supply.
The 2ry retroperitoneal organ has 2ry retroperitoneal
blood supply.
K: During ascending colectomy the surgeon should
take care of the ureter and the artery to the
ascending colon (Lt colic artery). Which of both of
these are anterior to each other??
 The ascending colon is a 2ry retroperitoneal
structure so it’s blood supply is also 2ry
retroperitoneal. The ureter is primarily 1ry
retroperitoneal structure.
So, the ureter is behind the left colic artery according to the embryologic origin.
2ry retroperitoneal organ is in front of 1ry retroperitoneal organs.
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UW: Case: Accident + retroperitoneal hematoma + hemodynamically stable patient  pancreatic
(retroperitoneal) trauma as it may cause mild to asymptomatic.
NB: injury transverse colon or spleen or liver  hemoperitoneum NOT retroperitoneal hematoma.
 UW: Duodenum:

The first part of the duodenum:
 At L1.
 The only part of the duodenum that is not retroperitoneal.

The second part of the duodenum
 Courses inferiorly from the level of L1 to L3.
 In close relation to the head of the pancreas and
 Contains the ampulla of Vater, the site where pancreatic and common bile duct
secretions are released.

The third part of the duodenum:
 Courses horizontally over L3, the abdominal aorta, and the inferior vena cave.
 It is in close association with the uncinate process of the pancreas and the superior
mesenteric artery and vein.
 Small bowel malignancies are rare: if they occur in the third part of the duodenum,
anterior tumor invasion could compromise the superior mesenteric vessels.

The fourth part of the duodenum
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 Courses superiorly and to the left of the L2 and L3 vertebrae and becomes the jejunum
past the ligament of Treitz.
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Superior mesenteric artery syndrome
The Pancreas:
The head, neck, and body of the pancreas are retroperitoneal, whereas the tail is peritoneal.
®The head of the pancreas lies in the curve of the duodenum and overlies the L2 vertebra with a portion
extending behind the superior mesenteric vessels (uncinate process).
®The neck lies anterior to the portal vein and superior mesenteric vessels.
®The body makes contact posteriorly with the aorta, left adrenal gland, left kidney, and renal vessels.
®The tail courses within the splenorenal ligament alongside the splenic vessels.
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The lesser omentum
 Is a double layer of peritoneum that extends from the liver to the lesser curvature of the stomach and
the beginning of the duodenum.
 Anatomically, the lesser omentum is divided into 2 ligaments:
1. Hepatogastric ligament: the portion connecting to the lesser curvature of the stomach.
2. Hepatoduodenal ligament: the portion connecting to the duodenum.
 Between the 2 layers of the lesser omentum; close to the right-sided free margin, lie the hepatic artery,
common bile duct, portal vein, lymphatics, and hepatic plexus. The right and left gastric arteries and
gastric veins also lie between the 2 layers, near where the lesser omentum attaches to the stomach.
Epiploic foramen
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UW: The portal triad:
Runs through the hepatoduodenal ligament
Composed of the hepatic artery, portal vein,
and common bile duct.
In the setting of traumatic liver injury with
persistent bleeding, occlusion of the
hepatoduodenal ligament can be performed
to identify the vascular source (ie, the Pringle
maneuver).
If liver bleeding does not cease when the
portal triad is occluded, it is likely that there
has been injury to the inferior vena cave or hepatic veins.
The greater omentum
 Large fold of visceral peritoneum that extends from the greater curvature of the stomach, travels
inferiorly over the small intestine, and then reflects on itself and ascends to encompass the transverse
colon before reaching the posterior abdominal wall.
 Formed by 2 ligament: Gastrocolic & gastrosplenic ligaments.

The gastrocolic ligament is the section that stretches from the greater curvature of the stomach
to the transverse colon. It forms part of the anterior wall of the lesser sac and is often divided
during surgery to provide access to the anterior pancreas and posterior wall of the stomach.
 UW: to access the anterior pancreas & posterior wall of the stomach  divide gastrocolic ligament to
reach the lesser sac as it forms the ant wall of the lesser sac.
 UW: in order to encircle the stomach, the band must pass through  lesser omentum. “Adjustable
gastric banding for obesity”  placed around gastric cardia  ↓passage of food.
 Lesser omentum: double layer of peritoneum. From the liver to the lesser curvature of the stomach and
the beginning of the duodenum. Between 2 layers
free margin  hepatic artery & common bile duct
& portal vein.
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UW: The integrity of the small intestinal mucosa depends on the complete end rapid neutralization of
hydrochloric acid in gastric contents. This is accomplished by alkaline secretions from 2 primary sources:
• Submucosal (Brunner) glands secrete copious amounts of alkaline mucus into the duodenum. These glands
are most numerous at the pylorus but may be found intermittently up to the ampulla of Vater. The ducts of
these glands pass through the muscularis mucosa and terminate in the mucosal crypts (crypts of Lieberkeihn).
• The epithelial cells of the pancreatic ductules and ducts produce watery secretions containing high
concentrations of bicarbonate ions. The strongly alkaline pancreatic secretions are then emptied into the
duodenum at the ampulla.
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THE alkaline secretions is stimulated by:
1-Tactile stimulation of the duodenal mucosa.
2-↑parasympathetic activity following meals.
3-The presence of acid in the duodenum and jejunum causes release of secretin from the mucosa; stimulating
secretion of bicarbonate from the submucosal glands and pancreas.
Excess gastric acid secretion, such as seen in Helicobacter pylori infection, can cause increased production of
secretin that, over time, can lead to hyperplasia of the submucosal glands.
 UW: Features of the large intestine:

1. Appendices epiploic

2. Sacculations (haustrations)

3. Taeniae coli: The taeniae coli meet together at the base of the
appendix where they form a complete longitudinal muscle coat
for the appendix.
 UW: Tinea Coli:

Used as surgical landmark for appendectomy.

Begin as a continuous layer of longitudinal muscle that
surrounds the rectum just below the serosa.

At the rectosigmoid junction, this layer condenses to form 3
distinct longitudinal bands that travel on the outside of the
entire colon before converging at the root of the vermiform
appendix.

The teniae coli have a similar function as the outer layer of the
muscularis externa in other portions of the digestive tract.

If the appendix cannot be identified by palpation during an
appendectomy, it can be located by following the teniae coli to its origin at the cecal base.
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
UW: Payer’s patches
in the ileum contains specialized cells called M cells.

Shigella exhibits specificity for the M (microfold) cells.

M cells are specifically designed to sample the contents of the gut lumen and transfer antigens
to their basal lamina within endosomes.

At the base of the cell, within a special pocket (microfold), await macrophages and lymphocytes,
ready to mount an immune response.

Shigella first penetrates the mucous membrane of the gut by passing through M cells.

Following host epithelial cell invasion and penetration of the mucosa, Shigella infection is
characterized by degeneration of the epithelium due to inflammation of the lamina propria and
bacterial spread laterally from M cells to other mucosal cells.

This results in denuding and ulceration of the mucosa, and subsequent leakage of blood,
inflammatory elements, and mucus into the intestinal lumen.

Patients pass frequent stools mixed with blood and mucus. As in most forms of diarrhea, stools
are frequent and loose because the absorption of water by the colon is inhibited.
 UW: Paneth cells:

Small group of cells at the base of intestinal crypts.

These have both phagocytic and secretory properties and thus provide the first line of immune
defense against intestinal microorganisms.

Secrete lysozyme, an enzyme capable of dissolving the cell wall of many bacteria, and defensins,
polypeptides that have antimicrobial and antiparasitic properties.
 UW: Histology of the stomach:



Surface - mucous glands
Upper glandular layer - Parietal cells  HCL + intrinsic factor secretion.
Deep glandular layer - Chief cells  pepsinogen secretion.
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ABDOMINAL AORTA
 UW: IVC:

Forms by the union of the Lt, RT common iliacs at the level of L4-L5.

Lies just anterior to the right renal artery.

Right of the aorta.
Enters into RA just above the diaphragm above T8.
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Azygous vein
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Celiac trunk
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 UW: splenic artery gives off  1-short gastric 2-pancreatic 3-left gastroepiploic 4-spleen.
 Due to poor anastomoses, the gastric tissue supplied by the short gastric arteries is vulnerable to
ischemic injury following splenic artery blockage.
 UW: Splenic vein thrombosis  isolated gastric varices.
 The short gastric veins drain blood from the gastric fundus into the splenic vein.
 Pancreatic inflammation (eg, pancreatitis, pancreatic cancer) can cause a blood clot within the
splenic vein, which can increase pressure in the short gastric veins and lead to gastric varices
only in the fundus.
 UW: Gastric ulcers  mostly from the lesser curvature at the transitional zone between acid secreting
epithelium of the corpus and the gastrin secreting epith at the antrum.
 UW: Duodenal ulcers
ant wall  perforation.
Posterior wall  hemorrhage from gastroduodenal artery.
 Rx: head of the pancreas is supplied by  superior pancreaticoduodenal artery from gastroduodenal
artery & inf pancreaticoduodenal artery from SMA.
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 UW: Stomach blood supply:
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 UW: The SMA and IMA are the 2 main vessels supplying the small and large intestines and are
connected by a pair of anastomoses:

The marginal artery of Drummond (marginal artery), which is the principal anastomosis,

And the inconsistently present arc of Riolan (mesenteric meandering artery).
 These anastomoses protect the intestines from ischemia.
 Due to the marginal artery, the IMA is not always reconnected during aortic aneurysm repair.
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Portosystemic anastomosis
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Pectinate line
 Formed where endoderm (hindgut) meets ectoderm.
 UW: neonate fails to pass meconium + anal dimple found instead of anal opening in the perineum?
Dx: Imperforate anus:

The anal canal extends from the anorectal junction (perineal flexure) to the perineal skin (anal
verge).

It is divided into upper and lower anal canal.

The upper anal canal (above the pectinate line) is formed from the hindgut (endoderm).

The lower part of the anal canal is derived from the invagination of surface ectoderm.

The junction between these canals is closed during embryonic life by an anal membrane that is
located at the level of the pectinate line.

The term “imperforate anus” covers a spectrum of disorders associated with abnormal
development of anorectal structures.

Absence of the anal opening is most often associated with urorectal, urovesical or urovaginal
fistulas.

When a fistula is present, meconium may discharge from the urethra or the vagina.
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
***Imperforate anus is most commonly associated with genitourinary disorders (renal agenesis,
hypospadias, epispadias, and bladder extrophy).

**Other congenital anomalies also occur in association with imperforate anus  VACTERL:
vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula, esophageal atresia,
renal anomalies, and limb anomalies.

VACTERL syndrome is much less common than isolated urogenital anomalies.
 UW: Lymphatic drainage of the rectum proximal to the anal dentate line occurs via the inferior
mesenteric and internal iliac lymph nodes. Areas distal to the dentate line drain primarily into the
inguinal nodes.
 Rx: inferior rectal artery  internal pudendal artery  internal iliac artery.
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Liver tissue architecture
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Rx: Kupffer cells in the liver  reticuloendothelial cells that remove the pathogens from blood stream.
Biliary structure
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 UW: Gallstone ileus:
 A large (typically >2.5 cm) gallstone causes formation of a cholecystenteric fistula between the
gallbladder and adjoining gut (most often the duodenum) due to pressure necrosis and erosion of
these tissues.
 Fistula formation allows passage of the gallstone into the small bowel, where it travels freely until
it becomes trapped in the ileum, the narrowest portion of the intestine.
 Patients consequently develop symptoms/signs of small bowel obstruction, including abdominal
pain/distension, nausea/vomiting, high-pitched (tinkling) bowel sounds, and tenderness to
palpation.
 Abdominal x-ray may reveal dilated loops of bowel with air-fluid levels due to intestinal
obstruction.
 Communication between the intestine and gallbladder may also allow gas to enter the biliary tree
(pneumobilia).
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Femoral region
Anterior Abdominal Wall Layers:
Skin  Superficial fascia [ Camper (fatty) & Scarpa
(fibrous) ]  External oblique  Internal oblique 
Transversus abdominis  Transversalis fascia 
Extraperitoneal connective tissue  Parietal
peritoneum.
Superficial fascia: The superficial fascia of the
anterior abdominal wall below the umbilicus consists
of 2 layers:
Camper (fatty) fascia is the outer, subcutaneous
layer of superficial fascia that is variable in thickness
owing to the presence of fat.
Scarpa’s (membranous) fascia is the deeper layer of
superficial fascia devoid of fat. It is continuous into the perineum with various perineal fascial layers
(Colles’ fascia, Darto’s fascia of the scrotum, superficial fascia of the clitoris or penis).
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Inguinal ligament is the inferior rolled
under aponeurotic fibers of the external oblique that
extend between the anterior superior iliac spine and
the pubic tubercle.
Medially, the fibers of the inguinal ligament form a
flattened, horizontal shelf called the lacunar
ligament that attaches deeply to the pectineal line of
the pubis and continues as the pectineal ligament.
Lacunar ligament forms the medial border of a
femoral hernia.
Superficial inguinal ring is a vertical
triangular cleft in the external oblique
aponeurosis that represents the medial opening of
the inguinal canal just superior and lateral to the
pubic tubercle. It transmits the structures of the
female and male inguinal canals.
External spermatic fascia is the outer layer
of the 3 coverings of the spermatic cord formed at
the superficial inguinal ring in males.
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
Conjoint tendon: is formed by the
combined arching fibers of the internal
oblique and the transversus
abdominis muscles that insert on the
pubic crest posterior to the superficial
inguinal ring.
-It forms & strengthens the medial part
of the posterior wall of inguinal canal.
-Nerve supply: ilio-inguinal nerve.
-Surgical importance:
1- Its weakness predisposes to direct
inguinal hernia.
2- Injury of ilio-inguinal n. during
appendectomy  paralysis of conjoint tendon  direct inguinal hernia (paralytic type).
3- Conjoint tendon prevents direct inguinal hernia from descending to scrotum. So, its defect 
descent of direct inguinal hernia to the scrotum
(funicular type).
Cremasteric muscle and fascia represent the middle layer of the spermatic fascia covering
the spermatic cord and testis in the male.
Deep (internal) inguinal ring is a small opening in the fascia transversalis immediately
above the midpoint of the inguinal ligament and represents the lateral and deep opening of
the inguinal canal. The inferior epigastric vessels are medial to the deep ring.

Inguinal canal: it is a passage in the anterior
abdominal wall extending from the internal
inguinal ring to the external inguinal ring.
Contents:
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Ilioinguinal nerve (L1):
In males: skin of the lateral and anterior scrotum.
In females: skin of the anterior part of the mons pubis and labia majora.
Triangle of Hasselbach’s (inguinal triangle):
It is a part of the posterior wall of the inguinal canal.
It is bounded by:
Laterally: inferior epigastric vessels.
Medially: Lateral border of rectus sheath.
Inferior: inguinal ligament (only medial half).
Surgical importance:
It is the triangle through which direct inguinal hernia passes.
Fascial Layers of Spermatic Cord:
1. External spermatic fascia is formed by the aponeuroses of the
external oblique at the superficial ring.
2. Middle or Cremasteric muscle and fascia are formed by
fibers of the internal oblique within the inguinal canal.
3. Internal spermatic fascia is formed by the transversalis
fascia at the deep ring.
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Hernias:
A 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, and fever.
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Diaphragmatic hernia:
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 Sliding hiatal hernia is most common.
Gastroesophageal junction is displaced upward; “hourglass stomach.”
 Paraesophageal hernia:
gastroesophageal junction is usually normal. Fundus protrudes into the thorax.
Descent of the Testes:
The testis develops from the mesoderm of the urogenital ridge within the extraperitoneal connective
tissue layer.
During the last trimester, the testis descends the posterior abdominal wall inferiorly toward the deep
inguinal ring guided by the fibrous gubernaculum  inguinal canal  superficial ring  scrotum.
An evagination of the parietal peritoneum and the peritoneal cavity extends into the inguinal canal called
the processus vaginalis.
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The open connection of the processus vaginalis with the peritoneal cavity closes before birth.
A portion of the processus vaginalis remains patent in the scrotum and surrounds the testis as the tunica
vaginalis.
A persistent process vaginalis often results in a congenital indirect inguinal hernia.
Indirect inguinal hernia
Goes through the internal (deep) inguinal ring, external (superficial) inguinal ring, and into the
scrotum.
Enters internal inguinal ring lateral to inferior epigastric vessels.
Occurs in infants owing to failure of processus vaginalis to close (can form hydrocele). Much
more common in males.
An indirect inguinal hernia follows the path of descent of the testes.
Covered by all 3 layers of spermatic fascia.
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Direct inguinal hernia
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Protrudes through the inguinal (Hesselbach) triangle.
Bulges directly through abdominal wall medial to inferior epigastric vessels.
Goes through the external (superficial) inguinal ring only.
Covered by external spermatic fascia. Usually in older men.
MDs don’t LIe:
Medial to inferior epigastric vessels = Direct hernia.
Lateral to inferior epigastric vessels = Indirect hernia.
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Femoral hernia
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Protrudes below inguinal ligament through femoral canal below and lateral to pubic tubercle.
More common in females.
More likely to present with incarceration or strangulation than inguinal hernias.
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Vessels of the anterior abdominal wall
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Umbilical hernia:
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Normally, the umbilical ring, or the congenital fascial opening for the umbilical cord, closes and
forms the linea Alba, a midline band of fibrous tissue.
Umbilical hernias are caused by an incomplete closure of the umbilical ring, thereby allowing
protrusion of bowel through the abdominal musculature.
Most umbilical hernias are reducible, asymptomatic, and resolve spontaneously in the first few
years of life.
They can occur in isolation or in association with other conditions, such as Down syndrome.
 UW: Appendicitis causes:
 Dull visceral pain at the umbilicus due to afferent pain fibers entering at the T10
level in the spinal cord.
 Progressive inflammation in the appendix irritates the parietal peritoneum and
abdominal wall to cause more severe somatic pain shifting from the umbilicus to
McBumey point (two-thirds of the distance from the umbilicus to the anterior
superior iliac spine).
 UW: Kehr’s sign: referred shoulder pain due to peritoneal irritation  (Rigid
abdomen + left shoulder pain).
 The patient presents with rigid abdomen with associated left shoulder pain,
hypotension, and tachycardia suggests a possible splenic laceration and
hemoperitoneum.
 The shoulder pain likely represents referred pain due to peritoneal irritation (Kehr’s
sign).
 The phrenic nerves originate from C3-5 and pass between the lung and heart to
provide motor function to the diaphragm.
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The phrenic nerves also provide sensory fibers to the pericardium, mediastinal pleura,
and diaphragmatic peritoneum.
The supraclavicular nerves originate from C3-C4 and their branches innervate the
stemoclavicular joint, local muscles (eg, stemocleidomastoid), and the skin of the
upper and posterior shoulder.
Any abdominal process (eg, ruptured spleen, peritonitis, hemoperitoneum) irritating
the sensory fibers around the diaphragm can cause referred pain via the phrenic nerve
to the C3-5 shoulder region.
Phrenic nerve irritation can also cause hiccups due to spasmodic diaphragmatic
contraction pulling air against a closed larynx.
 Rx: LUQ pain + left shoulder pain (Kehr’s sign) + nausea & vomiting + h/o embolic disorders 
splenic infarction.
CT Abdomen:
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KQB: Omeprazole  ↓HCL  ↑PH of the stomach  ↑Gastrin.
KQB: Gastrin is the only hormone produced in the antrum; and also found in duodenum & jejunum.
UW: Gastrin not only stimulates HCL secretion, but it also has a trophic effect on parietal cells.
UW: Somatostatin is secreted either from (hypothalamus↓GH) or (D-cells of pancreas..).
Somatostatinoma presentation:
Gallbladder stones d2 poor GB contractility d2 ↓CCK.
Hyperglycemia as it inhibit both insulin and glucagon but ↓
insulin more.
Steatorrhea d2 ↓secretin.
NB: High somatostatin level doesn’t affect GH as it doesn’t ↓GH from normal pituitary gland BUT
instead it does so in GH secreting adenomas.
Rx: the cause of pain in cholecystitis with fatty meals is ↑CCK in response to fatty meals.
UW: A prolonged course of total parenteral nutrition (TPN) is often complicated by the formation
of gallstones??!!
Caused by Biliary stasis from absent enteral stimulation secondary to decreased cholecystokinin
release.
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 UW: pancreatic juice
 Isotonic secretion, which normally contains Na- and K' in the same concentrations as
found in plasma, a higher HC03 concentration than in plasma and a lower Cl
concentration than in plasma.
 As pancreatic juice flow rates and secretin stimulation increase, the concentration
of HCO, increases and the concentration of Cl decreases.
 Regardless of flow rate or hormonal stimulation, the sodium concentration of
pancreatic secretions is identical to that of plasma.
 The chloride content of pancreatic secretions decreases as the bicarbonate content
increases, because chloride and bicarbonate are exchanged for one another at the
apical surfaces of pancreatic ductal cells.
 UW: Administration of exogenous secretin stimulates gastrin release from gastrinomas
and can be used to differentiate ZES from other causes of hypergastrinemia (eg, atrophic
gastritis). In contrast, secretin inhibits release of gastrin from normal gastric G cells.
KQB: GIP is the only hormone that is released by the three major stuffs (fats, PTN, CHO).
BUT CCK is released in response to fat and ptn only not CHO.
Gastrin  G cells
Secretin  S cells
Some Drugs (somatostatin, D cells)
Can Inhibit (CCK, I cells)
Gastric Kick (GIP, K cells)
 UW: Vasoactive intestinal peptide (VIP) is produced in the pancreas (non-α, non-β
islet cell) and stimulates:
 1- Intestinal water secretion  Watery Diarrhea
 2- Counteracts gastrin in the stomach  Achlorhydria
 3- Promotes bicarbonate secretion for the pancreas.
The diarrhea in VIPoma is secretory as with cholera.
 UW: Leptin:
 Satiety hormone.
 Produced by adipose tissue.
 Mutation of leptin gene  congenital obesity.
 Sleep deprivation or starvation ↑↑ leptin production.
 KQB: Absence of MMCs  ↑intestinal bacteria; as MMC function is to maintain low
bacterial count in the upper intestine as these waves migrate from intestine to colon.
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 Rx: Basal electrical rhythm of GIT motility = slow waves of the GIT  slow waves that are
precisely timed and rhythmic depolarization and repolarizations of the muscularis propria of
the GIT, independent of the presence or absence of stimulus. Move from oral to anal
direction.
 Find out what interstitial cells of Cajal are:
 Apparently they control gut motility.
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The stomach performs a number of important functions:

Protein digestion- Gastric parietal cells and chief cells produce hydrochloric acid (HCI) and
pepsinogen, respectively, HCI helps to denature dietary protein (improving proteolysis) and also
converts pepsinogen to its active form, pepsin, which preferentially cleaves polypeptides at
aromatic amino acid locations. Pancreatic and intestinal proteases further degrade dietary
proteins into basic amino acids in the small intestine.

Intrinsic factor (IF) secretion- Parietal cells in the body and fundus of the stomach also secrete
IF, a glycoprotein that normally binds to vitamin B12. The B12-IF complex is then absorbed by
enterocytes in the terminal ileum. However, in patients who have undergone total gastrectomy,
IF can no longer be produced and vitamin B12 cannot be effectively absorbed. Therefore, very
high-dose oral or parenteral vitamin B12 becomes necessary.

Gastric reservoir- The stomach also serves as a reservoir for ingested food. This function is lost
after total gastrectomy, and accelerated emptying of hyperosmolar food boluses into the small
bowel results in dumping syndrome (characterized by postprandial colicky abdominal pain,
nausea, and diarrhea). Avoidance of large meals and low dietary intake of simple sugars
improves these symptoms.
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Gastrointestinal secretory products
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Locations of gastrointestinal secretory cells
 Gastrin  acid secretion primarily through its effects on enterochromaffn-like (ECL)
cells (leading to histamine release) rather than through its direct effect on parietal cells.
 Gastric acid:
Secretion: Parietal cells (stomach)
Action: ↓stomach pH
Regulation: ↑by histamine, ACh, gastrin.
↓by somatostatin, GIP, prostaglandin, secretin.
 Pepsin:
Secretion: Chief cells (stomach)
Action: Protein digestion.
Regulation: ↑by vagal stimulation, local acid.
Pepsinogen (inactive) is converted to pepsin (active) in the presence of H+.
 Rx: chronic use of antacids  ptn maldigestion d2 inactivation of pepsinogen in the stomach.
 Bicarbonate:
Secretion: Mucosal cells (salivary glands, stomach, duodenum and pancreas) and Brunner
glands (duodenum).
Action: Neutralizes acid
Regulation: ↑by pancreatic and biliary secretion with secretin.
Trapped in mucus that covers the gastric epithelium.
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 UW: Systemic Mastocytosis  mast cell proliferation in BM  nests of mast cells within
mucosa  ↑Histamine release:
*↑HCL  peptic ulcer + ↓pancreatic secretion  diarrhea.
*nausea, vomiting and diarrhea.
*flushing, hypotension and bronchospasm.
*pruritis, urticaria.
 UW: Regulation of stomach acid secretion: Classically, the stimulation of acid secretion
within the stomach is separated into three phases:
 1-The cephalic phase is mediated primarily by cholinergic and vagal mechanisms, and
is triggered by the thought, sight, smell, and taste of food.
 2-The gastric phase is mediated by the presence of gastrin (which stimulates histamine
secretion and therefore, indirectly, acid secretion), and is triggered by the chemical
stimulus of food and distension of the stomach.
 3-The intestinal phase is initiated when protein-containing food enters the
duodenum, but this phase plays only a minor role in stimulating gastric acid secretion.
In fact, intestinal influences are effective in down-regulating gastric acid secretion
after a meal. The ileum and colon release peptide YY, which binds to receptors on the
endocrine, histamine-containing cells described as enterochromaffin-like (ECLs). Such
binding counteracts the cephalic and gastric phases of acid secretion by inhibiting
gastrin-stimulated histamine release from ECLs. Other factors that inhibit acid
secretion include somatostatin and prostaglandins.
Pancreatic secretions

Isotonic fluid:
 low flow  high Cl-.
 high flow  high HCO3-
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 UW: Mutations affecting the inactivating cleavage site of the enzyme (trypsinogen) 
pancreatitis (hereditary) d2 premature activation of trypsin  activation of pancreatic
enzymes  autodigestion.
 The body protect itself from premature activation of trypsin by 2 mechanisms:
 1. Serine peptidase inhibitor Kazal type 1 (SPINK1) is secreted by pancreatic acinar
cells and functions as a trypsin inhibitor. It impedes the activity of trypsinogen molecules
that become prematurely activated within the pancreas, preventing trypsin-mediated
activation of other proteolytic enzymes and autodigestion of pancreatic tissue.
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
2. In addition to functioning as its own activator, trypsin can also serve as its own
inhibitor by cleaving other trypsin molecules (rendering them inactive). This process is
critical in preventing large amounts of trypsin from forming within pancreatic tissue.
 Hereditary pancreatitis:
 Results from mutations involving the trypsinogen or SPINK1 genes.
 The most common mutation leads to the production of abnormal trypsin that is not
susceptible to inactivating cleavage by trypsin.
 Since there is always a small amount of trypsinogen that activates prematurely within the
pancreatic acini and ducts, these protective mechanisms are critical for preventing
pancreatic autodigestion. As such, patients with hereditary pancreatitis experience
recurrent attacks of acute pancreatitis.
 UW: Postprandial alkaline tide is defined as an increase in plasma HC03 and decrease in
plasma Chloride secondary to the surge of acid within the gastric lumen.
 UW: Gastric venous blood has a higher PH than arterial.
 Due to increased HCO3- reabsorption into veins during synthesis of gastric acid.
Carbohydrate absorption
 Only monosaccharides (glucose, galactose, fructose) are absorbed by enterocytes. Glucose and
galactose are taken up by SGLT1 (Na+ dependent).
 Fructose is taken up via Facilitated diffusion by GLUT5.
 All are transported to blood by GLUT2.
 D-xylose absorption test: distinguishes GI mucosal damage from other causes of malabsorption.
KQB: in rehydrating solution; why there is glucose with Na?  as glucose is transported in an
equivalent amount of Na.
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Vitamin/mineral absorption
 Rx: Divalent cations (Fe+2, Ca+2) are absorbed in the duodenum.
 UW: Case: patient with peptic ulcer resistant to ttt undergone gastrectomy with
gastrojejunostomy, what supplementation would you provide to this patient?
 B12, Iron, folate, fat-soluble vitamins (especially vitamin D), and calcium.
 Why iron also? Due to causes:
1- In this type of operation (Billroth II gastrojejunostomy), the gastric antrum is removed
to decrease gastrin production. A side-to-side anastomosis is then made between the
jejunum and the gastric body, creating a blind loop composed of duodenum and
proximal jejunum. Iron absorption occurs predominantly in the duodenum and proximal
jejunum, and bypass of this segment of small bowel invariably results in an iron
deficiency anemia.
2- The post-surgical decrease in gastric acidity also diminishes iron absorption and may
contribute to iron deficiency in these patients.
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Peyer patches
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Unencapsulated lymphoid tissue A found in 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.
Think of IgA, the Intra-gut Antibody. And always say “secretory IgA.”
UW: Shigella exhibits specificity for the M (microfold) cells that lie in the base of mucosal villi
within a Peyer's patch region of the ileal mucosa.
M cells are specifically designed to sample the contents of the gut lumen and transfer antigens to their
basal lamina within endosomes.
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Bile
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 UW: Lipid absorption:
 1- Dietary lipids (eg, triglycerides, phospholipids, cholesterol esters) are primarily
digested in the duodenum via the action of pancreatic enzymes (eg, lipase,
phospholipase A2, cholesterol esterase).
 2- Bile is also released into the duodenum, where bile salts emulsify the end products of
fat digestion (eg, fatty acids, monoglycerides) and form water-soluble micelles.
 3- In the jejunum, these micelles come into close contact with the gut epithelium, which
facilitates passive absorption of fatty acids, monoglycerides, and cholesterol across the
brush border into the enterocyte.
 The triglycerides, phospholipids, and cholesteryl esters are then reconstructed and
combined with apoproteins to form chylomicrons, which are then released into the
intestinal lymphatics.
Lipids digested in duodenum & absorbed in jejunum.
 Although storage and periodic release of bile from the gallbladder helps with digestion
(particularly of large fatty meals), the gallbladder is not essential for adequate
absorption of dietary lipids.
 Loss of the concentrating and storage functions of the gallbladder after
cholecystectomy results in a constant release of bile into the duodenum, allowing
most patients to tolerate a normal diet. However, this continuous biliary drainage can
overwhelm the absorptive capacity of bile salts in the ileum and may lead to chronic,
secretory diarrhea in some patients.
 NB: The stomach is able to absorb water and alcohol but is generally regarded as an
organ of digestion and storage, not absorption.
 The ileum is primarily involved in the absorption of bile salts and vitamin B12.
 The proximal colon is responsible for water and electrolyte absorption.
 Whereas the distal colon is primarily involved in the storage of feces.
 UW: lipid soluble vitamins are absorbed in the jejunum.
Ileum for absorption of 2Bs  B12 and Bile acids.
 Rx: Terminal ileum resection  osmotic diarrhea, steatorrhea as bile acids are absorbed from
terminal ileum.
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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.
 Indirect bilirubin—unconjugated; water insoluble.
 KQB: The unconjugated bilirubin exceeds conjugated bilirubin in portal vein??  As the
majority of bilirubin is synthesized in the spleen  splenic vein  portal vein.
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Oral cavity
Cleft lip & palate:
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
Cleft lip and palate usually occur together; isolated cleft lip
or palate is less common.
Due to failure of facial prominences to fuse: During early
pregnancy, facial prominences (one from superior, two
from the sides, and two from inferior) grow and fuse
together to form the face.
Failure of fusion between the frontonasal and maxillary
prominences will lead to cleft lip.
APHTHOUS ULCER:




Painful, superficial ulceration of the oral mucosa.
Arises in relation to stress and resolves spontaneously, but often
recurs.
Characterized by a grayish base surrounded by erythema.
Recurrent aphthous ulcer + genital ulcers + uveitis = BEHCET
SYNDROME.
BEHCET SYNDROME:



Recurrent aphthous ulcers, genital ulcers, and Uveitis.
Due to immune complex vasculitis involving small vessels.
Can be seen after viral infection, but etiology is unknown.
ORAL HERPES:




Vesicles involving oral mucosa that rupture, resulting in
shallow, painful, red ulcers
Usually due to HSV-1.
Primary infection occurs in childhood; lesions heal, but virus
remains dormant in ganglia of the trigeminal nerve.
Stress and sunlight cause reactivation of the virus, leading to
vesicles that often arise on the lips (cold sore).
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SQUAMOUS CELL CARCINOMA:
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
Malignant neoplasm of squamous cells lining the oral mucosa.
Tobacco and alcohol are major risk factors.
Floor of mouth is the most common location.
Oral leukoplakia and Erythroplakia are precursor lesions.
 1. Leukoplakia is a white plaque that cannot be scrapped away; often represents
squamous cell dysplasia.
 2. Leukoplakia is distinct from oral candidiasis (thrush) and hairy leukoplakia.
 Oral candidiasis is a white deposit on the tongue, which is easily scraped
away; usually seen in immunocompromised states.
 Hairy leukoplakia is a white, rough ('hairy') patch that arises on the lateral
tongue. It is usually seen in immunocompromised individuals (e.g., AIDS)
and is due to EBV-induced squamous cell hyperplasia; not pre-malignant.
 3. Erythroplakia (red plaque) represents vascularized leukoplakia and is highly
suggestive of squamous cell dysplasia.
 4. Erythroplakia and leukoplakia are often biopsied to rule out carcinoma.
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SALIVARY GLAND
MUMPS:
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
Infection with mumps virus resulting in bilateral inflamed parotid glands
Orchitis, pancreatitis, and aseptic meningitis may also be present.
Serum amylase is increased due to salivary gland or pancreatic involvement.
Orchitis carries risk of sterility, especially in teenagers (usually doesn’t occur before
the age of 10).
Suppurative parotitis in adults
Salivary gland tumors
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This picture represents pleomorphic adenoma. Note the irregular surface of the tumor makes it hard to
be excised completely and has a high recurrence rate.
Esophagus
Esophageal web




Thin protrusion of esophageal mucosa, most often in the upper esophagus.
Presents with dysphagia for poorly chewed food.
Increased risk for esophageal squamous cell carcinoma.
Plummer-Vinson syndrome is characterized by severe iron deficiency
anemia, esophageal web, and beefy-red tongue due to atrophic glossitis.
Achalasia
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Diffuse esophageal spasm (DES):





Periodic, non-peristaltic contractions of a large amplitude and long duration  dysphagia + chest
pain (mimics unstable angina).
Esophageal contractions are normally stimulated by esophageal distension from a food bolus. The
contractions originate above the site of distension and propel the bolus downward in a coordinated
fashion.
In DES, several segments of the esophagus contract inappropriately at the same time, which appears
as disorganized non-peristaltic contractions on esophageal manometry and "corkscrew" esophagus
on barium esophagogram.
Because the food bolus is inefficiently propelled toward the stomach, patients typically present with
intermittent solid/liquid dysphagia, chest pain, heartburn, and food regurgitation.
The pathogenesis of DES likely involves: Impaired inhibitory neurotransmission within the
esophageal myenteric plexus.
Mallory Weiss syndrome:

Mucosal lacerations at the gastroesophageal junction due to severe
vomiting.

Leads to painful hematemesis.

Usually found in alcoholics and bulimics.

Painless hematemesis  portal hypertension.

Painful hematemesis  Mallory Weiss syndrome.
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Boerhaave syndrome:



Transmural, usually distal esophageal rupture with
pneumomediastinum (arrows in A).
Due to violent retching; surgical emergency.
Hamman’s Sign: Crunching heart sound D2 pneumomediastinum.
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Eosinophilic esophagitis:

Infiltration of eosinophils in the esophagus often in atopic patients.

Food allergens  dysphagia, food impaction.

Esophageal rings and linear furrows often seen on endoscopy.

Unresponsive to GERD therapy.
Esophageal strictures
 Associated with caustic ingestion and acid reflux.
Esophageal varices


Dilated submucosal veins (red arrows in B C) in lower 1⁄3 of esophagus A 2° to portal
hypertension.
Common in cirrhotics, may be source of life-threatening hematemesis.
Esophagitis
 Associated with reflux, infection in immunocompromised (Candida: white pseudomembrane;
HSV-1: punched-out ulcers; CMV: linear ulcers), caustic ingestion, or pill esophagitis
(eg, bisphosphonates, tetracycline, NSAIDs, iron, and potassium chloride).
 UW: Esophagitis
white pseudomembrane  candida esophagitis.
Linear ulcers  CMV.
Punched out ulcer  HSV-1.
 Candida esophagitis:
 Endoscopy typically shows white plaques on an erythematous mucosa.
 Light microscopy demonstrates pseudohyphae and budding spores embedded in necrotic
debris.
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 UW: CMV esophagitis:
 Usually presents with odynophagia (pain with swallowing) or dysphagia (difficulty
swallowing) that can be accompanied by fever or burning chest pain.
 Endoscopy typically shows linear and shallow ulcerations in the lower esophagus that
sometimes diffusely involve the esophagus.
 Tissue biopsy usually shows enlarged cells with basophilic or eosinophilic intranuclear
inclusion bodies.
Gastroesophageal reflux disease





Commonly presents as heartburn, regurgitation, dysphagia.
May also present as chronic cough, hoarseness (laryngopharyngeal reflux). Associated with
asthma. Transient decreases in LES tone.
UW: Silent GERD  dysphagia + nocturnal cough + sore throat + NO heartburn.
UW: Acidic gastric contents irritate the esophageal mucosa, leading to characteristic
histologic findings that include basal zone hyperplasia, elongation of the lamina propria
papillae, and scattered eosinophils.
UW: New-onset odynophagia in the setting of chronic gastroesophageal reflux disease
usually indicates the presence of erosive esophagitis and the formation of an ulcer. Diagnosis is
made by upper endoscopy.
Plummer-Vinson syndrome


Triad of Dysphagia, Iron deficiency anemia, and Esophageal webs.
May be associated with glossitis. Increased risk of esophageal squamous cell carcinoma
(“Plumbers DIE”)
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Sclerodermal esophageal dysmotility




Esophageal smooth muscle atrophy  decrease LES pressure and dysmotility  acid reflux and
dysphagia  stricture, Barrett esophagus, and aspiration.
Part of CREST syndrome.
UW: CASE: severe heartburn resistant to ttt + fingertips ulceration + multiple telangectasias
 CREST syndrome.
Esophageal dysmotility  GERD. The cause of esophageal dysmotility is atrophy and
fibrous replacement of the muscularis in the lower esophagus.
Barret esophagus



Specialized intestinal metaplasia A —replacement of nonkeratinized stratified squamous
epithelium with intestinal epithelium (nonciliated columnar with goblet cells [stained blue in B ])
in distal esophagus.
Due to chronic gastroesophageal reflux disease (GERD).
Associated with increased risk of esophageal adenocarcinoma.
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Esophageal cancer
 Typically presents with progressive dysphagia (frst solids, then liquids) and weight loss; poor
prognosis.
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 UW: The most important risk factors for SCC is Smoking & alcohol.
 UW: Histologically, squamous cell carcinoma (SCC)
demonstrates:
 Flattened polyhedral or ovoid epithelial cells with
eosinophilic cytoplasm,
 Keratin nests or pearls
 Intercellular bridging.
 Large hyperchromatic cells with bizarre nuclei and
atypical mitoses are commonly observed.
 Location of lymph node spread depends on the level of the esophagus that is
involved.



Upper 1/3- cervical nodes.
Middle l /3- mediastinal or tracheobronchial nodes.
Lower 1/3- celiac and gastric nodes.
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Stomach
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Gastritis
Acute gastritis
 UW: *acute erosive gastritis (erosions)  limited to the mucous layer.
*Gastric ulcer  penetrate through mucosal layer and extends to submucosa.
 UW: Histology of the stomach:



Surface - mucous glands
Upper glandular layer - Parietal cells  HCL + intrinsic factor secretion.
Deep glandular layer - Chief cells  pepsinogen secretion.
Chronic gastritis

Mucosal inflammation, often leading to atrophy (hypochlorhydria  hypergastrinemia) and
intestinal metaplasia (increased risk of gastric cancers).
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 UW: “Mechanism H. pylori induced duodenal ulcer”
 H. Pylori in the antrum  destruction of the somatostatin secreting cells in the antrum
(delta cells)  ↑gastrin  ↑HCL  duodenal ulcer.
 BUT H. pylori-associated gastric ulceration results mainly from  destruction of the
local mucous layer and the local inflammatory response against the bacteria.
 NB: when you find a DU in the pulp find the H. Pylori in the antrum.
 UW: longstanding vague epigastric pain not related to food + endoscopy shows erythema of the
antral mucosa with inflammatory cell infiltration  Dx: Type B chronic gastritis (H. pylori in
gastric antrum).
 Chronic non-atrophic gastritis  caused by H. pylori  affects the antrum  risk for
duodenal ulcers.
 Chronic atrophic gastritis  can be caused by both H. pylori and autoimmune  affects the
body and the fundus  risk for gastric adenocarcinoma.
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Ménétrier disease




Hyperplasia of gastric mucosa  hypertrophied rugae (look like
brain gyri A).
Causes excess mucus production with resultant protein loss and
parietal cell atrophy with • acid production.
Precancerous.
Presents with epigastric pain, anorexia, weight loss, vomiting,
edema (due to protein loss).
 Hypertrophied stomach rugea
ZE  hypertrophy of the parietal cells.
Menetrier disease  atrophy of the parietal cells.
 UW: Transforming growth factor alpha (TGF-a):
 Potent stimulator of epithelial growth and is secreted by carcinomas, macrophages, and
epithelial cells.
 Menetrier disease is associated with overproduction of TGF-a, resulting in mucosal-cell
hyperplasia with gastric fold enlargement.
However, the condition causes hypoplasia of parietal/chief cells, resulting in glandular
atrophy with reduced gastric acid secretion.
Gastric cancer
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



Signet-ring carcinomas consist of cells that do not form
glands. Cells often contain abundant mucin droplets that push the
nucleus to one side and lead to the characteristic appearance of a
signet ring.
Intestinal-type adenocarcinomas closely resemble colon
cancers, showing well-formed glands that consist of columnar or
cuboidal cells.
UW: the diffuse involvement in signet ring carcinoma is d2 loss
of E-Cadherin.
Prognostic factors in gastric adenocarcinoma is:
 1-depth of invasion through the gastric wall
 2-LN involvement.
Peptic ulcer disease


UW: Abdominal pain + GERD or PU + Diarrhea  Zollinger Ellison.
UW: Stress Ulcer  multiple, small, circular  mainly in the stomach d2 impaired oxygenation
1. Curling Ulcer  in proximal duodenum.
2. Cushing Ulcer  in any site (esophagus or stomach or duodenum) d2 ↑ICP  ↑Vagus
 ↑HCL.

UW: most common site for DU is duodenal pulp (1st part of the duodenum).

UW: H. Pylori-induced duodenal ulcer:
 Site of the organism: prepyloric area of the gastric antrum (where there are few acid-secretory
parietal cells).
 As a result, biopsy of the prepyloric area would have the greatest yield of the organism.
 Colonization of the gastric antrum by H. pylori is associated with increased gastric acid
secretion, and the duodenal bulb is the area most exposed to this increase in acid
production.
 These organisms are susceptible to gastric acidity but are protected by the mucus layer
and endogenous urease production.
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





Urease converts urea to ammonia, alkalinizing the surrounding pH, which allows the
bacteria to survive but also injures gastric epithelial cells.
Damage to the gastric mucosa is compounded by localized inflammation due to the
immunologic response against H. pylori.
H. pylori-associated antral gastritis is usually seen as an early manifestation of H.
pylori infection.
Chronic antral inflammation leads to a decrease in the number of somatostatinproducing cells (delta cells).
Somatostatin is a hormone that inhibits gastrin release. In its absence, high gastrin levels
act both directly (via k cholecystokinin B receptors) and indirectly (via histamine release
by enterochromaffin-like cells) to increase hydrogen ion secretion by parietal cells.
This results in gastric fluid with very low pH that is not adequately neutralized by
duodenal bicarbonate production, leading to duodenal ulceration and duodenal gastric
metaplasia.
 H. pylori-associated gastric ulceration
 Results mainly from destruction of the local mucous layer and the local inflammatory
response against the bacteria.
 Acid secretion is most often low to normal in patients with gastric ulcers.
 However, normal levels of gastric acidity are sufficient to cause gastric ulceration when
the mucosal layer is degraded.
 Decreased numbers of somatostatin-producing cells do not contribute significantly to the
formation of gastric ulcers.
 UW: Rapid Urease test:
 For detection of H. pylori infection.
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

Urease converts urea to carbon dioxide and ammonia, causing a pH increase and resultant
color change of the phenol red pH indicator. An alkaline (pink) color persisting more
than five minutes is considered a positive test for H. pylori.
Although the pink color typically develops within 30 minutes when H. pylori is present,
the sample should be observed for 24 hours before being considered negative.
Ulcer complications
 UW: distal duodenal ulcer + upper normal limit gastrin which rises in response to IV secretin. 
Zollinger Ellison.
“Ulcer beyond the duodenal bulb  ZES”
normally, secretin decreases Gastrin. This test is used to distinguish atrophic gastritis (↓Gastrin)
& ZES (↑Gastrin)
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Malabsorption syndromes
 UW: Causes of Malabsorption:
 Pancreatic exocrine insufficiency:
1. Chronic pancreatitis and cystic fibrosis belong to this group of disorders.
2. Diminished production of digestive pancreatic enzymes leads to impaired
hydrolysis of nutrients in the small intestine.
 Intestinal mucosal defects:
1. Examples include celiac disease, tropical sprue, Whipple disease, Crohn's disease,
and many others.
2. Structural defect or injury to the intestinal epithelial cells hampers nutrient
transport from the intestinal lumen and/or from intestinal cells to peripheral
organs.
 Bacterial proliferation:
1. This occurs in the small bowel with surgically created blind loops, small-bowel
diverticulosis, and diabetic neuropathy.
2. Bacteria compete for nutrients, causing relative nutrient deficiency.
 C/P: diarrhea, steatorrhea, weight loss, weakness, vitamin and mineral deficiencies.
 UW: Vitamin E deficiency:
1. Vitamin E primarily serves to protect fatty acids from oxidation;
2. Vitamin E deficiency predisposes cell membranes to oxidative injury.
3. The cells that are most susceptible include:
 Neurons with long axons (due to large membrane surface area) and
 Erythrocytes (due to high oxygen exposure)  acanthocytes.
4. The most common clinical manifestations of vitamin E deficiency are
 Neuromuscular disease (eg. Skeletal myopathy, spinocerebellar ataxia,
polyneuropathy) and
 Hemolytic anemia.
 Involvement of the dorsal column in the spinal cord is associated with the
loss of proprioception and vibratory sense.
 Spinocerebellar tract involvement causes ataxia, and peripheral nerve
dysfunction results in hyporeflexia.
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 Dx: Screen for fecal fat (eg, Sudan stain).
 UW: 1st step for Dx of malabsorption  Sudan III stool stain and confirm by Fat in
stool > 7 gm /day.
 Celiac disease (Gluten-sensitive enteropathy, celiac sprue):




Autoimmune-mediated intolerance of gliadin (gluten protein found in wheat)
(hypersensitivity to gluten)  malabsorption and steatorrhea.
Associated with HLA-DQ2, HLA-DQ8, and northern European descent.
Dermatitis herpitiformis, ↓ bone density.
Findings:
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


1. IgA anti-tissue transglutaminase (IgA tTG), anti-endomysial, anti-deamidated
gliadin peptide antibodies;
2. villous atrophy (arrow in A shows blunting),
3. crypt hyperplasia (double arrows in A ), and
4. Intraepithelial lymphocytosis.
Moderately ↑ risk of malignancy (eg, T-cell lymphoma).
↓Mucosal absorption primarily affects distal duodenum and/or proximal jejunum.
D-xylose test: passively absorbed in proximal small intestine; blood and urine levels ↓
with mucosa defects or bacterial overgrowth, normal in pancreatic insufficiency.
Treatment: gluten-free diet.
 UW: IgA anti-tissue transglutaminase and IgA endomysial antibody are very sensitive and
specific for the diagnosis of celiac disease. Small
intestinal biopsy is confirmatory.
 UW: Dermatitis herpitiformis  group of small
vesicles on the extensor surfaces, extremely pruritic.
Immunofluorescence reveals IgA at the dermal
papillae.
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 Lactose intolerance





Lactase deficiency.
Normal-appearing villi, except when 2° to injury at tips of villi (eg, viral enteritis).
Osmotic diarrhea with ↓ stool pH (colonic bacteria ferment lactose).
UW: A confirmatory test for lactose intolerance is  ↓stool PH <6.
 The high amounts of undigested lactose in the bowel attract excess water in the
bowel lumen, leading to osmotic diarrhea.
 In addition, bacterial fermentation of lactose produces short-chain fatty acids
(acetate, butyrate, and propionate), which lower stool pH (<6), and hydrogen gas;
which causes flatulence.
Lactose hydrogen breath test: ⊕ for lactose malabsorption if postlactose breath
hydrogen value rises > 20 ppm compared with baseline.
 Pancreatic insufficiency



Due to chronic pancreatitis, cystic fibrosis, obstructing cancer.
Causes malabsorption of fat and fat-soluble vitamins (A, D, E, and K) as well as vitamin
B12.
↓duodenal pH (bicarbonate) and fecal elastase.
 UW: Recurrent pulmonary infections and malabsorption in a Caucasian child are suggestive
of cystic fibrosis.
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 Cystic fibrosis:
 Pathophysiology:
1. The cystic fibrosis transmembrane conductance regulator (CFTR) is nonfunctional.
2. This membrane protein is normally responsible for transporting chloride ions
across mucosal epithelial cell membranes.
3. When the CFTR gene is mutated, transport of chloride and water from the
cells is suppressed, leading to the secretion of viscous mucus.
4. There is stasis and accumulation of these viscous secretions in tissues.
5. The most pronounced changes in cystic fibrosis are seen in the respiratory tract
and pancreas.
6. The male reproductive system, liver and salivary glands may also be involved.
 Characteristic findings include:
1. Lungs:
 Increased viscosity of bronchial secretions leads to impaired mucociliary
clearance of bacteria.
 Repeated pulmonary infections, particularly with Pseudomonas
aeruginosa, are characteristic.
 Mucus plugging of bronchi causes dilatation and bronchiectasis.
2. Pancreas:
 Viscous pancreatic secretions are not transported to the intestinal lumen
and instead accumulate in pancreatic ducts.
 Pancreatic insufficiency causes the symptoms of malabsorption
(steatorrhea and poor weight gain).
 Pancreatic secretions form mucous plugs that with time totally obstruct the
ductal lumina, leading to fibrosis of pancreatic tissue.
3. Intestine:
 Decreased secretion of water by the intestinal epithelium may cause
intestinal obstruction.
 Neonates with cystic fibrosis may develop meconium ileus.
4. Reproductive:
 Male infertility due to associated bilateral absence of vas deference.

Diagnosis:
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1. Elevated sweat chloride levels.
2. Nasal potential difference measurements.
3. Genetic testing for CFTR mutations.
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 Tropical sprue




Similar findings as celiac sprue (affects small bowel), but responds to antibiotics.
Cause is unknown, but seen in residents of or recent visitors to tropics.
↓mucosal absorption affecting duodenum and jejunum but can involve ileum with time.
Associated with megaloblastic anemia due to folate deficiency and, later, B12 deficiency.
 Whipple disease
 Infection with Trophyryma whipplei (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.
 Foamy Whipped cream in a CAN.
 UW: Glycoprotein in Trophyryma whipplei  +ve PAS and diastase resistant. PAS
stains glycoproteins not neutral lipids.
Neutral lipids can be identified with a multitude of stains, including Nile red or Sudan
black (with the latter being useful for frozen sections).
 UW: after pancreatectomy which is normal  intestinal D-xylose absorption.
D-xylose, like glucose and galactose, is a monosaccharide that can be absorbed without the
action of pancreatic enzymes. D-xylose test  used to test the brush border absorptive
function independent of pancreatic function.
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 UW: Child + malabsorption + foamy epithelial cells
at the tip of the villi  Abetalipoproteinemia 
 Accumulation of lipids in the absorptive cells
in the intestinal epithelium.
 The enterocytes contain clear or foamy
cytoplasm (arrows) which is more prominent
at the tips of the villi.
 Caused by impaired formation of
apolipoprotein B (apoB)-containing
lipoproteins.
 ApoB-100 is found in VLDL, and apoB-48 is
present in chylomicrons.
 During the synthesis of apoB-containing lipoproteins, microsomal triglyceride
transfer protein (MTP) functions as a chaperone protein necessary for proper folding
of apoB and also participates in the transfer of lipids to newly formed chylomicrons
and VLDL particles.
 Abetalipoproteinemia is most commonly caused by an autosomal recessive, loss-of-
function mutation in the MTP gene.


C/P: It manifests during the first year of life with symptoms of malabsorption.
Laboratory studies show
 Very low plasma triglyceride and cholesterol levels, and chylomicrons.
 VLDLs, and apoB are entirely absent from the blood.
Educational objective:
Abetalipoproteinemia is an inherited inability to synthesize apolipoprotein B an
important component of chylomicrons and very low-density lipoprotein. Lipids
absorbed by the small intestine cannot be transported into the blood and accumulate
in the intestinal epithelium, resulting in enterocytes with clear or foamy cytoplasm.
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Inflamatory bowel diseases
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 Rx: recurrent attacks of RLQ pain + diarrhea + weight loss + young age  Crohn’s.
 UW: mutations in the NOD2 gene have shown a particularly strong association with Crohn
disease.
 NOD2 is expressed in epithelial cells and macrophages and helps regulate innate
immunity.
 It encodes an intracellular microbial receptor that recognizes bacterial
lipopolysaccharides and subsequently activates the NF-KB pathway.
 NF-KB is a proinflammatory transcription factor that increases cytokine production.
 In Crohn disease, mutations in NOD2 result in decreased activity of NF-KB, which
impairs the innate immune response of the intestinal mucosa (eg, antimicrobial peptide
synthesis, mucin secretion).
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
The loss of this natural barrier defense allows luminal bacteria to penetrate
submucosal tissues, causing an exaggerated response by the adaptive immune system
(↑TH1) that results in chronic gastrointestinal inflammation.
 UW: in crohn’s disease  ↑activity of TH1 
↑IFN-gamma & ↑IL-2 & ↑TNF.  Non-caseating
granuloma.
 UW: The image shows an accumulation of
epithelioid macrophages without central necrosis.
This is the typical appearance of a noncaseating
granuloma, a classic histologic finding in Crohn's
disease.
 UW: Gross picture of Crohn’s disease:
 Cobblestone appearance: Involved segments of the intestine are thick and edematous.





Long serpiginous or linear ulcers with spared intervening mucosa and areas of nodular
thickening lead to a cobblestone appearance.
Skip lesions: Diseased and healthy areas of the mucosa are sharply demarcated,
forming segments of normal mucosa interrupted by long stretches of disease.
String sign: Inflammation of the intestinal wall almost universally leads to the
narrowing of the involved intestinal segment. The strictures that commonly occur in
Crohn's disease can lead to symptoms of chronic intestinal obstruction.
Fistula formation between 2 adjacent loops of intestine or between the intestine and other
organs such as the bladder or vagina.
Perianal disease other than fistulas is also common and may include skin tags and
fissures.
Creeping fat.
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 UW: Crohn’s disease causes oxalate kidney stones, how? 
 Ca normally binds to oxalate in the intestine and excreted both.
 In Crohn’s there is malabsorption  ↑Fat in stool which binds Ca preventing it from
binding oxalate  ↑oxalate absorption  oxalate stone.
 UW: Crohn’s + gallbladder stone?  Cholesterol GB stone.
 Mech: ↓bile absorption in terminal ileum  cholesterol precipitate and forms gallstones.
 UW: Extra-intestinal complications of IBD:
 Skin: pyoderma gangerosum (more with UC), erythema nodosum.
 Joints: arthritis, ankylosing spondylitis.
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

Eyes: iritis, uveitis, episcleritis.
Liver: primary sclerosing cholangitis (more with UC), ↑risk of cholangiocarcinoma.
 UW: Ulcerative colitis has the
following unique characteristics:




The rectum is always
involved.
Inflammation is limited to the
mucosa and submucosa
only.
Mucosal damage is
continuous. There are no
areas of normal mucosa
between the affected
segments.
Bloody diarrhea, with or
without abdominal pain, is
the hallmark of ulcerative colitis (In Crohn's disease there may also be bloody diarrhea,
but abdominal pain is virtually always present.)
 UW: Toxic megacolon is a
 Complication of both but more common with UC.
 Mechanism  neuromuscular degeneration of the
intestinal wall  rapid dilatation.
 C/P: abdominal pain and distention + fever + diarrhea
+ signs of shock (↑HR, ↓BP).
 Next step: Plain abd. X-ray 
Colon diameter > 5.5 cm (barium enema and
colonoscopy are contraindicated). Free air may also
be visualized in the setting of intestinal rupture, which
presents with generalized peritonitis (eg, abdominal
rebound tenderness/guarding).
 Toxic megacolon can also be associated with Clostridium difficile infection and other
forms of infectious colitis.
Irritable bowel syndrome

Recurrent abdominal pain associated with ≥ 2 of the following:
 Related to defecation.
 Change in stool frequency.
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
 Change in form (consistency) of stool.
No structural abnormalities. Most common in middle-aged women.
Chronic symptoms may be diarrhea-predominant, constipation-predominant, or mixed.
Pathophysiology is multifaceted.
First-line treatment is lifestyle modification and dietary changes.
Rx: ttt of diarrhea with IBS  Loperamide & Diphenoxylate.
Appendicitis






Acute inflammation of the appendix (yellow arrows in A), can be due
to obstruction by fecalith
(red arrow in A) (in adults) or lymphoid hyperplasia (in children).
Initial diffuse periumbilical pain migrates to 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 β-hCG to rule out),
pseudoappendicitis.
Treatment: appendectomy.
UW: Obstruction of the lumen of the appendix is the first event in pathogenesis of acute
appendicitis. Fecoliths, Hyperplastic lymphoid follicles, foreign bodies, or tumors may cause
the obstruction. The most common obstructing agents are Fecoliths.
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Diverticula of the GI tract
UW: Diverticulosis: most patients are asymptomatic, but some may present with hematochezia due to
disruption of the arterioles adjacent to the diverticula.
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Zenker diverticulum
 UW: Pathophysiology of Zenker diverticulum:
 Diminished relaxation of cricopharyngeal (cricopharyngeal motor dysfunction) muscles
during swallowing results in increased intraluminal pressure in the oropharynx.
• This may eventually cause the mucosa to herniate through a zone of muscle
weakness in the posterior hypopharynx, forming a Zenker (false) diverticulum.
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 Deglutition (swallowing) is a complex process that involves 3 phases:
 The voluntary oral phase: the food bolus is collected in the back of the mouth
and lifted upward to the posterior wall of the pharynx.
 This initiates the pharyngeal phase, which consists of involuntary pharyngeal
muscle contractions that propel the food bolus to the esophagus.
 During the esophageal phase, food stretches the walls of the esophagus, stimulating
peristalsis just above the site of distension and moving the food downward.
Relaxation of the lower esophageal sphincter (LES) follows, allowing the food bolus
to enter the stomach.
Meckel diverticulum
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Hirschsprung disease
 UW: Rectum is always affected in Hirsprung disease as neural crest cells migrate caudally.
NB: the aganglionic segment is narrow because it can’t relax and there is compensatory dilatation
of the proximal segment.
Dx: fail to pass meconium in the first 48 hours of birth + bilious vomiting  rectal biopsy.
 UW: Sampling in Hirsprung disease  submucosa of the narrow part (Rectum).
 UW: Hirsprung disease  tight anal sphincter + empty rectum + colon distention.
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Malrotation
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Volvulus:
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


Twisting of portion of bowel around its mesentery.
Can lead to obstruction and infarction.
Can occur throughout the GI tract.
Midgut volvulus more common in infants and children.
Sigmoid volvulus (coffee bean sign on x-ray A) more common in elder.
Intussusception












Telescoping A of proximal bowel segment into a distal segment, commonly at ileocecal
junction.
Compromised blood supply  intermittent abdominal pain often with “currant jelly” stools.
Patient may draw legs to chest to ease pain.
Exam may reveal sausageshaped mass.
Ultrasound shows “target sign.”
Often due to a lead point, but can be idiopathic.
Most common pathologic lead point is a Meckel diverticulum (children) or intraluminal
mass/tumor (adults).
Majority of cases occur in children; unusual in adults.
May be associated with rotavirus vaccine, Henoch-Schönlein purpura, and recent viral infection
(eg, adenovirus; Peyer patch hypertrophy creates lead point).
UW: The most typical location for intussusception is at the ileocolic junction. The size
differences in the adjacent segments of the intestine allow the small bowel to invaginate into the
cecum.
Intussusception is most common in children younger than 2 years old. In this age group, it
often occurs without any structural cause (sometimes associated with viral infection).
In patients older than 2 years of age a lead point, such as Meckel diverticulum, foreign body, or
intestinal tumor, should be sought.
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
Barium enema is diagnostic and may be therapeutic. If the intussusception does not resolve
with barium enema, surgical intervention is mandated.
Mesenteric ischemia
 Ischaemic colitis  thumbprint appearance on X-ray.
 UW: Chronic mesenteric ischaemia:  atherosclerotic narrowing of the celiac trunk, SMA,
IMA.
 Pathogenesis:
 Similar to angina pectoris.
 When atherosclerosis involves the mesenteric arteries, the bowel can suffer from
diminished blood supply.
 Intestinal hypoperfusion, which can be very painful, is especially pronounced
within an hour after meals when more blood is needed for the
digestion/absorption of nutrients ("intestinal angina'').
 C/P:
 Epigastric or periumbilical pain occurs 30-60 minutes postprandial;
 Patients report severe pain but physical examination is usually benign.
 Weight loss (the patient fears to eat).
 Light microscopy:
 Mucosal atrophy & loss of villi.
 Dx:
 Angiography (expensive and invasive).
 Mesenteric duplex US.
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 UW: A 72-year-old Caucasian male develops hypotension
during surgical repair of an abdominal aortic aneurysm.
Postoperatively, he develops abdominal pain and bloody
diarrhea. Which of the following portions of large bowel is
most likely to be affected by this patient's condition?  Splenic
flexure.
Dx: ischemic colitis secondary to systemic hypotension.
The splenic flexure and distal sigmoid colon are the most
susceptible. The splenic flexure is a "border" area between the
distribution of the superior mesenteric (SMA) and inferior
mesenteric (IMA) arteries. The distal sigmoid colon lies between the areas supplied by IMA and
hypogastric arteries. Hence, ischemia affects these areas first and is called "watershed
infarction."
Clinically, patients present with abdominal pain and bloody diarrhea.
 Hematochezia in old age mostly due to:


High stress in the left side of the colon  diverticulosis.
High stress in the right side of the colon  angiodysplasia.
 Hereditary hemorrhagic telangectasia:




Autosomal dominant disorder.
resulting in thin-walled blood vessels,
Sites: especially in the nasopharynx and GI tract.
Rupture presents as bleeding.
 UW: HIV + bloody diarrhea + multiple hemorrhagic polypoid masses + spindle cells with
surrounding blood vessel proliferation  Kaposi sarcoma in GIT.
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 UW: HIV + CT scan of the abdomen shows ascites and large mass surrounding the small
intestine and on biopsy  uniform, round, medium-sized tumor cells with basophilic cytoplasm
+ proliferation fraction (Ki-67 fraction>99%)
Dx: Burkett’s lymphoma “high mitotic index is typical for Burkett’s lymphoma”
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UW: Necrotizing enterocolitis (NEC).
 NEC is one of the most frequent gastrointestinal emergencies
affecting newborns.
 It occurs predominantly in preterm infants secondary to
gastrointestinal and immunologic immaturity.
 Upon initiation of enteral feeding, bacteria are introduced
into the bowel where they proliferate excessively due to
compromised immune clearance.
 Impaired mucosal barrier function allows the bacteria to
invade the bowel wall, causing inflammation and ischemic
necrosis of the terminal ileum and colon.
 As the disease progresses, the bowel becomes congested and gangrenous with the formation of
intramural gas collections causing pneumatosis intestinalis (ie, air in the bowel wall), which
can be seen on abdominal x-ray as thin curvilinear areas of lucency that parallel the lumen.
 In an infant with abdominal distension and bloody stools, this finding is diagnostic for
necrotizing enterocolitis (NEC).
 Up to 30% of affected neonates die, especially when disease is complicated by intestinal
perforation. Survivors are at risk for strictures and bowel obstruction secondary to fibrosis that
occurs as the inflammation subsides.
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Colonic polyps



Growths of tissue within the colon A.
May be neoplastic or non-neoplastic. Grossly characterized as flat, sessile, or pedunculated (on a
stalk) on the basis of protrusion into colonic lumen.
Generally classified by histologic type.
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
UW: Adenomatous polyps:
 2nd most common type of colonic polyp
 Benign, but premalignant; may progress to adenocarcinoma via the adenoma-carcinoma
sequence.
 Types of Colonic adenomatous polyps:



Tubular adenomas: are composed of dysplastic colonic mucosal cells that form tubularshaped glands. Smaller and pedunculated.
Villous adenomas: dysplastic epithelial cells form villi-like projections that extend from
the polyp surface down to the stroma. Larger and more commonly sessile. Velvety or
cauliflower-like projections. More severely dysplastic. Bleeding, secretory diarrhea,
partial intestinal obstruction.
Tubulovillous adenomas: show a mixture of the two patterns.
 Symptoms of colonic adenomatous polyps: Although most of colon adenomas are
asymptomatic, larger ones can cause a number of symptoms:
 1. Lower intestinal bleeding causes guaiac-positive stool (fecal occult blood testing) and
microcytic hypochromic anemia. The bleeding is usually unknown to the patient, but
overt bleeding may also occur.
 2. Partial intestinal obstruction can manifest with bowel habit changes, crampy
abdominal pain, constipation, and abdominal distention.
 3. Villous adenomas may secrete large amounts of mucus, leading to secretory
diarrhea.
 4. Villous adenomas have a high risk of progression to adenocarcinoma.
 Peutz-Jeghers syndrome is associated with multiple hamartomatous polyps and black spots on
the skin and mucosa of young.
 The malignant potential of adenomatous polyps is determined by the following:
1. Size of the polyp: <1cm- unlikely to undergo malignant transformation. >4cm -40% risk of
malignancy.
2. Histologic appearance: villous adenomas are more prone to be malignant than tubular adenomas.
3. Degree of dysplasia.
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 Types of non-neoplastic polyps include:
1. Hyperplastic polyps: composed of well-differentiated mucosal cells that form glands and
crypts.
2. Inflammatory polyps: seen in ulcerative colitis and Crohn disease. They are composed of
regenerating intestinal mucosa.
3. Submucosal polyps: submucosal structures (eg, lipomas, lymphoid aggregates) that bulge up
into the mucosa.
4. Mucosal polyps: folds in the colonic mucosa that resemble polyps but are made of normal
mucosa.
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Polyposis syndromes
Lynch syndrome






Previously known as hereditary nonpolyposis colorectal cancer (HNPCC).
Autosomal dominant mutation of DNA mismatch repair genes with subsequent microsatellite
instability. ∼ 80% progress to CRC.
Proximal colon is always involved.
Associated with endometrial, ovarian, and skin cancers.
UW: colon cancer occurs at a young age (<50 years old) + Family history reveals high incidence
of colon and other cancers in first-degree relatives.  (HNPCC), or Lynch syndrome.
There are two types of Lynch syndrome:
 Lynch I is characterized by a family predisposition to colon adenocarcinoma.
 Lynch II causes predisposition to colon cancer (with features common to Lynch I) and
increased incidence of extraintestinal cancers. Endometrial and ovarian carcinoma, cancers of
the stomach, pancreas, and urothelial tract (among many others) may occur.
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Colorectal cancer
 UW: Right-sided colon cancers:
 Usually grow as exophytic masses.
 Patients generally do not develop intestinal obstruction because the ascending colon has a
larger caliber lumen than the descending colon and stool in the proximal colon is more
liquid.
 Right-sided colon cancers typically present with features of iron deficiency anemia (eg,
fatigue, pallor) due to occult blood loss.
 Nonspecific symptoms such as anorexia malaise, and unintentional weight loss may also
occur.
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 Left-sided colon cancers:
 Tend to infiltrate the intestinal wall and encircle the lumen, causing a change in bowel
habits (eg, constipation) and symptoms of intestinal obstruction (eg, abdominal pain,
distension, nausea/vomiting).
Molecular pathogenesis of colorectal cancer



Chromosomal instability pathway: mutations in APC cause FAP and most sporadic CRC (via
adenoma-carcinoma sequence; (fring order of events is AK-53).
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.
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 UW: The transformation of normal mucosal cells into malignant ones is caused by a series of
gene mutations called the "adenoma-to-carcinoma sequence. This sequence includes the
following steps:
1 . Progression from normal mucosa to a small polyp. The initial appearance of small
adenomatous polyps is attributed to mutation of the APC tumor suppressor gene.
2. Increase in the size of the polyps. Mutation of K-ras proto-oncogene is thought to facilitate
this step by leading to uncontrolled cell proliferation.
3. Malignant transformation of adenoma into carcinoma requires mutation of two genes: p53
and DCC.
 UW: CRC from Ulcerative Colitis differs from sporadic CRC in:
1. Affect younger patients.
2. Progress from flat and non-polypoid dysplasia. Sporadic CRC often arise from polypoid
lesions. This is in contrast to colitis-associated carcinoma which often arises from flat,
dysplastic lesions; thus making an early diagnosis more difficult.
3. Higher grade than sporadic carcinomas. Histologically appear mucinous and/or have
signet ring morphology.
4. Develop early p53 mutations and late APC gene mutations, opposite that of sporadic
disease.
5. Be distributed within the proximal colon (especially with Crohn's disease or concurrent
primary sclerosing cholangitis).
6. Multifocal in nature.
 The risk of developing CRC from IBD is dependent mainly on the duration. Usually develops
after 10 years of colitis.
Pancolitis is associated with the highest risk of CRC.
 UW: Case: Cancer colon + > 50 years + family history + other malignancies as endometrial
carcinoma.
Dx: HNPCC or Lynch syndrome  DNA mismatch repair  the patient inherit one allele
gene and mutation occurs in the other one in the adult life.
 UW: Carcinoembryonic antigen (CEA) level is increased in colon cancer as well as in
other malignancies and certain benign diseases. CEA cannot be used to diagnose colon cancer,
but is helpful for detecting disease recurrence. CEA is a glycoprotein involved in cell adhesion.
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 Carcinoid syndrome:










Rare syndrome caused by carcinoid tumors (neuroendocrine
cells).
Malignant transformations of neuroendocrine cells, most
commonly located in the gastrointestinal tract (eg, small
intestine, rectum, appendix), followed by the
bronchopulmonary system.
Most common malignancy in the small intestine.
Histology:
1. Prominent rosettes [arrow]. Composed of
islands or sheets of uniform cells with
eosinophilic cytoplasm and oval-to-round
stippled nuclei.
2. Cells: Fried egg like appearance
Prominent in metastatic small bowel tumors, which
secrete high levels of serotonin (5-HT). Not seen if
tumor is limited to GI tract (5-HT undergoes first-pass metabolism in liver).
Appendiceal carcinoids typically have a benign course but may cause appendicitis or,
rarely, carcinoid syndrome (eg, with liver metastasis).
C/P:
1. Skin: flushing, telangectasias, cyanosis
2. GIT: watery diarrhea, cramping
3. Pulmonary: bronchospasm, dyspnea, wheezing
4. Cardiac: valvular fibrous plaques (right > left)
Dx: ↑5-hydroxyindoleacetic acid (5-HIAA) in urine, niacin deficiency (pellagra).
Treatment: surgical resection, somatostatin analog (eg, octreotide).
Rule of 1/3s: 1/3 metastasize & 1/3 present with 2nd malignancy & 1/3 are multiple.
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Cirrhosis and portal hypertension
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 UW: Hyperestrenism in LCF:
1. Causes: due to
 Increased adrenal production of androstenedione with aromatization to estrone
and eventual conversion to estradiol.
 Estradiol induces sex hormone-binding globulin production (preferentially binds
testosterone) which results in increased testosterone binding and a decreased free
testosterone/estrogen ratio.
2. C/P: spider angioma & gynecomastia & testicular atrophy & ↓body hair.
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 UW: Spider angioma:
1. Subcutaneous vascular lesions consisting of a central arteriole surrounded by many
smaller vessels that blanch on compression.
2. Found on the trunk, face, and upper limbs
3. Acquired spider angioma: may also occur with other hyperestrogenic states (eg ,
pregnancy),
4. Possibly due to estrogen's effects on arteriolar dilation.
5. The number and size of these skin lesions generally correlate with the severity of liver
disease.
 UW: the regenerative nodules seen in the liver cirrhosis is composed of HEPATOCYTES. 
The stellate cells can differentiate into myofobroblast upon injury to the liver  fibrosis.
 FA: Spontaneous bacterial peritonitis:
1. Also known as 1° bacterial peritonitis.
2. Common and potentially fatal bacterial infection in patients with cirrhosis and ascites.
3. Often asymptomatic, but can cause fevers, chills, abdominal pain, ileus, or worsening
encephalopathy.
4. Commonly caused by aerobic gram -ve organisms, especially E coli.
5. Diagnosis: Paracentesis with ascitic fluid absolute neutrophil count (ANC) > 250
cells/mm3.
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Serum markers of liver pathology
 Signs of severe hepatic failure:
1. Increased PT.
2. Increased NH3 (ammonia).
 Acute Vs chronic hepatitis:
1. Acute:





Kupffer cell hypertrophy --> Lipofuschin may be seen
Panlobular lymphocytic infiltrate
Apoptosis  Councilman Bodies (black arrow).
Macrophage aggregates
Ballooning degeneration
2. Chronic -- Several months history (>6 mo or 3?)
 Bridging fibrosis
 Lymphoid aggregates
 Periportal necrosis (Piecemeal necrosis/Interface hepatitis)
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 HBV vs HCV hepatitis:
1. Ground glass cytoplasm - HBV
 Cytoplasm filled with spheres and tubules of HBsAg
 Finely granular eosinophilic appearance
2. Focal lobular Macrovesicular steatosis with lymphoid aggregates within the
portal tracts – HCV
 UW: Acute hepatitis A:
1. Self-limited infection.
2. C/P:
 1st week: prodromal symptoms (FAHM + right upper quadrant pain)
 2nd week: signs of cholestasis (eg. jaundice, pruritus, dark-colored urine, claycolored stool).
 UW: Acute viral hepatitis B:
 Incubation period of 30-180 days.
 Prodromal symptoms  typically described as "serum sickness-like." with patients
experiencing malaise, fever, skin rash, pruritus, lymphadenopathy and joint pain.
 Once the symptoms start to abate  ↑ALT > AST followed by rises in bilirubin and alkaline
phosphatase.
 UW: Antigen-antibody complexes of HBV: cause:
 Early symptoms of hepatitis B virus infection (eg arthralgias, arthritis, and urticaria)
 Chronic complications (eg, immune complex glomerulonephritis, cryoglobulinemia, and
vasculitis). These complexes are not responsible for hepatocellular damage.
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 UW: Hepatitis B virus infection can produce one of three syndromes:



Acute hepatitis with complete resolution (the most common >95%).
Chronic hepatitis with 20-25% risk of cirrhosis: or
Fulminant hepatitis with massive liver necrosis.
 UW: Mechanism of hepatic injury from HBV:
A. CD8 response to viral Ag on the cell surface.
B. “HBV doesn’t have a cytotoxic effect itself”.
C. Hepatitis B virus infection progresses through two phases:
1. The proliferative phase:
a) The entire virion and all related antigens of the episomal HBV DNA are
present.
b) On the hepatocyte cell surface, viral HBsAg and HBcAg are expressed in
conjunction with the major histocompatibility complex (MHC) class I
molecules.
c) This expression serves to activate the cytotoxic CD8+ T lymphocytes, which
respond by destroying the infected hepatocytes.
d) Note that the virion itself does not have a cytopathic effect.
2. In the integrative phase:
a) The HBV DNA is incorporated into the host genome of those hepatocytes that
survived the immune response. Infectivity ceases and liver damage tapers off
when the antiviral antibodies appear and viral replication stops.
The risk of hepatocellular carcinoma, however remains elevated because of
the HBV DNA that has been integrated into the host genome.
 UW: Clinical illness with hepatitis C is mild and patients are typically asymptomatic, though
some may complain of malaise, nausea, or right upper quadrant pain.
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 REYE SYNDROME:
A. Fulminant liver failure and encephalopathy in children.
B. Associated with viral infection (especially VZV and influenza B) that has been treated with
aspirin.
C. Likely related to mitochondrial damage of hepatocytes  microvesicular fatty change.
D. Mechanism: aspirin metabolites ↓ β-oxidation by reversible inhibition of mitochondrial
enzymes.
E. Avoid aspirin in children, except in those with Kawasaki disease.
F. Reye’s syndrome has 2 components:
1. Hepatic dysfunction:
a) Manifests with vomiting and hepatomegaly but jaundice is rare.
+hypoglycemia.
b) Liver function tests: ↑ALT, AST, ammonia, and bilirubin, and a ↑ PT and
PTT.
c) Light microscopy of a liver biopsy shows microvesicular steatosis. No
necrosis or inflammation is present in the liver.
d) Electron microscopy findings include swelling, a decreased number of
mitochondria and glycogen depletion.
2. Encephalopathy that may progress to coma and death.
 UW: microvesicular steatosis of hepatocytes without inflammation + cerebral edema  Reye’s
syndrome.
 UW: Fulminant hepatitis after surgery  “halothane induced hepatotoxicity”
1. Histology:
 Widespread centrilobular hepatocellular necrosis.
 Inflammation of the portal tract and parenchyma.
2. Gross picture: extensive hepatocellular damage causes the liver to rapidly atrophy and
appear shrunken.
3. C/P: FAHM + arthralgia + rash + jaundice + hepatomegaly + ↑liver enzymes + ↑PT +
eosinophilia
4. NB: no decrease in albumin as its half-life is 20 days.
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Alcoholic liver disease
 UW: Mechanism of alcohol induced steatosis 
 1- ↓FA oxidation d2 excess NADH production by the 2 major alcohol metabolism
enzymes, alcohol dehydrogenase and aldehyde dehydrogenase.
 2-↑TG synthesis
 3-↓lipoprotein assembly.
 UW: causes of thrombocytopenia in alcoholics  1-direct toxic effect on BM 2-hypersplenism and
splenic sequestration of platelets.
 UW: chronic alcoholism:
 Macrocytosis without anaemia (MCV>100) due to:
1. B12 and folate deficiency
2. Direct marrow toxicity of alcohol
 AST: ALT >2
 ↑GGT.
 Pancreatitis:
1. Ethanol induces high and low fluid pancreatic secretions
2. Spasm of sphincter of Oddi
3. Hypocalcemia because of all the Ca binding to saponified fat (nonspecific)
 Thrombocytopenia: due to:
1. Direct toxic effect on BM.
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2. Hypersplenism and splenic sequestration of platelets.
Nonalcoholic fatty liver disease



Metabolic syndrome (insulin resistance); obesity  fatty infiltration of
hepatocytes  cellular “ballooning” and eventual necrosis.
May cause cirrhosis and HCC. Independent of alcohol use.
ALT > AST (Lipids).
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Hepatic encephalopathy


Cirrhosis  portosystemic shunts  ↑ NH3 metabolism  neuropsychiatric dysfunction.
Reversible neuropsychiatric dysfunction ranging from disorientation/asterixis (mild) to difficult
arousal or coma (severe).
 Triggers:
1. ↑ NH3 production and absorption (due to dietary protein, GI bleed, constipation,
infection).
2. ↓ NH3 removal (due to renal failure, diuretics, bypassed hepatic blood flow post-TIPS).
 Treatment: lactulose (↑ NH4+ generation) and rifaximin or neomycin (↓ NH3 producing gut
bacteria).
 UW: Pathogenesis of hepatic encephalopathy:
 In chronic liver failure, hepatocyte dysfunction and the shunting of blood through
portosystemic collaterals of ammonia impair the liver detoxification ability.
 This leads to accumulation of ammonia and other neurotoxins in the circulation.
 Causing altered amino acid transport across the blood-brain barrier, impaired
neurotransmitter metabolism, and depressed cerebral glucose metabolism.
 These and other factors result in
 Increased inhibitory neurotransmission GABA.
 Impaired excitatory neurotransmitter release (eg, glutamate, catecholamines).
 UW: the role of lactulose in ttt of hepatic encephalopathy?
Catabolized by intestinal bacterial flora to short chain fatty acids, lowering the colonic pH and
increasing conversion of ammonia to ammonium which is trapped into the intestine.
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Hepatocellular carcinoma/hepatoma
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
Most common 1° malignant tumor of liver in adults A.
Associated with HBV (+/- cirrhosis) and all other causes of cirrhosis (including HCV, alcoholic
and nonalcoholic fatty liver disease, autoimmune disease, hemochromatosis, α1-antitrypsin
deficiency) and specific carcinogens (eg, aflatoxin from Aspergillus).
May lead to Budd-Chiari syndrome.
Findings: jaundice, tender hepatomegaly, ascites, polycythemia, anorexia.
Spreads hematogenously.
Diagnosis: ↑ α-fetoprotein; ultrasound or contrast CT/MRI B, biopsy.
 UW: Aflatoxin  transversion of G:CT:A in codon of P53 gene.
 UW: HBV can cause HCC through integration of the viral genome into host cells by:
 The viral protein HBx activates the synthesis of insulin-like growth factor II and
receptors for insulin-like growth factor I  stimulating cell proliferation.
 Suppression of the p53 tumor suppressor / cell cycle regulatory gene in host cells.
 It is also believed that chronic inflammation and regeneration induced by HBV infection
facilitates accumulation of mutations in hepatocytes leading to carcinogenesis.
 UW: In contrast, hepatitis C virus (an RNA virus), lacks reverse transcriptase and does not
integrate into the host genome.
 IGF type 2 overproduction causes hypoglycemia in HCC.
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Other liver tumors
 UW: the most common hepatic tumor is liver metastasis not HCC.
 UW: PECAM-1 (CD31):
 Expressed in angiosarcoma.
 Expressed on the surface of endothelial cells.
 Function: leukocyte migration through the endothelium.
 UW: most common benign hepatic tumor  cavernous hemangioma.
 It is congenital malformations that enlarge by ectasia,
 Not hyperplasia or hypertrophy.
 Well-circumscribed masses of spongy consistency typically measuring less than 5 cm in
width.
 UW: Staph Aureus can cause hepatic abscess through hematogenously seeding of the liver.
Enteric bacteria can cause hepatic abscess by ascending the biliary tract or directly invading
the adjacent area.
 UW: The liver is the second most common site of metastatic
spread (after the lymph nodes) because of its large size, dual
blood supply, high perfusion rate and the filtration function
of Kupffer cells.
 Even with significant metastatic involvement, patients may
have no clinical or laboratory signs suggestive of hepatic
insufficiency.
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 However, once the majority of the liver parenchyma is destroyed or the major bile ducts become
obstructed with tumor, patients tend to present with jaundice or abnormal hepatic enzymes.
 UW: Hepatoblastoma:
1. The most common liver neoplasm of children.
2. Associated with familial adenomatous polyposis and Beckwith-Wiedemann syndromes.
3. This neoplasm is usually fatal within a few years if not surgically resected.
Budd-Chiari syndrome




α1
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).
Painful hepatomegaly and ascites + absence of JVD  Budd-Chiari syndrome.
-antitrypsin deficiency




Misfolded gene product protein aggregates in hepatocellular ER  cirrhosis with PAS ⊕
globules A in liver.
Codominant trait.
Often presents in young patients with liver damage and dyspnea without a history of
smoking.
In lungs, ↓ α1-antitrypsin  uninhibited elastase in alveoli  ↓ elastic tissue  panacinar
emphysema.
 UW: Jaundice + exertional dyspnea 
Alpha1-antitrypsin deficiency:
1. Α1AT is enzyme produced from the liver.
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2. Inhibits several different proteolytic enzymes (most importantly neutrophil elastase) and
reduces inflammation.
3. Diagnosed by premature onset (<50years) of chronic bronchitis, emphysema or
dyspnea or COPD in non-smoker + history of neonatal hepatitis with cholestasis or
liver affection.
4. Histologically:
 Intracellular granules representing globules of unsecreted A1AT are seen within
the periportal hepatocytes of affected individuals. These globules stain reddishpink with the periodic acid-Schiff reaction (arrows) and resist digestion by
diastase.
5. Diagnosed by measuring A1AT level followed by genetic testing.
Jaundice
 UW: moderate elevation of ALP of unclear etiology should be followed up with gamma-
glutamyl transpeptidase. Useful in determining whether an elevated alkaline phosphatase is of
hepatic or bony origin.
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 Hereditary hyperbilirubinemias: All autosomal recessive
1. Gilbert syndrome
 Mildly ↓UDP-glucuronosyltransferase.
 ↓conjugation and impaired bilirubin uptake.
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



Asymptomatic or mild jaundice.
↑ unconjugated bilirubin without overt hemolysis.
Bilirubin ↑ with fasting and stress.
Very common. No clinical consequences.
2. Crigler-Najjar syndrome, type I:
 Absent UDP-glucuronosyltransferase.
 Presents early in life; patients die within a few years.
 Findings: jaundice, kernicterus (bilirubin deposition in brain),
 ↑unconjugated bilirubin.
 Treatment: plasmapheresis and phototherapy.
 Type II is less severe and responds to phenobarbital, which ↑ liver enzyme
synthesis.
3. Dubin-Johnson syndrome:
 Conjugated hyperbilirubinemia due to defective liver excretion.
 Absence of a biliary transport protein MRP2 (multidrug resistance protein 2);
used in the hepatocellular excretion of bilirubin glucuronides into bile canaliculi.
 Episodes of jaundice, which may only become evident in the context of a trigger
(eg. illness, pregnancy, oral contraceptive use).
 Grossly black liver due to impaired excretion of epinephrine metabolites that
accumulate within lysosomes. Benign.
 Histologically appear as dense pigments within lysosomes.
 Diagnosed by ↑direct bilirubin (2-5 mg/dL) without hemolysis + normal liver
function.
4. Rotor syndrome:
 Similar to Dubin-Johnson, but milder in presentation.
 Without black liver.
 Due to impaired hepatic uptake and excretion.
 UW: Which type of hyperbilirubinemia can cause kernicterus?  Unconjugated
bilirubin.
1. Conjugated bilirubin is water soluble, loosely bound to albumin, and excreted in urine
when present in excess.
2. In contrast, unconjugated bilirubin binds tightly to albumin and is highly insoluble in
water. When bound, this unconjugated bilirubin cannot be filtered by the glomerulus
and is therefore not excreted in the urine. Instead, the unconjugated bilirubin is gradually
deposited into various tissues, including the brain. These deposits can cause
kernicterus (bilirubin encephalopathy), which is a potentially fatal condition
characterized by severe jaundice and neurologic impairment.
 UW: Copper metabolism:
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1. Absorbed in the stomach and duodenum.
2. Then transported to the liver, where it is incorporated into ATP7B protein to form
ceruloplasmin.
3. The ceruplasmin is the complex of ATP7B protein + Copper.
4. The ceruloplasmin is then resecreted into plasma, where it accounts for 90-95% of
circulating copper.
5. Normal total body copper is estimated at 50-150 mg. Senescent (old) ceruloplasmin and
the remainder of ingested, unabsorbed copper are secreted into bile and excreted in
stool, which is the primary route for copper elimination.
6. Renal losses represent 5-15% of daily copper excretion.
7. In Wilson disease, the processes of incorporation of copper into ceruloplasmin and
excretion of excess copper into bile are impaired.
8. The transport of copper by the copper-transporting P-type ATPase is defective in Wilson
disease secondary to one of several mutations in the ATP7B gene.
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Wilson disease (hepatolenticular degeneration)


Autosomal recessive mutations in hepatocyte 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.

Wilson  Reduced incorporation of Cu into Ceruloplasmin; hence reduced Ceruloplasmin


synthesis.
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 UW: The main mechanism of excess copper removal in the healthy human body is: Hepatic
excretion into bile.
 UW: Dx of Wilson:
1. Liver biopsy: quantitive hepatic copper > 250 MCG/gram dry weight.
2. Low serum ceruplasmin < 20 mg/dl + ↑urinary copper or kayser-fleischer rings.
 UW: Kaiser-Fleischer rings are located in CORNEA in the Descement’s membrane. NOT iris.
Hemochromatosis
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 UW: mechanism of hemochromatosis:
 HFE mutation hepatocytes &
enterocytes falsely detect low iron
 1-enterocytes ↑expression of divalent metal
transporter-1 (DMT-1) which ↑intestinal
absorption of iron.
 2-hepatocytes ↓hepcidin synthesis which
lead to ↑ferroportin expression on
enterocytes leading to ↑iron secretion in
circulation.
 Excessive iron accumulation results in elevated levels of serum ferritin (cellular iron
storage protein) and increased saturation of transferrin (major iron transporter in the
plasma).
 UW: Iron poisoning: typically separated into four stages:
 First stage: nausea, diarrhea, and abdominal pain are experienced, often accompanied by
hemorrhage, hypovolemia, and shock in severe cases.
 Stage two: the gastrointestinal symptoms resolve and the patient appears better
 Stage three: metabolic acidosis, hepatic dysfunction, and hypoglycemia may set in.
 Stage four: is marked by scarring of the recovering gastrointestinal tract.
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Biliary tract disease


May present with pruritus, jaundice, dark urine, light-colored stool, hepatosplenomegaly.
Typically with cholestatic pattern of LFTs (↑ conjugated bilirubin, ↑ cholesterol, ↑ ALP).
 UW: primary biliary cirrhosis:
 Presentation:





Insidiously in middle-aged women.
Fatigue and pruritus (usually worse at night) are normally the first symptoms.
Hepatosplenomegaly and cholestasis (eg. jaundice, pale stool, dark urine).
Malabsorption of fat-soluble vitamins (eg. A, D, E, K).
Xanthelasma formation due to reduced biliary cholesterol excretion that may also
promote hypercholesterolemia.
 Late manifestations include cirrhosis and portal hypertension
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 Interlobular bile duct obstruction.
 Granulomatous inflammation (lymphocytes + plasma cells + macrophages +
eosinophils).
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 UW: chronic biliary obstruction  Vit A deficiency (dry skin + night blindness).
 UW: Extrahepatic biliary atresia: congenital obstruction of extrahepatic bile ducts:
 By the 3rd week of life, there is total obstruction (dark urine, acholic stools and a
conjugated
hyperbilirubinemia.)
 On physical examination there is a firm, enlarged liver.
 Liver biopsy is usually diagnostic , showing:
 1. Marked intrahepatic bile ductules proliferation.
 2. Portal tract edema and fibrosis.
 3. Parenchymal cholestasis.
 If biliary drainage is not restored surgically, bile stasis will cause development of biliary
cirrhosis by 6 months of life.
 Removal of excess cholesterol from the body occurs via 2 mechanisms:
 Excretion of free cholesterol into bile.
 Conversion of cholesterol into bile acids (7 α-hydroxylase.(
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
Causes of gallbladder stones:
Cholesterol and mixed gall stones:
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1. Disturbed bile salts cholesterol ratio: A certain ratio (25: 1) between bile
salts and phospholipids on one hand and cholesterol on the other hand has to be
maintained to keep cholesterol in solution. Any lowering of this ratio can lead to
supersaturated bile (lithogenic bile) with consequent cholesterol precipitation.
The following factors may disturb this ratio:
A. Reduced bile salt pool:
- Malabsorption of bile salts in the terminal ileum in crohn’s disease,
small bowel resection.
- Suppression of cholesterol 7a-hydroxylase activity (through fibrate
medications) reduces the conversion of cholesterol into bile acids,
resulting in an increased concentration of cholesterol within the bile.
- Diminished hepatic synthesis in liver disease.
- Estrogens reduce the concentration of bile salts in bile.
B. Increase cholesterol synthesis in obesity, high dietary fat and high
caloric diet.
- Estrogen ↑cholesterol synthesis by upregulating hepatic HMG-CoA
reductase activity, which causes the bile to become supersaturated with
cholesterol.
2. Stasis of bile  biliary sludge:
A. Progesterone causes relaxation and impaired emptying of the gall
bladder, estrogen, oral contraceptives and repeated pregnancy.
B. Following truncal vagotomy due to denervation of gall bladder
C. Diabetes mellitus
D. Obesity
E. Long term parenteral nutrition
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B-Pigment stones:
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1. Haemolytic anaemias.
2. Liver cirrhosis: due to decreased secretion of bile acids by the cirrhotic liver
leading to diminished solubility of any unconjugated bilirubin.
3. Infection: plays a role in the formation of brown pigment stones. Infection by
some strains of E.coli leads to the production of B-glucuronidase enzyme which
hydrolyses bilirubin glucuronide into the insoluble bilirubin which percipitate as
calcium bilirubinate.
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 UW: Risk factors of cholesterol gallstones: drugs (fibrates, octreotide, and ceftriaxone),
glucose intolerance, obesity and rapid weight loss, malabsorption of bile acids (ileal disease or
resection).
 UW: most common cause of pigment gallstones  INFECTION.
Infection  ↑beta-glucoronidase which is released from injured hepatocytes and bacteria 
hydrolysis of bilirubin glucuronide  ↑amount of unconjugated bilirubin.
Cholecystitis
 UW: definitive diagnosis of acute calcular cholecystitis is HIDA scan  failed GB
visualization.
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 UW: Gallbladder hypomotility  biliary sludge (cholesterol + Ca bilirubinate + mucous)
acute cholecystitis in 20%.
Risk factors: pregnancy + rapid weight loss+ TPN + octreotide + high spinal cord injury.
 UW: Hospitalized, severely ill patient + US shows edematous, enlarged GB without stones 
Dx: acute acalcular cholecystitis.
 UW: ↓GB stones with (↓cholesterol, ↑bile acids, ↑phosphatidylcholine which makes
cholesterol soluble).
 UW: Causes of pregnancy related GB stones:
1-Estrogen cholesterol hypersecretion d2 upregulation of HMG-CoA reductase.
2-progesteron  GB hypomotility.
 UW:
Porcelain gallbladder


Calcified gallbladder due to chronic cholecystitis; usually found
incidentally on imaging C.
Treatment: prophylactic cholecystectomy due to high rates of gallbladder
cancer (mostly adenocarcinoma).
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Acute pancreatitis
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 UW: How does alcohol cause pancreatitis??
a) Ethanol induces pancreatic secretions with a high protein concentration and low fluid
content.
b) These viscous secretions are prone to precipitate and form plugs that can obstruct the
lumen of the pancreatic ductules.
c) Alcohol also causes spasms of the sphincter of Oddi and has a direct toxic effect on the
acinar cells.
d) Alcohol-related acute pancreatitis is clinically indistinguishable from pancreatitis due to
other causes.
 Chronic Alcoholism:
a) Chronic alcohol use causes a number of systemic effects due to both the direct toxic
actions of ethanol and alcoholism-associated vitamin deficiencies.
b) Even in the absence of anemia, macrocytosis (mean corpuscular volume >100 fL) is
often seen and is likely related to poor nutrition (eg, folate deficiency), liver disease,
and/or direct toxicity of alcohol on the marrow.
c) Macrocytosis and an AST:ALT ratio >2 are indirect indicators of chronic alcohol
consumption. Alcohol-related macrocytosis can occur independently of folate deficiency.
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 UW: How can ↑TG causes pancreatitis?
a) High levels of circulating triglycerides lead to increased production of free fatty acids
within the pancreatic capillaries by pancreatic lipase.
b) Normally, fatty acids exist in serum bound to albumin. However, if serum triglyceride
levels rise to >1000 mg/dL, the concentration of free fatty acids exceeds the binding
capacity of albumin and leads to direct injury to the pancreatic acinar cells. Thus,
hypertriglyceridemia causes acute pancreatitis via direct tissue toxicity.
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 UW: Types
of pancreatitis:
1) Benign acute interstitial pancreatitis:
a) Pathogenesis:
 Duct obstruction leads to stasis of pancreatic secretions and digestion of
adipose cells by lipase.
 This results in formation of fatty acids that bind calcium ions and
precipitate as insoluble calcium salts.
 The areas of focal necrosis and calcium precipitation induce an
inflammatory reaction.
b) Gross picture: the pancreas looks edematous.
c) Light microscopy: interstitial edema, focal fat necrosis and calcium.
2) Acute necrotic (hemorrhagic) pancreatitis:
a) Pathogenesis:
 If the inflammatory process continues, blood flow to the pancreatic acini is
compromised as a result of the edema.
 Ischemia damages the acinar cells and causes abnormal intracellular
activation of trypsin.
 Trypsin then activates other proteolytic enzymes, thus initiating
autodigestion (autolysis) of pancreatic tissue.
 Destruction of blood vessel walls can cause hemorrhage into the necrotic
areas.
b) Gross picture:
 Areas of white chalky fat necrosis are visible in the pancreatic tissue.
They can spread onto the mesentery, omentum and other parts of
abdominal cavity.
 UW: Gallstones and alcoholism are the most common causes of acute pancreatitis.
Less common causes:
1. recent endoscopic retrograde cholangiopancreatography (ERCP) procedure
2. Drugs (eg, azathioprine, sulfasalazine, furosemide, valproic acid)
3. Infections (eg, mumps. Coxsackie virus, Mycoplasma pneumoniae)
4. Hypertriglyceridemia
5. Structural abnormalities of the pancreatic duct (strictures, cancer, pancreas divisum) or of the
ampullary region (choledochal cyst, stenosis of sphincter of Oddi)
6. Surgery (particularly of the stomach and biliary tract and after cardiac surgery)
7. Hypercalcemia
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 UW: chronic abdominal pain + distention + round fluidfilled space  pancreatic pseudocyst.
 The most common location for a pseudocyst is in the



lesser peritoneal sac; bordered by the stomach,
duodenum and transverse colon.
Pancreatic pseudocyst is a common complication of
acute pancreatitis.
It is a collection of fluid rich in enzymes and
inflammatory debris.
Its walls consist of granulation tissue and fibrosis. Unlike true cysts, pseudocysts aren’t
lined by epithelium.
Chronic pancreatitis





Chronic inflammation, atrophy, calcification of the pancreas A .
Major causes include alcohol 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).
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Pancreatic adenocarcinoma

UW: The most important risk factor for pancreatic carcinoma is SMOKING.

UW: C/P of pancreatic adenocarcinoma:
a) C/P of cancer head of the pancreas:
1. A palpable but nontender gallbladder (Courvoisier sign),
2. weight loss, and
3. Obstructive jaundice (associated with pruritus, dark urine, and pale stools) are
indicative of an adenocarcinoma at the head of the pancreas compressing the
common bile duct.
b) Cancers of the body and tail of the pancreas:
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1. Do not obstruct the common bile duct, and thus they usually do not produce
symptoms until they invade the splanchnic plexus and cause midepigastric
abdominal pain.
 FA: Zollinger-Ellison syndrome:
 Gastrin-secreting tumor (gastrinoma) of pancreas or duodenum.
 Acid hypersecretion causes recurrent ulcers (beyond the duodenal pulp or resistant to
treatment). Presents with abdominal pain (peptic ulcer disease), diarrhea
(malabsorption) because pancreatic/intestinal enzymes are inactivated by gastric acid and
cannot digest nutrients properly.
 Positive secretin stimulation test: gastrin levels remain elevated after administration of
secretin, which normally inhibits gastrin release.
 Administration of exogenous secretin stimulates gastrin release from gastrinomas
and can be used to differentiate ZES from other causes of hypergastrinemia (eg,
atrophic gastritis).
 In contrast, secretin inhibits release of gastrin from normal gastric G cells.
 May be associated with MEN 1.
 UW: Patients with ZES should undergo testing (eg. serum calcium, prolactin level) to exclude
multiple endocrine neoplasia type 1 due to the strong association between these conditions.
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 Lead poisoning:

Exposure: batteries, alloys and ammunition. Individuals working in these industries
and others (eg, mining, smelting, chemical processing, recycling, spray painting,
radiator repair) are regularly exposed to lead.
Exposure risk ↑ in old houses with chipped paint.
 C/P:





GIT: Colicky abdominal pain ("lead colic''), constipation.
CNS: Headaches, impaired concentration and deficits in short-term memory.
PNS: wrist and foot drop.
Bluish pigmentation ("lead line") at the gum-tooth line.
Microcytic hypochromic anemia and basophilic stippling on peripheral smear.

TTT:

Dimercaprol and EDTA are 1st line of treatment.
Succimer used for chelation for kids.
Dx: blood lead level exceeds 10 pg/dL (0.48 mmol/L) on a venous blood sample.
 Dimercaprol (eg, British Anti-Lewisite),
 Increases urinary excretion of heavy metals by forming stable, nontoxic soluble chelates.
 The sulfhydryl group of dimercaprol combines with arsenic and displaces arsenic ions
from the sulfhydryl groups of enzymes involved in cellular respiration.
 Dimercaprol has a very narrow therapeutic index, and serious side effects include
nephrotoxicity, hypertension, and fever.
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 UW: Most duodenal peptic ulcers are caused by H. pylori infection.
 The most effective method to prevent disease recurrence is to eradicate the infection with
antibiotic therapy (eg. amoxicillin plus clarithromycin).
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 Lubiprostone:
a. Rx for Irritable bowel syndrome.
b. Cl channel activator, helpful for constipation.
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 UW: The choice of antiemetic therapy depends on the source of the emetogenic stimulus.
 Conditions that cause gastrointestinal irritation (eg, infections, chemotherapy, and
distention) result in increased mucosal serotonin release and activation of 5-HT3 receptors
on vagal and spinal afferent nerves.
 These then relay their impulses to the medullary vomiting center, inducing emesis.
 5-HT3 receptor antagonists (eg. ondansetron) are well-tolerated medications that are very
effective
at reducing nausea and vomiting caused by gastrointestinal upset.
 Dopamine receptor antagonists (eg, metoclopramide, promethazine): are effective in
treating central nausea (seen in acute migraines) and also reduce migraine headache pain.
 First-generation H1 receptor antagonists (eg, diphenhydramine, meclizine) and
muscarinic acetylcholine receptor antagonists (eg, scopolamine) are frequently used to
treat vestibular nausea (eg, motion sickness). They can also cause significant sedation.
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 UW: function of the D2 receptors in the GIT:
Direct relaxant effect on the gut especially (LES & stomach antrum and fundus).
Inhibits the release of acetylcholine from intrinsic myenteric cholinergic neurons, which
leads to an indirect inhibition of the musculature.
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UW: Types of drug reactions:
UW: 1. Diphenoxylate is an opiate anti-diarrheal structurally related to meperidine. It
binds to mu opiate receptors in the gastrointestinal tract and slows motility.
Low therapeutic doses allow for potent anti-diarrheal effects without euphoric
effects Since higher doses can lead to euphoria and physical dependence,
the drug is combined with atropine at therapeutic doses to discourage abuse.
2. Octreotide is helpful for secretory diarrhea. Drugs that target secretory types of diarrhea include
bismuth subsalicylate, probiotics, and octreotide.
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 Congenital umbilical hernia P. 2
Failure of umbilical ring to close after physiologic herniation of midgut. Covered by skin C . Protrudes
with intra-abdominal pressure (eg, crying). May be associated with congenital disorders (eg, Down
syndrome, congenital hypothyroidism). Small defects usually close spontaneously.
 Digestive tract histology P. 20
Stomach Parietal cells are eosinophilic (pink, red arrow in B ), chief cells are basophilic (black arrow in B ).
Duodenum Villi and microvilli absorptive
 Diaphragmatic hernia P. 44
Abdominal structures enter the thorax. Most common causes:
1. Infants—congenital defect of pleuroperitoneal membrane left-sided herniation (right
hemidiaphragm is relatively protected by liver) A .
2. Adults—laxity/defect of phrenoesophageal membrane hiatal hernia (herniation of stomach through
esophageal hiatus).
3. Sliding hiatal hernia—gastroesophageal junction is displaced upward as gastric cardia slides into
hiatus; “hourglass stomach.” Most common type. Associated with GERD.
4. Paraesophageal hiatal hernia— gastroesophageal junction is usually normal
but gastric fundus protrudes into the thorax.
 Achalasia P. 71
Treatment: surgery, endoscopic procedures (eg, botulinum toxin injection).
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 Acute gastrointestinal bleeding P. 110
Upper GI bleeding—originates proximal to ligament of Treitz (suspensory ligament of duodenum).
Usually presents with hematemesis and/or melena. Associated with peptic ulcer disease, variceal
hemorrhage.
Lower GI bleeding—originates distal to ligament of Treitz. Usually presents with hematochezia.
Associated with IBD, diverticulosis, angiodysplasia, hemorrhoids, cancer.
 Celiac disease P. 86
 Microscopic colitis P. 108
Inflammatory disease of colon that causes chronic watery diarrhea. Most common in older females.
Colonic mucosa appears normal on endoscopy. Histology shows inflammatory infiltrate in lamina propria
with thickened subepithelial collagen band or intraepithelial lymphocytes.
 Autoimmune hepatitis P. 103
Chronic inflammatory liver disease. More common in females. May be asymptomatic or present with
fatigue, nausea, pruritus. May be associated with ⊕antinuclear, anti-smooth muscle and antiliver/kidney microsomal-1 antibodies. Labs: ALT and AST. Histology: portal and periportal
lymphoplasmacytic infiltrate.
 Focal nodular hyperplasia P. 130
Second most common benign liver tumor; occurs predominantly in females aged
35-50 years. Hyperplastic reaction of hepatocytes to an aberrant dystrophic artery. Marked by central
stellate scar. Usually asymptomatic and detected incidentally.
 Cholangiocarcinoma P. 139
Malignant tumor of bile duct epithelium. Risk factors include 1° sclerosing cholangitis, liver fluke
infections. Usually presents late with fatigue, weight loss, abdominal pain, jaundice. Imaging may show
biliary tract obstruction. Histology: infiltrating neoplastic glands associated with desmoplastic stroma.
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Anatomical relation of different parts of duodenum:
- 1st part → pass horizontally over L1, intra-peritoneal
- 2nd part → pass inferiorly from L1 – L3, related to head of pancreas, CBD, ampulla of Vater
- 3rd part → horizontally over L3, related to aorta, IVC, SMA, uncinate process
- 4th part → pass superiorly to the left of L2 – L3, Ligament of Treitz
Horizontal transection of the rectus abdominus carry the risk of injury to the superior & inferior epigastric
arteries as thay supply the rectus abdominus, inferior artery pass posterior to the rectus abdominus at the
level of the arcuate line → injury lead to significant hematoma due to loss of the the supporting posterior
rectus sheath.


Common iliac artery branches (before passing inguinal ligament) :
Inferior epigastric artery (pass medially, superiorly).
Deep circumflex iliac artery (pass laterally).
Renal vessels:
o Right renal: shorter, vein runs in front of artery, right gonadal vein drain directly into IVC.
o Left renal : longer, vein run between aorta & SMA causing its compression
“Nutcracker effect” → ↑↑ pressure in left renal vein (left testicular vein drain in the renal vein)
→ Varicocele; this why varciocele occur more on the left.
The origin of the left gonadal artery is abdominal aorta not left renal artery.
Lymphatic drainage of the rectum:
either internal iliac or inferior mesenteric → Either in bowel wall (epicolic), around arterial arcades
(paracolic), around mesenteric vessels (intermediate) → 1st site of nodal metastasis are the sentinel lymph
nodes first 1-4 nodes drain specific colon segment.
 Upper 1/3 rectum: superior rectal nodes → inferior mesenteric lymph nodes
 Middle & lower 1/3 rectum: either upward into inferior mesenteric lymph nodes or middle rectal →
internal iliac LNs.
 Below dentate line: mainly to inguinal lymph nodes, may reach inferior mesenteric & internal iliac lymph
nodes Left colic lymph nodes → drain hepatic flexure and upper descending colon.
Alkaline phosphatase  present in liver, bone, placenta, intestine, kidney, leukocytes, and neoplasm.
Threefold elevation in ALP = liver disease. Moderate elevated ALP  GGT.


Femoral triangle:
Femoral artery → mid-inguinal point (midway between pubic tubercle, ASIS).
Femoral vein cannulation → ~ 1 cm below the inguinal ligament, ~ 1 cm medial to femoral artery
pulsation.
Direct Vs indirect hernias
Direct hernia
Protrusion
through
triangle
Hasselbach.
Less prone to incarcerate
Less prone to descend to scrotum
Best felt with pulp of finger
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Indirect hernia
of Failure of obliteration of process
vaginalis
More common, more on Rt. side
Better felt by tip of finger
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Testicular descent :
- occur slowly from week 8 – full term, palpable testes at inguinal canal mostly descend spontaneously at
age of 6 months.
- The deep inguinal ring is an opening in the fascia transversalis lateral to the inferior epigastric vessels and
superior to the mid-inguinal point (midway between the ASIS and the pubic tubercle).
- The superficial inguinal ring is an opening in the external oblique muscle aponeurosis and lies above and
medial to the pubic tubercle.
The conjoint tendon is the common tendon of the transverses abdominis and internal oblique muscles. It
forms part of the posterior wall of the inguinal canal
There are 3 phases of gastric acid secretion:
1) Cephalic phase: stimulated by smell & taste of food, mediated by vagal stimulation
2) Gastric phase: stimulated by chemical irritation of the stomach, mediated by gastrin & histamine (from
ECL cells).
3) Intestinal phase: very minor role in gastric acid secretion. Ileum & colon produce peptide YY → inhibit
ECL cells → ↓↓ gastric acid production.
Post-surgical or post-intubation due to lack of salivation an dry mouse, may be complicated by infection and
cause suppurative parotitis.
Short bowel syndrome: massive small bowel resection & Crohn disease → ↓↓ in absorptive surface area →
postprandial voluminous diarrhea
Traction diverticulae Created by inflammation & scarring of the gut wall → pulling & outpouching of all gut
layers. Ex. I midesophagus due to pull by inflammatory mediatinal lymphadenitis.
Manometer patterns in esophageal diseases:
o
o
o
Achalasia: ↓↓ amplitude of peristalsis in mid esophagus, ↑↑ tone & incomplete relaxation at
LES.
Scleroderma: ↓ in LES & peristalisis.
Cricopharyngeus dysfunction → chocking, food sticking sensation on swallowing.
Other causes of Mallory Weis syndrome include + repeated abdominal strain, trauma, hiatal hernia (50%).
Leiomyoma: most common benign tumor; fascicles of spindle cells with fibrosis.
Reflux esophagitis: elongation of basal papillae, basal cell hypertrophy, intra epithelial eosinophils
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Pathogenesis of autoimmune gastritis

NSAIDs cause GI bleeding by ↓↓ PG E2 and ↓↓ platelet aggregation
Risk of GI bleeding ↑↑ even with low dose aspirin by 2 – 3 folds
Small intestinal bacterial overgrowth (SIBO):
Enteric bacteria cause :
1) ↑↑ production of vitamin K, folate
2) Inhibit proliferation of pathogenic bacteria
3) Digest unabsorbed sugars
 SIBO → ↑↑ vitamin K & folate level, although it cause malabsorption of fat soluble vitamins (DEKA).

Lactose intolerance :
o Prevelant in Asia & Africa population
o Other causes :
1) Primary lactase defieicny : Normal histological appearance
a. Hereditary : rare AR disease
b. Acquired due to lactose non persistence (↓↓ lactase producton by md
c. childhood) common in Asians 90%, Africans and Hispanic
2) Acquired inflammation → bacterial overgrowth, infectious enteritis, Crohn’s disease
Short bowel syndrome: massive small bowel resection & Crohn disease → ↓↓ in absorptive surface area →
postprandial voluminous diarrhea.
Paneth cell metaplasia:
 Paneth cells present normally in the intestine in the crypts of LiberKuhn with large eosinophilic cytoplasm
 Metaplasia occur in CD (and other IBD) , may be pre-neoplastic.
Complications follow the gastro-jujenostomy operation: iron deficiency anemia will occur as iron is absorbed
mainly in duodenum & proximal jujenum, also malabsorption of Vitamin D, B12, Calcium.
Liver functional reserve is an important determinant of prognosis patient with liver failure which can be
detected by serum albumin & prothrombin time levels.
Indications for use celecoxib: any patient need aspirin but have PUD or bleeding tendency as celecoxib have
potent anti-inflammatroy properties but without these effects.
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Dumping syndrome: after gastric bypass surgery, emptying of hyperosmolar chime into small intestine →
rapid shift of fluid from serum to intestine → postprandial GIT, vasomotor symptoms.
Describe the pertechnetate scan for diagnosis Meckel diverticulum:
 The Tc-ertechnetate has high affinity for parietal cells of the gastric mucosa
 ↑↑ uptake of the dye in the peri-umblical region or RLQ is characteristic for Meckel diverticulum
o
o
o
o
Colon carcinoma :
Right colon: IDA, nonspecific symptoms
Left colon: IO, change in bowel habits (alternating constipation & diarrhea is characteristic for IBS).
Recto-sigmoid : hematochazia.
Rectum: tenesmus, small caliber stool.
difference between cancer associated CRC & sporadic CRC
Adenoma carcinoma sequence (other gene abnormalities):
Inhibition of caspases → cysteine proteases that essential in apoptosis.
Increased activity of COX-2 enzyme → found in many forms of colon cancer & inherited polyposis
syndromes.
 This may be due to need for PGs → epithelial proliferation.
 Regular aspirin intake is associated with ↓↓ risk of colon cancer.
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Hepatitis A virus:
o Outbreaks usually from contaminated water, food, steamed shellfish (USA)
o Clinical picture : children  mostly silent or anicteric, adults  severe icteric , aversion to smoking
o Vaccine → given to high risk peoples, unvaccinated contact.
Hepatitis D virus :
o It resemble the Dane particle of HBV
o HDAg – replication defective as it must be coated by the external coat HBsAg to penetrate hepatocyte
either super/Co-infection.

Histo-pathology of acute viral hepatitis (all of them give the same picture)
 Panlobular lymphocytic infiltrates
 Ballooning hepatocytes
 Hepatocytic necrosis & apoptosis→ form rounded acidophilic bodies called Councilman bodies or
apoptotic bodies.
 Kupffer cells → phagocyte hepatocellular debris → hypertrophy & laden with lipofuscin pigment.
-
Causes of hepatic abscess :
Underdeveloped countries: usually caused by parasitic infestations (e.g. E. histolytica, ecchinococci)
Developed countries: ususally bacteria in 80% of cases through
 Biliary tract infection, direct invasion → Gram negative enteric bacteria (E.coli, Klebseilla) or
enterococci.
 Trauma/penetrating injury → mixed aerobic and anaerobic bacteria.
 Hepatic artery (systemic invasion) → usually Staph. Auerus.
 Portal lyemia → abdominal infectious processes e.g. appendicitis, food borne illness → Entameba.
Effect of rifaximin & uses :
 Action: ↓↓ bacterial RNA synthesis by binding with DNA dependant RNA polymerase.
 Non absorbable antibiotic that affect GUT flora.
 Used with lactulose (↓↓ PH → ↑↑ conversion of ammonia to ammonium)
Used in traveler’s diarrhea.
The cause of dubin Johson syndrome: AR disorder due to mutation in bilary transport protein called multidrug resistance protein 2.


-
Dubin Johnson syndrome :
Due to mutation in canalicuar membrane transport protein
The liver appears black → impaired excretion of epinephrine metabolite that accumulates in the
hepatocyte within lysosomes.
Some extra characters of hemochromatosis :
It cause impotence and arthropathy.
Lab : > 50% saturation of transferrin.
Risk factors for pancreatic cancer: (+) smoking (the most important environmental factor), MEN syndrome,
Peutz-Jeuher syndrome, Lynch syndrome.
Misoprostol → used for NSAIDs induced peptic ulcer.
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Primary biliary cirrhosis:
 Dense portal tract infiltrate of lymphocytes, macrophages → granulomatous destruction of intra-hepatic
interlobular bile ducts (florid duct lesion).
 Appear insidiously in middle aged ♀ by fever & pruritus that worse at night HSM, cholestasis → fatty malabsorption & ↓↓ cholesterol excretion → hypercholesterolemia.
 Jaundice is not a must, cholestatis may appear initially with ↑↑ cholesterol & ALP
 Diagnosis is confirmed by anti-mitochondrial IgM
 Associations: (+) autoimmune thyroid diseases, hypothyroidism, Raynaud’s $
Histological features of GVHD in liver :
 Similar to PBC: lymphocytic inflammation, destruction of IHBR, necrosis of periportal tissues, granulomas
& bile staining.
 GVHD → commonly affect skin, liver, GIT.
The pathogenesis of acute calcular cholecystitis:
 Begin by longstanding gallbladder outflow obstruction → hydrolysis of lecithin → ↑↑ Lysolecithin →
disruption of the protective mucosal layer
 Bile salts act as detergent to the exposed luminal epithelium → chemical irritation & prostaglandin release
 These changes → hypo-motility of the GB → accumulation of the content & ↑↑ internal pressure →
ischemia & bacterial invasion of the wall.
Pancreatic pseudo-cyst:
o Unlike true cysts lined by epithelia cells, pseudo-cysts lined by granulation tissue and fibrosis
o Mature psudocyst → after 4 – 6 weeks become fibrotic wall
o Mostly at lesser curvature.
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