Professional Documents
Culture Documents
Normal Gastrointestinal Embryology: Intestinal Malrotation
Normal Gastrointestinal Embryology: Intestinal Malrotation
UW: Case: newborn + bilious vomiting + Cecum is found in the RUQ, fixed with a fibrous band to the 2 nd part of
the duodenum?
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Tracheoesophageal anomalies
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
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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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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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.
Spleenmesoderm, *Liverendoderm, *Pancreasendoderm *kidneymesoderm.
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RETROPERITONEAL STRUCTURES
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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
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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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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Epiploic foramen
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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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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.
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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: 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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Rx: Kupffer cells in the liver reticuloendothelial cells that remove the pathogens from blood stream.
Biliary structure
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Femoral region
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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.
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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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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.
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Femoral hernia
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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Umbilical hernia:
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: 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: 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.
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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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.
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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.
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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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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.
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.
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
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
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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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:
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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SALIVARY GLAND
MUMPS:
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).
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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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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.
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).
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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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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.
Stomach
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Gastritis
Acute gastritis
Chronic gastritis
Mucosal inflammation, often leading to atrophy (hypochlorhydria hypergastrinemia) and
intestinal metaplasia (increased risk of gastric cancers).
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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).
Gastric cancer
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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 somatostatin-
producing 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.
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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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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.
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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 non-
functional.
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:
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).
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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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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.
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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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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
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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:
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
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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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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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Peutz-Jeghers syndrome is associated with multiple hamartomatous polyps and black spots on
the skin and mucosa of young.
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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
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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.
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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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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.
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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.
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Hepatic encephalopathy
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Hepatocellular carcinoma/hepatoma
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.
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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: 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.
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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
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.
α1 -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.
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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 reddish-
pink 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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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: chronic biliary obstruction Vit A deficiency (dry skin + night blindness).
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B-Pigment stones:
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).
Cholecystitis
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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:
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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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: 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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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.
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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DR/AHMED SHEBL
1
USMLE ENDPOINT/ GIT
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.
15
DR/AHMED SHEBL
2
USMLE ENDPOINT/ GIT
15
DR/AHMED SHEBL
3
USMLE ENDPOINT/ GIT
15
DR/AHMED SHEBL
4
USMLE ENDPOINT/ GIT
Lubiprostone:
a. Rx for Irritable bowel syndrome.
15
DR/AHMED SHEBL
5
USMLE ENDPOINT/ GIT
15
DR/AHMED SHEBL
6
USMLE ENDPOINT/ GIT
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.
15
DR/AHMED SHEBL
7
USMLE ENDPOINT/ GIT
15
DR/AHMED SHEBL
8
USMLE ENDPOINT/ GIT
15
DR/AHMED SHEBL
9