Gastrointestinal Flashcards
Midgut development
The midgut is the lower duodenum to the 2/3 transverse colon
6th week- physiologic midgut herniates though umbilical ring
10th week-returns to abdominal cavity and rotates around superior mesenteric artery for total 270 counterclockwise
Where is the defect in gastroschisis and omphaloceles during development?
lateral fold closure
extrusion of abdominal contents through abdominal folds (R of umbilicus) NOT covered by peritoneum or amnion?
Gastroschisis
Failure of lateral walls to migrate at umbilical ring results in persistent midline herniation of abdominal contents into umbilical cord. Gut contents are surrounded by peritoneum
Omphaloceles
“O” surrounds the gut
related to congenital anomalies
What is the most common tracheoesophageal anomaly?
Esophageal atresia with distal tracheoesophageal fistulae
presents with polyhydramnios in utero because unable to swallow
vomit with first feeding
Air can enter the stomach compared to a pure EA where the stomach is gas less
Pt is a 1-2 day old baby with downs syndrome that presents with bilious vomiting and abdominal distention. What is this baby likely to have? what is the xray sign?
duodenal atresia due to failure to recanalze
double bouble on xray
Pt presents with bilious vomiting and abdominal distention within first 1-2 days of life and the apple peel sign on xray
jejunal and ileal atresia
disruption of mesenteric vessels leading to ischemic necrosis and segmental resorption (bowel discontinuity)
What is the most common cause of gastric outlet obstruction in infants?
hypertrophic pyloric stenosis
Infant presents with a palpable olive shaped mass in the epigastric region and nonbillious projectile vomiting with visible peristaltic waves at 2-6 wks old
Hypertrophic pyloric stenosis
more in firstborn males
associated withe exposure to macrolides
vomiting empties gastric acid and results in hypokalemic and hypochloremic metabolic alkalosis
What becomes the body, tail, isthmus and accessory pancreatic duct?
dorsal pancreatic bud
What becomes the pancreatic head?
Both dorsal and ventral pancreatic bud
What becomes the uncinate process and the main pancreatic duct?
ventral pancreatic bud
Annular pancreas
abnormal rotation of ventral pancreatic bud results in a ring formation that encircles the second part of the duodenum causing duodenal narrowing and vomiting
When the ventral and dorsal buds fail to fuse at 8 weels
pancreas divisum
What is the spleen derived from?
mesoderm but has foregut supply from celiac trunks splenic artery
retroperitoneal organs
suprarenal/adrenal glands Aorta/IVC Duodenum (2nd through 4th part) Pancreas (except tail) Ureters Colon (descending and ascending) Kidneys Esophagus (thoracic portion) Rectum (partially)
“SAD PUCKER”
Falciform ligament
liver to anterior abdominal wall
contains the ligmentum teres hepatis and patent paraumbilical veins
Hepatoduodenal ligament
Liver to duodenum
contains the portal triad: proper hepatic artery, portal vein, common bile duct
Pringle manuver
Hepatoduodenal ligament may be compressed between thumb and index finger placed in omental foramen to control bleeding
Gatrohepatic ligament
liver to less curvature of stomach
contains the gastric vessels
Gatrocolic ligament
connects greater curvature and transverse colon
contains the gastroepiploic arteries
Gastrosplenic ligament
connects the greater curvature and spleen
contains teh short gastrics, left gastroepiploic vessels
Splenorenal ligament
connects the spleen to posterior abdominal wall
contains the splenic artery and vein, tail of pancreas
Layers of gut wall
Mucosa- epithelium –> lamina propria–> muscularis mucosa
submucosa- submucosal nerve plexus (meissner)
Muscularis externa - inner circular mm, myenteric nerve plexus (auerbach), outer longitudinal mm
Serosa if intraperitoneal/adventitia if retroperitoneal
Cell type in the esophagus?
nonkeratinized stratified squamous epithelium
Brunners glands
In duodenum
HCO3 secreting cells of submucosa
Crypts of lieberkuhn
In duodenum, jejunum, ileum, colon
contains stem cells ( in duodenum they can replace enterocytes/goblet cells and paneth cells tat secrete defensins, lysozyme, and TNF)
Plicae circulares
In distal duodenum, jejunum, proximal ileum
Peyers patches
in ileum
lymphoid aggregates in lamina propria and submucosa
Largets number of goblet cells in the small intestine is in the?
ileum
Colon also has abundant goblet cells
Vertebral levels of major abdominal arteries - celiac trunk, SMA, IMA? Bifurcation of aorta?
celiac- T12
SMA-L1
IMA-L3
Bifurcation of aorta at L4 “biFOURcation”
In low body weight patients, we worry about superior mesenteric artery syndrome…which is?
characterized by intermittent intestinal obstruction symptoms primarily post prandial pain
when SMA and aorta compress transverse (3rd) part of duodenum
Where is the colon prone to ischemia?
at watershed areas where you get distal arterial branches
1) splenic flexure -SMA and IMA
2) rectosigmoid junction - the last sigmoid arterial branch from the IMA and superior rectal artery
blood supply and innervation of foregut? midgut? hindgut?
foregut is celiac artery with parasymp innervation from vagus
Midgut is SMA with parasympathetic innervation from vagus
Hindgut is IMA with pelvic parasympathetics
Branches of celiac trunk?
hepatic, splenic, left gastric
Posterior duodenal ulcers run the risk of penetrating what artery and causing hemorrhage?
gastroduodenal artery
What is the risk with anterior duodenal ulcers?
perforate into the anterior abdominal cavity and potentiall lead to pneumoperitoneum
portal systemic anastomoses: esophagus
left gastric with azygos
clinical sign is esophageal varices
portal systemic anastomoses: umbilicus
paraumbilical with small epigastric veins of ant ab wall
clinical sign is caput medisae
portal systemic anastomoses: rectum
superior rectal with middle and inferior rectal
clinical sign is anorectal varices
Anorectal varices, caput medusae, esophageal varices are commonly seen with
portal HTN
TX then with transjugular intrahepatic portosystemic shunt (TIPS) between portal and hepatic vein that shunts blood to the systemic circulation, bypassing liver and reducing portal HTN
What is the pectinate/dentate line? why is it important?
where the endoderm (hindgut) meets ectoderm
above line: internal hemorrhoids (not painful because visceral innervation), adenocarcinoma
below line: external hemorrhoids (painful because somatic innervation from inferior rectal branch of pudendal nerve), anal fissures, squamous cell carcinoma
Anal fissures are most commonly located?
below pectinate line
posteriorly because poorly perfused
Liver tissue function unit and struture
the functional unit of the liver is made up of hexagonally arranged lobules surrounding the central vein with portal triads on the edges (consisting of portal vein, hepatic artery, bile ducts, lymphatics)
Kupffer cells
specialized macrophages in liver
Hepatic stellate (Ito) cells
in space of Disse store vitamin A and produce extracellular matrix when activated –> hepatic fibrosis
Liver zones
Zone I: perioportal zone - affected first by viral hepatitis and ingested toxins
Zone II: intermediate zone - related to yellow fever
Zone III: pericentral vein (Centrilobular)zone - affected first by ischemia, high cytochrome P450, most sensitive to metabolic toxins, site of alcoholic hepatitis
Tumors of the head of the pancrease commonly cause?
obstruction of the common bile duct that results in enlarged gallbladder with painless jaundice (courvoisier sign)
commonly andenocarcinoma
Femoral structures from lateral to medial? Whats in the femoral triangle? Femoral sheath?
- Nerve-Artery-Vein-Lymphatics - “NAVeL”
- NAV is in the femoral triangle - “Venous near the penis”
- sheath that is below the inguinal ligament that contains femoral vein, artery, and canal (deep inguinal lymph nodes) but not femoral nerve
Muscles of the inguinal canal
Transversus abdominis mm
Internal oblique mm
which fuse into a conjoined tenden
Spermatic cord structure
ICE tie
Internal spermatic fascia (transversalis fascia)
Cremasteric muscle and fascia (internal oblique)
External Spermatic fascia (external oblique)
Hesselbach triangle
Inguinal triangle
- inferior epigastric
- lateral border of ther ectus abdominis
- inguinal ligament
Diaphragmatic hernia? where is it more common?
abd structures enter the thorax. mostly on the left side because the liver protects the right side
Most common diaphragmatic hernia? What is the other type?
- sliding hiatal hernia is most common. The GE junction is displaced upward as gastric cardia slides into the esophageal hiatus . “hourglass stomach”
- paraesophageal hiatal hernia is when the gastric fundus herniates
This type of hernia follows the path of descent of the testes and is covered by all 3 layers of spermatic fascia
Indirect inguinal hernia - Lateral to inferior epigastrics (MDs dont LIe - medial is direct hernia, Lateral is indirect)
goes through the internal (deep) inguinal ring, external (superficial) inguinal ring, and into the scrotum
What causes an indirect inguinal hernia?
caused by failure of processus vaginalis to close and can form a hydrocele
more common in males
This type of hernia protrudes through the inguinal triangle
Direct inguinal hernia bulges directly though parietal peritoneum medial to the inferior epigastric vessels but lateral to rectus abdominis
ONLY goes through external (superficial) inguinal ring
This hernia protrudes below the inguinal ligament through the femoral canal below and lateral to pubic tubercles
Femoral hernia
mostly females
more likely to present with incarceration or strangulation than inguinal hernias
Gastrin
- From G cells of the antrum of stomach and duodenum
- increases H+ gastric secretion
- Increases gastric mucosa growth and motility
effect is due to enterochromaffin-like cells (ECL) that leads to histamine release rather than through its direct effect on parietal cells
Somatostatin
- From D cells in pancreatic islets and GI mucosa
- Decrease gastric acid and pepsinogen secretion
- Decrease pancreatic and small intestine fluid secretion
- Decrease gallbladder contraction
- Decrease insulin and glucagon release
high acidity induces release
Cholecystokinin
- From I cells in duodenum and jejunum
- Increase pancreatic secretion
- Increase gallbladder contraction
- Decrease gastric emptying
- Increase sphincter of Oddi relaxation
Secretin
- From S cells in the duodenum
- Increase pancreatic HCO3 secretion
- decrease gastric acid secretion
- increase bile secretion
Glucose-dependent insulinotropic peptide/gastric inhibitory peptide (GIP)
- From K cells (duodenum, jejunum)
- exocrine: decrease gastric H+ secretion
- endocrine: increase insulin release
Motilin
- From small intestine
- Produces migrating mtoor xomplexes (MMCs)
Vasoactive Intestinal Polypeptide
- From parasympathetic ganglia in sphincters, gallbladder, small intestine
- Increase intestinal water and electrolyte secretion
- Increase relaxation of intestinal smooth mm and sphincters
Nitric Oxide
- increase smooth muscle relaxation, including lower esophageal sphincter
- Loss of NO related to achalasia’s increase lower esophageal sphincter tone
Ghrelin
- From stomach
- Increases appetite
Intrinsic factor
- From parietal cells of stomach
- Vitamin B12 binding protein (required for B12 uptake in terminal ileum)
Gastric acid
- From parietal cells of stomach
- Decreases stomach pH
- Regulation: increases with histamine, vagal stimulation (ACh), gastrin. Decreases with somatostatin, GIP, secretin
Pepsin
-From chief cells (Stomach)
-Protein digestion
REgulation: increase by vagal stimulation (ACh)
Bicarbonate
- From mucosal cells in stomach, duodenum, salivary glands, pancreas and brunners glands in duodenum
- Neutralizes acid
Pancreatic alpha amylase
starch digestion
released in active form
Pancreatic lipases
fat digestion
Panctreatic proteases
protein digestion
trypsin, chymotrypsin, elastase, carboxypeptidases which are secreted as proenzymes
Pancreatic trypsinogen
converted to active trypsin (by enterokinase/enteropeptidase on brush border)
which then goes on to activate other proenzymes and cleaving of additional trypsinogen molecules into active trypsin
Where is Fe absorbed? Folate (B9)? B12?
- duodenum for Fe
- small bowel for folate
- terminal ileum for B12
Peyers patches
- unencapsulated lymphoid tissue found in lamina propria and submucosa of ileum
- specialized M cells sample and present antigens to immune cells
- B cells in germinal centers differentiate into IgA secreting plasma cells which will reside in lamina propria
- IgA receives protective secretory component and is then transported across epithelium to deal with intraluminal antigens
What are bile acids conjugates to
glycine
taurine
What is teh rate limiting step of bile acid synthesis
cholesterol 7alpha hydroxylase
Low bile salt absorption can result in what kind of stones and why
calcium oxalate kidney stones
Ca which normally binds oxalate, binds fat instead and so free oxalate is absorbed by gut and causes stones
Bilirubin pathway
1) macrophages break down RBCs and release heme which is metabolized by heme oxygenase to biliverdin which is reduced to bilirubin
2) unconjugated bilirubin/indirect is water insoluble and is in macrophages
3) enters bloodstream and joins albumin to form unconjugated bilirubin albumin complex
4) enters liver and via UDP-glucuronosyl-transferase –> conjugated bilirubin/direct bilirubin/water soluble
5) gut bacteria turns this into urobilinogen which 80% excreted by feces as stercobilin (brown color) and rest either excreted in urine as urobilin (yellow color) or go to liver via enterohepatic circulation
Sialolithiasis
Stones in salivary gland
single stone more common in submandibular gland (wharton duct)
caused by dehydration or trauma
Sialadenitis
inflammation of salivary gland
Salivary gland tumors
most commonly benign and in parotid gland
presents as painless mass/swelling
Facial pain or paralysis suggests malignant involvement of CN VII
The most common salivary gland tumor
pleomorphic adenoma- benign mixed tumor of chondromyxoid stroma and epithelium
The most common malignant tumor of salivary gland
Mucoepidermoid carcinoma
has mucinous and squamous components
A benign cystic tumor of salivary gland with germinal centers
warthin tumor (papillary cystadenoma lymphomatosum)
seen in smokers
Bilateral in 10%
Multifocal in 10%
Barium swallow shows dilated esophagus with an area of distal stenosis “birds beak sign”
Achalasia-Failure of LES to relax due to loss of myenteric (auerbach) plexus due to loss of postganglionic inhibitory neurons (which contain NO and VIP)
Increased risk of esophageal cancer
Pt presents with crepitus felt in neck region and chest wall
Boerhaave syndrome
Transmural (compared with mallory weiss which is non transmural)
Distal esophageal rupture with pneumomediastinum due to violent retching
subq emphysema may be due to dissecting air
Infiltration of eosinophils in the esophagus
Eosinophilic esophagitis
esophageal rings and linear furrows often seen on endoscopy
unresponsive to GERD therapy
Esophageal strictures
Associated with caustic ingestion (Strong acid/base) and acid reflux
Esophagitis
reflux, infection in immunocompromised (candida causes pseudomembrane, HSV-1 causes punched out lesion, CMV causes linear ulcers), caustic ingestion, or pill esophagitis
Mallory Weiss syndrome
partial thickness mucosal lacerations at gastroesophageal junction due to severe vomiting
alcoholics and bulimics
pt presents with triad of dysphagia, iron deficiency anemia, and esophageal webs
Plummer vinson syndrome
increased risk of esophageal squamous cell carcinoma
“Plumbers DIE”
Pt presents with esophageal smooth muscle atrophy as part of CREST syndrome
Sclerodermal esophageal dysmotility
decreased LES pressure and dysmotility –> acid reflux and dysphagia –> stricture, barrett esophagus, and aspiration
The replacement of nonkeratinized stratified squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells in distal esophagus)
Barrett esophagus
can cause esophageal adenocarcinoma
Esophageal cancer that affects the upper 2/3rd of the esophagus and is most common worldwide
squamous cell carcinoma due to alcohol, hot liquids, caustic strictures, smoking, achalasia
Esophageal cancer that affects the lower 1/3 of the esophagus and is most common in america
Adenocarcinoma due to chronic GERD, Barrett esophagus, obesity, smoking, achalasia
Why do NSAIDs cause erosions in acute gastritis?
they decrease PGE2 which decreases gastric mucosa protection
Curling ulcer in acute gastritis
Burns cause curling ulcer which has hypovolemia –> mucosal ischemia
“burned by the curling iron”
Cushings ulcer in acute gastritis
Brain injury causes increase in vagal stimulation causes increase in ACh and thus H+ production
“always cushion the brain”
hypochlorhydria
refers to states where the production of hydrochloric acid in gastric secretions of the stomach and other digestive organs is absent or low,
H pylori in chronic gastritis
affects antrum first and spreads to body of stomach
worry about MALT lymphoma
Menetrier disease
Hyperplasia of gastric mucosa causes hypertrophied rugae and causes excess mucus production with resultant protein loss and parietal cell atrophy with decrease acid production
precancerous
pt presents with epigastric pain, anorexia, weight loss, vomiting, edema (due to protein loss)
Gastric cancers are commonly _____
adenocarcinoma
can present with acanthosis nigricans and leser trelat sign
Associated with blood type A
Diffuse gastric cancer
signet ring cells (mucin filled cells with peripheral nuclei)
stomach wall grossly thickened and leathery (linitis plastica)
Intestinal gastric cancer
commonly on lesser curvature and looks like ulcer with raised margins
Virchow node
involvement of left supraclavicular node by metastasis from stomach
Krukenberg tumor
bilateral metastases to ovaries. abundant mucin secreting signet ring cells
Sister Mary joseph nodule
subq periumbilical metastasis
affect of meals on gastric ulcer? duodenal ulcer?
Gastric ulcer - greater pain with meals + weight loss
duodenal ulcer-paind ecreases with meals + weight gain
Ruptured gastric ulcer on the lesser curvature of stomach
bleeding from left gastric artery
Ruptured ulcer on the posterior wall of duodenum
bleeding from gastroduodenal artery
Duodenal hemorrhhaging is more common in post or ant?
post>ant
Duodenal perforation is more common in aant or post?
ant>post
Celiac disease/gluten sensitive enteropathy/celiac sprue
autoimmune mediated intolerance of gliadin protein in gluten –> malabsorption and steatorrhea. Can get dermatitis herpetiformis
Celiac dz is associated with what HLA?
HLA-DQ2
HLA-DQ8
couldnt eat her 28 DQ icecreams
pt presents with IgA anti tissue transglutaminase (IgA tTG), anti-endomysial, anti deamidated gliadin peptide antibodies
Celiac dz
- villous atrophy
- crypt hyperplasia
- intrapeithelial lymphocytosis
primarly affects distal duodenum and or proximal jejunum
Dxylose test
passive absorbed in proximal small intestine; blood and urine levels decrease with mucosa defects or bacterial overgrowth
Lactose hydrogen breath test
positive for lactose malabsorption if post lactose breath hydrogen value rises>20 ppm compared with baseline
Tropical sprue
similar to celiac sprue except responds to antibiotics
associated with megaloblastic anemia due to folate deficiency and later B12 deficiency
Disease caused by Tropheryma Whipplei, an intracellular gram +
PAS + foamy macrophages in intestinal lamina propria
Whipple disease causes mostly in older men
cardiac symptoms
Arthralgias
Neurologic symptoms
“foamy whipped cream in a CAN”
Crohns disease
- Any portion of GI tract can be affected but mostly ileum and colon
- Skip lesions with rectal sparring
- transmural inflammation causing fistulas
- Cobblestone mucosa, creeping fat, bowel wall thickening causes string sign on barium swallow xray
- non caseating granulomas and lymphoid aggregates
- Th1 mediated
- kidney stones due to calcium oxalate and gallstones
- anti-saccharomyces cerevisiae antibodies (ASCA)
Ulcerative colotis
- Continuous colonic lesions that extend proximally
- Rectal involvement
- mucosal and submucosal only
- superficial and deep ulcerations
- loss of haustra causes lead pipe appearance on imaging
- bloody diarrhea
- no granulomas
- Th2 mediated
- toxic megacolon
- associated with primary sclerosing cholangitis (p-ANCA)
Cause of appendicitis in adults? in children?
in adults its fecalith
In children its lymphoid hyperplasia
Diverticulum
blind pouch protruding from the alimentary tract that communicates with the lumen of the gut
Only mucosa and submucosa outpuch. Especially where the vasa recta perforate muscularis externa
if acquired then its a “false diverticula” or pseudodiverticulum
All gut layers outpouch
True diverticulum (i.e. Meckels)
Diverticulosis is common in the
sigmoid colon and caused by increase intraluminal pressure and focal weakness in colonic wall
can get painless hematochezia or diverticulitis –> LLQ, fever, leukocytosis
Patient is an elder male with dysphagia, obstruction, gurgling, aspiration, foul breath, and a neck mass
Zenker diverticulum - pharyngoesophageal false diverticulum
esophageal dysmotility causes hernaition of mucosal tissue at killian triangle between the thyropharyngeal and cricopharyngeal parts of the inferior pharygneal constrictor
Meckels diverticulum
true diverticulum
due to the persistence of the vitelline (omphalomesenteric) duct
findings: hematochezia, melena, RLQ pain, intussusception, volvulus, or obstruction near terminal ileum
Rules of 2 for Meckels diverticulum
2x more in males 2 inches long 2 feet from ileocecal valve 2% of population first 2 years of life 2 types of epithelia (gastric and pancreatic)
Patient presents with bilious emesis, abdominal distention, and failure to pass meconium within 48 hours (chronic constipation). A portion of the colon is dialated. Patient mentions having explosive expulsion of feces (squirt sign) and now has an empty rectum on digital exam
Hirschsprung disease
Congential megacolon that lacks gangion cells/enteric nervous plexus (auerbach and meissner plexuses) in distal segment of colon.
dilated portion is near the aganglionic segment and results in transition zone
risk increases with down syndrome
RET mutation int he RecTum
Treatment for hirschsprung disease
is resection
What is seen in the anomaly of improper midgut rotation
malrotation will show small bowel clumped on right side and colon on left
there is also formation of fibrous bands called ladd bands
can lead to volvulus and duodenal obstruction
What causes the coffee bean sign on xray
sigmoid volvulus
twisting of portion of bowel around its mesentery which can lead to obstruction and infarction
Type of volvulus seen in children? in elderly?
children see midgut volvulus
elderly see sigmoid volvulus which causes the coffee bean sign
What is intussusception and where is it commonly seen?
telescoping of proximal bowel segment into the distal segment, commonly at ileocecal junction
Patient presents with intermittent abdominal pain with currant jelly stools. Exam found a sausage shaped mass and the ultrasound showed the “target sign”
Intussusception
commonly due to Meckels diverticulum (children) or intraluminal mass (adults). Mostly children
can be related to Henoch Schonlein purpura, rotavirus, and recent viral infection where peyer patch hypertrophy creates lead point
Patient presents with abdominal pain thats out of proportion to physical findings, also you note red currant jelly stools
Acute mesenteric ischemia - critical blockage of intestinal blood flow often due to embolic occlusion of SMA –> causing small bowel necrosis
Patient has postprandial epigastric pain. She now has food aversion and weight loss
Chronic mesenteric ischemia - intestinal angina
atheroslerosis of celiac artery, SMA, or IMA causes intestinal hypoperfusion
Pt has crampy abdominal pain followed by hematochezia. On imaging you notice a thumbprint sign due to mucosal edema/hemorrhage
colonic ischemia - reduction of intestinal blood flow causes ischemia. commonly at watershed areas (splenic flexure and distal colon)
elderly
Angiodysplasia
- tortuous dilation of vessels –> hematochezia
- mostly found in R. sided colon
- older patients
- associated with aortic stenosis and von willebrand disease
- confirmed with angiography
What is the most common cause of small bowel obstruction?
adhesions
Ileus
intestinal hypomotility without obstruction
Meconium ileus is commonly seen in _____
in CF, meconium plug obstructs intestine, preventing stool passage at birth
Necrotizing enterocolitis
Seen in premature formula fed infants with immature immune system
primarily colonic necrosis with possible perforation
can lead to pneumatosis intestinalis, free air in abdomen, portal venous gas
Hamartomatous polyps
solitary lesions
no significant risk
normal colonic tissue with distorted architecture
associated with peutz-jeghers syndome and juvenile polyposis
Inflammatory pseudopolyps are seen in ___
inflammatory bowel disease - mucosal erosions
submucosal polyp examples
lipoma
leiomyomas
fibroma
What polyp type is most common
hyperplastic polyps that can evolve into serratted polyps and more advanced lesions
mostly in rectosigmoid region
adenomatous polyps
malignant potential (villous on histo > maligant potential than tubular)
mutations in APC and KRAS cause chromosomal instability
Serrated polyps
Premalignant –> 20% colorectal cancer
“sawtooth pattern” of crypts on biopsy
CpG island methylator phenotype (CIMP; cytosine base followed by guanine)
Defect may silence the MMR gene. Mutations lead to microsatellite instability and mutations in BRAF
thousands of polyps arise starting after puberty in a pancolonic fashion and always involves the rectum
Familial adenomatous polyposis –> 100% CRC
Autosomal dominant mutation of APC tumor suppressor gene on chromosome 5q21
give prophylactic colectomy
Gardner syndrome (familial colorectal polyposis)
1) FAP + osseous and soft tissue tumors
2) congential hypertorphy of retinal pigment epithelium
3) impacted/supernumerary teeth
Turcot syndrome
FAP/Lynch syndrome +malignant CNS tumor
Autosomal dominant syndrome featuring numerous hamartomas throughout GI tract. Pt also has hyperpigmented mouth, lips, hands, genitalia
Peutz-Jeghers syndrome
associated with increased risk of breast and GI cancers
Autosomal dominant syndrome in children <5 yo featuring numerous hamartomatous polyps in the colon, stomach, small bowel
Juvenile polyposis syndrome
associated with increased risk of CRC
Lynch syndrome
Hereditary nonpolyposis colorectal cancer (HNPCC)
autosomal dominant mutation of DNA mismatch repair genes with subsequent microsatellite instability
80% progress to CRC and proximal colon is always involved
Lynch syndrome is commonly associated with what cancers
- endometrial
- ovarian
- skin cancers
Colorectal cancer is most common in
Rectosigmoid>ascending>descending
if on the right side we see bleeding
If on the left side we see obstruction
see “apple core” on barium enema xray
ascending colorectal cancer
exophytic mass
Iron deficieny anemia
weight loss
if man >50 yo or postmenopausal woman has iron deficiency anemia, you have high suspicion
Descending colorectal cancer
infiltrating mass
partial obstruction
colicky pain
hematochezia
Screening for colorectal cancer
at 40 yo if family history or 10 years before the family members presentation
normally starts at 50 yo
use CEA marker for monitoring recurrence
Molecular pathogenesis of colorectal cancer
chromosomal instability pathway: mutations in APC cause normal colon to be at risk. Then a KRAS mutation will result in adenoma. Loss of tumor suppressor genes like p53 will result in carcinoma
APC loss causes decrease intercellular adhesion and increase proliferation
KRAS mutation causes unregulated intracellular signaling
Loss of tumor suppressor causes increase in tumorigenesis
Mutations in FAP? mutations in lynch?
FAP is related to APC mutation (chromosomal instability pathway)
Lynch syndrome is mutation or methylation of mismatch repair genes like MLH1 (microsatellite instability pathway)
This is a common and potentially fatal bacterial infection in patients with cirrhosis and ascites
spontaneous bacterial peritonitis also known as primary bacterial peritonitis
mostly aerobic gram negative orgnaisms
paracentesis of ascitic fluid absolute neutrophil count (ANC) >250
first line treatment is 3rd generation cephalosporin
aspartate aminotransferase (AST)
AST>ALT in alcoholic liver disease
if AST>ALT in non alcoholic liver disease then worry it has progressed to advanced fibrosis or cirrhosis
alanine aminotransferase (ALT)
ALT>AST in liver disease
alkaline phosphatase
increases in cholestasis,infiltrative disorders, bone disease
gamma glutamyl transpeptidase
increases in various liver and biliary diseases
but not in bone disease
associated with alcohol use
Bilirubin
increases in liver dz
Albumin
decreases in advanced liver dz
Prothrombin time
increases in advanced liver disease because decrease in production of clotting factors
Platelets
decrease in advanced liver disease (drop in thrombopoietin)
portal hypertension (splenomegaly/splenic sequestration)
Rare often fatal childhood hepatic encephalopathy
reye syndrome
“reye of sunSHINE”
S-steatosis of liver/hepatocytes H-hypoglycemia/hepatomegaly I-Infection (VZV, influenza that has been treated with aspirin) N-not awake (coma) E (encephalopathy)
mitochondrial abnormalities
fatty liver due to microvesicular fatty change
Why does aspirin increase the risk of reyes syndrome
aspirin decreases beta oxidation by reversible inhibition of mitochondrial enzymes
avoid in children unless have kawasaki disease
Alcoholic hepatitis histo findings
swollen and necrotic hepatocytes with neutrophilic infiltration
mallory bodies- intracytoplasmic eosinophilic inclusions of damaged keratin filaments
alcoholic liver disease progression
hepatic steatosis –> alcoholic hepatitis –> alcoholic cirrhosis
Non alcoholic fatty liver disease
ALT>AST
metabolic syndrome (insulin resistance)
obesity –> fatty infiltration of hepatocytes –> cellular ballooning and eventual necrosis
may cause cirrhosis and HCC independent of alcohol use
hepatic encephalopathy
cirrhosis causes a portosystemic shunt which decreases NH3 metabolism –> neuropsychiatric dysfunction
due to increased production and absorption OR decreased NH3 removal
treatment: lactulose if theres increased generation
and rifaximin or neomycin to decrease NH3 producing gut bacteria
Findings seen in hepatocellular carcinoma/hepatoma and how to dx
jaundice tender hepatomegaly ascites polycythemia anorexia spreads hematogenously
dx due to increase alpha feto protein, ultrasound, contrast CT/MRI, biopsy
The most common benign liver tumor that occurs at 30-50 yo. Do not biopsy because of risk of _____
cavernous hemangioma
do not because of hemorrhage risk
What benign liver tumor is often related to oral contraceptibe or anabolic steroid use
hepatic adenoma
may regress or rupture (abd pain and shock)
Liver tumor that malignant and related to arsenic and vinyl chloride exposure. Endothelial origin
Angiosarcoma
Thrombosis or compression of hepatic veins with centrilobular congestion and necrosis resulting in congestive liver disease. Risk in hepatocellular carcinoma/hepatoma, hypercoagulable states etc.
Budd chiari syndrome
hepatomegaly ascites varices abd pain liver failure absence of JVD may cause a nutmeg liver
alpha1-antitrypsin deficiency
results in misfolded gene product protein aggregates in hepatocellular ER –> cirrhosis with PAS + globules in liver
young pt, liver damage, dyspnea, no history of smoking
how does alpha1-antitrypsin deficiency affect the lings?
decrease in alpha1-antitrypsin causes uninhibited elastaste in alveoli and this decrease in elastic tissue and panacinar emphysema
Jaundice is due to an increase in ______ and is caused by _______, ______, ______, ________
high bilirubin
think HOT liver
H-hemolysis
O-obstruction
T-Tumor
Liver disease
Unconjugated (indirect) hyperbilirubinemia
hemolytic
physiologic (newborns)
crigler-najjar
Gilbert syndrome
conjugated (direct) hyperbilirubinemia
biliary tract obstruction biliary disease (primary sclerosing cholangitis and primary biliary cholangitis) excretion defects (dubin johnson syndrome or rotor syndrome)
Mixed (direct and indirect) hyperbilirubinemia
hepatitis
cirrhosis
Physiologic neonatal jaundice is due to immature _____
immature UDP-glucuronosyltransferase –> unconjugated hyperbilirubinemia –> jaundice/kernicterus (deposition of unconjugated lipid soluble bilirubin in the brain, particularly basal ganglia)
Treatment for physiologic neonatal jaundice
phototherapy (non-UV) isomerizes unconjugated bilirubin to water soluble form
occurs after first 24 hours of life and usually resolves without treatment in 1-2 weeks
______ are converted to bilirubin. _______ Bilirubin is bound to serum albumin and transferred to the liver where it is turned into _______ by ________. ______ is excreted into bile
Heme molecules (from hemoglobin)
Unconjugated (or indirect) –> water insoluble
conjugated (direct)/bilirubin diglucuronide –> water soluble
UDP-glucuronosyl transferase
Conjugated (direct) bilirubin is excreted into bile.
All hereditary hyperbilirubinemias are ______
autosomal recessive
Gilbert syndrome
Mild decrease in UDP-glucuronosyltransferase conjugation and impaired bilirubin uptake
increases unconjugated bilirubin without overt hemolysis
Crigler-Najjar syndrome, type I
absent UDP-glucuronosyltransferase causes increase in unconjugated bilirubin
presents early and die within few years. Need liver transplant to cure. Type II is less severe and responds to phenobarbital which increases liver enzyme synthesis
jaundice
kernicterus - bilirubin deposition in brain
Dubin Johnson syndrome
conjugated hyperbilirubinemia due to defective liver excretion
grossly black dark liver
benign
Rotor syndrome
similar to dubin johnson syndrome
milder and without black liver
due to impaired hepatic uptake and excretion
Wilsons disease (hepatolenticular degeneration) is _____ inheritence and a mutation in _______. Describe the pathophys
autosomal recessive
mutation in hepatocyte copper transporting ATPase (ATP7B gene; chromosome 13)
decrease copper incorporation into apoceruloplasmin and excretion into bile –> drop in serum ceruloplasmin
copper accumulates in liver, brain, cornea, kidneys
Kayser fleischer rings
deposits in descemet membrane of cornea in wilsons disease
deficits in wilsons disease
- neurologic
- liver
- psychiatric
- kayser fleischer rings
- hemolytic anemia
- renal disease
tx for wilsons disease
chelation with penicillamine or trientine, oral zinc
Hemochromatosis inheritence, mutation, HLA type
autosomal recessive
C282Y mutation on HFE gene of chromosome 6
associated with HLA A3
Abnormal iron sensing and increased intestinal absorption that causes iron overload. What is this disease? where does iron like to accumulate?
hemochromatosis
in liver, pancreas, skin, heart, pituitary, joints
iron can be identified with prussian blue stain
Patient is 40 yo and has liver cirrhosis, diabetes mellitus, and is now complaining of increase skin pigmentation. on blood work you notice there is >20 g total body iron. What is the pt diagnosis and what else are they at risk for? What is the common cause of their death? treatment?
hemochromatosis
restrictive cardiomyopathy (classic) or dilated cardiomyopathy (revesible)
hypogonadism
arthropathy due to calcium pyrophosphate deposition, esp in metacarpophalangel joints
high risk of HCC death
Treatment for hemochromatosis
repeated phlebotomy
chelation with deferasirox
deferoxamine
oral deferiprone
Pt presents with pruritis, jaundice, dark urine, and light colored stool. You also notice hepatosplenomegaly. Labs show high conjugated bilirubin, cholesterol, and ALP
Biliary tract disease
“onion skin” bile duct fibrosis
primary sclerosing cholangitis
bile duct fibrosis causes alternating strictures and dilation with beading of intra and extrahepatic bile ducts on ERCP
classically seen in middle aged men with IBD
associated with ulcerative cholitis, p-ANCA +, and high igM
Primary biliary chilangitis
autoimmune reaction that causes lymphocytic infiltrate + granulomas –> destruction of lobular bile ducts
classically seen in middle aged women
anti-mitochondrial antibody + and high igM
secondary biliary cholangitis
extrahepatic biliary obstruction that increases pressure in intrahepatic ducts –> injury/fibrosis and bile stasis
usually in patients with known obstructive lesions and may be complicated with ascending cholangitis
high cholesterol, high bilirubin, low bile salts, and gallbladder stasis can cause ____? What are the main risk factors for this disease?
Gallstones (cholelithiasis)
80% are cholesterol stones (radiolucent unless calcified)
Can also have pigment stones (black is radiopaque and brown is radiolucent)
4 Fs- female, fat, fertile (multiparity), forty
Biliary colic
pain occurs due to a gallstone temporarily blocking the bile duct.
choledocholithiasis
presence of gallstones in common bile duct
elevated ALP,GGT, direct bilirubin, and or AST/ALT
gallstone ileus
fistula between gallbladder and GI tract causes stone to enter GI lumen and obstruct at the ileocecal valve (narrowest point)
can see air in biliary tree (pneumobilia)
What kind of cancer is common in the porcelain gallbladder
calcified gallbladder has high risk of gallbladder adenocarcinoma
have prophylactic cholecystectomy
Charcot triad of cholangitis
jaundice
fever
RUQ pain
Reynolds pentad of cholangitis
charcots triad of cholangitis + altered mental status and shock
jaundice Fever RUQ pain altered mental status shock (hypotension)
acute pancreatitis
autodigestion of pancreas by pancreatic enzymes
on imaging the pancreas is surrounded by edema
causes:
- idiopathic
- gallstones
- Ethanol
- Trauma
- Steroids
- Mumps
- Autoimmune
- Scorpion sting
- Hypercalcemia/hypertriglyceridemia (>1000)
- ERCP
- Drugs
“I GET SMASHED”
Diagnosis criteria for acute pancreatitis
2 of the 3
- acute epigastric pain that radiates to the back
- high serum amylase or lipase (more specific) to 3x upper limit of normal
- characteristic imaging findings
complications of acute pancreatitis
pseudocyst lined by granulation tissue not epithelium abscess necrosis hemorrhage infection organ failure hypocalcemia
Chronic pancreatitis
chronic inflammation, atrophy, calcification of the pancreas
caused by alcohol abuse and genetic predisposition
complicated by pancreatic insufficiency ( <10% function and may manifest with steatorrhea and fat soluble vitamin deficiency, diabetes mellitus)
and pseudo cysts (surrounded by granulation tissue not epithelium)
Pancreatic adenocarcinoma
very aggressive tumor arising from pancreatic ducts (disorganized glandular structure with cellular infiltration)
often metastatic at presentation
associated with CA19-9 tumor marker and also CEA
patients presents with weight loss, redness and tenderness on palpation of extremities, and pain that radiates to the back
pancreatic adenocarcinoma
weight loss is due to malabsorption and anorexia
migratory thrombophlebitis (red and tender) is trousseau syndrome
courvoisier sign
courvoisier sign
obstructive jaundice with palpable, nontender gallbladder
