Flashcards in GI Tract Deck (493):
What are aphtous ulcers?
- painful superficial ulceration of oral mucosa
- stress induced, resolves spontaneously, often recurrs
How can one ID an aphtous ulcer
grayish base surrounded by erythema. the gray base represents granulation tissue
what is behcet's syndrome?
recurrent aphtous/genital ulcers, uveitis
- immune complex vasculitis : small vessels
- can be seen after viral infxn
What do oral herpes look like?
shallow, painful, red ulcers
- HSV 1 associated
When is the primary oral herpes infxn usually?
Virus stays dormant in ganglia of trigeminal nerve
- stress/ sunlight cause reactivation of virus
- vesicles often arise on lips (cold sores
What are the risk factors for SCC of mouth?
tobacco and EtOH
- floor of mouth is a common location
What are precursor lesions for SCC of mouth?
Leukoplakia or erythoplakia
What is leukoplakia?
What is hairy leukoplakia due to?
hairy, shaggy on lateral tongue
What is erythroplakia
Red plaque due to angiogenesis
- more suggestive of squamous dysplasia
What is the primitive gut tube made up of?
- incorporates yolk sac during development
- endoderm: epithelial lining of mucosa
- mesdoerm - all other layers
What are the divisions of the GI tract?
1. foregut = pharynx to duodenum
2. Midgut - duodenum to transverse colon
3. Hindgut = distal transverse colon to rectum
What are some development defects of anterior abdominal wall due to failure of...
a) rostral fold closure
b) lateral fold closure
c) caudal fold closure
a) sternal defects
b) omphalocele, gastroschisis
c) bladder exstrophy
What is gastroschisis?
extrusion of abdominal contents through lateral abdominal folds; not covered by peritoneum. hernia is right to umbilicus
What is omphalocele?
persistence of herniation of abdominal contents into umbilical cord, covered by peritoneum and amnion of umbilical cord
What are other things than an omphalocele associated w/?
Beckwith Wiedemann syndrome
congenital heart dz
What are jejunal, ileal, and colonic atresia due to?
vascular accident (apple peel atresia)
- bilious vomiting
What is seen on x-ray for the small and large bowel atresias?
1. distended bowl proximal to atresia
2. absence of air distal to atresia
What are the steps for midgut development?
6th wk = midgut herniates thru umbilical range
10th wk = returns to abdominal cavity and rotates around SMA
What is the most common esophagus anomaly?
esophageal atresia w/ distal tracheoesophageal fistula due to malformation of trachesophageal septum
What is the clinical presentation of trachesophageal fistula?
drooling, choking, and vomiting w/ first feeding
- allows air to enter stomach (visible on CXR)
- cyanosis is secondary to larngospasm (to avoid reflux related aspiration)
- polyhydraminos b/c can't digest amniotic fluid
What is the clinical test to dx trachesophageal fistula?
failure to pass NG tube into stomach
What is a H type esophagus anomaly?
What is seen on CXR of a pure esophageal atresia?
What is congenital pyloric stenosis?
- hypertrophy of pylorus causes obstruction
- palpable olive mass in epigastric region and nonbilious projectile vomiting at 2 wks of age
What is Rx for congenital pyloric stenosis?
who is congenital pyloric stenosis common in?
first born males
What is the pancreas derived from?
What makes up the components of the pancreas?
Ventral pancreatic bud and dorsal pancreatic bud
What does the ventral pancreatic bud form?
pancreatic head and main pancreatic duct
What does the dorsal pancreatic bud form?
body, tail, isthmus, and accessory pancreatic bud
What is annular pancreas?
ventral pancreatic bud abnormally encircles 2nd part of duodenum
- forms a ring of pancreatic tissue that may causes duodenal narrowing
2/3 pts usually Asx
What is associated a/ infantile annular pancreas?
polyhrdraminos, Down's, esophageal and duodenal atresia, imperforate anus, Meckel's diverticulum
What is associated w/ adult annular pancreas?
ab pain, postprandial fullness, nausea, peptic ulceration, pancreatitis
What is pancreas divisum?
ventral and dorsal parts fail to fuse at 8 wks
- MC pancreatic congenital anomaly
- usually Asx
- drainage is preserved via major/minor papillae
What are signs/symptoms of pancreas divisum?
occurs when orifice of minor papillae inadequately drains the accessory ducts
- recurrent pancreatitis
What does the spleen arise from?
arises in mesentery of stomach (mesodermal) but is supplied by foregut (celiac artery)
What are the retriperitoneal structures?
- include GI structures that lack a mesentery and non GI structures.
Aorta and IVC
Duodenum (2nd and 3rd part)
Pancreas (except tail)
Colon (descending and ascending)
Esophagus (lower 2/3)
Rectum (lower 2/3)
What is the parietal peritoneum innervated by?
intercostal, ilioinguinal, and iliohypogastric nerves
- sensitive and somatic pain = focal region of pain
What communicates w/ the lesser and greater sac in the GI tract?
omental foramen aka epiploic foramen of Winslow
What does the falciform ligament connect?
liver to anterior abdominal wall
- divides liver into 2 lobes
What is contained in the falciform ligament?
ligamentum teres hepatis (derivative of fetal umbilical vein)
What does the hepatoduodenal ligament connect?
liver to duodenum
What does the hepatoduodenal ligament contain?
portal triad thus ligament can be compressed b/w thumb and index finger to control bleeding.
What does the gastrohepatic ligament connect?
liver to lesser curvature of stomach
- may be cut during surgery to access lesser sac
- separates greater and less sac on the right
What does the gastrophepatic ligament contain?
What does the gastrocolic ligament connect and contain?
- greater curvature to transverse colon
- gastroepiploic arteries
- parter of greater omentum
What does the gastrosplenic ligament connect and contain?
- greater curvature to spleen
- contains short gastric, left gastroepiploic vessels
- separates greater and lesser sac on left
What does the splenorenal ligament connect and contain?
spleen to posterior abdominal wall
- contains splenic artery and vein, tail of pancreas
What happens during the early development of the GI tract?
1. dorsal embryonic mesentery - suspends all guts from dorsal body wall
2. ventral embryonic mesentery - suspends foregut from ventral body wall
3. visceral developement: spleen, pancreas, liver and biliary structures develop w/in mesentery
What are the layers of the digestive tract?
3. Muscularis externa
What makes up the mucosa of the GIT?
lamina propria (support) - loose CT
muscularis mucosa (motility) - thin SM
What makes up the submucosa of the GIT?
submucosal nerve plexus (meissner's) - loose CT, mucus secreting glands
What makes up the muscularis externa of the GIT?
includes myenteris nerve plexus (Auerbach"s) - peristalsis
- inner circular and outer longitudinal muscle layer
What makes up the serosa of the GIT?
when intraperitoneal called serosa
- when retroperitoneal called adventitia
How deep do ulcers extend? and erosions?
Ulcers- into submucosa, inner or outer muscular layer
Erosions - mucosa layer only
What are the frequencies of basal electric rhythm in the GIT?
1. stomach - 3 waves/min
2. Duodenum - 12 waves/ min
3. Ileum - 8-9 waves/min
What is the histology of the esophagus?
nonkeratinzed stratified squamous epithelium and mucous glands
What is the histology of the stomach?
gastric glands and pits, mucous glands, chief, parietal, and EE cells
What is the histology of the duodenum?
villi and microvilli increase absorptive surface, Brunner's glands in submucosa, crypts of Lierberkuhn, goblet, paneth and EE cells
- simple columnar epithelium
What is the histology of the jejunum?
villi, microvilli, goblet, paneth, and EE cells
- plicae circularies and crypts of Lieberkuhn
- simple columnar epithelium
What is the histology of the ileum?
- M cells
- Peyer's patches (lamina propria, submucosa)
- Plicae circulares (proximal ileum) and crypts of Lieberkuhn
- largest number of goblet cells in the small intestine to secrete Bicarb
- simple columnar epithelium
What is the histology of the colon?
crypts but NO villi
numerous goblet cells
absorptive cells, EE cells, lymphoid follicles
- Na/H20 reabsorption
K/ Bicarb secretion
What is the function of the GIT immune function?
- produce Vit K
- Assists digestion
- protect against overgrowth of pathogenic bacteria
What is the location of the esophagus?
behind trachea and left atrium
- enters abdominal cavity through esophageal hiatus of diaphragm at T10 level
What are the 4 narrow points of the esophagus?
1. at origin - pharynx
2. arch of aorta
3. left primary bronchiole
4. esophageal hiatus
Compare the muscles found in the esophagus?
upper 1/3 - skeletal muscle
lower 1/3 - smooth muscle
- middle 1/3 = mixed
What is the blood supply of the esophagus?
1. upper 1/3 = inferior thyroid artery branches
2. middle 1/3 = bronchial artery and aorta
3. lower 1/3 = inferior phrenic and left gastric artery branches
What is the venous drainage of the esophagus?
1. upper 1/3 = inferior thyroid veins
2. middle 1/3 = bronchial, azygos, and hemiazygos
3. portal venous system
What are the abdominal aorta branches?
1. Celia artery at T 12
2. Left inferior phrenic artery
3. SMA at L1
4. left middle suprarenral artery
5. renal arteries at L1
6. Gonadal arteries
7. IMA at L 3
8. Bifurcation of abdominal aorta at L4
What is SMA syndrome?
when transverse portion of duodenum is entrapped b/w SMA and aorta causing intestinal obstruction
What does the celiac artery supply?
foregut --> stomach to proximal duodenum, liver, gallbladder, pancreas, spleen (mesoderm)
What does the SMA supply?
midgut --> distal duodenum to proximal 2/3 of transverse colon
What does the IMA supply?
hindgut --> distal 1/3 of transverse colon to upper portion of rectum (above pectinate line)
How is the GIT innervated?
1. foregut - vagus and T12/L1 vertebral level
2. midgut - vagus and L1 vertebral level
3. hindgut - pelvic and L3 vertebral level
What is the referred pain for the GIT?
1 foregut - epigastric
2. midgut - umbilical
3. hindgut - hypogastric
What is the role of Paneth cells?
produce lysozymes/defensins to protect from pathogenic microorganisms, found at the base of crypts
What are the branches of celiac trunk?
common hepatic, splenic, left gastric
What are the branches of the common hepatic artery?
1. right gastric artery
2. hepatic artery proper
3. gastroduodenal artery ==> anterior superior pancreaticoduodenal and right gastroepiploic artery
What are some collateral circulations in the GIT?
1. superior epigastric (internal thoracic/mammary) and inferior epigastric (external iliac)
2. superior pancreaticoduodenal (celiac trunk) and inferior (SMA)
3. middle colic (SMA) and left colic (IMA)
4. superior rectal (IMA) and middle/inferior rectal (internal iliac)
What are the sites for the portosystemic anastomoses?
1. esophagus - esophageal varices
2. umbilicus - caput medusae
3. Rectum - internal hemorrhoids
What makes up the liver's dual blood supply?
1. 75% due to portal vein
2. 25% due to hepatic arteryy
What veins are involved in esophageal varices?
left gastric and esophageal veins
What veins are involved in caput medusae?
1. paraumbilical and superficial/inferior epigastric below the umbilicus
2. paraumbilical and superior epigastric/lateral thoracic above the umbilicus
What veins are involved in internal hemorrhoids?
superior rectal and middle/inferior rectal
What is TIPS ( transjugular intrahepatic portosystemic shunt)?
shunt exists b/w portal vein and hepatic vein percutaneously relieves portal HTN by shunting blood to systemic circulation
How does the liver develop?
- it's an outgrowth of foregut endoderm
- hepatic diverticulum enters vental mesentery
What does the embryonic liver differentiate into?
1. distally into liver and gall bladder
2. proximally into biliary duct system
What are hepatocytes?
- functionally polarized liver cells
- has multiple apical/basal surfaces
1. Apical surface is faces bile canaliculi
2. Basal surface is next to sinusoids
What is the space of Disse?
b/w capillary endothelial cells and hepatocytes
What is a kuffer cell?
What is an Ito cell (stellate cell)?
mesenchymal cells - store fat soluble vitamins
What are the different zones in the liver anatomy?
Zone 1 - periportal zone
Zone 2 - intermediate zone
Zone 3 - pericentral vein (centrilobular)
What zone in the liver is affected by viral hepatitis?
What is the function of zone 1 in the liver?
oxidative functions and synthesis of proteins/cholesterol
What zone in the liver plays a role in glycolysis, lipogenesis, alcohol detoxification?
What zone is affected 1st by ischemia?
What zone is the site of alcoholic injury?
what zone is most sensitive to toxic injury
what zone contains the P450 system?
What is a portal lobule in the liver?
- triangular structure
central vein at each corner
portal tract in center
bile flows from periphery to center
How do blood and bile flow in the liver?
1. blood flows from portal triad to central vein
2. bile flows from central vein to portal triad
What makes up the portal triad?
1. biel ductule
2. hepatic artery
3. portal vein
What is the function of the gall bladder?
- stores bile
What artery supplies the gall bladder?
cystic artery (branch of right hepatic artery)
What are the different parts of the pancreas bordered by?
1. uccinate process - crossed by SMA
2. neck - anterior to hepatic portal vein
3. body = left and anteriorly to aorta
What makes up the biliary tree?
1. The left and right hepatic duct connect to form the common hepatic duct
2. Common hepatic duct combines w/ the cystic duct to form the common bile duct
3. Common bile duct combines w/ main pancreatic duct to expel their contents at the ampulla of vater
What can cause obstruction of the common bile duct
gallstones at ampulla of Vater and in the common bile duct
- tumors that arise in head of pancreas
What does the femoral triangle contain?
femoral vein, artery, and nerve
what is the order of contents in the femoral region?
NAVEL from lateral to medial
- Nerve, artery, vein, empty, lymphatics
What is the femoral sheath?
fascial tube 3/4 cm below the inguinal ligament
- contains the femoral vein, artery, and canal (deep inguinal lymph nodes) but NOT femoral nerve
What are the border of the femoral triangle?
1. superior - inguinal ligament
2. laterally - sartorius muscle
3. medially - adductor longus muscle
What does the inguinal canal contain?
1. in women = found ligament of uterus
2. men = spermatic cord and contents
What is a diaphragmatic hernia?
abdominal structures enters the thorax
- may often occur in infants as a result of defective development of pleuroperitoneal membrane; complicated by lung hypoplasia
- most commonly a hiatal hernia
What is a hiatal hernia?
- stomach herniates upward through the esophageal hiatus of the diaphragm
What is a sliding hiatal hernia?
GE junction is displaced upward
- hourglass stomach
What is paraesophageal hernia?
- GE junction is normal
- fundus protrudes into the thorax
What is indirect inguinal hernia?
- goes thru the interal (deep) inguinal ring, external (superficial) inguinal ring, and into the scrotum
- enters internal inguinal ring lateral to inferior epigastric artery
What does an indirect inguinal hernia take place in infants?
- due to failure of processus vaginalis to close ( can form hydrocele); much more in common in males
What does an indirect inguinal hernia follow?
the path of descent of testes
- covered by all 3 layers of the spermatic fascia
What is a direct inguinal hernia?
- goes thru Hesselbach's triangle
- bulges directly through the abdominal wall medial to inferior epigastric artery
- goes thru external inguinal ring only
- covered by external spermatic fascia
Who does a direct inguinal hernia occur in?
How to remember the indirect and direct inguinal hernias?
MD's dont LIe:
Meidal to inferior epigastric artery = Direct
Lateral to inferior epigastric artery = Indirect
What is a femoral hernia?
- protrudes below inguinal ligament thru the femoral canal below and lateral to pubic tubercle
- more common in women
What is the leading cause of bowel incarceration?
What is in the Hesselbach's triangle?
=inferior epigastric vessels
- lateral border of rectum abdominis
- inguinal ligament
Where is gastrin made?
G cells in antrum of stomach
What is the role of gastrin?
- increase gastric acid secretion
- increases growth of gastric mucosa
- increases gastric motility
- increases pepsinogen secretion
How is gastrin regulated?
1. increased by stomach distention/alkalinization, amino acids, peptides, vagal stimulation
2. decreased by stomach pH < 1.5
What AA are potent stimulators of gastrin?
Phe and Trp
Where is CCK made?
I cells in duodenum and jejunum
What is the role of CCK?
1. increase pancreatic secretion
2. Increases gallbladder contraction
3. decrease gastric emptying
4. increase sphinter of Oddi relaxation
How is CCK regulated?
increased by fatty acids and amino acids
What does CCK act on to play it's role in the GIT?
muscarinic pathways to cause pancreatic secretion
Where is secretin made?
S cells of duodenum
What is the role of secretin?
1. increase pancreatic bicarb secretion
2. decrease gastric acid secretion
3. increase bile secretion
How is secretin regulated?
1. increased by acid, fatty acids in lumen of duodenum
Where is somatostatin made?
D cells of pancreatic islets and GI mucosa
What is the role of somatostatin?
1. decrease gastric acid and pepsinogen secretion
2. decrease pancreatic and small intestine fluid secretion
3. decrease gall bladder contraction
4. decreased insulin and glucagon release
How is somatostatin regulated?
- increased by acid entering duodenum
- decreased by vagal stimulation
Where is glucose-dependent insulinotropic peptide made? GIP
K cells of duodenum and jejunum
What is the role of GIP?
Exocrine - decrease gastric H secretion
Endocrine - increase insulin release
How is GIP regulated?
increased by fatty acids, amino acids, and oral glucose
Where is vasoactive intestinal peptide made (VIP)?
parasympathetic ganglia in sphincters, gall bladders, small intestine
What is the role of VIP?
1. increase intestinal water and electrolyte secretion
2. increase relaxation of intestinal smooth muscle and sphincters
How is VIP regulated?
- increased by distention and vagal stimulation
- decreased by adrenergic input
What is a VIPoma?
non-alpha, non-beta islet cell pancreatic tumor that secretes VIP
What are the symptoms of VIPoma?
- copious watery diarrhea
What is the role of NO?
increase SM relaxation, including LES
What is the role of motilin?
produces migrating motor complexes by initiating myenteric motor complexes
Where is intrinsic factor made?
parietal cells in stomach
What is the role of intrinsic factor?
vitamin B12 binding protein (required for B12 uptake in terminal ileum)
What happens w/ autoimmune destruction of parietal cells?
chronic gastritis and pernicious anemia
Where is gastric acid made?
parietal cells in stomach
What is the role of gastric acid?
1. decreases stomach pH
2. protects against bacteria
3. activates pepsinogen
How is gastric acid regulated?
1. increased by histamine, Ach, and gastrin
2. decreased by somatostatin, GIP, low pH, PGs, secretin
Where is pepsin made?
chief cells in stomach for protein digestion
How is pepsin regulated?
- increased by vagal stimulation, local acid, and gastrin
Where is bicarb made in the GIT?
- mucosal cells in stomach, duodenum, salivary glands, pancreas, and Brunner glands in duodenum
How is bicarb regulated?
- increased by pancreatic and biliary secretion w/ secretin and by vagal stimulation
How is saliva production regulated?
by both SNS and PNS in the salivary glands
1. parotid gland - 25% of saliva volume; serous
2. submandibular - 70% of volume; mucinous and serous
3. sublinguinal - 5% of volume; mixed as well
What are the contents of saliva?
- amylase - digests starch
- bicard - neutralized bacterial acids
- mucins - lubricate fod
- lipase, lysozyme, defensins, lactoferrin, IgA, growth factors
What is the concentration of saliva normally?
hypotonic b/c of absorption of Na and Cl at low flow rates
- isotonic w/ higher flow rates
Where is the parotid gland located?
- surface of masseter muscle
- anterior to external auditory meatus
- cranial nerve 7 runs thru it but is innervated by V3
What is the content of gastric secretions?
- high in H, K and Cl, low in Na
How does vagal stimulation activate gastric acid release from parietal cells?
1. GRP stimulates G cells to release gastrin
2. acts on M3 receptor of parietal cell for Gq to increase Ca and activate HKATPase --> This can be blocked by Atropine
How does gastrin activate gastric acid release from parietal cells?
1. binds to CCKB receptor on and Gq to increase Ca and activated HKATPase
2. activates histamine release from ECL cells
How does histamine activate gastric acid release from parietal cells?
released from ECL cells and bind to H2 receptors via Gs to increase cAMP to activate HKATPase
How do PGs, misoprostol, and somatostatin inhibit release of gastric acid from parietal cells?
- they activate Gi and decrease cAMP levels
What is the main enzyme needed to set up the H and Cl secretion from parietal cell?
- Carbonic anhydrase
exchanged Bicarb fro Cl and causes alkaline tide in venous blood
- H is secreted by HKATPase
What happens to Brunner glands in PUD?
What is the tonicity of pancreatic secretions?
1. low flow - high in Cl
2. high flow - high in Bicarb
What pancreatic enzyme is going to do the following digestions?
2. lipase, PLA2, colipase
3. proteases - trypsin, chymotrypsin, elastase, carboxypeptidases. secreted as proenzymes
What does trypsinogen do?
- converted to active trypsin and then activates teh other zymogens and creates more trypsinogen (positive feedback loop)
How is trypsinogen activated?
What enzymes are involved in carbohydrate digestion?
1. salivary amylase
2. pancreatic amylase
3. oligosaccharide hydrolases
What is the role of salivary amylase?
hydrolyzes alpha 1,4 linkages to yield disaccharides (maltose and alpha-limit dextrins)
What is the role of pancreatic amylase
hydrolyzes starch to oligosaccharides and disaccharides. highest concentration in duodenal lumen
What is the role of oligosaccharides hydrolases?
- at brush border
- rate limiting step in carb digestion
- producces monosaccharides from olio/disaccharides
- lactases, sucrases, alpha-dextrinases, etc
How are carbs absorbed in the GIT?
1. only monosaccharides are absorbed by enterocytes (glu, gal, fru)
2. glucose and galactose taken up by SGLT1 (Na dependent)
3. Fructose taken up by facilitated diffusion by GLUT-5
- all transported to blood by GLUT-2
Where is Fe absorbed in the GIT?
- as Fe2+ in duodenum via ATPases
Where is folate absorbed in GIT?
Where is B12 absorbed in GIT?
- terminal ileum along w/ bile acids, requires IF
Where are TGs absorbed in GIT?
- small intestine as CM via pancreatic lipase then goes thru lacteals
Where does the net absorption of water take place in the GIT?
What are Peyer's patches?
- unencapsulated lymphoid tissue found in lamina propria and submucosa of ileum
- contain specialized M cells that take up Ag
What happens to B cells stimulated in germinal centers of Peyer's 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 w/ intraluminal Ag
What is bile made up of?
bile salt (bile acids conjugated to glycine or taurine, making them water soluble); phospholipids, cholesterol, bilirubin, water, and ions
What is the E involved in the rate limiting step to make bile?
Cholesterol 7 alpha hydroxylase
What is the function of bile?
1. digestion/absorption of lipids and fat soluble vitamins
2. cholesterol excretion (body's only means of eliminating cholesterol)
3. antimicrobial activity via membrane disruption
What is the product of heme metabolism?
bilirubin - removed from blood by liver and conjugated w/ glucornate and excreted in bile
What are the steps of heme metabolism?
1. heme degraded to unconjugated bilirubin ( water insolube)
2. UCB binds to albumin and goes to liver
3. UDP glucuronosyltransferase conjugates the UCB so now water soluble
4. CB travels to gut and processed by bacteria to become urobilinogen
5. 80% of urobilinogen excreted in feces as stercobilin
6. 20% of urobilinogen undergoes enterohepatic cirulation and some excreted in urine as urobilin
What is the most common salivary gland tumor?
pleomorphic adenoma (benign mixed tumor)
How does a pleomorphic adenoma usually present?
- painless, mobile mass, circumscribed, recurs frequently b/c of irregular margins
What is a pleomorphic adenoma composed of?
cartilage and epithelium
What is a Warthin's tumor?
papillary cystadenoma lymphomatosum
- benign cystic tumor w/ germinal centers.
- 2nd MC tumor in salivary gland
What is the MC malignant tumor of salivary glands?
- mucoepidermoid carcinoma
What are the components of mucoepidermoid carcinoma?
- mucinous and squamous components
How does mucoepidermoid carcinoma present?
as a painful mass b/c of common involvement of the facial nerve
What is achalasia?
failure of relaxation of LES due to loss of myenteric plexus
- HIgh LES opening pressure and uncoordinated peristalsis --> progressive dysphagia to solids and liquids
How can one Dx achalasia?
- barium swallow shows dilated esophagus w/ an area of distal stenosis
When are some causes of secondary achalasia?
Chagas dz, Scelroderma (CREST syndrome)
What else is achalasia associated w/?
increased risk of esophageal SCC
What are risk factors for GERD?
EtOH, tobacco, obesity, fat rich diet, caffeine, hiatal hernia,
What are the common clinical findings of GERD?
heartburn and regurgitation due to decrease in LES tone upon lying down
- may also present w/ nocturnal cough and dyspnea, adult onset asthma,
What is esophageal varices?
painless bleeding of dilated submucosal veins in lower 1/3 of esophagus secondary to portal HTn
- MCC of death in cirrhois
What is esophagitis?
- associated w/ reflux, infxn, or chemical ingestion
What are the infxn related to esophagitis?
1. Candida - white psuedomembrane
2. HSV 1- punched out ulcers
3. CMV - linear ulcers
What is Mallory Weiss syndrome?
- mucosal lacerations at GEJ due to severe vomiting
- leads to painful hematemesis
- usually found in alcoholics and bulimics
What is BoerHaave Syndrome?
transmural esophageal rupture due to violent retching
- related to pneumothorax
What is esophageal strictures?
associated w/ lye ingestion and acid reflux
What is Plummer-Vinson syndrome?
1. Dysphagia due to esophageal webs
3. Iron deficiency anemia
What are esophageal webs?
- thin protrusion of esophageal mucosa often in upper esophagus
- increase risk of SCC
What infxn is known to infame parotid gland?
- Mumps ; also causes orchitis, pancreatitis, aseptic meningitis, serum amylase increased
What are causes of sialadenitis?
MCC is obstructing stone leading to S. Aureus and Strep Viridans infxn
- usually unilateral
What is Barrett's esophagus?
- Glandular metaplasia: replacement of nonkeratinized stratified squamous epithelium w/ intestinal epithelium in the distal esophagus
- due to chronic GERD
what can Barrett's esophagus be associated w?
esophagitis, esophageal ulcers, and increased risk of esophageal adenocarcinoma
What cancers arise in the esophagus?
1. upper 2/3 = squamous
2. lower 1/3 = adenocarcinoma
What are the risk factors for esophageal SCC?
achalasia, alcohol, tobacco, Zenker's diverticula, esophageal webs, hot liquids (china and iran)
What are the risk factors for adenocarcinoma SCC?
Barrett's esophagus, tobacco, fat (obesity), GERD
What is the lymph node drainage of the esophagus?
1. upper 1/3 = cervical
2. middle 1/3 = mediastinal or tracheobroncial
3. lower 1/3 = celiac and gastric
What are the symptoms of malabsorption syndromes?
- diarrhea, steatorrhea, wt loss, weakness, vitamin and mineral deficiencies
What is tropical sprue?
- unknown cause but responds to antibiotics
- can affect entire small bowel
- arises after infectious diseases
What is Whipple's Disease?
- infxn w/ Tropheryma whipplei (gram posiitve) - PAS stain
What are the symptoms of Whipple's Dz?
- cardiac symptoms
- neurologic symptoms are common
What is the histology of Whipple's Dz?
PAS positive foamy macrophages in intestinal lamina propria
What is the treatment for Whipple's Dz?
- IV Abx for 1 day
TMP-SMX for 1 year
What Abs are found in Celiac dz?
AutoAbs to gliadin, endomysial, transglutaminase
What is the histology of Celiac dz?
- blunting of villi
- lymphocytes in lamina propria (intraepithelially)
- crypt hyperplasia
What area of the GIT is commonly affected in Celiac dz?
What are the HLA associations of Celiac dz?
DQ2 and DQ8
What is associated w/ Celiac sprue?
1. Dermatits Herpetiforms - due to IgA deposition at tip of dermal papillae
- resolves w/ gluten free diet
2. moderately increased risk of malignancy - T cell lymphoma
What is the pathogenesis of celiac dz?
- deamidated gliadin is presented by APCs via MHC II
-helped T cells mediate tissue damage
What is the most common disaccharidase deficiency?
lactase deficiency --> milk intolerance
- osmotic diarrhea
- abdominal distention
What does acquired disaccharidase deficiency arise from?
aging and GI infxn
How do you dx lactose tolerance test?
positive for lactase deficiency if
1. admin of lactose produces symptoms
2. glucose rises < 20 mg/dl
Histology of disaccharidase deficiency?
- normal appearing villi
What is abetalipoproteinemia?
- decreased synthesis of apolipoprotein B --> inability to generate CM --> decreased secretions of cholesterol, VLDL into bloodstream --> fat accumulation in enterocytes
When does abetalipoproteinemia present?
in childhood w/ malabsorption and neurologic manifestations
What are causes of pancreatic insufficiency?
- CF, obstructing cancer, chronic pancreatitis
What are malabsorption syndromes?
1. tropical sprue
2. Whipple's Dz
3. Celiac sprue
4. Disaccharidase deficiency
6. Pancreatic insufficiency
What cancer is found above the pectinate line? below?
below - SCC
What type of hemorrhoids are found above the pectinate line? below?
above - internal
below - external
What is the arterial supply above the pectinate line? below?
above - superior rectal artery (branch of IMA)
below- inferior rectal artery (branch of internal pudendal artery)
What is the venous drainage above the pectinate line? below?
above - superior rectal vein --> IM vein --> portal system
below - inferior rectal vein --> internal pudendal vein --> internal iliac vein --> IVC
What is the embryologic germ layer above the pectinate line? below?
above - mesoderm
below - ectoderm
Why are internal hemorrhoids not painful?
b/c of visceral innervation and are therefore not painful
Why are external hemorrhoid painful?
b/c of somatic innervation from the inferior rectal branch of pudendal nerve
What is the lymphatic drainage above and below the pectinate line?
- above - deep nodes
below - superficial inguinal nodes
What are common causes of acute gastritis (erosive)?
- NSAIDS (decrease PGE1 = decreased gastric mucosa protection)
- Burns (Curling's ulcer - decreased plasma volume --> sloughing of gastric mucosa)
- brain injury due to increased intracranial pressure (Cushing's Ulcer --> increased vagal stimulation --> increased Ach --> increased H production)
What are causes of chronic gastritis?
1. Type A - autoimmune mediated (10%)
2. Type B - H. Pylori meidated (90%)
Where is type A and type B chronic gastritis found in the GIT?
1. Type A = fundus/body
2. Type B = antrum
What is the MCC of vitamin B12 deficiency?
Type A chronic gastritis due to autoAbs to parietal cells - lack of IF
What findings are associated w/ Abs to parietal cells?
- Pernicious anemia and Achlorhydria
What is the consequence of achlorhydria in pernicious anemia?
- low acid production leads to increased gastrin levels and antral G cell hyperplasia
How does H. pylori cause chronic gastritis?
- urease and proteases weaken mucosal defenses b/c of virulence factors that penetrate through mucus layer and cause damage
What cancer is at increased risk due to H. pylori?
MALT lymphoma and gastric adenocarcinoma
What dz is associated w/ gastric hypertrophy w/ protein loss, parietal cell atrophy, and increased mucus cells?
Menetrier's dz - precancerous. Rugae of stomach are so hypertrophied that they look like brain gyri
What is the most common stomach cancer?
adenocarcinoma - early aggressive local spread and node/liver mets. often presents w/ acanthosis nigricans
What is intestinal adenocarcinoma causative agents?
- H pylori
- dietary nitrosamines (smoked foods)
- chronic gastritis
- type A blood
What is the location of intestinal adenocarcinoma on the stomach?
lesser curvature, looks like an ulcer w/ heaped up margins and non-radiating rugal folds
What is diffuse type stomach cancer?
- not assoicated w/ H pylori
- signet ring cells
- stomach wall grossly thickened and leathery (linitis plastica)
What are the lymph nodes mets associated w/ stomach cancer?
- Virhchow's node
- Sister Mary Joseph's nodule
What is Virchow's node?
- left supraclavicular node by metastasis from stomach
What is Sister Mary Joseph's nodule?
- subcutaneous periumbilical metastasis
Name this finding: bilateral metastases to ovaries w/ abundant mucus and signet ring cells?
Where are ulcers seen in PUD?
1. gastric - 10%, distal
2. Duodenal - 90%
What are the characteristics of gastric ulcers?
1. pain greater w/ meals= wt loss
2. 70% due to H pylori infxn
3. caused by decreased mucosal protection against gastric acid and NSAIDS
4. increased risk of carcinoma
5. often occurs in older pts
What are the characteristics of duodenal ulcers?
1. pain decreases w/ meal = wt gain
2. 100% due to H pylori
3. caused by decreased mucosal protection or increased gastric acid secretion (ZE syndrome)
4. generally benign and no increase in cancer
5. Hypertrophy of brunner glands
What are the characteristics of a benign ulcer?
- small, punched out, flar margins
What are the characteristics of a malignant ulcer?
- irregular, larger, piling up of mucosa
What are complications of PUD?
1. Hemorrhage - gastric, duodenal (posterior > anterior): on lesser curvature bleeding from left gastric. Posterior bleeding from gastroduodenal artery
2. perforation - duodenal (anterior> posterior)
What is the classic presentation of IBD?
young female w/ recurrent bloody diarrhea and ab pain
- more prevalent in west especially whites and E. european jews
What is the location of Crohn's dz in the GIT?
- any portion of the GIT usually the terminal ileum and colon. Skips lesions and rectal sparring
What is the location of ulcerative colitis in the GIT?
- colon inflammation that starts at rectum and is continuous so no skip lesions
What is the gross morphology of Crohn's Dz?
- transmural inflammation
Cobblestone mucosa, creeping fat, bowel wall thickening (string sign on barium swallow x-ray), linear ulcers, fissures, fistulas
What is the gross morphology of ulcerative colitis?
mucosal and submucosal inflammation only.
- friable mucosal pseudopolps w/ freely hanging mesentery
- loss of haustra - lead pipe appearance
What is the microscopic morphology of Crohn's dz?
- noncaseating granuloma
- lymphoid aggregates (Th1 mediated)
What is the microscopic morphology of ulcerative colitis?
- crypt abscesses and ulcers, bleeding, no granulomas (Th2 mediated)
What are complications of Crohn's dz?
- strictures, fistulas, perianal dz, malabsorption, nutritional depletion, CRC, oxalate stones
What are complications of Ulcerative colitis?
- malnutrition, sclerosing cholagnitis, toxic megacolon, CRC (wrose w/ right sided colitis and pancolitis)
What are the intestinal manifestations of Crohn's and ulcerative colitis?
- Crohn's: diarrhea that may/may not be bloody
- UC: bloody diarrhea
What are the extraintestinal manifestations of Crohn's dz?
- migratory polyarthritis, erythema nodosum, ankylosing spondylitis, uveitis, kidney stones
What are the extraintestinal manifestations of Ulcerative colitis?
- pyoderma gangrenosum, primary sclerosing cholangitis, ankylosing spondylitis, uveitis, P-ANCA
What is the treatment for Crohn's dz?
Steroids, azathioprine, MTX, infliximab, adalimumab, S-ASA agents for mild dz
What is the treatment for ulcerative colitis?
ASA preparations (sulfasalazine) , 6MP, infliximab, colectomy can be curative
What are the smoking associations of Crohn's and UC?
- Crohn's: smoking increases risk
- UC: smoking is protective
What are the symptoms of Irritable bowel syndrome?
- recurrent abdominal pain associated w/ at least 2 of the following symptoms
1. pain improves w/ defecation
2. change in stool frequency
3. change in appearance of stool
4. bloating, flatulence, and change in bowel habits
5. diarrhea, constipation or alternating symptoms.
How do you dx irritable bowel syndrome?
- dx of exclusion: check TSH, CBC, ESR, stool leukocytes
- everything will be normal: no structural abnormality, chronic symptoms
What is the goal of Rx w/ irritable bowel syndrome?
What is the cause of appendicitis?
- acute inflammation of appendix due to obstruction by fecalith (in adults) or lymphoid hyperplasia in kids
What are the findings for appendicitis?
- initial diffuse periumbilical pain that migrates to McBurney's point.
- Nausea, fever, may perforate and cause peritonitis
- guarding and rebound tenderness
What is the location of McBurney's point?
1/2 the distance from anterior superior iliac spine to umbilicus
What is a diverticulum?
a blind pouch protruding from the alimentary tract that communicates w/ lumen of the gut
- most are acquired and false in taht they lack or have an attenuated muscularis externa.
What is the MC location of diverticulum?
What is the difference btw and true and a false diverticulum?
True - all 3 gut layers outpouch
False - only mucosa and submucosa outpouch, occur especially where vasa recta perforate muscularis externa
What age group is diverticulosis common in?
- 60 yo and older
What is a diverticulosis caused by?
increased intraluminal pressure and focal weakness in colonic wall. Associated w/ low fiber diets.
- they are many false diverticula
What are the symptoms of diverticulosis?
- often asx or associated w/ vague discomfort
- common cause of hematochezia
- complications include diverticulitis and fistulas
What is diverticulitis?
- inflammation of diverticular classically causing LLQ pain, fever, leukocytosis
- may perforate to cause peritonitis, abscess formation, or bowel stenosis
- Give Abx
What has diverticulitis also been called?
left sided appendicitis due to overlapping clinical presentation
What is the treatment for diverticulitis?
- metronidazole, TMP-SMX, ciprofloxacin
What is Zenker's diverticulum?
- False diverticulum above the UES
- herniation of mucosal tissue at Killian's triangle b/w the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor
What are the presenting symptoms of Zenker's diverticulum?
- halitosis (due to trapped food particles), dysphagia, and obstruction
What is a traction diverticulum?
false outpouching near midpoint of esophagus
What is epiphrenic diverticulum?
false outpouching immediately above the LES
What is a Meckel's diverticulum?
- failure of vitelline duct to obliterate wk 5-6 of embryogenesis
- connection of gut lumen and umbilicius
- meconium drainage from umbilicus
What is associated w/ Meckels diverticulum?
- ectopic acid-secreting gastric mucosa and/or pancreatic tissue
- Melena, RLQ pain, intussuception, volvulus, or obstruction near the terminal ileum
What is the most common congential anomaly of the GIT?
- Meckel's diverticulum
How can you dx Meckel's diverticulum?
- pertechnetate study
What are the five 2's of Meckel's diverticulum?
- 2 inches long
- 2 ft from ileocecal valve
- 2% of population
- commonly presents in first 2 yrs of life
- many have 2 type of epithelia (gastric and pancreatic)
What causes telescoping of 1 bowel segment into distal segment commonly at the ileocecal junction?
What is seen w/ intussusception?
- currant jelly stools
compromise blood supply
- unusual in adults (associated w/ intraluminal mass or tumor)
- majority of cases w/ kids usually idiopathic, may be viral adenovirus
What is volvulus?
- twisting portion of bowel around its mesentery
- can lead to obstruction and infarction
- may occur at cecum - young adults
- at sigmoid - elderly
- USUALLY in elderly so think SIGMOID
What is a transmural small bowel infarction do to?
- embolism/thrombosis of SMA of thrombosis of mesenteric vein
- can be due to polycythemia vera, Atrial fibrillation, or vasculitis
What is a mucosal small bowel infarction do to?
- marked hypotension b/c furthest away from blood supply
What are clinical features of small bowel infarction?
ab pain, bloody diarrhea, deceased bowel sounds
What causes Hirschsprung's dz?
- congenital megacolon due to lack of ganglino cells/enteric nervous plexuses
- due to failure of neural crest cell migration
How does Hirschsprung's dz present?
- chronic constipation early in life
- dilated portion of colon proximal to the aganglionic segment (megacolon) resulting in transition zone
- involves rectum
- usually failure to pass meconium
- associated w/ Down's
What is ileus?
high pitched bowel sounds
What are symptoms of duodenal atresia?
- early bilious vomiting w/ proximal stomach distention
- shows up as double bubble on X-ray b/c of failure of recanalization of small bowel
- associated w/ Down's
What is meconium ileus found in?
- CF b/c meconium plug obstructs intestine preventing stool passage at birth
- Hirschsprung's dz
What is necrotizing enterocolitis?
- necrosis of intestinal mucosa and possible perforation
- colon is usually involved but can involved entire GI tract
In whom is necrotizing enterocolitis more common in?
preemies due to decreased immunity
What is ischemic colitis?
- reduction in intestinal blood flow causes ischemia
- Pain out of proportion w/ physical findings
- pain after eating = wt loss
- commonly seen as splenic flexure and distal colon
- typically affect elderly
What is the MCC cause of small bowel obstruction?
Adhesions - fibrous band of scar tissue; commonly forms after surgery
What is angiodysplasia?
- tortuous dilation of vessels causing hematochezia
- most often found in cecum, terminal ileum and ascending colon
- more common in old people
What are colonic polyps?
masses protruding into gut lumen
- 90% are non-neoplastic
- often found in rectosigmoid
- can be tubular or villous
What are precancerous colon polyps?
- adenomatous especially sessile and villous
Malignant risk of colon polyps are associated w/ what?
- increased size, villous histology, increased epithelial dysplasia
What are colon polyp symtpoms?
often Asx, lower GI bleed, partial obstruction, secretory diarrhea
What are hyperplastic colon polyps?
- MC non-neoplastic polyp
- serrated/stellate appearance
What are juvenile colon polyps?
- mostly sporadic lesions in kids less than 5
- 80% in rectum
- if single then no malignant potential
- when multiple then increased risk of adenocarcinoma
What is Peutz-Jegher syndrome?
- AD syndrome featuring multiple nonmalignant hamartomas thru-out GIT along w/ hyperpigmented mouth, lips, hands, gentalia
- associated w/ increased risk of CRC and other visceral malignancies such as breast, GYN, and other GI
- single polyps are not malignant
What mutation is Familial adenomatous polyposis associated w/?
- AD mutation of APC gene on chromosome 5q
- 2 hit hypothesis and 100% progress to CRC
Where are the polyps in FAP?
always involves rectum, thousands of polyps, pancolonic
What condition is known as FAP + osseous and soft tissue tumors, congenital hypertrophy of retinal pigment epithelium?
What condition is known as FAP + malignant CNS tumor?
What CRC is associated w/ AD mutation of DNA mismatch repair genes?
- Hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome)
- 80% progress to CRC and proximal colon is always involved
What other cancers are associated w/ HNPCC and Lynch syndrome?
- increased risk of ovarian and endometrial cancer
What are additional risk factor besides the genetics for CRC?
- IBD, tobacco use, large villous adenomas, juvenile polyposis syndrome, Peutz-Jeghers syndrome
What area of the colon is affected w/ CRC?
- rectosigmoid > ascending > descending
What type of lesion are seen w/ CRC in the ascending colon?
- Raised lesions usually = exophytic masses that cause Fe deficiency anemia and wt loss - usually a vague pain
What type of lesion are seen w/ CRC in the descending colon?
- Napkin-Ring lesion = infiltrating mass, partial obstruction, colicky pain, hematochezia
What bacteremia is associated w/ CRC?
How can one Dx CRC?
1. Fe deficiency anemia in males (> 50) and postmenopausal females raises suspicion
2. Screen pts > 50 w/ colonscopy or stool occult blood test
3. Apple core lesions on barium enema x-ray
4. CEA tumor marker, good for monitoring recurrence, not useful for screening
What are the 2 molecular pathways that lead to CRC?
1. Microsatellite instability pathway (15%)
2. APC/Beta Catenin pathway (85%)
What is involved in the microsatellite instability pathway for CRC?
- DNA mismatch repair gene mutations --> sporadic and HNPCC symptoms.
- mutations accumulate but no defined morphologic correlates
What is involved in the adenoma- carcinoma sequence of CRC?
1. Normal colon initially but then a loss of APC gene = decreased intercellular adhesion and increased proliferation
2. Colon at risk then get KRAS mutation = unregulated intracellular signal transduction
3. Adenomas forms then acquires loss of P53 = increased tumorigenesis
What is the most common small bowel tumor?
- carcinoid tumor of neuroendocrine cells
What is the immunostain for carcinoid tumors?
- synaptophysin and chromogranin
What are the most common sites for carcinoid tumors?
- appendix, ileum, and rectum
What is seen on EM for carcinoid tumor?
dense core bodies on EM
What leads to carcinoid syndrome?
When the cancer has metastasized to the liver where it can no longer efficiently metabolize the 5HT w/ MAO.
- there are high levels of 5HT
What are the symptoms for carcinoid syndrome?
2. right side heart valve disease
3. wheezing due to bronchospasm
What is the treatment for carcinoid tumor?
What are the clinical effects of portal HTN?
1. esophageal varices
3. peptic ulcers
6. caput medusae, ascites
7. portal hypertensive gastropathy
What are the effects of liver cell failure?
1. coma, scleral icterus, fetor hepaticus (musty breath)
2. spider nevi
3. gynecomastia, jaundice, testicular atrophy
4. liver flap = asterixis (coarse hand tremor)
5. bleeding tendency (decreased clotting factors and increased PT time)
6. anemia and ankle edema
What is cirrhosis?
diffuse fibrosis and nodular regeneration destroys normal architecture of liver
- increased risk for HCC
what are the common causes of liver cirrhosis?
1. viral hepatitis
3. biliary dz
What type of heart disease is associated w/ carcinoid tumor?
- right sided valvular fibrosis
- tricupsid regurg and pulmonary valve stenosis
What are the serum markers of liver pathology?
1. ALT and AST
What conditions are associated w/ increased ALT and AST?
1. Viral hepatitis - ALT > AST
2. Alcoholic hepatitis AST > ALT
What conditions are associated w/ increased ALP?
- obstructive liver disease (HCC), bone disease, and bile duct disease
What conditions are associated w/ increased GGT?
- increased in various liver and biliary dz like ALP but not in bone disease
What are serum markers for the pancreas?
- amlyase : increased in acute pancreatitis and mumps
- lipase : increased in acute pancreatitis
What is Reye's syndrome?
- rare, often fatal childhood hepatoencephalopathy
- due to giving kids ASA after a viral infxn
When is the only time to give ASA to kids?
What are the pathologic findings for Reye's syndrome?
1. mitochondrial abnormalities
2. fatty liver w/ microvesicular fatty change
What is the mechanism of damage for Reye's syndrome?
- aspirin metabolits decrease beta- oxidation by reversible inhibition of mitochondrial enzyme
What are initial signs of alcoholic liver disease?
hepatic steatosis - short term change w/ moderate alcohol intake
- macrovesicular fatty changes that may be reversible w/ alcohol cessation
What happens w/ sustained, long term consumption of alcoholic liver dz?
- alcoholic hepatitis - swollen and necrotic hepatocytes w/ neutrophilic infiltration
- mallory bodies (intracytoplasmic eosinophilic inclusions) are present
What is the irreversible form of alcoholic liver dz?
- alcoholic cirrhosis
What is seen w/ alcoholic cirrhosis?
- micronodular, irregularly shrunken liver w/ hobnail appearance.
- sclerosis around central vein (zone III)
- has manifestations of chronic liver disease (jaundice and hypoalbuminemia)
What is the fibrosis in liver cirrhosis mediated by?
- stellate cells via TGF-beta
- stellate cells are beneath endothelial cells that line the sinusoids
What are the symptoms of alcoholic cirrhosis?
1. portal HTN
2. decreased detoxification of metabolites - mental states changes, asterixis, coma all due to increased ammonia
3. decreased protein synthesis - monitor w/ PT
What are the symptoms of Acute viral hepatitis?
- jaundice (mixed CB and UCB) w/ dark urine, fever, malaise, and nausea
What happens to liver enzymes during acute viral hepatitis?
- ALT >> AST
What is seen in microscopic pathology of acute viral hepatitis?
- inflammation w/in portal tracts and w/in lobules of liver
What is the most common primary tumor of the liver?
What are risk factors for HCC?
1. Hep B and C
2. Wislon's dz
4. alpha1 antitrypsin deficiency
5. alcoholic cirrhosis
6. carcinogens such as aflatoxin from Aspergillus
What are the clinical findings for HCC?
How does HCC commonly spread?
- hematogenous dissemination
What are some other liver tumors?
1. carvenous hemangioma
2. hepatic adenoma
What tumor is most common for the liver?
mets from stomach, pancreas, lung, colon, and breast
- they are multiple nodules in liver. Detected as hepatomegaly w/ nodules on free edge of liver
What is cavernous hemangioma?
- common, benign liver tumor
- typically occurs 30-50 yrs of age
- biopsy is contraindicated b/c of risk of hemorrhage
What is a hepatic adenoma?
- benign liver tumor associated w/ OCPS or steroid use
- can regress spontaneously
- there is a risk of rupture and intraperitoneal hemorrhage especially during pregnancy
What is an angiosarcoma?
- malignant tumor of endothelial origin; associated w/ exposure to arsenic and PVC
What happens to the liver when there is passive congestion of blood due to right sided heart failure and Budd- Chiari syndrome?
What happens if a nutmeg liver's conditions persists?
- centrilobular congestion and necrosis can result in cardiac cirrhosis
What is Budd- Chiara syndrome?
- occlusion of IVC or hepatic vein w/ centrilobular congestion and necrosis, leading to congestive liver dz (hepatomegaly, ascites, abdominal pain, and eventual liver failure)
What is Budd- Chiari syndrome associated w/?
- hypercoaguable state, polycythemia vera, pregnancy, and HCC
What can develop w/ Budd-Chiari syndrome?
- varices and visible abdomina/back veins
- absence of JVD
What happens to the liver w/ alpha1 antitrypsin deficiency?
- misfolded gene products aggregate in hepatocellular ER leading to cirrhosis w/ PAS positive globules in liver
What happens to the lungs w/ alpha 1 antitrpsin deficiency?
- lack of functioning enzyme = decreased elastic tissue = panacinar emphysema
What is the basic cause of jaundice?
- yellow skin and/or sclera due to elevated bilirubin caused by direct hepatocellular injury, obstruction of bile flow, and hemolysis (extravascular) or ineffective erythopoiesis
What is associated w/ obstructed bile flow?
- gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites
- HLD, xanthomas, steatorrhea w/ malabsorption
What kind of bilirubin is elevated w/ hepatocellular damaged type jaundice?
- direct and indirect elevated
- increased urine bilirubin
- normal/decreased urine urobilinogen
What kind of of bilirubin is elevated w/ obstructive type of jaundice?
- increased urine bilirubin = dark urine
- decreased urine urobilinogen
What kind of bilirubin is elevated w/ hemolytic type of jaundice?
- no urine bilirubin
- increased urine urobilinogen = dark urine b/c the UCB is converted to urobilinogen
What is the pathogenesis of physiologic neonatal jaundice?
- at birth, there are immature UDP-glucuronyl transferase --> UCB --> jaundice/kernicterus
Why does kernicterus happen w/ physiologic neonatal jaundice?
- b/c UCB is fat soluble and can deposit in teh basal ganglia leading to neurologic deficits and even death
What are the hereditary hyperbilirubinemia disorders?
1. Gilbert- UCB
2. Crigler Najjar - UCB
3. Dubin- Johnson - CB
- all are AR
What is Gilbert's syndrome?
- mildly decreased UDP-glucuronyl transferase or decreased bilirubin uptake
- elevated UCB w/ overt hemolysis, fasting, and stress
What is Crigler-Najjar syndrome type I?
- absent UDP-glucuronyl transferase
- presents early in life and pts die w/in a few years
What are the findings of Crigler-Najjar syndrome type I?
- jaundice, kerniterus, increased UCB
What are the findings of Crigler-Najjar syndrome type II?
- less severe and responds to phenobarbital which increases liver enzyme synthesis
What is the treatment for Crigler-Najjar syndrome type I?
plasmaphereis and phototheraphy
What is Dubin-Jonhnson syndrome?
- CB b/c of defective liver excretion = grossly black liver
What is Rotor's syndrome?
- similiar to Dubin-JOhnson but even milder and does not cause black liver
What is the pathogenesis of Wilson's dz?
inadequate hepatic copper excretion and failure of copper to enter circulation as ceruloplasmis
- due to defect in copper transporting ATPase (ATP7B gene)
- AR (Ch13)
Where do copper accumulate in Wilson's dz?
- liver, brain, cornea, kidneys, and joints
What is Wilson's disease characterized by?
1. decreased ceruloplasmin, cirrhosis, corneal deposits leading to Kayser-Fleischer rings
3. hemolytic anemia
4. Basal ganglia degenerations (Parkinsonian symptoms)
6. Dementia, Dyskinesia, Dysarthria
What is the treament for Wilson's dz?
- pencillamine chelate coppers
What is the classic triad of hemochromatosis?
1. micronodular cirrhosis
2. DM - brittle
3. Skin pigmentation - bronzed
What is the pathogenesis of hemochromatosis?
- deposition of hemosidern (Fe)
- excess Fe deposition due to C282Y gene or H63D mutation on HFE gene
- associated a/ HLA-A3
What are other associations of hemochromatosis?
testicular atrophy in males and increased risk of HCC
What are the primary and secondary causes of hemochromatosis?
Primary - AR - loss of HFE gene; loss of enterocyte mediated Fe absorption dependent on body demand
Secondary - chronic transfusion therapy
What are the lab findings for hemochromatosis?
increased ferritin, Fe, and increased saturation
- decreased TIBC
What is the treatment for hemochromatosis?
- phlebotomy, deferasirox, and deferoxamine
What is the pathogenesis for Primary biliary cirrhosis?
- autoimmune destruction of intraheptaic bile ducts ,lymphocytic infiltrate and granulomas
- think WOMEN aged 40
What is the pathogenesis of primary scleosing cholangitis?
- unknown cause of concentric onion skin bile duct fibrosis --> alternating strictures and dilations w/ beading of intra and extra hepatic bile ducts on ERCP
- think MEN
What is the patogenesis of secondary biliary cirrhosis?
- extrahepatic biliary obstruction (gallstones, biliary stricture, chronic pancreatitis, carcinoma of pancreatic head) --> increased pressure in intrahepatic ducts --> injury/fibrosis and bile stassis
What presents as pruritus, jaundice, dark urine, light stools, hepatosplenomegaly?
Secondary biliary cirrhosis
Primary biliary cirrhosis
Primary scleorsing cholangitis
What are the labs associated w/ PBC and PSC?
- increased CB
- increased cholesterol
- increased ALP
What antibodies is associated w/ Primary biliary cirrhosis?
- increased serum mitochondrial Abs including IgM
- associated w/ other autoimmune conditions (eg CREST, RA, and Celiac dz)
What is associated w/ Primary sclerosing cholangitis?
- Hypergammaglobulinemia (IgM)
- Associated w/ ulcerative colitis
- can lead to secondary biliary cirrhosis
- P-ANCA can be positive and there is an increased risk of cholangiocarcinoma
What is biliary atresia?
- failure to form extrahepatic biliary tree lumen
- leads to biliary obstruction w/in 1st months of life
- presents w/ Jaundice and progresses to cirrhosis due to CB
- icterus, clay colored stools, dark colored urine
What is ascending cholangitis?
- bacterial infxn of bile ducts
- usually due to ascending infxn w/ enteric gram negative bacteria
- presents as sepsis, jaundice, and abdominal pain
- increased incidence of choledocholithiasis
What are causes of gallstones?
- increased cholesterol and/or bilirubin
- decreased bile salts
- gall bladder stasis
What are the types of stones?
1. cholesterol - radiolucent w/ some califications
2. Pigment - radiopaque. Black = hemolysis. Brown = infxn
What diseases are associated w/ cholesterol stones?
- obesity, Crohn's, CF, advance age, cirrhosis, clofibrate, estrogens, multiparity, rapid wt loss, and Native American origin
What diseases are associated w/ pigment stones?
- chronic hemolysis, alcoholic cirrhosis, advanced age, and biliary infxn
What is biliary colic?
- neurohormonal activation triggers contraction of gallbladder, forcing a stone into cystic duct. may present w/out pain= waxing and waning RUQ pain
What are complications of gallstones?
- fistulas btw gallbladder and small intestine leading to air in the biliary tree
- can obstruct ileocecal valve
How do you dx gallstones?
- USG, radiouclide biliary scan (HIDA), cholescystectomy
What are the risk factors for gallstones?
3. Fertile (pregnancy)
What is Charcot's traid of cholangitis?
- RUQ pain
What is a positive Murphy's sign?
- inspiratory arrest on deep RUQ palpation due to pain
What is cholecystitis?
- inflammation of gall bladder
- usually from gallstones, rarely ischemia of infxns (CMV)
- increased ALP if bile duct becomes involved
What is acute cholecystitis?
- RUQ pain that radiates to right scapula
- Fever w/ increased WBC, N/V
- risk of rupture if left untreated
What is chronic cholecystitis?
- due to chemical irriation from longstanding cholethiasis
- porcelain gallbladder = late complication
- dystrophic calcifications
- Rokitansky Aschoff sinus formation
What is the pathogenesis of acute pancreatitis?
- autodigestion of pancreas by pancreatic enzymes
What are causes of acute pancreatitis?
- gall stones, EtOH = main causes
- trauma, steroids, mumps, autoimmune dz, scorpion sting, hypercalcemia, Hyper TGs (>1000), ERCP, drugs
What are the labs for acute pancreatitis?
- elevated amylase, lipase
- hypocalcemia due to fat saponification
What are complications of acute pancreatitis?
- DIC, ARDS
- diffuse fat necrosis
- pseudocyst formation
- multiorgan failure
What is the pathology of chronic pancreatitis?
- chronic inflammation, atrophy, calcification of pancreas, fibrosis of pancreas parenchyma
- islet damage
What are causes of chronic pancreatitis?
- Alcohol abuse and idiopathic
CF in kids
What can chronic pancreatitis lead to?
- pancreatic insufficiency --> steartorrhea, fat soluble vitamin deficiency, DM and increased risk of pancreatic adenocarcinoma
What are risk factors for pancreatic adenocarcinoma?
- tobacco use
- chronic pancreatitis
- Jewish and African American males
Tell me about pancreatic adenocarcinoma?
- prognosis averages 6 months of less
- very aggressive tumor arising from pancreatic duct
- usually already metastasized at presentation
- tumors are common in pancreatic head
- associated w/ CA19-9 and CEA
What does pancreatic adenocarcinoma usually present w/?
- abdominal pain radiating to back
- wt loss (due to malabsorption and anorexia)
- migratory thrombophlebitis - redness and tenderness on palpation of extremities (Trousseau's syndrome)
- obstructive jaundice w/ palpable, nontender gallbladder (courvoisier's sign)
What is the treatment for pancreatic adenocarcinoma?
Whipple procedure, chemotherapy, radiation therapy
What are the H2 blockers?
cimetidine, ranitidine, famotidine, nizatidine
what is the mechanism of the H2 blockers?
- reversible block of histamine H2 receptors --> decreased H secretion by parietal cells
What is the clinical use of H2 blockers?
- peptic ulcer, gastritis, mild esophageal reflux
What is the toxicity of H2 blockers?
1. Cimetidine - potent inhibitor of CYP450, decreases renal excretion of Creatinine, antiandrogenic effects (prolactin release, gynecomastia, impotence, decreased libido in males, can cross BBB (confusion, dizziness, headaches) and placenta
2. Ranitidine - decreases renal excretion of creatinine
What are the proton pump inhibitors?
Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole
MOA of PPIs?
irreversibly inhibits HKATPase in stomah parietal cells
Clinical use of PPIs
- peptic ulcer, gastritis, esophageal reflux, ZE syndrome
ADE of PPIs
- increased risk of C difficile infxns, pneumonia, hip fractures, decreased serum Mg w/ long term use
MOA of bismuth and sucralfate
- binds to ulcer base, providing physical protection and allowing Bicarb secretion to reestablish pH gradient in the mucous layer
- sucralfate needs acidic pH to function
clinical use of bismuth and sucralfate
increases ulcer healing, traveler's diarrhea
MOA of MIsoprostol
- PGE analog, increased production and secretion of gastric mucous barrier, decreased acid production
Clinical use of misoprostol
- prevention of NSAID induced peptic ulcers; maintenance of a patent ductus arteriosus
- also used to induce labor (ripens cervix)
ADE of Misoprostol
- contraindicated in women of childbearing potential (abortifacient)
MOA of octreotide
- long acting somatostatin analog
clinical use of octreotide
- acute variceal bleeding, acromegaly, VIPoma, carcinoid tumor
ADE of octreotide
- nausea, cramps, steatorrhea
What are antacids used for?
- can affect absortion, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying
- all cause hypokalemia
What are the antacids?
- Al OH
- Ca carbonate
ADE of AlOH
- constipation and hypophosphatemia, proximal muscle weakness, osteodystrophy, seizures
ADE of MgOH
- diarrhea, hyporeflexia, hypotension, cardiac arrest
ADE of Ca carbonate
- hypercalcemia, rebound acid increase
- can chelate and decrease effectiveness of other drugs
What are some osmotic laxative?
- Mg citrate
MOA of osmotic laxatives
- provide osmotic load to draw water out
what is the cinical use for osmotic laxatives
clinical use for lactulose
- treats hepatic encephalopathy since gut flora degrade it into metabolites (lactic acid and acetic acid) that promote nitrogen excretions as Nh4
ADE of osmotic laxatives
- diarrhea, dehyrdation, may be abused by bulimics
- TNF alpha mab
Clinical use for infliximab
- Crohn's disease, ulcerative colitis, RA
- infection (including reactivation of latent TB)
MOA of sulfasalazine
- combo of sulfapyridine (antibacterial) and 5 aminosalicylic acid (anti-inflammatory)
activated by colonic bacteria
clinical use of sulfazalazine
- ulcerative colitis and Crohns
ADE of sulfasalazine
- malaise, nausea, sulfonamide toxicity, reversible oligospermia
MOA of ondansetron
5HT antagonist, powerful centralacting antiemetic
Clinical use of ondansetron
- control vomiting postoperatively and in pts undergoing cancer chemotherapy
ADE of ONdansetron
MOA of Metoclopramide
- D2 receptor antagonist, increase resting tone, contractility, LES tone, motilits
- does not influence colon transport time
clinical use of metoclopramide
- diabetic and post-surgery gastroparesis, antiemetic
ADE of metoclopramide
1. increase parkinsonian effect
2. restlessness, drowsiness, fatigue, depression, nausea, diarrhea
3. drug interaction w/ Digoxin and diabetic agents
4. contraindicated in pts w/ small bowel obstruction of Parkinson's disease
MOA of prokinetic agents of GIT
- increase Ach, increase 5HT, decrease D2