Flashcards in CM- Pancreas and Hepatobiliary Diseases Deck (45)
How does the duodenum respond to the presence of HCl within the lumen?
endocrine S cells release secretin which stimulates biliary and pancreatic epithelial cells to secrete bicarbonate and water
How does the duodenum respond to the presence of fat and amino acids?
endocrine I cells release CCK which
1. stimulates vagal pathways to pancreatic acinar cells to release enzymes (and proenzymes)
2. contracts the gall bladder and relaxes the sphincter of Oddi
When do enzymes released from acinar cells of the pancreas become active?
They are released as inactive proenzymes and when they pass through the sphincter of Oddi into the duodenum trypsinogen is hydrolyzed into trypsin by enterokinase.
Trypsin then activates the other proteases
How do cholesterol bile stones form?
What are risk factors for this?
If more cholesterol is secreted into bile than can be maintained in solution, the bile is "supersaturated". The excess can precipitate out and form stones.
3. fertile (pregnant)
Where do cholesterol gallstones form ?
ONLY in the gallbladder lumen. They cannot form freely in the bile duct (a difference from pigmented stones)
How do pigmented bile stones form?
They are composed of calium bilirubinate and form in response to anything that increased bilirubin formation (hemolysis)
Bacteria can also chemically alter bile leading to precipitation of gallstones.
How do bacteria cause pigmented gallstones?
Bacteria can chemically alter bile leading to precipitation of stones.
Ex. E. coli has glucuronidase which unconjugates bilirubin forming black stones
Ex. phospholipase produces FFA which precipitates with calcium for soft brown stones .
What are the major inciting factors of acute pancreatitis?
Gallstones (and choledolithiasis**)
What genetic mutations lead to chronic pancreatitis?
1. PRSS1 - "super trypsin" is resistant to cleavage
2. SPINK1/PST1 - inactive trypsin inhibitor
3. CFTR- impaired bicarb secretion
What does chronic pancreatitis lead to?
1. loss of endocrine and exocrine cells
3. duct deformity
4. fat malaborption and diabetes
What drives the progression to pacreatic adenocarcinoma?
1. overexpression of TGFa, EGF
2. activated oncogene K-Ras
3. inactivated tumor suppression p53, p16
4. overexpression of TGFB which drives fibrosis without inhibiting cellular proliferation
This leads to precursor lesions in the pancreatic duct called PanINs.
Why is pancreatic adenocarcinoma able to metastasize so quickly?
Factors derived from tumor cells drive angiogenesis, neural invasion, and mestastatic spread.
The tumor is protected from the immune system because it requires minimal vascular supply and is in a dense fibrous stroma
Most gallstones are asymptomatic and do not require surgical removal of stones, What are the 4 main exceptions to this rule?
1. Sickle Cell Anemia (hemolysis increases bilirubin)
2. extreme remote assignments
3. liver transplant recipients
4. Diabetics ( neuropathy makes it so they can't feel the pain potentially missing sepsis)
What is the pathophysiology of biliary colic?
It is episodic abdominal pain caused by the gallbladder attempting to contract in the presence of a stone/obstruction in the cystic duct
A patient presents with pain in the RUQ but it is poorly localized. They say the pain started just after eating, got worse over a span of 15 minutes and then stayed bad for 4 hours.
The physical exam is normal with slight mild tenderness.
What is the likely problem?
What is the main imaging modality used for diagnosis of biliary colic?
What do you do in the absence of demonstrable cholelithiasis?
Ultrasonography can detect gallstones in 95% of cases.
If you don't see stones on ultrasound the next test is CCK HIDA scan.
You inject dye intravenously, and it gets excreted into the bile so you will see it fill the liver and go down the bile duct. If the dye fails to enter the gall bladder, it is fully obstructed and should be removed.
Next you give CCK which causes the gallbladder to contract. Measure the GBEF
If the patient seems to have biliary colic, but there is not demonstrable stones, what test would you do? What would the results tell you?
HIDA- shows if bile is getting into the gallbladder
CCK- contracts the gall bladder to measure GBEF.
If the patient has low GBEF and reproducible symptoms of the biliary colic, there is a biliary source of symptoms.
What is treatment for biliary colic?
laproscopic cholecystectomy because the risk of recurrent attack is 70%
What is the pathophysiology of acute cholecystitis?
when the gallbladder wall is acutely inflamed due to chemical irritation of the epithelium which eventually spreads the full thickness of the wall
What are the major causes of acute cholecystitis?
1. Gallstones (stasis of bile and chemical irritation)
3. S. typhosa
A patient presents with RUQ pain, tenderness over the gallbladder and fever. The pain has lasted 6 hours and is localized.
The person has a positive Murphy's sign. What are you highly suspicious of?
What is Murphy's sign?
What is a positive Murphy's sign highly specific for?
When the patient takes a deep breath and has inspiratory arrest when the palpating hand touches the inferior of the gallbladder.
A positive sign is highly specific for acute cholecystitis.
What lab tests are ordered if you are suspicious of acute cholecystitis?
US - cholelithiasis, thickened walls, pericholecystic fluid
HIDA- confirm or exclude cystic duct obstruction (hot spot on the gallbladder excludes it)
What is treatment for acute cholecystitis?
2. antibiotics if febrile or suspected of gangrenous or perforated gallbladder
What is the pathophysiology of ascending cholangitis?
There is an obstruction of the common bile duct (choledolithiasis) leading to stagnant bile prior to the obstruction that secondarily gets infected by bacteria
An elderly patient presents with jaundice, RUQ pain, fever. He looks very septic-looking and delerious. What are you suspicious of ?
Ascending cholangitis due to the presence of Reynold's Pentad
What labs and tests are run for ascending cholangitis?
1. CBC- leukocytosis due to infection, schistocytes, left shift
2. elevation of liver enzymes including bilirubin
3. US- dilated common bile duct
4. ERCP- if stabilized with fluid/antibiotics to remove stone (most likely cause of obstruction)
What is treatment for ascending cholangitis?
3. Decompression of the bile duct (ERCP, PTC)
What physical exam findings and radiologic evidence support acute pancreatitis?
epigastric abdominal pain preceded by nausea and vomiting associated with elevated lipase and amylase.
Radiographically- edema and necrosis