GB and Biliary Tree Diseases (Nichols/Tomb) Flashcards
Function of bile acids in bile?
solubilization of cholesterol
Modulation of Intestinal motility
Function of phospholipid in bile?
Solubilization of cholesterol
Protection of bile duct epithelium
Function of IgA and IgM in bile?
bacteriostasis
Function of mucus in bile?
prevention of bacterial adhesion
Function of glutathione in bile?
induction of bile flow
Most frequent type of gallstones?
Pured and mixed cholesterol stones
What are pure and mixed cholesterol stones comprised of?
- Monohydrate cholesterol crystals
- Matrix of mucin glycoprotein
- Ca salts of unconjugated bilirubin
What are brown pigmented stones comprised of?
Ca salts
deconjugated bilirubin
cytoeskeleton of bacteria
Brown pigmented stones most commonly occur in patients with:
previous srx
duodenal diverticula
Black pigmented stones most commonly occur in patients with:
liver disease, hemolysis, older age
What are black pigmented stones comprised of?
- -Pure Ca bilirubinate
- -calcium copper
- -mucin glycoprotein
How does age cause cholesterol hypersecretion?
age-related decr in 7-alpha-hydroxylase
How does estrogen cause cholesterol hypersecretion?
Increased cholesterol uptake (Increased lipoprotein receptors B and E)
How does obesity cause cholesterol hypersecretion?
Incr cholesterol synthesis
increase HMG coA activity
How does progesterone cause cholesterol hypersecretion?
Increased free cholesterol
Inhibitor of AcoA CAT, Decreased conversion of cholesterol to cholesteryl ester stores
Bile acid Synthesis: The rate-limiting enzyme is :
7-alfa hydroxylase
How does marked weight reduction cause cholesterol hypersecretion?
Mobilization of tissue cholesterol
How does ileal disease/resection/bypass cause cholesterol hypersecretion?
Impaired bile acid absorption or excessive losses
What is “supersaturated” bile?
Bile that has a CSI greater than 1, which means the amt of cholesterol exceeds the max holding capacity of micelle
What are vesicles?
very large carriers of cholesterol, which do NOT contain bile salts
Multilamelar vesicles permit:
crystal formation
What is crystal formation?
Aggregation process by which a crystal particle is formed from supersaturated bile
How are crystals generated?
vesicular fusion and aggregation
What changes in bile composition enhance crystal formation?
high cholesterol saturation and an increased deoxycholate content
5 Factors which inhibit crystal formation:
- low total lipid conc
- decr cholesterol saturation
- biliary proteins not binding Con-A
- Apolipoprotein A-I and A-II
- Ig
How does gallbladder emptying relate to gallstone formation?
delay in gallbladder emptying
= gallstone
4 GB-related abn that are risk factors for gallstones:
- Defective acidification of gallbladder bile
- > pH higher ppt of Ca salts
- GB stasis can cause incr mucin, which interferes w/ mechanical emptying
- Decr response to CCK
Cholesterol gallstone pathogenesis:
Hepatic chol hypersecretion causes:
- GB hypomotility
- mucin hypersecretion
- chol gallstone formation
Incr intestinal conversion to deoxycholate,
- directly causes GS formation
- hepatic chol hypersecretion
Risk factors for black pigment stone formation:
Hemolysis
Advancing age
Long term TPN
Cirrhosis
GB-related risk factors for black pigment stone formation
- decreases in bilirubin solubilizers
- GB stasis
- incr bilirubin secretion
Causes of brown pigment stones?
- Bacterial infection
- Decreasing biliary secretory IgA
- High activity of B-glucuronidase
Pathophysiology of brown pigment gallstone formation:
- bacterial degradation of biliary lipids (into free bile acids, free FA, unconj bilirubin)
- Ca ppt, bacterial glycoproteins, cholesterol form stones
Cholelithiasis has a high prevalence rate in ___ countries, and a low prevalence rate in ___ countries.
Latin Am
Asian
Pt risk factors associated with cholesterol gallstones?
Fat
Female
Forty
Fertile (hormones +pregnancy)
also: Rapid weight reduction; Gallbladder stasis; Inborn disorders of bile acid metabolism; Hyperlipidemia syndromes
Pt risk factors associated with pigment gallstones?
Asian > Western rural > urban Chronic hemolytic syndr Biliary infection GI disorders: ileal disease (e.g., Crohn disease), ileal resection or bypass, CF with pancreatic insufficiency
Clinical Manifestation of Biliary colic:
abd pain
Clinical Manifestation of Acute Cholecystitis:
abd pain
fever
Clinical Manifestation of Choledocholithiasis with Cholangitis:
abdominal pain
fever
jaundice
Clinical Manifestation of Biliary pancreatitis:
abdominal pain, increased amylase
most sensitive test for the diagnosis of gallstone?
abd US
radiologic finding highly suggestive of acute cholecystitis?
presence of air at the gallbladder wall
“Emphysematous cholecystitis”
Common findings in acute cholecystitis?
gallbladder is usually enlarged + tense
90% of cases = stones present (obstructing neck of GB or cystic duct)
acute inflammation
Possible findings in chronic cholecystitis?
GB may be contracted, normal size, or enlarged
fibrosis, mural lymphocytes
Intrahepatic causes of Cholestasis?
Extrahepatic causes of Cholestasis?
PBC, drugs, malignancy, etc
Stones
Benign causes of mechanical cholestasis?
Post-surgical complications
Primary sclerosing cholangitis
Infections
Chronic pancreatitis
How do pts present w/ Post liver transplantation biliary stricture?
cholestatic pattern of liver enzymes (high alkaline phosphatase, GGT, etc)
Epidemiology for Primary Sclerosing cholangitis?
M>F
80% of pts have IBD
What is Primary Sclerosing cholangitis?
Chronic cholestatic disease of the intrahepatic and extrahepatic bile ducts
onion skin bile duct fibrosis with alternating strictures and dilation
Patients with Primary Sclerosing cholangitis are at an incr risk for developing:
bile duct malignancy (cholangiocarcinoma)
Primary Sclerosing cholangitis: Clinical presentation?
What does this resemble radiologically?
symptoms of chronic cholestasis (jaundice, dark urine, light stool, hepatosplenomegaly)
HIV cholangiopathy
Trx for Primary Sclerosing cholangitis?
liver transplantation
Clinical presentation of chronic pancreatitis?
cholestatic pattern of liver enzymes in the presence of chronic pancreatitis
Trx of chronic pancreatitis?
biliary stent placement and/or surgery
Clinical presentation of Hemobilia?
jaundice, melena and abdominal pain
How does GB-related malignancy present?
progressive painless jaundice and weight loss
What locations of malignancies cancause cholestasis?
- Ampullary
- Gall-bladder
- Bile ducts
- Pancreatic
Epidemiology of Cholangiocarcinoma?
men at 50-70 years old
Risk factors for Cholangiocarcinoma?
Primary sclerosing cholangitis, Hepatitis C related cirrhosis, toxin exposure, infection with liver flukes (clonorchis)
Presentation of Cholangiocarcinoma?
biliary obstruction causing painless jaundice
incr total bilirubin, alk phos, 5’-nucleotidase + GGT
incr tumor marker Ca 19-9
Presentation of pancreatic cancer w/ GB obstr?
progressive painless jaundice and weight loss
MC cause of biliary obstruction by malignancy?
pancreatic
