1
Q
What are the components of bile (and their functions)?
A
- BILE ACIDS: solubilization of cholesterol and modulation of intestinal motility -> essential for fat absorption
- PHOSPHOLIPID: solubilization of cholesterol and protection of bile duct epithelium
- IgA and IgM: bacteriostasis
- MUCUS: prevention of bacterial adhesion
- GLUTATHIONE: induction of bile flow
- 500-600mL per day, and isoosmotic w/plasma
2
Q
What 3 types of stones can form in the gallbladder?
A
- CHOLESTEROL: more frequent, yellow-white, Ca salts of unconjugated bilirubin, matrix of mucin glyoprotein, only occasionally seen by x-ray
- BLACK (pigmented): hemolysis, liver disease, age, TPN, pure calcium bilirubinate, calcium copper, mucin glycoprotein
- BROWN (pigmented): primary biliary, infection, prior surgery, duodenal diverticula, calcium salts and deconjugated bilirubin (high activity of beta-glucuronidase), cytoskeleton of bacteria, DEC biliary secretory IgA
3
Q
Describe cholesterol metabolism. Hypersecretion? Risk factors for cholesterol stones?
A
- Total body pool of cholesterol: 1) syn from acyl-CoA, 2) dietary absorption, 3) cholesterol pool
1. Solubilized and secreted unmodified in bile, and converted to bile acids -> most important ways body gets rid of cholesterol - HYPERSECRETION:
1. Estrogen: INC receptors for lipoproteins, INC free cholesterol
2. Progesterone: DEC synthesis of cholesterol ester from free cholesterol - RISK FACTORS: female, older, obese, pregnant pts after delivery
- NOTE: remember all of these risk factors, and how they happen
4
Q
What are the 3 most important contributing factors to the pathophys of cholesterol stone formation?
A
- Cholesterol supersaturation
- Accelerated nucleation
- Gallbladder hypomotility
- REMEMBER: balance b/t bile acid (good guy) and cholesterol (bad guy) is what is important
1. Cholesterol virtually insoluble in water, but bile acids, due to their unique amphiphatic properties, are able to solubilize cholesterol and phospholipid
5
Q
What are 6 causes of cholesterol hypersecretion?
A
- OBESITY: hyperlipoproteinemia -> INC cholesterol synthesis (INC HMG CoA activity)
- PROGESTERONE: oral contraceptives INC free cholesterol -> INH AcoA CAT, DEC conversion of cholesterol to cholesterol ester stores
- ESTROGENS: INC cholesterol uptake via INC lipoprotein B and E receptors
- AGE: age-related DEC in 7-alpha-hydroxylase
- MARKED WEIGHT REDUCTION: mobilization of tissue cholesterol
- ILEAL DISEASE, bypass, or resection: impaired bile acid absorption or excessive losses
6
Q
What is this?
A
- Abetalipoproteinemia: small bowel mucosa shows characteristic CLEAR ENTEROCYTES due to lipid accumulation
- Usually present as babies with failure to thrive
- Can’t get TG’s out of enterocytes, so they build up, and you get foamy, or frothy appearance from buildup of TG’s and lipoproteins in the enterocytes
- Note the difference b/t normal and diseased in the attached image
7
Q
What is the cholesterol saturation index? How can cholesterol in bile be found?
A
- CSI: ratio of amt of cholesterol in a bile sample to its max cholesterol micellar-holding capacity -> max amt of cholesterol you can deal with considering the amt of bile acid you have available
- Bile that has a CSI >1 is supersaturated
- Cholesterol in bile can be found as the following:
1. Mixed micelle: bile acids (BA), cholesterol, bilirubin, PC (phosphatidyl choline)
2. Simple micelle: BA, cholesterol, bilirubin
3. Vesicles: 10x larger, no bile salts -> when these converge, you get stones
4. Multi-lamellar vesicles: unstable, and permit crystals formation
8
Q
How can enterohepatic recirculation affect gallstone formation?
A
- Not enough bile acid can lead to imbalance b/t bile acids and cholesterol, so anything that can interfere with this circulation can get you into trouble
- Cycle occurs 6-10x daily
- Actively transported through the hepatocyte, stored in gallbladder, sent to small bowel, low absorption in jejunum, then active/passive absorption in ileum, and transport back to liver
9
Q
What is accelerated nucleation?
A
- People who develop crystals much more quickly than others: some of these reasons we know, and others we do not
1. INC CSI = too much cholesterol for bile acid - Crystal formation: aggregation process by which a crystal particle is formed from supersaturated bile
1. Crystals generation: vesicular fusion and aggregation
10
Q
If 2 pts have cholesterol hyper-secretion, will they both have gallstones?
A
- MAYBE: don’t need to remember all of these in attached image, but know that there are other contributing factors -> 2 pts could have cholesterol hyper-secretion and 1 could have gallstones, and the other not
1. Hyper-secretion and hyper-saturation are 2 different things - Several factors identified that promote or INH the kinetics of cholesterol crystal formation:
1. Concentrating bile and secretion of mucin glycoprotein INC cholesterol crystal formation
2. Changes in bile composition, incl high cholesterol saturation and INC deoxycholate content enhance cholesterol crystallization
11
Q
How can gallbladder emptying affect the formation of cholesterol stones? Provide an example.
A
- TPN: no food in duodenum, but gallbladder does not know, and NOT contract -> risk factor for stones
- Even w/o TPN, some ppl have more gallbladder activity than others
- People with gallstones tend to have hypo-active gallbladders, or delayed emptying
12
Q
What are the gallbladder events in cholesterol gallstone formation? Possible risk factors? Tx?
A
- Possible RISK FACTORS:
1, Defective acidification of gallbladder bile
- > pH higher precipitation of calcium salts
- Gallbladder stasis can produce INC mucin secretion from gallbladder epithelium, and interfere with mechanical emptying
- Decreased response to CCK
- TX: remove gallbladder -> 95% of the time, you correct the problem - For most people, this is a gallbladder disease, with the exception of brown stones
13
Q
What 4 factors are implicated in the pathophys of cholesterol gallstone formation?
A
- Hepatic cholesterol hypersecretion
- INC intestinal conversion to deoxycholate (2o bile acid)
- Mucin hypersecretion
- Gallbladder hypomotility
14
Q
What are the clinical risk factors for black gallstone?
A
- Hemolysis, i.e., pts with sickle cell
1. A lot of bilirubin, which can precipitate with Ca salt, giving you small, hard stones (cholesterol stones are softer) - Advancing age
- Long-term TPN
- Cirrhosis
- High level of unconjugated bilirubin is main component -> beta-glucuronidase is the enzyme that un-conjugates bilirubin
15
Q
What are the risk factors for brown pigmented stones?
A
- Infection, primary biliary stones (formed in bile ducts, not gallbladder), prior surgery
1. Pts with intervention in the bile ducts; more frequently in older patients - DEC biliary secretory IgA
- High activity of B-glucuronidase
- Develop infection, inflammation, and bigger, softer, brown stones
16
Q
Describe the anatomy of the extrahepatic biliary tree.
A
- Note that the common bile duct (CBD) passes through pancreas before duodenum, getting together with main pancreatic duct
17
Q
What are the clinical manifestations of biliary colic?
A
- Abdominal pain
18
Q
What are the clinical manifestations of acute cholecystitis?
A
- Abdominal pain
- FEVER
- Abdominal US: thickening of gallbladder wall and pericholecystic fluid (CT can also help)
1. Diagnostic
19
Q
What are the clinical manifestations of choledocolithiasis with cholangitis?
A
- Abdominal pain
- Fever
- JAUNDICE
20
Q
What are the clinical manifestations of biliary pancreatitis?
A
- Abdominal pain
- INC amylase
21
Q
ER: 50-y/o obese F w/epigastric, RUQ abdominal pain (7/10) that lasts around 30 mins. Severe pain that goes up, stays there, then starts going down. No fever, but some tenderness in RUQ. No rebound or irritation.
You give her something for pain, and 30 mins later she is fine, and wants to eat.
What is going on? What should you do?
A
- BILIARY COLIC
- Send pt home, but tell her this can happen again
- Will need to schedule a surgery to take the gallbladder out
22
Q
Pt. previously seen for biliary colic comes back w/severe pain that lasts longer, and travels to shoulder. Feeling sick: febrile, tachycardic, hypotensive, high WBC, tachypnic.
What is going on? What should you do?
A
- ACUTE COLECYSTITIS
- Stone trying to come out for longer period of time, and gallbladder distended, leading to inflammation (not the same as infection)
- These pts need to be admitted to hospital:
1. Give IV AB
2. Call surgeons -> gallbladder can rupture, leading to peritonitis, sepsis, and high rate of mortality
23
Q
30-y/o F who delivered 1 wk ago (high estrogen and progesterone) presents w/abdominal pain, jaundice, dark urine, stools a little lighter.
What is going on? What should you do?
A
- CHOLANGITIS
- Stone fighting to get through made it, went into CBD, and obstructed it -> bile can’t get through, and is backtracking, entering blood, and causing jaundice
- Admit to hospital -> may call surgeons, but def call GI doc who can go in by endoscopy, make cut, and clean
1. If you don’t do anything, infection goes into liver, blood, and causes sepsis: needs to be treated within 24 hours
24
Q
What is biliary pancreatitis? Presentation? Dx?
A
- Stone obstructing bile ducts AND main pancreatic duct, INC pressure in main pancreatic duct, and causing inflammation of pancreas
- Pain is a belt pain that wraps around to back, and is worse when lying down flat on bed
- INC in amylase and lipase
- DIAGNOSIS: 2 of these 3 changes:
1. Clinical -> severe pain (7 or 8/10, frequently with N/V)
2. INC in amylase/lipase
3. Changes in CT
25
What clinical features are key to diagnosing the spectrum of gallbladder disease?
- Biliary colic = only pain
- Add fever and high WBC, inflammation = acute cholecystitis
- Jaundice = choledocholithiasis with cholangitis
- INC amylase, changes on CT = biliary pancreatitis
26
What is the tx for choledocholithiasis?
- Stones extraction by endoscopic retrograde cholangiography (**ERCP**): attached image shows filling defects consistent with choledocholithiasis
1. 10% of patients with cholelithiasis will have choledocholithiasis
2. Sent to surgeons to get rid of gallbladder (cholecystectomy) when choledocholithiasis is resolved
- Choledocholithiasis is found in 12% to 15% of patients who undergo cholecystectomy
1. Cholecystectomy: most common elective abdominal operation
27
What is a sphincterotomy?
- Small incision in the opening of the bile duct, which can help small gallstones and bile to drain appropriately
- Balloon extraction of common bile duct stones after sphincterotomy attached here
28
What is this? Describe the histo and gross appearance. Arrows?
- **Acute cholecystitis**: just means _inflammation_; have to see + cholelithiasis for stones too
- HISTO: no specific morphologic differences b/t acute acalculous and calculous cholecystitis, save the absence of stones in the acalculous form.
1. Arrows: _neutrophils_ -\> in glands, not just lamina propria
- GROSS: enlarged and tense bright red, blotchy to green-black discoloration, imparted by subserosal hemorrhages
1. Frequently covered by a fibrinous or even _fibrinopurulent exudate_
- INC over holidays, and a lot of these are taken out
29
What is this?
- Calculous cholecystitis can have various exudates, from turbid bile to pus
- When the exudate is virtually pure pus, the condition is referred to as **gallbladder empyema**
- _Empyema_: pus within an anatomic pocket
30
What is this?
- _Calculous cholecystitis_: obstructing stone is usually present in the neck of the gallbladder or the cystic duct
31
What is going on here?
- **Acute emphysematous cholecystitis**: invasion of gas-forming organisms, notably clostridia and coliforms, can cause this
- Not hemorrhage in bottom right, but congestion; not fat in the wall, but air
32
What happened here?
- **Gangrenous cholecystitis**: severe cases where gallbladder is transformed to green-black necrotic organ, with _small-to-large perforations_ (before this, wall is thickened, edematous, and hyperemic)
- Inflammation is predominantly _neutrophilic_
33
What do you see here?
- **Chronic cholecystitis**: serosa usually smooth and glistening, but may be dulled by _subserosal fibrosis_
- MICRO: scattered lymphos, plasma cells, macros
1. Mostly looking for diving down of glands into sinuses
- Reactive proliferation of mucosa and fusion of the mucosal folds may give rise to buried crypts of epithelium within the gallbladder wall = **Rokitansky-Aschoff sinuses** (\*)
- Presence of acute inflam = acute on chronic
34
What is this?
- **Cholesterolosis**: strawberry gallbladder
- Can see this if fatty meal eaten: epi and sub-epi accumulation of cholesterol
- NOTE: not tied to cholelithiasis or cholecystitis
35
What is going on here?
- **Xanthogranulomatous cholecystitis**: triggered by _rupture of Rokitansky-Aschoff sinuses_ into wall of gallbladder followed by accumulation of macros that have ingested biliary phospholipids
- Lipid-containing cells with foamy cytoplasm called _xanthoma cells_ (bubbly, fat, stuffed up macros full of lipid)
- FRONT IMAGE: thickened, fibrotic gallbladder wall with a centrally located xanthogranulomatous cholecystitis lesion (arrows) containing _chronic inflammatory cells, bile pigment, and foamy pigment-laden macrophages_
36
What is cholestasis? 2 types? How can you distinguish these clinically?
- Condition where bile can't flow from liver to the duodenum, leading to _conjugated hyper-bilirubinemia_ and _high alkaline phosphatase_
- Types:
1. OBSTRUCTIVE: mechanical blockage in duct system (extrahepatic) -\> flow
2. METABOLIC: disturbances in bile formation (intrahepatic) -\> making it
- Can distinguish these clinically by:
1. Medical history
2. PE
3. Abdominal US looking for intrahepatic biliary ductal dilation (indicating obstruction)
37
What are some of the causes of extrahepatic and intrahepatic cholestasis?
- EXTRAHEPATIC (mechanical): stones, malignancy, large ducts primary sclerosing cholangitis, post-surgical complications, chronic pancreatitis, other
- INTRAHEPATIC (metabolic): primary biliary cirrhosis, medication, malignant infiltration, small ducts primary sclerosing cholangitis, other
- PSC: Crohn's, UC
38
What findings lead you to suspect extrahepatic cholestasis? Diagnostic techniques?
- EXTRAHEPATIC:
1. Cholestatic pattern of liver enzymes: _alk phos, GGT, and bilirubin_ all elevated
2. Biliary ductal dilatation by US
- DIAGNOSIS:
1. Clinical findings
2. MRCP (magnetic resonance cholangial pancreatography) and/or ERCP (endoscopic retrograde cholangio pancreatography)
3. EUS
- NOTE: attached images are of MRCP (left) and ERCP (right)
39
What is this?
- **Cholestasis**: impaired bile formation and bile flow that gives rise to _accumulation of bile pigment_ in the hepatic parenchyma
- Can be caused by extrahepatic or intrahepatic obstruction of bile channels, or by defects in hepatocyte bile secretion
- Can have bile plugs, which are more green than hemosiderin (brown) or lipofuscion
40
What do you see here?
- Hepatocytes and Kupffer cells full of granular brown deposits of **hemosiderin** from accumulation of excess iron in the liver
41
Describe what you see here.
- Normal bile duct travelling just above portal system
- Look for portal vein on US: if nothing above it of similar size, this is normal
42
What do you see here? Unlabeled arrows?
- **Biliary ductal dilatation** (top left arrow)
- Hyper-echoic structure sitting inside CBD and shadow behind what is there that is typical for stones (top right arrow)
43
What malignancy most commonly causes biliary obstruction? How does it present?
- **Pancreatic malignancy**: when tumor is located at the head of the pancreas
- Note in the attached image that the bile duct must go through the pancreas
- As with most of the pancreatobiliary malignancies, pancreatic cancer presents clinically w/_progressive painless jaundice and weight loss_
44
Female with complete colonectomy due to genetic disease that predisposes to colon cancer. Now, she has this ulcerated mass in her ampulla.
What genetic disease does she have? What is this mass? Tx?
- **FAP**: pts with FAP can develop adenomas in the second portion of the duodenum, and can develop duodenal and ampullary adenocarcinoma
- Not frequent, and slow growth
- TX: surgery and/or stent placement
- NOTE: image of normal apulla attached here
45
What is primary sclerosing cholangitis? Associations? Presentation? Tx?
- _Chronic cholestatic disease_ of intra- and extra-hepatic bile ducts -\> nobody really knows how this happens, and there is no real treatment
1. Reaction to something in bile duct (maybe coming from colon; toxin): leads to _scar tissue, and segmental narrowing of bile ducts_
2. Severe ITCHING as part of cholestasis
- More common in AA, M
- Present with _cholestatic pattern of liver enzymes_: elevated GGT, alk phos, and bilirubin
- **Association with IBD**: 70% of these people also have UC; less frequently Crohn’s
1. 20-30% chance for _cholangiocarcinoma_
- TX: liver transplantation
- NOTE: HIV cholangiopathy presents similar radiologic findings
46
What do you see here?
- **Primary sclerosing cholangitis**:
1. LARGE DUCT inflam: acute, neutrophilic infiltration of epithelium superimposed on a chronic inflammation
2. SMALL DUCTS have little inflammation and show striking circumferential “**onion skin**” fibrosis around atrophic duct lumen, with eventual obliteration
- Culminates in **biliary cirrhosis** (attached image), much like that seen with chronic obstruction and primary biliary cirrhosis -\> _irregular, puzzle-piece appearance_
1. When we talk about hepatitis and cirrhosis of liver, the pattern is a little different: more nodular, regular, and even
- Biliary intraepithelial neoplasia may devo and _cholangiocarcinoma_ -\> usually w/fatal outcomes
47
What is going on here?
- **PSC**: degenerating bile duct with "ONION SKIN" fibrosis (compare to attached normal image)
- Cholestasis: gold pigment
- Biliary cirrhosis: pretty far advanced because pt already has some cirrhosis
48
What is this? What neoplasm might you be worried about? Describe it.
- Stricture due to PSC -\> can lead to devo of cholangiocarcinoma
- RISK FACTORS: most freq in 50-70-y/o M
1. PSC, Hep C-related cirrhosis, toxin exposure, infection w/liver flukes (clonorchis)
- Commonly present w/biliary obstruction causing painless jaundice
1. _Labs suggest biliary obstruction_: elevated total bilirubin, alk phos, 5’-nucleotidase, GGT
2. May have high tumor markers, like **Ca 19-9**
- DX: ERCP, MRCP
- TX: _surgery_, endoscopic palliation -\> need to get early dx in order to offer some kind of tx
1. Not good for transplant because cancers come back -\> very selective pts can be presented for this, but only some centers, incl Memphis, and protocol very detailed
2. Mostly fatal in a few months
49
How does cholangiocarcinoma advance?
- Progressively: starts with an in situ lesion
1. Note the Rokitansky-Aschoff sinus in the chronic inflammatory lesion
- Do NOT memorize all of these; images are what is important here
50
What do you see here?
- **Infiltrating cholangiocarcinoma** (of gallbladder): more common; usually appears as a poorly defined area of _diffuse mural thickening_ and induration
- Deep ulceration can cause direct penetration into the liver or _fistula formation_ to adjacent viscera into which the neoplasm has grown
- Need to look at wall to see if thickened: may be from edema, but if solid, tan-white, then area of tumor
- Note the attached histo image
- Other gross pattern: exophytic (both types are adenocarcinomas)
51
What is this?
- **Exophytic cholangiocarcinoma** (of gallbladder): grows into lumen as an irregular, _cauliflower mass_, but at the same time _invades the underlying wall_
- This type is much more rare
- Note the attached histo image
- Other gross pattern: infiltrative -\> both types are adenocarcinomas
52
What do you see in these 3 images?
- Normal gallbladder (left) vs. carcinoma (right two images)
- Invasive adenocarcinoma
- _Dysplasia at top, and atypical glands going down_
- Can be tough b/t Rokitansky-Aschoff and cancer sometimes: R-A will never go horizontal
1. Cytology should also give it away -\> loss of polarity, hyperchromasia, ugly, elongated cells in cancer
53
What is this?
- **Porcelain gallbladder**: rare, caused by extensive dystrophic calcification in the gallbladder wall
- Notable for a _markedly INC incidence of assoc cancer_
54
How are chronic pancreatitis and biliary obstruction related? Tx?
- 20% of pts w/chronic pancreatitis will present with biliary obstruction
1. Clinical presentation: cholestatic pattern of liver enzymes + chronic pancreatitis
- Compression as CBD enters pancreas due to chronic pancreatitis + inflammation: compressed from outside, OR:
1. Stone inside pancreatic duct: different than biliary -\> hard Ca stone from chronic pancreatitis
- TX: biliary stent placement (to decompress the obstruction) and/or surgery
55
What do you see here (post-liver transplantation)?
- 2 cystic ducts: one from patient and one from donor -\> anastamosis can get narrow and get _strictures_
- Can tx with _balloon dilatation_ through scope (most do well after this)
- Biliary complications in 5% of pts after liver transplantation -\> present with a cholestatic pattern of liver enzymes
1. DX: ERCP, MRCP
2. TX: endoscopic mgmt successful in many pts; complex complications require surgery
56
What is hemobilia? Signs? Presentation? Tx?
- 3 SIGNS: 1) jaundice, 2) melena, 3) abdominal pain
1. Only thing that will give you this combo
- Blood from biliary treee: can happen as a cx of gallbladder surgery, trauma, etc.
- Tx: radiologic procedures with embolization or surgery
GI
flashcards
Decks in class (25)
# Cards
-
Johnson - Physiology95
-
Gupta - Pathology148
-
Sweatman - GI System Pharm23
-
Ray - Gastroparesis35
-
Jackson - Gastric Neoplasia44
-
Jackson - Colon Polyps to Cancer66
-
Cross - ID73
-
Howden - GERD27
-
Howden: PUD30
-
Howden - IBD33
-
Marino - Pathophys of Diarrhea44
-
Tombazzi - Carcinoid, GIST, Lymphoma36
-
Tombazzi - Vascular GI Disorders61
-
Bahouth - Diarrhea and Constipation28
-
Sweatman - Drugs for HCV/HBV32
-
Waters - Liver169
-
Sweatman - Tx for C. diff11
-
Bilal - Constipation/Megacolon39
-
Sweatman - Salivary Flow17
-
Howden - Acid-Suppressing Drugs32
-
Ryan/Nair - Hepatitis69
-
Ray - Malabsorption49
-
Tombazzi - Gallbladder56
-
Marino - Pancreas73
-
Sweatman - GI Cancer18
