General Surgery Liver and Gallbladder

Question 1

Describe the anatomy of the biliary tree

Answer 1

Gall bladder leads to cystic duct

Right and left hepatic ducts join to form common hepatic duct

Cystic duct joins common hepatic duct to form the common bile duct

Common bile duct and main pancreatic duct join at the hepatopancreatic ampulla (of Vater), which empties into duodenum

Question 2

What is the the role of the sphincter of Oddi

Answer 2

Around ampulla of Vater and regulates flow of bile and pancreatic juice

Question 3

What are the two muscular sphincters in the biliary tree

Answer 3

Around common bile duct and sphincter of Oddi

Question 4

what is bile composed of

Answer 4

bile composed of
bile salts (50%)
phospholipids (40%) including lecithin
cholesterol (4%)
bilirubin (2%)
water
electrolytes

Question 5

Origin of bile, destination and amount per day

Answer 5

bile is secreted by the liver into GI tract (~0.5L daily)

Question 6

Function of bile

Answer 6

secrete bile salts to aid in digestion and reabsorption of dietary fat and fat soluble vitamins

excretory route for cholesterol (bile is the only excretory route for cholesterol)

excretory route for bilirubin

excretory route for detoxified hydrophobic endogenous metabolites and drugs

Question 7

What’s the deal with bile salts and the colon

Answer 7

bile salts are toxic to the colon

in colon, bile salts inhibit NaCl and water absorption while stimulating NaCl and water secretion, causing secretory diarrhea

therefore, bile salts need to be reabsorbed in small intestine, so that it does not enter colon

also, reabsorption of bile salts do not place a huge metabolic demand of liver to synthesize new bile salts

Question 8

Enterohepatic circulation

Answer 8

1) bile salts synthesized in liver and transported into bile duct
between meal, the sphincter of Oddi is closed, so the bile will flow into gallbladder where the gallbladder stores and concentrates bile
during meal, the sphincter of Oddi is open, the bile will flow via bile duct into duodenum

2) ingestion of fat increase CCK (secreted by duodenum), which contracts gallbladder contraction and relaxes sphincter of Oddi to allow bile enter duodenum
3) in duodenum, bile salts participate in digestion and absorption of fat

4) the bile salts are reabsorbed in terminal ileum into blood, where it is returned via portal circulation into liver
other components of bile (bilirubin, other hydrophobic substances) are not absorbed and continues down GI tract to be excreted

Question 9

Secretin regulation of bile

Answer 9

acidic chyme enter the duodenum cause secretion of secretin by duodenum

secretin increase secretion of bicarbonate and water through the hepatic bile duct

Question 10

Bile in the gallbladder

Answer 10

gallbladder concentrates bile by 6-10 folds

gallbladder reabsorb electrolytes and fluid from bile to concentrate bile salt, bilirubin, cholesterol and calcium

by concentrating bile and pumping out bicarbonate (HCO3), the gallbladder bile is more acidic than hepatic bile, which prevent from precipitation of calcium

gallbladder also secrete mucus to protect its wall from toxic effect of bile salts

Question 11

What are bile acids, how are they made, what do they do and what is the consequence of not having them

Answer 11

bile salts = bile acids compounded with a cation (Na)

synthesized by smooth ER of hepatocytes and undergo enterohepatic recirculation

bile acids emulsify food lipids to facilitate digestion by pancreatic lipase and assist in lipid absorption in small intestine

absence of bile salt impair lipid digestion & absorption, resulting in fat malabsorption and steatorrhea (excretion of fat in stool)

Question 12

Primary vs secondary bile acids

Answer 12

primary bile acids are conjugated and include cholic and chenodeoxycholic acid
secondary bile acids are unconjugated and include deoxycholic and lithocholic acid

Question 13

Synthesis of bile acids

Answer 13

1) in liver, cholesterol is converted to primary bile acids
HMG CoA reductase is a rate limiting enzyme in synthesis of cholesterol from acetyl CoA, which is inhibited by statin
7alpha-hydroxylase is a rate limiting enzyme in synthesis of bile acids from cholesterol
7alpha-hydroxylase inhibited by negative feedback, so its activity is inhibited by high concentration of bile acid in hepatocyte

2) in intestine, bacteria convert primary bile acid into secondary bile acid

Question 14

Reabsorption of bile acids

Answer 14

both primary (conjugated) and secondary (deconjugated) bile acid are reabsorbed in ileum
95% of secreted bile acids are reabsorbed by ileum, where the rest are converted to secondary (unconjugated) bile acids by bacteria to be excreted
primary (conjugated) bile acid is absorbed into ileal epithelial enterocytes by carrier coupled with Na co-transport
secondary (unconjugated) bile acid diffuses across membrane of ileal epithelial enterocytes
in ileal epithelial enterocytes, primary and secondary bile acids are bound to cellular component and transported to portal blood to liver

liver hepatocytes re-uptake bile acids from portal blood
99% of bile acids in portal blood is taken up by hepatocytes

failure to reabsorb bile salts result in fat malabsorption (steatorrhea, weight loss, malnutrition, kidney stone), secretory diarrhea
giving cholestyramine will prevent bile salt’s toxic effect on colon (secretory diarrhea), but will not prevent steatorrhea

Question 15

Use of bile acids in lowering plasma cholesterol

Answer 15

bile acid resin (cholestyramine) used to lower cholesterol
1) bile acid resin bind and trap bile acids in intestine, so that the bound bile acids cannot be reabsorbed
2) the unabsorbed bile acids bound by resin are excreted as waste
36
3) the depletion of bile acids due to failure to reabsorb bile acid stimulate synthesis of bile acid in the liver
4) new bile acids are synthesized by liver from cholesterol, thereby depleting cholesterol

Question 16

Cholesterol in bile

Answer 16

cholesterol is very hydrophobic

bile salt and lecithin (phospholipid) in bile help dissolve cholesterol in bile
both bile salt and lecithin have both hydrophobic and hydrophilic part to help dissolve cholesterol in water

Question 17

Formation of cholesterol stones in bile

Answer 17

cholesterol is not very soluble in aqueous solution

presence of bile salts and lecithin stabilize cholesterol in solution
lecithin and bile salt form micelles containing cholesterol inside
micelle is cylindrical in shape consisting of a hydrophilic exterior and a hydrophobic interior
bile salt form outer surface of micelle
cholesterol is solubilized in lipid rich interior of micelle next to long chain fatty region of lecithin
lethicin have hydrophobic tail in interior of micelle with cholesterol and hydrophilic head in exterior of micelle with water

a specific proportion of cholesterol, lecithin and bile salt is required to keep cholesterol solubilized

change in any proportion of cholesterol, lecithin or bile salt can destabilize cholesterol, resulting in precipitation of cholesterol stones

Question 18

Characteristics of bilirubin

Answer 18

bilirubin in its native (unconjugated) state is toxic to cell

bilirubin is hydrophobic

to reduce toxicity and increase solubility, bilirubin is conjugated to glucuronic acid by liver

conjugated bilirubin is excreted via bile

Question 19

Metabolism of bilirubin

Answer 19

1) in spleen, old red blood cells are broken down where heme is broken down to bilirubin
2) bilirubin is bound to albumin and transported via blood to liver
3) in liver, bilirubin is conjugated and then secreted into bile

4) in colon, bacteria metabolize bilirubin to urobilinogen, which is further oxidized into stercobilin and urobilin
some urobilinogen is reabsorbed in intestine back into portal blood blood
reabsorbed urobilinogen can be uptake by kidney or liver
kidney convert urobilinogen into urobilin to excrete it in urine
liver can secrete urobilinogen into bile

5) urobilinogen, stercobilin and urobilin is excreted by feces
kidney is also able to adapt to hyperbilirubinemia by conjugating bilirubin and excreting it in urine
high level of bilirubin in urine turns urine dark, which is a sign of hyperbilirubinemia

Question 20

Cholelithiasis definition

Answer 20

stone formation in galbladder

Question 21

biliary colic definition

Answer 21

transient / intermittent obstruction of cystic duct that is symptomatic (painful)

Question 22

Cholecystitis definition

Answer 22

obstruction of cystic duct by a gallstone causing inflammation of gallbladder

Question 23

Choldedocholithiasis definition

Answer 23

obstruction of common bile duct (without infection)

Question 24

Cholangitis definition

Answer 24

infection and inflammation of common bile duct, usually due to choledocholithiasis

Question 25

What is the prevalence of cholelithiasis

Answer 25

10%

Question 26

Cholesterol stones risk factors

Answer 26

4 Fs: female, fair skin (Scandinavian), fat and fertile (pregnancy, increase parity)

increasing age

ethnicity: Aboriginal > Caucasian > Black

rapid or cyclic weight loss

drugs: ceftriaxone, post menopause estrogen

family history of gallstone disease

terminal ileal disease, resection or bypass

gallbladder dysmotility due to starvation, total parenteral nutrition, diabetes, truncal vagotomy

high tryglyceride and how HDL

Question 27

Pigmented stone risk factors

Answer 27

Cirrhosis

Chronic hemolytic states

Bile stasis due to stricture or biliary infection

Question 28

Pathophysiology of cholelithiasis

Answer 28

cholesterol supersaturation, impaired gallbladder motility and cholesterol crystal nucleation lead to cholesterol precipitation and formation of stones

stones can be impacted in neck of gallbladder or cystic duct, which obstruct and cause inflammation of gall bladder (cholecystitis)

stones can obstruct in the common bile duct (choledocholithiasis), which cause stasis of bile and infection within the common bile duct (cholangitis)
obstruction of common bile duct result in back up of bile into liver, damaging the liver (increasing cholestatic liver enzymes)
failure to get rid of bile result in in increased conjugated bilirubin, causing jaundice
back up of bile due to choledocholithiasis could result in reflux of bile into pancreatic duct into pancreas, irritating the pancreas causing pancreatitis

Question 29

Proportion of cholesterol vs pigmented gall stones

Answer 29

80% gall stones are cholesterol stones; 20% gall stones are pigmented stones

Question 30

Clinical presentation of cholelithiasis

Answer 30

80% patients with gallstone are asymptomatic

gallstone can cause any of the following:

biliary colic (10-25% gallstone patients)

cholecystitis

choledocholithiasis (8-15% gallstone patients)

cholangitis

gallstone pancreatitis

gallstone ileus

Question 31

What changes in labs might you see with gallstone diseases

Answer 31

CBC: leukocytosis in cholecystitis, cholangitis

liver enzymes: elevated cholestatic enzymes ALP, GGT in biliary obstruction (choleducholithiasis, cholangitis)

bilirubin: elevated in obstruction of common bile duct (choleducholithiasis)

pancreatic enzymes: elevated amylase and lipase in gallstone pancreatitis

Question 32

Imaging methods of the biliary tree

Answer 32

Abdominal Ultrasound
abdominal ultrasound is the diagnostic procedure of choice for imaging of biliary tree
visualization: localization of gallstone, biliary tree for obstruction and signs of inflammation of gallbladder

MRCP (Magnetic Resonance Cholangiopancreatography)
visualization: upper GI tract, biliary tree, pancreatic ducts, ampullary region
MRCP can provide better visualization of any stone obstructed in biliary tree

ERCP (Endoscopic Retrograde Cholangiopancreatography)
visualization: upper GI tract, biliary tree, pancreatic ducts, ampullary region
ERCP is therapeutic, where it can remove obstructed stone in biliary tree and perform sphincterectomy to prevent future stone obstruction

Question 33

What are potential complications of performing ERCP

Answer 33

pancreatitis

pancreatic sepsis

biliary sepsis

Question 34

Biliary colic pathophysiology

Answer 34

gallstone transiently impacted in cystic duct

no inflammation and no infection of gallbladder

Question 35

Biliary colic clinical presentation

Answer 35

GI: steady severe dull RUQ pain radiating to right shoulder crescendo-decrescendo pattern lasting minutes to hours with full resolution, usually worse after fatty meal or at night

by definition, biliary colic will have full resolution of RUQ pain

no systemic signs

abdomen exam: soft, may have RUQ tenderness, negative Murphy, no peritoneal signs

Question 36

Biliary colic investigations and their findings

Answer 36

normal labs
abdominal

ultrasound: cholelithiasis

Question 37

Biliary colic treatment

Answer 37

colic episode: analgesia, rehydration

if recurrent, elective cholecystectomy (95% success) booked as outpatient

Question 38

Cholecystitis pathophysiology

Answer 38

sustained gallstone impaction in cystic duct or Hartmann’s pouch, resulting in inflammation of gallbladder

in 5-10% cholecystitis cases, there is no cholelithiasis (acalculous cholecystitis) usually due to gallbladder ischemia or stasis in ICU patients on TPN

Question 39

Cholecystitis clinical presentation

Answer 39

GI: persistent epigastric or RUQ pain lasting hours to days that may radiate to right sub-scapular region (Boas’ sign), anorexia, nausea & vomiting

systemic: low grade fever

abdomen exam: RUQ tenderness, positive Murphy’s sign

Question 40

Potential complications of acute cholecystitis

Answer 40

empyema of gallbladder = suppurative cholecystitis with pus in gallbladder due to infection

emphysematous cholecystitis = bacterial infection resulting in gas in gallbladder lumen, wall or pericholecystic space

gangrenous gallbladder (20% cases) -> perforation (2% cases), which may result in abscess formation or peritonitis

cholecystoenteric fistula = repeated cholecystitis resulting in fistula formation from gallbladder to intestine, which can lead to gallstone ileus (gallstone traversing through fistula into
intestines causing obstruction)

Mirizzi syndrome = extra-luminal compression of common bile duct or common hepatic duct due to large stone in cystic duct or Hartmann’s pouch, causing transient fever, RUQ pain
and jaundice

gallbladder mucocele (hydrops) = mucus accumulation in gallbladder

Question 41

Cholecystitis investigations

Answer 41

labs: leukocytosis, mild elevated liver enzymes (AST, ALT, ALP, GGT) and bilirubin

abdominal ultrasound:

1) cholelithiasis
2) thickening of gallbladder wall >4mm
3) peri-cholecystic fluid
4) sonographic Murphy’s sign

abdominal ultrasound 98% sensitive for acute cholecystitis

Question 42

Cholecystitis management

Answer 42

1) Disposition
admit to hospital

2) Supportive management
NPO, hydration, analgesia

3) Consider antibiotics
if fever, leukocytosis, consider antibiotics Ciprofloxacin + Metronidazole IV to cover for E. coli, Klebsiella, Enterococcus and Clostridium

4) Surgery
cholecystectomy as definitive treatment to prevent complications of cholecystitis and prevent further episodes of cholecystitis

if cholecystitis complications especially infection, emergent cholecystectomy

if uncomplicated cholecystitis, elective cholecystectomy early within 72 hours since onset of symptoms or delayed after 6 weeks since onset of symptoms
72 hours to 6 weeks is outside operative window, due to prolonged inflammation of gallbladder, which make surgery difficult due to alteration of anatomy from inflammation

laparoscopic cholecystectomy is standard of care, but may convert to open cholecystectomy for complication or difficult case
laparoscopic cholecystectomy have lower risk of wound infection, shorter hospital stay and reduced post-op pain, but increased risk of bile duct injury

5) Other interventions
intra-operative cholangiography to clarify bile duct anatomy, for obstructive jaundice, for history of biliary pancreatitis, for small stones in gallbladder with wide cystic duct, for
single faceted stone in gallbladder, bilirubin >137umol/L
alternative to surgery = percutaneous cholecystostomy tube to drain gallbladder if critically ill or general anesthetic contraindicated

Question 43

Potential complications of cholecystectomy

Answer 43

biliary injury -> biliary leak -> peritonitis

uncontrolled bleeding

bowel injury -> perforation

post-cholecystectomy syndrome (persistent
abdominal pain and dyspepsia)

Question 44

Choledocholithiasis pathophysiology

Answer 44

choledocholithiasis = stone in common bile duct, resulting in biliary obstruction and cholestasis

Question 45

Difference between choledocholithiasis primary and secondary stones

Answer 45

primary stone = stone formed in bile duct, usually in bile duct pathology (biliary stricture, sclerosing cholangitis, choledochal cyst, cystic fibrosis)

secondary stone = stone formed in gallbladder (85% cases)

Question 46

Clinical presentation choledocholithiasis

Answer 46

50% cases are asymptomatic

GI symptoms: history of biliary colic, epigastric or RUQ pain, hyperbilirubinemia (jaundice, acholic stool, dark urine)

systemic symptoms: low grade fever

abdomen exam: RUQ tenderness, negative Murphy’s sign

Question 47

Complications of choledocholithiasis

Answer 47

cholangitis

pancreatitis

biliary stricture

biliary cirrhosis

Question 48

Choledocholithiasis investigations

Answer 48

labs: elevated liver enzymes (cholestatic pattern: elevated ALP and GGT), high bilirubin

abdominal ultrasound: intra/extra hepatic duct dilatation, common bile duct dilatation

MRCP: visualization of stone and cholestasis (90% sensitive, 100% specific)

Question 49

Choledocholithiasis management

Answer 49

ERCP for stone extraction and sphincterotomy followed by elective cholecystectomy

indication for ERCP = common bile duct dilatation with increasing and elevated bilirubin

Question 50

Cholangitis pathophysiology

Answer 50

cholangitis = infection of common bile duct

infection micro-organism: “KEEPS” = Klebsiella, E. coli, Enterobacter, Enterococcus, Pseudomonas, Proteus, Serratia, B. fragilis

biliary obstruction -> cholestasis -> bacterial overgrowth -> bacterial infection of common bile duct, which can lead to pus and biliary sepsis

cause for biliary obstruction: choledocholithiasis in 60% cases, biliary stricture, neoplasm (pancreatic, biliary), extrinsic compression (pancreatic pseudocyst, pancreatitis),
instrumentation of bile duct (ERCP), biliary stent

Question 51

Cholangitis clinical presentation

Answer 51

Charcot’s triad: fever, jaundice, RUQ pain

Reynold’s pentad: fever, jaundice, RUQ pain, hypotension, confusion / altered mental status (combination of Charcot’s triad with shock and altered mental status)

GI symptoms: nausea & vomiting, RUQ pain radiating to right shoulder, hyperbilirubinemia (jaundice, scleral icterus, echoic stool, dark urine)

systemic symptoms: fever, chills, rigors

vitals: may have sepsis

abdomen exam: RUQ tenderness

Question 52

Cholangitis investigations

Answer 52

labs: leukocytosis, elevated liver enzymes (cholestatic pattern: elevated ALP and GGT)
may have positive blood culture

abdominal ultrasound: intra/extra hepatic duct dilatation, common bile duct dilatation

Question 53

Cholangitis management

Answer 53

1) Disposition
admit to hospital

2) Supportive management
NPO, fluid resuscitation

3) Antibiotic therapy
broad IV antibiotics:

1st line = Ceftriaxone + Metronidazole

2nd line = Meropenem or Ertapenem

4) ERCP
ERCP to remove stone in common bile duct and sphincterotomy

consider laparotomy with CBD exploration and T-tube placement if ERCP fails

5) Surgery
elective cholecystectomy

Question 54

What is a t tube

Answer 54

It is put in place after bile duct surgery to drain bile while the duct is healing. The tube drains into a bag that is attached to your body.

Question 55

Etiologies of acute pancreatitis

Answer 55

I = idiopathic
G = gallstone
E = ethanol
T = trauma
S = steroids, surgery, sphincter of Oddi dysfunction
M = mumps
A = autoimmune
S = scorpion bite
H = high calcium, high triglycerides, hypothermia
E = ERCP
D = drugs (NSAIDs, diuretics, immunosuppressor)

Question 56

What are the most important causes for acute pancreatitis

Answer 56

gallstone and ethanol pancreatitis are the most important causes for acute pancreatitis

Question 57

Pathophysiology of acute pancreatitis

Answer 57

acute pancreatitis = acute inflammation of pancreas with restoration of normal anatomy and function following resolution

pancreatic inflammation cause release of degradative pancreatic enzymes

Question 58

Acute pancreatitis clinical presentation

Answer 58

GI symptoms: nausea & vomiting, severe abdominal pain (classically epigastric radiating to back)

vitals: fever, tachycardia, hypotension, low O2 saturation (due to ARDS)

general appearance: jaundice and scleral icterus if gallstone pancreatitis

abdominal exam: bruising around flanks (Grey-Turner’s) or umbilicus (Cullen’s) due to hemorrhagic pancreatic necrosis, epigastric tenderness, may have peritoneal signs

Question 59

Local complications of acute pancreatitis

Answer 59

1) Pancreatic necrosis
pancreatic necrosis is sterile and have 10% mortality risk
pancreatic necrosis have risk of being infected
infected pancreatic necrosis is most severe complication with high (25%) mortality risk

2) Pancreatic pseudocyst
pancreatic pseudocyst = collection of pancreatic juice surrounded by granulation tissue due to pancreatic duct leakage (usually >4 weeks post pancreatitis), usually
communicating with pancreatic duct
pancreatic pseudocyst can erode into adjacent vessels (commonly splenic artery, gastroduodenal artery or pancreaticoduodenal artery), causing pseudo-aneurysm and
hemorrhage
pancreatic pseudocyst can compress on adjacent structures, causing obstruction and pain
pancreatic pseudocyst can be infected, forming an abscess

3) Thrombosis (splenic vein, superior mesenteric vein, portal vein)
inflammation cause blood stasis in nearby veins, causing thrombosis, commonly at splenic vein, superior mesenteric vein or portal vein
vein thrombosis can also rupture

4) Fistula
pancreas can form fistula with adjacent structures, commonly with colon at splenic flexure

Question 60

Acute pancreatitis systemic complications

Answer 60

metabolic: hypocalcemia, hyperglycemia, hypertriglyceridemia, acidosis
vascular: vascular thrombosis
infectious: sepsis / septic shock
hematologic: anemia, DIC (disseminated intravascular coagulopathy), leucocytosis
dermatologic: painful subcutaneous fat necrosis
neurologic: psychosis, encephalopathy, cerebral emboli, blindness
heart: arrhythmia, hypovolemia and shock (which may lead to myocardial infarction), pericardial effusion
respiratory: ARDS (acute respiratory distress syndrome), hypoxemia, atelectasis, effusion, pneumonitis

GI: ileus, obstruction, gastrointestinal hemorrhage, gastric varices (secondary to splenic vein thrombosis), ascites

liver: jaundice, portal vein thrombosis
renal: renal artery or vein thrombosis, renal failure

Question 61

Acute pancreatitis investigations

Answer 61

CBC: leukocytosis, high hematocrit if volume depleted, thrombocytosis due to inflammation

pancreatic enzymes: elevated amylase and lipase (>3 times upper limit of normal), where lipase is more sensitive and specific than amylase for pancreatitis

liver enzymes: elevated cholestatic liver enzymes ALP, GGT, bilirubin if biliary obstruction

renal function: elevated BUN and creatinine due to volume depletion

imaging:

abdominal ultrasound

abdominal CT with IV contrast

abdominal ultrasound: to see gallstone, which would confirm gallstone pancreatitis

consider MRCP if suspected biliary obstruction where ultrasound and bilirubin are equivocal

abdominal CT with IV: can establish cause, assess severity and detect complications, usually indicated in moderate to severe pancreatitis or pancreatitis that does not resolve within first 48 hours

Question 62

Acute pancreatitis diagnosis

Answer 62

acute pancreatitis if patient satisfy 2 of the following criteria:

1) symptoms consistent with pancreatitis
severe epigastric pain radiating to back

2) lab serum amylase or lipase greater than 3 times the upper limit of normal
3) imaging (CT or US or MRCP) confirming inflammation of pancreas

Question 63

Acute pancreatitis management

Answer 63

1) Risk stratification
stratify mortality risk based on Ranson’s criteria

2) Treat according to risk

a) Mild pancreatitis
disposition: hospitalize
fluids: aggressive rehydration (dextrose in normal saline)
feeding: enteral nutritional support (nasojejunal feeding) once pain improves and lab results normalize (nasojejunal feeding)
sympatomatic relief: pain relief (morphine)
monitor: monitor hemodynamic and laboratory serum parameters

b) Severe pancreatitis
disposition: ICU admission
investigations: CT with contrast to identify pancreatic or peri-pancreatic necrosis
fluids: aggressive volume replacement
feeding: NPO for first 48 hours, then enteral nutritional support (nasojejunal feeding)
sympatomatic relief: pain relief (morphine)

3) Treat complications

if pancreatitis with infectious complications, then IV broad spectrum antibiotics (Ceftriaxone + Metronidazole; Ciprofloxacin + Metronidazole; or Imipenem)

indication for antibiotics: cholangitis, infected necrosis, abscess or infected pseudocyst on abdominal CT or deterioration despite current treatment

if infected necrosis, then surgical debridement

if infected pseudocyst, then endoscopic or percutaneous drainage

if pseudo aneurysm, angiogram and embolization by interventional radiology

if abscess, then drainage

if gallstone and obstructive jaundice, then urgent ERCP

4) Address underlying cause
if gallstone pancreatitis, then cholecystectomy at same hospital admission to prevent recurrence (25-60% recurrence risk of gallstone pancreatitis if no surgery)

Question 64

What is Ranson’s criteria

Answer 64

Risk stratifying criteria for acute pancreatitis

on admission
“GA LAW” =

glucose >10mmol/L

age >55 years

LDH >350 IU/L

AST >250 IU/L

WBC count >16

during first 2 days of pancreatitis, “C & HOBBS)

Ca <2 mmol/L

HCT fall >10%

Oxygen (hypoxemia PaO2 <60mmHg)

Base deficit >4mEq/L

BUN increase by
>1.8mmol

sequestration of fluids >6L

mild pancreatitis = Ranson score 0-3 (<15% mortality)

severe pancreatitis = Ranson score >4 (>40% mortality)

Question 65

Ineffective treatment for acute pancreatitis not recommended

Answer 65

nasogastric tube or total parental nutrition (TPN)

prophylactic antibiotic for all patients

control of acid secretion

pancreatic secretion inhibitor

Question 66

Surgery indications and procedure for acute pancreatitis

Answer 66

Indications:
necrotizing pancreatitis refractory to medical management with sepsis (usually in ICU admission)

Procedure:
surgical debridement of necrotic pancreatic tissue and drain placement

Question 67

Chronic pancreatitis definition

Answer 67

chronic pancreatitis is chronic inflammation of pancreas with irreversible morphological and functional deterioration

Question 68

Causes of chronic pancreatitis

Answer 68

majority (70%) of cases due to chronic alcohol

genetic: hereditary pancreatitis (PRSS mutation); cystic fibrosis (CFTR mutation)
metabolic: hypercalcemia, hyperlipidemia, hypertriglyceridemia

mechanical (benign obstructive causes): pancreatic duct stricture, sphincter of Oddi dysfunction / stenosis, duodenal wall or pancreatic cyst, pancreas divisum

malignancy (causing obstruction): any duodenal, ampulla or pancreatic tumor

autoimmune: autoimmune pancreatitis
other: post-necrotic chronic pancreatitis, tropical chronic pancreatitis

idiopathic

Question 69

Pathophysiology of alcohol chronic pancreatitis

Answer 69

chronic exposure to toxin (alcohol) lead to repeat pancreatitis, resulting in collagen deposition, fibrosis and chronic inflammation

ethanol also result in abnormal secretion by pancreas and precipitation in pancreatic duct, resulting in protein plug blocking the pancreatic ducts

blocked pancreatic duct cause inflammation and increase pressure in parenchyma causing pain

ingestion of food cause release of pancreatic enzyme from pancreas down obstructed ducts, which result in pain

the pancreatic enzyme trapped in pancreatic duct auto-digests the pancreas, resulting in continuous destruction of pancreas

continuous decline in pancreatic function result in symptoms
loss of exocrine function result in malabsorption, causing steatorrhea, weight loss
loss of endocrine function result in diabetes

Question 70

Chronic pancreatitis pathology

Answer 70

atrophy of parenchyma with dilated pancreatic duct and intraductal calculi

Question 71

Chronic pancreatitis disease course

Answer 71

usually chronic pancreatitis span over >10 years

over time, the pain decreases from severe to moderate, which correlate with worsening structural and functional changes in pancreas

Question 72

Local complications of chronic pancreatitis

Answer 72

recurrent acute pancreatitis

pseudocyst (in 25-30% cases), which can rupture, get infected, bleed or obstruct surrounding structure

pancreatic cancer (in 15-40% cases)

pancreatic ascites or pleural effusion (in <10% cases)

splenic vein thrombosis, resulting in portal hypertension or gastric varices (<1% cases)

Question 73

Systemic complications of chronic pancreatitis

Answer 73

Diabetes in >40% cases

Bile duct, duodenal or gastric obstruction in 5-10% of cases

Question 74

Chronic pancreatitis clinical presentation

Answer 74

symptoms: chronic epigastric pain radiating to back aggravated by food and relieved with siting upright

GI symptoms: steatorrhea

constitutional symptoms: weight loss

complications: diabetes, recurrent episodes of acute pancreatitis, malnutrition, vitamin deficiency

Question 75

Chronic pancreatitis investigations

Answer 75

Labs
CBC: leukocytosis
pancreatic enzymes: amylase and lipase are not specific for chronic pancreatitis, where it can be normal or mildly elevated in chronic pancreatitis
liver enzymes, bilirubin: elevated cholestatic liver enzymes if biliary obstruction
fasting blood glucose: high in diabetes secondary to chronic pancreatitis

pancreatic function test: secretin / CCK stimulation with direct enzyme test, Bentiromide test, fecal chymotrypsin concentration, fecal elastase ELISA
not specific for chronic pancreatitis, but useful for suspected chronic pancreatitis with normal CT

Imaging
abdominal imaging: imaging modality of choice for signs of chronic pancreatitis (calcification in pancreatic duct, pancreatic ductal dilatation, pseudocyst, necrosis, pancreatic
parenchyma atrophy, thrombosis, pseudo aneurysm)

endoscopic ultrasound: 1st line diagnosis for early chronic pancreatitis (normal abdominal CT), which can also perform fine needle aspiration biopsy

ERCP: gold standard for diagnosis of chronic pancreatitis, usually reserved for early chronic pancreatitis with normal abdominal CT and normal pancreatitis function test

Question 76

Chronic pancreatitis diagnosis

Answer 76

diagnosis of chronic pancreatitis made based on clinical presentation and imaging study

1) clinical suspicion based on alcohol use, symptoms, signs or lab

2) CT with contrast
if signs of chronic pancreatitis (especially calcification) on CT, then diagnose with chronic pancreatitis
if normal but with high clinical suspicion, then EUS with FNAB and pancreatic test
if cystic or mass (suspected for malignancy), then EUS with FNAB

3) staging
MRCP used for staging chronic pancreatitis
ERCP if MRCP is not available

Question 77

Management of chronic pancreatitis

Answer 77

1) Conservative management
lifestyle changes: discontinuation of alcohol and smoking; frequent small low fat meals (to minimize pancreatic secretion)
pain management: 1st line = Tylenol or NSAID; 2nd line = opioid narcotics
consider adding tricyclic anti-depressants or SSRI for depression and pain

pancreatic suppression: pancreatic enzyme with proton pump inhibitor
pancreatic enzyme cleave / inactivate CCK-RF in duodenum, inhibiting CCK secretion to decrease CKK stimulated pancreatic secretion, treating pain
pancreatic enzyme treat malabsorption, steatorrhea and weight loss

2) Treat complications
relieve obstruction with surgery or stent

consider endoscopic procedure to
treat symptomatic stone by stone removal
treat ductal decompression (stricture) by sphincterotomy or stent
treat pseudocyst by pancreatic rest and drainage
drain pancreatic duct to relieve pain from ductal obstruction

if any obstruction of surrounding structure, hemorrhage or suspected neoplasia, then surgery

3) Surgery
last line of treatment (i.e. failure of medical treatment) = surgery
pancreaticojejunustomy to relieve pain
cystenterostomy for pseudocyst
resection (e.g. Whipple) for mass or small duct disease
last line = distal pancreatectomy

Question 78

Chronic pancreatitis surgery indications

Answer 78

anatomical abnormality causing recurrent pancreatitis

failure of medical treatment

debilitating abdominal pain

pseudocyst complications: persistent pseudocyst, hemorrhage, infection, rupture

obstruction: common bile duct, duodenal obstruction

fistula

variceal hemorrhage secondary to splenic vein thrombosis

rule out pancreatic cancer

Question 79

Chronic pancreatitis surgery pre-op

Answer 79

Pre-op CT and/or ERCP mandatory to delineate anatomy and plan surgery

Question 80

Chronic pancreatitis surgery procedure

Answer 80

1) Pain relief
if dilated pancreatic duct, improve pancreatic drainage by Puestow procedure (longitudinal pancreatojejunostomy)

if no dilated duct, then pancreatectomy
proximal pancreatic disease - Whipple procedure (pancreatoduodenectomy)
distal disease - distal pancreatectomy with Roux-en-Y pancreatojejunostomy
refractory disease = total pancreatectomy

denervation of celiac ganglion and splanchnic nerves

2) Pseudocyst
percutaneous catheter drainage

surgical drainage by cystgastrostomy, cysenterostomy or resection

endoscopic drainage: cystgastrostomy, cysduodenostomy

surgical biopsy of cyst wall to rule out cystuadenocarcinoma

Question 81

Clinical signs of hyperbilirubinemia

Answer 81

jaundice

scleral icterus (yellowing of sclera)

pruritus

bilirubinuria (dark urine)

acholic (pale) stool

Question 82

Definition of jaundice

Answer 82

yellow pigmentation of skin on clinical exam due to hyperbilirubinemia (high level of bilirubin in blood)

Question 83

Cause and labs for pre-hepatic jaundice

Answer 83

Caused by hemolysis

Indirect bili high
Direct bili normal

Urine Urobilinogen high
Bilirubin urine negative

Fecal
urobilinogen high

High LDH
High reticulocytes
Low haptoglobin

Question 84

Cause and labs for intra-hepatic jaundice

Answer 84

Causes - hepatic cellular

Indirect bili high
Direct bili high

Urine Urobilinogen high
Bilirubin urine positive

Fecal
urobilinogen high

High AST and ALT

Question 85

Cause and labs for post-hepatic jaundice

Answer 85

Causes - cholestasis

Indirect bili normal
Direct bili high

Urine Urobilinogen high
Bilirubin urine positive

Fecal
urobilinogen none

High GGT and ALP

Question 86

Approach to hyperbilirubinemia/jaundice

Answer 86

Tony’s pg 101

Question 87

Lab results with Gilbert’s syndrome

Answer 87

increased bilirubin after fasting, UGT1A1 DNA mutation

Question 88

Hemolysis work-up

Answer 88

CBC

Reticulocyte count

Blood film

LDH

Haptoblobin

Biliruibin

Question 89

What can cause AST and ALT in the thousands

Answer 89

viral hepatitis

Tylenol toxicity

Ischemia

Question 90

Hepatic cellular causes of hyperbilirubinemia and how to diagnose them

Answer 90

alcohol hepatitis: chronic alcohol abuse on history

NASH: metabolic syndrome (diabetes, dyslipidemia, obesity)

Hepatitis A: positive anti-Hepatitis A virus IgM antibodies

Hepatitis B: positive HBsAg, positive anti-HBs Ab

Hepatitis C: positive HCV RNA

medication: medication on history

Hemachromatosis: high ferritin (>1000), high transferrin, high % iron saturation (>50%), genetic test C282/C282Y positive for hereditary hemochromatosis

Wilson’s disease: low ceruloplasmin, high 24 hours urinary copper

alpha1 anti-trypsin deficiency: low alpha1 antitrypsin level

autoimmune chronic active hepatitis: positive ANA, positive anti-smooth muscle antibody

Question 91

Cholestasis causing hyperbilirubinemia labs and differential

Answer 91

cholestatic hyperbilirubinemia usually have primarily elevated ALP and GGT, which is much higher than AST and ALT

cholestasis differentiated into intra-hepatic and extra-hepatic cholestasis based on ultrasound

dilated bile duct on ultrasound suggests extra-hepatic cholestasis

non-dilated bile duct on ultrasound suggests intra-hepatic cholestasis

Question 92

Extra-hepatic cholestasis causing hyperbilirubinemia causes differential and how to diagnose them

Answer 92

differential diagnoses can be narrowed based on abdominal ultrasound findings

gall stone: stone visualized on abdominal ultrasound

malignancy: mass visualized on abdominal ultrasound or other imaging, malignancy confirmed on biopsy

PSC: positive ANA, positive anti-smooth muscle antibody, positive peri-nuclear anti-neutrophil cytoplasmic antibodies

Question 93

Intra-hepatic cholestasis causing hyperbilirubinemia causes differential and how to diagnose them

Answer 93

medication: medication on history
sepsis: sepsis based on clinical evaluation
pregnancy: positive serum or urine bHCG

TPN: TPN on examination

PBC: positive anti-mitochondrial antibody (AMA), positive ANA

Question 94

Pancreatic cancer epidemiology

Answer 94

2nd most common GI cancer after colorectal cancer

4th leading cause of cancer death

poor prognosis with <20% 1-year survival and 5% 5-year survival

Question 95

Risk factors for pancreatic cancer

Answer 95

common in blacks

age >45

male (1.3 times more risk compared to female)

chronic pancreatitis (2% risk of pancreatic cancer per decade)

alcohol, smoking

diabetes mellitus (usually diagnosed 2 years before cancer diagnosis)

diet that is high in fat, high in meat or low in fruits

genetic: hereditary pancreatitis, familial pancreatic cancer, hereditary cancer syndromes (p16, p53, K-ras, HNPCC, BRCA2, Peutz-Jehgers syndrome, cystic fibrosis)

pancreatic cysts

Question 96

Pancreatic cancer pathophysiology

Answer 96

pancreatic cancer can be located in head of pancreas or body / tail of pancreas

majority (70%) of pancreatic cancer located in head of pancreas

minority (20%) of pancreatic cancer located in pancreas body and / or tail

95% of malignant pancreatic cancer are exocrine, which include adenocarcinoma

3 types of adenocarcinoma

1) ductal adenocarcinoma arising from pancreatic duct, most common & worst prognosis
2) neuroendocrine adenocarcinoma from Islet of Langerhans cell, best prognosis
3) acinar adenocarcinoma from acinus cells

90% of pancreatic cancer are ductal adenocarcinoma

5% malignant pancreatic cancer are endocrine

Question 97

Clinical presentation of pancreatic cancer

Answer 97

pancreatic cancer usually present at late stage with only obstructive painless jaundice

pancreatic tumor at body or tail can present much later with jaundice

weight loss

vague mid-epigastric abdominal pain, often worse at night and may radiate to back

sudden onset diabetes

Question 98

Physical exam pancreatic cancer

Answer 98

physical exam can be normal

abdominal exam: palpable tumour mass in epigastric area

hepatosplenomegaly

Courvoisier’s sign

other:
left supraclavicular lymphadenopathy (Virchow’s node)

recurring superficial thrombophlebitis

Sister Mary Joseph node (palpable nodule bulging into umbilicus due to
peritoneal spread)

Question 99

What is Courvoisier’s sign

Answer 99

Jaundice with enlarged non-tender gall-bladder

Question 100

Pancreatic cancer investigations

Answer 100

high ALP, GGT, bilirubin due to biliary obstruction

lipase and amylase can be low, normal or high

CA19-9 is tumor marker with high sensitivity and specificity with cut off of >37 for pancreatic cancer

imaging: abdominal ultrasound followed by abdominal CT with contrast

all patients with suspected pancreatic cancer undergo abdominal ultrasound followed by abdominal CT with contrast for staging

biopsy: fine needle biopsy guided by endoscopic ultrasound, CT, MRCP or ERCP

Question 101

Pancreatic cancer diagnosis

Answer 101

diagnosis based on pathology of tissue biopsy and staging by abdominal CT with contrast

Question 102

Pancreatic cancer prognosis

Answer 102

very poor prognosis with 5 year survival of 5-10%

median survival ~5 months

Question 103

Pancreatic cancer management

Answer 103

1) staging to determine course of treatment
CT to determine metastasis and if tumor is resectable or not

2) treatment according to stage

if surgical resectable, then Whipple (pancreaticoduodenectomy) procedure is done

if positive margin from Whipple specimen, then chemotherapy
chemotherapy: gemcitabine, FOLFIRINOX (FOL = Folinic acid, F = 5-FU Fluorouracil, IRIN = Irinotecan, OX = Oxaliplatin)

if not resectable, then palliative treatment with pain control, relief of obstruction and possibly chemotherapy and radiotherapy

relief of biliary / duodenal obstruction with endoscopic stunting or double bypass procedure (choledochoenterostomy and gastroenterostomy)

Question 104

Criteria that must be met to complete a Whipple in pancreatic cancer

Answer 104

1. no invasion of cancer to adjacent structure (stomach, spleen, colon, adrenal gland)
2. no encasement of major blood vessels (splenic artery, superior pancreaticoduodenal artery, celiac trunk, superior mesenteric artery, common hepatic artery, portal vein, IVC)
3. no metastasis to liver or peritoneum
4. tumor is borderline resectable which may become resectable following neoadjuvant chemotherapy or tumors that abut the major blood vessels

Question 105

Whipple procedure

Answer 105

minority (20%) of pancreatic cancer is resectable at diagnosis

Whipple procedure used for tumours on head of pancreas, tumor in common bile duct, tumor in duodenal papilla and tumor in duodenum

Whipple procedure is resection of antrum of stomach, 1st & 2nd part of duodenum, head of pancreas, common bile duct and gallbladder

attachment of remaining pancreas and remaining bile duct to remaining duodenum

attachment of remaining stomach to jejunum

surgery have 2% mortality and 10-20% morbidity risk

25% 5-year survival after procedure

Question 106

What does biliary tract cancer affect

Answer 106

biliary cancer include gallbladder and common bile duct cancer (cholangiocarcinoma)

Question 107

biliary tract cancer epidemiology

Answer 107

~7500 cases of biliary tract cancer per year

majority (2/3) are gallbladder cancer

minority (1/3) are common bile duct cancer (cholangiocarcinoma)

intra-hepatic bile duct cancer are classified as liver cancer

higher prevalence in Asia

Question 108

Risk factor for gallbladder cancer

Answer 108

increasing age (>50 years)

past history of gallstone disease

risk factors of gallstone disease (cholecystitis, cholangitis): female, obesity

gallbladder polyps >1cm in size

porcelain gallbladder

anomalous pancreatico-biliary ductal junction

chronic infection with Salmonella Typhi

Question 109

Risk factor for cholangiocarcinoma

Answer 109

male

primary sclerosing cholangitis (PSC), especially with intra-ductal stones

southeast Asian due to infections of Opisthorchis Viverrini and Chlonorchis Sinensis

smoking

rare risk factors: 
bile duct adenoma
multiple biliary papilomatosis
choledochal cyst
Caroli’s disease
exposure to thorotrast

Question 110

Biliary tract cancer pathology (types, location and spread)

Answer 110

majority of biliary tract cancer are adenocarcinoma (intestinal and fovelar type)

3 types of biliary tract cancer

1) majority are gallbladder cancer (2/3)
early local extension into liver and extension into stomach or duodenum
early metastasis to liver, lung, bone

2) minority are common bile duct cancer (cholangiocarcinoma)
majority (2/3) of cholangiocarcinoma are peri-hilar (Klatskin tumor), at where the left and right hepatic bile duct joins to form the common hepatic bile duct
minority (1/4) of cholangiocarcinoma are extrahepatic
may have growth into portal vein or hepatic artery
uncommon to have early metastasis

3) very few biliary tract cancers arise from ampulla of Vater

Question 111

Biliary Tract Cancer clinical presentation

Answer 111

jaundice, clay coloured stool, tea-colored urine and pruritus due to high bilirubin

gallbladder cancer: localized vague RUQ pain

cholangiocarcinoma: usually painless jaundice

constitutional symptoms: fatigue, malaise, weight loss

can also present with
diabetes
steatorrhea
gastric outlet obstruction, resulting in nausea and vomiting
cholecystitis, cholangitis or pancreatitis

Question 112

Biliary Tract Cancer physical exam

Answer 112

general: jaundice, scleral icterus

abdominal exam: palpable tumour mass or gallbladder, hepatomegaly, Courvoisier’s sign (jaundice with enlarged non-tender gall-bladder)

other: supraclavicular lymphadenopathy (Virchow’s node)

Question 113

Biliary Tract Cancer investigations

Answer 113

high ALP, GGT, bilirubin due to biliary obstruction

CA19-9 is tumor marker with high sensitivity and specificity with cut off of >180 for cholangiocarcinoma

high blood glucose if diabetes

increased INR if malabsorption of fat-soluble vitamin

imaging:
1) abdominal ultrasound
2) abdominal CT with IV contrast
3) endoscopic ultrasound with fine needle aspiration or ERCP with duct brushing

abdominal ultrasound as 1st test to confirm biliary obstruction

CT with IV contrast as 2nd test to look for tumor, invasion, metastases, lymph nodes and resectability

if CT contraindicated, MRCP and MRI instead

Question 114

Management of gallbladder cancer

Answer 114

if stage 0 or 1, then laparoscopic cholecystectomy

if stage >1, then radical cholecystectomy with open surgery and removal of adjacent liver and hepatoduodenal lymph nodes

Question 115

Gallbladder cancer prognosis

Answer 115

poor prognosis of 10% 5-year survival

Question 116

Management of extra-hepatic bile duct cancer

Answer 116

if resectable, then biliary drainage and surgical resection with wide excision margin

if upper third lesion and resectable, then biliary duct resection + Roux-en-Y hepaticojejunostomy +/- liver resection

if middle third lesion: biliary duct resection + Roux-en-Y hepaticojejunostomy

if lower third lesion and resectable, Whipple procedure
surgery have 2% mortality and 10-20% morbidity risk
if positive margin from Whipple specimen, then chemotherapy
10-25% 5-year survival after procedure

if not resectable, then palliative radiation and / or chemotherapy
radiation include external beam radiation or brachytherapy
chemotherapy agents include 5-FU, mitomycin, methotrexate, cisplatin, gemcitabine
radiation and / or chemotherapy have minor improvement in survival and associated with significant side effects

palliation of symptoms
for biliary obstruction, stent by ERCP, percutaneous drainage by interventional radiology or surgical bypass
for pain, narcotics and celiac - axis blocks