General Surgery Liver and Gallbladder Flashcards
Describe the anatomy of the biliary tree
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
What is the the role of the sphincter of Oddi
Around ampulla of Vater and regulates flow of bile and pancreatic juice
What are the two muscular sphincters in the biliary tree
Around common bile duct and sphincter of Oddi
what is bile composed of
bile composed of bile salts (50%) phospholipids (40%) including lecithin cholesterol (4%) bilirubin (2%) water electrolytes
Origin of bile, destination and amount per day
bile is secreted by the liver into GI tract (~0.5L daily)
Function of bile
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
What’s the deal with bile salts and the colon
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
Enterohepatic circulation
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
Secretin regulation of bile
acidic chyme enter the duodenum cause secretion of secretin by duodenum
secretin increase secretion of bicarbonate and water through the hepatic bile duct
Bile in the gallbladder
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
What are bile acids, how are they made, what do they do and what is the consequence of not having them
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)
Primary vs secondary bile acids
primary bile acids are conjugated and include cholic and chenodeoxycholic acid
secondary bile acids are unconjugated and include deoxycholic and lithocholic acid
Synthesis of bile acids
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
Reabsorption of bile acids
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
Use of bile acids in lowering plasma cholesterol
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
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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
Cholesterol in bile
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
Formation of cholesterol stones in bile
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
Characteristics of bilirubin
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
Metabolism of bilirubin
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
Cholelithiasis definition
stone formation in galbladder
biliary colic definition
transient / intermittent obstruction of cystic duct that is symptomatic (painful)
Cholecystitis definition
obstruction of cystic duct by a gallstone causing inflammation of gallbladder
Choldedocholithiasis definition
obstruction of common bile duct (without infection)
Cholangitis definition
infection and inflammation of common bile duct, usually due to choledocholithiasis
What is the prevalence of cholelithiasis
10%
Cholesterol stones risk factors
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
Pigmented stone risk factors
Cirrhosis
Chronic hemolytic states
Bile stasis due to stricture or biliary infection
Pathophysiology of cholelithiasis
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
Proportion of cholesterol vs pigmented gall stones
80% gall stones are cholesterol stones; 20% gall stones are pigmented stones
Clinical presentation of cholelithiasis
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
What changes in labs might you see with gallstone diseases
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
Imaging methods of the biliary tree
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
What are potential complications of performing ERCP
pancreatitis
pancreatic sepsis
biliary sepsis
Biliary colic pathophysiology
gallstone transiently impacted in cystic duct
no inflammation and no infection of gallbladder
Biliary colic clinical presentation
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
Biliary colic investigations and their findings
normal labs
abdominal
ultrasound: cholelithiasis
Biliary colic treatment
colic episode: analgesia, rehydration
if recurrent, elective cholecystectomy (95% success) booked as outpatient
Cholecystitis pathophysiology
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
Cholecystitis clinical presentation
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
Potential complications of acute cholecystitis
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
Cholecystitis investigations
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
Cholecystitis management
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
Potential complications of cholecystectomy
biliary injury -> biliary leak -> peritonitis
uncontrolled bleeding
bowel injury -> perforation
post-cholecystectomy syndrome (persistent
abdominal pain and dyspepsia)
Choledocholithiasis pathophysiology
choledocholithiasis = stone in common bile duct, resulting in biliary obstruction and cholestasis
Difference between choledocholithiasis primary and secondary stones
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)
Clinical presentation choledocholithiasis
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
Complications of choledocholithiasis
cholangitis
pancreatitis
biliary stricture
biliary cirrhosis
Choledocholithiasis investigations
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)
Choledocholithiasis management
ERCP for stone extraction and sphincterotomy followed by elective cholecystectomy
indication for ERCP = common bile duct dilatation with increasing and elevated bilirubin
Cholangitis pathophysiology
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
Cholangitis clinical presentation
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
Cholangitis investigations
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
Cholangitis management
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
What is a t tube
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.
Etiologies of acute pancreatitis
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)
What are the most important causes for acute pancreatitis
gallstone and ethanol pancreatitis are the most important causes for acute pancreatitis
Pathophysiology of acute pancreatitis
acute pancreatitis = acute inflammation of pancreas with restoration of normal anatomy and function following resolution
pancreatic inflammation cause release of degradative pancreatic enzymes
Acute pancreatitis clinical presentation
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
Local complications of acute pancreatitis
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
Acute pancreatitis systemic complications
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
Acute pancreatitis investigations
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
Acute pancreatitis diagnosis
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
Acute pancreatitis management
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)
What is Ranson’s criteria
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)
Ineffective treatment for acute pancreatitis not recommended
nasogastric tube or total parental nutrition (TPN)
prophylactic antibiotic for all patients
control of acid secretion
pancreatic secretion inhibitor
Surgery indications and procedure for acute pancreatitis
Indications:
necrotizing pancreatitis refractory to medical management with sepsis (usually in ICU admission)
Procedure:
surgical debridement of necrotic pancreatic tissue and drain placement
Chronic pancreatitis definition
chronic pancreatitis is chronic inflammation of pancreas with irreversible morphological and functional deterioration
Causes of chronic pancreatitis
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
Pathophysiology of alcohol chronic pancreatitis
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
Chronic pancreatitis pathology
atrophy of parenchyma with dilated pancreatic duct and intraductal calculi
Chronic pancreatitis disease course
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
Local complications of chronic pancreatitis
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)
Systemic complications of chronic pancreatitis
Diabetes in >40% cases
Bile duct, duodenal or gastric obstruction in 5-10% of cases
Chronic pancreatitis clinical presentation
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
Chronic pancreatitis investigations
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
Chronic pancreatitis diagnosis
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
Management of chronic pancreatitis
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
Chronic pancreatitis surgery indications
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
Chronic pancreatitis surgery pre-op
Pre-op CT and/or ERCP mandatory to delineate anatomy and plan surgery
Chronic pancreatitis surgery procedure
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
Clinical signs of hyperbilirubinemia
jaundice
scleral icterus (yellowing of sclera)
pruritus
bilirubinuria (dark urine)
acholic (pale) stool
Definition of jaundice
yellow pigmentation of skin on clinical exam due to hyperbilirubinemia (high level of bilirubin in blood)
Cause and labs for pre-hepatic jaundice
Caused by hemolysis
Indirect bili high
Direct bili normal
Urine Urobilinogen high
Bilirubin urine negative
Fecal
urobilinogen high
High LDH
High reticulocytes
Low haptoglobin
Cause and labs for intra-hepatic jaundice
Causes - hepatic cellular
Indirect bili high
Direct bili high
Urine Urobilinogen high
Bilirubin urine positive
Fecal
urobilinogen high
High AST and ALT
Cause and labs for post-hepatic jaundice
Causes - cholestasis
Indirect bili normal
Direct bili high
Urine Urobilinogen high
Bilirubin urine positive
Fecal
urobilinogen none
High GGT and ALP
Approach to hyperbilirubinemia/jaundice
Tony’s pg 101
Lab results with Gilbert’s syndrome
increased bilirubin after fasting, UGT1A1 DNA mutation
Hemolysis work-up
CBC
Reticulocyte count
Blood film
LDH
Haptoblobin
Biliruibin
What can cause AST and ALT in the thousands
viral hepatitis
Tylenol toxicity
Ischemia
Hepatic cellular causes of hyperbilirubinemia and how to diagnose them
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
Cholestasis causing hyperbilirubinemia labs and differential
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
Extra-hepatic cholestasis causing hyperbilirubinemia causes differential and how to diagnose them
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
Intra-hepatic cholestasis causing hyperbilirubinemia causes differential and how to diagnose them
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
Pancreatic cancer epidemiology
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
Risk factors for pancreatic cancer
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
Pancreatic cancer pathophysiology
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
Clinical presentation of pancreatic cancer
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
Physical exam pancreatic cancer
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)
What is Courvoisier’s sign
Jaundice with enlarged non-tender gall-bladder
Pancreatic cancer investigations
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
Pancreatic cancer diagnosis
diagnosis based on pathology of tissue biopsy and staging by abdominal CT with contrast
Pancreatic cancer prognosis
very poor prognosis with 5 year survival of 5-10%
median survival ~5 months
Pancreatic cancer management
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)
Criteria that must be met to complete a Whipple in pancreatic cancer
- no invasion of cancer to adjacent structure (stomach, spleen, colon, adrenal gland)
- no encasement of major blood vessels (splenic artery, superior pancreaticoduodenal artery, celiac trunk, superior mesenteric artery, common hepatic artery, portal vein, IVC)
- no metastasis to liver or peritoneum
- tumor is borderline resectable which may become resectable following neoadjuvant chemotherapy or tumors that abut the major blood vessels
Whipple procedure
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
What does biliary tract cancer affect
biliary cancer include gallbladder and common bile duct cancer (cholangiocarcinoma)
biliary tract cancer epidemiology
~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
Risk factor for gallbladder cancer
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
Risk factor for cholangiocarcinoma
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
Biliary tract cancer pathology (types, location and spread)
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
Biliary Tract Cancer clinical presentation
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
Biliary Tract Cancer physical exam
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)
Biliary Tract Cancer investigations
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
Management of gallbladder cancer
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
Gallbladder cancer prognosis
poor prognosis of 10% 5-year survival
Management of extra-hepatic bile duct cancer
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
