Gallbladder and Biliary Tract Disease Flashcards
What does the biliary system refer to?
The liver, gallbladder, bile ducts, and how they work together to make, store, and secrete bile.
What does bile consist of?
Water, electrolytes, bile acids, cholesterol, phospholipids, and conjugated (bilirubin)
Liver produces 500 to 1500 mL of bile per day
Pathway of bile from the lvier
Tonic contraction of the sphincter of oddi during fasting diverts about half og the bile to the cystic duct –> gallbladder where it is stored and concentrated.
Hepatic vs concentrated bile in the GB
Hepatic is isotonic fluid while concentrated (made in the GB) has removed some water and electrolytes through active transport of sodium.
Cholecystokinin (CCK)
Hormone synthesized and secreted by enteroendocrine cells that is released after food is ingested and causes relaxation of sphincter of oddi to allow bile into duodenum.
Secretin
Hormone synthesize in duodenum that enhances the effects of CCK by signaling for release of digestive enzymes from the pancreas and bicarbonate from the liver.
Enterohepatic circulation
Bile acids are efficiently reabsorbed by the small intestinal mucosa in the terminal ileum (95%) and then recycled to the liver for re-excretion.
Diseases that damage the ileum can cause a loss of bile salts which can end up in the stool causing bile acid diarrhea.
Bilirubin
Yellow breakdown product of normal heme catabolism.
Reminder to go through the bilirubin break down process again slides 13-15.
Review** Indirect (unconjugated hyperbilirubinemia)
Increased bilirubin production via hemolysis (increased destruction of of RBCs) and dyserythropoiesis (ineffective erythropoiesis)
Still conjugating and excreting now an increased amount of conjugated bilirubin
↑ conjugated bilirubin enter the gut resulting in ↑ urobilinogen
Hyperbilirubinemia and jaundice
Hyperbilirubinemia causes increased levels of bilirubin in the extracellular fluid.
Causes a yellowish pigmentation of skin, the bulbar conjunctiva, and mucous membrane.
Concentration of total bilirubin greater than 2.5-3mg/dL leads to jaundice
Prehepatic jaundice lab findings
Serum: increased unconjugated (indirect) bilirubin
Urine
no bilirubin present
urobilinogen > 2 units
Stool: increased fecal urobilinogen
Review** Hepatocellular jaundice
Interference in all major steps of bilirubin metabolism:
Uptake, conjugation, excretion (usually to the greatest extent)
Indirect (unconjugated) bilirubin rises if →
Liver has difficulty taking up bilirubin from the circulation
Liver has difficulty conjugating indirect bilirubin
Direct (conjugated) bilirubin rises if → Excretion into the bile is obstructed. Conjugated bilirubin leaks back out and is returned to the blood.
Hepatocellular jaundice lab findings
Serum:
increased total bilirubin
increased direct (conjugated) bilirubin
increased indirect (unconjugated) bilirubin
Urine:
decreased urobilinogen
+ conjugated bilirubin
dark color
Stool:
pale color, decreased fecal urobilinogen
**Review posthepatic or obstructive jaundice
Caused by an interruption to the drainage of bile.
Most common causes
Gallstones in the common bile duct(CBD)
Pancreatic cancer in the head of the pancreas.
Posthepatic jaundice lab findings
Serum:
increased total bilirubin
increased conjugated(direct) bilirubin
normal unconjugated bilirubin
Urine:
decreased or no(in complete obstruction) urobilinogen
+conjugated bilirubin
dark color
Stool:
pale color
Obstructive disease and enzymes
Bile duct epithelial cells are damaged in result of the obstructive process –> leads to increased enzymes in circulation. Measuring these enzymes will indicate bile duct obstruction.
Examples of these enzymes: Alkaline Phosphatase (ALP),
Alkaline phosphatase (ALP)
Function to remove phosphate groups from proteins and other molecules.
Found in the epithelium of the biliary tract and liver as well as osteoblasts, intestinal epithelium, and placenta.
Gamma-glutamyltransferase (GGT)
An enzyme that correlates more with obstruction and cholestasis. Can be ordered with ALP in order to determine if damage is hepatic in origin.
Hepatocellular function enzymes
Those that are essential for the production of the correct amino acids needed to synthesize proteins in the liver –> associated with hepatocellular damage.
ex: Aminotransferases (ASL/ALT) Aspartate aminotransferase (AST) Alanine aminotransferase (ALT)
Protein metabolism
Most of the blood plasma proteins are made in the liver and are synthesize by amino acids.
Hepatocytes are also responsible for breaking down worn out protein into urea.
Most than 90% of overall liver function must be lost before urea and amino acid regulation are measurably affected.
Serum albumin
Measure of proteins in the blood. When severe hepatocellular disease lasts more than 3 weeks this will be decreased.
Decreased levels caused reduced plasma oncotic pressure which pulls fluid out causes ascites and edema.
Liver: Coagulation factors
Liver synthesizes most coagulation proteins. Some are also dependent on vitamin K (Factors II (prothrombin), VII, IX, and X).
If these levels are declined could be due to hepatocellular dysfunction or insufficient vitamin K.
Coagulation factors: PT and PTT
Prothrombin time (PT) and partial thromboplastin time (PT) represent the time it takes for a clot to form in a blood specimen.
Factors that affect PT
II, VII, and X
** Factor VII has the shortest half life so its levels will fall first –> PT will be prolonged earlier than PTT.
Factors that affect PTT
II, IX, and X
Cholelithiasis
Stone formation within within the gallbladder as a concentration of bile components. Typically are formed in the gallbladder by may pass to other parts of the biliary tract.
Choledocholithiasis
Presence of 1 or more gallstones in the common bile duct (CBD).
Gallstone ileus
In severe inflammation, gallstones may erode through the gallbladder into adherent bowel.
Process of stone formation in the gallbladder
When bile is concentrated in the GB it can be supersaturated with bile substances –> crystals are trapped in GB mucus which produces gallbladder sludge–> overtime sludge crystals fuse to form macroscopic stones
What are the 2 main substances that are involved in gallstone formation?
Cholesterol (~80%)
Calcium bilirubinate
Cholesterol stones
Main factors in determine stone formation:
- Amount of cholesterol secreted by hepatocytes relative to lecithin and bile salts.
- Degree of concentration and extent of stasis of bile in the gallbladder.
Estrogen and cholesterol stones
Increased estrogen levels may increase cholesterol in bile and decreased GB movement
Ex: Pregnancy, hormone therapy, use of estrogen containing OCP.
Black pigment stones (calcium bilirubinate)
Represents ~10-20% of gallstones in US.
Increased unconjugated bilirubin concentrations in the bile which eventually crystalized to form solution and stones that are a jet-black color.
Cholelithiasis- mixed stones
Cholesterol gallstones may become colonized with bacteria.
Over time, cholesterol stones may accumulate a substantial proportion of calcium bilirubinate and other calcium salts, producing mixed gallstones. These may develop a surface rim of calcium which may be visible of plain abdominal xray as eggshell appearance.
Cholesteroal gallstone formation risk factors (The five F’s)
Fair Fertile Female Forty Flatulent Fat (BMI>30)
Other risk factors: Metabolic syndrome (inc. cholesterol secretion), Prolonged fasting of TPN, rapid weight loss, hx of multiple pregnancies, dysfunction of the ileum (liver making more bile and overloading GB)
What are the 4 stages of gallstone disease?
Lithogenic state (conditions favor gallstone formation)
Asymptomatic gallstones
Symptomatic gallstones (biliary colic)
Complicated cholelithiasis (acute cholecystitis, choledocholithiasis, acute cholangitis, gallstone pancreatitis, gallstone ileus)
Asymptomatic cholelithiasis clinical presentation
Usually discovered incidentally.
Does not require treatment in most cases BUT 25% of patients will go on to develop symptoms.
Symptomatic cholelithiasis (biliary colic)
Typical pain felt by patients with cholelithiasis in the absence of cholecystitis.
Occurs with gallstones or sludge impact cystic duct during gallbladder contraction.
Collins sign
Pain that radiates to R scapular tip
Symptomatic cholelithiasis (biliary colic) clinical presentation
Episodes typically begin postprandially (~10-20 minutes after eating) and are described as dull intense pain. Can also include diaphoresis and N/V.
Pain is constant in nature and is not relived by vomiting, antacids, defacation, flatus, or positionally.
Biliary colic physical exam
GB NOT inflamed
Pain is poorly localized without guarding or rebound
No fever or tachycardia
Cholelithiasis labs
Labs: CBC Liver and pancreatic enzymes Bilirubin and ALP (should be normal in asymptomatic or biliary colic)
Cholelithiasis imagign
US is the imaging procedure of choice in suspected gallbladder or biliary disease.
BUT CBD stones are frequently missed on US.
Can also do endoscopic ultrasound but it is not as common, but is more specific for CBD stone.
Uncomplicated gallstone disease
Stones in the gallbladder
Associated with biliary colic
Absence of complications (acute cholecystitis, cholangitis, or gallstone pancreatitis)
Symptomatic gallstones (biliary colic) treatment
Definitive surgical intervention
Laparoscopic cholecystectomy is the gold standard treatment for symptomatic cholelithiasis
High risk surgical patients: Oral bile salt therapy with ureodeoxycholic acid, lithotripsy.
Porcelain gallbladder
Refers to a gallbladder with calcification in the wall most likely due to chronic gallbladder inflammation and gallstones.
This is typically asymptomatic and found incidentally on plain AXR or US. Called porcelain due to the brittle nature of the calcified wall.
Porcelain gallbladder treatment
Prophylactic cholecystectomy is recommended due to association between porcelain gallbladder and gallbladder carcinoma.
Primary vs secondary choledocholithiasis
Most cases are secondary to the passage of gallstones from the gallbladder into the CBD (In Western countries)
Primary choledocholithiasis (i.e., formation of stones within the common bile duct). This typically occurs in the setting of bile stasis.
Choledocholithiasis clinical presentation
Biliary-type pain (RUQ or epigastric with N/V)
Typically pain is more prolonged than with typical biliary colic.
Murphy’s sign is commonly negative.
Jaundice and clay-colored stool occasionally.
If uncomplicated patients are typically afebrile with normal CBC and pancreatic enzyme. Patients can also be asymptomatic with incidental lab findings.
Choledocholithiasis labs
Laboratory testing reveals a cholestatic pattern of liver test abnormalities
Elevated liver enzymes
Elevated bilirubin and ALP
Diagnosis may be suspected in asymptomatic patients with abnormal liver enzymes or incidental imaging.
Courvoisier’s sign
A palpable gallbladder on physical exam that may be seen when gallbladder dilatation develops because of an obstruction of the CBD.
More often seen with malignant CBD obstruction but can be see with stones as well.
Choledocholithiasis: Ball-valve effect
Some have intermittent pain due to transient blockage of the CBD. Occurs when there is retention and floating of stones or debris.
Choledocholithiasis laboratory tests
Serum ALT and AST typically elevated early in the course of biliary obstruction
Later liver tests are typically elevated in a cholestatic pattern: Increases in serum bilirubin, ALP, and GGT exceed the elevations in serum ALT and AST
Prolonged cases → INR may increase due to a decrease in vitamin K absorption
Decreased bile flow reduces fat breakdown and therefore absorption of fat soluble vitamins
Choledocholithiasis diagnostic imaging
Transabdominal US: Often gas within the duodenum obstructs view of CBD.
MRCP (magnetic resonance cholangiopancreatography), EUS(endoscopic US) or ERCP (invasive and usually done with therapeutic intent).
MRCP or ERCP confirms diagnosis!
Choledocholithiasis treatment
ERCP allows for diagnosis and extraction of bile ducts stones. Should be used when there is high clinical suspicion for CBD stones.
After, gallbladder should be surgically removed from bile ducts.
Choledocholithiasis complications: pancreatitis
One of the most common causes of acute pancreatitis when gallstone pass into bile duct and lodge at the sphincter of Oddi.
Biliary pancreatitis typically present with choledocholithiasis signs and symptoms plus:
Increased N/V
Elevations in serum amylase and lipase(greater than 3x the upper limits of normal)
And/or imaging findings suggestive of acute pancreatitis.
Choledocholithiasis complications: Acute cholangitis
Infection of the bile duct that often presents with charcot’s triad and leukocytosis.
Charcot’s triad
Fever, RUQ pain, and jaundice
Seen in acute cholangitis
Reynold’s pentad
Charcot’s triad (fever, RUQ pain, and jaundice) PLUS
Hypotension and AMS
Signals severe cases of bacteremia and sepsis.
Choledocholithiasis complications: Secondary sclerosing cholangitis
Untreated chronic obstruction from bile duct stones can lead to chronic inflammation.
Not as immediate of a concern as acute.
Gallstone pancreatitis clinical presentation
Upper epigastric abdominal pain is the cardinal symptom and it is typically boring and steady while gradually worsening.
Gallstone pancreatitis: PE
Fever
Tachycardia
Hypotension
Abdominal TTP and guarding in upper abdomen
Jaundice
Dyspnea from irritation of the diaphragm (in some)
Gallstone pancreatitis: Labs
Dx based on a threefold increase in the blood of either amylase or lipase.
Gallstone pancreatitis treatment
ERCP is done to open pancreatic duct that is blocked by a stone.
Cholecystectomy is often recommended during admission to prevent recurrence.
Acute cholangitis pathophysiology
Caused primarily by bacterial infection (often ascending from duodenum) in a patient with biliary obstruction. Consider this diagnosis in all patients with sepsis.
Most common organisms in bile include those that are common in the gut: E coli, kelsiella, entocuccus, strep, enterbacter, pseudomonas
Acute cholangitis lab tests
Elevated WBC count with left shift
Cholestatic pattern of liver abnormalities.
Acute hepatocyte necrosis formation in the liver.
Obtain blood cultures!
Acute cholangitis treatment
Antibiotics should be administered immediately!
Should cover gm negative aerobic, gram positive, and anaerobes
Extended spectrum cephalosporin, metronidazole, and ampicillin for combination regiment.
Single agents: Zosyn, Meropenem, ampicillin sulbactam + metronidazole.
Mild acute cholangitis
80-90% will respond to medical therapy of broad-spectrum antibiotics and IVF.
Severe acute cholangitis
15% do not respond to antibiotics and require immediate surgical or endoscopic decompression
ERCP is the treatment of choice for establishing biliary drainage in acute cholangitis (This can be either urgent or within 24-48 hours depending on response to therapy)
Primary sclerosing cholangitis (PSC)
Characterized by a progressive course of cholestasis with inflammation, fibrosis, and stricturing of medium and large ducts in the intrahepatic and/or extrahepatic biliary tree.
Underlying cause is believed to be autoimmunity (strongly associated with UC)
Can progress to many biliary and liver complications including cirrhosis and cancer.
PSC clinical presentation
Initial presentation of fatigue, jaundice, pruritus, and RUQ pain (or may be asymptomatic)
Symptoms may remit and then recur spontaneously.
As the disease progresses you may see signs of liver disease on physical exam.
PSC labs
Elevated serum ALP usually 3-5X reference-range values
Elevated serum GGT (cholestasis rather than bone disease)
Elevated serum aminotransferase levels (not markedly)
Elevated serum bilirubin levels (conjugated)
PSC diagnostic imaging
ERCP → criterion standard for confirming Dx
Multiple strictures and dilations of the intrahepatic and extrahepatic biliary ducts characteristic “beaded” appearance.
Magnetic resonance cholangiopancreatography (MRCP)
Rapidly developing as the preferred study to evaluate the bile ducts
Non-invasive
PSC complications
Bile duct strictures Cholangiocarcinoma Choledocholithiasis Bacterial cholangitis Cirrhosis: Most patients will eventually develop cirrhosis with all its complications (ascites, portal hypertension, varices, etc.)
PSC treatment
No approved or proven therapy exists
Pharmacotherapy aimed at treating symptoms and managing complications: Immunosuppressants, chelators(removes metals/minerals(calcium) from the body), bile-acid resins (pruritus) and steroids
Liver transplant is the only therapy that can alter the eventual outcome. This can increase 5 and 10 year survival rates.
ERCP to dilate strictures can help alleviate symptoms.
Secondary sclerosing cholangitis
Chronic biliary inflammation with an identifiable cause or pathological process. Most present and are morphologically similar to primary sclerosing cholangitis
Most develop from untreated chronic biliary obstruction of the CBD
Can develop after an episode of severe bacterial cholangitis
Also from insult to the biliary tree by obstructive cholangitis secondary to choledocholithiasis, surgical damage, trauma, vascular insults, parasites, or congenital fibrocystic disorders
Acute cholecystitis
Syndrome of RUQ pain, fever, and leukocytosis that is associated with gallbladder inflammation.
Concentrated bile, pressure, and sometimes bacterial infection irritate and damage the gallbladder wall –>
Results in inflammation and swelling of the GB
Can be caused by a stone (most common) or extremely concentrated bile.
Acute calculous cholecystitis
Obstruction of the cystic duct of the gallbladder which leads to 90% of cases of cholecystitis.
Acute cholecystitis clinical presentation
Upper abdominal pain (most common presenting symptom)
Begins in the epigastric region and then localizes to the RUQ.
May initially be described as colicky then becomes constant (>6hrs)
May radiate to right shoulder or scapula (Collins sign)
Signs of peritoneal irritation may be present: N/V, fever, fatty food ingestion prior to onset.
Often hx of biliary colic
Acute cholecystitis PE
Fever
Tachycardia
Tenderness in the RUQ or epigastric region (often with guarding or rebound)
Murphy sign (Specific but not sensitive for cholecystitis)
Palpable gallbladder or fullness of the RUQ (30-40% of cases)
Jaundice (15% of patients): If severe, consider possible choledocholithiasis
Spectrum from mildly ill appearing to acutely ill with signs of systemic infection/sepsis, shock and hypotension
Acute cholecystitis labs
Leukocytosis with a left shift (WBC >11,000)
ALT and AST levels used may be elevated
Bilirubin and ALP may be elevated (CBD obstruction)
Elevated ALP in 25% of pts with cholecystitis
Amylase/Lipase elevated if concomitant pancreatitis in CBD obstruction
Amylase may also be elevated mildly in cholecystitis
Acute cholecystitis diagnostic imaging
US is the preferred initial imaging
Findings typically include: Pericholecystic (surrounding the gallbladder) fluid
Gallbladder wall thickening greater than 4 mm
Sonographic Murphy sign
Gallstones
If US is not diagnostic can use Hepatic imilodiacetic acid (HIDA) scan:
No disease → GB visualized within 1 hr of the injection of the radioactive tracer
Cholecystitis or cystic duct obstruction → GB not visualized within 4 hrs after the injection
Acute cholecystitis complications: Gallbladder gangrene
Most common complication of gas-forming organisms that can lead to gallbladder perforation, fistula, and emphysematous cholecystitis.
Acute cholecystitis treatment
IV antibiotics IV hydration Correction of electrolyte abnormalities Analgesia Bowel rest (Keep NPO for expectant surgery).
Stanford guide recommendations for antibiotic treatment: piperacillin/tazobactam (Zosyn) ampicillin/sulbactam (Unasyn) meropenem
In severe life-threatening cases, imipenem/cilastatin (Primaxin)
Definitive therapy is cholecystectomy–> call surgery!
Chronic cholcystitis
Occurs after repeated episodes of acute cholecystitis (usually due to gallstones)
Can range in severity from asymptomatic to more severe case of acute cholecystitis.
Gallstone ileus
Infrequent cause of mechanical bowel obstruction caused by impaction of a gallstone in the ileum after being passed through fistula.
Gallstone first erodes through the gallbladder wall into the small bowel, then the stone causes a bowel obstruction (usually terminal ileum).
Treatment is removal of the obstruction.
Gallstone ileus clinical presentation
“Tumbling obstruction“ -Transient gallstone impaction produces diffuse abdominal pain and vomiting. Subsides as the gallstone becomes disimpacted, recurs again as the stone lodges in the more distal bowel lumen
Typically an older woman with episodic subacute obstruction.
Gallstone ileus
Confirmed by radiologic evaluation of in surgery.
AXR → reveals air in the biliary tree with dilated loops of bowel and air fluid levels
If should be suspected in older adults with clinical features suggestive of acute or subacute SBO.
Gallstones: Mirizzi syndrome
Rare complication in which a gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common bile duct (CBD) or common hepatic duct
Multiple large gallstones can become impacted in Hartmann’s pouch of the gallbladder –> chronic inflammation –> compression of CBD
