CH11 - Exocrine Pancreas, Gallbladder, and Liver Pathology Flashcards
What is annular pancreas?
Developmental malformation in which the pancreas forms a ring around the duodenum
In annular pancreas what is there a risk of?
duodenal obstruction
What is acute pancreatitis?
Inflammation and hemorrhage of the pancreas
What is acute pancreatitis due to?
autodigestion of pancreatic parenchyma by pancreatic enzymes
What does premature activation of trypsin lead to?
activation of other pancreatic enzymes
What does acute pancreatitis result in?
liquefactive hemorrhagic necrosis of the pancreas and fat necrosis of the peripancreatic fat
What is acute pancreatitis most commonly due to?
alcohol and gallstones;
Beside alcohol and gallstones what are some other causes of acute pancreatitis?
include trauma, hypercalcemia, hyperlipidemia, drugs, scorpion stings, mumps, and rupture of a posterior duodenal ulcer
What are the clinical features for acute pancreatitis?
1) Epigastric abdominal pain that radiates to the back 2) Nausea and vomiting 3) Periumbilical and flank hemorrhage 4) Elevated serum lipase and amylase - lipase is more specific for pancreatic damage 5) Hypocalcemia - calcium is consumed during saponification in fat necrosis
In acute pancreatitis why is there periumbilical and flank hemorrhage?
necrosis spreads into the periumbilical soft tissue and retroperitoneum
In acute pancreatitis why is there elevated serum lipase and amylase?
lipase is more specific for pancreatic damage
What are the complications for acute pancreatitis?
- Shock 2. Pancreatic pseudocyst 3. Pancreatic abscess 4. DIC and ARDS
In acute pancreatitis why is shock one of the complications?
Its due to peripancreatic hemorrhage and fluid sequestration
In acute pancreatitis what happens in pancreatic pseudocyst?
Its formed by fibrous tissue surrounding liquefactive necrosis and pancreatic enzymes
How does a pancreatic pseudocyst present?
as an abdominal mass with persistently elevated serum amylase
What happens when a pancreatic pseudocyst ruptures?
it is associated with release of enzymes into the abdominal cavity and hemorrhage.
What is pancreatic abscess often due to?
Ecoli
How does pancreatic abscess present?
with abdominal pain, high fever, and persistently elevated amylase
What happens in chronic pancreatitis?
Fibrosis of pancreatic parenchyma, most often secondary to recurrent acute pancreatitis
What is chronic pancreatitis most commonly due to?
Alcohol in adults and cystic fibrosis in children, many cases are idiopathic.
What does acute pancreatitis leading to pancreatic insufficiency result in?
malabsorption with steatorrhea and fat soluble vitamin deficiencies. Amylase and lipase are not useful serologic markers of chronic pancreatitis.
What are the clinical features of acute pancreatitis?
- epigastric abdominal pain that radiates to the back 2. Pancreatic insufficiency 3. Dystrophic calcification of pancreatic parenchyma on imaging, contrast studies reveal a [chain of lakes] pattern due to dilatation of pancreatic ducts. 4. Secondary diabetes mellitus 5. Increased risk for pancreatic carcinoma
In acute pancreatitis why is there a chain of lakes pattern on contrast studies?
It is due to the dilation of pancreatic ducts and dystrophic calcification of pancreatic parenchyma
How is secondary diabetes mellitus related to acute pancreatitis?
It?s a late complication due to destruction of the islets
What is pancreatic carcinoma?
Adenocarcinoma arising from the pancreatic ducts
What is pancreatic carcinoma most commonly seen in?
the elderly (average age is 70 years)
What are the major risk factors for pancreatic carcinoma?
smoking and chronic pancreatitis.
What are the clinical features for pancreatic carcinoma?
They usually occur late in disease. 1. Epigastric abdominal pain and weight loss 2. Obstructive jaundice with pale stools and palpable gallbladder 3. Secondary diabetes mellitus 4. Pancreatitis 5. Migratory thrombophlebitis (Trousseau sign) 6. Serum tumor marker is CA 19-9
What tumor is secondary diabetes mellitus associated with?
It?s associated with tumors that arise in the body or tail
How does Trousseau sign present?
as swelling, erythema, and tenderness in the extremities (seen in 10% of patients)
For pancreatic carcinoma with obstructive jaundice with pale stools and palpable gallbladder what is it associated with?
tumors that arise in the head of the pancreas (most common location)
What does surgical resection of the pancreatic carcinoma involve?
en bloc removal of the head and neck of pancreas, proximal duodenum, and gallbladder (Whipple procedure).
What is the prognosis for pancreatic carcinoma?
Very poor prognosis; 1-year survival is < 10%
What is biliary atresia?
Failure to form or early destruction of extra hepatic biliary tree
What does biliary atresia lead to?
biliary obstruction within the first 3 months of life
What does biliary atresia present with?
jaundice and progresses to cirrhosis
What does cholelithiasis lead to?
(gallstones) Solid, round stones in the gallbladder
What is cholelithiasis due to?
precipitation of cholesterol (cholesterol stones) or bilirubin (bilirubin stones) in bile
What does cholelithiasis arise with?
(1) supersaturation of cholesterol or bilirubin, (2) decreased phospholipids (e.g., lecithin) or bile acids (normally increase solubility), or (3)stasis
What is the most common type of cholelithiasis?
cholesterol stones (yellow) are the most common type (90%), especially in the West
How is cholelithiasis usually described?
radiolucent - 10% are radiopaque due to associated calcium
What are the risk factors for cholelithiasis?
They are age (40s), estrogen (female gender, obesity, multiple pregnancies and oral contraceptives), dofibrate, Native American ethnicity, Crohn disease, and cirrhosis.
What are bilirubin stones (pigmented) composed of?
bilirubin
How do bilirubin stones appear?
They are usually radiopaque
What are the risk factors for bilirubin stones?
They are extravascular hemolysis (increased bilirubin in bile) and biliary tract infection (eg. E coli, Ascaris lumbricoides, and Clonorchis sinensis).
How is Ascitris lumbricoides related to bilirubin stones?
it is a common roundworm that infects 25% of the world’s population, especially in areas with poor sanitation (fecal-oral transmission); infects the biliary tract, increasing the risk for gallstones
How is Clonorchis sinensis related to bilirubin stones?
It is endemic in China, Korea, and Vietnam (Chinese liver fluke); infects the biliary tract, increasing the risk for gallstones, cholangitis, and cholangiocarcinoma
What are the symptoms for gallstones?
they are usually asymptomatic;
What are the complications for gallstones?
They include biliary colic, acute and chronic cholecystitis, ascending cholangitis, gallstone ileus, and gallbladder cancer.
What is biliary colic?
Waxing and waning right upper quadrant pain
What is biliary colic due to?
the gallbladder contracting against a stone lodged in the cystic duct
How are the symptoms for biliary colic relieved?
if the stone passes.
What may common bile duct obstruction result in?
acute pancreatitis or obstructive jaundice.
What is acute cholecystitis?
Acute inflammation of the gallbladder wall
What does an impacted stone in the cystic duct result in?
dilatation with pressure ischemia, bacterial overgrowth (E coli), and inflammation
How does acute cholecystitis present?
with right upper quadrant pain, often radiating to right scapula, fever with increased WBC count, nausea, vomiting, and increased serum alkaline phosphatase (from duct damage), risk of rupture if left untreated
What is chronic cholecystitis?
Chronic inflammation of the gallbladder
What is chronic cholecystitis due to?
chemical irritation from longstanding cholelithiasis, with or without superimposed bouts of acute cholecystitis
What is chronic cholecystitis characterized by?
herniation of gallbladder mucosa into the muscular wall (Rokitansky-Aschoff sinus formation)
How does chronic cholecystitis present?
with vague right upper quadrant pain, especially after eating
What is a late complication of chronic cholecystitis?
Porcelain gallbladder is a late complication
What is porcelain gallbladder?
- Shrunken, hard gallbladder due to chronic inflammation, fibrosis, and dystrophic calcification 2. Increased risk for carcinoma
What is the treatment for porcelain gallbladder?
it is cholecystectomy, especially if porcelain gallbladder is present
What is ascending cholangitis?
Bacterial infection of the bile ducts
What is ascending cholangitis usually due to?
ascending infection with enteric gram-negative bacteria
What does ascending cholangitis present as?
sepsis (high fever and chills), jaundice, and abdominal pain
With what is there increased incidence of ascending cholangitis?
Increased incidence with choledocholithiasis (stone in biliary ducts)
What is gallstone ileus?
Gallstone enters and obstructs the small bowel
What is the gallstone ileus due to?
cholecystitis with fistula formation between the gallbladder and small bowel
What is gallbladder carcinoma?
Adenocarcinoma arising from the glandular epithelium that lines the gallbladder wall
What is a major risk factor for development of gallbladder carcinoma?
gallstones are a major risk factor, especially when complicated by porcelain gallbladder.
How does gallbladder carcinoma classically present?
as cholecystitis in an elderly woman
What is the prognosis for gallbladder carcinoma?
poor
What is jaundice?
Yellow discoloration of the skin; earliest sign is scleral icterus (yellow discoloration of the sclera)
What is jaundice due to?
Increased serum bilirubin, usually > 2.5 mg/dL
What does jaundice arise with?
disturbances in bilirubin metabolism
What happens to RBC?s in bilirubin metabolism?
RBCs are consumed by macrophages of the reticuloendothelial system.
What happens to the protoporphyrin after the reticuloendothelial system?
The protoporphyrin (from heme) is converted to unconjugated bilirubin (UCB)
What happens to the unconjugated bilirubin?
The albumin carries UCB to the liver
What happens to the UCB (unconjugated bilirubin) in the liver?
Uridine glucuronyl transferase (UGT) in hepatocytes conjugates bilirubin
What happens to conjugated bilirubin?
it is transferred to bile canaliculi to form bile, which is stored in the gallbladder
Where is bile released?
It is released into the small bowel to aid in digestion.
What happens to the conjugated bilirubin when it is in the intestines?
Intestinal flora convert CB to urobilinogen, which makes the stool brown.
How is conjugated bilirubin related to why urine is yellow?
Urobilinogen (which is what CB is converted into in the intestines) is also partially reabsorbed into the blood and filtered by the kidney, making the urine yellow
What is the etiology for Extravascular hemolysis or Ineffective erythropoiesis?
High levels of UCB overwhelm the conjugating ability of the liver.
What are the lab findings for extravascular hemolysis or Ineffective erythropoiesis?
Increased UCB
What are the clinical features for extravascular hemolysis or ineffective erythropoiesis?
dark urine due to increased urine urobilinogen (UCB is not water soluble and, thus, is absent from urine)
For extravascular hemolysis or ineffective erythropoiesis what is there an increased risk for?
pigmented bilirubin gallstones
What is the etiology of physiologic jaundice of the newborn?
Newborn liver has transiently low UGT activity.
What is the laboratory finding for physiologic jaundice of the newborn?
increased UCB
What is the clinical findings for physiologic jaundice of the newborn?
UCB is fat soluble and can deposit in the basal ganglia (kernicterus) leading to neurological deficits and death.
What is the treatment for physiologic jaundice of the newborn?
phototherapy (makes UCB water soluble),
What is the etiology for Gilbert syndrome?
Mildly low UGT activity; autosomal recessive
What are the laboratory findings for physiologic jaundice of the newborn?
Increased UCB
What are the clinical features for physiologic jaundice of the newborn?
Jaundice during stress (e.g., severe infection); otherwise, not clinically significant
What is the etiology for Crigler-Najjar syndrome?
Absence of UGT
What are the lab findings for Crigler-Najjar syndrome?
Increased UCB
What are the clinical features for Crigler-Najjar syndrome?
Kernicterus; usually fatal
What is the etiology for Dubin-Johnson syndrome?
Deficiency of bilirubin canalicular transport protein; autosomal recessive
What are the laboratory findings for Dubin-Johnson syndrome?
Increased CB
What are the clinical features for Dubin-Johnson syndrome?
The liver is dark; otherwise, not clinically significant
What is similar to Dubin-Johnson syndrome and how can you tell the difference?
Rotor syndrome is similar to Dubin-Johnson syndrome, but lacks liver discoloration.
What is the etiology for biliary tract obstruction (obstructive jaundice)?
Associated with gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites, and liver fluke (Clonorchii sinensis)
What are the lab findings for biliary tract obstruction (obstructive jaundice)?
Increased CB, decreased urine urobilinogen, and increased alkaline phosphatase
What are the clinical features for biliary tract obstruction (obstructive jaundice)?
Dark urine and pale stool, Pruritus, Hypercholesterolemia with xanthomas, Steatorrhea with malabsorption of fat-soluble vitamins
In biliary tract obstruction (obstructive jaundice) why is there dark urine?
Its due to bilirubinuria
In biliary tract obstruction (obstructive jaundice) why is there pruritis?
due to increased plasma bile acids
What is the etiology for viral hepatitis?
inflammation disrupts hepatocytes and small bile ductules.
What are the laboratory findings for viral hepatitis?
Increase in both CB and UCB
What are the clinical features for viral hepatitis?
Dark urine due to increased urine bilirubin; urine urobilinogen is normal or decreased.
How is HAV and HEV transmitted?
Hepatitis A (HAV) and Hepatitis E (HEV) fecal-oral transmission
HAV is commonly acquired by
travelers.
HEV is commonly acquired from
contaminated water or undercooked seafood.
Is HAV chronic or acute?
Acute hepatitis; no chronic state.
Is HEV chronic or acute?
Acute hepatitis; no chronic state.
In hepatitis what marks active infection?
anti-virus IgM
In hepatitis what does antivirus IgG mean?
Its in HAV and HEV, it is protective, and its presence indicates prior infection or immunization
What is hepatitis immunization available for?
HAV only
What is HEV infection in pregnant women associated with?
fulminant hepatitis (liver failure with massive liver necrosis)
How is Hepatitis B (HBV) transmitted?
Parenteral transmission (e.g., childbirth, unprotected intercourse, and intravenous drug abuse [IVDA])
What does Hepatitis B result in?
acute hepatitis; chronic disease occurs in 20% of cases
How is Hepatitis C (HCV) transmitted?
Parenteral transmission (e.g., IVDA, unprotected intercourse, needle stick); risk from transfusion is almost nonexistent due to screening of the blood supply.
What does hepatitis C result in?
acute hepatitis: chronic disease occurs in most cases
What confirms HCV infection?
HCV-RNA test confirms infection; decreased RNA levels indicate recovery; persistence indicates chronic disease.
How is Hepatitis D (HDV) transmitted?
Dependent on HBV for infection: superinfection upon existing HBV is more severe than coinfection (infection with HBV and HDV at the same time)
For HBV what is the first serologic marker to rise?
HBsAG
What defines the chronic state of HBV?
HBsAG > 6 months
When is there both HBcAG and HBV DNA?
In the acute and maybe in chronic phase
What indicates infectivity for the HBV?
Presence of HBeAG or HBV DNA
With HBcAB what immunoglobulin is seen in the acute stage of HBV?
IgM
With HBcAB what immunoglobulin is seen in the window stage of HBV?
IgM
With HBcAB what immunoglobulin is seen in the resolved stage of HBV?
IgG
With HBcAB what immunoglobulin is seen in the chronic stage of HBV?
IgG
With HBsAB what immunoglobulin is seen in the resolved stage of HBV?
IgG (protective)
With HBsAB what immunoglobulin is seen in the immunization stage of HBV?
IgG (protective)
What is viral hepatitis?
Inflammation of liver parenchyma, usually due to hepatitis virus
What is viral hepatitis usually due to and what are some other causes for it?
EBV and CMV
What does the hepatitis virus cause?
acute hepatitis, which may progress to chronic hepatitis.
How does acute hepatitis present?
as jaundice (mixed CB ?conjugated bilirubin and UCB ?unconjugated bilirubin) with dark urine (due to CB), fever, malaise, nausea, and elevated liver enzymes (ALT > AST),
For acute hepatitis what does acute inflammation involve and how is it characterized?
It involves lobules of the liver and portal tracts, and is characterized by apoptosis of hepatocytes
What are the symptoms for acute hepatitis?
Some cases may be asymptomatic with elevated liver enzymes. Symptoms last < 6 months,
What is chronic hepatitis characterized by?
symptoms that last > 6 months
What does inflammation in chronic hepatitis predominantly involve?
the portal tract
For chronic hepatitis what is there a risk of?
progression to cirrhosis
What is cirrhosis?
End-stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes
In cirrhosis how is fibrosis mediated?
by TGF-beta from stellate cells which lie beneath the endothelial cells that line the sinusoids.
What are the clinical features for cirrhosis due to?
- Portal hypertension 2. Decreased detoxification 3. Decreased protein synthesis
For the clinical features of cirrhosis what does portal hypertension lead to?
1) Ascites (fluid in the peritoneal cavity) 2) Congestive splenomegaly/hypersplenism 3) Portosystemic shunts (esophageal varices, hemorrhoids, and caput medusae) 4) Hepatorenal syndrome (rapidly developing renal failure secondary to cirrhosis)
For the clinical features of cirrhosis what does decreased detoxification lead to?
1) Mental status changes, asterixis, and eventual coma (due to T serum ammonia); metabolic, hence reversible 2) Gynecomastia, spider angiomata. and palmar erythema due to hyperestrinism 3) jaundice
For the clinical features of cirrhosis what does decreased protein synthesis lead to?
1) Hypoalbuminemia with edema 2) Coagulopathy due to decreased synthesis of clotting factors; degree of deficiency is followed by prothrombin time (PT).
What happens in alcohol related liver disease?
Damage to hepatic parenchyma due to consumption of alcohol
What is the most common cause of liver disease in the West?
Consumption of alcohol
What is fatty liver?
it is the accumulation of fat in hepatocytes
What does fatty liver result in?
a heavy, greasy liver
How does fatty liver resolve?
with abstinence
What does alcoholic hepatitis result from?
chemical injury to hepatocytes; generally seen with binge drinking
With alcoholic hepatitis what mediates damage?
Acetaldehyde (metabolite of alcohol) mediates damage
What is alcoholic hepatitis characterized by?
swelling of hepatocytes with formation of Mallory bodies (damaged cytokeratin filaments), necrosis, and acute inflammation
How does alcoholic hepatitis present?
with painful hepatomegaly and elevated liver enzymes (AST > ALT), may result in death
What is a long term complication of alcoholic hepatitis?
Cirrhosis, chronic alcohol-induced liver damage;
What is the frequency of cirrhosis in alcoholic hepatitis?
occurs in 10-20% of alcoholics
What is non-alcoholic fatty liver disease?
Fatty change, hepatitis, and/or cirrhosis that develop without exposure to alcohol (or other known insult)
What is non-alcoholic fatty liver disease associated with?
obesity
How do you diagnose non-alcoholic fatty liver disease?
Diagnosis of exclusion; ALT > AST
Wha is hemochromatosis?
Excess body iron leading to deposition in tissues (hemosiderosis) and organ damage (hemochromatosis)
In hemochromatosis what mediates tissue damage?
It is mediated by generation of free radicals.
What is hemochromatosis due to?
autosomal recessive defect in iron absorption (primary) or chronic transfusions (secondary)
What is primary hemochromatosis due to?
mutations in the HFE gene, usually C282Y (cysteine is replaced by tyrosine at amino acid 282)
When does hemochromatosis present?
in late adulthood
What is the classic presentation for hemochromatosis?
Classic triad is cirrhosis, secondary diabetes mellitus, and bronze skin; other findings include cardiac arrhythmias and gonadal dysfunction (due to testicular atrophy).
What are the lab findings for hemochromatosis?
Labs show increased ferritin, decreased TIBC, increased serum iron, and increased % saturation.
For hemochromatosis, what does liver biopsy reveal?
accumulation of brown pigment in hepatocytes
For hemochromatosis liver biopsy, what is the accumulated brown pigment in the hepatocytes?
Lipofuscin
For hemochromatosis liver biopsy how do you identify the lipofuscin?
Prussian blue stain distinguishes iron (blue) from lipofuscin
What is lipofuscin?
it is a brown pigment that is a by-product from the turnover (wear and tear) of peroxidized lipids
Where does lipofuscin commonly present?
in hepatocytes
In hemochromatosis, what is there an increased risk of?
hepatocellular carcinoma
In hemochromatosis, what is the treatment?
It is phlebotomy
What is Wilson?s Disease?
Autosomal recessive defect (ATP7B gene) in ATP-mediated hepatocvte copper transport
What does Wilson?s Disease result in?
lack of copper transport into bile and lack of copper incorporation into ceruloplasmin which leads to copper build up in hepatocytes which leaks into serum, and deposits in tissues
In Wilson?s Disease what leads to tissue damage?
Copper-mediated production of hydroxyl free radicals leads to tissue damage
When does Wilson?s Disease present?
in childhood with: 1) cirrhosis 2) neuologic manifestations 3) Kayser-Fleisher rings in the cornea
What are the neurologic manifestations in Wilson?s Disease?
behavioral changes, dementia, chorea, and Parkinsonian symptoms due to deposition of copper in basal ganglia
In Wilson?s Disease what does the labs show?
increased urinary copper, decreased serum ceruloplasmin, and increased copper on liver biopsy.
In Wilson?s Disease what is there an increased risk for?
hepatocellular carcinoma
What is the treatment for Wilson?s Disease?
D-penicillamine (chelates copper)
What is primary biliary cirrhosis?
Autoimmune granulomatous destruction of intrahepatic bile ducts
In whom does primary biliary cirrhosis classically arise?
in women, the average age is 40 years
What is primary biliary cirrhosis associated with?
other autoimmune diseases
What is the etiology for primary biliary cirrhosis?
It is unknown; antimitochondrial antibody is present.
How does primary biliary cirrhosis present?
It presents with features of obstructive jaundice
What is a late complication for primary biliary cirrhosis?
cirrhosis
What is primary sclerosing cholangitis?
Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts
What is the appearance of primary sclerosing cholangitis?
- Periductal fibrosis with an onion-skin appearance
In primary sclerosing cholangitis what is seen in the uninvolved regions?
they are dilated resulting in a beaded appearance on contrast imaging
What is the etiology for primary sclerosing cholangitis?
it is unknown, but associated with ulcerative colitis; p-ANCA is often positive
What is p-ANCA?
Perinuclear Anti-Neutrophil Cytoplasmic Antibodies
How does primary sclerosing cholangitis present?
It presents with obstructive jaundice; cirrhosis is a late complication.
What is there an increased risk for with primary sclerosing cholangitis?
cholangiocarcinoma
What is Reye syndrome?
Fulminant liver failure and encephalopathy in children with viral illness who take aspirin
What is Reye syndrome likely related to?
mitochondrial damage of hepatocytes
How does Reye syndrome present?
with hypoglycemia, elevated liver enzymes, and nausea with vomiting; may progress to coma and death
What is hepatic adenoma?
Benign tumor of hepatocytes
What is hepatic adenoma associated with?
oral contraceptive use; regresses upon cessation of drug
In hepatic adenoma, what is there a risk of?
rupture and intraperitoneal bleeding, especially during pregnancy
In hepatic adenoma, describe the tumors?
they are subcapsular and grow with exposure to estrogen
What is hepatocellular carcinoma?
Malignant tumor of hepatocytes
What are some risk factors for hepatocellular carcinoma?
- Chronic hepatitis (e.g., HBV and HCV) 2. Cirrhosis (e.g., alcohol, nonalcoholic fatty liver disease, hemochromatosis, Wilson disease, and A1AT deficiency) 3. Anatoxins derived from Aspergillus- (induce p53 mutations)
In hepatocellular carcinoma, what is there an increased for?
Increased risk for Budd-Chiari syndrome
What happens in Budd-Chiari syndrome as a result of hepatocellular carcinoma?
- Liver infarction secondary to hepatic vein obstruction
How does Budd-Chiari syndrome as a result of hepatocellular carcinoma present?
Presents with painful hepatomegaly and ascites
What is the prognosis for hepatocellular carcinoma?
Tumors are often detected late because symptoms are masked by cirrhosis; poor prognosis
What is the serum tumor marker in hepatocellular carcinoma?
alpha-fetoprotein.
How common is metastasis to liver?
It?s more common than primary liver tumors; most common sources include colon, pancreas, lung, and breast carcinomas.
What does hepatocellular carcinoma result in?
multiple nodules in the liver
How might hepatocellular carcinoma be detected clinically?
it may be detected as hepatomegaly with a nodular free edge of the liver
