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Pathoma 11 - Exocrine pancreas, Gallbladder, & Liver zhester

Chapter 11 - Exocrine pancreas, Gallbladder, & Liver
What is annular pancreas?
Developmental malformation in which the pancreas forms a ring around the duodenum.
Risk of duodenal obstruction.
Annular pancreas increases the risk for what?
Duodenal obstruction
What happens in acute pancreatitis? What are 10 causes?
Inflammation and hemorrhage of the pancreas.
Due to autodigestion of pancreatic parenchyma by pancreatic enzymes (usually all made and secreted in inactive form- activated in duodenum). Premature activation of trypsin → activation of other pancreatic enzymes.
Liquefactive hemorrhagic necrosis & fat necrosis of peripancreatic fat.
EtOH- causes contraction of sphincter of oddi- enzymes back up, prematurely activate.
Gallstones- get stuck at ampulla- causes backup and activation of enzymes
Others- trauma (MVAs in kids), cystic fibrosis, hypercalcemia, hyperipidemia, drugs, scorpion stings, mumps, rupture of posterior duodenal ulcer (sits in front of head of pancreas)
What are the clinical features in acute pancreatitis?
Epigastric abdominal back that radiates to back.
Nausea & vomiting.
Periumbilical & flank hemorrhage - necrosis spreads into periumbilical soft tissue & retroperitoneum.
Elevated serum lipase & amylase - Lipase more specific for pancreatic damage.
Hypocalcemia - calcium consumed during saponification in fat necrosis
What are the complications of acute pancreatitis?
Shock - hemorrhage & fluid sequestration.
Pancreatic psuedocyst - fibrous tissue surrounding liquefactive necrosis & enzymes. Abd. mass w/ persistently ↑ serum amylase. Can rupture, -> hemorrhage in abd. cavity
Pancreatic abscess - E. coli. Abdominal pain, ↑ fever, & persistently ↑ serum amylase.
DIC - ↓ coagulation factors due to enzymes in blood
ARDS - Enzyme destruction of alveolar-capillary interface.
What are the clinical features of chronic pancreatitis? Causes?
Epigastric abdominal pain that radiates to back.
Pancreatic insufficiency - results in malabsorption with steatorrhea and fat-soluble vitamin deficiencies. Amylase and lipase no longer good markers.
Dystrophic calcification of pancreatic parenchyma (chain of lakes) due to dilatation of pancreatic ducts
Secondary diabetes mellitus (late complication due to destruction of islets)
Increased risk for pancreatic carcinoma

d/t recurrent acute pancreatitis- MC d/t EtOH and cystic fibrosis
What is pancreatic carcinoma? Demographic? RFs?
Adenocarcinoma arising from the pancreatic ducts.
RFs smoking, chronic pancreatitis
What are the clinical features of pancreatic carcinoma?
Epigastric abdominal pain and weight loss.
SECONDARY DM (body or tail tumors)- thin elderly with new onset DM
Migratory trombophlebitis (Trousseau sign); swelling, erythema, & tenderness in extremities.
Serum marker is CA 19-9
Tx for pancreatic carcinoma. prog?
Whipple procedure- surgical resection of head and neck on pancreas, gallbladder, prox. duodenum. Poor prognosis- <1 yr.
What is biliary atresia?
Failure to form or early destruction of extrahepatic biliary tree.
Biliary obstruction within 3 months of life (can be congenital non-formation or destruction by infection within 3 months).
Jaundice (conjugated bilirubin) & progression to cirrhosis.
What is cholelithiasis (gallstones)? general cause? complications?
Solid, round stones in the gallbladder.
Due to supersaturation of cholesterol or bilirubin, decreased phospholipids (lecithin) or bile acids (normally ↑ solubility in chol.)- (cholestyramine binds bile acids and inhibits recycling for chol lowering-> dec. bile acids-> ^ risk for chol. stones), or stasis (^ risk of bacteria, can deconjugate BR -> bilirubin stones).
complications: biliary colic, acute and chronic cholecystitis, ascending cholangitis, gallstone ileus, gallbladder cancer, pancreatitis and obstructive jaundice (CB)
What are cholesterol stones? 6 RF
Most common type (90%).
Radiolucent (10% opaque due to calcium)
Risk factors - fat, fertile, 40. Age (40s), estrogen (oral contraceptives, mult. preg., females, obesity) (^ HMGco-A reductase-> ^ chol. synth AND ^ lipoprotein receptors on hepatocytes, ^ uptake of chol by liver), clofibrate (lipid lowering agent- ^ HMG co-A reductase activity, dec. conversion of chol to bile acids), Native american ethnicity, crohn disease (dec. uptake of bile salts and acids), & cirrhosis (dec. prod. of bile salts).
Bilirubin stones- def., causes
pigmented. Radiopaque. RFs- extravascular hemolysis, biliary tract infection (bugs deconjugate bilirubin-> ^ bilirubin stones)
. Usually asymptomatic.
What likes to infect the biliary tract?
E. Coli,

Clonorchis sinensis (in China, Korea, vietnam (chinese liver fluke)- infects biliary tract-> ^ risk for gallstones (esp. bilirubin), cholangitis, cholangiosarcoma

Ascaris lumbricoides- roundworm in areas of poor sanitation (fecal-oral txmission). ^ risk for gallstones
What is biliary colic?
Waxing and waning RUQ pain.
Due to gallbladder contracting against stone in cystic duct.
Symptoms are relieved if the stone passes
Common bile duct obstruction may result in acute pancreatitis or obstructive jaundice
What is acute cholecystitis? s/s? comp?
Acute inflammation of the gallbladder wall. Impacted stone in the cystic duct results in dilations with pressure ischemia, bacterial overgrowth (E coli), & inflammation.

Clinical presentation - RUQ pain often radiating to right scapula, fever w/ ↑ WBC count, nausea, vomiting, and ↑ serum alkaline phosphatase (cells in walls of biliary tract and liver have alk. phos).

Risk of rupture if untreated.
What is chronic cholecystitis?
Due to chemical irritation from longstanding choleithiasis.
Herniation of gallbladder mucosa into the muscular wall (Rokitanky-Aschoff sinus).
Postprandial vague RUQ pain.
Late complication is porcelain gallbladder (dystrophic calcification and fibrosis - increased risk for carcinoma)
tx: cholecystectomy
What is ascending cholangitis?
Bacterial infection of the bile ducts.
Due to ascending infection with enteric gram- bacteria.
Sepsis (high fever & chills), jaundice, and abdominal pain.
Increased incidence with choledocolithiasis (stones in biliary ducts)
What is gallstone ileus?
Gallstone enters and obstructs the small bowel.
Due to cholecystitis with fistula formation between gallbladder and small bowel- large stones can get in.
gallbladder carcinoma-def., RF, Pres, Prog.
Adenocarcinoma from gallbladder epith that lines GB wall.
Porcelain gallbladder (late complication of chronic cholecystitis) & gallstones.
MC presentation is cholecystitis in elderly woman- poor prog.
Describe normal bilirubin metab.
RBCs live 120 days. Splenic macrophages (or other reticulendo system) break down RBC into heme and globin. Globin recycled into AAs. Heme broken into Fe and Porphyrin. Porphyrin converted to Unconjugated bilirubin.

UCB taken by Albumin in serum to liver. Liver conjugates bilirubin (via UGT) and transfers CB to bile canaliculi (using canalicular txport protein), which drain to bile ducts to gall bladder to duodenum to help solubilize fats. Bile= CB, bile salts (bile acids conjugated with taurine or glysine to make them water soluble), cholesterol, H2O, Phospholipids (lecithin), ions. Cholesterol alpha 7 hydroxylase is rate limiting step.

In duod., intestinal flora convert CB in bile to urobilinogen. UBG makes stool brown, is partially reabsorbed into blood and filtered by kidney, making urine yellow.
What is the earliest sign of jaundice?
Sceral icterus
Extravascular hemolysis or ineffective erythropoiesis?
Lab findings
Clinical features
RBCs die in circ. d/t damage or in marrow d/t defective synth.
Etiology - ↑ levels of UCB overwhelms the conjugating ability of the liver.
Lab findings - ↑UCB.
Clinical features - Dark urine due to ↑ urine urobilinogenn* NOT UCB (UCB not soluble). ↑ risk for pigmented bilirubin gallstones (^ CB in bile as liver conjugates at max capacity).
Physiologic jaundice of the newborn?
Lab findings
Clinical features
Etiology - Newborn has ↓ UGT activity.
Lab findings - ↑UCB.
Clinical features - UCB is fat soluble and can deposit in the basal ganglia (kernicterus) leading to neuro deficits & death.
Treatment - Phototherapy (makes UCB water soluble).
Gilbert syndrome?
Lab findings
Clinical features
Etiology - Autosomal recessive, slight ↓ UGT activity.
Lab findings - ↑UCB.
Clinical features - Jaundice during stress.
Crigler-Najjar syndrome?
Lab findings
Clinical features
Etiology - near absence of UGT.
Lab findings - ↑UCB.
Clinical features - congenital Kernicterus, usually fatal.
Dubin-Johnson syndrome?
Lab findings
Clinical features
Etiology - Autosomal recessive, deficiency of bilirubin canalicular transport protein.
Lab findings - ↑CB
Clinical features - Liver is dark. Sx not needed. No liver discoloration in Rotor syndrome
Rotor syndrome
Lab findings
Clinical features
Etiology - Autosomal recessive, deficiency of bilirubin canalicular transport protein.
Lab findings - ↑CB
Clinical features - No liver discoloration in Rotor syndrome- liver dark in Dubin-Johnson
Biliary tract obstruction?
Lab findings
Clinical features
AKA obstructive jaundice
Etiology - Gallstones, carcinoma, parasites, & liver fluke (Clonorchis sinensis).
Lab findings - ↑CB, ^ plasma bile acids and salts (->pruritis), hypercholesterolemia (->xanthomas), ↓ urine urobilinogen, & ↑ alkaline phosphatase.
Clinical features - Dark urine (d/t bilirubinuria) & pale stool with steatorrhea and ADEK deficiency. Pruritus d/t ↑ plasma bile salts. Hypercholesterolemia w/ xanthomas.
jaundice d/t Viral hepatitis
Lab findings
Clinical features
Etiology - Inflammation disrupts hepatocyte & small bile ductules
Lab findings - ↑UCB & ↑CB.
Clinical features - Dark urine d/t ↑ urine CB, urine urobilinogen is normal or decreased.
What is viral hepatitis?
Inflammation of liver parenchyma, usually d/t hepatitis virus; other causes include EBV & CMV.
Acute presentation - Jaundice (CB & UCB), dark urine (CB), fever, malaise, nausea, and ↑liver enzymes (ALT>AST))*. Inflammation involves lobules & portal tracts with apoptosis of hepatocytes via CD8 destruction
Chronic presentation - > 6 months. Inflammation predominantly involves portal tracts.
hepatitis A
Fecal-oral transmission, travelers.
Acute hepatitis only- no chronic.
IgM = Active infection
IgG = Protective. Prior infection or immunization.
What is fulminant hepatitis?
liver failure with massive liver necrosis
How is hepatitis E
Fecal-oral transmission, contaminated water of undercooked foods (esp seafood).
Acute hepatitis only- no chronic.
IgM = Active infection
IgG = Protective. Prior infection (no immunization available)

Infection in pregnant women associated with fulminant hepatitis (liver failure w/ massive liver necrosis).
How is hepatitis B
transmitted? prevalence? Stages?
Parenteral transmission (childbirth, sex, IV drugs).
Acute hepatitis mainly. 20% go to chronic.
Stages- acute, window (virus knocked out, IgM still prevalent), resolved, chronic, immunized
Serologic markers of Hep B virus
HBsurfaceAG - Sign of infections- first to rise in acute phase, first to disappear, > 6 months = chronic.
HBenvelopeAG - High infectivity.
HBV DNA - High infectivity.
HBcoreAB - IgM during acute/window phase. IgG during resolved/chronic.
HBsurfaceAB - IgG- Sign of victory. Protective. Not present in chronic state. From resolved state or from immunization.
How is hepatitis C
Parenteral transmission (childbirth, sex, IV drugs)Little-no risk for infection from blood supply because we screen supply for HCV.
Acute hepatitis that usually goes to chronic.
HCV-RNA test confirms.
RNA levels indicate recovery/persistence (chronic disease).
hepatitis D
Dependent on HBV for infection.
Superinfection upon existing HBV infection is more severe than coinfection (same time).
What is cirrhosis? What mediates it?
End-stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrosis & regenerative nodule of hepatocytes.
Firbrosis is mediated by TGF-β from stellate cells which lie beneath the endothelial cells that line sinusoids
What are the clinical features of cirrhosis?
(1)Portal hypertension → Ascites, congestive splenomegaly/hypersplenism(enlarged spleen-> RBC consumption), portosystemic shunts (esophageal varices, hemorrhoids), & hepatorenal syndrome (rapid renal failure).

(2)Decreased detoxification → Reversible mental status changes and asterixis and coma (d/t ↑ serum ammonia), gynecomastia, spider angiomata & palmar erythema d/t hyperestrinism (liver removes estrgen from blood), & jaundice.

(3)Decreased protein synthesis → Hypoalbuminemia w/ edema. Coagulopathy (coag factors, activated vit. K via epoxide reductase) (measured by PT- similar to Warfarin effect).
What is alcohol-related liver disease?
Damage to hepatic parenchyma d/t alcohol.
Fatty change- reversible- heavy, greasy liver. Fat accumulates in hepatocytes

Alcoholic hepatitis d/t chemical injury to hepatocytes, generally d/t binge drinking.
(1)Acetaldehyde mediates damage.
(2)Swelling of hepatocytes w/ formation of Mallory bodies (damaged cytokeratin intermediate filaments -pink blobs).
(3)Painful hepatomegaly, and elevated liver enzymes (AST > ALT- AST is in mitochondria- EtOH damages mito preferentially).

cirrhosis- chronic EtOH damage
What is nonalcoholic fatty liver disease?
Fatty change, hepatitis, and/or cirrhosis w/o alcohol.
Associated with obesity.
Describe the normal process of taking up Fe from diet.
Almost all Fe in gut is taken up by enterocyte, but held there unless Fe is low in blood. (regulation disrupted in primary hemochromatosis).
What is hemochromatosis? cause? S/S? labs? tx? comp?
Excess body iron leading to deposition in tissues (hemosiderosis) & organ damage (hemochromatosis).
Tissue damage d/t free radicals (Fenton reaction).
Can be primary (defective regulation by enterocyte in gut d/t AR defect (HFE gene, C282Y- cysteine replaced by tyrosine at AA 282)) or secondary (chronic txfusions- RBCs broken down to Fe)

s/s: presents in late adulthood. cirrhosis, secondary DM, bronze skin and pancreas, arrhythmias, gonadal dysfxn.

^ ferritin, Dec. TIBC, ^ serum Fe, ^ %sat
Biopsy- brown pigment in hepatocytes. Use prussian blue stain to distinguish Fe (blue) from lipofuscin (wear and tear protein from breakdown of peroxidized lipids collecting in lysosomes)

Treatment is phlebotomy.

^ risk for hepatocellular carcinoma
What is wilson disease? S/S? labs? Tx? comp?
AR defect (ATP7B gene) in ATP-mediated heptocyte copper transport (can't put Cu into bile and can't incorporate into ceruloplasmin). Copper builds up in hepatocytes and leaks all over. Hydroxyl FRs formed, damage tissues.
Clinical presentation - Child with cirrhosis, neruo manifestations (deposits in basal ganglia-> behavioral changes, chorea, dementia, Parkinson's), & gold Kayser-Fleisher rings in the cornea.
Labs - ↑ urinary copper, decreased serum ceruloplasmin, & ↑ copper on liver biopsy.
Treatment is D-penicillamine.
^ risk of hepatocellular carcinoma.
What is primary billiary cirrhosis? S/S? labs? comp?
Autoimmune granulomatous destruction of intraherpatic bile ducts.
Women around 40 y/o with features of obstructive jaundice.
Antimitochondrial antibody is present.
presents with obstructive jaundice. Cirrhosis is late comp.
What is primary sclerosing cholangitis? s/s? labs? comp?
Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts.
Periductal fibrosis with onion skin & beaded appearance on image (uninvolved regions dilated.
Associated with ulcerative colitis, p-ANCA is often positive.
presents with obstructive jaundice. Cirrhosis is late comp. ^risk for cholangiocarcinoma
What is reye syndrome?
Fulminant liver failure and encephalopathy in children with viral illness who take aspirin (likely due to mitochondrial damage of hepatocytes)
Presents with hypoglycemia, elevated liver enzymes, & nausea/vomiting. Can be fatal.
*Kawasaki's syndrome can look like viral illness but requires aspirin.
What is hepatic adenoma?
Benign tumor of hepatocytes.
Associated with oral contraceptive use. Regresses when OC discontinued.
Risk of rupture & intraperitoneal bleeding, especially with pregnancy (tumors are subcapsular and grow with exposure to estrogen)
What is hepatocellular carcinoma
RF? comp? prog? Marker?
Malignant tumor of hepatocytes.
Risk factor - Chronic hepatitis, cirrhosis, aflatoxins derived from aspergillus (in grain stores-> induced p53 mutations).
Increased risk for Budd-Chiari syndrome (liver infarction secondary to hepatic vein obstruction, presents with painful hepatomegaly and ascites)
Tumors are detected late bc symptoms are masked by cirrhosis (poor prognosis)
Marker is alpha fetal protein
What tumors metastasize to liver?
More common than primary.
Sources include colon, pancreas, lung, & breast.
Results in multiple nodules in the liver.
Hepatomegaly with papable nodules on the free edge of liver.
What are 8 causes of acute pancreatitis?
Most common cause: alcohol & gallstones
Other causes include trauma (seatbelt), hypercalcemia (enzyme activator), hyperlipidemia, scorpion stings, mumps, & rupture of posterior duodenal ulcer.
What is chronic pancreatitis?
Fibrosis of pancreatic parenchyma, secondary to recurrent acute pancreatitis.
Adults - Alcohol.
Children - Cystic fibrosis.
Are amylase and lipase good serologic markers for chronic pancreatitis?
What are the major risk factors for pancreatic carcinoma?
Chronic pancreatitis
What is the serum marker for pancreatic cancer?
Serum tumor maker is CA 19-9.
What is the treatment for pancreatic carcinoma?
Whipple procedure (removal of head/neck of pancreas, proximal duodenum, & gallbladder).
What are the risk factors for cholesterol stones (6)?
Age (40s)
Clofibrate (lipid lowering agent)
Native american ethnicity
Crohn disease
What are the complications of cholelithiasis (gallstones)?
Usually asymptomatic
Complications include biliary colic, acute/chronic cholecystitis, ascending cholangitis, gallstone ileus, gallbladder cancer
What does common bile duct obstruction result in?
May result in acute pancreatitis or obstructive jaundice.
Where does the pain in acute cholecystitis radiate to?
RUQ pain radiates to right scapula
What are Rokitanky-Aschoff sinuses?
Characterized by herniation of gallbladder mucosa into muscular wall
Occurs in chronic cholecystitis
What is the classic presentation of gallbladder carcinoma?
Cholecystitis in an elderly women
What is gallbladder carcinoma?
Adenocarcinoma arising from glandular epithelium of gallbladder wall.
What is the mechanism of normal bilirubin metabolism?
(1) RBCS consumed by macrophages of the reticuloendothelial system
(2) Protoprophyrin (from heme) is converted to UCB.
(3) Albumin carries UCB to liver.
(4) Uridine glucoronyl transferase (UGT) in hepatocytes conjugates bilirubin.
(5) CB is tranferred to bile canaliculi to for bile (stored in liver).
(6) Bile released into small bowel to aid in digestion.
(7) Intestinal flora convert CB to urobilinogen, which makes stool brown, and urine yellow.
What causes jaundice?
Increase in serum bilirubin > 2.5mg/dL
Disturbance to bilirubin metabolism:
(1) RBCS consumed by macrophages of the reticuloendothelial system
(2) Protoprophyrin (from heme) is converted to UCB.
(3) Albumin carries UCB to liver.
(4) Uridine glucoronyl transferase (UGT) in hepatocytes conjugates bilirubin.
(5) CB is tranferred to bile canaliculi to for bile (stored in liver).
(6) Bile released into small bowel to aid in digestion.
(7) Intestinal flora convert CB to urobilinogen, which makes stool brown, and urine yellow.
What is the treatment for physiologic jaundice of newborn?
Phototherapy - makes UCB water soluble
Is the liver dark in Rotor or Dubin Johnson Syndrome?
Dubin-Johnson Syndrome
Why is the urine dark in extravascular hemolysis or ineffective erythropoeisis?
Increase in urine urobilinogen
What is the serum tumor marker for hepatocellular carcinoma?
What are the risk factors for hepatocellular carcinoma?
Chronic hepatitis (HBV, HCV)
Cirrhosis (alcohol, NAFLD, hemochromatosis, Wilson disease, A1AT deficiency)
Alflatoxins derived from aspergillus (induce p53 mutations)
What is the mechanism of Reye Syndrome?
mitochondrial damage to hepatocytes
What condition is HEV infection in pregnant women associated with?
Fulminant hepatitis (liver failure with massive liver necrosis)
What is the treatment of hemochromatosis?
phlebotomy decreases iron load
What gene is mutated in primary hemochromatosis?
Mutations in HFE gene (usually C282Y). Cysteine is replaced by tyrosine at amino acid 282
What is the classic triad for hemochromatosis?
Secondary DM
Bronze skin

Other findings: cardiac arrhythmias, gonadal dysfunction (testicular atrophy).
What are the lab findings for hemochromatosis?
Increased ferritin
Decreased TIBC
Increased serum iron
Increased % sat
What does liver biopsy for hemochromatosis show?
Accumulation of brown pigment in hepatocytes
Prussian blue stain distinguishes iron (blue) from lipofuscin. Lipofuscin is a brown pigment that is a by-product from turnover (wear and tear) of peroxidized lipids. Commonly present in hepatocytes
What is the treatment for Wilson Disease?
D-penicillamine (chelates copper)
What are the labs for Wilson Disease?
Increased urinary copper
Decreased serum ceruloplasmin
Increased copper on liver biopsy
How does Wilson's Disease present in childhood?
Neurologic manifestations (behavioral changes, dementia, chorea, Parkinsonian symptoms due to deposition of copper in basal ganglia)
Kayser-Fleisher rings in cornea (check with slit light test)
What level of bilirubin in blood usually starts jaundice?
2.5 mg/dl
What are 5 important causes of cirrhosis?
Alcoholic hepatitis, NAFLD, hemochromatosis, Wilson's, A1A deficiency