Exocrine Pancreas and Liver Pathology (Pathoma)

Question 1

Annular Pancreas

Answer 1

Devolopmental malformation of pancreas forming ring around the duodenum.

Risk of duodenal obstruction

Question 2

Acute Pancreatitis

Answer 2

Liquefactive necrosis and fat necrosis and hemorrhage of pancreas

Due to autodigestion of pancreatic parenchyma by pancreatic enzymes

Premature activation of TRYPSIN leads to activation of other enzymes.

MCC: Alcohol (contraction of sphincter of oddi –> decrease pancreatic drainage) or Gallstones

Other causes: Trauma (kid wearing seatbelt), hypercalcemia (autoactivation) and hyeprlipidemia, drugs, scorpion stings, mumps, rupture of posterior duodenal ulcer

Clinical Features: Epigastric pain that radiates to back. N/V. Periumbilical and flank hemorrhage.

Elevation of serum lipase (best test) and amylase. Hypocalcemia

Complications: Shock, pancreatic pseudocyst (can rupture), pancreatic abscess (E. coli infection of abscess), DIC and ARDS (pancreatic enzymes active on clotting factors and endothelium when in blood).

Question 3

Chronic Pancreatitis

Answer 3

Fibrosis of pancreatic parenchyma secondary to recurrent acute pancreatitis

MC due to alcohol and cystic fibrosis (thick secretions –> blockage). Many are idiopathic.

Clinical features: Epigastric abdominal pain radiating to back, pancreatic insufficiency (steatorrhea w/ ADEK def.), dystrophic calcification of pancreas, secondary DM, increased risk for carcinoma

Amylase and Lipase are not good markers

Question 4

Pancreatic Carcinoma

Answer 4

Adenocarcinoma arising from pancreatic ducts

MC in elderly (70 = avg. age)

Major risk factors = smoking and chronic pancreatitis

Clinical features: Epigastric pain and weight loss. Usually late. Obstructive jaundice w/ pale stools and palpable gallbladder (head of pancreas). Secondary DM (body or tail)

*Think if thin elderly w/ new DM

Can cause pancreatitis, migratory thrombophlebitis (Trousseu’s sign in 10%)

Serum marker CA 19-9 used to track progress of tumor

Rx: Whipple procedure (En bloc removal of head neck of pancreas, duodenum, and gallbladder)

Terrible outcomes (less than 10% one year survival)

Question 5

Biliary Atresia

Answer 5

Failure to form or early destruction of extrahepatic biliary tree

Leads to biliary obstruction within first 3 months

Presents w/ jaundice (CB) and progresses to cirrhosis (back pressure)

Question 6

Colelithiasis

Answer 6

Gall stones

Due to precipitation of cholesterol or bilirubin in bile due to supersaturation, decreased phospholipids (i.e. cholestyramine), or stasis (increase bacteria –> increased UCB –> stone

Cholesterol is MC stone in West –> radiolucent. Yellow in color

Risk factors: Female (estrogen), Fat (cholesterol), Forty, and Fertile (estrogen), Cofibrate, Native American, Crohn’s disease (decreased bile salts/acids from ileum), Cirrhosis (decreased bile salt production)

Bilirubin stone (usually radiopaque) and looks black in color.

Risk factor: Extravascular hemolysis, biliary tract infection (E. coli, Ascaris lumbricoides, and Clonorchis sinesis) –> increased UCB Bilirubin

Gallstones are usually asymptomatic.

Complications:
Biliary colic -
Acute and chronic cholecystitis
Ascending cholangitis
Gallstone ileus
Gallbladder cancer

Question 7

Cholesterol Stones

Answer 7

MC stone in West. Radiolucent and yellow in color

Risk factors: Female (estrogen), Fat (cholesterol), Forty, and Fertile (estrogen), Cofibrate, Native American, Crohn’s disease (decreased bile salts/acids from ileum), Cirrhosis (decreased bile salt production)

Question 8

Bilirubin Stones

Answer 8

Usually radiopaque and black in color.

Risk factor: Extravascular hemolysis, biliary tract infection (E. coli, Ascaris lumbricoides, and Clonorchis sinesis) –> increased UCB Bilirubin

Question 9

Bilary Colic

Answer 9

Waxing and waning RUQ pain.

Due to gallbladder contracting against stone in cystic duct.

Question 10

Acute Cholecystitis

Answer 10

Acute inflammation of gallbladder wall

Impacted stone in cystic duct results in dilitation w/ pressure ischemia, bacterial overgrowth, and inflammation

Presents w/ RUQ *radiating to RIGHT SCAPULA. Fever and elevated WBC, N/V, Increased alk phosp, risk of rupture.

Question 11

Chronic Cholecystitis

Answer 11

Chronic inflammation of gallbladder due to chemical irritation from longstanding cholelithiasis

*Hallmark is formation of Rokitansky-Aschoff sinus (mucosa diving into smooth muscle)

Presents w/ vague RUQ pain, especially after eating.

Porcelain gallbladder is a late complication (dystrophic calcification)

Rx: Cholecystectomy, especially if porcelain gallbladder is present (increased cancer risk)

Question 12

Ascending Cholangitis

Answer 12

Bacterial infection of bile ducts

Usually due to ascending infection w/ enteric gram negative bacteria (e. coli)

Presents as sepsis, jaundice, and abdominal pain

Increased incidence with choledocholitiiasis

Remember stasis –> infection behind

Question 13

Gallstone Ileus

Answer 13

Gallstone enters and obstructs the small bowel after fistula formation

Obstructs I/C valve. Air in biliary tree!

Question 14

Gallbladder Adenocarcinoma

Answer 14

Arises from glandular epithelium that lines the gallbladder wall.

Gallstones = major risk factor; esp. porcelain gallbladder

Clasically presents as cholecystitis in elderly woman (not normal age of onset for cholecystitis)

Poor prognosis

Question 15

Jaundice

Answer 15

Yellow discoloration of skin; earlies sign is scleral icterus

Due to increased serum bilirubin (>2.5mg/dl

Arises w/ disturbances in bili metabolism.

Causes: Extravascular hemolysis or ineffective erythropoesis, phsyiologic jaundice of the newborn, gilbert syndrome, Crigler-Najjar syndrome, Dubin-Johnson syndrome, Biliary obstruction, viral hepatitis

Question 16

Extravascular hemolysis

Answer 16

Etiology: High levels of UCB overwhelm liver

Labs: High UCB

Clinical Features: Dark urine (increased urobilinogen –> UCB is not water soluble)

Increased risk for pigmented bili stone

Question 17

Physiologic jaundice of the newborn

Answer 17

Newborn liver has transiently low UGT activity

Labs: High UCB

Clinical features: UCB is fat soluble and can deposit in the basal ganglia (kernicterus) leading to neuro deficits and death.

Rx: phototherapy (makes UCB water soluble –> gets rid of riboflavin (b2)!

Question 18

Gilbert syndrome

Answer 18

Mildly low UGT activity; automal recessive

Labs: High UCB

Clinical Features: Jaundice during stress (infection). Otherwise not clincally significant

Question 19

Criggler-Najjar syndrome

Answer 19

Absence of UGT

Labs: High UCB

Kernicterus; usually fatal

Question 20

Dubin-Johnson syndrome

Answer 20

Deficiency of bilirubin canalicular transport protein; autosomal recessive

Labs: Increased CB

**Liver is dark; otherwise not clincally significant. Rotor syndrome is similar to DJS but lacks liver discoloration

Question 21

Biliary Tract Obstruction

Answer 21

Associated w/ gallstones, pancreatic adenocarcinoma, cholangiocarcinoma, parasites, and liver fluke (Clonorchis sinensis)

Labs: Increased CB, Decreased urine urobilinopgen, and increased Alk Phosph

Clinical Features: Dark urine (due to bilirubinuria) and pale stools. Pruritis due to increased plasma bile acids. Hypercholestemia w/ xanthomas. Steatorrhea w/ malabsorbtion of ADEK

Question 22

Viral Hepatitis

Answer 22

Inflammation of parenchyma disrupts hepatocytes and small bile ductules

Labs: Increased CB and UCB

Clinical Features: Dark urine due to urine CB; urine urobilinogen is normal or decreased.

Due to Hep ABCDE virus, EBV, and CMV

Hep BCD can progress from acute hepatitis to chronic hepatitis

Question 23

Acute Hepatitis

Answer 23

Jaundice (mixed CB and UCB) with dark urine (CB), fever, malaise, and nausea

Elevated liver enzymes (ALT >AST) –> Remember two L’s rule –> alcohol is opposite

Sx last less than 6 months

Question 24

Chronic Hepatitis

Answer 24

Sx and serology for more than 6 months

Risk for advance to cirrhosis

Question 25

Hepatitis A Virus

Answer 25

Fecal Oral transmission MC in travelers Acute hepatitis only Anti-virus IgM marks active infection. Anti-virus IgG is protective, and its presence indicates prior infection or immunizaiton

Question 26

Hepatitis E

Answer 26

Fecal Oral transmission MC from contaminated water or undercooked seafood Acute hepatitis only Anti-virus IgM marks active infection. Anti-virus IgG is protective, and its presence indicates prior infection Infection in pregnant women is associated w/ fulminant hepatitis (liver failure w/ massive liver necrosis)

Question 27

Hepatits B

Answer 27

Parenteral transmission (i.e. childbirth, sex, iv drugs, needlestick) Results in acute hepatitis; chronic disease in 20% HBsAG is is first serologic marker to rise and key marker of infection --> if present more than 6 months defines chronic state HBcAB IgM = key marker of acute battle HBsAB IgG is indicator of won battle HBeAG and HBV DNA indicates infectivity (mail a letter to a friend) Acute (HBsAG, HAeAG, HBcAB IgM); Window (HBcAB IgM); Resolved (HBcAB IgG, HBsAB IgG); Chronic (HBsAG for greather than 6 months, +/-HBeAG, HBcAB IgG); Immunization (HBsAB IgG)

Question 28

Hepatitis C

Answer 28

Parenteral transmission (ie. IV drugs, intercourse, needle stick) risk from transfusion is almost none due to screening of blood supply. Results in acute hepatitis; chronic disease in most states. HCV-RNA test confirms infection; decreased RNA levels indicate recovery; persistence indicates chronic disease

Question 29

Hepatitis D

Answer 29

Dependent on HBV for infection; superinfection upon coexisting HBV is more sever than coinfection.

Question 30

Cirrhosis

Answer 30

End-stage liver damage Disruption of normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes (think alcoholic who quits and relapses) Mediated by stellate cell that secretes TGF-B. Lie beneath endothelial cells that line sinusoids. Portal HTN Decreased detoxification Decreased protein synthesis (hypoalbuminemia and coagulopathy --> follow PT)

Question 31

Portal HTN

Answer 31

Ascitis Congestive splenomegaly/hypersplenism (consumption of RBCs and platelets) Portosystemic shunts (varices, caput medusa, internal hemorrhoids) Hepatorenal syndrome (rapid renal failure secondary to cirrhosis)

Question 32

Decreased detoxification

Answer 32

Mental status changes, asterixis, and coma (due to increased ammonia --> reversible!) Gynecomastia, spider angiomata, and palmar erythema (decreased estrogen breakdown) Jaundice

Question 33

Alcohol-Related Liver Disease

Answer 33

Damage to hepatic parenchyma due to consumption of alcohol MCC of liver disease in West Three patterns of injury: 1. ) Fatty Liver 2. ) Alcoholic Hepatitis 3. ) Cirrhosis

Question 34

Fatty Liver

Answer 34

Accumulation of fat in the hepatocytes resulting in heavy, greasy liver. Resolves w/ abstinence

Question 35

Alcoholic Hepatitis

Answer 35

Chemical injury to hepatocytes; generally seen w/ binge drinking Acetaldehyde mediates damage Mallory body = damaged intermediated filaments in hepatocytes. Presents w/ painful hepatomegaly and elevated liver enzymes (AST > ALT) --> Remember 2 L rule. AST is in mitochondria May result in death

Question 36

Nonalcoholic Fatty Liver Disease

Answer 36

Fatty change, hepatitis, and/or cirrhosis Develops w/o exposure to alcohol Associated w/ obesity Dx of exclusion; ALT > AST (AST is mitochondial enzyme)

Question 37

Hemochromatosis

Answer 37

Excess body iron leading to deposition in tissues and organ damage Damage is mediated by generation of free radicals (Fenton-RXN) HLA- A3 Primary hemochromatosis is due to mutations in HFE, most commonly C282Y Loss of regulation of enterocyte iron absorbtion May be secondary to transfusions (i.e. Sickle Cell) Cirrhosis, secondary DM, bronze skin, cardiac arrhythmia (also restricitve cardiomyopathy) and gonadal dysfunction Labs: Increased Ferritin, decreased TIBC, increased serum Fe, Increased percent sat Presents in late adulthood Brown pigment in hepatocytes --> prussian blue stain (vs. lipofuschin) Rx: Phlebotomy Increased risk for hepatocellular carcinoma

Question 38

Wilson Disease

Answer 38

Autosomal recessive defect (ATP7B gene) in ATP-mediated hepatocyte copper transport Results in lack of copper transport into ible and lack of copper incorporation into ceroplasmin Copper builds up in hepatocytes, leaks into serum, and deposits in tissues Copper mediated production of hyrdroxyl free radicals leads to tissue damage Sx: Cirrhosis, Neurologic manifestations (parkinson's like, chorea like), Kayer'Fleisher rings in cornea, Increased risk for hepatocellular carcinoma Presents in childhood Rx: D-penicillamine Labs increased urinary copper, decreased serum ceroloplasmin, copper in hepatocytes

Question 39

Primary Biliary Cirrhosis

Answer 39

AI granulomatous destruction of intrahepatic bile duct. Classically arises in women (avg. age 40) Associated w/ other AI diseases Antimitochondrial antibody! Cirrhsosis is a late complication

Question 40

Primary Sclerosing Cholangitis

Answer 40

Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts Periductal fibrosis w/ onion skin appearance Uninvolved regions are dilated resulting in beaded appearance on imaging Associated w/ ulcerative colitis and p-ANCA Present w/ obstructive jaundice Cirrhosis is a late complication Increased risk for cholangiocarcinoma

Question 41

Reye Syndrome

Answer 41

Fulminant liver failure and encephalopathy w/ viral illness (esp chickenpox) who take aspirin Related to mitochondrial damage of hepatocytes Present w/ hypoglycemia, elevated liver enzymes, and N/V May progress to coma and death. Kawasakis is exception!

Question 42

Hepatic Adenoma

Answer 42

Benign tumor of hepatocytes Associated w/ OCPs --> regresses upon sessation, recurs w/ pregnancy Risk of rupture and intraperitoneal hemorrhage, esp. during pregnancy.

Question 43

Hepatocellular Carcinoma

Answer 43

Risk Factors: Chronic hepatitis, Cirrhosis, Aflotoxins derived from Aspergillis (high incidence in countries that store grain for long periods of time --> p53 mutation. Increased risk for Budd-Chiari Poor prognosis --> found late due to cirrhosis hiding it Alpha-fetoprotein = serum tumor marker

Question 44

Budd-Chiari

Answer 44

Liver infarction secondary to hepatic vein obstruction Presents w/ painful hepatomegaly and ascites

Question 45

Metastasis to Liver

Answer 45

MC liver cancer MC sources: Colon (MCC), pancreas, lung, and breast Multiple nodules in liver Clinically may be detected as hepatomegaly w/ nodular free edge of liver