Exocrine Pancreas and Liver Pathology (Pathoma) Flashcards
Annular Pancreas
Devolopmental malformation of pancreas forming ring around the duodenum.
Risk of duodenal obstruction
Acute Pancreatitis
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).
Chronic Pancreatitis
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
Pancreatic Carcinoma
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)
Biliary Atresia
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)
Colelithiasis
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
Cholesterol Stones
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)
Bilirubin Stones
Usually radiopaque and black in color.
Risk factor: Extravascular hemolysis, biliary tract infection (E. coli, Ascaris lumbricoides, and Clonorchis sinesis) –> increased UCB Bilirubin
Bilary Colic
Waxing and waning RUQ pain.
Due to gallbladder contracting against stone in cystic duct.
Acute Cholecystitis
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.
Chronic Cholecystitis
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)
Ascending Cholangitis
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
Gallstone Ileus
Gallstone enters and obstructs the small bowel after fistula formation
Obstructs I/C valve. Air in biliary tree!
Gallbladder Adenocarcinoma
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
Jaundice
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
Extravascular hemolysis
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
Physiologic jaundice of the newborn
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)!
Gilbert syndrome
Mildly low UGT activity; automal recessive
Labs: High UCB
Clinical Features: Jaundice during stress (infection). Otherwise not clincally significant
Criggler-Najjar syndrome
Absence of UGT
Labs: High UCB
Kernicterus; usually fatal
Dubin-Johnson syndrome
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
Biliary Tract Obstruction
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
Viral Hepatitis
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
Acute Hepatitis
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
Chronic Hepatitis
Sx and serology for more than 6 months
Risk for advance to cirrhosis
Hepatitis A Virus
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
Hepatitis E
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)
Hepatits B
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)
Hepatitis C
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
Hepatitis D
Dependent on HBV for infection; superinfection upon coexisting HBV is more sever than coinfection.
Cirrhosis
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)
Portal HTN
Ascitis
Congestive splenomegaly/hypersplenism (consumption of RBCs and platelets)
Portosystemic shunts (varices, caput medusa, internal hemorrhoids)
Hepatorenal syndrome (rapid renal failure secondary to cirrhosis)
Decreased detoxification
Mental status changes, asterixis, and coma (due to increased ammonia –> reversible!)
Gynecomastia, spider angiomata, and palmar erythema (decreased estrogen breakdown)
Jaundice
Alcohol-Related Liver Disease
Damage to hepatic parenchyma due to consumption of alcohol
MCC of liver disease in West
Three patterns of injury:
- ) Fatty Liver
- ) Alcoholic Hepatitis
- ) Cirrhosis
Fatty Liver
Accumulation of fat in the hepatocytes resulting in heavy, greasy liver.
Resolves w/ abstinence
Alcoholic Hepatitis
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
Nonalcoholic Fatty Liver Disease
Fatty change, hepatitis, and/or cirrhosis
Develops w/o exposure to alcohol
Associated w/ obesity
Dx of exclusion; ALT > AST (AST is mitochondial enzyme)
Hemochromatosis
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
Wilson Disease
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
Primary Biliary Cirrhosis
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
Primary Sclerosing Cholangitis
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
Reye Syndrome
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!
Hepatic Adenoma
Benign tumor of hepatocytes
Associated w/ OCPs –> regresses upon sessation, recurs w/ pregnancy
Risk of rupture and intraperitoneal hemorrhage, esp. during pregnancy.
Hepatocellular Carcinoma
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
Budd-Chiari
Liver infarction secondary to hepatic vein obstruction
Presents w/ painful hepatomegaly and ascites
Metastasis to Liver
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
