Chapter 14: The Liver, Biliary System,

Question 1

End stage liver damage
Diffuse bands of fibrosis and nodular regeneration destroys normal architecture of liver
Fibrosis is mediated by what?
Increased risk of hepatocellular carcinoma (HCC)
60-70% due to EtOH, or viral hepatitis, biliary disease, hemochromatosis
Portosystemic shunts partially alleviate portal HTN: esophageal varices, caput medusae, hemorrhoids

Answer 1

Cirrhosis

TGF-beta from stellate cells underneath the endothelial cells lining sinusoids mediate fibrosis

Question 2

Results of what cause the following?
Esophageal varices (=> hematemesis)
Peptic ulcer
(BOTH cause Melena)
Splenomegaly
Caput medusae
Ascites
Anorectal varices (=> hemorrhoids)

Answer 2

Effects of portal HTN

Question 3

Results of what cause the following?
Hepatic encephalopathy
Scleral icterus
Jaundice
Fetor Hepaticus (breath smells musty)
Liver flap = asterixis (coarse hand tremor)
bleeding tendency (indecreased clotting factors, increased prothrombin time)
anemia
ankle edema
Spider nevi
Gynecomastia
Testicular atrophy

Answer 3

Effects of liver cell failure

The last 3 are due to hyperestrogenism since damaged liver no longer breaks down estrogen

Question 4

What does liver cirrhosis look like on CT? Histology?

Answer 4

CT = nodularity of liver contour secondary to regenerating macronodules
Histology = regenerative nodules and bridging fibrosis

Question 5

Decreased ceruloplasmin is seen in?

Answer 5

Wilson disease

Question 6

Increased alk phos is seen in?

Answer 6

Obstructive hepatobiliary disease, hepatocellular carcinoma, bone disease

Question 7

If ALT > AST?

Answer 7

viral hepatitis

Question 8

If AST >ALT?

Answer 8

Alcoholic hepatitis

Question 9

IF increased amylase?

Answer 9

acute pancreatitis or mumps

Question 10

If increased gamma-glutamyl transpeptidase (GGT)?

Answer 10

Increased in various liver and biliary disease (like ALT)
BUT NOT INCREASED in bone disease
Associated with EtOH use

Question 11

Increase lipase?

Answer 11

Acute pancreatitis (Most Specific)

Question 12

Fulminant liver failure and encephalopathy in children with viral illness (which ones?) who take aspirin
Likely related to mitochondrial damage of hepatocytes
Mech: aspirin metabolites decrease beta-oxidation by reversible inhibition of mitochondrial enzyme
WHEN IS THE ONLY TIME A CHILD SHOULD GET ASPIRIN?

S/S: hypoglycemia, elevated liver enzymes, fatty liver, hepatomegaly and nausea w/vomiting, may progress to coma/death

Answer 12

Reye Syndrome

Viruses: VZV, influenza B

Kawasaki disease

Question 13

Reversible change with moderate alcohol intake
Macrovesicular fatty change that may be reversible with EtOH cessation
Accumulation of fat in hepatocytes

Answer 13

Alcoholic liver disease:

hepatic steatosis or fatty liver

Question 14

Requires sustained, long term EtOH consumption
Chemical injury to hepatocytes due to acetaldehyde
Swollen and necrotic hepatocytes w/neutrophilic infiltration
Mallory bodies (damaged cytokeratin filaments, eosinophilic inclusions)

S/S: painful hepatomegaly and liver enzymes?
Seen with binge drinkers

Answer 14

EtOH hepatitis

Increased AST > ALT (ratio > 1.5)

Question 15

Final and irreversible
long term complication of chronic EtOH induced liver damage
Micronodular
Irregularly shrunken liver with “hobnail” appearance
Sclerosis around central vein (zone 3)
jaundice, hypoalbuminemia

Answer 15

EtOH cirrhosis

Question 16

Metabolic syndrome (insulin resistance, obesity) => fatty infiltration of hepatocytes => cellular ballooning and eventual necrosis
May cause cirrhosis and HCC
Independent of EtOH use, diagnosis of exclusion
Liver enzymes?

Answer 16

Non-alcoholic fatty liver disease

Increased ALT > AST (L=lipids)

Question 17

Cirrhosis => portosystemic shunts => decreased NH3 metabolism => neuropsychiatric dysfxn
Spectrum:
Disorientation/mild asterixis to difficult arousal or coma (severe).
Triggers:
Increase NH3 production (due to dietary protein, GI bleed, constipation, infection)
Decreased NH3 removal (due to renal failure, diuretics, post-TIPS)
Treatment?

Answer 17

Hepatic encephalopathy

Treat: lactulose (increases NH4+ generation), low protein diet, and rifaximin kills intestinal bacteria

Question 18

Most common primary malignant tumor of the liver in adults
Associated with Hepatitis B and C, Wilson disease, hemochromatosis, alpha1-antitrypsin deficiency, alcoholic cirrhosis, and carcinogens (aflatoxin from Aspergillus induces p53 mutation)
May lead to Budd-Chiari syndrome
Findings: Jaundice, tender hepatomegaly, ascites, and anorexia, spreads hematogenously
Diagnosis: Increased alpha-fetoprotein, ultrasound or contrast CT

Answer 18

Hepatocellular carcinoma

Question 19

Occlusion of IVC or hepatic veins w/centrilobular congestion and necrosis, leading to congestive liver disease (hepatomegaly, ascites, abdominal pain, and eventual liver failure)
May develop varices and have visible abdominal and back veins. Absence of JVD. Associated with hypercoagulable states, polycythemia vera, pregnancy, and HCC

Answer 19

Budd-Chiari Syndrome

Question 20

Common, benign liver tumor; typically occurs at age 30-50 years. Biopsy contraindicated because risk of hemorrhage

Answer 20

Cavernous hemangioma

Question 21

Rare, benign liver tumor
Subcapsular and grow with estrogen
Associated with oral contraceptive use or anabolic steroid use
Regress upon cessation of drug or could rupture spontaneously and have intraperitoneal bleeding

Answer 21

Hepatic adenoma

Question 22

Malignant tumor of endothelial orgin

Associated with exposure to arsenic, vinyl chloride

Answer 22

Angoisarcoma

Question 23

Result of backup of blood into liver
Commonly caused by R. sided heart failure and Budd-Chiari syndrome
Liver appears mottled
If condition persists: centrilobular congestion and necrosis can result in cardiac cirrhosis

Answer 23

Nutmeg liver

Question 24

Misfolded gene product protein aggregates in hepatocellular ER => cirrhosis with PAS + globules in liver. Codominant trait.
In lung, decrease in this protein => uninhibited elastase in alveoli => decreased elastic tissue => panacinar emphysema

Answer 24

Alpha1-antitrypsin deficiency

Question 25

Earliest sign involves sclera High serum bilirubin at what level causes symptom? Occurs 2ndary to increased production of bilirubin or defective metabolism

Answer 25

Jaundice | Bilirubin > 2.5 mg/dL

Question 26

Where and what conjugates bilirubin? | What is urobilinogen all about? What happens to urobilinogen?

Answer 26

The liver Uridine glucuronyl transferase Intestinal flora turns Conjugated bilirubin to urobilinogen. Urobilinogen is oxidized to stercobilin (makes stool brown) and urobilin (makes urine yellow)

Question 27

What diseases could cause unconjugated (indirect) hyperbilirubinemia? What would be in the urine?

Answer 27

Hemolytic, physiologic (newborns), Crigler-Najjar, Gilbert syndrome Increased urine urobilinogen

Question 28

What disease could cause conjugated (direct) hyperbilirubinemia? What would be in the urine?

Answer 28

Biliary tract obstruction: gallstones, pancreatic liver cancer, liver fluke Biliary tract disease: Primary sclerosing cholangitis, Primary biliary cirrhosis Excretion defect: Dubin-Johnson syndrome, Rotor syndrome Decreased urine urobilinogen

Question 29

What diseases could cause mixed (indirect + direct) hyperbilirubinemia? What would be in the urine?

Answer 29

Hepatitis, cirrhosis | Normal or increased urine urobilinogen

Question 30

At birth, immature UDP-glucuronosyltransferase => unconjugated hyperbilirubinemia => jaundice/kernicterus (kernicterus involves severe mental defects etc)

Answer 30

Physiologic neonatal jaundice

Question 31

AR disease Mildly decreased UDP-glucuronosyltransferase conjugation activity => decreased bilirubin uptake by hepatocytes. Asymptomatic (No jaundice) or mild jaundice Elevated UCB (unconj bilirubin) Jaundice during stress (severe infection) otherwise clinically insignificant, common

Answer 31

Gilbert Syndrome

Question 32

Absent UDP-glucuronosyltransferase Presents early in life; patients die within a few years Jaundice, kernicterus (bilirubin deposition in the brain) Very high UCB Treatment?

Answer 32

Crigler-Najjar syndrome (Type 2 less severe: responds to phenobarbital which increase liver enzyme synthesis) Plasmapheresis and phototherapy

Question 33

Deficiency of bilirubin canalicular transport protein to excrete AR disease Increased conjugated bilirubin Liver is grossly black, otherwise benign

Answer 33

Dubin-Johnson syndrome

Question 34

Conjugated hyperbilirubinemia due to defective liver excretion but VERY mild NO grossly black liver

Answer 34

Rotor syndrome

Question 35

AR disease Defect of ATP7B gene chrom 13 in ATP-mediated copper transport Inadequate hepatic copper excretion in bile and failure of copper to enter circulation as ceruloplasmin Copper accumulation: liver, brain, joints, kidneys, cornea (Kayser-Fleischer ring)

Answer 35

Wilson Disease

Question 36

Presents in childhood: cirrhosis, neurologic (behavioral changes, dementia, chorea, and Parkinsonian symptoms), Brown ring around cornea Remember: Copper is Hella BAD

Answer 36

Wilson Disease decreased Ceruloplasmin, Cirrhosis, Corneal deposits, Copper accumulation, Carcinoma (HCC) Hemolytic anemia Basal ganglia degeneration (Parkinsonism) Asterixis Dementia, Dyskinesia, Dysarthria

Question 37

Excess body iron leading to deposition in tissues (hemosiderosis) and organ damage (______) Tissue damage mediated by free radicals (Co can go in Fenton Rxn) AR disease: defect in Fe absorption b/c HFE gene mutation (C282Y), associated with HLA-A3 OR chronic transfusions

Answer 37

Hemochromatosis

Question 38

Classic triad presents in late adulthood Cirrhosis Diabetes Mellitus and Bronze skin (bronze diabetes) Other: CHF (dilated cardiomyopathy), cardiac arrhythmias and gonadal dysfxn due to testicular atrophy Increased risk of HCC Treatment?

Answer 38

Hemachromatosis If hereditary: repeated phlebotomy, deferasiroz, deferoxamine

Question 39

Liver biopsy shows accumulation of brown pigment in hepatocytes Why must you use Prussian blue stain? Labs: Increased ferritin, Decreased TIBC, increased serum iron, and increased % transferrin saturation

Answer 39

Hemachromatosis Prussian blue stain distinguises iron (blue) from lipofuscin

Question 40

Extrahepatic biliary obstruction Due to gallstone, biliary stricture, chronic pancreatitis, carcinoma of the pancreatic head, cholangiocarcinoma, parasites, liver fluke (Clonorchis sinensis), complicated by ascending cholangitis Increased pressure in intrahepatic ducts => injury/fibrosis and bile stasis S/S: pruritius, jaundice, dark urine, pale stool, hepatosplenomegaly, xanthomas, steatorrhea Increased conjugated bilirubin, increased cholesterol, increased Alk phos, decreased urine urobilinogen

Answer 40

Secondary Biliary Cirrhosis | aka Biliary tract obstruction, obstructive jaundice

Question 41

Autoimmune rxn => lymphocytic infiltrate => + granulomas => destruction of intralobular bile ducts Associated with CREST, SjoS, RA, Celiac Antimitochondrial Antibody Presents with obstructive jaundice features, Increased conj bilirubin, cirrhosis a late complication Classic in women 40 y

Answer 41

Primary biliary cirrhosis

Question 42

Unknown cause of concentric "onion skin" bile duct fibrosis => alternating strictures and dilation with "beading"of intra-and extra hepatic bile ducts on contrast imaging Associated with ulcerative colitis p-ANCA positive Increased risk of 2ndary biliary cirrhosis and cholangiocarcinoma

Answer 42

Primary sclerosing cholangitis

Question 43

Stones in the gallbladder Radiolucent = don't show up on x-ray 10% can be radiopaque (why?) Risk factors: Female, fat, fertile (pregnant), forty (estrogen increases cholesterol uptake, clofibrate (increase HMGCoA reductase which increases cholesterol syn and decrease bile acids), Native American, Crohn disease (terminal ileum damage decreased bile salt/acid uptake), cirrhosis (decreased bile salts)

Answer 43

``` Cholesterol stones (cholelithiasis) Yellow grossly ```

Question 44

Pigment stones in gallbladder 1) Radiopaque type (color?) = can be seen on x-ray 2) Radiolucent type (color?) Risk factors: extravascular hemolysis (1) and biliary tract infections (2), alcoholic cirrhosis, advanced age

Answer 44

Cholelithiasis 1) black 2) brown

Question 45

Most common complications of cholelithiasis

Answer 45

Usually asymptomatic Comp: biliary colic, acute and chronic cholecystitis, ascending cholangitis, gallstone ileus, gall bladder cancer, bile stasis, acute pancreatitis

Question 46

What is the Charcot Triad of cholangitis?

Answer 46

Jaundice Fever RUQ pain

Question 47

What do the following infect? What are they? E. coli Ascaris lumbricoides Clonorchis sinensis

Answer 47

infects biliary tract, increasing risk for gall stones, cholangitis, and cholangiocarcinoma A. lumbricoides = roundworm, due to poor sanitation C. sinensis = liver fluke, endemic in China, Korea, Vietnam

Question 48

Waxing and waning RUQ pain Due to gallbladder contracting against a stone lodged in the cystic duct Relief if stone passes Common bile duct obstruction may => acute pancreatitis or obstructive jaundice

Answer 48

Biliary Colic

Question 49

Impacted stone in the cystic duct results in dilatation with pressure ischemia, bacterial overgrowth, and inflammation S/S: RUQ pain, often radiating to the right scapula, fever with increased WBC count, nausea, vomiting, and increased serum alk phos (from duct damage, ascending cholangitis)

Answer 49

Acute Cholecystitis

Question 50

Chemical irritation from long standing cholelithiasis, with or without superimposed bouts of acute cholecystitis Characterized by herniation of gall bladder mucosa into the muscular wall, name the special name of this sinus! What is a late complication? S/S: vague RUQ pain, especially after eating

Answer 50

Chronic Cholecystitis Rokitansky-Aschoff sinus (I hope to one day have a butthole malformation named after me, the Patel Pothole or something) Porcelain gallbladder is a late complication (dystrophic calcification, shrunken hard gallbladder)

Question 51

What would be a POM physical finding for cholecystitis?

Answer 51

+ Murphy's sign BITCH, inspiratory arrest on RUQ palpation, due to pain.

Question 52

Bacterial infection of bile ducts Ascending infection with enteric gram - bacteria S/S: sepsis (high fever and chills), jaundice, and abdominal pain Increased incidence with choledocholithiasis (??)

Answer 52

Ascending cholangitis Choledocholithiasis = stone in biliary ducts

Question 53

Extremely elderly woman presents with cholecystitis, poor prognosis, used to have a lot of gallstones complicated by having porcelein gallbladder

Answer 53

Gallbladder carcinoma