Lecture 7.2: Liver, Gallbladder, Pancreas

Question 1

This is a remind to review the clip of slide 4 (lobular anatomy)

Question 2

What are the 4 categories of Mechanisms of Hepatic Injury/ Repair?

Answer 2

1) Reversible change
2) Death
3) Scar
4) Inflammation/ immunologic

Question 3

Mechanisms of Hepatic Injury/ Repair; give example(s) of:
1) Reversible change (1)
2) Death (2 types, multiple examples)
3) Regeneration (2 types)

Answer 3

1) i.e. accumulations (lipid vacuoles or “steatosiInfs”)
2) Necrosis (hypoxia & ischemia)
Apoptosis (viral, autoimmune, & drug/toxin induced)
3) Acute: primarily mitotic replication of adjacent hepatocytes
Chronic: managed by stem cell proliferation and differentiation

Question 4

Mechanisms of Hepatic Injury/ Repair:
1) What can scars follow? What do they more often follow?
-How do they occur (like, on a cellular level)?
2) Inflammation/immunologic: how does this mechanism work? What cells are involved?

Answer 4

1) Can follow severe acute injury; more often follows chronic injury
-Hepatic stellate cells > myofibroblasts
2) Systemic inflammation → alteration of metabolic activity and biosynthesis → ↑ acute phase (CRP, Serum amyloid)
-CD4 and CD8 cells

Question 5

List the 3 types of liver failure

Answer 5

1) Acute
2) Chronic
3) Acute on chronic

Question 6

Define acute liver failure

Answer 6

Liver disease that produces hepatic encephalopathy <6 months of diagnosis

Question 7

1) Cirrhosis is a ____________ change
2) True or false: Not all chronic liver disease ends in cirrhosis. Explain.
3) True or false: Not all cirrhosis leads to end-stage liver disease. Explain.

Answer 7

1) morphologic
2) True; i.e. chronic biliary tract disease
3) True; i.e. tx’d hep C or autoimmune hepatitis

Question 8

Common Causes of cirrhosis
(this answer is weird)

Answer 8

Stuff happens. . .
(VW)

Question 9

What is *Acute-on-Chronic Liver Failure & Cirrhosis

Answer 9

Stable, well compensated disease → develop acute liver failure

Question 10

Symptoms of Liver Failure:
Both acute and chronic can have jaundice and icterus, but which is more likely to have severe jaundice?

Answer 10

Chronic

Question 11

Acute vs chronic liver failure:
1) Which is more likely to have pruritis? Explain.
2) Which is more likely to have cholestasis?

Answer 11

1) Chronic; seen with other disorders of cholestasis, prob due to ↑ bile salts
2) Acute

Question 12

List 3 Sx of acute liver failure

Answer 12

1) Portal HTN: Usually, intrahepatic
-> Leads to ascites
2) Coagulopathy: ↓ production of clotting factors
3) Hepatic Encephalopathy*
Range of neuro symptoms, often see asterixis
↑ammonia levels

Question 13

Chronic liver failure Sxs:
1) Why is Hepatorenal syndrome a Sx?
2) Why is Portal HTN a Sx? (2 reasons)
3) Hepatocellular ____ risk ↑↑↑

Answer 13

1)Systemic vasodilation  decreased systemic vascular resistance = ↓ renal perfusion → ↓UOP & ↑BUN/Cr
2) Portico-systemic shunts (i.e. varices)
Congestive splenomegaly
3) CA

Question 14

Hepatitis A:
1) Route of transmission
2) Incubation period
3) Frequency of chronic liver disease
4) Describe the severity + duration of the infection

Answer 14

1) Fecal-oral (i.e. contaminated food or water)
2) 2-6 weeks
3) Never
4) Usually a benign self –limited infection

Question 15

Hepatitis B: What is best predictor of chronicity?

Answer 15

Age @ time of infection

Question 16

Hepatitis B:
1) What are the 3 routes of transmission?
2) Incubation period
3) Frequency of chronic liver disease is _______%
4) Outcomes vary widely; why?

Answer 16

1) Parenteral, perinatal, or sexual
2) 2-26 weeks (mean 8 weeks)
3) 5-10%
4) Host response is main determinate

Question 17

Hepatitis C:
1) Route of transmission & a risk factor
2) Incubation period
3) Frequency of chronic liver disease
4) What type of infection and Sx?
5) What are the hallmarks of HCV infection?

Answer 17

1) Parenteral; intranasal cocaine is a risk factor
2) 4-26 weeks (mean = 9 weeks)
3) >80%
4) Acute infection; often asymptomatic
5) Persistent infection and chronic hepatitis

Question 18

Alcoholic Liver Disease is a common cause of what?

Answer 18

Fatty liver disease

Question 19

Alcoholic Liver Disease:
1) Can be caused by ____ g of ETOH Qday
2) ____ beers
3) 8-9 oz of ____ proof liquor
4) What type of drinking is riskier?

Answer 19

1) 80g
2) 5-6 beers
3) 80 proof
4) Binge > steady

Question 20

Drug & Toxin-Induced Injury: What organ is susceptible because it is the main drug-metabolizing and detoxifying organ?

Answer 20

Liver

Question 21

Predictable (intrinsic) Type Drug & Toxin-Induced Liver Injury:
1) Reactions affect individuals in a ___________ pattern; classic example is _____________.
2) Toxic agent is the metabolites of the _________________.
3) Damages _______________ , but can extend to entire lobule

Answer 21

1) dose-dependent; acetaminophen
2) cytochrome P-450
3) centrilobular

Question 22

Hemochromatosis:
1) Define it and what organs it effects.
2) What are the 2 forms?

Answer 22

1) Excessive absorption of iron which deposits is parenchymal organs
-Liver & Pancreas ( but also heart & joints)
2) Heredity or Acquired (from parenteral administration; usually transfusions)

Question 23

Hemochromatosis clinical features:
1) Who does it affect more?
2) Sx?

Answer 23

1) Men > Women (secondary to blood loss associated with menstruation)
2) Hepatomegaly, abdominal pain, skin pigmentation in sun exposed areas, impaired glucose tolerance, cardiac dysfunction, and atypical arthritis

Question 24

Hemochromatosis causes Hepatic Injury (after 20 g of stored Fe accumulated) through what 3 mechanisms?

Answer 24

1) Lipid peroxidation
2) Collagen formation after activation of stellate cells
3) DNA damage by ROS

Question 25

Bilirubin: 1) What is it the end-product of? 2) Where does 85% this come from? 3) Where does the 15% come from?

Answer 25

1) Heme degradation 2) Heme degradation in spleen, liver, and bone marrow by macrophages 3) Turnover of hepatic heme or hemoproteins

Question 26

Pathophysiology of Jaundice: What are the 2 types of bilirubin?

Answer 26

1) Conjugated bilirubin (bilirubin glucuronides) and 2) Unconjugated bilirubin

Question 27

Pathophysiology of Jaundice: List 4 characteristics of Conjugated Bilirubin

Answer 27

1) Water soluble 2) Non-toxic 3) Loosely bound to albumin 4) Excreted in urine

Question 28

Pathophysiology of Jaundice: Where is most Unconjugated Bilirubin found?

Answer 28

1) Mostly bound to albumin -(Unbound fraction)

Question 29

Pathophysiology of Jaundice: How does unbound fraction increase? (2 ways)

Answer 29

1) Via Hemolytic Disease 2) Via protein binding drugs displace bilirubin from albumin

Question 30

Pathophysiology of Jaundice: [Unbound fraction] Bilirubin diffuses into tissues and causes toxic injury.; give an example

Answer 30

Hemolytic disease of newborn (erythroblastosis fetalis) causes injury to the brain (kernicterus)

Question 31

1) Define Cholestasis 2) What are 3 clinical Sx?

Answer 31

1) Impaired excretion of bile 2) Jaundice, Pruritis, Skin Xanthomas

Question 32

List 2 kinds of Autoimmune Cholangiopathies

Answer 32

1) Primary Biliary Cholangitis -formerly called “primary biliary cirrhosis” 2) Primary Sclerosing Cholangitis

Question 33

Autoimmune Cholangiopathies: **Primary Biliary Cholangitis**: 1) This type of cholangitis is formerly called what? 2) It involves __________, inflammatory destruction of _______________-sized ______hepatic bile ducts. 3) What are characteristic of this?

Answer 33

1) “Primary biliary cirrhosis” 2) non-suppurative; small & medium; intrahepatic 3) Anti-mitochondrial antibodies

Question 34

Autoimmune Cholangiopathies: **Primary Sclerosing Cholangitis**: 1) What leads to dilation of preserved segments? 2) Sclerosing of bile ducts leads to what? List the chain rxn.

Answer 34

1) Inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts of all sizes 2) Sclerosing of bile ducts > back up of bile > hepatitis > fibrosis

Question 35

Autoimmune Cholangiopathies: **Primary Sclerosing Cholangitis**: 1) Often seen in workup for ↑ __________ in someone who has UC. 2) Who is it seen in? (demographic) 3) Strong association with ___________ disease, particularly ________________.

Answer 35

1) alk phos 2) Younger men 3) inflammatory bowel; ulcerative colitis

Question 36

Circulatory Disorders of the Liver: List the 3 main pathogeneses and their manifestations *"won't be hammered on this on a test, just get the big picture" (slide 46)*

Answer 36

1) **Impaired blood inflow**: esophageal varices, splenomegaly, intestinal congestion. 2) **Impaired intrahepatic blood flow**: -ascites or esophageal varices (cirrhosis), hepatomegaly, elevated aminotransferases. 3) **Hepatic vein outflow obstruction** -similar to that of Impaired intrahepatic blood flow

Question 37

Circulatory Disorders of the Liver: For each of the 3 main pathogeneses, list potential causes *"won't be hammered on this on a test, just get the big picture"*

Answer 37

1) **Impaired blood inflow**: portal vein obstruction, intra/extrahepatic thrombosis 2) **Impaired intrahepatic blood flow**: cirrhosis, *sinusoid occlusion* 3) **Hepatic vein outflow obstruction**: Hepatic vein Thrombosis (Budd-Chiari) or Sinusoidal obstructive syndrome

Question 38

Aminotransferases will not be found with what type of pathogenesis of Circulatory Disorders of the Liver?

Answer 38

impaired blood flow

Question 39

Hepatocellular Adenoma (Benign): 1)Develops from ___________ ; subclassified on the basis of _____________ 2) Malignant potential? 3) 1 main pt of presentation? 4) What risk factors is it associated with?

Answer 39

1) hepatocytes; molecular changes 2) Varying degrees 3) Pain - usually from mass distending the liver capsule. 4) Oral Contraceptives Androgens (e.g. anabolic steroids) Cessations of sex hormones usually causes tumor regression

Question 40

Hepatocellular Carcinoma (Malignant): list the 4 main causes

Answer 40

1) Chronic liver disease (most common) 2) Hep B &C - chronic inflammation & cellular regeneration are predisposing factors for HCC 3) Alcoholic Cirrhosis-90% develop in cirrhotic livers 4) Hemochromatosis

Question 41

Hepatocellular Carcinoma (Malignant) morphology

Answer 41

1) Unifocal- large mass 2) Multifocal-widely distributed nodules of variable size 3) Diffusely infiltrative

Question 42

Hepatocellular Carcinoma (Malignant): characteristics

Answer 42

1) Invades blood vessels 2) Recapitulates normal liver architecture to varying degrees 3) Often arises from pre-malignant precursor lesions a) Hepatic Adenoma b) Low grade dysplasia → high grade dysplasia → ↑↑↑ risks

Question 43

Cholangiosarcoma (Malignant)

Answer 43

Tumor involving intrahepatic or extrahepatic bile ducts

Question 44

Cholangiosarcoma (Malignant) 1) Risk factors 2) Exposure to ___________ (endemic to southeast asia) causes a 30-40x higher risk

Answer 44

1) Chronic inflammation & cholestasis Primary sclerosing cholangitis Hepatolithiasis Fibropolycystic liver disease Hep B & C NAFLD 2) liver flukes

Question 45

List the 2 types of gallstone disease

Answer 45

1) Cholesterol stones (Western) 2) Pigment Stones (Asian)

Question 46

Gallstone Disease 1) Cholesterol stones (Western): define supersaturation in this context. 2) Pigment Stones (Asian): Describe how they occur and give examples of causes

Answer 46

1) Cholesterol exceed solubilizing capacity of bile → crystallizes out of solution 2) Unconjugated bilirubin in biliary tree (i.e. hemolysis; certain infections (liver flukes)) Precipitates are insoluble bilirubinate salts

Question 47

**Acute Calculous Cholecystitis** (most common): 1) Inflammation of the gallbladder containing stones is initially from what? 2) _____% of obstructions happen at gallbladder neck or cystic duct

Answer 47

1) Initially from chemical irritation and inflammation from obstructed bile outflow 2) 90%

Question 48

1) List the symptoms and signs of **Acute Calculous Cholecystitis** (most common): 2) What are they classic Sx? 3) What abt on US?

Answer 48

1) Biliary pain >6 hours RUQ pain with radiation to the right shoulder ↑ conjugated hyperbilirubinemia 2) fever, nausea, leukocytosis 3) Gallstones and thickened gallbladder wall

Question 49

**Acute Calculous Cholecystitis** complications include 3 things: 1) ________ _____________-infection leading to cholangitis or sepsis. 2) Gallbladder __________ and local sepsis. 3) ________ ________ fistula: purpose to empty, but allows air and bacteria into biliary tree.

Answer 49

1) Bacterial superinfection 2) perforation 3) Biliary-enteric

Question 50

**Acute Calculous Cholecystitis** is the most common reason for what?

Answer 50

Cholecystectomy

Question 51

Acute Acalculous Cholecystitis 1) What does it **not** contain? 2) Sx are often obscured by what?

Answer 51

1) Gallstones 2) Comorbid condition

Question 52

Acute Acalculous Cholecystitis 1) Usually seriously ill patient with predisposing factors, such as what? (4) 2) What are some other contributors?

Answer 52

1) Major surgery, Severe trauma, Severe burns, Sepsis 2) Dehydration; Stasis and sludging; Vascular compromise; Bacterial infections

Question 53

Chronic Cholecystitis: 1) May develop as a sequelae of ___________. 2) What may it develop without? 3) Associated with risk of what?

Answer 53

1) acute attacks 2) Any antecedent history of attacks 3) Gallbladder carcinoma

Question 54

1) Most common malignancy of the extrahepatic biliary tract is what? 2) Who is it common in? What is the 5 yr survival? 3) Is it resectable at discovery?

Answer 54

1) Carcinoma of the Gallbladder 2) Women > Men; 5-12% 3) Rarely resectable at discovery

Question 55

List 3 carcinoma of the Gallbladder risk factors that play a role in its development

Answer 55

1) Gallstones (most important)-likely secondary to inflammation 2) Carcinogenic derivatives of bile acids play a role 3) Primary sclerosing cholangitis plays a role.

Question 56

List 5 common congenital pancreatic abnormalities

Answer 56

1) Agenesis 2) Pancreas Divisum (most common) 3) Annular Pancreas 4) Ectopic Pancreas 5) Congenital Cysts

Question 57

1) In what condition is the pancreas totally absent? What is it often (but not always) assoc. with? 2) What is the most common pancreatic congenital abnormality? Define it

Answer 57

1) Pancreas is totally absent; often assoc. w. malformation incompatible w/ life 2) Pancreas Divisum: Malformation of pancreatic ducts

Question 58

1) "A ring of pancreatic tissue completely encircles the duodenum" Describes what? What Sx does it have? 2) What is ectopic pancreatitis? Where is it most common?

Answer 58

1) Annular pancreas; Sx of duodenal obstruction (gastric distention & vomiting, etc) 2) Aberrantly situated, or ectopic, pancreatic tissue located in other parts of GI tract. -MC: stomach and duodenum.

Question 59

1) Congenital Cysts result from anomalous development of what? 2) What do benign cysts contain? Why is this important?

Answer 59

1) The pancreatic ducts. 2) Clear serous fluid; important pt of distinction from pancreatic cystic neoplasms, which often are mucinous

Question 60

What are the two types of pancreatitis? Which is reversible?

Answer 60

1) Acute > reversible parenchymal changes and inflammation 2) Chronic > irreversible parenchymal changes and scar

Question 61

List 3 clinical features of acute pancreatitis

Answer 61

1) Abdominal pain 2) ↑ lipase (72-96 hours) 3) Exclusion of other abdominal pathologies

Question 62

Chronic Pancreatitis: 1) What is the pathogenesis? 2) What are some etiologies?

Answer 62

1) Longstanding inflammation → irreversible destruction of exocrine pancreas → eventual loss of Islets of Langerhans (endocrine function) 2) Duct Obstruction, Tropical pancreatitis (Africa & Asia), Hereditary pancreatitis, Chronic pancreatitis associated with CFTR mutations (seen in cystic fibrosis), Autoimmune pancreatitis (IgG disease), Important: responds to steroids

Question 63

Chronic Pancreatitis: List 4 Clinical Manifestations in chronological order

Answer 63

1) Repeated bouts of jaundice 2) Vague indigestion 3) Persistent or recurrent abdominal and back pain 4) May be entirely silent until pancreatic insufficiency and diabetes mellitus develop (the latter as a consequence of islet destruction)

Question 64

What tumors are typically silent until their extension impinges on some other structure? List their parts and percents

Answer 64

Pancreatic Carcinoma: 1) Head (60%): Obstructive jaundice → blocking distal common bile duct 2) Body (15%) 3) Tail (5%): Usually not detected until late

Question 65

When may there be unusual manifestations of pancreatic carcinoma?

Answer 65

1) Trousseau's syndrome: migratory thrombophlebitis form elaboration of platelet aggregating factors and procoagulants from the tumor 2) New onset DM: may be first manifestation

Question 66

Unpredictable (idiosyncratic) type Drug & Toxin-Induced Liver Injury: **What are 2 examples of causes? What are the outcomes of each?**

Answer 66

1) **Chlorpromazine:** cholestasis in people who are slow metabolizers 2) **Halothane:** fatal immune mediated hepatitis after repeated exposure

Question 67

List 5 potential outcomes of Hepatitis B

Answer 67

1) Acute hepatitis w/ recovery and viral clearance 2) Non-progressive chronic hepatitis 3) Progressive chronic disease w/ cirrhosis 4) Fulminant hepatitis w. massive necrosis 5) Asymptomatic carrier