Lecture 7.2: Liver, Gallbladder, Pancreas Flashcards
This is a remind to review the clip of slide 4 (lobular anatomy)
What are the 4 categories of Mechanisms of Hepatic Injury/ Repair?
1) Reversible change
2) Death
3) Scar
4) Inflammation/ immunologic
Mechanisms of Hepatic Injury/ Repair; give example(s) of:
1) Reversible change (1)
2) Death (2 types, multiple examples)
3) Regeneration (2 types)
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
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?
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
List the 3 types of liver failure
1) Acute
2) Chronic
3) Acute on chronic
Define acute liver failure
Liver disease that produces hepatic encephalopathy <6 months of diagnosis
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.
1) morphologic
2) True; i.e. chronic biliary tract disease
3) True; i.e. tx’d hep C or autoimmune hepatitis
Common Causes of cirrhosis
(this answer is weird)
Stuff happens. . .
(VW)
What is *Acute-on-Chronic Liver Failure & Cirrhosis
Stable, well compensated disease → develop acute liver failure
Symptoms of Liver Failure:
Both acute and chronic can have jaundice and icterus, but which is more likely to have severe jaundice?
Chronic
Acute vs chronic liver failure:
1) Which is more likely to have pruritis? Explain.
2) Which is more likely to have cholestasis?
1) Chronic; seen with other disorders of cholestasis, prob due to ↑ bile salts
2) Acute
List 3 Sx of acute liver failure
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
Chronic liver failure Sxs:
1) Why is Hepatorenal syndrome a Sx?
2) Why is Portal HTN a Sx? (2 reasons)
3) Hepatocellular ____ risk ↑↑↑
1)Systemic vasodilation decreased systemic vascular resistance = ↓ renal perfusion → ↓UOP & ↑BUN/Cr
2) Portico-systemic shunts (i.e. varices)
Congestive splenomegaly
3) CA
Hepatitis A:
1) Route of transmission
2) Incubation period
3) Frequency of chronic liver disease
4) Describe the severity + duration of the infection
1) Fecal-oral (i.e. contaminated food or water)
2) 2-6 weeks
3) Never
4) Usually a benign self –limited infection
Hepatitis B: What is best predictor of chronicity?
Age @ time of infection
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?
1) Parenteral, perinatal, or sexual
2) 2-26 weeks (mean 8 weeks)
3) 5-10%
4) Host response is main determinate
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?
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
Alcoholic Liver Disease is a common cause of what?
Fatty liver disease
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?
1) 80g
2) 5-6 beers
3) 80 proof
4) Binge > steady
Drug & Toxin-Induced Injury: What organ is susceptible because it is the main drug-metabolizing and detoxifying organ?
Liver
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
1) dose-dependent; acetaminophen
2) cytochrome P-450
3) centrilobular
Hemochromatosis:
1) Define it and what organs it effects.
2) What are the 2 forms?
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)
Hemochromatosis clinical features:
1) Who does it affect more?
2) Sx?
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
Hemochromatosis causes Hepatic Injury (after 20 g of stored Fe accumulated) through what 3 mechanisms?
1) Lipid peroxidation
2) Collagen formation after activation of stellate cells
3) DNA damage by ROS
Bilirubin:
1) What is it the end-product of?
2) Where does 85% this come from?
3) Where does the 15% come from?
1) Heme degradation
2) Heme degradation in spleen, liver, and bone marrow by macrophages
3) Turnover of hepatic heme or hemoproteins
Pathophysiology of Jaundice:
What are the 2 types of bilirubin?
1) Conjugated bilirubin (bilirubin glucuronides) and
2) Unconjugated bilirubin
Pathophysiology of Jaundice:
List 4 characteristics of Conjugated Bilirubin
1) Water soluble
2) Non-toxic
3) Loosely bound to albumin
4) Excreted in urine
Pathophysiology of Jaundice: Where is most Unconjugated Bilirubin found?
1) Mostly bound to albumin
-(Unbound fraction)
Pathophysiology of Jaundice: How does unbound fraction increase? (2 ways)
1) Via Hemolytic Disease
2) Via protein binding drugs displace bilirubin from albumin
Pathophysiology of Jaundice: [Unbound fraction] Bilirubin diffuses into tissues and causes toxic injury.; give an example
Hemolytic disease of newborn (erythroblastosis fetalis) causes injury to the brain (kernicterus)
1) Define Cholestasis
2) What are 3 clinical Sx?
1) Impaired excretion of bile
2) Jaundice, Pruritis, Skin Xanthomas
List 2 kinds of Autoimmune Cholangiopathies
1) Primary Biliary Cholangitis
-formerly called “primary biliary cirrhosis”
2) Primary Sclerosing Cholangitis
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?
1) “Primary biliary cirrhosis”
2) non-suppurative; small & medium; intrahepatic
3) Anti-mitochondrial antibodies
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.
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
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 ________________.
1) alk phos
2) Younger men
3) inflammatory bowel; ulcerative colitis
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)
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
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”
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
Aminotransferases will not be found with what type of pathogenesis of Circulatory Disorders of the Liver?
impaired blood flow
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?
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
Hepatocellular Carcinoma (Malignant): list the 4 main causes
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
Hepatocellular Carcinoma (Malignant) morphology
1) Unifocal- large mass
2) Multifocal-widely distributed nodules of variable size
3) Diffusely infiltrative
Hepatocellular Carcinoma (Malignant): characteristics
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
Cholangiosarcoma (Malignant)
Tumor involving intrahepatic or extrahepatic bile ducts
Cholangiosarcoma (Malignant)
1) Risk factors
2) Exposure to ___________ (endemic to southeast asia) causes a 30-40x higher risk
1) Chronic inflammation & cholestasis
Primary sclerosing cholangitis
Hepatolithiasis
Fibropolycystic liver disease
Hep B & C
NAFLD
2) liver flukes
List the 2 types of gallstone disease
1) Cholesterol stones (Western)
2) Pigment Stones (Asian)
Gallstone Disease
1) Cholesterol stones (Western): define supersaturation in this context.
2) Pigment Stones (Asian): Describe how they occur and give examples of causes
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
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
1) Initially from chemical irritation and inflammation from obstructed bile outflow
2) 90%
1) List the symptoms and signs of Acute Calculous Cholecystitis (most common):
2) What are they classic Sx?
3) What abt on US?
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
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.
1) Bacterial superinfection
2) perforation
3) Biliary-enteric
Acute Calculous Cholecystitis is the most common reason for what?
Cholecystectomy
Acute Acalculous Cholecystitis
1) What does it not contain?
2) Sx are often obscured by what?
1) Gallstones
2) Comorbid condition
Acute Acalculous Cholecystitis
1) Usually seriously ill patient with predisposing factors, such as what? (4)
2) What are some other contributors?
1) Major surgery, Severe trauma, Severe burns, Sepsis
2) Dehydration; Stasis and sludging; Vascular compromise; Bacterial infections
Chronic Cholecystitis:
1) May develop as a sequelae of ___________.
2) What may it develop without?
3) Associated with risk of what?
1) acute attacks
2) Any antecedent history of attacks
3) Gallbladder carcinoma
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?
1) Carcinoma of the Gallbladder
2) Women > Men; 5-12%
3) Rarely resectable at discovery
List 3 carcinoma of the Gallbladder risk factors that play a role in its development
1) Gallstones (most important)-likely secondary to inflammation
2) Carcinogenic derivatives of bile acids play a role
3) Primary sclerosing cholangitis plays a role.
List 5 common congenital pancreatic abnormalities
1) Agenesis
2) Pancreas Divisum (most common)
3) Annular Pancreas
4) Ectopic Pancreas
5) Congenital Cysts
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
1) Pancreas is totally absent; often assoc. w. malformation incompatible w/ life
2) Pancreas Divisum: Malformation of pancreatic ducts
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?
1) Annular pancreas; Sx of duodenal obstruction (gastric distention & vomiting, etc)
2) Aberrantly situated, orectopic,pancreatic tissue located in other parts of GI tract.
-MC: stomach and duodenum.
1) Congenital Cysts result from anomalous development of what?
2) What do benign cysts contain? Why is this important?
1) The pancreatic ducts.
2) Clearserousfluid; important pt of distinction from pancreatic cystic neoplasms, which often aremucinous
What are the two types of pancreatitis? Which is reversible?
1) Acute > reversible parenchymal changes and inflammation
2) Chronic > irreversible parenchymal changes and scar
List 3 clinical features of acute pancreatitis
1) Abdominal pain
2) ↑ lipase (72-96 hours)
3) Exclusion of other abdominal pathologies
Chronic Pancreatitis:
1) What is the pathogenesis?
2) What are some etiologies?
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
Chronic Pancreatitis: List 4 Clinical Manifestations in chronological order
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)
What tumors are typically silent until their extension impinges on some other structure? List their parts and percents
Pancreatic Carcinoma:
1) Head (60%): Obstructive jaundice → blocking distal common bile duct
2) Body (15%)
3) Tail (5%): Usually not detected until late
When may there be unusual manifestations of pancreatic carcinoma?
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
Unpredictable (idiosyncratic) type Drug & Toxin-Induced Liver Injury:
What are 2 examples of causes? What are the outcomes of each?
1) Chlorpromazine: cholestasis in people who are slow metabolizers
2) Halothane: fatal immune mediated hepatitis after repeated exposure
List 5 potential outcomes of Hepatitis B
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
