36. Pathogenesis of Cirrhosis/Liver Tumors Flashcards
Review: blood enters the liver via what vessel? exits via what vessel?
What does that mean for possible ischemia?
What about toxins? viral hepatitis?
Blood enters via portal veins (zone 1); exits via central vein (zone 3).
Zone 1: Affected first by viral hepatitis.
Zone 3: affected first by ischemia, toxic injury, alcoholic hepatitis.
What is meant by countercurrent in the liver?
If you were looking for mitotic figures in hepatocytes, where would you look?
Countercurrent: blood moves from portal area to central vein; bile moves from central vein area to bile duct (opposite direction)
Hepatocytes proliferate at the Portal area and mature as they move to central vein area. Mitotic figures (of normal hepatocytes) would be found at Portal triad area.
Arrows are pointing to what?
RBCs in sinusoid areas.
Bile canaliculi are formed from walls of adjacent liver cells.
What’s this?
Features?
EM picture of the inside of a sinusoid, (fenestrated). Works like a sieve becuase the epithelial cells have holes in them.
The liver doesn’t work when it becomes fibrotic and cirrhotic due to loss of these fenestrations.
Note also Space of Disse (marked SD on pic)
The three patterns of inflammation experienced by the liver?
- Portal only (confined to area of portal triad)
- Interface (spilling out from portal triad area)
- Lobular/parenchymal (more diffuse)
The liver generally has the capacity to regenerate, but at what point can it no longer regenerate?
Liver can regeneration after inflammation and after some fibrosis, but once fibrosis progresses to a late stage, it is not reversible.
How does fibrosis occur? what cells are responsible? where are they located?
Activation and proliferation of stellate cells lead to
excessive collagen deposition and liver fibrosis.
Stellate cells located in Space of Disse.
Pic: normally there is very little collagen in Space of Disse. But with fibrosis, stellate cells proliferate and cause fibrogenesis. Kupffer cells also release cytokines that promote collagen growth.
?
Cirrhotic liver.
Scars, nodules.
?
Cholestasis - accumulated bile.
Some regenerative nodules (apparently)??
name the process happening in each pic.
Portal fibrosis -> periportal fibrosis -> bridging fibrosis -> cirrhosis
name 7 etiologies of cirrhosis?
•Viral hepatitis
•Non-Alcoholic steatohepatitis (NASH)
•Alcoholic liver disease
- Biliary diseases
- Primary hemochromatosis
- Wilson disease
- Alpha1-antitrypsin deficiency
(last 4 infinitely more rare than first 3)
What’s this? what will the other organs of the body look like?
Hemochromatosis.
One of the only causes of cirrhosis you can see on gross. (everything else is like roadkill: you can see on the first day what it was, but after 2 weeks it all looks the same)!!!
Liver here described as mahoghany/rusty brown.
Other organs will become brown as well.
With PAS stain the iron shows up blue
Clinical manifestations of liver failure? (very general)
- Jaundice
- hypoalbuminemia –> peripheral edema
- loss of coag factors -> bleeding
- hyperammonia –> encephalopathy
- hyper-estrogen –> palmar erythema, spider angiomas, hypogonad, gynecomastia
The three main ways you can die from cirrhosis?
- Liver failure –> hepatic coma
- Bleeding varices
- Hepatocellular carcinoma
Liver tumors: most of the tumors found in the liver are primary or metastases from somewhere else?
Mostly liver tumors are secondary (ie metastases from elsewhere - frequently from GI tract))
Recognizing that most liver tumors are metastases from somewhere else, there are still some primary liver tumors.
What are the points of origin for liver tumors? name a benign and a malignant version of each type.
Origin = hepatocyte:
Benign = hepatic adenoma, focal nodular hyperplasia
Malignant = hepatocellular carcinoma, hepatoblastoma
Origin = Biliary epithelium:
Benign = Bile duct adenoma
Malig = cholangiocarcinoma
Origin = Mesenchymal
Benign = Hemangioma
Malig = angiosarcoma.
(Bolded tumors got more than 2 slides in the lecture)
Hepatocellular adenoma (aka hepatic adenoma)
Males v females?
associated with use of what meds?
Clinical significance?
Benign
Females > Males
Associated with oral contraceptive use (duration, potency)
Treatment = resection if > 5cm, otherwise leave alone
Main clinical significance: they can be mistaken for Hepatocellular Carcinoma (HCC) or they can rupture and cause hemorrhage.
Hepatoblastoma: benign or malig?
Males v females? age?
associated with what?
Clinical presentation?
Prognosis?
Malignant.
Most occur under 5y old, males predominate.
Associated with congenital anomalies (Beckwith-Wiedemann and Down’s)
Presentation: rapidly enlarging abdominal mass (parent will notice that the diaper doesn’t fit). Usually the kid is acting perfectly healthy otherwise.
Prognisis is very good.
Picture: left = hepatoblastoma. Right = fetal liver in 3rd trimester. Similar cell appearance (ok, whatever)
Hepatocellular Carcinoma (HCC)
Benign or malig? Males v females?
Globally, areas of highest incidence?
Malignant.
HCC accounts for 90% of liver tumors.
Males > females.
Map indicates global incidence (China, Korea, Taiwan, South Africa).
HCC: global incidence is rising or falling? why?
Rising
Due to rising incidence of Hep C (“epidemic”)
HCC Etiology: what are the main causes in the developing world?
What are the main causes in the western world?
Developing world:
Hep B
Aflatoxin (contaminant of grains)
Western world:
Hep C
alcoholic liver disease
NASH
(pic shows etiology in US: mainly Hep C +/- Alcohol)
What does HCC look like?
How much HCC is associated with cirrhosis?
(Pic: cirrhotic liver w cancer foci)
Just some pics of HCC….
90% of HCC occurs alongside cirrhosis.
What’s this?
Fibrolamellar HCC
NOT associated with cirrhosis or chronic liver disease (note healthy liver at upper left side of pic)
More favorable prognosis than HCC that is cirrhosis-related.
Cholangiocarcinoma: where does it originate from?
Benign or malignant?
Frequency?
Characteristics?
Malignant.
Less frequent than HCC
NO relation to cirrhosis (note on pics that surrounding liver tissue is not cirrhotic)
May invade portal vein -> “Hilar”
How can I tell if a tumor is HCC vs Cholangiocarcinoma?
HCC generally occurs in cirrhotic livers. Gross appearance is soft and hemorrhagic. Labs: Alpha-fetoprotein is increased, CEA is normal.
Choleangiocarcinoma generally occurs in otherwise normal livers. Gross appearance is hard and white. Labs: Alpha-fetoprotein is normal, CEA is increased.
(no idea if we need to know labs)
HCC: what is the best treatment?
Why is it difficult?
Transplant is curative.
Problem is finding the HCC early enough: often they are asymptomatic. Therefore we screen people with liver cirrhosis every 6 months for HCC.
Very difficult to resect only the tumor, as patients’ livers are not usually healthy enough to survive the surgery. Need a transplant.
55 yo male presents with abdominal distention, lower extremety edema.
IVdrug use in early eyars, heavy alcohol use.
Obvious ascites, splenomegaly, spider angiomas, palmar erythema.
What kind of cancer is most likely?
HCC.
Suspect HCC until proven otherwise in patients with reason to have cirrhotic liver.
What is alpha-fetoprotein?
Significance?
Alpha-fetoprotein is a glycoprotein that is normally produced during gestation by the fetal liver and yolk sac, the serum concentration of which is often elevated in patients with HCC.
A raised AFP along with a CT or MR that suggests HCC is sufficiency to diagnose HCC.
Cholangiocarcinoma: clinical presentation?
Pruritis
Abdominal pain
Weight loss
Fever
