Hepatobiliary and Pancreatic Pathology

Describe the Lobular Model of Liver Anatomy

-hexagonal

-terminal hepatic vein at the center

-portal tracts at the periphery

Describe the Acinus Model of Liver Anatomy

3 defined zones

-zone 1 --> closet to the blood supply

-zone 2--> furtherest from the blood supply

What are the clinical syndromes of the liver?

-hepatic failure

-cholestasis & jaundice

-cirrohis

-portal hypertension

what is the most severe form of liver disease?

liver failure (hepatic failure)

chronic liver disease

widespread necrosis from severe damage of hepatocytes caused by years of progressive liver injury

• most common cause of liver failure

• associated with fibrosis/cirrhosis

What is the most common cause of liver failure?

chronic liver disease

acute liver disease

less common form of liver disease but more deadly (80% mortality)

*leads to organ failure, respiratory distress syndrome, acute renal failure, & cirrhosis

What can acute liver disease lead to?

-organ failure

-respiratory distress syndrome

-acute renal failure

-cirrhosis

How much of the functional capacity of the liver most be lost for the liver disease to be considered liver failure?

80-90%

Chronic Liver Failure

diffuse remodeling into parenchymal nodules surrounded by fibrous bands & vascular shunting ==> most often associated with advanced fibrosis/cirrhosis

*Leading causes:

-chronic Hep B

-chronic Hep C

-nonalcoholic fatty liver disease (NAFD)

-alcoholic liver disease

Which clinical syndrome of the liver is most often associated with advanced fibrosis/cirrhosis?

chronic liver failure

What are the leading causes of chronic liver failure?

-chronic Hep B

-chronic Hep C

-Nonalcoholic fatty liver disease (NAFLD)

-alcoholic liver disease

acute liver failure

liver disease that is usually associated with massive heaptic necrosis

-50% of adult cases in the US are from ingestion of acetaminophen

-autoimmune hepatitis, other drugs/toxins, & acute hep A and B infections account for most of the remaining cases

How does acute hepatic failure appear clinically?

1st manifests with nausea, vomiting, & jaundice --> then encephalopathy & coagulation defects + initial swelling as parenchyma is destroyed the liver shrinks -->>> multisystem organ failure occurs --> patients dies (if no liver transplant)

how does chronic hepatic failure appear clinically?

-asymptomatic until advanced stages

-nonspecific symptoms --> anorexia, wt loss, weakness

-displays signs similar to acute failure --> encephalopathy, coagulopathy, & jaundice

bilirubin

toxic end product of heme degradation that is processed by the liver & excreted in bile

cholestasis

retention of bilirubin in response to injured or dysfunctional hepatocytes

-potentially reversible

-may manifest as jaundice & icterus**

What may cholestasis manifest as?

-jaundice --> yellow discoloration of the skin

-icterus --> yellow discoloration of the sclera of the eye

*due to retention of bilirubin

What are the normal adult serum bilirubin levels?

0.3 - 1.2 mg/dL

At what range of serum bilirubin levels does jaundice become evident?

2 - 2.5 mg/dL

How does jaundice appear?

yellow discoloration of the skin due to excess bilirubin accumulation

icterus

yellow discoloration of the sclera of the eye due to excess bilirubin accumulation

hyperbilirubinemia

unconjugated or conjugated bilirubin in the blood (jaundice)

*causes of unconjugated

-excess production due to hemolytic anemia (RBC destruction) --> most common cause

-excess production due to ineffective erythropoiesis (RBC production)

-defective conjugation (due to immaturity or hereditary cause)

*causes of conjugated

-obstruction of bile flow or bile duct injury--> tumor, stricture, gallstones in bile ducts

-hepatocellular disease--> viral or drug-induced hepatitis , cirrhosis

What is the most common cause of unconjugated hyperbilirubinemia (jaundice)?

excess production due to hemolytic anemia (RBC destruction)

What causes unconjugated hyperbilirubinemia (jaundice)?

-excess production due to hemolytic anemia (RBC destruction) --> most common cause

-excess production due to ineffective erythropoiesis (RBC production)

-defective conjugation (due to immaturity or hereditary cause)

kernicterus

brain damage due to excess bilirubin in tissues

what causes conjugated hyperbilirubinemia?

-obstruction of bile flow or bile duct injury

>tumor

>stricture

>gallstones in bile ducts

-hepatocellular disease

>viral induced hepatitis or cirrhosis

>drug induced hepatitis or cirrhosis

cirrhosis

diffuse fibrosis/scarring of the liver==> remodeling of the liver into nodules surrounded by fibrous bands

*due to hepatocellular injury

-chronic hep B or hep C

-alcoholic or non-alcoholic steatohepatitis (fatty liver disease)

-autoimmune disease

- iron overload

*associated w/ liver failure but isn't the same thing--> not all cirrhosis leads to liver failure & not all end stage liver disease is cirrhotic

*cirrhosis is not a specific diagnosis --> has varying prognostic implications

what causes cirrhosis?

due to hepatocellular injury

-chronic hep B or hep C

-alcoholic or non-alcoholic steatohepatitis (fatty liver disease)

-autoimmune disease

- iron overload

True or False: Not all cirrhosis leads to liver failure, but all end stage liver disease is cirrhotic.

False ==> not all cirrhosis leads to liver failure & not all end stage liver disease is cirrhotic

True or False: Cirrhosis has varying prognostic implications.

True ==> b/c cirrhosis isn't a specific diagnosis

What is the gross presentation of micronodular cirrhosis?

What is the histopathological presentation of micronodular cirrhosis?

What is the histopatholgical presentation of alcoholic cirrhosis?

*thick bands of collagen separate rounded cirrhotic nodules

What is the gross presentation of macronodular cirrhosis?

What is the histopathological presentation of macronodular cirrhosis?

What is the gross presentation of alcoholic cirrhosis?

enlarged liver with nodule formation

hemochromatosis

excessive iron absorption that gets deposited in organs (mostly in liver & pancreas)

-most often due to an autosomal recessive hereditary disorder of HFE gene*

-usually manifests after accumulation of 20g of stored iron*

When does hemochromatosis usually manifest?

after accumulation of 20g of stored iron

Which gene is usually mutated in hereditary hemochromatosis?

HFE gene

What is the normal iron storage range?

300mg - 2g

(300 mg in menstruating female)

Which organs are affected the most by hematochromatosis?

-liver

-pancreas

How is the lover effected by hemochromatosis?

-turns rusty brown color

-increased risk of hepatocellular carcinoma

hemosiderosis

iron overload due to any cause other than excessive absorption==> secondary hemochromatosis

*ex: can be caused by frequent transfusions or dietary overconsumption

How does hereditary hemochromatosis present histologically?

wilson disease

inadequate hepatic excretion of copper that causes copper accumulation in the liver, brain, & eyes due to mutation of ATP7B gene (autosomal recessive)

-kayser-fleischer rings --> deposition of copper in cornea

-causes cirrhosis & degenerative changes in brain--> tremor, poor coordination, gait distrubances, psychiatric symptoms

-diagnosed via decreased serum ceruloplasmin

What gene is mutated in wilson's disease?

ATP7B (autosomal recessive mutation)

Kayser-Fleischer Rings

pathognomonic deposition of copper in cornea seen in wilson's disease

How does wilson's disease affect the liver?

copper accumulation causes cirrhosis

How does wilson's disease affect the brain?

degenerative changes

-tremor

-poor coordination

-gait disturbances

-psychiatric symptoms

how is wilson's disease diagnosed?

decreased serum ceruloplasmin ==> protein that copper is normally bound to for transport to the body

acute hepatitis

necrosis & inflammation of liver cells that's most often due to viral infections or toxins

chronic hepatitis

continued liver inflammation for more than 6 months

*may lead to fibrosis

hepatotrophic viruses

viruses that have an affinity for the liver

-Hep A

-HepB

-Hep C

-Hep D

-Hep E

Non-hepatotrophic infections/viruses that cause hepatitis

-Epstein-barr virus

-cytomegalovirus

-herpes simplex virus

-yellow fever

-autoimmune hepatitis

What kind of hepatitis does Hep A virus cause?

acute hepatitis

What kind of hepatitis does Hep E virus cause?

acute hepatitis

True or False: Hep B causes chronic hepatitis

True

True or False: Hep C causes acute hepatitis

False ==> causes chronic hepatitis

What kind of hepatitis does Hep D virus cause?

chronic hepatitis

What is special about Hep D virus?

it requires hep B co-infection

Which hepatitis viruses put patients at increased risk for hepatocellular carcinoma?

-Hep B

-Hep C

True or False: Autoimmune hepatitis is more common in females

True ==> 2:1 females predilection

True or False: Autoimmune hepatitis is often present with other autoimmune disorders

True ==> other autoimmune diseases in up to 60% of patients

True or False: Autoimmune hepatitis is concurrent with viral hepatitis infections

False ==> autoimmune hepatitis is absent of viral hepatitis

What causes alcoholic fatty liver?

alcoholism

What are some causes of nonalcoholic fatty liver disease (NAFLD)?

-obesity

-type 2 diabetes

-hypertension

-dyslipidemia

Alcoholic liver disease causes __________% of cirrhosis in the US

50%

hepatic steatosis

fatty liver; increased fat in the liver

True or False: Short-term ingestion of as little as 80g of alcohol over several days produces mild, reversible, hepatic steatosis.

True

The risk of severe liver injury becomes significant with intake greater than __________________ g/day

80 g/day

True or False: Daily ingestion of 160g or more for 10-20 years is frequently associated with liver injury

True

Why do only 10-15% of alcoholics develop cirrhosis?

factors other than alcoholism influence development & severity

-gender

-genetics

-comorbid conditions

Is alcoholic liver disease more common on men or women?

men

Are men or women more susceptible to alcoholic liver disease?

women

-metabolize alcohol differently

-estrogen makes the gut more permeable to toxins

Why are women more susceptible to alcoholic liver disease?

-metabolize alcohol differently

-estrogen makes the gut more permeable to toxins

What ethnic population experiences higher rates of cirrhosis due to alcoholism?

African Americans have higher cirrhosis rates than caucasians despite similar alcohol consumption

*suggests genetic component in alcohol induced liver disease ==> genetic variation in alcohol detoxifying enzymes may play a role in different populations

Despite similar alcohol consumption, different ethnic groups have varying rates of alcohol induced liver disease. Why?

genetic variation in alcohol detoxifying enzymes may play a role in different populations

What are some comorbidities associated with alcoholic liver disease?

-HCV

-HBV

-iron overload

*may synergize with alcohol & increase disease severity

True or False: Hepatic steatosis is irreversible

False ==> reversible --> adequate diet & no alcohol intake is sufficient treatment

True or False: Alcoholic hepatitis appears acutely after a bout of heavy drinking

True

What are common symptoms of alcoholic hepatitis?

-fever & malaise

-anorexia/weight loss

-hepatomegaly

-jaundice

True or False: The outlook of alcoholic hepatitis is unpredictable

True ==> each episode carries a 10-20% risk of death

What percent of patients with alcoholic liver disease induced cirrhosis develops carcinoma?

10-20%

What do patients with alcoholic liver disease induced cirrhosis usually die from?

-hepatocellular carcinoma

-hepatorenal syndrome

-hemorrhage

-hepatic failure

What is the gross presentation of hepatic steatosis?

yellow, greasy, enlarged liver ==> fatty vacuoles displace hepatocellular nuclei peripherally

What are the main characteristics of alcoholic hepatitis?

-swelling and necrosis of hepatocytes

-acute inflammation

-cholestasis

-early fibrosis

What is the histological presentation of hepatic steatosis?

What is the most common primary liver cancer?

hepatocellular carcinoma (hepatoma)

-associated w/ infection, hepatitis, cirrhosis, hemochromatosis, & AAT deficiency

-symptoms--> ab pain, swelling, weight loss, weakness, jaundice, fever, loss of apeptite

-propensity for vascular invasion (inclination to invade vascular system)

-death due to hemorrhage and liver failure

-may be cured by liver transplant

What is hepatocellular carcinoma (hepatoma) associated with?

-infection

-hepatitis

-cirrhosis

-hemochromatosis

-AAT deficiency

What are the symptoms of hepatocellular carcinoma (hepatoma)?

-abdominal pain

-swelling

-weight loss

-weakness

-jaundice

-fever

-loss of appetite

True or False: Hepatocellular carcinoma has a propensity for vascular invasion.

True

What do patients with hepatocellular carcinoma typically die of?

-hemorrhage

-liver failure

What is the 5 year survival rate of hepatocellular carcinoma?

16%

*only 3% if distant metastasis

what is the the median survival of hepatocellular carcinoma without resection (surgical removal)?

7 months

True or False: Transplants are unable to cure hepatocellular carcinomas.

False ==> transplant may be curative

hepatoblastoma

rare malignancy of the liver that usually occurs in children under 3yrs old

angiosarcoma

malignancy in liver often due to exposure to vinyl chloride or arsenic

What is the most common malignant tumor of the liver?

metastatic carcinoma ==> most commonly from the lung, colon, breast, or pancreas

What is the function of the gallbladder

reservoir for bile made in liver

-stores 30-50ml

-fills passively

-contracts at mealtime