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DEMS > Adult liver disease - neoplasms, infections and cirrhosis > Flashcards

Adult liver disease - neoplasms, infections and cirrhosis Flashcards

1
Q

What are the three malignant adult liver neoplasms we are to know?

A 
• Hepatocellular carcinoma (HCC)
	• Cholangiocarcinoma
	• Metastatic disease to liver
What is the epidemiology/etiology of HCC?
	• 90% of patients are cirrhotic
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2
Q

What are the gross findings in a case of cholangiocarcinoma?

A
  • Densely fibrotic mass in the hilar region with infiltrative edges
    • Tan-white in color
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3
Q

What are the gross findings in a case of HCC?

A
  • Hepatocellular carcinoma
    • Distinct mass in a cirrhotic liver
    • Invasion of main branch of portal vein or hepatic artery
    • May have green-yellow color (like bile)
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4
Q

What is the epidemiology/etiology of cholangiocarcinoma?

A
  • May be intra or extra hepatic
    • PSC is major risk factor
    • Usually presents at an advanced stage
    • Survival is 25% at one year and 13% at 2 years
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5
Q

What does a biopsy show in a case of HCC (microscopic)

A
  • Thickened hepatic plates
    • Invasion of fibrous tissue/vessels
    • Unpaired arteries
    • No true portal areas
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6
Q

What does a biopsy show in a case of cholangiocarcinoma (microscopic)

A

• Invasive gland forming tumor with abundant desmoplastic response

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7
Q

What are the three benign liver neoplasms we are supposed to know?

A
  • Hemangioma
    • Focal nodular hyperplasia (FNH)
    • Hepatocellular adenoma
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8
Q

What is the epidemiology/etiology of Hepatocellular adenoma?

A
  • Occurs in women of child-bearing age
    • 1:9 male to female ratio
    • Associated with oral contraceptive use
    • Present with RUQ pain, most are asymptomatic
    • Risk of ruptor into abdome with hemorrhage
    • Low risk of malignant transformation
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9
Q

What is the epidemiology/etiology of Focal nodular hyperplasia (FNH)?

A
  • Second most common primary hepatic mass
    • Presumed hyperplastic parenchyma due to vascular anomaly
    • Commonly found in association with hemangiomas
    • More common in women than men 4 to 1
    • Diagnosed in 30s or 40s usually
    • Usually asymptomatic
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10
Q

What is the epidemiology/etiology of Hemangioma?

A
  • Benign neoplasm of dilated vascular spaces
    • Most common primary hepatic tumor
    • Incidence of 2%
    • More common in females 1:4
    • Most common presentation is vague RUQ pain, early satiety, nausea, vomiting
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11
Q

What are the gross characteristics of the benign hemangioma?

A
  • Well circumscribed mass in a non-cirrhotic liver

* Spongy hemorrhagic cut surface with areas of infarction and thrombosis

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12
Q

What are the gross characteristics of the benign hepatocellular adenoma?

A

• Well circumscribed mass in a non-cirrhotic liver
• Soft fleshy cut surface
○ As opposed to spongy in the hemangioma

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13
Q

What are the gross characteristics of the benign focal nodular hyperplasia?

A
  • Central stellate scar

* KNOW THIS PATHOGNOMONIC

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14
Q

What are the microscopic biopsy findings in the setting of benign hemangioma?

A
  • Dilated thin walled vascular spaces
    • Infarction
    • Thrombosis
    • Benign appearing endothelial cells
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15
Q

What are the microscopic biopsy findings in the setting of benign hepatocellular adenoma?

A
  • Proliferation of benign hepatocytes
    • Normal hepatocyte plate thickness
    • Numerous unpaired arteries
    • No bile ducts or portal areas
    • May be difficult to distinguish between adenoma and well differentiated HCC
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16
Q

What are the microscopic biopsy findings in the setting of benign focal nodular hyperplasia?

A
  • Central stellate scar
    • Aberrant malformed vascular structures
    • Ductular reaction
    • No true portal areas
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17
Q

What are the 5 examples of cellular accumulation to keep in mind with liver pathology?

A 
• Fat
		○ steatosis
	• Bile
		○ cholestasis
	• Iron
		○ hemosiderosis
	• Copper
		○ Wilson's disease or cholestasis
	• Viral particles
		○ Viral hepatitis
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18
Q

What are the two types of hepatocyte death, what do they look like and what do they suggest is going on?

A

• Ballooning degeneration and necrosis/apoptosis
• Ballooning
○ Hepatocyte swelling with clumping of hepatocyte organelles and keratin filaments with clearing of cytoplasm
○ Most common in steatohepatitis
• Necrosis/apoptosis
○ Characterized by decreasing cell size with increased eosinophilia of the cytoplasm and a small dark nucleus
○ Often seen in ischemia and chronic viral hepatitis
○ Called acidophils, councilman bodies, or single necrotic hepatocytes
• Wide spread ischemia typically shows confluent zone 3 ischemic necrosis
• Autoimmune hepatitis and viral hepatitis often show acidophils at the interface zone

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19
Q

Though the simple presence of an inflammatory infiltrate is not very specific for a given disease, what are the clues given by the types of inflammation?

A

• Neutrophils - steatohepatitis
• Eosinophils - drug reaction
• Plasma cells - autoimmune hepatitis
• LOCATION
○ In the lobule is a major factor in lobular disarray
○ Portal based - biliary disease
○ Interface inflammation - autoimmune and viral hepatitis
○ Zone 3 - autoimmune hepatitis or acute cellular rejection (transplant)

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20
Q

What kind of hepatocyte death does cholestasis usually result in?

A

• Ballooning degeneration

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21
Q

What is the bile ductular reaction?

A

• Obstructive cholestasis, bile outflow is impaired and there is build up
○ Zone 1
• Hepatocytes undergo metaplasia to become similar to bile duct cells to take care of increased bile
• Result is lots of bile duct-esque structures at the interface zone
• Usually also has edema and neutrophilic inflammation

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22
Q

Where does fibrosis happen?

A
  • Common end result of inflamamtion and injury
    • From the activated stellate cells in the space of Disse depositing collagen
    • Progressive fibrosis leads to cirrhosis
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23
Q

What is acute hepatitis and what are the common etiologies?

A

• New onset of symptomatic disease that has lasted less than 6 months and is associated with laboratory evidence of hepatocyte injury with elevations of AST and ALT
• Common causes
○ Viral
○ Autoimmune
○ Adverse drug reaction
○ Idiopathic
• Usually the liver shows marked lovular disarray and inflammation with numerous single necrotic hepatocytes and cholestasis
• The background architecture of the liver should not contain significant fibrosis
○ Suggestive of more chronic disease

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24
Q

what are the Characteristic Signs of Severe Hepatic Dysfunction

A 
Characteristic Signs of Severe Hepatic Dysfunction
Jaundice and cholestasis
Hypoalbuminemia
Hyperammonemia
Hypoglycemia
Palmar erythema
Spider angiomas
Hypogonadism
Gynecomastia
Weight loss
Muscle wasting
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25
Q

what are the signs of portal hypertension associated with cirrhosis?

A

Portal Hypertension Associated with Cirrhosis
Ascites with or without spontaneous bacterial peritonitis
Splenomegaly
Esophageal varices
Hemorrhoids
Caput medusae—abdominal skin

26
Q

What are the important complications of hepatic failure?

A

Complications of hepatic failure:
Coagulopathy
Hepatic encephalopathy

Hepatorenal syndrome
*Hepatorenal syndrome (HRS) is the development of renal failure in patients with advanced chronic liver disease[1] and, occasionally, fulminant hepatitis, who have portal hypertension and ascites. Estimates indicate that at least 40% of patients with cirrhosis and ascites will develop HRS during the natural history of their disease.

Portopulmonary hypertension
Hepatopulmonary syndrome

27
Q

What tests do you order to investigate hepatocyte integrity?

A

Cytosolic hepatocellular enzymes:
Serum aspartate aminotransferase (AST)
Serum alanine aminotransferase (ALT)
Serum lactate dehydrogenase (LDH)

28
Q

What is chronic hepatitis?

A

• Evidence of injury/inflammation for greater than 6 months
• Common causes
○ Viral hepatitis
○ Autoimmune hepatitis
○ Adverse drug reactions
• Specimens show:
○ Lobular disarray, less prominent inflammation,
○ Rare single necrotic hepatocytes and the slow progression of fibrosis over time
○ Grade in this context = necroinflammatory activity
○ STAGE in this context = degree of fibrosis

29
Q

When worried about biliary execretory function, what labs do you order?

A 
Look at the substances in bile
*Substances secreted in bile †
Serum bilirubin
Total: unconjugated plus conjugated
Direct: conjugated only
Delta: covalently linked to albumin
Urine bilirubin
Serum bile acids
Plasma membrane enzymes † (from damage to bile canaliculi)
Serum alkaline phosphatase
Serum γ-glutamyl transpeptidase
Serum 5′-nucleotidase
30
Q

when worried about hepatocyte function what tests do you order?

A

look at the Proteins secreted into the blood (by hepatocytes)
Serum albumin ‡
Prothrombin time † (factors V, VII, X, prothrombin, fibrinogen)
Hepatocyte metabolism
Serum ammonia †
Aminopyrine breath test (hepatic demethylation)
Galactose elimination (intravenous injection)

31
Q

What are the stages of the Batts-Ludwig grading system?

A
  • Stage 0 - no fibrosis
    • Stage 1 - portal fibrosis
    • Stage 2 - periportal fibrosis
    • Stage 3 - bridging fibrosis
    • Stage 4 - cirrhosis
32
Q

What are the GRADES in the Batts-Ludwig system?

A
  • As opposed to stages
    • Has to do with interface and lobular activity
    • 1 - focal inflammation, no necrosis
    • 2 - focal necrosis with mild inflammation
    • 3 - confluent necrosis without bridging and moderate inflammation
    • 4 - bridging necrosis with severe inflammation
33
Q

What is cirrhosis?

A

• The end stage of any liver disease
• Dx is made pathologcially
• Bridging fibrous septa with distortion of the architecture and regenerative nodules
• Clinical
○ Portal hypertension and poor synthetic function
○ Increased risk for hepatocellular carcinoma

34
Q

What are the important virus specific information to know about the hepatitis virus agents?

A

• B - dsDNA
○ All the others are ssRNA
• A - fecal oral route, contaminated food or water
• E - fecal oral route
• A - NEVER causes chronic liver disease
• C- 80% of the time causes chronic liver disease
• B - 10% of time causes chronic liver disease
• E - NEVER causes chronic liver disease

35
Q

Which two hepatitis viruses are essentially the same?

A

• E and A. fecal oral route, both are ssRNA viruses and both are tested by looking for IgM and igG antibodies

36
Q

What’s up with HBV?

A

Hepatitis B virus
• Only DNA virus of the hepatotropic viruses
• Can integrate into host genome
• Blood and body fluids transmission
• Look for ground glass hepatocytes and sanded nuclei
○ Viral particles within hepatocytes

37
Q

What’s up with HCV?

A

• Hepatitis C virus
• Increasing problem - 80% of exposed develop chronic liver disease
• Transmission is via blood and body fluids (parenteral)
• Look for ongoing infection with PCR
• Rarely present as acute hepatitis
• Non-specific histology
○ Nodular aggregates of lymphocytes in portal areas are a common finding

38
Q

What’s up with autoimmune hepatitis?

A

• Hepatic inflammation and damage usually associated with prominent plasma cells on histology
• Often presents with acute flare
• Then settles into a chronic hepatitis
• 78% of patients are females
• Increased AST and ALT with normal ALP
• Usually at least one positive autoantibody in serum (80% of cases)
○ ANA, ASMA, anti-LKMB
• Treatment = steroids
• Disease is active, histology shows ongoing interface and centrolobular necroinflammatory stuff with zones of confluent hepatocyte necrosis and a prominent plasma cell component

39
Q

What is PBC?

A

• Primary biliary cirrhosis = PBC
• Autoimmune disease primarily involving the intrahepatic bile ducts with inflammatory bile duct destruction
• Usually insidious presentation pruritus before jaundice
• Again, heavily female with 85% of cases
• Liver tests
○ Elevated ALP, GGT, bilirubin
○ Normal AST and ALT (or barely elevated)
○ Positive AMA antibody test 90% and elevated IgM

40
Q

What are the histological signs of PBC?

A

• PBC = primary biliary cholangitis
• Acute or chronic changes can be seen
• Acute - lymphohistiocytic and plasma cell rich inflammation of the portal areas with active lymphocytic cholangitis and bile duct destruction
○ These go together to form a “florid duct lesion”
• Chronic - bile duct loss and ductular reaction and periportal copper accumulation
• Fibrosis will begin to develop in the periportal regions with eventual bridging fibrosis and cirrhosis

41
Q

What is primary sclerosing cholangitis?

A

• PSC is an idiopathic disease characterized by patchy inflammation and eventual obliterative fibrosis of the bile ducts
• Usually affects the extrahepatic bile ducts but may also involve intrahepatic ducts
• Common presentation:
○ Persistently elevated alkaline phosphatase and no other signs/symptoms
○ Over time, as the disease progresses patients experience increasing fatigue, pruritus, jaundice
• Strong association with IBD and UC more than crohns
• Huge increase in cholangiocarcinoma risk
• Increased ALP, GGT and bilirubin

42
Q

How do you diagnose PSC?

A

• Other liver diseases are clinicopathologic correlation, but PSC is clinicoradiologic correlation
○ Endocopic or MR scanning
○ ERCP or MRCP
• Cholangiography shows beading of the extra and intra hepatic bile ducts with multiple biliary strictures alternating with areas of dilation (string of pearls)
• Histologic
○ Lymphocytic periductular inflammation around the larger bile ducts with progressive fibrosis
○ Peri-ductular fibrosis is concentric around the ducts creating an onion skin pattern
○ “onion skin fibrosis”

43
Q

What is secondary sclerosing cholangitis?

A

• Several disease processes can increase the risk
○ Cholelithiasis, biliary atresia, choledochal cysts, and cystic fibrosis
• These other processes RESULT in sclerosis/fibrosis of the biliary tree
• End stage, both primary and secondary sclerosing diseases can be indistinguishable

44
Q

What has to happen to make you think “drug induced liver disease”?

A

• Wide variety of drugs have been reported to cause liver injury and elevated liver function testing
• Of all adverse drug reactions - 10% affect liver (which is high or low depending on how you think about it)
• Presentations VARY, so it should ALWAYS be on your differential
• Histologic changes may show necrosis, cholestasis, biliary injury, autoimmune-like hepatitis, acute hepatitis or chronic hepatitis
• MOST COMMON - acetaminophen is most common cause
○ Represents a large proportion of cases of acute liver failure leading to liver transplant in US
○ Causes confluent coagulative necrosis beginning in zone 3 (centrolobular)
○ Dose dependent progression to pan-lobular necrosis

45
Q

What are the four metabolic liver diseases in adults you need to know by sight and sound?

A
  • Steatosis/steatohepatitis
    • Hereditary hemochromatosis (AR)
    • Wilson’s disease (AR)
    • Alpha-1-antitrypsin deficiency (AR)
46
Q

What is the histologic triad of steatohepatitis?

A

• Steatosis, lobular inflammation and hepatocyte ballooning degeneration
○ Unfortunately these histologic changes are non-specific and are seen in many conditions

47
Q

Describe the two different clinical subtypes of steatohepatitis

A

• Alcohol -
○ Clinical history of alcohol exposure and the histologic triad on liver biopsy (dx criteria)
○ Lab - AST:ALT ratio greater than 2, and normal ALP with increased GGT
○ IHC /Histology- mallory hyaline and lots of neutrophils in the infiltrate
• NASH
○ Common picture in obesity, diabetes, hypertriglyceridemia and adverse drug reaction
○ Increasing prevalence of this disease with increasing obesity

48
Q

What’s up with steatohepatitis?

A

• Remember the histological triad, and match that to an alcoholic clinical picture
○ Steatosis, lobular inflammation and hepatocyte ballooning degeneration
• Clinically separated into alcoholic and non-alcoholic forms
○ ASH and NASH
• NASH is usually seen in patients with diabetes, metabolic syndrome, obesity, or adverse drug reaction
• END RESULT - hepatic fibrosis over time and a 20% risk of cirrhosis
• Fibrosis begins in the centrolobular region (3) and shows a prominent sinusoidal pattern (chicken wire)
• Cirrhosis pattern = micronodular pattern secondary to fine sinusoidal fibrosis

49
Q

What is HH in the context of liver disease?

A
  • HH - hereditary hemochromatosis
    • C282Y and H63D mutations
    • Autosomal recessive inheritance pattern
    • Symptoms manifest in males more than females who don’t handle the iron overload as well
    • Main problem = iron overload from messed up iron absorption pathway, eventual deposition of iron in tissues (liver) leading to oxidation and cell death
    • Iron absorption is in small intestine
50
Q

How can you differentiate secondary from primary hemosiderosis?

A
  • Secondary comes from excessive ingestion, repeated transfusions, hemolysis and underlying liver disease
    • Secondary causes lead to iron deposition in Kupffer cells more than hepatocytes
51
Q

What are the histologic features of HH?

A
  • Progressive iron depositions within the cytoplasm of hepatocytes
    • Begins in periportal region first
    • Iron acts an an oxidant and results in hepatocyte injury and fibrosis
    • Dx is primarily genetic testing for mutations that cause the disease
52
Q

What is the inheritance pattern of HH?

A
  • Autosomal recessive inheritance pattern
    • C282Y and H63D mutations
    • Symptoms manifest in males more than females who don’t handle the iron overload as well
53
Q

What are the clinical and histological features of wilson’s disease?

A
  • Main problem is too much copper
    • See the particular Kayser-fleischer rings on ophthalmologic examination
    • See patchy copper accumulation in hepatocytes on histology
    • Rest of parenchyma shows steatosis and acute/chronic hepatitis changes
54
Q

What is wilson’s disease?

A
  • AR disease b/c of mutations in ATP7B gene on chromosome 13
    • Copper transport protein that is involved in the biliary excretion of copper
    • Lots of different mutations have been described so it’s not just one exon and one point mutation, it’s many places along that gene
55
Q

What is the inheritance pattern of wilson’s disease?

A

• AR disease b/c of mutations in ATP7B gene on chromosome 13

56
Q

What’s up with alpha-1-antitrypsin?

A

• If there is a mutation in this gene the resulting disease has liver, pancreas and lung manifestations
• Characterized by decreased production of a protease inhibitor
• AR inheritance pattern
• Protease inhibitor usually keeps the secretions of neutrophils in check and limits tissue damage
• Nomenclature -
○ PiMM - normal
○ PiMZ - heterozygote/carrier
○ PiZZ - homozygous and disease phenotype
• Lab - levels less than 10% of normal
• Pulmonary emphysema is primary clinical manifestation and 10% patients have liver disease
• Histologic features - intracytoplasmic accumulation of PAS positive, diastase resistant hyaline globules with progressive fibrosis
○ Represent abnormally folded A1A

57
Q

What are the important causes of bad hepatic blood flow?

A

• Very acute hepatic artery thrombosis can cause ischemic infarcts
○ But since there is dual artery supply, this is rare
• Portal vein thrombosis is an important cause of non-cirrhotic portal hypertension
○ 50% of cases are idiopathic
○ Shows prominent congestion of the sinusoids with associated hepatocyte atrophy

58
Q

What can a problem in hepatic blood flow look like in the liver?

A

• Shows marked centrolobular sinusoidal dilation, congestion, and hemorrhage
• Grossly - enlarged and tense liver
• Budd - Chiari syndrome
○ Liver enlargement
○ Pain
○ Ascites
○ Main hepatic vein occlusion is the cause
• End result
○ Subsinusoidal fibrosis and cirrhosis if not corrected
○ Heart failure patients - “cardiac sclerosis”

59
Q

What laboratory evidence points to cholestasis?

A

A characteristic laboratory finding (in cholestasis) is elevated serum alkaline phosphatase, an enzyme present in bile duct epithelium and in the canalicular membrane of hepatocytes.

  • (why it isn’t especially specific) A different alkaline phosphatase isozyme normally is expressed in many other tissues such as bone, and so hepatic origin must be verified.
  • Reduced bile flow also causes intestinal malabsorption including inadequate absorption of the fat-soluble vitamins A, D, and K.
60
Q

What might a changed INR indicate?

A

Since some of the clotting factors produced by the liver have half lives in hours, that is used to indicate acute liver injury
*albumin is more of a chronic liver injury marker

61
Q

Alk phos elevation is specific or not?

A

Not super specific, you need to make sure it’s coming from the liver itself.
*can use GGT to correlate and make sure liver origin for alk phos

62
Q

Alk phos elevation is specific or not?

A

Not super specific, you need to make sure it’s coming from the liver itself.
*can use GGT to correlate and make sure liver origin for alk phos

DEMS (30 decks)

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