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Yr 3 - December lectures 2018 > Pathology of the liver > Flashcards

Pathology of the liver Flashcards

1
Q

What is the relevance of doing a liver biopsy?

A

establish primary diagnosis

- provide additional info in cases where a primary diagnosis has already been established by other investigations

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2
Q

What does it mean by sampling variability of liver biopsies?

A

average needle biopsy samples a tiny fraction of the whole liver
however lesions affecting liver diffusely can still be reliably assessed
this could be an issue if the disease had uneven distribution (e.g. fibrosis in chronic cholestatic disease)
problems can occur with inversely proportional to the length and diameter of the biopsy specimen

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3
Q

Why are liver biopsies so useful?

A

most common patterns of liver damage have more than one potential cause
therefore final interpretation depends on clinics-pathological correlation

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4
Q

What are the different zones of the liver?

A

Zone 1: periportal
Zone 2: mid-zonal
Zone 3: perivenular or centrilobular = furthest away from portal blood supply, high conc of p450 enzymes

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5
Q

What are the different causative agents of viral hepatitis?

A

A-G

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6
Q

What is the causative agent, incubation period and route of transmission for hepatitis A?

A

RNA virus (picornavirus) 27nm diameter
15-40 days
faecal-oral route

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7
Q

What is the causative agent, incubation period and route of transmission for hepatitis B?

A 
DNA virus (hepadnavirus) 42nm diameter
4-26 weeks
- mainly blood/bloody products
- other body secretions 
- vertical tranmission (mother to baby)
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8
Q

What is the causative agent, incubation period and route of transmission for hepatitis C?

A 
RNA virus (flavivirus) 30-40nm diameter 
2-26 weeks 
- mainly blood / blood products 
- other body fluids 
- sporadic infection
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9
Q

What are the outcomes for the following things in terms of hepatitis A infection?

  • asymptomatic carrier
  • acute hepatitis
  • fulminant hepatitis
  • chronic hepatitis
  • cirrhosis
  • hepatocellular carcinoma
A
  • asymptomatic carrier = no
  • acute hepatitis = Yes
  • fulminant hepatitis = very rare
  • chronic hepatitis = no
  • cirrhosis = no
  • hepatocellular carcinoma = no
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10
Q

What are the outcomes for the following things in terms of hepatitis B infection?

  • asymptomatic carrier
  • acute hepatitis
  • fulminant hepatitis
  • chronic hepatitis
  • cirrhosis
  • hepatocellular carcinoma
A
  • asymptomatic carrier = yes
  • acute hepatitis = yes
  • fulminant hepatitis = rare
  • chronic hepatitis yes (5-10%)
  • cirrhosis = yes
  • hepatocellular carcinoma = yes
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11
Q

What are the outcomes for the following things in terms of hepatitis C infection?

  • asymptomatic carrier
  • acute hepatitis
  • fulminant hepatitis
  • chronic hepatitis
  • cirrhosis
  • hepatocellular carcinoma
A
  • asymptomatic carrier = yes
  • acute hepatitis = yes
  • fulminant hepatitis = very rare
  • chronic hepatitis = yes >70%
  • cirrhosis = yes
  • hepatocellular carcinoma = yes
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12
Q

What histopathological features are common in acute hepatitis?

A

spotty inflammation and lobular disarray
acidophil body
in severe cases = panacinar necrosis

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13
Q

What are the features of hepatitis D?

A

defective RNA virus
can only be replicated when encapsulated by hep B surface antigens
increases severity of HBV

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14
Q

What are the features of hepatitis E?

A 
RNA virus - 32-34 diameter 
transmitted by water-borne route 
acute self-limiting illness
high mortality in pregnant women
can cause chronic liver disease in immunocompromised pts
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15
Q

What are the features of hepatitis F?

A

no definite viral agent found yet

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16
Q

What are the features of hepatitis G?

A

RNA virus (flavivirus)
transmitted via blood
associated with acute and chronic hepatitis
BUT pathogenetic role in liver disease uncertain

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17
Q

What is the definition of chronic hepatitis?

A

inflammation of the liver continuing without improvement for at least 6 months
HOWEVER
- most chronic liver disease has an inflammatory component that persists for >6 months
therefore term is restricted to number of diseases

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18
Q

What are the causes of chronic hepatitis?

A

viral - hep B, C, D
autoimmune (types 1-3)
Biliary - primary biliary cholangitis or primary sclerosing cholangitis
metabolic - alpha-1 -antitrypsin deficiency, wilson’s disease
fatty liver disease - alcoholic or non-alcoholic
drugs - methyldopa, isoniazid, nitrofurantoin
unknown

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19
Q

How is chronic hepatitis classified?

A

Etiology
necroinflammatory activity (grade)
fibrosis (stage)

20
Q

What is portal/periportal inflammation: interface hepatitis?

A

inflammation at the interface between connective tissue (portal tract, fibrous septa) and the liver parenchyma

21
Q

What are the causes of fatty liver disease?

A

alcohol
- commonest cause of cirrhosis in UK - increasing

non-alcoholic

  • now commonest cause of newly diagnosed chronic liver disease
  • only 6% deaths in patients with NAFLD are from liver disease
22
Q

What are the histological features of steatohepatitis?

A 
hepatocellular injury
- fatty change 
- ballooning 
- mallory-dene bodies
- apoptosis/necrosis 
inflammation 
- neutrophil polymorphs 
- other cells 
fibrosis 
- perisinusoidal 
- pericellular
23
Q

What are examples of chronic (autoimmune) biliary disease?

A

primary biliary cholangitis
primary sclerosing cholangitis
overlap syndromes (pbc/psc/autoimmune hepatitis)

24
Q

What are the clinical features of primary biliary cholangitis?

A 
peak incidence 40-60 
F:M = 9/10:1
Signs/symptoms:
- pruritus, lethargy, jaundice, diarrhea, bone symptoms, portal hypertension, liver failure (late)
biochem
- elevated ALP and bile acids
- bilirubin increases later 
immunology 
- AMA (anti-mitochondrial ab)
- raised IgM 
associated conditions 
- sjorgen's syndrome, RA, autoimmune thyroiditis, coeliac disease 
prognosis = progressive liver disease, with survival of 5-10 years
25
Q

What are the histological features of PBC?

A

stage 1: inflammatory (granulomatous) bile duct destruction
stage 2: periportal (interface) hepatitis / bile ductular reaction
stage 3: periportal fibrosis
stage 4: cirrhosis
lots of overlap between stages
fibrosis unevenly distributed within the liver

26
Q

What are the clinical features of primary sclerosing cholangitis?

A 
any age, peak incidence 20-50 
F:M = 2/3:1
Signs/symptoms 
- progressive/intermittent jaundice, recurrent acute cholangitis
biochem 
- raised ALP and bilirubin 
immunology 
- HLA-B8 and DR3 phenotype
- hypergammaglobinaemia 
- anti-neutrophil abs 
radiology 
- cholangiography - strictures and beading 
associated conditions 
- IBD (mainly UC (60-70%))
- retroperitoneal fibrosis, mediastinal fibrosis 
prognosis 
- most develop progressive disease 
- survival 5-15 years 
- cholangiocarcinoma in up to 20%
27
Q

What are the histological features of PSC?

A

1) small ducts - usually disappear without trace
2) medium sized ducts - periductal inflammation/fibrosis, nodular scars
3) large intrahepatic ducts = inflammation, ulceration, dilatation (cholangiectasia)
4) extraheptaic ducts = inflammation, ulceration, fibrosis

28
Q

What is the definition of cirrhosis?

A

irreversible condition affecting the whole liver, characterized by:
- loss of normal lobular architecture
- nodular regeneration
- fibrosis
(fibrosis and early cirrhosis may be reversible)

29
Q

How is cirrhosis classified?

A

micro nodular
macro nodular
mixed

30
Q

What are the common causes of cirrhosis ?

A

fatty liver disease - alcoholic or non-alcoholic

viral - hepatitis B, C (rarely E)

31
Q

What are the less common causes of cirrhosis?

A

biliary - PBC, PSC, secondary biliary cirrhosis
metabolic - alpha -1 antitrypsin deficiency, cystic fibrosis, wilson’s disease, hemochromatosis
Vascular - chronic venous congestion
Drugs - methotrexate, isoniazid
autoimmune - autoimmune hepatitis

32
Q

What are the complications of cirrhosis ?

A

hepatocellular failure
portal hypertension
hepatocellular carcinoma - 10-15%

33
Q

What are the common features of hepatocellular failure?

A

jaundice
hypoalbuminaemia - edema and ascites
bleeding tendency - reduced synthesis of clotting factors (II, VII, IX, X)
neurological disturbances - hepatic encephalopathy
endocrine disturbances - gynaecomastia, testicular atrophy, palmar erythema, spider nave
renal failure - hepatorenal syndrome
spontaneous infections
pulmonary arteriovenous shunting and hypertension

34
Q

What are the effects of portal hypertension?

A

ascites
portosystemic shunts - lower oesophagus, rectum, umbilicus, retroperitoneum, varies, hemorrhoids, caput medusae
splenomegaly

35
Q

What should you always consider as a differential diagnosis for liver disease?

A

drug induced - most commonly used drugs are hepatotoxic

can take sometime to present clinical following drug admin

36
Q

What are the histological features of drug induced liver damage?

A

fatty change - macro vesicular or micro vesicular (corticosteroids, alcohol)

cholestasis - oral contraceptive

zonal necrosis - paracetamol

granulomas - phenylbutazone

hepatitis - methyldopa, isoniazid, halothane

cirrhosis - methotrexate

vascular problems - azathioprine

hepatic neoplasms - contraceptive, anabolic steroids, vinyl chloride monomer

37
Q

How can hepatic neoplasms be divided?

A

benign

malignant - primary and secondary

38
Q

What are examples of benign primary liver tumors?

A 
epithelial 
- hepatocelular adenoma 
- bile duct adenoma 
mesenchyme 
- hemangioma 
- angiomyolipoma 
tumor like lesions 
- cysts
- focal nodular hyperplasia 
- nodular regenerative hyperplasia 
- mesenchymal harmartoma 
- inflammatory pseudotumour
39
Q

What are examples of malignant primary liver tumors?

A

hepatocellular carcinoma
hepatoblastoma
cholangiocarcinoma
bile duct cystadenomcarcinoma

angiosarcoma
epithelia hamangioendothelioma
embryonal sarcoma

40
Q

What is hepatocellular adenoma?

A

benign tumor - hepatocyte origin
affects more women
hormonal factors - oral contraceptive
highly vascular - risk of hemorrhage

41
Q

What is bile duct adenoma?

A

usually small and asymptomatic, probably not a true neoplasm

42
Q

What are haemargioma?

A

affects blood vessels
usually asymptomatic
may be hamartoma rather than true neoplasm

43
Q

What are focal nodular hyperplasia?

A

mixed cell type

hyperplastic lesion occurring in response to abnormal blood supply

44
Q

What are hepatocellular carcinomas?

A 
common malignant neoplasm 
- cell origin is hepatocyte 
commonest primary hepatic neoplasm 
50-90% cirrhotic livers 
alpha fetoprotein is raised 
poor prognosis 
small tumors may be treated by resection of liver transplantation
45
Q

What are cholangiocarcinomas?

A

malignant neoplasm of bile duct
pre-existing bile duct disease in 20%
also associated with non-biliary chronic disease
central or peripheral location

46
Q

What is more common primary liver tumors or metastatic liver tumors?

A

metastatic liver tumors are far more common
- commonest site is epithelial tumors (carcinomas)
tumors of GIT and pancreas - particular tendency to spread to liver

47
Q

What is the prognosis of metastasis colorectal carcinoma to the liver?

A

medium survival without treatment= 6-9 months
survival with chemo = 12-24 months
surgical resection = 5 years, approx 30-40%

Yr 3 - December lectures 2018 (15 decks)

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