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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
What are the histological features of PBC?
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
What are the clinical features of primary sclerosing cholangitis?
``` 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
What are the histological features of PSC?
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
What is the definition of cirrhosis?
irreversible condition affecting the whole liver, characterized by: - loss of normal lobular architecture - nodular regeneration - fibrosis (fibrosis and early cirrhosis may be reversible)
29
How is cirrhosis classified?
micro nodular macro nodular mixed
30
What are the common causes of cirrhosis ?
fatty liver disease - alcoholic or non-alcoholic | viral - hepatitis B, C (rarely E)
31
What are the less common causes of cirrhosis?
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
What are the complications of cirrhosis ?
hepatocellular failure portal hypertension hepatocellular carcinoma - 10-15%
33
What are the common features of hepatocellular failure?
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
What are the effects of portal hypertension?
ascites portosystemic shunts - lower oesophagus, rectum, umbilicus, retroperitoneum, varies, hemorrhoids, caput medusae splenomegaly
35
What should you always consider as a differential diagnosis for liver disease?
drug induced - most commonly used drugs are hepatotoxic | can take sometime to present clinical following drug admin
36
What are the histological features of drug induced liver damage?
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
How can hepatic neoplasms be divided?
benign | malignant - primary and secondary
38
What are examples of benign primary liver tumors?
``` epithelial - hepatocelular adenoma - bile duct adenoma mesenchyme - hemangioma - angiomyolipoma tumor like lesions - cysts - focal nodular hyperplasia - nodular regenerative hyperplasia - mesenchymal harmartoma - inflammatory pseudotumour ```
39
What are examples of malignant primary liver tumors?
hepatocellular carcinoma hepatoblastoma cholangiocarcinoma bile duct cystadenomcarcinoma angiosarcoma epithelia hamangioendothelioma embryonal sarcoma
40
What is hepatocellular adenoma?
benign tumor - hepatocyte origin affects more women hormonal factors - oral contraceptive highly vascular - risk of hemorrhage
41
What is bile duct adenoma?
usually small and asymptomatic, probably not a true neoplasm
42
What are haemargioma?
affects blood vessels usually asymptomatic may be hamartoma rather than true neoplasm
43
What are focal nodular hyperplasia?
mixed cell type | hyperplastic lesion occurring in response to abnormal blood supply
44
What are hepatocellular carcinomas?
``` 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
What are cholangiocarcinomas?
malignant neoplasm of bile duct pre-existing bile duct disease in 20% also associated with non-biliary chronic disease central or peripheral location
46
What is more common primary liver tumors or metastatic liver tumors?
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
What is the prognosis of metastasis colorectal carcinoma to the liver?
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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