tbl 6 pathology

Question 1

simple apoptotic hepatocyte with an eosinophilic body with or without nuclear pknosis

Answer 1

councilman body/ acidophil body

Question 2

small clusters of hepatocytes marked by lymphocytic infiltrate and macrophages

Answer 2

Spotty, focal necrosis

Question 3

Zonal necrosis

Answer 3

can be centrilobular, midzone, periportal

Question 4

Confluent necrosis

Answer 4

zonal necrosis over multiple lobules

Question 5

Bridging necrosis

o Portal-portal, portal-central, central

Answer 5

necrotic hepatocytes linking portal triads and central veins

Question 6

Terms used in inflammation
- _____________ (within a lobule) and portal
inflammation (based at portal tracts)
- Interface hepatitis – seen in chronic hepatitis where portal inflammatory cells spill into ______________ to focal destruction of limiting plate hepatocytes

Answer 6

Lobular hepatitis;

periportal lobular parenchyma due

Question 7

Terms used in fibrosis

• ___________ – at the portal triad with extension of portal tracts
• _____________ – fibrous extensions to the lobule from portal tract
• ____________ – can be portal to portal, portal to central or central to central
• Pericellular fibrosis – usually seen in alcoholic hepatitis, _____________ around individual hepatocytes mainly at centrilobular areas
• Periductal fibrosis – seem in certain autoimmune cholangitis e.g. __________________________

Answer 7

Portal fibrosis;

Fibrous septa;

Bridging fibrosis;

“chicken wire” fibrosis;

PSC, with concentric fibrosis around ducts

Question 8

Other terms
- _______________- – swollen liver cells filled with HBsAg in chronic Hepatitis B infection
o Finely pink granular cytoplasm seen in microscopy
- Ballooning degeneration – swollen hepatocytes due to sublethal lipotoxic injury
o Clear granular cytoplasm in place of normal pink cytoplasm, clumps of _______________ in cells (Mallory-Denk bodies)
- Feathery degeneration – seen in cholestasis, _____________________ hepatocytes due to damage by detergent action of bile acids

Answer 8

Ground glass hepatocytes;

intermediate filaments;

pale swollen

Question 9

Acute hepatitis
- Predominantly _________________________
- No fibrosis or portal inflammation (none to minimal)
- Lobular hepatitis with ______________ – due to necrosis leading to liver cell regeneration which results in architectural distortion
o Necrosis is a hallmark of acute hepatitis
o _______________ seen – necrosis can be spotty, confluent, bridging, submassive or massive
- Inflammatory cells – lymphocytes and macrophages forming a mononuclear cell infiltrate
- Causes – acute viral hepatitis, autoimmune hepatitis, drugs and toxins
o e.g. paracetamol poisoning can lead to submassive or massive necrosis

Progression of necrosis in acute hepatitis

• Necrosis begins in the ________________ (nearest to central vein)
• Progresses in to ______________________ if adjacent lobules are involved
• As necrosis progresses, lobules are collapsed due to collapse of reticular framework when intervening hepatocytes are lost

Answer 9

lobular inflammation and hepatocellular damage;

lobular disarray;

Councilman bodies;

centrilobular area;

bridging necrosis and confluent necrosis

Question 10

Chronic hepatitis

• Predominantly ________________ with varying lobular inflammation with varying portal fibrosis – fibrosis is an important characteristic of chronic hepatitis
• Portal Inflammation – _____________ with or without lymphoid follicles e.g. seen in hepatitis C infections
• Interface hepatitis with varying lobular hepatitis and focal necrotic cells
• Portal tract fibrosis – expansion of portal triad to fibrous septae, leading to bridging fibrosis and to cirrhosis (at the end stage) with regenerative nodule formation

Microscopic features of chronic hepatitis
- _____________ with active disease – chronic and active hepatitis (mononuclear infiltrate seen)

Answer 10

portal inflammation;

mononuclear inflammation;

Interface hepatitis

Question 11

Staging : Measure of ________________ from minimal interface hepatitis to bridging necrosis

Answer 11

fibrosis and architectural distortion

Question 12

Grading: Measure of ________________ activity – from portal fibrosis to cirrhosis

Answer 12

necro-inflammatory

Question 13

Viral hepatitis
- Presentation depends on different type of hepatitis viruses
o Acute hepatitis – asymptomatic (hepatitis A and B), can be symptomatic
o Fulminant hepatitis – particularly _______________, sometimes hepatitis A
o Carrier – __________________
o Long standing chronic hepatitis B and C have a risk of cirrhosis and hepatocellular carcinoma

• Chronic hepatitis – hepatitis B with or without hepatitis D, hepatitis C, sometimes by hepatitis E in _____________ (never by Hepatitis A)
  o _____________ most common cause of chronic hepatitis (80%)
  o Extrahepatic manifestations – due to deposition if immune complexes leading to ______________________ (hepatitis B and C)
  o Hepatitis C – can present with cryoglobulinemia
• Hepatitis B is endemic in South-East Asia
• Differential diagnosis for viral hepatitis – autoimmune hepatitis and drugs/toxins
• Inflammatory cells are T lymphocytes

Answer 13

hepatitis B;

hepatitis B and C;

immunocompromised cases;

Hepatitis C;

vasculitis and glomerulonephritis

Question 14

Hepatitis C infection – natural history
- Hepatitis C is an important cause of chronic hepatitis worldwide – genetically unstable and difficult to eradicate
o Severity spikes as there is repeated bouts of hepatic damage either due to _______________________
o Progression of fibrosis can be different
- _____________ intake worsen prognosis and accelerate disease progression

Answer 14

reactivation of existing infection or a new strain of HCV;

HIV and alcohol

Question 15

Autoimmune hepatitis
- Chronic progressive necro-inflammatory autoimmune process, commonly in women (70%)
o Type 1 – _______________ (SMA) and _____________ (older women)
o Type 2 – ______________ (LKM-1) and _____________ (ACL-1) (young)
- Features – acute or chronic hepatitis with fibrosis, necrosis, interface hepatitis and typically prominent plasma cells (fulminant hepatitis is also possible)
- Complications – acute or chronic liver failure, cirrhosis and HCC

Answer 15

anti smooth muscle actin; anti-nuclear antibody

anti-liver-kidney microsomal antibody; anti-liver cytosol 1

Question 16

Hepatic steatosis
- Liver cells distended by fat globules – starting at the ________________
o Macrovesicular – large fat globules, with nucleus at _____________
o Microvesicular – multiple small lipid droplets with central nucleus

• No inflammation, fibrosis, grossly large, yellow and greasy liver
• Seen in nearly all chronic alcoholics – reversible if injurious agent is removed
• Histology – macrovesicular steatosis is seen in alcoholic FLD and microvesicular steatosis is rare, seen in ___________________________

Answer 16

periphery;

centrilobular area;

fatty liver of pregnancy and Reye’s syndrome

Question 17

Steatohepatitis

• Steatosis with lobular inflammation and ballooned hepatocytes – centrilobular and not portal based
• Hepatocyte swelling (ballooning) with ________________ commonly seen in alcoholic FLD – ubiquitinated tangled intermediate filaments, seen as __________________ within ballooned hepatocytes
• Lobular inflammation – typically neutrophils around the injured hepatocytes (lobular inflammation and hepatitis)
• Lymphocytes and macrophages may be present

Answer 17

Mallory-Denk bodies; cytoplasmic eosinophilic inclusions

Question 18

Steatofibrosis and cirrhosis
- Steatofibrosis – fibrosis appears first in the centrilobular region as central vein sclerosis
o ___________ appears next in the space of Disse of the centrilobular region and then spreads outward, encircling individual or small clusters of hepatocytes in a chicken wire fence
o Tendrils of fibrosis eventually link to portal tracts and then condense to create __________________
o As these become more prominent, the liver takes on a nodular, cirrhotic appearance
- If the injurious agent persists, cirrhosis will develop – typically micronodular
o In end stages, there is _________________ (burned out) – fatty acid changes may not be present

Steatofibrosis – _____________ showing fibrosis at the centrilobular area extending to hepatocytes in a pericellular manner

Answer 18

Perisinusoidal scarring;

central portal fibrous septa;

cryptogenic cirrhosis;

Mallory-trichrome stain;

Question 19

Pathogenesis of alcoholic FLD – normally, fatty acid from the gut and liver is used in production of triglycerides or catabolised
- Pathogenesis of steatosis – due to alcohol
o Increased fatty acid delivery to liver due to increased ___________
o Alcoholic metabolism produce _________, leading to increased fatty acid production, increase in triglyceride production
o There is a decrease of catabolism of fatty acids and ____________________
o Increased levels of triglycerides lead to steatosis - Pathogenesis of steatohepatitis and fibrosis – unclear yet
o Toxic by-products of alcoholic metabolism thought to lead to damage of hepatocytes
o Acetaldehyde and reactive oxygen species lead to _________________
o Cytoskeleton and membrane abnormalities lead to _____________
o Alcohol also lead to ___________ , accentuating cell injury
- As metabolism of alcohol is mainly in the ______________, AFLD begins to progress from there

Answer 19

lipolysis;

acetaldehyde;

lipoprotein formation;

lipid peroxidation;

balloon degeneration;

mitochondrial damage;

centrilobular zone

Question 20

Pathogenesis of NAFLD – proposed 2-hit model
- Insulin resistance – leads to __________
- Liver cell oxidative injury – leads to ____________
- Obesity is important in pathogenesis – leads to
altered _______ and increased metabolic syndrome, promoting apoptosis and inflammation
- NAFLD is a common hepatic manifestation metabolic syndrome – presents as steatosis, _____________ and steatofibrosis
o Histologically similar to Alcoholic FLD – clinical correlation is important as NAFLD is a diagnosis of exclusion
- Paediatric NAFLD – more ________ steatosis, portal fibrosis and _____________________

Answer 20

steatosis;

necrosis and inflammation;

adipocytokines;

steatohepatitis (NASH);

diffuse; parenchymal mononuclear inflammation

Question 21

Possible routes of progression in NAFLD
- 80% of NAFLD presents as simple steatosis with no increased risk of progression or death
o <20% of NAFLD cases result in NASH
- NASH – <10% of case results in cirrhosis
- 30% of cirrhotic cases will lead to decompensation or liver failure and <7% will develop HCC
- NAFLD is associated with _______________________

Answer 21

metabolic syndromes and cardiovascular disease

Question 22

Microscopic features of cholestatic liver diseases
- Bile pigment in the __________
- Bile plugs in _____________ – may rupture leading to extravasated bile with Kupffer cells ingestion
- ________________ – hepatocytes with fine foamy cytoplasm especially in periportal areas, a sign of damage by bile acids
- Acute duct obstruction – triad of ___________________________
- Chronic duct obstruction leads to portal fibrosis and biliary cirrhosis
- Compared to normal hepatocytes – enlarged and intracellular pigment, with dilated bile canaliculi
o Kupffer cells ingest bile pigment
- Compared to normal portal triad – ductular proliferation

Answer 22

hepatocytes;

dilated bile canaliculi;

Feathery degeneration;

oedema, ductular reaction and neutrophil infiltrate in portal tracts

Question 23

Primary biliary cirrhosis

• non- suppurative inflammatory destruction of ____________
• chronic autoimmune cholangitis
• more common in _________

serology: _____ positive

Progressive duct destruction- jaundice and cirrhosis

• Inflammation of portal tracts – centred around bile ducts leading to damage
• ___________, is the pathological hallmark – leads to bile duct loss
• Granulomas are may be present – mostly loose collection of histiocytes surrounding an injured bile duct

Answer 23

small and medium intrahepatic ducts;

middle aged females;

AMA positive;

Florid duct lesion

Question 24

Primary sclerosing cholangitis (PSC)

• Inflammation and obliterative fibrosis of __________________ – can lead to strictures and dilatation of uninvolved segments (typically beaded appearance on radiology)
• Fibrosing disease of unknown aetiology, often associated with IBD (mainly ulcerative colitis)
• Serology: ____ positive
• Periductal fibrosis
• Diffuse or segmental areas of inflammation and fibrosis resulting in multifocal intrahepatic and extrahepatic biliary strictures
• Smaller ducts show ________________ eventually leading to ductal obliteration

Answer 24

intra and extrahepatic ducts;

ANCA;

periductal onion-skinning fibrosis

Question 25

Haemochromatosis – iron deposition in liver and other organs due to increased absorption
- Primary – due to _____________________
- Secondary – blood transfusions, ineffective erythropoiesis and MDS
- More common in males (5:1) in the 5th decade, with variable penetrance of mutations
- Haemosiderin deposition in multiple organs – liver, pancreas, heart, pituitary, thyroid/parathyroid glands, joints and skin
o Leads to cirrhosis and pancreatic __________
o Other – __________ pigmentation of skin, enlarged heart and psuedogout
- Clinical features (reflect tissue deposition of iron) – hepatomegaly, glucose intolerance, cardiac arrhythmias, arthritis, skin pigmentation, hypogonadism, risk of HCC (x200)
o Early detection can prevent disease progression

Answer 25

HFE gene mutations (C282Y);

slate grey;

fibrosis

Question 26

Wilson disease (hepatolenticular degeneration) – due to a genetic abnormality (ATP7B) inherited in an autosomal recessive manner that leads to impairment of cellular copper transport, presenting at young or middle age (average age of 12)
- Impaired copper excretion and attachment to _______________ – accumulation of copper in liver and decreased ceruloplasmin
o Excess copper is initially bound to ______________ and distributed evenly throughout the cytoplasm – with progressive copper accumulation, the capacity of metallothionein is exceeded and hepatocyte injury occurs
- Effects of copper accumulation –
o Liver – steatosis, acute fulminant hepatitis, chronic hepatitis, cirrhosis
§ Increased copper in hepatocytes – toxic effects
o Brain – _______________ (neurological signs)
o Eye – ________________, brownish or graygreen
rings that result from fine pigmented granular deposits of copper in Descemet’s membrane in the cornea close to the endothelial surface

Haemolytic anaemias – due to deficiency of ceruloplasmin (copper transport protein), excessive inorganic copper in the blood circulation accumulating in red blood cells

Answer 26

ceruloplasmin;

metallothionein ;

basal ganglia injury;

Kayser-Fleischer rings

Question 27

A1AT deficiency – autosomal recessive with misfolded A1AT protein
- A1AT inhibits proteases particularly from neutrophils in inflammatory sites
- Mutation results in glutamine to ________ substitution in the PiZ protein
- Liver – accumulation of abnormal A1AT proteins
visualised as _______________, ranging from hepatitis to cirrhosis
- Lung – emphysema (due to increased protease activity in the absence of A1AT leading to alveolar wall destruction)

Answer 27

lysine;

PASD positive globular inclusions (periportal);

Question 28

Budd-Chiari syndrome increases mortality in the acute setting (may be due to acute thrombosis of the main hepatic veins or IVC)

• Hepatic vein outflow obstruction leads to marked sinusoidal congestion and _________ necrosis
• Manifestations also include _________________

Answer 28

centrilobular;

portal hypertension

Question 29

Chronic passive venous congestion (CPVC) – hepatic manifestation of a systemic vascular compromise

• Due to ____________ – increased back pressure of systemic veins, venous blood congestion in the liver leading to chronic ischemia if prolonged
• Grossly ___________ liver

Answer 29

right heart failure ;

nutmeg