tbl 6 pathology Flashcards
simple apoptotic hepatocyte with an eosinophilic body with or without nuclear pknosis
councilman body/ acidophil body
small clusters of hepatocytes marked by lymphocytic infiltrate and macrophages
Spotty, focal necrosis
Zonal necrosis
can be centrilobular, midzone, periportal
Confluent necrosis
zonal necrosis over multiple lobules
Bridging necrosis
o Portal-portal, portal-central, central
necrotic hepatocytes linking portal triads and central veins
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
Lobular hepatitis;
periportal lobular parenchyma due
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. __________________________
Portal fibrosis;
Fibrous septa;
Bridging fibrosis;
“chicken wire” fibrosis;
PSC, with concentric fibrosis around ducts
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
Ground glass hepatocytes;
intermediate filaments;
pale swollen
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
lobular inflammation and hepatocellular damage;
lobular disarray;
Councilman bodies;
centrilobular area;
bridging necrosis and confluent necrosis
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)
portal inflammation;
mononuclear inflammation;
Interface hepatitis
Staging : Measure of ________________ from minimal interface hepatitis to bridging necrosis
fibrosis and architectural distortion
Grading: Measure of ________________ activity – from portal fibrosis to cirrhosis
necro-inflammatory
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
hepatitis B;
hepatitis B and C;
immunocompromised cases;
Hepatitis C;
vasculitis and glomerulonephritis
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
reactivation of existing infection or a new strain of HCV;
HIV and alcohol
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
anti smooth muscle actin; anti-nuclear antibody
anti-liver-kidney microsomal antibody; anti-liver cytosol 1
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 ___________________________
periphery;
centrilobular area;
fatty liver of pregnancy and Reye’s syndrome
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
Mallory-Denk bodies; cytoplasmic eosinophilic inclusions
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
Perisinusoidal scarring;
central portal fibrous septa;
cryptogenic cirrhosis;
Mallory-trichrome stain;
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
lipolysis;
acetaldehyde;
lipoprotein formation;
lipid peroxidation;
balloon degeneration;
mitochondrial damage;
centrilobular zone
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 _____________________
steatosis;
necrosis and inflammation;
adipocytokines;
steatohepatitis (NASH);
diffuse; parenchymal mononuclear inflammation
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 _______________________
metabolic syndromes and cardiovascular disease
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
hepatocytes;
dilated bile canaliculi;
Feathery degeneration;
oedema, ductular reaction and neutrophil infiltrate in portal tracts
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
small and medium intrahepatic ducts;
middle aged females;
AMA positive;
Florid duct lesion
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
intra and extrahepatic ducts;
ANCA;
periductal onion-skinning fibrosis
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
HFE gene mutations (C282Y);
slate grey;
fibrosis
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
ceruloplasmin;
metallothionein ;
basal ganglia injury;
Kayser-Fleischer rings
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)
lysine;
PASD positive globular inclusions (periportal);
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 _________________
centrilobular;
portal hypertension
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
right heart failure ;
nutmeg
