Liver pathology Flashcards
Broadly describe the histology of the liver
“Lobular Model” 1-2mm
- Central veins in centre (drain to hepatic vein).
- Portal tracts/triad at periphery.
- Hepatic artery.
- Portal vein.
- Bile duct.
- Zones:
- Reflects oxygenation gradient (useful for pathophysiology).
- Zone 1 (closest to arterial supply).
- Zone 2.
- Zone 3 (closest to central vein).- due to low BP or toxic stress, is most susceptible to ischaemia
Describe the architecture of the liver
- Plates of hepatocytes, one cell thick - limited by a thin layer of fibrous tissue. Supported by reticulin
- Between vascular sinusoids (mixed portal venous, and hepatic arterial blood). - i.e. sinusoids separate the plates
- Space of Disse: underneath endothelial cells, contain protruding microvilli of hepatocytes. between the sinusoids and hepatocytes
- Kupffer cells (mononuclear phagocytes).
- Stellate cells (fat storing, in space of Disse).
Describe the features of hepaticytes
- large epithelial cells with abundant pink granular cytoplasm
- polygonal shape
- large nuclei
- prominent nucleoli
- cytoplasmic alterations e.g. brown lipofuscin pigment (others may also be seen in disease)
- accumulates as a result of wear and tear, more apparent in disease states
Describe the flow of bile
- Hepatocytes secrete bile.
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Bile canaliculi:
- Lie between adjacent hepatocytes.
- Tight junctions separate them from vascular space.
- Canals of Hering.
- Bile ductules (periportal).
- Terminal Bile ducts (portal tracts) ➔ Extrahepatic biliary tree.
Describe vascular flow
- Arterial Blood via branches of Hepatic Artery.
- Portal Venous Blood.
- Mixed arterial and venous blood in sinusoids.
- Central Veins (Centrilobular venules).
- Hepatic Vein ➔ Vena Cava.
List and briefly describe some other important cells of the liver
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Stellate/Ito Cells:
- Found in space of Disse.
- Storage of vitamin A, activation + secrete collagen in liver fibrosis.
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Kupffer Cells:
- Mononuclear phagocytes, lining sinusoids.
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Endothelial Cells:
- Sinusoidal endothelium is discontinuous + fenestrated.
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Bile Ductular Cells:
- Simple cuboidal epithelial cells on a basement membrane, conduit for bile drainage.
Describe the broad pathophysiology of liver diseases
- A wide variety of insults may damage liver cells (metabolic, toxic, microbial, vascular, neoplastic).
- Hepatic injury may be:
- ACUTE or CHRONIC
- REVERSIBLE or IRREVERSIBLE
- Irreversible damage may result in:
- Hepatocyte necrosis:
- Individual cell necrosis (cell swelling/ballooning, burst, disappear).- single cell
- Confluent necrosis when severe (may lead to Zonal or Bridging necrosis).
- Hepatocyte apoptosis (apoptotic bodies = Councilman or acidophil bodies). - single cell
- Hepatocyte necrosis:
There are diverse types of iver injury but…
- LIMITED NUMBER REACTION PATTERNS IN LIVER
- Hepatocyte cell death.
- Cholestasis (bile plugging).
- Bile duct damage or loss.
- Portal inflammation.
- Interface hepatitis (inflammatory attack of periportal hepatocytes).
- Lobular hepatitis (inflammatory attack of lobular hepatocytes).
- Cytoplasmic alterations of hepatocytes.
- Vascular alterations.
- Granulomas.
- Fatty liver disease.
Describe individual cell death and confluent necrosis
idual Cell Death
- Acidophil body/Councilman Body: apoptotic hepatocyte with pyknotic nucleus and eosinophilic cytoplasm.
- Balloon Degeneration: osmotic dysregulation leads to ballooning of the cell with necrosis and dropout. Dead cells covered by clusters of macrophages ingesting debris
Confluent Necrosis: Bridging or Zonal Necrosis
- Zone 3 necrosis: pallor and loss of nuclei of hepatocytes in affected areas.
- Zonal necrosis: death of a particular zone of hepatocytes.
- Bridging necrosis: necrosis forms bridges between PT’s or PT + CV.
Liver Cell Dropout: Reticulin Stain
- Evidence of prior liver cell death (reticulin fibres are packed together as the hepatocytes between them have died).
Describe the mechanisms of liver fibrosis
- Generally restricted to conditions causing chronic liver damage.
- Options for liver after Irreversible liver cell damage and loss:
- Regeneration (mitotic replication of adjacent hepatocytes) – unfortunately with time replicative senescence occurs.
- Scarring and fibrosis.
Describe cirrhosis
- The end-stage of many types of chronic liver disease/injury.
- Not all end-stage liver diseases are cirrhotic.
- Potential for reversal of fibrosis in future?
- Reflects significant liver damage with scarring/fibrosis and functional/vascular derangements.
- Consequences:
- Liver dysfunction/failure.
- Portal hypertension (bleeding).
- Risk of hepatocellular carcinoma.
Describe cirrhosis macroscopy and microscopy
Cirrhosis Macroscopy
- Liver may be shrunken and firm with knobbly surface.
- Parenchyma replaced diffusely by nodules:
- Micronodular (<3mm).
- Macronodular (>3mm).
Cirrhosis Microscopy
- Nodules of regenerating hepatocytes + Circumferential bands of fibrosis enclosing nodules = minimum Dx criteria.
- Bile ductular proliferation may also occur “ductular reaction” (at the edges of portal tracts). - as a response to increased resistance
- Functional derangement of vasculature/blood flow is an important component of cirrhosis, but one which is not visible microscopically.
Describe the clinical history and relevant investigations in liver disease
- Clinical History.
- Symptoms.
- Timecourse (acute vs. chronic).
- Known liver diseases.
- ETOH + illegal drugs.
- Drugs.
- Miscellaneous (travel etc).
- Past medical Hx (e.g. inflammatory bowel disease, Hepatitis).
- Family Hx of genetic conditions.
- Relevant investigations:
- hepatocyte integrity: AST, ALT, LDH; biliary excretory function: serum bilirubin, bile acids; hepatocyte synthetic function: albumin, coagulation factors
- Autoimmune serology.
- Viral serology.
- Wilson’s disease.
- A1AT.
- Iron studies.
Define and describe acute liver failure
- Definition: acute liver injury + encephalopathy within 26 weeks of initial liver injury + absence of preexisting liver disease.
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Major causes:
- Drugs/toxins e.g., acetaminophen over ingestion, deathcap mushrooms (Canberra).
- Autoimmune hepatitis.
- Acute Viral hepatitis (Hep A, B, E).
Describe histology of acute liver failure
- Confluent/massive Hepatocyte necrosis.
- Some forms of acute liver injury may cause microvesicular steatosis (reflecting mitochondrial dysfunction).
- Some regeneration may be seen.
Can see zone 3 necrosis in paracetamol overdose, microvesicular steatosis (tiny fatty vesicles)
What is the role of the liver biopsy?
- Determining/confirming the cause of liver disease.
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Activity of the disease:
- Degree of active liver cell damage reflecting the aggressiveness of the disease
- #### Disease Activity (How much inflammation and cell death there is)
- Amount of Portal Inflammation.
- Interface Hepatitis.
- Lobular damage:
- Individual cell damage- (ballooning or acidophil bodies).- sign of stress
- Liver cell dropout (reticulin collapse).
- confluent/zonal/bridging necrosis if severe
-
Stage of the disease:
- Degree of fibrosis reflecting progression to cirrhosis.
Describe fatty liver disease and histologic findings
Fatty Liver Disease
- Identical histologic findings in both alcoholic and non-alcoholic forms (Clinical History !!!).
- Histologic Findings:
1. Evidence of excess fat in hepatocytes (steatosis):
- Macrovesicular (one large droplet) > microvesicular (multiple small droplets).
2. Evidence of damage to hepatocytes (steatohepatitis):
- Ballooning degeneration.
- Mallory-Denk bodies (degenerate intermediate filaments complexed with ubiquitin)., can be surrounded on neurtophils
- Neutrophilic infiltrates.
3. +/- Fibrosis (begins “pericellular”).–progresses
Describe viral hepatitis, chronic viral hepatitis, hepatitis B and C
Viral Hepatitis
- Infiltration by lymphocytes with any combination of:
- Portal tract inflammation.
- Interface hepatitis.
- Lobular hepatitis (death of hepatocytes).
- Variable degrees of fibrosis.
- Viral serology is essential.
Chronic viral hepatitis
- dominated by lymphocytes
- occurs in lobules, around portal tract, at interface
Hepatitis B
- ground glass hepatocytes: cytoplasmic inclusions
- accumulation fo surface antigen - HepBsAg
- can be seen on HE and on IHC
Hepatitis C
- often prominent lymphoid follicles
- bile duct damage may be present
- often steatosis
Describe autoimmmune hepatitis
-
Background:
- F>M, peaks (middle age, kids/teenagers).
- Autoantibodies (ANA, AMSA, LKM).
- Absence of other liver diseases.
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Findings:
- Plasma cell predominance.
- Severe hepatitis (severe interface hepatitis, often confluent necrosis). - aka florid chronic inflammation and cell death
- clockface chromatin and eccentric nuclei
Describe PBC
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Clinical:
- F», middle age.
- Anti-mitochondrial antibodies.
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Histology:
- Bile ducts actively destroyed by lymphoplasmacytic inflammation +/- granulomas.
- Progressive fibrosis.
Describe PSC
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Clinical:
- Intra + extrahepatic biliary obstruction (cholestatic).
- Beading on radiographs.
- Inflammatory bowel disease esp. UC (70%).
- Only 4% of UC pts have PSC.
- M>.
- Lifetime risk cholangiocarcinoma 20%.
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Histology:
- Chronic inflammation around bile ducts of all sizes.
- Onion-skinning fibrosis.
Describe genetic an dmetabolic disorders
Alpha-1 Antitrypsin Deficiency
- Findings:
- H+E pink globules.
- Serum A1AT levels.
- A1AT genetic testing.
- Findings:
- Pink cytoplasmic globules on H+E and PAS.
Cirrhosis and COPD risk.
Haemochromatosis
- Findings:
- Brown iron deposition in hepatocytes H+E.
- Important to distinguish clinically between primary (hereditary) + secondary forms.
- Iron studies.
Wilson’s Disease
- Clinical correlation is essential, serum ceruloplasmin.
- +/- Cu/gram weight liver.
- Findings:
- Steatosis.
- Increased red/orange copper on Rhodamine staining.
- Chronic hepatitis.
