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)
