Liver Pathology Flashcards
What are some major liver diseases
Viral hepatitis
NAFLD (non-alcoholic fatty liver disease)
ALD (Alcoholic liver disease)
HCV (Hepatocellular carcinoma)
What are some secondary causes of liver damage
Heart failure
Disseminated cancer
Extrahepatic infections
What are some major liver diseases
Viral hepatitis
NAFLD (Non-Alcoholic Fatty Liver Disease)
ALD (Alcoholic Liver Disease)
HCC (Hepatocellular Carcinoma)
What are some secondary causes of liver damage
Heart failure
Disseminated cancer
Extra-hepatic infections
What are some mechanisms of liver damage repair
Hepatocyte and Parenchymal Responses
Scar formation and regression
Inflammation and Immunity
Ballooned hepatocytes are a hallmark of ……….. (what condition)
Alcohol-induced or non-alcoholic steato-hepatitis
What are some morphological changes the liver can undergo
Fat accumulation (Steatosis)
Bilirubin accumulation (Cholestasis)
Ballooning (cell swelling, cytoplasmic clearing, clumping of intermediate filament, Mallory’s Hyaline)
What is the histology of liver steatosis
Multiple vacuoles of fat have been deposited in the liver
The vacuoles did not stain for glycogen nor was hepatocellular glycogenosis observed, although normal amounts of glycogen are apparent in hepatocytes
A chacteristic feature of steatosis is fatty droplets and displaced nuclei.
Steatosis is associated with diabetes and other metabolic diseases.
Alcoholism can also induce steatosis because the metabolism of ethanol produces NADH which shifts the metabolism of hepatocytes toward lipid synthesis.
What is the histology of cholestasis
Canaliculi are not visible under normal circumstances but can be seen in cholestasis when they become dilated with inspissated bile plugs
Bile pigment can be identified as golden granular material within hepatocytes or as phagocytosed debris within Kupffer cells.
Cholestasis is characterized by feathery degeneration (cytoplasmic swelling with protein condensation) of hepatocytes
What is liver ballooning
Hepatocellular ballooning is a key finding in nonalcoholic steatohepatitis (NASH)
•It is conventionally defined by hematoxylin and eosin (H&E) staining showing enlarged cells with rarefied cytoplasm and by changes in the cytoskeleton
•There is cellular enlargement 1.5-2 times the normal hepatocyte diameter
Ultrastructural Features
• A dilated endoplasmic reticulum sometimes referred to as hydropic change
•Enlarged cells, often with degenerative changes, containing multiple small fat droplets along with a lesser degree of dilated endoplasmic reticulum
•Ballooned cells may come in association with Mallory-Denk bodies
Nb: Immunohistochemical studies have demonstrated that ballooned cells contain oxidized phosphatidylcholine in the phospholipid-rich rim of fat droplets, and show altered expression of fat droplet associated (PAT family) proteins which regulate insulin-sensitive droplet lipase activity
What is the histology of liver ballooning
Liver showing ballooning degeneration of hepatocytes and fibrous tissue proliferation around hepatic lobules, HE stain. Magnification × 100
What are the two mechanisms through which hepatocytes die
Necrosis and apoptosis
Describe how hepatocytes die by necrosis
Na+-K+ pumps fails, causing ionic imbalance
*Osmotic dysregulation-excess H2O enter cell, cell swells and ruptures
*Increased intracellular calcium mitochondrial dysfunction
Necrosis is the primary cause of cell death in Ischemia, hypoxia and oxidative stress
Also in necrosis:
*Remnants of necrotic cells are phagocytosed by macrophages which tend to cluster and mark sites of necrosis
*Morphologically, necrotic cells contain pas-positive intracellular materials derived from necrotic hepatocytes
Nb: Necrosis, unlike apoptosis, induces an inflammatory response
How does necrosis look like under the microscope
Accumulation of macrophages with ingested necrotic materials
Clusters with pas-positive intracellular materials from necrotic hepatocytes
Describe apoptosis
•Programmed cell death
•Hepatic shrinkage
•Chromatin condensation (pyknosis)
•Chromatin fragmentation (Karyorrhexis)
•Cell fragments into apoptotic bodies (as implicated in yellow fever and acute chronic hepatitis)
Nb: Apoptosis does not stimulate an inflammatory response