Molecular Basis of Liver Flashcards
What organ is only found in vertebrates?
The liver
What is liver regeneration?
a logical adaptation to function due to it being the main detoxification organ
What occurs during partial hepatectomy?
surgical resection of two-thirds of liver mass
What is the result of partial hepatectomy?
resection triggers process of regeneration
What does partial hepatectomy ensure?
It ensures proliferation and expansion of all liver cell types > enables restoration of hepatic mass within 8-15 DAYS
What occurs immediately after partial hepatectomy?
Dramatic change in hemodynamics (due to same volume of blood through 1/3 of tissue), AKA sheer stress
What two things lead to the stimulation of hepatocyte proliferation?
Hypoglycemia and sheer stress
What is hypoglycemia?
What changes occur within minutes of partial hepatectomy?
changes in gene expression
What is the baseline of Hepatocyte Injury, Repair and Death?
Hepatocytes undergo degenerative changes that may be reversible or not
What is an example of reversible Hepatocyte Injury
accumulation of fat, steatosis
What are two examples of when Hepatocyte Injury is not reversible?
hepatocytes die by two mechanisms, necrosis or apoptosis
What is hepatocyte necrosis?
predom mode of death in ischemic/hypoxic injury > significant to oxidative stress
Hepatocyte apoptosis
predom mode of death in acute and chronic hepatitis
What is the main type of cell involved in scar deposition?
Hepatic stellate cell
What is Non-Alcoholic fatty liver disease (NAFLD)?
the accumulation of fat in hepatocytes (steatosis) > in the absence of alcohol intake
What does the spectrum of NAFLD entail?
simple steatosis (NAFL) to NASH steatosis with inflammation and hepatocyte injury
What is the most common cause of chronic liver disease in Canada?
NAFLD as it affects 25% of the population
What percentage of people does NASH occur in if they have NAFLD?
20% of people with NAFLD > can progress to hepatocellular carcinoma (HCC)
What syndrome is most commonly associated with NAFLD?
metabolic syndrome
What is metabolic syndrome?
clinical features linked to visceral obesity
What is included in metabolic syndrome?
Insulin resistance, dyslipidemia, hypertension
What is the liver manifestation of metabolic syndrome?
NAFLD
Where does normal blood sugar regulation usually take place?
Primarily in the myocyte
Fasting state of the liver
gluconeogenesis > production of hepatic glucose > maintains blood glucose level
Fed State of liver
glucose > enters Krebs > used for fatty acid biosynthesis
What does insulin do in relation to normal glucose regulation in the liver?
inhibitor of hepatic glucose production > activator of glycolysis
Why do fat laden myocytes not uptake glucose?
they are resistant to insulin
What is the role of adipose tissue in the body?
it supplies a positive energy balance and stores triglycerides
What occurs after the storage of triglycerides in adipose tissue?
there is an increase in free fatty acid > which is then released into circulation.
What occurs when there are increased FFA uptake levels in the liver?
development of hepatic steatosis and inflammation
What is associated with macrophage accumulation in adipose tissue and low-grade inflammation?
obesity
What occurs after adipose tissue inflammation when cytokines and chemokines are secreted?
hepatocyte apoptosis and activation of stellate cells > scar tissue deposition
What occurs if there is disruption in the Gut-liver axis?
changes to intestinal microbiota > altered intestinal permeability (leaky gut) > increased endotoxin levels
What is Alcoholic Liver Disease?
excessive alcohol consumption > but shares many histological features as well as molecular and physiologic pathogenic mechs with NAFLD
What is the relation between alcohol metabolism and generation of oxidative stress?
liver is the principle organ for alcohol metabolism > oxidation of ethanol = toxic metabolites.
What leads to the inability of the liver to maintain redox homeostasis?
excessive drinking which leads to excessive NADH generation
What will be promoted if there is a redox imbalance?
promotes hepatic steatosis
Where do ALL changes in alcoholic liver disease begin?
Acinus zone 3 > then extend outward toward portal tracts with increase in severity
How is fatty change reversible?
it is reversible if there is abstention from further intake of alcohol
What is Alcoholic steatohepatitis?
hepatocyte swelling and necrosis > neutrophilic reaction > Mallory-Dank Bodies
What is alcoholic steatofibrosis
the prominent activation of sinusoidal stellate cells and portal fibroblasts > leading to fibrosis
What is alcoholic cirrhosis?
webs of scars that link portal tracts > condensed into central-portal fibrous septa > nodule diffusion on surface
What is rare about alcoholic cirrhosis?
It is rare because there is no to little regression
How are hepatic tumors noticed?
epigastric fullness and discomfort/routine physical examination/radiographic
What are examples of benign hepatic tumors?
Hemangioma and Hepatocellular Adenoma
What are examples of Malignant tumors
Hepatoblastoma and Hepatocellular carcinoma
What are hepatoocellular Adenoma
Benign neoplasm developing from hepatocytes
What is hepatocellular adenoma associated with?
estrogen-containing oral contraceptives or androgen-containing steroid anabolic drugs
What are hepatoblastomas?
most common liver tumor in early childhood > rarely occurring over age of 3
What occurs in the tumor cells of Hepatoblastoma?
cells recapitulating the embryological stages of hepatic development
What is the epithelial type of Hepatoblastoma?
fetal/small embryonal cells form structures vaguely > recapitulating liver development
What is the mixed epithelial and mesenchymal type of Hepatoblastoma?
epithelial cell types + mesenchymal components like myofibroblastic
What is Hepatocellular Carcinoma?
most common primary neoplasm in the liver > 85% of all primary liver malignant tumors > 5.4 % of all cancers
What are the most common underlying factors in hepatocarcinogenesis?
Viral infections like HBV or HCV and toxic injuries
