Molecular Basis of Liver

Question 1

What organ is only found in vertebrates?

Answer 1

The liver

Question 2

What is liver regeneration?

Answer 2

a logical adaptation to function due to it being the main detoxification organ

Question 3

What occurs during partial hepatectomy?

Answer 3

surgical resection of two-thirds of liver mass

Question 4

What is the result of partial hepatectomy?

Answer 4

resection triggers process of regeneration

Question 5

What does partial hepatectomy ensure?

Answer 5

It ensures proliferation and expansion of all liver cell types > enables restoration of hepatic mass within 8-15 DAYS

Question 6

What occurs immediately after partial hepatectomy?

Answer 6

Dramatic change in hemodynamics (due to same volume of blood through 1/3 of tissue), AKA sheer stress

Question 7

What two things lead to the stimulation of hepatocyte proliferation?

Answer 7

Hypoglycemia and sheer stress

Question 8

What is hypoglycemia?

Question 9

What changes occur within minutes of partial hepatectomy?

Answer 9

changes in gene expression

Question 10

What is the baseline of Hepatocyte Injury, Repair and Death?

Answer 10

Hepatocytes undergo degenerative changes that may be reversible or not

Question 11

What is an example of reversible Hepatocyte Injury

Answer 11

accumulation of fat, steatosis

Question 12

What are two examples of when Hepatocyte Injury is not reversible?

Answer 12

hepatocytes die by two mechanisms, necrosis or apoptosis

Question 13

What is hepatocyte necrosis?

Answer 13

predom mode of death in ischemic/hypoxic injury > significant to oxidative stress

Question 14

Hepatocyte apoptosis

Answer 14

predom mode of death in acute and chronic hepatitis

Question 15

What is the main type of cell involved in scar deposition?

Answer 15

Hepatic stellate cell

Question 16

What is Non-Alcoholic fatty liver disease (NAFLD)?

Answer 16

the accumulation of fat in hepatocytes (steatosis) > in the absence of alcohol intake

Question 17

What does the spectrum of NAFLD entail?

Answer 17

simple steatosis (NAFL) to NASH steatosis with inflammation and hepatocyte injury

Question 18

What is the most common cause of chronic liver disease in Canada?

Answer 18

NAFLD as it affects 25% of the population

Question 19

What percentage of people does NASH occur in if they have NAFLD?

Answer 19

20% of people with NAFLD > can progress to hepatocellular carcinoma (HCC)

Question 20

What syndrome is most commonly associated with NAFLD?

Answer 20

metabolic syndrome

Question 21

What is metabolic syndrome?

Answer 21

clinical features linked to visceral obesity

Question 22

What is included in metabolic syndrome?

Answer 22

Insulin resistance, dyslipidemia, hypertension

Question 23

What is the liver manifestation of metabolic syndrome?

Answer 23

NAFLD

Question 24

Where does normal blood sugar regulation usually take place?

Answer 24

Primarily in the myocyte

Question 25

Fasting state of the liver

Answer 25

gluconeogenesis > production of hepatic glucose > maintains blood glucose level

Question 26

Fed State of liver

Answer 26

glucose > enters Krebs > used for fatty acid biosynthesis

Question 27

What does insulin do in relation to normal glucose regulation in the liver?

Answer 27

inhibitor of hepatic glucose production > activator of glycolysis

Question 28

Why do fat laden myocytes not uptake glucose?

Answer 28

they are resistant to insulin

Question 29

What is the role of adipose tissue in the body?

Answer 29

it supplies a positive energy balance and stores triglycerides

Question 30

What occurs after the storage of triglycerides in adipose tissue?

Answer 30

there is an increase in free fatty acid > which is then released into circulation.

Question 31

What occurs when there are increased FFA uptake levels in the liver?

Answer 31

development of hepatic steatosis and inflammation

Question 32

What is associated with macrophage accumulation in adipose tissue and low-grade inflammation?

Answer 32

obesity

Question 33

What occurs after adipose tissue inflammation when cytokines and chemokines are secreted?

Answer 33

hepatocyte apoptosis and activation of stellate cells > scar tissue deposition

Question 34

What occurs if there is disruption in the Gut-liver axis?

Answer 34

changes to intestinal microbiota > altered intestinal permeability (leaky gut) > increased endotoxin levels

Question 35

What is Alcoholic Liver Disease?

Answer 35

excessive alcohol consumption > but shares many histological features as well as molecular and physiologic pathogenic mechs with NAFLD

Question 36

What is the relation between alcohol metabolism and generation of oxidative stress?

Answer 36

liver is the principle organ for alcohol metabolism > oxidation of ethanol = toxic metabolites.

Question 37

What leads to the inability of the liver to maintain redox homeostasis?

Answer 37

excessive drinking which leads to excessive NADH generation

Question 38

What will be promoted if there is a redox imbalance?

Answer 38

promotes hepatic steatosis

Question 39

Where do ALL changes in alcoholic liver disease begin?

Answer 39

Acinus zone 3 > then extend outward toward portal tracts with increase in severity

Question 40

How is fatty change reversible?

Answer 40

it is reversible if there is abstention from further intake of alcohol

Question 41

What is Alcoholic steatohepatitis?

Answer 41

hepatocyte swelling and necrosis > neutrophilic reaction > Mallory-Dank Bodies

Question 42

What is alcoholic steatofibrosis

Answer 42

the prominent activation of sinusoidal stellate cells and portal fibroblasts > leading to fibrosis

Question 43

What is alcoholic cirrhosis?

Answer 43

webs of scars that link portal tracts > condensed into central-portal fibrous septa > nodule diffusion on surface

Question 44

What is rare about alcoholic cirrhosis?

Answer 44

It is rare because there is no to little regression

Question 45

How are hepatic tumors noticed?

Answer 45

epigastric fullness and discomfort/routine physical examination/radiographic

Question 46

What are examples of benign hepatic tumors?

Answer 46

Hemangioma and Hepatocellular Adenoma

Question 47

What are examples of Malignant tumors

Answer 47

Hepatoblastoma and Hepatocellular carcinoma

Question 48

What are hepatoocellular Adenoma

Answer 48

Benign neoplasm developing from hepatocytes

Question 49

What is hepatocellular adenoma associated with?

Answer 49

estrogen-containing oral contraceptives or androgen-containing steroid anabolic drugs

Question 50

What are hepatoblastomas?

Answer 50

most common liver tumor in early childhood > rarely occurring over age of 3

Question 51

What occurs in the tumor cells of Hepatoblastoma?

Answer 51

cells recapitulating the embryological stages of hepatic development

Question 52

What is the epithelial type of Hepatoblastoma?

Answer 52

fetal/small embryonal cells form structures vaguely > recapitulating liver development

Question 53

What is the mixed epithelial and mesenchymal type of Hepatoblastoma?

Answer 53

epithelial cell types + mesenchymal components like myofibroblastic

Question 54

What is Hepatocellular Carcinoma?

Answer 54

most common primary neoplasm in the liver > 85% of all primary liver malignant tumors > 5.4 % of all cancers

Question 55

What are the most common underlying factors in hepatocarcinogenesis?

Answer 55

Viral infections like HBV or HCV and toxic injuries