Liver Pathophysiology

Question 1

What is gradually occuring in this photo?

Answer 1

• Loss of structure from R->L in Hepatocytes
• Zone 1 Necrosis

Question 2

Identify green and red

Answer 2

Green - endothelial cell
Red - sinusoid containing RBC

Question 3

What happens to Zone 1 if it is exposed to too much oxygen?

Answer 3

• Zone 1 becomes more prone to oxidative stress due to the overproduction of ROS.

Question 4

Name 2-3 things that can cause ballooning?

Answer 4

• NAFLD: excessive fat in liver -> cellular stress
  -> cellular injury and swelling
• Oxidative Stress: overproduction of ROS -> swelling -> death
• Toxins/Drug

Question 5

What type of metabolism does Zone 3 rely on?

Answer 5

• **Zone 3 **relies more on anaerobic glycolysis due to the lower oxygen levels compared to Zone 1.

Question 6

Why is Zone 3 more prone to hypoxic injury?

Answer 6

• Zone 3 has the lowest oxygen levels because it is furthest from the blood supply, making it more susceptible to hypoxia.

Question 7

Why is Zone 3 more vulnerable to damage from reactive metabolites?

Answer 7

• Low oxygen levels in Zone 3 make it harder for the cells to neutralize reactive metabolites, leading to **oxidative stress **and cell damage.

Question 8

What is the role of the liver?

Answer 8

• Regulates most chemical levels in the blood
• Excretes bile, helps break down fat
• Produces cholesterol, converts glucose into glycogen
• Converts ammonia (toxic by product) to urea (excreted through urine)

Question 9

What is conjugated bilirubin?

Answer 9

• Water-soluble
• Processed by the liver and excreted into bile

Question 10

Why is Zone 1 the first to encounter toxins and oxygen in the liver?

Answer 10

• Zone 1 is closest to the** portal triad**, where blood from the hepatic artery and portal vein enters the liver.

Question 11

What is the main cause of oxidative stress in Zone 1?

Answer 11

• High oxygen levels leading to the overproduction of reactive oxygen species (ROS), which need to be neutralized by antioxidants like glutathione.

Question 12

What is the role of the bile duct in the portal triad?

Answer 12

• The bile duct transports bile produced by hepatocytes out of the liver to the gallbladder or small intestine for digestion

Question 13

What is the role of glutathione in Zone 1?

Answer 13

• Glutathione is an antioxidant that neutralizes ROS, protecting liver cells from oxidative stress.

Question 14

What are the two blood sources that flow into the liver lobule, and where do they come from?

Answer 14

• Blood from the hepatic artery (oxygenated) and portal vein (deoxygenated, nutrient-rich) flows into the lobule via the sinusoids -> to the central vein

Question 15

What is unconjugated bilirubin?

Answer 15

• Fat-soluble
• Not processed by the liver and cannot be excereted

Question 16

What is the primary function of Zone 3 in the liver?

Answer 16

• Detoxification via the cytochrome P450 enzyme system

Question 17

What are the key features of acute hepatitis

Answer 17

Acute Hepatitis
* short term inflammation
* ballooning, necrosis, and inflammation around the PT
* reversible

Question 18

Fibrosis vs Cirrhosis

Answer 18

Fibrosis: first tissue injury, turns into scar tissue, its reversible

Cirrhosis: follows fibrosis, severe, irreversible, scar tissue affects liver function

Question 19

Identify both reds

Answer 19

Left to right: CV -> PT

Question 20

What could high levels of conjugated bilirubin in the blood indicate?

Answer 20

• Liver or bile ducts dysfunction

Question 21

What are the key features of apoptosis

Answer 21

• Organized, needs ATP, does not cause inflammation

Question 22

What are sinusoids, and what is their role in the liver lobule?

Answer 22

• Specialized capillaries where blood from the hepatic artery and portal vein mixes and is filtered by hepatocytes before flowing into the central vein

Question 23

What is the portal triad made up of?

Answer 23

• Hepatic Artery
• Portal Vein
• Bile Duct

Question 24

What is an acinus, and what are its zones?

Answer 24

• The acinus is the functional unit of the liver with three zones:

Zone 1: Closest to the portal triad (most oxygenated)

Zone 2: Intermediate zone

Zone 3: Closest to the central vein (least oxygenated)

Question 25

What are the key features of chronic hepatitis

Answer 25

Chronic Hepatitis
* long term inflammation
* necrosis, apoptosis, fibrosis
* irreversible

Question 26

What are the arrows pointing at?

Answer 26

Bile duct

Question 27

What are the key features of necrosis

Answer 27

• Unorganized, no ATP, and causes inflammation

Question 28

What are features of healthy hepatocytes?

Answer 28

• granular cytoplasm
• round and prominent centrally placed nuclei
• sometimes can be binucleated

Question 29

How does cytochrome P450 in Zone 3 contribute to liver damage during an overdose?

Answer 29

• Cytochrome P450 produces reactive metabolites when detoxifying substances, and in excess, these metabolites can cause** cell damage **if not neutralized.

Question 30

Identify black and red

Answer 30

Red - Sinusoids
Black - Central Vein

Question 31

This is not the control. What is this H& E stain showing us?

Answer 31

• Liver Fibrosis & Cirrhosis
• Fibrosis is reversible
• Cirrhosis is not reversible