Liver Pathophysiology Flashcards
What is gradually occuring in this photo?
- Loss of structure from R->L in Hepatocytes
- Zone 1 Necrosis
Identify green and red
Green - endothelial cell
Red - sinusoid containing RBC
What happens to Zone 1 if it is exposed to too much oxygen?
- Zone 1 becomes more prone to oxidative stress due to the overproduction of ROS.
Name 2-3 things that can cause ballooning?
- NAFLD: excessive fat in liver -> cellular stress
-> cellular injury and swelling - Oxidative Stress: overproduction of ROS -> swelling -> death
- Toxins/Drug
What type of metabolism does Zone 3 rely on?
- **Zone 3 **relies more on anaerobic glycolysis due to the lower oxygen levels compared to Zone 1.
Why is Zone 3 more prone to hypoxic injury?
- Zone 3 has the lowest oxygen levels because it is furthest from the blood supply, making it more susceptible to hypoxia.
Why is Zone 3 more vulnerable to damage from reactive metabolites?
- Low oxygen levels in Zone 3 make it harder for the cells to neutralize reactive metabolites, leading to **oxidative stress **and cell damage.
What is the role of the liver?
- 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)
What is conjugated bilirubin?
- Water-soluble
- Processed by the liver and excreted into bile
Why is Zone 1 the first to encounter toxins and oxygen in the liver?
- Zone 1 is closest to the** portal triad**, where blood from the hepatic artery and portal vein enters the liver.
What is the main cause of oxidative stress in Zone 1?
- High oxygen levels leading to the overproduction of reactive oxygen species (ROS), which need to be neutralized by antioxidants like glutathione.
What is the role of the bile duct in the portal triad?
- The bile duct transports bile produced by hepatocytes out of the liver to the gallbladder or small intestine for digestion
What is the role of glutathione in Zone 1?
- Glutathione is an antioxidant that neutralizes ROS, protecting liver cells from oxidative stress.
What are the two blood sources that flow into the liver lobule, and where do they come from?
- Blood from the hepatic artery (oxygenated) and portal vein (deoxygenated, nutrient-rich) flows into the lobule via the sinusoids -> to the central vein
What is unconjugated bilirubin?
- Fat-soluble
- Not processed by the liver and cannot be excereted
What is the primary function of Zone 3 in the liver?
- Detoxification via the cytochrome P450 enzyme system
What are the key features of acute hepatitis
Acute Hepatitis
* short term inflammation
* ballooning, necrosis, and inflammation around the PT
* reversible
Fibrosis vs Cirrhosis
Fibrosis: first tissue injury, turns into scar tissue, its reversible
Cirrhosis: follows fibrosis, severe, irreversible, scar tissue affects liver function
Identify both reds
Left to right: CV -> PT
What could high levels of conjugated bilirubin in the blood indicate?
- Liver or bile ducts dysfunction
What are the key features of apoptosis
- Organized, needs ATP, does not cause inflammation
What are sinusoids, and what is their role in the liver lobule?
- Specialized capillaries where blood from the hepatic artery and portal vein mixes and is filtered by hepatocytes before flowing into the central vein
What is the portal triad made up of?
- Hepatic Artery
- Portal Vein
- Bile Duct
What is an acinus, and what are its zones?
- 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)
What are the key features of chronic hepatitis
Chronic Hepatitis
* long term inflammation
* necrosis, apoptosis, fibrosis
* irreversible
What are the arrows pointing at?
Bile duct
What are the key features of necrosis
- Unorganized, no ATP, and causes inflammation
What are features of healthy hepatocytes?
- granular cytoplasm
- round and prominent centrally placed nuclei
- sometimes can be binucleated
How does cytochrome P450 in Zone 3 contribute to liver damage during an overdose?
- Cytochrome P450 produces reactive metabolites when detoxifying substances, and in excess, these metabolites can cause** cell damage **if not neutralized.
Identify black and red
Red - Sinusoids
Black - Central Vein
This is not the control. What is this H& E stain showing us?
- Liver Fibrosis & Cirrhosis
- Fibrosis is reversible
- Cirrhosis is not reversible
