Liver Pathology

Question 1

What is the portal triad made up of?

Answer 1

hepatic artery, portal vein, and bile duct.

Question 2

What does the liver do?

Answer 2

Is a heck good filter!

1. regulates most chemical levels in the blood.
2. excretes bile which is very important bc it carries away waste and breaks down fats.
3. very important organ in producing cholesterol, glucose into glycogen, and poisonous ammonia to urea.
4. clears/ filters blood

Question 3

what is cirrhosis?

Answer 3

A very bad liver disease; ascites in abdomen.
- if you get it in your 50-60s= very hard to stop damage.

Question 4

What cell is the liver made up of?

Answer 4

Hepatocytes.

Question 5

What do hepatocytes in normal liver look like?

Answer 5

They have round, centrally placed nuclei, prominent nucleoli, and granular cytoplasm (key to good, healthy liver).
Sometimes there can be binucleate hepatocyte.

Question 6

Describe the blood supply to the liver, along with flow of bile.
* Know the orientation and direction of blood and bile flow*

Answer 6

Blood supply TOWARDS the central vein come from 2 main sources:
1. Portal vein : 75% of blood supply
2. Hepatic artery: 25%

nutrient rich blood travel from the portal vein into the sinusoids then gets mixed in with oxygen rich blood form the hepatic artery and the mixed blood flows into the central vein.
While this is happening, the hepatocytes are making bile that goes through the bile canaliculi (parallel to the sinusoid and between hepatocytes) –> bile duct–> either gallbladder for storage or small intestine for digestion.

Question 7

What does the exchange of bile and blood do for the liver?

Answer 7

It helps hepatocytes filter out blood. If there are any problems with blood or bile duct = filter issues.

Question 8

Hepatic lobule vs Acinus

Answer 8

Hepatic lobule: an anatomical unit shaped like a hexagon, with a central vein in the middle and portal triads at the corners (6 of them), emphasizing blood flow from the triads to the central vein; is made up of hepatocytes.

Acinus: Shape: a functional unit that spans parts of multiple lobules (usually 2), divided into 3 zones based on the oxygen gradient, and describes how liver cells receive and process blood from the portal triads.
- Zone 1 (closest to the portal triad) is more involved in nutrient metabolism (like gluconeogenesis) and detoxification of nutrients, as it receives oxygen-rich blood.
- Zone 2 (intermediate).
- Zone 3 (closest to the central vein) is primarily involved in drug detoxification (via the cytochrome P450 system) and is more prone to damage due to the lower oxygen supply.

Question 9

What are sinusoids?
Describe its structure and the role of endothelial cells.
What are some of the cons to endothelial cells?

Answer 9

• They are the white spots around hepatocytes; they allow blood supply to go through the liver.
• Sinusoids are lined by a single layer of endothelial cells and transport blood from the PT to the CV.
• Endothelial cells are essential for filtering blood, facilitating nutrient exchange, supporting immune defense, and regulating blood flow through the liver.
• Because of how thin the endothelial layer is (1 cell thick), the sinusoids are very vulnerable to damage.

Question 10

Describe what happens during fibrosis.
Where would you see fibrosis?
When is it a very concerning issue? How doe sage play a factor?

Answer 10

• Collagen/ fibers take up space of sinusoid–> permanent scaring.
• You would see fatty/lipid droplets take the place of hepatocytes in the liver and damage to neighboring cell.
• Anyone over the age of 40 has a bit of lipid droplets in their liver. While we can afford to lose a couple of hepatocytes to the fatty droplets, it becomes a very big issue when this loss becomes chronic –> lots of damage if chronic and may even become irreversible (cirrhosis).

Question 11

What is a cholangiocyte?

Answer 11

biliary epithelial cell

Question 12

Where are bile ducts ?

Answer 12

They are around hepatocytes; they do not go into the sinusoid–> have own system.

Question 13

What is bile formation ?
What does it contain?
Why is it important?
** What’s important about bile secretion and where is it secreted?

Answer 13

• Is a specialized function of the liver.
• Bile contains bile acids GSH, phospholipids, cholesterol, organic anions, protein, metals, ions, and xenobiotics (lots of things).
• Importance: Formation is essential for the uptake of lipids, protection of the small intestines from oxidative insults, and excretion of endogenous and xenobiotic compounds.

** Secretion into the biliary ducts is an IMPORTANT step in toxicant clearance –> we want this to function so that our waste products get out of us. **

Question 14

What is bilirubin? Why is it important? Where is it processed?

What are the 2 types of bilirubin?

Answer 14

• It is a yellowish pigment that is produced during the normal breakdown of red blood cells (RBCs).
• It is a blood marker of decreased liver function.
• Is a waste product that’s produced by the breakdown of RBCs and is the end-product of heme metabolism.
  -Bilirubin is processed by the liver and helps in waste elimination.
• Elevated levels can indicate liver dysfunction or blood-related issues, leading to conditions like jaundice.

1. Unconjugated (indirect) bilirubin: Fat-soluble and initially formed; it travels to the liver bound to albumin.
2. Conjugated (direct) bilirubin: Water-soluble; formed in the liver, allowing it to be excreted in bile through the intestines or urine.

Question 15

Describe the process of bilirubin metabolism and excretion

Answer 15

refer to flow chart in notes

Question 16

Stages of liver disease:
normal liver, fatty liver, liver fibrosis, and liver cirrhosis.
What color would each of these stages have ?

Answer 16

normal: pale yellow (normal)
and then progressively getting darker as disease progresses. Cirrhosis is the darkest bc liver is basically dying at this point.

Question 17

What are the types of liver cells?

Answer 17

There are 4 types:
1. hepatocytes
2. hepatic stellate cell
3. Kupffer cell
4. sinusoidal endothelial cells

Question 18

What percentage of the liver do hepatocytes make up?

Answer 18

95%

Question 19

Describe hepatotoxicants.

Answer 19

Hepatotoxicants are substances that can cause damage to the liver (hepatotoxicity).
- These toxicants can lead to liver injury by affecting the liver’s normal function, potentially causing a range of issues from mild inflammation to severe liver failure.
- Hepatotoxicants can be chemicals, drugs, environmental toxins, or natural substances that are harmful to liver cells.

Question 20

Name the liver diseases discussed in class and their % in the US
- which can be ruled out by diagnostic testing?
- What’s difficult about diagnosing liver disease in older people?

Answer 20

1. Nonalcoholics fatty live disease or NAFLD- 59%
2. Hep B virus- 29%
3. Hep C virus- 9%
4. Alcoholic liver disease or ALD- 2%

• We can use diagnostic testing to rule out Hep B and C but not the other 2, we would have to trust patient history to help diagnose/ treat.
• Some of the symptoms of liver disease or cirrhosis are also symptoms of aging so hard to tell. Also people with fibrosis have normal lab results so hard to test for.

Question 21

What does ascites and encephalopathy do in terms of liver disease?

Answer 21

Ascites causes the sinusoids to close up –> fluid comes out where fluid shouldn’t.

Encephalopathy is brain damage due to toxin buildup/ toxin not getting filtered out of body –> confusion.

Question 22

Liver toxicants

Answer 22

There are many!

• Know at least one:
  Acetaminophen
  CCl4- mainly in 1960 fridges, some in metal degreasers and household products of old US, gone now in household stuff.
  Iron- iron overload problem in most kids.

Question 23

For the following phenotypes, what are their causative agents?

1. Necrosis
2. Fibrosis and Cirrhosis

Answer 23

1. Acetaminophen, allyl alcohol, ethanol, Fe, carboxyatractyloside, cresols, gossypol, alpha- amanitin, CCl4
2. CCl4, ethanol, vitamin A, vinyl chloride

Question 24

What are the clinical chemistry/ enzymes for liver function?

Answer 24

Aspartate Aminotransferase (AST)
Alanine Transferase (ALT)
Alkaline Phosphatase (ALP)

Question 25

Liver fibrosis and cirrhosis
- what are the causes

Answer 25

Fibrosis is the initial, potentially reversible stage of liver damage where there is an excessive accumulation of extracellular matrix proteins (ie collagen)–> causes scarring.

Cirrhosis is the advanced, irreversible state where the liver’s structure and function are significantly compromised due to extensive scarring.

Causes:
- chronic HCV infection
- alcohol abuse
- Nonalcoholic steatohepatitis (NASH): fatty lipid droplets

Question 26

Answer 26

Question 27

Acute hepatitis vs Chronic hepatitis

Answer 27

Acute:
- Hepatocyte ballooning and necrosis
- Cholestasis
- Steatosis
- Inflammatory infiltrates

Chronic:
- All of the above PLUS,
- Varying degrees of necrosis and fibrosis.
- Detected by presence of liver enzymes in the blood.

Question 28

What is jaundice?

Answer 28

Jaundice is characterized by the yellowing of the skin and eyes due to the accumulation of bilirubin, a breakdown product of hemoglobin from red blood cells.

Question 29

What are the 3 main types of jaundice based on where the dysfunction occurs:

Answer 29

1. Pre-Hepatic Jaundice (Acholuric Jaundice):
   Cause: Results from hemolysis (the excessive breakdown of red blood cells).
   Bilirubin type: Produces unconjugated (indirect) bilirubin, which is not water-soluble and cannot be excreted in the urine.–> Urine remains pale because unconjugated bilirubin does not appear in the urine.
   Example Conditions: Hemolytic anemia, malaria, or any condition that causes red blood cells to break down more rapidly than normal.
2. Hepatic Jaundice (Intrahepatic Jaundice):
   Cause: Due to hepatocellular injury (damage to liver cells) often caused by drugs, toxins, or liver disease.
   Bilirubin type:
   - Unconjugated (indirect) bilirubin can accumulate if the liver is damaged and cannot properly conjugate bilirubin.
   - Conjugated (direct) bilirubin can also accumulate if the bile flow within the liver is obstructed.
   Swelling or obstruction: Hepatocellular injury may lead to swelling or canicular obstruction in the bile ducts–> preventing the normal flow of bile.
   Example Conditions: Viral hepatitis, cirrhosis, or drug-induced liver damage.
3. Post-Hepatic Jaundice (Obstructive Jaundice):
   Cause: Due to biliary obstruction, where bile cannot flow from the liver to the intestines.
   Bilirubin type: Produces conjugated (direct) bilirubin, which is water-soluble and can be excreted in the urine.
   Urine: Urine may be dark or “colored” due to the presence of conjugated bilirubin.
   Example Conditions: Gallstones, tumors blocking the bile ducts, or pancreatic cancer.

Question 30

Steatosis and CCl4
-How was CCl4 used?

Steatosis and ethanol.

Answer 30

Carbon tetrachloride (CCl₄) is associated with steatosis (fatty liver) because it induces lipid accumulation in liver cells as part of its toxic effect on the liver.

Process of CCl4:
CCl4 + P450–> radical formation–> lipid peroxidation–> lipid aldehyde formation–> forms biomolecule adducts–> cell death.

• Historical use as solvent and industrial use persists.

Process of ethanol:
acetate formation–> fatty acid synthesis.
* Increased fatty acid synthesis due to chronic ethanol exposure leads to the accumulation of fat in liver cells, contributing to the development of steatosis.*

Question 31

What type of cell death is this?

Answer 31

Ballooning degeneration reflects severe hepatocyte stress or injury, seen in conditions like steatohepatitis or toxic liver injury.–> can lead to necrosis (caused by toxic/immunologic insult).

Question 32

What type of cell death is this?

Answer 32

Councilman bodies: hyaline body or apoptotic body, is an eosinophilic globule of apoptosis heterocyte cell fragments.
- are indicators of hepatocyte apoptosis, commonly associated with viral or immune-mediated liver diseases.

Question 33

What is the leading cause of poisoning deaths in children younger than 6 yrs old?

Answer 33

Hemochromatosis (iron overload)
iron-generated oxyradicals and lipid per oxidation –> damage to mitochondria and lysosomes. –> death by liver failure.

Question 34

which takes longer, apoptosis or necrosis?

Answer 34

takes longer for cells to go apoptotic than necrotic

Question 35

What are the clinical chemistry for liver function? What do they look like when there is liver dysfunction (simplified)

Answer 35

Question 36

Once you have cirrhosis, about how much time do you have.

Answer 36

no more than 10 years–> can’t do transplant bc liver is pretty much dead and the other organs are going into failure.

Question 37

Explain what cirrhosis does that’s so bad.

Answer 37

Chronic fibrosis –> cirrhosis which results in excessive formation of extracellular matrix proteins (of collagen formation)–> clogs up white space between lumen and hepatocyte–> hepatocytes can’t communicate with many things and blood flow stops.

Question 38

There is an apoptotic body, what is happening in the tissue?

Answer 38

An apoptotic body indicates that a cell is undergoing apoptosis, which is a controlled process of cell death. The cell is breaking down into small, membrane-bound fragments (apoptotic bodies) that will be safely cleared by neighboring cells or immune cells, without causing inflammation or damage to the surrounding tissue.

Question 39

Describe these liver
tissue histos

Answer 39