01: Liver Anatomy & Histology

Question 1

Classification of portal HTN

Answer 1

• Pre-hepatic (2/2 portal vein thrombosis)
• Intrahepatic (2/2 cirrhosis)
• Post-hepatic (2/2 congenital web of IVC)

NB: Dx w/ pressure > 10 mmHg

Question 2

What is a bile canaliculus?

Answer 2

• Thin tube that collects bile secreted by hepatocytes; merge and form bile ductules, which eventually become common hepatic duct.
• Modifications of two adjacent hepatocytes, with tight junctions on either sides to prevent the leaking of bile into blood.
• Receive bile from hepatocytes via transporter proteins.

Question 3

Describe the basic organization of liver paranchyma

Answer 3

1. Blood enters via portal vein & hepatic artery branches
2. Blood enters sinusoids, flowing toward central veins
3. Central veins connect with hepatic veins, which connect with the IVC

Question 4

Describe the portal tract

Answer 4

Composed of hepatic artery, portal vein and bile duct. Surrounded by type 1 collagen.

Question 5

Describe how mixing of portal venous and hepatic arterial blood occurs.

Answer 5

Hepatic artery branches give off small twigs which empty oxygenated arterial blood into periportal sinusoids directly outside the portal tract connective tissue.

Question 6

What is the limiting plate of hepatocytes?

Answer 6

Ring of hepatocytes abutting the connective tissue of the portal triad. Region of inflammation & hepatocyte death in chronic hepatitis

Question 7

What is interface hepatitis?

Answer 7

Inflammatory cells escaping beyond limiting plate area.

Question 8

What liver disease disrupts the normal 1-cell architecture of hepatocyte plates/cords?

Answer 8

Cirrhosis

Question 9

What is lipofuscin pigment?

Answer 9

“Wear & tear” debris located within phagolysosomes; more prominent in elderly patients (80yo+).

Question 10

Describe the functional & structural heterogeneity of the liver.

Answer 10

• Periportal (zone 1): the seven cells surrounding the portal tract; responsible for gluconeogenesis and bile salt synthesis; NH3 metabolism to urea (using **OTC **& PTS enzymes); inflammed in chronic hepatitis; PO2 = 65mmHg
• Midzonal (zone 2)
• Centrilobular (zone 3): the seven cell surrounding the central vein; contains drug-metabolizing enzymes and glutamine synthetase (last enzyme of urea cycle); most vulnerable to shock/ischemia; PO2 = 35mmHg

Question 11

What is the function of the stellate (ito) cell?

Answer 11

Resting fibroblast; stores vitamin A; when liver damage, release Vitamin A and cell becomes elongated and produces collagen.

Question 12

What is the Space of Disse?

Answer 12

Sub-endothelial space between hepatocytes and central vein; no basement membrane, other than some type 3 collagen.

Question 13

What is the function of the sieve plate?

Answer 13

Allows small molecules from the sinusoids to reach hepatocyte microvilli.

Question 14

What is the function of the Pit (NK) cell?

Answer 14

Lymphocyte/tumor surviellance cell located in sinusoids.

Question 15

What is the function of the Kupffer cell?

Answer 15

Very large macrophage within sinusoids; receives blood from the stool-filled GI tract and phagocytoses any bacteria, thus preventing it from reaching the heart.

Question 16

What cell is shown below?

Answer 16

Stellate (ito) cell.

(Have triangular-shaped nuclei.)

Question 17

How do stellate cells regulate blood flow?

Answer 17

Contract via endothelin.

Relax via NO.

May narrow the space between epithelial cells, thus reducing blood flow.

Question 18

Name and list the function of the hepatocyte transporter proteins.

Answer 18

1. Bile salt export pump (BSEP): pumps bile from hepatocyte to canaliculus
2. Familial intrahepatic cholestasis-1 (FIC-1): phospholipid translocation across membranes
3. Organic anion transport pump (OATP): reuptake of organic anions from blood on basolateral surface (sinusoid side)

NB: inhibition of these transporters –> inhibited bile excretion –> jaundice

Question 19

What is cholestasis?

Answer 19

Impaired bile secretion

Question 20

How does sepsis cause cholestasis?

Answer 20

Gram (-) endotoxin (LPS) inhibits BSEP (nothing wrong with bile ducts themselves; bile simply stuck in hepatocytes)

Question 21

Identify the markers in a liver function test (LFT).

Answer 21

• CHOLESTATIC ENZYMES
  
  • Total bilirubin/direct (conjugated) bilirubin
  • **Alkaline phosphatase (AP) **(NB: cannot distinguish btw abnl 2/2 liver or bone, therefore measure GGT as well)
  • Gamma glutamyl transferase (GGT)
• HEPATIC ENZYMES
  
  • Aspartate aminotransferase (AST)
  • Alanine aminotransferase (ALT)
• SYNTHETIC PROTEINS
  
  • Total protein
  • Albumin
  • Clotting factors (I, II, V, VII, IX)

Question 22

Describe normal hepatocyte turnover.

Answer 22

• Divide every 400 days (capable of ~70 divisions)
• Able to regenerate after cell injury (e.g., in hepatitis)
• In case of severe loss of tissue, regenerated by progenitor cell activation (e.g., in fulminant hepatitis); inadequate replacement; transplant necessary

Question 23

What is cirrhosis?

Answer 23

Abnormal regeneration of hepatocytes with abnormally thick cell plates; contains diffuse fibrosis + architecturally abnormal regenerative nodules.

Question 24

Describe embryology of the liver.

Answer 24

1. 3 weeks (22 days): Hepatic diverticulum (liver bud) forms out of foregut diverticulum into the septum transversum; **vitelline veins **begin to form.
2. 26 days: Cystic bud (becomes GB + cystic duct) forms off foregut endoderm; vitelline veins form liver sinusoids.
3. 7-8 weeks: Liver cords form (many cells thick); portal tracts form, iwth portal vein.
4. 9-10 weeks: Bile duct plates (BDP) develop around portal tracts via differentiation of periportal hepatocytes.
5. 23 weeks: Regression/remodeling of BDPs results in tubulogenesis and entry of bile duct; native bile duct present in each portal tract.