01: Liver Anatomy & Histology Flashcards
Classification of portal HTN
- 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
What is a bile canaliculus?
- 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.
Describe the basic organization of liver paranchyma
- Blood enters via portal vein & hepatic artery branches
- Blood enters sinusoids, flowing toward central veins
- Central veins connect with hepatic veins, which connect with the IVC
Describe the portal tract
Composed of hepatic artery, portal vein and bile duct. Surrounded by type 1 collagen.
Describe how mixing of portal venous and hepatic arterial blood occurs.
Hepatic artery branches give off small twigs which empty oxygenated arterial blood into periportal sinusoids directly outside the portal tract connective tissue.
What is the limiting plate of hepatocytes?
Ring of hepatocytes abutting the connective tissue of the portal triad. Region of inflammation & hepatocyte death in chronic hepatitis
What is interface hepatitis?
Inflammatory cells escaping beyond limiting plate area.
What liver disease disrupts the normal 1-cell architecture of hepatocyte plates/cords?
Cirrhosis
What is lipofuscin pigment?
“Wear & tear” debris located within phagolysosomes; more prominent in elderly patients (80yo+).
Describe the functional & structural heterogeneity of the liver.
- 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
What is the function of the stellate (ito) cell?
Resting fibroblast; stores vitamin A; when liver damage, release Vitamin A and cell becomes elongated and produces collagen.
What is the Space of Disse?
Sub-endothelial space between hepatocytes and central vein; no basement membrane, other than some type 3 collagen.
What is the function of the sieve plate?
Allows small molecules from the sinusoids to reach hepatocyte microvilli.
What is the function of the Pit (NK) cell?
Lymphocyte/tumor surviellance cell located in sinusoids.
What is the function of the Kupffer cell?
Very large macrophage within sinusoids; receives blood from the stool-filled GI tract and phagocytoses any bacteria, thus preventing it from reaching the heart.
What cell is shown below?
Stellate (ito) cell.
(Have triangular-shaped nuclei.)
How do stellate cells regulate blood flow?
Contract via endothelin.
Relax via NO.
May narrow the space between epithelial cells, thus reducing blood flow.
Name and list the function of the hepatocyte transporter proteins.
- Bile salt export pump (BSEP): pumps bile from hepatocyte to canaliculus
- Familial intrahepatic cholestasis-1 (FIC-1): phospholipid translocation across membranes
- 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
What is cholestasis?
Impaired bile secretion
How does sepsis cause cholestasis?
Gram (-) endotoxin (LPS) inhibits BSEP (nothing wrong with bile ducts themselves; bile simply stuck in hepatocytes)
Identify the markers in a liver function test (LFT).
- 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)
Describe normal hepatocyte turnover.
- 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
What is cirrhosis?
Abnormal regeneration of hepatocytes with abnormally thick cell plates; contains diffuse fibrosis + architecturally abnormal regenerative nodules.
Describe embryology of the liver.
- 3 weeks (22 days): Hepatic diverticulum (liver bud) forms out of foregut diverticulum into the septum transversum; **vitelline veins **begin to form.
- 26 days: Cystic bud (becomes GB + cystic duct) forms off foregut endoderm; vitelline veins form liver sinusoids.
- 7-8 weeks: Liver cords form (many cells thick); portal tracts form, iwth portal vein.
- 9-10 weeks: Bile duct plates (BDP) develop around portal tracts via differentiation of periportal hepatocytes.
- 23 weeks: Regression/remodeling of BDPs results in tubulogenesis and entry of bile duct; native bile duct present in each portal tract.
