Intro to the Liver

Liver blood supply

Dual supply: hepatic artery (oxygenated) + portal vein (nutrient-rich)

Portal triad components

Portal venule, hepatic arteriole, bile duct

Hepatic lobule blood flow direction

From portal triad → sinusoids → central vein

Bile flow direction

From hepatocytes → canaliculi → bile ducts (opposite blood flow)

Hepatocyte functions

Protein synthesis, metabolism, detoxification, bile formation

Endothelial cell features

Fenestrated, allow plasma filtration into Space of Disse

Kupffer cell function

Resident macrophages, phagocytosis, immune surveillance

Stellate (Ito) cell function

Vitamin A storage

Pit cell function

NK lymphocytes for immune surveillance

Space of Disse

Site of nutrient exchange between blood and hepatocytes, liver regeneration

Sinusoidal oxygen gradient

Highest O₂ in Zone 1, lowest in Zone 3

Zone 1 functions

Gluconeogenesis, glycogenolysis, fatty acid β-oxidation, urea cycle(NH3 detox), protein synthesis, bile formation

Zone 3 functions

Glycogen synthesis, Glycolysis, lipogenesis, drug metabolism (CYP450), glutamine synthesis, hormone deactivation

Portal hypertension mechanism

Fibrosis → ↑ portal–venous gradient → ↑ lymph → ascites

Ascites formation

Lymph production exceeds lymphatic drainage due to cirrhosis

Vitamin storage in liver

Vitamins A, D, B12

Bilirubin source

Breakdown of heme from senescent RBCs

Heme → biliverdin enzyme

Heme oxygenase

Biliverdin → bilirubin enzyme

Biliverdin reductase

Unconjugated bilirubin transport

Bound to albumin in plasma

Bilirubin conjugation enzyme

UDP‑glucuronyl transferase (UDP‑GT)

Conjugated bilirubin transporter into bile

MRP2

Emergency bilirubin efflux transporter

MRP3

Bilirubin → urobilinogen location

Intestinal bacterial metabolism of glucose on the bilirubin

Urobilinogen fates

Reabsorbed → urine (urobilin) OR feces (stercobilin)

Unconjugated hyperbilirubinemia causes

Hemolysis, Gilbert syndrome, Crigler‑Najjar, neonatal jaundice

Conjugated hyperbilirubinemia causes

Dubin‑Johnson, Rotor, cholestasis

Mixed hyperbilirubinemia causes

Hepatocellular injury, bile duct obstruction

Hemolytic anemia bilirubin pattern + cause

↑ total bili, normal direct, ↑ urobilinogen, no urine bilirubin; all caused by a decreased RBC lifespan and inc RBC destruction

Gilbert syndrome defect

↓ UDP‑GT activity (~25% normal)

Gilbert syndrome features

Mild jaundice during stress/fasting

Crigler‑Najjar type I defect

Absent UDP‑GT

Crigler‑Najjar type I features

Severe unconjugated hyperbilirubinemia, kernicterus risk

Crigler‑Najjar type II defect

~10% UDP‑GT activity

Crigler‑Najjar type II treatment

Phenobarbital (induces UDP‑GT) + phototherapy

Neonatal jaundice cause

Delayed UDP‑GT activity

Phototherapy mechanism

Converts bilirubin to water‑soluble isomers excreted without conjugation

Dubin‑Johnson syndrome defect

MRP2 transporter deficiency

Dubin‑Johnson features

Conjugated hyperbilirubinemia, black liver, benign

Rotor syndrome defect

OATP transporter defect (sinusoidal uptake)

Rotor syndrome features

Bilirubin has difficulty getting into and stored in liver cell via OATP “door” defect» will travel to blood stream »Conjugated hyperbilirubinemia, normal liver pigmentation

Urine bilirubin significance

Indicates conjugated bilirubin (water‑soluble)

Urine urobilinogen significance

Elevated in hemolysis

Cholestasis bilirubin pattern

↑ direct bilirubin, pale stools, dark urine

Portal vein function

Delivers nutrient‑rich blood from GI tract to liver