Gross Anatomy
The liver is the largest internal organ (~1500 g) located in the right upper quadrant under the diaphragm. It has four lobes: right (largest), left, caudate, and quadrate.
Lobar Anatomy
- Falciform ligament — separates right and left lobes on anterior surface; contains ligamentum teres (remnant of umbilical vein)
- Porta hepatis — hilum containing portal vein, hepatic artery, and bile duct (portal triad)
- Bare area — peritoneum-free area on posterior surface in direct contact with the diaphragm
Blood Supply
| Vessel | % O₂ Supply | % Blood Flow | Notes |
|---|---|---|---|
| Portal vein | 50-60% | ~75% | Nutrient-rich blood from GI tract and spleen |
| Hepatic artery | 40-50% | ~25% | Branch of celiac trunk; O₂-rich |
The liver has dual blood supply — portal hypertension results when portal venous pressure rises, causing varices, splenomegaly, and ascites.
Microscopic Anatomy
Hepatic Lobule
Classic hexagonal lobule with central vein and portal triads at each corner. Hepatocytes radiate from the central vein in cords/plates.
Acinar Zones (Rappaport)
| Zone | Location | O₂ Level | Vulnerable To |
|---|---|---|---|
| Zone 1 | Near portal triad | Highest | Toxic injury (phosphorus, beryllium) |
| Zone 2 | Intermediate | Intermediate | Yellow fever necrosis |
| Zone 3 | Near central vein | Lowest | Ischemic necrosis; acetaminophen; alcohol |
Zone 3 (centrilobular) = acetaminophen toxicity, alcoholic liver disease, ischemic hepatitis. Zone 1 = toxic damage from phosphorus, beryllium, salicylates.
Key Cell Types
- Hepatocytes — main metabolic/synthetic cells; 80% of liver mass
- Kupffer cells — resident macrophages in sinusoids
- Stellate (Ito) cells — store vitamin A; activated → collagen → fibrosis
- Space of Disse — perisinusoidal space between hepatocytes and endothelium
"Ito = Italian sculptor" — stellate cells sculpt/scar the liver. Store fat+vitamin A normally; when activated produce collagen causing fibrosis.
Function
- Carbohydrate metabolism — glycogenesis, glycogenolysis, gluconeogenesis
- Protein synthesis — albumin, clotting factors (I, II, V, VII, IX, X, XI), complement, transport proteins
- Lipid metabolism — FA oxidation, ketogenesis, VLDL synthesis, cholesterol synthesis
- Detoxification — CYP450 system; first-pass metabolism; ammonia → urea
- Bile production — ~600-1000 mL/day; bile salts emulsify dietary fats
- Storage — glycogen, TG, vitamins A, D, E, K, B12, iron (ferritin)
Bilirubin Pathway
| Step | Location | Form | Transport |
|---|---|---|---|
| Heme breakdown | Spleen/macrophages | Unconjugated (indirect) | Bound to albumin |
| Conjugation | Hepatocytes (UGT1A1) | Conjugated (direct) | Water-soluble |
| Excretion | Bile → gut → urobilinogen | Stercobilin/urobilin | Stool/urine |
Ethanol Metabolism
- Alcohol dehydrogenase (ADH) — Ethanol → Acetaldehyde → Acetate (ALDH)
- Microsomal ethanol-oxidizing system (MEOS) — CYP2E1; produces free radicals; inducible
Alcohol ↑ NADH/NAD+ ratio → inhibits gluconeogenesis (hypoglycemia) + FA oxidation → fatty liver. Acetaldehyde is directly hepatotoxic. Progression: Steatosis → Alcoholic hepatitis (AST:ALT >2:1) → Cirrhosis → HCC.
Embryology
Liver develops from the hepatic diverticulum of foregut endoderm at ~week 4.
- Hepatic bud → hepatocytes + intrahepatic bile ducts
- Septum transversum mesoderm → Kupffer cells, stellate cells, connective tissue
- Ligamentum teres — remnant of umbilical vein
- Ligamentum venosum — remnant of ductus venosus
"Liver = Foregut" — hepatic diverticulum grows from foregut at week 4. Liver and pancreas both bud off the foregut simultaneously.
Clinical Pearls
| Condition | Key Features | Lab Clue |
|---|---|---|
| Hepatitis A | Fecal-oral; self-limited; no chronic form | Anti-HAV IgM (acute) |
| Hepatitis B | Blood/sexual; can be chronic; HBsAg+ | HBsAg, HBeAg, anti-HBc |
| Hepatitis C | Mostly chronic; leads to cirrhosis/HCC | Anti-HCV Ab; RNA PCR |
| Alcoholic hepatitis | Fatty change, neutrophils, Mallory bodies | AST:ALT >2:1; ↑GGT |
| Wilson disease | Copper; Kayser-Fleischer rings | ↓ceruloplasmin; ↑urine Cu |
| Hemochromatosis | Iron overload; bronze diabetes | ↑ferritin, ↑transferrin sat. |
Child-Pugh (Bilirubin, Albumin, PT/INR, Ascites, Encephalopathy) assesses cirrhosis severity. MELD score predicts 90-day mortality and is used for transplant prioritization.