Carbohydrate and Glucose Metabolism
| State | Hepatic Response | Key Hormones |
|---|---|---|
| Fed state (postprandial) | Glycogenesis (glucose to glycogen storage); lipogenesis; glycolysis | Insulin (dominant); promotes GLUT2 uptake |
| Fasting (early) | Glycogenolysis (glycogen breakdown → glucose release) | Glucagon; epinephrine |
| Prolonged fasting | Gluconeogenesis (amino acids, lactate, glycerol → glucose) | Glucagon, cortisol |
| Stress / catabolism | Increased gluconeogenesis; decreased glycogen synthesis | Cortisol, epinephrine, glucagon |
⭐ Boards PearlThe liver is the only organ that releases glucose into the blood (via glucose-6-phosphatase). Muscle glycogen is used only by muscle (no G6Pase). In liver failure, gluconeogenesis fails → fasting hypoglycemia.
Lipid Metabolism
- Fatty acid synthesis — occurs in cytoplasm in the fed state (insulin promotes); uses acetyl-CoA from glucose; stored as triglycerides in liver or exported as VLDL
- Beta-oxidation — fatty acids broken down to acetyl-CoA for energy in fasting/starvation; occurs in mitochondria
- Ketogenesis — excess acetyl-CoA (prolonged starvation, DKA) → ketone bodies (acetoacetate, beta-hydroxybutyrate); used by brain and muscle
- Cholesterol synthesis — rate-limiting step: HMG-CoA reductase (target of statins)
- Lipoprotein production — liver synthesizes VLDL, IDL, HDL; converts IDL to LDL
🩹 Non-Alcoholic Fatty Liver Disease (NAFLD)Excess hepatic lipogenesis (insulin resistance) → triglyceride accumulation in hepatocytes → steatosis → NASH (with inflammation) → fibrosis → cirrhosis. Associated with metabolic syndrome (obesity, DM, HTN, dyslipidemia).
Protein Synthesis and Nitrogen Metabolism
| Protein | Function | Clinical Note |
|---|---|---|
| Albumin | Oncotic pressure, drug/hormone binding, transport | Half-life 20 days; low in malnutrition, liver failure, nephrotic syndrome, chronic inflammation |
| Clotting factors | Coagulation cascade (all factors except VIII and vWF) | PT/INR elevated in liver failure; Vitamin K needed for factors II, VII, IX, X |
| Fibrinogen | Converted to fibrin by thrombin | Acute-phase reactant; decreased in DIC and liver failure |
| SHBG, TBG, CBG | Bind sex hormones, thyroid hormones, cortisol | Decreased in cirrhosis → altered hormone distribution |
| Urea cycle | Converts ammonia → urea for excretion | Liver failure → hyperammonemia → hepatic encephalopathy |
Bile Production and Bilirubin Metabolism
Bilirubin pathway: Heme (from RBC breakdown) → unconjugated bilirubin (lipid-soluble, bound to albumin) → liver → conjugated bilirubin (water-soluble, glucuronyl transferase) → bile → gut → urobilinogen (urine) or stercobilin (stool brown color).
| Type | Elevated In | Urine Bilirubin | Urine Urobilinogen |
|---|---|---|---|
| Pre-hepatic (hemolysis) | Unconjugated | Absent (can't be filtered) | Increased |
| Hepatic (hepatitis, cirrhosis) | Both | Present | Variable |
| Post-hepatic (bile duct obstruction) | Conjugated | Present (dark urine) | Decreased (pale stool) |
Detoxification and Drug Metabolism
The liver metabolizes drugs and toxins primarily via CYP450 enzymes (Phase I: oxidation/reduction/hydrolysis) and conjugation reactions (Phase II: glucuronidation, sulfation, acetylation). Phase I often activates intermediates; Phase II makes them water-soluble for excretion.
⭐ CYP450 Inducers and Inhibitors (High Yield)Inducers (increase CYP → decrease drug levels): Rifampin, Carbamazepine, Phenytoin, Phenobarbital, St. John's Wort, Griseofulvin, Chronic EtOH. Inhibitors (decrease CYP → increase drug levels/toxicity): Cimetidine, Grapefruit juice, Erythromycin, Ketoconazole, Isoniazid, Acute EtOH. Mnemonic: "QRPCPS" for inducers vs. "CAGE KID" for inhibitors.
Clinical Pearls
⭐ LFT InterpretationAST and ALT (transaminases): hepatocellular injury. ALT is more liver-specific. AST:ALT ratio greater than 2 suggests alcoholic hepatitis. ALP and GGT: cholestatic pattern (bile duct obstruction, PBC, PSC). Total bilirubin: all causes of jaundice. Albumin and PT: synthetic function (chronic liver disease severity).
🧐 Child-Pugh ScoreAssesses cirrhosis severity using: Bilirubin, Albumin, PT/INR, Ascites, Encephalopathy. "BAAE" — Bilirubin, Albumin, Ascites, Encephalopathy. Class A (5-6) = well-compensated; Class C (10-15) = decompensated.