Makindo Medical Notes

Related Subjects: |Cardiac Physiology |Renal Physiology |Liver Physiology |Pulmonary Physiology |Pancreas Physiology |Spleen Physiology |Gastrointestinal tract Physiology |Brainstem Physiology |Bone Physiology

🧠🧪 The liver is a metabolic “command centre”: it buffers blood glucose, packages and redistributes fats, synthesises key proteins (albumin, clotting factors), produces bile for fat absorption, and detoxifies endogenous and exogenous compounds. Because it sits between the gut and systemic circulation via the portal vein, it is uniquely positioned to regulate what reaches the body.

🧭 Key Concepts

• 🧩 Anatomy & microanatomy
  • 📍 Located in the right upper quadrant, protected by the rib cage; divided into lobes (right, left, caudate, quadrate).
  • 🧱 Functional architecture:
    • Hepatic lobule: plates of hepatocytes arranged around a central vein.
    • Portal triad at the periphery: portal venule, hepatic arteriole, bile ductule.
    • 🩸 Sinusoids lined by fenestrated endothelium allow exchange; Kupffer cells (macrophages) clear bacteria/endotoxin.
    • 🧬 Space of Disse: interface for exchange; stellate (Ito) cells store vitamin A and drive fibrosis when activated.
  • 🌡️ “Zonation” matters clinically:
    • Zone 1 (periportal): best oxygenation; first to see toxins from portal blood.
    • Zone 3 (centrilobular): lowest oxygen; rich in CYP450 → vulnerable to ischaemia and some drug/toxin injury.
• 🩸 Blood supply & flow
  • 🔀 Dual inflow:
    • 🫀 Hepatic artery (oxygen-rich; ~25% of flow).
    • 🍽️ Portal vein (nutrient-rich; ~75% of flow).
  • ➡️ Outflow via hepatic veins to the IVC.
  • 📈 Clinical link: raised portal resistance (e.g. cirrhosis) → portal hypertension (varices, ascites, splenomegaly).
• ⚙️ Metabolic functions
  • 🍞 Carbohydrate metabolism
    • 🍬 Glycogenesis: stores glucose as glycogen after meals (insulin-driven).
    • 🔓 Glycogenolysis: releases glucose during fasting (glucagon/adrenaline).
    • 🧪 Gluconeogenesis: makes glucose from lactate, glycerol, and amino acids during prolonged fasting/illness.
    • 🧠 Clinical link: liver failure → impaired gluconeogenesis → hypoglycaemia risk, especially in sepsis/alcohol misuse.
  • 🧈 Lipid metabolism
    • 🧱 Synthesises cholesterol (membranes; steroid hormones; bile acids).
    • 🚚 Packages fats into lipoproteins (VLDL export; HDL handling).
    • 🔥 β-oxidation produces energy; during fasting forms ketone bodies (alternative fuel).
    • 🧩 Clinical link: insulin resistance → ↑ hepatic fat storage → MASLD/NAFLD.
  • 🥚 Protein & nitrogen metabolism
    • 🧴 Produces albumin (oncotic pressure; drug binding) and many transport proteins.
    • 🩸 Produces most clotting factors (II, VII, IX, X, fibrinogen) and anticoagulants (protein C/S) → explains coagulopathy in liver disease.
    • 🧪 Urea cycle: converts ammonia to urea for renal excretion (critical for neuroprotection).
    • 🧠 Clinical link: urea cycle failure → ↑ ammonia → astrocyte swelling and neurotransmitter changes → hepatic encephalopathy.
• 🧫 Detoxification & biotransformation
  • 🏭 Makes compounds more water-soluble for excretion in bile/urine.
  • 🧪 Phase I (CYP450): oxidation/reduction/hydrolysis — may activate or create reactive metabolites.
  • 🧴 Phase II: conjugation (glucuronidation, sulphation, glutathione) → safer, excretable metabolites.
  • 🍺 Clinical link: chronic alcohol induces CYP2E1 → alters drug metabolism; paracetamol toxicity worsens when glutathione depleted.
• 🟡 Bile production & bilirubin handling
  • 🧪 Hepatocytes produce bile; bile flows opposite to blood (from hepatocytes → canaliculi → bile ducts).
  • 🧈 Bile acids emulsify fats and enable absorption of fat-soluble vitamins (A, D, E, K).
  • 🟠 Bilirubin pathway:
    • RBC breakdown → unconjugated bilirubin (albumin-bound) → hepatic uptake.
    • Conjugation (UGT) → conjugated bilirubin → excreted into bile.
  • 🔎 Clinical link: cholestasis → ↑ ALP/GGT, pruritus, fat malabsorption, vitamin K deficiency.
• 🏦 Storage & immune functions
  • 📦 Stores glycogen; vitamins A, D, B12; minerals iron (ferritin/haemosiderin) and copper.
  • 🛡️ Kupffer cells clear bacteria from portal blood → important barrier against gut translocation.
  • 🧪 Produces acute-phase proteins (e.g. CRP) in inflammation.

🔬 Detailed “process” examples (high-yield physiology)

• ♻️ Lactate recycling (Cori cycle): lactate from muscle/RBCs → liver converts to glucose → supports exercise and fasting physiology.
• 🧪 Ammonia detoxification: gut bacteria/protein load → ammonia → urea cycle; failure contributes to encephalopathy.
• 🧯 Drug metabolism: first-pass effect for many oral drugs; cirrhosis can increase bioavailability → dose adjustment often needed.

🩺 Clinical relevance (how physiology shows up on the ward)

• 🦠 Hepatitis
  • Hepatocellular injury pattern: ↑ ALT/AST (often very high in acute viral/toxic injury).
  • Symptoms can be systemic (malaise, fever) before jaundice appears.
• 🪨 Cirrhosis & portal hypertension
  • Fibrosis + nodular regeneration → ↑ resistance to portal flow → varices/ascites.
  • Reduced synthetic function: ↓ albumin, ↑ INR, thrombocytopenia (hypersplenism).
• 🧈 Fatty liver (MASLD/NAFLD)
  • Driven by insulin resistance → hepatic triglyceride accumulation; can progress to steatohepatitis and fibrosis.
  • Often asymptomatic; mild ALT rise, metabolic syndrome context.
• 💊 Drug-induced liver injury (DILI)
  • Patterns: hepatocellular (ALT↑), cholestatic (ALP/GGT↑), or mixed; timing and drug history are crucial.
  • Always consider paracetamol toxicity in acute liver injury (treat early with NAC).
• 🎗️ Hepatocellular carcinoma (HCC)
  • Usually arises on a background of cirrhosis/chronic viral hepatitis; surveillance pathways target high-risk groups.

✅ Summary: The liver regulates energy supply, manufactures essential proteins, processes bilirubin and bile acids, and detoxifies drugs and toxins. Most “liver problems” clinically map to one of three physiology domains: hepatocellular injury (ALT/AST), cholestasis (ALP/GGT), or synthetic failure (INR/albumin/glucose), often with portal hypertension as disease advances.