Liver Physiology Blood Supply and Functional Organization The liver receives blood from two sources.
Source Blood supplied Main significance Portal vein Nutrient-rich blood from the GI tract and spleen Delivers absorbed substances for processing Hepatic artery Oxygenated systemic blood Supplies oxygen to hepatic tissue
Blood passes through hepatic sinusoids and drains into central veins, then hepatic veins and the inferior vena cava.
Important liver cells Cell Function Hepatocytes Metabolism, bile production, protein synthesis and detoxification Kupffer cells Resident macrophages that remove particles and microorganisms Hepatic stellate cells Store vitamin A; contribute to fibrosis when activated Sinusoidal endothelial cells Specialized fenestrated lining that facilitates exchange
Major Liver Functions Function Key processes Carbohydrate metabolism Glycogenesis, glycogenolysis and gluconeogenesis Protein metabolism Amino acid processing, urea synthesis and plasma protein production Lipid metabolism Fatty acid oxidation, triglyceride synthesis and cholesterol metabolism Bile production Bile acid secretion and bilirubin excretion Detoxification Drug metabolism and modification of endogenous substances Storage Glycogen, iron and selected vitamins Synthetic function Albumin and many coagulation proteins Immune function Removal of pathogens and debris from portal blood
State Main hepatic response Fed state Glycogenesis, glycolysis and lipogenesis increase Early fasting Glycogenolysis maintains blood glucose Prolonged fasting Gluconeogenesis becomes increasingly important; ketogenesis increases Protein breakdown Amino groups are processed and nitrogen is converted to urea
Clinical markers of liver injury and function Test What it primarily indicates ALT and AST Hepatocellular injury ALP and GGT Cholestatic pattern when elevated in the appropriate context Bilirubin Bilirubin production, processing and excretion Albumin Synthetic function, influenced by nutrition and other conditions PT/INR Synthesis of clotting factors; may change relatively rapidly in severe dysfunction
Exam tip: Transaminases primarily indicate cell injury, not the liver's remaining functional capacity. Albumin and PT/INR help assess synthetic function.
Feature Unconjugated Bilirubin (Indirect) Conjugated Bilirubin (Direct) Delta Bilirubin (Δ) Water Solubility Lipid-soluble (Water-insoluble) Water-soluble Water-soluble Transport Protein Reversibly bound to Albumin Free in plasma (unbound) Covalently bound to Albumin Liver Processing Pre-hepatic / Arriving at liver Post-hepatic (Conjugated with glucuronic acid by UGT1A1 ) Formed when conjugated bilirubin accumulates chronically Excretion in Urine? NO (Cannot cross glomerular filter)YES (Causes dark "tea-colored" urine)NO (Albumin-bound, too large to filter)Toxicity High (can cross blood-brain barrier Kernicterus ) Non-toxic Non-toxic Elevated In Hemolysis, Gilbert's syndrome, Crigler-Najjar syndrome Biliary obstruction (gallstones, pancreatic cancer), Dubin-Johnson, Rotor Prolonged obstructive jaundice (slow to clear due to long half-life of albumin approx 20 days)
Bilirubin is produced mainly from heme breakdown.
Normal pathway Senescent red blood cells are broken down by macrophages. Heme is converted to biliverdin, then unconjugated bilirubin. Unconjugated bilirubin circulates bound to albumin. Hepatocytes take it up and conjugate it with glucuronic acid via UGT1A1. Conjugated bilirubin is secreted into bile. Intestinal bacteria convert bilirubin derivatives into urobilinogen-related compounds. Most pigment is eliminated in feces; a smaller fraction is reabsorbed, and some ultimately appears in urine as urobilin. Unconjugated versus conjugated bilirubin Feature Unconjugated Conjugated Water solubility Poor Higher Albumin binding in plasma Strong Less tightly bound Appears in urine No, under ordinary conditions Yes, when elevated in plasma Typical mechanism of elevation Increased production or impaired conjugation Impaired canalicular excretion or cholestasis
Types of jaundice Type Main mechanism Typical pattern Prehepatic/hemolytic Bilirubin production exceeds hepatic processing capacity Predominantly unconjugated bilirubin Hepatocellular Impaired uptake, conjugation and/or excretion due to hepatocyte injury Mixed pattern possible Posthepatic/obstructive Impaired bile flow Often conjugated hyperbilirubinemia, dark urine and pale stools
Important inherited disorders Disorder Defect Typical clue Gilbert syndrome Mildly reduced UGT1A1 activity Intermittent mild unconjugated hyperbilirubinemia Crigler–Najjar syndrome type I Near-complete absence of UGT1A1 activity Severe unconjugated hyperbilirubinemia Crigler–Najjar syndrome type II Markedly reduced UGT1A1 activity Less severe than type I; some response to phenobarbital Dubin–Johnson syndrome Impaired canalicular transport of conjugated bilirubin Conjugated hyperbilirubinemia; classically darkly pigmented liver Rotor syndrome Impaired hepatic handling/storage of conjugated bilirubin Conjugated hyperbilirubinemia without the characteristic dark liver of Dubin–Johnson
MCQ tip: Gilbert and Crigler–Najjar involve conjugation; Dubin–Johnson and Rotor involve handling of conjugated bilirubin.
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