Liver – Blood Supply

Master answer

Hepatic blood flow

• 1.5l/min
• Anatomy
  • Afferent via Hepatic Artery (branch of ceoliac trunk) contributing 30% and Portal Vein (confluence of inferior mesenteric, superior mesenteric and splenic veins) contributing 70% of hepatic blood flow
    • Hepatic artery supplies 50% of O₂ delivery
    • Portal venous blood has PO₂ of 80% due to mesenteric AV anastamosis
  • Blood flows through low pressure hepatic sinusoidal system to ventral vein
  • Efferent via Hepatic Vein → IVF

Regulation

Intrinsic

• Hepatic arterial and Portal venous pressure – Hepatic venous pressure / Hepatic vascular resistance (low)
• Autoregulation to systolic blood pressure 80mmHg
• Metabolic autoregulation
  • Vasodilation in response to H⁺, CO₂, lactate
• Semi-reciprocal relationship
  • Hepatic arterial blood flow increases when protal venous flow decreases

Extrinsic

• Respiration
  • Diaphragmic contraction → Decreased intrathoracic (and IVC) pressure and increased abdominal pressure → Favours hepatic blood flow
• Post-prandial
  • Increased splanchnic blood flow post-prandially → Increased hepatic blood flow
• Neural
  • Sympathetic
    • α adrenoceptors present in portal vein AND hepatic artery
    • β adrenoceptors only present in hepatic artery
    • Therefore sympathetic input tends to venoconstrict the portal vein and dilate the hepatic artery
• Hormonal
  • Adrenaline
    • α constricts protal veins and decreases HBF
    • β dilates hepatic arteries and increases HBF
  • Glucagon increases hepatic blood flow
  • Vasopressin decreases hepatic blood flow
  • Angiotensin II decreases hepatic blood flow
  • Vasoactive Intestinal Peptide (VIP) and secretin increase hepatic artery flow

Changes to drug metabolism when liver blood flow decreases:

• The two major determinants of hepatic clearance are the efficiency of drug removal from the blood and the efficiency of blood delivery to the liver.
• Efficiency of drug removal by the liver = hepatic extraction ratio
  • fraction of the drug entering the liver in the blood which is irreversibly removed (extracted) during one pass of the blood through the liver.
  • determined largely by:
    • the free (unbound) fraction of the drug and
    • the intrinsic clearance rate (the intrinsic ability of the liver to remove (metabolise) the drug in absence of restrictions imposed on drug delivery to the liver cell by blood flow or protein binding.)
• The effect of liver blood flow on hepatic clearance depends on the hepatic extraction ratio of the drug.

With decreasing hepatic blood flow, hepatic extraction ratio will increase for all drugs.

• For drugs with low intrinsic clearance:
  • Hepatic extraction ratio will increase with decreasing hepatic blood flow
  • Hepatic clearance will not decrease significantly with decreasing blood flow
• For drugs with high intrinsic clearance:
  • Hepatic extraction ratio will increase slowly with decreasing blood flow
  • Hepatic clearance will decrease in a fairly linear fashion, in proportion to hepatic blood flow

Also, Drugs which enjoy enterohepatic recirculation may have decreased half-lives due to failure of recirculation

Sakurai / JC 2019

Answer by JC, Sakurai