Liver

Hepatic Anatomy

  • The Liver

    • Largest internal organ
    • Located in the right upper quadrant of the abdomen

  • Functional Units of the Liver

    • Lobule
    • Hexagonal in cross-section
    • Central vein at the center
    • Portal veins at its six corners
    • Contains 50,000 to 100,000 lobules in the liver
    • Acinus
    • Functionally classifies liver tissue based on the terminal branch of the hepatic artery
    • Organized into zones (1 to 3) based on proximity to portal triad and central vein
    • Zone 1: Most oxygenated, least susceptible to ischemic injury
    • Zone 3: Most oxygenated, highest concentration of CYP450 enzymes, most susceptible to ischemic injury

  • Kupffer Cells

    • Remove bacteria from portal blood before it enters systemic circulation

  • Bile Production and Flow

    • Produced by hepatocytes and stored in the gallbladder
    • Path from hepatocytes to duodenum:
    • Canaliculi → Bile duct → Common hepatic duct → Common bile duct → Ampulla of Vater → Duodenum

  • Lymph and Protein Drainage

    • Drain into space of Disse and then into lymphatic duct.

Glisson's Capsule and Ligament Structure

  • Glisson's Capsule

    • Connective tissue covering of the liver
    • Covers parts of hepatic artery, portal vein, and bile ducts

  • Ligaments:

    • Falciform ligament: Connects liver to anterior abdominal wall
    • Round ligament: Remnant of umbilical vein
    • Coronary ligament: Connects liver to diaphragm
    • Triangular ligaments: Left and right; connect liver to diaphragm

  • Autonomic Innervation:

    • SNS innervation from T3-T11

Lobule Structure

  • Components of a Lobule

    • Central vein
    • Hepatocytes
    • Bile canaliculi
    • Bile duct
    • Space of Disse
    • Sinusoid
    • Kupffer cells
    • Branches of hepatic artery and portal vein

  • Terminology of Blood Flow:

    • Arterioles = Terminal branches of hepatic artery and portal vein
    • Sinusoids = Capillaries
    • Central vein = Venules

Acinus Structure

  • Three Zones of Acinus

    • Zone 1: Most oxygenated, enriched with nutrients
    • Zone 2: Intermediate oxygen and nutrient levels
    • Zone 3: Least oxygenated, highest concentration of CYP450 enzymes, most susceptible to ischemic injury

  • Function of Acinus:

    • Significant bacterial load from portal vein blood drainage
    • Kupffer cells help in removing bacteria before blood flowing into the vena cava

Biliary Tree

  • Bile Pathway

    • Canaliculi drain bile into bile duct
    • Ducts converge to form common hepatic duct
    • Cystic duct (from gallbladder) and pancreatic duct join common hepatic duct before entering duodenum
    • Sphincter of Oddi: Controls bile flow from common hepatic duct
    • Contraction increases biliary pressure (opioids cause this)

  • Functions of Bile:

    1. Absorption of fat and soluble vitamins (D, A, K, E)
    2. Excretion pathway for bilirubin and metabolic products
    3. Alkalization of duodenum

  • Cholecystokinin (CCK):

    • Released in response to eating fat and protein; stimulates gallbladder contraction and increases bile flow

  • Lymphatic Drainage:

    • Lymph and proteins are drained into space of Disse before entering lymphatic duct; liver accounts for about 50% of body's lymph production

Hepatic Blood Flow

  • Blood Supply
    • Receives approximately 30% of cardiac output (1,500 mL/min)
    • Portal Vein:
    • Provides 75% of total liver blood flow
    • Supplies 50% of liver’s oxygen content
    • Hepatic Artery:
    • Supplies 25% of total liver blood flow and 50% of liver’s oxygen content
    • Portal blood flow is not autoregulated; increased vascular resistance can decrease blood flow
    • Hepatic Arterial Buffer Response: Compensatory mechanism increases hepatic arterial flow alongside reduction in portal vein flow
    • Impact of Anesthesia: Both general and neuraxial anesthesia can reduce MAP and cardiac output, which in turn can diminish liver blood flow in a dose-dependent manner

Hepatic Venous Flow (Portal Vein)

  • Portal Vein Blood Flow Characteristics:

    • Receives blood that has already passed through the splanchnic circulation; flow through the portal vein is not autoregulated
    • Increased vascular resistance affects blood flow (SNS stimulation, pain, hypoxia, etc.)

  • Portal Perfusion Pressure Equation:
    extPortalPerfusionPressure=extPortalVeinPressure−extHepaticVeinPressureext{Portal Perfusion Pressure} = ext{Portal Vein Pressure} - ext{Hepatic Vein Pressure}

  • Normal Pressures:

    • Portal vein: 7-10 mmHg
    • Sinusoids: 0 mmHg

  • Hepatic Venous Pressure Gradient (HVPG):

    • Normal: 1-5 mmHg
    • Clinically significant portal hypertension: >10 mmHg
    • Variceal rupture risk: >12 mmHg

  • Effects of Portal Hypertension:

    • Reduced blood flow in liver; backpressure on splanchnic organs leads to splenomegaly & esophageal varices
    • Physiological consequences: ascites, spider angiomas, hemorrhoids, enteropathy

Hepatic Arterial Flow and Buffer Mechanism

  • Compensatory Mechanism of Hepatic Blood Flow:

    • When portal flow is reduced, hepatic arterial flow increases to maintain oxygen delivery
    • Hepatic Artery Perfusion Pressure Equation:
      extHepaticArteryPerfusionPressure=extMAP−extHepaticVeinPressureext{Hepatic Artery Perfusion Pressure} = ext{MAP} - ext{Hepatic Vein Pressure}

  • Severe Liver Disease Implications:

    • Abolished hepatic arterial buffer response; hypotension greatly increases risk of inadequate hepatic blood flow and oxygen delivery

  • Anesthetic Considerations:

    • General & neuraxial anesthesia, as well as intraabdominal surgery can also lower hepatic blood flow

Liver Function Overview

  • Roles of the Liver:

    • Protein synthesis
    • Carbohydrate, protein, and lipid metabolism

  • Clotting Factors:

    • Liver produces all clotting factors except factor 3, factor 4, and von Willebrand factor
    • Vitamin K-dependent Factors:
    • Factors 2, 7, 9, and 10; includes proteins C, S, and Z

  • Plasma Proteins Production:

    • All produced except immunoglobulins; albumin is the most abundant plasma protein
    • Albumin serves as a drug reservoir (acidic and basic drugs)
    • Alpha-1 acid glycoprotein is a reservoir for basic drugs

  • Effects of Liver Disease:

    • Reduced pseudocholinesterase production, prolonging effects of succinylcholine and possibly ester-type local anesthetics
    • Failure to clear ammonia leads to hepatic encephalopathy
    • Bilirubin metabolism via conjugation affects excretion and can be neurotoxic in an unconjugated state

  • Drug Biotransformation:

    • Liver's primary role in drug metabolism and clearance

Pharmacokinetics Related to Liver Function

  • Bilirubin Dynamics:

    • RBC lifecycle ~120 days; breakdown occurs in spleen to produce unconjugated bilirubin, which is lipophilic and transported to the liver
    • In the liver, bilirubin is conjugated with glucuronic acid to form conjugated bilirubin for excretion

  • Metabolism and Clearance:

    • Key processes: glycogenesis, glycogenolysis, gluconeogenesis for carbohydrate metabolism
    • Protein deamination produces ammonia, converted to urea in the liver, contributing to hepatic encephalopathy risk
    • Lipid roles include storage, energy release, and synthesis of cholesterol and lipoproteins

Liver Function Tests Overview

  • Safety Value (Normal Ranges):

    • PT: 12-14 sec; sensitive to acute injury
    • AST/ALT: Markers of hepatocellular injury, ratio > 2 indicates cirrhosis or alcoholic liver disorder
    • Alkaline Phosphatase: 45-115 units/L; poor specificity for liver disease, increased with biliary obstruction
    • GGT: 0-30 units/L; more sensitive than alkaline phosphatase; indicates cholestasis

  • Causative Factors of Results:

    • Identify patterns of enzyme elevation, and changes with liver disease, segment between prehepatic, hepatocellular, and posthepatic issues

Types of Hepatitis

  • Definition:

    • Liver inflammation marked by hepatocellular injury
    • Causes: viruses, hepatotoxins, autoimmune responses

  • Types of Hepatitis:

    • Hepatitis A: Oral-fecal route; common, usually asymptomatic for 1-2 weeks before onset of fever, malaise, jaundice
    • Hepatitis B/C: More chronic, commonly lead to cirrhosis and liver cancer

  • Drug-Induced Hepatitis:

    • Common agents include acetaminophen, halothane, alcohol
    • Acetaminophen overdose leads to hepatotoxicity due to toxic metabolites (NAPQI); treat with N-acetylcysteine

  • Chronic Hepatitis:

    • Characterized by >6 months inflammation; causes cirrhosis, hepatic failure; risk factors include alcohol and hepatitis C infection
    • Signs: jaundice, fatigue, thrombocytopenia

Anesthetic Considerations in Hepatitis & Alcohol Use Disorder

  • Assessment of Surgery Timing:

    • Postpone non-emergent surgery if acute hepatitis symptoms are present; stable chronic hepatitis allows for surgical procedures.

  • Management of Patients:

    • Maintain blood flow, avoid hepatotoxic drugs, monitor neuromuscular junction during anesthesia
    • MAC alterations depending on acute versus chronic alcoholic state

  • Withdrawal Syndrome:

    • Signs 6-8 hours post-alcohol cessation, peak at 24-36 hrs; early symptoms include tremors, late symptoms include cardiovascular instability

Cirrhosis Overview

  • Definition:

    • Cellular death replaces healthy liver tissue with fibrous nodules reducing functional hepatocytes and vessel count
    • Leads to portal hypertension due to increased vascular resistance

  • Assessment Tools:

    • MELD and Child-Pugh scores predict perioperative mortality risk.

  • Common Complications:

    • Ascites, edema, hepatocellular failure, variceal bleeding
    • Risks include hyperdynamic circulation due to vasodilatory dysregulation in end-stage liver disease

  • TIPS Procedure: Transjugular intrahepatic portosystemic shunt helps minimize portal pressure; procedural risks include hemorrhage and minimal complications

Liver Transplant Overview

  • Common Indications:

    • Hepatitis C, alcoholic liver disease, malignancy

  • Surgical Phases:

    • Pre-anhepatic, anhepatic, neohepatic phases each with unique objectives and risks

  • Post-Operative:

    • Focus on graft function, hemodynamic stability, prevention of infection; caution with anesthetic agents due to coagulopathy risks

Gallbladder Pathophysiology

  • Common Diseases:

    • Caused by obstruction/inflammation; biliary stones impede bile and pancreatic enzyme flow

  • Symptoms:

    • RUQ pain (worse with inspiration), fever, and leukocytosis; Murphy's sign indicated gallbladder irritation

  • Surgical Treatment: Cholecystectomy for gallbladder issue management, ERCP for common bile duct stones

Anesthetic Considerations for Cholecystectomy

  • Procedure Characteristics:

    • Laparoscopic typically, avoid N2O, select muscle relaxants carefully if liver dysfunction present

  • Pain Management: Opioids may induce sphincter spasm; consider adjunct medications cautiously to ensure no negative outcomes.

  • Avoid Drugs: Naloxone in surgical settings, glucagon due to PONV risk.