Hepatic Anatomy & Physiology and Anesthetic Implications

General Characteristics of the Liver

• Size and Weight: The liver is the largest parenchymal organ in the human body.

  • In an adult, it weighs approximately $1500$ to $1600\,g$.

  • It represents approximately $2\%$ of the total adult body weight.

• Blood Flow Basics:

  • Normal blood flow is $100\,mL/100\,g$ of tissue per minute.

  • This equates to approximately $25\%$ to $30\%$ of the resting cardiac output ($CO$).

  • Total liver blood flow is approximately $1500\,mL/min$.

• Functional Reserve: The liver possesses a large functional reserve. Consequently, clinically significant hepatic dysfunction following anesthesia and surgery is relatively uncommon in healthy patients.

• Nerve Supply: Coverage extends through $T3$ to $T11$.

Hepatic Blood Supply and Oxygenation

• Portal Vein Supply ($75\%$ of total flow):

  • The portal vein carries blood that is partially deoxygenated due to oxygen extraction by digestive organs.

  • Portal vein oxygen saturation is approximately $85\%$.

  • Despite being partially deoxygenated, it provides $35\%$ to $50\%$ of the total oxygen delivered to the liver.

  • Supply is determined by blood flow to the gastrointestinal (GI) tract and the spleen.

• Hepatic Artery Supply ($25\%$ of total flow):

  • The hepatic artery provides $50\%$ to $65\%$ of the oxygen delivered to the liver.

  • Supply is primarily dependent on metabolic demand.

Macro and Micro Anatomy

• Lobar Anatomy:

  • The liver consists of two lobes of unequal size separated by the falciform ligament, which serves as a key anatomical landmark.

  • Surgical Segments: Surgical anatomy defines a total of eight segments (I through VIII).

  • Major Sections: Right posterior section, Right anterior section, Left medial section, and Left lateral section.

  • Vascular Components: Includes the Hepatic vein, Middle hepatic vein, Left hepatic vein, Inferior vena cava, Hepatic artery, Portal vein, and Hepatic duct.

  • Gallbladder Components: Gallbladder, Cystic duct, and Bile duct.

  • Remnants: Umbilical vein (remnant).

• Lobules (Functional Units):

  • The liver contains $50,000$ to $100,000$ discrete units called lobules.

  • Hepatocytes: Each lobule is composed of a plate of hepatocytes arranged around a central vein.

  • Sinusoids: Blood from the hepatic artery and portal vein co-mingle in the sinusoids and drain into the central vein.

  • Lining Cells of Sinusoids:

    • Endothelial cells.

    • Kupffer cells (Macrophages): These cells are responsible for removing bacteria from the blood before it returns to the vena cava.

Vascular and Cleansing Functions

• Control of Hepatic Blood Flow:

  • Hepatic Artery: Regulated by $\alpha_1$, $\beta_2$, and Dopa-1 ($D_1$) receptors.

    • Sympathetic stimulation causes decreased blood flow.

    • $\beta$ stimulation results in vasodilation.

    • Beta-blockers cause decreased hepatic blood flow.

  • Portal Vein: Regulated by $\alpha_1$ and $\text{Dopa-1}$ receptors.

    • Sympathetic stimulation results in decreased blood flow.

• Reservoir Function:

  • The sinusoids comprise a low-pressure system allowing for large volumes of blood storage.

  • Normal storage is approximately $450\,mL$ (nearly $10\%$ of total blood volume).

  • Hemorrhage Response: A decrease in hepatic venous pressure allows blood to shift to the central circulation (up to $300\,mL$) to augment volume.

  • Congestive Heart Failure (CHF): Increased hepatic venous pressure allows up to $1\,L$ of blood to be stored and removed from active circulation.

• Blood Cleansing Function:

  • Kupffer cells perform phagocytic functions.

  • From Portal Circulation: Removes colonic bacteria and endotoxins.

  • From Systemic Circulation: Removes cellular debris, viruses, proteins, and particulate matter.

Metabolic Functions and Drug Metabolism

• Carbohydrate Metabolism: The liver is the primary regulator of serum glucose. It clears insulin from circulation; liver failure significantly increases the risk of hypoglycemia.

• Fat and Protein Metabolism:

  • Produces all plasma proteins except for immunoglobulins.

  • Coagulation Factors: Produces all factors EXCEPT factor III (tissue factor), factor VIII, and von Willebrand factor ($vWF$).

• Plasma Protein Synthesis:

  • Albumin: Binds acidic drugs.

  • $\alpha_1$-acid glycoprotein: Binds basic drugs.

• Bile Formation: Involved in bilirubin excretion, which is the end product of hemoglobin metabolism.

• Succinylcholine Considerations: In severe liver disease, succinylcholine may be prolonged due to decreased pseudocholinesterase production; this is generally not the case in mild or moderate disease.

Laboratory Manifestations of Hepatic Dysfunction

• Limitations of Tests: Many common tests lack sensitivity or specificity and only assess narrow aspects of function.

• Category 1: Markers of Liver Injury (Hepatic Enzymes):

  • Aminotransferases: AST ($\text{Aspartate Aminotransferase}$) and ALT ($\text{Alanine Aminotransferase}$).

    • An $AST/ALT$ ratio > 2 is suggestive of cirrhosis or alcoholic liver disease.

  • Lactate Dehydrogenase (LDH).

  • $5\text{-nucleotidase (5NT)}$: A specific indicator for biliary obstruction.

  • Alkaline Phosphatase (ALP) and Gamma-Glutamyl Transpeptidase (GGTP).

• Category 2: Markers of Liver Function (Synthetic Capability):

  • Albumin levels (reflects long-term synthetic function).

  • Prothrombin Time (PT) (reflects acute synthetic capacity and clotting factor status).

• Category 3: Markers of Hepatic Clearance:

  • Ammonia.

  • Bilirubin.

Anesthetic Effects on Hepatic Function

• Hepatic Blood Flow Changes:

  • Blood flow decreases during both regional and general anesthesia ($GA$).

  • Regional: Via decreased blood pressure ($BP$).

  • General: Via decreased $BP$ and decreased cardiac output ($CO$).

  • Positive Pressure Ventilation (PPV): Decreases venous return, increases hepatic venous pressure, and decreases $CO$.

  • Surgical Manipulation: Procedures near the liver can reduce hepatic blood flow by up to $60\%$ via sympathetic activation, local reflexes, and direct vessel compression.

• Pharmacologic Effects on Flow:

  • Decrease Flow: Beta-blockers, $\alpha_1$ agonists, and vasopressin.

  • Increase Flow: Low-dose dopamine infusion.

• Metabolic Effects:

  • The endocrine stress response (due to fasting and surgical trauma) mobilizes carbohydrate and protein stores, leading to hyperglycemia and a negative nitrogen balance (catabolism).

• Biliary Function:

  • All opioids can cause spasm of the Sphincter of Oddi.

  • Potency for causing spasm: \text{Fentanyl} > \text{Morphine} > \text{Meperidine} > \text{Butorphanol} > \text{Nalbuphine}.

• Postoperative Jaundice: The most common cause is the overproduction of bilirubin due to the reabsorption of a large hematoma or RBC breakdown following a transfusion.

Hepatitis Overview

• Definitions: Persistent hepatic inflammation for longer than $6\text{ months}$ as evidenced by LFTs is classified as chronic.

• Viral Hepatitis:

  • Hepatitis A and E: Transmitted via the fecal-oral route.

  • Hepatitis B and C: Transmitted via contact with blood and body fluids. The clinical course for B and C is often more complicated and prolonged.

  • Hepatitis D (Delta Virus): Requires the presence of Hepatitis B to infect the host; can be transmitted via both routes.

  • Clinical Course: Progresses from a $1$ to $2\text{ week}$ prodromal phase (fatigue, malaise, fever, N/V) to possible jaundice ($2$ to $12\text{ weeks}$). Recovery takes up to $4\text{ months}$.

• Drug-Induced Hepatitis (DIH):

  • Caused by direct dose-dependent toxicity or idiosyncratic reactions.

  • Alcoholic hepatitis is the most common form.

  • Acetaminophen: Ingestion of $25\,g$ or more usually results in fatal fulminant disease.

• Chronic Hepatitis Classifications:

  • Chronic Persistent: Inflammation of portal tracts; architecture preserved; usually does not progress to cirrhosis.

  • Chronic Lobular: Recurrent exacerbations with inflammation in hepatic lobules; usually does not progress to cirrhosis.

  • Chronic Active: Destruction of normal architecture; leads to cirrhosis; commonly a sequela of Hep B or Hep C.

Cirrhosis and Systemic Impacts

• Pathophysiology: Healthy tissue is replaced by nodules and fibrotic tissue, reducing the number of functioning hepatocytes and sinusoids. This creates resistance to flow, resulting in portal hypertension.

• Causes: Alcohol (most common), chronic active hepatitis, biliary obstruction, right-sided CHF, Wilson's disease, and Alpha-1 antitrypsin deficiency.

• Systemic Manifestations:

  • Cardiovascular: Hyperdynamic state, low systemic vascular resistance ($SVR$), cirrhotic cardiomyopathy, and systemic AV shunts.

  • Pulmonary: Increased intrapulmonary shunting, decreased $FRC$, pleural effusions, restrictive ventilation defects, and respiratory alkalosis.

  • Renal: Increased Na+ reabsorption, impaired free water clearance, and Hepatorenal syndrome.

  • Hematologic: Anemia, coagulopathy, thrombocytopenia, and leukopenia (secondary to hypersplenism).

  • Neurologic: Hepatic encephalopathy (cerebral edema, elevated ICP).

Perioperative Risk Assessment and Management

• Risk Scores:

  • MELD (Model for End-Stage Liver Disease).

  • Child-Pugh Score: Evaluates Albumin, PT, Bilirubin, Ascites, and Encephalopathy.

    • Class A and B: May proceed to the OR.

    • Class C: Should be medically managed/optimized; surgery generally avoided.

• Management Strategies by Condition:

  • Acute Hepatitis: Postpone surgery until biochemical profiles normalize. If urgent, preserve hepatic flow, maintain normocapnia, and avoid PEEP. Cisatracurium is the neuromuscular blocker (NMB) of choice due to non-hepatic metabolism.

  • Obstructive Jaundice: Focus on fluid resuscitation; goal of PT within $2\text{ seconds}$ of normal using Vitamin K or FFP.

  • Cirrhosis: Correct coagulopathy (Goal: PT within $2\,s$ of normal). Anticipate relative hypovolemia. Utilize invasive monitoring (A-line/CVP). Be aware of Citrate toxicity from massive PRBC transfusion (citrate binds Calcium, leading to hypocalcemia and prolonged QT).

• Acute Liver Failure: Anesthesia should only be administered for life-saving emergencies. Focus on managing elevated ICP (head elevation, osmotic diuretics, barbiturates).

Specialized Procedures

• TIPS (Transjugular Intrahepatic Portosystemic Shunt):

  • Creates a pathway between a hepatic vein (outflow) and a portal vein branch (inflow) using a stent to reduce portal pressure.

  • Indications: Refractory variceal hemorrhage and ascites.

  • Contraindications: Sepsis, severe heart failure, or severe coagulopathy.

• Hepatic Resection:

  • Fluid Management: Two strategies exist—Euvolemic (traditional) or Restrictive volume (Low CVP helps decrease bleeding during dissection).

  • Massive Transfusion: High risk; alert blood bank; have blood in the room prior to resection.

  • Regional/Epidural: Controversial due to potential postoperative coagulopathy.

• ERCP (Endoscopic Retrograde Cholangiopancreatography):

  • Requires sedation or GA. Patients are often hypovolemic and experiencing N/V.

  • Caution: Narcotics may cause sphincter of Oddi spasm.

Summary of Anesthetic Preferences

• Induction: Propofol preferred.

• Maintenance: Isoflurane is the preferred inhalational agent (most preserved blood flow).

• Opioids: Fentanyl is preferable.

• Paralytics: Cisatracurium for acute/severe failure; Vecuronium with caution.