Liver Anatomy and Physiology


Anatomy

  1. Gross Anatomy

    1. General Description
      • largest gland in the body, accounting for 2% of the body weight of an adult and 5% of the body weight of a newborn
      • its large size reflects the complexity of its functions

    2. Surface Anatomy
      • completely covered by peritoneum (Glisson’s capsule) except for the bare area on its posterosuperior surface adjacent to the inferior vena cava and hepatic veins

      1. Falciform Ligament
        • attaches the liver to the anterior abdominal wall from the diaphragm to the umbilicus
        • ligamentum teres, or round ligament, (obliterated left umbilical vein) is enclosed in its lower border

      2. Coronary Ligaments
        • consists of anterior and posterior leaves which, in continuity with the falciform ligament, connect the liver to the diaphragm
        • anterior and posterior leaves fuse laterally to form the right and left triangular ligaments
        • bare area is the area encompassed by the falciform, coronary, and triangular ligaments

        Hepatic Ligaments
      3. Lesser Omentum
        • comprised of the gastrohepatic ligament and the hepatoduodenal ligament
        • hepatoduodenal ligament contains the portal triad: hepatic artery, common bile duct, and portal vein
        • gastrohepatic ligament may contain aberrant or accessory vessels to the liver

        Lesser Omentum
    3. Lobar Anatomy
      • division of the liver into right and left lobes is based on the right and left branches of the hepatic artery and portal vein
      • this division has no topographical landmark, but instead occurs along Cantlie’s line, which is a plane passing from the gallbladder fossa anteroinferiorly to the vena cava posteriorly

      Cantlie's Line
      1. Couinaud’s Segmental Classification
        • functional division of the liver based on the hepatic venous drainage
        • liver is divided into two lobes by the middle hepatic vein
        • right hepatic lobe is divided into two sectors by the right hepatic vein; the left hepatic lobe is divided into two sectors by the left hepatic vein
        • each sector is divided into two segments, which correspond to the portal vein and hepatic artery branches
        • liver contains a total of 8 segments: segment I = caudate lobe, segments II to IV = left lobe, and segments V to VIII = right lobe
        • each segment has its own vascular inflow, outflow, and biliary drainage
        • each segment is a self-contained unit that can be resected without damaging the others
        • resection lines parallel the hepatic veins

        Couinad's Segmental Anatomy of the Liver

    4. Blood Supply
      1. Hepatic Artery
        • provides 25% of hepatic blood flow and 50% of the liver’s oxygen
        • originates from the celiac axis
        • gives off the gastroduodenal and right gastric arteries
        • ascends in the hepatoduodenal ligament to the left of the common bile duct and anterior to the portal vein
        • bifurcates outside the liver into right and left branches
        • inside the liver, the hepatic arteries run parallel to the portal vein branches
        • ligation of the hepatic artery proximal to the gastroduodenal artery will not damage the liver because of abundant collaterals
        • most patients can also tolerate ligation of either the right or left hepatic artery without serious sequelae
        • ‘normal’ anatomy only occurs ~60% of the time

        Normal Hepatic Artery Anatomy
        1. Replaced Right Hepatic Artery
          • originates from the SMA in 11% to 22% of patients
          • usually lies to the right and posterolateral to the bile duct and portal vein
          • can be palpated along the posterior aspect of the hepatoduodenal ligament by placing a finger through the foramen of Winslow
          • occurs as an accessory vessel in 7% of cases

        2. Replaced Left Hepatic Artery
          • occurs in 4% to 10% of patients
          • originates from the left gastric artery
          • runs through the gastrohepatic ligament
          • occurs as an accessory vessel in 8% of cases

          Hepatic Artery Variations
      2. Portal Vein
        • accounts for 75% of hepatic blood flow and 50% of the liver’s oxygen requirement
        • drains the gastrointestinal tract, pancreas, and spleen
        • formed behind the neck of the pancreas by the confluence of the superior mesenteric and splenic veins
        • lies posterior to the common bile duct and hepatic artery in the hepatoduodenal ligament
        • blood from the superior mesenteric vein flows preferentially into the right lobe of the liver
        • contains numerous rudimentary collaterals with the systemic circulation that can become clinically significant if portal hypertension develops:
          • submucosal veins of the proximal stomach and distal esophagus
          • umbilical and periumbilical veins
          • middle and inferior hemorrhoidal veins
          • retroperitoneal veins

        Extrahepatic Portal Vein Anatomy
      3. Hepatic Veins
        • begin in the liver as the central veins into which the sinusoids empty
        • right hepatic vein (RHV) provides the principal drainage of the right lobe
        • in addition, multiple small veins drain directly from the right lobe into the vena cava
        • middle hepatic vein (MHV) drains the medial segment of the left lobe and a portion of the anterior segment of the right lobe
        • left hepatic vein (LHV) drains the left lateral segment
        • caudate lobe drains directly into the vena cava
        • the most common pattern for the 3 hepatic veins is an independent RHV and a common trunk for the MHV and LHV

        Hepatic Venous Drainage
  2. Microscopic Anatomy

    1. Hepatic Lobule
      • functional unit of the liver
      • made up of a central vein surrounded by 4 to 6 portal triads that form a polygonal unit
      • blood flows from the terminal hepatic arterioles and portal venules into the sinusoids
      • blood in the sinusoids bathes the hepatocytes before it empties into the hepatic veins
      • bile is made in the hepatocytes and empties into terminal canaliculi

      Hepatic Lobule
    2. Major Cell Types
      1. Hepatocytes
        • perform the major metabolic and excretory functions of the liver
        • arranged in cords or plates one cell thick
        • surrounded by the sinusoids

      2. Endothelial Cells
        • make up the specialized capillary bed of the hepatic sinusoids
        • do not form a continuous cell layer – the gaps between the cells are wide
        • the sinusoids are porous and allow migration of most large molecules into the space of Disse between the sinusoids and the hepatocytes
        • pressure within the sinusoids is only 2 to 3 mm Hg
        • flow into the space of Disse is very sensitive to increases in hydrostatic pressure as seen in cirrhosis or the Budd-Chiari syndrome
        • fluid in the space of Disse is removed by hepatic lymphatics

      3. Kupffer Cells
        • lie within the sinusoids
        • tissue macrophages that function as phagocytic cells and antigen-presenting cells
        • function as part of the reticuloendothelial system

      4. Bile Canaliculus
        • forms the origin of the biliary system
        • formed by the plasma membranes of adjoining hepatocytes
        • separated from the space of Disse by tight junctions and desmosomes
        • drain into ductules within the portal triads and then follow the portal vein and hepatic artery retrograde to the hilum of the liver

Physiology

  1. Metabolism
    1. Carbohydrates
      • liver plays a central role in glucose homeostasis
      • provides a continuous source of glucose for the CNS and RBCs

      1. Fed State
        • liver removes 50% of the glucose presented to it by the portal vein
        • glucose absorbed by the hepatocytes is converted to glycogen for storage (up to 65 grams of glycogen / kg of liver tissue)
        • excess glucose is converted into fatty acids and stored in adipose tissue

      2. Fasting State
        • in early fasting (<24 hr), liver glycogen is the primary source of glucose
        • after <24 hours of fasting, liver glycogen is used up and muscle protein (mainly alanine) must be converted by the liver into glucose (gluconeogenesis)
        • lactate, produced by anaerobic metabolism or in red cells, is converted into glucose in the liver by the Cori cycle

    2. Lipids
      • free fatty acids are esterified with glycerol to form triglyceride, which is then exported with very low density lipoprotein (VLDL)
      • liver is the major organ involved in the synthesis, esterification, and excretion of cholesterol
      • site of phospholipid production
      • site of beta oxidation of fatty acids to produce ketone bodies, which provide energy in the fasting state

    3. Proteins
      • in prolonged fasting, muscle proteins, particularly alanine, are converted in the liver to glucose
      • site of synthesis of many important serum proteins, including albumin, coagulation factors, lipoproteins
      • acute-phase reactants are produced by the liver under the influence of IL-6 and systemic inflammatory states
      • principal site of urea synthesis

    4. Vitamins
      • liver is responsible for the modification of most vitamins into their active co-enzyme form
      • liver is also responsible for the storage and excretion of vitamins and their metabolites
      • absorption of the fat-soluble vitamins A, D, E, and K is dependent upon bile production
      • initial step in vitamin D activation (25-hydroxylation) occurs in the liver

  2. Bile Production
    • bile serves 2 main functions: 1) route of excretion for certain substances (bilirubin, cholesterol, steroids, antibiotics); 2) facilitates intestinal absorption of lipids and fat-soluble vitamins
    • normal daily production of bile is 1500 ml
    • formed at 2 sites: bile canaliculi and bile ductules
    • principal organic compounds include bile acids, cholesterol, phospholipids, and proteins
    • under the influence of secretin

  3. Coagulation
    • all the procoagulant factors except von Willebrand’s factor are produced by the liver
    • factors II, VII, IX, and X are dependent upon vitamin K for their activation
    • factor VII has the shortest half-life (5 to 7 hrs)
    • synthetic function of the liver may be assessed by measuring the prothrombin time, which is dependent upon factor VII

  4. Detoxification
    • drug and toxin metabolism is primarily a hepatic function
    • detoxification reactions include oxidation, reduction, hydrolysis, and conjugation with an endogenous molecule
    • cytochrome P-450 enzyme system is responsible for most of the oxidation reactions

  5. Immune Function
    • liver contains the largest number of fixed macrophages in the body
    • Kupffer cells lie entirely within the sinusoids and thus are in constant contact with the bloodstream
    • Kupffer cells also act as modulators of hepatocyte function by means of cytokine secretion in response to septic stimuli

Assessment of Liver Function

  1. Routine Screening Tests
    • ALT and AST are markers of hepatocellular necrosis
    • elevated alkaline phosphatase level suggests cholestasis or biliary obstruction
    • elevated conjugated (direct) bilirubin suggests mechanical obstruction or cholestasis; elevated unconjugated (indirect) bilirubin suggests hemolysis or drug effects
    • hypoalbuminemia is a marker of severe liver disease or chronic malnutrition
    • elevated prothrombin time or INR is a marker of advanced liver disease
    • LFTs are non-specific and have little or no prognostic value

  2. Scoring Systems
    1. Child-Pugh Score
      • originally designed to predict mortality in patients with cirrhosis and to select patients who might benefit from an elective portocaval shunt
      • also predicts mortality after major abdominal operations
      • based on clinical observations and standard liver function tests
      • Child class A patients can generally tolerate a major hepatectomy or a major abdominal operation with low mortality (~10%)
      • elective surgery is contraindicated in Child class C patients because of a prohibitively high mortality (70% - 80%)

      Child-Pugh Classification
    2. MELD Score
      • developed to predict 3 month survival in patients with cirrhosis
      • major use is to prioritize patients for liver transplant
      • can also be used to access risk for elective surgery
      • calculated using serum bilirubin, serum creatine, and INR

      Mortality Rates by MELD Score






References

  1. Sabiston, 20th ed., pgs 1418 - 1436
  2. Schwartz, 10th ed., pgs 1263 - 1277
  3. UpToDate. Hepatic Resection Techniques. Steven A. Curley MD, FACS, Evan S. Glazer, MD, PhD, MPH, FACS. Dec 02, 2019. Pgs 1 – 44
  4. Simmons and Steed, pgs 246 – 254