Handbook of Clinical Anesthesia
Hepatic Anatomy, Function and Physiology
The liver provides a diverse spectrum of vital physiologic functions and plays an essential role in maintaining perioperative homeostasis (Table 48-1) (Kaufman BS, Roccaforte JD: Hepatic anatomy, function, and physiology. In Clinical Anesthesia. Edited by Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Philadelphia: Lippincott Williams & Wilkins, 2009, pp 1247–1278). Normal liver function may be present in humans when as much as 80% of the organ has been resected. Insidious hepatic diseases such as chronic hepatitis C can progress silently and destroy the majority of the liver before symptoms develop. A careful preoperative history and physical examination help identify patients in whom laboratory evaluation of liver function is appropriate. These patients are often at increased risk for perioperative morbidity and mortality, including postoperative development of overt liver dysfunction, particularly after major procedures.
- Hepatic Homeostasis
- Vascular Supply
- The liver receives about 25% of the cardiac output via the hepatic artery and portal vein. The hepatic artery delivers about 25% of the total hepatic blood flow but nearly 50% of the hepatic oxygen delivery. The portal vein provides the remaining 75% of total hepatic blood flow and 50% of hepatic oxygen delivery.
- Because portal venous blood has already perfused the preportal organs (stomach, intestines, spleen, and pancreas), it is partially deoxygenated and enriched with nutrients and other substances absorbed from the gastrointestinal tract.
- When patients develop portal hypertension, connections form large portosystemic shunts, permitting
portal venous blood to return to the systemic circulation without traversing the liver (esophageal varices).
Table 48-1 Major Physiologic Functions of the Liver
- Hepatic arterial pressure is similar to aortic pressure, and the mean portal vein pressure is approximately 6 to 10 mm Hg.
- Periportal hepatocytes located close to the terminal vascular branches of the portal vein and hepatic artery are the first to be supplied with oxygen and nutrients (zone 1). The perivenular (centrilobular) area, which is the most distant from these terminal vascular branches, has the least resistance to metabolic and anoxic damage (zone 3).
- Smooth endoplasmic reticulum is more abundant in these cells. Zone 3 is a primary site for glycolysis and lipogenesis. It is also the site for general
detoxification and biotransformation of drugs, chemicals, and toxins.
- The anaerobic milieu of zone 3, however, is also its Achilles heel because these cells are exquisitely susceptible to injury from systemic hypoperfusion and hypoxemia. Sharply defined zone 3 necrosis is also characteristic of injury resulting from accumulation of toxic products of biotransformation as seen in toxicity from hepatotoxic drugs.
- Hepatic Blood Flow.Although the liver as a whole receives 25% of the cardiac output, regional blood flow within the organ is such that certain areas are highly prone to ischemia. The hepatic circulation is regulated by both intrinsic (regional microvascular) and extrinsic (neural and hormonal) mechanisms.
- Innervation of the Liver.The liver is predominantly innervated by two plexuses that enter at the hilum and supply both sympathetic and parasympathetic nerve fibers.
- Drug metabolism is primarily a hepatic event, and the liver influences the plasma concentration of most orally and parenterally administered drugs through its synthesis of drug-binding proteins. Albumin and α1-acid glycoprotein act as sinks to decrease plasma concentrations.
- The goal of metabolism is to convert drugs into inactive water-soluble substances that can be excreted in the bile or urine.
- Patients with significant liver disease may have marked alterations of pharmacokinetics and pharmacodynamics.
- Portosystemic shunts allow orally administered drugs to bypass the liver.
- Decreases in hepatic blood flow seen in patients with liver disease may prolong the elimination half-time of high-extraction drugs.
III. Assessment of Hepatic Function
- Laboratory Evaluation of Hepatic Function(Table 48-2). Liver function tests (LFTs) can be classified into several broad categories.
Table 48-2 Laboratory Evaluation of Hepatic Function
Table 48-3 Causes of Hyperbilirubinemia
- Indices of Hepatocellular Damage.Increased serum activities of aspartate aminotransferase (AST; formerly serum glutamic oxalacetic transaminase [SGOT]) and alanine aminotransferase (ALT; formerly serum glutamic pyruvic transaminase [SGPT]) are detected when hepatocellular injury and necrosis are present.
- Indices of Obstructed Bile Flow.
- Alkaline phosphatase (AP) elevations that are disproportionate to changes in AST and ALT occur with intrahepatic or extrahepatic obstruction to bile flow. (This is a highly sensitive test for assessing the integrity of the biliary system.)
- Hyperbilirubinemia is classified as either predominantly unconjugated or predominantly conjugated (Table 48-3).
- Indices of Hepatic Synthetic Function
- Measurement of serum albumin level and assays of coagulation function are the most widely used methods for assessing hepatic synthetic function.
- Because the half-life in serum is as long as 20 days, the serum albumin level is not a reliable indicator of hepatic protein synthesis in patients with acute liver disease.
- The prothrombin time (PT) and international normalized ratio (INR) are sensitive indicators of severe hepatic dysfunction whether patients have acute or chronic liver disease because of the short half-life of factor VII. A progressively increasing PT is usually ominous in patients with acute hepatocellular disease, suggesting an increased likelihood of acute hepatic failure.
- Indices of Hepatic Blood Flow and Metabolic Capacity
- Elimination of the dye indocyanine green (ICG) from the blood provides an estimate of hepatic perfusion and hepatocellular function because it is highly extracted (70% to 95% by the liver after an intravenous injection).
- Hepatic function can also be assessed with substances that are metabolized selectively by the liver (e.g., lidocaine is metabolized by oxidative N-demethylation to monoethylglycinexylidide [MEGX]).
- Hepatobiliary Imaging
- Ultrasonography is the primary screening test for hepatic disease, gallstones, and biliary tract disease.
- Computed tomography provides better and more complete anatomic definition than ultrasonography.
- Percutaneous transhepatic cholangiography may be used to determine the level and cause of biliary obstruction, confirm the presence of cholestasis without obstruction, and evaluate whether a proximal cholangiocarcinoma is surgically resectable.
- Endoscopic retrograde cholangiopancreatography (ERCP) uses endoscopy to visualize the ampulla of Vater and guide insertion of a guidewire and catheter through the ampulla to permit selective injection of contrast material into the pancreatic and common bile ducts, which are then imaged radiographically. ERCP is the imaging technique of choice in patients with choledocholithiasis because sphincterotomy and stone extraction can often be performed.
- Liver biopsyhas a central role in the evaluation of patients with suspected liver disease because it provides the only means of determining the precise nature of hepatic damage (necrosis, inflammation, steatosis, or fibrosis). The presence of coagulopathy (PT that is 3 seconds greater than the control or platelet count <60,000 cells/mL3)
contraindicates percutaneous liver biopsy, although trans-jugular liver biopsy can be performed safely in these patients.
- Hepatic and Hepatobiliary Diseases
Liver diseases are divided into parenchymal and cholestatic diseases (Table 48-4).
- Cirrhosis: A Paradigm for End-Stage Parenchymal Liver Disease
(Tables 48-5, 48-6 and 48-7)
Table 48-4 Classification of Liver Disease
Table 48-5 Pathophysiology of Hepatic Cirrhosis
- Uncommon Causes of Cirrhosis
VII. Hepatocellular Carcinoma
- Primary hepatocellular carcinoma (HCC) is one of the most common tumors in the world and is the third most frequent cause of death from cancer.
- HCC usually arises in a cirrhotic liver. The most common presenting complaint is abdominal pain, and the most frequent finding on physical examination is an abdominal mass.
Table 48-6 Differential Diagnosis of Acute Azotemia in Patients with Liver Disease
Table 48-7 Modified Child-Pugh Score
Table 48-8 Uncommon Causes of Cirrhosis
VIII. Pregnancy-Related Disorders
- Acute fatty liver of pregnancyoccurs in the late stages of pregnancy.
- Affected women usually present in the third trimester with symptoms related to hepatic failure.
- When acute fatty liver is diagnosed, delivery of the fetus is expedited. (The disease usually improves in response to termination of pregnancy.)
- Preeclampsia and HELLP Syndrome(increased liver transaminases, thrombocytopenia, and hyperbilirubinemia). Prompt delivery of the fetus is indicated if the syndrome develops beyond 34 weeks of gestation or earlier if life-threatening morbidity develops in the mother.
- Hepatic Rupture, Hematoma, and Infarct.These conditions occur in women with preeclampsia and may be the extreme end of the spectrum of HELLP syndrome.
- Cholestatic Disease
- Cardiovascular Dysfunction.The presence of bile salts in circulating blood (cholemia) can impair myocardial contractility.
- Coagulation Disorders.Cholestatic disease predisposes the patient toward development of coagulopathy primarily related to vitamin K deficiency. The coagulation disorders are usually moderate, and parenteral vitamin K corrects the problem. If such patients need urgent surgery, the coagulopathy requires immediate treatment with fresh-frozen plasma.
- Perioperative Management
- Causes of Postoperative Liver Dysfunction Unrelated to Perioperative Factors
- Asymptomatic and Pre-Existing Hepatic Injury.Although postoperative liver dysfunction may result from anesthetic or surgical interventions, it is often unrelated to perioperative factors (pre-existing liver disease).
- Congenital Disorders
- Gilbert's syndrome(familial unconjugated hyperbilirubinemia) is the most common cause of jaundice. It is
a benign metabolic disorder characterized by a decrease in the activity of the hepatic enzyme bilirubin glucuronyltransferase, which is required for hepatocyte uptake of unconjugated bilirubin.
Table 48-9 Perioperative Management of Patients with Liver Disease
- Patients with Crigler-Najjar syndrome(congenital nonhemolytic jaundice) exhibit either an absence (type 1) or marked decrease (type 2) of bilirubin glucuronyltransferase, producing unconjugated hyperbilirubinemia.
- Surgical and anesthesia-related problems are apparently minimal in patients with Gilbert's and Crigler-Najjar syndromes.
XII. Conclusion: Prevention and Treatment of Postoperative Liver Dysfunction
- Identifying patients at high risk for developing liver dysfunction or for having an exacerbation of pre-existing liver disease is of utmost importance for minimizing the morbidity and mortality in such patients (careful preoperative evaluation).
- When liver abnormalities are recognized preoperatively, it is prudent to defer elective procedures until the course of the disease can be determined.
- For operations that cannot be deferred, clinically significant pathophysiologic changes associated with the liver disease (coagulopathy, fluid and electrolyte abnormalities) should be corrected.
- The choice of anesthesia is usually an insignificant issue for peripheral or minor surgery (operations that do not affect splanchnic blood flow).
- The selection of pharmacologic anesthetic agents may have important implications in patients undergoing major operations.
- A primary goal during the maintenance of anesthesia is to ensure the adequacy of splanchnic, hepatic, and renal perfusion, especially in patients with severe liver disease who undergo major abdominal operations.
Table 48-10 Causes of Postoperative Liver Dysfunction
- When postoperative hepatic injury occurs, the mainstay of therapy is supportive (Table 48-10).
- The hepatotoxic potentials of all medications merit consideration. Any medication that is suspect should be discontinued.
- Extrahepatic biliary obstruction should be considered in the differential diagnosis because it may require prompt surgical intervention.
Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.; Stock, M. Christine
Title: Handbook of Clinical Anesthesia, 6th Edition
Copyright ©2009 Lippincott Williams & Wilkins
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