The Anatomy of the Liver and How It Functions

CE Article #2 The Anatomy of the Liver and How It Functions CERTAIN DISEASE PROCESSES can cause liver failure; therefore, it is crucial that technicians understand not only how the liver functions but also how to test for the presence of and treat various liver diseases. Technicians who can conduct the different tests used to diagnose liver disease play a key role in client education and are able to provide better care for their patients. Anatomy The liver, a brownish-red, friable organ, is the largest gland in the body. It is located in the cranial abdomen and is shaped to fit around neighboring structures for example, its caudal surface is concave (to fit around the stomach), and its cranial surface curves with the diaphragm. 1 Most of the liver is encased in peritoneum. The liver consists of six lobes. 2 The lobes are separated into tiny hepatic lobules, which help filter blood through the liver. 3 The hepatic cells (i.e., hepatocytes) line the lobules and radiate toward a central vein. 3 As an animal ages, its liver atrophies; therefore, the liver in young animals weighs more than the liver in adult animals. 1 The liver has a unique venous system called the hepatic portal system, which receives both oxygenated and deoxygenated blood. 4 All products of digestion are filtered through the liver, 4 and approximately 80% of the blood that flows into the liver enters via the portal vein and originates from the stomach and intestines. 3 The hepatocytes are nourished by this blood, which is rich in nutrients but not in oxygen. 3 As the blood enters the lobules, plasma flows across the hepatocytes and filters into the central vein; the blood then travels from the central vein into the hepatic vein and eventually into the caudal vena cava. 5 As the blood is filtered through the liver, it passes through Kupffer cells, which help to remove Amy N. Breton, CVT, VTS (ECC) Veterinary Emergency and Specialty Center of New England Waltham, Massachusetts bacteria. The hepatic artery supplies the remaining 20% of the blood to the liver. This blood, which is rich in both oxygen and nutrients, supports the high metabolic activity of the hepatocytes. The hepatocytes secrete hormones and bile, a yellowish-green digestive liquid. The bile is carried through channels of increasing size to the gallbladder and the common bile duct, which leads to the duodenum, where the bile is released. 4 Physiology Bile plays an important role in digestion, and bile production is one of the main functions of the liver. Bile consists primarily of bile salts, water, and bile pigments such as bilirubin (which is created when old red blood cells break down) and biliverdin. 3 Bile salts enhance the absorption of fatty acids and some fat-soluble vitamins, such as vitamins A, D, E, and K. 3 Without bile salts, vitamin deficiencies can occur. One of the most important functions of bile is to emulsify fat so that it can be broken down by digestive enzymes in the gut. 6 The liver also plays an important role in carbohydrate metabolism; in a process called glycolysis, the liver metabolizes carbohydrates by converting excess glucose into glycogen, which is then stored. 7 Stored glycogen is converted back into glucose and released into the body to supply energy. 7 The entire process (glycogenolysis) is controlled by the hormone glucagon, which is produced byαcells in the islets of Langerhans in the pancreas. When glucagon is released, glycogenolysis begins. Patients with liver failure may have decreased glucose levels. The liver also plays a vital role in deamination, in which amino acids are broken down by removal of an amino group. Because excess amino acids cannot be stored, they are converted into enzymes or energy by various tissues in the body. The discarded amino group, however, is converted into ammonia and then 38 JANUARY 2008 Veterinary Technician

Peer Reviewed into urea or uric acid, which is excreted safely through renal filtration. 1,3 Animals with liver failure may have increased levels of ammonia and decreased levels of blood urea nitrogen. The liver also synthesizesα- andβ-globulins, which transport lipids and fat-soluble vitamins throughout the body. 3 Prothrombin is one of the most important α-globulins produced by the liver. Factor X an enzyme that requires vitamin K for synthesis and calcium ions help convert prothrombin into thrombin. 3 Prothrombin and thrombin are necessary for coagulation. If the liver is damaged, the body s ability to coagulate blood may be affected. In addition to synthesizing globulins, the liver helps to synthesize lipoproteins, phospholipids, and cholesterol and aids in fat metabolism by oxidizing fatty acids at a high rate. 3 It also helps to convert carbohydrate molecules into protein molecules and fat, 3 which is then transported by the blood back into the adipose tissue, where it is stored and may be used for energy. 3 The liver stores many substances, including iron and vitamins A, D, and B12. 3 It also helps destroy damaged red blood cells and foreign substances (e.g., drugs), 7 alters toxins such as alcohol by detoxifying them, and excretes toxins in bile. The liver is the primary organ involved in drug and toxin metabolism. The liver plays a role in thermoregulation by helping to produce heat and maintain body temperature through cellular metabolism (i.e., the more active the cells, the more heat they produce). Disease Processes Certain disease processes can cause liver failure. To maintain high-quality patient care, it is important to conduct diagnostic tests to diagnose liver problems. If any of the following diseases or conditions is present, liver disease should be suspected. Although any inflammatory disease can affect the liver, the condition usually must be severe (e.g., anaphylactic shock, systemic inflammatory response syndrome, pancreatitis). Because a large amount of blood is filtered through the liver, any change in the circulatory system could affect the liver. Severe anemia can result in hypoxia, thereby affecting the liver. 8 When the blood supplied to the liver is not appropriately oxygenated, the liver can be damaged. If the liver is damaged because of injury or disease, it may not be able to store vitamins sufficiently, including vitamin B12, which is needed for hemoglobin production. Because the liver helps to regulate glucose, liver disease should be suspected when a patient presents with hypoglycemia. Shock can lead to liver damage. In dogs, the liver and gastrointestinal tract are the main body structures affected by shock. 9 In cats, the main organ affected by shock is the lungs. 9 In cats with anorexia, hepatic lipidosis is a major concern. Triglycerides accumulate in the blood, overwhelming the liver and potentially causing severe liver dysfunction. When petechiae or ecchymoses are observed on a patient, liver involvement should be suspected. Because the liver plays a vital role in coagulation, bleeding under the skin indicates that the body s clotting ability may be jeopardized. To determine if there are any signs of hemorrhage, each patient should undergo a complete physical examination, including inspection of the mucous membranes, sclera, and inguinal areas. Diagnostic Testing Serum Chemistry Profile The most common laboratory tests conducted to evaluate the liver are those that measure the level of specific enzymes, such as alkaline phosphatase (ALP), aspartate aminotransferase (AST),γ-glutamyltransferase (GGT), and alanine transaminase (ALT). An elevation in the level of any of these enzymes usually indicates liver damage resulting from trauma or disease. Liver in a dog with hepatic neoplasia. Note the nodules present. Amy N. Breton, CVT, VTS (ECC) Veterinary Technician JANUARY 2008 39

CE Article #2: The Liver Increased levels of other blood components, such as ammonia and bilirubin, may also be indicative of liver disease. In addition, urinalysis and coagulation testing can be used to determine whether the liver is functioning properly. Alkaline Phosphatase ALP is an enzyme in the biliary duct cells of the liver. ALP levels in plasma increase because of bile duct obstruction, intrahepatic cholestasis, or infiltrative diseases of the liver. 8 Aspartate Aminotransferase AST is an intracellular enzyme that aids the transfer of amino groups during conversion from amino acids toα-oxoacids. 8 AST levels increase when hepatocytes degenerate or undergo necrosis; they may also increase after a patient takes medications, such as antiseizure drugs, or after a traumatic injury (e.g., being struck by an automobile). AST and ALT levels are related to the number of damaged hepatocytes; however, the damage may be reversible. 8 γ-glutamyltransferase GGT, an enzyme found in the bile ducts, is usually tested in conjunction with ALP in order to rule out cholestasis. When GGT testing is conducted in conjunction with ALP testing, it has been shown that the diagnostic value of these tests is improved compared with either test alone. 8 Alanine Transaminase ALT is an enzyme in hepatocytes. When a cell is damaged, ALT enters the bloodstream. ALT levels increase dramatically in patients with acute liver disease; however, an elevated ALT level does not necessarily indicate liver damage. A patient can have normal fluctuations in ALT levels throughout the day. 10 Certain drugs, such as corticosteroids, as well as hepatic injury (e.g., resulting from being struck by an automobile) can also cause an increase in ALT levels. 10 Albumin Albumin, which is synthesized in the liver, is a major protein found in plasma. It is responsible for maintaining colloid osmotic pressure and helping to prevent plasma loss from the capillaries. Patients with chronic liver disease can have decreased albumin levels. 11 By themselves, tests measuring albumin levels cannot determine the degree of liver damage; however, these tests can be used as an additional diagnostic tool. Ammonia Ammonia levels in the blood increase when the liver is not able to convert ammonia into urea. Elevated ammonia levels may indicate the presence of a liver shunt or hepatitis. 12 Bilirubin Bilirubin a product of the breakdown of hemoglobin undergoes conjugation, a process in which the liver makes bilirubin water soluble. In patients with liver damage, conjugation may not occur, causing total bilirubin levels to increase (hyperbilirubinemia). Total bilirubin, the total amount of bilirubin detected in the blood, includes conjugated and unconjugated bilirubin. Some conditions, such as bile duct obstruction or 40 JANUARY 2008 Veterinary Technician

CE Article #2: The Liver hemolytic anemia, can cause increases in total bilirubin levels. 12 Direct bilirubin includes only the portion of bilirubin that has undergone conjugation. If the direct bilirubin level is normal and the total bilirubin level is high, then it is likely that the patient has excessive unconjugated bilirubin (e.g., hemolysis). However, if the direct bilirubin level is high, then the patient has excessive conjugated bilirubin, potentially signaling the presence of a condition such as neoplasia or gallstones. 12 Blood Urea Nitrogen Blood urea nitrogen may be decreased in patients with advanced liver disease because they are not able to convert nitrogenous waste products into urea. Coagulation Tests It is important that abdominal taps, multiple venipunctures (especially those involving the jugular veins), and cystocentesis are not performed until the patient s clotting times are checked and are within normal limits. Prothrombin Time Prothrombin is anα-globulin needed for the coagulation of blood. The prothrombin time (PT) test is performed to assess the extrinsic pathway of the coagulation cascade. Liver disease should be suspected in any patient that has a prolonged PT; however, a prolonged PT does not specifically indicate the presence of liver disease, and a normal PT does not indicate the absence of liver disease. Activated Partial Thromboplastin Time Thromboplastin is a clotting factor that converts prothrombin into thrombin. The activated partial thromboplastin time test assesses the intrinsic pathway of the coagulation cascade to determine how long it takes a patient s blood to clot. PT and activated partial thromboplastin time tests are generally conducted at the same time. Urinalysis Urinalysis should be conducted to determine whether bilirubin is present in the urine (i.e., bilirubinuria). Trace amounts of bilirubin are normal in a concentrated urine sample from a dog, but such findings are abnormal in a cat. 9 If bilirubinuria is evident, additional diagnostic testing should be conducted to rule out liver disease. Imaging Abnormal results on certain blood tests usually indicate that a patient has some type of liver damage. Although some diseases can be ruled out after test results are obtained, the cause of liver damage cannot usually be determined by blood tests alone. Imaging can be used to reveal tumors, obstructions, or other abnormalities. Radiography Radiography is a useful tool but does not usually provide a diagnosis. For example, hepatomegaly can often be observed on a radiograph; however, a tumor originating from the liver rarely can be seen on a radiograph. If neoplasia is suspected, it is important to obtain left, right, and ventrodorsal chest views to look for metastases. Ultrasonography Ultrasonography can also be used as a diagnostic tool when managing a patient with liver disease. Gallbladder obstructions, tumors, bile duct obstructions, and lipidosis can often be diagnosed with ultrasonography. Ultrasonography can distinguish between solid and fluidfilled masses; however, it cannot yield a definitive diagnosis. It is important that a qualified ultrasonographer ideally, one who is board certified conduct the test. For example, finding a liver shunt (portosystemic shunt) in a small puppy can be difficult even for a highly trained individual. Serum Protein Electrophoresis Serum protein electrophoresis is used to measure the levels of different types of proteins. This test is useful for evaluating patients that have abnormal results on liver function tests because it allows a direct quantification of multiple serum proteins, such as total protein, albumin, and α-, β-, and γ-globulins. Different liver diseases can cause elevations in different globulins. 4 Biopsy Ultrasound-Guided Fine-Needle Aspiration Fine-needle aspiration biopsy can be a very useful diagnostic tool; however, it is associated with an increased risk of complications be- 42 JANUARY 2008 Veterinary Technician

Peer Reviewed cause patients with liver disease may have clotting abnormalities and may hemorrhage. Fine-needle aspiration biopsy can also be performed blindly, without ultrasonography. However, samples obtained blindly are often of poor diagnostic quality. Because the liver plays a role in the coagulation cascade, it is important to rule out any clotting problems before obtaining a sample. Little to no sedation is generally needed to perform the biopsy procedure; however, patient movement may result in liver laceration and retrieval of an inadequate sample. Certain diseases or types of neoplasia can be diagnosed using this method; however, the sample obtained does not always yield a diagnosis. A percutaneous needle can also be used to obtain a biopsy sample. The sample obtained using a percutaneous needle is larger than that obtained using a fine needle but can also be nondiagnostic. Laparoscopic Compared with needle biopsy, laparoscopic biopsy can be used to obtain a larger sample of the affected area of the liver, and the laparoscope provides a better view of the liver than does ultrasound imaging. Laparoscopic biopsy is more invasive than ultrasoundguided fine-needle aspiration biopsy; therefore, patients are placed under general anesthesia. However, just as with needle biopsy, it is important to ensure that the patient does not have any clotting problems before laparoscopic biopsy is performed. Treatment Once a diagnosis has been made, a treatment plan should be formulated. Because there are many treatment options available for patients with liver disease, it is important that clients be informed of and understand these options. Even if the pet s overall prognosis is good, some clients may decide to forgo treatment because it can be expensive and timeconsuming; other clients may choose to euthanize their pet if it requires long-term care or extended hospitalization. The overall treatment goal for a patient with liver disease is to provide supportive care. During treatment, it is also important to manage complications associated with liver failure, such as gastrointestinal ulceration, anemia, infection, ascites, edema, and coagulopathy. 9 Because infection is always a potential complication of liver disease, antibiotics may be used as a preventative. When caring for a patient with liver disease, the technician should frequently monitor all vital systems (e.g., cardiovascular, respiratory, neurologic). Because the technician likely spends the most time with the patient, he or she can alert the veterinarian to early signs of complications. It is also important for the technician to thoroughly evaluate the patient during monitoring. For example, if the color of a patient s mucous membranes is not checked regularly, the technician may not recognize that anemia has developed. In addition, the color of a jaundiced patient can change hourly, and it is important to notify the veterinarian if any changes occur. Aggressive fluid therapy is one of the most important treatment options when managing a patient with liver disease. Fluid therapy helps to improve hepatic circulation and prevent complications such as disseminated intravascular coagulation, shock, or renal failure. 9 Often, 0.45% sodium chloride is used to help prevent sodium retention and portal hypertension. 9 Colloids such as hetastarch may be used to help restore oncotic pressure. Electrolyte levels should be monitored, and fluid adjustments should be made accordingly. Ascites may need to be drained in order to in- Glossary Anisocoria Change in pupil size Ascites Accumulation of fluid in the abdomen Cholestasis Cessation of the flow of bile from the liver Coagulation cascade Sequence of enzymatic reactions leading to blood clot formation Extrinsic pathway Pathway that is initiated by tissue thromboplastin (factor III) and involves calcium ions and factor VII Gland Group of cells that excrete a substance Hemolysis Destruction of red blood cells Hepatomegaly Enlargement of the liver Intrinsic pathway Pathway in which factors VIII, IX, XI, and XII are activated by exposure to subendothelial collagen or foreign substances Keto acids Organic acids containing a ketone group and a carboxylic group Neoplasia Formation of a tumor Peritoneum Abdominal lining Veterinary Technician JANUARY 2008 43

Peer Reviewed crease comfort and ease breathing. When treating a patient with liver disease, proper nutrition is essential. During the initial treatment stages, the patient may not be allowed any food by mouth. Patients that appear nauseous or are vomiting should not be fed. However, in patients that require long-term care, nutritional needs must be considered. A feeding tube may be placed if an animal is unwilling to eat. 12 A feeding tube allows for controlled, effective feedings compared with force-feedings using a syringe. Technicians can encourage the patient to eat by offering it a variety of foods or hand-feeding it. Because patients with certain liver diseases require special diets, the veterinarian should be consulted before any feedings are initiated. In patients with diseases such as feline hepatic lipidosis, nutrition plays a crucial role in recovery. 9 Certain treatments may be necessary if a patient experiences complications associated with liver disease. For example, mannitol and furosemide may be used to help reduce cerebral edema, which may develop in patients with severe liver disease. Technicians should immediately notify the veterinarian of anisocoria or changes in neurologic status. If a patient develops coagulopathy, freshfrozen plasma may be given. A technician may also be the first person to notice petechiae on the patient. Follow-Up Often, patients are discharged from the hospital even though they remain slightly jaundiced or have elevated levels of liver enzymes. In some cases, it may take months for a patient s liver to fully recover; therefore, rechecking blood work and/or performing ultrasonography can ensure that treatment is continuing to be effective. Occasionally, a patient may be readmitted to the hospital if its condition worsens. Technicians should educate owners about signs indicating that a pet s condition has worsened; for example, technicians can explain that the owner can look for signs of jaundice by checking the color of the pet s mucous membranes and sclera. If the pet becomes lethargic, develops anorexia, begins vomiting, suffers from diarrhea, or exhibits worsening jaundice, the owner should ensure that the pet receives immediate medical attention. Prognosis Some patients recover quickly from liver disease. Within 24 hours, an animal s condition can change drastically an animal that is very jaundiced and lethargic can become alert and exhibit no jaundice. However, some animals experience severe complications from liver disease, potentially resulting in a wide variety of sequelae. Patients with acute liver failure generally have a good prognosis if the disease is diagnosed early and treatment is started immediately. 9 Patients with chronic liver disease, however, have a variable prognosis. Patients with neoplasia may have a favorable outcome if complete resection is possible and chemotherapy is started early. However, the Veterinary Technician JANUARY 2008 45

CE Article #2: The Liver prognosis is guarded in most patients with hepatic neoplasia. 9 Conclusion Technicians should know how to test for the presence of and treat various liver diseases and should be able to recognize complications in affected patients. If a technician understands how liver disease affects a patient, he or she can notify the veterinarian about important changes in the patient s condition. References 1. Dyce KM, Sack WO, Wensing CJ: Textbook of Veterinary Anatomy. Philadelphia, WB Saunders, 1987. 2. Rosenfeld AJ: Liver, in The Veterinary Medical Team Handbook: The Team Approach to Veterinary Medicine. Ames, IA, Blackwell Publishing, 2007. 3. Hole J: Essentials of Human Anatomy and Physiology, ed 5. Dubuque, IA, William C. Brown, 1995. 4. Dyce KM, Sack WO, Wensing CJ: Textbook of Veterinary Anatomy, ed 3. Philadelphia, WB Saunders, 2002. 5. Aspinall V, O Reilly M: Introduction to Veterinary Anatomy and Physiology. Edinburgh, Butterworth- Heinemann, 2004. 6. Bowen R: Secretion of Bile and the Role of Bile Acids in Digestion. Accessed December 2007 at www.vivo.colostate.edu/hbooks/pathphys/ digestion/liver/bile.html. 7. Aspinall V: Essentials of Veterinary Anatomy and Physiology. London, Elsevier, 2005. 8. Dial SM: Clinicopathologic evaluation of the liver. Vet Clin North Am Small Anim Pract 25(2):257 273, 1995. 9. Wingfield WE, Raffe MR: The Veterinary ICU Book. Jackson Hole, WY, Teton NewMedia, 2002. 10. Hall RL: Laboratory evaluation of liver disease. Vet Clin North Am Small Anim Pract 15(1):3 19, 1985. 11. Lehrer JK: Medical Encyclopedia: Albumin-Serum. Accessed December 2007 at www.nlm.nih.gov/ medlineplus/ency/article/003480.htm. 12. Tilley L, Smith F: The 5-Minute Veterinary Consult: Canine and Feline, ed 2. Philadelphia, Lippincott Williams & Wilkins, 2000. ABOUT THE AUTHOR Amy N. Breton, CVT, VTS (ECC) Understanding how the liver functions is essential for technicians, says Amy, who works in the emergency room at the Veterinary Emergency and Specialty Center of New England in Waltham, Massachusetts, and runs her own behavior consulting service. She and her husband, Joe, have two dogs, one cat, one rabbit, and a tank full of fish. 46 JANUARY 2008 Veterinary Technician