ELDER TIP In elderly people, the blood supply to the liver decreases, and certain liver enzymes become less active. As a result, the liver loses some of its ability to metabolize drugs and higher levels of drugs remain in the circulation, causing more intense drug effects. This increases the risk of drug toxicity.
As still another example of its amazing versatility, the liver forms vitamin A from certain vegetables and stores vitamins K, D, and B12. It also stores iron in the form of ferritin.
Metabolic functions
The liver figures indispensably in the metabolism of the three major food groups: carbohydrates, fats, and proteins. In carbohydrate metabolism, the liver plays one of its most vital roles by extracting excess glucose from the blood and reserving it for times when blood glucose levels fall below normal, when it releases glucose into the circulation, and then replenishes the supply by a process called glyconeogenesis.To prevent dangerously low blood glucose levels, the liver can also convert galactose or amino acids into glucose (gluconeogenesis). The liver also forms many critical chemical compounds from the intermediate products of carbohydrate metabolism.
The liver performs more than half the body’s preliminary breakdown of fats because liver cells metabolize fats more quickly and efficiently than do other body cells. Liver cells break fats down into glycerol and fatty acids and convert the fatty acids into small molecules that can be oxidized. The liver also produces substantial quantities of cholesterol and phospholipids, manufactures lipoproteins, and synthesizes fat from carbohydrates and proteins to be transported in lipoproteins for eventual storage in adipose tissue.
Like so many of its functions, the liver’s role in protein metabolism is essential to life. The liver deaminates amino acids so they can be used for energy or converted into fats or carbohydrates. It forms urea to remove ammonia from body fluids and all plasma proteins (as much as 50 to 100 g/day) except gamma globulin. The liver is such an effective synthesizer of protein that it can replenish as much as half its plasma proteins in 4 to 7 days. The liver also synthesizes nonessential amino acids and forms other important chemical compounds from amino acids.
Production of plasma proteins
The liver synthesizes most of the body’s large molecules of plasma proteins, including all of the albumin, which binds many substances in plasma and maintains colloid osmotic pressure.
Normally, plasma proteins and amino acid levels maintain equilibrium in the blood. When amino acid levels decrease, the plasma proteins split into amino acids to restore this equilibrium. Reacting to decreased levels of amino acids, the liver steps up production of the plasma proteins. The liver may synthesize approximately 400 g of protein daily; for this reason, significant liver damage leads to hyperproteinemia, which in turn disrupts the colloid osmotic pressure and amino acid levels.
The liver also produces most of the plasma proteins necessary for blood coagulation, including prothrombin and fibrinogen, which are the most abundant. The liver forms prothrombin in a process dependent on vitamin K and the production of bile. Fibrinogen, a large-molecule protein formed entirely by the liver, is an essential factor in the coagulation cascade.
Together, the plasma proteins maintain colloid osmotic pressure throughout the capillaries. Because the plasma protein molecules are too large to cross the capillary membrane, they concentrate at the capillary line and produce an osmotic pressure of pull. This constant colloid osmotic pressure at the arteriolar and venular sections of the capillary provides the major osmotic force regulating the return of fluid to the intravascular compartment.
Because of their large molecular size, the plasma proteins don’t easily cross into the interstitial spaces. Their only route for return to the bloodstream is through lymphatic drainage. The lymphatic vessels drain into the lymphatic and thoracic ducts, which drain directly into the superior vena cava.
Assessing for liver disease
In many cases, a careful physical examination and patient history can detect hepatic disease. Watch especially for its cardinal signs: jaundice (a result of increased serum bilirubin levels), ascites (commonly with hemoconcentration, edema, and oliguria), and hepatomegaly. Other signs and symptoms may include right upper quadrant abdominal pain, lassitude, anorexia, nausea, and vomiting. To detect hepatomegaly, palpate the liver’s left lobe, in the epigastrium between the xiphoid process and the umbilicus. Another primary sign is portal hypertension (portal vein pressure greater than 6 to 12 cm H 2O) revealed by auscultation of a venous hum over the patient’s abdomen. Surgical insertion of a catheter into the portal vein allows measurement of portal vein pressure.
Carefully assess the patient’s neurologic status because neurologic symptoms, such as those associated with hepatic encephalopathy (confusion, muscle tremors, and asterixis), may signal the onset of life-threatening hepatic failure. Other common signs of hepatic disease include pallor (commonly linked to cirrhosis or carcinoma), parotid gland enlargement (in alcohol-induced liver damage), Dupuytren’s contracture, gynecomastia, testicular atrophy, decreased axillary or pubic hair, bleeding disorders (ecchymosis and purpura), spider angiomas, and palmar erythema.
Careful abdominal palpation and auscultation can also detect hepatocellular carcinoma or metastasis, which turn the liver rock-hard and cause abdominal bruits. In hepatitis, the liver is usually enlarged; palpation may elicit tenderness at the liver’s edge. In cirrhosis, the atrophic liver is difficult to palpate. In neoplastic disease or hepatic abscess, auscultation may detect a pleural friction rub.
Comprehensive history essential
Ask if the patient has ever had jaundice, anemia, or a splenectomy. Ask about occupational or other exposure him to toxins (carbon tetrachloride, beryllium, or vinyl chloride), which may predispose him to hepatic disease.Consider recent travel or contact with persons who have traveled to areas where hepatic disease is endemic.
Make sure to ask about alcohol consumption, a significant factor in suspected hepatic disease. Remember, an alcoholic may deliberately underestimate his alcohol intake, so interview the patient’s family as well. Ask about recent contact with a jaundiced person and about any recent blood or plasma transfusions, blood tests, tattoos, or dental work. Find out if the patient takes any drugs that may cause liver damage, such as sedatives, tranquilizers, analgesics, and diuretics that cause potassium loss. Ask if the onset of symptoms was abrupt or insidious or if it followed abdominal injury that could have damaged the liver. Ask if the patient bruises or bleeds easily. Check the color of stools and urine, and ask about any change in bowel habits. Also ask if the patient’s weight has fluctuated recently.
Liver function studies
Numerous tests are available to detect hepatic disease. Perhaps the most useful tests are liver function studies, which measure serum enzymes and other substances. Typical findings in hepatic disease include:
❑ increased bilirubin levels
❑ increased alkaline phosphatase and 5'-nucleotidase levels
❑ elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT): possible hepatocellular damage, viral hepatitis, or acute hepatic necrosis
❑ elevated gamma-glutamyltransferase levels: especially helpful because this enzyme level rises even when hepatic damage is still minimal
❑ hypoalbuminemia: subacute or massive hepatic necrosis or cirrhosis
❑ hyperglobulinemia: chronic inflammatory disorders
❑ prolonged prothrombin time or partial thromboplastin time: hepatitis or cirrhosis
❑ elevated serum ammonia levels: hepatic encephalopathy
❑ decreased serum total cholesterol levels: liver disease
❑ positive lupus erythematosus cell test (in chronic active hepatitis and the presence of hepatitis B antigen).
Liver function studies are less reliable after liver trauma. For instance, tests done long after the injury might miss an initial rise in serum AST and ALT levels. Several less specific blood tests for detecting hepatic disease are urine urobilinogen, lactate dehydrogenase, and ornithine carbamoyltransferase.
Other useful diagnostic tests include the following:
❑ Plain abdominal X-rays may indicate gross hepatomegaly and hepatic masses by elevation or distortion of the diaphragm and may show calcification in the gallbladder, biliary tree, pancreas, and liver.
❑ Barium studies may indicate an elevated left hepatic lobe by displacing the barium-filled stomach laterally and posteriorly.
❑ Oral cholecystography is useful because parenchymal dysfunction and impaired bile excretion decrease the excretion of the contrast material and prevent visualization of the gallbladder.
❑ Percutaneous transhepatic cholangiography distinguishes mechanical biliary obstruction from intrahepatic cholestasis.
❑ Angiography demonstrates hepatic arterial circulation (altered in cirrhosis) and helps diagnose primary or secondary hepatic tumor masses.
❑ Radioisotope liver scans (scintiscans) may show an area of decreased uptake (a “hole”) using a colloidal or bengal scan or an area of increased uptake (a “hot spot”) using a gallium scan in hepatoma or hepatic abscess.
❑ Computed tomography scan produces in-depth, three-dimensional images of the biliary tract (the liver as well as the pancreas) that help distinguish between obstructive and nonobstructive jaundice and also helps identify space-occupying hepatic lesions.
❑ Portal and hepatic vein manometry localizes obstructions in the extrahepatic portion of the portal vein and portal inflow system or increased pressure in the presinusoidal vessels.
❑ Percutaneous or transvenous liver biopsy can determine the cause of unexplained hepatomegaly, hepatosplenomegaly, cholestasis, or persistently abnormal liver function tests; it’s also useful when systemic infiltrative disease (such as sarcoidosis) or primary or metastatic hepatic tumors are suspected.
❑ Laparoscopy visualizes the serosal lining, liver, gallbladder, spleen, and other organs and is useful in unexplained hepatomegaly, ascites, or an abdominal mass.
Gallbladder anatomy
The gallbladder is a pear-shaped organ that lies in the fossa on the underside of the liver and is capable of holding 50 ml of bile. Attached to the large organ above by connective tissue, the peritoneum, and blood vessels, the gallbladder is divided into four parts: the fundus, or broad inferior end; the body, which is funnel-shaped and bound to the duodenum; the neck, which empties into the cystic duct; and the infundibulum, which lies between the body and the neck and sags to form Hartmann’s pouch. The hepatic artery supplies the cystic and hepatic ducts with blood, which drains out of the gallbladder through the cystic vein. Rich lymph vessels in the submucosal layer also drain the gallbladder as well as the head of the pancreas.
The biliary duct system provides a passage for bile from the liver to the intestine and regulates bile flow. The gallbladder itself collects, concentrates, and stores bile. The normally functioning gallbladder also removes water and electrolytes from hepatic bile, increases the concentration of the larger solutes, and reduces its pH to less than 7.In gallbladder disease, bile becomes more alkaline, altering bile salts and cholesterol and predisposing the organ to stone formation.
Mechanisms of contraction
The gallbladder responds to sympathetic and parasympathetic innervation. Sympathetic stimulation inhibits muscle contraction, mild vagal stimulation causes the gallbladder to contract and the sphincter of Oddi to relax, and stronger stimulation causes the sphincter to contract. The gallbladder also responds to substances released by the intestine. For instance, after chyme (semiliquid, partially digested food) enters the duodenum from the stomach, the duodenum releases cholecystokinin (CCK) and pancreozymin (PCZ) into the bloodstream and stimulates the gallbladder to contract. The gallbladder also produces secretin, which stimulates the liver to secrete bile and CCK-PCZ. The gallbladder may also respond to some type of hormonal control, a theory based in part on the fact that the gallbladder empties more slowly during pregnancy.
Assessing for gallbladder disease
During your physical examination of a patient with suspected gallbladder disease, look for its telltale signs and symptoms: pain, jaundice (a result of blockage of the common bile duct), fever, chills, indigestion, nausea, and intolerance of fatty foods. Pain may range from vague discomfort (as when pressure within the common bile duct gradually increases) to deep visceral pain (as when the gallbladder suddenly distends). Abrupt onset of pain with epigastric distress indicates gallbladder inflammation or obstruction of bile outflow by a stone or spasm.
The onset of jaundice also varies. If the gallbladder is healthy, jaundice may be delayed several days after bile duct blockage; if the gallbladder is absent or diseased, jaundice may appear within 24 hours after the blockage. Other effects of obstruction — pruritus, steatorrhea, and bleeding tendencies — may accompany jaundice. Gallbladder disorders rarely cause internal bleeding, but when they do — as in cholecystitis or obstructive clots in the biliary tree from GI bleeding — they can be fatal.
Diagnostic tests
After taking a thorough patient history and carefully assessing the clinical features, the next step in accurate diagnosis of gallbladder disease is cholecystography, in which X-rays are taken of the gallbladder after the patient has ingested radiopaque dye.However, visualization depends on absorption of the dye from the small intestine, the liver’s capacity to remove the dye from the blood and excrete it in bile, the patency of the ductal system, and the ability of the gallbladder to concentrate and store the dye.Normally, the gallbladder fills about 13 hours after ingestion of the dye. Presence of stones or failure to visualize the gallbladder is significant.
Other diagnostic tests for gallbladder disease include the following:
❑ Percutaneous transhepatic cholangiography differentiates extrahepatic from intrahepatic obstructive jaundice and helps detect biliary masses and calculi. Needle insertion in a bile duct permits withdrawal of bile and injection of dye. Fluoroscopic tests evaluate the filling of the hepatic and biliary trees. The test also permits palliative internal or external placement of biliary catheters for free flow of bile.
❑ Duodenal drainage diagnoses cholelithiasis, choledocholithiasis, biliary obstruction, hepatic cirrhosis, and pancreatic disease and differentiates types of jaundice. A tube is passed through the GI tract into the duodenum, and CCK-PCZ is given to stimulate the gallbladder, permitting measurement of bile flow and also specimen collection, which is examined for mucus, blood, cholesterol crystals, pancreatic enzymes, cancer cells, bacteria, or calcium bilirubinate. Duodenal drainage is especially useful when gallbladder function is poor or absent, when cholecystography fails to visualize the gallbladder or yields negative results despite continuing symptoms, or when cholecystography is contraindicated because of the patient’s condition.
❑ In endoscopic retrograde cholangiopancreatography, duodenal endoscopy with dye injection and fluoroscopy are used to cannulate and visualize biliary and pancreatic ducts. This test is useful in locating obstruction, calculi, carcinoma, or stricture and for obtaining bile or pancreatic juice for analysis. Internal stents can be inserted to allow free flow of bile or pancreatic juice.
❑ In gallbladder ultrasound, sound waves are used to visualize the gallbladder and locate obstruction, stones, and tumors. This test is 95% accurate in detecting stones.
Other appropriate tests for biliary disease are the same as those for hepatic disease.
Book Source Details
- Book Title: Professional Guide to Diseases (Eighth Edition)
- Author(s): Springhouse
- Year of Publication: 2005
- Copyright Details: Professional Guide to Diseases (Eighth Edition), Copyright © 2005 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
» Next page: Infants with greater than 20% of their bilirubin in the direct form have cholestasis or obstruction to bile flow. The first step in evaluation of prolonged jaundice is to measure total and fractional bilirubin concentrations (Avoiding Common Pediatric Errors)
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