The Liver and Biliary Tract






Figure 8.1


Normal liver in situ, gross

Here is the normal liver in situ in the upper abdomen, as seen at autopsy. The liver lies below the diaphragm (▲), and the chest cavity is above with the heart (♦) and lungs (∗). As can be seen, the liver is the largest parenchymal organ. The right lobe (◼) (on the left ) is larger than the left lobe (□). The falciform ligament (+) is the rough dividing line between the two lobes. Embryologically, the liver is primarily derived from an endodermal bud of foregut.



Figure 8.2


Normal liver, gross

The external surface of a normal liver is shown. The color is brown, and the surface is smooth. The normal liver in adults weighs 1400 to 1600 g. There is a dual blood supply, with one-third of the blood flow but most of the oxygenated blood supplied by the hepatic artery, and two-thirds of the blood flow coming through the portal venous system draining from the intestines. Bile formed in the liver drains from the canaliculi of hepatic lobules through increasing diameters of branching ducts to coalesce into right and left hepatic ducts that join at the hilum just outside the inferior hepatic surface to form the common bile duct.



Figure 8.3


Normal liver, gross

The cut surface of a normal liver has a uniform brown color. Near the hilum, note the portal vein (◼) carrying blood to the liver, which branches at center left, with accompanying hepatic artery and bile ducts. At the lower right is a branch of hepatic vein (□) draining blood from the liver to the inferior vena cava. The liver performs numerous metabolic functions, including the processing of dietary amino acids, carbohydrates, and lipids. Hepatocytes detoxify and excrete waste products through the bile and synthesize many plasma proteins.



Figure 8.4


Normal liver zones, microscopic

The liver is functionally divided into lobules with a central vein and peripheral triads. Hepatic cords radiate from the central vein as single plates of one hepatocyte thickness sandwiching a bile canaliculus flowing toward the triad. Hepatocytes adjacent to the triad form a “limiting plate.” The lobule has three zones, defined by their relationship to the portal triad at the upper right and the central vein at the lower left. Zone 1 is periportal and receives blood with the highest oxygen concentration. Zone 2 encompasses the central portion of a liver lobule (mid-zonal). Zone 3 is centrilobular. Within the triad are branches of bile ducts, hepatic artery, and portal vein.



Figure 8.5


Normal liver, microscopic

The normal liver is seen at low power with a reticulin stain to outline the connective tissue support by the dark reticulin fibers. The hepatic cord architecture, with plates of hepatocytes staining pink, and sinusoids between, is outlined. A portal triad appears at the right, and a central vein is in the center. Hepatocytes are in the resting phase of the cell cycle, and in response to injury can reenter the cycle and proliferate to regenerate hepatic parenchyma. Perisinusoidal stellate cells in the space of Disse can be transformed into myofibroblasts in response to hepatic inflammation.



Figure 8.6


Normal liver, CT image

Abdominal CT scan with contrast enhancement shows the appearance of the normal liver. The attenuation (brightness) of the liver (▪) and spleen (♦) is similar. Bright orally administered contrast material fills the stomach, seen here between the liver and spleen. Intravenous contrast material in the hepatic veins is brighter than the surrounding hepatic parenchyma. The right lobe of the liver is much larger than the left lobe, which extends across the midline. Because the liver is the largest abdominal organ, it may be injured with blunt abdominal trauma, producing surface lacerations through the thin Glisson capsule, leading to hemoperitoneum.



Figure 8.7


Jaundice, gross

The end product of heme degradation is bilirubin. The hepatocytes take up unconjugated bilirubin and conjugate it with glucuronic acid and excrete it into bile. Increased bilirubin production, decreased hepatic conjugation and excretion, or biliary tract obstruction leads to increasing bilirubin levels in the blood. This is observed as the physical examination finding of jaundice, or icterus. The normally white sclera of the eye is yellow here because of jaundice. Transient neonatal jaundice results from β-glucuronidases in maternal milk that deconjugate bilirubin diglucuronides in the gut, which are reabsorbed.



Figure 8.8


Jaundice, gross

Increased amounts of circulating bilirubin in the blood can lead to the physical examination finding of icterus, or jaundice, as seen here with the yellowish hue of the skin. With hemolysis of erythrocytes, there is an increase in unconjugated (indirect) bilirubin to produce icterus. An increase in the conjugated (direct) fraction of bilirubin suggests intrahepatic disease, such as hepatitis, or biliary tract obstruction. Direct and indirect bilirubin concentrations in serum add to the total serum bilirubin. An elevation in serum alkaline phosphatase suggests biliary tract obstruction because an isoenzyme of alkaline phosphatase is produced in bile ductular epithelium and in hepatocyte canalicular membranes.



Figure 8.9


Kernicterus, gross

Unconjugated bilirubin is tightly bound to circulating albumin and is not excreted in urine; in premature newborns without the mature hepatic capacity to clear bilirubin, blood levels increase, and bilirubin accumulates in the brain to cause neurologic damage. The yellow staining (◀) in the brain of a neonate is known as kernicterus . Coronal sections of medulla in the left panel and cerebral hemisphere in the right panel show kernicterus in deep gray matter. Increased unconjugated bilirubin, which accounts for the kernicterus, is toxic to brain tissue. Kernicterus is more likely to occur with prematurity, low birth weight, and increased bilirubin levels.



Figure 8.10


Cholestasis, microscopic

The yellowish pigmentation (◀) seen in the hepatocyte cytoplasm on the right is due to the accumulation of bile pigments. Intrahepatic cholestasis can result from hepatocyte dysfunction or biliary tract obstruction. Continuing biliary obstruction can also lead to bile duct proliferation, with more than one ductule in an expanded portal tract seen on the left. The catabolism of heme derived from developing, damaged, and senescent erythrocytes produces bilirubin loosely bound to albumin in the blood. Bilirubin is taken up into hepatocytes, bound to cytosolic glutathione- S -transferases, conjugated with glucuronic acid by uridine diphosphate-glucuronyl transferase, and excreted into the bile canaliculus.



Figure 8.11


Cholestasis, microscopic

The yellowish green accumulations of bile pigment are seen here in expanded liver canaliculi. Obstruction of the biliary tree leads to intrahepatic biliary stasis and formation of bile lakes. Proliferation of bile ducts may occur in response to chronic obstruction. If prolonged, there can be portal fibrosis with “biliary” cirrhosis. Bile acts as an emulsifier and is an important component of lipid digestion in the small intestine. Lack of bile secretion into the duodenum leads to acholic (clay-colored) stools and possible steatorrhea with increased stool fat. Malabsorption of fat-soluble vitamins A, D, E, and K can occur. Some vitamin D and K is synthesized endogenously.



Figure 8.12


Hepatic necrosis, gross

Necrosis and hepatic lobular collapse are seen here as areas of hemorrhage with irregular furrows and granularity over the cut surface. Extensive necrosis can follow hepatocyte injury from toxins, infections (e.g., fulminant viral hepatitis), and ischemia. Alanine aminotransferase and aspartate aminotransferase enzymes are released into the blood (the former more specific for liver injury). Extensive loss of hepatocyte function can lead to decreased protein synthesis, with hypoalbuminemia and decreased production of clotting factors II, VII, IX, and X (initially manifested by an elevated prothrombin time), and decreased metabolic function, as in the urea cycle, with hyperammonemia.



Figure 8.13


Cirrhosis, gross

Cirrhosis occurs when diffuse chronic hepatic injury leads to formation of fibrous septa that extend between portal tracts, disrupting the normal hepatic architecture along with formation of regenerative nodules of parenchyma. The normal vascular inflow and outflow patterns are disrupted, with development of portal hypertension. This external appearance has a markedly bumpy appearance of the liver capsule. The regenerative hepatocyte nodules average less than 3 mm in size. Cirrhosis requires at least a decade to develop from chronic liver injury, and a cirrhotic liver tends to decrease in size over time. Reversal of cirrhosis is potentially possible to some extent but slow. Here, hepatic failure is marked by hyperbilirubinemia with green-tinged appearance of some nodules after formalin fixation (with oxidation of bilirubin to biliverdin).



Figure 8.14


Cirrhosis, gross

In micronodular cirrhosis, regenerative nodules average 3 mm or less in size. The yellow-brown appearance of these nodules is due to concomitant hepatic steatosis. The most common cause of micronodular cirrhosis and steatosis is chronic alcohol abuse. A fine reticular fiber network of type III collagen is normally present in the liver, but with cirrhosis, there is extensive deposition of type I and III collagen generated from activated perisinusoidal stellate cells. Cirrhosis may remain clinically silent for many years until complications of portal hypertension, such as esophageal varices or ascites develop, or there is significant loss of functional liver parenchyma with diminished metabolic capacity.



Figure 8.15


Cirrhosis, gross

Macronodular cirrhosis seen here on the inferior hepatic surface has multiple nodules greater than 3 mm in size with extensive deposition of tan-appearing collagen surrounding these regenerative nodules. This is end-stage decompensated cirrhosis; some cases remain well-compensated (no metabolic derangements) or partially compensated. The most common cause of macronodular cirrhosis is viral hepatitis. Most causes of cirrhosis can produce both patterns and a mixed micro- and macronodular cirrhosis; the nodular pattern provides no reliable clue to underlying etiology.



Figure 8.16


Cirrhosis, CT image

With this abdominal CT scan, the small, nodular cirrhotic liver (▪) has more parenchymal heterogeneity (light and dark areas) than a normal liver. The abnormal blood flow through cirrhotic liver leads to an elevation in portal venous pressure. Portal hypertension leads to splenomegaly (♦), as shown here. Increased collateral venous blood flow may also lead to formation of esophageal varices, dilated superficial abdominal veins (caput medusae), and hemorrhoids. Chronic alcohol abuse, nonalcoholic fatty liver disease, viral hepatitis B and C, biliary tract disease, hereditary hemochromatosis, Wilson disease, and α 1 -antitrypsin deficiency can lead to cirrhosis. When no identifiable cause is found, the term cryptogenic cirrhosis is employed.



Figure 8.17


Cirrhosis, MRI

This abdominal T2-weighted MR image in axial view shows a small, shrunken cirrhotic liver (▪). The spleen (♦) is larger than normal from portal hypertension and can reach 1 kg in size. Transudation from the intravascular compartment producing an ascites often accompanies cirrhosis. These ascites result from multiple mechanisms, including hepatic sinusoidal hypertension, hypoalbuminemia, increased lymph drainage into the peritoneal cavity, leakage from intestinal capillaries, and secondary hyperaldosteronism with renal sodium and water retention. In addition, “hepatorenal syndrome” occurs with decreased renal function caused by diminished renal perfusion coupled with renal afferent arteriolar vasoconstriction.



Figure 8.18


Cirrhosis, microscopic

Micronodular hepatic cirrhosis shown at low power has regenerative nodules of hepatocytes ringed by thick bands (♦) of collagenous fibrosis. Within and between the fibrous bands are lymphocytic infiltrates and a proliferation of bile ductules. The hepatocyte proliferation from nodular regeneration increases the risk for hepatocellular and (to a lesser extent) cholangiolar carcinoma. Liver injury leads to Kupffer cell activation with release of cytokines, such as platelet-derived growth factor and tumor necrosis factor, which stimulate stellate cells in the space of Disse to proliferate into myofibroblastic cells that contribute to the fibrogenesis.



Figure 8.19


Cirrhosis and ascites, CT image

This abdominal CT scan shows ascites with extensive fluid collections (♦) in the peritoneal cavity, a complication of cirrhosis of the liver with portal hypertension. The cirrhotic liver has diminished protein synthetic function, leading to hypoalbuminemia and diminished intravascular oncotic pressure. This is combined with increased sodium and water retention by the kidneys and increased hydrostatic pressure in veins and capillaries to promote this extravascular fluid collection. The patient may note increasing abdominal girth, and a fluid wave may be observed on physical examination. There is risk for spontaneous bacterial peritonitis.



Figure 8.20


Caput medusae, gross

Portal hypertension results from the abnormal hepatic blood flow. The increased pressure is transmitted to portal collateral venous channels that may become dilated. Caput medusae consists of dilated superficial veins (▲) radiating from the umbilicus toward the rib margins, as seen here on the abdominal skin of a patient with cirrhosis of the liver. Other venous collaterals affected by portal hypertension include the esophageal plexus and the hemorrhoidal veins. In addition to cirrhosis, portal hypertension may result from infiltrative granulomatous diseases, schistosomiasis, and marked steatosis.



Figure 8.21


Hepatic encephalopathy, microscopic

The brain damage with toxic injury in hepatic encephalopathy can include Alzheimer type 2 cells (▲) found in the lower layers of the cortex and in the basal ganglia. These are enlarged protoplasmic astrocytes that are responding to the toxins (primarily ammonia) that are not cleared by the urea cycle in the failing liver. These two cells as shown here have an enlarged watery nucleus with no visible cytoplasm and prominent nucleoli. Patients may exhibit muscular rigidity, hyperreflexia, and asterixis before onset of confusion progressing to stupor and coma.



Figure 8.22


Viral hepatitis, gross

Viral hepatitis may produce acute infection with areas of necrosis and collapse of the liver lobules. The necrosis is seen here as ill-defined, pale yellow areas between more viable areas of light brown hepatic parenchyma. Note the irregularity of the capsular surface on the right from lobular collapse. If a significant portion of the parenchyma becomes necrotic, the liver becomes pale and shrunken—diffuse massive necrosis—a rare complication most likely to occur with the ordinarily subclinical hepatitis A infection, or in some cases of hepatitis B infection, particularly with hepatitis D coinfection, and hepatitis E. Patients may present with nausea, anorexia, malaise, and fever, then icterus, and progress to hepatic encephalopathy.



Figure 8.23


Viral hepatitis, microscopic

There is ballooning degeneration of many hepatocytes (arrows) in this case of acute fulminant hepatitis. This ballooning is a manifestation of apoptosis (single cell necrosis). Hepatitis A, a picornavirus with single-stranded RNA within a capsid, hepatitis B, an enveloped virus with double-stranded DNA, or hepatitis C, an enveloped virus with a single-stranded RNA genome, may induce cytotoxic CD8 lymphocytes to attack the virally infected hepatocytes. Drugs and toxins that produce hepatic necrosis, such as halothane or isoniazid, may be directly cytotoxic to hepatocytes. There are vaccines for hepatitis A and B.



Figure 8.24


Viral hepatitis E, microscopic

Note the presence of both lymphocytes (mainly in the portal tract— left panel ) and neutrophils (mainly at the interface with adjacent hepatocytes— right panel ) representative of hepatitis E virus (HEV) infection. HEV is more common in developing nations, where it is most often sporadic and epidemic in men, causes acute icteric hepatitis, and rarely leads to chronic hepatitis. Mortality is low except in pregnant women. It is most often spread through contaminated water. A less common form of endemic HEV infection occurs in developed nations with foodborne contamination (pigs as a vector).



Figure 8.25


Viral hepatitis, microscopic

Ongoing chronic hepatitis can lead to lobular irregularity, with fibrosis and inflammation (♦) seen between the lobules. In this case of hepatitis C virus (HCV) infection, there is a minimal degree of steatosis as well. This case is at a high stage, with extensive fibrosis and beginning progression to macronodular cirrhosis, as evidenced by the large regenerative nodule (◼). Serologic testing for diagnosis of this form of viral hepatitis includes the HCV antibody test. Polymerase chain reaction testing for HCV RNA can identify HCV subtypes. Hepatitis C accounts for many (but not all) cases formerly called non-A , non-B hepatitis . About 85% of HCV cases proceed to chronic hepatitis, which remains stable in 80%, but leads to cirrhosis in 20%.



Figure 8.26


Viral hepatitis, microscopic

This portal triad is expanded by mainly mononuclear inflammatory cell infiltrates, and the limiting plate of hepatocytes around the triad has been breached, with extension of the inflammation into adjacent hepatic parenchyma, along with focal interface necrosis (▲) of the hepatocytes. This is typical of a chronic active form of hepatitis. The aspartate aminotransferase and alanine aminotransferase enzymes would be expected to remain elevated in the patient’s serum. In this case, the hepatitis B surface antigen and hepatitis B core antibody were positive, along with hepatitis B “e” antigen (HBeAg) from continued viral proliferation. Chronic hepatitis C viral infection can appear similarly.



Figure 8.27


Viral hepatitis, microscopic

The extent of chronic hepatitis can be graded by the degree of activity (necrosis and inflammation) and staged by the degree of fibrosis. In this case, hepatitis C virus (HCV) has progressed to chronic hepatitis, and necrosis and inflammation are prominent, and there is some steatosis (♦). Regardless of the grade or stage, the etiology of the hepatitis must be sought because the treatment may depend on knowing the cause, and chronic liver diseases of different etiologies may appear microscopically and grossly similar. Treatment with antiviral drugs can be effective for HCV and for hepatitis B virus infection.



Figure 8.28


Hepatic abscesses, gross and microscopic

Pyogenic abscesses in liver are often bacterial and result from spread of infection to hepatic parenchyma with septicemia through the arterial supply, via abdominal infection through portal vein, through an ascending biliary tract infection (cholangitis), with direct spread from an adjacent intra-abdominal infection, or from direct introduction of organisms with penetrating trauma. The left panel shows multiple microabscesses (▲) in a patient with septicemia. The right panel shows a microabscess containing numerous neutrophils producing focal liquefactive necrosis, along with the formation of an organizing abscess wall with some pink fibrin. Patients with abscesses can have fever, right upper quadrant pain, and hepatomegaly. Parasitic and helminthic infections may also cause hepatic abscesses.



Figure 8.29


Acetaminophen toxicity, microscopic

Pale pink areas (♦) represent necrotic hepatocytes. The rate of serum aspartate aminotransferase and alanine aminotransferase increase indicates the extent of hepatic necrosis. Acetaminophen toxicity may be more severe with accidental overdose in many cases because of an additional risk factor of chronic alcohol abuse. Therapeutic drug levels are metabolized by hepatic conjugation with glucuronidation and sulfation, but acute ingestion of more than 140 mg/kg overwhelms normal metabolic pathways, so more acetaminophen is metabolized to the toxin N -acetyl- p -benzoquinone imine (NAPQI) by cytochrome P-450. NAPQI is normally detoxified by glutathione, but chronic alcoholism and malnutrition can deplete glutathione and induce P-450, increasing toxicity.



Dec 29, 2020 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on The Liver and Biliary Tract
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