tbl 5 pathology readings Flashcards
Within the lobule, hepatocytes are organized into anastomosing sheets or “plates” extending from portal tracts to the terminal hepatic veins. Between the trabecular plates of hepatocytes are vascular sinusoids. Blood traverses the sinusoids and exits into the terminal hepatic veins through numerous orifices in the vein wall. Hepatocytes are thus bathed by well-mixed portal venous blood on one side and hepatic arterial blood on the other. The sinusoids are lined by a ________ endothelium that overlies a perisinusoidal space (the space of Disse) into which abundant hepatocyte microvilli protrude.
Attached to the luminal face of the sinusoids are scattered Kupffer cells, specialized long-lived tissue macrophages that arise early in embryogenesis. Another specialized cell type, the hepatic stellate cell, is found in the ________ and has a role in the storage of vitamin A. Between abutting hepatocytes are bile canaliculi, channels 1 to 2 µm in diameter that are formed by grooves in the plasma membranes of adjacent hepatocytes and are separated from the vascular space by tight junctions. These channels drain successively into the ____________, periportal bile ductules, and finally into the terminal bile ducts within the portal tracts.
fenestrated;
space of Disse;
intralobular canals of Hering
Injured hepatocytes may show several potentially reversible changes, such as accumulation of fat and bilirubin (cholestasis); when injury is not reversible, hepatocytes die by necrosis or apoptosis. Necrosis is commonly seen following hepatic injury caused by __________________. Apoptotic cell death predominates in ___________________ hepatitides.
Widespread death of hepatocytes may produce confluent necrosis . This may be seen in acute toxic or ischemic injuries or in severe chronic viral or autoimmune hepatitis. Confluent necrosis begins as a zone of hepatocyte dropout around the central vein. With increasing severity necrosis “bridges” central veins and portal tracts or adjacent portal tracts
hypoxia and ischemia;
viral, autoimmune, and drug- and toxin-induced;
Regeneration of lost hepatocytes takes place primarily by mitotic replication of hepatocytes adjacent to those that have died. In more severe forms of acute liver injury hepatic stem cells located in a niche near the ____________ may also begin to divide, but the contribution of stem cells to the replenishment of hepatocytes in the setting of acute liver damage remains uncertain. In longstanding chronic liver diseases, however, there is clear evidence that stem cell proliferation and differentiation make significant contributions to parenchymal restoration, probably following the replicative senescence of preexisting hepatocytes. The differentiating progeny of these tissue stem cells produce duct-like structures, called ductular reactions, a morphologic marker of stem cell–mediated liver regeneration.
Scar formation may follow very severe acute injury, but occurs more often as a reaction to chronic injury. The principal cell type involved in scar deposition is the perisinusoidal hepatic stellate cell. Following liver injury, stellate cells may become activated and convert into highly _____________ which produce the fibrous scar. Stellate cell activation involves complex interactions between Kupffer cells, hepatocytes, and inflammatory cells. When there is severe injury that causes death of large number of hepatocytes and the drop out of liver cells, there may be collapse of the underlying reticulin, precluding orderly regeneration of hepatocytes. In such cases, there is activation of stellate cells, and the areas of liver cell loss are replaced by fibrous septae. Eventually, these fibrous septa encircle surviving, regenerating hepatocytes in late-stage chronic liver disease, many forms of which are described as cirrhosis .
canal of Hering;
fibrogenic myofibroblasts,
Acute liver failure is defined as a liver disease that produces ______________ within 6 months of the initial diagnosis. The condition is known as _____________ when the encephalopathy develops within 2 weeks of the onset of jaundice, and as subfulminant liver failure when the encephalopathy develops within 3 months. In the United States, accidental or deliberate ingestion of acetaminophen accounts for almost 50% of cases of acute liver failure, while autoimmune hepatitis, other drugs and toxins, and acute hepatitis A and B infections account for the remainder of cases. In Asia, _____________ predominate as causes of acute liver failure.
The clinical syndrome of acute liver failure is reflected anatomically and histologically as massive hepatic necrosis. The liver is small and shrunken due to loss of __________. Microscopically, there are large zones of destruction surrounding occasional islands of regenerating hepatocytes. Scar is mostly absent given the acute nature of the process.
hepatic encephalopathy;
fulminant liver failure;
acute hepatitis B and E;
parenchyma;
Acute liver failure manifests with nausea, vomiting, jaundice, and fatigue, which are followed by the onset of life-threatening encephalopathy, coagulation defects, and portal hypertension associated with ascites. Typically, _________________- levels in the serum are elevated into the thousands. The liver is initially enlarged by swelling and edema related to inflammation, but then as parenchyma is destroyed the liver shrinks dramatically. Eventually, as hepatocytes are lost, serum transaminase values level off and then decline rapidly as their source disappears. Worsening jaundice, coagulopathy, and encephalopathy develop; with unabated progression, the end result is multiorgan failure and, without transplantation, death.
Manifestations of acute liver failure include the following:
- ______________ (yellow discoloration of the skin and sclera, respectively) due to retention of bilirubin, and cholestasis due to systemic retention of not only bilirubin but also other solutes eliminated in bile.
- Hepatic encephalopathy encompasses a spectrum of disturbances in consciousness ranging from subtle behavioral abnormalities, to confusion and stupor, to coma and death. Encephalopathy may develop over days, weeks, or a few months after acute injury. Fluctuating neurologic signs, including rigidity, hyperreflexia, and asterixis, may develop. ___________ refers to a nonrhythmic rapid extension-flexion movement of the head and extremities, best seen as “flapping” of the hands when the arms are held in extension with dorsiflexed wrists. Elevated ammonia levels in blood and the central nervous system correlate with impaired neuronal function and brain edema.
- Coagulopathy. The liver is the source of a number of coagulation factors that decline in the face of liver failure, leading to easy bruising and bleeding. Paradoxically, disseminated ______________ also may occur due to failure of the damaged liver to remove activated coagulation factors.
- Portal hypertension arises when there is diminished flow through the portal venous system, which may occur because of obstruction at the prehepatic, intrahepatic, or posthepatic level. While it can occur in acute live failure, portal hypertension is more commonly seen with chronic liver failure. In acute liver failure, the obstruction is usually intrahepatic and the major clinical consequences are _______________. In chronic liver disease, portal hypertension develops over months to years, and its effects are more complex and widespread.
- Hepatorenal syndrome is a form of renal failure occurring in individuals with liver failure in whom there are no intrinsic morphologic or functional causes for kidney dysfunction. Sodium retention, impaired free-water excretion, and decreased ____________________ are the main renal functional abnormalities. There is decreased renal perfusion pressure due to systemic vasodilation, activation of the renal sympathetic nervous system and vasoconstriction of the ____________, and increased activation of the renin-angiotensin axis, causing vasoconstriction that further decreases glomerular filtration. The syndrome’s onset begins with a decrease in urine output and rising blood urea nitrogen and creatinine levels.
Jaundice and icterus;
transaminase;
Asterixis;
intravascular coagulation;
ascites and hepatic encephalopathy;
renal perfusion and glomerular filtration rate;
afferent renal arterioles
Cirrhosis is the morphologic change most often associated with chronic liver disease; it refers to the diffuse transformation of the liver into regenerative parenchymal nodules surrounded by fibrous bands. The leading causes of chronic liver failure worldwide include chronic hepatitis B, chronic hepatitis C, _______________, and alcoholic liver disease. While cirrhosis is a common feature of a number of chronic liver diseases, it is not a specific entity, and it is important to recognize that not all chronic liver disease terminates in cirrhosis, and that not all cirrhosis leads to end-stage liver disease. For example, chronic biliary tract diseases often do not give rise to cirrhosis even at end stage, whereas patients with treated autoimmune hepatitis or cured hepatitis C may have adequate liver function in the face of cirrhosis. Even in diseases that are likely to give rise to cirrhosis, such as untreated viral hepatitis, alcoholic liver disease, NAFLD, and metabolic diseases, the morphology and pathophysiology of cirrhosis in each may be different.
Liver failure in chronic liver disease is most often associated with cirrhosis, which is marked by the diffuse transformation of the entire liver into __________________ surrounded by fibrous bands . The nodular nature of the process is readily evident both grossly and microscopically. The size of the nodules, the pattern of scarring (linking of portal tracts to each other vs. linking of portal tracts to central veins), the degree of parenchymal loss, and the frequency of vascular thrombosis (particularly of the portal vein) all vary between diseases and even, in some cases, between individuals with the same disease.
As mentioned earlier, ____________ activation and differentiation gives rise to duct-like structures, the so called ductular reactions. In chronic liver disease, ductular reactions increase with disease progression and are usually most prominent in cirrhosis. Ductular reactions may incite some of the scarring in chronic liver disease and thus may have a negative effect on progressive liver disease.
Regression of fibrosis and even of fully established cirrhosis may follow disease remission or cure. Scars become thinner, more densely compacted, and eventually start to fragment. As fibrous septa break apart, adjacent nodules of regenerating parenchyma coalesce into larger islands. All cirrhotic livers show elements of both progression and regression, with the balance being dictated by the severity and persistence of the underlying disease.
non-alcoholic fatty liver disease (NAFLD);
regenerative parenchymal nodules;
stem cell;
Chronic Liver Failure Clinical Manifestations
About 40% of individuals with cirrhosis are asymptomatic until the most advanced stages of the disease. Even at late stages, they present with nonspecific clinical manifestations, such as __________________, and, eventually signs and symptoms of liver failure discussed earlier. Jaundice, encephalopathy, and coagulopathy may result from chronic liver disease, much the same as in acute liver failure. However, there are some significant additional features:
Chronic severe jaundice can lead to pruritus (itching), the intensity of which may be so profound that patients scratch their skin raw and risk repeated bouts of potentially life-threatening infection. In some patients, severe pruritus is the primary indication for liver transplantation. Pruritus also is frequently seen in other disorders associated with ____________-, suggesting that it is somehow related to the build up of bile salts in the body, but its precise pathogenesis is unknown.
Portal hypertension is more frequent and manifests in more complex ways in chronic liver failure than in acute liver failur. Portosystemic shunts develop when blood flow is reversed from the portal to systemic circulation. These shunts are principally produced by dilation of collateral vessels. Most notably, venous bypasses develop wherever the systemic and the portal circulations share common capillary beds, the most clinically important of which are _________________, which appear in about 40% of individuals with advanced-stage liver disease . These often cause massive, frequently fatal hematemesis, particularly when there is compounding coagulopathy. Portal hypertension often occurs and may lead to _________________, which can lower the platelet count due to sequestration of these elements in the expanded red pulp.
anorexia, weight loss, weakness;
cholestasis;
esophagogastric varices;
congestive splenomegaly;
Acute-on-Chronic Liver Failure
Some individuals after years of stable, well-compensated, chronic disease suddenly develop signs of acute liver failure . In such patients, there is often established cirrhosis with extensive vascular shunting, or large volumes of functioning liver parenchyma with a borderline vascular supply, both of which leave the liver vulnerable to superimposed, potentially lethal insults. The short-term mortality of patients with this form of liver failure is around 50%.
Hepatic insults that cause sudden decompensation of patients with chronic liver disease include: __________ superinfection in those with chronic hepatitis B; emergence of resistance to medical therapy in those with viral hepatitis; development of ascending ___________ in patients with primary sclerosing cholangitis; or replacement of liver parenchyma by primary or metastatic carcinoma. In other instances the cause may be a systemic disorder, such as sepsis, acute cardiac failure or a superimposed toxic injury that tips a well-compensated cirrhotic patient into liver failure.
hepatitis D; bacterial cholangitis
Chronic Liver Failure Clinical Manifestations
Hyperestrogenemia due to impaired estrogen metabolism in male patients with chronic liver failure can give rise to _______________ (a reflection of local vasodilatation) and spider angiomas of the skin. Such male hyperestrogenemia also leads to hypogonadism and ______________ . Hypogonadism also may occur in women from disruption of hypothalamic-pituitary axis functioning.
Most chronic liver diseases predispose to development of _______________.
The course and severity of chronic liver disease with cirrhosis vary widely from patient to patient. Even in instances in which cirrhosis regresses following disease remission or cure, portal hypertension may persist due to the presence of irreversible shunts. The causes of death are liver failure (as in acute liver disease) and HCC. Clinical and laboratory findings are the main criteria used to gauge prognosis and disease progression. It some centers, ____________- are measured to assess the degree of vascular obstruction. Liver biopsy findings correlate with the presence and severity of portal hypertension. For example, specimens with thin fibrous septa and large islands of regenerated parenchyma are unlikely to be associated with portal hypertension, whereas broad bands of fibrosis and loss of parenchyma portend the development of portal hypertension and end-stage liver disease.
palmar erythema;
gynecomastia;
hepatocellular carcinoma ;
portal venous wedge pressures
