05-27-2008, 01:57 PM
most frequent asked topics in USMLE.
might be this can help to some1.
Acute acalculous cholecystitis is an acute inflammation of the gallbladder in the absence of gallstones.
It is most commonly seen in hospitalized patients in the following conditions:
1. Extensive burns
2. Severe trauma
3. Prolonged TPN.
4. Prolonged fasting
5. Mechanical ventilation.
Involved pathophysiology is localized or generalized ischemia, biliary stasis, infection, or external compression of the cystic duct. It generally presents with right upper quadrant abdominal pain with fever, leucocytosis, and abnormal liver function tests. It can lead to complications like gangrene, perforation, and emphysematous cholecystitis. The initial investigation of choice is an ultrasonogram, which shows signs of acute cholecystitis and no gallstones; however, CT scan and HIDA scans are more sensitive and specific for the diagnosis. It is important to have a high degree of suspicion in high-risk patients in order to correctly identify this problem.
Non Alcoholic Hepatic Steatosis (NASH). Some of the risk factors for NASH are:
1. Obesity: The incidence of NASH has increased in parallel with the increase in obesity. 40% of the obese patients have some degree of steatosis on liver biopsy.
2. Diabetes mellitus: Disorder of hepatic insulin sensitivity has been thought to be responsible for this.
3. Total parental nutrition (TPN)
4. Hyperlipidemia
5. Drugs like amiodarone
6. Bypass surgery for obesity
liver biopsy shows steatosis, polymorphonuclear cellular infiltrates, and necrosis.
Treatment of NASH aims to control the underlying co morbid conditions. Ursodeoxycholic acid has also being found to decrease the transaminase levels in patients with NASH.
1. Chronic active hepatitis: These patients have piecemeal necrosis, (erosion of the limiting plate of hepatocytes surrounding the portal triad), hepatocellular regeneration, along with foci of necrosis and inflammation in the liver lobule.
2. Chronic persistent hepatitis: A mononuclear inflammatory infiltrate is localized to and contained within portal tracts. The "limiting plate" of periportal hepatocytes is intact, and there is no extension of the necroinflammatory process into the liver lobule.
Liver biopsy is the most reliable way to distinguish chronic active from chronic persistent hepatitis.
Chronic hepatitis C is associated with number of extra hepatic complications like:
1. Cryoglobulinemia.
2. B cell lymphomas.
3. Plasmacytomas.
4. Autoimmune diseases like Sjögren™s syndrome and thyroiditis.
5. Lichen planus.
6. Porphyria cutanea tarda.
7. Idiopathic thrombocytopenic purpura.
Membranous glomerulonephritis is an important one associted with hep C.
If patient has recurrent pancreatitis for which no obvious cause is identified. In this situation ERCP would be the best investigation to search for the underlying cause, ERCP in this case would help to diagnose ductal abnormalities including pancreatic divisum, choledochal cysts, and common bile duct stones. It would also allow for gall bladder aspiration of bile to look for biliary crystals or microlithiasis.
Dubin Johnson and Rotor™s syndrome are two familial disorders of hepatic bile secretion, which leads to conjugated hyperbilirubinemia.
Dubin Johnson syndrome is a benign, rare, autosomal recessive disorder characterized by predominantly conjugated hyperbilirubinemia. Total bilirubin is typically between 2-5 mg/dl, but higher and lower values are possible. The degree of hyperbilirubinemia may change with acute stress, OCP, and pregnancy. Liver enzymes are normal and these patients are generally asymptomatic. Pruritus is not seen in this condition. Histologically, it is characterized by the presence of dark granular pigments (composed of polymers of epinephrine metabolites) in lysosomes of liver cells and black discoloration of liver on gross inspection.
Rotor™s syndrome is another benign autosomal recessive disease even less common than D-J syndrome, characterized by predominantly conjugated hyperbilirubinemia. Total bilirubin is in the same range as Dubin Johnson syndrome and liver enzymes are normal. The striking difference form the Dubin Johnson syndrome is the absence of pigmented granules in the lysosomes of hepatocytes.
.
Gilbert™s syndrome, Crigler Najjar type 1 and 2 are three familial disorders characterized by different degrees of unconjugated hyperbilirubinemia due to different degrees of deficiency in the ability to conjugate bilirubin due to a defect in UDP glucuronyl transferase activity. Gilbert's syndrome affects up to 5% of the population.
Gilbert™s syndrome has also been called "constitutional hepatic dysfunction" and "familial nonhemolytic jaundice" and it is characterized by:
1. Mild unconjugated hyperbilirubinemia (< 3.0mg/dl) in young adult patients. It is rarely diagnosed before puberty.
2. More elevated values of bilirubin are associated with fasting, stress, fatigue, alcohol use, and reduced caloric intake, while increased caloric intake or administration of enzyme-inducing agents produce lower bilirubin levels. The cause of hyperbilirubinemia during fasting is probably multifactorial. Unconjugated hyperbilirubinemia on serial testing is required to make the diagnosis.
3. A normal complete blood count, blood smear, and reticulocyte count.
4. Normal liver enzymes and histology.
5. Complete reversal of hyperbilirubinemia to normal with phenobarbital administration. This is rarely necessary in clinical practice.
C-J 1 is characterized by:
1. Unconjugated hyperbilirubinemia of 8-30mg/dl.
2. Normal liver enzymes and histology.
3. High rates of kernicterus
4. No response to Phenobarbital
C-J 2 is characterized by:
1. Unconjugated hyperbilirubinemia of 250/L, SAAG >1.1 and presence of gram-negative bacilli on the gram stain in a cirrhotic patient is highly suggestive of SBP. Presence of >10,000 WBC/L, multiple organisms, or failure to improve after 48 hours of standard therapy is highly suggestive of secondary peritonitis. Children with nephrotic syndrome can also have SBP due to pneumococci. Suspected SBP should be treated with empirical cefotaxime or an ampicillin with an aminoglycoside. Antibiotic therapy is highly effective but recurrence is very common.
Caroli™s syndrome is a rare congenital disorder characterized by intrahepatic dilatation of biliary tree. It is often associated with autosomal recessive adult polycystic kidney disease (APKD) but less commonly with autosomal dominant APKD.
Patients with Caroli™s syndrome can present in following ways:
1. Intermittent abdominal pain due to bile stasis or intermittent passage of stone.
2. Cholangitis leading to fever and right upper quadrant abdominal pain.
3. Portal hypertension leading to hematemesis and melena.
4. Renal complaints due to APKD.
Primary sclerosing cholangitis is caused by inflammatory destruction of both the intrahepatic and extrahepatic biliary ducts. It is equally prevalent in males and females and is associated with inflammatory bowel disease especially ulcerative colitis in 70% of cases. Patients with primary sclerosing cholangitis have variable presentations, with jaundice, pruritus, RUQ abdominal pain, or acute cholangitis suggestive of chronic or intermittent biliary obstruction. It may progress later to complete biliary obstruction, secondary biliary cirrhosis, hepatic failure, or portal hypertension. ERCP is the investigation of choice as involvement of intrahepatic duct might make percutaneous cholangiography difficult. Cholangiography shows characteristic ˜beading™ due to strictures and dilation of intra and extra-hepatic ducts. Liver function tests show a very high alkaline phosphatase with mild elevation of transaminases. The serum aminotransferases are typically less than 300 IU/L. Additional serologic findings in patients with PSC include.
1. Hypergammaglobulinemia ” 30%
2. Increased serum IgM levels ” 40 to 50%
3. Atypical perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) ” 30 to 80%
4. A number of other autoantibodies (ANA, Anti SMA, anticardiolipin, thyroperoxidase, and rheumatoid factor) may also be present, but they have uncertain clinical significance.
Treatment is directed toward the relief of obstruction and treatment of the infectious complications. Liver transplantation is indicated in deteriorating PSC.
Ascites in patients of cirrhosis is due to a number of mechanisms, most of which lead to secondary hyperaldosteronism. Treatment of ascites in the cirrhotic patient should be as follows:
1. All the patients with ascites should have a diagnostic paracentesis done.
2. Salt restricted diet (SRD) (800-1000mg/day) is the corner stone of the therapy and can achieve complete resolution in 10-20 percent of patients without additional therapy.
3. Patients not controlled with SRD should begin treatment with spironolactone. Spironolactone is an aldosterone receptor antagonist and is the diuretic of choice in ascites secondary to cirrhosis as is the case of this patient. The ascites is mainly due to secondary hyperaldosteronism. Other potassium sparing diuretics can be used to substitute for spironolactone. Thiazide diuretic a loop diuretic can be added in patients not responding to spironolactone or to get the maximal benefit.
4. Recalcitrant ascites can be treated with TIPS.
5. Very severe ascites should be treated with paracentesis initially.
Primary biliary cirrhosis usually presents in middle age and 90 percent of patients are females. Pruritus is generally the first symptom and is very severe, especially at night. It is characterized by markedly elevated serum cholesterol levels, alkaline phosphatase, IgM, and minimally elevated aminotransferases. Jaundice and osteopenia occur in later stages of disease.
Primary biliary cirrhosis may be associated with Sjögren™s disease, RA, and CREST syndrome. Liver biopsy is pathognomonic, with granulomatous destruction of bile ducts in portal triad. The presence of anti mitochondrial antibodies is characteristic, and is found in 90% of patients. Ursodeoxycholic acid decreases the pruritus and slows the rate of progression. The definitive treatment is liver transplantation, which has a 5yr survival rate of more than 70%.
Indications for screening for HCV are:
1. I.V drug users
2. Persons who received blood transfusions or organ transplantation before July 1992.
3. Hemodialysis patients
4. Persons with chronic elevation of ALT levels.
5. Children born to HCV positive mothers.
6. Health care workers after a needle stick injury or mucosal exposure to HCV positive blood.
7. Patients who received blood transfusions from a donor who later on became seropositive for HCV.
Cholangiocarcinoma is a complication of PSC especially in smokers with concurrent ulcerative colitis. One of the early manifestations of cholangiocarcinoma is a severe stricture in the biliary tree leading to cholangitis characterized by fever, jaundice, and leucocytosis. Cholangiocarcinoma can occur in up to 20% of patients with long term PSC, so any severe stricture of biliary tree in patients with PSC should be biopsied to rule out cholangiocarcinoma.
Cholangiocarcinoma can complicate primary sclerosing cholangitis especially in presence of ulcerative colitis and smoking.
A choledochal cyst is a congenital abnormality of the biliary ducts characterized by the dilatation of intra or extra-hepatic biliary ducts or both. It has a multifactorial origin, but most of the cases are related to an anomalous pancreaticobiliary junction, which leads to weakness and dilatation of the biliary wall due to the reflux of alkaline pancreatic secretions into the biliary tree Various types of choledochal cysts are:
Type 1: Most common type, features the dilatation of the entire common hepatic and common bile ducts or segments of each.
Type 2: Relative isolated protrusions or diverticulae from the common bile duct wall.
Type 3: Cyst found in the intraduodenal part of common bile duct.
Type 4: Multiple dilatations in the intra and extra hepatic biliary tree.
Type 5: Isolated dilatation of intrahepatic bile ducts.
The clinical presentation varies with the age. In infants it may present with jaundice and the passage of acholic stools. In children it causes abdominal pain, jaundice, and attacks of recurrent pancreatitis, which may be evident by increases in the amylase and lipase levels. Adults with choledochal cysts commonly present with vague epigastric or right upper quadrant abdominal pain or cholangitis. Choledochal cysts can degenerate into cholangiocarcinoma. The initial investigation of choice is an ultrasonogram followed by CT scan or magnetic resonance imaging (MRI) as needed.
Wilson™s disease is a rare autosomal recessive disease characterized by low ceruloplasmin levels, leading to abnormal copper deposition in liver, basal ganglia (hepatolenticular degeneration), and cornea. Liver involvement in Wilson™s disease can be in the form of fulminant hepatitis, chronic hepatitis, or macro nodular cirrhosis. Wilson™s disease also causes hemolytic anemia and neuropathy. The diagnosis is made by the finding of low serum ceruloplasmin levels, increased urinary copper and hepatic copper deposition on liver biopsy. Treatment consists of copper chelators like d-penicillamine. Fulminant hepatitis requires liver transplantation.
might be this can help to some1.
Acute acalculous cholecystitis is an acute inflammation of the gallbladder in the absence of gallstones.
It is most commonly seen in hospitalized patients in the following conditions:
1. Extensive burns
2. Severe trauma
3. Prolonged TPN.
4. Prolonged fasting
5. Mechanical ventilation.
Involved pathophysiology is localized or generalized ischemia, biliary stasis, infection, or external compression of the cystic duct. It generally presents with right upper quadrant abdominal pain with fever, leucocytosis, and abnormal liver function tests. It can lead to complications like gangrene, perforation, and emphysematous cholecystitis. The initial investigation of choice is an ultrasonogram, which shows signs of acute cholecystitis and no gallstones; however, CT scan and HIDA scans are more sensitive and specific for the diagnosis. It is important to have a high degree of suspicion in high-risk patients in order to correctly identify this problem.
Non Alcoholic Hepatic Steatosis (NASH). Some of the risk factors for NASH are:
1. Obesity: The incidence of NASH has increased in parallel with the increase in obesity. 40% of the obese patients have some degree of steatosis on liver biopsy.
2. Diabetes mellitus: Disorder of hepatic insulin sensitivity has been thought to be responsible for this.
3. Total parental nutrition (TPN)
4. Hyperlipidemia
5. Drugs like amiodarone
6. Bypass surgery for obesity
liver biopsy shows steatosis, polymorphonuclear cellular infiltrates, and necrosis.
Treatment of NASH aims to control the underlying co morbid conditions. Ursodeoxycholic acid has also being found to decrease the transaminase levels in patients with NASH.
1. Chronic active hepatitis: These patients have piecemeal necrosis, (erosion of the limiting plate of hepatocytes surrounding the portal triad), hepatocellular regeneration, along with foci of necrosis and inflammation in the liver lobule.
2. Chronic persistent hepatitis: A mononuclear inflammatory infiltrate is localized to and contained within portal tracts. The "limiting plate" of periportal hepatocytes is intact, and there is no extension of the necroinflammatory process into the liver lobule.
Liver biopsy is the most reliable way to distinguish chronic active from chronic persistent hepatitis.
Chronic hepatitis C is associated with number of extra hepatic complications like:
1. Cryoglobulinemia.
2. B cell lymphomas.
3. Plasmacytomas.
4. Autoimmune diseases like Sjögren™s syndrome and thyroiditis.
5. Lichen planus.
6. Porphyria cutanea tarda.
7. Idiopathic thrombocytopenic purpura.
Membranous glomerulonephritis is an important one associted with hep C.
If patient has recurrent pancreatitis for which no obvious cause is identified. In this situation ERCP would be the best investigation to search for the underlying cause, ERCP in this case would help to diagnose ductal abnormalities including pancreatic divisum, choledochal cysts, and common bile duct stones. It would also allow for gall bladder aspiration of bile to look for biliary crystals or microlithiasis.
Dubin Johnson and Rotor™s syndrome are two familial disorders of hepatic bile secretion, which leads to conjugated hyperbilirubinemia.
Dubin Johnson syndrome is a benign, rare, autosomal recessive disorder characterized by predominantly conjugated hyperbilirubinemia. Total bilirubin is typically between 2-5 mg/dl, but higher and lower values are possible. The degree of hyperbilirubinemia may change with acute stress, OCP, and pregnancy. Liver enzymes are normal and these patients are generally asymptomatic. Pruritus is not seen in this condition. Histologically, it is characterized by the presence of dark granular pigments (composed of polymers of epinephrine metabolites) in lysosomes of liver cells and black discoloration of liver on gross inspection.
Rotor™s syndrome is another benign autosomal recessive disease even less common than D-J syndrome, characterized by predominantly conjugated hyperbilirubinemia. Total bilirubin is in the same range as Dubin Johnson syndrome and liver enzymes are normal. The striking difference form the Dubin Johnson syndrome is the absence of pigmented granules in the lysosomes of hepatocytes.
.
Gilbert™s syndrome, Crigler Najjar type 1 and 2 are three familial disorders characterized by different degrees of unconjugated hyperbilirubinemia due to different degrees of deficiency in the ability to conjugate bilirubin due to a defect in UDP glucuronyl transferase activity. Gilbert's syndrome affects up to 5% of the population.
Gilbert™s syndrome has also been called "constitutional hepatic dysfunction" and "familial nonhemolytic jaundice" and it is characterized by:
1. Mild unconjugated hyperbilirubinemia (< 3.0mg/dl) in young adult patients. It is rarely diagnosed before puberty.
2. More elevated values of bilirubin are associated with fasting, stress, fatigue, alcohol use, and reduced caloric intake, while increased caloric intake or administration of enzyme-inducing agents produce lower bilirubin levels. The cause of hyperbilirubinemia during fasting is probably multifactorial. Unconjugated hyperbilirubinemia on serial testing is required to make the diagnosis.
3. A normal complete blood count, blood smear, and reticulocyte count.
4. Normal liver enzymes and histology.
5. Complete reversal of hyperbilirubinemia to normal with phenobarbital administration. This is rarely necessary in clinical practice.
C-J 1 is characterized by:
1. Unconjugated hyperbilirubinemia of 8-30mg/dl.
2. Normal liver enzymes and histology.
3. High rates of kernicterus
4. No response to Phenobarbital
C-J 2 is characterized by:
1. Unconjugated hyperbilirubinemia of 250/L, SAAG >1.1 and presence of gram-negative bacilli on the gram stain in a cirrhotic patient is highly suggestive of SBP. Presence of >10,000 WBC/L, multiple organisms, or failure to improve after 48 hours of standard therapy is highly suggestive of secondary peritonitis. Children with nephrotic syndrome can also have SBP due to pneumococci. Suspected SBP should be treated with empirical cefotaxime or an ampicillin with an aminoglycoside. Antibiotic therapy is highly effective but recurrence is very common.
Caroli™s syndrome is a rare congenital disorder characterized by intrahepatic dilatation of biliary tree. It is often associated with autosomal recessive adult polycystic kidney disease (APKD) but less commonly with autosomal dominant APKD.
Patients with Caroli™s syndrome can present in following ways:
1. Intermittent abdominal pain due to bile stasis or intermittent passage of stone.
2. Cholangitis leading to fever and right upper quadrant abdominal pain.
3. Portal hypertension leading to hematemesis and melena.
4. Renal complaints due to APKD.
Primary sclerosing cholangitis is caused by inflammatory destruction of both the intrahepatic and extrahepatic biliary ducts. It is equally prevalent in males and females and is associated with inflammatory bowel disease especially ulcerative colitis in 70% of cases. Patients with primary sclerosing cholangitis have variable presentations, with jaundice, pruritus, RUQ abdominal pain, or acute cholangitis suggestive of chronic or intermittent biliary obstruction. It may progress later to complete biliary obstruction, secondary biliary cirrhosis, hepatic failure, or portal hypertension. ERCP is the investigation of choice as involvement of intrahepatic duct might make percutaneous cholangiography difficult. Cholangiography shows characteristic ˜beading™ due to strictures and dilation of intra and extra-hepatic ducts. Liver function tests show a very high alkaline phosphatase with mild elevation of transaminases. The serum aminotransferases are typically less than 300 IU/L. Additional serologic findings in patients with PSC include.
1. Hypergammaglobulinemia ” 30%
2. Increased serum IgM levels ” 40 to 50%
3. Atypical perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) ” 30 to 80%
4. A number of other autoantibodies (ANA, Anti SMA, anticardiolipin, thyroperoxidase, and rheumatoid factor) may also be present, but they have uncertain clinical significance.
Treatment is directed toward the relief of obstruction and treatment of the infectious complications. Liver transplantation is indicated in deteriorating PSC.
Ascites in patients of cirrhosis is due to a number of mechanisms, most of which lead to secondary hyperaldosteronism. Treatment of ascites in the cirrhotic patient should be as follows:
1. All the patients with ascites should have a diagnostic paracentesis done.
2. Salt restricted diet (SRD) (800-1000mg/day) is the corner stone of the therapy and can achieve complete resolution in 10-20 percent of patients without additional therapy.
3. Patients not controlled with SRD should begin treatment with spironolactone. Spironolactone is an aldosterone receptor antagonist and is the diuretic of choice in ascites secondary to cirrhosis as is the case of this patient. The ascites is mainly due to secondary hyperaldosteronism. Other potassium sparing diuretics can be used to substitute for spironolactone. Thiazide diuretic a loop diuretic can be added in patients not responding to spironolactone or to get the maximal benefit.
4. Recalcitrant ascites can be treated with TIPS.
5. Very severe ascites should be treated with paracentesis initially.
Primary biliary cirrhosis usually presents in middle age and 90 percent of patients are females. Pruritus is generally the first symptom and is very severe, especially at night. It is characterized by markedly elevated serum cholesterol levels, alkaline phosphatase, IgM, and minimally elevated aminotransferases. Jaundice and osteopenia occur in later stages of disease.
Primary biliary cirrhosis may be associated with Sjögren™s disease, RA, and CREST syndrome. Liver biopsy is pathognomonic, with granulomatous destruction of bile ducts in portal triad. The presence of anti mitochondrial antibodies is characteristic, and is found in 90% of patients. Ursodeoxycholic acid decreases the pruritus and slows the rate of progression. The definitive treatment is liver transplantation, which has a 5yr survival rate of more than 70%.
Indications for screening for HCV are:
1. I.V drug users
2. Persons who received blood transfusions or organ transplantation before July 1992.
3. Hemodialysis patients
4. Persons with chronic elevation of ALT levels.
5. Children born to HCV positive mothers.
6. Health care workers after a needle stick injury or mucosal exposure to HCV positive blood.
7. Patients who received blood transfusions from a donor who later on became seropositive for HCV.
Cholangiocarcinoma is a complication of PSC especially in smokers with concurrent ulcerative colitis. One of the early manifestations of cholangiocarcinoma is a severe stricture in the biliary tree leading to cholangitis characterized by fever, jaundice, and leucocytosis. Cholangiocarcinoma can occur in up to 20% of patients with long term PSC, so any severe stricture of biliary tree in patients with PSC should be biopsied to rule out cholangiocarcinoma.
Cholangiocarcinoma can complicate primary sclerosing cholangitis especially in presence of ulcerative colitis and smoking.
A choledochal cyst is a congenital abnormality of the biliary ducts characterized by the dilatation of intra or extra-hepatic biliary ducts or both. It has a multifactorial origin, but most of the cases are related to an anomalous pancreaticobiliary junction, which leads to weakness and dilatation of the biliary wall due to the reflux of alkaline pancreatic secretions into the biliary tree Various types of choledochal cysts are:
Type 1: Most common type, features the dilatation of the entire common hepatic and common bile ducts or segments of each.
Type 2: Relative isolated protrusions or diverticulae from the common bile duct wall.
Type 3: Cyst found in the intraduodenal part of common bile duct.
Type 4: Multiple dilatations in the intra and extra hepatic biliary tree.
Type 5: Isolated dilatation of intrahepatic bile ducts.
The clinical presentation varies with the age. In infants it may present with jaundice and the passage of acholic stools. In children it causes abdominal pain, jaundice, and attacks of recurrent pancreatitis, which may be evident by increases in the amylase and lipase levels. Adults with choledochal cysts commonly present with vague epigastric or right upper quadrant abdominal pain or cholangitis. Choledochal cysts can degenerate into cholangiocarcinoma. The initial investigation of choice is an ultrasonogram followed by CT scan or magnetic resonance imaging (MRI) as needed.
Wilson™s disease is a rare autosomal recessive disease characterized by low ceruloplasmin levels, leading to abnormal copper deposition in liver, basal ganglia (hepatolenticular degeneration), and cornea. Liver involvement in Wilson™s disease can be in the form of fulminant hepatitis, chronic hepatitis, or macro nodular cirrhosis. Wilson™s disease also causes hemolytic anemia and neuropathy. The diagnosis is made by the finding of low serum ceruloplasmin levels, increased urinary copper and hepatic copper deposition on liver biopsy. Treatment consists of copper chelators like d-penicillamine. Fulminant hepatitis requires liver transplantation.