Disorders of the liver and biliary system Flashcards
Acute Hepatitis (liver inflammation)
Less than 6 months duration.
Often symptomatic: jaundice, fatigue, nausea
Anicteric acute hepatitis: influenza-like and digestive tract symptoms but no jaundice.
Icteric acute hepatitis: preceded by days to weeks of non-specific symptoms including malaise, nausea, and decreased appetite; the urine darkens and is followed by jaundice that may last up to a month.
Cholestatic acute viral hepatitis: a prolonged (2 months to 2 years) jaundice and pruritus (severe itching of skin), even though other symptoms weaken; with time, the cholestasis (condition in which the bile flow from the liver stops or slows) will pass.
Causes: viral hepatotropic (A, B, C, D, E), viral non-hepatotropic; CMV, HSV, EBV, medications that can do this: ACETAMINOPHEN, ischemia because of shock, autoimmune, alcohol.
Systemic illness and can cause a variety of problems; Guillain-Barre Syndrome, glomerulonephritis, cryoglobulinemia.
3 options: death or liver transplantation, self-limited (recovery), chronic evolution.
Acute Liver Failure/Fulminant Hepatic Failure
A sudden, severe acute hepatic injury accompanied by overt liver failure.
Rare
Hallmark is the development of cognitive problems, change in consciousness, and eventually overt coma.
Vomiting, fetter hepaticus (bad liver breath), and fever are seen.
Prolonged prothrombin time; hallmark of liver failure; severity of transaminate elevation and jaundice (which can both be profound) are no good indicators.
The injury is so bad that they won’t survive without a liver transplant=acute liver failure.
Chronic Hepatitis
Inflammation for greater than 6 months.
Usually asymptomatic until discovered accidentally.
Ongoing inflammation directed toward the hepatocytes; hepatocyte injury continues until either the stimulus is removed or the inflammatory response is diminished.
Causes: Autoimmune, alcohol, HBV, HCV, HDV, Drugs, Copper overload (Wilson’s disease), Non-alcoholic fatty liver disease, alpha 1 antitrypsin deficiency, iron overload (hereditary hemochromatosis), nonalcoholic steatohepatitis, cholestatic liver diseases, primary biliary cirrhosis, primary sclerosing cholangitis, alcoholic liver disease.
Some causes are genetic, some are acquired.
Fiborsis accumulates with time; cirrhosis (extensive fibrosis).
Cirrhosis and Liver Failure
The normal functions and structure of the liver is lost.
As the liver becomes inflamed the cells die and scar tissue forms.
Over time, these bands of scar tissue become thicker and more intertwined.
At the point of cirrhosis, the regenerating hepatocytes create nodules surrounded by scar tissue and the normal liver architecture is lost.
Any cause of chronic hepatits can lead to cirrhosis.
Causes: alcohol, hepatitis B and C, hemochromatosis, Wilson disease, primary biliary cirrhosis, scleorsing cholangitis, drugs, cystic fibrosis.
Cell necrosis and inflammation leads to wound healing (scarring=collagen).
ESLD (end stage liver disease)=Complications of Cirrhosis
3 principle complications of cirrhosis:
1. Liver failure; loss of liver synthetic function.
Low serum albumin due to inadequate production by the liver.
Jaundice due to increased serum bilirubin.
Prolonged prothrombin time because the liver stops making adequate levels of clotting proteins (increased INR)
2. Portal Hypertension; extensive scar tissue accumulation in the liver begins to result in increased blood pressures in the portal venous system that bring blood into the liver.
The blood leaving the spleen exits through the portal venous system, the spleen becomes congested with blood and enlarges (splenomegaly).
Other veins that feed into the portal venous system become engorged with blood and enlarged (varices)-esophagus, stomach, rectum.
Develop fluid retention in the abdominal cavity (ascites) and impairment of cognition (hepatic encephalopathy, accumulation of toxins, ammonia).
3. Hepatocellular carcinoma
PORTAL VEIN: brings blood into the liver and drains it from intestines and spleen.
Alcoholic Liver Disease (ALD)
Risk related to amount consumed
Other risk factors:
Chronic viral hepatits
Obesity (non alcoholic fatty liver disease)
female
CAN HAVE MORE THAN ONE FACTOR THAT PUSHES YOU TO DEVELOPMENT OF ALD
Preventable epidemic; model of toxic injury to the liver.
Spectrum of ALD:
Fatty Liver: Steatosis; early on, alcohol causes fat accumulation in the liver without any other effects, due to increased synthesis of fatty acids AND decreased oxidation and export of these products.
NO inflammation, just bland fat.
Asymptomatic, reversible with abstinence.
Alcoholic Hepatitis: Steatosis plus inflammation (neutrophils) and fibrosis.
Servere manifestation of ALD.
May cause significant symptoms: abdominal pain, fever, jaundice, and signs of portal hypertension.
Often >100g/day.
Under the microscope, abundant steatosis (fat accumulation), also extensive inflammation (neutrophils), hepatocyte ballooning (damage), fibrosis (scar); cytoplasm contains mallory bodies
Liver failure and often fatal.
Cirrhosis: End stage of liver disease (complications of cirrhosis) may present even if there was not a course of severe alcoholic hepatitis.
Treatment: ABSTINENCE, nutrition, transplantation, corticosteroids
Non alcoholic fatty liver disease (NAFLD)/ Non alcoholic steatohepatitis (NASH)
NAFLD is a fatty liver.
NASH is fatty liver and inflammation and fibrosis.
No clinical syndrome similar to alcoholic hepatitis where you suddenly get very sick.
Can look indistinguishable from ALD.
NAFLD/NASH most commonly seen in the context of the “metabolic syndrome,” defined by the presence of three or more of the following criteria:
Waist circumference >102 cm in men and >88 cm in women, BP>130/85 mmHg, S-glucose >110mg/dl, S-triglycerides >150 mg/dl, HDL cholesterol
Hepatitis A
Causes acute hepatitis.
Found worldwide.
Jaundice, small risk of liver failure.
No risk for cirrhosis.
Self-limited recovery.
A small RNA enterovirus; replicates in the hepatocyte exclusively, then passed into the bile, and then onto the feces.
FECAL-ORAL ROUTE.
Shed in feces for 2 weeks before jaundice appears.
Majority of cases are anicteric (no jaundice).
May relapse before eradication.
Lifetime immunity conferred after infection.
Prevention: immune serum globulin, vaccination available.
Hepatitis B
Double stranded DNA virus.
Major world health problem.
In highly endemic areas (Asia).
Vertical Infections (mother to fetus); childhood infections.
Unlikely to develop symptoms of acute infection, 90% chance of chronic infection.
The risk of developing chronic HBV infection is directly related to method and age of acquisition!!!!!!
In low endemic areas (US); sex, drugs, rock and roll infection; most occur as an adult; most get symptomatic acute infection (jaundice); 5% develop chronic infection.
Its core contains DNA polymerase core antigen (HBcAg) and e antigen (HBeAg); the core is surrounded by a coating of proteins, lipids, and CHO, and contains the hepatitis B surface antigen (HbsAg); HBsAg is secreted in large amounts from the infected hepatocytes and is immunogenic but will not cause infection.
Combination of HbsAg and case is the Dane particle and is infectious.
Screening for hepatitis B has greatly reduced risk of receiving HBV contaminated blood products.
Active infectious HBV is found in blood, saliva, and semen.
Routes of infection: maternal-fetal, blood products, contaminated needles and intimate contact.
HepB can follow 4 courses:
1. Acute, self-limited: typical course of acute viral hepatitis, but is typically more severe; incubation is 2 months, can be 6 months; in children, anicteric (no jaundice) and goes unnoticed.
HBsAg (HepB surface antigen) is the first marker seen in the blood- disappear during recovery phase, antibody to HBsAg found shortly after, MARKING COMPLETE RECOVERY.
Mild course patients will not shed HBsAg into the blood; core elements not found in the blood, but anti-hcb is seen about the time transaminases rise; both antibodies remain elevated for life.
HBeAg appears after HBsAg and before clinical symptoms; CORRELATES WITH THE HIGHEST RATE OF VIRAL REPLICATION=TIME OF HIGHEST INFECTIVITY.
Circulating immune complexes of HBsAg and anti-HBsAg cause variety of problems including glomerulonephritis, rash, polyartritis, arthritis, cryoglobulinemia, myocarditis, PMR, pancreatitis.
2. Fulminant HepB/acute liver failure: relatively rare, though more commonly seen than HepA; enhanced response of the immune system; HBsAG may be low or undetected because of this; IgM anti-HBc can be found and is a useful marker in this scenario.
3. Chronic hepatitis
4. Chronic, carrier state
Prevention: HepB Immunoglobulin (HBIG) is effective if given prophylactically or within a few hours of exposure.
Hep B vaccine relies on high immunogenic potential of HBsAg, revaccination.
Chronic Hepatits B is mild and associated with no symptoms; HOWEVER, over time it may lead to cirrhosis and hepatocellular carcinoma. Worldwide, HBV is the most common cause of cirrhosis and liver cancer.
Treatment: antiviral meds (early: lamivudine, adefovir, later: tenofovir, entecavir); cannot eradicate the virus, some patients require lifelong therapy.
Hepatitis D- Delta virus
A single stranded RNA virus, when in the blood is coated with HBsAg.
Associated EXCLUSIVELY with hepatitis B infection.
Defective virus, must have HBV present to make HbsAg; requires HBV for vision assembly.
Suppresses HBV replication.
More aggressive infection, quicker progression to cirrhosis than with HBV alone.
Infection occurs in 2 forms:
1. Co-infection: HBV and HDV simultaneously; similar course as HBV because HDV can only replicate when HBsAg is being synthesized.
2. Super-infection: occurs in patient later in the course of HBV=worsening of hepatitis; may lead to fulminant (sudden) course.
Hepatitis C
IN THE US, the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation. LIVER TRANSPLANT DOES NOT CURE THE INFECTION!!!
Single stranded, enveloped RNA virus (flavivirus); codes for a single 3000 protein AA that requires post-translational cleaving by a serine protease.
RNA polymerase has lack of proofreading ability, so tendency to mutate.
Variation in the envelope accounts for different genotypes; in US genotype 1 most common.
Risk factors: exposure to infected blood, DRUG USE DRUG USE DRUG USE, sexual transmission is rare.
Most acute infections aren’t a big deal; non specific symptoms, rarely jaundiced.
Most become chronic; smoldering damage; cirrhosis, liver cancer; process can be accelerated by alcohol use.
Quite mild clinical presentation compared to HepB
Incubation about 5-12 weeks.
Anti-HCV seen in about 2 months into symptoms, ALT, bilirubin return to normal.
Extra-hepatic manifestations can occur: cryoglobulinemic vasculitis, membranoproliferazive glomerulonephritis, porphyris cutanea tarda, lichen planus, diabetes.
THE HCV ANTIBODY DOES NOT CONFER IMMUNITY AND REINFECTION CAN OCCUR.
Hepatitis E
A small single stranded, unenveloped RNA virus.
Like HepA; acute infection, spontaneous resolution; pregnant women more likely to get acute liver failure; in 3rd trimester.
Most common in developing counties.
Transmitted via sewage.
Enterically transmitted.
Less virulent genotype in US, no symptoms of infection; high antibody rate; hog farms.
Gallstones (Cholelithiasis)
Collections of chemicals normally found in bile and have precipitated out; extremely common and most often asymptomatic.
Biliary colic: spastic pain after eating, right upper abdomen, radiates back,
Gallbladder contracts against obstructed cystic duct.
Primarily cholesterol stones with calcium.
Bile becomes super saturated with cholesterol, too much cholesterol and not enough bile salts.
Nucleation: precipitates out on a small particle, possibly duet increased production of mucus.
Risk factors: being female, over 40, obesity and rapid weight loss, diabetes.
Black stones associated with hemolytic anemia or parasitic infection (brown stones).
Grow slow, metastasize slow.
Gallbladder dysfunction
- Acute cholecystitis; infection of the bile in the gallbladder due to a stone obstructing the cystic (gallbladder) duct.
Causes severe pain in the right upper quadrant with radiation to the lower angle of the shoulder blade with signs of acute infection (fever, elevated WBC count); usually not associated with jaundice unless the common bile duct is also blocked by stones, murphy sing, more constant pain.
Treatment: removal of gallbladder (cholecystectomy). - Chronic cholecystits: vague symptoms without signs of infection; galbladder might have sludge like material and no stones; gallbladder may lose ability to contract well in response to fatty meal (biliary dyskinesia).
Bile duct Diseases
- Choledocholithiasis; common duct stones or stones on the loose; gallstone migrates out of cystic duct and lodges in the common bile duct.
Pain: biliary colic.
Elevated liver tests and bilirubin; flow of bile is obstructed.
They can become impacted at the opening of the duct to the duodenum and cause pain, jaundice, life threatening infection (ascending cholangitis).
If stones don’t pass, removed endoscopically or surgically.
Ascending cholangitis: biliary colic, fevers (often very high), septic shock (low BP), jaundice (bile flow interrupted), ERCP; infection of bile in the bile duct.
