Viral Hepatitis Flashcards
Within liver anatomy, during hepatitis, where does the inflammation occur?
-around the portal triads
Numerous viruses can infect the liver; however, the term viral hepatitis is reserved for those viruses that ___________.
- target the liver specifically
- they are hepatotropic
T/F: Hepatitis A-E is caused by related viruses.
- false- not related to eachother
- while all hepatitis viruses cause hepatitis, the viruses themselves are quite different and the severity of their symptoms can vary in important ways
What is the mechanism of acute hepatitis?
-immune-mediated damage to infected hepatocytes
What are the symptoms of acute hepatitis (ranging from less specific to more specific)?
- fever, fatigue, malaise, nausea, vomiting
- abdominal pain
- right upper quadrant abdominal pain
- hepatomegaly
- jaundice (icteric phase)
- fulminant hepatitis
What is fulminant hepatitis?
- massive hepatic necrosis leading to death
- rare outcome of acute hepatitis
Describe common manifestations of jaundice. What is jaundice?
- yellow discoloration of skin, sclera, and mucus membranes due to systemic retention of pigmented bilirubin in tissues
1. dark urine, pale stools
2. pruritus (itchy skin)
3. scleral icterus: white of eyes are yellow
What causes jaundice to be yellow?
-systemic retention of pigmented bilirubin in tissues
Describe the breakdown of heme
- RBCs are degraded in spleen and bone marrow, releasing Hb, which is degraded to heme
- heme is converted into unconjugated bilirubin in macrophages of the spleen and BM, bound to plasma albumin and transported to the liver
- there it is conjugated to glucuronic acid, making it soluble for excretion
What 2 forms of bilirubin occur in the blood and tissues? Together these two forms add to make the total bilirubin.
- conjugated:direct
2. unconjugated: indirect
Conjugated bilirubin is excreted from the liver into the bile and passed into the intestine where it is further metabolized to stercobilin; what is stercobilin responsible for?
-colors feces brown
Which forms of bilirubin are soluble and insoluble.
- unconjugated is not soluble (hence why it is transferred to liver by albumin)
- conjugated form (occurs in liver) improves solubility
Which forms of bilirubin are considered direct and indirect?
- direct: conjugated
- indirect: unconjugated
Jaundice can result from increased production, decreased excretion, or both of bilirubin. Give 3 mechanisms that result in elevated unconjugated (indirect) bilirubin. Give 2 to cause elevated conjugated bilirubin.
- Unconjugated: increased bilirubin production (hemolytic anemias like malaria); reduced hepatocellular uptake (drug interferences with transport systems); impaired conjugation (diffuse hepatocellular disease like hepatitis)
- Conjugated: decreased hepatocellular excretion (Dubin-Johnson syndrome); impaired bile flow (biliary obstruction)
In addition to measuring bilirubin levels, what else can one measure to determine severity of hepatitis?
- Liver Function Tests
- death of hepatocytes releases various enzymes that LFT measure
4 enzymes measures in LFT and their specificity
- ALT (alanine aminotransferase): more specific for liver abnormalities than other enzyme tests
- AST: Aspartate aminotransferase: less specific since its also found in muscle and other tissues
- AP (alkaline phosphatase): less specific, but indicative of bile duct injury
- GT (gamma glutamyl transpeptidase): often elevated in those who use alcohol or other liver toxic substances to excess
When measuring bilirubin and LFTs, if patient was merely suffering from just hemolytic anemia, what results would you expect?
-high bilirubin but normal LFTs
T/F: Chronic Hepatitis can be caused by HAV or HAC.
- False
- only hep B or Hep C
If the acute infection is not cleared, patient may develop chronic hepatitis; what forms of hepatitis viruses cause this, describe generally if symptoms occur, and what it can lead to?
- Hep B or Hep C with variable frequency
- can be asymptomatic (chronic persistent hepatitis)
- can be symptomatic (chronic active hepatitis; CAH)
- can lead to cirrhosis or hepatocellular carcinoma
What does cirrhosis refer to?
-the way the liver scars due to damage
What forms of Hepatitis viruses can cause Hepatocellular Carcinoma?
- Hep B or C, but NEVER A
- this makes sense since this is associated with chronic hepatitis, which A does not cause
3 general outcomes of infection with a hepatitis virus
- asymptomatic carrier
- acute hepatitis
- chronic hepatitis
What is hepatitis referred to in a chronically infected individual who is asymptomatic vs. symptomatic?
- asymptomatic: chronic persistent hepatitis
- symptomatic: chronic active hepatitis
Describe a cirrhotic liver compared to a normal liver and what are the major causes of cirrhosis in the US? What is microscopically seen in a cirrhotic liver?
- shrunken, micronodular, and very firm to touch
- bridging fibrosis seen microscopically; connect portal triads
- chronic alcohol abuse, hepatitis C, hepatitis B
T/F: If a liver is cirrhotic, all signs point to hepatitis virus.
-false; cirrhosis can have many causes, it truly is insightful into something being chronic, beyond that it is not helpful in diagnosing
Why is fibrosis in the liver during cirrhosis called bridging cirrhosis?
- it connects portal triads
- due to anything cause chronic hepatic necrosis
Cirrhosis is essentially a rigid, non-compliant liver that is harder for blood to flow through. What are consequences of this?
- portal hypertensin leads to increased venous pressure throughout and leads to fluid transudation (ascites)
1. esophageal varices due to gastric vein backup
2. splenomegaly due to splenic vein backup
3. Hemorrhoids due to superior rectal backup
4. ascites due to backup in superior mesenteric vein and periumbilical vein
Physical consequences of cirrhosis lead to ascites and varices/splenomegaly. Are there any other consequences?
- metabolic consequences
- jaundice and hepatic encephalopathy; coagulopathy, hypoglycemia, and increased ammonia (hepatic encephalopathy)
What causes hepatic encephalopathy?
- increased ammonia due to cirrhosis
- metabolic consequence of cirrhosis
Describe the structure and infection type caused by Hepatitis A virus.
- RNA picornavirus
- pico=small (30nm diameter)
- RNA + strand genome
- nonenveloped and thus stable outside of the body
- causes acute disease and asymptomatic infection ONLY (NO CHRONIC)
- NOT cytopathic;
What are the symptoms of Hepatitis A virus due to?
- immune-mediated destruction of virus-infected cells
- the virus itself is not cytopathic which makes sense in an acute infection because you cannot kill host before you have change to replicate
Describe pathogenesis of Hepatitis A virus
- enters bloodstream through oropharynx, replicates in GI tract then viremia spreads to liver
- virus produced and released into bile, and then shed into stool for about 10 days BEFORE symptoms appear
- replicates slowly in liver and is not cytopathic; instead immune response causes liver pathology and symptoms