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First branch of the "Jaundice Scheme"

Unconjugated Bilirubin vs. Conjugated Bilirubin

Branches of the unconjugated bilirubin node of the jaunice scheme

Direct antibody(-)
Direct antibody(+)

Branches of the conjugated bilirubin node of the jaundice scheme

Normal LFT's
Abnormal LFT's

What microorganisms can contribute to unconjugated bilirubin jaundice

TORCH: TOxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex.

These organisms can cause accelerated RBC destruction.

What microorganisms can contribute to conjugated bilirubin jaundice

Viral Hepatitis, parasitic liver infection.

Viruses that "can cause" viral hepatitis: (not liver tropic, but can infect)

Adenovirus, Cytomegalovirsus, EBV, Herpes simplex, Varicella, Yellow-fever virus.

Viruses that "do cause" viral hepatitis: (strong liver tropism)

Hepatitis A, B, C, D, E, G

Route of infection for Hepatitis A and E

Fecal oral: uptaken in the intestine, replication in liver, shed into bile duct-->intestine, passed in feces.

Route of infection for Hepatitis B, C, D

Bodily fluid: Replicate in liver, released into bloodstream.

Immune response to Hepatitis infections:

CD8+ T-cells kill infected hepatocytes.

Two possible outcomes of hepatitis virus infection:

Resolution: with a sufficiently robust immune response the infection can be overcome. It's easier with certain subtypes than others.

Chronic infection: Inadequate immune response allows for a persistent infection. More common with some subtypes than others.

Which Hepatitis subtypes are most likely to be spontaneously destroyed by the immune system?

Almost all HepA and HepE infections.

95% of HepB infections will spontaneously resolve.

Which hepatitis subtypes are most likely to produce chronic infections

Hepatitis C virus. 80%-85% of infections will be chronic.

Which hepatitis virus infections have an abrupt onset?

A,D,E

Which hepatitis virus infections have an insidious onset?

B,C

Which hepatitis virus is known for producing a subclinical and typically chronic infection?

HepC

Which Hepatitis virus in known as a "defective virus" and must co-infect with hepatitis B?

HepD.

Which hepatitis virus exacerbates the symptoms caused by HBV?

HepD

Which viral family does Hepatitis A belong to?

Picornaviridae

Which viral family does Hepatitis B belong to?

Hepadnaviridae

Which viral family does Hepatitis C belong to?

Flaviviridae

Which viral family does Hepatitis D belong to?

Deltaviridae

Which viral family does Hepatitis E belong to?

Caliciviridae

Describe the Genome and envelope of HepA virus

positive sense, single strand RNA

No envelope

Describe the genome and envelope of HepB virus

DNA

Envelope

Describe the genome and envelope of HepC virus

Positive sense, single strand RNA

Envelope

Describe the genome and envelope of HepD virus

Negative sense, single strand RNA

Envelope

Describe the genome and envelope of HepE virus

Positive sense, single strand RNA

No envelope.

Hepatitis A and E viruses are highly resistant to gastric acidity; what allows for this and how does it influence the route of infection?

The lack of an outer envelope (usually composed of lipid bilayer stolen from the host cell) lends itself to being acid resistant. It also gives bile resistance etc.

As a result, these are the two subtypes of Hepatitis virus that infect through the fecal-oral route.

Name the reservoirs of Hepatitis A virus.

Humans are the only reservoir.

How many serotypes are there for HepA virus?

Just one (vaccine available)

Symptoms of HepA infection:

Fatigue, abdominal pain, jaundice (60% of adult cases, 20% or less of children).

Laboratory findings in HepA infection

Elevated liver enzymes, Dark urine, light stool.

What portion of patients infected with Hepatits A will recover completely?

99%, patients then have lifelong immunity.

Treatment for HAV?

No specific treatment, just supportive care for symptoms.

Active vs. Passive immunization for HAV?

Active immunization is the injection of inactive virus.

Passive immunization is the injection of immune globulin. Used as prophylaxis for people exposed to the virus.

How is hepatitis E contracted:

Fecal oral route, usually through contaminated food or water.

How to distinguish HepA from HepE

Similar in routes of transmission, and disease pattern. Serological ID is the way to distinguish between the two.

Main difference between HepA and HepE

Symptoms of HepE can be more severe than in HepA. Particularly for pregnant women (20% fatality).

HepB has an outer envelope, there is one thing about it that doesn't typically line up with having an envelope, what is it?

It is detergent resistant.

There are 3 forms of surface envelope antigens in HepB viruses (HBsAg). What are they?

S, M, L

What is an HBsAg particle?

DNA-less particle containing mostly S antigen.

The presence of serum HBsAg indicates what?

Active, chronic infection.

What are the significance of core proteins (HBcAg)?

The body will generate antibodies. The presence of serum anti HB-c (Hep B core protein) indicates exposure.

What is the significance of E antigen (HBeAg)?

It's a processed form of core protein, it is secreted into the blood. Serum HBeAg is indicative of active viral replication.

What is a "Dane Particle"

Named after british pathologist (Dane David Maurice Surrey). It is the name given to an HBV virion. Consists of Surface antigen, Core antigens (HBcAg and HBeAg), DNA, DNA polymerase, and Protein Kinase.

Outline the replication pattern of HBV (6 steps)

1. Attachment (HBsAg)-->uncoating
2. dsDNA genome completed and transported to the nucleus.
3. Transcription of viral mRNA's (or genome integration if possible)
4. Viral mRNA translation.
5. Assembly of core proteins, DNA synthesized by viral reverse transcriptase.
6. Core snatches some membrane (including HBsAg) and is released by exocytosis.

What are extrahepatic manifestations of HBV?

They are diseases resembling serum sickness (fever, skin rashes, arthralgia, arthritis) and usually subside with the onset of jaundice.

The two major complications are: Polyarteritis nodosa, and glomerular disease.

How does someone become a chronic carrier of HepB?

By the failure to generate anti-HBsAg antibodies. Can't clear the infection.

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