Hepatitis Viruses Flashcards
What is the relationship between different hepatitis viruses ?
Just that they cause hepatitis and are split on acute and chronic
What are the acute Hepatitis viruses ?
What are the chronic hepatitis viruses?
A/E are acute
B/C/D are chronic
The liver facts
Weighs up to 2kg
Key function in metabolism/homeostasis
Blood supply from small intestine via portal vein. And from aorta via hepatic artery
How often does blood in the body go through liver
Every 8 mins where it is constantly sampled and altered
Ultrastructure of Liver?
Blood from hepatic artery and portal vein mix in the sinusoid which is loomed with endothelial cells called fenestrations
- fenestrations enable blood to diffuse through the endothelial later to hepatocytes
Space between hepatocytes and endothelium is know as Space of Disse and contains macrophages etc
Other side of hepatocytes is bile canaliculus, which enables hepatocytes to release bile into bile duct
How much of the liver is hepatocytes?
Number 2x10^11
60% of liver
80% of mass
Metabolically active but not replicating
What do hepatocytes do?
Metabolise carbohydrates,fats and proteins into glucose
Glucose->glycogen ->glucose
What are the functions of hepatocytes
Fat metabolism
Protein metabolism
Detoxification
Bile production
How are hepatocytes involved in fat metabolism?
Oxidation of triglycerides (lipids) produces energy
Synthesise lipoproteins
Conversion of excess carb+protein-> lipid, which is exported to adipose tissue for storage
How are hepatocytes involved in protein metabolism?
Aminotransferases perform Deamination + trans animation of amino acids –> glucose/lipid
Remove ammonia via urea synthesis
Synthesise non-essential amino acids and serum proteins, e.g. Albumins and clotting factors
How are hepatocytes involved in detoxification?
Metabolic waste ammonia, insecticide residues, drugs and alcohol
How are hepatocytes involved in bile production?
Bile acids derived from cholesterol and crucial for digestion of fat and fat soluble vitamins in small intestine
Key route for excretion of waste products
Percentage excreted in bile recirculating and what is cycle
Liver -> gall bladder-> small intestine
Then 5% excreted or recirculated back to liver
How does normal Uninfectwd liver function
- Phagocyte uptakes senescent RBC
- Phagocyte breaks this down into components, including gene –>bilirubin(green,yellow)
- Released and conjugated to albumin, to keep it soluble
- Bilirubin is taken up by hepatocytes, conjugate to glucuronic acid
- This is released into bile and into small intestine
Pathology of acute hepatitis?
Jaundice is due to hepatocytes dysfunction due to inability to break down bilirubin
Accumulation of toxins also causes Abdominal swelling and pain Prolonged itchy skin Dark urine Pale stools Bloody/tat like stool Chronic fatigue and loss of appetite
How to diagnose acute hepatitis?
Look at serum levels of liver enzyme/metabolic products as hepatocytes damage results in
Increased alanine aminotransferase as released from damaged hepatocytes
Decreased albumin
Increased bilirubin
Chronic hepatitis shows?
Results in induction of liver Fibrosis/scarring, involves deposition of ECM macromolecules(collagen etc), induced by hepatic stellate cells - is reversible however
Fibrosis can develop into liver cirrhosis
- more widespread damage, leading to liver failure, resulting in restricted blood flow due to EVM buildup- portal hypertension
Can develop into hepatocellular carcinoma - a very aggressive and difficult to treat cancer
Can only be diagnosed by liver biopsy
Features of acute hepatitis viruses?
Non-enveloped and enteric transmission can’t survive in bile due to high acidity and high concentration of detergents
Features of chronic hepatitis viruses?
Enveloped viruses and parenteral blood transmission
What is Hepatits A virus?
HAV
A PICORNAVIRUS
7.5kb linear +ve ssRNA genome
30nm in diameter
Has 5’IRES + VPg, polyA tail, producing single poly protein, cleaved into p1,p2, p3 which are then cleaved into all the proteins
Patients produce huge amounts of HAV which can be viewed via EM of faeces
Epidemiology of HAV?
Prevalent in Southern Hemisphere e.g. South Africa/Asia/America
Low in Northern Europe
Spread via close personal contact
Household/sexual/child day care centres
Contaminated food/water (infected handlers/shellfish)- most common
Blood exposure (IV drugs/transfusions) -rare Endemic countries have exposure of less than 100% aged 10
How has HAV evolved?
Thought to only be present in primates with 3 closet related simian genotyoes and 3 closely related human genotypes
Felix see Lee studies show more distributed
-13 novel species found in bats, hedgehogs, rodents and shrews.
Showed no evidence of disease but high amounts of virus in liver
HAV clinical features ?
Usually mild disease
Fatality rate 0.4%
1.75% in >49year olds
Average incubation 30 days with sudden onset symptoms fever, malaise , abdominal discomfort and jaundice
Can be followed by monitoring blood born markers ALT/Ab be HAV
HAV therapy options?
Vaccines
E.g. One based on virus grown in MRC-5 cells, formaldehyde inactivated and aluminium adjuvant
Epaxal(crucell) - virosome based (no AI), artificial liposomes containing lecithin/cephalin studded with influenza NA/HA and intact HAV particles - well tolerated and highly immunogenic. One dose ensures 97% seroprotection at 2 weeks
