Flashcards in Week 205 - Alcoholism and Hepatitis Deck (76)
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Week 205 - Alcoholism and Hepatitis: What is the metabolism pathway for alcohol?
• Ethanol is converted to Acetaldehyde - (Enzyme ADH)
• Acetaldehyde is converted into acetate - (Enzyme ALDH and reduction of NAD+ to NADH)
2
Week 205 - Alcoholism and Hepatitis: What are the risk factors for liver disease?
• Alcohol consumption
• Genetics, women>men + ethnicity
• BMI
• Diabetes
• Immune factors
3
Week 205 - Alcoholism and Hepatitis: What are the three degrees of alcoholic liver disease?
• Fatty liver
• Alcoholic hepatitis
• Hepatic fibrosis or cirrhosis.
4
Week 205 - Alcoholism and Hepatitis: What is the process of fatty deposition in the space of Disse in fatty liver disease?
• Decreased NAD+ (From increased use during alcohol metabolism)
• This results in decreased gluconeogenesis which results in an increase in fatty acids.
5
Week 205 - Alcoholism and Hepatitis: In which potential space are fatty acids deposited in the liver due to over consumption of alcohol?
Space of Disse, this is between hepatocytes and sinusoids.
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Week 205 - Alcoholism and Hepatitis: What percentage of fatty livers develop into cirrhosis?
5-15%
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Week 205 - Alcoholism and Hepatitis: What is the cause of alcoholic hepatitis?
This is from the toxic effect of acetaldehyde.
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Week 205 - Alcoholism and Hepatitis: What are the signs and symptoms of alcoholic hepatitis?
Change in appetite, tiredness, weakness, fever, hepatomegaly, right upper quadrant pain, jaundice, nausea and vomitting.
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Week 205 - Alcoholism and Hepatitis: What is the pathology of cirrhosis?
Inflammation and fibrosis that results in necrosis and tissue scarring.
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Week 205 - Alcoholism and Hepatitis: What is the presentation of cirrhosis?
• S/S of alcoholic hepatitis - change in appetite, tiredness, weakness, fever, hepatomegaly, right upper quadrant pain, jaundice, nausea and vomiting.
• PLUS - oedema, ascites, bruising/bleeding, haematemesis, malaena.
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Week 205 - Alcoholism and Hepatitis: What are the percentage risk of alcoholics developing the triad of alcoholic liver disease?
• Fatty liver - 90%
• Alcoholic hepatitis - 10-35%
• Cirrhosis - 10-20%
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Week 205 - Alcoholism and Hepatitis: What is the infective agent for hepatitis C?
• Hepatitis C Virus (HVC)
• A member of the Flaviviridae family.
13
Week 205 - Alcoholism and Hepatitis: Hepatitis C is commonly asymptomatic, but how can it present?
• Malaise
• Anorexia
• Weakness
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Week 205 - Alcoholism and Hepatitis: What is the standard treatment for Hepatitis C?
• Ribivarin and Interferon.
15
Week 205 - Alcoholism and Hepatitis: Aside from alcoholic liver disease and Hepatitis C what is the other major cause of chronic liver disease?
Obesity
16
Week 205 - Alcoholism and Hepatitis: What are the routes of transmission for Hepatitis A-E
• Oral-faecal - A + E
• Parenteral - B + C (D in the presence of active B)
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Week 205 - Alcoholism and Hepatitis: What is the prodrome of viral hepatitis?
Flu-like symptoms; anorexia, nausea and vomitting, fatigue, malaise, low-grade fever, myalgia and mild headache.
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Week 205 - Alcoholism and Hepatitis: What are the signs of symptoms of viral hepatitis during the icteric phase?
Dark urine, pale stools, jaundice, abdominal pain, itch, arthralgia and skin rash.
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Week 205 - Alcoholism and Hepatitis: Aside from Hep A-EE what other organisms can cause viral hepatitis?
Adenovirus, EBV, CMV, Herpes simplex
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Week 205 - Alcoholism and Hepatitis: What is the management for viral hepatitis?
• Prevention - Vaccination A,B and E
• Post-exposure prophylaxis - HBIG for Hep. B
• Acute illness - supportive care, anti-viral B +C
• Chronic illness - anti-viral B + C
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Week 205 - Alcoholism and Hepatitis: What is the geographic distribution of hepatitis E?
Roughly equatorial with china.
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Week 205 - Alcoholism and Hepatitis: What are the clinical features of HEV?
• Cholestasis, jaundice, malaise, anorexia, nausea, vomitting, abdominal pain, fever, hepatomegaly.
• Less common features include diarrhoea, arthritis, pruritus, urticarial rash.
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Week 205 - Alcoholism and Hepatitis: Hepatitis B can be found world wide, but in which areas of the world are suffering from an endemic?
• Sub-saharan africa
• China, Kazakstan, Mongolia
• Indonesia
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Week 205 - Alcoholism and Hepatitis: What are the aims of HBV treatment?
• Loss of viral replication
• Normalisation of transaminases
• Improvement in liver histology
• Loss of e antigen
• Loss of surface antigen
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Week 205 - Alcoholism and Hepatitis: What is the medical treatment of HBV?
• Peginterferon
• Entecavir
• Tenofovir
• Lamivudine
• Adefovir
• Telbivudine
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Week 205 - Alcoholism and Hepatitis: What is the natural history of HCV infection?
• Exposure - 15% resolve, 85% become chronic
• Chronic - 80% stable, 20% develop cirrhosis
• Cirrhosis - 75% slowly progressive, 25% death/transplant
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Week 205 - Alcoholism and Hepatitis: Interferon is used for the treatment of hepatitis, but is frequently in-tolerated due to its side effects, what are they?
Flu-like symptoms, injection site reactions, myalgia and arthralgia, neuropsychiatric, bone marrow suppression, thyroid dysfunction, exacerbation of auto-immune disease.
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Week 205 - Alcoholism and Hepatitis: What are the adverse effects of Ribavirin?
Teratogenic, haemolytic anaemia, skin rash, cough, insomnia.
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Week 205 - Alcoholism and Hepatitis: What are the functions of the liver? (5)
• Storing glycogen
• Production of clotting factors
• Processing medication
• Helping to remove toxins from the body
• Production of bile
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Week 205 - Alcoholism and Hepatitis: What are the principle reactions of drug metabolism in the liver?
• Most drugs are lipid soluble, these are broken down during phase one reactions into products of oxidation, reduction or hydrolysis.
• Phase II reactions then couple these products with endogenous substrates to form water soluble metabolites.
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Week 205 - Alcoholism and Hepatitis: What family of enzymes is responsible for catalysing the Phase one reactions of the liver?
• cytochrome P450
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Week 205 - Alcoholism and Hepatitis: What is acetate metabolised to during alcohol metabolism?
Acetate -> CO2 and H20
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Week 205 - Alcoholism and Hepatitis: How can hypoglycaemia occur after excess alcohol consumption?
• If a large amount of alcohol is being metabolised by the liver the amount of NAD+ will reduce.
• This results in the equilibrium of lactate dehydrogenase reaction towards lactate production.
• This decreases the amount of pyruvate available for gluconeogenesis.
34
Week 205 - Alcoholism and Hepatitis: What are the pharmacological effects of alcohol?
• Inhibition of calcium entry through voltage gated calcium channels.
• Enhancement of GABA-mediated synaptic inhibition.
• Antagonism of excitatory amino acids.
• Inhibition of neurotransmitter release.
35
Week 205 - Alcoholism and Hepatitis: What are the 6 features of a LFT?
• ALT - Alanine transaminase
• AST - Aspartate aminotransferase
• ALP - Alkaline phosphatase
• Albumin
• Bilirubin (Conjugated+unconjugated)
• Total protein
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Week 205 - Alcoholism and Hepatitis: What is ALT in a liver function test?
• Alanine transaminase
• When liver is injured or inflamed there is normally a high level in the blood.
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Week 205 - Alcoholism and Hepatitis: What is AST in a liver function test?
• Aspartate aminotransferase
• High levels associated with liver injury but can also be raised if heart or skeletal muscle is damaged, therefore not very specific.
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Week 205 - Alcoholism and Hepatitis: What is ALP in a liver function test?
• Alkaline phosphatase
• Found in liver cells and bones.
• Raised in some liver diseases and bone disease.
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Week 205 - Alcoholism and Hepatitis: What is albumin and what is its significance in an LFT?
• Main protein produced by the liver, circulates in the blood.
• A low level occurs in some liver disorders.
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Week 205 - Alcoholism and Hepatitis: What is the significance of bilirubin in a liver function test?
• High level of conjugated bilirubin occurs in various liver and bile duct conditions, particularly raised in obstructive causes.
• High levels of unconjugated bilirubin occurs when there is excessive breakdown of red blood cells, e.g. haemolytic anaemia.
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Week 205 - Alcoholism and Hepatitis: Gamma-glutamyl transferase (GGT/Gamma-GT) is useful test for identifying what?
• This is a enzyme associated with the clearance of alcohol.
• Raised levels indicated high levels of alcohol consumption.
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Week 205 - Alcoholism and Hepatitis: What are the two major functional neuronal targets of ethanol?
• Potentiates inhibition with GABA receptors.
• Reduces excitation of NMDA receptors and voltage-opening calcium channels.
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Week 205 - Alcoholism and Hepatitis: What effect does alcohol have on GABA receptors? What larger effect does this have?
• When alcohol binds to the GABA receptor it enables it to stay open for longer.
• This allows more chloride ions to enter the postsynaptic hub, which reduces the likelihood of an action potential.
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Week 205 - Alcoholism and Hepatitis: What effect does alcohol have on NMDA receptors?
• Reduces the activity of NMDA receptors so glutamate has less of an effect, therefore reducing the excitatory pathway.
45
Week 205 - Alcoholism and Hepatitis: How do benzodiazapines interact with alcohol?
• Both affect the GABA receptor in the same way, they have an additive effect.
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Week 205 - Alcoholism and Hepatitis: What is the definition of tolerance?
Decreased response to the effects of a set drug concentration after continued use. The body develops mechanisms to adapt to the presence of a drug.
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Week 205 - Alcoholism and Hepatitis: What is the definition of dependance?
The need to take a drug in order to avoid the withdrawal effects due to the compensatory mechanisms that the body has developed.
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Week 205 - Alcoholism and Hepatitis: What is the definition of addiction?
• Continued use of a drug despite known adverse consequences.
• Compulsive drug seeking behaviour.
• Can occur in the absence of tolerance and dependance.
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Week 205 - Alcoholism and Hepatitis: What are the mechanisms behind chronic tolerance?
• Significant increase in number and activity of enzymes involved in alcohol metabolism.
• Long-lasting change in abundance and function of targets.
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Week 205 - Alcoholism and Hepatitis: What is acute tolerance and what is the mechanism behind it?
• Occurs within same session i.e. 'Drink yourself sober'
• Similar mechanism as chronic tolerance, due to changes in function of GABA/NMDA function.
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Week 205 - Alcoholism and Hepatitis: What is the Himmelsbach Hypothesis?
This looks at withdrawal occurring due to the effects of adaptation developed due to tolerance being active without the drug in the system.
• Crudely, symptoms of withdrawal are opposite to acute effects of the drug.
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Week 205 - Alcoholism and Hepatitis: What medication is commonly used for acute withdrawal of alcohol?
Benzodiazepines (Act similarly, so can be seen as hair of the dog)
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Week 205 - Alcoholism and Hepatitis: What are the three medical treatments for alcoholism and how effective are they?
• Naltrexone + Nalfemene - Opioid receptor antagonists.
• Acamprosate - NMDA receptor antagonist.
• Behavioural therapy.
• None of the above work particularly well, but combinations of the above are more effective.
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Week 205 - Alcoholism and Hepatitis: What is replacement therapy?
• Replace a fast acting drug with a slow releasing one (i.e. smoking, nicotine patches)
• Does not work very well.
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Week 205 - Alcoholism and Hepatitis: What are the common features of addictive drugs?
• Fast on
• Fast off
• Short duration
• Strong
(Route of administration effects all four)
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Week 205 - Alcoholism and Hepatitis: What are the three types of opioid receptor?
• Mu
• Delta
• Kappa
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Week 205 - Alcoholism and Hepatitis: Of the three opioid receptors which has the strongest reaction? Which drugs target it?
Mu
- Heroin, Morphine, Oxycodone, Fentanyl
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Week 205 - Alcoholism and Hepatitis: What is used to treat opioid overdose?
Naloxone (opioid antagonist)
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Week 205 - Alcoholism and Hepatitis: What is the mechanism of psychostimulants? Give some examples.
• Puts dopamine transporter in reverse, also has a similar effect on noradrenaline transporter, results in high concentration of both in synapse.
• Amphetamines, Methamphetamines, Cocaine.
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Week 205 - Alcoholism and Hepatitis: What effect do psychostimulants have?
Alertness, Bruxism, Weight-loss, euphoria.
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Week 205 - Alcoholism and Hepatitis: What is the treatment for an overdose of a pyschostimulant?
Haloperidol
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Week 205 - Alcoholism and Hepatitis: What are the withdrawal symptoms of psychostimulants?
Ravenous appetite, exhaustion and mental depression.
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Week 205 - Alcoholism and Hepatitis: How does the reward circuit work?
• Dopamine is produced by the VTA (Ventral tegmental area) in response to opioids produced by 'rewards'
• The dopamine acts as a learning signal, it is produced in anticipation of a reward. If the reward is obtained dopamine is actually inhibited.
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Week 205 - Alcoholism and Hepatitis: What is the mesolimbic dopamine system?
• This is the projection from the VTA (Ventral tegmental area) to the nucleus accumbens.
• It is the reward circuit.
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Week 205 - Alcoholism and Hepatitis: How do psychostimulants affect the mesolimbic dopamine pathway?
These act on dopamine transporters by reversing their action, resulting an abundance of dopamine in the synapse.
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Week 205 - Alcoholism and Hepatitis: How do opioids affect the mesolimbic dopamine pathway?
They inhibit cells that are responsible for the inhibition of dopamine release. Therefore, they increase the abundance of dopamine.
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Week 205 - Alcoholism and Hepatitis: How does nicotine affect the mesolimbic dopamine pathway?
Nicotine acts directly on the neurones which release dopamine.
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Week 205 - Alcoholism and Hepatitis: How does ethanol affect the mesolimbic dopamine pathway?
Ethanol activates neurones that secrete dopamine and also cause the release of endogenous opioids.
69
Week 205 - Alcoholism and Hepatitis: Which part of the brain is responsible for executive function and what is it?
• Prefrontal lobe
• Allows us to do long-term planning and withhold impulsive actions.
• It is impaired in addicts.
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Week 205 - Alcoholism and Hepatitis: What is the primary physiological effect of ketamine?
NMDA antagonist.
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Week 205 - Alcoholism and Hepatitis: What is the physiological effect of caffeine?
Adenosine receptor antagonist.
Adenosine = sleep.
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Week 205 - Alcoholism and Hepatitis: What is the medical term for fatty liver?
Hepatic steatosis.
73
Week 205 - Alcoholism and Hepatitis: What are some of the signs of alcoholic liver disease?
• Palmar erythema
• Dupuytens contracture
• Caput madusae
• Spider Naevi
• Ascites
• Gynaecomastia
• umbilical hernia
• Jaundice
74
Week 205 - Alcoholism and Hepatitis: What is Wernicke's encephalopathy?
• Acute neurological symptoms, due to damage to the cns due to insufficiency of thiamine.
• Encephalopathy, oculomotor disturbance, gait ataxia.
• Common in alcohol withdrawal.
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Week 205 - Alcoholism and Hepatitis: What is Korsakoff's syndrome?
• Irreversible dementia with confabulation, which can be develop due to Wernicke's encephalopathy.
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