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Week 205 - Alcoholism and Hepatitis Flashcards

1
Q

Week 205 - Alcoholism and Hepatitis: What is the metabolism pathway for alcohol?

A
  • Ethanol is converted to Acetaldehyde - (Enzyme ADH)

* Acetaldehyde is converted into acetate - (Enzyme ALDH and reduction of NAD+ to NADH)

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2
Q

Week 205 - Alcoholism and Hepatitis: What are the risk factors for liver disease?

A
  • Alcohol consumption
  • Genetics, women>men + ethnicity
  • BMI
  • Diabetes
  • Immune factors
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3
Q

Week 205 - Alcoholism and Hepatitis: What are the three degrees of alcoholic liver disease?

A
  • Fatty liver
  • Alcoholic hepatitis
  • Hepatic fibrosis or cirrhosis.
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4
Q

Week 205 - Alcoholism and Hepatitis: What is the process of fatty deposition in the space of Disse in fatty liver disease?

A
  • Decreased NAD+ (From increased use during alcohol metabolism)
  • This results in decreased gluconeogenesis which results in an increase in fatty acids.
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5
Q

Week 205 - Alcoholism and Hepatitis: In which potential space are fatty acids deposited in the liver due to over consumption of alcohol?

A

Space of Disse, this is between hepatocytes and sinusoids.

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6
Q

Week 205 - Alcoholism and Hepatitis: What percentage of fatty livers develop into cirrhosis?

A

5-15%

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7
Q

Week 205 - Alcoholism and Hepatitis: What is the cause of alcoholic hepatitis?

A

This is from the toxic effect of acetaldehyde.

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8
Q

Week 205 - Alcoholism and Hepatitis: What are the signs and symptoms of alcoholic hepatitis?

A

Change in appetite, tiredness, weakness, fever, hepatomegaly, right upper quadrant pain, jaundice, nausea and vomitting.

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9
Q

Week 205 - Alcoholism and Hepatitis: What is the pathology of cirrhosis?

A

Inflammation and fibrosis that results in necrosis and tissue scarring.

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10
Q

Week 205 - Alcoholism and Hepatitis: What is the presentation of cirrhosis?

A
  • 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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11
Q

Week 205 - Alcoholism and Hepatitis: What are the percentage risk of alcoholics developing the triad of alcoholic liver disease?

A
  • Fatty liver - 90%
  • Alcoholic hepatitis - 10-35%
  • Cirrhosis - 10-20%
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12
Q

Week 205 - Alcoholism and Hepatitis: What is the infective agent for hepatitis C?

A
  • Hepatitis C Virus (HVC)

* A member of the Flaviviridae family.

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13
Q

Week 205 - Alcoholism and Hepatitis: Hepatitis C is commonly asymptomatic, but how can it present?

A
  • Malaise
  • Anorexia
  • Weakness
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14
Q

Week 205 - Alcoholism and Hepatitis: What is the standard treatment for Hepatitis C?

A

• Ribivarin and Interferon.

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15
Q

Week 205 - Alcoholism and Hepatitis: Aside from alcoholic liver disease and Hepatitis C what is the other major cause of chronic liver disease?

A

Obesity

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16
Q

Week 205 - Alcoholism and Hepatitis: What are the routes of transmission for Hepatitis A-E

A
  • Oral-faecal - A + E

* Parenteral - B + C (D in the presence of active B)

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17
Q

Week 205 - Alcoholism and Hepatitis: What is the prodrome of viral hepatitis?

A

Flu-like symptoms; anorexia, nausea and vomitting, fatigue, malaise, low-grade fever, myalgia and mild headache.

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18
Q

Week 205 - Alcoholism and Hepatitis: What are the signs of symptoms of viral hepatitis during the icteric phase?

A

Dark urine, pale stools, jaundice, abdominal pain, itch, arthralgia and skin rash.

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19
Q

Week 205 - Alcoholism and Hepatitis: Aside from Hep A-EE what other organisms can cause viral hepatitis?

A

Adenovirus, EBV, CMV, Herpes simplex

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20
Q

Week 205 - Alcoholism and Hepatitis: What is the management for viral hepatitis?

A
  • 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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21
Q

Week 205 - Alcoholism and Hepatitis: What is the geographic distribution of hepatitis E?

A

Roughly equatorial with china.

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22
Q

Week 205 - Alcoholism and Hepatitis: What are the clinical features of HEV?

A
  • Cholestasis, jaundice, malaise, anorexia, nausea, vomitting, abdominal pain, fever, hepatomegaly.
  • Less common features include diarrhoea, arthritis, pruritus, urticarial rash.
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23
Q

Week 205 - Alcoholism and Hepatitis: Hepatitis B can be found world wide, but in which areas of the world are suffering from an endemic?

A
  • Sub-saharan africa
  • China, Kazakstan, Mongolia
  • Indonesia
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24
Q

Week 205 - Alcoholism and Hepatitis: What are the aims of HBV treatment?

A
  • Loss of viral replication
  • Normalisation of transaminases
  • Improvement in liver histology
  • Loss of e antigen
  • Loss of surface antigen
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25
Q

Week 205 - Alcoholism and Hepatitis: What is the medical treatment of HBV?

A

• Peginterferon

  • Entecavir
  • Tenofovir
  • Lamivudine
  • Adefovir
  • Telbivudine
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26
Q

Week 205 - Alcoholism and Hepatitis: What is the natural history of HCV infection?

A
  • Exposure - 15% resolve, 85% become chronic
  • Chronic - 80% stable, 20% develop cirrhosis
  • Cirrhosis - 75% slowly progressive, 25% death/transplant
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27
Q

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?

A

Flu-like symptoms, injection site reactions, myalgia and arthralgia, neuropsychiatric, bone marrow suppression, thyroid dysfunction, exacerbation of auto-immune disease.

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28
Q

Week 205 - Alcoholism and Hepatitis: What are the adverse effects of Ribavirin?

A

Teratogenic, haemolytic anaemia, skin rash, cough, insomnia.

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29
Q

Week 205 - Alcoholism and Hepatitis: What are the functions of the liver? (5)

A
  • Storing glycogen
  • Production of clotting factors
  • Processing medication
  • Helping to remove toxins from the body
  • Production of bile
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30
Q

Week 205 - Alcoholism and Hepatitis: What are the principle reactions of drug metabolism in the liver?

A
  • 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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31
Q

Week 205 - Alcoholism and Hepatitis: What family of enzymes is responsible for catalysing the Phase one reactions of the liver?

A

• cytochrome P450

32
Q

Week 205 - Alcoholism and Hepatitis: What is acetate metabolised to during alcohol metabolism?

A

Acetate -> CO2 and H20

33
Q

Week 205 - Alcoholism and Hepatitis: How can hypoglycaemia occur after excess alcohol consumption?

A
  • 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
Q

Week 205 - Alcoholism and Hepatitis: What are the pharmacological effects of alcohol?

A
  • 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
Q

Week 205 - Alcoholism and Hepatitis: What are the 6 features of a LFT?

A
  • ALT - Alanine transaminase
  • AST - Aspartate aminotransferase
  • ALP - Alkaline phosphatase
  • Albumin
  • Bilirubin (Conjugated+unconjugated)
  • Total protein
36
Q

Week 205 - Alcoholism and Hepatitis: What is ALT in a liver function test?

A
  • Alanine transaminase

* When liver is injured or inflamed there is normally a high level in the blood.

37
Q

Week 205 - Alcoholism and Hepatitis: What is AST in a liver function test?

A
  • Aspartate aminotransferase
  • High levels associated with liver injury but can also be raised if heart or skeletal muscle is damaged, therefore not very specific.
38
Q

Week 205 - Alcoholism and Hepatitis: What is ALP in a liver function test?

A
  • Alkaline phosphatase
  • Found in liver cells and bones.
  • Raised in some liver diseases and bone disease.
39
Q

Week 205 - Alcoholism and Hepatitis: What is albumin and what is its significance in an LFT?

A
  • Main protein produced by the liver, circulates in the blood.
  • A low level occurs in some liver disorders.
40
Q

Week 205 - Alcoholism and Hepatitis: What is the significance of bilirubin in a liver function test?

A
  • 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.
41
Q

Week 205 - Alcoholism and Hepatitis: Gamma-glutamyl transferase (GGT/Gamma-GT) is useful test for identifying what?

A
  • This is a enzyme associated with the clearance of alcohol.

* Raised levels indicated high levels of alcohol consumption.

42
Q

Week 205 - Alcoholism and Hepatitis: What are the two major functional neuronal targets of ethanol?

A
  • Potentiates inhibition with GABA receptors.

* Reduces excitation of NMDA receptors and voltage-opening calcium channels.

43
Q

Week 205 - Alcoholism and Hepatitis: What effect does alcohol have on GABA receptors? What larger effect does this have?

A
  • 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.
44
Q

Week 205 - Alcoholism and Hepatitis: What effect does alcohol have on NMDA receptors?

A

• Reduces the activity of NMDA receptors so glutamate has less of an effect, therefore reducing the excitatory pathway.

45
Q

Week 205 - Alcoholism and Hepatitis: How do benzodiazapines interact with alcohol?

A

• Both affect the GABA receptor in the same way, they have an additive effect.

46
Q

Week 205 - Alcoholism and Hepatitis: What is the definition of tolerance?

A

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.

47
Q

Week 205 - Alcoholism and Hepatitis: What is the definition of dependance?

A

The need to take a drug in order to avoid the withdrawal effects due to the compensatory mechanisms that the body has developed.

48
Q

Week 205 - Alcoholism and Hepatitis: What is the definition of addiction?

A
  • Continued use of a drug despite known adverse consequences.
  • Compulsive drug seeking behaviour.
  • Can occur in the absence of tolerance and dependance.
49
Q

Week 205 - Alcoholism and Hepatitis: What are the mechanisms behind chronic tolerance?

A
  • Significant increase in number and activity of enzymes involved in alcohol metabolism.
  • Long-lasting change in abundance and function of targets.
50
Q

Week 205 - Alcoholism and Hepatitis: What is acute tolerance and what is the mechanism behind it?

A
  • Occurs within same session i.e. ‘Drink yourself sober’

* Similar mechanism as chronic tolerance, due to changes in function of GABA/NMDA function.

51
Q

Week 205 - Alcoholism and Hepatitis: What is the Himmelsbach Hypothesis?

A

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.

52
Q

Week 205 - Alcoholism and Hepatitis: What medication is commonly used for acute withdrawal of alcohol?

A

Benzodiazepines (Act similarly, so can be seen as hair of the dog)

53
Q

Week 205 - Alcoholism and Hepatitis: What are the three medical treatments for alcoholism and how effective are they?

A
  • 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.
54
Q

Week 205 - Alcoholism and Hepatitis: What is replacement therapy?

A
  • Replace a fast acting drug with a slow releasing one (i.e. smoking, nicotine patches)
  • Does not work very well.
55
Q

Week 205 - Alcoholism and Hepatitis: What are the common features of addictive drugs?

A 
• Fast on
• Fast off
• Short duration
• Strong
(Route of administration effects all four)
56
Q

Week 205 - Alcoholism and Hepatitis: What are the three types of opioid receptor?

A
  • Mu
  • Delta
  • Kappa
57
Q

Week 205 - Alcoholism and Hepatitis: Of the three opioid receptors which has the strongest reaction? Which drugs target it?

A

Mu

- Heroin, Morphine, Oxycodone, Fentanyl

58
Q

Week 205 - Alcoholism and Hepatitis: What is used to treat opioid overdose?

A

Naloxone (opioid antagonist)

59
Q

Week 205 - Alcoholism and Hepatitis: What is the mechanism of psychostimulants? Give some examples.

A
  • Puts dopamine transporter in reverse, also has a similar effect on noradrenaline transporter, results in high concentration of both in synapse.
  • Amphetamines, Methamphetamines, Cocaine.
60
Q

Week 205 - Alcoholism and Hepatitis: What effect do psychostimulants have?

A

Alertness, Bruxism, Weight-loss, euphoria.

61
Q

Week 205 - Alcoholism and Hepatitis: What is the treatment for an overdose of a pyschostimulant?

A

Haloperidol

62
Q

Week 205 - Alcoholism and Hepatitis: What are the withdrawal symptoms of psychostimulants?

A

Ravenous appetite, exhaustion and mental depression.

63
Q

Week 205 - Alcoholism and Hepatitis: How does the reward circuit work?

A
  • 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.
64
Q

Week 205 - Alcoholism and Hepatitis: What is the mesolimbic dopamine system?

A
  • This is the projection from the VTA (Ventral tegmental area) to the nucleus accumbens.
  • It is the reward circuit.
65
Q

Week 205 - Alcoholism and Hepatitis: How do psychostimulants affect the mesolimbic dopamine pathway?

A

These act on dopamine transporters by reversing their action, resulting an abundance of dopamine in the synapse.

66
Q

Week 205 - Alcoholism and Hepatitis: How do opioids affect the mesolimbic dopamine pathway?

A

They inhibit cells that are responsible for the inhibition of dopamine release. Therefore, they increase the abundance of dopamine.

67
Q

Week 205 - Alcoholism and Hepatitis: How does nicotine affect the mesolimbic dopamine pathway?

A

Nicotine acts directly on the neurones which release dopamine.

68
Q

Week 205 - Alcoholism and Hepatitis: How does ethanol affect the mesolimbic dopamine pathway?

A

Ethanol activates neurones that secrete dopamine and also cause the release of endogenous opioids.

69
Q

Week 205 - Alcoholism and Hepatitis: Which part of the brain is responsible for executive function and what is it?

A
  • Prefrontal lobe
  • Allows us to do long-term planning and withhold impulsive actions.
  • It is impaired in addicts.
70
Q

Week 205 - Alcoholism and Hepatitis: What is the primary physiological effect of ketamine?

A

NMDA antagonist.

71
Q

Week 205 - Alcoholism and Hepatitis: What is the physiological effect of caffeine?

A

Adenosine receptor antagonist.

Adenosine = sleep.

72
Q

Week 205 - Alcoholism and Hepatitis: What is the medical term for fatty liver?

A

Hepatic steatosis.

73
Q

Week 205 - Alcoholism and Hepatitis: What are some of the signs of alcoholic liver disease?

A
  • Palmar erythema
  • Dupuytens contracture
  • Caput madusae
  • Spider Naevi
  • Ascites
  • Gynaecomastia
  • umbilical hernia
  • Jaundice
74
Q

Week 205 - Alcoholism and Hepatitis: What is Wernicke’s encephalopathy?

A
  • Acute neurological symptoms, due to damage to the cns due to insufficiency of thiamine.
  • Encephalopathy, oculomotor disturbance, gait ataxia.
  • Common in alcohol withdrawal.
75
Q

Week 205 - Alcoholism and Hepatitis: What is Korsakoff’s syndrome?

A

• Irreversible dementia with confabulation, which can be develop due to Wernicke’s encephalopathy.

76
Q

Week 205 - Alcoholism and Hepatitis: What is the recommended consumption of alcohol?

A
  • Men 3-4 units/day

* Women 2-3 units/day

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