Week 205 - Alcoholism and Hepatitis Flashcards Preview

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Flashcards in Week 205 - Alcoholism and Hepatitis Deck (76):
1

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.

6

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

5-15%

7

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

This is from the toxic effect of acetaldehyde.

8

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.

9

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

Inflammation and fibrosis that results in necrosis and tissue scarring.

10

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.

11

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%

12

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

14

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)

17

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.

18

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.

19

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

Adenovirus, EBV, CMV, Herpes simplex

20

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

21

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

Roughly equatorial with china.

22

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.

23

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

24

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

25

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

• Peginterferon

• Entecavir
• Tenofovir

• Lamivudine
• Adefovir
• Telbivudine

26

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

27

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.

28

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

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

29

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

30

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.

31

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

• cytochrome P450

32

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

Acetate -> CO2 and H20

33

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

36

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.

37

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.

38

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.

39

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.

40

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.

41

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.

42

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.

43

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.

44

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.

46

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.

47

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.

48

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.

49

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.

50

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.

51

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.

52

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)

53

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.

54

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.

55

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)

56

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

• Mu
• Delta
• Kappa

57

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

Mu
- Heroin, Morphine, Oxycodone, Fentanyl

58

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

Naloxone (opioid antagonist)

59

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.

60

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

Alertness, Bruxism, Weight-loss, euphoria.

61

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

Haloperidol

62

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

Ravenous appetite, exhaustion and mental depression.

63

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.

64

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.

65

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.

66

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.

67

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

Nicotine acts directly on the neurones which release dopamine.

68

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.

70

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

NMDA antagonist.

71

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

Adenosine receptor antagonist.
Adenosine = sleep.

72

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.

75

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

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

76

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

• Men 3-4 units/day
• Women 2-3 units/day