Week 205 - Alcoholism and Hepatitis Flashcards
(76 cards)
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)
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
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.
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.
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.
6
Q
Week 205 - Alcoholism and Hepatitis: What percentage of fatty livers develop into cirrhosis?
A
5-15%
7
Q
Week 205 - Alcoholism and Hepatitis: What is the cause of alcoholic hepatitis?
A
This is from the toxic effect of acetaldehyde.
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.
9
Q
Week 205 - Alcoholism and Hepatitis: What is the pathology of cirrhosis?
A
Inflammation and fibrosis that results in necrosis and tissue scarring.
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.
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%
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.
13
Q
Week 205 - Alcoholism and Hepatitis: Hepatitis C is commonly asymptomatic, but how can it present?
A
- Malaise
- Anorexia
- Weakness
14
Q
Week 205 - Alcoholism and Hepatitis: What is the standard treatment for Hepatitis C?
A
• Ribivarin and Interferon.
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
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)
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.
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.
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
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
21
Q
Week 205 - Alcoholism and Hepatitis: What is the geographic distribution of hepatitis E?
A
Roughly equatorial with china.
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.
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
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
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
