Alcoholism

Question 1

Where in hepatic acina does alcohol metabolism occur?

Answer 1

Zone 1

Question 2

Describe alcohol metabolism

Answer 2

• In the cytosol, alcohol in converted to acetaldehyde by alcohol dehydrogenase
  
  • Peroxisomes also produce acetaldeyhyde through catalase action
  • Microsomal Ethanol Oxidising system also causes acetaldehyde production through the use of CYP2E1
• Acetaldehyde is converted to Acetate in the mitochondria by Aldehyde dehydrogenase
• Acetate converted to Acetyl CoA which due to high levels of NADH produced in metabolic pathways, converted to fatty acids and then TAGS

Question 3

Describe the effect alcohol has in the body

Answer 3

• Gram negative bacteria in the stomach release lipopolusaccharide into the blood in the presence of alcohol.
• This travels to the liver where it is recognised by TLRs on kupffer cells
• Kupffer cells and ROS produced in metabolism produce cytokines (TNF-alpha, IL-1, IL-6 and IL-12) which encourage WBCs into the liver, inducing inflammatory response
• WBCs also activate stellate cells which become myofibrocytes and produce collagen - leads to fibrosis
• Increased fatty acid synthesis causes liver steatosis and steatorrhoea
• Excess ethanol conusmption leads to vitamin B1 (thiamines) deficiency which are essential for metabolic pathwyas, causing:
  
  • Beri Beri - inflammation of peripheral nerves causing pain and paralysis or extremites
  • Wernickes encephalopathy - confusion, nystagmus and unsteady gait
  • Korssakoffs psychosis - memory loss and deterioration

Question 4

What is an alcoholic?

Answer 4

Someone who is dependent on alcohol, doesnt just abuse it

Question 5

How can alcoholism be treated?

Answer 5

Disulfriam - inhibits ALDH, causing build up of acetaldehyde and therefore bad side effects causign patient to not want to drink anymore

Naltrexone - opiate receptor antagonist

Acamprosate - functional glutamate antagonist to inhibit cravings of alcohol

Question 6

List symptoms of foetal alcohol syndrome

Answer 6

• microcephaly
• short palebral fissures
• epicanthic folds
• smooth philtrum
• ptosis
• short upturned nose
• strabsmus

Question 7

What is the difference between apoptosis and necrosis?

Answer 7

Apoptosis is programmed cell death, caused by cell signals. It is beneficial and producs fragments which are able to send signals that facilitate phagocytosis

Necrosis is traumatic cell death. stimulated by factors external to the cells. It can be fatal, and cannot send signals, leading to the build up of dead tissue and cell debris

Question 8

Explain the process of apoptosis

Answer 8

Intrinsic pathway - initiated by oxidative stress, leading to the leackage of pro-apoptotic factors from mitochondira, regulated by Bcl-2 proteins. Theses activate caspases, leading to cell degradation

Extrinsic pathway = initiated by TNF-alpha which binds to TNF receptors, leading to caspase activation via FADD and TRADD

Capsases degrade cellular organelles which are then broken down into vesicles (apoptotic bodies) and released from the cell. These send signals to recruit macrophages for phagocytosis

Question 9

Anticholinergic toxidrom

Answer 9

dry mouth
hot
flushed
dry skin
tachycardia
dilated and unreactive pupils
hallucinations

Question 10

Cholinergic toxidrome

Answer 10

“DUMBBELS”:

• Defaecation
• Urination
• Miosis
• Bronchoconstriction
• Bradycardia
• Emesis
• Lacrimation
• Salivation

Question 11

Stimulant toxidrome

Answer 11

tachycardia
hypertension
arrhythmia
sweaty
agitation
dilated pupils
elevated temperature