Alcohol Symposium Flashcards by A.M.C.T Kate

What is the importance of solubility of alcohol?

it is water-soluble
those with a higher BMI (fat) will have a higher blood alcohol levels
hence why females usually have higher blood alcohol than men?

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How is alcohol metabolised?

Ethanol –> Acetalhdye –> Acetate

Alcohol dehydrogenase major enzyme pathway way for both reactions
P4502E1 (at higher levels of alcohol) and Catalase can convert Ethanol to Acetaldehyde

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What is a common alcohol dehydrogenase polymorphisms?

individuals of Asian descent who have B2 ADH isoform, metabolise ethanol 20% faster than northern Europeans who posses the B1 ADH polymorphism

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What is the effect of alcohol on the redox state?

Increases lactate: pyruvate ratio
Increase beta-hydroxybutyrate: acetoacetate ratio
this reduces the conversion of NAD to NADH
inhibition of: glycolysis, citric acid cycle, fatty acid oxidation. gluconeogenesis
all resulting in hypoglycaemia

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What is the effect of alcohol on lipid levels?

stimulates fatty acid synthesis: these are then esterified and with glycerol and stored as triglycerides

Oxidant stress

lipid peroxidation which is associated with acute tissue damage and fibrosis
free radicals attack cellular and mitochondrial DNA causing deletions and mutations

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Describe the metabolism of Methanol

What is the resultant impact?

metabolised using alcohol dehydrogenase to give Formic acid
Formic acid converted to CO₂ and H₂O in the presence of Folate
if there is a folate deficiency or excess Formic acid this can cause blindness
dialysis may be needed to remove the methanol from the bloodstream

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Explain how Ethylene glycol (antifreeze) is metabolised

What is its resultant impact?

Oxalic acid binds to calcium which deposits in renal tubules –> acute renal failure
Glycolic acid causes a metabolic acidosis: requires IV NaHCO₃
can use ethanol and fomepizole as ca competitive inhibitor of ethylene glycol
may need dialysis
treat with calcium and thiamine and pyridoxine

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How much is 1 unit of alcohol?

= 10mL or 8g of pure alcohol

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What is the effect of ethanol on individuals?

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What is alcohol ketoacidosis?

Metabolic acidosis with an increased anion gap.
Typically chronic alcoholics who binge with little nutrition intake.

Caused by:

Extracellular volume depletion
Glycogen depletion
Increased NADH/NAD ratio
Insulin suppressed
Lipolysis and ketones increased (beta-hydroxybutyrate)

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What is the treatment of alcoholic ketoacidosis?

IV glucose
IV fluids to overcome dehydration

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What are the endocrine effects of alcohol?

Decreased testerone- testicular atrophy
Pseudo Cushing
Metabolic syndrome and Dyslipidemia

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What are nutritional issues associated with alcohol

Low calcium: linked to diet, decreased vitamin D
Low phosphate: linked to diet, increased PTH
Low Mg, K: linked to diet, urinary loss, hyperaldosteronism

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What are typical Liver function tests?

Gamma Glutamyl Transferase (GGT) increased by liver enzyme induction
Transaminases (ALT and AST) increased by hepatocellular damage
Globulin increased in cirrhosis
Bilirubin & INR increased and albumin decreased by liver failure and escape into the peritoneal cavity (ascites)

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What are other relevant blood tests that may be used when alcohol is involved?

alcohol causes Macrocytosis – seen in raised MCV in a full blood count
Raised serum ferritin concentration
Hyperuricaemia: high purine content in alcoholic drinks, competition with ketone bodies and lactate for excretion
Hypertriglyceridaemia
Increased carbohydrate-deficient transferrin ( have they actually stopped drinking, this would be high days after a binge)

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How does alcohol cause hypertension?

impairment of the baroreceptors
increase of sympathetic activity
stimulation of the renin-angiotensin-aldosterone system
an increase in plasma cortisol
an increase of intracellular calcium with subsequent increase in vascular reactivity
endothelial e.g. inhibition of endothelium-dependent nitric oxide production

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What is the cause of Thiamine deficiency?

Ethanol interference with GI absorption
Hepatic dysfunction, which hinders storage and activation of thiamine
Malnourishment

What three enzymes is thiamine an important co-factor for?

Pyruvate dehydrogenase in glycolysis: leads to a build-up of pyruvate and depleted production of Acetyl-CoA
alpha- Ketoglutarate dehydrogenase in the TCA: leads to accumulation of GABA and glutamate
Transketolase enzymes in the Pentose Phosphate pathway: important for the formation of amino ribose-5-phosphate –> nucleic acids, complex sugars and coenzymes

What are the zones of the liver?

How are they organised?

this is the functional classification of sections of the liver that pertain to its oxygen supply
Zone 1: Peritoneal, near the portal tract- high oxygen
Zone 2: Transitional
Zone 3: Centrilobular- site of drug and xenobiotic metabolism

most susceptible to

hypoxia
to detoxification injury
passive congestion in heart failure

What is the need for a liver biopsy?

To make a diagnosis
Stage/grade the disease
To monitor treatment
To inform prognosis

What key things are monitored/ looked for in a liver biopsy?

Microvesicular fatty change
Extend of fibrosis
Amount of MD bodies
Intrahepatic cholestasis

What are the three main consequences of alcoholic liver disease?

Steatosis: macrovesicular and microvesicular
Steatohepatitis: ballooning of hepatocytes, inflammation (puts of neutrophils), necrosis of hepatocytes, Mallory Denk bodies
Fibrosis/ cirrhosis (irreversible): first seen in Zone 3 in the perivenular area then speeds to more oxygenated Zone 1

What are Mallory Denk bodies?

red structures that are cytokeratin scaffolding of the hepatocytes destroyed by the inflammatory process
not specific to alcoholic liver disease, but often presents itself and adds to confirmation of the diagnosis

What are the consequences of long-standing cirrhosis?

likely hood of getting Hepatocellular carcinoma increases

Portal hypertension:

collaterals found largely in the oesophagus: oesophageal
varices rupture is life-threatening, the umbilical vein: seen as caput medusa

What are the symptoms of alcohol withdrawal?

* Tremor/shaking * Sweating * Tachycardia * Nausea * Agitation * Siezures * Visual hallucinations

What are CAGE questions?

- Cut down alcohol, have you ever thought to do so - Annoyed of others criticism of your drinking - Guilty about your drinking habits - Eye opener, drink in the morning to get yourself going Yes to two of these needs further investigation for potential alcohol dependency - use the AUDIT questionnaire to do so

What is treatment/ management of alcohol withdrawal? what are the potential hazards of these treatments?

* CHLORDIAZEPOXIDE – used at BSUH * DIAZEPAM _Hazards_ * Severe liver disease - precipitation of hepatic encephalopathy * Respiratory depression * Reluctance to prescribe more * Concomitant alcohol consumption ( cant be taken the same time as alcohol)

What is the classic triad of Wernicke's Encephalopathy?

- Confusion - Eye Signs- ophthalmoplegia (inhibited eye movement) and nystagmus (rapid eye movements) - Ataxia Only seen in 10% of cases

What are three indicators/ results of Korsakoff's psychosis?

- Permanent brain damage - Severe short term memory loss - Confabulation

What treatment is given to Wernicke-Korsakoff syndrome?

* PABRINEX: -Thiamine 250mg + others * Give IV for 2-5 days depending on the response, do this before giving dextrose or feeding them * Rarely causes anaphylaxis * Continue oral thiamine and other vitamins after initial treatment * check glucose levels hypoglycaemia trumps low thiamine, but you usually give them together.

What is the relationship between alcohol and violence?

- 1/3 of domestic violence is alcohol-related - 1/5 of calls to childlike are related to parents alcohol consumption - RTA- 1in 7 of those killed on UK roads - 53% of violent crime in England (2014)

What is Sensible on Strength?

- local action in Brighton that reduces maximum strength alcohol at off-licence stores - increase training to staff with dealing with anti-social behaviour - it seemed to have worked

What is the Cumulative Impact Zone initiative in Brighton and Hove?

- if your starting a business that may be selling alcohol in an area that already does so, you might not be allowed to, in order to reduce the impact in specific areas

What are the two distinctions of drinking cultures?

- Wet: normalized - Dry: don't usually drinking, when they do drink it can be in excess, is a commodity that people do need to be protected from

What are the 3 main motives for drinking alcohol?

Enhancement: to feel better, to do things otherwise impossible Social: to be sociable, to celebrate parties Coping: because it makes you forget your problems Conformity: because others do so, to fit in

How can we change how people drink using different motives for drinking?

- Using the IMB model - give them information, this will inform and potentially change their motivation - and this will also change the behavioural skills to change their drinking behaviour

How is community alcohol detox managed?

* Benzodiazepines (chlordiazepoxide) * Vitamins tablets – Vitamin B complex / Thiamine / Vit BPC * Pabrinex IM * Relapse prevention meds – Acamprosate * 2 week CBT based group * Further weekly groups * 1:1 care coordination * AA / NA / CA groups

What are mild/ moderate signs of alcohol dependence?

usually occurs within 6-8 hours after a fall in blood alcohol level - Insomnia and fatigue - Tremors - Mild anxiety/restlessness/agitation - N&V - Headache - Excessive sweating - Palpitations - Craving for alcohol

What is the progression of alcohol withdrawal in dependent individuals?

- Signs of physical dependence within 6-8 hours - Alcoholic Hallucinations: 12-24 hours after reduced alcohol consumption (crawling insects, snakes and rats) - Alcohol withdrawal seizures: 6-48 hours (lasting 2-3 days), 80% occur within 48 hours, largely in patients with long history of chronic alcoholism - Delirium Tremens: 48-96 hours after reduced alcohol consumption

What occurs in Delirium Tremens?

* Hallucinations * Heightened anxiety * Severe agitation * Delusions * Tachycardia * Hypotension * Hypothermia * Tachypnoea * Altered electrolytes – hypokalaemia / Hypomagnesemia

How is a non-medical detox managed?

- Planned reduction - Drink diaries - Stabilisation - Gradually reduce - Consider the form of alcohol, strength and size of the vessel - which drinks should you not have, plan day based on that