Alcohol metabolism, alcoholic liver disease and alcoholism Flashcards
Define alcohol
“Alcohol” is non-specific, and includes methanol, ethanol, propanol etc.
In usual parlance, however, alcohol often means ethanol.
How is ethanol distributed and lost?
Ethanol is water soluble – so distribution to lean body mass only
Some endogenous production
Approx 10% lost through breath/urine – rest metabolised
Metabolism nearly all in liver some in brain, pancreas and stomach
Complete the equation
What are alcohol dehydrogenase polymorphisms?
Several isoforms of this enzyme are present, with variable activity in individuals depending on genetic makeup, gender and other factors.
For example, individuals of Asian descent who have the B2 ADH isoform, metabolise ethanol 20% faster than northern Europeans who posses the B1 ADH.
What is NAD role in alcohol metabolism and what is the consequence of this?
Both alcohol dehydrogenase and aldehyde dehydrogenase reactions reduce NAD to NADH
Increases:
lactate:pyruvate ratio
beta-hydroxybutyrate:acetoacetate ratio
Inhibits:
Glycolysis
Citric acid cycle – ketogenesis
Fatty acid oxidation
Gluconeogenesis
What is oxidant stress?
Lipid peroxidation which is associated with both acute tissue damage & fibrosis
Free radicals attack cellular & mitochondrial DNA causing deletions & mutations
What is 1 unit?
1 Unit = 10mL or 8g of pure alcohol
In 2016 the safe limit was reduced to ___U per week for both genders in at least ___ doses.
14 units
3 doses
Legal limit for driving in the UK is blood ethanol ≤ ___mg/dL.
Legal limit for driving in the UK is blood ethanol ≤ 80mg/dL.
≤ 2-3 units in females
≤ 3-4 units in men
Why should pregant women not drink alcohol?
Pregnant women or women trying to conceive should not drink alcohol. Ethanol crosses the placenta. Alcohol can seriously affect foetal development (foetal alcohol syndrome).
What is alcoholic ketoacidosis?
Metabolic acidosis with increased anion gap.
Typically occurs in chronic alcoholics who binge with little nutrition intake.
What is the pathophysiology of alcoholic ketoacidosis?
Glycogen depletion/inhibited gluconeogenesis
Lipolysis and ketones increased (beta hydroxybutyrate) Insulin suppressed
Extracellular volume depletion/dehydration/stress - increase counter regulatory hormones further supressing insulin
How does alcohol cause hypoglycaemia?
Ethanol causes hypoglycaemia through:
- decreased intake of glucose (CHO)
- depletion of glycogen
- blockade of gluconeogenesis
Prompt treatment with glucose is life-saving
Need to give parenteral thiamine as well to prevent CNS damage in case there is also thiamine deficiency
What endocrine issues can alcohol cause?
- Decreased testosterone (testicular atrophy)
- Pseudo Cushings
- Metabolic Syndrome and Dyslipidaemia
What general nutrition issues can alcohol cause?
- Low calcium (diet, decreased vitamin D)
- Low phosphate (diet, increased PTH)
- Low Mg, K (diet, urinary loss, hyperaldosteronism)
What LFTs change in alcohol?
- 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
What are the causes of thiamine deficiency?
- Ethanol interferes with GI absorption
- Hepatic dysfunction, which hinders storage and activation
- Malnourishment
What other relevant blood tests would you do for an alcohol patient?
- Macrocytosis – raised MCV in a full blood count
- Raised serum ferritin concentration
- Hyperuricaemia
- Hypertriglyceridaemia
- Increased carbohydrate-deficient transferrin or CDT
How does alcohol cause hypertension?
- impairment of the baroreceptors (which sense blood pressure)
- 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