alcohol symposium Flashcards
how many adults drink and don’t drink
80% drank in the last year (48% in the last week) and 20% didn’t
proportion drinking inc with age
what is the CMO guidance for alcohol units
low risk <14 over >3 days
inc risk men 14-50, women 14-35
high risk men >50, women >35, risk of alcohol related health problems
how does alcohol consumption link to income
non drinkers inc as household income dec
proportion of adults drinking >14u dec with income
how does alcohol link to young people
inc with age parents don't discourage recent drug use drinkers at home smoking
what is the impact of alcohol on health
early death
disease and injury
social, economic
influences on alcohol consumption
individual factors family culture and community socioeconomics country/laws taxes
Policies to limit consumption and reduce harm
taxation (affordability, raise revenue)
regulation and legislation (promotion, price, driving)
eg minimum unit pricing, sensible on strength, cumulative impact zone
how is ethanol metabolised
water soluble, distribution to lean body mass only
some endogenous production
10% lost via breath/urine, rest metabolised (liver, some brain, pancreas and stomach)
ethanol to (via alcohol DH) acetaldehyde to (via Aldehyde DH) acetate
Alcohol dehydrogenase polymorphisms
Several isoforms of this enzyme present with variable activity depending on genetic makeup, gender and other factors.
Eg individuals of Asian descent who have the B2 ADH isoform metabolise ethanol 20% faster than northern Europeans who posses the B1 ADH.
what is alcohol dehydrogenase’s effect on redox state
reduce NAD+ to NADH Increases: lactate:pyruvate ratio beta-hydroxybutyrate:acetoacetate ratio Decreases: Glycolysis Citric acid cycle – ketogenesis Fatty acid oxidation Gluconeogenesis
toxic and metabolic effects of alcohol
Oxidant stress
Lipid peroxidation, associated with both acute tissue damage & fibrosis
Free radicals attack cellular & mitochondrial DNA causing deletions & mutations
how is methanol metabolised
methanol to (alcohol DH) formaldehyde to (aldehyde DH) formic acid to (folate) CO2 and H20
ethylene glycol metabolism
antifreeze poisoning
ethylene glycol
uses thiamine and pyridoxine
what does a unit mean
10ml or 8g pure alcohol
how does ethanol link to driving
legal limit in UK
blood ethanol <80mg/dL
<2-3 units in women and <3-4 in men
measured via breath
blood ethanol and symptoms
sporadic -euphoria, gregariousness, incoordination to slurred speech, drowsiness, lethargy, vomiting to coma and respiratory depression
chronic - less effect, euphoria and mild emotional/motor changes later to drowsiness, have to drink a lot more to become lethargic, coma
what is alcohol ketoacidosis
metabolic acidosis (inc anion gap)
binge with little nutritional intake
Glycogen depletion/inhibited gluconeogenesis
Lipolysis and ketones increased, Insulin suppressed
Extracellular volume depletion/dehydration/stress - increase counter regulatory hormones further supressing insulin
how does alcohol cause hypoglycaemia
decreased intake of glucose (CHO)
depletion of glycogen
blockade of gluconeogenesis
CNS damage as may be thiamine deficiency
endocrine effect of alcohol
Decreased testosterone (testicular atrophy) Pseudo Cushings Metabolic Syndrome and Dyslipidaemia
nutrition issues with alcohol
Low calcium (diet, decreased vitamin D) Low phosphate (diet, increased PTH) Low Mg, K (diet, urinary loss, hyperaldosteronism)
Typical Liver Function alcohol effects
Gamma Glutamyl Transferase (GGT) increased by enzyme
Transaminases (ALT and AST) increased by hepatocellular damage
Globulin increased in cirrhosis
Bilirubin & INR increased and albumin decreased by liver failure
thiamine deficiency via alcohol
Ethanol interferes with GI absorption
Hepatic dysfunction, which hinders storage and activation
Malnourishment
other relevant blood tests for alcohol effects
Macrocytosis – raised MCV in a full blood count
Raised serum ferritin concentration
Hyperuricaemia
Hypertriglyceridaemia
Increased carbohydrate-deficient transferrin or CDT
how does alcohol causes hypertension
impairment of the baroreceptors
increase of sympathetic activity
stimulation of RAAS
increase in plasma cortisol
increase of intracellular calcium with subsequent increase in vascular reactivity
endothelial e.g. inhibition of endothelium-dependent NO production
effect of thiamine deficiency
cofactor in glycolysis and TCA
also in PPP
what is the structure of the liver
hepatic lobules with portal triads
(portal vein, hepatic arteriole and bile duct) central vein, sinusoids flow mixed blood from triad giving hepatocytes time to interact with blood as it flows to central vein
flows via zones 1, 2, 3 (o2 dec, met activity inc)
most vulnerable to injury
why is the liver biopsied
To make a diagnosis
Stage / grade the disease
To monitor treatment
To inform prognosis
percutaneous or venous approach
what does a liver biopsy find
Microvesicular fatty change Extend of fibrosis Amount of MD bodies Intrahepatic cholestasis
what are alcoholic liver diseases
Steatosis (fatty liver) macrovesicular microvesicular
Steatohepatitis ballooning of hepatocytes inflammation via neutrophils necrosis of hepatocytes Mallory Denk bodies
Fibrosis / cirrhosis
steatosis - macrovesicular
single large fat droplets to osmicated fat (black droplets in varying size)
fat not seen under microscope, stained specially
Steatosis - microvesicular
hepatocytes distended by large number of fat droplets surrounding central nuclei, also can have enlarged mt
Steatohepatitis - ballooning
lack of cytoplasmic keratins (bigger and cytoplasm fragments in early stage of necrosis), plus clumped aggregates
Steatohepatitis- inflammation
neutrophils (small purple dots surrounding hepatocytes)
heal by fibrosis and scarring
Steatohepatitis - Mallory denk bd
dead hepatocytes clump together
Fibrosis / cirrhosis
permanent long term and irreversible
little oxygen, lots of metabolism, red collagen fibres
Fibrosis / cirrhosis mechanisms
inflammation and necrosis cause increase in cytokines and growth factors (TGF-beta, MCP-1) that activate fibroblasts/myofibroblasts to deposit collagen (Disse’s space)
centrilobular fibrosis - reversible
septal fibrosis - increasingly irreversible
what is the end result of fibrosis
Macronodular cirrhosis/portal hypertension
nodules surrounded by thick fibrosis to inc PV pressure
can also lead to fibrosis
portal hypertension consequences
impaired intestinal function and malabsorption
splenomegaly with anaemia and thrombocytopenia
portal bypass circulations - haemorrhoids, caput medusae (paraumbilical veins engorged), oesophageal veins (varices)
vasodilatation and compensatory inc in CO toxic metabolites (NH3, fatty acids, biogenic amines) bypass the liver and may cause portosystemic (hepatic) encephalopathy
what are the types of drinking cultures
in “wet” drinking cultures, there is integration of alcohol into daily life as a consumer commodity like any other; in dry drinking cultures, alcohol is marginalized as an especially powerful and hazardous commodity
why do people drink
People drink alcohol for various reasons e.g., Drinking Motives Questionnaire measures enhancement social conformity coping
why do people not drink
short term - poisoning, accidents/injury, violence, antisocial behaviour
long term - cirrhosis, cancers, stroke, premature death + suicide
also hangovers, ALDH-2 deficiency, religion and culture
ca it be changed how people drink
efforts focus on motives for drinking and not drinking
gain framed or loss framed
eg IMB or psychosocial (need social context and factors eg health, fitting in, reputation and image)
how does awareness effect drinking
people tend to have poor knowledge and lack the requisite skills to stop
so personalised feedback on drink pouring
- improves knowledge
- enhances behavioural skills
- reduces alcohol intake
using unit-marked glasses affects IMB components
cluster-randomised-controlled trial
and follow-up survey
greater use of glasses resulted in
- better knowledge of guidelines
- better capacity to monitor intake
- better attitudes toward using guidelines
… but no significant reductions in intake
population interventions: Dry January
Abstinence challenges allow people to - perform behavioural experiments - boost motivation - enhance behavioural skills Benefits of not drinking majority report better sleep, concentration, saving money + a minority report weight loss Enduring effects 40% drink less 6 months later (50% return to previous drinking) and greater sense of control over drinking
Alcohol withdrawal
Physiological dependence
The ‘need’ to drink to avoid unpleasant symptoms - ‘Relief Drinking’
Delirium Tremens
Symptoms of withdrawal
Tremor/shaking Sweating Tachycardia Nausea Agitation Seizures Visual hallucinations
types of alcohol withdrawal
Planned:
in community or in hospital/detox facility
Unplanned:
known alcohol problems + another
medical problem or alcohol history not known in patient presenting with a separate problem
what should be considered about alcohol withdrawal
Importance of alcohol history in all inpatients
High index of suspicion
Often occurs 2-3 days after admission
Look for corroborative evidence
how is alcohol withdrawal managed
diazepam
chlordiazepoxide (RSCH and PRH)
Alcohol Withdrawal Potential Hazards
Severe liver disease - precipitation of hepatic encephalopathy
Respiratory depression
Reluctance to prescribe more
Concomitant alcohol consumption
What is delirium
Disturbance of consciousness
Change in cognition or a perceptual disturbance (hallucination)
Tendency to fluctuate
Behaviour overactive or underactive
Other features: disorganized thinking, poor memory, delusions and mood lability
Other Causes of Delirium
Any infection Drug side effect Hypoxia Drug overdose Alcohol intoxication Wernicke encephalopathy Hypoglycaemia Meningitis / encephalitis Psychiatric illness Head injury Constipation (elderly) Hepatic encephalopathy Etc…etc….
what is WKS
WERNICKE-KORSAKOFF SYNDROME Wernicke’s Encephalopathy Korsakoff’s Psychosis THIAMINE treated with oral or IV thiamine (check glucose first)
Dietary sources of thiamine
Wheat Yeast Nuts Oatmeal Potatoes Pork Marmite intake 1mg, body stores 30mg deficiency after a month of none
use of thiamine
Co-enzyme: Glucose and lipid metabolism Production of amino acids Production of glucose derived neurotransmitters
THIAMINE: causes of deficiency
Alcoholism commonest cause
(inadequate intake, inhibition of active intestinal absorption by alcohol and malnutrition)
Chronic vomiting e.g. hyperemesis gravidarum
Famine
signs of wernicke’s encephalopathy
Confusion
Eye Signs - opthalmoplegia and nystagmus
Ataxia
10% cases, under diagnosed
results from wernicke’s encephalopathy
Brain damage:
Multiple small haemorrhages especially in upper brainstem, hypothalamus and thalamus, mamillary bodies
20% mortality if untreated
what is Korsakoff’s Psychosis
Permanent brain damage
Severe short term memory loss
Confabulation
