Alcohol Flashcards
What is alcohol?
A drug
Also Organic liquids with hydroxyl group OH
What are the first 4 compounds of the alcohol class?
methanol, ethanol, propanol, butanol
What is Methanol used for?
Anti-freeze, solvents and some fuels
What effect does methanol have on the body?
TOXIC! Metabolised to formaldehyde and then formic acid - acidosis is toxic = blindness
How would you treat Methanol Toxicity?
Alcohol +/- dialysis (ethanol competitively inhibits alcohol dehydrogenase)
What is the recommended intake of alcohol (ethanol)?
14 units a week Same for both men and women Spread over at least 3 days No more than 6 units consumed in a single sitting Several rest days
Where is alcohol absorbed?
Mainly in small bowel (limited absorption in the stomach)
Where and how is alcohol initially metabolised?
alcohol dehydrogenase in stomach – only limited
What effect does a full stomach have on alcohol metabolism?
Slows gastric emptying, therefore alcohol is in the stomach longer and is more metabolized before entering small bowel
Also increases portal blood flow increasing metabolism
More metabolised in stomach prevents saturation of enzymes in liver
Which medications cause an increase in absorption of alcohol?
Antihistamines and metaclopramide etc as they increase gastric emptying
Does champagne go to your head quicker and why?
Aerated drinks are absorbed faster
What effect does drinking spirits have?
Absorption actually slower at high level and spirits irritate gastric mucosa and delay emptying
What conditions allow for quickest absorption?
concentrations of 20-30% (not too high) on an empty stomach.
- drinking sherry
Why do women have a lower tolerance for alcohol?
Alcohol is water soluble
Females have a higher subcut fat percentage. Males have more lean mass and a higher blood volume even for the same weight
Males have a bigger pool for dilution
Also – women in general have a lower level of alcohol dehydrogenase
What is the pathway for the metabolism of alcohol?
Alcohol - (alcohol dehydrogenase) - acetaldehyde - (aldehyde dehydrogenase) - acetate + CO2 + H2O
Where does the majority of the metabolism occur?
90% occurs in liver
Small volume in pancreas and brain!
Where does the excretion of alcohol occur?
All routes
5% breath
At what rate is alcohol removed from the blood?
15mg/100ml/hour. Roughly one unit an hour.
Which ethnic groups can’t handle alcohol as well, and why?
Aborigines, inuits, eskimos, Japanese
Because they lack alcohol dehydrogenase
Why do south east asians often get flushing when drinking alcohol?
Deficient or ineffective variant of aldehyde dehydrogenase
Acetaldehyde is unpleasant and toxic.
Does drinking regularly increase your tolerance?
It is possible to up regulate alcohol dehydrogenase activity
In heavy drinking analagous and alternative pathways activated including MEOS – microsomal enzyme oxidase system, Catalase and Induction of CP450
What consequences does activation of the MEOS pathway have?
Production of hydrogen ions (REDOX) which must be disposed of by
- Inhibition of hepatic gluconeogensis - munchies and hypoglycaemia
- Citric acid cycle (Krebs) inhibition = prodution of lactic acid
- Fatty acid oxidaition impairment - excess ketogenesis and lipid syntehsis = FAT
What is alcoholic ketoacidosis?
Associated with malnourished state. Excess NADH, impaired fatty acid metabolsim (increased substrate available), fasting state
In contrast to diabetic ketoacidosis – low or normal glucose with high ketones (usually beta-hydroxybutyrate). Can result in death
What effects does Alcohol have on the CNS?
CNS depressor as it increases levels of GABBA which is a neurotransmitter inhibitor
What effect does alcohol have on areas of the brain?
Cortex – disinhibtion, talkativeness, anxiolytic
Limbic system – memory loss, confusion, disorientation
Cerebellum – Loss of muscular coordination and slurred speech
Reticular formation (upper brain stem) – consciousness
Lower brain stem – control of breathing and blood pressure
Why does alcohol make you pee more?
Volume of fluid drank
Inhibits ADH - reduces water reabsorption and clearer urine
What effect does alcohol have on the heart?
Heavy heart beat - Alcohol is a negative inotrope so our hearts beat faster to maintain the same cardiac output
Why does alcohol cause a headache during hangover?
Contains certain substances - congeners and serotonin
What biochemical investigations would you do to test if someone was a chronic drinker?
Gamma GT (ethanol induces gamma GT when entering cycle)
MCV
Triglycerides (indicates alcohol excess - caused by increased synthesis in the liver)
What would you test in a comatose patient to exclude alcohol as a cause?
Glucose - diabetes?
Serum Osmolality - (normal 275-295)
If normal can calculate osmolal gap - if bigger than normal indicates something in blood
What investigations would you do in a patient with known alcohol related health disease presenting with abdominal pain?
LFTs
Amylase - would indicate pancreatitis as a cause
What differentials would you have for someone with known alcohol related health disease, presenting with abdominal pain?
Peptic ulceration +/- perforation, pancreatitis, alcoholic hepatitis, ascites +/- peritonitis
What makes up the liver function test?
ALT (alanine aminotransferase) Bilirubin “Alk phos” (alkaline phosphatase) Albumin GGT (“gamma GT” or glutamyl transpeptidase) PTR (prothrombin ratio)
What is ALT and what does it indicate?
Found especially in liver
Present in hepatocytes and released when they release their contents
Marker of liver damage rather than function
What is ALP and what does it indicate?
Found in liver, bone, small intestine, kidneys, placenta
Liver – especially bile canaliculi
Bone – osteoblasts
Kidneys – proximal tubules
Small intestine – epithelium
What is Gamma GT and what does it indicate?
Found in liver (also kidneys, pancreas, prostate)
Cell membranes of bile ducts, GB etc
Sensitive – too sensitive!
Most labs no longer offer as first-line LFT
Can reflect enzyme induction (see next slide)
What is albumin and what does it indicate?
Synthesised in liver
Half-life is ~3 weeks
Albumin falls in the systemic inflammatory response – capillary permeability associated with inflammation causes redistribution
So not terribly useful as a marker of current liver synthetic function
What is prothrombin ratio and what does it indicate?
Clotting factors synthesised in liver
Half-life 3-4 days
Much better indicator of current liver synthetic function
Also, crucially – gives indication of patient’s bleeding tendency
What is bilirubin and what does it indicate?
result of the breakdown of haemoglobin - comes in unconjugated and conjugated forms
Raised causes jaundice
What biochemical markers would you test in a patient presenting with vomiting?
U&E
LFT
Amylase
ABG
What biochemical markers would you test in a patient presenting with haematemesis?
U&E
LFT
PTR
Lactate
What is the cut of phenomenon?
intoxicating effect of alcohol icnreases exponentially as number of carbons increases from 1 to 5, reaches a maximum at 6 to 8, then decreases after this
What is the relationship between lipid solubility and intoxicating potency of alcohols?
Correlate - i.e. intoxicating potency increases as lipid solubility increases
What are the structure of Cys-loop receptors?
Extracellular domain – binding site for neurotransmitter and competitive antagonists
Transmembrane domain – forms the central ion channel and is also the binding site for allosteric regulators, including ethanol and general anaesthetics
Intracellular domain – interacts with the cytoskeleton and harbours sites for channel regulation by phosphorylation
Which 3 receptors are the leading LGIC candidates?
Glutamate receptors of the NMDA subtype
GABAA receptors
Strychnine-sensitive glycine receptors
How is alcohol made?
Fermentation and potentially also distillation
How many kcals does 1g of alcohol contain?
7kcals
How would you reduce calories when drinking alcohol?
Have a non-alcoholic drink spaced inbetween alcoholic drinks, select light options, always have food in stomach, drink water, make drinks last longer
How can alcohol increase risk of deficiencies?
Alters food intake and appetite
Decreases secretion of pancreatic enzyme and bile
Damages cells lining stomach and intestines preventing transport of some nutrients
ethanol metabolism relies on some micronutrients (thiamine)
Decreased liver stores of vitamins (vit A) and increased fat excretion
What links are there between alcohol dependence and nutritional status?
Alcoholism increases levels of ghrelin decreasing appetite
Alcohol hepatitis can cause loss of appetite
Muscle wasting and weight loss common in alcoholic liver disease
Nutritional deficiencies common
What biological processes is Thiamine important?
ATP production
Normal nerve conduction
Maintenance of neural membranes
Why are levels of Thiamine reduced in chronic alcohol disease?
Poor intake Decreased conversion to coenzyme Reduced storage in fatty liver Inhibited intestinal absorption Increased metabolic demand - use of thiamine for ethanol metabolism
What are the clinical features of thiamine deficiency?
Dry beriberi - Nervous system – polyneuropathy, weakness,
numbness, paralysis, usually lower limbs
Wet Beriberi - • CV system – increased HR, SOB, high output cardiac
failure
Wernicke Korsakoff Syndrome
What are the features of Wernicke Korsakoff Syndrome?
Wernickes encephalopathy - reversible if identified
early = Neurological disease: confusion, inability to
coordinate voluntary movement (ataxia), and eye
(ocular) abnormalities.
Korsakoff - mostly irreversible = Mental disorder: Retrograde (then anterograde)
amnesia, confabulation
Other than thiamine, what other nutritional deficiencies does alcohol cause?
Water soluble Vits (B+C)
Fat soluble Vits (A, D, E, K)
Minerals e.g. calcium, zinc and selenium
Link between alcohol consumption and CVD
Heavy drinking = highest risk of CVD
Light drinking = lowers risk of CVD
Which cancers does alcohol cause an increased risk of?
BREAST, bowel, liver, mouth/throat, oesophageal and stomach
Why which mechanisms does alcohol increase risk of cancer?
Carcinogenic breakdown
products - e.g. acetaldehyde
Solvent - Makes it easier for
carcinogens to enter cells
Combined effect with
oestrogen - Increase the risk of breast cancer
Nutritional deficiencies - Found in heavy consumers.
Makes tissue susceptible to carcinogenesis.
Alcohol and blood glucose
Alcohol interferes with all 3
+ insulin and glucagon
+ hypoglycaemic medications
What are the guidelines of drinking when pregnant?
DO NOT DRINK when pregnant or when trying to pregnant
What risks to the foetus does alcohol have?
First trimester - risk of miscarriage and premature birth
Above 1-2 units - increased risk of low birth weight, pre term birth
Foetal alcohol syndrome
Foetal alcohol spectrum disorders
What effect does alcohol have when breastfeeding?
Alcohol in bloodstream = alcohol in milk
<1-2 units once or twice a week recommended
What is alcohol dependence?
Also known as “alcoholism”
Uncontrolled drinking with compulsion
Disruptive
Tolerance/withdrawal
What is the crime, social and economic harm of alcohol?
1,434 alcohol-related crimes in 2013/14
Alcohol a factor in 58% of serious assaults
1 in 2 people report having experienced harm from someone else’s drinking
39 (25.5%) child protection registrations due to parental alcohol misuse
Estimated cost to Dundee City £71 million
What is the association between alcohol availability and consumption?
The extent to which alcohol is available is strongly associated with alcohol consumption and, in turn, alcohol-related harm
What are the onset and symptoms of mild alcohol withdrawal?
(12-36hrs from last drink)– fine tremor, sweating, anxiety, hyperactivity, ^HR, ^BP, fever, anorexia, nausea, retching
What are the onset and symptoms of moderate alcohol withdrawal?
(12hrs to 5 days) – coarse tremor, shaking agitation, confusion, disorient ation, paranoia, seizures (especially 24-48hrs), hallucinations
What are the onset and symptoms of severe alcohol withdrawal?
(12 hrs – 7+ days) – more severe and prolonged, risk of DTs around 48 hrs – severe agitation, anxiety, confusion, delusions, hallucinations (tactile visual – crawling beesties). Circulatory collapse and death can occur
What is the management of withdrawal?
Diazepam and symptom trigger withdrawal management
With alcohol consumption, what effect does it have on the brain and NS?
Sedative, mild anaesthetic
Activates pleasure / reward centres (dopamine, serotonin release)
Sense of well being, disinhibition, euphoria
With alcohol intoxication, what effect does it have on the brain and NS?
Increased risk of accidental injury Garrulous, elated, aggressive behaviours Drowsiness Slurred speech, unsteadiness Loss of consciousness
In what ways can alcohol cause seizures?
Through alcohol withdrawal and by precipating seizures in susceptible individuals (epilepsy)
What is peripheral neuropathy?
damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain.
What is compression neuropathy?
temporary damage to myelin sheath - ‘Saturday night palsy’
radial nerve compression at humeral head
What are the symptoms of Wernickes Encephalopathy?
Ocular dysfunction (nystagmus -> complete opthalmoparesis)
Ataxic gait
Acute confusion
(caused by Thiamine deficiency and cytotoxic oedema in Mamillary bodies)
What are the symptoms of Korsakoff syndrome?
Profound anterograde amnesia (unable to retain new information)
Variable retrograde amnesia – episodic memory (lose big chunks)
Confabulation – replaces memory with information able to retain at that time – believes it to be true
(caused by cerebral atrophy resulting from WE)
Other than CVD risk, how else does alcohol effect the heart?
Cardiomyopathy
Arrhythmias - (acute = AF, SVT) (chronic = long QT)
What is the progession of alcohol related cirrhosis?
Progressive fibrosis -> architectural distortion -> cirrhosis +/- portal hypertension
How would you treat alcohol related cirrhosis?
Abstinence Vitamins support (long term thiamine) Nutrition Endoscopic Pharmacological – Bblockers, lactulose, Rifaximin Radiological – TIPPS Surgical – Transplant (strict criteria)
Name some pharmacological interventions for alcohol consumption?
Acamprosate – reduces cravings
Naltrexone – reduces desire for alcohol
Disulfiram – aversion therapy drug
Nalmefene – opiod anatagonist
The drink driving limit is
50mg/100ml blood
What is palmar erythema?
A clinical sign is seen as redness of the palms. The cause is unclear but is usually related to underlying liver cirrhosis. Increased oestrogen levels are thought to cause changes in the small anastomoses in the hand increasing vascularity.
What is Dupuytren’s Contracture?
benign fibrosis of the flexor tendons of the fingers
What is Caput Medusae?
prominent veins around the umbilicus
- occurs secondary to portal hypertension (blood that normally goes to liver is redirected to blood vessels)
How does alcohol cause a subdural haematoma?
Due to Wernicke-Korsakoff syndrome, patient could fall and hit head
What effect can alcohol have on the lungs?
Aspiration pneumonia due to vomiting. Effects superior aspect of right lower lobe
Why does aspiration pneumonia effect the right lung?
Right bronchus is more vertically orientated therefore vomit more likely to go down that side
What is the disease process of acute fatty liver disease?
Acute fatty liver 24-48
Alcohol ingestion has varied effects on fatty metabolism that all lead to accumulation of intracellular fat with or without inflammation.
Increased peripheral free fatty acid production delivered to liver
NAD is converted by alcohol to NADH which stimulates lipid synthesis
Mitochondrial oxidation of fatty acids is reduced by alcohol
There is decreased transport of fat out of hepatocytes due to intracellular tubulin impairment
What is alcoholic steatohepatitis?
This can present with fever, liver tenderness and jaundice. Acute hepatitis is caused by direct toxicity of alcohol. At a microscopic level, acute inflammatory cells are seen within the liver and areas of hepatocyte ballooning can be seen. There is a profound cellular steatosis and Mallory’s hyaline (a dense pink inclusion in the cell cytoplasm) is often seen. Previously this was thought to be pathognomonic of alcohol toxicity but is now known to be a non-specific reaction.
How does alcohol cause gastritis?
Due to alcohol being an irritant to the gastric mucosa. The gastritis is mixed and non-specific in nature with of acute inflam cells if erosive but more commonly striking epithelial regeneration in keeping with a chemical type or reactive gastritis
What is Mallory-Weissntear and Boerhaave syndrome?
With protracted vomiting comes repeated marked contraction of the mucous smooth muscle and therefore recurrent stresses on the wall. This can result in mucosal tears with catastrophic haemorrhage if large (Mallory-Weiss) or oesophageal rupture (Boerhaave syndrome). Small tears often result in a little fresh haemorrhage which is in turn vomited. Notably, this consists of fresh blood and follows prolonged “normal” vomitus.
How does alcohol cause Reflux oesophagitis and Barretts Mucosa?
Alcohol is a smooth muscle relaxant - leads to reflux - over time causes the squamous epithelium to become columnar
How does alcohol cause oesophageal varices?
Portal hypertension leads to blood following oesphageal veins, leading to swelling
What effects can alcohol have on the pancreas?
Alcohol is toxic to pancreatic acinar cells or ductal epithelial cells, causing release of amylase
Acute - inflam changes due to ingestion of fat
Chronic - scarring, pseudocysts
