Hepato-biliary: Alcoholism Flashcards
How does alcohol act as a drug?
https://www.youtube.com/watch?v=e5DxD6Tuxxw
- Non-specific effects on neuronal cell wall fluidity and permeability
- Enhancement of GABA-A transmission - anxiolytic effect
- Release of dopamine in mesolimbic system - euphoriant and reward effects
- Inhibition of NMDA-mediated glutaminergic transmission - amnesic effects
What is the physiology behind the anxiolytic effects of alcohol?
Enhancement of GABA-A Transmission
What is the physiology behind the euphoriant and rewarding effects of alcohol?
Dopamine release in the mesolimbic system
What is the physiology behind the amnesic effects of alcohol?
Inhibition of NMDA-mediated glutaminergic transmission
What are the steps in the pathway of alcohol breakdown?
Ethyl-alcohol -> alcohol dehydrogenase -> acetaldehyde -> acetaldehyde dehydrogenase -> Acetate
Where is alcohol absorbed in the GI tract?
- Mouth
- Stomach
- Small intestine
What are the acute effects alcohol in low doses?
- Elevated mood/Reduced anxiety
- Sociability
- Impaired judgment
- Disinhibition
What are the acute effects of alcohol intoxication?
- Impaired attention and judgement
- Unsteadiness
- Flushing
- Nystagmus
- Mood lability
- Slurring
- Dilated pupils
- Stupor
Where is alcohol mostly oxidised in the body?
Liver
What are the three pathways for alcohol metabolism?
- Alcohol dehydrogenase pathway
- Microsomal ethanol oxidizing system (MEOS)
- Catalase pathway - located in peroxisomes
When are peak blood ethanol concentrations achieved?
1 hour after ingestion
What factors influence the levels of alcohol attained in the blood after ingestion?
- Speed of intake
- Food cunsumed
- Rate of gastric emptying
- Body habitus
Why do women obtain higher blood ethanol concentrations than men after drinking the same amount of alcohol?
Primarily because their body water, and hence the compartment in which the ethanol distributes, is significantly smaller than in men. There may also be differences in gastric ADH activity between genders
What is the hourly rate of ethanol elimination from the body?
7-10g per hour
What is the rate limiting factor for ethanol metabolism?
Dissociation of NADH-NAD enzyme complex - ADH mediated oxidation of ethanol results in transfer of hydrogen to the co-factor NAD converting it to NADH. The rate at which the liver re-oxidizes NADH to NAD is the limiting factor
In chronic alcohol misuse, why does the metabolic rate of ehtnaol increase?
Increased action of MEOS system
What problems can occur if the redox hoemeostatic capacity of the liver is exceeded (i.e. capacity of liver to convert NADH to NAD)
- Hypo/hyperglycaemia
- Lactic acidosis
- Ketoacidosis
- Hyperuricaemia
- Abnormal lipid metabolism
What range of blood alcohol concentration would produce definite impairment of cognitive function?
150-250 mg/100ml
What factors will influence the blood alcohol concentration required to produce intoxication?
- Rate of increase in blood levels
- Degree of tolerance
- Simultaneous effects of other drugs
What are the affects of severe alcohol intoxication?
- Drowsiness
- Coma
- Hypotension
- Hypothermia
- Decreased respiratory effort - shallow and sterterous
How can death occur in alcohol acute alcohol intoxication?
- Respiratory depression
- Vomit aspiration
What is the recommend alcohol intake for males and females?
14 units per week
What blood alcohol is often regarded as being a fatal level?
>450 mg/100ml
How many grams of alcohol are in 1 unit?
8g
What volume of 3-4% beer contains 1 unit of alcohol?
284 ml - 1/2 pint
What volume of average strength table wine would contain 1 unit of alcohol?
125ml - a single small glass
What volume of spirit would contain 1 unit of alcohol?
25 ml - single measure
What is the defintion of alcohol dependence?
Harmful use + established dependence syndrome:
-
DEPENDENCE SYNDROME
- Cravings
- Difficulty controlling use
- Primacy
- Increased tolerance
- Psychological withdrawal on reduction of intake
- Persitence despite harmful consequences
What is regarded as harmful use of alcohol?
Non-dependent pattern of use causing damage to physical or mental health for > 1 month, or repeatedly over 12 months
In men, how many units per week would be classed as harmful?
50 units
In women, how many units per week is regarded as drinking harmfully?
35 units per week
What percentage of harmful drinkers will develop liver cirrhosis?
20%
What are acute physical complications can occur due to alcohol intoxication?
- Accident/injury
- Acute alcohol poisoning
- Aspiration pneumonia
- Oesophagitis
- Mallory-Weiss tear
- Gastritis
- Pancreatitis
- Cariac Arrhythmias
- CVA
- Neupraxia
- Myopathy/Rhabdomyolysis
- Hypoglycaemia/hypokalaemia
- Respiratory depression
What systems are most commonly affected through chronic alcohol misuse?
- Hepatic/Gastrointestinal
- Malignancy
- Cardiovascular
- Respiratory
- Neurological
- GU
- Musculoskeletal
Summarise signs on exam of alcohol missuse
-
Malnutrition
- Thin arms and legs, swollen abdo
- Red tongue - iron defficiency anaemia
- Dry skin
-
Endocrine
- Gynaecomastia
- Testicular atrophy
- Loss of body hair
- “Pseudo cushings”
-
Face/skin
- Easy bruising
- Spider naevi
- Deupretruens contracture
-
Neuromuscular
- Tremor
- Memory loss
- Peropheral myopathy
- Epilepsy
What is this, and what might it indicate?
Spider naevi - chronic alcohol misuse
What percentage of alcohol misusers develop pancreatitis?
15%
What are the cutaneous/superficial signs suggestive of chronic alcohol misuse?
- Spider naevi
- Telangiectasia
- Facial mooning
- Parotid enlargement
- Palmar erythema
- Dupuytren’s contracture
- Gynaecomastia
- Loss of axillary/pubic hair
- Ascites
What is this, and what can it indicate?
Telangiectasia - chronic alcohol misusue
What is this, and what could cause it?
Sialadenosis (Parotid hypertrophy) - palpable as a soft, bilateral, symmetrical and non-tender enlargement of the parotid glands. Thought to be caused by cellular hypertrophy and disturbed fat metabolism
Found in chronic alcohol misuse
What is the following, and what might it indicate?
Palmar erythema - chronic alcohol misuse - specifically alcohol related liver disease
What is the following, and what is it associated with?
Dupuytren’s contracture - chronic alcohol misuse
What is this, and what does it indicate?
Gynaecomastia - chronic liver disease
What is the distribution of spider naevi?
Only in the distribution of the superior vena cava - most commonly face and anterior chest wall
How do spider naevi occur?
Failure of the sphincteric muscle surrounding a cutaneous arteriole. The central red dot is the dilated arteriole and the red “spider legs” are small veins carrying away the freely flowing blood.
What is telangiectasia?
Broken veins - commonly occur on the face
Why does gynaecomastia occur in cirrhotic liver disease?
Increased secretion of androgenic hormones from the adrenal gland, which is converted to oestrogen. Levels of free testosterone also decrease
What is the mechanism behind the development of palmar erythema in liver disease?
Increased perfusion to the hands, mainly caused by increased oestrogen levels, increased oestrogen-to-testosterone ratios or raised circulating free oestrogens. Oestrogen is thought to increase capillary density in the palms, similar to its effects on the endometrium.
Other factors that may play a role include:
- disordered hepatic metabolism of bradykinin and other vasoactive substances
- abnormal cutaneous vasoconstrictor/vasodilator reflexes.
How can Mallory-Weiss tears occur from alcohol consumption?
Violent vomiting which causes a tear in the cardio-oesophageal junction, with often profuse GI bleeding as a result
How can alcohol cause GORD, and what are the outcomes of the development of GORD?
Alcohol reduces sphincter pressue at both ends of the oesophagus and impedes persitalsis. In chronic misusers -> GORD develops
This leads to oesophagitis, distal oesophageal ulceration and Barrett’s oesophagus