Alcohol Biochemistry; Pharmacology Flashcards
(138 cards)
1
Q
Gamma GT
A
Found in bile canaliculi.
When ethanol is metabolised -p450 enzymes and Gamma GT are induced
Very sensitive
Marker of how much they are drinking
Gamma GT levels can rise due to other causes however
2
Q
Raised MCV
A
Increased percentage of immature red blood cells.
Chronic alcohol excess
3
Q
Raised triglycerides
A
Alcohol excess.
Increased synthesis in liver
Blood looks milky when centrifuged.
4
Q
What tests would you run if the patient is drinking chronically?
A
Gamma GT
MCV
Triglycerides
5
Q
What tests would you run if the patietn is in a COMA?
A
Glucose and serum osmolality
6
Q
What is the glucose test useful/important for?
A
Do not want to miss HYPOGLYCAEMIA
7
Q
Serum osmolality
A
All dissolved solutes contribute to serum osmolality.
Can calculate from concentration of measured electolytes.
e.g. Na, K, Ca, Urea, Glucose
Serum osmolality = 2 x[Na]
8
Q
What is the equation for calculated serum osmolality
A
2 x [Na]
In practice sodium dwarfs everything else
9
Q
What is the reference interval for serum osmolality
A
275-295mmol/kg
10
Q
Sometimes there is a gap between measured (in clinic) and calculated serum osmolality. What is this gap called?
A
OSMOLOL GAP
(most cases due to ethanol)
Clinicians know that theres something else in patient’s blood contributing to osmolality but not measured.
11
Q
What tests would you do for abdominal pain?
A
Amylase (pancreatitis)
LFTs
(Ascetic fluid analysis)
12
Q
ALT (alanine aminotransferase)
A
Found in liver
Present in hepatocytes
Marker of liver DAMAGE.
13
Q
Alk phos (alkaline phosphatase)
A
> Rise comes from liver (bile canaliculi)/bone (osteoblasts)
Check GAMMA GT
Kidney - proximal tubules
Think BONES if only this is elevated and other LFTs are normal.
14
Q
Why is albumin not a good marker for current synthesis?
A
Half life is 3 weeks.
Systemic inflammatory response
15
Q
Prothrombin ratio
A
Clotting factos synthesised in liver
Half life of 3-4 days
Better indicator of liver function.
16
Q
What kind of bilirubin does an obstruction lead to
A
Conjugated hyperbilirubinaemia
17
Q
Tests for Vomiting?
A
U&Es, LFTs, Amylase, ABG
Acute gastritis
Oesophageal stricture
Pyloric stenosis
18
Q
When vomiting, acidosis or alkalosis?
A
Metabolic alkalosis
Losing acid from stomach when vomiting
Very low chloride
For every hydrogen ion you lose – you gain a bicarbonate
Raised bicarbonate = metabolic alkalosis
Hence ABGs are used.
19
Q
What may occur in pyloric stenosis if the patient is vomiting?
A
Only losing fluid from stomach (due to stenosis of pyloric - little fluid lost from duodenum (bicarb))
Losing more acid
Metabolic alkalosis
20
Q
What tests would you run for Haematemesis
A
U&Es, LFT, PTR, Lactate
21
Q
GI bleed. What happens to the red blood cells?
A
They are absorbed and then go into portal circulation
Urea produced (protein in RBCs)
22
Q
What is secreted when losing blood volume?
A
Secretion of aldosterone
Retains sodium and water
Also secrete ADH
- reabsorption of water
- pee out less
- concentrated urine
23
Q
Methanol and ethylene glycol are both…
A
toxic alcohols
24
Q
Why are methanol and ethylene glycol toxic?
A
Very acidic metabolites
25
What is ethylene glycol present in?
Antifreeze
26
Methanol toxicity
--> Formaldehyde --> formic acid
Acidosis is toxic.
Blindness
27
Alcohol is initially metabolised by
Alcohol dehydrogenase in the stomach.
28
Does eating before you drink slow down absorption?
Yes.
the longer the food is in the stomach, the longer it is metabolised before getting to the small bowel.
Full stomach slows gastric emptying.
29
Which drugs increase gastric emptying rate and increase absorption?
Antihistamines
Metoclopramide
Absorb alcohol much faster.
30
The higher the concentration of alcohol, the...
slower is it absorbed
Spirits irritate gastric mucosa and delay emptying
Aerated drinks are absorbed faster
31
Women become intoxicated more quickly than men, why? (generally)
Lower levels of alcohol dehydrogenase
Higher subcutaneous fat percentage
32
Metabolism of ethanol
Ethanol (alcohol dehydrogenase) --> acetaldehyde (aldehyde dehydrogenase) --> acetate + CO2 + H2O
90% occurs in liver
Small volume in pancreas and brain
33
How fast is alcohol removed from blood?
15mg/100ml/hour
1 unit an hour roughly
34
When does alcohol concentration peak?
60 mins after consumption and the decreases linearly.
35
Aborigines, Inuits, Japanese have low levels of
alcohol dehydrogenase
36
Flushing & feeling sick
Aldehyde responsible.
Often south east asians
Deficient or ineffective varian of aldehyde dehydrogenase
Antabuse mimics this
37
What happens when you drink a lot?
Increased tolerance
Possible to up regulate alcohol dehydrogenase
Heavy drinkers - analogous and alternative pathways are activated
Induction of CP450
38
MEOS pathway induction
Heavy drinkers
Production of hydrogen ions (REDOX).
Disposed of by:
1. Inhibition of hepatic gluconeogenesis
2. Citric acid cycle
3. Fatty acid oxidation impairment
Higher resting energy expenditure
39
Effects of alcohol (general)
Cortex - disinhibition, talkativeness, anxiolytic
Limbic system - memory loss, confusion, disorientation
Cerebellum - loss of muscular coordination, slurred speech
Reticular formation (upper brainstem) - consciousness
Lower brain stem - control of breathing and blood pressure
40
Effects of alcohol by concentration
< 100 - excitement, fun, disinhibited, still in some control
100-200 - slurring of speech.blurred vision, falls, wide emotions
>200 - stupor. difficult to rouse. loud SNORING
Dangerous if brain stem is inhibited - decreased consciousness and breathing.
41
at what age are you legally allowed to drink alcohol at home?
5 years old.
42
Where does ADH take effect?
Distal tubules
Promotes water reabsorption.
Concentrates urine
43
Effect of alcohol on ADH?
Inhibits ADH
Reduced water reabsorption and clearer urine
DEHYDRATION.
44
Alcohol effect on heart (acute)
Negative inotrope
45
Holiday heart syndrome
Associated with binge drinking
Most commonly an SVT
Spontaneous resolution
46
Hangover
Congeners (substances other than alcohol in the drink)
Serotonin - produced from sulphites, tannins, phenols
Dehydration
Acetic acid
47
Heart burn due to alcohol
Muscle relaxant
Smooth muscle in sphincter relaxes --> reflux/ heart burn
48
Snoring after alcohol consumpton
Relaxation of smooth muscle in pharynx/oropharynx
49
Grey turner's sign
Bruised flanks
sign of pancreatitis
50
Cullen's sign
"Bruised umbilicus"
sign of pancreatitis
51
Ethanol is what type of alcohol
Aliphatic
52
How many hydrogen bond acceptors/donors does ethanol have?
1 of each
53
Does ethanol have stereoisomers?
No
54
What is the strongest bond in ethanol?
hydrogen bond
55
Ethanol's partition coefficient in octane/water?
-0.08
Very close to zero
i.e. miscible in BOTH water and organic solvents
56
The intoxicating effect of n-alcohols increases exponentially as...
the number of carbon atoms within the molecule increases from 1 (methanol) to 5 (pentanol)
Reaches a maximum at 6 (hexane) to 8 (octane) and above this decreases.
57
When does the intoxicating effect of n-alcohols reach a max?
6-8 carbon atoms (hexane-octanol) then decreases.
58
Lipid solubility and membrane disordering effect of n alcohols. Is there a "cut off"?
Lipid solubility and membrane disordering increases exponentially
59
What is GABA
Gamma Aminobutyric acid
60
Potentiation of Inhibitory Neurotransmission is mediated by?
GABA, or glycine
61
Inhibition of Excitatory neurotransmission is mediated by?
Glutamate
62
Enhancement of inhibition and suppression of excitation is anticipated to cause..
CNS depression
Major action of ethanol
63
What structure mediates FAST excitatory and inhibitory neurotransmission in the CNS?
Ligand-Gated Ion channels.
64
Cys-Loop LGICs general structure
Pentamer of subunits
Each subunit has 3 functional modules
i) Extracellular domain//
-- binding site for neurotransmitter and competitive antagonists
ii) transmembrane domain
-- forms the central ion channel and is also the binding site for allosteric regulators, including ethanol and general anaesthetics
iii) intracellular domain
-- interacts with the cytoskeleton and harbours sites for channel regulation by phosphorylation
65
GLIC
proton activated bacterial homologue of Cys loop receptors
66
Drink drive limit in Scotland?
50mg EtOH per 100mL of blood
= 10.9mM
"0.05g per 100ml"
67
Effect of ethanol on Glutamate receptors of the NMDA
Ethanol inhibits their function.
68
Effect of ethanol on GABAa receptors
Ethanol enhances function.
69
Effect of alcohol on Strychnine-sensitive glycine receptors
Ethanol enhances their function
70
Alcohol dependence syndrome
3 or more of?
- Strong desire or compulsion to take alcohol
- Difficulties in controlling use
- Persistent use despite clear evidence of harm
- Preoccupation with substance use
o Where do I get my next drink?
- Increased tolerance
- Psychological withdrawal state
o People keep using the substance to avoid withdrawal symptoms
71
Dependence syndrome - treatment
- Medically Assisted Alcohol Withdrawal (MAAW)
-- Community - chlordiazepoxide/ diazepam
-- Inpatient - Oxazepam
72
Oxazepam is used in patients with
Known liver damage.
73
Complications of alcohol withdrawal
> Minor/major withdrawal (4-12 hours)
> withdrawal seizures (60% of heavy drinking population)
> Delirium tremens (3-10 days)
> Wernicke-Korsakoff syndrome
74
How many days after withdrawal from alcohol do DTs (delirium tremens) arise?
3-10 days
75
Delirium tremens
- signs
- management
> Lillipution hallucination
- objects/people shrunken in size
> Formication
- sensation of insects on skin
---
Management
- inpatient detox
- BENZODIAZEPINE reducing regime
- anticonvulsants, antipsychotics
- Pabrinex
76
Is Wernicke's encephalopathy reversible?
Yes
Korsakoff's is not.
77
Is Korsakoff's syndrome reversible?
NO
urgent treatment
78
Antabuse/Disulfiram
Inhibits acetaldehyde dehydrogenase
Hangover effects experienced as soon as alcohol is consumed.
79
Alcoholic hallucinosis
Chronic drinkers
During or shortly after periods of heavy drinking
- acoustic hallucinations
- delusions
- mood disturbances
can progress to frank (clinically obvious) psychotic illness
80
Wernicke Korsakoff syndrome
Thiamine deficiency
Ocular disturbances (6th nerve spasm, double vision)
Nystagmus (involuntary eye movement)
Ataxia
Mental state changes
Confabulation
Apathy, indifference
81
When does BAC peak?
~30-60 minutes after consumption
82
Does anything help speed up alcohol excretion/metabolism
Nothing except time.
83
1g of alcohol = kcals
7 kcals
84
Beriberi
Dry - nervous system. Weakness, numbness, polyneurpathy , paralysis
Wet - CV system. Increased HR, SOB, high output cardiac failure
85
Korsakoff's syndrome
Mental disorder
Retrograde amnesia
Then anterograde and current memory
86
Most common cancer associated with alcohol?
Breast cancer.
Also bowel, liver, oral/oesophageal and stomach cancer.
Breakdown products of alcohol are carcinogenic
Acetaldehyde is carcinogenic
As alcohol increases, less metabolised on first pass through liver and circulating alcohol then metabolised by ADH (alcohol dehydrogenase) at other sites.
Acetaldehyde unable to be converted to acetate at these sites due to absence of AlDH (aldehyde dehydrogenase)
87
Can alcohol be transferred to breast milk?
Yes.
Could severely affect baby's liver as it has not yet fully developed.
88
Foetal alcohol spectrum
- low interlligence
- abnormal appearance
- low body weight
- behavioural problems
- sight and hearing problems
- severity and nature linked to amount consumed and developmental stage
89
If drinking in first trimester, what are risks?
Miscarriage and high rate of premature birth
Low birth weight
90
Percent of NHS spending on hospitals
12% towards alcohol related illness.
91
Alcohol withdrawal
- Mild
- Moderate
- Severe
Mild (12-36hrs from last drink)– fine tremor, sweating, anxiety, hyperactivity, ^HR, ^BP, fever, anorexia, nausea, retching
Moderate (12hrs to 5 days) – coarse tremor, shaking agitation, confusion, disorient ation, paranoia, seizures (especially 24-48hrs), hallucinations
Severe (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
92
Alcohol withdrawal seizures
Sudden cessation/reduction in alcohol in 12-24 hours
Generalised tonic-clonic
Clustered over few hours
93
Epileptic seizures in alcoholics
Alcohol ingestion precipitates seizures in susceptible individuals
Usually morning AFTER acute intoxication
Any pattern - Tonic-clonic vs focal
94
Alcohol - effect on nerves and muscles
> Peripheral neuropathy - sensorimotor axonal polyneuropathy "glove and stocking"
> Burning, pain, weakness
- direct damage to peripheral nerves from alcohol
- nutritional deficiencies
- Compression neuropathy
95
Compression neuropathy
Temporary damage to myelin sheath - Saturday night palsy
Radial nerve compression at humeral head
96
Wernicke's encephalopathy
Thiamine deficiency and cytotoxic oedema in maxillary bodies
- ocular dysfunction
- ataxic gait
- acute confusion
Urgent recognition needed.
Without treatment it can end in development of Korsakoff's syndrome
97
Korsakoff's syndrome
Cerebral atrophy from WE
- Profound anterograde amnesia
Variable retrograde amnesia - episodic memory
COnfabulation
98
Alcoholic cardiomyopathy
8-9 units/day for 5+ years
Alcohol impairs ventricular function
Prolonged exposure leads to chronic inflammation/ fibrosis of myofibrils
Arrhythmias
AF, SVT - acute
Chronic --> Long QT
Dilated cardiomyopathy
99
Alcohol related steatosis
> Heavy drinkers
> Common presentation - abnormal LFTs
> Hepatocytes swell with triglycerides
> Reverses with cessation
100
Alcohol related hepatitis
> Acute
> Parenchymal inflammation and hepatocyte damage
> Jaundice, coagulopathy, liver failure
> Severe AH has 50% mortality
> Renal failure, bleeding, infections likely
101
Alcohol related Cirrhosis
> Progressive fibrosis -> architectural distortion --> Cirrhosis ± portal hypertension
Compensated
Decompensated
102
Compensated Alcohol related cirrhosis
Normal Liver function
| Normal physical function
103
Decompensated alcohol related cirrhosis
Impaired synthetic function
Ascites
Encephalopathy
104
Portal hyperetnsion
Variceal bleeding
Ascites
SBP - spontaneous bacterial peritonitis (25-40% in hospital mortality)
Hepatic encephalopathy
HEPATOCELLULAR CARCINOMA
Nutritional decline
105
Treatment for alcohol abuse - liver disease
ABSTINENCE
Vitamins
Nutrition
Endoscopic
Pharmacological - beta blockers, lactulose, rifamixin
Radiological - TIPPS
Surgical - transplant (last line)
106
Oestrogen levels are...in alcohol drinkers
INCREASED
Important in post-menopausal women
107
Brief intervention
Identification and Brief Advice
feedback on the person’s alcohol use and any related harm
clarification as to what constitutes low-risk consumption
information on the harms associated with risky alcohol use
benefits of reducing intake
motivational enhancement to support change
analysis of high-risk situations for drinking
coping strategies and the development of a personal plan to reduce consumption
---
Alcohol Support Services
assessment and engagement
care planning and case management
withdrawal management
addressing physical and psychiatric co-morbidity
psychosocial interventions
pharmacotherapy for relapse prevention
recovery, aftercare & reintegration
108
Government role in reducing impact of alcoholism
Lowered drink drive limit
Increased taxation
Minimum unit pricing
Health warnings on packaging.
109
Management of withdrawal
Symptom trigger withdrawal therapy
Regular assessment of patient - signs and symptoms
Scored at predefined times
Decide amount of benzodiazepine to give patient
110
Foetal alcohol syndrome - facial features
```
> Epicanthal folds
> Flat nasal bridge
> Small palpebral fissures
> Railroad track ears
> Upturned nose
> Smooth philtre
> Thin upper lip
```
111
Types of "cost" due to alcohol
Direct - borne by government, health/socail care, police, justice, unemployment, welfare
Indirect - borne by society; losses in productivity, premature death
Intangible - pain, suffering, loss of income
112
Binge drinking
| Men & women
Men - 8 units in one sitting
Women - 6 units in one sitting
113
The extent to which alcohol is available is strongly associated with...
alcohol consumption and alcohol related harm
Higher densities of off-sales outlet largely found in most deprived areas of Scotland.
114
How much is in a unit?
10mls of pure alcohol (8g)
115
Aspiration pneumonia typically occurs in
Superior segment of the right lower lobe.
116
Ligamentum teres formed from which embryological structure?
Umbilical vein
117
What may be used to assess perfusion in a patient with a severe GI bleed?
Lactate
118
Liver enzyme AST
Aspartate aminotransferase
119
Facial flushing and general feeling of unwell is caused by
Aldehyde
120
Dupuytren's contracture caused by?
Scarring of palmar fascia
121
Severe hepatitis is associated with?
Hepatorenal syndrome
122
Useful screening tool for alcohol dependence disorder?
AUDIT
123
Alcoholic liver disease presenting with Upper GI bleed. What gives most useful info about liver synthetic function
Prothrombin time
124
Portal hypertension is most associated with...
splenomegaly
125
Fibrosis/cirrhosis of the liver is mediated by which type of cell?
Interstitial cells of Ito
126
Which microscopic feature is not present within a portal tract?
Hepatocyte
127
Alcohol can increase/decrease HDL?
Increase blood HDL levels
128
Alcoholic hepatitis - jaundice caused by
CONJUGATED bilirubin
129
Normal metabolic pathway the substance from which bilirubin is formed is...
Biliverdin
130
Which biochemical findings is commonly seen in patients with established alcoholic liver disease (ALD) (cirrhosis)?
Hyperbilirubinaemia
131
Alcohol causes a diuresis because of
Decreased ADH levels
132
Microscopically, hepatocytes are bordered by
The space of Disse
133
Which clotting factor is NOT made in the liver
VIII
134
Death certification part 2 refers to
Conditions contributing to but not directly responsible for death
135
Effects of domperidone on alcohol absorption?
Leads to faster rate of absorption
136
Normal LFTs, normal GGT, AST and ALT with HIGH Alk phos - what should be considered?
Bone disease
137
Treatments intended to manage ascites in cirrhosis aim to reduce what levels?
Sodium levels
Sodium restriction
138
Diabetic ketoacidosis
> No available energy source
> Mobilise free fatty acids to form ketone bodies from which energy can be produced.
> Ketone body - acetoacetate
> No insulin - sugar is there, just not utilised.
High sugar levels, but high ketone bodies.
Smells like acetone
