Alcohol, liver disease, drugs Flashcards
Cells in the liver
Hepatocytes - 70-80% of mass
Space of DIsse:
Stellate cells 0 store vit A
Kupffer cells - macophages metbaolise dead RBC + debris
Blood supply to liver
Hepatic artery 10%
Portal vein 90%
Dual
Leaves via hepatic vein -> IVC
What can cause steatosis/ fatty liver disease?
Alcoholic liver disease
NAFLD - metabolic syndrome
eg obesity, type 2 diabetes mellitus, hypertension, hypercholesterolemia
Causes of NAFLD
Drugs-corticosteroids, oestrogen, amoxicillin, Nifedipine, Diltiazem
Viral hepatitis-hepatitis C virus
Nutritional disorders-total parenteral nutrition (TPN), postsurgical ( gastric bypass, jejunoileal bypass, small bowel resections)
Systemic disorders-inflammatory bowel disease, febrile illnesses, heatstroke
Non-insulin related metabolic disorders-Wilson’s disease, Galactosemia, tyrosinaemia
Other-Small bowel diverticulosis with bacterial overgrowth
What happens in steatohepatitis?
Histologically ballooned hepatocytes- essential finding-indicative of microtubular disruption
*may contain Mallory-Denk bodies (cytoskeletal aggregates. p62 immunohistochemistry
*Necroinflammation-Lobular inflammation-lymphocytes, macrophages and neutrophils
*Hepatic fibrosis-characteristic early fibrosis that is perivenular/pericellular
Definition of cirrhosis
Bridging fibrous septa – portal- portal
Parenchymal nodule formation
Disruption of the architecture of the entire liver – diffuse changes involving the whole liver
Stages cirrhosis development
Fatty liver disease
Liver fibrosis - scar tissue forms
Cirrhosis - scar tissue liver hard and unable to function
Causes of cirrhosis in developed countries
Top 3:
Alocholic liver disease
NAFLD
Chronic viral hepatitis hep B or C
Other causes:
Haemochromatosis
Autoimmune hepatitis
Primary and secondary biliary cirrhosis
Primary sclerosing cholangitis
Medications (eg, methotrexate, isoniazid)
Wilson disease
Alpha-1 antitrypsin deficiency
Celiac disease
Idiopathic adulthood ductopenia
Granulomatous liver disease
Idiopathic portal fibrosis
Polycystic liver disease
Infection (eg, brucellosis, syphilis, echinococcosis)
Right-sided heart failure
Hereditary hemorrhagic telangiectasia
Veno-occlusive disease
Signs of cirrhosis
Portal hypertnesion
Synthetic dysfunction
Hepatorenal syndrome
Hepatopulmonary syndrome
Encephalopathy
Hepatocellular carcinoma
Signs of portal hypertension
Ascites
Hypersplenism
Oesophageal varices
Synthetic dysfuntion of the liver signs
Coagulopathy
Hypoalbuminaemia
How is acute liver failure defined?
development of severe acute liver injury with encephalopathy and impaired synthetic function (INR of ≥1.5) in a patient without cirrhosis or preexisting liver disease
What can cause acute liver failure?
fulminant hepatic failure, acute hepatic necrosis, fulminant hepatic necrosis, and fulminant hepatitis
How long does liver failure have to occur for to be chronic?
<26 weeks
Cardinal symptoms of liver disease
Jaundice
Encephalopathy
Oedema
Abdo paun
Ascites
Pruritis
Dark urine, pale faeces
N+V, decreased appetitie
Bruises easily
Chronic fatigue
Functions of liver
Glucose storage
IMmune factors and filters bacteria
Drug and nutrient metabolism
Clears nitrogenous waste
Iron storage
Produces bile
Protein production and clotting factors
What alvumin lvel indicates chronic liver disease?
<30g/L
% of men and women who exceed recommended units a week?
31% men
16% women
How does SE status affect alcohol?
Intake is the same
Lower SE more likely to experience physical and psychological impact as a consequence of drinking
Harmful physical effects of alcohol
Acute poisonning
Most comon cause of chronic hepatitis - abdo pain and steatorrhea
Aspiration pneumonia
Mallory Weiss syndrome
Oesophagitis
Gastritis
Pancreatitis
Malabsorption and refeeding
HPTN
Cardiomyopthaty
Strokes
Seizures and DTs
Liver damage
Brain damage
Peripheral neuropathy
Myopathy
Osteoporosis
Skin disorders
Malignancies
Sexual dysfunction
Infertility
Foetal damage
Withdrawal syndrome
Psychological effects of alcohol
INsomina
Depression
Suicide/attempted
Anxiety states
Personality change
Psychotic illness
Alcoholic hallucinosis
Morbid jealousy
Amnesia
Delerium tremensn
What is 1 unit of alcohol uk?
8g
(ml x alcohol %) / 1000
What is a harmful levle of drinking?
> 50U for men
35 for women
How is hazardous drinking defined?
Pattern of alcohol increases someones risk of hamr
Physical/mental health, social consequences
Between 14 and 35 0r 50 units /week
What is harmful drinking?
Level or pattern drinking causing damage to persons physical or mental heath
Includes dependece syndrome
Acute or chronic
What is low risk drinking?
<14 units over 3 or more days
What are the features of dependent drinking?
Strong desire or compulsion to drink
Difficulties in controlling drinking
Physiological withdrawal syndrome
Evidence of tolerance
Neglect of other pursuiits because of time spent drinking or recovering from drinking
Persisting with drinking behaviour despite clear evidence of harm
3+ features over previous year
Physiological withdrawal syndrome
(tremor, sweating, anxiety, N+V, agitation, insomnia)
How to detect problem drinkers
Ask routinely at GP
FAST screening tool
How often do you have more than 8 units men 6 units women or more on one occasion?
How often in last year have you not been able to remember what happened when drinking the night before?
Hoe often in last year have you failed to do what was expected of you because of drinking?
In the last year has a relative/friend/doctor/health worker been concerned about your drinking or advised you to cut down?
0-4 for each one
4 = daily
0 = never
What score indicates harmful or hazardous drinking in fast?
> 3
What is GGT? What does elevated levels mean?
Enzyme in liver
Damage to liver -> leaks into blood
eg liver disease or bile duct damage
What use to assess alcohol level in A+E?
Blood alcohol level
What is acute intoxication?
Transient condition after intake psychoactive substance -> conscioussness, cognition, perception, affect or behaviour
What is dependence?
> 2 of:
Control (powerlessness) (onset, intensity, duration, termination, frequency, context)
Precedence (BPS model)
Physiological (tolerance, withdrawal use to prevent/alleviate)
For >12 months (or 3 months if continious)
Physical exam and investigations in alcogol dependence
Examination
Face
Hands and Body
CNS
CVS
Abdomen
Genitourinary
Investigations
Blood tests
US liver
Liver biopsy
Physical exam and investigations in alcogol dependence
Examination
Face
Hands and Body
CNS
CVS
Abdomen
Genitourinary
Investigations
Blood tests
US liver
Liver biopsy
Physical exam and investigations in alcogol dependence
Examination
Face
Hands and Body
CNS
CVS
Abdomen
Genitourinary
Investigations
Blood tests
US liver
Liver biopsy
What would bloods of alcoholic look like?
GGT increased
Macrocytic anaemia
Deranged LFTs
Treatment of alcohol dependence
Alcohol Detoxification
Pharmacotherapy
Manage physical illness occurring as consequence of alcohol (e.g. Liver Transplant)
Psychotherapy
Social Interventions
Residential Rehabilitation
What drug use in alcoholism when dont require detoxification?
Nalmefene
How long can you give Acamprosate for?
up to 6 months
Stop if drinking persists after 4-6 weeks
How long can you give Acamprosate for?
up to 6 months
Stop if drinking persists after 4-6 weeks
What does acamprosate do?
Prevents cravings
What is naltrexone and how does it work?
Opioid receptor antagonist
Blockage of mu opioid receptors - reduces reinforcing effects of alcohol creased feeling intoxication and fewer cravings
How long naltrexone used for?
6 months or longer if needed
Stop 4-6 weeks if still drinking
When initiate disulfiram?
24 hours after last acloholic drink
What need to do before prescribe disulfiram?
LFTs and U+Es
Cl in severe heart disease, stroke, hypertension
Supervision when taking disulfiram?
Supervision every 2 weeks for first 2 months, thne monthly for 4 months
Interactions of disulfiram
Alcohol - food, perfume, aerosols
-> Flushing, nausea, palpitations, arrhytmias, hypotnesion, collapse
What is a rare complication of disulfiram that is v dangerous?
Rapid and unpredicatble of rare complication of hepatoxicity jaundice or feel unwell - send help
Psychotherapies for alcoholism
Brief interventions
MI/MET
CBT
Behaviorual therapy interventions eg cue exposire
Relapse prevention
12 step approach
smart recovery
What to do in motivational intervieiwng?
Helping people recognise problems or potential problems associated with their drinking
Helping to resolve ambivalence and encourage positive change
Adopting a persuasive and supportive rather than argumentative and confrontational position
When consider inpatient assistanve with alcohol withdrawal?
> 30 untis/day
30 on SADQ
Hisotry of epilepsy/withdrawal seizures/DT
When put on commnity based programme with alcohol withdrawal?
> 15 units per day and/or score more than 20 on audit
Limited social support
Complex physical or psychiatric co-mobordities
Not responded to initial community based interventions
What drugs class is trazadone?
SNRI
What happens on a community based programme?
Intensity depends on severity
Drug regimen (chlordiazepoxide/oxazepam) + psychosocial support
When offer acamprosate or naltrexone?
If psychological therapies alonge has failed or drug treatment is preferred
Alongside individual therapy
What can offer for mild dependence in withdrawal?
Offer psychological therapies (CBT) focussed on alcohol related cognitions, behaviour, problems and social networks or behavioural couples therapy
Offer acamprosate or naltrexone
Moderate to severe dependence support following withdrawal
Consider acamprosate or naltrexone with psychological therapy
Consider disulfiram with therapy
When do you consider disulfiram with psychological therapy in moderate to severe alcohol dependence?
Have goal abstinence, acamprosate or naltrexone arent suitbale
Prefer disulfiram
Balance and movement signs of wernickes encephalopathy
Tremors
Unsteady gait
Wide stance and short steps
Limb weakness
What is the triad for wernickes encephalopathy?
Confusion
Ataxia
Nystagmus
Symptoms/signs of wernickes encephalopathy
Balance and movement
Confusion
Nystagmus
Drowsiness
Postural hypotension
Tachycardia
Thiaminereplacement treatment
IM/IV Pabrinex 5 days
PO Thiamine min 4 weeks
What is korsakoff syndrome also related to ecept alcohol?
AIDS, infections, cancers, poor nutrtion, post bariatric surgery
Symptoms of korsakoff syndrome
Loss of short term memory
Anterograde
Hallucinations
Receptive aphasia
Confabulation
Substances that are often misused
Opiates
Benzodiazepines
Stimulants
Cannabis
Dissociative anaesthetics
Hallucinogens
Novel psychoactive substances
Other prescription medications eg pregabalin
Solvents etc
Which substances can cause psychosis?
Alcoholic hallucinosis
Cannabis – good evidence
Steroids
Stimulants
Cocaine
Hallucinogens
What happens in opioid intoxication?
Dysfunctional behaviour as evidenced at least one of:
Apathy and sedation
Disinhibition
Psychomotor retardation
Impaired attention
Impaired judgement
Interference with personal functioning
AND at least one fo the following signs:
Drowsiness
Slurred speech
Pupillary constriction (except in anoxia from severe overdose when dilatation occurs)
Decreased level of consciousness (stupor or coma)
Reason for presentation with drugs
In crisis
Impending court case/in prison/ referred from courts
Referred from/recommended by other medical practitioner/SW etc
Wanting information on effects of drug use
Recent health risk or anxieties re drug misuse
Behaviour causing concern to others
Suffering mental illness
Pregnant
“had enough”/ usual source not available
Wanting help with drug misuse and motivated to change
Drugs hisotry
Age of initiation
Past & current drug use
Types and quantities
Frequency & routes of administration
Symptoms of withdrawal/ other signs of dependence
Periods of abstinence / relapse
Accidental overdose
Funding/risky behaviours
Impact
How to assess injecting hisotry/blood borne virus risk?
Current IV use
Past IV use
Use of clean equipment
Supply of needles
Sharing
Injecting techniques
Disposal of needles
Knowledge of infectious diseases
Practice of safe sex
How to assess injecting hisotry/blood borne virus risk?
Current IV use
Past IV use
Use of clean equipment
Supply of needles
Sharing
Injecting techniques
Disposal of needles
Knowledge of infectious diseases
Practice of safe sex
Investgiations for drug use patients
Urine drug screen
blood tests if indicated
Pregnancy test
Infectious diseases - counselling + informed consent
Collateral history from GP/family/friends
Building recovery from addiction
Advice /information
Harm reduction
Self help e.g. AA, NA, SMART recovery groups
Prescribing ( if appropriate )
Goal directed counselling and psychological support
Structured day programmes
Detox
Rehabilitation
Aftercare
Strategies of harm reduction
Education
on risks of infection/OD/safe sex/cleaning equipment
Needle exchange/condom provision
Hepatitis B immunisation
Blood Borne Virus testing
Substitute oral drugs
Aim of harm reduction measures
Stop drug use
If using- reduce use/stop injecting
If injecting - reduce/stop sharing of injecting equipment/avoid contaminated equipment
If sharing - clean equipment
What are subsitiute treatments for opiates?
Methadone
Buprenorphine
injectables - diamorphine, methadone
Assessment for methadone
establish dependence
motivation for change
Assessment for methadone
establish dependence
motivation for change
What to do when commencing methaodne?
titrate against withdrawal symptoms
observe hourly/ daily appointments
build up over 3 days
mixture used - not tablets
in specialist treatment centres (drug services)
Functions of perscription
Retention in treatment
Reduce the risks associated with injecting
Reduce / prevent withdrawal symptoms
Stabilise lifestyle
Maintain contact with vulnerable groups
Reduce criminal activity
How to ensure concordance/safety?
aily pick up
Supervised consumption 3 -6 months
Regular and spot urine testing
Security (diversion/ home storage)
Options for detoxification of opioids
Methadone
Buprenorphine
Antieemetics
Antidepressants, hypnotics etc
Considering - severity of dependence, stability of the user, support, network/environemnt and co-morbidities
How long should opioid detoc be?
4 weeks inpatient
No longer than 12 weeks communtiy
What is accelerated detox/rapid detox?
Shortened duration of detox using high dose opioid antagonists
1-5 dyas with supportive and sedative measures
Use naltrexone to prevent realpse
Not routinely offered
Relapse prevention what consisits of
Mainly Psychological
Supportive Psychotherapy
Self help
Peer support
Goal directed counselling
Structured day programme
Residential Rehab
Treatment of any Mental Illness
Stimulant dependence treatment
Mainly Psychological Treatment (CBT)
?Benzodiazepines- short course
Antidepressants
X Anti-craving agents
X Dopamine agonists
Dexamphetamine (substitution in amphetamine dependence).
