Hepato-biliary: Alcoholism Flashcards
1
Q
How does alcohol act as a drug?
A
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
2
Q
What is the physiology behind the anxiolytic effects of alcohol?
A
Enhancement of GABA-A Transmission
3
Q
What is the physiology behind the euphoriant and rewarding effects of alcohol?
A
Dopamine release in the mesolimbic system
4
Q
What is the physiology behind the amnesic effects of alcohol?
A
Inhibition of NMDA-mediated glutaminergic transmission
5
Q
What are the steps in the pathway of alcohol breakdown?
A
Ethyl-alcohol -> alcohol dehydrogenase -> acetaldehyde -> acetaldehyde dehydrogenase -> Acetate
6
Q
Where is alcohol absorbed in the GI tract?
A
- Mouth
- Stomach
- Small intestine
7
Q
What are the acute effects alcohol in low doses?
A
- Elevated mood/Reduced anxiety
- Sociability
- Impaired judgment
- Disinhibition
8
Q
What are the acute effects of alcohol intoxication?
A
- Impaired attention and judgement
- Unsteadiness
- Flushing
- Nystagmus
- Mood lability
- Slurring
- Dilated pupils
- Stupor
9
Q
Where is alcohol mostly oxidised in the body?
A
Liver
10
Q
What are the three pathways for alcohol metabolism?
A
- Alcohol dehydrogenase pathway
- Microsomal ethanol oxidizing system (MEOS)
- Catalase pathway - located in peroxisomes
11
Q
When are peak blood ethanol concentrations achieved?
A
1 hour after ingestion
12
Q
What factors influence the levels of alcohol attained in the blood after ingestion?
A
- Speed of intake
- Food cunsumed
- Rate of gastric emptying
- Body habitus
13
Q
Why do women obtain higher blood ethanol concentrations than men after drinking the same amount of alcohol?
A
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
14
Q
What is the hourly rate of ethanol elimination from the body?
A
7-10g per hour
15
Q
What is the rate limiting factor for ethanol metabolism?
A
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
16
Q
In chronic alcohol misuse, why does the metabolic rate of ehtnaol increase?
A
Increased action of MEOS system
17
Q
What problems can occur if the redox hoemeostatic capacity of the liver is exceeded (i.e. capacity of liver to convert NADH to NAD)
A
- Hypo/hyperglycaemia
- Lactic acidosis
- Ketoacidosis
- Hyperuricaemia
- Abnormal lipid metabolism
18
Q
What range of blood alcohol concentration would produce definite impairment of cognitive function?
A
150-250 mg/100ml
19
Q
What factors will influence the blood alcohol concentration required to produce intoxication?
A
- Rate of increase in blood levels
- Degree of tolerance
- Simultaneous effects of other drugs
20
Q
What are the affects of severe alcohol intoxication?
A
- Drowsiness
- Coma
- Hypotension
- Hypothermia
- Decreased respiratory effort - shallow and sterterous
21
Q
How can death occur in alcohol acute alcohol intoxication?
A
- Respiratory depression
- Vomit aspiration
22
Q
What is the recommend alcohol intake for males and females?
A
14 units per week
23
Q
What blood alcohol is often regarded as being a fatal level?
A
>450 mg/100ml
24
Q
How many grams of alcohol are in 1 unit?
A
8g
25
What volume of 3-4% beer contains 1 unit of alcohol?
284 ml - 1/2 pint
26
What volume of average strength table wine would contain 1 unit of alcohol?
125ml - a single small glass
27
What volume of spirit would contain 1 unit of alcohol?
25 ml - single measure
28
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
29
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
30
In men, how many units per week would be classed as harmful?
50 units
31
In women, how many units per week is regarded as drinking harmfully?
35 units per week
32
What percentage of harmful drinkers will develop liver cirrhosis?
20%
33
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**
34
What systems are most commonly affected through chronic alcohol misuse?
* **Hepatic/****Gastrointestinal**
* **Malignancy**
* **Cardiovascular**
* **Respiratory**
* **Neurological**
* **GU**
* **Musculoskeletal**
35
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
36
What is this, and what might it indicate?
Spider naevi - chronic alcohol misuse
37
What percentage of alcohol misusers develop pancreatitis?
15%
38
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**
39
What is this, and what can it indicate?
Telangiectasia - chronic alcohol misusue
40
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
41
What is the following, and what might it indicate?
**Palmar erythema** - chronic alcohol misuse - specifically alcohol related liver disease
42
What is the following, and what is it associated with?
**Dupuytren's contracture** - chronic alcohol misuse
43
What is this, and what does it indicate?
Gynaecomastia - chronic liver disease
44
What is the distribution of spider naevi?
Only in the distribution of the superior vena cava - most commonly face and anterior chest wall
45
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.
46
What is telangiectasia?
Broken veins - commonly occur on the face
47
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
48
What is the mechanism behind the development of palmar erythema in liver disease?
## Footnote
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.
49
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
50
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
51
How would a patient present if they had acute alcohol induced gastritis?
* **Nausea**
* **Vomiting**
* **Epigastric pain**
**SYMPTOMS DISAPPEAR 48-72 hrs after**
52
What symptom associated with the small intestine can be associated with either acute or chronic alcohol misuse and reflects changes in small intenstinal permeability and motor activity?
Diarrhoea
53
Chronic alcohol misuse is associated with what defective process in the small intestine?
Absorption of nutrients, glucose, amino acids, vitamins
54
Why does progressive, irreversible damage to the pancreas occur in chronic alcohol misuse?
Chronic alcohol misuse cause pancreatic inflammation, acinar atrophy, and ultimately fibrosis resulting in endo- and exocrine insufficiency
55
How would someone with alcohol-related pancreatitis present?
Acute episode on top of chronic pancreatitis
* Epigastric pain which radiates to the back
* Nausea and vomiting
* Profound metabolic abnormalities
* Malabsorption
* Diabetes
56
What changes in the liver will occur in the majority of those who misuse alcohol?
**Hepatic steatosis** - Fatty changes in the liver which occur due to altered fat metabolism linked to excess hydrogen ions generated ib ethanol oxidation
57
58
What proportion of individuals who chronically misuse alcohol develop alcoholic hepatitis?
\<20%
59
What are the signs/symptoms of alcoholic hepatitis?
**Alcohol use, plus:**
* **Asymptomatic, or**
* **Symptomatic**
* Tender hepatomegaly +/- Jaundice
* Ascites
* Encephalopathy
* Malnutrition -\> Anorexia
* Malaise
* Decompensated hepatic function
60
What factors determine whether an individual with alcoholic hepatitis will develop alcoholic liver cirrhosis?
* **Drinking behaviour**
* **Gender**
* **Severity of histiological lesions**
61
What are signs and symptoms of alcoholic liver cirrhosis?
Chronic alcohol use, plus
* **Asymptomatic** - compensated disease
* **Symptomatic** - decompensated disease
* Portal hypertension
* Jaundice
* Fluid retention
* Abnormal bleeding
* Hepatic encephalopathy
* Variceal haemorrhage
62
What is the outcome of patients with alcoholic liver cirrhosis determined by?
* **Degree of decompensation**
* **Subsequent drinking behaviour**
63
What effects does alcohol have on the electrophysiology of the heart?
* **Depression of left ventricular function**
* **Premature ventricular beats**
* **AF** - more severe intoxication
64
What effects does alcohol have on blood pressure?
Increased systolic + diastolic pressure
65
What effect does alcohol have on the heart muscle?
**Can develop Alcoholic cardiomyopathy** - \>60 g daily for more than 10 years
66
How could you reverse alcoholic cardiomyopathy?
Abstinence
67
What cardiovascular problems are caused by alcohol intake?
* **Arrythmias** - esp AF
* **Dilated cardiomyopathy**
* **Hypertension**
* **CVA**
* **CHD**
68
What gastro-intestinal problems can be caused by alcohol use?
* **Gastritis**
* **GORD -\> barrett's oesophagus**
* **Mallory-Weiss tear**
* **Peptic ulceration**
* **Chornic diarrhoea**
* **Chornic pancreatitis**
69
What cancers can alcohol use cause?
* **Hepatocellular**
* **Oesophageal**
* **Stomahc**
* **Mouth**
* **Tongue**
* **Pharynx**
70
What are the different criteria assessed in the glasgow alcoholic hepatitis scoring system?
* **Age**
* **WCC**
* **Urea**
* **INR**
* **Bilirubin**
71
What respiratory problems can occur due to alcohol misuse?
* **Tuberculosis**
* **Klebseilla/pneumococcal pneumonia**
* **Aspiration pneumonia**
72
What neurological problems can occur with alcohol misuse?
* **Alcohoic dementia**
* **Wernicke-Korsakoff syndrome**
* **Peripheral neuropathy**
* **Central pontine myelinolysis**
* **Cerebellar degeneration**
* **Optic atrophy**
* **Alcoholic myopathy**
73
What genitourinary problems can occur from alcohol misuse?
* **Erectile dysfunciton**
* **Hypogonadism in men**
74
What musculoskeletal problems can occur as a result of alcohol misuse?
* **Accidents/trauma -** Saturday night palsy, fractures, lacerations, battered alcoholic syndrome etc.
* **Osteoporosis**
* **Gout**
* **Acute/Chronic myopathy**
75
Which type of stroke does chronic alcoholiosm increase the risk of?
Haemorrhagic stroke
76
What is steatosis?
Also called fatty change, is the process describing the abnormal retention of lipids within a cell. It reflects an impairment of the normal processes of synthesis and elimination of triglyceride fat. Excess lipid accumulates in vesicles that displace the cytoplasm
77
What is non-alcoholic steatohepatitis (NASH)?
**Fatty changes in the liver + inflammation**
Characterised by cellular swelling, Mallory's hyaline and signs of inflammation. In contrast to NAFLD, this process causes cell death and fibrosis
1/4 of those with NASH progress to liver cirrhosis
78
How would you investigate suspected alcoholic hepatitis?
* **History/examination** - alcohol + acute liver signs
* **LFTs** - raised bilirubin, raised GGT and AlkP
* **Exclude other causes** - blockage etc.
79
How would you treat alcoholic hepatitis?
* **Supportive**
* **Abstinence**
* **Nutritional treatment** - thiamine (pabrinex), high energy feeds
80
What score on the the glasgow alcoholic hepatitis scoring system would indicate the use of steroids to treat alcoholic hepatitis?
\>9
81
What is spontaneous bacterial peritonitis?
The development of a bacterial infection in the peritoneum causing peritonitis, despite the absence of an obvious source for the infection. It occurs almost exclusively in people with portal hypertension (increased pressure over the portal vein), usually as a result of cirrhosis of the liver. Ascites has to be present for this to occur
82
How does spontaenous bacterial peritonitis present?
* **Abdominal pain**
* **Septic picture** - Fever, Rigors
* **Renal impairment**
83
If you suspected spontaneous bacterial peritonitis, what investigations would you do?
Ascitic tap (paracenteisis)
* **Fluid protein and glucose (protein \<25g/l)**
* **Cultures**
* **WCC**
* **Neutrophil count \>0.25 x 10^9** (defined by ascitic fluid neutrophil count \>250 whether or not there is culture growth)
Exclude surgical cuse of peritonitis
84
How would you treat someone with spontaenous bacterial periotnitis?
* **IV Abx**
* **Ascitic drainage**
* **IV Albumin infusion (indicated in those with renal dysfunction)**
85
What is wernicke-Korsakoffs syndrome?
The combined presence of Wernicke's encephalopathy (WE) and Korsakoff's syndrome - this develops in those who are thiamine deficient. These syndromes can also exist on their own
86
What is wernicke's encephalopathy, and what are it's characteristic features?
[https://www.youtube.com/watch?v=olpyoHDZZGM](https://www.youtube.com/watch?v=olpyoHDZZGM)
The acute phase of werkicke-korsakoffs syndrome (single disease process). Wernicke's can occur with classic Triad of presenting symptoms/signs:
* **Acute confusion**
* **Ocular signs**
* **Ataxia**
Other signs include peripheral neuropathy, resting tachycardia, disorientation, disturbed memory.
87
What occular signs can be seen in Wernicke's encephalopathy?
* **Nystagmus**
* **Gaze palsies/****Opthalmoplegia** - most commonly 6th nerve
88
What percentage of those with wernicke's encephalopathy have the classic triad of symptoms/signs?
**10%** - about 80% of cases present with just confusion
89
What is the pathology of wernicke's encephalopathy?
Haemorrhages and secondary gliosis in periventricular and periaqueductal grey matter. Areas involved include:
* **Mamillary bodies**
* **Hypothalamus**
* **Colliculi**
* **Tegmentum of midbrain**
90
How does heavy drinking cause thiamine deficiency?
* **Poor calorie/nutritional intake**
* **Reduced absorption**
* **Impaired hepatic storage**
91
How would you manage someone with wernicke's encephalopathy?
* **IV Pabrinex** - parenteral
* **Treat alcohol withdrawal**
92
What is korsakoff's syndrome?
Usually occurs after wernicke's encephalopathy, but not always
An amnesic state in which there is profound impairment of both retrograde (previous) and anteretrograde (new) memory but relative preservation of other intellectual abilities. Working, emotional and procedural memory is also preserved. Other features include:
* **Confabulation**
* **Nystagmus**
* **Ataxia**
These tend to indicate combined Wernicke-Korsakoff's syndrome
93
How would you treat someone with Korsakoff's syndrome?
Oral thiamine and multivitamin supplementation - 2 years
OT assessment
Cognitive rehabilitation
94
What is hepatic encephalopathy?
Fluctuations in metnal status and cognitive function in the presence of severe liver disease - either chronic (cirhosis) or acute (fuminant hepatic liver)
95
What can cause hepatic encephalopathy?
CIRRHOSIS
Infection
Drugs
Constipation
GI bleed
Electrolyte disturbances
(Exclude infection, hypoglycaemia, intracranial bleed)
96
Pathopolgy of hepatic encephalopathy and therefore diagnosis
Ammonia not detoxified by liver - affects GABA receptors
Diagnosis relies on increased ammonia levels and assessment with MMSE
97
Management hepatic encephalopthy
**Laxatives - Lactulose first line:** Decreases absorption of ammonia in the bowel
**Enemas**
**Antibiotics**: reduce ammonia production from micro-organisms
98
What percentage of heavy drinkers will have a fatty liver?
90%
99
What is alcoholic hallucinosis?
Substance induced psychotic illness which is a rare complication of prolonged heavy alcohol misuse. The sufferer experiences hallucinations - usually auditory - while sober. Can start as elemental hallucinations which progress to formed voices (usually derogatory) with continued alcohol use
100
If an individual presented with hallucinations with prolonged alcohol misuse, what would be your differential diagnosis?
* **Alcoholic hallucinosis**
* **Transitory hallucinatory/illusionary experiences while intoxicated**
* **Delerium tremens**
* **Psychotic illnesses**
101
What is Othello syndrome?
**Pathological jealousy** - monosymptomatic delusional disorder seen most commonly secondary to current or previous alcohol abuse. Content is a primary delusion in which the content is that the patient's spouse or partner has been/is being unfaithful
102
What is alcohol induced amnesia?
Transient amnesic episodes related to periods of intoxication. Characteristically report a gap in their memory lasting severeal hours with global or partial amnesia for their actions during that time
103
What is alcohol withdrawal syndrome?
Sydrome that occurs when someone who is alcohol dependent stops consuming alcohol either substantially or completely.
104
What are the different alcohol withdrawal syndromes?
* **Uncomplicated alcohol withdrawal**
* **Alcohol withdrawal with seizures**
* **Delerium tremens**
105
What are the characteristic features of uncomplicated alcohol withdrawal/alcohol withdrawal syndrome with seizures?
Occurs 4-12 hrs after last drink, peak at 48 hrs, and last 2-5 days
* **Coarse tremor**
* **Sweating**
* **Insomnia**
* **Tachycardia**
* **Nausea and vomiting**
* **Psychomotr agitation**
* **Generalised anxiety**
* **Occasional hallucinations**
* **Seizures**
106
What is delerium tremens, and what are the characterisitc features?
Acute confusional state secondary alcohol withdrawal, which has the features of uncomplicated withdrawal, plus:
* **Clouding of consciousness**
* **Disorientation**
* **Amnesia - recent events**
* **Hallucinations** - tactile, visual, auditory
* **Marked fluctuation hour by hour**
* **Profound psychomotor agitation**
107
What are the characteristic hallucinations that those going through Delerium Tremens experience?
**Lilliputian hallucinations** - hallucinations of diminutive people or animals
108
If someone developed symptoms/signs which pointed towards a diagnosis of delerium tremens, what else would you consider as part of a differential diagnosis?
* **Hepatic encephalopathy**
* **Head injury**
* **Pneumonia**
* **Acute psychotic illness**
* **Other cause of delerium**
109
How can death occur when someone is going through delerium tremens?
* **Sudden cardiovascular collapse**
* **Infection**
* **Hyperthermia**
* **Self-injury**
110
How would you manage someone going through alcohol withdrawal?
Detox
* **Decide setting** - inpatient vs outpatient
* **Psychological support**
* **Benzodiazepines** - withdrawal symptoms - reducing regimen
* **Chlordiazepoxide** **prefered**
* **Observation**
* **Nutritional supplementation**
111
What indications would make you think it would be safer to detox a patient as an inpatient?
* **PH of complicated withdrawals** - seizures/DTs
* **Current confusional/delerious symptoms**
* **Comorbidities**
* **Symptoms of WKS**
* **Severe vomiting/malnutrition**
112
What are the indications for prescribing a reducing regimen of benzodiazepines when treating alcohol withdrawal?
* **Clinical symptoms**
* **History of dependence**
* **Consumption \> 10 units/day over the previous 10 days**
113
What are the components to the CAGE questionnaire?
## Footnote
**Cut down** - Have you tried to cut down?
**Annoyed** - Have you felt annoyed by people criticising your drinking?
**Guilt** - Have you felt guilty about drinking?
**Eye-opener** - have you felt the need to have an eye-opener in the morning
114
What disorders would usggest underlying alcohol abuse?
* **Hepatitis**
* **Cryptogenic cirrhosis**
* **Seizures**
* **Gastritis**
* **Anaemia**
* **Cardiomyopathy**
* **TB**
* **Head injury**
* **Impotence**
115
What blood tests might indicate excess alcohol consumption?
Elevated:
* **MCV**
* **GGT**
* **CDT** - carbohydrate-deficient transferrin
116
How would you manage someone in an attempt to maintain abstinence?
* **Individual/group therapy** - AA
* **Pharmacological support**
* **Advise regarding relapse**
* **Consideration for residential rehabilitation**
117
What Medications can be used to help those who are attempting to achieve alcohol abstinence?
* **Aversive drugs** - Disulfiram (Antabuse)
* **Anticraving drugs** - acamprosate, Naltrexone, Baclofen
118
What are examples of anti-craving drugs used for alcoholics?
* **Acamprosate**
* **Naltexone**
* **Baclofen**
119
How does disulfiram work?
Irreversible inhibition of ALDH, leading to a build up of Acetaldehyde. This causes unpleasent symptoms of flushing, headache, nausea and vomiting, and tachycardia
120
When managing severe alcohol intoxicaiton in hospital, how should the individual be monitored?
* **Assessed hourly**
* **Continuous ECG monitoring**
* **Urine output**
* **Blood Glucose, Electrolytes and gases** - every 4 hours
121
How would you manage someone with severe acute alcohol intoxication?
* **IV fluids**
* **Oral glucose/IV 5% or 10% dextrose as required**
* **Assist ventilation**
* **Haemodialysis** - exceptionally high blood ethanol
122
What is fetor hepaticus?
Condition seen in portal hypertension where portosystemic shunting allows thiols to pass directly into lungs.
Is a late sign of liver failure and is one of the clinical features of hepatic encephalopthy.
123
Key blood tests done in alcohol related liver disease
* FBC
* Macrocytic anaemia (due to PHT causing splenomegaly)
* Low Hb
* High MCV
* Thrombocytopenia
* Clotting screen
* Raised INR/PT time
* LFTs
* AST/ALT ratio \>2
* Gamma glutamyl transferase
124
Describe the changes of the liver in alcoholic hepatits
* Excess alcohol
* Steatosis (simple fatty liver balooned hepatocyes (fat globules accumulate in cytoplasm of hepatocytes)
* Alcoholic steatohepatitis (fatty liver with inflammation)
* Fibrosis (persistent liver inflammation)
* Cirrhosis (liver covered by scar tissue)
125
How do you treat alcohol withdrawal?
Thiamine - Vit B1 deficiency
Pabrinex - contains vit C, B1, B2, B3 and B6
Benzodiazepine - eg diazepam to decrease seizures/N+V/pain and tremors
