Makindo Medical Notes.com

Related Subjects: |Chronic liver disease |Cirrhosis |Alkaline phosphatase (ALP) |Liver Function Tests |Ascites Assessment and Management |Budd-Chiari syndrome |Autoimmune Hepatitis |Primary Biliary Cirrhosis |Primary Sclerosing Cholangitis |Wilson disease |Hereditary Haemochromatosis |Alpha-1 Antitrypsin (AAT) deficiency |Non alcoholic steatohepatitis (NASH) |Spontaneous Bacterial Peritonitis |Alcoholism and Alcoholic Liver Disease

Assesses the degree of dependence rather than quantity of alcohol taken

Alcohol

• Alcohol is a common cause of morbidity and mortality and it is important to understand its actions and metabolism

Metabolism

• Ethanol is metabolised in the liver by 3 different enzyme systems
  • 1. Ethanol + NAD+ ? Acetaldehyde + NADH + H⁺ catalysed by Alcohol dehydrogenase
  • 2. Acetaldehyde + NADPH + H⁺ ? Acetic acid + NADP + 2 H₂O by the liver microsomal enzyme oxidizing system P450 system CYP2EI which is inducible by alcohol and only becomes important with chronic intake
  • 3. Catalase - Least important of all
• The metabolism of alcohol leads to an alteration of the redox state of the cell. It uses up NAD+

Acetaldehyde

• Acetaldehyde CH3CHO is the end product of the first two reactions and it is highly reactive and can be potentially toxic. It is responsible for many of the systemic toxic effects of alcohol, such as nausea, headaches, and flushing. It is converted to acetate by aldehyde dehydrogenase.
• A defect in this enzyme such that it is ineffective is seen in Orientals who then suffer severe toxic effects when they drink alcohol such as flushing and tachycardia.

Ethanol

• Highly lipid-soluble and water-soluble so distributes in total body water
• Elimination and clearance is by the liver
• Metabolism by alcohol and aldehyde dehydrogenases is zero-order and can become saturated
• Produces 2 molecules of NADH per ethanol molecule

Clinical clues

• Weight gain, hypertension, Tired all the time, accidents, falls, Back pain, poor sleep
• Liver disease
  • RUQ pain & tenderness, encephalopathy, GI bleeding, ascites, jaundice, Telangiectasia
  • Palmar erythema, Dupuytren's contracture, gynecomastia & testicular atrophy (in men)
  • Hepatomegaly, splenomegaly, asterixis, fetor hepaticus

Binge drinking

• Taking twice daily limit in one day

Limits

• Alcohol is eliminated at about 1 unit per hour
• Women 14 u a week = 2 small glasses of wine
• Men 21 u a week which is 3 small glasses of wine
• 1 glass of wine = a half pint of beer
• The recommended daily intake results in a blood alcohol level legal for driving is not correct as there will be exceptions and factors such as weight are important.
• The only safe intake level is none.

Adverse effects

• Physical and psychological dependence
• Oedema and ascites, Liver enzyme induction
• Cardiomyopathy, AF and other arrhythmias
• Alcoholic liver disease, Anaemia, Macrocytosis
• Thiamine deficiency and malnutrition
• Depression, Fetal alcohol syndrome
• Social - violence, child abuse, financial, criminal justice, drink driving

Investigations

• FBC: Raised MCV
• AST>ALT (both usually <300 IU/L; AST/ALT > 2) 
• Elevated alkaline phosphatase, elevated GGT, elevated uric acid 
• Elevated WBC, increased MCV 
• Elevated glucose, high triglyceride, low K⁺, low phosphorus, low Mg++
• Elevated GGT, Bilirubin
• Prolonged Prothrombin time
• Abdominal US or CT: not diagnostic: Rule out other hepatic lesions. Cirrhosis & collaterals w/ advanced disease
• CT: Subdural, Cerebellar atrophy

CAGE Question

• Have you ever felt you should CUT back on your drinking
• Has anyone ANNOYED you by criticising your drinking
• Have you ever felt bad or GUILTY about your drinking
• Have you ever taken alcohol in the morning as an EYE OPENER - to get rid of a hangover or to steady nerves

Management

• Acutely: Start IV vitamins immediately; Pabrinex/parenteral vitamin B and C should be used for the first 3 days. Thiamine 100 mg TDS PO throughout the admission
• Severe alcoholic hepatitis: consider Prednisolone or methylprednisolone for 4 wk followed by taper & discontinuation over 2–4 wk
• Consider Chlordiazepoxide reducing regimen to prevent DTs. Signs of withdrawal include a hyperactive delirium with sweating, Shaking, Vomiting, Agitation, Hallucinations
• Following abstinence, Consider Acamprosate 666 mg TDS. This drug acts by enhancing GABAergic inhibition
• Huge element of denial and relative ambivalence to the damage caused to self and those surrounding them. There is a great variety in the types of harmful relationship between some patients and alcohol.
• Suggest Alcoholic anonymous for support and advice - local branch in the phone book
• Difficult to engage patients in a treatment plan but some do respond and it's a lifelong struggle.
• Aid genuine attempts at Drying out - Reducing dose of Chlordiazepoxide to reduce risk of the DTs usually through a community addictions team
• thiamine and vitamin supplementation as Nutrition based on alcohol is high in calories but nutritionally poor
• Specialist help will be likely be needed before considering Acamprosate and Disulfiram

Links

• Alcoholics Anonymous
• Alcohol Concern