10. Alcohol related disease Flashcards
Outline pathways of alcohol metabolism.
Oxidative metabolism:
- Alcohol dehydrogenase converts ethanol to acetaldehyde which is then converted to acetate by acetaldehyde dehydrogenase.
Microsomal enzyme oxidation system:
- ethanol to acetaldehyde by Cytochrome P4502E1
Ethanol is metabolized by above two pathways, resulting in an increase in the NADH/NAD ratio. The altered redox potential causes increased hepatic fatty acid synthesis with decreased fatty acid oxidation; both events lead to hepatic accumulation of fatty acid, which is then esterified to glycerides.
Alcohol and The Liver:
- Define steatosis.
- Define steatohepatitis
- Steatosis - (Fatty Liver: cells become swollen with fat)
- Steatohepatitis - (Fatty Liver with Inflammation). Neutrophil infiltration. Fibrosis, Cirrhosis (Build up of scar tissue).
What is CAGE?
Questions to ask during history from someone with alcohol dependency. CAGE:
Have you ever felt the need to Cut down?
Have you been Annoyed by criticism of your drinking?
Have you felt Guilty about your drinking?
Do you need an Eyeopener?
What are the physical findings related to alcoholic liver disease?
- Majority no physical findings until advanced liver disease
- Signs of chronic liver disease: Spider naevi, palmar erythema, gynaecomastia, loss of axillary and pubic hair, ascites, encephalopathy
- Jaundice
- Muscle wasting (Drinking alcohol lowers your intake of good diet which leads to muscle wasting)
What investigations would you do for alcoholic liver disease?
Labs:
- Aspartate Amino Transferase (AST) > alanine Amino Transferase (ALT). Ratio >2
- Raised Gamma Glutamyl Transferase
- Macrocytosis
- Thrombocytopenia (low platelets)
- USS fatty liver
Hepatic Encephalopathy:
- What is it?
- How is it graded?
- What should you exclude?
- Defined as a spectrum of neuropsychiatric abnormalities in patients with liver failure, after exclusion of other known brain disease.
- Graded 1-4. 1 = mild confusion, 4 = Coma
- Infection, Hypoglycaemia, Intra Cranial Bleed
What causes hepatic encephalopathy?
- Considered to be caused by the body’s inability to remove ammonia from the blood stream, and the accumulation of neurotoxins in the blood affects brain function.
- Common precipitants:
- Infection
- Drugs
- Constipation
- GI Bleed
- Electrolyte Disturbance
How is hepatic encephalopathy treated?
- Use lactulose or bowel enemas to reduce nitrogen load from the gut.
- Antibiotics (better to treat with broad spectrum ones). Can use neomycin to lower amino acid production by decreasing the concentration of ammonia-forming colonic bacteria
- Supportive: ITU, airway support. Nasogastric tube for meds.
Define Spontaneous Bacterial Peritonitis.
An infection of ascitic fluid that cannot be attributed to any intra-abdominal, ongoing inflammatory, or surgically correctable condition. Seen in cirrhosis and end stage liver disease.
What are the symptoms of Spontaneous Bacterial Peritonitis?
Abdominal Pain
Fever, Rigors
Renal impairment
Signs of Sepsis, tachycardia, temperature
How would you diagnose Spontaneous Bacterial Peritonitis?
Ascitic Tap: - Fluid Protein and Glucose levels - Cultures - White Cell Content Results: Protein <25g/L Defined by an ascitic fluid absolute neutrophil count >0.25x109 /L (>250 cells/mm³), whether or not there is culture growth.
How is Spontaneous Bacterial Peritonitis treated?
IV Antibiotics
Ascitic Fluid Drainage
IV Albumin Infusion (20% ALBA): to increase fluid in blood vessels to perfuse the kidneys. This is given if kidney dysfunction is present.
How does alcohol hepatitis present?
- Jaundice
- Encephalopathy
- Infection common
- Decompensated hepatic function: (Low albumin and raised prothrombin time/INR)
How is alcohol hepatitis diagnosed?
- Raised Bilirubin
- Raised GGT and AlkP
- Alcohol History (people are not honest about it or don’t know how much they are taking exactly so important ask how big is the glass of wine)
- Exclude other causes
How is alcohol hepatitis treated?
- Supportive
- Treat infection
- Treat encephalopathy
- Treat alcohol withdrawal
- Protect against GI bleeding
- Airway Protection / ITU care
- Steroids: Only if grading severe i.e. Glasgow Alcoholic Hepatitis Score >9. Score takes in account age, WCC, urea, INR, bilirubin. Remember Steroids increases risk of GI bleeding.
- Maddreys discriminent function >32: Treat with Oral Steroids. 4.6 x (PT - control PT) + Bilirubin
- Nutritional support as most are malnourished. Thiamine deficiency causes permanent brain damage
