ALD Flashcards
Which is the main enzyme that converts alcohol to acetdehyde?
Alcohol dehydrogenase
• Cytochrome P450 2E1 (CYP2E1)also converts alcohol to acetaldehyde, and this enzyme tends to be up-regulated in heavy alcohol consumers
Acetaldehyde is a carcinogen- true or false?
TRUE- contributes to the development of HCC independent of effects from cirrhosis
AFLD- what happens
Triglycerides accumulate amongst liver tissue as a result from:
- Reduction in fat export due to a decrease in liver fatty acid oxidation and lipoprotein reduction
- Increased input of lipids to hepatic tissue - increased peripheral lipolysis and triglyceride synthesis
Alcoholic hepatitis features
Combined liver statosis and inflammation with focal regions of liver necrosis
Cirrhosis features
Progression of hepatic tissue inflammation, degeneration and regeneration- excessives fibrogenesis and scarring
- Liver tissue is replaced by excess extra-cellular matrix and collagen
- Reduces functional capcity of liver
Clinical features of ALD
NON SPECIFIC
- Fatigue
- Malaise
- Abdominal pain
- Anorexia
- Weakness
- Nausea and/or vomiting
Alcoholic hepatitis clinical features
- Jaundice
- RUQ pain
- Hepatomegaly - enlarged with smooth edge (irregular and hard in cirrhosis or metastatic)
- Palmar erythema
- Peripheral oedema
- Clubbing
- Dupuytren’s contracture- present in 30% with ALD
Pruritis- ITCHING
cholestasis leading to bile salt deposition in skin
Xanthomas - Spider naevi
Oestrogen damage in liver disease- why?
Estrogenic effects?
Liver metabolises oestrogen- progressive liver damage and oestrogen rises
• Gynaecomastiaand testicular atrophy (in males)
• Loss of body hair
• Amenorrhoea (in females)
Loss of libido
Portal hypertension features
- Ascites(within 10 years of the diagnosis of cirrhosis, >50% of patients will develop this)
- Dilated veins (e.g. caput medusae)
- Variceal bleeding and haemorrhage
- Splenomegaly
Ratio of AST:ALT in alcoholic hepatitis
• Ratio of AST:ALT is normally >2, a ratio of >3 is strongly suggestive of acute alcoholic hepatitis
Serumm GGT is raised in?
Chronic heavy alcohol consumption
Not specific to ALD- may be raised in other patholgies - obesity, NAFLD, biliary obstruction and HCC
ALP raised in?
Cholestatic pattern of liver injury
Four markers raised in comparison of each other in liver disease
ALD, AST, ALT, GGT
ALD- AST and ALT will be raised much more compared to the ALP and or GGT levels
In AFLD- solitary mild increase in AST and ALT
Conjugated and non-conjugated bilirubin fraction in liver disease and haemolysis/gilbert’s syndrome
○ Liver disease (many types, including ALD) will have elevatedconjugatedbilirubin
○ Haemolysis or Gilbert’s syndrome will have elevatednon-conjugatedbilirubin, more than 90% of total bilirubin will be unconjugated
Albumin in liver disease
Reduced serum albumin
Liver synthesises albumin- low levels indicated diminished syntheetic function
Serum prothrombin time, INR in liver disease
Elevated PT and INR due to diminished synthetic function of liver
Liver ultrasound
- May be used to differentiateabnormal liver function testscaused by other pathologies e.g. hepatocellular carcinoma, cholestasis, liver mass/abscess
- If known ALD andcirrhosis, is useful to screen for hepatocellular carcinoma development
Liver biopsy- two ways of performing it
Percutaneous and Transgular
Histological findings of alcoholic hepatitis
Mallory-Denk bodies, neutrophil-rich inflammation with necrosis, hepatocyte ballooning
Serum ceruloplasmin levels in ALD and Wilson’s
○ May be normal or raised in ALD
Low inWilson’s disease
Serum iron, transferrin and ferritin checked to rule out which disorder?
Haemochromatosis
Alpha 1 antitrypsin
• Alpha-1 antitrypsin levels
○ To rule out alpha-1 antitrypsin deficiency
Drugs for alcohol withdrawal?
Benzodiazepines- diazepam
Quick-acting benzodiazepine- lorazepam for alcohol withdrawal seizures
First-line treatment for delirium tremens
Oral lorazepam
Acute alcoholic Hepatitis therapy
Glucocorticoids- prednisolone
• Pentoxifylline can be used as an alternative to glucocorticoids if they are contraindicated (e.g. hepatitis B viral infection, tuberculosis, other serious infection)
End stage ALD treatment
Transplant but has to be alcohol free >6 months
Hepatic encephalopathy features
• Confusion • Drowsiness • Hyperventilation • Asterixis Fetor hepaticus
Encephalopathy features
Supportive care plus lactulose
Portal hypertension features
Occurs once liver cirrhosis is established
Blood vessels are blocked due to severe liver fibrosis, a high pressure develops in the portal venous system
Leads to varices- ascites, splenomegaly,
How to manage Portal Hypertension
TIPSS- Transjugular intrahepatic portal-systemic shunt if there is acute bleeding, particularly if gastric varices are present
Hepato-renal syndrome
- As a result of portal hypertension, there is widespread splanchnic vasodilation
- This leads to a reduction in the effective circulating volume, which can reduce the blood flow to the kidneys, compromising the renal system and potentially leading to a life-threatening acute kidney failure
HCC risk and screening
- Once liver cirrhosis is established, there is a significantly increased risk in development of hepatocellular carcinoma
- Hepatic ultrasound should be undertaken serially approximately every 6 months to yearly to screen for liver cancer development
