MET3 Revision: Hepatology II Flashcards
Damage to which part of the brain is responsible for the neurological symptoms seen in Wilsons diseae? [1]
Basal ganglia
Describe the extra-hepatic symptoms of Wilsons disease [5]
Blue nails
Kayser fleischer ring
Haemolytic anaemia
Cardiomyopathy
Neurological:
- Cognitive decline
- Lack of co-ordination leading to PD like symptoms
- Dementia
- Pyschosis
-
What are the major clinical manifestations of haemochromatosis? [5]
Cirrhosis of the liver
Diabetes mellitus
Arthritis
Cardiomyopathy
Hypogonadotropic hypogonadism
Describe the impact of haemochromatosis on reproductive system [3]
Amenorrhoea
Erectile dysfunction
Testicular atrophy
Describe the pathophysiology of chronic liver disease [4]
- Chronic liver disease may result from repeated insults that cause inflammation (i.e. chronic hepatitis) or cholestasis (i.e. impairment of bile flow)
- Excess deposition of fat in the liver (i.e. steatosis) can also promote an inflammatory response (e.g. NAFLD)
- Leads to scarring known as fibrosis: the normal liver architecture is replaced by fibrotic tissue and regenerative nodules
- If fibrogenesis continues then the end result is cirrhosis, which describes irreversible liver remodeling
The severity of cirrhosis can be graded using the []
The severity of cirrhosis can be graded using the Child-Pugh score.
What LFT results would indicate alcoholic hepatitis? [2]
AST: ALT >2.5
Associated with Alcoholic hepatitis
Raised GGT (sensitive to alcohol ingestion, but non-specific to hepatocellular damage)
What are the arrows pointing to? [1]
What pathology does this indicate? [1]
Mallory bodies are highly eosinophilic and thus appear pink on H&E stain. The bodies themselves are made up of intermediate keratin filament proteins that have been UBIQUINATED, or bound by other proteins such as heat shock protein
Found in ALCOHOLIC HEPATITIS
What are signs & symptoms of alcoholism associated with:
- CNS [6]
CNS:
- Reduced memory
- cortical atropy
- fits & falls
- wide based gait (cerebellar dysfunction)
- Korsakoffs (memory disorder that results from vitamin B1 deficiency and is associated with alcoholism)
- W.Enceph.
What are signs & symptoms of alcoholism associated with the gut [5]
- Obesity
- D&V
- Gastric erosions
- varices
- oesoph. rupture
- Boerrhave syndrome (transmural tear of oesophagus due to vomiting)
What are signs & symptoms of alcoholism associated with the blood [3]
- Increased MCV: non-megaloblastic macrocytic anaemia
- anaemia from marrow depression
- Folate deficiency: decreased intake; inhibits folate absorption
What are signs & symptoms of alcoholism associated with the heart [4]
- increased BP:decreasing the vasodilators such as NO in the vascular endothelium either due to inhibition of endothelial nitric oxide synthase (eNOS) or inflammatory/oxidative injury to the endothelium.
- arrythmias: can trigger atrial fibrillation
- cardiomyopathy
- sudden death in binge drinkers
What are signs & symptoms of alcoholism associated with reproduction [4]
- testicular atrophy
- decreased testosterone and progesterone
- increased oestrogen
- fetal alcohol withdrawal
Describe the three HIT hypothesis for the pathogenesis of alcohol related liver injury:
Metabolic:
- alcohol
- obesity
- insulin resistance
Inflammatory:
- translation of lipid signal in inflammation (chemokines / cytokines / kupffer ells / endothelial cells & gut microbiota all contribute to inflammatory cascade)
Genetic disturbance of lipid metabolism:
- PNPLA3
- TM6SF2
- MBOAT7
Give a basic overview of the metabolism of alcohol [2]
Describe why this is clinically significant [1]
Metabolism:
- Alcohol is metabolised to acetaldehyde via alcohol dehydrogenase
- Cytochrome P450 2E1 (CYP2E1) also converts alcohol to acetaldehyde (and this enzyme tends to be up-regulated in heavy alcohol consumers). This reaction results in oxidative damage to hepatic tissue
Significance:
- Acetaldehyde is a highly reactive, toxic metabolite: carcinogenic so increases risk of hepatocellular carcinoma
Which score is used to calculate risk of alcohol dependence? [1]
AUDIT
Describe the treatment plan for alcohol withdrawal [2]
Benzodiazapenes:
- Chlordizepoxide: give for 1st 3D 10-50mg/6hrs, then plan on weaning
- Lorazepan (for patients with underlying cirrhosis)
What type of diet should be provided to patients of alcoholic hepatitis? [3]
A high protein diet should be instituted: use NG feed if need
Vitamins:
* Vitamin K
* Thiamine (can give Pabrinex
Describe the different symptoms for alcohol withdrawal symptoms for the following time periods:
6-12 hours: [1]
12-24 hours [1]
24-48 hours: [1]
24-72 hours: [1]
6-12 hours: tremor, sweating, headache, craving and anxiety
12-24 hours: hallucinations
24-48 hours: seizures
24-72 hours: delirium tremens
Explain why alcohol withdrawal syndrome can lead to mortality [2]
Chronic alcohol use results in the GABA system becoming down-regulated and the glutamate system becoming up-regulated to balance the effects of alcohol
When alcohol is removed, the GABA system under-functions and the glutamate system over-functions, causing extreme excitability of the brain and excessive adrenergic (adrenalin-related) activity
How does NAFLD present? [4]
Most are asymptomatic and the condition is often discovered incidentally during routine blood tests or imaging studies.
Patients may present with non-specific symptoms such as:
* fatigue
* malaise
* right upper quadrant discomfort (~50%)
- Hepatomegaly
NAFLD is associated with which syndrome? [1]
Metabolic syndrome, which is a combination of hypertension, obesity and diabetes.
Metabolic syndrome is common and dramatically increases the risk of cardiovascular disease and other health problems.
Describe which tests may pick up that somone has NAFLD [6]
- Often no clinical markers until cirrhosis
- ALT/AST > 1
- Liver ultrasound can confirm the diagnosis of hepatic steatosis (fatty liver), seen as increased echogenicity. (Ultrasound does not indicate the severity, function of the liver or presence of fibrosis. It can be normal in NAFLD)
- Enhanced liver fibrosis (ELF) blood test is the first-line investigation for assessing fibrosis in non-alcoholic fatty liver disease.
NAFLD Fibrosis Score (NFS) is another option for assessing liver fibrosis in NAFLD. It is based on an algorithm of age, BMI, liver enzymes (AST and ALT), platelet count, albumin and diabetes.
Fibrosis 4 (FIB-4) score is another option for assessing liver fibrosis in NAFLD. It is based on an algorithm of age, liver enzymes (AST and ALT) and platelet count.
Transient elastography (“FibroScan”) can be used to assess the stiffness of the liver using high-frequency sound waves. It helps determine the degree of fibrosis (scarring) to test for liver cirrhosis. It is used where the enhanced liver fibrosis (ELF) test indicates advanced fibrosis.
TOM TIP: Both the NFS and FIB-4 scores use the AST:ALT ratio to assess the severity of liver fibrosis.
The normal ratio is []/
A ratio [] in NAFLD suggests advanced fibrosis
. An AST:ALT ratio [] indicates alcohol-related liver disease rather than NAFLD.
TOM TIP: Both the NFS and FIB-4 scores use the AST:ALT ratio to assess the severity of liver fibrosis.
The normal ratio is less than 1.
A ratio greater than 0.8 in NAFLD suggests advanced fibrosis.
An AST:ALT ratio greater than 1.5 (meaning a disproportionately high AST) indicates alcohol-related liver disease rather than NAFLD.
Name 3 drugs that are associated with increasing risk factor for NAFLD [3]
Name a surgery that is associated associated as a risk factor for NAFLD [1]
Describe nutrition that is associated with increasing risk factor for NAFLD [2]
Drugs:
- Steroids
- Amiodarone
- Methotrexate
Weight reducing surgery:
- jejuno-ileal by pass
Nutrition
* Protein calorie malnutrition & TPN
Describe the treatment algorithm for NAFLD [6]
- Weight loss: diet & exercise
- Consider vitamin E
- Consider pioglitazone (reduces peripheral insulin resistance)
- Consider weight loss medication: orlistat
- Consider bariatric surgery if BMI > 35 and one other obesity co-morbid / BMI > 40.
- Liver transplant
BMJ BP
Diagnosis of NAFLD? [3]
The diagnosis requires the presence of
- ultrasound findings of a fatty liver
- risk factors
- excluding other causes of liver disease with a careful alcohol history and full non-invasive liver screen.
- Liver biopsy is the gold standard test.
Viral hepatitis:
- Which viruses cause acute hepatitis [2]
- Which viruses cause chronic hepatitis [3]
Acute:
- Hepatitis A
- Hepatitis E
Chronic:
- Hepatitis B
- Hepatitis C
- Hepatitis D
Which hepatitis viruses are transmissable via faecal-oral routes? [2]
Which hepatitis viruses are transmissable via bodily fluids ? [3]
Faecal-oral::
- Hepatitis A
- Hepatitis E
Bodily fluids::
- Hepatitis B
- Hepatitis C
- Hepatitis D