W.9: Liver diseases Flashcards
What is the weight of the human liver?
1-1,5kg
How much of the cardiac output does the liver get?
25%
Which substance gets excreted through the liver?
Copper
What happens to bilirubin in the liver?
It gets conjugated with glucoronic acid
A condition that is NOT known to be caused by liver disease?
High blood pressure
How many percent of the blood supply to the liver goes through the hepatic a.?
20% (systemic, oxygenated)
How many percent of the blood supply to the liver goes through the portal vein?
80% (rich in nutrients, deoxygenated)
Exocrine function of the liver
- Bile production
- Excretion of cholesterol, bilirubin, copper
- Emulsification of fat
Characteristic for zone 1 of the liver (outer)
- Good oxygenation
- Metabolism: gluconeogenesis, urea cycle
- Sensitive to: direct toxins
Characteristic for zone 3 of the liver (inner)
- Poor oxygenation
- Metabolism: Glycolysis, lipogenesis
- Sensitive to: Secondary toxins (toxins that the liver produces itself), circulatory problems, biliary obstruction
What are the macrophages of the liver called?
Kupffer cells (80% of all tissue macrophages)
Filtration of the blood of the splanchnic bed
- Filtration of microbes, immunogenic materials
- Biotransformation
- Temporary storage of materials (not lipids)
Filtration of systemic blood
Excretion, synthesis, metabolism
Phases of biotransformation
- Activation: Apolar substance absorbed and gets activated to a reactive substance by cytochrome P450
- Increase of polarity: Reactive, active substance is transformed to a polar substance (eg. via conjugation with glucuronic acid, glutathione or methylation)
What can happen with biotranformation eg. in the case of alcohol abuse?
The two phases can be unsynchronized, phase 1 can become faster than phase 2 and leads to increased toxicity (reactive substances that will damage the liver)
Metabolic consequences of liver diseases: Carbohydrates
- Postprandial hyperglycemia
- Hypoglycemia after prolonged fasting in alcoholics
Metabolic consequences of liver diseases: Proteins
- Decrease in albumin and coagulation factors (albumin only produced in the liver)
- Hepatic coma
Metabolic consequences of liver diseases: Lipids
Fatty liver
Clinical signs of liver diseases
- Nausea, temp., fatigue
- Palpable, tender liver, splenomegaly
- Jaundice, palmar erythema, spider naevi, excorations, less body hair
- Bleeding tendency
- Confusion, coma
What are the symptoms of portal hypertension?
- Ascites
- Caput Medusae
- Esophageal varices
Causes of aquired parenchymal liver diseases
- Toxic effects: Alcohol, mushroom, drugs
- Infections (hepatotropic and other viruses)
- Autoimmune disorders
Causes of congenital parenchymal liver diseases
- Inherited hyperbilirubinemias
- Other genetic syndromes (eg. hemochromatosis, Wilson’s disease)
When do we use the CAGE test?
To find out if someone is an alcoholic
CAGE test - What does the letters stand for?
- Have you felt the need to Cut down on your drinking?
- Have you ever felt Annoyed by criticism of your drinking?
- Have you had Guilty feelings about drinking?
- Do you ever take a morning Eye opener (a drink first thing in the morning to steady your nerves or get rid of a hangover)?
Systemic biochemical consequences of alcohol intake
Lactate acidosis (-> plasma uric acid increase)
Cytosolic biochemical consequences of alcohol intake
Inhibition of gluconeogenesis (-> fasting hypoglycemia)
Mitochondrial biochemical consequences of alcohol intake
- Inhibition of the citrate cycle
- Inhibition of beta-ox. of fatty acids (-> statosis)
Threshold dose for liver injury in case of alcohol
Men: 60-80g/day over years
Women: 20-40g/day
Why is the alcohol threshold for liver disease lower in woman than in men?
Because the alcohol dehydrogenase activity of the stomach is less in women than in men
Most common cause of severe acute liver injury?
Paracetamol poisoning
There exists a vaccine against which hepatitis types?
HAV, HBV, HDV, HEV
A vaccine does not exist for which type of hepatitis?
HCV
Route of infection: HAV
Fecal-oral
Route of infection: HBV
Percutaneous, perinatal, sexual
Route of infection: HCV
Percutaneous
Route of infection: HDV
Percutaneous, perinatal, sexual
Route of infection: HEV
Water
Can hepatitis caused by HAV and HEV become chronic?
No, never
How many of the cases of hepatitis caused by HCV becomes chronic? (%)
50-70%
Can hepatitis caused by HCV be cured?
Yes, effective drugs exist and can cure most cases, but the therapy is really expensive
What causes chronic hepatitis?
Virus, drugs or autoimmune diseases
Hepatic cirrhosis leads to
Progressive, irreversible destruction of liver parenchyma
What causes liver cirrhosis?
Alcohol (Laennec cirrhosis), NASH, chronic infection, biliary obstruction, congestion, inherited metabolic desease
What does NAFLD stand for and how common is it?
Non-alcoholic fatty liver, 30% of the population
NAFLD can progress to …? In how many percent of the cases?
NASH (non alcoholic steatohepatis) in around 10% in 10 years
NASH can progress to…? In how many percent of the cases?
Cirrhosis in around 10% of the cases in 10 years
Cirrhosis can progress to
HCC (hepatic carcinoma)
Prevention of NASH
Slow, mild weight reduction and increasing physical activity
Consequences of liver cirrhosis
Destruction of cells, fewer microvilli, fibrosis, capillarization
Clinical consequences of cirrhosis: Portal hypertension
- Esophageal varices, bleeding
- Splenomegaly, hypersplenia
- Spontanous bacterial peritonitis
- Ascites
- Hepatic encephalopathy
Clinical consequences of cirrhosis: Loss of parenchyma
- Ascites
- Hepatic encephalopathy
- Bleeding tendency
- Hypalbuminemia
Clinical consequences of cirrhosis: Other
- Hepatorenal syndrome
- Hepatocellular carcinoma
Why is bleeding from esophageal varices dangerous?
Because the pressure is high, it is difficult to access, the patient may have a bleeding tendency, the protein getting into the stomach may trigger the development of hepatic coma
What is caput medusae?
Dilation of the periumbilical veins
What are the two main factors playing a role in the development of ascites?
Decreased albumin synthesis and increased portal pressure
Major factor in the development of hepatic encephalopathy
Insufficiency of the urea cycle in the liver
Hepatorenal syndrome
- Renal failure developing as a result of hepatic insufficiency with unknown cause
- Kidneys sense severe hypovolemia, no parenchymal damage in the kidneys so they can be successfully transplanted
