Liver Failure and Jaundice Flashcards
When is jaundice detectable?
When serum bilirubin is >50 micro mol/L.
How is bile mainly produced?
From Hb breakdown in the spleen.
Explain bilirubin metabolism
- Unconjugated bilirubin bound to albumin and travels to liver.
- Glucuronyl transferase conjugates bile into bilirubin glucuronide, which makes bile water soluble.
- Bilirubin glucuronide excreted to duodenum. Bacteria in the gut degrade bilirubin glucuronide into urobilinogen or stercobilinogen (both water soluble).
- Some urobilinogen reabsorbed and excreted by kidneys. Some converted to stercobilinogen.
- Stercobilinogen (majority) oxidised to stercobilin in GI tract.
- 10% stercobilin reabsorbed and returns to liver via portal circulation.
How are bile salts reabsorbed from portal circulation into the liver?
Via an active transport mechanism.
What % of bile salts are old and recycled?
95%
What are the 3 types of Jaundice?
- Haemolytic - haemolytic anaemias (e.g. SCD - more RBC breakdown). Increased serum urobilinogen but otherwise normal liver biochemistry.
- Congenital - impaired conjugation of bilirubin with glucuronic acid/inappropriate handling of bilirubin. Raised bilirubin, otherwise normal.
- Cholestatic - failure of bile secretion by the liver/bile duct obstruction.
Does unconjugated bilirubin pass into urine?
No
Gilberts syndrome is a form of congenital jaundice. Explain
Autosomal dominant.
UDP-glucuronyl transferase mutation, less conjugation of bilirubin.
Differentiate intrahepatic cholestasis and extra hepatic cholestasis
Intrahepatic cholestasis = hepatocellular swelling/abnormalities at a cellular level of bile secretion
Extrahepatic cholestasis = obstruction of bile flow distal to bile canaliculi. Charcterised by pale stool and dark urine.
Which proteins are not synthesised in the liver?
Gamma globulins
4 functions of the liver
- Synthesis/metabolism of protein
- Blood sugar maintenance
- Lipid metabolism
- Metabolism, excretion of bilirubin and bile acids
What are the 2 most common causes of liver disease?
Alcohol
Non-alcoholic fatty liver disease
In the developing world, chronic viral hepatitis B and C are the commonest
What are the symptoms of liver disease?
Lethargy Anorexia Malaise Pruritus (itchy skin) RUQ pain
Later on: Peripheral swelling Abdominal bloating Bruising Vomiting blood Confusion/somnolence
What are some signs of liver disease
- Jaundice
- Spider naevi
- Loss of body hair
- Gynaecomastia
- Testicular atrophy
- Palmar erythema
- Xanthelasma
- Finger clubbing
- Dupuytrens contracture
- Ascites
- Hepato(/spleno)megaly
- Caput medusa
- Oedema
- Weight loss
What is cirrhosis?
Often final common pathway for liver disease.
Necrosis of liver cells, then fibrosis and nodule formation. Leads to portal hypertension
What are the causes of cirrhosis?
Alcohol
Hep B/C
Develops in response to chronic liver injury
What are the 2 types of liver cirrhosis?
Micronodular - uniform, small nodules. Ongoing alcohol damage/biliary tract disease
Macronodular - often following viral chronic hepatitis.
(can also be mixed)
When does acute liver failure occur?
Massive loss of hepatocytes.
“Severe hepatic dysfunction occurring within 6 months of onset of liver disease symptoms. Clinical manifestation is hepatic encephalopathy or coagulopathy”
What are the 3 classes of acute liver failure?
- Hyperacute - 1 week of jaundice onset
- Acute - 8-28 after jaundice
- Subacute - 5-12 weeks after jaundice
What are the clinical features of acute liver failure?
- JAUNDICE
- CNS complications
- Renal failure - v lethal
- Sepsis - v common
- CVS complications - HF / hypotension
- Metabolic complications - hypoglycaemia and hypoxia
What roles does the liver play in coagulation?
- Synthesis of coagulation factors. Factor V affected first, factor 7 declines first due to short half life.
- Inhibition of fibrinolysis
- Clearance of activated coagulation factors
- Absorption of vitamin K
3 signs of coagulation defect?
Bleeding
Oozing at venipuncture sites (excessive fibrinolysis)
Bruising
Chronic liver failure - when?
Deterioration in liver function superimposed on chronic liver disease.
