Alimentary System 7 - Jaundice and liver failure Flashcards
What percentage of bile is water?
97%
How much bile is produced daily, and where is it produced?
- 500ml produced daily
- 60% hepatocytes
- 40% cholangiocytes
How to cholangiocytes affect bile composition?
- Alter pH, fluidity, and modify bile
- Water drawn in
- Bicarbonate and chloride secreted into bile
- Cholangiocytes introduce IgA by exocytosis
What moleules control bile flow and excretion of salts and toxins?
- Biliary transporters
- Bile salt excretory pump
- MDR related proteins
- Products of familial intrahepatic cholestasis gene and multidrug resistance gene
What is the function of the bile salt excretory pump (BESP)?
- Active transport of bile acids into the bile
- Major determinant of bile flow
What is the function of MDR related proteins?
- MDR1 mediates excretion of xenobiotics and cytotoxins
- MDR 3 encodes a phospholipid transporter protein that translocates phosphatidylcholine from the inner to outer leaflet of the canalicular membrane
What are the two primary bile acids?
- Cholic acid
- Chenodeoxycholic acid
How are secondary bile acids formed? List the two main acids.
- Formed by conversion of primary acids via colonic bacteria
- Cholic acid produces deoxycholic acid
- Chenodeoxycholic acid forms lithocholic acid
What are bile salts?
Sodium and potassium salts of bile acids to glycine and taurine
List the functions of bile salts
- Reduce surface tension of fats
- Emulsify fat to prepare for digestion and absorption
- Form micelles
Describe the composition of micelles
- Hydrophilic domains face out
- Hydrophobic domains face in with free fatty acids and cholesterol inside
What is the issue with bile salts?
They are cytotoxic in high concentrations
List the pathway taken by bile in the biliary system
- Produced in liver
- Right+left hepatic duct form common hepatic duct
- Enter the cystic duct to be stored in the gall bladder
- Cystic duct unites with the common hepatic duct to form the common bile duct
- Common bile duct joins with pancreatic duct to form ampulla of Vater
How is bile flow regulated?
- Eating causes the sphincter of Oddi to relax
- This is due to cholecystokinin
- Cholecystokinin also causes the gall bladder to contract
Describe the circulation of bile salts between the stomach and liver
- Called enterohepatic circulation
- Bile salts travel to the GIT then back to the liver via blood, and the cycle continues
- This also happens with some drugs present in the bile, and can prolong the action of drugs
What happens to the bile salts that are not absorbed by the ileum?
- 95% absorbed - 5% enter the colon and form secondary bile ducts
- Deoxycholate is absorbed
- Lithocholate is excreted in the stool
How are bile salts absorbed in the ileum?
Using a sodium/bile salt co-transporter system with the sodium/potassium pump
What happens to bile salts in terminal ileal resection or disease?
- Decreased bile salt reabsorption, and increased bile in the stool
- This is because enterohepatic circulation is interrupted
What happens if bile is stopped from entering the gut?
- Malabsorption of fat soluble vitamins (ADEK)
- 50% ingested fat appears in faeces
List the functions of the gall bladder
- Stores bile
- Acidifies bile
- Concentrates bile (absorption of ions), reducing volume by 80-90%
What are the effects of cholecystectomy?
- Gall bladder is removed
- Digestion is mostly functional, but foods with high fat content need to be avoided
What is bilirubin?
A water insoluble yellow pigment
List the ways bilirubin is made and their relative proportions
- 75% haemoglobin breakdown (spleen)
- 22% catabolism of other haem proteins
- 3% ineffective bone marrow erythropoiesis
Describe the pathway taken by bilirubin to the gut
- Bound to albumin from the spleen
- Travels to the liver and dissociates
- Conjugated to glucoronic acid by UDPGT to form diglucoronic acid
- Transported into bile canaliculi to the GIT
What does total bilirubin equal?
conjugated + unconjugated bilirubin
What are urobilinogens and where are they formed?
- Water soluble colourless derivatives of bilirubin formed by action of GIT bacteria
- Mainly formed in the intestines and reabsorbed to be excreted in the kidney
What is GIT mucosa permeable to with relation to bilirubin?
- Permeable to unconjugated bilirubin and urobilinogens
- Impermeable to conjugated bilirubins
How is urobilinogen excreted in the stool?
- As stercobilinogen
- Oxidised to sercobilin which makes faeces brown
What is jaundice?
- A disease characterised by yellowing of the eyeballs (first) and the skin
- Can be caused by cholestasis (slow bile flow) and resulting buildup of bilirubin in the blood
- Bilirubin over 40-50microM/L
List the causes of prehepatic jaundice
- Haemolysis
- Massive Transfusion
- Haematoma resorption
- Ineffective erythropoiesis
List the causes of hepatic jaundice
- Defective uptake, conjugation or bilirubin excretion
- Caused by liver failure (acute/chronic)
List the posthepatic causes of jaundice
- Defective transport due to blockage of the biliary duct system
- Bile duct stones
- Malignancy
- Causes pale faeces due to decreased sercobilin and darker urine
How can the three types of jaundice be distinguished?
- Post hepatic will have high conjugated bilirubin and dilated bile ducts
- Pre/hepatic jaundice have high unconjugated bilirubin, so ask about history of liver function to distinguish
What is Gilberts syndrome?
- Commonest hereditory cause of jaundice
- Relatively asymptomatic except in times of stress
- Affects 5% of the population
- Caused by a reduction in activity of the UDPGT enzyme
What is liver failure?
When the rate of hepatocyte death is higher than rate of regeneration
Compare acute and chronic liver failure
- Acute caused by paracetamol, as well as some diseases of pregnancy
- Chronic caused by viral hepatitis, alcohol excess, and autoimmune diseases
List the consequences of hepatocyte failure
- Encephalopathy and cerebral oedema
- Hypoglycaemia
- Bleeding
- Increased suseptability to infection
- Renal failure
What are the issues with liver transplants?
- 10% mortality in 1 year
- Lifelong immunosuppression
- Expensive
- Lack of donors
List the early symptoms of liver disease
- Lethargy
- Anorexia
- Malaise
- Pruritus (itchy skin)
- Right upper quadrant pain
List the late symptoms of liver disease
- Peripheral swelling
- Abdominal bloating
- Bruising
- Vomiting of blood
- Confusion and somnolence
List the physical signs of liver disease
- Jaundice
- Gynaecomastia, testicular atrophy
- Spider naevi
- Loss of body hair
- Palmar erythema
- Xanthelasma
- Finger clubbing
- Ascites
- Oedema
Define liver cirrhosis
- Necrosis of liver cells followed by progressive fibrosis and nodule formation
- Leads to impairment of liver cell function, and distortion of the liver architecture
List the common causes of cirrhosis
- Alcohol (western world)
- Hepatitis B and C world wide
- Response to chronic liver injury
Compare the two types of cirrhosis
- Micronodular (uniform, small nodules up to 3mm in diameter, caused by ongoing alcohol damage)
- Macronodular cirrhosis (varying size, seein in hepatitis)
- Can be mixed
Define acute liver failure
Severe hepatic dysfunction occuring within 6 months of the onset of symptoms of liver disease
Describe the classification of acute liver failure
- Hyperacute is where encephalopathy occurs within 7 days of jaundice
- Acute is 8-28 days after jaundice
- Subacute is 5-12 weeks after onset of jaundice
List the clinical features of acute liver failure
- CNS complications (hepatic encephalopathy)
- Jaundice
- Coagulopathy (bleeding and easy bruising)
- Renal failure
- Sepsis
- Cardiovascular complications
- Metabolic complications
Define chronic liverfailure
- Deterioration in liver function superimposed on chronic liver disease
- Also called decompensation
