05 Liver Failure And Jaundice Flashcards
What are the functions of bile
Cholesterol Homeostasis
Absorption/emulsification of fat and fat soluble vitamins
Removal of xenobiotics(steroid hormone/cholesterol metabolites)
How much of bile is produced a day and what percentage of bile is secreted in the 2 types of bile secreting cells
500 ml/day
Hepatocytes: 60%
Cholangiocytes: 40%
What is the role of biliary tree/cholangiocytes
Secretion of
- HCO3-, Cl- and water
- IgA antibody
Absorption of
1. Glucose and organic acids
What are the transporters on cholangiocytes and what do they do
BSEP (bile salt excretory pump) - secretes bile
MRP-1 and 3
FIC1 (familial intrahepatic cholestasis gene)
MDR-1 and 3 - MDR-1 secretes xenobiotics and MDR-3 translocates phosphatidylcholine from inner to outer leaflet
Name primary and secondary bile salts and explain how they are converted between the two.
Differentiate their reabsorption pattern in the GI tract
Cholic acid and chenodeoxycholic
Deoxycholic and lithocholic acid
Primary bile salt is converted to secondary bile salt in the colon by commensal bacteria
Lithocholic acid is 99% not reabsorbed whereas deoxycholic is reabsorbed
List the functions of bile and explain how the micelle forms
Reduce surface tension of fat
Emulsifies fat/fat soluble vitamins to increase surface area for absorption
bile is amphipathic with hydrophilic end on the outer side and the hydrophobic part on the inner side together with cholesterol and fatty acid and fat soluble vitamins. Then it is transported to GIT epithelial cells for absorption
Describe how bile is released after food intake
Nutrients (FA > AA > CHO) enter duodenum causes the release of CCK and this causes the contraction of the gall bladder and the release of Sphincter of Oddi to allow bile into the duodenum
Describe enterohepatic circulation of bile salts
Bile salts are released into the duodenum and 95% of them is reabsorbed in terminal ileum by Na+/bile symporter. 5% of them is converted to secondary bile salts where lithocholic acid is mostly excreted via faeces.
Describe the process of the removal of bilirubin
75% of bilirubin comes from degradation of haemoglobin from spleen. 22% from other haem proteins and 3% from failure of erythropoiesis. Bilirubin binds to albumin to go to the liver and become conjugated to glucoronic acid by UDPGT. This is then released into the duodenum. In the gut, glucoronic bilirubin is degraded in the gut and bilirubin is converted to urobilinogen and maybe further into stercobilinogen. Some urobilinogen is reabsorbed and excreted in the kidneys. 10% of stercobilinogen is reabsorbed and return to the liver. The rest can be oxidised in the gut into stercobilin and gives the brown colour of faeces
What are the causes of pre-hepatic jaundice
Haemolysis
Massive transfusion
Failure of erythropoesis
Haematoma resorption
What is the clinical finding of the unconjugated bilirubin level of patient with pre-hepatic jaundice
Increased
What are the causes of hepatic jaundice
Defective conjugation
Defective excretion
These can arise as a result of liver failure
What is the clinical finding of a patient with hepatic jaundice
Increased bilirubin and urobilinogen levels in the urine
What are the causes of obstructive/post-hepatic jaundice
Pancreatic cancer and gall stone (cholelithiasis)
Describe what is Gilbert’s Syndrome in terms of its hereditary pattern, causes, symptoms and treatment
It can be both autosomal recessive and dominant disease depending on the mutation. The mutation causes reduced activity of UDPGT by 70-80%. Patient normally does not experience jaundice, except certain situations such as stress, fasting, infection and exertion. No treatment needed, provide reassurance to the patient
Define acute liver failure
Severe hepatic dysfunction occurring within 6 months of the onset of symptoms of liver disease, with a clinical manifestation of hepatic encephalopathy or coagulopathy
What are the 3 classifications of acute liver failure and how are they differentiated
Hyperacute: when encephalopathy occurs within 7 days of onset of jaundice
Acute: when encephalopathy occurs after 8-28 days of jaundice
Subacute: when encephalopathy occurs 5-12 weeks after the onset of jaundice
What are the clinical features of acute liver failure
Central nervous system complications - encephalopathy
CVS complications due to reduced TPR
Metabolic complications: hypoglycaemia
Renal failure
Sepsis: without fever and leukocytosis
Coagulopathy: due to 1) failure of the synthesis of coagulatory factors, 2) reduced inhibition of anticoagulatory proteins such as Protein C and S
Define chronic hepatic failure
Deterioration in liver function superimposed on chronic liver disease
What is the main cause of liver disease
Western: alcohol and drugs (paracetamol)
Developing world: hepatitis B and C virus
What are the common symptoms of liver disease
Malaise Lethargy Anorexia Pruritis - itchy skin Upper right quadrant pain
It can further develop into:
- Peripheral oedema
- Abdominal bloating
- Bruising
- Vomiting blood
- Confusion
What are the signs of liver disease
Jaundice Spider naevi Loss of body hair Gynaecomastia Testicular atrophy Palmer erythema
What are the other signs of chronic liver disease
Xanthelasma Finger clubbing Caput medusa Pruritis Dupuytren’s contracture Ascites Hepatomegaly Bruising Weight loss Oedema
What is cirrhosis and what does it develop from
It is characterised by necrosis of liver cells with progressive fibrosis and nodule formation which lead to a change in morphology, cellular function and portal hypertension.
It develops from chronic liver injury
Histologically, what are the two types of cirrhosis
Micronodular: uniform, small (< 3mm) nodules caused by alcohol
Macronodular: variable size caused by viral hepatitis
