Normal liver physiology Flashcards
What is the blood supply to the liver?
Hepatic portal vein (SMV, IMV and Splenic Vein) Hepatic artery (from Coeliac Trunk)
What are the key functional zones of the liver?
Zone 1 - periportal hepatocytes (outermost and most oxygenated) - specialise in oxidative metabolism, gluconeogenesis and urea synthesis
Zone 3 - pericentral hepatocytes - specialise in drug metabolism, glycolysis and lipogenesis
What are sinusoids?
Vascular spaces running between plates of hepatocytes
Lined with epithelial cells
Are are the major cell types of the liver?
Hepatocytes
Cholangiocytes
Reticuloendothelial cell meshwork (made up of endothelial cells, Kupffer cells and lipocytes)
What is the function of cholangiocytes?
Line bile duct and secrete bicarbonate ions and water into the bile
What is the function of endothelial cells in the reticuloendothelial cell meshwork?
Line sinusoids
What is the function of Kupffer cells in the reticuloendothelial cell meshwork?
Immune cells anchored to the walls of sinusoids
Phagocytose bacteria and ingest inflammatory mediators
What is the function of lipocytes in the reticuloendothelial cell meshwork?
Found in space of Disse (between hepatocyte plate and sinusoid)
Storage of fat
What cells are affected in Cirrhosis?
Lipocytes - secrete collagen affecting structure of liver
What are the major functions of the liver?
DESPICES:
Drug metabolism and detoxification Energy metabolism and substrate interconversion Synthesis of plasma proteins Production of bile Immune functions Cholesterol processing Excretion of bilirubin Storage of vitamins and minerals
What molecules are metabolised for energy in the liver?
Carbohydrates (glycogenolysis, gluconeogenesis, glycogen synthesis, glycolysis)
Lipids (ketogenesis, triglyceride synthesis from fatty acids)
Proteins (deamination, urea formation)
What is the major plasma protein and its function?
Albumin
Able to carry various proteins and maintain osmotic pressure of plasma
Transports molecules in blood
What factors are synthesised in the liver for haemostasis and fibrinolysis?
Fibrinogen (for coagulation)
Alpha-1 antitripsin (coagulation inhibitor)
Plasminogen (fibrinolysis)
What carriage/ binding proteins are synthesised in the liver?
Transferrin (carries iron)
Sex hormone binding globulin
Thyroid-binding globulin
What are apolipoproteins?
Synthesised in liver
Bind lipids to form lipoproteins for transportation of lipids through lymphatic and circulatory systems
Where does cholesterol come from?
15% from diet
85% synthesised in body
What vitamins and minerals are stored in the liver?
Fat soluble vitamins: A, D, E, K
Minerals: Iron, Copper
How is bilirubin excreted?
Conjugated with glucoronic acid by hepatocytes to allow it to be exported into bile
What is bilirubin?
Bile pigment formed from the breakdown of red blood cells into haem in the spleen and bone marrow
Where is bile produced and stored?
Produced in liver
Stored in gallbladder (where water and salts are drawn out to increase concentration)
How much bile is secreted per day?
0.7-1.2 litres
What are the 6 major components of bile?
- Bile salts
- Lecithin
- Bicarbonate ions
- Cholesterol
- Bile pigments
- Trace metals
What are the functions of bile salts?
Conjugated to taurine to increase solubility (become conjugated bile salts)
Exported down bile canaliculus to be excreted
Work to emulsify and digest fats in small intestine
What is the fate of bile salts?
95% returned to liver via portal circulation
5% excreted in faeces
What happens to the bile salts that are returned to the liver?
75% recycled as intact bile salts
25% deconjugated by bacteria in the terminal ileum and colon
What forms the portal vein?
Superior mesenteric vein
Splenic vein
What functions of the liver can malfunction in hepatobiliary diseases?
- Filter failure
- Elimination failure
- Metabolic failure
How can filter failure manifest?
Portal hypertension (can cause bleeding)
How can elimination failure manifest?
Jaundice (due to inability to remove bile)
How can metabolic failure manifest?
Acidosis, muscle loss, coagulopathy, hepatorenal syndrome
What occurs when there is a combination of filter, elimination and metabolic failure?
Encephalopathy
What are some key signs of chronic liver disease?
Clubbing Ascites Spider Naevi Palmar erythema Dupuytren's contracture Gynaecomastia Jaundice Oedema Splenomegaly
What are the common causes of pancreatitis?
[I GET SMASHED]
Idiopathy Gallstones Ethanol Trauma Steroids Mumps/ malignancy Autoimmune Scorpion bites Hyperlipidemia, hypercalcaemia, hyperparathyroidism ERCP Drugs
What are the common causes of liver injury?
Fat (non-alcohol fatty liver disease, non-alcohol steatohepatitis)
Alcohol
Virus
Iron
What blood tests can be done to assess liver damage?
ALT/ AST (enzymes secreted by hepatocytes - elevated if damage)
Alk Phos/ yGT (test for bile duct damage - elevated if damage)
What are ‘true’ tests of liver function?
Prothrombin Time Bilirubin Albumin Urea/ Creatinine pH
What imaging can be used to assess liver damage?
Ultrasound
CAT
MRI
Liver fibroscan (looks for elasticity of liver)
What investigations are typically used to identify gallstones?
Ultrasound
No changes in blood test results
What would raised bilirubin and Alk phos levels indicate?
Biliary obstruction
What would differ in blood test results between acute and chronic pancreatitis?
Acute - raised amylase
Chronic - none
How is cholesterol transported in the body?
Complex with lipoproteins
What is the role of the liver in cholesterol processing?
Synthesises cholesterol from Acetyl CoA
Synthesises lipoproteins (used for cholesterol transport)
Exports cholesterol to body cells for synthesis of key products (e.g. steroid hormones)
Synthesis of bile salts
Extracts excess cholesterol from plasma
Exports excess cholesterol into bile for excretion in faeces
How does cholesterol aid in bile salt formation?
Broken down into primary bile salts and conjugated with Taurine to form conjugated bile salts which enters bile canaliculus
What hormones are involved in bile production and secretion?
Cholecystokinin (CCK) - secreted by the duodenum, stimulates secretion of bile (by stimulating contraction of gallbladder) and secretion of enzymes from the exocrine pancreas
Secretin - secreted by the duodenum (especially in response to acidity), stimulates production of bile in the liver and secretion of bicarbonate ions from the pancreas
