Liver Function 1 Flashcards
Describe the liver
Largest solid organ Protected by ribs RUQ Diaphragm ‘roof’ 2, 4 lobes, 8 segments Hepatic artery, portal vein, hepatic veins, bile duct
Which ligament runs between the right and left lobes of the liver?
Falciform ligament
Which ligament is at the end of the falciform ligament?
Round ligament
What cells make up the liver?
Hepatocytes (60%) Kupffer cells (30%) Stellate Cells Endothelial cells Biliary epithelium
What is the role of hepatocytes?
Hepatocytes are involved in synthesizing protein, cholesterol, bile salts, fibrinogen, phospholipids and glycoproteins.
They ensure that our blood coagulates so we don’t bleed to death, that cell communication s good and that we are able to carry fats in the bloodstream.
Other functions of the hepatocytes include the transformation of carbohydrates (from alanine, glycerol and oxaloacetate), protein storage, start of the formation and secretion of bile and urea, and detoxification and excretion of substances.
Thanks to these main cells, we are able to fight off disease, produce waste, transport materials throughout the body and process everything from drugs and insecticides to steroids and pollutants.
What is the role of liver endothelial cells?
Since they do not have tight membranes, these cells act as “scavengers” of nearby cells - collecting and circulating hepatocytes in the blood, for instance.
Responsible for transporting white blood cells and other material from the blood to the liver and for increasing the immune system’s tolerance of the liver.
They can absorb ligands, which serve as biological markers and binders for pharmaceutical drugs. When stimulated, endothelial cells secrete cytokines, which is a form of cellular communication signal.
What is the role of Kupffer cells?
Kupffer cells are located within the sinusoidal lining of the liver and hold a quarter of the liver lysosomes.
The lysosomes digest and dispose of dying cells, unnecessary proteins, bacteria and foreign microbes. If stimulated, kupffer cells secrete mediators of the immune response system, and they can perform a complex array of functions–from disarming foreign substances to removing damaged red blood cells from circulation.
In a way, the kupffer cells are like bodyguards and assassins for the hepatocytes, protecting them from invaders and cell refuse.
What is the role of hepatic stellate cells?
The livers reserve army.
Most of the time, this 5 to 8 percent of the liver’s cells just sit around in an inactive “quiescent” state, storing vitamin A and a number of important receptors.
When activated (by an event like liver injury), the cell promotes ion movement, the production of antibodies, genesis of natural killer T-cells and the proliferation of chemical responses to stress.
Researchers believe that hepatic stellate cells play a key role in releasing collagen scar tissue and encouraging liver scarring.
What is bile?
Green/yellow fluid made up of water, electrolytes and organic molecules (bilirubin, bile acids, phospholipids and cholesterol)
What do epithelial cells in the bile ducts secrete?
Water and bicarbonate
How is bile secreted?
Bile is secreted by hepatocytes Through canaliculi Small ducts Left/right hepatic duct Common hepatic duct Common bile duct
What are the functions of bile?
Responsible for fat digestion and absorption
Bile and pancreatic juice neutralise gastric juice
Gets rid of waste products of blood such as bilirubin and cholesterol
What does the liver produce?
Proteins, lipoproteins, coagulation factors (fibrinogen, prothrombin, clotting factors. Vitamin K s essential for formation of prothrombin and factors II,VII,IX,X)
Hormones and pro-hormones
Carrier proteins (transferrin)
What does the liver store?
Carbohydrates, fat, ADEK, B12, folate, ferritin, metals
What are the roles of the liver?
Production, storage, metabolism, excretion
How does the liver metabolise proteins?
- Transamination: one amino acid is converted to another (adding/removing elements from R group)
- Deamination: getting rid of excess amino acids by removing amino group (NH2). NH2 is converted to NH3 (ammonia) and NH3 enters the urea cycle. Urea is then excreted in urine.
What proteins are synthesised by the liver?
Fibrinogen, albumin, globulin, CRP, complement proteins C1-4
What is the role of the liver in response to high blood glucose levels?
Insulin released by pancreas, glucose is converted to glycogen and stored in the liver, decreased gluconeogenesis, decreases glycogenolysis
What is the role of the liver in response to low blood glucose?
Glucagon released by pancreas, glycogen converged into glucose and released, increases gluconeogenesis and increases glycogenolysis
What are lipids metabolised by the liver?
Triglycerides are oxidised in hepatocytes to produce energy
Excess proteins and carbohydrates are converted into fatty acids and triglycerides and stored in adipose tissue
Liver produced lipoproteins
Synthesises cholesterol and phospholipids
What happens to cholesterol in the liver?
Cholesterol s excreted in bile or converted to bile acids
How does the liver metabolise alcohol?
Alcohol dehydrogenase converts ethanol to acetaldehyde
Acetaldehyde dehydrogenase converts acetaldehyde to acetate
Acetate is broken down to water and carbon dioxide for easy elimination
Which enzyme converts ethanol to acetaldehyde?
Alcohol dehydrogenase
Which enzymes converts acetaldehyde to acetate?
Acetaldehyde dehydrogenase
What occurs in phase 1 of drug metabolism?
Oxidation/reduction/hydrolysis
Oxidation is catalysed by cytochrome P450 in SER to make drug more active
Which enzyme catalysts the oxidation of a drug in drug metabolism?
Cytochrome P450 in SER
What occurs in phase 2 of drug metabolism?
Conjugation
Attachment of ionised group to the drug (glutathione/methyl/acetyl), to make drug water soluble to facilitate excretion
What occurs in phase 3 of drug metabolism?
Drug eliminated via ATPase pumps
What can you test to check liver function?
Albumin ALT (alanine aminotransferase) ALP (alkaline phosphatase) Bilirubin GGT (gamma glutamyl transpeptidase) AST (aspartate aminotransferase)
What are the markers of hepatocellular damage?
- AST: liver, heart, skeletal muscle, kidneys, brain, RBC’s
In liver 20% activity is cytosolic and 80% is mitochondrial
Clearance by sinusoidal cells
Half life: 17hrs - ALT: specific to liver, very low concentrations in kidney and skeletal muscles
In liver totally cytosolic
Half life 47hrs
What are the markers of cholestasis?
-ALP: liver and bone
Hepatic ALP present on surface of bile duct epithelia and accumulating bile salts increase to release from cell surface
Half life is 1 week
- ALP isoenzymes, 5-NT or gamma GT may be necessary to evaluate the origin of ALP
What is GGT useful for?
- Hepatocytes and biliary epithelial cells, pancreas, renal tubes and intestine
- Very sensitive but non specific
- Cholestasis or hepatocellular
- Alcohol
- Helps to interpret ALP
- Isolated increase does not need further investigations, only if other LFT’s become abnormal then investigate
How does GGT help to interpret ALP?
- ALP>GGT: bone disease, pregnancy
- GGT>ALP: alcohol, medications
What happens when bilirubin is taken up into hepatocytes?
It is conjugated to glucuronic acid - bilirubin diglucuronide - bilirubin monoglucuronide - secreted into bile
What happens to conjugated bilirubin?
It is water soluble and excreted in bile
It is degraded to urobilinogen
May be reabsorbed by gut and returned to liver
Converted to urobilin > reabsorbed into plasma for excretion by kidneys
How does bilirubin cause the brown colour of faeces?
Bilirubin may be acted upon by bacterial enzymes within the gut to form bile pigment stercobilinogen > stercobilin > brown colour of faeces
What causes pre hepatic jaundice?
Unconjugated hyper bilirubinaemia
What causes post hepatic jaundice?
Unconjugated and conjugated hyper blirubinaemia
What causes obstructive jaundice?
Failure of bilirubin to reach the gut (light coloured stool, dark urine)
What are the clinical markers of obstructive jaundice?
Light coloured stool and dark urine
What occurs in the reticuloendothelial system?
Heme from RBC converted to biliverdin by heme oxygenase, this then converted to bilirubin. Bilirubin-albumin taken up by liver (unconjugated). This converted to bilirubin glucuronide by UDP glucuronyl transferase. Secretion of bilirubin glucuronide, degraded to urobilinogen.
Urobilinogen gives brown colour to faeces and also goes into portal circulation and small amounts to urine
What is albumin?
A protein made by the liver
Low albumin levels in chronic liver disease or malnutrition
What is a sensitive indicator of liver fibrosis?
Thrombocytopenia
