The Liver: An Intro To Its function Flashcards
What are the major function influencing structural features in the liver?
Vascular system, biliary tree, 3D arrangement of liver cells with the vascular and biliary system
How many lobes are in the liver and what are they divided by?
2- falciform ligament
Where does 75% of the blood supply to the liver come from?
Portal vein
Where does the other 25% of liver blood supply come from?
Hepatic artery (straight from the aorta)
Where do the central veins of the liver lobules drain into?
Hepatic vein and back to the inferior vena cava
What are the types of cells in the liver?
Hepatocytes (60%) Kupffer cells (30%) Liver endothelial and Stellate cells
What function do hepatocytes carry out?
Most metabolic functions
What functions do kupffer cells carry out?
Clear gut derived endotoxins from the blood in the portal vein
What is the functional unit in the liver?
Hepatic lobule
What are the hepatic lobules?
Hexagonal plates of hepatocytes around the central hepatic vein
At each corner there is a portal vein, hepatic artery and bile duct
How does the microstructure of the liver support its roles?
Huge SA for exchange of molecules
Sophisticated separation of blood from bile
What do kupffer cells function as?
A mononuclear phagocyte system
Where are kupffer cells found?
In sinusoids
What lines the lumen of the sinusoid?
Liver sinusoidal epithelial cells
What is behind the liver sinusoidal epithelial cells?
Perisinusoidal space
What is in bile?
Water, electrolytes and organic molecules
What organic molecules are in bile?
Bile acids, cholesterol, bilirubin and phospholipids
How much bile does the average adult produce in a day?
400-800 ml
What are the two stages of bile secretion?
Hepatocytes synthesise the organic constituents
Epithelial cells lining the bile ducts secrete large quantities of watery solution
Describe the enterohepatic circulation of bile acids
Cholesterol -> primary bile acids -> bile salts -> duodenum where its deconjugated into primary bile acids -> broken down into secondary bile acids -> reabsorbed into circulation in the small intestine
How are the bile salts transported into the duodenum?
Active transport into the bile cannuliculi by ATP dependent transporters
How are bile salts deconjugated into primary bile acids?
Loosing a glycine or taurine
How are primary bile acids broken down into secondary bile acids?
Intestinal bacteria
What % of secondary bile acids are lost in the faeces?
5%
How is bile formation controlled?
Negative feedback mechanism -> too much bile means bile synthesis is inhibited
What is the physiological significance of bile?
- emulsification of fats
- neutralise gastric juice
- Eliminate waste products like bilirubin and cholesterol
What causes gallstone formation?
Inbalance in the chemical makeup of bile inside the gallbladder
What are the two types of gallstones and their prevalence?
Cholesterol (80%) or pigment (20%)
What are the risk factors for cholesterol gallstones?
High fat diet and increased cholesterol synthesis
Why are cholesterol gallstones formed?
If the gallbladder epithelium is inflamed it changes the absorptive characteristic of the mucosa so cholesterol concentrates
What are the risk factors for gallstones?
Women, obesity, excess oestrogen, hormone replacement therapy
Why are pigment gallstones formed?
Excess breakdown of RBCs into bilirubin
Where can gallstones form?
Anywhere along the biliary tract
What is bilirubin?
Yellow pigment formed from the breakdown of haemoglobin
Why must bilirubin be removed?
Toxic and made in large quantities (6g/day)
Where are senescent RBCs broken down?
Spleen
What is haemoglobin broken down into?
Haem and globin
What does haem oxygenase break down haem into?
Bilivirdin
What enzyme catalyses bilivirdin -> bilirubin?
Bilivirdin reductase
What is unconjugated bilirubin bound to?
Albumin
Where is the unconjugated bilirubin transported?
Liver
What happens to the unconjugated bilirubin in the liver?
Conjugated with glucuronic acid and then secreted into bile
What converts bilirubin into urobilinogen?
Intestinal bacteria
What happens after the urobilinogen is formed?
It’s reabsorbed into the portal vein and excreted in urine or turned into stercobolin and excreted in faeces
What causes jaundice?
When plasma bilirubin concentration exceeds 1.5 mg/day
What are the three groups of jaundice?
Prehepatic (haemolytic)
Hepatic
Post hepatic (obstructive)
What causes prehepatic jaundice?
Excessive breakdown of RBCs or an excess of conjugated bilirubin
What causes hepatic jaundice?
Damaged hepatocytes which leads to an excess of conjugated and/or unconjugated bilirubin
What causes post hepatic jaundice?
Excess conjugated bilirubin due to an obstruction in the duodenum so it enters the circulation and urine
What are sunlight canopies and what do they do?
Help with neonatal jaundice in global south countries
Filters out most light rays, to allow the therapeutic blue light to pass through
What is the use of blue light in jaundice?
Conjugates unconjugated bilirubin into conjugated bilirubin
What are the blood clotting factors?
Fibrinogen, prothrombin, basically all other factors (V, VI, IX, X, XII)
Why is vitamin K essential?
Converts prothrombin and factors II, VII, IX and X into their functional forms
What does warfarin do?
Blocks oxidised vitamin k -> vitamin K
What’s stored in hepatocytes?
Vitamins A, D, E and K
How much vitamin B12 does the average person have stored?
Enough to last 2-3 years
What does a vitamin B12 deficiency lead to?
Pernicious anaemia
When is folate required?
Early pregnancy
Where is folate stored?
Liver
What is iron stored as in the liver?
Ferritin
What are the four (groups of) things the liver metabolises?
Bilirubin, ammonia, hormones, drugs and exogenous toxins
What is gynaecomastia?
Breast enlargement in males due to alcoholic cirrhosis
What phase of development are adult hepatocytes in normally?
G0
How much liver is removed in a partial hepatectomy?
70%
What happens to the surviving adult hepatocytes after a partial hepatectomy or a toxic injury?
Rapidly reenter the cell cycle and proliferate
When does proliferation of new liver tissue stop?
Once the original mass of the liver is reestablished
What are the two pathways that have been hypothesised for regeneration of the liver?
- growth factor mediated pathway -> most important HGF and TGF alpha
- cytokine signalling pathway using ILG vie TNF alpha binding to its receptor on kupffer cells
What do liver function tests do?
Check the levels of certain enzymes and proteins in the blood
What can liver function tests be used to measure?
- Progression of a disease and how well a treatment is working
- severity of a disease- scarring of the liver
- possible side effects of medications
What does a high alanine aminotransferase or aspartate aminotransferase mean?
Hepatitis or alcohol induced Liver damage
What does high alkaline phosphatase levels indicate?
Obstruction in bile flow
What does high gamma gutamyl transverase levels indicate?
Obstruction in bile flow
What does high bilirubin levels indicate?
Jaundice
What do low albumin levels indicate?
Chronic liver disease/ malnutrition
