The Liver: An Introduction to its function Flashcards
Generally, describe the liver’s anatomy and structure.
It is the largest gland and the second largest organ in the body.
It has numerous functions - it impacts on all the body systems.
The major aspects of its structure which influence its function are:
- vascular system
- biliary tree
- 3D arrangement of liver cells with the vascular and biliary systems
Describe the blood supply to the liver.
The majority (75%) of the liver’s blood supply is venous blood from the portal vein, carrying blood returning from the GI full of digested products.
The remaining 25% is from the hepatic artery. Blood from the central veins in the liver lobules drain into the hepatic vein and then into the vena cava.
Describe the functional anatomy of the liver (ie. its different cells and its functional unit).
The two primary cells of the liver are: HEPATOCYTES (60%) - they perform the most metabolic functions KUPFFER CELLS (30%) - a type of tissue macrophage
Other cell types are LIVER ENDOTHELIAL CELLS and STELLATE CELLS.
The functional unit is the hepatic lobule. It consists of hexagonal plates of hepatocytes around the central hepatic vein. At each of the 6 corners is a triad of branches of the portal vein, hepatic artery and bile duct.
The blood enters the lobules through branches of the portal vein and hepatic artery, then flows through small channels called sinusoids that are lined with primary liver cells (hepatocytes). The hepatocytes remove toxic substances, including alcohol, from the blood, which the exits the lobule through the central vein (ie. the hepatic venule). The flow of blood is in the opposite direction to the flow of bile.
The blood entering the lobule (at the hepatic artery) is relatively oxygen-rich, but the blood leaving the lobule contains low levels of oxygen (at the terminal hepatic venule) because hepatocytes along the sinusoids have used up much of the available oxygen.
How does the biliary system go (in terms of structures)?
- bile is secreted by hepatocytes
- goes through series of channels between cells (canalinculi)
- goes to small ducts
- goes to large ducts
- anastamose onto common bile duct
How does the liver’s microstructure support its roles?
- massive surface area for exchange of molecules
- sophisticated separation of blood from bile
- specific positioning of pumps to achieve specific localisation of materials (at a cellular level)
How do Kupffer cells act as a protective barrier?
As blood flows through intestinal capillaries, it picks up many bacteria from the intestine. A sample of blood taken from the portal veins before it enters the liver is almost always going to grow colon bacilli when cultured, where as growth of colon bacilli from systemic blood is rare.
The Kupffer cells efficiently cleanse the blood as it passes through the sinus. When a bacterium comes in contact with Kupffer cells, in <0.01 seconds, the bacterium passes inwards through the wall of the Kupffer cells to become permanently lodged there till digested. Probably <1% of the bacteria entering the portal blood from the intestines succeeds in passing through the liver into the systemic circulation.
What is bile?
It is a greenish-yellow liquid consisting of a complex mix of water, electrolytes and organic molecules (such as bile acids, cholesterol, bilirubin and phospholipds). Adults humans produce 400-800ml of bile every day.
Initially, the hepatocytes secrete bile into the canaliculi, which flows into the bile ducts and contains a large amount of bile salts, cholesterol and other organic constituents. it is then modified by water and bicarbonate-rich secretion from epithelal ductal cells.
What does bile do?
It is essential for fat digestion and absorption via emulsification.
Bile and pancreatic juice neutralises gastric juice as it enters the small intestine and aids digestive enzymes.
It helps in the elimination of waste products from the blood, in particular bilirubin and cholesterol.
How does bile enter the duodenum?
it enters via the major duodenal paillae (the Sphincter of Odii; it controls bile’s entry).
Bile can also be diverted into the gall blader via the cystic duct where it is stored and concentrated 5-fold.
What is bilirubin?
It is a yellow pigment formed from the breakdown of haemoglobin; it is what gives bile its colour.
It is useless and toxic, but it’s made in large quantities (~6g/day), so it has to be eliminated.
In general, describe the destruction of aged RBCs.
Dead or damaged RBCs are digested by macrophages throughout the body.
The Fe is recycled.
The globin chains are proteins, so they are catabolised to various amino acids and then reused.
Haem (porphyrin) cannot be recycles, so it has to be eliminated. Thus, haem is converted in a series of steps into bilirubin.
Describe the formation and elimination of bilirubin.
As the senescent red cell is broken down (into globin, haem and iron), the haem is converted into free bilirubin in a series of steps. This bilirubin is released into the plasma and carried around bound to albumin.
Albumin-bound bilirubin is then stripped of the albumin and absorbed into hepatocytes, where it is conjugated with glucuronic acid. The conjugated bilirubin is then secreted into the bile, where it is metabolised by the bacteria of the intestinal lumen.
Bacteria in the intestinal lumen metabolise bilirubin to a series of other compounds which are ultimately eliminated either in faeces or, after reabsortion, in urine. The major metabolite of bilirubin in faeces is stercobilin, which gives feces their characteristic brown color. In the urine, we have yellow urobilin and urobilinogen.
The renal excretion of urobilin and stercobilinogen is increased in cases of hepatitis and other damage to hepatocytes.
What is jaundice and what can cause it?
Jaundice comes from the French word ‘jaune’, which means yellow.
It is when excessive quantities of either free or conjugated bilirubin accumulate in the ECF. A yellow discolouration of the skin, sclera (the opaque, usually white, fibrous outer layer of the eye) and mucous membranes is observed.
What was the rare case of ‘green’ jaundice reported?
A very rare case of ‘green’ jaundice was reported, caused by a mutation of the biliverdin reductase gene, hence biliverdin was not converted to bilirubin and instead built up in the serum, giving it the green colour (aggravated by alcohol cirrhosis).
Describe the pre-hepatic (haemolytic) causes of jaundice.
Increased haemolysis can cause excess bilirubin and the liver has no capacity to process/conjugate it.
Unconjugated bilirubin cannot be excreted in the urine and remains in the circulation.
Neonates have increased red cell mass for their survival in utero. At birth and during the first few days of life, the increased rate of RBC destruction as foetal Hb is replaces with adult Hb results in normal physiological jaundice. In addition, the liver is still a bit immature, so there is a delay in processing.
Ligth therapy is used to treat cases of neonatal jaundice through the isomerisation of bilirubin, and consequently, the transformation into water-soluble compounds that the newbron can excrete via urine and stools. All newborns have raised unconjugated bilirubin, and in 50-60% of full-term healthy neonates, levels rise sufficiently to cause jaundice.
