Liver Physiology
Last updated 4th March 2020 - Tom Heaton
The liver is an incredibly important organ with a wide range of essential functions.
This page aims to cover some of the key features.
This page aims to cover some of the key features.
Anatomy
This is a good overview video from Armando Hasudungan: https://www.youtube.com/watch?v=a1vgszd5_yM
The liver can be split into 2 anatomical or 2 physiological lobes.
Anatomically, the margin is the falciform ligament, but this has no functional significance, producing a smaller left lobe.
Physiologically, there are 2 roughly equally lobes, roughly demarcated by a line joining the IVC groove and the gallbladder.
This is based on separate blood and bilious connections.
These can then further be subdivided into a total of 8 segments, 4 in each true lobe.
The liver can be split into 2 anatomical or 2 physiological lobes.
Anatomically, the margin is the falciform ligament, but this has no functional significance, producing a smaller left lobe.
Physiologically, there are 2 roughly equally lobes, roughly demarcated by a line joining the IVC groove and the gallbladder.
This is based on separate blood and bilious connections.
These can then further be subdivided into a total of 8 segments, 4 in each true lobe.
Blood Supply
The liver has 2 main vessels supplying blood to it:
Each contributes about 50% of the oxygen delivery.
The total hepatic blood flow is about 1ml/g/min, which equates to about 25% of total cardiac output.
These enter the liver at the porta hepatis, where the bilious tree and lymphatics exit.
They run together and divide to supply each functional segment, and ultimately run together in the end jointly supply blood to the hepatic sinusoids.
There is a single vein draining the liver, the hepatic vein, which feeds into the inferior vena cava.
The volume of blood within the liver is usually around 450ml, but this can increase by 500-1000ml with venous back pressure, thus acting as a reservoir.
The blood flow to the liver is under some control, and will vary with certain situations.
The control may be:
- Hepatic artery
- Hepatic portal vein
Each contributes about 50% of the oxygen delivery.
The total hepatic blood flow is about 1ml/g/min, which equates to about 25% of total cardiac output.
These enter the liver at the porta hepatis, where the bilious tree and lymphatics exit.
They run together and divide to supply each functional segment, and ultimately run together in the end jointly supply blood to the hepatic sinusoids.
There is a single vein draining the liver, the hepatic vein, which feeds into the inferior vena cava.
The volume of blood within the liver is usually around 450ml, but this can increase by 500-1000ml with venous back pressure, thus acting as a reservoir.
The blood flow to the liver is under some control, and will vary with certain situations.
The control may be:
- Intrinsic - including the hepatic artery buffer response
- Neuronal - minimal, mainly just the hepatic artery
- Humoral
Functional Organisation
The liver is made of a number of smaller units, again being split into anatomical and functional in nature:
The lobule is the more structurally apparent representation.
It is made of hexagonal arrangements of the key tissues within the liver.
At the centre of each lobule is the hepatic venule, which subsequently drains into the hepatic veins.
Around the outside are the portal tracts, containing:
The vascular components of this both give rise to the hepatic sinusoids.
The sinusoids are specialised capillaries, with wide fenestrations allowing effective plasma mixing (something that is lost in hepatic fibrosis).
They are also lined with other important cells:
In contrast, the hepatic acinus represents the functional hepatic unit.
This is the area around the final divisions of the portal tracts, where the blood leaves these vessels, into the sinusoids and comes into contact with the hepatocytes.
It then passes to the hepatic venules, to be drained from the liver.
Along this journey, it becomes more deoxygenated, and this is represented by the labelling of different zones, from 1 to 3.
Zone 1 receives the most oxygenated blood, and so has high levels of mitochondria, and performs high levels of oxidative metabolic processes.
Zone 3 receives less well oxygenated blood, and is where a large amount of biotransformation activity happens.
- Lobule
- Liver acinus
The lobule is the more structurally apparent representation.
It is made of hexagonal arrangements of the key tissues within the liver.
At the centre of each lobule is the hepatic venule, which subsequently drains into the hepatic veins.
Around the outside are the portal tracts, containing:
- Hepatic arteriole
- Portal venule
- Biliary duct
The vascular components of this both give rise to the hepatic sinusoids.
The sinusoids are specialised capillaries, with wide fenestrations allowing effective plasma mixing (something that is lost in hepatic fibrosis).
They are also lined with other important cells:
- Kupffer cells - macrophages with important immune function (make up 10% of liver mass)
- Stellate cells - have a structural role and store vitamin A.
In contrast, the hepatic acinus represents the functional hepatic unit.
This is the area around the final divisions of the portal tracts, where the blood leaves these vessels, into the sinusoids and comes into contact with the hepatocytes.
It then passes to the hepatic venules, to be drained from the liver.
Along this journey, it becomes more deoxygenated, and this is represented by the labelling of different zones, from 1 to 3.
Zone 1 receives the most oxygenated blood, and so has high levels of mitochondria, and performs high levels of oxidative metabolic processes.
Zone 3 receives less well oxygenated blood, and is where a large amount of biotransformation activity happens.
Physiology
The key functions of the liver can be considered as:
Synthesis of proteins
Metabolic
Excretion
Biotransformation
Immunological
Blood
Storage
- Protein synthesis
- Metabolic
- Excretion
- Biotransformation
- Immunological
- Blood
- Storage
Synthesis of proteins
- Albumin
- Immune factors
- Hormones
- Clotting
- Carrier proteins
Metabolic
- Carbohydrate metabolism
- Amino acid
- Urea cycle
- Lipids
Excretion
- Bile salts
- Bile pigments
Biotransformation
- Drugs
- Toxins
- Hormones
- Haem metabolism
Immunological
- Kupffer cell phagocytic activity
Blood
- Haemoglobin synthesis in utero
- Blood reservoir
Storage
- Glycogen
- Vitamins
- Copper
- Iron
A number of these functions are covered elsewhere e.g. in the details of specific metabolic pathways.
Some additional aspects are described in more detail here.
Some additional aspects are described in more detail here.
Biotransformation
Also known as detoxification, this is an essential role of the liver to break down exogenous substances e.g. drugs/toxins, into safe molecules that can be subsequently excreted from the body (usually increased water solubility).
The processes are similar to those for handling endogenous substances.
The reactions that occur can result in major changes to the pharmacokinetics and dynamics of the substance, and so is very relevant for physicians.
The liver is the most important site in the body for such reactions, but they can occur at other sites too.
The types of reactions are typically divided:
Phase I reactions are usually oxidation or reduction reactions that alter the biochemistry of the substance.
The cytochrome p450 family of enzymes are major contributors to this step.
Common effects of this include:
Phase II reactions are synthetic in nature, with conjugation to produce a non-toxic and hydrophilic molecule, suitable for excretion.
This can be glucuronidation or sulphation.
The enzymes that conduct the reactions are termed transferases.
Larger molecules tend to be excreted in the bile, with smaller ones in the urine.
The processes are similar to those for handling endogenous substances.
The reactions that occur can result in major changes to the pharmacokinetics and dynamics of the substance, and so is very relevant for physicians.
The liver is the most important site in the body for such reactions, but they can occur at other sites too.
The types of reactions are typically divided:
- Phase I
- Phase II
Phase I reactions are usually oxidation or reduction reactions that alter the biochemistry of the substance.
The cytochrome p450 family of enzymes are major contributors to this step.
Common effects of this include:
- Increased water solubility, allowing excretion
- Preparation for subsequent metabolism e.g. phase II reactions
- Bioactivation - sometimes to toxic molecules
Phase II reactions are synthetic in nature, with conjugation to produce a non-toxic and hydrophilic molecule, suitable for excretion.
This can be glucuronidation or sulphation.
The enzymes that conduct the reactions are termed transferases.
Larger molecules tend to be excreted in the bile, with smaller ones in the urine.
Bile Production
The production of bile is another important function of the liver.
Bile is composed of:
Functions of the bile include:
Bile salts are modified steroid molecules, with the modification in the hepatocytes.
The result is an amphipathic molecule (having both lipophilic and hydrophilic properties) which provides them with detergent properties.
This aids the digestion and absorption of lipids.
Primary bile salts are synthesised by the liver e.g. cholic acids, and secondary salts are the result of bacterial metabolism e.g. deoxycholic acid.
These are actively transported into the bile canaliculi, and pass down the bile ducts, ultimately to the gallbladder.
About 90% of these are reabsorbed from the gut (particularly terminal ileum and colon), undergoing enterohepatic circulation as they pass back to the liver in the portal circulation.
Bile is composed of:
- Water
- Bile salts
- Bile pigments - bilirubin, biliverdin
- Inorganic electrolytes
- Lipids - Cholesterol, phospholipids
Functions of the bile include:
- Facilitating digestion and absorption of fats
- Facilitating absorption of fat soluble vitamins (A,D,E,K)
- Elimination of substances
- Bilirubin
- Lipids - cholesterol, phospholipids
- Drug metabolites
- Bilirubin
Bile salts are modified steroid molecules, with the modification in the hepatocytes.
The result is an amphipathic molecule (having both lipophilic and hydrophilic properties) which provides them with detergent properties.
This aids the digestion and absorption of lipids.
Primary bile salts are synthesised by the liver e.g. cholic acids, and secondary salts are the result of bacterial metabolism e.g. deoxycholic acid.
These are actively transported into the bile canaliculi, and pass down the bile ducts, ultimately to the gallbladder.
About 90% of these are reabsorbed from the gut (particularly terminal ileum and colon), undergoing enterohepatic circulation as they pass back to the liver in the portal circulation.
Haem Metabolism
RBCs are undergoing continuous renewal, with large numbers undergoing destruction daily.
This is primarily by the reticuloendothelial system, such as the spleen and Kupffer cells.
The breakdown products of haemoglobin are haem and globin.
The globin chains are reutilised, and the haem undergoes breakdown to release the Fe2+ at its centre, which enters the iron pool.
The remains are biliverdin, which is converted to bilirubin.
Other sources of bilirubin include the other hemoproteins, such as myoglobin and the cytochrome enzymes.
Bilirubin in its new, unconjugated form, is notably toxic.
It binds to specific binding sites on albumin to negate this toxicity.
Importantly, some drugs can compete for this binding site e.g. warfarin, radiographic dyes.
It is transported to the liver where it is conjugated (with glucuronic acid) and actively excreted into the bile.
In the gut, bacteria metabolism results in breakdown of the conjugated bilirubin to urobilinogen.
Some of this undergoes enterohepatic circulation, with some also being excreted in the urine.
This is primarily by the reticuloendothelial system, such as the spleen and Kupffer cells.
The breakdown products of haemoglobin are haem and globin.
The globin chains are reutilised, and the haem undergoes breakdown to release the Fe2+ at its centre, which enters the iron pool.
The remains are biliverdin, which is converted to bilirubin.
Other sources of bilirubin include the other hemoproteins, such as myoglobin and the cytochrome enzymes.
Bilirubin in its new, unconjugated form, is notably toxic.
It binds to specific binding sites on albumin to negate this toxicity.
Importantly, some drugs can compete for this binding site e.g. warfarin, radiographic dyes.
It is transported to the liver where it is conjugated (with glucuronic acid) and actively excreted into the bile.
In the gut, bacteria metabolism results in breakdown of the conjugated bilirubin to urobilinogen.
Some of this undergoes enterohepatic circulation, with some also being excreted in the urine.
Links & References
- Hasudungan, A. Liver anatomy and blood supply. Youtube. 2013. https://www.youtube.com/watch?v=a1vgszd5_yM
- Hasudungan, A. Liver physiology. Youtube. 2013. https://www.youtube.com/watch?v=L61Z2uV-jOw
- Jooste, C. Functional liver anatomy and blood supply. e-LFH. 2012. https://portal.e-lfh.org.uk/Component/Details/561958
- Jooste, C. Metabolic and synthetic functions of liver 1. e-LFH. 2012. https://portal.e-lfh.org.uk/Component/Details/561963
- Katawala, T. Liver physiology. Update in anaesthesia. https://www.wfsahq.org/components/com_virtual_library/media/dda54c572bac3d79fa55dac2ebffb91a-Liver-Physiology--Update-24-2-2008-.pdf
