Hey guys, it’s been awhile since my last blogpost. I’ve been posted to a district hospital so I had some issues in adapting to the area which results the delay of this blogpost. This is my 17th blogpost since I’ve joined this amazing Steemit community. I hope I have made some contribution to the Steemit society, knowledge-wise of course.
The title of this blogpost is taken from the gorgeous Queen Daenerys of House Targaryen. She has a ridiculous mouthful title engraved to her name - "Daenerys Stormborn of the House Targaryen, First of Her Name, the Unburnt, Queen of the Andals and the First Men, Khaleesi of the Great Grass Sea, Breaker of Chains, and Mother of Dragons". God I love Game of Thrones so much. I can't wait for S8 to be released.
Alright, let's go back to the main topic. I'll get back to GoT someday.
Without further ado, here’s my very first Gastro post which I am going to talk about one of the most crucial organs in the body, which is the liver.
The liver is the human body’s largest internal organ and its typical weight is about 1.2-1.5kg. Apart from that, it is the largest gland in the whole body. A gland is defined as a structure of the human body which secretes particular chemical substance for certain use of the body. Other common examples of glands are the pituitary gland of the brain, adrenal glands, thyroid glands and etc. The liver is situated below the diaphragm and overlies the gallbladder.
The abdomen is divided anatomically into 9 regions, namely the right hypochondriac, epigastric, left hypochondriac, right flank, umbilicus, right lumbar, right iliac fossa, suprapubic, and left iliac fossa (arranged from right to left, and up to down). Liver is usually situated in the right hypochondriac region because it is enlarged, it can extend until the epigastric as well as the right flank regions. We’ll discuss about its enlargement later. I will emphasize more about its structures now.
The liver can be categorized functionally into right larger lobe and left lobe and it is divided by the falciform ligament (means sickle-shaped ligament in Latin). The right lobe is further subdivided into the caudate and quadrate lobes. The caudate lobe is situated more superior (above) compared to the quadrate lobe which is located much more inferiorly (below). The deep transverse fissure (known as Porta Hepatis) separates both caudate and quadrate lobes and this region contains the vessels, nerves and ducts entering and leaving the liver with the exception of hepatic veins. Hepatic means liver, or anything to do with liver.
The hepatic blood supply is delivered via the hepatic artery which carries oxygen rich blood from the aorta and hepatic portal vein which received nutrient-rich blood directly from the intestines. Unlike most structures which gets their blood supply mainly from arteries, the liver mostly obtain its blood from the portal vein. The portal vein received blood from the spleen and most of the gastrointestinal tract. The normal portal pressure is about 5-8mmHg which increases after intake of foods. This enables the liver to filter/detoxify substances from the intestines before transmitting all the nutrients to the whole body. Just imagine that the liver is the main gate that has strict police patrol that continuously monitors the blood and nutrients received from the intestines. The venous drainage of the liver is mainly done by the hepatic veins. The central veins of each hepatic lobules form collecting veins which is then combined to form multiple hepatic veins and finally towards the inferior vena cava. The inferior vena cava is a large veins that carries deoxygenated blood to the heart.
The nerve supply of the vein is supplied by the hepatic plexus which contains the coeliac plexus and vagus nerve. Vagus nerve is the 10th cranial nerve that arises from the brain. The fibrous coverings of the liver, which is known as the Glisson’s capsule, is innervated by the lower intercostal nerves. The lower intercostal nerves supply the chest wall. Thus, when there is distension of the liver capsule, the person will feel a sharp and localized pain at the region.
The French surgeon, Claude Couinaud made some significant contributions to the hepatobiliary field of surgery. He founded a system that divides the anatomy of the liver into 8 different functional segments based on a transverse plane through the bifurcation of the main portal vein. Each segment has its own vascular inflow, outflow and biliary drainage. Furthermore, in each segment there is a branch of the portal vein, hepatic artery and bile duct. The system is called the Couinaud system, which is referring to its founder. This great contribution of Couinaud allows the division of the liver into independent units, which means the liver can be resected into units without damaging the other units. The surgical resection of liver parts is known as hepatectomy.
Microscopically, there are two major types of liver cells. The parenchymal hepatocytes and the non-parenchymal cells. The former constitutes up to 85% of the liver volume. Cells of the liver are arranged in lobules. There as the structural units of the liver. Each anatomical lobule is hexagonal in shape and it is drained by a central vein. At the edge of the hexagon, there are three structures known as the portal triad. Arteriole (a branch of hepatic artery), venule (a branch of hepatic portal vein) and bile duct (a branch of bile duct leaving the liver).
Functions of the Liver
I can provide you with at least 10 main purpose of liver's existence in our body. The liver takes part in many metabolism pathways, bile acid and coagulation factor synthesis, toxin deactivations, immunological roles, and even contributes to our body’s blood pressure.
Metabolism:
Hepatic cells are metabolic overachievers in the body. They play essential roles in generating molecules that supports the other parts of the human body. They convert a molecule to another and regulates energy balances.
Carbohydrate Metabolism:
It is critical for humans to have their own blood glucose level within the normal range, as to prevent hypoglycemia and hyperglycemia complications. The liver contributes a significant amount of power in maintaining the body’s sugar level. Hepatocytes contain multiple enzymes those are involved in all sorts of metabolic pathways. In circumstances such as during after an ingestion of a meal, excess glucose absorbed by the intestine travels to the liver via the hepatic portal vein.
In the liver, these excessive glucose are converted into glycogen (a large polymer) in the process known as glycogenesis. The liver approximately stores up to 80g of glycogen. In other situations when the blood sugar level drops, these glycogen is converted back to glucose in the process called glycogenolysis. This explains why during starvation or fasting, the blood glucose level could be normal or even higher than usual as the liver actively converts the stored glycogen to glucose via glycogenolysis. When the glycogen storage gets exhausted, does the liver gives up? NO! Instead, they recognize the problems and convert other molecules to glucose. For instance, amino acids and non-hexose carbohydrates are converted to glucose via gluconeogenesis.
Fat Metabolism:
The liver is the main site of converting excess carbohydrates and proteins into fatty acids and triglycerides. Lipids are insoluble in water and transported into the bloodstream as macromolecule complexes. In order for it to be transported as a stable molecule, it needs lipoprotein. Moreover, these lipoproteins act as an ID for these fat molecules as they allow receptors of the whole body to recognize the fats. These products are then exported and stored in the adipose tissue throughout the body. There are five principle types of lipoprotein, namely the chylomicron, very low density lipoprotein (VLDL), low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and high density lipoprotein (HDL). I’m sure some of you guys might heard LDL and HDL especially those who usually run for cholesterol checkups at the clinic/hospital. The measurements of cholesterol via blood test is mainly determined by the person’s LDL, HDL and triglycerides levels. Furthermore, the liver synthesizes a large amount of cholesterol and phospholipids. The majority of lipoproteins are synthesized here in the liver.
Chylomicrons are produced in the small intestine after someone has taken its meal. They contain triglycerides and small amounts of cholesterols. These chylomicrons aid the transportation of dietary fat to liver and peripheral tissues from the intestines. As I said earlier, these chylomicrons contain tags which acts as an ID to the receptors throughout the body. Hence these chylomicrons are able to transfer those dietary fats to their targeted cells.
Very Low Density Lipoproteins are generated continuously by the liver and it contains most of the body’s endogenously synthesized triglycerides (triglycerides produced by the liver, not from dietary intake). These VLDLs are the main source of energy during conditions such as prolonged fasting. After some time in the circulating and transferring triglycerides to the cells in the body, the triglyceride-depleted form is known as the IDL or Intermediate Density Lipoprotein . Further removal of triglyceride changes IDL to LDL or Low Density Lipoprotein. Since LDL has fewer triglycerides compared to the other lipoproteins, LDL becomes the main carrier of cholesterol and its job is to deliver it to the liver as well as to the other cells in the body. LDLs are degraded in the liver via liposomes.
High Density Lipoproteins or HDL are synthesized by the liver and the intestines. They are good lipoproteins, as in we need more of HDL in our body. The main reason is that this HDL transports away cholesterol from the peripheries to the liver or VLDL.
The reason why individuals need to fast before checking their blood cholesterol level is to eliminate the triglyceride-rich chylomicrons from the measurements. The triglyceride concentration hugely reflects the circulating VLDL and LDL level in the body. Majority of the total cholesterol consists of LDL particles and about 20-30% of HDL particles.
Statins or more famously known as the anti-cholesterol drug, lowers the LDL’s cholesterol content. Statins are HMG-CoA reductase inhibitors (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors). What a long name huhh. HMG-CoA reductase is the rate limiting enzyme in cholesterol synthesis, or in other words is this HMG-CoA reductase is the main culprit that aids in cholesterol production in our body. By inhibiting this enzyme, the LDLs will have fewer cholesterol content. Hence, lesser cholesterol will be distributed throughout the body which reduces the risk of atherosclerosis or cholesterol plaque formation in blood vessels. I have mentioned about atherosclerosis in a few blogposts before this. Check them out. Examples of statins are Simvastatin, Atorvastatin and Lovastatin. Studies have shown that cholesterol synthesis usually occurs at night. Thus, some short acting Statins should be taken at night.
Synthesis and Storage:
The liver is the primary site of synthesis of almost all circulating proteins. It regulates the plasma level as usually plasma has 60-80g/L of protein (mainly albumin, globulin and fibrinogen). The main function of albumin is to maintain intravascular oncotic pressure and to carry water insoluble substances such as bilirubin, hormones, fatty acids and drugs. In chronic liver disease or in severe malnutrition, the albumin level can be very low.
Carrier proteins such as transferrin (which carries iron) and caeruloplasmin (which carries copper) are produced in the liver too.
The liver plays an important role in synthesizing of all coagulation factors. Hence, individuals with liver problems might get easily bruised because of this. The liver stores Vitamin A, D and B12. Minerals such as iron and copper are stored in the liver too. Hence in conditions which causes iron overload such as frequent blood transfusions (as hemoglobin contains iron), the iron can build up in the liver causing severe damage to the hepatocytes.
Degradation of Nitrogen products:
Amino acids are degraded to produce ammonia which is then converted to produce urea and excreted by the kidneys. This is the main pathway to eliminate these unwanted toxic products. In severe liver disease, there can be buildup of ammonia. These small molecules can cross the blood brain barrier and metabolized by the astrocytes in the brain. Astrocytes use ammonia to produce glutamine from glutamate. High glutamine level increases osmotic pressure in the astrocytes, making it swollen. These will cause brain edema which disrupts the normal pathways in the brain, which results in a condition called hepatic encephalopathy. Hepatic encephalopathy manifests as neuropsychological symptoms.
- The first stage of hepatic encephalopathy is characterized by inverted sleep-wake pattern as in the person might sleep during the day and stay awake at night.
- The second stage is marked by personality changes and tiredness.
- The third stage is described as worsening confusion.
- The final or fourth state is when the individual progresses into coma.
Hormone and Drug inactivation:
The liver is the principal site of hormones deactivation such as insulin, glucagon, oestrogens, growth hormones, glucocorticoids and parathyroid hormones. Furthermore, liver is the main organ that metabolized drugs and alcohol. Drugs that is fat soluble are converted to water soluble substances in order for them to be excreted via the kidneys. Hence, doctors treating individuals with liver diseases should be more cautious in prescribing drugs as some drugs might stay longer in the body due to the impairment of the degradation process.
Immunological functions:
As you guys know, the contents that are absorbed through the intestines such as nutrients might contain dangerous microorganisms. The liver acts as a sieve as it filters out all the content from the portal vein. The liver contains Kupffer cells which are macrophages that involves in breakdown of microorganisms. The liver’s lymphocytes are rich in natural killer and T cells which further aids in the clearing up process. In addition, hepatocytes are responsible in the synthesis of immune proteins such as the complement components.
The other function of liver which I have not discussed here in this blogpost is the Bilirubin Metabolism. I think it is a huge topic that deserves its own blogpost so I didn’t include them in this post. There are many types of liver diseases, all which come with their own reasons for being inflicted on each individual. Chronic hepatitis C infection and alcoholic liver disease are the leading causes of liver cirrhosis in the Unites States and this condition is irreversible condition marked by accumulation of scar tissues in the liver. Liver disease is the only major cause of death still increasing annually which is quite worrying. Liver disease in fact, kills more people than Diabetes and Road Deaths combined. In short, separating the facts and myths surrounding this wonderful organ removes fear while inspiring us to take liver wellness to the next level. With that, thank you for reading :)
References
- Kumar P., Clark M., Kumar & Clark's Clinical Medicine. Ninth Edition. London: ElSevier, 2017. Print
- 5 Facts About Liver Disease. American Liver Foundation. Retrieved on May 10th, 2018, from https://liverfoundation.org/5-facts-about-liver-disease/
- 18 Little Known Facts About Liver Disease. liversupport.com. Retrieved on May 10th, 2018 from https://www.liversupport.com/18-little-known-facts-about-liver-disease/
- Liver. Wikipedia. Retrieved on May 10th, 2018, from https://en.wikipedia.org/wiki/Liver
- The Liver. Teachmeanatomy. Retrieved on May 10th, 2018 from http://teachmeanatomy.info/abdomen/viscera/liver/
- Claude Couinoud. Wikipedia. Retrieved on May 10th, 2018 from https://en.wikipedia.org/wiki/Claude_Couinaud