Liver

The liver is a critical organ in the human body responsible for an array of functions that help support metabolism, immunity, digestion, detoxification, and vitamin storage, among other functions.[2] The liver is the largest solid organ in the body.[3] It comprises around 2% of an adult's body weight.[2]

Anatomy and Location

It is located beneath the rib cage in the right upper abdomen.[3] Your liver looks like a spongy, reddish-brown wedge of tissue. The wedge, which may be about the size and shape of a football, may weigh between 3 and 5 pounds.[4] The liver is found inferior to the diaphragm and occupies most of the abdomen's right upper quadrant (RUQ). It is mostly intraperitoneal, from the fifth intercostal space in the midclavicular line to the right costal margin.[10]

Lobes and Structure

The liver has two lobes (sections). The lobe on the right is slightly larger than the lobe on the left.[4] Anatomically, the liver has 4 lobes: right, left, caudate, and quadrate.[10] The liver has 2 main sections (lobes). Both are made up of 8 segments. The segments are made up of a thousand small lobes (lobules).[5]

The functional unit of the liver is the lobule. Each lobule is hexagonal, and a portal triad (portal vein, hepatic artery, bile duct) sits at each corner of the hexagon.[2] Both lobes contain many blood vessels and thousands of smaller lobes (lobules) that are tiny clusters of liver cells (hepatocytes).[4]

Blood Supply

The liver is unique due to its dual blood supply from the portal vein (approximately 75%) and the hepatic artery (approximately 25%).[2] Hepatic portal vein (75%) – supplies the liver with partially deoxygenated blood, carrying nutrients absorbed from the small intestine. This is the dominant blood supply to the liver parenchyma and allows the liver to perform its gut-related functions (such as detoxification).[7]

Functions

More than 500 vital functions have been identified with the liver.[1] Your liver's biggest job is filtering harmful substances and waste from your blood. Every day, your liver filters more than 250 gallons of blood.[4]

Metabolic Functions

Conversion of excess glucose into glycogen for storage (glycogen can later be converted back to glucose for energy) and to balance and make glucose as needed · Regulation of blood levels of amino acids, which form the building blocks of proteins[1] Regulates Amino Acids: The production of proteins depend on amino acids. The liver makes sure amino acid levels in the bloodstream remain healthy.[3]

The liver manages the synthesis of nearly every plasma protein in the body, and some examples include albumin, binding globulins, protein C, protein S, and all the clotting factors of the intrinsic and extrinsic pathways besides factor VIII.[2]

Detoxification and Bile Production

The liver regulates most chemical levels in the blood and excretes a product called bile.[1] Bile Production: Bile is a fluid that is critical to the digestion and absorption of fats in the small intestine.[3] Bile helps to break down fats, preparing them for further digestion and absorption.[5]

The liver processes this blood and breaks down, balances, and creates the nutrients and also metabolizes drugs into forms that are easier to use for the rest of the body or that are nontoxic.[1]

Storage and Other Functions

Stores Vitamins and Minerals: The liver stores significant amounts of vitamins A, D, E, K, and B12, as well as iron and copper.[3] Regulates Blood Clotting: Blood clotting coagulants are created using vitamin K, which can only be absorbed with the help of bile, a fluid the liver produces.[3]

Regeneration

The liver is the only solid organ that uses regenerative mechanisms to ensure that the liver-to-bodyweight ratio is always at 100% of what is required for body homeostasis.[29] Two-thirds hepatectomy was successfully performed on rodents in the 1930s, and the remarkable ability of the liver to regenerate was recognized.[21]

The unique regenerative abilities of the liver have been a highly motivating subject of research for several decades. First, understanding liver regeneration could unlock mechanisms of regeneration on other organs. Second, it has important clinical applications, ranging from large liver resections, to acute liver failure, to living-donor liver transplantation.[22]

Liver regeneration is a complex process involving the crosstalk of multiple cell types, including hepatocytes, hepatic stellate cells, endothelial cells and inflammatory cells. The healthy liver is mitotically quiescent, but following toxic damage or resection the cells can rapidly enter the cell cycle to restore liver mass and function. During this process of regeneration, epithelial and non-parenchymal cells respond in a tightly coordinated fashion.[27]

Prometheus Bound

The liver holds a unique place in Greek mythology through the story of Prometheus, a connection that has fascinated modern researchers studying liver regeneration. Stem-cell biologists and those involved in regenerative medicine are fascinated by the story of Prometheus, the Greek god whose immortal liver was feasted on day after day by Zeus' eagle. This myth invariably provokes the question: Did the ancient Greeks know about the liver's amazing capacity for self-repair?[11]

Prometheus suffers a gruesome punishment in Greek myth. By day an eagle tears at his liver; by night the liver fully regenerates. Repeat.[12] Zeus then sent an eagle to eat his liver. The bird would eat the liver every day and the organ would grow back every night.[17]

However, scholarly analysis suggests this connection may be coincidental. Since the 1990s it's been fashionable to take the story as describing a real medical phenomenon, the liver's unique ability to regenerate. But how did the Greeks know about liver regeneration? Easy: they didn't. Liver regeneration wasn't discovered until the 1800s.[12]

Nevertheless, there is no convincing evidence that ancient Greeks had any specific knowledge about liver regeneration, a concept introduced in the early 19th century.[16] Instead, the choice of the liver in Prometheus's punishment likely relates to its cultural significance. The liver is seen as the source of passion, or emotion, within Greek mythology and is frequently associated with anger and wrath specifically. Bile, which is produced by the liver, is often said to rise in instances of extreme emotion, principally anger.[19]

The myth of Prometheus isn't about liver regeneration: it's about revenge.[12] Prometheus's liver, as the source of his passion and reason and, presumably, his own anger at his fate, will be eaten by Zeus's "winged hound," a representation of Zeus himself. In this vein, Zeus will consume Prometheus's own passion and use it against him in the form of Zeus's never-ending wrath. By eating Prometheus's liver, Zeus not only destroys Prometheus's passion but also fuels his own wrath and power, so to speak.[19]

Liver Diseases

There are over 100 types of liver diseases, but they fall into a handful of subtypes.[4] Common conditions include hepatitis, cirrhosis, fatty liver disease, and liver cancer. Alcohol-induced hepatitis: Heavy alcohol use can cause acute or chronic hepatitis (inflammation in your liver). If it's frequent or lasts a long time, it can lead to cirrhosis and liver failure.[4]

Additionally, cirrhosis, steatosis, and age can have detrimental effects on the liver's ability to regenerate. Little evidence exists to explain how altered liver pathology affects the process of liver regeneration.[25]

Clinical Significance

Liver transplantation represents a milestone in liver regeneration. The first successful human liver transplant was performed by Thomas E. Starzl in 1963. It represents not only represents a significant breakthrough in clinical medicine, providing new hope to patients with advanced liver disease, but also enriches our scientific understanding of liver biology, particularly the regenerative capacity.[21]

Liver function tests (LFTs) are a commonly ordered panel among clinicians to help assess a patient's liver. Its components, aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, alkaline phosphatase, and gamma-glutamyltranspeptidase (GGT), help portray a portrait of what is occurring in the liver, the panel merely identifies the degree of cell damage if any, occurring in the liver.[2]