Liver

• 1. The Chemical Factory

  ›

  The liver is the only organ in the body that nature did not learn how to replace. Doctors can put a person on dialysis when the kidneys quit. They can wire a failing heart to a machine. But when the liver gives out completely, the source is blunt about the choice that remains: a transplant, or nothing. Artificial livers do not exist for long-term use, and liver dialysis buys only short stretches of time. Estimates of how many separate functions this organ performs vary, but the figure cited is around 500, which is why it has sometimes been called the body's chemical factory. It sits in the right upper quadrant of the abdomen, below the diaphragm, mostly hidden behind the lower right rib cage. A normal human liver weighs roughly 1.5 kilograms and measures about 15 centimeters across. It is both the heaviest internal organ and the largest gland in the human body. How does one wedge of dark reddish brown tissue manage detoxification, digestion, protein synthesis, and the storage of years' worth of vitamins all at once? Why did the ancient Greeks chain a Titan to a rock and feed his liver to a bird? And why would a tribe in Sudan brew a drink from the liver of a giraffe and swear it brings on dreams? The answers begin with how this organ is built.

• 2. Lobes And Lobules

  ›

  Glisson's capsule, the fibroelastic layer that wraps the entire liver, carries the name of Francis Glisson, a British doctor. This connective tissue does more than cover the surface. It reaches inside the organ, traveling alongside the blood vessels, ducts, and nerves that enter at the hepatic hilum. From above, the liver divides into a right and a left lobe, split at the surface by the falciform ligament. From below, two more appear: the caudate and quadrate lobes. A line imagined from the left of the vena cava forward, dividing liver and gallbladder into halves, is called Cantlie's line. The functional units of the organ are the hepatic lobules, roughly hexagonal, each built from plates of hepatocytes radiating from a central vein. At each corner runs the portal triad: the hepatic artery, the portal vein, and the common bile duct. On a liver ultrasound this trio appears as a Mickey Mouse sign, with the portal vein as the head and the artery and bile duct as the ears. The Couinaud classification system carves the functional lobes into eight independent segments, each with its own inflow, outflow, and biliary drainage. Segment one, the caudate lobe, is unusual: it draws blood from both the right and left branches of the portal vein. That dual supply makes it a structure apart from everything around it.

• 3. Two Rivers Of Blood

  ›

  About 75 percent of the liver's blood arrives not through an artery but through the hepatic portal vein, carrying venous blood drained from the spleen, the gastrointestinal tract, and their associated organs. The hepatic arteries supply the remaining quarter, bringing oxygen-rich blood from the aorta. Oxygen comes from both rivers in near-equal measure, with roughly half the demand met by each. The liver consumes a striking share of the body's energy budget, accounting for about 20 percent of resting total body oxygen use. Because the liver is expandable, it doubles as a blood reservoir. Its normal blood volume, in the hepatic veins and sinuses combined, is about 450 milliliters, almost a tenth of all the blood in the body. When pressure builds in the right atrium and backs up into the liver, the organ swells, holding half a liter to a full liter of extra blood. This happens especially in cardiac failure with peripheral congestion. The liver also generates lymph in remarkable quantity. The pores in its sinusoids are so permeable that fluid and protein pass freely into the perisinusoidal space, producing lymph with a protein concentration of about 6 grams per deciliter. Roughly half of all the lymph formed in the resting body originates here.

• 4. What It Builds And Breaks

  ›

  All plasma proteins except the gamma-globulins are made in the liver, and the list of what it manufactures reads like a roster of the blood's machinery. It produces coagulation factors numbered I through XIII, including fibrinogen and prothrombin, along with protein C, protein S, and antithrombin. It is a major site for thrombopoietin, the hormone that tells the bone marrow to make platelets. Glycogen is the liver's pantry. It synthesizes and stores around 100 grams of it through glycogenesis, then breaks it back down into glucose when the body runs short. When even that runs out, gluconeogenesis builds fresh glucose from amino acids, lactate, or glycerol. Albumin, the most abundant protein in blood serum, comes from the liver and maintains oncotic pressure while ferrying fatty acids and steroid hormones. The same organ tears things down. It converts ammonia into urea through the urea cycle, sending the waste out in urine. It breaks down insulin and other hormones, and it handles bilirubin through glucuronidation so the pigment can leave the body in bile. Drug metabolism happens here too, though the process can backfire in toxication, where the new metabolite is more poisonous than the substance it came from. Among its stores, the liver holds a 3 to 5 year supply of vitamin B12 and a 1 to 2 year supply of vitamin A.

• 5. When The Factory Fails

  ›

  Nonalcoholic fatty liver disease is the most common chronic liver disease in the world, affecting an estimated one-third of the global population. Scarring from almost any cause leads to cirrhosis, which raises resistance to blood flow and can drive portal hypertension. Hepatitis, inflammation of the liver, is usually viral, and the main types run from A through E. Chronic infection with hepatitis B or C is the leading cause of liver cancer. Globally, about 248 million people are chronically infected with hepatitis B and 142 million with hepatitis C. The symptoms of a failing liver are written on the body. Bilirubin that the liver can no longer clear deposits in the skin and the whites of the eyes, producing jaundice and an intense itch that drugs often cannot relieve. Itching is the most common complaint among people in liver failure. Pale stools appear when stercobilin is missing, urine darkens as bilirubin spills into it, and the ankles swell because the liver has stopped making albumin. There is one strange piece of good news from the kitchen: regular caffeine has been shown to guard against cirrhosis and liver cancer in moderate coffee drinkers. A 2017 study found the benefit held regardless of how the coffee was brewed.

• 6. The Organ That Grows Back

  ›

  As little as 25 percent of a liver can grow into a whole liver again, making it the only human internal organ capable of natural regeneration of lost tissue. In mammals this is not true regeneration but compensatory growth. The lobes that were removed do not regrow, and what returns is function rather than original form. In zebrafish the process is more complete, restoring both the shape and the size of the organ. The engine of this recovery is the hepatocyte itself, leaving its quiescent G0 phase, entering G1, and dividing, a process switched on by the p75 receptors. Scientific and medical writing on this subject keeps returning to one figure from Greek myth: the Titan Prometheus, chained to a rock in the Caucasus, his liver devoured by an eagle each day and regrown each night. The myth hints that the ancient Greeks may have already grasped the organ's capacity for self-repair. Human liver transplants were first performed by Thomas Starzl in the United States and Roy Calne in Cambridge, England, in 1963 and 1967. Living donor transplantation arrived in 1989 for children, since only 20 percent of an adult's liver, Couinaud segments 2 and 3, is needed for an infant. Adult-to-adult transplants now use the donor's right hepatic lobe, about 60 percent of the organ, a riskier operation that a 2006 publication linked to at least fourteen donor deaths.

• 7. Seat Of The Soul

  ›

  In Plato and in later physiology, the liver was held to be the seat of the darkest emotions, specifically wrath, jealousy, and greed, the feelings that drive men to action. The Talmud names it the seat of anger, with the gallbladder set against it as a counterweight. Across the Near East and the Mediterranean, ancient peoples practiced haruspicy, a divination that read the future in the livers of sheep and other animals. The organ left deep marks on language. In Persian, Urdu, and Hindi, the word jigar stands for courage and strong feeling, and the endearment jan e jigar means the strength of my liver. In Zulu, the word for liver, isibindi, is the same as the word for courage. English keeps the opposite sense in lily-livered, a term for cowardice rooted in the medieval belief that the liver held bravery. In biblical Hebrew the word for liver also means heavy, used to describe the rich and the honored. The Romance languages took a different path entirely. Their word for liver, the French foie and Spanish higado, descends not from the Latin anatomical term jecur but from ficatum, meaning stuffed with figs, a reference to geese fattened on figs for their livers. That culinary root points toward the strangest chapter of all, where a liver is not eaten but drunk.

• 8. Umm Nyolokh

  ›

  Umm nyolokh is a non-alcoholic drink made from the liver and bone marrow of the giraffe by the Humr, a tribe of the Baggara people native to southwestern Kordofan in Sudan, who speak Chadian Arabic. They claim it is intoxicating, using the word sakran, and say it brings on dreams and even waking hallucinations. The puzzle is that the Humr are Mahdists and strict abstainers from alcohol, so a Humrawi is never drunk on liquor or beer, yet he reaches for the same word to describe what umm nyolokh does to him. The anthropologist Ian Cunnison joined the Humr on a giraffe hunt in the late 1950s and recorded their belief that once a person has drunk umm nyolokh he will return to giraffe again and again. Cunnison himself could not credit it. Writing in 1958, he concluded that there was likely no intoxicating substance in the drink and that the effect was a matter of convention, perhaps brought about subconsciously. Later the account traveled from his obscure paper into mainstream writing through a conversation between W. James of Oxford and R. Rudgley, who speculated that the compound N,N-Dimethyltryptamine in giraffe liver might explain the claims. The liver has carried poison as well as visions. Certain Tungusic peoples of northeast Asia once made arrow poison from rotting animal livers, later applying it to bullets, a method the Tungus themselves compared to the poisoning of arrows. Whether anything truly psychoactive resides in a giraffe's liver remains unproven, still waiting on detailed analysis of the organ and the drink made from it.