Abstract
The liver, recognised as the largest gland in the human body, consists of a spongy arrangement of wedge-shaped lobes and performs numerous metabolic and secretory roles. This research article aims to provide a comprehensive overview of the liver’s anatomy. Additionally, it will elucidate the three main functions of the liver which include bile production, storage functions, and metabolism of drugs.
The Liver’s Structural Characteristics
I - Introduction and Basic Anatomy
The liver is situated in the upper right quadrant of the abdominal cavity, positioned beneath the diaphragm and above the stomach, right kidney and intestines. This organ, which resembles a cone, has a dark reddish-brown hue and typically weighs approximately three pounds. Blood supply to the liver is derived from two primary sources: the hepatic artery, which delivers oxygenated blood, and the hepatic portal vein, which brings nutrient-rich blood [1].
The falciform ligament is a slender, fibrous structure that delineates the two lobes of the liver while anchoring it to the abdominal wall. The glisson’s capsule refers to a layer of loose connective tissue that envelopes the liver along with its associated arteries and ducts. Furthermore, The peritoneum is a membrane that encases the liver, forming its outer layer [4]. At any given time, the liver contains about one pint, or 13%, of the total blood volume in the body.
It is composed of two principal lobes, each divided into eight segments that contain approximately 1000 lobules – these are smaller lobes. These lobules are linked to minor ducts that converge into larger ducts, ultimately forming the common hepatic duct. This duct is responsible for transporting bile produced by liver cells to the gallbladder and duodenum (the initial section of the small intestine) through the common bile duct [1,2].
II - Lobules
The liver’s functional unit is known as the lobule. Each lobule exhibits a hexagonal shape with a portal triad (comprising the portal vein, bile duct and hepatic artery) located at each vertex of the hexagon. The core of the lobule consists of hepatocytes, which possess distinct apical and basolateral membranes that serve different physiological functions. Hepatocytes are categorised into three zones based on their functional roles and blood supply.
Zone I, recognized as the periportal area, is characterised by optimal perfusion and is the first to undergo regeneration due to its proximity to oxygen-rich blood and essential nutrients. This zone significantly contributes to oxidative metabolic processes, including bile synthesis, cholesterol production, and the catabolism of amino acids.
Zone II is identified as the pericentral region, situated between zones I and III. Zone III, in contrast, experiences the least perfusion owing to its distance from the portal triad. This zone is primarily involved in detoxification processes and drug metabolism [3,5].
Physiology of the Liver
I - Bile Production
Bile serves a crucial role in the human body, facilitating elimination of substances that the kidneys do not excrete and supporting the digestion and absorption of lipids through the action of bile salts and acids. This fluid is synthesised by hepatocytes and primarily consists of water, electrolytes, bile salts, bile acids, cholesterol, bilirubin and phospholipids among other components [3].
Once produced, bile is secreted from hepatocytes into the bile canaliculi, progressing through larger ducts until it reaches the duodenum or is stored in the gallbladder, where it is concentrated based on the pressures exerted by the duct and the sphincter of Oddi. After its release into the duodenum, bile participates in enterohepatic circulation where it fulfils its digestive functions in the intestine. Components of bile that are not excreted are recycled; gut bacteria convert them into bile acids, which are then reabsorbed in the ileum and transported back to the liver for reuse [3,6].
II - Storage Functions
The liver primarily stores metabolic fuels which include glycogen and lipids. The liver regulates blood glucose flow. 20% of carbohydrates consumed during a meal are stored in the liver and released gradually in between meals. Hepatic glycogen, a branching glucose polymer, where carbohydrates are stored. Less than 75g (400 kcal) of glycogen is typically stored by the liver, making up 20% of the body’s total glycogen reserve (the remainder is stored skeletal muscle [3,7].
Lipids are stored in the liver in the form of triglycerides within vacuoles of hepatocytes. The normal fat content in the liver is maintained at less than 5%. Triglycerides are synthesised from surplus glucose when carbohydrate consumption surpasses the liver’s glycogen storage capacity [7].
III - Drug Metabolism
Drug metabolism constitutes a biotransformation mechanism through which both endogenous and exogenous substances are transformed into more polar derivatives, thereby enhancing excretion from the organism. This metabolic process is categorised into three distinct phases. Phase I metabolism encompasses functionalization reactions, while Phase II metabolism involves conjugation reactions. Phase III pertains to the transporter-mediated removal of drugs and/or their metabolites from the body, typically occurring through the liver, gastrointestinal tract, kidney or lungs [8].
Resources
https://www.hopkinsmedicine.org/health/conditions-and-diseases/liver-anatomy-and-functions#:~:text=Functions%20of%20the%20liver&text=All%20the%20blood%20leaving%20the,body%20or%20that%20are%20nontoxic. - article posted on John Hopkins’ official website
https://www.sciencedirect.com/topics/medicine-and-dentistry/liver-blood-flow - Hepatobiliary System by Harvey A. Ziessman MD and James H. Thrall MD
https://www.ncbi.nlm.nih.gov/books/NBK535438/#:~:text=The%20liver%20is%20a%20critical,of%20an%20adult's%20body%20weight. - Physiology, Liver by Arjun Kalra; Ekrem Yetiskul; Chase J. Wehrle; Faiz Tuma.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091928/ - Bile Formation and Secretion by James L. Boyler
https://derangedphysiology.com/main/cicm-primary-exam/required-reading/liver-physiology/Chapter%20111/storage-functions-liver#:~:text=Vitamin%20storage%20in%20the%20liver,stellate%20cells%20as%20retinyl%20palmitate. - 2023 CICM Primary Syllabus
https://pubmed.ncbi.nlm.nih.gov/27842765/ - Drug Metabolism in the Liver by Omar Abdulhameed Almazroo, Mohammad Kowser Miah and Raman Venkataramanan
great!