Where is the liver located in the human body. How does the liver function as a critical organ. What are the main components of liver anatomy. How does liver development occur in the fetus. What are the key functions of the liver in metabolism and detoxification. How is the liver’s blood supply structured. What are the unique features of liver cellular architecture.

The Liver’s Location and Anatomical Structure

The liver is a crucial organ in the human body, accounting for approximately 2% of an adult’s body weight. Its location and structure are fundamental to its diverse functions. But where exactly is the liver situated?

The liver is located in the upper right quadrant of the abdominal cavity, just below the diaphragm. It is protected by the ribcage, which highlights its importance and vulnerability. The organ’s unique shape allows it to fit snugly against the surrounding structures, maximizing space efficiency in the abdominal cavity.

What makes the liver’s anatomy so special? The liver’s structure is complex and highly organized:

• It is divided into two main lobes: the larger right lobe and the smaller left lobe
• These lobes are further subdivided into segments
• The liver is encased in a fibrous capsule called Glisson’s capsule
• It is anchored to the abdominal wall by the falciform ligament

This intricate structure allows the liver to perform its myriad functions efficiently while maintaining its position within the body.

The Liver’s Dual Blood Supply: A Unique Circulatory System

One of the most fascinating aspects of liver anatomy is its dual blood supply. How does this unique circulatory system work?

The liver receives blood from two sources:

1. The portal vein (approximately 75% of blood supply)
2. The hepatic artery (approximately 25% of blood supply)

This dual blood supply is crucial for the liver’s function. The portal vein brings nutrient-rich blood from the digestive system, while the hepatic artery supplies oxygen-rich blood. This arrangement allows the liver to efficiently process nutrients and toxins from the digestive tract while maintaining its own high metabolic activity.

Why is this dual blood supply important? It enables the liver to perform its diverse functions, including:

• Detoxification of harmful substances
• Synthesis of proteins and cholesterol
• Storage of vitamins and minerals
• Production of bile for digestion

Understanding this unique circulatory system is key to appreciating the liver’s central role in maintaining overall health.

The Liver Lobule: The Functional Unit of Liver Physiology

At the cellular level, the liver’s structure is even more intricate. The functional unit of the liver is called the lobule. But what exactly is a liver lobule and how does it work?

A liver lobule is a hexagonal structure with the following key components:

• Portal triads at each corner, consisting of a portal vein, hepatic artery, and bile duct
• Hepatocytes (liver cells) arranged in plates radiating from the central vein
• Sinusoids (blood channels) between the plates of hepatocytes
• A central vein in the middle of the lobule

This arrangement allows for efficient exchange of substances between the blood and hepatocytes. Blood flows from the portal triads towards the central vein, while bile flows in the opposite direction, towards the bile ducts.

The lobule structure is further divided into three functional zones based on oxygen and nutrient supply:

1. Zone I (periportal): Best perfused, first to regenerate
2. Zone II (transitional): Intermediate zone
3. Zone III (pericentral): Lowest perfusion, most susceptible to damage

This zonal arrangement allows different parts of the lobule to specialize in various liver functions, enhancing overall efficiency.

The Space of Disse: A Crucial Microenvironment in Liver Function

Within the liver’s complex structure, there’s a small but critically important area called the space of Disse. What is this space, and why is it so vital to liver function?

The space of Disse is the area between the sinusoidal lumen and the surrounding basolateral membrane of hepatocytes. Its unique features include:

• Microvilli extending from hepatocytes into this space
• An extracellular matrix composed of various collagens and proteins
• Presence of specialized cells like Kupffer cells and Ito cells

Why is the space of Disse so important? It serves several crucial functions:

1. Facilitates exchange of substances between blood and hepatocytes
2. Provides structural support for hepatocytes and the lobule
3. Houses immune cells (Kupffer cells) that filter out harmful substances
4. Contains Ito cells that store fat and can aid in liver regeneration

The space of Disse exemplifies how even the smallest structures in the liver play significant roles in its overall function and health.

Liver Development: From Embryo to Functional Organ

The liver’s complex structure begins to form early in fetal development. How does this vital organ develop from a simple embryonic structure to the multifunctional organ we know?

Liver development occurs in several stages:

1. Formation of the hepatic diverticulum from the foregut around the fourth week of gestation
2. Growth and interaction with the septum transversum
3. Differentiation into liver primordium and gallbladder
4. Development of hepatic cords and sinusoids
5. Assumption of hematopoietic function around the sixth week
6. Commencement of bile production around the 12th week

This developmental process is guided by various molecular signals, including:

• Wnt/B-catenin pathway
• Fibroblast growth factors (FGF)
• MAPK pathway
• VEGF for sinusoid formation

Understanding liver development provides insights into congenital liver disorders and potential regenerative therapies.

The Liver’s Role in Metabolism: A Biochemical Powerhouse

The liver’s complex structure supports its role as a metabolic hub. But what specific metabolic functions does the liver perform?

The liver is involved in numerous metabolic processes, including:

• Carbohydrate metabolism: glycogenesis, glycogenolysis, gluconeogenesis
• Protein metabolism: synthesis of plasma proteins, amino acid interconversion
• Lipid metabolism: synthesis of cholesterol and triglycerides, lipoprotein production
• Bile acid synthesis and secretion
• Drug metabolism and detoxification

These functions are distributed across the liver’s zones:

1. Zone I: Oxidative metabolism, gluconeogenesis, bile formation
2. Zone II: Intermediate functions
3. Zone III: Drug detoxification, glycolysis, lipogenesis

This zonal specialization allows the liver to efficiently manage multiple metabolic processes simultaneously, maintaining bodily homeostasis.

The Liver’s Immune Function: Guardian of the Body

Beyond its metabolic roles, the liver plays a crucial part in the body’s immune defense. How does the liver contribute to immunity?

The liver’s immune functions include:

• Production of acute-phase proteins in response to inflammation
• Removal of pathogens and foreign particles from the blood
• Tolerance induction to food antigens
• Regulation of systemic immunity

Key players in the liver’s immune function are:

1. Kupffer cells: Resident macrophages that engulf and destroy pathogens
2. Hepatic stellate cells: Regulate immune responses and fibrosis
3. Liver sinusoidal endothelial cells: Present antigens and regulate T cell responses

The liver’s unique position, receiving blood from the gut via the portal vein, makes it a critical checkpoint for immune surveillance. Its ability to balance immune responsiveness with tolerance is crucial for maintaining overall health.

In conclusion, the liver’s complex anatomy and physiology make it a truly remarkable organ. From its unique dual blood supply to its intricate cellular architecture, every aspect of the liver’s structure contributes to its diverse functions. Understanding these features not only deepens our appreciation of this vital organ but also informs medical approaches to liver health and disease treatment.

Physiology, Liver – StatPearls – NCBI Bookshelf

Introduction

The liver is a critical organ in the human body that is responsible for an array of functions that help support metabolism, immunity, digestion, detoxification, vitamin storage among other functions. It comprises around 2% of an adult’s body weight. The liver is a unique organ due to its dual blood supply from the portal vein (approximately 75%) and the hepatic artery (approximately 25%).

Cellular Level

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. The foundation of the lobule is composed of hepatocytes, which have physiologically distinct apical and basolateral membranes. Based on function and perfusion, hepatocytes are divided into 3 zones.

1. Zone I is considered to be the periportal region of hepatocytes and are the best perfused and first to regenerate due to their proximity to oxygenated blood and nutrients. Due to its high perfusion, zone I plays a large role in oxidative metabolisms such as beta-oxidation, gluconeogenesis, bile formation, cholesterol formation, and amino acid catabolism.

2. Zone II is defined as the pericentral region of the hepatocytes and zone II sits between zones I and III.

3. Zone III has the lowest perfusion due to its distance from the portal triad. It plays the largest role in detoxification, biotransformation of drugs, ketogenesis, glycolysis, lipogenesis, glycogen synthesis, and glutamine formation.

Bile flow is further facilitated by bile canaliculi, which are formed by apical membranes of neighboring hepatocytes. Due to the 3-dimensional arrangements of hepatocytes, the canaliculi form a lattice-like network or “chicken-wire pattern,” that helps increase the surface area of flow. It is important to recognize that bile and blood flow in opposite directions to each other. This makes sense as the liver produces bile, so bile in the ducts are leaving the liver; whereas, the dual blood supply is entering the liver to perfuse it. Blood drains into the branch of the hepatic vein that lies in the lobule’s center via sinusoidal lumens of the lobule.[1]

The space between the sinusoidal lumen and the surrounding basolateral membrane of hepatocytes is called the space of Disse. This space is occupied by microvilli extending from the basolateral membrane of the hepatocytes that communicate with the capillary, allowing the hepatocyte to reach its’ blood supply. The space of Disse houses an extracellular matrix composed of a variety of collagens, proteoglycans, and other proteins that help provide scaffolding for the hepatocytes and, by extension, the lobule as a whole. The importance of the scaffolding that takes place in the space of Disse is amplified further by the fact that hepatocytes do not contain a true basement membrane. The space of Disse also contains Kupffer cells (macrophages) and Ito cells (stellate cells). The Kupffer cells sit in the space to filter out unnecessary or pathologic material from the circulation. The Ito cells serve as storage for fat, such as vitamin A. In the right setting, they can also serve as myofibroblasts and aid in the regeneration of the liver.[2]

Development

The liver arises as a part of the foregut. It stems from endodermal cells and starts as the hepatic diverticulum around the fourth week of development. It forms within the peritoneum and is anchored to the abdominal wall by the falciform ligament which arises from the ventral mesentery. The umbilical vein passes through the falciform ligament on its way from the umbilical cord to the liver.

The diverticulum is believed to be induced by a combination of several pathways, mainly the Wnt/B-catenin pathway and fibroblast growth factors (FGF), which are secreted by fetal cardiac cells, which is induced by the MAPK pathway.[2] The diverticulum then grows and interacts with the septum transversum, a structure that divides the heart from the abdominal cavity and later contributes to the formation of the diaphragm. The diverticulum then differentiates into the primordium of the liver or the gallbladder. As the primordium liver grows, it develops into hepatic cords that anastomose around spaces lined by endothelium, forming the primordium of the hepatic sinusoids. VEGF plays an important role in the formation of the hepatic sinusoids.[2]

The portal vein, which arises from umbilical and vitelline veins is the central vessel in which the hepatic cords form around. This helps explain why the portal vein is the primary blood supply for the liver as opposed to the hepatic artery. The hepatic artery develops with the biliary tract and continues to develop post-birth.[1] Around the sixth week, the liver becomes responsible for hematopoiesis, and hepatocytes create bile around the 12th week.

Organ Systems Involved

The liver plays a role in nearly every organ system in the body. It interacts with the endocrine and gastrointestinal systems by aiding in digestion and metabolism. The liver is the storage location for fat-soluble vitamins and handles cholesterol homeostasis. It stores iron and copper. It plays a role in hematology with clotting factor and protein synthesis. The liver plays a role in heme breakdown into unconjugated bilirubin and conjugates it. It plays a role in sex hormone metabolism and produces carrier proteins that are important in reproduction and development. Finally, Kupffer cells and Pit cells play an important role in the body’s immunologic system.

Function

Bile Production

Bile is an important fluid as it helps excrete material not excreted by the kidneys and aids in the absorption and digestion of lipids via secretion of bile salts and acids. Bile is produced by hepatocytes and is mainly composed of water, electrolytes, bile salts, bile acids, cholesterol, bile pigment, bilirubin, and phospholipids in addition to other substances. Bile is secreted from hepatocytes into the bile canaliculi where it travels from smaller ducts to the larger ducts eventually ending up in the duodenum or being stored in the gallbladder for storage and concentration as determined by the duct and sphincter of Oddi pressures. Following secretion of bile into the duodenum, it undergoes enterohepatic circulation, where it performs its job in the bowel, and bile components that are not excreted are recycled by conversion into bile acids by gut bacteria for reuse by absorption in the ileum and transport back to the liver.

Fat-Soluble Vitamin Storage and/or Metabolism

Most fat-soluble vitamins reach the liver via intestinal absorption in the form of chylomicrons or VLDL. The liver stores and/or metabolizes fat-soluble vitamins. As discussed earlier, vitamin A is stored in Ito cells. It can undergo oxidation into retinal followed by retinoic acid for phototransduction, or retinoic acid can be conjugated into glucuronide for secretion into bile. Whether vitamin D3 comes from the skin, animal products, or plant products, it must undergo 25-hydroxylation by the hepatic CYP-450 system, which is further hydroxylated in the kidney to achieve its functional form. The hepatic CYP-450 system then hydroxylates carbon 24 to render vitamin D inactive. The liver receives vitamin E in its alpha and gamma-tocopherol forms. Alpha-tocopherol is integrated with VLDL or HDL in the liver and is then secreted back into circulation while the liver metabolizes the gamma-tocopherol form for excretion. While vitamin K is not stored or metabolized in the liver, its presence is essential as the liver enzyme, gamma-glutamyl carboxylase requires it for gamma-carboxylation of coagulation factors II, VII, IX, X, and protein C and protein S.

Drug Metabolism

Another critical function of the liver is metabolism and/or detoxification of xenobiotics. The liver uses lysosomes for some of these substances, but a major route of metabolism and detoxification is through biotransformation. The liver functions to transform xenobiotics mainly by converting them from a lipophilic form to a hydrophilic form through 2 reactions: phase I and phase II. These reactions mainly take place in the smooth endoplasmic reticulum of hepatocytes. Phase I reactions create a more hydrophilic solute via oxidation, reduction, and hydrolysis using primarily the cytochrome P450 (CYP450) family of enzymes. The product of phase I has an oxygen species that reacts better with enzymes involved with phase II reactions. Phase II reactions conjugate the metabolites created in phase I to make them more hydrophilic for secretion into blood or bile. There are three main avenues for conjugation performed in phase II reactions: conjugation to glucuronate, glutathione, or sulfate. Conjugation to glucuronate, such as with bilirubin, takes place in the smooth endoplasmic reticulum. Substances undergoing sulfate conjugation, such as alcohols, are usually done in the cytosol due to the location of the needed enzymes. Most glutathione conjugation occurs in the cytosol, with a minority occurring in the mitochondria. It is essential that glutathione is reduced and depletion of reduced glutathione for conjugation can allow the buildup of toxic metabolites as seen in acetaminophen overdose. Some describe the transport of metabolites produced from these reactions as phase III. Other organs, such as the kidney and gut can aid in drug metabolism. Multiple factors such as age, gender, drug-drug interactions, diabetes, pregnancy, liver or kidney disease, inflammation, or genetics to name a few, affect drug metabolism. [3]

Bilirubin Metabolism

The liver plays a significant role in the breakdown of heme. Hemolysis takes place in multiple locations throughout the body, including the liver, spleen, and bone marrow. Heme is broken down into biliverdin, which is then reduced to unconjugated bilirubin. The liver receives unconjugated bilirubin bound to albumin from the circulation. The unconjugated bilirubin then undergoes conjugation via the uridine diphosphate glucuronyltransferase (UGT) system, a phase II process, to become hydrophilic. The newly conjugated bilirubin then is secreted via bile canaliculi into the bile or small amounts dissolve in the blood where it then gets filtered for excretion by the kidneys. Most conjugated bilirubin enters the bile and is excreted with bile in feces as it is not absorbable by the intestinal wall. Some bilirubin is converted to urobilinogen or unconjugated bilirubin by gut bacteria for reabsorption to undergo enterohepatic circulation.[4][5]

Other Functions

The liver plays a role in thyroid hormone function as the site of deiodination of T4 to T3. The liver manages the synthesis of nearly every plasma protein in the body, some examples include albumin, binding globulins, protein C, protein S, and all the clotting factors of the intrinsic and extrinsic pathways besides factor VIII.

Related Testing

Liver function tests (LFTs) are a commonly ordered panel among clinicians to help assess a patient’s liver. While 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. The reason these levels better reflect the presence of injury is that these enzymes are components of hepatocytes that get released into the circulation upon hepatocyte damage. ALT and AST are important enzymes in gluconeogenesis, with ALT being more specific for the liver as AST is found in a variety of tissues. Alkaline phosphatase (ALP) can be found in the bone as well as the biliary tree, so it is not as specific, but when used in combination with the rest of the panel, it supplies evidence of hepatocellular injury. In particular, elevated ALP signals damage to the lining of the biliary tract.[6]

A true test to assess the liver’s function is its ability to synthesize protein. While albumin is an important protein the liver produces, albumin levels do not only provide an idea of how the liver is functioning, but its levels are also influenced by other factors, such as nutrition status and nephrotic syndromes. In addition, albumin has a half-life of 15 to 20 days and therefore may not identify acute liver dysfunction. As such, albumin levels are combined with coagulation studies to provide insight into the liver’s functional capacity. All clotting factors except for factor VIII are produced by the liver. The coagulation proteins used in the extrinsic pathway are tested with the PT test. These factors must be carboxylated in the liver, with a pathway that uses vitamin K, meaning an elevated PT could signal liver damage, vitamin K deficiency or current warfarin therapy.[6]

Ultrasound is an inexpensive and noninvasive imaging modality commonly used in the assessment of the liver. Most commonly, right upper quadrant ultrasounds are used to assess the biliary tree for obstruction and/or inflammation, such as in cholecystitis or choledocholithiasis. Ultrasound has the ability to reveal various liver pathologies and show various characteristics, such as border regularity, solid or cystic, and location.

Triple phase imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) studies is used to characterize and diagnose liver lesions. These studies use contrast and scan images at specific time points to gather a portal venous phase, arterial phase, and venous phase. Depending on how the lesion takes up the contrast, clinicians can better diagnose the lesion, sometimes without needing to perform invasive procedures, such as needle biopsy. For example, hepatocellular carcinoma (HCC) as discussed below, demonstrates arterial hyperenhancement in most cases as they gather their blood supply from the hepatic artery. While CT is generally cheaper, MRI may be more beneficial due to its ability to show soft tissue better, potentially detailing the lesion better.[7][8]

Pathophysiology

Cirrhosis is a result of continuous liver injury, inflammation, fibrosis, and necrosis. Alcoholism and chronic hepatitis B and C commonly cause cirrhosis. Hepatitis C is the most damaging. The fibrosis present in cirrhosis occurs from the secretion of TGF-beta from the Ito cells in the space of Disse.

Cirrhosis usually represents with end-stage liver disease and, as such, liver function is greatly compromised. The diminished ability to produce protein and detoxify substances results in symptoms of portal hypertension, hyperestrinism, and hypoalbuminemia. Decreased clotting factor synthesis results in coagulopathy. Its presentation arises from manifestations from diminished hepatic function and portal hypertension.[9]

Sequelae of portal hypertension include portosystemic shunts that result in varices in various locations, caput medusae, and hemorrhoids. Other manifestations of portal hypertension include ascites, spider angiomas, hepatic encephalopathy, hepatorenal syndrome, and splenomegaly. Esophageal varices are the most common cause of death in cirrhotic patients.

The Child-Pugh score and model for end-stage liver disease (MELD) score are both used to assess and determine prognosis in cirrhotic patients. Both look at a combination of variables to score the patient. The Child-Pugh score evaluates ascites, hepatic encephalopathy (HE), total bilirubin, albumin, and prothrombin time or INR. The MELD score uses creatinine, bilirubin, and INR. While both are used to create a predictive model for cirrhotic patients, the MELD score is the scale of choice for the evaluation of liver transplant patients. [10]

Jaundice is often a sign of altered bilirubin metabolism. The first sign of jaundice is often yellowing under the tongue, followed by scleral icterus (yellowing of the sclera). There are numerous causes for jaundice, which can typically be classified by getting a fractionated bilirubin where indirect bilirubin (unconjugated bilirubin) and direct bilirubin (conjugated bilirubin) are measured. The result of the fractionated bilirubin can help identify the etiology of the cholestasis into prehepatic and intrahepatic or extrahepatic causes.

A common etiology of prehepatic jaundice is hemolysis where the level of hemolysis overwhelms the conjugating capacity of the liver, resulting in a buildup of unconjugated bilirubin, causing jaundice. Causes of intrahepatic cholestasis can be congenital diseases, such as Gilbert syndrome, and Crigler-Najjar syndrome. In these congenital diseases, the enzyme responsible for bilirubin conjugation, UGT, is mildly deficient or completely deficient, respectively. Dubin-Johnson and Rotor syndrome are causes of direct bilirubinemia as there is a defect in canalicular transport of conjugated bilirubin. Other causes of post-hepatic cholestasis are an obstruction, such as due to a stone or malignancy. Viral hepatitis can result in both indirect and direct hyperbilirubinemia.[11]

Clinical Significance

A variety of viruses can lead to liver damage. Hepatitis viruses A and E lead to acute hepatitis without resulting in chronic hepatitis, although hepatitis E can lead to fulminant hepatitis in pregnant patients. Hepatitis A and E are typically seen in travelers and from contaminated water or seafood sources. They are usually self-limiting illnesses that present with jaundice and vomiting.[12] Hepatitis B, C, and D are viruses that can cause acute hepatitis that result in chronic hepatitis. Hepatitis D relies on hepatitis B for reproduction. It can either occur at the same time as hepatitis B, called coinfection, or on top of hepatitis B, called superinfection. The distinction is important as superinfection can lead to more severe disease. Hepatitis B and C can both occur from contaminated needles, as in tattoos, intravenous drug use, or iatrogenically.[13] Hepatitis B can also be sexually transmitted. The best treatment for hepatitis A, B, and C is vaccination, and IgG is a marker that shows vaccination or prior exposure, whereas IgM shows acute infection. There have been advancements in the treatment of hepatitis C, to where it can be cured using combination antiviral agents like sofosbuvir/velpatasavir.[14]

Primary biliary cholangitis (PBC) formerly known as primary biliary cirrhosis, is believed to be an autoimmune disease leading to chronic liver disease, eventually leading to end-stage liver disease and cirrhosis. It is most commonly seen in middle-aged women. Like other liver diseases, PBC can present with right upper quadrant and/or discomfort. Laboratory workup can reveal nonspecific elevations in liver enzymes. Anti-mitochondrial antibodies are the most specific marker for PBC and can be detected via ELISA. Treatment for PBC includes ursodeoxycholic acid to slow disease progression and other medications targeted at immune modulation such as methotrexate, steroids, and in some situations, calcineurin 2 inhibitors. A liver transplant is the only curative treatment.[15]

Alcoholism has deleterious long-term effects on the liver. The liver is responsible for the breakdown of alcohol and over time, constant alcohol use leads to cell injury due to toxic metabolite buildup, usually from acetaldehyde. As this process continues, the liver becomes cirrhotic, developing all the features of cirrhosis discussed above. Diagnosis is clinical and can be accomplished via clinical history, physical exam findings, laboratory findings, as well as questionnaires. Screening in clinics can be performed using the CAGE questionnaire. A paper and pencil questionnaire that can be administered is the AUDIT. Alcoholism can present with symptoms of portal hypertension as mentioned above, alcohol withdrawal, delirium tremens, or complications, such as Wernicke encephalopathy, Korsakoff syndrome, and hepatic encephalopathy. Some laboratory biomarkers used to assess for alcoholism include AST, ALT with the classic ratio of AST/ALT being 2:1, GGT, MCV, blood alcohol, and ethyl glucuronide. Treatment is centered around behavioral modification, usually with alcoholics anonymous, and can be supplemented by medications, such as disulfiram.

Besides malignant lesions, there are a variety of benign liver lesions. The four most commonly discussed are hemangiomas, which are the most common, focal nodular hyperplasia (FNH), hepatocellular adenomas, and hepatic cysts. FNH occurs in the setting of congenital vascular formations or vascular disruptions and it is not uncommon for them to be seen in association with hemangiomas.[16] These can be differentiated from hemangiomas macroscopically based on the presence of a central stellate scar and do not have as high of a risk of rupture that hemangiomas do. Imaging workup specific for FNH if prior workup is ambiguous includes sulfur colloid imaging or use of eovist.[17] Hepatocellular adenomas are well-defined lesions that are frequently caused by oral contraceptives and anabolic steroids and can grow during pregnancy. Treatment is centered on discontinuing known causative agents. They are only very rarely premalignant in the healthy population. There is an association of glycogen storage disorders with hepatocellular adenomas, which are more dangerous as there is an increased frequency of transformation into hepatocellular carcinoma in these situations.[18] Overall management can be conservative with serial imaging, but adenoma must be resected if greater than 5 cm, male gender, or the lesion is bleeding. If the patient is not an ideal surgical candidate, embolization can be performed.

The liver is susceptible to malignancy. Most cases of malignancy involving the liver are a result of metastasis to the liver due to it receiving blood from so much of the body. The most common primary malignancy of the liver is hepatocellular carcinoma. As discussed, HCC can arise from hepatocellular adenomas, but can also arise from cirrhosis, which occurs for a variety of reasons, such as primary biliary cirrhosis, alcoholism, NAFLD, chronic hepatitis B or C and more. Treatment for any malignant lesion depends on the patient’s clinical picture and involvement of the liver; if not too much of the liver is involved, resection and embolization or microwave ablation can be performed. Otherwise, systemic chemotherapy/radiation can be performed to minimize tumor burden.

Non-alcoholic, fatty liver disease (NAFLD) is a spectrum of liver disease ranging from benign steatosis to cirrhosis requiring a liver transplant. It is one of the most common chronic liver conditions necessitating a liver transplant. There are a variety of causes of NAFLD, ranging from metabolic syndrome, pregnancy, nutrition, drugs, toxins, and more. It is most commonly seen in diabetics and obese patients. It can also present in asymptomatic patients receiving workup for other reasons. It can sometimes present with right upper quadrant pain and/or discomfort. Liver enzymes can be elevated, classically with an elevated ALT:AST ratio. It is managed with lifestyle modification of diet, exercise, and weight loss. This can be further augmented by pharmacologic treatment with drugs that target insulin resistance like metformin, thiazolidinediones, lipid modulators, and vitamin E, which serves as an anti-oxidant.[19][20]

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Disclosure: Arjun Kalra declares no relevant financial relationships with ineligible companies.

Disclosure: Ekrem Yetiskul declares no relevant financial relationships with ineligible companies.

Disclosure: Chase Wehrle declares no relevant financial relationships with ineligible companies.

Disclosure: Faiz Tuma declares no relevant financial relationships with ineligible companies.

The Radiology Assistant : Liver

Robin Smithuis and Eduard E. de Lange

Radiology Department of the Alrijne Hospital, Leiderdorp, the Netherlands and University of Virginia Health System, Charlottesville, USA.

Publicationdate 2006-05-07 / update 2015-10-15 / 2022-06-13

The anatomy of the liver can be described using two different aspects: morphological anatomy and functional anatomy.

The traditional morphological anatomy is based on the external appearance of the liver and does not show the internal features of vessels and biliary ducts branching, which are of obvious importance in hepatic surgery.
The French surgeon and anatomist Claude Couinaud was the first to divide the liver into eight functionally indepedent segments allowing resection of segments without damaging other segments.

Segmental anatomy

Segmental anatomy according to Couinaud. Click to enlarge.

Couinaud classification

The Couinaud classification of liver anatomy divides the liver into eight functionally indepedent segments.
Each segment has its own vascular inflow, outflow and biliary drainage.
In the centre of each segment there is a branch of the portal vein, hepatic artery and bile duct.
In the periphery of each segment there is vascular outflow through the hepatic veins.
The liver is divided in three vertical planes:

• The plane of the right hepatic vein divides the right lobe into anterior and posterior segments.
• The plane of the middle hepatic vein divides the liver into right and left lobes or right and left hemiliver. This plane runs from the inferior vena cava to the gallbladder fossa.
• The umbilic plane runs from the falciform ligament to the inferior vena cava and divides the left lobe into a medial part, which is segment IV and a lateral part formed by segment II and III. This division is the only vertically oriented plane that is not defined by a hepatic vein. 

Here another illustration of the functional segmental liver anatomy.

Portal vein 
The portal vein divides the liver into upper and lower segments.
The left and right portal veins branch superiorly and inferiorly to project into the center of each segment.

Left hepatic vein
The significance of the left hepatic vein is somewhat controversial. Some authors have shown it to coincide with the umbilical fissure, but in reality the left hepatic vein courses to the lateral to the umbilical fissure [fig].
While some authors have claimed that the division between segments II and III is formed by the transverse plane of the left portal vein, most investigators feel that it is the plane defined by the left hepatic vein.
In actual practice, when a lesion is located within the lateral segment of the left lobe, both Couinaud segments II and III are usually removed based on the plane formed by the umbilical fissure (i.e. left lateral segmentectomy). 

On a frontal view of the liver the posteriorly located segments VI and VII are not visible.

The illustration above is a schematic presentation of the liver segments.
In reality however the proportions are different.
On a normal frontal view the segments VI and VII are not visible because they are located more posteriorly.
The right border of the liver is formed by segment V and VIII.
Although segment IV is part of the left hemiliver, it is situated more to the right.

Couinaud divided the liver into a functional left and right liver by a main portal scissurae containing the middle hepatic vein.
This is known as Cantlie’s line.
Cantlie’s line runs from the middle of the gallbladder fossa anteriorly to the inferior vena cava posteriorly.

Clockwise numbering of the segments

Segments numbering

There are eight liver segments.
Segment IV is sometimes divided into segment IVa and IVb according to Bismuth.
The numbering of the segments is in a clockwise manner.
Segment I (the caudate lobe) is located posteriorly.
It is not visible on a frontal view.

Image at the level of the superior liver segments.

Transverse anatomy

This figure is a transverse image through the superior liver segments, that are divided by the right and middle hepatic veins and the falciform ligament.

Image at the level of the left portal vein.

This is a transverse image at the level of the left portal vein.
At this level the left portal vein divides the left lobe into the superior segments (II and IVa) and the inferior segments (III and IVb).
The left portal vein is at a higher level than the right portal vein.

Image at the level of the right portal vein.

This image is at the level of the right portal vein.
At this level the right portal vein divides the right lobe of the liver into superior segments (VII and VIII) and the inferior segments (V and VI).
The level of the right portal vein is inferior to the level of the left portal vein.

Image at the level of the splenic vein.

At the level of the splenic vein, which is below the level of the right portal vein, only the inferior segments are visible.

How to separate liver segments on cross sectional imaging

Left liver: lateral(II/III) vs medial segment (IVA/B)
Extrapolate a line along the falciform ligament superiorly to the confluence of the left and middle hepatic veins at the IVC (blue line).

Left vs Right liver: IVA/B vs V/VIII
Extrapolate a line from the gallbladder fossa superiorly along the middle hepatic vein to the IVC (red line).

Right liver: anterior (V/VIII) vs posterior segment (VI/VII)
Extrapolate a line along the right hepatic vein from the IVC inferiorly to the lateral liver margin (green line).

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Video of MRI anatomy

Hypertrophy of caudate lobe in a patient with livercirrhosis. Notice the small lobulated right hemiliver.

Caudate lobe

The caudate lobe or segment I is located posteriorly.
The caudate lobe is anatomically different from other lobes in that it often has direct connections to the IVC through hepatic veins, that are separate from the main hepatic veins.
The caudate lobe may be supplied by both right and left branches of the portal vein.

This CT-image is of a patient with liver cirrhosis with extreme atrophy of the right lobe, normal volume of the left lobe and hypertrophy of the caudate lobe.
Due to a different blood supply the caudate lobe is spared from the disease process and hypertrophied to compensate for the loss of normal liverparenchyma.

Liver surgery

Right hepatectomy

segment V, VI, VII and VIII (± segment I).

Extended Right or right trisectionectomy
segment IV, V, VI, VII and VIII (± segment I).

Left hepatectomy
segment II, III and IV (± segment I).

Extended Left or left trisectionectomy
segment II, III, IV, V and VIII (± segment I).

Many surgeons prefer to use the term “extended” instead of trisectionectomy to indicate that some adjacent tissue of segment 4, or 5/8, as applicable is included rather than the entire segment 4, or 5/8.

Right posterior sectionectomy

segment VI and VII

Right anterior sectionectomy

segment V and VIII

Left medial sectionectomy

segment IV

Left lateral sectionectomy

segment II and III

1. Portal venous and segmental anatomy of the right hemiliver: observations based on three-dimensional spiral CT renderings

   MS van Leeuwen, J Noordzij, MA Fernandez, A Hennipman, MA Feldberg and EH Dillon
   Department of Radiology, University Hospital Utrecht, The Netherlands

2. Clinical and anatomical basis for the classification of the structural parts of liver

   Saulius Rutkauskas et al.
   Clinic of Radiology, Institute of Anatomy, Clinic of Surgery, Kaunas University of Medicine, Lithuania

3. Division of the Left Hemiliver in Man Segments, Sectors, or Sections

   by Anna C. Botero and Steven M. Strasberg
   Liver Transplantation and Surgery, Vol 4, No 3 (May), 1998: pp 226-231

4. Liver Resection Guidelines

anatomy, structure, diagnosis of liver diseases and treatment by a gastroenterologist at the MCC “Proxima” (Sochi)

Liver (lat., other Greek – hepar ) -intestinal tract), but is part of the digestive system. In addition to digesting food, the liver performs other vital functions.

Anatomy and Physiology

The liver is the largest gland in our body . Its mass in an adult is 1300-1800 g. The liver is located in the upper abdomen. Most of the organ is located to the right of the median vertical axis of the body. And only a small fragment goes to the left of it.

Two surfaces are distinguished in the liver – upper convex, diaphragmatic , and lower concave, visceral . On the visceral surface there are two longitudinal and one transverse grooves in the form of the letter H. These grooves divide the organ into two main lobes – a large right and a smaller left. There are two more small lobes – square and caudate.

From the visceral surface to the liver are adjacent: the gallbladder, the site of the inferior vena cava, the right kidney with the adrenal gland, the right or hepatic flexure of the colon. Here are the so-called. portal of the liver, which includes:

• Branches of the hepatic artery;
• Branches of the portal vein. Collecting blood from the stomach, intestines, spleen;
• Right and left bile ducts;
• Lymphatic vessels.

The liver as a glandular organ consists of stroma and parenchyma. Stroma is a supporting protective frame of the liver. It is represented by a connective tissue capsule, which, like a case, covers the organ. Connective tissue partitions extend from the capsule into the thickness of the liver, dividing it into parts.

Perenchyma is a functional tissue in which all physiological and biochemical processes take place. The parenchyma is made up of hepatocytes. These cells are combined into structural elements, hepatic lobules. Each of the slices, 1.5-2 mm in size, has the appearance of a hexagon on the cut. And in total there are up to 500 thousand lobules in the liver. In the lobules, bile is formed, the blood is cleansed of toxins and waste products, and its enrichment with nutrients.

Basic functions of the liver:

• Digestive . The role of the liver in digestion is carried out through the produced bile. During the day, the liver produces up to 1 liter of bile. The bile acids included in its composition provide emulsification of dietary fats and their absorption in the duodenum 12. Bile activates the digestive enzymes of the pancreas, stimulates intestinal motility (muscle contractions). Bile has a slightly alkaline reaction, and protects the duodenal mucosa from damage by acidic gastric juice.
• Protective . Bile has bactericidal properties, and together with gastric juice, it has a detrimental effect on pathogens that enter the gastrointestinal tract as part of food.
• Metabolic . The liver regulates all types of metabolism (metabolism) – proteins, fats, carbohydrates, minerals. Here, blood plasma proteins and lipids (fats and fat-like compounds) are synthesized. A valuable lipid is high-density cholesterol. This is the so-called. “good” cholesterol, from which hormones, vitamins, and other biologically active substances are synthesized. In the liver, glycogen is broken down into glucose and gluconeogenesis, the synthesis of glucose from proteins and fats. Vitamins A, E, D, C, group B, as well as some electrolytes, incl. iron, copper.
• Hemostatic . The liver synthesizes all the basic substances that provide hemostasis, blood clotting and stop bleeding.
• Detox . The liver neutralizes alcohol, drugs, and other exogenous toxins – poisons that enter the body from the outside. It also neutralizes endogenous toxins – metabolic products. So, during the breakdown of proteins, highly toxic ammonia is formed. The liver converts it into harmless urea, which is excreted in the bile. Waste hormones are inactivated in the liver. Here, red blood cells are destroyed, and bilirubin, a breakdown product of hemoglobin, binds to bile acids.

These are just the main activities of the liver. In total, this body performs about 500 functions.

Diseases and symptoms

The most common disease is hepatitis , inflammation of the liver parenchyma. Most often, hepatitis is of a viral nature, and is caused by hepatitis A, B, C viruses. Recently, hepatitis D, E, F viruses have been identified. Viral hepatitis occurs acutely or chronically.

Non-infectious hepatitis is usually chronic. The cause of these diseases is intoxication with alcohol, drugs, industrial emissions.

The liver is affected secondarily in some diseases and pathological conditions:

• Diseases of the gallbladder and biliary tract.
• Systemic circulatory disorders in heart failure.
• Metabolic disorders.
• Autoimmune diseases (the liver, along with other organs, is damaged by its own immune system).

Structural changes in the liver during its chronic inflammation take on the character of steatohepatosis, when adipose tissue accumulates in the parenchyma. Subsequently, fibrous connective tissue grows in the parenchyma – fibrosis . The extreme degree of fibrosis is cirrhosis, when almost the entire parenchyma is replaced by connective tissue. The lobular structure is lost, and the liver cannot perform its functions. Against the background of cirrhosis, liver cancer sometimes develops. Although liver cancer is not always associated with cirrhosis.

Main symptoms and syndromes (sets of symptoms) of hepatic disorders:

• Pain in the right hypochondrium, in the projection of the liver. Optional feature. The parenchyma does not hurt, the stroma, the capsule hurts. Therefore, pain appears only when the liver is enlarged and its capsule is stretched, or when the gallbladder and biliary tract are involved in the pathological process.
• Jaundice (icterus). Bilirubin not excreted with bile accumulates in the skin and mucous membranes, staining them yellow. Jaundice is not always indicative of liver disease. Other causes include cholelithiasis, hemolysis, massive destruction of red blood cells in some poisonings, and infectious diseases.
• Dyspeptic disorders. Nausea, vomiting, abdominal pain, bloating, flatulence associated with eating, especially fatty, sour, and spicy foods.
• Changes in stool. In acute viral hepatitis, white or acholic feces. In chronic hepatitis, accompanied by dyspepsia – alternating diarrhea and constipation.
• Changes in urine: dark staining of urine in acute viral hepatitis.
• Portal hypertension. Syndrome characteristic of cirrhosis. Manifested by spider veins on the skin and an expanded venous network on the anterior abdominal wall (“jellyfish head”). The abdomen is enlarged, the navel protrudes due to ascites, the accumulation of free fluid in the abdominal cavity.
• Liver failure. Disorders of all types of metabolism, secondary changes in internal organs. Consciousness is depressed due to damage to the brain by toxins. Specific “liver” smell from the mouth. Violation of the synthesis of blood coagulation factors provokes bleeding of their esophagus and other parts of the gastrointestinal tract, which can be fatal.

Diagnosis

Laboratory blood tests:

• Bilirubin – elevated with jaundice. Hepatic diseases are characterized by an increase in indirect or free bilirubin.
• Urea – increased due to violation of the excretory function of the liver.
• Protein . In case of violation of the protein-synthesizing function, the total protein in the blood plasma is reduced. At the same time, the specific content of large molecular weight proteins of globulins increases in comparison with low molecular weight albumins.
• Transaminases . An increase in the level of intracellular enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is a sign of massive destruction of hepatocytes in acute hepatitis.
• Coagulogram . A decrease in PTI (prothrombin index) and other coagulation factors indicates severe liver damage and the risk of bleeding.
• To identify the virus in viral hepatitis, immunodiagnostics is carried out (ELISA, enzyme immunoassay).
• Modern, more informative method PCR (polymerase chain reaction) allows you to detect the virus by its DNA or RNA.

Instrumental diagnostic methods – ultrasound and radioisotope scintigraphy. For scintigraphy, the radioisotope of technetium is administered intravenously. The radiation emitted by technetium is recorded using a special device, a gamma camera. By the way the liver accumulates and removes the isotope, a conclusion is made about its function. Radioisotope scanning is not hazardous to the health of the patient.

Why the liver hurts, what are its functions and how to help it

On the right side under the ribs is one of the most important organs in the human body – the liver, which performs more than 500 different functions. This is a kind of chemical laboratory, working around the clock inside the human body.

However, how often do we think about what harm our lifestyle does to the liver?

The liver protects our body from processed products, from external toxins, neutralizes everything that enters the body. Liver cells trap harmful substances and toxins, preventing them from entering the bloodstream. In addition to being involved in metabolism, the liver is also a blood filter, a blood-containing and bile-forming organ, and is actively involved in digestion and fat metabolism.

This organ regulates blood sugar metabolism and is involved in maintaining a constant body temperature.

What symptoms should I look out for?

The liver is our devoted but silent helper. She does not signal her problems for a long time, but lets know only when they are already quite pronounced.

Many people believe that if it hurts in the right hypochondrium, then it hurts the liver. In fact, these pains most often have completely different causes, for example, diseases of the gallbladder, spasm of the large intestine, pinched nerves and other causes.

Pay attention to the following signs: on the slide (below).

Most common liver diseases

According to the UK National Health Service there are five most common liver diseases. These include:

• viral hepatitis;
• primary biliary cirrhosis of the liver;
• non-alcoholic fatty liver disease (NAFLD), one of the main development factors of which is obesity;
• alcoholic liver disease due to long-term use of toxic doses of alcohol;
• pigmentary cirrhosis (hemochromatosis) is a hereditary disease in which iron metabolism in the body is disturbed.

There can be many causes of the disease, but there are three main risk factors:

• alcohol abuse;
• obesity;
• viral hepatitis.

Magic pills and miracle drops are not a panacea, their unproven effectiveness, at best, will not hurt much, but will not help get rid of liver problems. The most effective means of dealing with liver ailments is a healthy lifestyle.

Proper nutrition for liver health

A balanced diet is essential for liver health. Experts recommend eating legumes up to three times a week, and eating more fruits and vegetables. About 40% of all daily calories should be fats, mostly vegetable, not animal. This is especially important for people who are on a diet or engaged in heavy physical labor.

What about coffee? The stereotype that the liver does not like coffee has long been destroyed. Natural coffee contains substances that improve blood microcirculation of internal organs and are hepatoprotectors, but this is provided that a person drinks no more than 2 cups of espresso per day.

Alcohol and the liver

According to medical recommendations, you should consume no more than 10 g of pure alcohol per day – about 250 ml of beer or 100 ml of dry wine (even more in fortified ethyl alcohol) or 30 ml of vodka. This is the maximum daily dose. However, this does not mean that if a person does not drink for a week, he can drink all seven doses in one day.

Uncontrolled drug intake

Often there is such a clinical problem as drug-induced liver damage, which is caused by uncontrolled drug intake.

The most hepatotoxic drugs are antibiotics. The second place in the ranking is occupied by dietary supplements. In the United States, the leading cause of liver transplantation is acute liver failure due to dietary supplementation.

Paracetamol is also one of the most dangerous drugs for the liver. Moreover, patients take it not only as a separate drug, but also as a component of various antiviral drugs.

Uncontrolled use of these drugs and self-medication can cause liver damage.

Paracetamol liver toxicity is one of the most common causes of poisoning death in the United States, often not from overdose but from prolonged use.

Physical activity

In addition to proper nutrition, physical activity is very important for liver health.