Table of Contents
Location of the Liver
The liver weighs approximately 1.5 kg. It is both the largest internal organ and the largest gland in the human body. It is located in the upper abdomen, with three quarters in the right and one quarter in the left upper quadrant of the abdominal cavity. Thus, the liver extends from the right hypochondriac region across the epigastric region to the left hypochondriac region.
It is fused with the lower surface of the diaphragm. Therefore, its upper limit is equivalent to the height of the diaphragmatic cupolae and its location is breath-dependent. Hence, the liver sinks down the diaphragm during deep inspiration. The lower limit is equivalent to the curve of the costal arch on the right side and runs upwards at a slight angle across the epigastrium to the left.
External Shape of the Liver
The liver is soft and its shape adjusts with the neighboring organs. The two areas that blend into each other at the clearly demarcated Inferior Margin include the convex facies diaphragmatica that lies flat against the diaphragm and the facies visceralis, which faces the visceral organs. The porta hepatis in conjunction with the ductus hepaticus communis, the vena portae hepatis and the arteria hepatica propria are located in the hepatoduodenal ligament. They maintain their relationship all the way to the hepatic lobule. These three structures are referred to as the ‘portal triad’.
Macroscopically, the liver is divided into four lobes. The ligamentum falciforme located in the front of the facies diaphragmatica divides the liver into a big lobus hepatis dexter and a small lobus hepatis sinister. In addition, the lobus caudatus and the lobus quadratus are located on the facies visceralis dorsally. The two lobes are divided by two sagittal incisions of the bigger lobes.
Indentations of the gallbladder (fossa vesicae biliaris) and the inferior caval vein (sulcus venae cavae inferioris) form the right fissure (fissura portalis principalis). Indentations of the round and vein ligament (fissura ligamenti teretis and venosi) form the left fissure (umbilical fissure). In conjunction with the porta hepatis that traverses the fissures, they form an ‘H’. The reddish-brown organ is encased by a coarse fibrous capsule (capsula fibrosa).
In addition to the four lobes mentioned above, the liver can be further divided into eight functional segments, which are not apparent from the outside. The segments are mostly independent of each other, which facilitates the excision of a specific part of the liver during liver resection. The segments follow the common path of the portal triad (see above).
The vessels are initially distributed into two large segments, pars dextra, and pars sinistra, which further split into eight segments. Segments I–IV are located in the pars sinistra, whereas segments V–VIII are located in the pars dextra. Segment I is equivalent to the lobus caudatus.
Liver: Peritoneal Attachments
The liver is located intraperitoneally. It is covered by the peritoneum. However, a part of the liver is peritoneum-free dorsally and shines roughly through the coarse fibrous capsule: the area nuda. The liver is associated with the diaphragm and the posterior abdominal wall in the area nuda. It is also the spot where the liver veins (venae hepaticae) exit the liver. The peritoneum folds back on itself on the area nuda to form the coronary ligament, which transitions into the right and left triangular ligaments that connect the liver to the diaphragm.
The liver is connected to the abdominal cavity via numerous peritoneal ligaments:
- Ligamentum hepatoduodenale contains the ductus choledochus (right), the vena portae hepatis (posterior) and the arteria hepatica propria (anterior on the left). The lesser omentum (omentum minus) is formed by the ligamentum hepatoduodenale and the ligamentum hepatogastricum (peritoneal ligament extending between the liver and the small curvature of the stomach).
- Ligamentum falciforme is located between the facies diaphragmatica and the abdominal wall. It contains the ligamentum teres hepatis and transitions into the ligamenta triangularia and ligamentum coronarium (see above).
- Ligamentum teres hepatis represents the desolate umbilical vein (v. umbilicalis).
- Ligamentum venosum represents the desolate ductus venosus.
The hepatoduodenal ligament and its structures are especially popular topics covered in exams.
Liver: Neighboring Organs
The diaphragm separates the liver from the right lung and the heart. The characteristic impressions on the facies visceralis are caused by the soft consistency of the liver:
- Impressio ösophageale on the upper margin of the left lobe due to the esophagus
- Impressio gastrica due to the stomach occupies almost the whole left lobe next to the esophageal impression.
- Impressio colica on the lower margin of the right lobe due to the flexura coli dextra and the transverse colon (colon transversum)
- Impressio duodenalis on the right lobe due to the pars superior of the duodenum
- Impressio renalis in the middle of the right lobe due to the superior pole of the right kidney
- Impressio suprarenalis due to the right adrenal gland next to the renal impression
Hint: Knowledge about the topography of the liver yields points in the preliminary medical examination!
Microscopic Anatomy of the Liver
The liver lobules (lobuli hepatis) are the smallest elements of the liver and are separated from each other by thin strands of connective tissue. The periportal zone is close to the entering vascular supply whereas the periportal space lies between the stroma of the portal canal and the outermost layer of liver cells in the hepatic lobule. The portal triad is made of small branches of the vena portae hepatis, the arteria hepatica propria and the bile ducts and contains lymphatics and branches of the vagus nerve.
The liver is divided into three units: the central vein lobule, the portal vein lobule and the acinus of the liver. The central vein lobule is clearly designated morphologically, whereas the remaining units are functional.
Central vein lobule in the liver
The central vein lobule is referred to as the classic liver lobule. The central vein (vena centralis) is located in the middle of the usually hexagonal area. It conducts blood into the venae hepaticae and finally to the vena cava. The edges of the lobule are marked by the portal triad (see above). The vessels located between neighboring lobules are referred to as interlobular artery and vein, as well as ductus biliferi interlobularis.
Liver cells (hepatocytes) are radially arranged around the central vein. The sinusoids between the liver cells carry mixed blood from the interlobular artery and vein from the periphery to the central vein (see above). Small biliary ducts (canaliculi biliferi) exist between the hepatocytes in the direction of the ductus biliferi interlobularis and conduct bile in a direction opposite to the blood flow.
Contrary to the sinusoids, the canaliculi do not carry their own wall. Therefore, bile can enter the bloodstream in case of cholestasis, which can lead to jaundice (icterus).
Portal vein lobules in the liver
The biliary tract system is a key element in the portal vein lobule. The portal triad with its vessels forms the center of the triangular lobule, whereas the edges are formed by the central vein. Thus, the three central vein lobules belong to a single portal vein lobule.
Acinus of the liver
The acinus of the liver has a rhomboid shape. The edges are built by central veins and periportal areas that are situated across each other. It should be considered that blood composition changes in this functional unit along the periphery to the center of the central vein lobule.
- Zone 1 (outer zone): Periphery of the central vein lobule, high nutrient, and oxygen concentration
- Zone 2 (middle zone): Transitional zone of the central vein lobule, low nutrient, and oxygen concentration
- Zone 3 (inner zone): Center of the central vein lobule, bad nutrients, and oxygen supply, especially susceptible to damage
Functional units of the liver
The sinusoids are enlarged capillaries located between hepatocytes. They conduct oxygen-rich blood from the interlobular arteries (arteriae interlobulares) and nutrient-rich blood from the interlobular veins (venae interlobulares) to the central veins. The small space filled with blood plasma that lies between the discontinuous endothelium of the sinusoids and the liver parenchyma is called perisinusoidal space (or space of Disse).
This space is populated with vitamin A-storing hepatic stellate cells. They are also called Ito cells and play an important role in the development of liver cirrhosis (see below). The endothelial cells are accompanied by macrophages, the so-called Kupffer cells. They phagocytize particles and microorganisms as well as digest aged erythrocytes, especially in asplenia. Pit cells accompany the endothelial cells and act as liver-specific lymphocytes.
Parenchyma cells of the liver
The liver parenchyma is mainly composed of polyhedral hepatocytes containing multiple organelles in their cytoplasm associated with metabolic processes. The parenchyma cells carry large nuclei and show polyploidy. A few cells are binucleate.
A hepatocyte contains one apical biliary pole (adjoins biliary tracts) and one basolateral blood pole (adjoins sinusoid). Endothelial cell plates are formed via hepatocyte aggregation and radiate to the central veins.
The liver is a nutrient reservoir and energy supplier
One of the most essential tasks of the liver is the storage and supply of nutrients to somatic cells. The dietary intake of nutrients does not always meet the cellular demand. The liver stores an abundance of nutrients and prevents any deficiency.
The liver is also involved in fetal hematopoiesis until the seventh month of pregnancy.
The liver reacts differently to food intake and fasting, and is therefore involved in the regulation of blood sugar levels. Excessive glucose levels in the blood, e.g., food intake triggers the release of insulin in the pancreas. Glucose is stored in the liver as glycogen. Furthermore, the liver carries insulin-independent glucose transporters (GLUT2) for the uptake of glucose into hepatocytes.
During fasting periods, in the absence of glucose, the liver converts glycogen into glucose with the help of the hormone glucagon and releases it into the bloodstream. The glycogen stores in the liver usually do not last for longer than 24 hours without food intake.
If the glucose reserves are depleted and in the absence of food intake, hepatocytes initiate the process of gluconeogenesis using glucogenic amino acids. Fructose and galactose are also transformed into glucose.
Protein metabolism in the liver
The liver provides essential components for protein metabolism: albumin (maintenance of colloid osmotic pressure), proteins of the complement system (acute phase proteins, which are components of nonspecific defense) and coagulation factors (fibrinogen and prothrombin). Abnormalities associated with these proteins include albumin deficiency leading to ascites, acute-phase protein deficiency leading to an elevated susceptibility to infection, and a deficiency of coagulation factors triggering unstoppable bleeding.
Continuous degradation and conversion of proteins and amino acids leads to the formation of urea as an end-product of amino acid metabolism. Urea enters the kidney via blood and is excreted in the urine.
The liver produces glutamine with the help of transaminases: glutamate oxaloacetate transaminase (GOT=ASAT=AST) and glutamate pyruvate transaminase (GPT=ALAT=ALT).
In case of liver damage or disease, large volumes of liver enzymes are released into the bloodstream and are detected in blood serum. Gamma-glutamyltransferase is another important enzyme mediating amino acid metabolism. Its elevation is the most critical parameter in liver and gallbladder injury.
Fat metabolism in the liver
The liver converts free fats from the blood to triglycerides for storage, and release as needed. Rapid depletion of fat reserves, e.g., during fasting or diabetes mellitus, leads to the formation of ketone bodies. They represent an additional key energy source besides glucose.
The liver plays a role in fat metabolism via bile formation. Bile is needed by cells of the gut to absorb fats. Further, the liver is responsible for cholesterol synthesis.
It also converts the bile colorant bilirubin from its indirect form into its direct water-soluble form. Bilirubin accumulates during the degradation of erythrocytes in the spleen and is initially water-insoluble. Therefore, it is bound to albumin (= indirect bilirubin) until it reaches the liver, where it is separated from the protein for absorption by the liver cells. Bilirubin is attached to glucuronic acid (= direct bilirubin) to increase its water solubility and release it into the gut via bile.
Note: The liver stores vitamins like vitamin A and B12 as well as trace elements such as iron.
The liver is a detoxifying and excretory organ
The biotransformation system in the liver facilitates the elimination of endo- as well as exogenous toxic compounds, which are mostly lipophilic substances modified by enzymes in several steps to make them water-soluble. Thus, they can be excreted via the biliary tract or kidneys. The degradation products enter the digestive tract after resorption and enter directly via the portal vein into the liver.
First-pass effect: When drug levels need to be maintained in a steady state, they cannot be administered orally because after their gut absorption they pass through the liver that can inactivate them, rendering them ineffective and thus unreliable. Therefore, intravenous, muscular, subcutaneous, or rectal administration is recommended.
Another important task of the liver is the degradation of ammonia. Ammonia accumulates during bacterial decomposition of indigestible constituents in the gut and is converted to urea by the liver. Inhibition of hepatic detoxification and prevention of ammonia degradation lead to damage to the central nervous system via hepatic encephalopathy, which can lead to deadly hepatic coma.
Diseases of the Liver
The most common causes of liver cirrhosis are chronic alcohol abuse and viral hepatitis B and C. Fibrotic conversion of the lobule structure including replacement of the liver parenchyma with connecting tissue is triggered by the degradation and death of liver cells and replacement with scar tissue.
The liver atrophies and loses its functions. Scar tissue around the vena portal hepatis can lead to the accumulation of blood and result in portal hypertension. The blood drained away via collateral circulation (portocaval anastomoses) leads to esophageal varicosities and caput medusa (protrusion of navel vein).
Ascites is another complication of portal hypertension, which is defined as an accumulation of free fluid in the abdominal cavity. The synthetic ability of the liver is further reduced and is manifested by elevated bleeding tendency because of decreased levels of coagulation factors. Neurotoxic substances (e.g., ammonia) accumulate due to abnormal detoxification, resulting in hepatic encephalopathy and hepatic coma. Liver transplantation is the only life-saving option for patients with advanced liver cirrhosis.
Steatohepatitis is defined as an accumulation of triglycerides in hepatocytes. There are two defined basic disease types: nonalcoholic fatty liver disease (NAFLD) mainly caused by metabolic syndrome and diabetes mellitus type 2 and alcoholic fatty liver disease (AFLD).
In case of a classic fatty liver, there are no complaints besides the enlargement of the organ. Nevertheless, in the second state, it leads to nonalcoholic fatty liver hepatitis (NASH) with non-specific symptoms such as nausea and weight loss.
Icterus, pain in the right upper abdomen and fever may occur especially in case of alcoholic fatty liver hepatitis (ASH). The liver parenchyma usually appears more hyperechoic, therefore lighter, during ultrasound than the adjacent parenchyma in the right kidney. Weight normalization, optimal management of diabetes, exercise, and strict alcohol abstinence are common therapeutic recommendations. Fatty liver and fatty liver hepatitis are still reversible whereas the third state, the micronodular liver cirrhosis, is irreversible.
Hepatitis is liver inflammation induced by various factors. It can result in liver failure or liver cirrhosis (see above). Inflammation of the liver is mostly triggered by virus infection or autoimmune disorders.
The most common virus strains causing hepatitis are virus types A–E. There are only a few cases reporting CMV, EBV and unknown hepatitis virus strain as etiological factors. Hepatitis A and E are spread via a fecal-oral transmission (contaminated water and foods). However, hepatitis B–D is transmitted parenterally (blood and sexual contact).
The prodromal stage, lasting two to seven days, is clinically defined by general symptoms like fever, fatigue and joint pain. Nausea, vomiting, and discomfort in the right upper abdomen may appear as well.
The stage of hepatic disease manifestation, lasting four to eight weeks, may follow with an anicteric (without jaundice) as well as icteric state (involving sclera and skin, pruritus and dark discoloration of urine). Types B, C, and D may transition into chronic hepatitis resulting in liver cirrhosis as the final stage. Hepatitis A and E are treated symptomatically via other types by antiviral therapy. Active immunization may be induced prophylactically in case of infections with hepatitis A and B.
Please note: Medical students should already get vaccinated against hepatitis A and B at the beginning of their studies!
Alterations of the immune system may lead to immune cells attacking hepatocytes, resulting in significant physical complaints. This disease is often associated with other autoimmune diseases such as autoimmune thyroiditis, vasculitis or chronic inflammatory bowel diseases. Patients need to undergo lifelong immunosuppressive therapy without which the prognosis of autoimmune hepatitis is dismal.
Hepatic encephalopathy is a complication of liver cirrhosis (see above). Neurotoxic substances such as ammonia, mercaptan, and GABA accumulate due to liver insufficiency, in the absence of detoxification.
The stages of hepatic encephalopathy vary from asymptomatic condition to increasing sleepiness and liver failure coma (hepatic coma) with hepatic fetor (liver breath). Triggering factors include protein-rich food or gastrointestinal bleeding, which leads to elevated intestinal ammonia production. Hepatic coma ends deadly in most cases.
Malignant liver tumors
Hepatic carcinoma (HCC, also known as liver cell carcinoma) is one of the most frequent cancerous conditions. Men are more often affected than women. Liver cirrhosis is the main risk factor for the development of HCC. Chronic hepatitis B or C, as well as cirrhosis caused by alcohol abuse or hemochromatosis (iron storage disease), may transition into liver cell carcinoma.
Aflatoxin is a carcinogen derived from Aspergillus flavor, which is a fungus growing on crops and nuts. HCC is either a solitary, multicentric or diffusely infiltrating cancer. The symptoms are nonspecific at first, for e.g., pain in the right upper abdomen, icterus, cachexia, and ascites as well as palpable tumors. Chemical analysis reveals elevated levels of the tumor marker alpha-fetoprotein. Partial hepatectomy is the therapy of choice.
Liver metastases occur even more often than hepatocellular carcinomas. They are generally multiple and occur when cancer cells attain access to the vena porta. Therefore, organs of portal circulation (stomach, pancreas, large intestine, and gallbladder) are usually affected by liver metastases.
Metastases are highly variable sonographically (hypo- or hyperechoic). Single metastases can be excised via partial liver resection. However, palliative therapy is the only option for advanced stages.
The dog tapeworm (Echinococcus granulosus) is the cause of cystic echinococcosis. Large fluid-filled cysts are formed in the liver parenchyma, and their rupture leads to life-threatening allergic reactions since foreign proteins are released into the peritoneal cavity. The therapy includes the removal of the cyst.
The fox tapeworm (Echinococcus multilocularis) leads to cyst formation in the liver as well. Instead of one large cyst, several small cysts are formed, which spread like a malignant tumor. Resection is not always possible and chemotherapy with albendazole is indicated.
Examination of the Liver
Among the numerous tests and procedures for the examination of liver the important ones are:
|Percussion||The liver has a damp sound whereas the lung is sonorous and the intestines have a tympanic percussion, thereby the upper and lower liver borders can be identified.|
|Liver scratch test||The stethoscope is placed over the epigastrium. The patient’s skin is carefully scratched with a finger or a wooden spatula parallel to the costal arch from cranial to caudal in intervals of about 1 cm. The sound of the noise changes at the liver border.|
|Palpation||In a lying position and during deep inspiration, the lower liver margin slides in a caudal direction. The left hand of the examiner lies over the right costal arch, whereas the right hand lies in the epigastric angle. The lower margin of the liver is palpable with fingers 2 to 5 as soft or hard, smooth or gibbous, sharp or blunt to touch over the skin.|
|X-ray||The liver is radiodense and, therefore, appears light radiographically, which can be used to define its proximity to the lung. However, it is not possible to delimit it from the heart, which shows a light appearance as well. Therefore, sonography and computed tomography are used to assess the liver.|
|Scintigraphy||Due to multiple metabolic processes, the liver accumulates numerous substances, and therefore, manifests organ enlargement in scintigraphy.|
|Sonography||The liver and its vessels, as well as the gallbladder, are easily felt during deep inspiration. Fatty liver, haemangioma, cyst, metastases or gallstones are diagnosable. The sonographic sizing involves the midclavicular line (MCL) in the cranial-caudal direction (max. 14 cm).|
|Liver puncture||Under constant sonographic monitoring, a long hypodermic needle is pierced through the abdominal wall to puncture an approx. 1 mm column of the parenchyma. Later, the tissue is examined microscopically.|