Human liver
Anatomy and Physiology of the Human Liver
The human liver is a vital organ located in the upper right quadrant of the abdomen, beneath the diaphragm. It is the largest internal organ and gland in the human body, weighing approximately 1.4 to 1.6 kilograms in adults. The liver performs a wide array of essential functions, including metabolism, detoxification, protein synthesis, and the production of biochemicals necessary for digestion.
Structure
The liver is divided into two main lobes, the right and the left, by the falciform ligament. The right lobe is significantly larger than the left. Each lobe is further subdivided into smaller lobes and segments, which are defined by the branching of the hepatic artery, portal vein, and bile ducts. The liver is encapsulated by Glisson's capsule, a thin layer of connective tissue that provides structural support and protection.
The liver's parenchyma consists of hepatocytes, which are the primary functional cells. These cells are organized into lobules, the basic functional units of the liver. Each lobule is hexagonal in shape and contains a central vein surrounded by radiating plates of hepatocytes. Between these plates are sinusoids, which are specialized capillaries that facilitate the exchange of substances between the blood and liver cells.
Blood Supply
The liver receives a dual blood supply from the hepatic artery and the portal vein. The hepatic artery delivers oxygenated blood from the systemic circulation, while the portal vein carries nutrient-rich blood from the gastrointestinal tract. This unique arrangement allows the liver to process and detoxify substances absorbed from the intestines before they enter the systemic circulation.
Blood from the hepatic artery and portal vein flows through the sinusoids, where it is filtered by hepatocytes. The cleansed blood then drains into the central veins of the lobules, which converge to form the hepatic veins. These veins ultimately empty into the inferior vena cava, returning blood to the heart.
Bile Production and Excretion
One of the liver's critical functions is the production of bile, a digestive fluid that emulsifies fats and aids in their absorption. Bile is produced by hepatocytes and secreted into bile canaliculi, small ducts that merge to form larger bile ducts. These ducts eventually converge to form the common hepatic duct, which joins the cystic duct from the gallbladder to form the common bile duct. Bile is either stored in the gallbladder or directly released into the duodenum, the first segment of the small intestine.
Functions of the Liver
The liver performs numerous vital functions that are essential for maintaining homeostasis. These functions can be broadly categorized into metabolic, synthetic, storage, and detoxification roles.
Metabolic Functions
The liver plays a central role in carbohydrate, lipid, and protein metabolism. It regulates blood glucose levels by storing excess glucose as glycogen (glycogenesis) and releasing it during periods of fasting (glycogenolysis). The liver also participates in gluconeogenesis, the synthesis of glucose from non-carbohydrate precursors.
In lipid metabolism, the liver synthesizes cholesterol, phospholipids, and lipoproteins. It also converts excess carbohydrates and proteins into fatty acids and triglycerides, which are stored in adipose tissue. The liver is involved in the oxidation of fatty acids to produce energy and the synthesis of ketone bodies during prolonged fasting or starvation.
Protein metabolism in the liver includes the synthesis of plasma proteins such as albumin, clotting factors, and transport proteins. The liver also deaminates amino acids, producing ammonia, which is converted to urea and excreted by the kidneys.
Synthetic Functions
The liver synthesizes a variety of essential proteins and biochemicals. Albumin, the most abundant plasma protein, is produced exclusively by the liver and plays a crucial role in maintaining oncotic pressure and transporting various substances in the blood. The liver also produces clotting factors necessary for hemostasis, including fibrinogen, prothrombin, and factors V, VII, IX, and X.
In addition to plasma proteins, the liver synthesizes acute-phase proteins in response to inflammation, such as C-reactive protein and serum amyloid A. These proteins play a role in the immune response and help to limit tissue damage during infections and injuries.
Storage Functions
The liver serves as a storage site for various essential nutrients and compounds. It stores glycogen, vitamins (such as A, D, E, K, and B12), and minerals (including iron and copper). The liver's ability to store and release these substances as needed helps to maintain metabolic balance and prevent deficiencies.
Iron is stored in the liver as ferritin and hemosiderin, and it is released into the bloodstream when needed for erythropoiesis (red blood cell production). Vitamin A is stored in hepatic stellate cells and is essential for vision, immune function, and cellular growth. The liver also stores vitamin B12, which is necessary for DNA synthesis and neurological function.
Detoxification Functions
The liver is the body's primary detoxification organ, responsible for metabolizing and excreting various endogenous and exogenous substances. Hepatocytes contain enzymes, such as cytochrome P450, that catalyze the biotransformation of drugs, toxins, and metabolic byproducts into more water-soluble forms for excretion.
Phase I reactions involve the oxidation, reduction, or hydrolysis of substances, often introducing or unmasking a functional group. Phase II reactions involve conjugation with endogenous molecules, such as glucuronic acid, sulfate, or glutathione, to increase solubility and facilitate excretion.
The liver also detoxifies ammonia, a byproduct of protein metabolism, by converting it to urea through the urea cycle. Urea is then excreted by the kidneys. Additionally, the liver metabolizes bilirubin, a byproduct of hemoglobin breakdown, into a water-soluble form that is excreted in bile.
Liver Diseases and Disorders
The liver is susceptible to a variety of diseases and disorders that can impair its function. These conditions can be broadly categorized into infectious, metabolic, toxic, and neoplastic diseases.
Infectious Diseases
Hepatitis is an inflammation of the liver caused by viral infections, alcohol, drugs, or autoimmune conditions. Viral hepatitis is the most common form and is caused by hepatitis A, B, C, D, and E viruses. Chronic hepatitis B and C infections can lead to cirrhosis and hepatocellular carcinoma.
Liver abscesses, which are collections of pus within the liver, can result from bacterial, parasitic, or fungal infections. Pyogenic liver abscesses are typically caused by bacteria such as Escherichia coli and Klebsiella pneumoniae, while amebic liver abscesses are caused by the parasite Entamoeba histolytica.
Metabolic Diseases
Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder characterized by the accumulation of fat in hepatocytes. NAFLD can progress to non-alcoholic steatohepatitis (NASH), which involves inflammation and fibrosis, potentially leading to cirrhosis and liver failure.
Hemochromatosis is a genetic disorder characterized by excessive iron accumulation in the liver and other organs. This condition can lead to liver cirrhosis, diabetes, and heart disease if left untreated. Wilson's disease is another genetic disorder that results in copper accumulation in the liver, brain, and other tissues, causing hepatic and neurological symptoms.
Toxic Diseases
Alcoholic liver disease (ALD) is caused by chronic alcohol consumption and includes a spectrum of conditions ranging from fatty liver to alcoholic hepatitis and cirrhosis. The toxic effects of alcohol on hepatocytes lead to inflammation, fibrosis, and eventual liver failure.
Drug-induced liver injury (DILI) can result from the hepatotoxic effects of various medications, including acetaminophen, antibiotics, and anticonvulsants. DILI can present as acute hepatitis, cholestasis, or mixed patterns of liver injury.
Neoplastic Diseases
Primary liver cancers include hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC is the most common type of liver cancer and is often associated with chronic hepatitis B or C infection, cirrhosis, and aflatoxin exposure. Cholangiocarcinoma arises from the bile ducts and can occur within or outside the liver.
Metastatic liver cancer is more common than primary liver cancer and occurs when cancer from other organs, such as the colon, breast, or lung, spreads to the liver. The liver's rich blood supply makes it a frequent site for metastasis.
Diagnostic and Therapeutic Approaches
The diagnosis and management of liver diseases involve a combination of clinical evaluation, laboratory tests, imaging studies, and sometimes liver biopsy.
Clinical Evaluation
A thorough clinical history and physical examination are essential for diagnosing liver diseases. Symptoms of liver dysfunction may include jaundice, fatigue, abdominal pain, and swelling. Physical examination findings may reveal hepatomegaly, ascites, and signs of chronic liver disease such as spider angiomas and palmar erythema.
Laboratory Tests
Liver function tests (LFTs) are a group of blood tests that assess the liver's ability to produce proteins, clear bilirubin, and detoxify substances. Common LFTs include measurements of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, and albumin levels.
Additional laboratory tests may include viral serologies for hepatitis, autoimmune markers, and genetic tests for conditions such as hemochromatosis and Wilson's disease.
Imaging Studies
Imaging studies are crucial for evaluating liver anatomy and detecting structural abnormalities. Ultrasound is often the first-line imaging modality for assessing liver size, texture, and the presence of masses or fluid collections. Computed tomography (CT) and magnetic resonance imaging (MRI) provide more detailed images and can help characterize liver lesions and guide biopsy procedures.
Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) are specialized imaging techniques used to visualize the bile ducts and diagnose conditions such as cholangiocarcinoma and bile duct stones.
Liver Biopsy
Liver biopsy remains the gold standard for diagnosing certain liver diseases and assessing the extent of liver damage. The procedure involves obtaining a small tissue sample from the liver, which is then examined under a microscope. Liver biopsy can help diagnose conditions such as hepatitis, NASH, and cirrhosis, and guide treatment decisions.
Therapeutic Approaches
The treatment of liver diseases depends on the underlying cause and the severity of liver damage. Management strategies may include lifestyle modifications, pharmacotherapy, and surgical interventions.
For viral hepatitis, antiviral medications can suppress viral replication and reduce liver inflammation. In cases of autoimmune hepatitis, immunosuppressive drugs such as corticosteroids and azathioprine are used to control the immune response.
Lifestyle modifications, including weight loss, dietary changes, and alcohol cessation, are essential for managing NAFLD and ALD. Pharmacological treatments for NAFLD and NASH are currently under investigation, with some promising agents targeting metabolic pathways and fibrosis.
In advanced liver disease, liver transplantation may be necessary. Liver transplantation involves replacing the diseased liver with a healthy donor liver and is indicated for patients with end-stage liver disease, acute liver failure, or certain liver cancers.