Liver

Liver

The liver is the largest internal organ in the body and has many functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion. The liver is divided into four lobes: right, left, caudate, and quadrate. The liver receives blood from two main sources:
  • the hepatic artery, which supplies oxygenated blood, and
  • the portal vein, which brings nutrient-rich blood from the gastrointestinal tract.
    • Bile produced by the liver is transported to the gallbladder and duodenum via the bile ducts.
    The liver is surrounded by a connective tissue capsule called Glisson's capsule.


    liver histology


    Histology

        Hepatic lobules: The functional units of the liver, consisting of hepatocytes arranged in plates around a central vein.
        Portal triads: Located at the corners of the hepatic lobules, containing a branch of the hepatic artery, a branch of the portal vein, and a bile duct.
        Sinusoids: Specialized capillaries that allow blood to percolate through the liver.
        Kupffer cells: Specialized macrophages located in the sinusoids that help to remove debris and pathogens from the blood.
    The hepatic lobule is further divided into three zones based on their proximity to the blood supply:
        Zone 1 (periportal zone): Closest to the portal triad, receives the most oxygenated blood, and is the first to be affected by toxins.
        Zone 2 (intermediate zone): Intermediate zone between zones 1 and 3. Here the hepatocytes perform various metabolic functions.
        Zone 3 (centrilobular zone): Closest to the central vein, receives the least oxygenated blood, and is most susceptible to ischemic injury.

    liver histology


    Pathology

    Hepatitis

    Is an inflammation of the liver that can be caused by viral infections (such as hepatitis A, B, C, D, and E), alcohol abuse, toxins, or autoimmune diseases. In hepatitis, you will see hepatocyte necrosis, inflammatory infiltrates (mainly lymphocytes and macrophages) in the portal tracts and lobules, and ballooning degeneration of hepatocytes. In chronic hepatitis, you may also see fibrosis and cirrhosis.
        Symptoms: include fatigue, jaundice (often first evident in the sclera of the eyes), abdominal pain, nausea, vomiting, and elevated liver enzymes (ALT, AST).
        Diagnosis: is typically made through a combination of clinical presentation, laboratory tests (liver function tests, serology for viral hepatitis), and imaging studies such as ultrasound or liver biopsy.
        Treatment: depends on the underlying cause but may include antiviral medications, corticosteroids, lifestyle changes (such as abstaining from alcohol), and supportive care.

    Fatty liver disease (steatosis)

    Is characterized by the accumulation of fat within hepatocytes. This can be caused by alcohol abuse (alcoholic fatty liver disease) or metabolic conditions such as obesity, diabetes, and hyperlipidemia (non-alcoholic fatty liver disease). In fatty liver disease, you will see macrovesicular steatosis, where large fat droplets displace the nucleus to the periphery of the hepatocyte.
        Symptoms: often asymptomatic but can sometimes cause fatigue, hepatomegaly, and elevated liver enzymes.
        Diagnosis: is typically made through imaging studies (ultrasound, CT scan) that show increased liver echogenicity, and can be confirmed with a liver biopsy.
        Treatment: usually involves lifestyle changes such as weight loss, dietary modifications, and management of underlying conditions like diabetes and hyperlipidemia. In alcoholic fatty liver disease, abstaining from alcohol is crucial.

    Cirrhosis

    Is the end-stage of chronic liver disease characterized by fibrosis and the formation of regenerative nodules. It can result from various causes, including chronic hepatitis, alcohol abuse, and non-alcoholic fatty liver disease. In cirrhosis, you will see extensive fibrosis that disrupts the normal liver architecture, regenerative nodules of hepatocytes, and portal hypertension.
        Symptoms: include fatigue, jaundice, ascites, variceal bleeding, hepatic encephalopathy, and spider angiomas.
        Diagnosis: is typically made through a combination of clinical presentation, laboratory tests (liver function tests, coagulation profile), imaging studies (ultrasound, CT scan), and liver biopsy.
        Treatment: focuses on managing complications (such as ascites and variceal bleeding), treating the underlying cause, and in severe cases, liver transplantation may be necessary.

    Liver cancer (hepatocellular carcinoma)

    Is a primary malignancy of the liver that often arises in the setting of chronic liver disease and cirrhosis. In hepatocellular carcinoma, you will see malignant hepatocytes forming trabecular, pseudoglandular, or solid patterns, with cellular atypia and increased mitotic activity.
        Symptoms: include weight loss, abdominal pain, hepatomegaly, jaundice, and elevated alpha-fetoprotein (AFP) levels.
        Diagnosis: is typically made through imaging studies (ultrasound, CT scan, MRI) that show a liver mass, and can be confirmed with a liver biopsy.
        Treatment: depends on the stage of the cancer and may include surgical resection, liver transplantation, locoregional therapies (such as radiofrequency ablation or transarterial chemoembolization), and systemic therapies (such as targeted therapy or immunotherapy).

    Liver abscess

    Is a localized collection of pus within the liver parenchyma, usually caused by bacterial, fungal, or parasitic infections. In liver abscess, you will see necrotic tissue, pus, and inflammatory infiltrates (mainly neutrophils) within the abscess cavity.
        Symptoms: include fever, right upper quadrant pain, jaundice, and hepatomegaly.
        Diagnosis: is typically made through a combination of clinical presentation, laboratory tests (elevated white blood cell count, liver function tests), and imaging studies such as ultrasound or CT scan.
        Treatment: usually involves antibiotics to treat the underlying infection and drainage of the abscess, either percutaneously or surgically.

    Hemochromatosis

    Is a genetic disorder characterized by excessive absorption and accumulation of iron in the body, leading to iron overload in various organs, including the liver. In hemochromatosis, you will see iron deposits within hepatocytes and Kupffer cells, which can be visualized using special stains such as Prussian blue.
        Symptoms: include fatigue, joint pain, abdominal pain, hepatomegaly, and skin hyperpigmentation.
        Diagnosis: is typically made through a combination of clinical presentation, laboratory tests (elevated serum ferritin and transferrin saturation), genetic testing for HFE mutations, and liver biopsy to assess iron deposition.
        Treatment: involves regular phlebotomy (blood removal) to reduce iron levels in the body, along with dietary modifications to limit iron intake.

    Wilson's disease

    Is a genetic disorder characterized by impaired copper metabolism, leading to copper accumulation in various organs, including the liver. In Wilson's disease, you will see copper deposits within hepatocytes, which can be visualized using special stains such as rhodanine or orcein. The genetic defect is in the ATP7B gene, which encodes a copper-transporting ATPase, and leads to decreased biliary copper excretion and increased copper accumulation. It is inherited in an autosomal recessive manner.
        Symptoms: include fatigue, jaundice, abdominal pain, hepatomegaly, and neurological symptoms such as tremors and psychiatric disturbances (personality changes, mood disorders and even psychosis). If severe, it can lead to cirrhosis and liver failure. Kayser-Fleischer rings (copper deposits / brown stain around the outer side of the cornea) may also be present, if symptoms have been long standing.
        Diagnosis: is typically made through a combination of clinical presentation, laboratory tests (low serum ceruloplasmin, elevated urinary copper excretion), genetic testing for ATP7B mutations, and liver biopsy to assess copper deposition.
        Treatment: involves chelating agents (such as penicillamine or trientine) to promote copper excretion, along with dietary modifications to limit copper intake.

    Gallbladder

    Gallbladder

    Stores and concentrates bile from the liver. It releases bile into the duodenum via the common bile duct to aid in the digestion of fats.
    It is located on the underside of the liver and has three main parts:
  • Fundus: the rounded, distal portion that projects beyond the liver margin.
  • Body: the main, central portion that lies against the liver.
  • Neck: the narrow, proximal portion that connects to the cystic duct.

    • Blood supply:
  • Arterial supply: Cystic artery (a branch of the right hepatic artery).
  • Venous drainage: Cystic vein (drains into the portal vein or directly into the liver).
  • Lymphatic drainage: Cystic lymph nodes (located near the neck of the gallbladder).



    • gallbladder histology

    Histology

    The gallbladder wall is composed of four main layers:
        Mucosa: Microvilli that are folded into rugae to increase surface area for absorption, and lined by simple columnar epithelium. Beneath the epithelium is the lamina propria, which contains connective tissue, blood vessels, and lymphatics.
        Muscularis Mucosa: Thin layer of smooth muscle.
        Subserosa/Adventitia: Connective tissue with blood vessels and nerves.
        Serosa: Outer layer of connective tissue covered by mesothelium.
    gallbladder histology




    Pathology


    Cholesterolosis

    Is when lipid accumulates in the walls of the gallbladder. Macrophages in the lamina propria then eat this lipid, turning them into foamy histiocytes (macrophages with cytoplasm filled with tiny coarse vacuoles). When there is a massiv accumulation of them sometimes polyps form, just a polypoid extrution of the lamina propria with these foamy little fellows.
        Symptoms: often asymptomatic but can sometimes cause biliary colic or discomfort in the right upper quadrant.
        Diagnosis: is typically made incidentally during imaging studies (ultrasound, CT scan) or histological examination after cholecystectomy.
        Treatment: usually not necessary unless symptomatic, in which case cholecystectomy may be performed.
    cholesterolosis histology pathology





    Acute cholecystitis

    Is caused by blockage of the cystic duct, which is most often caused by stones but can also be caused by a tumor or even cocaine induced, though rare. This blockage of bile fluid can lead to inflammation and with time edema, which in turn can to vascular insufficiency which leads to wall ishemia and necrosis. Microscopically you will see edema and bleeding within the walls in combination with necrosis. At this stage you might see neutrofils in walls of the gallbladder. As this blockage of bile fluid leads to increased pressure within the gallbladder, that leads to stasis within veins, that leads to thombi formation in the small veins, which can even lead to fibrinoid necrosis. Sometimes gas-forming bacteria might infect the walls and cause air-bubbles, leading to emphysematous cholecystitis.
        Symptoms: include right upper quadrant pain, fever, nausea, vomiting, and a positive Murphy's sign.
        Diagnosis: is typically made through a combination of clinical presentation, laboratory tests (elevated white blood cell count, liver function tests), and imaging studies such as ultrasound or HIDA (hepatobiliary iminodiacetic acid) scan.
        Treatment: usually involves hospitalization, intravenous fluids, antibiotics, and pain management. In many cases, surgical removal of the gallbladder (cholecystectomy) is necessary, either urgently or electively after the acute inflammation has resolved.
    acute cholecystitis histology pathology

    Chronic cholecystitis

    Most often caused by gallstones, that leads to hyperkinesia. Hyperkinesia than leads to thickened muscularis (hypertrophy of the muscles), chronic inflammation and fibrosis in the subserosa. As gallstones are most often caused by increase biliary secreation of cholesterol, sometimes foamy histiocyte are formed in the lamina propria, which is a histiocytes (macrophage) with cytoplasm filled with tiny coarse vacuoles. You will also see Rokitansky-Aschoff sinuses, which are invaginations or protrusions of the gallbladder epithelia that can reach the either perimuscular or the subserosal connective tissue. This is caused by increased luminal pressure in the gallbladder and weakened muscular layer.
        Symptoms: include recurrent episodes of right upper quadrant pain, nausea, and vomiting, often triggered by fatty meals.
        Diagnosis: is typically made through a combination of clinical presentation, laboratory tests (mildly elevated liver function tests), and imaging studies such as ultrasound, which may show gallstones and thickening of the gallbladder wall.
        Treatment: usually involves elective cholecystectomy to prevent further episodes and complications such as acute cholecystitis or gallbladder perforation.
    chronic cholecystitis histology pathology