In pathology, a Councilman body, also known as a Councilman hyaline body or apoptotic body, is an eosinophilic globule of apoptotic hepatocyte cell fragments. Ultimately, the fragments are taken up by macrophages or adjacent parenchymal cells. [1] They are found in the liver of individuals suffering from acute viral hepatitis, yellow fever, and other viral syndromes. [2]
When referring to Councilman bodies, it is crucial to understand the term "apoptotic body". Apoptotic bodies are a peculiar type of extracellular vesicle that are left over pieces from cells that have undergone apoptosis, programming cell death. [3] The dying cells release varying amounts of closed, subcellular pieces that are often large for extracellular vesicles that may include forms of protein, DNA and RNA fragments, chromatin, lipids, cytosol, and organelles.
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Councilman bodies were first identified in yellow fever, which characteristically shows a midzonal hepatic necrosis on biopsy. Similar inclusions are observed in other viral hemorrhagic fevers and all of the viral hepatitides. Liver biopsy of acute viral hepatitis shows panlobular lymphocytic infiltrates with ballooning hepatocytes. [4]
Hepatocytes are the liver's primary parenchymal cells, forming 80% of the liver's mass and 60% of its cells. They are round in shape and contain a nucleus and organelles that contribute to metabolic and secretory functions. [5] Hepatocytes also play a pivotal role in liver inflammation. [6] Councilman bodies are often named for the hepatocytes undergoing apoptosis, which occurs in the portal tracts and lobules of the liver. Inflammation of the liver is caused by the cytotoxic killing of hepatocytes, or Councilman bodies. Eventually, this inflammation leads to liver damage in viral hepatitis. [7] Through the use of double immune fluorescence methods, HBsAg and/or HBcAg (hepatitis B core antigen) are present in Councilman bodies in the liver. [8]
Councilman bodies are named after American pathologist William Thomas Councilman (1854–1933), who discovered them.
With a bright field microscope, Councilman described typical, discrete, necrotic lesions in human hepatic cells of those infected with yellow fever. [9] He noted that the bodies appeared to be red in hematoxylin and eosin-stained sections of hepatic tissue, while being circumscribed, varying in size, round or irregular shape, and having numerous vacuoles of different sizes.
While Councilman bodies are identified in patients with yellow fever, the yellow fever virus does not cause the bodies. Yellow fever virus particles are not found in Councilman bodies under an electron microscope, agreeing with William Thomas Councilman's suggestion. [9] It is not possible to find membranous components or lipid droplets within the bodies. This means that Councilman bodies appear to be formed from general toxemia, rather than from the viral particles.
In Rio de Janeiro, numerous wild primates died during an outbreak of yellow fever. All deceased primates were submitted for necropsy and yellow fever diagnosis for the Brazilian Ministry of Health's surveillance program. 56 out of 1,304 primates tested positive for yellow fever from liver samples using real time RT-PCR diagnostics. The official diagnosis included that the liver contained hepatocellular degeneration and necrosis with Councilman bodies and intracytoplasmic lipid. [4]
Hideyo Noguchi was born in 1876 in Aizu. Throughout his life, he became a well known scientist in Japan for his work in investigating yellow fever between 1918 and 1924 in Central and South America. He believed that Leptospira icteroides was the cause of yellow fever. However, his theory was discredited in 1927. Unfortunately, he developed yellow fever from a laboratory infection and passed away in Africa at 51 years old. His theorized vaccine against L. icteroides was ineffective for preventing yellow fever. His liver samples showed Councilman bodies in the hepatocytes in their intermediate zones that revealed eosinophilic cytoplasmic coagulation. [10]
Five adults with hepatitis, two children with hepatoma, and three mongrel dogs provided tissue samples for study have an auxiliary liver transplant into the pelvis. The tissues were fixed immediately in ice-cold 1% osmium tetroxide, buffered with veronal acetate, and sucrose. Sections were cut, stained with lead hydroxide or citrate, and viewed under an electron microscope. The results showed the both canine and human tissue were intact, but altered hepatocytes were observed. [11] The doctors declared that councilman bodies were observed as vacuolated acidophilic bodies within the tissue samples.
An LEC rat, an inbred mutant rat, which suffered from hereditary hepatitis, was examined for elucidation during the development of the acute phase of hepatitis by quantitative analyses of the liver and laboratory data on serum enzymes. The progression of the acute hepatitis in the LEC rat was observed, showing only a few enlarged hepatocytes and Councilman bodies in its early life. These appeared around 8 weeks of age without any clinic signs of hepatitis. The acute phase of hepatitis started with a major increase of Councilman bodies, large nuclei, and hepatocytes in mitosis in the liver around 3-4 weeks before the onset of fulminant hepatitis. From these observations, three stages of progression of acute hepatitis were proposed in the LEC rat. [12]
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.
A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role.
Liver function tests, also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin time (aPTT), albumin, bilirubin, and others. The liver transaminases aspartate transaminase and alanine transaminase are useful biomarkers of liver injury in a patient with some degree of intact liver function.
Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in:
Alcoholic hepatitis is hepatitis due to excessive intake of alcohol. Patients typically have a history of at least 10 years of heavy alcohol intake, typically 8–10 drinks per day. It is usually found in association with fatty liver, an early stage of alcoholic liver disease, and may contribute to the progression of fibrosis, leading to cirrhosis. Symptoms may present acutely after a large amount of alcoholic intake in a short time period, or after years of excess alcohol intake. Signs and symptoms of alcoholic hepatitis include jaundice, ascites, fatigue and hepatic encephalopathy. Mild cases are self-limiting, but severe cases have a high risk of death. Severity in alcoholic hepatitis is determined several clinical prediction models such as the Maddrey's Discriminant Function and the MELD score.
Hep G2 is a human liver cancer cell line.
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Kupffer cells comprise the largest population of tissue-resident macrophages in the body. Gut bacteria, bacterial endotoxins, and microbial debris transported to the liver from the gastrointestinal tract via the portal vein will first come in contact with Kupffer cells, the first immune cells in the liver. It is because of this that any change to Kupffer cell functions can be connected to various liver diseases such as alcoholic liver disease, viral hepatitis, intrahepatic cholestasis, steatohepatitis, activation or rejection of the liver during liver transplantation and liver fibrosis. They form part of the mononuclear phagocyte system.
Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:
Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease of the liver which lasts over a period of six months. It consists of a wide range of liver pathologies which include inflammation, liver cirrhosis, and hepatocellular carcinoma. The entire spectrum need not be experienced.
In histology, the lobules of liver, or hepatic lobules, are small divisions of the liver defined at the microscopic scale. The hepatic lobule is a building block of the liver tissue, consisting of a portal triad, hepatocytes arranged in linear cords between a capillary network, and a central vein.
The liver is a major metabolic organ exclusively found in vertebrate animals, which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and various other biochemicals necessary for digestion and growth. In humans, it is located in the right upper quadrant of the abdomen, below the diaphragm and mostly shielded by the lower right rib cage. Its other metabolic roles include carbohydrate metabolism, the production of hormones, conversion and storage of nutrients such as glucose and glycogen, and the decomposition of red blood cells.
In histopathology, ballooning degeneration, formally ballooning degeneration of hepatocytes, is a form of liver parenchymal cell death.
Piecemeal necrosis generally refers to a necrosis that occurs in fragments.
Liver cytology is the branch of cytology that studies the liver cells and its functions. The liver is a vital organ, in charge of almost all the body’s metabolism. Main liver cells are hepatocytes, Kupffer cells, and hepatic stellate cells; each one with a specific function.
Liver regeneration is the process by which the liver is able to replace damaged or lost liver tissue. The liver is the only visceral organ with the capacity to regenerate. The liver can regenerate after partial hepatectomy or injury due to hepatotoxic agents such as certain medications, toxins, or chemicals. Only 51% of the original liver mass is required for the organ to regenerate back to full size. The phenomenon of liver regeneration is seen in all vertebrates, from humans to fish. The liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. The process of regeneration in mammals is mainly compensatory growth or hyperplasia because while the lost mass of the liver is replaced, it does not regain its original shape. During compensatory hyperplasia, the remaining liver tissue becomes larger so that the organ can continue to function. In lower species such as fish, the liver can regain both its original size and mass.
George K. Michalopoulos is a Greek-American pathologist and academic. He served as Maud L. Menten Professor of Experimental Pathology and Chair of the Department of Pathology at the University of Pittsburgh and UPMC from 1991 to 2023.
Hyperbilirubinemia is a clinical condition describing an elevation of blood bilirubin level due to the inability to properly metabolise or excrete bilirubin, a product of erythrocytes breakdown. In severe cases, it is manifested as jaundice, the yellowing of tissues like skin and the sclera when excess bilirubin deposits in them. The US records 52,500 jaundice patients annually. By definition, bilirubin concentration of greater than 3 mg/dL is considered hyperbilirubinemia, following which jaundice progressively develops and becomes apparent when plasma levels reach 20 mg/dL. Rather than a disease itself, hyperbilirubinemia is indicative of multifactorial underlying disorders that trace back to deviations from regular bilirubin metabolism. Diagnosis of hyperbilirubinemia depends on physical examination, urinalysis, serum tests, medical history and imaging to identify the cause. Genetic diseases, alcohol, pregnancy and hepatitis viruses affect the likelihood of hyperbilirubinemia. Causes of hyperbilirubinemia mainly arise from the liver. These include haemolytic anaemias, enzymatic disorders, liver damage and gallstones. Hyperbilirubinemia itself is often benign. Only in extreme cases does kernicterus, a type of brain injury, occur. Therapy for adult hyperbilirubinemia targets the underlying diseases but patients with jaundice often have poor outcomes.