9.4: Cells of the liver
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The liver parenchyma is primarily comprised of hepatocytes. Hepatocytes are polygonal epithelial cells with abundant eosinophilic, granular cytoplasm and large, centrally located round nuclei. Hepatocyte nuclei often contain a prominent nucleolus. Binucleated hepatocytes (= containing two nuclei) are not uncommon.
Hepatocytes contain many mitochondria and have extensive smooth and rough endoplasmic reticulum and Golgi apparatus, all of which contribute to the eosinophilic staining of their cytoplasm. However, the microscopic appearance of hepatocyte cytoplasm can vary based on the nutritional status of the animal (recall that the liver plays a major role in energy and nutrient metabolism). The most common cytoplasmic changes are due to intracytoplasmic glycogen and lipid. Histologically, glycogen appears as irregular, poorly-defined non-staining (clear) spaces within the cytoplasm. In contrast, lipid appears as either a single, large non-staining, sharply-defined cytoplasmic vacuole or as multiple variably-sized non-staining vacuoles. Both glycogen and lipid are largely “washed-out” during routine processing of histology slides, which accounts for their lack of staining in tissue section. While both of these changes can be physiologically normal (or clinically inconsequential), excessive accumulation of lipid within hepatocytes can be pathologic, and is referred to as hepatic lipidosis.
Hepatocytes are arranged in radiating cords (hepatic cords) approximately one to two cells in thickness. Adjacent hepatic cords are separated by vessels: the sinusoidal capillaries (sinusoids). These capillaries are lined by endothelial cells, which are difficult to appreciate in normal histologic section due to their flattened nuclei. More on hepatic architecture as well as the vasculature and blood supply to the liver will be discussed later in this chapter.
Ito cells are also known as stellate cells, fat storing cells, or lipocytes. Ito cells reside in the perisinusoidal region known as the space of Disse. The space of Disse is the narrow region located between endothelial cells and hepatocytes. These cells are identified histologically by their large lipid vacuoles. Ito cells function in the uptake, storage and maintenance of vitamin A (retinol), as well as the production of extracellular matrix (collagen types I and III), regulation of sinusoidal blood flow, and hepatic tissue repair following injury.
Kupffer cells are phagocytes (“phago” = eating, “cyto” = cells) derived from monocytes and located within the vascular spaces of hepatic sinusoids lining the endothelial surfaces. These Kupffer cells function in removing aged red blood cells from circulation and in phagocytizing and removing blood-borne microbes or endotoxins absorbed from the gastrointestinal tract. Histologically, Kupffer cells are individualized round cells within sinusoids that are difficult to identify on histology unless they contain phagocytized cytoplasmic material, such as red blood cells.
Oval cells are pluripotent stem cells that, due to their ability to differentiate into several different cell types (“pluri” = several), serve a primary role in the repopulation of hepatocytes and other hepatic cells (e.g. biliary epithelium) following hepatic injury. These cells are not readily identifiable in normal tissue sections.
Pit cells are short-lived granular lymphocytes that reside within hepatic sinusoids and contribute to immunity.
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