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== '''Microscopic anatomy''' == * Structure of a lobule ** Each lobule is made up of a central terminal hepatic venule, surrounded by 4-6 terminal portal triads that form a polygonal unit ** In between the vein and triad, hepatocytes are arranged in once-cell-thick plates, surrounded on each side by endothelium-lined and blood-filled sinusoids - the functional unit of the liver ** Blood flows from the portal triad through the sinusoids into the terminal hepatic venule through three zones, which have different enzymatic makeups and respond differently to toxin exposure and hypoxia *** Zone 1 (periportal): rich in nutrients and oxygen *** Zone 2 (intermediate): poorer *** Zone 3 (peri-venular zone): poor, and most susceptible to decreases in oxygen delivery (explains the phenomenon of centrilobular necrosis) ** Bile is formed within the hepatocytes and empties into terminal canaliculi, which form on the lateral walls of the intercellular hepatocyte, and ultimately coalesce into bile ducts and flow toward the portal triads * Hepatic microcirculation ** Arterial and PV flow varies inversely in the sinusoids and can be compensatory. Local control likely depends on arteriolar sphincters, and contraction of the sinusoidal lining by endothelial cells and hepatic stellate cells or portal myofibroblasts. ** Unidirectional flow from zone 1 to zone 3 and then into the terminal hepatic venule ** Sinusoidal endothelial cells *** The sinusoids are 7-15microm wide but can increase up to 10-fold *** Should be a low-resistance and low-pressure (2-3mmHg) system *** Sinusoidal endothelial cells account for 15-20% of the total hepatic cell mass *** Sinusoidal endothelial cells are separated from hepatocytes by the space of Disse (peri-sinusoidal space), where hepatocytes project microvilli *** Endothelial cells fenestrated and have no intercellular junctions/basement membrane ** Kupffer cells *** Derived from macrophage-monocyte system, phagocytic *** Line the sinusoids, insinuating between endothelial cells *** Trap foreign substances and initiate inflammatory responses *** Natural killer, CD4 T and CD8 T cells also exist ** Hepatic stellate cells *** Vitamin A storage and synthesis of extracellular collagen and other ECM proteins *** Activated to a myofibroblast state in acute and chronic liver injuries *** Key role in progression of fibrosis to cirrhosis ** Hepatocytes *** Make up 60% of the hepatic cellular mass *** Every hepatocyte has contact with adjacent hepatocytes, the biliary space and the peri-sinusoidal space *** Functions **** Uptake, storage and release of nutrients **** Synthesis of glucose, fatty acids, lipids, and numerous plasma proteins (including CRP and albumin) **** Production and secretion of bile for digestion of dietary fats **** Degradation and detoxification of toxins *** Bile canaliculi form a ring around the hepatocyte that drains into small bile ducts known as canals of Hering, which empty into a bile duct at a portal triad *** The monoclonal antibody HepPar1 (hepatocyte paraffin 1) identifies a unique antigen on hepatocyte mitochondria and can be used to identify hepatocytes on immunohistochemical examination *
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