Blood sinusoids, endothelium

The passage of most foreign compounds from the blood into the liver normally is not restricted because the endothelium of the hepatic blood sinusoids behaves as a porous membrane. Hence, drugs with molecular weights lower than those of most protein molecules readily reach the hepatic extracellular fluid from the plasma. A number of compounds are taken up into the liver by carrier-mediated systems, while more lipophilic... 

In the simplest analysis, a compound which is excreted in the bile has to pass from the plasma into the liver cells and then into the bile canaliculi. First the compound has to cross from the plasma to the extracellular fluid of the liver. According to Schanker (1962b), the endothelium of the blood sinusoids is a very permeable membrane and all molecules whose size is less than that of protein molecules readily equilibrate between plasma and the extracellular fluid of the liver. The compound then has to enter the liver cell and for substances which are secreted into bile in a higher concentration than in plasma, there appears to be a specialized process for their uptake by the cell (see Section III, B, 6, and Schanker, 1968). A further transport mechanism seems to be involved in the transfer of secreted substances from hepatic cell to bile. Thus, there are at least three membranes which such compounds have to cross in their passage from plasma to bile. The first seems ver> porous, but the latter two ap-... 

Figure 25-2. The formation and secretion of (A) chylomicrons by an intestinal cell and (B) very low density lipoproteins by a hepatic cell. (RER, rough endoplasmic reticulum SER, smooth endoplasmic reticulum G, Golgi apparatus N, nucleus C, chylomicrons VLDL, very low density lipoproteins E, endothelium SD, space of Disse, containing blood plasma.) Apolipoprotein B, synthesized in the RER, is incorporated into lipoproteins in the SER, the main site of synthesis of triacylglycerol. After addition of carbohydrate residues in G, they are released from the cell by reverse pinocytosis. Chylomicrons pass into the lymphatic system. VLDL are secreted into the space of Disse and then into the hepatic sinusoids through fenestrae in the endothelial lining.

Figure 5.1 Schematic illustration of the structure of the wall of different classes of blood capillaries. (1) Continuous capillary (as found in the general circulation). The endothelium is continuous with tight junctions between adjacent endothelial cells. The subendothehal basement membrane is also continuous. (2) Fenestrated capillary (as found in exocrine glands and the pancreas). The endothelium exhibits a series of fenestrae which are sealed by a membranous diaphragm. The subendothehal basement membrane is continuous. (3) Discontinuous (sinusoidal) capillary (as found in the liver, spleen and bone marrow). The overlying endothelium contains numerous gaps of varying size. The subendothehal basement is either absent (hver) or present as a fragmented interrupted structure (spleen, bone marrow)...

Hepatic stellate cells (HSC) are star-shaped cells with long cytoplasmic extrusions. They were first described over 150 years ago hy von Kupffer, but for many years their function remained a mystery. They are found in the space of Disse adjacent to the overlying endothelium and hepato-cytes, and in the normal liver they represent 5-8% of all liver cells. Under resting conditions HSC store retinoids in numerous vitamin A-rich lipid droplets and are thought to regulate sinusoidal blood flow via contractile intracellular filaments. HSC are the principal cells involved in liver fibrosis, remodelling extracellular matrix and synthesising scar tissue in response to liver injury. 

Sinusoids lined by specialized endothelium are blood channels located between hepatocyte cords. The endothelial lining of the sinusoids is discontinuous and has fenestrae to facilitate movement of fluid and molecules less than 259 kDa (Treinen-Moslen, 2001 Plumlee, 2004 Watkins, 1999). This material enters the space of Disse, which is located between the endothelium and the hepatocytes. Within the space of Disse, hepatocytes contact free and protein-bound molecules which may be absorbed by diffusion or active transport. 

Kishi et al. (169)evaluated the acute toxicity of Lipiodol infusion into the hepatic arteries (HAD of beagles and found the influence of Lipiodol HAI to be dose dependent. The infused Lipiodol first passed through an arterioportal communication and distributed through the hepatic sinusoids to pulmonary capillaries and thence into systemic blood circulation. The circulation and embolization of oil droplets were found in the renal tubular cells of supracapsular cortex, the choroid plexus, the vascular endothelium, and the pancreatic duct epithelium, showing a process of intracellular collection of Lipiodol from the systemic blood circulation and of further metabolism-provoking cellular reactions. 

Cavernomas are endothelium lined sinusoidal blood cavities without other features of normal blood vessels like muscular or adventitial layers. No brain tissue is present between the blood cavities Cavernomas may occur sporadically, after radiation, or hereditarily following an autosomal dominant trait... 

Fig. 2.1. Histology of a typical cavernoma with endothelium-lined, sinusoidal cavities without other features of normal blood vessels, such as muscular or adventitial layer...

---