Plasma sinusoidal

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.

Zimmerli, B., J. Vaiantinas, and P. J. Meier. Multispecificity of Na+-dependent taurocholate uptake in basolateral (sinusoidal) rat liver plasma membrane vesicles. J. Pharmacol. Exp. Ther. 1989, 250, 301-318. 

If the unbound drug concentrations in plasma are higher than their K values on the transporters, then transporter function may be significantly affected [106], Following a pharmacokinetic analysis of the effect of probenecid on the hepatobiliary excretion of methotrexate, it has been shown the extent of an in vivo drug-drug interaction can be quantitatively predicted from the kinetic parameters for transport across the sinusoidal and bile canalicular membranes determined in vitro [107]. 

The factor f reduces the oscillation amplitude symmetrically about R - R0, facilitating straightforward calculation of polymer refractive index from quantities measured directly from the waveform (3,). When r12 is not small, as in the plasma etching of thin polymer films, the first order power series approximation is inadequate. For example, for a plasma/poly(methyl-methacrylate)/silicon system, r12 = -0.196 and r23 = -0.442. The waveform for a uniformly etching film is no longer purely sinusoidal in time but contains other harmonic components. In addition, amplitude reduction through the f factor does not preserve the vertical median R0 making the film refractive index calculation non-trivial. 

Protein-bound bile acids in plasma are removed with high efficiency by the hepatocyte, partly due to the liver sinusoids that allow protein-bound material... 

Plasma Membranes and Derived Transporters Measurement of transported calcium in synaptosomes, 174, 3 glutamate accumulation into synaptic vesicles, 174, 9 identification of bile acid transport protein in hepatocyte sinusoidal plasma membranes,... 

LIVER Use of isolated perfused liver in studies of biological transport processes, 192, 485 measurement of unidirectional calcium ion fluxes in liver, 192, 495 preparation and specific applications of isolated hepatocyte couplets, 192, 501 characterizing mechanisms of hepatic bile acid transport utilizing isolated membrane vesicles, 192, 517 preparation of basolateral (sinusoidal) and canalicular plasma membrane vesicles for the study of hepatic transport processes, 192, 534. 

Reduced hepatic mass reduced hepatic blood flow. Often decreased metabolizing isoenzyme activity. PseudocapiUar-ization of hepatic sinusoids Reduced renal plasma flow reduced glomerular filtration rate, altered tubular transport function... 

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... 

Ranitidine Continuous TV infusion 6.25 mg/h (or) Sinusoidal infusion from 3.0-9.4 mg/h over 24 h Highest plasma concentrations at 2200 h (-41% change) No circadian rhythm after sinusoidal rate infusion 4... 

Bowden N, Huck WTS, Paul KE, Whitesides GM (1999) The controlled formation of ordered, sinusoidal structures by plasma oxidation of an elastomeric polymer. Appl Phys Lett 75 2557-2559... 

The central event in the development of liver fibrosis is the enhanced sinusoidal deposition of extracellular matrix proteins that are mainly produced by activated HSC [86, 112, 113] and to a minor extent by endothelial cells [44-46] and hepatocytes [114, 115]. So far, no evidence has been found that KC are directly involved in the production of extracellular matrix proteins [39]. The accumulation of extracellular matrix proteins is caused by a disturbed balance between the synthesis and the degradation of the matrix proteins. This imbalance leads to a 5 to 10-fold increase in the total amount of matrix molecules and to an altered composition of the extracellular matrix. In contrast to normal livers, the sinusoids in fibrotic livers are stuffed with the fibrillar collagens type I and III. This colla-genization of the sinusoids, referred to as sinusoidal capillarization, causes severe disturbances of the blood flow and an impaired exchange of proteins between the liver cells and blood. Furthermore, this capillarization is accompanied by a loss of fenestration of the sinusoidal endothelial lining, which further hampers the diffusion of proteins between plasma and hepatic cells. 

Meier PJ, Boyer JL. Preparation of basolateral (sinusoidal) and canahcular plasma membrane vesicles for the study of hepatic transport processes. Methods Enzymol 1990 192 534-545. 

The size of the VLDL particle in plasma diminishes and its density increases as triglyceride is hydrolyzed by endothelial lipoprotein lipase, and the particles are thus converted to intermediate-density lipoproteins (IDL) (B32, S35). The IDL detach from the endothelium, and some are taken up by hepatic B-100, E receptors. The remaining particles in the circulation are further depleted of some cholesteryl ester (by an unknown mechanism), and most of the remaining triglyceride (probably by hepatic triglyceride lipase, in the liver sinusoids) (D5). Hie resulting LDL particles are largely composed of cholesteryl ester as the core lipid and apoB-100 as the apolipoprotein. 

Process Reactive MF magnetron sputtering. Sinusoidal plasma excitation (40 kHz, Advanced Energy PEII). Static deposition. Boxcoater Pfeiffer PLS 580. Process operation in the metallic mode of the discharge. ... 

Drainage of interstitial fluid IgG into lymphatics depends on the concentration gradient and occurs passively via convection [l].The leg lymph fluid of humans contains less than 25% of the amount of IgG found in plasma [65], Other specialized lymphatic channels drain peritoneal, pleural, or pericardial cavities. Lymphatic drainage enters lymph nodes via the subcapsular sinus, and the lymph fluid IgG is available for reticuloendothelial clearance of IgG (subcapsular sinus, perivascular or parenchymal macrophages, perivascular or parenchymal dendritic cells, sinusoidal endothelium) as detailed next. 

Mononuclear phagocytes (macrophages, Kupffer cells, spleen or lymph node) and sinusoidal or other specialized endothelium remove IgG from plasma, most frequently as IgG-containing immune complexes, IgG aggregates, or IgG bound to cell-associated epitopes [66-69], The initial binding event often occurs between the Fc portion of the IgG molecule and specific Fc receptors (FcyR) on reticuloendothelial cells (Figure 11.2). 

As mentioned above, the liver has a dual blood supply. The hepatic artery delivers material from the systemic circulation and the portal blood flow delivers directly from the gastrointestinal system. The portal system is involved in the first pass effect , where the nutrients and xenobiotics that are absorbed from the stomach and intestines are filtered through the liver before reaching the systemic circulation (Treinen-Moslen, 2001). The space of Disse allows close contact between circulating plasma, plasma proteins, and hepatocytes, allowing for rapid diffusion of lipophilic compounds across the hepatocyte membrane. Some compounds are specifically taken up by sinusoidal transporters, including... 

Although the sinusoidal cells (31 million/mg liver) make up only a relatively small proportion of the liver volume (6.3%), they constitute 30-40% of the total cell number. The total surface area of their plasma membranes is 26.5% of the total membrane surface of all liver cells. (3, 5, 23, 27, 44, 52, 56, 59) (s. figS. 2.8, 2.9)... 

Liver cell degenerations (hydropic swelling, eosinophilic degeneration, pin cells, hyaline bodies) and cell polymorphy, single cell necrosis in the form of (acidophilic) Councilman bodies, infiltration of lymphocytes, macrophages and activated stellate cells (yet only few plasma cells and neutrophilic granulocytes), proliferation of sinusoidal cells. 

Plasmocytoma Extramedullary plasmocytic lymphoma likewise has its origin in immunoglobulin-secreting B-lymphocytes. It is also termed multiple myeloma. The condition occurs most frequently in 7 decade of life and ends fatally after 1-2 (-3) years. In the liver, there are sometimes sinusoidal and portal infiltrations of B-lym-phocytes and plasmocytic tumour cells nodular formation can also occur. Generally, however, liver involvement is found in 40% of cases. (47, 61) (s. fig. 38.12) Recently, patients with non-response or relapse after high-dose chemotherapy were treated successfully with thalidomide (starting with 200 mg daily, the dose was increased by 200 mg every two weeks until it reached 800 mg per day). (48, 56) Plasma cell leukaemia is a rare complicative variant which tends to have its own individual course. 

Ciclosporin can cause cholestasis and cellular necrosis by an inhibitory effect on hepatocyte membrane transport proteins at both sinusoidal and canalicular levels. It induces oxidative stress by accumulation of various free radicals. Ademetionine (5-adenosylmethionine) is a naturally occurring substance that is involved in liver detoxification processes. The efficacy of ademetionine in the treatment and prevention of ciclosporin-induced cholestasis has been studied in 72 men with psoriasis (89). The patients who were given ciclosporin plus ademetionine had low plasma and erythrocyte concentrations of oxidants and high concentrations of antioxidants. The authors concluded that ademetionine may protect the hver against hepatotoxic substances such as ciclosporin. 

---