Portal-venous system

FIGURE 19-1. The portal venous system. (From Timm EJ, Stragand JJ. Portal hypertension and cirrhosis. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 694, with permission.)... 

Lignocaine s clearance by the liver is flow dependent. In heart failure cardiac output may be very low and therefore hepatic blood flow through both the hepatic artery and the portal venous system is also low. This meant a lower extraction of the drug from the blood and accumulation of lignocaine until the high plasma concentration produced the central nervous system toxicity. 

Rate, of uptake through the intestinal wall into the portal venous system... 

Control of thyroid function via thyroid-pituitary feedback is also discussed in Chapter 37. Briefly, hypothalamic cells secrete thyrotropin-releasing hormone (TRH) (Figure 38-3). TRH is secreted into capillaries of the pituitary portal venous system, and in the pituitary gland, TRH stimulates the synthesis and release of thyrotropin (thyroid-stimulating hormoneTSH). TSH in turn stimulates an adenylyl cyclase-mediated mechanism in the thyroid cell to increase the synthesis and release of T4 and T3. These thyroid hormones act in a negative feedback fashion in the pituitary to block the action of TRH and in the hypothalamus to inhibit the synthesis and secretion of TRH. Other hormones or drugs may also affect the release of TRH or TSH. 

Portal hypertension most commonly occurs as a consequence of chronic liver disease. Portal hypertension Is caused by Increased blood flow within the portal venous system and increased resistance to portal flow within the liver. Splanchnic blood flow is increased in patients with cirrhosis due to low arteriolar resistance that is mediated by increased circulating vasodilators and decreased vascular sensitivity to vasoconstrictors. Intrahepatic vascular resistance is increased in cirrhosis due to fixed fibrosis within the spaces of Disse and hepatic veins as well as reversible vasoconstriction of hepatic sinusoids and venules. Among the consequences of portal hypertension are ascites, hepatic encephalopathy, and the development of portosystemic collaterals—especially gastric or esophageal varices. Varices can rupture, leading to massive upper gastrointestinal bleeding. 

Distribution is the phase in which the compound is carried to tissues by the bloodstream or lymphatic system. Compounds are usually first absorbed into the portal venous system after oral administration, directing them to the liver where they may be removed (extracted/ metabolized) (first-pass effect). The blood (plasma) level reflects the concentration at the... 

Thyrotropin-releasing hormone, or protirelin, is a tripeptide hormone found in the paraventricular nuclei of the hypothalamus as well as in other parts of the brain. TRH is secreted into the portal venous system and stimulates the pituitary to produce thyroid-stimulating hormone (TSH, thyrotropin), which in turn stimulates the thyroid to produce thyroxine (T4) and triiodothyronine (T3). TRH stimulation of thyrotropin is blocked by thyroxine and potentiated by lack of thyroxine. 

In view of the fact that we have evolved in a manner in which we obtain our energy primarily by way of the gastrointestinal (GI) system, this route also became the most likely portal for the inadvertent introduction of toxic substances. Therefore, as a survival necessity, the body had to evolve a strategy for the early interception and processing of potentially lethal xenobiotic substances. Anatomically, this is accomplished by the hepatic-portal venous system, which delivers substrates absorbed from the gut directly to a succession of chemical-transforming enzyme systems located in the liver. 

The portal venous system carries blood from the gastrointestinal tract (GIT) to the liver. This blood carries any nutrients, drugs or toxins that have been absorbed via the enteral route. The liver s handling of drugs and toxins is discussed later in this chapter. 

Varices are dilated anastamoses between the portal and systemic venous systems which form in an attempt to decompress the portal venous system when the pressure within undergoes sustained elevation. Those in the lower oesophagus or gastric body are prone to rupture because they are thin-walled and lie just below the mucosa. 

Portal pressure is a function of resistance in the portal venous system and ih.e flow of blood through it. In cirrhosis, portal venous resistance is increased, and inflow of blood is increased by splanchnic vasodilatation and elevation of cardiac output. Variceal bleeding is increasingly likely as the pressure gradient between the portal and systemic venous systems rises beyond 12 mmHg. 

Reduction of portal pressure. Vasopressin (anti-duiretic hormone, see p. 711), in addition to its action on the renal collecting ducts (through receptors), constricts smooth muscle (Vj receptors) in the cardiovascular system (hence its name), and particularly in splanchnic blood vessels, so reducing blood flow in the portal venous system. Unfortunately, coronary vasoconstriction can also occur, and treatment has to be withdrawn from 20% of patients because of myocardial ischaemia. Glyceryl trinitrate (transdermally, sublingually, or intravenously) reduces the cardiac risk and, advantageously, further reduces portal venous resistance and pressure. 

Taylor, C.R. Computed tomography in the evaluation of the portal venous system. J. Clin. Gastroenterol. 1992 14 167—172... 

Digital subtraction angiography of the portal venous system. Amer. J. Roentgenol. 1983 140 497 -499... 

Blood from the haemorrhoidal venous plexus passes via the azygous superior rectal vein into the inferior mesenteric vein and thereafter into the portal vein. By contrast, the paired middle rectal vein and inferior rectal vein discharge their blood via the iliac vein into the inferior vena cava. In portal hypertension, anorectal varices are found in the region of the rectum, the anal canal and the external anal region. Haemorrhoids are distended and dislocated cavernous bodies in the rectum, which have no connection to the portal venous system. Although haemorrhoids and anorectal varices are two different clinical pictures, it is quite possible for them to occur simultaneously. The frequency of anorectal varices (40-80%) is dependent upon the extent and duration of portal hypertension. The bleeding tendency is low (7-14%). However, there have also been reports of massive haemorrhages. (21,45,55,66,83,105,156) (s. tab. 14.10)... 

Fraser-Hill, M.A., Atri, M., Bret, P.M., Aldis, A.E., Dlescas, F.F., Herschorn, S.D. Intrahepatic portal venous system variations demonstrated with duplex and color doppler US. Radiology 1990 177 523-526... 

Matsumoto, S., Mori, H., Takaki, H., Ishitobi, F., Sbuto, R., Yoko-yama, S. Malignant lymphoma with tumor thrombus in the portal venous system. Abdom. Imag. 2004 29 460—462... 

Mahmoud, A.E.A., Helmy, A.S., Billlngham, L., Ellas, E. Poor prognosis and limited therapeutic options in patients with Budd-Chiari syndrome and portal venous system thrombosis. Eur. J. Gastroenterol. Hepatol. 1997 9 485 - 489... 

Lai, L., Brugge, W.R. Endoscopic ultrasound is a sensitive and specific test to diagnose portal venous system thrombosis (PVST). Amer. J. Gastroenterol. 2004 99 40-44... 

Extraperitoneal perforation and leakage of barium may cause few immediate symptoms, but delayed endo-toxic shock can develop some 12 hours later, often causing death. Bowel infarction can also result. Barium granulomata can occur, causing painful masses, rectal strictures, or ulcers. On proctoscopy, an ulcer with a whitish base can mimic a carcinoma. In one rare case, perforation of a barium enema into a sigmoid abscess was followed by intravasation into the portal venous system (11). 

Sudden overload of the portal venous system related to splanchnic vasodilatation was a possible provoking factor in this case. Gastroesophageal reflux secondary to a lower esophageal sphincter tone and causing mucosal erosion was an alternative explanation. 

Intraperitoneal insulin application represents the route of choice for insulin delivery, as absorption is physiological, being into the portal venous system, avoiding peripheral hyperinsulinaemia. Cases of acute peritonitis, however, have brought this method into disrepute (Selam et al.. 1985). More experience is required before it can become clinical reality. 

Figure 47-1 i The portal-venous system. HY, Hepatic vein IVC, inferior vena cava IMV, inferior mesenteric vein LGV, left gastric vein LRV, left renal vein PV, porta vein RRV, right renal vein ... 

AVhen portal pressure increases, the portal venous system becomes dilated and forms collateral connections to the sys-... 

The oral bioavailability (F) of a drug is dependent on (a) the absorption of the drug from the gastrointestinal (GI) tract and (b) the capability of the liver to clear the drug during its first pass through the portal venous system. Oral bioavailability may be described as the fraction of the total oral dose for which systemic exposure is achieved. It is a measurement of the extent of exposure and contrasts with the rates of absorption or elimination discussed above. 

The most important clinical sequelae of PHT are the development of varices or alternative routes of blood flow from the portal to the systemic circulation, bypassing the liver (see Fig. 37-1). Varices decompress the portal venous system and return blood to the systemic circulation. Varices can occur at any level of the GI tract however, the route with the most clinical significance is through the left gastric vein with the development of esophageal varices. Patients with cirrhosis are at risk for variceal bleeding when portal venous pressure is... 

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