Splanchnic circulation

Ascites. Patients with cirrhosis, especially fiver cirrhosis, very often develop ascites, ie, accumulation of fluid in the peritoneal cavity. This is the final event resulting from the hemodynamic disturbances in the systemic and splanchnic circulations that lead to sodium and water retention. When therapy with a low sodium diet fails, the dmg of choice for the treatment of ascites is furosemide, a high ceiling (loop) diuretic, or spironolactone, an aldosterone receptor antagonist/potassium-sparing diuretic. 

Portal hypertension in cirrhotic patients leads to arterial vasodilation in the splanchnic circulation, owing to an increased production of nitric oxide and other vasodilatory substances. This results in a low peripheral vascular resistance and a hyperdynamic circulation, with the development of arterial hypotension. In order to compensate for this... 

Portosystemic collaterals can divert up to 80% of the portal vein blood away from the liver. This initially results in haemodynamic disorders with subsequent (multifactorial) hyperdynamic splanchnic circulation. More and more varices develop around the bypasses in various venous areas, primarily in the form of oesophageal varices. Damage to the mucous membrane in the stomach and in the colon takes the form of hypertensive... 

The overriding aim of therapy is to increase renal blood flow. This can be achieved either indirectly through splanchnic vasoconstriction or directly by encouraging renal vasodilation. Hereby, certain problems arise concerning substances which spill over into the splanchnic circulation causing splanchnic vasoconstriction and at the same time exacerbating the renal vasoconstriction already present. (5-7, 10, 12, 19, 33, 43, 58, 60, 63)... 

In bleeding oesophageal varices, adjuvant medication therapy is advisable for reducing portal hypertension. This can be achieved by (i.) lowering vascular resistance with the help of vasodilators, (2.) cutting down the blood flow into the oesophageal collaterals with the help of substances which restrict the arterial splanchnic circulation, or (3.) applying a combination of these two therapeutic procedures. (61,83,100,150,160,190)... 

On the other hand, for any drug that is degraded at a point between the postabsorption site and entry into the systemic circulation, the systemic availability— bioavailability— will be less than the absorption. An orally administered drug that undergoes extensive first-pass hepatic clearance may give rise to poor oral bioavailability despite being efficiently absorbed from the gastrointestinal (GI) tract into the splanchnic circulation. 

Parenteral delivery routes are those that do not give rise to drug absorption into the splanchnic circulation. Thus, they avoid the possibility of hepatic first-pass metabolism. It should be noted that some parenteral routes do not avoid other first-pass metabolism effects (e.g., pleural metabolism for some inhaled drugs). Some major parenteral drug delivery routes are intraarterial, intrathecal, intravenous, intramuscular, trans-dermal, intranasal, buccal, inhalation, intraperitoneal, vaginal, and rectal. 

Enteral routes of drug absorption are from the stomach and the small and large intestine. Substances absorbed from these areas enter the splanchnic circulation and pass through the liver before entering the systemic circulation. 

Drugs may be transported away from the serosal side of the Gl tract by one or both of two mechanisms. The Gl tract is supplied by a blood capillary network from the splanchnic circulation. Drugs may also be taken up by the lymph vessels in the Gl epithelium... 

The reason for this appears to lie in the relative flow rates of blood and lymph. The rate of blood flow in the splanchnic circulation is 1.0-1.5 L/min, or 30% of cardiac output. This rate may increase to 2 L/min after a meal. Lymph flow through the same region is only l-2ml/min, but may increase to 5-20ml/min after a meal. Lymph flow in this region is thus 500-700 times slower than blood flow. Relatively fast splanchnic blood flow establishes virtual sink conditions on the serosal side of the GI epithelium and ensures a steep concentration gradient. These conditions promote efficient absorption into the bloodstream rather than into lymph. 

The majority of compounds absorbed from the stomach and intestines enter the splanchnic circulation. This leads to the portal vein, the liver, and then to the general circulation. Compounds absorbed via this route must therefore pass through the liver and will do so initially at a higher concentration relative to when they eventually distribute into the general circulation and elsewhere. 

The blood flow is important in carrying the absorbed drug from the absorption site to the systemic circulation. A large network of capillaries and lymphatic vessels perfuse the duodenal region and peritoneum. The splanchnic circulation receives about 28% of the... 

Price HL, Cooperman LH, Warden JC. Control of the splanchnic circulation in man. Role of beta-adrenergic receptors. Circ Res 1967 21(3) 333 0. 

Recent studies have focused on the effects of dobutamine on gastric mucosal flow and the splanchnic circulation. The addition of dobutamine (held constant at 5 mcg/kg per minute) to norepinephrine improves gastric mucosal perfusion without increasing cardiac index. This is consistent with findings that dobutamine may improve pHi and mucosal perfusion in septic patients. The addition of dobutamine to epinephrine-treated patients has been shown to improve gastric mucosal perfusion, as measured by improvements in pHi, arterial lactate concentrations, and PCO2 gap. Duranteau and colleagues ... 

De Backer D, Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock Which is best Crit Care Med 2003 31 1659-1667. 

Chu, T. M., and Reddy, N. P. (1992). A Lumped Parameter Mathematical Model of the Splanchnic Circulation, ASME Journal of Biomechanical Engineering, 114,222-226. 

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