The splanchnic circulation includes the blood flow through the stomach, small intestine, large intestine, pancreas, spleen, and liver (Fig. 24-7A). The majority of flow to the liver occurs through the portal vein, which carries the venous blood draining from all of these organs except the liver itself.
FIGURE 24-7 Splanchnic circulation.
The vascular supply to the gut is highly interconnected
The celiac artery is the primary blood supply to the stomach, pancreas, and spleen. The superior and inferior mesenteric arteries supply the large and small intestines, as well as parts of the stomach and pancreas. The superior mesenteric artery is the largest of all the splanchnic branches from the aorta, carrying >10% of the cardiac output. The extensive interconnections between the arcading arterial branches (see Fig. 24-7B) provide multiple collateral pathways through which blood can reach each portion of the intestines. This arrangement lessens the risk that the intestines may become ischemic should one of the arteries become occluded.
The microvascular network in the small intestine (see Fig. 24-7C) is representative of that throughout the gastrointestinal tract. After penetrating the wall of the intestine, small arteries course through the various muscle layers and reach the submucosa, where they branch into arterioles. Some arterioles remain in the submucosa to form a submucosal vascular plexus. Others project toward the intestinal lumen and into the mucosa, including the villi. Still others project away from the mucosa and course along the bundles of smooth muscle. Venules emerging from the villi and mucosal and muscularis layers converge into veins. These exit the intestinal wall, paralleling the arterial supply.
The arrangement of microvessels within a villus is like a fountain (see Fig. 24-7C). The incoming arteriole courses up the center of the villus, branching into many capillaries along the way to the tip of the villus. Capillaries converge into venules and carry blood back to the base of the villus. Capillaries also interconnect the arteriole and the venule all along the villus. These microvessels of villi are highly permeable to solutes of low molecular weight, thereby facilitating the absorption of nutrients.
The arrangement just described can create a countercurrent exchange system that enables permeable solutes to move from the arteriole to the venule without having to traverse the entire length of the villus, particularly when blood flow to the villi is low. With prolonged transit times, blood-borne O2 can diffuse from the arteriole to the venule before reaching the tip of the villus, which makes it susceptible to anoxic damage. In contrast, when blood flow through the villi is high (particularly after a meal), the tips of the villi are well oxygenated (as in Fig. 24-7D), and the effects of countercurrent exchange are reduced.
Because the capillaries in the villi are fenestrated (i.e., they have large pores) and have a large surface area, they are well suited for absorbing nutrients from the intestinal lumen. The venous blood carries away the majority of water-soluble nutrients absorbed from the gut, eventually delivering them to the portal vein. Lipophilic nutrients absorbed from the intestinal lumen enter the central lacteal of the villus (see Fig. 24-7D), which merges with the intestinal lymphatics. The lymph then delivers these substances into the bloodstream via the thoracic duct.
Blood flow to the gastrointestinal tract increases up to eight-fold after a meal (postprandial hyperemia)
Throughout the gastrointestinal tract, blood flow in each layer of the gut wall closely correlates with the local metabolism (which reflects digestive and absorptive activity). Intestinal blood flow at rest, in the fasting state, is typically 30 mL/min for each 100 g of tissue. However, flow can reach 250 mL/min for each 100 g during peak hyperemia after a meal. The increase in blood flow with the ingestion and digestion of a meal reflects a complex interplay of several factors.
First, the CNS initiates an “anticipatory” response that increases splanchnic blood flow with the mere thought of food—corresponding to the “cephalic phase” of gastric (see p. 871) and pancreatic secretion (see p. 890).
Second, mucosal metabolic activity during digestion and absorption primarily depends on the rate of active transport of substances across the epithelium. These activities consume O2 and produce vasodilator metabolites (e.g., adenosine and CO2) that increase blood flow locally.
Third, the absorption of nutrients generates hyperosmolality in both the blood and the lymphatic vessels of the villus. Hyperosmolality itself stimulates an increase in blood flow.
Fourth, during digestion, the gastrointestinal tract releases several hormones, some of which are vasoactive. Of these, cholecystokinin and neurotensin (see Table 41-1) may reach high enough concentrations in the local circulation to promote intestinal blood flow. N24-7 The intestinal epithelium also releases various kinins (e.g., bradykinin and kallidin), which are powerful vasodilators. The magnitude of the postprandial hyperemia further depends on the nature of the luminal content. Bile acids and partially digested fats are particularly effective in promoting hyperemia by acting on chemoreceptors in the intestinal mucosa.
Vasoactive Enteric Hormones
Contributed by Steve Segal
As noted in the text, the cholecystokinin and neurotensin released by the gastrointestinal (GI) tract may reach high enough concentrations in the local circulation to promote intestinal blood flow. However, these substances do not affect blood flow in other vascular beds because these hormones are too dilute, because other vascular beds lack appropriate receptors, or possibly because the hormones are destroyed as they pass through the liver. The intestinal mucosa releases additional peptide hormones (e.g., vasoactive intestinal peptide, gastrin, and secretin), but their effect on blood flow under physiological conditions is questionable.
In addition to the vasoactive hormones released by the GI tract, the carbohydrates and amino acids absorbed by the small intestine increase local osmolality, which in turn leads to an increase in blood flow. It has been suggested that amino acids may cause vasodilation independent of the osmolality effect.
The circulatory system does not distribute the increased splanchnic blood flow equally to all digestive organs, nor does it distribute the flow equally throughout the wall of even one segment of bowel. During and after a meal, as digestion and absorption proceed, blood flow increases sequentially along the gastrointestinal tract, first in the stomach and then in progressively more distal segments of the intestine. In all segments, blood flow through the muscularis layers primarily provides nutrition for the smooth-muscle cells. However, flow through the villi and submucosal vessels supports the absorption of foodstuffs as well as the secretion of electrolytes, fluids, and enzymes. After a meal, splanchnic blood flow remains elevated for 2 to 4 hours, primarily reflecting the vasodilation in the mucosal layer.
As in the heart and skeletal muscle, muscle contraction in the intestine (i.e., peristalsis) decreases blood flow, probably as a result of the compression applied by the muscularis in conjunction with the distending pressure of the luminal contents.
Sympathetic activity directly constricts splanchnic blood vessels, whereas parasympathetic activity indirectly dilates them
The gastrointestinal tract is endowed with its own division of the ANS, the enteric nervous system (ENS; see pp. 339–340 and 855–856). At one level, the ENS is its own independent nervous system, with sensory neurons, the capacity to integrate and to process sensory data, and motor neurons. One of the components of the ENS, the myenteric (or Auerbach's) plexus, releases vasoactive neurotransmitters. However, this plexus probably achieves its major influence on blood flow by controlling the peristaltic activity of the intestinal smooth muscle.
The enteric division sends sensory information upstream to the peripheral ganglia and to the CNS. The ENS also receives important input from the sympathetic and parasympathetic divisions of the ANS. Postganglionic sympathetic neurons originate in the celiac, superior mesenteric, and inferior mesenteric ganglia and send nerve fibers that travel along the corresponding major arteries to all splanchnic organs. Except for the capillaries, all splanchnic blood vessels receive sympathetic innervation. The predominant neural influence is sympathetic vasoconstriction, mediated by norepinephrine acting on α adrenoceptors on VSMCs. The vasoconstriction occurs to a similar extent in both the muscularis and mucosal layers, without redistribution of flow between the layers. Vasoconstriction elicited by sympathetic nerve activity can reduce blood flow to <10 mL/min per 100 g of tissue (i.e., ~ of resting values).
Parasympathetic preganglionic fibers travel to the intestine via vagal or pelvic nerves, which contact postganglionic parasympathetic neurons in the intestinal wall. The effect of parasympathetic activity on blood flow is indirect. Parasympathetic activity stimulates intestinal motility and glandular secretion, which in turn increases intestinal metabolism, thereby enhancing blood flow to the gut.
Changes in the splanchnic circulation regulate total peripheral resistance and the distribution of blood volume
The splanchnic circulation serves both as a site of adjustable resistance and as a major reservoir of blood. During exercise, when blood flow increases to active skeletal muscle, sympathetic constriction of the splanchnic resistance vessels decreases the proportion of cardiac output directed to the viscera. Therefore, abdominal cramping can result from attempts to exercise too soon after eating, when the gastrointestinal tract still demands blood flow to support its digestive and absorptive activities. N24-8
Myth of No Eating before Swimming
Contributed by Emile Boulpaep, Walter Boron
For information on eating before swimming, visit the following websites:
1. http://www.dukemedicine.org/blog/myth-or-fact-should-you-wait-swim-after-eating (accessed September 2015).
2. http://www.medicinenet.com/script/main/art.asp?articlekey=47368 (accessed December 2014).
3. http://www.todayifoundout.com/index.php/2011/01/swimming-within-an-hour-after-eating-is-not-dangerous/ (accessed December 2014).
The splanchnic circulation contains ~15% of the total blood volume, with the majority contained in the liver. During increases in sympathetic tone, splanchnic arteriolar constriction reduces perfusion, resulting in the passive collapse of the splanchnic veins. Blood contained in these veins moves into the inferior vena cava, thus increasing the circulating blood volume. With a greater increase in sympathetic activity, as would occur with intense exercise or severe hemorrhage, active venoconstriction mobilizes even more venous blood, thereby helping to maintain arterial pressure while promoting blood flow to active muscles. N24-9
The Spleen as a Blood Reservoir
Contributed by Steve Segal
In aerobic animals such as dogs and horses, and in diving animals such as seals, the spleen serves as an important reservoir of blood; it contains up to 10% of the total blood volume with a hematocrit that is about 10% higher than that in the systemic circulation. Sympathetic stimulation in these animals causes the capsule of the spleen to contract, ejecting this hemoconcentrated blood into the systemic circulation. In humans and cats, the spleen is principally a reticuloendothelial organ, having little role as a blood reservoir.
Exercise and hemorrhage can substantially reduce splanchnic blood flow
A reduction in blood flow leads to the production of vasodilator metabolites (e.g., adenosine and CO2), which stimulate arteriolar dilation and increase O2 delivery. Nevertheless, during maximal exercise or severe hemorrhage, blood flow through the gut may fall to <25% of its resting value. Fortunately, temporary reductions in splanchnic flow can occur without serious O2 deprivation; at rest, the viscera normally extract only ~20% of the O2 carried in the blood, so that extraction can increase several-fold. However, extended periods of compromised splanchnic blood flow can irreversibly damage the intestinal parenchyma.
After a severe hemorrhage and sustained splanchnic vasoconstriction, the ischemic mucosal epithelia slough off, even after repletion of the blood volume and restoration of blood flow. Sloughing occurs particularly at the tips of the villi, where the epithelial cells are susceptible to ischemia because of countercurrent flow (see p. 567). As these cells slough, pancreatic enzymes generate toxic “activators” that enter the circulation and produce multiple organ failure, which can lead to an irreversible decline in cardiovascular function. In an experimental setting, one can avoid damage to the heart by collecting the blood draining from the gut during the first several minutes of reperfusion and thereby preventing access of these blood-borne substances to the heart. Another major consequence of damage to the epithelium is endotoxic shock, which results from disruption of the barrier that normally prevents bacteria and toxins from escaping the intestinal lumen and entering the systemic circulation and peritoneal cavity.
The liver receives its blood flow from both the systemic and the portal circulation
The liver receives nearly one fourth of resting cardiac output. Of this blood flow, ~25% is arterial blood that arrives via the hepatic artery. The remaining 75% of the hepatic blood flow comes from the portal vein, which drains the stomach, intestines, pancreas, and spleen (see Fig. 24-7A). Because the portal venous blood has already given up much of its O2 to the gut, the hepatic artery is left to supply ~75% of the O2 used by the liver.
We discuss the anatomy of the hepatic circulation in more detail on page 946. Small branches of the portal vein give rise to terminal portal venules, and branches of the hepatic artery give rise to hepatic arterioles. These two independent sources of blood flow enter the liver lobule at its periphery. Blood flows from these terminal vessels into the sinusoids, which form the capillary network of the liver. The sinusoids converge at the center of the lobule to form terminal hepatic venules (i.e., central veins), which drain into progressively larger branches of the hepatic veins and finally into the inferior vena cava. Within the sinusoids, rapid exchange occurs between the blood and the hepatocytes because the vascular endothelial cells have large fenestrations and gaps. Thus, the liver sinusoids are more permeable to protein than are capillaries elsewhere in the body. As blood from the gastrointestinal tract passes the Kupffer cells of the liver (see p. 946), they remove bacteria and particulate matter, thereby preventing the access of potentially harmful material to the general circulation.
The mean blood pressure in the portal vein is normally 10 to 12 mm Hg. In contrast, the pressure in the hepatic artery averages 90 mm Hg. These two systems, with very different pressures, feed into the sinusoids (8 to 9 mm Hg). The sinusoids drain into the hepatic veins (~5 mm Hg), and these in turn drain into the vena cava (2 to 5 mm Hg). These remarkable values lead us to three conclusions. First, there must be a very high “precapillary” resistance between the hepatic artery (90 mm Hg) and the sinusoids (8 to 9 mm Hg), causing the arterial pressure to step down to sinusoidal values. If the sinusoidal pressure were as high as in typical capillaries (e.g., 25 mm Hg), blood would flow from the hepatic artery to the sinusoids and then backward into the portal vein. Second, because the pressure in the portal vein (10 to 12 mm Hg) is only slightly higher than that in the sinusoids (8 to 9 mm Hg), the precapillary resistance of the portal inflow (75% of the total blood flow entering the liver) must be very low. Third, because the pressure in the sinusoids is only slightly higher than that in the hepatic vein, the resistance of the sinusoids must also be extremely low.
As a result of the unique hemodynamics of the liver, changes in pressure within the hepatic vein have profound effects on fluid exchange across the wall of sinusoids. For example, in right-sided congestive heart failure, an elevated vena cava pressure can result in transudation of fluid from the liver into the peritoneal cavity, a condition known as ascites.
A change in the blood flow through one of the inputs to the liver (e.g., portal vein) leads to a reciprocal change in flow through the other input (i.e., hepatic artery). For example, if the inflow through the hepatic artery decreases, the pressure inside the sinusoids falls slightly, leading to an increase in flow from the portal vein into the sinusoids. When the inflow through the portal vein decreases, metabolic factors (e.g., decreases in metabolites carried by the portal blood) trigger an increase in flow from the hepatic arteriolar system. The hepatic arterial supply displays autoregulation (see p. 481), which is absent in the portal venous system. However, these adjustments do not fully stabilize total hepatic blood flow. With changes in O2 delivery, the liver compensates with corresponding changes in O2 extraction ratio. Hence, the liver tends to maintain constant O2 consumption (Box 24-2).
The cirrhotic liver is hard, shrunken, scarred, and laced with thick bands of fibrotic tissue. The most common cause of this in the United States is chronic alcoholism, but worldwide, hepatitis B and hepatitis C are also leading causes. Less commonly, inherited diseases, such as hemochromatosis (iron overload) and Wilson disease (altered copper metabolism), can be responsible, as can diseases of unclear etiology, such as biliary cirrhosis and sclerosing cholangitis.
When damage to the liver becomes severe, the clinical consequences of cirrhosis can become life-threatening. The 5-year survival rate is the same as that for primary lung cancer—less than 10%. The three major complications of cirrhosis are metabolic abnormalities, portal hypertension, and hepatic encephalopathy.
The liver's inability to maintain its normal synthetic activities (see pp. 964–971) results in a range of metabolic problems. Both albumin and cholesterol levels fall, and the prothrombin time rises, indicating failure of the liver to manufacture proteins in the coagulation cascade. The decreased plasma volume leads to renal hypoperfusion and renal failure—hepatorenal syndrome.
The scarring that accompanies cirrhosis causes increased resistance to blood flow through the liver. When the portal venous pressure rises, the signs and symptoms of portal hypertension can appear. The increased portal venous pressure leads to increased pressure in the splanchnic capillaries. The Starling forces (see pp. 471–472) thus promote the filtration and extravasation of fluid. The result is abdominal edema (i.e., fluid accumulation in the interstitium), which can progress to frank ascites. As the portal pressure rises further, a portion of the portal blood begins to flow through and dilate the portal anastomoses with systemic veins. These anastomoses are present in the lower esophagus, around the umbilicus, at the rectum, and in the retroperitoneum.
Dilation of the vessels in the lower esophagus can lead to the development of esophageal varices. These veins, and similar veins in the stomach, can burst and cause life-threatening hemorrhage. When varices are associated with persistent or recurrent bleeding, the physician can inject sclerosing agents directly into the varices, a procedure called sclerotherapy. However, even after sclerotherapy, recurrent bleeding is not uncommon, and complications include perforation, stricture formation, infection, and aspiration. It is possible to prevent rupture of the varices in some patients by placing an intrahepatic portosystemic shunt. One introduces a catheter through the jugular vein and into the liver, and then a stent is placed between a branch of the hepatic vein and a branch of the portal vein, allowing portal blood to bypass the liver and flow directly into the vena cava.
In some cases of portal hypertension, surgical intervention is necessary. Portacaval shunts (i.e., those linking the portal vein and inferior vena cava) can stop rebleeding and reduce portal hypertension, but hepatic encephalopathy (see next) can occur and overall mortality is not improved. The distal splenorenal shunt is now the more popular choice of treatment. It is effective in preventing rebleeding, and because it diverts only a portion of the blood flow away from the liver (i.e., just the blood exiting the spleen; see Fig. 24-7A), it is associated with a much lower incidence of encephalopathy.
Even as hepatic scarring increases vascular resistance through the liver, hepatic perfusion continues for a while. However, as we have just seen, eventually some of the portal blood flow shunts around the damaged liver into systemic veins, through pre-existing anastomoses. Because the liver is critical for removal and inactivation of naturally occurring toxic metabolites (see pp. 955–956), as well as pharmacological agents, toxins that bypass the liver directly enter the systemic veins and can build up in the plasma. If these toxins (e.g., NH3; see Fig. 39-6) cross the blood-brain barrier, they can cause acute delirium.