Portal hypertension is a rare problem in pediatrics that can affect multiple organ systems. Prolonged increases in portal pressure can result in life-threatening complications and lead to an array of chronic morbidities. The most common causes of portal hypertension in children are biliary atresia (BA) and extrahepatic portal vein thrombosis (EHPVO); however, portal hypertension can be caused by a wide variety of pediatric liver disorders. There have been a number of advances in the understanding and treatment of portal hypertension in adults, with updated guidelines published. Although comparable data for portal hypertension in children are wanting, expert opinion recommendations based on adult and pediatric data have been published. This chapter highlights the pathogenesis, clinical features, diagnosis, and therapy of portal hypertension in the pediatric population.
Pathogenesis of Portal Hypertension
The portal system drains the capillaries of the intestinal mesentery and the spleen, ending in the hepatic sinusoids ( Figure 76-1 ). The portal vein constitutes about 75% of total hepatic blood flow and supplies partially oxygenated blood rich in nutrients absorbed from the gut. The remaining 25% of flow is provided by the hepatic artery, which supplies highly oxygenated blood distributed to the portal triads, liver capsule, and the walls of larger vessels. The liver is a high compliance, low-resistance system that can accommodate a large blood volume. Blood flow to the liver is autoregulated between the hepatic artery and portal vein, such that any disturbance to flow in one of these vessels can be offset by increased flow through the other vessel, a phenomenon known as the hepatic arterial buffer response. Blood from both the portal venous system and the hepatic arterial system combines within the sinusoids.
Portal hypertension occurs as a result of increased portal resistance, increased portal blood flow, or both ( Figure 76-2 ). Pressure within the portal system is proportional to blood flow and resistance to that flow, demonstrated by Ohm’s Law: P = q × R, where q is blood flow and r is resistance. Resistance is inversely related to the radius of the lumen of the blood vessel, such that small changes in vasculature radius can create large increases in resistance. Portal hypertension is caused by a combination of an increase in resistance, primarily within the hepatic sinusoids, and hemodynamic changes leading to an increase in flow. The portal venous system has a low baseline pressure of 7 to 10 mm Hg, and the hepatic venous pressure gradient (HVPG) ranges from 1 to 4 mm Hg. Portal hypertension is defined as a portal pressure greater than 10 mm Hg or a gradient greater than 5 mm Hg. Pressure gradients of greater than 10 mm Hg have been associated with esophageal varices, and those greater than 12 mm Hg are associated with ascites and variceal bleeding in adult patients. To obtain a measurement of the portal pressure gradient, a catheter can be wedged into the hepatic vein and a wedged hepatic venous pressure (WHVP) measurement can be obtained. The catheter is then retracted into a free-flowing hepatic vein and free hepatic venous pressure (FHVP) is measured. The HVPG is the difference between the WHVP and the FHVP. Causes of portal hypertension can be suggested by the HVPG. In pre-sinusoidal obstruction, the HVPG is normal but the WHVP is slightly raised, whereas in cirrhosis both the WHVP and the HVPG are increased ( Table 76-1 ).
|Cause of Portal Hypertension||Hepatic Venous Pressure Gradient Measurements|
|Wedged Hepatic Venous Pressure||Free Hepatic Venous Pressure||Hepatic Venous Pressure Gradient|
|Intrahepatic: sinusoidal (cirrhosis)||Raised||Normal||Raised|
|Posthepatic: hepatic venous obstruction||Raised||Raised||Normal|
|Intrahepatic: presinusoidal||Mildly raised||Normal||Normal|
|Prehepatic: portal venous obstruction||Normal||Normal||Normal|
Hepatocyte function is typically well preserved in early portal hypertension, and manifestations of portal hypertension may result prior to appearance of hepatocellular dysfunction. Vasoactive substances play a role in regulating intrahepatic resistance. In liver disease, the ability of the hepatic sinusoidal endothelial cells to secrete and respond to vasodilators such as nitric oxide (NO) are impaired, whereas expression of vasoconstrictors such as endothelin 1 are elevated. Other vascular mediators implicated can include carbon monoxide (CO), norepinephrine, angiotensin, prostaglandins, thromboxane, leukotrienes, and hydrogen sulfide. In addition to regenerative nodules and fibrotic bands, other mechanical factors include capillarization of the sinusoids and swelling of cells.
Hyperdynamic circulation can contribute significantly to the development of portal hypertension. Cirrhosis in both adults and children is associated with hyperdynamic circulatory state, characterized by increased cardiac output, decreased splanchnic tone, and decreased splanchnic vasoconstrictor responsiveness. Because of the decrease in systemic vascular resistance, there is both an increase in blood return to the heart and diminished afterload. This vasodilation leads to both increased sodium retention and vascular volume as a result of the renal response to vasodilation. There is thus increased portal flow (above baseline) with elevated portal pressures. This leads to further portosystemic shunting (to various collateral connections) and further exacerbation of the hyperdynamic state. Thus, the portal pressure slowly climbs. Later, as a result of shunting, blood flow moves through the various collaterals to form varices. Starling forces within the intestines force fluid into the peritoneum forming ascites.
Clinically, portal hypertension causes splenomegaly and the formation of collateral circulation. Collaterals develop in response to elevation of the portal pressure, and they form in the cardia of the stomach, the anus, the falciform ligament through remnants of the fetal umbilical circulation, and the retroperitoneum. In prehepatic obstruction, collaterals form in order to bypass the blockage and enter directly into the liver at the porta hepatis (cavernous transformation).