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Classification and functional aspects of portal hypertension
GUEST
LECTURE
Classification and Functional Aspects of Portal Hypertension Sheila Sherlock,
MD, London,
England
Portal blood pressure depends on splanchnic blood flow, resistance t.o outflow from the liver, and the pressure in the inferior vena cava. In evaluating portal hypertension, the part played by each factor must be assessed. Increased resistance to hepatic blood flow is the most important. The advent of newer radiologic and pressuremeasuring methods, combined with hepatic needle biopsy, allows the portal circulation to be evaluated much more clearly. There is now no excuse for a surgeon to be surprised to find a congested portal vascular bed and portal hypertension at operation. Indeed, there is little excuse for operating without precise knowledge of the type of portal hypertension and the location of any portosystemic collaterals. In the individual patient, these factors must be established: first, the existence of portal hypertension; second, the site of any portal obstruction; third, the anatomy of portosystemic collaterals; and fourth, the cause. Technics
of Evaluation
Portal Pressure Measurements. The pressure measurement taken through a needle passed percutaneously into the pulp of the spleen reflects closely the pressure in the splenic vein. At operation the pressure in the main portal vein may be estimated. This does, however. necessitate intervention and the results obtained are affected by such factors as anesthesia, hemchanges in intra-abdominal pressure, and orrhage, kinking of the vein. Perhaps the greatest advance has been that of umbilical vein catheterization [l-3] which
From the Department of Medicine, Royal Free Hospital School of Medicine, University of London, London, England. This work was supported by the Ingram Trust. Reprint requests should be addressed to Dr Sherlock. Department of Medicine, Royal Free Hospital School of Medicine, Gray’s Inn Road, London, WCI, England. Presented at the Fourteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, New York, New York, May 22 and 23.1973
Volume 127, February
1974
has allowed measurement of the pressure in the main portal vein in unanesthetized patients. The umbilical vein of adult patients is only collapsed and, especially in the presence of portal hypertension, can be reopened, dilated, and catheterized, allowing access to the left branch of the portal vein and hence to the portal venous system [4]. With the patient under local, general, or epidural anesthesia, an incision is made half-way between the umbilicus and the xiphoid process. The umbilical vein remnant is found in the free edge of the falciform ligament and dilsted, and the catheter is introduced and advanced into the portal vein. The technic is not an easy one: the failure rate is high, being 50 to 90 per cent in patients with cirrhosis, but it decreases with experience. Complications include hemorrhage, wound infection, and, possibly, thrombosis of the portal vein. It is generally agreed to be a safe procedure but one t.hat requ:lres a surgical team for its performance. A catheter wedged in a hepatic venous radicle produces stasis as far as the first freely anastomosing sinusoidal area. It therefore reflects sinusoidal pressure. In patients with chronic liver disease the pressure in the free left branch of the portal vein, measured through an umbilical catheter, approximates the wedged hepatic venous pressure [Z]. The area of stasis induced by the catheter extends over a wide area, even to the portal venous inflow. This implies that the portal hypertension of cirrhosis is not, simply postsinusoida1 but extends right through the hepatic vein and sinusoids to the main portal vein. In cond.itions in which there is obstruction to flow at a presinusoidal level, for instance, schistosomiasis, the wedged hepatic venous pressure is normal. This presumably reflects normal anastomoses between small hepatic vascular units that prevent the catheter from creating a large area of stasis. (Figure 1.) The portal hypertension of cirrhosis, therefore, can no longer be regarded as predominantly postsinusoidal. No purpose is served by retaining the distinction between post- and presinusoidal portal hypertension. A satisfactory classification is comprised of two groups: (1) presinusoidal, which includes lesions in the main portal vein and in the portal veins in the por-
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Sherlock
vein [6] in patients suspected of having the Budd-Chiari syndrome. Needle Biopsy of the Liver. This technic permits the etiologic factors of the portal hypertension to be determined in many instances. in all but the greatest emergency this is essential, both to determine the cause and to formulate the management. For instance, acute alcoholic hepatitis may improve with medical treatment and surgery should be postponed if possible until all benefit has accrued from this; surgery may not be necessary. The diagnosis of hepatic malignancy, whether primary or secondary, contraindicates surgical procedures on the portal system except as a preliminary to hepatic resection or transplantation. Primary Portal Hypertension Figure
7. Contrast material flowing info a catheter wedged info a hepatic venous radicle causes stasis in a relatively large area. The stasis includes the sinusoidal bed of many small hepatic vascular units.
of the liver; and (2) intrahepatic, which includes all the cirrhoses and the hepatic venous occlusions (Budd-Chiari syndrome). (Figure ‘2.) Radiologic Procedures. These allow the location of any anatomic block and the identification of the portosystemic collateral circulation [5]. The simplest is splenic venography, which is a necessary preliminary to all surgical procedures on the portal venous system. It is contraindicated in the presence of jaundice or an increase of more than three seconds in the one-stage prothrombin time. If a technically satisfactory splenic venogram fails to. show gastroesophageal collaterals, bleeding from varices is unlikely. Splenic venography is essential before portacaval shunt procedures because it shows the availability of the vein for the procedure. Although thrombosis of the portal vein itself is an unusual complication of cirrhosis, it could be caused by complicating primary cancer of the liver. Such an obstruction would be shown by the splenic venogram and would p~sclude portosystemic shunting procedures. Selective superior mesenteric angiography may also be used. A bolus of contrast material introduced into the superior mesenteric artery returns via the superior mesenteric and portal veins, which can be seen in films exposed at appropriate intervals. This technic does not give as clear a picture of the portal vascular bed as does splenic venography. However, it is safer and is of particular value in showing the portal vein in patients who have undergone splenectomy and in those in whom a tendency to bleed contraindicates splenic venography. It may resolve the problem of a nonvisualized portal vein on splenic venography. A hepatic arteriogram may also be obtained and is useful in showing abnormal vasculature in cases of malignant disease. Portal venograms can also be obtained via the umbilical vein catheter [3]. In certain instances, transhepatic venography may be performed, as may hepatic venography through a catheter wedged in the hepatic tal tracts
122
In addition to the two main groups of presinusoidal and intrahepatic types of portal hypertension, the problem of primary portal hypertension must be considered. (Figure 3.) Reports from Italy [7j, France [8], Uganda [9], Calcutta [IO], and the United States [II] have described patients with portal hypertension but no very obvious obstruction of the portal venous system. Such patients usually have a very large spleen, and this condition is sometimes termed idiopathic tropical splenomegaly. Chronic malaria may play a part in some instances. A similar situation occurs with myeloid metaplasia. The portal hypertension has been related to increased splenic blood flow [9]. In addition, however, intrahepatic resistance is usually increased, indicating some obstruction to portal flow. Splenic venography shows secondary and subsequent branches of the portal vein to be narrowed. Liver biopsies from the Calcutta series [IO] and those of another series from the United States [12] have shown sclerosis and sometimes obliteration of the intrahepatic portal vascular bed. This may represent an occlusive process in the intrahepatic portal venous system related to any form of portal hypertension. Similar findings on hepatic biopsy have been reported from the United States in patients with obstruction of the main portal veins. Hepatic biopsy specimens showed subtle changes with derangement of the lobular architecture and sometimes thickening of the portal vein radicles. Phlebosclerosis of the extrahepatic portal vein was also seen. Thrombosis and internal thickening of the whole portal system have been reported from Hong Kong, not only in patients with massive splenomegaly but also in those with cirrhosis [13]. Impaired distensibility of the liver as a whole despite increased splenic blood flow must also be considered.
The American Journal of Surgery
Presinusoidal
Portal
Hypertension
r------s? INTRAHEPATK’ _ ~~- -ftt-_-_-
CLASSIFICATION
This group of diseases is characterized by a high intrasplenic pressure but a wedged hepatic venous pressure that is normal or only slightly increased. Delay in diagnosis is usually caused by failure to perform hepatic biopsy and splenic venography. In children, both studies may be carried out at the same procedure with the patient under general anesthesia: the intrasplenic pressure can be estimated at t ‘he same time. Extrahepatic
Presinusoidal
Portal Hypertension
In these diseases the obstruction is in the main portal vein at any point in its course. The venae comitantes enlarge in an attempt to deliver portal blood to the liver and assume a leashlike cavernous appearance. The portal vein, represented by a fibrous strand. usually is recognized with difficulty in the multitude of small vessels. This change is not developmental but follows any block in the main vein. In infant,s and children, the cause is usually infective, for instance, umbilical sepsis or unrecognized appendicitis. In adults, infection is also important but other conditions, such as clotting diseases (polycythemia) and tumors (primary hepatocellular carcinoma), become more important. Splenic arteriovenous fistulas can cause portal hypertension and have been diagnosed by arteriography [14]. Hepatic artery-portal vein aneurysms, often congenital, are rare, but have been demonstrated more often since the advent of hepatic angiography [ 151. Functional Aspects. It is important to distinguish this extrahepatic disease from the intrahepatic forms, for in these the liver cell generally functions well. Hepatic encephalopathy is therefore unusual. Moreover, clotting factors are pro duced normally and, despite low platelet counts, any variceal bleeding usually ceases promptly. However, the shunting of portal blood away from the liver cells might be expected to impair hepatic function. In fact, as age increases, and particularly after the age of forty, signs of hepatic failure, including ascites and hepatic encephalopathy, may develop. Bromsulphthalein retention increases [16]. These changes may represent an acceleration of the usual effects of aging on hepatic function. Ascit,es and encephalopathy may also be precipitated by acute thrombosis of the portal vein or by hemorrhage. It is generally agreed that the renal failure that develops in cirrhotic patients in the absence of
Volume
127.
February
1974
Wedged hepatic vein
iranshepatic
~~Urnbilical t&;g, vein PRESSURE RECORDING;
lntraspimic
Figure 2. Portal hypertension can be classified into two main groups, presinusoidal and intrahepatic. The presinusoidal is further divided into extrahepatic, in which the obstruction is in fhe main portal vein, and presinusoidal, in which the obstruction is usually in the portal tracts. Pressure recordings allow the anatomic site of the obstruction to be located.
primary renal disease has a funct~ional basis. It has been associated particularly with an increased renal vascular resistance and a redistribution of renal blood flow away from the cortex [I 7.-191. Rather similar changes can be seen in noncirrhotic patients with port al hypertension. Using the 133xenon washout technic, renal blood flow is reduced. which is accompanied by a redistribution of intrarenal blood flow; the distribul ion and flow rates to the outer cortex are reduced whereas juxtamedullary ancl medullary flows are maintained [20]. (Figure 4.) The relation between renal and portal circulations has received little investigaFAILUREOF LIVERTO DISTEND
SPLENOMEGALY
Figure 3. Factors concerned in primary portal hypertension. Splenic blood flow is increased. The splenic and portal veins may show secondary sclerosis and thrombosis. The intrahepatic resistance is raised, parfly because of porfal zone lesions.
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Sherlock
0 Control Portal
l
5 hypertension
lntrahepatic Presinusoidal
80
"OU
‘% distribution cortex
to outer
Figure 4. Correlation between the percentage distribution of blood flow to the outer renal cortex and creatinine clearance in patients with noncirrhotic portal hypertension, Note the reduced cortical perfusion in some patients even when glomerular filtration is well maintained. (From Kew et a/ [31].)
tion. These observations raise the possibility that portal hypertension or portal circulatory changes may play a role in the pathogenesis of the renal hemodynamic changes and functional renal failure that frequently complicate advanced hepatic cirrhosis. These observations are, at the moment, of theoretic rather than of practical importance because patients with advanced cirrhosis of the liver in whom functional renal failure develops are rarely fit enough to undergo portal decompression. One patient with advanced cirrhosis, however, did have a shunt procedure and apparently benefited
Lw Management. Variceal bleeding can, in most instances, be controlled with blood transfusion with or without the use of vasopressin and a Sengstaken-Blakemore tube. It is vital to preserve all veins needed for transfusion and to make sure that all blood used is compatible in all respects so that antibodies to its constituents do not develop. When surgery is needed and the state of the portal or splenic vein allows it, portacaval or splenorenal anastomosis is very successful. Unfortunately, too often there is no satisfactory splenic or portal vein for the shunt, in which case mesocaval anastomosis can be used and is usually successful in experienced hands [22]. A knitted DaArsenic
TABLE I
and Noncirrhotic
Portal Hypertension* Pressures
Sex and Age 00 of Patient
Dose of Arsenic
M,49 M,59
25-29 6.5
* From
124
Morris
(gm)
et al [29].
Varices ++ ++
cron@ graft has been interposed between the side of the inferior vena cava and the side of the superior mesenteric vein with encouraging results [23]. This may make mesocaval operation technically possible in some patients in whom the usual procedure would fail. It remains to be established how long this prosthetic shunt will remain patent.
Splenic
Wedged Hepatic Venous
17 30
7 12
Portal
Hypertension
In this group of diseases are included all forms of portal hypertension originating in the liver but without the associated nodules of cirrhosis or the lesions in the hepatic venous outflow tract of the Budd-Chiari syndrome. Anatomically, the obstruction is usually in the portal veins but may be along the sinusoids in the space of Disse. Here again the intrasplenic pressure and umbilical (portal) venous pressure are increased but the wedged hepatic venous pressure is virtually normal. Causes. Schistosomiasis: The parasitic ova are deposited in the portal tracts around the terminal branches of the portal vein where they cause a granulomatous reaction. The granulomas change into fibrous tissue and thus periportal fibrosis ensues. As the fibrous tissue shrinks, the terminal branches of the portal veins are constricted, producing portal hypertension. Schistosomal hepatic fibrosis results in presinusoidal venous obstruction ~241. Myeloproliferative diseases: Portal hypertension may be the result of infiltration of the portal zones with primitive hemopoietic tissue. Portal hypertension has been reported with myelosclerosis and myeloid leukemia. Patients with Hodgkin’s disease or myelosclerosis may even bleed from radiologically demonstrable esophageal varices. Wedged hepatic venous pressure is normal whereas intrasplenic pressure is increased. Observations of hepatic blood flow have given divergent results. In one series, hepatic blood flow was normal [25]; in another, hepatic blood flow was increased and, in addition to portal zone obstruction, increased splenic blood flow was incriminated [26]. Sarcoidosis: Portal hypertension has been related both to granulomas in the portal vein and to increased splenic blood flow. Congenital hepatic fibrosis: Histologically, this consists of broad, densely collagenous bands surrounding otherwise normal hepatic zones. The bands contain large numbers of small microscopic, well formed bile ducts, some of which may contain bile. Associated portal hypertension may be due to defects in the main portal vein. More often it is
The American
Journal
of Surgery
Portal
due to hypciplasia or compression of portal zone radicles in the fibrous bands. The portal hypertension is usually presinusoidal [27]. Arsenic toxicity: Presinusoidal portal hypertension may develop in patients treated with arsenic for long periods, for instance, those with psoriasis. (Table I.) This can be related to fibrosis and sclerosis of portal veins in portal tracts (28,291. This may be due to a direct effect of arsenic on the intrahepatic portal veins. Primaq biliap cirrhosis: Although primary biliary cirrhosis is called “cirrhosis,” a much better term would be chronic, nonsuppurative destructive cholangitis, because the nodular regeneration of cirrhosis is a late feature. Despite this, portal hypertension is a frequent and quite early finding. Bleeding from esophageal varices was an initial complaint in fifteen of twenty-three patients with primary biliary cirrhosis who required portal decompression therapy [30]. Although this high rate of bleeding as an initial symptom could not be confirmed in other series, there is no doubt that portal hypertension can be an early finding [31]. Evidence of port,al hypertension was found in fifty of one hundred nine patients with primary biliary cirrhosis. and in twenty-one it had bee’n diagnosed within two years of the onset of symptoms. The mechanism of the portal hypertension remains uncertain. (Figure 5.) In some patients in the later stages. nodular regeneration such as that in cirrhosis was undoubtedly involved. In others, portal zone fibrosis may be implicated. However, there is difficulty in correlating portal hypertension with features such as portal zone infiltration and fibrosis. Nor can definite evidence of obstruction of efferent veins at, a sinusoidal level by mononuclear cell infiltration. hyperplasia, or hypertrophy of Kupffer cells or of narrowing of sinusoids by consistent twin hepatocyte plates be demonstrated. It is difficult to know. therefore, the mechanism of the portal hypertension of primary biliary cirrhosis in those patients in whom nodular regeneration cannot be demonstrated. Management. As in the extrahepatic group of diseases. variceal bleeding is usually controlled and operative intervention is not required. In patients with congenital hepatic fibrosis, schistosomiasis, prirnary biliary cirrhosis, and, occasionally, sarcoidosis. this is not always so and hemorrhage can be serious and rerseated. The reaction of watients with intrahepatic presinusoidal portal hypertension to portosystemic shunting procedures should be good, for hepatocellular function is maintained. Indeed. this is generally the case and
Volume
127.
February
1974
H,jpertension
certainly true of patients with congenital hepatlc fibrosis or sarcoidosis. When hepatocellular changes are associated, results are Iess favorable. In schistosomiasis, cirrhosis is often present in ad dition to the presinusoidal venous obstruction and a shunting operation is often followed by serious encephalopathy. This has led to more local operations, such as esophageal transection. in these patients. Similarly, primary biliary cirrhosis should be considered with the cirrhoses rather than with the presinusoidal (diseases, although results after portosystemic shunting tend to be better in those patients with primary biliary cirrhosis than in those with cirrhosis [32]. There is certainly a lower inc,idence of later encephalopathy and longer survival. lntrahepatic
Portal Hypertension
The presinusoidal group of diseases has already been discussed. Of the remainder, cirrhosis of all types constitutes by far the most impon:ant group. Other causes include the hepatic outflow blocks (the Budd-Chiari syndrome) and, finally, a rarity, partial nodular transformation of the liver. The Cirrhoses. All forms of cirrhosis lead to hepatic portal hypertension. The mechanism is complex. The portal vascular bed is distorted and diminished and the portal blood flow is mechanically obstructed. Some of the portal venous blood is diverted into collateral venous channels. This is well shown by the so-called nonfilled portal vein seen in some splenic venograms. In addition, some portal venous blood bypasses the nodules of liver cells and is shunted directly into hepatic venous radicles in the fibrous septums 1331. The hepatic vein is displaced further and further outward until it lies in a fibrous septum linked with the portal venous radicle by the original sinusoid. The regenerating nodules become separated from their por-
REGENERATING NODULES
PORTAL TRACT LESIONS
NARROWING OR CELLULAR INFILTRATION
Figure 5. Primary biliary cirrhosis: factors concerned in portal hypertension include regenerating nodules (postsinusoidal), lesions of the portal tract (presinusoidal), and narrowing or cellular infiltration of the sinusoids (sinusoidal).
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Sherlock
Esophageal Transection Variceal Bleeding*
TABLE II
Cirrhosis Portal vein block * From
George
for Uncontrolled
Liver Failure
Leaking Anastomosis
Cardiorespiratory Failure
14
10
3
3
5
0
0
0
Number of Patients
Survived
30 5 et al [39].
tal blood supply and are nourished by the hepatic artery. About one third of the total blood perfusing the cirrhotic liver may bypass the sinusoids, and hence functioning hepatic tissue, through these channels [33]. The hepatic venous radicles and sinusoids are readily compressed by the regenerating nodules. The portal venous radicles, being supported by connective tissue in the portal triad, withstand the pressure. Nodule formation seems to be more important in the etiology of portal hypertension than does fibrosis. This has led to the concept of hepatic venous outflow block as a major factor in the etiology of portal hypertension in cirrhosis. This concept was supported by the observation that the pressure in the main portal vein exceeded that in the wedged hepatic vein, and the obstruction was assumed to be in the sinusoidal bed. However, as previously discussed, umbilical catheterization has allowed free portal pressure to be measured, and the wedged hepatic venous pressure and free portal venous pressure are virtually identical in cirrhosis [2]. This means that the stasis extends to the portal inflow vessels. The concept of a simple postsinusoidal portal hypertension in cirrhosis should be abandoned. The portal venous obstruction of cirrhosis is therefore classified in general terms as intrahepatic and involving increased resistance in portal zones, sinusoids, and hepatic veins. The hepatic artery provides the liver with a small volume of blood at a high pressure; the portal vein delivers a large volume of blood at a low These two systems are equilibrated in pressure. the sinusoids. The hepatic artery delivers blood directly to the sinusoid and so raises the intrasinusoidal pressure. Even in the normal subject, the elevation of portal venous pressure may depend on the hepatic arterial pressure. In the cirrhotic liver more direct arterioportal shunting has been suspected. Microangiographic studies show arterioles entering the venous channels surrounding the nodules instead of the sinusoids. A pathway between hepatic arterial and portal venous branches 126
certainly exists in the cirrhotic liver, because retrograde flow can be shown, although rarely, in the portal vein [34]. This does not prove that the increased transmission of hepatic arterial pressure is responsible for the portal hypertension in cirrhosis. In addition to mechanical obstruction (backward flow theory), the role of increased splanchnic blood flow in portal hypertension must also be considered (forward flow theory). Total splenic blood flow is indeed increased and splenic vascular resistance reduced in patients with cirrhosis [35]. However, total splenic flow increases further after end to side portacaval anastomosis although the portal venous pressure has returned to normal. This suggests that the increased splenic flow can only contribute a minor part to the portal hypertension of cirrhosis. The mechanism of the increased splenic flow after portacaval shunt is obscure but is probably part of the general vasodilatory state in cirrhosis. Management. The problem of bleeding esophageal varices in cirrhosis is quite a different matter from that complicating other forms of portal hypertension. In these patients, hepatocellular failure is always a possibility and bleeding frequently recurs during hospitalization. Management should always be planned by the physician and surgeon in consultation. End© should be performed as soon as possible. Measures such as adequate transfusion, preferably with fresh blood, and avoidance of sedation must be re-emphasized. Intravenous administration of vasopressin is the best method for initial control of bleeding. If the hemorrhage ceases spontaneously or after vasopressin and does. not recur, surgery is not performed. The consideration of whether a later, elective procedure is needed, and if so what type, depends on the state of the patient and the judgment of his physicians [35]. There is no place for prophylactic shunting. The bleeding episode must have been sufficiently severe to have required blood transfusion or produced shock, and there should have been no encephalopathy even after massive hemorrhage. Any preoperative encephalopathy will inevitably be associated with significant postoperative encephalopathy [32] and is a contraindication to end to side shunting procedures. The nature of the operation to be performed is a matter of debate. Current views favor maintaining hepatic blood flow, and such procedures as mesentericocaval, distal splenorenal [371, and portacaval anastomoses with proximal arterialization [38] are being evaluated. The American Journal of Surgery
F’cri;si ”
If the bleeding does not cease after one infusion of l’itressin* or recurs during that hospital stay, a definite decision must be made whether to prepare the pajient for immediate surgery or, if he is too poor a risk, to stop active measures. Delay at. this stage will result in further deterioration and the reasonably good surgical risk will become an impossible one. If surgery is decided on, much is to be gaineti by introducing a Sengstaken-Blakemore tube. Control of’ bleeding confirms that the source is variceal. Time is allowed for adequate transfusion. Within a few hours operation is carried out. In general, portacaval shunts are not satisfact.or$ under these emergency conditions. At the Royal Free Hospital, transt horacic esophageal transection is carried out [39]. (Table II.) Result,s show a high mortality of 45 per cent, but the cirrhot.ic, patients who underwent the procedure were very poor risks. Efforts are now being made to perform I he procedure earlier. After recovery, a decision is again made whether further (shunt) surgery is desirable.
Budd-Chiari Syndrome
(Hepatic
Venous Obstruction)
This condition is usually associated with the names of Budd and Chiari, although Budd’s description omitted the clinical features and Chiari’s report was not the first to describe t,he clinical picture. It may arise from obstruction of hepat.ic veins at any site from the efferent vein of the lobule to t,he entry of the inferior vena cava into the right atrium. (Figure 6.) A similar syndrome may be produced by constrictive pericarditis or rightsided heart failure. and these must be distinguished. The syndrome comprises hepatomegaly, abdominal pain, ascites, and hepatic histologic features of centrizonal sinusoidal distention and pooling. Membranous obstruction of t.he suprahepatic segment of the inferior vena cava is an important condition because it is potentially curable by surgery [40]. The web varies from a thin membrane to a thick fibrotic band and may continue inferiorly as a stricture. It lies above the right and often below the main left hepatic vein orifice [40]. The largest series comes from Japan [41]. The web is presumed to be congenital, but if so, its presentation in adults in their thirties is surprising. It can also be acquired as a result of organized thrombosis after trauma, particularly automobile accidents. Other causes include clotting diseases, primary and secondary cancer of the liver, kidney, and adrenals, veno-occlusive disease. acute alco-
Volume
127.
February
1974
l
Congenital
,
Hvpf3rterlsjCn
webs
Oral contraceptives Tumours . CLotting diseases
l
R.Atrlum
l
. Trauma
\
--Veti -occlusive t disease Tumours Acute alcoholic Kidney hepatitis Adrenal
Renal vein
t
Thromlbosis
Figure 6. Factors concerned in the hepafic sfruction (Budd-Chiari) syndrome.
venous
ob-
holic hepatitis, and react.ions to some oral contraceptive drugs. In many instances, the cause remains unknown. The advent of more sophisticated investigations of the hepatic venous system, including hepatic venography, angiography, and scanning and needle biopsy of the liver have reduced considerably the number of cases in which the cause is unknown. In the more chronic cases, the caudate lobe, which has separate venous drainage into the cava, is enlarged. This is shown by a centrally located opacity on a hepatic scintiscan. The inferior vena cava is compressed side to side by this lobe as it passes posterior to the liver. Areas less affected by obstruction become hypertrophied in a nodular fashion. In such cases the spleen may be enlarged and the portal collateral circulation seen. There may be terminal thrombosis of mesente-ric vessels. Summary Portal, hypertension can be classified into two main groups, presinusoidal (intrahepatic and extrahepatic) and intrahepatic. Presinusoidal extrahepatic portal hypertension is unlikely to be associated with hepatocellular failure. Increased splenic flow pla,ys a. minor role in its’ cause. Renal cortical perfusion may be reduced. Causes of presinusoidal intrahepat ic portal hypertension include schistosomiasis, myeloproliferative diseases, sarcoidosis, congenital hepatic fibrosis, chronic arsenic poisoning, and primary bil-
127
Sherlock
iary cirrhosis. Portosystemic shunt operations are well tolerated unless there is associated hepatocelIular damage. In cirrhosis. the mortal hvnertension is nresinusoidal, sinusoidal, and postsinusoidal. The problem of bleeding esophageal varices is largely that of hepatocellular failure. The Budd-Chiari (hepatovenous obstruction) syndrome has many causes, including “congenital” webs and trauma. These may be susceptible to a surgical approach. &
UL
L
References 1. Viallet A, Legare A, Lavoie P: Hepatic and umbilico-portal catheterization in portal hypertension. Ann NY Acad Sci 170: 177,197O. 2. Reynolds TB, Ito S, lwatsuki SM: Measurement of portal pressure and its clinical application. Am J Med 49: 649, 1970. 3. Kessler RE, Tice DA, Zimmon DS: Value, complications and limitations of umbilical vein catheterisation. Surg Gynecol Obstet in press. 4. Gonzales CO: Hepatoportografia por via umbilical. Rev Sanid Milit (Mex) 12: 42, 1959. 5. Kreel L: Radiology of the portal system. Gut 11: 620, 1970: 6. Clain D, Freston J. Kreel L, Sherlock S: Clinical diagnosis of the Budd-Chiari syndrome. A report of six cases. Am J Med 43: 544,1967. 7. Sotgiu G: L’hypertension portal par hyperafflux splenique. J Med Montpellier 3: 382, 1968. 8. Benhamou JP, Guillemot R, Tricot R, Leger L, Fauvert R: Hypertension portale essentielle. Presse Med 70: 2397, 1962. 9. Williams R, Parsonson A, Somers K, Hamilton PJS: Portal hypertension in idiopathic tropical splenomegaly. Lanckt1: 329,1966. 10. Bover JL. Guota KPS. Biswas SK. Pal NC. Mallick KCB. iber FL, Basu AK: Idiopathic p&al hypertension. Ann Intern Med 66: 41, 1967. 11. Mikkelson WP, Edmondson HA, Peters RL, Redeker AG, Reynolds TB: Extra- and intra-hepatic portal hypertension without cirrhosis (hepato-portal sclerosis). Ann Surg 162: 602, 1965. 12. Tisdale WA, Klatskin G, Glenn WWL: Portal hypertension and bleeding esophageal varices. Their occurrence in the absence of both intrahepatic and extrahepatic obstruction of the portal vein. N Engl J Med 261: 209, 1959. 13. Hou PC, McFadzean AJS: Thrombosis and intimal thickening in the portal system in cirrhosis of the liver. J Pathol89: 473, 1965. 14. Stone HH, Jordan WD, Acker JJ, Martin JD Jr: Portal arteriovenous fistulae. Review and case report. Am J Surg 109: 191, 1965. 15. Foley WJ, Turcotte JG, Hoskins PA, Brant RL, Ause RG: lntrahepatic arteriovenous fistulas between the hepatic artery and portal vein. Ann Surg 174: 849, 1971. 16. Thompson EN, Williams R, Sherlock S: Liver function in extrahepatic portal hypertension. Lancet 2: 1352, 1964. 17. Cohn JN, Tristani FE, Khatri IM: Renal vasodilator therapy in the hepato-renal syndrome. Med Ann DC 39: 1, 1970. 18. Epstein M, Berk DP, Hollenberg NK, Adams DF, Chalmers TC, Abrams HL, Merrill JP: Renal failure in the patient with cirrhosis. The role of active vasoconstric-
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tion. Am J Med 49: 175, 1970. 19. Kew MC, Brunt PW. Varma RR, Hourigan KJ, Williams HS, Sherlock S: Renal and intrarenal blood-flow in cirrhosis of the liver. Lancet 2: 504, 1971. 20. Kew MC, Limbrick C, Varma RR, Sherlock S: Renal and intrarenal blood flow in non-cirrhotic portal hypertension. Guf 13: 763, 1972. 21. Schroeder ET. Numann PJ. Chamberlain BE: Functional renal failure in cirrhosis. Recovery after portacaval shunt. Ann intern Med 72: 923, 1970. 22. Tank ES, Wallin W Jr, Turcotte JG, Child CG III: Surgical management of bleeding gastro-esophageal varices in children. Arch Surg 98: 451, 1969. 23. Drapanas T: Interposition mesocaval shunt for treatment of portal hypertension. Ann Surg 176: 435, 1972. 24. Hassab MA: Nonshunt operations in portal hypertension without cirrhosis. Surg Gynecol Obstet 131: 648, 1970. 25. Shaldon S, Sherlock S: Portal hypertension in the myeloproliferative syndrome and the reticuloses. Am J Med 32: 758, 1962. 26. Rosenbaum DL, Murphy GW, Swisher SN: Hemodynamic studies of the portal circulation in myeloid metaplasia. Am J Med 41: 360,1966. 27. Kerr DNS, Harrison CV, Sherlock S, Walker RM: Congenital hepatic fibrosis. Q J Med 30: 91, 1961. 28. Viallet A, Guillaume E, C&B J, LBgare A, Lavoie P: Presinuosoidal portal hypertension following chronic arsenic administration. Gastroenterology 62: 177, 1972. 29. Morris JS, Schmid M, Newman S, Scheuer PJ. Sherlock S: Arsenic and non-cirrhotic portal hypertension. Gastroenterology in press. 30. Zeegen R, Stansfeld AG, Dawson AM, Hunt AH: Bleeding oesophageal varices as the presenting feature in primary biliary cirrhosis. Lancet 2: 9, 1969. 31. Kew MC, Varma RR, DOS Santos HA, Scheuer PJ, Sherlock S: Portal hypertension in primary biliary cirrhosis. Gut 12: 830, 1971. 32. Hourigan K, Sherlock S, George P, Mindel S: Elective end-to-side portacaval shunt: results in 64 cases. Br MedJ4:473,1971. 33. Shaldon S, Chiandussi L, Guevara L, Caesar J, Sherlock S: The measurement of hepatic blood flow and intrahepatic shunted blood flow by colloid heat-denatured human serum albumin labelled with l131. J C/in invest 40: 1346, 1961. 34. Kessler RE, Tice DA, Zimmon DS: Retrograde flow of portal vein blood /n patients with cirrhosis. Radiology 92: 1038,1969. 35. Gitlin N, Grahame GR, Kreel L, Williams HS, Sherlock S: Splenic blood flow and resistance in patients with cirrhosis befdre and after portacaval anastomoses. Gastroenferology 59: 208, 1970. 36. Winkler K: Selection of patients with cirrhosis of the liver for shunt surgery. Stand J Gastroenterol7: 679, 1972. 37. Zeppa R, Warren WD: The distal splenorenal shunt. Am J Surg 122: 300,1971. 38. Maillard JN, Benhamou JP, Rueff R: Arterialisation of the liver with portacaval shunt in the treatment of portal hypertension due to intrahepatic block. Surgery 67: 883, 1970. 39. George P, Brown C, Ridgway G, Crofts B, Sherlock S: Emergency oesophageal transection in uncontrolled variceal haemorrhage. Br J Surg in press. 40. Takeuchi J, Takada A, Hasumura Y, Matsuda Y, Ikegami F: Budd-Chiari syndrome associated with obstruction of the inferior vena cava. Am J Med 51: 11, 1971. 41. Schaffner F, Gadboys HL, Safran AP, Baron MG, Aufses AH: Budd-Chiari syndrome caused by a web in the inferior vena cava. Am J Med 42: 838,1967.
The American Journal of Surgery
LECTURE
Classification and Functional Aspects of Portal Hypertension Sheila Sherlock,
MD, London,
England
Portal blood pressure depends on splanchnic blood flow, resistance t.o outflow from the liver, and the pressure in the inferior vena cava. In evaluating portal hypertension, the part played by each factor must be assessed. Increased resistance to hepatic blood flow is the most important. The advent of newer radiologic and pressuremeasuring methods, combined with hepatic needle biopsy, allows the portal circulation to be evaluated much more clearly. There is now no excuse for a surgeon to be surprised to find a congested portal vascular bed and portal hypertension at operation. Indeed, there is little excuse for operating without precise knowledge of the type of portal hypertension and the location of any portosystemic collaterals. In the individual patient, these factors must be established: first, the existence of portal hypertension; second, the site of any portal obstruction; third, the anatomy of portosystemic collaterals; and fourth, the cause. Technics
of Evaluation
Portal Pressure Measurements. The pressure measurement taken through a needle passed percutaneously into the pulp of the spleen reflects closely the pressure in the splenic vein. At operation the pressure in the main portal vein may be estimated. This does, however. necessitate intervention and the results obtained are affected by such factors as anesthesia, hemchanges in intra-abdominal pressure, and orrhage, kinking of the vein. Perhaps the greatest advance has been that of umbilical vein catheterization [l-3] which
From the Department of Medicine, Royal Free Hospital School of Medicine, University of London, London, England. This work was supported by the Ingram Trust. Reprint requests should be addressed to Dr Sherlock. Department of Medicine, Royal Free Hospital School of Medicine, Gray’s Inn Road, London, WCI, England. Presented at the Fourteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, New York, New York, May 22 and 23.1973
Volume 127, February
1974
has allowed measurement of the pressure in the main portal vein in unanesthetized patients. The umbilical vein of adult patients is only collapsed and, especially in the presence of portal hypertension, can be reopened, dilated, and catheterized, allowing access to the left branch of the portal vein and hence to the portal venous system [4]. With the patient under local, general, or epidural anesthesia, an incision is made half-way between the umbilicus and the xiphoid process. The umbilical vein remnant is found in the free edge of the falciform ligament and dilsted, and the catheter is introduced and advanced into the portal vein. The technic is not an easy one: the failure rate is high, being 50 to 90 per cent in patients with cirrhosis, but it decreases with experience. Complications include hemorrhage, wound infection, and, possibly, thrombosis of the portal vein. It is generally agreed to be a safe procedure but one t.hat requ:lres a surgical team for its performance. A catheter wedged in a hepatic venous radicle produces stasis as far as the first freely anastomosing sinusoidal area. It therefore reflects sinusoidal pressure. In patients with chronic liver disease the pressure in the free left branch of the portal vein, measured through an umbilical catheter, approximates the wedged hepatic venous pressure [Z]. The area of stasis induced by the catheter extends over a wide area, even to the portal venous inflow. This implies that the portal hypertension of cirrhosis is not, simply postsinusoida1 but extends right through the hepatic vein and sinusoids to the main portal vein. In cond.itions in which there is obstruction to flow at a presinusoidal level, for instance, schistosomiasis, the wedged hepatic venous pressure is normal. This presumably reflects normal anastomoses between small hepatic vascular units that prevent the catheter from creating a large area of stasis. (Figure 1.) The portal hypertension of cirrhosis, therefore, can no longer be regarded as predominantly postsinusoidal. No purpose is served by retaining the distinction between post- and presinusoidal portal hypertension. A satisfactory classification is comprised of two groups: (1) presinusoidal, which includes lesions in the main portal vein and in the portal veins in the por-
121
Sherlock
vein [6] in patients suspected of having the Budd-Chiari syndrome. Needle Biopsy of the Liver. This technic permits the etiologic factors of the portal hypertension to be determined in many instances. in all but the greatest emergency this is essential, both to determine the cause and to formulate the management. For instance, acute alcoholic hepatitis may improve with medical treatment and surgery should be postponed if possible until all benefit has accrued from this; surgery may not be necessary. The diagnosis of hepatic malignancy, whether primary or secondary, contraindicates surgical procedures on the portal system except as a preliminary to hepatic resection or transplantation. Primary Portal Hypertension Figure
7. Contrast material flowing info a catheter wedged info a hepatic venous radicle causes stasis in a relatively large area. The stasis includes the sinusoidal bed of many small hepatic vascular units.
of the liver; and (2) intrahepatic, which includes all the cirrhoses and the hepatic venous occlusions (Budd-Chiari syndrome). (Figure ‘2.) Radiologic Procedures. These allow the location of any anatomic block and the identification of the portosystemic collateral circulation [5]. The simplest is splenic venography, which is a necessary preliminary to all surgical procedures on the portal venous system. It is contraindicated in the presence of jaundice or an increase of more than three seconds in the one-stage prothrombin time. If a technically satisfactory splenic venogram fails to. show gastroesophageal collaterals, bleeding from varices is unlikely. Splenic venography is essential before portacaval shunt procedures because it shows the availability of the vein for the procedure. Although thrombosis of the portal vein itself is an unusual complication of cirrhosis, it could be caused by complicating primary cancer of the liver. Such an obstruction would be shown by the splenic venogram and would p~sclude portosystemic shunting procedures. Selective superior mesenteric angiography may also be used. A bolus of contrast material introduced into the superior mesenteric artery returns via the superior mesenteric and portal veins, which can be seen in films exposed at appropriate intervals. This technic does not give as clear a picture of the portal vascular bed as does splenic venography. However, it is safer and is of particular value in showing the portal vein in patients who have undergone splenectomy and in those in whom a tendency to bleed contraindicates splenic venography. It may resolve the problem of a nonvisualized portal vein on splenic venography. A hepatic arteriogram may also be obtained and is useful in showing abnormal vasculature in cases of malignant disease. Portal venograms can also be obtained via the umbilical vein catheter [3]. In certain instances, transhepatic venography may be performed, as may hepatic venography through a catheter wedged in the hepatic tal tracts
122
In addition to the two main groups of presinusoidal and intrahepatic types of portal hypertension, the problem of primary portal hypertension must be considered. (Figure 3.) Reports from Italy [7j, France [8], Uganda [9], Calcutta [IO], and the United States [II] have described patients with portal hypertension but no very obvious obstruction of the portal venous system. Such patients usually have a very large spleen, and this condition is sometimes termed idiopathic tropical splenomegaly. Chronic malaria may play a part in some instances. A similar situation occurs with myeloid metaplasia. The portal hypertension has been related to increased splenic blood flow [9]. In addition, however, intrahepatic resistance is usually increased, indicating some obstruction to portal flow. Splenic venography shows secondary and subsequent branches of the portal vein to be narrowed. Liver biopsies from the Calcutta series [IO] and those of another series from the United States [12] have shown sclerosis and sometimes obliteration of the intrahepatic portal vascular bed. This may represent an occlusive process in the intrahepatic portal venous system related to any form of portal hypertension. Similar findings on hepatic biopsy have been reported from the United States in patients with obstruction of the main portal veins. Hepatic biopsy specimens showed subtle changes with derangement of the lobular architecture and sometimes thickening of the portal vein radicles. Phlebosclerosis of the extrahepatic portal vein was also seen. Thrombosis and internal thickening of the whole portal system have been reported from Hong Kong, not only in patients with massive splenomegaly but also in those with cirrhosis [13]. Impaired distensibility of the liver as a whole despite increased splenic blood flow must also be considered.
The American Journal of Surgery
Presinusoidal
Portal
Hypertension
r------s? INTRAHEPATK’ _ ~~- -ftt-_-_-
CLASSIFICATION
This group of diseases is characterized by a high intrasplenic pressure but a wedged hepatic venous pressure that is normal or only slightly increased. Delay in diagnosis is usually caused by failure to perform hepatic biopsy and splenic venography. In children, both studies may be carried out at the same procedure with the patient under general anesthesia: the intrasplenic pressure can be estimated at t ‘he same time. Extrahepatic
Presinusoidal
Portal Hypertension
In these diseases the obstruction is in the main portal vein at any point in its course. The venae comitantes enlarge in an attempt to deliver portal blood to the liver and assume a leashlike cavernous appearance. The portal vein, represented by a fibrous strand. usually is recognized with difficulty in the multitude of small vessels. This change is not developmental but follows any block in the main vein. In infant,s and children, the cause is usually infective, for instance, umbilical sepsis or unrecognized appendicitis. In adults, infection is also important but other conditions, such as clotting diseases (polycythemia) and tumors (primary hepatocellular carcinoma), become more important. Splenic arteriovenous fistulas can cause portal hypertension and have been diagnosed by arteriography [14]. Hepatic artery-portal vein aneurysms, often congenital, are rare, but have been demonstrated more often since the advent of hepatic angiography [ 151. Functional Aspects. It is important to distinguish this extrahepatic disease from the intrahepatic forms, for in these the liver cell generally functions well. Hepatic encephalopathy is therefore unusual. Moreover, clotting factors are pro duced normally and, despite low platelet counts, any variceal bleeding usually ceases promptly. However, the shunting of portal blood away from the liver cells might be expected to impair hepatic function. In fact, as age increases, and particularly after the age of forty, signs of hepatic failure, including ascites and hepatic encephalopathy, may develop. Bromsulphthalein retention increases [16]. These changes may represent an acceleration of the usual effects of aging on hepatic function. Ascit,es and encephalopathy may also be precipitated by acute thrombosis of the portal vein or by hemorrhage. It is generally agreed that the renal failure that develops in cirrhotic patients in the absence of
Volume
127.
February
1974
Wedged hepatic vein
iranshepatic
~~Urnbilical t&;g, vein PRESSURE RECORDING;
lntraspimic
Figure 2. Portal hypertension can be classified into two main groups, presinusoidal and intrahepatic. The presinusoidal is further divided into extrahepatic, in which the obstruction is in fhe main portal vein, and presinusoidal, in which the obstruction is usually in the portal tracts. Pressure recordings allow the anatomic site of the obstruction to be located.
primary renal disease has a funct~ional basis. It has been associated particularly with an increased renal vascular resistance and a redistribution of renal blood flow away from the cortex [I 7.-191. Rather similar changes can be seen in noncirrhotic patients with port al hypertension. Using the 133xenon washout technic, renal blood flow is reduced. which is accompanied by a redistribution of intrarenal blood flow; the distribul ion and flow rates to the outer cortex are reduced whereas juxtamedullary ancl medullary flows are maintained [20]. (Figure 4.) The relation between renal and portal circulations has received little investigaFAILUREOF LIVERTO DISTEND
SPLENOMEGALY
Figure 3. Factors concerned in primary portal hypertension. Splenic blood flow is increased. The splenic and portal veins may show secondary sclerosis and thrombosis. The intrahepatic resistance is raised, parfly because of porfal zone lesions.
123
Sherlock
0 Control Portal
l
5 hypertension
lntrahepatic Presinusoidal
80
"OU
‘% distribution cortex
to outer
Figure 4. Correlation between the percentage distribution of blood flow to the outer renal cortex and creatinine clearance in patients with noncirrhotic portal hypertension, Note the reduced cortical perfusion in some patients even when glomerular filtration is well maintained. (From Kew et a/ [31].)
tion. These observations raise the possibility that portal hypertension or portal circulatory changes may play a role in the pathogenesis of the renal hemodynamic changes and functional renal failure that frequently complicate advanced hepatic cirrhosis. These observations are, at the moment, of theoretic rather than of practical importance because patients with advanced cirrhosis of the liver in whom functional renal failure develops are rarely fit enough to undergo portal decompression. One patient with advanced cirrhosis, however, did have a shunt procedure and apparently benefited
Lw Management. Variceal bleeding can, in most instances, be controlled with blood transfusion with or without the use of vasopressin and a Sengstaken-Blakemore tube. It is vital to preserve all veins needed for transfusion and to make sure that all blood used is compatible in all respects so that antibodies to its constituents do not develop. When surgery is needed and the state of the portal or splenic vein allows it, portacaval or splenorenal anastomosis is very successful. Unfortunately, too often there is no satisfactory splenic or portal vein for the shunt, in which case mesocaval anastomosis can be used and is usually successful in experienced hands [22]. A knitted DaArsenic
TABLE I
and Noncirrhotic
Portal Hypertension* Pressures
Sex and Age 00 of Patient
Dose of Arsenic
M,49 M,59
25-29 6.5
* From
124
Morris
(gm)
et al [29].
Varices ++ ++
cron@ graft has been interposed between the side of the inferior vena cava and the side of the superior mesenteric vein with encouraging results [23]. This may make mesocaval operation technically possible in some patients in whom the usual procedure would fail. It remains to be established how long this prosthetic shunt will remain patent.
Splenic
Wedged Hepatic Venous
17 30
7 12
Portal
Hypertension
In this group of diseases are included all forms of portal hypertension originating in the liver but without the associated nodules of cirrhosis or the lesions in the hepatic venous outflow tract of the Budd-Chiari syndrome. Anatomically, the obstruction is usually in the portal veins but may be along the sinusoids in the space of Disse. Here again the intrasplenic pressure and umbilical (portal) venous pressure are increased but the wedged hepatic venous pressure is virtually normal. Causes. Schistosomiasis: The parasitic ova are deposited in the portal tracts around the terminal branches of the portal vein where they cause a granulomatous reaction. The granulomas change into fibrous tissue and thus periportal fibrosis ensues. As the fibrous tissue shrinks, the terminal branches of the portal veins are constricted, producing portal hypertension. Schistosomal hepatic fibrosis results in presinusoidal venous obstruction ~241. Myeloproliferative diseases: Portal hypertension may be the result of infiltration of the portal zones with primitive hemopoietic tissue. Portal hypertension has been reported with myelosclerosis and myeloid leukemia. Patients with Hodgkin’s disease or myelosclerosis may even bleed from radiologically demonstrable esophageal varices. Wedged hepatic venous pressure is normal whereas intrasplenic pressure is increased. Observations of hepatic blood flow have given divergent results. In one series, hepatic blood flow was normal [25]; in another, hepatic blood flow was increased and, in addition to portal zone obstruction, increased splenic blood flow was incriminated [26]. Sarcoidosis: Portal hypertension has been related both to granulomas in the portal vein and to increased splenic blood flow. Congenital hepatic fibrosis: Histologically, this consists of broad, densely collagenous bands surrounding otherwise normal hepatic zones. The bands contain large numbers of small microscopic, well formed bile ducts, some of which may contain bile. Associated portal hypertension may be due to defects in the main portal vein. More often it is
The American
Journal
of Surgery
Portal
due to hypciplasia or compression of portal zone radicles in the fibrous bands. The portal hypertension is usually presinusoidal [27]. Arsenic toxicity: Presinusoidal portal hypertension may develop in patients treated with arsenic for long periods, for instance, those with psoriasis. (Table I.) This can be related to fibrosis and sclerosis of portal veins in portal tracts (28,291. This may be due to a direct effect of arsenic on the intrahepatic portal veins. Primaq biliap cirrhosis: Although primary biliary cirrhosis is called “cirrhosis,” a much better term would be chronic, nonsuppurative destructive cholangitis, because the nodular regeneration of cirrhosis is a late feature. Despite this, portal hypertension is a frequent and quite early finding. Bleeding from esophageal varices was an initial complaint in fifteen of twenty-three patients with primary biliary cirrhosis who required portal decompression therapy [30]. Although this high rate of bleeding as an initial symptom could not be confirmed in other series, there is no doubt that portal hypertension can be an early finding [31]. Evidence of port,al hypertension was found in fifty of one hundred nine patients with primary biliary cirrhosis. and in twenty-one it had bee’n diagnosed within two years of the onset of symptoms. The mechanism of the portal hypertension remains uncertain. (Figure 5.) In some patients in the later stages. nodular regeneration such as that in cirrhosis was undoubtedly involved. In others, portal zone fibrosis may be implicated. However, there is difficulty in correlating portal hypertension with features such as portal zone infiltration and fibrosis. Nor can definite evidence of obstruction of efferent veins at, a sinusoidal level by mononuclear cell infiltration. hyperplasia, or hypertrophy of Kupffer cells or of narrowing of sinusoids by consistent twin hepatocyte plates be demonstrated. It is difficult to know. therefore, the mechanism of the portal hypertension of primary biliary cirrhosis in those patients in whom nodular regeneration cannot be demonstrated. Management. As in the extrahepatic group of diseases. variceal bleeding is usually controlled and operative intervention is not required. In patients with congenital hepatic fibrosis, schistosomiasis, prirnary biliary cirrhosis, and, occasionally, sarcoidosis. this is not always so and hemorrhage can be serious and rerseated. The reaction of watients with intrahepatic presinusoidal portal hypertension to portosystemic shunting procedures should be good, for hepatocellular function is maintained. Indeed. this is generally the case and
Volume
127.
February
1974
H,jpertension
certainly true of patients with congenital hepatlc fibrosis or sarcoidosis. When hepatocellular changes are associated, results are Iess favorable. In schistosomiasis, cirrhosis is often present in ad dition to the presinusoidal venous obstruction and a shunting operation is often followed by serious encephalopathy. This has led to more local operations, such as esophageal transection. in these patients. Similarly, primary biliary cirrhosis should be considered with the cirrhoses rather than with the presinusoidal (diseases, although results after portosystemic shunting tend to be better in those patients with primary biliary cirrhosis than in those with cirrhosis [32]. There is certainly a lower inc,idence of later encephalopathy and longer survival. lntrahepatic
Portal Hypertension
The presinusoidal group of diseases has already been discussed. Of the remainder, cirrhosis of all types constitutes by far the most impon:ant group. Other causes include the hepatic outflow blocks (the Budd-Chiari syndrome) and, finally, a rarity, partial nodular transformation of the liver. The Cirrhoses. All forms of cirrhosis lead to hepatic portal hypertension. The mechanism is complex. The portal vascular bed is distorted and diminished and the portal blood flow is mechanically obstructed. Some of the portal venous blood is diverted into collateral venous channels. This is well shown by the so-called nonfilled portal vein seen in some splenic venograms. In addition, some portal venous blood bypasses the nodules of liver cells and is shunted directly into hepatic venous radicles in the fibrous septums 1331. The hepatic vein is displaced further and further outward until it lies in a fibrous septum linked with the portal venous radicle by the original sinusoid. The regenerating nodules become separated from their por-
REGENERATING NODULES
PORTAL TRACT LESIONS
NARROWING OR CELLULAR INFILTRATION
Figure 5. Primary biliary cirrhosis: factors concerned in portal hypertension include regenerating nodules (postsinusoidal), lesions of the portal tract (presinusoidal), and narrowing or cellular infiltration of the sinusoids (sinusoidal).
125
Sherlock
Esophageal Transection Variceal Bleeding*
TABLE II
Cirrhosis Portal vein block * From
George
for Uncontrolled
Liver Failure
Leaking Anastomosis
Cardiorespiratory Failure
14
10
3
3
5
0
0
0
Number of Patients
Survived
30 5 et al [39].
tal blood supply and are nourished by the hepatic artery. About one third of the total blood perfusing the cirrhotic liver may bypass the sinusoids, and hence functioning hepatic tissue, through these channels [33]. The hepatic venous radicles and sinusoids are readily compressed by the regenerating nodules. The portal venous radicles, being supported by connective tissue in the portal triad, withstand the pressure. Nodule formation seems to be more important in the etiology of portal hypertension than does fibrosis. This has led to the concept of hepatic venous outflow block as a major factor in the etiology of portal hypertension in cirrhosis. This concept was supported by the observation that the pressure in the main portal vein exceeded that in the wedged hepatic vein, and the obstruction was assumed to be in the sinusoidal bed. However, as previously discussed, umbilical catheterization has allowed free portal pressure to be measured, and the wedged hepatic venous pressure and free portal venous pressure are virtually identical in cirrhosis [2]. This means that the stasis extends to the portal inflow vessels. The concept of a simple postsinusoidal portal hypertension in cirrhosis should be abandoned. The portal venous obstruction of cirrhosis is therefore classified in general terms as intrahepatic and involving increased resistance in portal zones, sinusoids, and hepatic veins. The hepatic artery provides the liver with a small volume of blood at a high pressure; the portal vein delivers a large volume of blood at a low These two systems are equilibrated in pressure. the sinusoids. The hepatic artery delivers blood directly to the sinusoid and so raises the intrasinusoidal pressure. Even in the normal subject, the elevation of portal venous pressure may depend on the hepatic arterial pressure. In the cirrhotic liver more direct arterioportal shunting has been suspected. Microangiographic studies show arterioles entering the venous channels surrounding the nodules instead of the sinusoids. A pathway between hepatic arterial and portal venous branches 126
certainly exists in the cirrhotic liver, because retrograde flow can be shown, although rarely, in the portal vein [34]. This does not prove that the increased transmission of hepatic arterial pressure is responsible for the portal hypertension in cirrhosis. In addition to mechanical obstruction (backward flow theory), the role of increased splanchnic blood flow in portal hypertension must also be considered (forward flow theory). Total splenic blood flow is indeed increased and splenic vascular resistance reduced in patients with cirrhosis [35]. However, total splenic flow increases further after end to side portacaval anastomosis although the portal venous pressure has returned to normal. This suggests that the increased splenic flow can only contribute a minor part to the portal hypertension of cirrhosis. The mechanism of the increased splenic flow after portacaval shunt is obscure but is probably part of the general vasodilatory state in cirrhosis. Management. The problem of bleeding esophageal varices in cirrhosis is quite a different matter from that complicating other forms of portal hypertension. In these patients, hepatocellular failure is always a possibility and bleeding frequently recurs during hospitalization. Management should always be planned by the physician and surgeon in consultation. End© should be performed as soon as possible. Measures such as adequate transfusion, preferably with fresh blood, and avoidance of sedation must be re-emphasized. Intravenous administration of vasopressin is the best method for initial control of bleeding. If the hemorrhage ceases spontaneously or after vasopressin and does. not recur, surgery is not performed. The consideration of whether a later, elective procedure is needed, and if so what type, depends on the state of the patient and the judgment of his physicians [35]. There is no place for prophylactic shunting. The bleeding episode must have been sufficiently severe to have required blood transfusion or produced shock, and there should have been no encephalopathy even after massive hemorrhage. Any preoperative encephalopathy will inevitably be associated with significant postoperative encephalopathy [32] and is a contraindication to end to side shunting procedures. The nature of the operation to be performed is a matter of debate. Current views favor maintaining hepatic blood flow, and such procedures as mesentericocaval, distal splenorenal [371, and portacaval anastomoses with proximal arterialization [38] are being evaluated. The American Journal of Surgery
F’cri;si ”
If the bleeding does not cease after one infusion of l’itressin* or recurs during that hospital stay, a definite decision must be made whether to prepare the pajient for immediate surgery or, if he is too poor a risk, to stop active measures. Delay at. this stage will result in further deterioration and the reasonably good surgical risk will become an impossible one. If surgery is decided on, much is to be gaineti by introducing a Sengstaken-Blakemore tube. Control of’ bleeding confirms that the source is variceal. Time is allowed for adequate transfusion. Within a few hours operation is carried out. In general, portacaval shunts are not satisfact.or$ under these emergency conditions. At the Royal Free Hospital, transt horacic esophageal transection is carried out [39]. (Table II.) Result,s show a high mortality of 45 per cent, but the cirrhot.ic, patients who underwent the procedure were very poor risks. Efforts are now being made to perform I he procedure earlier. After recovery, a decision is again made whether further (shunt) surgery is desirable.
Budd-Chiari Syndrome
(Hepatic
Venous Obstruction)
This condition is usually associated with the names of Budd and Chiari, although Budd’s description omitted the clinical features and Chiari’s report was not the first to describe t,he clinical picture. It may arise from obstruction of hepat.ic veins at any site from the efferent vein of the lobule to t,he entry of the inferior vena cava into the right atrium. (Figure 6.) A similar syndrome may be produced by constrictive pericarditis or rightsided heart failure. and these must be distinguished. The syndrome comprises hepatomegaly, abdominal pain, ascites, and hepatic histologic features of centrizonal sinusoidal distention and pooling. Membranous obstruction of t.he suprahepatic segment of the inferior vena cava is an important condition because it is potentially curable by surgery [40]. The web varies from a thin membrane to a thick fibrotic band and may continue inferiorly as a stricture. It lies above the right and often below the main left hepatic vein orifice [40]. The largest series comes from Japan [41]. The web is presumed to be congenital, but if so, its presentation in adults in their thirties is surprising. It can also be acquired as a result of organized thrombosis after trauma, particularly automobile accidents. Other causes include clotting diseases, primary and secondary cancer of the liver, kidney, and adrenals, veno-occlusive disease. acute alco-
Volume
127.
February
1974
l
Congenital
,
Hvpf3rterlsjCn
webs
Oral contraceptives Tumours . CLotting diseases
l
R.Atrlum
l
. Trauma
\
--Veti -occlusive t disease Tumours Acute alcoholic Kidney hepatitis Adrenal
Renal vein
t
Thromlbosis
Figure 6. Factors concerned in the hepafic sfruction (Budd-Chiari) syndrome.
venous
ob-
holic hepatitis, and react.ions to some oral contraceptive drugs. In many instances, the cause remains unknown. The advent of more sophisticated investigations of the hepatic venous system, including hepatic venography, angiography, and scanning and needle biopsy of the liver have reduced considerably the number of cases in which the cause is unknown. In the more chronic cases, the caudate lobe, which has separate venous drainage into the cava, is enlarged. This is shown by a centrally located opacity on a hepatic scintiscan. The inferior vena cava is compressed side to side by this lobe as it passes posterior to the liver. Areas less affected by obstruction become hypertrophied in a nodular fashion. In such cases the spleen may be enlarged and the portal collateral circulation seen. There may be terminal thrombosis of mesente-ric vessels. Summary Portal, hypertension can be classified into two main groups, presinusoidal (intrahepatic and extrahepatic) and intrahepatic. Presinusoidal extrahepatic portal hypertension is unlikely to be associated with hepatocellular failure. Increased splenic flow pla,ys a. minor role in its’ cause. Renal cortical perfusion may be reduced. Causes of presinusoidal intrahepat ic portal hypertension include schistosomiasis, myeloproliferative diseases, sarcoidosis, congenital hepatic fibrosis, chronic arsenic poisoning, and primary bil-
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Sherlock
iary cirrhosis. Portosystemic shunt operations are well tolerated unless there is associated hepatocelIular damage. In cirrhosis. the mortal hvnertension is nresinusoidal, sinusoidal, and postsinusoidal. The problem of bleeding esophageal varices is largely that of hepatocellular failure. The Budd-Chiari (hepatovenous obstruction) syndrome has many causes, including “congenital” webs and trauma. These may be susceptible to a surgical approach. &
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