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The Diagnosis of Portal Hypertension
The Diagnosis of Portal Hypertension With Notes on Treatm.ent J. GARROTT ALLEN, M.D., F.A.C.S.* LOUIS R. HEAD, M.D. **
PORTAL hypertension is a silent clinical syndrome until one or more of esophageal or gastric varices begin to bleed. The symptoms of massive hemorrhage into the upper gastrointestinal tract soon appear. The stomach becomes distended and hematemesis ensues. The manifestations and extent of the hypovolemic shock depend upon the rapidity and volume of blood that is lost. In patients over 30 years of age, massive bleeding into the upper gastrointestinal tract arises from portal hypertension in only 10 to 15 per cent of cases. The vast majority (80 to 85 per cent) are patients whose bleeding is from peptic ulcer. In children and young adults, however, massive hematemesis is much more often from the bleeding varix of portal hypertension than peptic ulcer. The diagnosis in any case is usually made under rather unfavorable circumstances. The importance of establishing the diagnosis is obvious as the need for therapy is urgent and the type of treatment depends upon the source of the hemorrhage.
PATHOGENESIS OF PORTAL HYPERTENSION
Three sites of obstructions to portal blood flow may give rise to portal hypertension and later on to esophageal and gastric varices. These are: 1. Right heart failure or tumor compression of the hepatic veins. More often this type of obstruction creates ascites than bleeding varices. Terminal hematemesis is occasionally encountered, but the serious nature of the primary disease is often fatal before varicosities become a serious problem. This group of patients will not be discussed here. 2. Cirrhosis of tl.e liver. This is probably the most common cause.and site of portal hypertension after the age of 30; cirrhosis is a fairly common From the Department of Surgery, University of Chicago, Chicago.
* Professor, Department of Surgery, University of Chicago School of Medicine.
** Senior Assi.9tant Resident, Department of Surgery, University of Chicago School of Medicine.
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late sequelae of virus hepatitis and this cause in time may come to exceed that of all others among adults. Ascites mayor may not be present, depending upon sodium retention and related adrenal function, the concentration of serum albumin and portal hypertension. Biliary cirrhosis from prolonged obstruction to the common duct or the smaller intrahepatic ducts may also give rise to portal hypertension in due course. In these patients, like those with portal cirrhosis, the course of the liver disease tends to run ahead of the development of the bleeding varix. Bleeding from a varix usually is a late symptom of cirrhosis and for this reason appraisal of hepatic function should be made prior to embarking upon any procedure involving surgical intervention, wherever possible. The long-known association between alcoholic consumption and portal cirrhosis has not yet been fully explained. Its existence cannot be denied, how it comes about is a matter of debate. By the time these patients develop bleeding varices, their cirrhosis is usually far advanced. It tends to progress and liver failure with or without hematemesis is the rule rather than the exception. The recent observation of Wangensteen and his associatesl suggests that peptic esophagitis may account for erosion of the varix and its bleeding. The stimulating effect of alcohol upon gastric secretion has long been known and employed as a test of gastric function; this is further reason why the patient with cirrhosis should abandon alcoholic habits. Other hepatic toxins probably playa less important role in the pathogenesis of cirrhosis as exposure to them usually is brief, disagreeable and seldom repeated. 3. Thrombosis of the major radicals of the portal vein or obliterative disease of other origin is the chief cause of portal hypertension in children and young adults. The pathogenesis of the thrombosis is not underliltood. It may occur in the neonatal period and presumably as the result of an extension of the obliterative phlebitis of the umbilical vein. It may be due to an acquired phlebitis associated with neonatal omphalitis, or from other intra-abdominal disorders in early childhood. These young patients differ from the older group in that portal hypertension often' is noti associated with cirrhosis of the liver. If ascites is present in the young patient, the portal hypertension is likely the result of cirrhosis ra.ther than obliterative phlebitis of the major portal radicals. CLINICAL HISTORY OF PORTAL HYPERTENSION
The outstanding feature in the history of portal hypertension is hematemesis. Gastric or duodenal ulcer may also bleed massively but many of the hemorrhagic episodes in ulcer patients are moderate and less severe. The varix which bleeds for the first time more often bleeds massively than does the peptic ulcer which is bleeding for the first time. The gastric ulcer tends to bleed more extensively than the' duodena.l~.',The
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child with varices tends to develop more extensive and diffuse collaterals earlier than does the adult with varices from cirrhosis. For these reasons, the bleeding varix in the adult with cirrhosis is more likely to be fatal for any given episode than is a single episode of bleeding in a child. Viral hepatitis, whether infectious or serum hepatitis, is often found to be the only preceding fact to explain cirrhosis and its consequences; namely, portal hypertension, bleeding and ascites. The authors have performed splenorenal anastomoses in five patients with chronic ulcerative colitis who received transfusions of blood five to ten years previously in the course of treatment of their ulcerative colitis. Whether these earlier transfusions represent an etiologic relationship in that serum hepatitis may have occurred and which gave rise to the latent cirrhosis cannot be established. It is a possibility, however, that cannot be lightly dismissed. PHYSICAL EXAMINATION
The important corollaries of portal hypertension evident from physical examination are hepatomegaly, splenomegaly and ascites. These are findings which suggest that bleeding is from varices rather than ulcer. However, all physical signs are confirmatory rather than diagnostic of portal hypertension. Portal hypertension can be diagnosed accurately only by measurement of portal pressure in one of the branches of the portal system. It can be strongly suspected upon the bases of its secondary manifestations. Spider nevi are less commonly noted than discussed. The caput medusae is good evidence of an extensive collateral circulation and is more commonly encountered in portal hypertension than are spider nevi. The presence of cutaneous collaterals on the anterior surfaces of the abdomen and chest can occasionally be demonstrated better by infra-red photography than by direct view. Edema tends to obscure them. These are diagnostic of portal obstruction but not necessarily of portal hypertension. Ascites is often present and detectable in the adult patient suffering from cirrhosis. It is more commonly encountered in portal cirrhosis than in posthepatic or biliary cirrhosis. In children and young adults with portal hypertension ascites is seldom present. Loss of turgor of the skin and the drawn facies characteristic of the dehydration of extracellular water deficits are often observed when ascites is present, particularly if repeated tappings of the abdomen have been performed. Such patients also suffer from a loss of muscular tone and substances; this in part is the result of dehydration but also represents the impairment of protein metabolism in advanced cirrhosis. The liver is often palpable below the costal margin. It mayor may not be tender. If it is tender, the possibility of recent right heart failure or of a recurrent bout of hepatitis should be considered. A nodular liver favors the diagnosis of latent cirrhosis or tumor.
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Splenomegaly is nearly always present in portal hypertension whether or not liver enlargement is present. However, before the enlarged spleen may be felt upon examination, it must be enlarged two to three times greater than its normal size. If it remains posteriorly as it occasionally does, it may be difficult to palpate in spite of its size. Percussion of the spleen when not palpable is subject to many errors and has little merit when evaluated in the face of the operative findings. Still others have studied the size of the liver or spleen by pneumoperitoneum wherein air contrast enables a study of the outline of these two organs by roentgenographic techniques. The information provided by these ancillary procedures is seldom important to diagnosis or to the treatment to be followed. The presence or absence of internal hemorrhoids is seldom cause for serious consideration of portal hypertension although the patient with portal hypertension frequently has hemorrhoids also. Their occurrence is so commonly unrelated to portal hypertension that their presence in liver disease, otherwise unrecognized, is usually meaningless. Peripheral edema is not likely to be present in patients with cirrhosis of the liver if they do not also have ascites. In general, the edema is associated with sodium retention and hypoalbuminemia. Edema may involve also the sacral area and that of the back if the patient is bedridden. The recent observations on the action of the salt-retaining hormone of the adrenal cortex, aldosterone, may playa role in the pathogenesis of ascites and edema in liver disease. 2 Aldosterone is said to be increased in liver disease, heart disease, glomerulonephritis and eclampsia. It may be that this hormone exerts its effect upon tubular absorption and by this mechanism favors sodium retention. Aldosterone will doubtless be a subject for renewed interest in salt and water balance and may result in a better understanding of the physiologic mechanisms normally involved. RADIOLOGIC AIDS IN DIAGNOSIS
The presence of portal hypertension is inferred by the fluoroscopic demonstration of the esophageal or gastric varices. During the early phases of portal hypertension, esophageal varices may be evident. N egative fluoroscopic results do not exclude the possibility of portal hypertension. A series of films over a period of several years often demonstrates clearly the increase in size and number of varices in patients with unrelieved portal hypertension. Varices are said to disappear after shunting procedures. In reality they remain but become less conspicuous when their intraluminal pressure is relieved. Once an effective shunting procedure is performed, varices are much more difficult to distend by the Valsalva maneuver and may lead one to the erroneous conclusion that they no longer exist. Although they
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remain, they are generally harmless as long as the shunt effectively reduces portal pressure (Fig. 29). It is important to search for the presence of gastric varices at fluoroscopy, as varices in this location can bleed just as briskly as varices of the esophagus. One of the reasons for failure of tamponade to control the
Fig. 29. Varices present preoperatively (above) are no longer demonstrated, 4 years after splenorenal anastomosis (below). Patient's ascites disappeared within 2 months after operation and she remains free of symptoms of portal hypertension.
bleeding of portal hypertension is the bleeding gastric varices beyond the reach of the balloon employed. Oversewing varices in the esophagus when hemorrhage is from those of the stomach has accounted for some of the failures of this form of surgical treatment. A second and more recent use of roentgenography of patients with portal hypertension concerns itself with the preoperative demonstration of the location of venous obstruction. This procedure is known as splenog-
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raphy and has proved a valuable adjunct when surgical shunting procedures are to be performed. S ENDOSCOPIC AIDS IN DIAGNOSIS
It is desirable to determine the site at which bleeding arises in the presence of esophageal and gastric varices. Esophagoscopy has been frequently employed as a means for injecting sclerosing agents into the esophageal varices. Although this procedure has been largely abandoned in favor of newer techniques, it remains very useful diagnostically for detecting the presence of varices at the time of acute upper gastrointestinal bleeding. Tanner' reports its diagnostic merits outweigh its imagined disadvantages and that esophagoscopy is often the only diagnostic procedure which can be successfully employed at the time of hemorrhage. If varices are not found, gastroscopy may prove useful in some patients. LABORATORY AIDS IN DIAGNOSIS
There is no specific laboratory test which will demonstrate the presence or absence of portal hypertension short of its manometric measurement. There are, however, several tests which are useful as indices of the presence or absence of severe liver diseases and of the secondary hypersplenism which occasionally is associated with the splenomegaly of portal hypertension. These tests, if considered with other factors, may prove very useful in the choice of management to be followed. Tests of liver function are, in themselves, not always diagnostic of liver disease. A given test seldom measures more than one function of the liver. It is therefore advisable to employ several tests, each of which attempts to measure different types of hepatic function. In the selection of tests to be employed, several points should be considered. They should be simple to perform and of reproducible accuracy. They should provide data not likely to result from disease in other organs. They should be inexpensive to perform. Among such functions which may be usefully tested in liver disease are: 1. Excretory Function. This is best evaluated by the Bromsulphalein test wherein a standard quantity of this dye is known to be completely excreted within a stated period of time if the serum bilirubin is of normal value. One milligram of Bromsulphalein per kilograms of body weight is injected intravenously after first withdrawing a sample of blood for control. At the end of 30 minutes no Bromsulphalein should remain within the circulation. If some of the dye is still present, it is diagnostic of impaired excretory function. 2. Protein Metabolism. This is an important function of the liver. Because serum albumin appears to be produced only by the liver, this is a simple means of assessing this function. In the absence of abnormal losses of albumin through the kidneys, large burned surface areas, ascites and
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starvation, a reduction in serum albumin implies an impairment of the liver's capacity to produce this protein. Serum albumin values of less than 3 grams per 100 cc. argue strongly for delay wherever possible of any surgical procedure, particularly the extensive operations needed for the relief of bleeding esophageal varices. The more nearly normal the value of serum albumin the better is hepatic function; the better hepatic function is, the better any surgical operation may be tolerated. 3. Prothrombin Activity. This should also be established in surgical patients with suspected liver disease. If the level is above 75 per cent by the one-stage technique, there is little fear of abnormal bleeding unless hepatic failure intervenes. In hepatic failure most functions of the liver deteriorate, including that of prothrombin production. Prothrombin is formed by the liver and only if the liver is capable, provided adequate quantities of vitamin K are present. If the intravenous or intramuscular administration of 25 mg. of Kl oxide does not elevate the prothrombin time to near normal values after one to two days, there is cause for concern. However, the failure of prothrombin response to vitamin K administration is not as ominous a sign in the authors' opinion as is a refractory hypoalbuminemia to a high protein diet. 4. Esterification of Cholesterol. This is a function of the liver that can easily be measured by most laboratories. Normally 25 to 40 per cent of the total serum cholesterol is conjugated or esterified by the liver. In serious liver disease this function is impaired and less than 10 per cent of the total cholesterol may be esterified. Esterification of cholesterol generally is not impaired save in advanced liver disease. 5. Cephalin Flocculation. This is a test useful in detecting liver disease but it is often difficult to relate quantitatively to the degree of hepatic failure or impairment. Two other tests have been used in patients with liver disease but for other reasons. Acute disorders of renal function often occur in conjunction with hepatic failure, particularly bile nephrosis. Therefore the serum nonprotein nitrogen and the urea clearance may provide useful information as they may herald the onset of renal as well as hepatic failure. 6. Needle Biopsy of the Liver. This has proved a most accurate method of establishing the diagnostic nature of liver disease-short of laparotomy. This procedure stands alone in importance and should be employed whenever possible if the diagnostic nature of liver disease is important to the selection of treatment. Bleeding is seldom encountered and usually is due to a perforation of a superficially located small intrahepatic artery rather than from hypoprothrombinemia or thrombocytopenia. Most feel that its value should exceed 50 per cent of normal by the Quick one-stage technique. The treatment of hemorrhage from needle biopsy seldom requires surgical intervention and this rare unpleasant experience does not mitigate against needle biopsy when
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indicated. Many patients with cirrhosis and portal hypertension suffer primarily from the late effects of virus hepatitis. It is well to know in advance of operation whether hepatitis is still in an active phase. Only through biopsy can such information be obtained. 7. Portal Pressure. Most often has been measured manometrically at the time of operation. This should be performed as soon as the abdomen is opened. It yields accurate information provided the systolic arterial blood pressure is normal for the patient and the varix is not momentarily bleeding. A value of 230 mm. in excess of water pressure is diagnostic of portal hypertension. Readings between 500 and 600 mm. of water are occasionally found. Other methods for measuring portal pressure include pressure measurements taken through the esophagoscope, piercing the varix under direct vision. The venous pressure of the internal hemorrhoidal veins has been advocated by some but has not been employed in this clinic. Julian and Dye 5 call attention to the disappearance of varicosities previously evident upon fluoroscopic and/or esophagoscopic examination. This is the exception rather than the rule in that portal hypertension tends to increase until relieved by shunting the portal circulation. Julian's observations suggest that the occasional patient may develop so many collaterals that the effects of surgery are occasionally achieved by nature. SECONDARY HYPERSPLENISM IN PORTAL HYPERTENSION
Studies of Doan 6 and others clearly demonstrate that occasionally the enlarged spleen in portal hypertension may take on abnormal functions. These are more likely excesses in normal function than newly acquired functions. They include anemia, leukopenia and thrombocytopenia. These may appear separately, in pairs, or as a triad known as "panhypersplenism." Hypersplenism as a complication of portal hypertension is an indication for splenectomy, particularly if thrombocytopenia is present. Splenectomy should not be undertaken, however, unless the surgeon is prepared to perform a splenorenal shunt at the same time. Failure to take advantage of a shunting procedure is to leave the portacaval anastomosis as a presumed alternative when it may not actually exist. We were recently presented with an unusual case; it was that of a 65 year old woman suffering from portal hypertension, gastric and esophageal varicef. and mild ascites associated with thrombocytopenia (60,000) and leukopenia (3150) from portal cirrhosis and splenomegaly. In addition there was present a carcinoma of the rectum without evident metastasis. Under spinal anesthesia augmented with hypotensive drugs, a transabdominal splenorenal anastomosis and a combined abdominal resection of the rectal carcinoma were successfully completed with prompt return to normal of the leukocyte and platelet counts and recovery of the patient.
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THE BLEEDING VARIX
Surgical treatment of the patient with a bleeding varix becomes necessary if tamponade fails to control bleeding. Every reasonable effort should be made to avoid surgical intervention during the acute episode of hemorrhage. Usually measures of tamponade will succeed if carefully applied. This permits a surgical procedure to be carried out under less duress, with a lower operative mortality and a better end result among survivors. Massive bleeding into the intestinal tract may have its own consequence in the patient with liver disease. The work of McDermont,7 Eisman 8 and Stewart 9 demonstrate that ammonia intoxication is often a serious problem in hepatic failure and may be one of the causes of death. Restriction of meat in the late stages of liver disease is desirable, particularly in patients with end-to-side portacaval anastomosis where venous blood is shunted away from the liver. This allows for a larger than usual accumulation of blood ammonia as less blood passes through the liver which is the organ which converts ammonia to urea. This function may already be impaired as the result of cirrhosis and will be still further impaired by diversion of all portal blood flow. If meat fed to such patients can induce ammonia intoxication, there is no reason to believe that the absorption of his blood proteins in the course of an extensive and continuing hemorrhage into the upper intestinal tract would be any less devastating. Thus the problem that ammonia intoxication presents argues strongly for early control of hemorrhage as well as in favor of a partial diversion of portal blood as in a splenorenal shunt rather than a total diversion of portal blood from the liver as in end-to-side portacaval anastomosis. Failing to secure a temporary arrest of the bleeding episode, several operations have been employed to achieve surgical hemostasis. 1. Suturing Esophageal Varices. This requires the transthoracic approach and commits the surgeon to the use of general anesthesia. This procedure has been used extensively by Linton,10 Crilell and others. Care must be taken that the suturing commence at the proximal end of the varix and proceed distally up the esophagus in order that bleeding be minimized. It is advisable to free the lower end of the esophagus and place across it a rubber-shod clamp to reduce the pressure within the varix and consequently the extent of bleeding. This has the disadvantage of allowing the veins to collapse and therefore to make more difficult their identification when oversewing. 2. Partial Esophagogastrectomy. This procedure was designed and first performed by Phemister in 1945. 12 It is indicated when obliterative phlebitis of the portal vein and previous splenectomy make a shunting procedure impossible. The two patients originally comprising his report are currently doing well. One subsequently developed recurrent bouts of
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bleeding and in 1954 an anastomosis of the superior mesenteric vein to the inferior vena cava was performed elsewhere. The second patient has had no recurrence of bleeding in ten years. 3. Gastric Bisection. This was first performed by Tanner13 and two years later by us. We attempted this procedure without prior knowledge of Tanner's work. Our first patient was one with uncontrolled bleeding from esophageal varices who came to operation with an extensive aspiration pneumonitis in the right lung. The transthoracic approach required to oversew the varices appeared to be more than this patient could with-
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Fig. 30. Sketch of gastric bisection and the devascularization of upper gastric segment, including the vasa brevia of spleen with or without splenectomy. Phrenic veins as well as coronary vein and left gastric artery are ligated and divided. Line of bisection must be high enough that necrosis of upper segment will not occur. Lower segment receives blood supply from right gastroepiploic artery and vein. Pyloroplasty or gastroenterostomy should also be performed.
stand. Accordingly, under spinal anesthesia and through the abdominal approach, the stomach was freed from its vascular attachments to the spleen. The right gastric artery remained. The upper gastric segment was devascularized so that its blood supply came only from the lower esophagus. The stomach was divided next at the level of the usual site for a high subtotal gastric resection. It was then resutured (Fig. 30). Of four patients treated in this manner, none has bled again although two of the four died on the fifth and the ninth day of their pneumonia. One lived ten months and died in hepatic failure without bleeding and the fourth is alive and well without hemorrhage after three years. Two of the four
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were operated transthoracically which proved an easier approach than the transabdominal one. We intended gastric bisection as an emergency procedure, to be followed later by a shunting operation under more favorable circumstances. AmpIe'argument can be marshalled that a subtotal gastric resection would do equally well if not better. Bisection also performs a vagotomy and should be accompanied by gastroenterostomy or pyloroplasty. Bisection and resection have the a.dvantage that control of hemorrhage is easier and more reliable than with oversewing of the esophageal varices. In addition, if acid peptic digestion is a factor in the erosion of the varix, this tendency is also reduced by resection or bisection. These procedures have the disadvantage that the spleen may need to be sacrificed and that a splenorenal anastomosis may not be practical in combination with these additional procedures. In our pati~nt who lived nine months, a portacaval anastomosis was also performed at the time of his transthoracic gastric bisection. We have recently performed our fifth gastric bisection with pyloroplasty and a splenorenal shunt during a bout of bleeding uncontrolled by tamponade after an eight day trial. SUMMARY 1. The diagnosis of portal hypertension is less difficult or complex when made before rather than during a bleeding episode. 2. Simple measures of evaluation of liver function are discussed. Portal hypertension is less frequently associated with cirrhosis in children than in later life. 3. The accumulation of blood in the intestinal tract may produce ammonia intoxication and this possibility in itself argues strongly for prompt hemostasis; in addition there remain the hazards of hypovolemic shock if prompt blood replacement and hemostasis are not obtained. 4. Methods of treatment of the patient in an acute episode of bleeding from varices are discussed. 5. Death is frequently due to the aspiration of blood and its sequelbronchopneumonia. REFERENCES 1. Wangensteen, O. H.: Surgical Lesions of the Esophagus. Rev. Gastroentrol. 19:
540, 1952. 2. Conn, J. W.: Primary Aldosteronism. J. Lab. & Clin. Med. 45: 3, 1955. 3. Dogliotti, A. M. and Beatici, S.: Transparietal Splenoportal l'toentgenography and Research on Portal Hypertension. Surgery 34: 503, 1954. 4. Tanner, N. C.: Hematemesis and Melena. Brit. M. J. 1: 110, 1949. 5. Dye, W. and Julian, 0.: Observations on the Inconstancy of Portal Hypertension in Hepatic Cirrhosis. Surgical Forum, Clinical Congress, Americari College of Surgeons, 1952, p. 496. 6. Doan, C. A.: Hypersplenic Syndromes. Cecil's Textbook of Medicine, 1951, p.977. 7. McDermont, W. V.: Episodic Stupor Associated with an Eck Fistula in the
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8. 9. 10. 11. 12. 13.
J. Garrott Allen, Louis R. Head
Human with Particular Reference to the Metabolism of Ammonia. J. Clin. Investigation 33: 5-7, 1954. Eiseman, G., Lindeman, G. and Johnson, J.: A Method for Determining the Patency of a Portacaval Shunt. Surgical Forum, Clinical Congress of American College of Surgeons, 1954, p. 200. Stewart, J. D.: Ammonia Intoxication from Portal Diversion and Hepatic Failure. Presented at The American Surgical Association, April 28, 1955. Linton, R.: The Selection of Patients for Portocaval Shunts. Ann. Surg. 134: 433, 1951. Crile, G. Jr.: Transesophageal Ligation of Bleeding Esophageal Varices, Arch. Surg., 61: 654, 1950. Phemister, D. and Humphries, E.: Gastro-Esophageal Resection and Total Gastrectomy in the Treatment of Bleeding Varices in Banti's Syndrome. Ann. Surg. 126: 397, 1947. Tanner, N. C.: Hemorrhage as a Surgical Emergency. Proc. Roy. Soc. Med. 43: 147-152, 1950.
950 E. 59th Street Chicago 37, Illinois
PORTAL hypertension is a silent clinical syndrome until one or more of esophageal or gastric varices begin to bleed. The symptoms of massive hemorrhage into the upper gastrointestinal tract soon appear. The stomach becomes distended and hematemesis ensues. The manifestations and extent of the hypovolemic shock depend upon the rapidity and volume of blood that is lost. In patients over 30 years of age, massive bleeding into the upper gastrointestinal tract arises from portal hypertension in only 10 to 15 per cent of cases. The vast majority (80 to 85 per cent) are patients whose bleeding is from peptic ulcer. In children and young adults, however, massive hematemesis is much more often from the bleeding varix of portal hypertension than peptic ulcer. The diagnosis in any case is usually made under rather unfavorable circumstances. The importance of establishing the diagnosis is obvious as the need for therapy is urgent and the type of treatment depends upon the source of the hemorrhage.
PATHOGENESIS OF PORTAL HYPERTENSION
Three sites of obstructions to portal blood flow may give rise to portal hypertension and later on to esophageal and gastric varices. These are: 1. Right heart failure or tumor compression of the hepatic veins. More often this type of obstruction creates ascites than bleeding varices. Terminal hematemesis is occasionally encountered, but the serious nature of the primary disease is often fatal before varicosities become a serious problem. This group of patients will not be discussed here. 2. Cirrhosis of tl.e liver. This is probably the most common cause.and site of portal hypertension after the age of 30; cirrhosis is a fairly common From the Department of Surgery, University of Chicago, Chicago.
* Professor, Department of Surgery, University of Chicago School of Medicine.
** Senior Assi.9tant Resident, Department of Surgery, University of Chicago School of Medicine.
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late sequelae of virus hepatitis and this cause in time may come to exceed that of all others among adults. Ascites mayor may not be present, depending upon sodium retention and related adrenal function, the concentration of serum albumin and portal hypertension. Biliary cirrhosis from prolonged obstruction to the common duct or the smaller intrahepatic ducts may also give rise to portal hypertension in due course. In these patients, like those with portal cirrhosis, the course of the liver disease tends to run ahead of the development of the bleeding varix. Bleeding from a varix usually is a late symptom of cirrhosis and for this reason appraisal of hepatic function should be made prior to embarking upon any procedure involving surgical intervention, wherever possible. The long-known association between alcoholic consumption and portal cirrhosis has not yet been fully explained. Its existence cannot be denied, how it comes about is a matter of debate. By the time these patients develop bleeding varices, their cirrhosis is usually far advanced. It tends to progress and liver failure with or without hematemesis is the rule rather than the exception. The recent observation of Wangensteen and his associatesl suggests that peptic esophagitis may account for erosion of the varix and its bleeding. The stimulating effect of alcohol upon gastric secretion has long been known and employed as a test of gastric function; this is further reason why the patient with cirrhosis should abandon alcoholic habits. Other hepatic toxins probably playa less important role in the pathogenesis of cirrhosis as exposure to them usually is brief, disagreeable and seldom repeated. 3. Thrombosis of the major radicals of the portal vein or obliterative disease of other origin is the chief cause of portal hypertension in children and young adults. The pathogenesis of the thrombosis is not underliltood. It may occur in the neonatal period and presumably as the result of an extension of the obliterative phlebitis of the umbilical vein. It may be due to an acquired phlebitis associated with neonatal omphalitis, or from other intra-abdominal disorders in early childhood. These young patients differ from the older group in that portal hypertension often' is noti associated with cirrhosis of the liver. If ascites is present in the young patient, the portal hypertension is likely the result of cirrhosis ra.ther than obliterative phlebitis of the major portal radicals. CLINICAL HISTORY OF PORTAL HYPERTENSION
The outstanding feature in the history of portal hypertension is hematemesis. Gastric or duodenal ulcer may also bleed massively but many of the hemorrhagic episodes in ulcer patients are moderate and less severe. The varix which bleeds for the first time more often bleeds massively than does the peptic ulcer which is bleeding for the first time. The gastric ulcer tends to bleed more extensively than the' duodena.l~.',The
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child with varices tends to develop more extensive and diffuse collaterals earlier than does the adult with varices from cirrhosis. For these reasons, the bleeding varix in the adult with cirrhosis is more likely to be fatal for any given episode than is a single episode of bleeding in a child. Viral hepatitis, whether infectious or serum hepatitis, is often found to be the only preceding fact to explain cirrhosis and its consequences; namely, portal hypertension, bleeding and ascites. The authors have performed splenorenal anastomoses in five patients with chronic ulcerative colitis who received transfusions of blood five to ten years previously in the course of treatment of their ulcerative colitis. Whether these earlier transfusions represent an etiologic relationship in that serum hepatitis may have occurred and which gave rise to the latent cirrhosis cannot be established. It is a possibility, however, that cannot be lightly dismissed. PHYSICAL EXAMINATION
The important corollaries of portal hypertension evident from physical examination are hepatomegaly, splenomegaly and ascites. These are findings which suggest that bleeding is from varices rather than ulcer. However, all physical signs are confirmatory rather than diagnostic of portal hypertension. Portal hypertension can be diagnosed accurately only by measurement of portal pressure in one of the branches of the portal system. It can be strongly suspected upon the bases of its secondary manifestations. Spider nevi are less commonly noted than discussed. The caput medusae is good evidence of an extensive collateral circulation and is more commonly encountered in portal hypertension than are spider nevi. The presence of cutaneous collaterals on the anterior surfaces of the abdomen and chest can occasionally be demonstrated better by infra-red photography than by direct view. Edema tends to obscure them. These are diagnostic of portal obstruction but not necessarily of portal hypertension. Ascites is often present and detectable in the adult patient suffering from cirrhosis. It is more commonly encountered in portal cirrhosis than in posthepatic or biliary cirrhosis. In children and young adults with portal hypertension ascites is seldom present. Loss of turgor of the skin and the drawn facies characteristic of the dehydration of extracellular water deficits are often observed when ascites is present, particularly if repeated tappings of the abdomen have been performed. Such patients also suffer from a loss of muscular tone and substances; this in part is the result of dehydration but also represents the impairment of protein metabolism in advanced cirrhosis. The liver is often palpable below the costal margin. It mayor may not be tender. If it is tender, the possibility of recent right heart failure or of a recurrent bout of hepatitis should be considered. A nodular liver favors the diagnosis of latent cirrhosis or tumor.
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Splenomegaly is nearly always present in portal hypertension whether or not liver enlargement is present. However, before the enlarged spleen may be felt upon examination, it must be enlarged two to three times greater than its normal size. If it remains posteriorly as it occasionally does, it may be difficult to palpate in spite of its size. Percussion of the spleen when not palpable is subject to many errors and has little merit when evaluated in the face of the operative findings. Still others have studied the size of the liver or spleen by pneumoperitoneum wherein air contrast enables a study of the outline of these two organs by roentgenographic techniques. The information provided by these ancillary procedures is seldom important to diagnosis or to the treatment to be followed. The presence or absence of internal hemorrhoids is seldom cause for serious consideration of portal hypertension although the patient with portal hypertension frequently has hemorrhoids also. Their occurrence is so commonly unrelated to portal hypertension that their presence in liver disease, otherwise unrecognized, is usually meaningless. Peripheral edema is not likely to be present in patients with cirrhosis of the liver if they do not also have ascites. In general, the edema is associated with sodium retention and hypoalbuminemia. Edema may involve also the sacral area and that of the back if the patient is bedridden. The recent observations on the action of the salt-retaining hormone of the adrenal cortex, aldosterone, may playa role in the pathogenesis of ascites and edema in liver disease. 2 Aldosterone is said to be increased in liver disease, heart disease, glomerulonephritis and eclampsia. It may be that this hormone exerts its effect upon tubular absorption and by this mechanism favors sodium retention. Aldosterone will doubtless be a subject for renewed interest in salt and water balance and may result in a better understanding of the physiologic mechanisms normally involved. RADIOLOGIC AIDS IN DIAGNOSIS
The presence of portal hypertension is inferred by the fluoroscopic demonstration of the esophageal or gastric varices. During the early phases of portal hypertension, esophageal varices may be evident. N egative fluoroscopic results do not exclude the possibility of portal hypertension. A series of films over a period of several years often demonstrates clearly the increase in size and number of varices in patients with unrelieved portal hypertension. Varices are said to disappear after shunting procedures. In reality they remain but become less conspicuous when their intraluminal pressure is relieved. Once an effective shunting procedure is performed, varices are much more difficult to distend by the Valsalva maneuver and may lead one to the erroneous conclusion that they no longer exist. Although they
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remain, they are generally harmless as long as the shunt effectively reduces portal pressure (Fig. 29). It is important to search for the presence of gastric varices at fluoroscopy, as varices in this location can bleed just as briskly as varices of the esophagus. One of the reasons for failure of tamponade to control the
Fig. 29. Varices present preoperatively (above) are no longer demonstrated, 4 years after splenorenal anastomosis (below). Patient's ascites disappeared within 2 months after operation and she remains free of symptoms of portal hypertension.
bleeding of portal hypertension is the bleeding gastric varices beyond the reach of the balloon employed. Oversewing varices in the esophagus when hemorrhage is from those of the stomach has accounted for some of the failures of this form of surgical treatment. A second and more recent use of roentgenography of patients with portal hypertension concerns itself with the preoperative demonstration of the location of venous obstruction. This procedure is known as splenog-
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raphy and has proved a valuable adjunct when surgical shunting procedures are to be performed. S ENDOSCOPIC AIDS IN DIAGNOSIS
It is desirable to determine the site at which bleeding arises in the presence of esophageal and gastric varices. Esophagoscopy has been frequently employed as a means for injecting sclerosing agents into the esophageal varices. Although this procedure has been largely abandoned in favor of newer techniques, it remains very useful diagnostically for detecting the presence of varices at the time of acute upper gastrointestinal bleeding. Tanner' reports its diagnostic merits outweigh its imagined disadvantages and that esophagoscopy is often the only diagnostic procedure which can be successfully employed at the time of hemorrhage. If varices are not found, gastroscopy may prove useful in some patients. LABORATORY AIDS IN DIAGNOSIS
There is no specific laboratory test which will demonstrate the presence or absence of portal hypertension short of its manometric measurement. There are, however, several tests which are useful as indices of the presence or absence of severe liver diseases and of the secondary hypersplenism which occasionally is associated with the splenomegaly of portal hypertension. These tests, if considered with other factors, may prove very useful in the choice of management to be followed. Tests of liver function are, in themselves, not always diagnostic of liver disease. A given test seldom measures more than one function of the liver. It is therefore advisable to employ several tests, each of which attempts to measure different types of hepatic function. In the selection of tests to be employed, several points should be considered. They should be simple to perform and of reproducible accuracy. They should provide data not likely to result from disease in other organs. They should be inexpensive to perform. Among such functions which may be usefully tested in liver disease are: 1. Excretory Function. This is best evaluated by the Bromsulphalein test wherein a standard quantity of this dye is known to be completely excreted within a stated period of time if the serum bilirubin is of normal value. One milligram of Bromsulphalein per kilograms of body weight is injected intravenously after first withdrawing a sample of blood for control. At the end of 30 minutes no Bromsulphalein should remain within the circulation. If some of the dye is still present, it is diagnostic of impaired excretory function. 2. Protein Metabolism. This is an important function of the liver. Because serum albumin appears to be produced only by the liver, this is a simple means of assessing this function. In the absence of abnormal losses of albumin through the kidneys, large burned surface areas, ascites and
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starvation, a reduction in serum albumin implies an impairment of the liver's capacity to produce this protein. Serum albumin values of less than 3 grams per 100 cc. argue strongly for delay wherever possible of any surgical procedure, particularly the extensive operations needed for the relief of bleeding esophageal varices. The more nearly normal the value of serum albumin the better is hepatic function; the better hepatic function is, the better any surgical operation may be tolerated. 3. Prothrombin Activity. This should also be established in surgical patients with suspected liver disease. If the level is above 75 per cent by the one-stage technique, there is little fear of abnormal bleeding unless hepatic failure intervenes. In hepatic failure most functions of the liver deteriorate, including that of prothrombin production. Prothrombin is formed by the liver and only if the liver is capable, provided adequate quantities of vitamin K are present. If the intravenous or intramuscular administration of 25 mg. of Kl oxide does not elevate the prothrombin time to near normal values after one to two days, there is cause for concern. However, the failure of prothrombin response to vitamin K administration is not as ominous a sign in the authors' opinion as is a refractory hypoalbuminemia to a high protein diet. 4. Esterification of Cholesterol. This is a function of the liver that can easily be measured by most laboratories. Normally 25 to 40 per cent of the total serum cholesterol is conjugated or esterified by the liver. In serious liver disease this function is impaired and less than 10 per cent of the total cholesterol may be esterified. Esterification of cholesterol generally is not impaired save in advanced liver disease. 5. Cephalin Flocculation. This is a test useful in detecting liver disease but it is often difficult to relate quantitatively to the degree of hepatic failure or impairment. Two other tests have been used in patients with liver disease but for other reasons. Acute disorders of renal function often occur in conjunction with hepatic failure, particularly bile nephrosis. Therefore the serum nonprotein nitrogen and the urea clearance may provide useful information as they may herald the onset of renal as well as hepatic failure. 6. Needle Biopsy of the Liver. This has proved a most accurate method of establishing the diagnostic nature of liver disease-short of laparotomy. This procedure stands alone in importance and should be employed whenever possible if the diagnostic nature of liver disease is important to the selection of treatment. Bleeding is seldom encountered and usually is due to a perforation of a superficially located small intrahepatic artery rather than from hypoprothrombinemia or thrombocytopenia. Most feel that its value should exceed 50 per cent of normal by the Quick one-stage technique. The treatment of hemorrhage from needle biopsy seldom requires surgical intervention and this rare unpleasant experience does not mitigate against needle biopsy when
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indicated. Many patients with cirrhosis and portal hypertension suffer primarily from the late effects of virus hepatitis. It is well to know in advance of operation whether hepatitis is still in an active phase. Only through biopsy can such information be obtained. 7. Portal Pressure. Most often has been measured manometrically at the time of operation. This should be performed as soon as the abdomen is opened. It yields accurate information provided the systolic arterial blood pressure is normal for the patient and the varix is not momentarily bleeding. A value of 230 mm. in excess of water pressure is diagnostic of portal hypertension. Readings between 500 and 600 mm. of water are occasionally found. Other methods for measuring portal pressure include pressure measurements taken through the esophagoscope, piercing the varix under direct vision. The venous pressure of the internal hemorrhoidal veins has been advocated by some but has not been employed in this clinic. Julian and Dye 5 call attention to the disappearance of varicosities previously evident upon fluoroscopic and/or esophagoscopic examination. This is the exception rather than the rule in that portal hypertension tends to increase until relieved by shunting the portal circulation. Julian's observations suggest that the occasional patient may develop so many collaterals that the effects of surgery are occasionally achieved by nature. SECONDARY HYPERSPLENISM IN PORTAL HYPERTENSION
Studies of Doan 6 and others clearly demonstrate that occasionally the enlarged spleen in portal hypertension may take on abnormal functions. These are more likely excesses in normal function than newly acquired functions. They include anemia, leukopenia and thrombocytopenia. These may appear separately, in pairs, or as a triad known as "panhypersplenism." Hypersplenism as a complication of portal hypertension is an indication for splenectomy, particularly if thrombocytopenia is present. Splenectomy should not be undertaken, however, unless the surgeon is prepared to perform a splenorenal shunt at the same time. Failure to take advantage of a shunting procedure is to leave the portacaval anastomosis as a presumed alternative when it may not actually exist. We were recently presented with an unusual case; it was that of a 65 year old woman suffering from portal hypertension, gastric and esophageal varicef. and mild ascites associated with thrombocytopenia (60,000) and leukopenia (3150) from portal cirrhosis and splenomegaly. In addition there was present a carcinoma of the rectum without evident metastasis. Under spinal anesthesia augmented with hypotensive drugs, a transabdominal splenorenal anastomosis and a combined abdominal resection of the rectal carcinoma were successfully completed with prompt return to normal of the leukocyte and platelet counts and recovery of the patient.
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THE BLEEDING VARIX
Surgical treatment of the patient with a bleeding varix becomes necessary if tamponade fails to control bleeding. Every reasonable effort should be made to avoid surgical intervention during the acute episode of hemorrhage. Usually measures of tamponade will succeed if carefully applied. This permits a surgical procedure to be carried out under less duress, with a lower operative mortality and a better end result among survivors. Massive bleeding into the intestinal tract may have its own consequence in the patient with liver disease. The work of McDermont,7 Eisman 8 and Stewart 9 demonstrate that ammonia intoxication is often a serious problem in hepatic failure and may be one of the causes of death. Restriction of meat in the late stages of liver disease is desirable, particularly in patients with end-to-side portacaval anastomosis where venous blood is shunted away from the liver. This allows for a larger than usual accumulation of blood ammonia as less blood passes through the liver which is the organ which converts ammonia to urea. This function may already be impaired as the result of cirrhosis and will be still further impaired by diversion of all portal blood flow. If meat fed to such patients can induce ammonia intoxication, there is no reason to believe that the absorption of his blood proteins in the course of an extensive and continuing hemorrhage into the upper intestinal tract would be any less devastating. Thus the problem that ammonia intoxication presents argues strongly for early control of hemorrhage as well as in favor of a partial diversion of portal blood as in a splenorenal shunt rather than a total diversion of portal blood from the liver as in end-to-side portacaval anastomosis. Failing to secure a temporary arrest of the bleeding episode, several operations have been employed to achieve surgical hemostasis. 1. Suturing Esophageal Varices. This requires the transthoracic approach and commits the surgeon to the use of general anesthesia. This procedure has been used extensively by Linton,10 Crilell and others. Care must be taken that the suturing commence at the proximal end of the varix and proceed distally up the esophagus in order that bleeding be minimized. It is advisable to free the lower end of the esophagus and place across it a rubber-shod clamp to reduce the pressure within the varix and consequently the extent of bleeding. This has the disadvantage of allowing the veins to collapse and therefore to make more difficult their identification when oversewing. 2. Partial Esophagogastrectomy. This procedure was designed and first performed by Phemister in 1945. 12 It is indicated when obliterative phlebitis of the portal vein and previous splenectomy make a shunting procedure impossible. The two patients originally comprising his report are currently doing well. One subsequently developed recurrent bouts of
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bleeding and in 1954 an anastomosis of the superior mesenteric vein to the inferior vena cava was performed elsewhere. The second patient has had no recurrence of bleeding in ten years. 3. Gastric Bisection. This was first performed by Tanner13 and two years later by us. We attempted this procedure without prior knowledge of Tanner's work. Our first patient was one with uncontrolled bleeding from esophageal varices who came to operation with an extensive aspiration pneumonitis in the right lung. The transthoracic approach required to oversew the varices appeared to be more than this patient could with-
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Fig. 30. Sketch of gastric bisection and the devascularization of upper gastric segment, including the vasa brevia of spleen with or without splenectomy. Phrenic veins as well as coronary vein and left gastric artery are ligated and divided. Line of bisection must be high enough that necrosis of upper segment will not occur. Lower segment receives blood supply from right gastroepiploic artery and vein. Pyloroplasty or gastroenterostomy should also be performed.
stand. Accordingly, under spinal anesthesia and through the abdominal approach, the stomach was freed from its vascular attachments to the spleen. The right gastric artery remained. The upper gastric segment was devascularized so that its blood supply came only from the lower esophagus. The stomach was divided next at the level of the usual site for a high subtotal gastric resection. It was then resutured (Fig. 30). Of four patients treated in this manner, none has bled again although two of the four died on the fifth and the ninth day of their pneumonia. One lived ten months and died in hepatic failure without bleeding and the fourth is alive and well without hemorrhage after three years. Two of the four
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were operated transthoracically which proved an easier approach than the transabdominal one. We intended gastric bisection as an emergency procedure, to be followed later by a shunting operation under more favorable circumstances. AmpIe'argument can be marshalled that a subtotal gastric resection would do equally well if not better. Bisection also performs a vagotomy and should be accompanied by gastroenterostomy or pyloroplasty. Bisection and resection have the a.dvantage that control of hemorrhage is easier and more reliable than with oversewing of the esophageal varices. In addition, if acid peptic digestion is a factor in the erosion of the varix, this tendency is also reduced by resection or bisection. These procedures have the disadvantage that the spleen may need to be sacrificed and that a splenorenal anastomosis may not be practical in combination with these additional procedures. In our pati~nt who lived nine months, a portacaval anastomosis was also performed at the time of his transthoracic gastric bisection. We have recently performed our fifth gastric bisection with pyloroplasty and a splenorenal shunt during a bout of bleeding uncontrolled by tamponade after an eight day trial. SUMMARY 1. The diagnosis of portal hypertension is less difficult or complex when made before rather than during a bleeding episode. 2. Simple measures of evaluation of liver function are discussed. Portal hypertension is less frequently associated with cirrhosis in children than in later life. 3. The accumulation of blood in the intestinal tract may produce ammonia intoxication and this possibility in itself argues strongly for prompt hemostasis; in addition there remain the hazards of hypovolemic shock if prompt blood replacement and hemostasis are not obtained. 4. Methods of treatment of the patient in an acute episode of bleeding from varices are discussed. 5. Death is frequently due to the aspiration of blood and its sequelbronchopneumonia. REFERENCES 1. Wangensteen, O. H.: Surgical Lesions of the Esophagus. Rev. Gastroentrol. 19:
540, 1952. 2. Conn, J. W.: Primary Aldosteronism. J. Lab. & Clin. Med. 45: 3, 1955. 3. Dogliotti, A. M. and Beatici, S.: Transparietal Splenoportal l'toentgenography and Research on Portal Hypertension. Surgery 34: 503, 1954. 4. Tanner, N. C.: Hematemesis and Melena. Brit. M. J. 1: 110, 1949. 5. Dye, W. and Julian, 0.: Observations on the Inconstancy of Portal Hypertension in Hepatic Cirrhosis. Surgical Forum, Clinical Congress, Americari College of Surgeons, 1952, p. 496. 6. Doan, C. A.: Hypersplenic Syndromes. Cecil's Textbook of Medicine, 1951, p.977. 7. McDermont, W. V.: Episodic Stupor Associated with an Eck Fistula in the
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8. 9. 10. 11. 12. 13.
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Human with Particular Reference to the Metabolism of Ammonia. J. Clin. Investigation 33: 5-7, 1954. Eiseman, G., Lindeman, G. and Johnson, J.: A Method for Determining the Patency of a Portacaval Shunt. Surgical Forum, Clinical Congress of American College of Surgeons, 1954, p. 200. Stewart, J. D.: Ammonia Intoxication from Portal Diversion and Hepatic Failure. Presented at The American Surgical Association, April 28, 1955. Linton, R.: The Selection of Patients for Portocaval Shunts. Ann. Surg. 134: 433, 1951. Crile, G. Jr.: Transesophageal Ligation of Bleeding Esophageal Varices, Arch. Surg., 61: 654, 1950. Phemister, D. and Humphries, E.: Gastro-Esophageal Resection and Total Gastrectomy in the Treatment of Bleeding Varices in Banti's Syndrome. Ann. Surg. 126: 397, 1947. Tanner, N. C.: Hemorrhage as a Surgical Emergency. Proc. Roy. Soc. Med. 43: 147-152, 1950.
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