Malignant Hypertension as a Cause of Massive Intestinal Bleeding Myung Soo Shin, MD, Birmingham, Alabama Kang-Jey Ho, MD, PhD, Birmingham, Alabama
Few conditions in clinical medicine are as distressing
to the patient and his physician as massive hemorrhage from the gastrointestinal (GI) tract. Massive upper GI hemorrhage is commonly caused by bleeding peptic ulcer, erosive or hemorrhagic gastritis, ,ruptured esophageal varices, ulcerative gastric cancer, and Mallory-Weiss syndrome [I]. Lower GI bleeding, on the other hand, is usually associated with diverticulosis, colon cancer, and bowel infarction due to either mesenteric thrombosis or splanchnic vasospasm [l-3]. With advances in selective visceral arteriography, necrotizing angitis has also been found to be an important cause of massive GI bleeding 14-61. Necrotizing angitis is a collective term for several conditions, characterized by primary inflammation and necrosis of vessels, including polyarteritis nodosa [4], arteritis associated with drug abuse [6], hypersensitivity angitis [7], and malignant hypertension [B]. Among these, polyarteritis nodosa is most commonly reported to be associated with massive GI bleeding [4]. Presented herein is a case of massive lower GI bleeding caused by necrotizing angitis secondary to malignant hypertension, with particular emphasis on the importance of angiographic diagnosis and pathologic findings of this entity. Case Report A forty-one year old man was admitted with profuse, bright red, rectal bleeding of 4 to 5 hours’ duration. He had a history of hypertension for three years with blood pressure occasionally recorded greater than 250/150 mm Hg despite treatment with several antihypertensive drugs. On admission, the patient’s blood pressure had dropped to 90/60 mm Hg and the packed cell volume was only 18 per cent. Proctoscopy to 20 cm failed to disclose a definite bleeding site. Barium enema examination results were also negative. After transfusion of 14 units of whole blood within 5 hours, his blood pressure increased gradually to 200/120 mm Hp. Mesenteric arteriograms showed moderate sparsity of vessels, scattered segmental stenosis of terminal arterial branches, and pooling of dye suggestive From the Departments of Diagnostic Radiology and Pathology, School of Medicine, University of Alabama in Birmingham, Birmingham, Alabama. Reprint requests should be addressed to M. S. Shin, MD, Department of Diagnostic Radiology, School of Medicine, University of Alabama in Birmingham, Birmingham, Alabama 35233.
742
of microaneurysms. (Figure 1.) Such changes were more obvious in the ileocolic and middle colic branches of the superior mesenteric artery. Because of continuing profuse bleeding from the rectum, exploratory laparotomy was carried out. Three enterotomies were performed showing no blood in the gastric and intestinal lumen. Colotomy was then done in the midtransverse colon. The right side of the colon contained fresh blood, and several small mucosal erosions were identified. The right hemicolon together with the cecum and terminal ileum were then removed. Histologic examination of the resected bowel revealed the following findings characteristic of malignant hypertension: (1) hyperplastic arteriosclerosis with onionskin concentric laminated thickening of the walls of arterioles and small arteries which resulted in severe narrowing of the lumina (Figure 2); (2) necrotizing arteriolitis with fibrinoid deposition in the arteriolar walls (Figures 2 and 3); and (3) formation of microaneurysms of arterioles as a consequence of necrotizing arteriolitis (Figure 3). Ruptured aneurysms were not identified because the necrotic vessels in the sections taken from the hemorrhagic area had been destroyed. Hemorrhages were seen in the mucosa and submucosa, but no evidence of enterocolitis was noted. There were no pathologic changes suggestive of polyarteritis nodosa or other forms of necrotizing angitis. Approximately 6 hours after the right hemicolectomy, the patient went into shock, with bright red blood coming from his nasogastric tube. A second exploratory laparotomy was carried out immediately. Multiple stress gastric ulcers, which had not been present when the first laparotomy was done, were noted by gastrotomy. Bilateral truncal vagotomy was then performed. The patient began receiving Amicar@ and vitamin K, and his bleeding came under moderate control. Postoperatively, the patient continued to bleed intermittently through the rectum, passing red blood at times. The following very distressing phenomenon was observed throughout the rest of his course. The patient’s systolic blood pressure increased to approximately 200 mm Hg whenever his hematocrit increased to approximately 25 per cent after transfusion. At this time, the patient would have severe rectal bleeding. His systolic blood pressure would then decrease to approximately 100 mm Hg, the hematocrit would decrease to approximately 10 per cent, and the rectal bleeding would cease. After subsequent blood transfusion, his hematocrit and blood pressure would increase again, and another episode of rectal bleeding would ensue. Attempts were made to control his blood pressure with methyldopa and Apresolinee, but these measures were
The American Journal of Surgery
Malignant Hypertension
and Massive Intestinal Bleeding
Figure 1. Superior mesenteric arteriogramnrveaMngpoot&9ofcontrast mediaWggestiveofmkrvanellrysms ( arrows )’ in the iieocolic branch.
Figure 2. Hyperplastic arteriosclerosis with fibrinoid necrosis in the submucosa of colon. ( Hematoxyiin and egsin stain; original magnification X 250: reduced 3 1 per cent. )
unsuccessful. Another important factor that contributed to his bleeding diathesis was uremia secondary to malignant arteriolonephrosclerosis. On admission, the patient’s blood urea nitrogen and serum creatinine levels were 63 and 5.6 mg/lOO ml, respectively, but gradually increased to 200 and 7.0 mg/lOO ml, respectively. Cardiomegaly and signs of congestive heart failure also became evident. The patient’s condition gradualiy deteriorated, and he finally developed agonal respiration and died two weeks after admission. An autopsy was not performed. Comments The history and histologic
of uncontrolled high blood evidences of hyperplastic
Volume 133, June 1977
pressure arterio-
sclerosis, necrotizing arteriolitis, and formation of microaneurysms in this case strongly favor the diagnosis of malignant hypertension as the cause of massive intestinal bleeding. However, a definite causal relationship cannot be proved because the ruptured small vessels at the bleeding sites had been destroyed and could not be identified. Pathogenesis. Malignant hypertension is usually associated with high plasma renin and aldosterone activity [9]. The most characteristic morphologic change is the onionskin thickening of small arteries and arterioles as a hyperplastic cellular reaction to stress. The luminal narrowing increases peripheral resistance and &hernia which, in turn, induce more
743
Shin and Ho
Figure 3. Fibrtnoid necrosis of a submucosat arteriole wtttt destruction of the wall and microaneurysm formation. (Hematoxylin an+ eosin stain; original magntfkation X 250; reduced 3 7 per cent. )
renin production, forming a vicious cycle. The necrotizing angitis characterized by fibrinoid necrosis of arteriolar walls is an inconstant lesion which results from rapid and very severe elevation of blood pressure [IO]. At a diastolic pressure greater than 140 mm Hg the pulse waves destroy the arteriolar wall. The weakened vascular wall may rupture or form microaneurysms before rupture. In solid parenchymatous organs such as the kidneys, bleeding is limited to the perivascular region due to pressure from the surrounding tissue. In hollow organs such as the intestine, the ruptured vessels in the mucosa and submucosa may bleed into the lumen. Massive hemorrhage ensues because of the presence of high blood pressure and possible coagulation defects associated with uremia secondary to malignant arteriolonephrosclerosis. Control of blood pressure is essential for the prevention and control of such massive GI bleeding but is very often difficult to achieve, as in the present case. History of malignant hypertension is important for the differential diagnosis. Selective visceral angiograms are required for localizing the site of bleeding. However, it is often impossible to differentiate various types of necrotizing angitis. Microaneurysms, segmental luminal irregularity, indistinct vessel outlines, and thrombotic occlusion of vessels can be seen in all types of necrotizing angitis [6]. Tissue biopsy is usually required for establishment of a definite diagnosis.
744
Summary
A forty-one year old man with a three year history of malignant hypertension developed massive rectal bleeding. A mesenteric arteriogram showed vascular changes compatible with necrotizing angitis. Histologic examination of the resected right hemicolon confirmed malignant hypertension as the cause of angitis. References 1. Amir-Ahmadi H, McCray RS, Martin F, et al: Reassessment of massive upper gastrointestinal hemorrhage in the wards of the Boston City Hospital. Surg C/in North Am 49: 715, 1969. 2. Knight CD: Massive hemorrhage from diverticular disease of the colon. Surgery 42: 853, 1957. 3. Williams LF Bosniak Jr, MA, Wittenberg et al: J, lschemic colitis. Am J Surg 117: 254, 1969. 4. Bron KM, Strott CA, Shapiro AP: The diagnostic value of angiographic observations in polyarteritis nodosa. Arch Intern Med 116: 450, 1965. 5. Menguy R: Diagnosis and management of upper gastrointestinal bleeding. South bled J 69: 225, 1976. 6. Halpern M, Citron BP: Necrotizing angitis associated with drug abuse. Am J Roent.genol Radium Ther Nucl Med 111: 663, 1971. 7. Churg J, Strauss L: Allergic ganulomatosis, allergic angitis and oeriarteritis nodosa. Am J P&ho/ 27: 277, 1951. 8. Wolfgarten M, Magarey FR: Vascular fibrinoid necrosis in hypekension. J P&ho/ 77: 597, 1959. 9. McAllister RG Jr. Van Wav CW Ill. Davani K. et al: Malignant hypertension: effect of therapy on renin and aldosterone. Circ Res 28 Suppl2: 160, 1971. 10. Linton AL: Microangiopathic hemolytic anemia and the pathogenesis of malignant hypertension. Lancet 1: 1277. 1969.
The American Journal of Surgery
Few conditions in clinical medicine are as distressing
to the patient and his physician as massive hemorrhage from the gastrointestinal (GI) tract. Massive upper GI hemorrhage is commonly caused by bleeding peptic ulcer, erosive or hemorrhagic gastritis, ,ruptured esophageal varices, ulcerative gastric cancer, and Mallory-Weiss syndrome [I]. Lower GI bleeding, on the other hand, is usually associated with diverticulosis, colon cancer, and bowel infarction due to either mesenteric thrombosis or splanchnic vasospasm [l-3]. With advances in selective visceral arteriography, necrotizing angitis has also been found to be an important cause of massive GI bleeding 14-61. Necrotizing angitis is a collective term for several conditions, characterized by primary inflammation and necrosis of vessels, including polyarteritis nodosa [4], arteritis associated with drug abuse [6], hypersensitivity angitis [7], and malignant hypertension [B]. Among these, polyarteritis nodosa is most commonly reported to be associated with massive GI bleeding [4]. Presented herein is a case of massive lower GI bleeding caused by necrotizing angitis secondary to malignant hypertension, with particular emphasis on the importance of angiographic diagnosis and pathologic findings of this entity. Case Report A forty-one year old man was admitted with profuse, bright red, rectal bleeding of 4 to 5 hours’ duration. He had a history of hypertension for three years with blood pressure occasionally recorded greater than 250/150 mm Hg despite treatment with several antihypertensive drugs. On admission, the patient’s blood pressure had dropped to 90/60 mm Hg and the packed cell volume was only 18 per cent. Proctoscopy to 20 cm failed to disclose a definite bleeding site. Barium enema examination results were also negative. After transfusion of 14 units of whole blood within 5 hours, his blood pressure increased gradually to 200/120 mm Hp. Mesenteric arteriograms showed moderate sparsity of vessels, scattered segmental stenosis of terminal arterial branches, and pooling of dye suggestive From the Departments of Diagnostic Radiology and Pathology, School of Medicine, University of Alabama in Birmingham, Birmingham, Alabama. Reprint requests should be addressed to M. S. Shin, MD, Department of Diagnostic Radiology, School of Medicine, University of Alabama in Birmingham, Birmingham, Alabama 35233.
742
of microaneurysms. (Figure 1.) Such changes were more obvious in the ileocolic and middle colic branches of the superior mesenteric artery. Because of continuing profuse bleeding from the rectum, exploratory laparotomy was carried out. Three enterotomies were performed showing no blood in the gastric and intestinal lumen. Colotomy was then done in the midtransverse colon. The right side of the colon contained fresh blood, and several small mucosal erosions were identified. The right hemicolon together with the cecum and terminal ileum were then removed. Histologic examination of the resected bowel revealed the following findings characteristic of malignant hypertension: (1) hyperplastic arteriosclerosis with onionskin concentric laminated thickening of the walls of arterioles and small arteries which resulted in severe narrowing of the lumina (Figure 2); (2) necrotizing arteriolitis with fibrinoid deposition in the arteriolar walls (Figures 2 and 3); and (3) formation of microaneurysms of arterioles as a consequence of necrotizing arteriolitis (Figure 3). Ruptured aneurysms were not identified because the necrotic vessels in the sections taken from the hemorrhagic area had been destroyed. Hemorrhages were seen in the mucosa and submucosa, but no evidence of enterocolitis was noted. There were no pathologic changes suggestive of polyarteritis nodosa or other forms of necrotizing angitis. Approximately 6 hours after the right hemicolectomy, the patient went into shock, with bright red blood coming from his nasogastric tube. A second exploratory laparotomy was carried out immediately. Multiple stress gastric ulcers, which had not been present when the first laparotomy was done, were noted by gastrotomy. Bilateral truncal vagotomy was then performed. The patient began receiving Amicar@ and vitamin K, and his bleeding came under moderate control. Postoperatively, the patient continued to bleed intermittently through the rectum, passing red blood at times. The following very distressing phenomenon was observed throughout the rest of his course. The patient’s systolic blood pressure increased to approximately 200 mm Hg whenever his hematocrit increased to approximately 25 per cent after transfusion. At this time, the patient would have severe rectal bleeding. His systolic blood pressure would then decrease to approximately 100 mm Hg, the hematocrit would decrease to approximately 10 per cent, and the rectal bleeding would cease. After subsequent blood transfusion, his hematocrit and blood pressure would increase again, and another episode of rectal bleeding would ensue. Attempts were made to control his blood pressure with methyldopa and Apresolinee, but these measures were
The American Journal of Surgery
Malignant Hypertension
and Massive Intestinal Bleeding
Figure 1. Superior mesenteric arteriogramnrveaMngpoot&9ofcontrast mediaWggestiveofmkrvanellrysms ( arrows )’ in the iieocolic branch.
Figure 2. Hyperplastic arteriosclerosis with fibrinoid necrosis in the submucosa of colon. ( Hematoxyiin and egsin stain; original magnification X 250: reduced 3 1 per cent. )
unsuccessful. Another important factor that contributed to his bleeding diathesis was uremia secondary to malignant arteriolonephrosclerosis. On admission, the patient’s blood urea nitrogen and serum creatinine levels were 63 and 5.6 mg/lOO ml, respectively, but gradually increased to 200 and 7.0 mg/lOO ml, respectively. Cardiomegaly and signs of congestive heart failure also became evident. The patient’s condition gradualiy deteriorated, and he finally developed agonal respiration and died two weeks after admission. An autopsy was not performed. Comments The history and histologic
of uncontrolled high blood evidences of hyperplastic
Volume 133, June 1977
pressure arterio-
sclerosis, necrotizing arteriolitis, and formation of microaneurysms in this case strongly favor the diagnosis of malignant hypertension as the cause of massive intestinal bleeding. However, a definite causal relationship cannot be proved because the ruptured small vessels at the bleeding sites had been destroyed and could not be identified. Pathogenesis. Malignant hypertension is usually associated with high plasma renin and aldosterone activity [9]. The most characteristic morphologic change is the onionskin thickening of small arteries and arterioles as a hyperplastic cellular reaction to stress. The luminal narrowing increases peripheral resistance and &hernia which, in turn, induce more
743
Shin and Ho
Figure 3. Fibrtnoid necrosis of a submucosat arteriole wtttt destruction of the wall and microaneurysm formation. (Hematoxylin an+ eosin stain; original magntfkation X 250; reduced 3 7 per cent. )
renin production, forming a vicious cycle. The necrotizing angitis characterized by fibrinoid necrosis of arteriolar walls is an inconstant lesion which results from rapid and very severe elevation of blood pressure [IO]. At a diastolic pressure greater than 140 mm Hg the pulse waves destroy the arteriolar wall. The weakened vascular wall may rupture or form microaneurysms before rupture. In solid parenchymatous organs such as the kidneys, bleeding is limited to the perivascular region due to pressure from the surrounding tissue. In hollow organs such as the intestine, the ruptured vessels in the mucosa and submucosa may bleed into the lumen. Massive hemorrhage ensues because of the presence of high blood pressure and possible coagulation defects associated with uremia secondary to malignant arteriolonephrosclerosis. Control of blood pressure is essential for the prevention and control of such massive GI bleeding but is very often difficult to achieve, as in the present case. History of malignant hypertension is important for the differential diagnosis. Selective visceral angiograms are required for localizing the site of bleeding. However, it is often impossible to differentiate various types of necrotizing angitis. Microaneurysms, segmental luminal irregularity, indistinct vessel outlines, and thrombotic occlusion of vessels can be seen in all types of necrotizing angitis [6]. Tissue biopsy is usually required for establishment of a definite diagnosis.
744
Summary
A forty-one year old man with a three year history of malignant hypertension developed massive rectal bleeding. A mesenteric arteriogram showed vascular changes compatible with necrotizing angitis. Histologic examination of the resected right hemicolon confirmed malignant hypertension as the cause of angitis. References 1. Amir-Ahmadi H, McCray RS, Martin F, et al: Reassessment of massive upper gastrointestinal hemorrhage in the wards of the Boston City Hospital. Surg C/in North Am 49: 715, 1969. 2. Knight CD: Massive hemorrhage from diverticular disease of the colon. Surgery 42: 853, 1957. 3. Williams LF Bosniak Jr, MA, Wittenberg et al: J, lschemic colitis. Am J Surg 117: 254, 1969. 4. Bron KM, Strott CA, Shapiro AP: The diagnostic value of angiographic observations in polyarteritis nodosa. Arch Intern Med 116: 450, 1965. 5. Menguy R: Diagnosis and management of upper gastrointestinal bleeding. South bled J 69: 225, 1976. 6. Halpern M, Citron BP: Necrotizing angitis associated with drug abuse. Am J Roent.genol Radium Ther Nucl Med 111: 663, 1971. 7. Churg J, Strauss L: Allergic ganulomatosis, allergic angitis and oeriarteritis nodosa. Am J P&ho/ 27: 277, 1951. 8. Wolfgarten M, Magarey FR: Vascular fibrinoid necrosis in hypekension. J P&ho/ 77: 597, 1959. 9. McAllister RG Jr. Van Wav CW Ill. Davani K. et al: Malignant hypertension: effect of therapy on renin and aldosterone. Circ Res 28 Suppl2: 160, 1971. 10. Linton AL: Microangiopathic hemolytic anemia and the pathogenesis of malignant hypertension. Lancet 1: 1277. 1969.
The American Journal of Surgery
