Gastrointestinal hemorrhagic necrosis

Gastrointestinal Hemorrhagic Necrosis* Report of Ten Cases DAVID BIALOSTOZKY, M .D ., RAUL CONTRERAS, M .D ., CARLOS A . TINAJEROS, M .D . and SALVADOR FRANCO-BROWDER, M .D .

Mexico City, Mexico The clinical syndrome of gastrointestinal hemorrhagic necrosis is relatively frequent . The appearance of abdominal pain and distention, and adynamic ileus with or without evidence of overt hemorrhagic tendency in a patient with chronic congestive heart failure should arouse the suspicion of this disorder especially when accompanied by hypotension or arrhythmias and when there is a history of antecedent treatment with large doses of digitalis or norepinephrine . The importance of clinical recognition of this syndrome, to avoid unnecessary surgery, is stressed . The pathologic findings in these cases include absence of demonstrable mesenteric obstruction (intrinsic or extrinsic) ; the presence of diffuse or patchy hemorrhagic lesions in the gastrointestinal tract distributed throughout the stomach, small and large bowel, localized in most cases to the mucosa and submucosa but potentially involving all layers, causing perforation ; and marked vasodilation of the arterioles, venules and capillaries around the affected areas . Although the pathogenesis of gastrointestinal hemorrhagic necrosis is not known, there is enough information to show that the following factors could be among the more important ones: diminished cardiac output and mesenteric capillary vasoconstriction, with blood slowing and sludging. The presence of microscopic vascular dilatation and hemorrhagic necrosis points to the possibility that liberation of vasoactive amines could be one of the mechanisms producing vasodilatation and hemorrhagic necrosis of the gastrointestinal tract .

G

ASTROINTESTINAL hemorrhagic necrosis can

these lesions may be reversible . Even though these pathogenic characteristics seem bizarre enough to suggest that this syndrome would be infrequent, there are reports that reveal a comparatively high frequency, such as the one

be produced, clinically and experimentally, in the absence of demonstrable obstructive vascular changes in the injured areas . This hemorrhagic necrosis might be caused by the additive effects of manifold factors-hemodynamic, including chronic congestive heart

presented by Ming [1] . The purpose of this paper is to present the clinical and pathologic findings in ten proved cases of gastrointestinal hemorrhagic necrosis and to discuss its pathogenesis .

failure, vasoactive amines, blood clotting factors, endotoxins, drugs and the like-which are capable of giving a clinicopathologic picture similar to that due to mesenteric vascular obstruction . Among the most interesting features of this syndrome are the absence of extrinsic or intrinsic vascular obstruction capable of altering the normal mesenteric blood flow, the absence of local inflammatory changes prior to the appearance of gastrointestinal hemorrhagic necrosis and the possibility that

MATERIAL AND METHODS In 3,000 consecutive autopsies performed at the Institute Nacional de Cardiologla de Mdxico, we found ten cases of gastrointestinal hemorrhagic necrosis without demonstrable mesenteric, arterial or venous, obstruction . In each patient we analyzed the following data : age, sex, cardiomegaly and heart failure, the last in respect to duration and

• From the Institute National de Cardiologfa de Mexico and the Escuela Superior de Medicina, Institute Politecnico National, Mexico 17, D . F. Requests for reprints should be addressed to David Bialostozky, M .n-, Institute National de Cardiologia, Ave . Cuauhtemoc 300, Mexico 7, D .F . Manuscript received December 28, 1967 . 90

AMERICAN JOURNAL OF MEDICINE

Case No.

o.

78,F

51,F Rheumatic heart disease ; cardiomegaly grade 3

62,F

45,F

35,F

17,M

23,M

17,M

2

3

4

5

6

7

8

9

10

rv

5 yr .

6 hr .

L.

AF

lntoxication

Normal

Normal

Adynamic ilcua (x-ray) tents 4 gu ac 4d

rte can . No

No Adynamicdean (s-ray)4day?duralion

Normal

Yes

Terminal slwok, 20 ruin .

en

No Unnoticed Yes

1 yr .

L.

Shock, I hr.

3 yr .

tv

No

Severe pain and distention ; herontemesis, melena and enterorrhagia 4 days' duration Normal

Normal

Yes

2 yr .

it

n

No

Yea §

Severe pain and distention ; enteror- No rtagia 3 hr . duration .

Adynamic ileus (x-ray) stool and gastric : 4+ guaiac ; 4 days duration

No

Distention and melena 3 days' dnralion

Normal

35% (without noticeagulants)

No

Adynamlc ileus (x-ray) 24 hr . dnralion

Yes

50,000 diminished adhesiveness and agglutination

No

Surgery

General severe pain and distention ; 5 hr. duration

Abdominal Findings

10 .

Yes

Normal

Normal

Prochrombin Time

III

AF

Intoxication

AF with bigeminy

Platelets

Sudden death

36 hr .

. . .

ntoxication

Yes

Digitalis

AF

Amhytthms (

Yes

Yearn

5 mo.

Drugs :

Hypotenaion Duration

i yr .

III

vs

tv 4 mo.

6 mo,

DCDuragreen Lion

Cardiac Insufficiency

tv

TABLE I FINDINGS IN GASTROINTESTINAL HEMORRHAGIC NECROSIS

» ClaBifted according to the New York Heart Association criteria . t L . - bitartrate of uorepinephrine (Levophed), V . = mcthoxamine hydrochloride (Vasnxyl) . : AF = Auricular fibrillation (chronic) . ; the mesemeric artery polsa§ Multiple necrotic areas throughout the attire small bowel ; no perforation was seen, but there was scrolls exudate, adhering the small bowel loops, that were easily separated tions were visible aad palpable . No intestinal reseeelon seas performed .

Rheumatic heart disease ; cardiomegaly ,rude 4

Rheumatic heart disease with subacute bacterial cadocarditla ; cardiomegaly grade 2

Rheumatic heart disease with subacute bacterial endocarditis ; cardiomegaly grade 3

Arterial hypertension secondary to renal artery thrombosis ; bilateral pyelenephritis, uremia ; cardiomegaly grade 4

Syphilitic aortitis with aortic insulficiency ; cardiomegaly grade 3

Chronic cor pulmanalc ; arteriosclerotic heart disease ; essential arterial hyper . tension ; cardiomegaly grade 2

30,F Cystic medial necrosis of the ascending aorta and arch ; cardiomegaly grade 3

Arteriaxlerotic heart disease ; chronic car pulmonale ; cardiomegaly grade 2

53,M

Intemtrial septal defect ; arteriosclerotic heart disease ; chronic cor pulmonale ; cardiomegaly grade 3

Clinical and Anatomic Diagnosis

I

and Sex

a

K

Age

(yr .)

ti y z C y

A a

r D



0 r+

p

O

to

N



92

Gastrointestinal Hemorrhagic Necrosis Bialostozky

et al .

Fic. 1 . A, large portion of the small bowel with extensive necrosis . After Careful dissection of the arteries, no extrinsic or intrinsic obstructive lesion can be seen . B, in the lower portion extensive dark areas of intestinal necrosis ran be seen. The mesenteric arteries and the finer branches have been carefully dissected and opened . No thrombi, emboli, occlusive or stenos . ing intrinsic or extrinsic lesions are present.

IA

1B

degree classified according to the New York Heart Association criteria ; also the association with hypotension, arrhythmias,, infection (including subacute bacterial endocarditis), presence of thromboembolic disease, hepatic dysfunction, hemorrhagic tendency and medication used . With regard to the manifestations in the abdomen we considered duration, localization and intensity of the abdominal pain and associated symptoms : distention, rebound phenomena, muscular rigidity, peristalsis, overt gastrointestinal bleeding, ileus and x-ray findings (flat film of the abdomen) . The laboratory studies performed included complete blood count (also platelets), liver profile and prothrombin time and blood chemical findings (Table I) .

Fir . 2 .

Extensive areas of necrosis of the small bowel, some of them of dark and others grayish, irregularly distributed and involving almost all the small bowel .

Attention was given to the pathologic changes in regard to the extent and distribution of the hemorrhagic necrotic lesions ; different levels of intestinal wall involvement ; presence of inflammation, search for vascular obstruction, intrinsic or extrinsic, studies of the arterioles, venules and capillaries around the affected areas and the presence of platelet thrombi .

RESULTS (TABLE I) All of our patients had chronic congestive heart failure grade 2 to 4 with cardiomegaly that varied from grade 2 to 4. Arrhythmias, hypotension, digitalis effect and/or intoxica-

Fic . S . Inner aspect of the stomm . 4 . Extensive necrosis (dark ach showing small superficial color) of the small bowel . The ulcers of different shapes and arrow shows the perforation parsizes giving the superficial mu- tially covered over by a whitish cosa a spotted aspect . fibrinous membrane .

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93

Fro . 5 . A and B, intestinal wall . Necrosis of all layers of the small

bowel. The blood vessels, including the capillaries, are very dilated and full of blood . No thrombi, emboli or parietal lesions can be seen, Eosin and hematoxylin stain . A = arterioles ; V = vennles; C = capillaries .

tion were present in less than half of our patients . In one patient the platelets and the prothrombin time were low, causing us to suspect consumption of the coagulation factors, such as was described by McKay [2] and Hardaway [3] . Hemoglobin and hematocrit were normal, moderate leukocytosis was present in five patients . Abdominal pain was the presenting symptom in eight patients ; this appeared in different areas but readily became generalized . The pain was severe to moderate . Abdominal distention was the most constant and precocious sign, without muscular rigidity or rebound phenomena ; peristalsis was absent in four patients, and the roentgenologic findings were compatible with adynamic ileus . Nausea, vomiting and diarrhea were present in most patients . Hematemesis developed in three, enterorrhagia in two and melena in three more . The abdominal manifestations, when present, lasted from hours to four days . Two patients had associated subacute bacterial endocarditis without thromboembolic phenomena and one with bilateral pyelonephritis . Four had chronic auricular fibrillation . The postmortem findings can be summarized as follows : The common denominator was the presence of hemorrhagic necrotic lesions in the gastrointestinal tract distributed throughout the stomach, small intestine and large bowel . We were not able to find any obstructions, intrinsic or extrinsic, due to VOL . 46, JANUARY 1969

thromboembolism or stenosing lesions of arteries or veins (Fig . 1) . Necrotic lesions were diffuse in two patients, involving the entire small and large bowel (Fig . 2) . The remaining patients had patchy necrosis of the large and small bowel and one of them also had ulcerations of the stomach (Fig . 3) . Another had a 2 mm. perforation in the terminal portion of the ileum, with peritonitis (Fig . 4) . It is interesting to note that hemorrhagic necrotic lesions localized only to the large bowel were not found . Microscopically we noted hemorrhagic necrosis of the intestinal wall, with marked dilatation of the arterioles, venules and capillaries around the affected areas (Fig . 5 and 6) . In eight cases the mucosa and submucosa were involved and in the other two, the lesions extended through the serosa . No platelet thrombi were found microscopically . COMMENTS

There are some features of the clinical picture which suggest the diagnosis of gastrointestinal hemorrhagic necrosis . The appearance of generalized abdominal distention and pain, adynamic ileus, with or without demonstrable gastrointestinal bleeding in a patient with cardiac insufficiency of long duration should arouse suspicion of this syndrome . The clinical picture can be of sudden onset and may last several days ; it is frequently associated with arrhythmias and/or hypotension . This syn-



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Gastrointestinal Hemorrhagic Necrosis-Bialostozky el al .

drome mimics an "acute abdomen" but surgery must be avoided if possible . In one of our patients (Table t) an exploratory laparotomy was performed and the surgeon found generalized involvement with multiple necrotic areas in the small intestine, with a pulsating mesenteric artery ; a bowel resection was not performed . Even though the clinical picture of gastrointestinal hemorrhagic necrosis is fairly well characterized, its pathogenesis is not clear. Our findings illustrate several facts related to this diagnosis and show the need for an improved therapeutic approach through a better understanding of the pathophysiology of gastrointestinal hemorrhagic necrosis . Any type of heart disease accompanied by moderate to severe heart failure of long duration can produce (through decreased cardiac output) anoxia and/or mesenteric ischemia [4] that can initiate or complete a series of events that may lead to gastrointestinal hemorrhagic necrosis . Chronic congestive heart failure, with its accompanying decrease, slowing and sludging of the mesenteric blood flow, particularly at the level of the intramural vessels of the gastrointestinal tract [5], may contribute to production and increase of mesenteric ischemia . This effect may be greatly enhanced by hypotension . Hypotension, congestive heart failure, arrhythmias and shock can produce mesenteric ischemia . Vasoconstriction of the mesenteric capillary bed is the result of a compensatory mechanism which tries to divert blood to vital organs [6] . Shock alone is capable of producing these hemodynamic changes, partially due to a marked increase in epinephrine and norepinephrine secretion [7] . Similar pharmacologic agents administered to patients in this condition may augment the vasoconstriction of the mesenteric vascular bed, and may help to precipitate the appearance of gastrointestinal hemorrhagic necrosis . Experimentally, it has been demonstrated that hemorrhagic shock or administration of adrenaline and digitalis in large doses produces vasoconstriction of the portal and hepatic veins [6,8] . It is obvious that this additive effect has to be kept in mind by the clinician who is planning to use these drugs with patients in shock . Of course shock, cardiac insufficiency and hypotension produce mesenteric ischemia but not necessarily gastrointestinal hemorrhagic necrosis . It is important to emphasize in our cases

the absence of demonstrable obstruction of mesenteric vessels at different levels : artery, vein, arteriole, venule and capillary bed . Nevertheless, intestinal intramural ischemia is produced by the factors already mentioned . In other words, the combined effect of vasoconstriction, diminished cardiac output with consequent decrease of perfusion pressure and severe passive congestion may produce serious local tissue anoxia . Franco-Browder et al . [9] demonstrated experimentally in rats that gastrointestinal hemorrhagic necrotic lesions can be elicited with histamine-liberators . The probability that vasoactive amines may participate in the ulcerogenic effects of histamine-liberators is suggested by the protective effect of antihistaminic (Phenergang) and/or antiadrenergic (Dibenzyline®) drugs against .these lesions experimentally in rats [9] . The mechanism of gastrointestinal ulceration in this experimental model is probably one of submucosal hyperemia, vasodilatation and stasis followed by hemorrhage .

Microscopic examination of the gastrointestinal wall in all our cases showed vasodilatation and hemorrhagic necrosis (Fig. 5) . Is liberation of vasoactive amines responsible or a contributing factor for the marked vasodilatation of the mesenteric capillaries seen in our cases at autopsy? There are other hypotheses to explain the pathogenesis of this syndrome, such as the one presented by McKay [2] and Hardaway [3] suggesting consumption of coagulation factors, and also that of Fine [10] who believes that endotoxin shock, through its sympathetic vasoconstrictive action, may play a role in this syndrome . Freiman [5] points out the resemblance of the alterations in this syndrome to those of the localized Shwartzmann reaction . In brief, we believe that all these factors play a role in the pathogenesis of gastrointestinal hemorrhagic necrosis, but individual reactivity and the predominance of each factor differs from one patient to another, conditioning the severity of the syndrome and its final outcome .

Acknowledgment : We appreciate the help of Dr. Bruce L . Lipton, Los Angeles, California, in corrections of the manuscript . REFERENCES

Hemorrhagic necrosis of the gastrointestinal tract and its relation to cardiovascular status. Circulation, 32 : 332, 1965.

1 . MINC, S . C.

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Gastrointestinal Hemorrhagic Necrosis-Bialostozky 2 . McKAY, G . D . Disseminated Intravascular Coagulation. An Intermediary Mechanism of Disease . New York, 1965 . Paul B . Hoeber, Inc 3 . HAIDAwAY, R. M ., III. Syndromes of Disseminated Intravascular Coagulation . With Special References to Shock and Hemorrhage. Springfield, Ill ., 1966. Charles C Thomas. 4- Corny, E, IRVwc, D. W ., GOLD, H., BERENSTEIN, H . and SRELTON, R . B . T. Mesenteric vascular in. sufficiency. Intestinal ischemia induced by remote circulatory disturbances . Am . J . Med ., 33 : 365 . 1965 . 5 . FREIMAN, G . D. Editorial . Hemorrhagic necrosis of the gastrointestinal tract . Circulation, 32 : 329 . 1965.

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6. CORDAY, E. and WILLIAMS, J . H. Effect of shock and vasopressor drugs on the regional circulation of the brain, heart, kidney and liver. Am . J . Med ., 29 : 228, 1960 . 7 . BYRNE, J . J . Shock. New England J . Med., 275 : 543, 1965. 8 . GAZES, P . C ., HOLMES, C . R., MOSELEY, V. and PRArrTHOMAS, H . R . Acute hemorrhage and necrosis of the intestine associated with digitalization . Circulation," : 358, 1961 . 9. FRANco-BRowDER, S., MAsso&, G . M . C. and CoRcoRAN, A . C . Induction of acute gastric lesions by histamine-liberators in rats . J . Allergy, 30 : 1, 1959 . 10. FINE, J . Septic shock . J,A .MA, 188 : 427, 1964.