ischaemic bowel disease - journal of clinical pathology |...

J. clin. Path., 30, Suppl. (Roy. Coll. Path.), 11, 68-77

Ischaemic bowel diseaseT. ALSCHIBAJA AND B. C. MORSON

From the Department ofPathology, St Mark's Hospital, London

A supply of oxygenated blood appropriate to the tis-sue needs of the gut is essential to the maintenance ofits vital functions. The splanchnic vascular systemserves this purpose and much of our knowledge ofischaemic bowel disease has developed from studiesof radiological and pathological abnormalities of thissystem. The purpose of this paper is to summarizecurrent information concerning the histopathology ofintestinal ischaemia in the light of our better under-standing of the micro-circulation of the gut in healthand disease; also to describe the difficulties we havein understanding the pathogenesis of ischaemicbowel disease because of the growing spectrum ofsystemic disorders with which it is associated.

Nomenclature

Until recent times ischaemic bowel disease was a

clinical entity recognized usually in its irreversiblefatal forms and less frequently in its reversiblechronic forms. Protean clinical manifestations andresemblance to inflammatory disorders of the bowelled to a multiplicity of names for presumablyseparate entities with common pathological features-names such as haemorrhagic necrosis, necrotizingenterocolitis, membranous or pseudomembranousenterocolitis, infarction, gangrene, ischaemic stric-ture, clostridial or staphylococcal enterocolitis,uraemic enterocolitis, necrotizing enterocolitis, phleg-monous enterocolitis, etc (table I). This report

Ischaemic enterocolitisInfarction of the intestinal tractIntestinal gangreneHaemorrhagic enterocolitisNeonatal necrotizing enterocolitisUraemic enterocolitisPhlegmonous or croupous enterocolitisClostridial enterocolitisPseudomembranous or antibiotic enterocolitis

Table I Nomenclature of ischaemic bowel disease

describes ischaemic bowel disease in general no mat-ter what its cause and describes gross and micro-scopic pathological features differentiating thisentity in particular from inflammatory bowel disease.

Natural history

The natural history of ischaemic bowel disease canbe described as a complex but related series of cel-lular and tissue reactions to anoxic injury producedby interruption of a supply of oxygenated bloodsufficient for the functions of the bowel, no matterwhat the cause. The extent and the forms of thesereactions vary with the severity and duration of theischaemia, the adequacy of collateral avenues ofblood supply and the capability of the affected cellsand tissues to survive and regenerate. The alterationsprovoked in this cycle of reaction to injury rangefrom minor degrees of change in the most vulnerablecells of the mucosal villi through major but reversibledegrees of destruction of the mucosa and submucosato irreversible full-thickness gangrene of the bowelwall. There are many gradations and overlapsin the stages of survival and restoration of tissues andmany variations in the resultant gross and micro-scopic features, all reflected to varying degrees in aspectrum of clinical events and radiological findings.The section of gut affected, the extent and multi-plicity of the sites involved, the patterns of involve-ment and secondary alterations such as stenosis,megacolon, ulceration, 'cobblestoning', etc, add tothe morphological diversity of the disorder and tendto obscure the identity of its cause.Major vascular occlusion is not required to pro-

duce a serious degree of ischaemia in the bowel. Theoccurrence of intestinal gangrene without demon-strable vascular occlusion is recognized clinically andexperimentally (Williams et al, 1967; Marston, 1972;Whitehead, 1972; Marcuson, 1974). Occlusion dueto functional constriction, cardiogenic shock, low-flow states or remote partial organic obstruction isusually operative in these instances. The essence ofthe matter is that the gut is equally susceptible toischaemic necrosis from a summation of minorvascular deficiencies as well as from single demon-strable major occlusions.The reaction to moderately severe ischaemia fol-

lows a predictable course of inflammation and repairdivisible into three general phases: (1) acute, withhaemorrhage and necrosis; (2) reparative, with

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Ischaemic bowel disease

granulation tissue formation and fibrosis and (3) laterforms of residual pathology with bowel constrictionand chronic complications (table II). The pre-dominant gross and microscopic features charac-teristic of these phases are described in the followingsections. A transient, 'self-healing' form of intestinalischaemia is known experimentally and is thought tooccur in humans also when the initial injury is slightor of short duration and collateral blood flow isadequate. Severe and prolonged ischaemia causessegmental infarction of the bowel and subsequentgangrene leading to perforation and peritonitis(Marston et al, 1966).

Phases of Injury and Repair

Category Types of Response Tissue Alterations

1 Acute Oedema, haemorrhage,necrosis

2 Repair Epithelial regeneration,granulation tissueformation, chronicinflammation, muralfibrosis

3 Residual pathology Panmural fibrosis,Stenosis

Table II Natural history of ischaemic bowel disease

Location of ischaemic bowel disease

The location and extent of ischaemic lesions of theintestine reflect the anatomy and physiology of theblood supply and the anastomosing network ofsecondary vessels which supply the various divisionsof the alimentary tract. The ischaemic lesions them-selves vary from focal forms such as the sharplylocalized annular ulcers of the ileum associated withthe intake of enteric-coated potassium tablets to themassive forms of infarction seen with acutemesenteric arterial thrombosis or venous occlusion.In some instances the location of the ischaemicinjury is determined by the anatomy of the bloodsupply and the precipitating cause, ie, compressionof the superior mesenteric artery by an adhesivebond or occlusion of the inferior mesenteric arteryby aortic aneurysm. In other cases the injury is soextensive that it can only be the manifestation of ageneralized vascular disorder such as heart failure orhypotension, Es occurs in myocardial infarction or bya widespread small vessel occlusion due to spasm orintravascular coagulation.

Ischaemia may involve any portion of the colon.However, the area of maximum susceptibility is thewatershed area between the superior and inferiormesenteric vessels and thus the common site ofischaemic lesions is the region of the splenic flexure.The splenic flexure is the point where the superiorand inferior mesenteric arteries anastomose; it has

been shown that the blood supply at this point isprecarious as the anastomosis is frequently deficient(Marston, 1972). Ischaemic stricture of the rightcolon is rare perhaps because this part of the gut hasa rich blood supply.

Whilst rectal involvement was considered initiallyrare or even non-existent, rectal lesions are nowrecognized with increasing frequency (Kilpatrick etal, 1968). The distribution and the pattern of involve-ment bear no relationship to the severity of theischaemia, but specific precipitating causes ofischaemic damage appear to show a predilection forcertain areas. Thus ligation of the inferior mesentericartery usually results in ischaemic lesions of thesigmoid colon, while low-flow state affects primarilythe splenic flexure. Similarly the length of bowelinvolved varies with the aetiology: atheromatousocclusion produces short segmental damage, whilelow-flow states result in much longer lesions(Marston et al, 1966).

Analysis of 358 clinical examples of ischaemiccolitis in which segmental location of the lesion wasdescribed gives the following distribution (fig 1)(McGovern and Goulston, 1965; Marston et al,1966; Moller and Stjernvall, 1971; Marcuson, 1972,1974; Kaminski et al, 1973; Williams and Willenberg,1975).

Right colon ....................... 27Transverse colon .................... 54Splenic flexure ...................... 84Descending and sigmoid colon ........ 99

Fig 1 Distribution of358 cases of ischaemic colitis.

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T. Alschibaja and B. C. Morson

The blood supply of the small intestine benefitsfrom the abundant system of anastomosing arcadeswhich are less numerous in the colon and which per-haps explain the less frequent occurrence of vasculardamage in the small bowel. Segmental ischaemiclesions of the small intestine are usually confined tothe jejunum and ileum and most often result fromexternal vascular obstruction due to compression ortwisting (adhesive band, volvulus, internal hernias,neoplasms, trauma). Ischaemia due to intramuralvascular occlusion is caused by small vessel throm-bosis or stenosis and is usually associated withsystemic vascular disorders, hypotension or the useof the enteric-coated potassium or thiazide treatmentfor hypertension.

In 27 cases of ischaemic en;erocolitis reported byMcGovern and Goulston there were 12 instances ofinvolvement of the small intestine (McGovern andGoulston, 1965). The ileum alone was involved in onecase (internal hernia). The terminal ileum and rightcolon were involved in three cases (myocardiacinfarction; hypertension). The ileum and the trans-verse colon were involved in one case (aorticinsufficiency due to atherosclerosis). The entire smallbowel was involved in one case due to postoperativehypotensive shock and in six cases these authorsreported infarction of the entire small bowel andcolon (myocardiac infarction; rheumatoid disease).The susceptibility of the colon to ischaemia can be

demonstrated at necropsy when careful microscopicexamination often reveals early mucosal lesions,many of which could be agonal in nature.

Pathology: Acute phase

Classic descriptions of the pathology of acuteischaemic bowel disease start with the phase ofimpending infarction. The bowel segment is bloated,purple-red, moist and soggy with a dull granularserosa, thickened wall and oedematous, focallyhaemorrhagic mesentery. Arteries are usually con-tracted and veins dilated and sometimes pluggedwith clotted blood. The lumen may be distended orcontracted and,contains serosanguinous fluid, mucusand cellular debris. The mucosal surface appearsflattened due to elevation and widening of its rugalfolds and the submucosa thickened by oedema andhaemorrhage (fig 2)). The whole wall is soggy ortense depending on the state of dilatation or con-traction and the serosa is commonly hyperaemic andmarked by petechial haemorrhage, oedema and earlyinflammation. The muscularis mucosae is visible as athin band separating the wide zone of oedematoussubmucosa from the more compact hyperaemicmucosa. Careful inspection of the surface of themucosa with the aid of a magnifier may be necessary

Fig 2 Acute ischaemic necrosis of the ileum. Massivehaemorrhage and oedema of the submucosa inmpart apseudopolypoid character to the mucosal surface. Thismacroscopic appearance corresponds to the radiologicalsign of 'thumb-printing'.

in order to detect small slits and erosions or ulcera-tions where the epithelium has become haemorrhagicand necrotic. Unless there is full-thickness gangreneor megacolon, the muscularis propria is preservedbut the subserosa usually reflects to an appreciabledegree the oedema and haemorrhage so conspiciousin the submucosa and mucosa. The serosa may bemarked by fibrin deposits and blood. Generally thegut is soft, flexible and resistant to tearing but it mayalso be so diffusely congested and oedematous thatit is friable and easily torn.The microscopic alterations of the acute phase of

ischaemic bowel disease are dominated by vascularcongestion, oedema, haemorrhage and necrosis (fig3). The latter may be only microscopic and it is pos-sible to have multiple fields with oedema, conges-tion (fig 4) and petechial haemorrhage of the sub-mucosa without necrosis or ulceration of the mucosa.However, in surgical specimens, it is common tofind focai necrosis of the surface epithelial cells ofthe mucosa and petechial haemorrhage in the laminapropria. The muscularis mucosae is thin and intactuntil ulceration of the mucosa disrupts it by oedemaand inflammation and the muscle fibres separate and

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fragment. Unless ischaemic damage has been severe,the muscularis propria is minimally affected. Oedemaalong the vascular pathways, slight separation ofmuscle fibres (fig 5), swelling and cytoplasmicvacuolization of ganglia, venous engorgement andloose scatterings of lymphocytes and occasionalneutrophil leucocytes are often the only signs of thedamage which has occurred at the mucosal and sub-mucosal levels. More definite changes such asoedema, congestion, petechial haemorrhage, fibrindeposition and early inflammation may be observedin the subserosal and serosal zones.

In specimens with more severe acute ischaemia,the markings of mucosal ulceration and/or pseudo-membranous enterolitis may predominate. The latteris sometimes better appreciated after one or twohours of fixation in formalin. This exposure impartsenough hardening and pallor to the mucosal exudateto produce a discrete mottling and coarse granu-larity which is resistant to scraping although mixedwith mucus. Ulcerations and pseudomembranes mayboth be present. These macroscopic features are theresult of a combination of oedema of the submucosa

Fig 3 Histology of an early acute ischaemia. There isstructural necrosis of the most inner zone of the mucosawith preservation of the deeper crypts and the muscularismucosae. Inflammatory infiltrate and vasculardilatation are seen in the subjacent submucosa(H&E x 40).

Fig 4 Thrombosis of submucosal vein (H & E x 90).

and patchy necrosis of the mucosa associated withpartial or complete destruction of glands, outpouringof mucus from gland lumens and mingling ofepithelial cells, mucus, fibrin, erythrocytes and acutepurulent exudate on the internal surface of the gutwith the formation of a tenaceous 'pseudo-membrane'. The uniqueness of this histological pat-tern is accentuated by the presence of zones of intactmucosa between these islands of necrosis andpartially destroyed, hypersecreting mucus glandsalong with zones where the mucosa has been totallydestroyed.

Pathology: Reparative phase

The phase of acute inflammatory reaction is followedin a sequential manner and to varying degrees bysubacute and chronic inflammation of a proliferativeor 'productive' type because granulation tissueformation (fig 6) and fibroplasia are its majorattributes. Where islands of mucosa have survived,the intervening ulceration is the area where necroticmucosa has been sloughed and digested and replaced

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Fig 5 Histology ofan acute ischaemia. In severe ischaemic injury the necrosis extends to the more resistantmuscularis propria. In this picture the circular layer shows signs of an early necrosis with lysis and separation of themuscle fibres (H & E x 90).

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Fig 6 Histology of reparative phase. Proliferative inflammation with granulation tissueformation extends into the muscularis propria breaking up and partly replacing the musclebundles (H & E x 90).

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by a matrix of granulation tissue and a mixedpopulation of acute and chronic inflammatory cells.Pockets of suppuration may be present or denseinfiltrates of plasma cells and lymphocytes pre-dominate in the field. Capillary proliferation, macro-phage activity and fibroblast production completethe chief activities until the mucosal epitheliumbegins to regenerate. Microscopic fissures may leaddown to or into the muscularis propria at points ofdeeper anoxic damage. Entrapped particles offoreign material may provoke a giant-cell reaction.The granulation tissue reaction is generally exuberantand, in conjunction with the residual islands ofinflamed and sometimes hyperplastic mucosalglands, presents a pattern mimicking Crohn'sdisease or chronic active ulcerative colitis. Eosinophilleucocytes and iron pigment-laden histiocytes are avariable element. The presence of iron-positivegranules in histiocytes is associated with priorhaemorrhages in the submucosa and mucosa and isimportant in differentiating ischaemic from inflam-matory bowel disease. Epithelial cell regeneration isvisible at the margins of the mucosal ulcers in theform of young cells growing in a thin sheet over thebed of inflamed granulation tissue or mingling withthe fibrin and leucocyte exudate and the populationof lymphocytes and histiocytes on the gut luminalsurface. Bacteria can sometimes be demonstrated atthe mucosal surface but rarely penetrate deeper tis-sues unless gangrene is present.

Pathology: Late sequelae

The portion of gut thus altered undergoes continuingchange in the form of tissue repair and functionalrestoration or further deterioration due to additionalvascular deficiency. Survival is manifested by pro-gressive fibrosis and mucosal reorganization. Theend result is ischaemic constriction (fig 7). Usuallymucosal ulcers persist and the lamina propria whenpresent continues to be inflamed. Frequently, themucosal epithelium regenerates sufficiently to covermost of the luminal surface and rests on a bed ofgranulation tissue. Atrophic glands in disarray andinfiltrates of plasma cells, lymphocytes and histio-cytes mark this attenuated regenerated mucosa. Thereepithelialized luminal surface is often flat andsmooth and productive of copious mucus. In somecases islands of surviving mucosa acquire a pseudo-polypoid character and futher obstruct the narrowedgut lumen.The submucosa gradually is converted into a

diffuse zone of dense, hyalinized connective tissuepoor in blood vessels and lymphatics but vested withfoci of persistent inflammation in which histiocytes,plasma cells and lymphocytes predominate. This

Fig 7 Ischaemic stricture of the sigmoid colon.There is an abrupt stenotic deformity of the bowel wallassociated with mutal thickening, cicatrizing serositisand patchy mucosal ulceration.

collar of diffuse, unyielding fibrosis filling the sub-mucosal zone of the bowel wall extends minimally orextensively into the muscularis propria (fig 8)involving in severe cases the serosa and mesenterictissues. Tubular stenosis or discontinuous saccula-tions of the bowel are radiological and gross expres-sions of this reparative scarring of the gut wall.Vascular and lymphatic and neural structures aretrapped in the fibroplasia and examples of vascularintimal fibrosis or luminal recanalization can usuallybe found. A distinctive form of atrophy and linearseparation of fibres ofthe inner zone of the muscularispropria resulting from ischaemia and fibrosis is amark of diagnostic significance (Morson, 1971).Serosal fibrosis and adhesion formation may also beconspicuous. Mesenteric lymph nodes are notenlarged and are free of granulomas. Although therectum is usually spared, recent reports by Kilpatricket al (1968) and Shearburn et al (1955) describenecrotic, ulcerating and fibrosing alterations charac-teristic of ischaemia here as elsewhere in the bowel.

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Fig 8 Histology of ischaemic stricture. There is deepmural fibrosis with partial destruction of the muscularispropria and disorganization of the muscle fibres.The separation of the fibres of the inner circular zonefrom the main muscle body is diagnostic (H & E x 40).

Differential diagnosis

Certain gross and microscopic features are helpful indifferentiating ischaemic bowel disease from majorinflammatory diseases of the bowel (Morson, 1971).The gross distribution of lesions in ulcerative colitisis classically that of a diffuse inflammatory processprogressing in continuity from the rectum to moreproximal segments of the colon with the severestdegrees of injury and reaction in the distal areas ofdisease. Typical Crohn's disease and ischaemicenterocolitis occur in a segmental or regional pat-tern, the former often in the ileum and the latter mostfrequently in the left colon and rarely involving therectum. Submucosal haemorrhages are conspicuous inacute ischaemia with early infarction and are notpresent in ulcerative colitis and Crohn's disease.


Acute pseudomembranous enterocolitis does notoccur in Crohn's disease and ulcerative colitis. Slit-like fissuring ulcers pathognomonic of Crohn'sdisease are never seen in ulcerative colitis andischaemic bowel disease. Primary gangrene of thefull thickness of the gut wall does not occur in Crohn'sdisease and ulcerative colitis and is pathognomonicof severe ischaemia. Sacculation of the bowel wallbetween zones of stricturing ulceration and fibrosisrarely occurs other than with ischaemia. Theextensive circumferential denudation of mucosa withreplacement by richly vascularized granulation tissueis a pattern rarely occurring except in ulcerativecolitis. Mucosal pseudopolyposis is common in theinflammatory colitides and uncommon in ischaemicdisease. Acute dilatation of the colon is a well knowncomplication of ulcerative colitis but also occurs inischaemic colitis without prior gangrene. Spontan-eous fistulae and perianal granulomatous inflam-mation are significant manifestations of Crohn'sdisease but rarely if ever are seen in ischaemicproctitis or ulcerative colitis. Microscopic transmuralinflammation, focal lymphoid tissue aggregates inthe submucosa, sarcoid-type granulomas and slit-like fissures of the mucosa are pathognomonic ofCrohn's disease. Cryptabscess formation, gobletcell depletion, atypical glandular proliferation in themucosa and sparing of the muscularis propria despitewidespread destruction of the mucosa and sub-mucosa are hallmarks of ulcerative colitis. Patchymucosal necrosis associated with marked submucosaloedema and pseudomembranous exudate rich inmucus, fibrin and bacteria is characteristic ofischaemic colitis. Serositis is minimal in ulcerativecolitis and always present in established Crohn'sdisease and ischaemic bowel disease. Diffusestricturing fibrosis involving the submucosa andextending into the muscularis propria is characteristicof ischaemic enterocolitis. Indeed, it is often thedestruction of the muscle layers by granulation tis-sue and fibrosis which is the most useful feature inseparating ischaemic bowel disease from inflam-matory bowel disorders.

Aetiology and pathogenesis

In the strict sense the aetiology of ischaemic boweldisease is irreversible anoxic injury to cells of theintestines and its pathogenesis concerns mechanismsinitiating this type of injury and alterations ofinflammation and repair which follow. Allowing foruncontrollable variations, it is possible to analysemany of the anatomical and functional changesoccurring in cells and tissues of the gut affected byischaemia in terms of alterations or causes which areintrinsic to the bowel and those which are extrinsic

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I Arterial occlusion by atherosclerosisIt Pathology of mural vasculature

Vasculitis: collagen diseases: compression: intravascularcoagulation: Buerger's disease: amyloidosis

lIt Venous occlusionOral contraceptives: blood dyscrasia: volvulus

IV Non-occlusive ischaemiaCardiac failure: hypovolaemia-shock: splanchnic

vasconstriction-drugs; trauma

Table III Pathogenesis of ischaemic bowel disease

(table III).Chief among the extrinsic causes of ischaemia of

the gut are occlusive disorders of the major branchesof the splanchnic arterial circulation. This system andits pathology are well described by Marston (1972)and Thompson (1972). Congenital anomalies, athero-sclerosis, thrombosis, embolism, dissecting aneu-rysms, surgical interference, traumatic occlusion orrupture, volvulus, intussusception, strangulatedhernia, haemorrhage (as in haemophilia and inpatients on anticoagulant therapy), complications ofabdominal angiography, complications of neoplasia(compression, invasion or secondary metaboliceffects), intravascular coagulation and arteritis areprincipal among the many conditions which mayseriously interrupt or modify the supply of blood tothe gut through major extrinsic arterial channels.Phlebitis and venous thrombosis may be equallyserious because the perfusion of oxygen in the targettissues of the intestinal mucosa and submucosa isturned off by retrograde venous blood flow as well asby collapse of the blood supply and pressure gra-dients on the arterial side of the circulation. Counter-balancing all of these obstructive conditions is theimportant line of anastomoses between the superiorand inferior mesenteric arteries and the capacity ofthese and other natural channels of collateral circula-tion to expand sufficiently to maintain an adequatesupply of blood to the tissues at risk from anoxia.The above causes are associated with abnormal

morphological states of the splanchnic vasculaturebut cessation of adequate blood flow to support thevital activities of intestinal tissues may also resultfrom 'resistance' in the peripheral vascular bed orfrom 'low flow states' produced by heart failure withdiminished cardiac output (ie, arrythmias, coronaryartery insufficiency, digitalis intoxication, myo-carditis, hypertension and valvular disease) or fromshock secondary to trauma, burns sepsis, blood loss,poisoning and metabolic acidosis. These disturbancesof blood supply and tissue perfusion act primarilywithin the wall of the intestine itself and are intrinsiccauses of ischaemic bowel disease. In addition togeneral states of circulatory failure such as shock,toxaemia and pump failure, there are many otherpathological conditions of the intramural blood ves-

sels of the bowel capable of initiating ischaemia pro-gressing to gangrene or constrictive fibrosis. Theseinclude periarteritis nodosa, systemic sclerosis,rheumatoid arthritis, disseminated lupus erythemato-sis, thromboangiitis obliterans, allergic vasculitis,diabetic sclerosis, potassium-induced vasculitis,uraemic vasculitis, radiation injury, intravascularcoagulation syndrome, prolonged use of systemicbirth control medications and immunosuppressivetherapy following organ transplantation (Whitehead,1972; Hardie, 1974; Marcuson, 1974). It is appro-priate to mention in this context that tissues haveneeds other than oxygen-such as proteins, carbo-hydrates, lipids, water, electrolytes, vitamins, etc.The capacity of cells to obtain these nutrients and toextract oxygen from the blood is intimately associa-ted with their membrane structure and internalmetabolism. Ischaemia and inflammation pro-foundly affect these structures and their functions;as do also bacteria, intestinal metabolites, hormonesand circulating drugs, antibiotics, anaesthetics andthe array of chemotherapeutic agents the sick andelderly are exposed to almost daily. These may actalone or in combination to disturb the homeostaticstate of the tissues and cells of the bowel.

In essence, the pathogenesis of ischaemic boweldisease can be defined at the level of molecularbiology and pathology as the balance between thedemand of increased tissue needs (caused bydiminished blood flow, oedema, inflammation,anoxic injury and infection) and the capacity of thebody to deliver the substances necessary to compen-sate for all serious deficiencies in cell structure andfunction. Conditions which create the imbalance inthe vital economy of tissues and cells of the intestinesmay be primarily within the wall of the bowel itselfor in the major and intermediate vessels of the splan-chnic circulation or in disorders of the general cardio-vascular and related systems. These conditions mayact alone or together and they may be simultaneousor discontinuous. They can in general be classified asdegenerative, inflammatory, traumatic, metabolicand of unknown aetiology. But for the general pur-poses of clinical diagnosis, pathological descriptionand rational therapy these disorders are categorizedas reversible or irreversible and as severe with gan-grene, chronic with constrictive fibrosis, or transientand self-healing. In this discussion of pathogenesiswe have considered them also in relation to causeswhich are extrinsic to the intestines themselves andthose which are intrinsic within their walls (fig 9).The interpretation of the pathology of ischaemic

bowel disease in individual specimens and differentia-tion from other types of bowel disease requiressystematic observation of gross and microscopicdetails and a knowledge of the salient features of

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76 T. Alschibaja and B. C. Morson

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W-3E~~-NFig 9 The fibrotically thickened submucosa contains an artery occluded by an organized cholesterol thrombus. Thethrombus contributed to the ischaemic episode (H & E x 90).

differential significance in each of the major enter-colitides. Moreover, experience with the subcellularmorphology and experimental pathology of alimen-tary tract disorders is increasingly important fromthe standpoint of intestinal biopsy interpretation andrationale of therapy.

Ultimately the pathogenesis of ischaemic boweldisease begins with the need to restore the physicalstructure of intestinal cells injured by ischaemia andto re-establish the chemical equilibrium of theirinternal milieu and normal mechanisms of energyexchange and regeneration. This restoration isachieved by renewal of blood flow, nutrient suppliesand metabolic pathways. This is the cure sought bymedical treatment and the goal of surgical removal ofnecrotic tissues or segments of bowel threatening thenormal motility and function of the gut. There isunity in the various causes and stages of developmentof ischaemic bowel disease. This unity flows from arecognition of its pathogenesis in terms of ischaemiccellular damage and a sequence of predictable inflam-matory and reparative alterations in the tissues of thewall and mesentery.

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