Postgrad Med J: first published as 10.1136/pgmj.31.355.234 on 1 May 1955. Downloaded from

234

iACUTE PANCREATITIS By ROBERT Cox, M.B.E., F.R.C.S. Assistant Surgeon, Westminster Hospital; Surgeon, All Saints' Hospital

Among the many problems presented by the and indeed we have in our small series at West- class of patients usually referred to as the acute minster Hospital a case of a child, dying with abdominal emergencies, none is of greater interest congenital tricuspid atresia, in whom haemor- than that of acute pancreatitis. Acute pan- rhagic pancreatitis was a terminal feature seen at creatitis is a difficult disease; its incidence is low, post mortem. so that the average surgeon sees it relatively The peak incidence is about 50 years of age. infrequently. Its aetiology is not known and is the subject of much argument; the pathology Aetiology is protean and complex; its treatment calls for A vast amount of conjectural and controversial skill and a well organised clinico-pathological literature has been produced on the cause of effort; the prognosis is always serious and oft pancreatitis, but we can sum up by saying that times of the gravest. Nevertheless, all these we do not know the cause, and that there are inby copyright. difficulties have undergone some mitigation in fact probably several mechanisms by which the recent years because of an increasing interest in pathological processes can be set in train. Among the disease, developments in knowledge of the the more popular theories are: physiology of the gland, improved diagnostic i. Bile reflux. Claude Bernard in i856 pro- aids, and better understanding of the principles duced pancreatitis in animals by injecting bile into of treatment, so that the overall picture which the pancreatic duct, but it was Opie, who in this disease presents is not, nowadays perhaps, describing in 190o his case of pancreatitis in a quite so forbidding. patient with a gall stone impacted at the ampulla of who be said to have laid the Vater, may largest http://pmj.bmj.com/ Incidence foundation stone in the fabric of this theory. Owing to variations in nomenclature, errors of But the Opie type of stone, like foundation case recording, etc., it is difficult to arrive at an stones, does not occur veryfrequently and moreover accurate estimate of the rate at which this disease Hicken and McAllister (1952) using radio opaque makes its appearance. injections have shown that fluid can always pass In a five year period at Westminster Hospital these stones and that obstruction is not complete. however, five undoubted cases of acute pancreatitis Cattell states that whereas pancreatic enzymes were recorded and over the same period 90 cases are always found in the gall bladder in acute on September 23, 2021 by guest. Protected of perforated peptic ulcer. Enquiries from other pancreatitis-which may indicate either intra London teaching hospitals have elicited com- ductal reflux or vascular blood borne trans- parable figures. ference of enzymes-bile is only found in the With regard to sex incidence, contradictory pancreatic ducts in a few cases. statements are to be found in the literature, but The more of these cases that are seen, the more most reliable large series show a slight pre- the literature is studied, the more obvious it ponderance of male cases. For instance MacKenzie becomes that whereas some cases may be due to (1954) in his series quotes 56 males to 41 females. bile reflux, many cannot be caused in this way. This male preponderance is of interest, since 2. Infection. This is a possible cause of acute biliary disease is undoubtedly more common in pancreatitis which has in the past not attracted the female, and may possibly be due to the greater much favour, possibly because all the inflam- gusto the male exhibits in his consumption of matory changes noted at operation or autopsy food and alcohol. could be so readily explained by the escape of With regard to age incidence, the disease is highly active and damaging enzymes. But Holt, known to occur through the whole adult range, (1954), in an excellent and well balanced review of Postgrad Med J: first published as 10.1136/pgmj.31.355.234 on 1 May 1955. Downloaded from lMay 1955 COX: Acute Pancreatitis 235 this subject, has recently pointed out with much Pathology cogency that the pancreas is a compound racemose Though the aetiological factors are uncertain, gland, and does not differ essentially in its subacute once they have set the pathological processes in inflammations from other analogous glands such train the latter are easy to understand. as the parotid or submaxillarygland: in these, when The pancreatic ferments, trypsin, lipase and some degree of obstruction to the duct system diastase are liberated into the tissues outside the and ascending infection occur together, severe ducts. The proteolytic properties of trypsin and sudden acute inflammation makes its appear- ensure that the process is for a time a progressive ance. Moreover, it is not without interest that one with digestion of gland substance, and damage an uncommon but well recognized complication to vessels causing both haemorrhage and throm- of mumps is acute pancreatitis. bosis. If the thrombosis is slight or moderate, 3. Pancreatic duct obstruction. Many workers oedema and blood stained peritoneal exudate may have produced acute pancreatitis by ligaturing the be the only effect, but if it is severe and extensive, main duct of the gland and then stimulating the result may be necrosis of large portions of secretion, but Rich and Duff (1936) were probably the gland which, should the patient recover, may the first to draw attention to metaplasia in the subsequently be discharged or require removal epithelium lining the ducts which could be an as pancreatic sequestra. obstructive factor. This obstruction combined With so much tissue damage occurring in close with an intra ductal rise of pressure during active proximity to the intestine, and with tissue response secretion could produce rupture with consequent impaired by vascular damage, bacterial invasion leakage of trypsin into the extra ductal tissues. and suppuration follow very readily, leading to It is well recognized that there is some connection pancreatic abscess which can present anteriorly between heavy intake of alcohol and the onset of or in the flank. acute pancreatitis, and many cases of the subacute Thus the result of the proteolytic enzyme relapsing form of the disease can relate their escape may be the production of oedematous, attacks to bouts. drinking Alcohol of course haemorrhagic, suppurative or necrotic pancrea-by copyright. excites a considerable flow of secretin-which titis, all merely stages in the one process though activates the pancreas-and has also been accused in years gone by, distinguished by some as of causing spasm of the sphincter of Oddi. separate entities. 4. Vascular factors. In the most severe types Two other aspects of the proteolytic enzyme of acute pancreatitis, haemorrhage and thrombosis escape are worthy of notice. Trypsin is clearly are striking features and it is therefore not most destructive and thus causes much tissue surprising that a vascular basis has been suggested insult with consequent collapse, the latter perhaps for the disease, but it is probably only sometimes being contributed to by the production of proteoses in action and is not then to be so as in the circulation. likely simple http://pmj.bmj.com/ a straightforward embolus or thrombosis. The other aspect is the development of a MacKenzie has drawn attention to recent work spreading upper abdominal peritonitis and a local in America which suggests that the vascular ileus of the transverse colon and first loop or two lesions are thrombotic, and occur as a result of of the jejunum, which are the portions of gut sensitization to bacterial toxins. closest in contact with the gland. This ileus may 5. Trauma. This is an undoubted factor in give rise to suggestive X-ray findings. certain cases but is an uncommon one. Most Lipase when free in the tissues attacks the frequently the trauma is surgical, but it may be a fat depots particularly in the mesocolon, on September 23, 2021 by guest. Protected blunt injury such as a run-over accident. Even in omentum and extra-peritoneal fat, but its effects surgical cases injury of the pancreas is only rarely may be seen even in the limbs. The fat is split, followed by acute inflammation of that organ. the fatty acids thus released picking up calcium Posterior gastric and duodenal ulcers commonly from the tissue fluids to form soaps which give the involve the pancreas but no experienced surgeon characteristic appearance to the pearly grey areas regards pancreatitis as a practical hazard following of fat necrosis. gastrectomy for such cases. Diastase or amylase is important not for any The author has seen a case dying of acute pathology which it causes but because it can be pancreatitis after a Polya gastrectomy for anterior estimated quickly and easily in serum or urine, and duodenal ulcer, but the mechanism on this this investigation has done a great deal to advance occasion was an afferent loop obstruction due to the diagnosis and knowledge of the disease, rotation, which seems to have caused duodenal particularly in its less severe or subacute forms. contents under high pressure to reflux into the Serum and urinary amylase tests should be within pancreatic ducts and thus activate the enzymes the capacity of any reasonably set up pathological there. laboratory and can be performed within 1-2 Postgrad Med J: first published as 10.1136/pgmj.31.355.234 on 1 May 1955. Downloaded from 236 POSTGRADUATE MEDICAL JOURNAL May 1955 hours, whereas lipase estimations are not so is by far the worst. Even the agony caused by frequently undertaken, and take 24 hours to carry perforation of a gastric or duodenal ulcer is less out. than that in acute pancreatitis. The pain too is Before leaving the subject of enzymes, it is remarkable in that it comes so frequently after a necessary to point out that all three are produced good meal and for its area of distribution: it is of in other parts of the alimentary tract, viz. diastase fiercest intensity in the epigastrium, but it is felt in the parotid and the small intestine, trypsin in also in the back and often in both loins.' the succus entericus, and that in certain circum- Moynihan is of course writing about a severe stances such as acute parotitis or acute upper acute attack. Oftentimes there have been other small intestine obstruction they can be absorbed milder preceding attacks, not recognized, and into the blood stream and give abnormal serum mistaken for cholecystitis or gall stone colic. concentrations, but rarely so high as in well Vomiting follows quickly on the onset of pain developed pancreatitis. Where the damage to and is in most cases persistent; if not, nausea and the pancreas is severe and widespread the islet retching are observed, and these symptoms may cells also suffer so that sugar metabolism is cause confusion with high intestinal obstruction disturbed. Frank glycosuria and diabetes mellitus though in the latter the nature of the vomit is are most often seen in the relapsing chronic form different and the quantity greater. of pancreatitis, while in acute inflammation a Collapse and shock are usually marked. The sugar tolerance curve may be required to demon- patient is cold, sweating, pallid with a cyanotic strate an abnormality. Recovery from islet cell tinge which is said to be characteristic. The damage after the acute attack always occurs to pulse is weak and rapid and the blood pressure some extent so that prognosis on this aspect seriously depressed to nigh unrecordable levels. should not be hasty. Respirations are shallow and rapid. Examination When death occurs it may either be within a of the abdomen reveals a tense upper abdomen, matter of hours of the onset of the disease from but not the degree of rigidity seen with a perfora- toxaemia and or tion: the lower abdomen be soft. overwhelming haemorrhage, may quite by copyright. more commonly about the ioth to the I4th day, of There is exquisite tenderness in the epigastrium exhaustion, electrolyte disturbance and possibly and this may also be present in the left costo- peritonitis, a picture which at one time was vertebral angle. called pancreatic asthenia. After the passage of 24 hours or longer, certain other signs may make their appearance. Dis- The Clinical Picture and Diagnosis coloration at the umbilicus and in the flanks, due From what has been said already about to extravasation of altered blood is associated pathology, it is obvious that there can be great with the name of Grey Turner. There is often variation in the clinical the distension limited to the abdomen, which picture presented by upper http://pmj.bmj.com/ patient suffering from acute pancreatitis. Further, was called epigastric peritonitis by Fitz, a Boston as stated when discussing incidence, most of us physician who gave the first account of acute see the disease only rarely and regrettably there is pancreatitis. It is said that the swollen pancreas thus a tendency to forget it, to omit it from our can be felt in some cases but it is more likely that diagnostic list. Reference to the writings of a the oedematous mesocolon, colon and omentum previous generation is often surprisingly fruitful in fact form most of what is palpable. and never more than when Moynihan is the author A straight X-ray of the abdomen is most and the subject abdominal surgery. He puts the helpful, since if gas is not present under the on September 23, 2021 by guest. Protected present matter thus-and I make no excuse for diaphragm, perforation is a less likely diagnosis quoting at length from his 'Abdominal Opera- and sometimes the distended transverse colon and tions' (1926): first loop of ileum are clearly seen. In cases with ' Unless a surgeon has seen previously two or many previous attacks, pancreatic calcification three cases of acute pancreatitis, or unless he may show, as will opaque gall stones when they keeps the condition constantly in mind, it is are present. seldom that a correct diagnosis is made before The most important ancillary investigation is opening the abdomen. So many forms of ab- the serum diastase estimation, which is normally dominal disaster are seen and among them so few below 2oo units. Between 200 and 500 units the involve the pancreas, that thought of this organ result may be regarded as equivocal, since as slips from the memory. I have found in not a already mentioned other conditions can cause a few instances, that the moment the diagnosis is rise, but a figure over 500 units is pathognomonic. suggested it meets with eager acquiescence. The urinary diastase can also be estimated and The first and chiefest symptom is pain; and of all has the virtue that an increased figure (normal up the pains that the human body can suffer, this to 30 units) may be found hours after the blood Postgrad Med J: first published as 10.1136/pgmj.31.355.234 on 1 May 1955. Downloaded from

May 1955 COX: Acute Pancreatitis 237 figure has fallen, which it may do rapidly, especially 2. Correction of shock. in less severe attacks. 3. Suppression of pancreatic activity. The rise of serum diastase may be so evanscent 4. Prevention of ileus. that it escapes observation, and we have one patient 5. Control of electrolyte and fluid balance. who is proven beyond doubt by laparotomy, who When first seen the most pressing requirement was admitted with a classical clinical picture, a of the patient is to relieve his agony and morphia systolic blood pressure of 60 mm. and yet the will be required in full doses. Theoretically serum diastase level was but I20 units, nor was there is an objection to morphia in that it induces any rise observed in the urine diastatic index over a spasm of the sphincter of Oddi, and pethidine or the next 24 hours. demerol have been recommended as alternatives; Serum and urinary lipase estimations are not in these two drugs are in practice found to be less general use and are in any event less reliable than efficient analgesics, and in any event the outlet of diastase investigations, but have the virtue that the pancreatic ducts is probably compromised by they reach their peak about three days after the oedema. American writers on this subject re- onset of the attack, thus being of help in the commend such manoeuvres as splanchnic block diagnosis of the late case. and even continuous epidural analgesia, but four From the third day of the disease to about the or six hourly morphia injections is a method which seventh, the serum calcium level may be depressed is found to work well in practice. and where this occurs it is indicative of much fat Shock demands the usual treatment and since necrosis. Occasionally the depression is suffi- intravenous therapy is going to be required for cient to be clinically evidence as tetany. some days a cannula should be introduced into a The electrocardiogram is liable to show changes vein and dextran or plasmosan given in order to brought about, it is thought, by electrolyte correct the fall in blood pressure. Subsequently disturbances, and these changes (inversion of T suitable fluid and electrolyte solutions will be waves and depression of S-T segments) should administered as indicated by daily blood chemistry not be confused with the changes in acute coronary estimations. The serum calcium may be loweredby copyright. occlusion (Howat 1952). and in these circumstances calcium gluconate is a suitable preparation for intravenous Treatment administration. During the past 25 years there has been a steady Atropine should be administered in doses of trend of opinion towards the non-operative treat- gr. i/ioo four or six hourly unless cardiac irregu- ment of these patients in the acute stage. Yet larity appears. This drug serves two purposes, there are still those who maintain that surgery it inhibits the neurogenic activity of the pancreas plays a part especially in the most serious types, and relaxes, at any rate in theory, the sphincter of but even in these opinion tends to less extensive Oddi. An intranasal Ryles tube should be http://pmj.bmj.com/ procedures within the peritoneum. introduced into the stomach and the patient In any event, a number of patients do come to put on continuous gastric aspiration, so that acid laparotomy because the diagnosis is not appreciated gastric contents will be prevented from passing and in these it is generally accepted that the into the duodenum and there causing the forma- minimum of disturbance of the pancreas itself tion of secretin and pancreozymin, which if should be the aim. Whether the common bile liberated, cause further activity of the damaged duct should be drained is less certain, Some authorities Alludrox 2 drachms though gland. give on September 23, 2021 by guest. Protected most writers now advise against such a step, four hourly by mouth in addition. leaving the correction by operation of any biliary The use of the Ryles tube, morphia and pathology to a later date when the pancreas has intravenous fluids together constitute the treat- recovered. ment for, or prophylaxis against, ileus. Post-operative burst abdomen is a common Both heparin and the methonium drugs have complication and the surgeon who has opened the been suggested in the treatment of this disease, abdomen would do well to pay more than the usual heparin on the basis that much of the pathology is attention to its meticulous closure, and consider due to spreading thrombosis, the methonium drugs also whether in such circumstances it is not wiser as ganglion blocking agents which will stop the to substitute thread or silk for catgut if the latter afferent visceral pain impulses and efferent be the material he routinely uses for suturing. secretomotor impulses. Both in our opinion are To say that the treatment is non-operative is dangerous; heparin especially, a dangerous drug not implying that it should be anything less than at any time, may well in these circumstances energetic. Treatment is directed to five main determine fatal haemorrhage. The methonium principles: drugs if used in sufficient dosage to have anv I. Relief of pain. ganglion blocking effect will produce a low blood Postgrad Med J: first published as 10.1136/pgmj.31.355.234 on 1 May 1955. Downloaded from 238 POSTGRADUATE MEDICAL JOURNAL May 1955 pressure which is clearly undesirable in the be guarded, both in terms of the short and long presence of thrombotic lesions. term outlook. Antibiotics should be used in order to try and As already indicated severe acute pancreatitis prevent bacterial invasion of the damaged tissues is often but one incident in a series of lesser adding its quota of trouble to the patient's illness. subacute attacks which may continue to occur, Despite these aids some patients will develop and should cause a search to be made for aetio- abscesses and these will have to be dealt with on logical f stio ome caies the condition general principles as they arise. When opened, progresses to chronic pancreatitis with evidence they frequently contain dark brown or black thick of increasing fibrisis and failure of both internal fluid, and sometimes pancreatic sloughs. and external secretion of the gland. The measre&s outlined above shouldcBe continued until the patient's cinical appearance, BIBLIOGRAPHY rate, of abdominal tenderness, CATTELL, R. B. and WARREN, K. W. (1953), 'Surgery of the pulse disappearance Pancreas,' 51. and blood chemistry indicate cessation of activity FITZ, R. (1899), Med. Rec., 35, 225. and a start to healing. HICKEN, N. F. and McALLISTER, A. J. (1952), Amer. J. Surg., the convalescent consideration 83, 781. During period HOLT, R. L. (1954), Annals of R.C.S., I5, 34. should be given to two questions. Has the HOWAT, H. T. (1952), 'Modern Trends in Gastro-Enterology,' diabetic tendencies ? What 766. patient developed MacKENZIE, WALTER C. (1954), 'Pancreatitis,' Annals of is the state of his biliary system ? If gall stones R.C.S., 15, 220. are present, plans will need to be laid for appro- MOYNIHAN, Sir B. (1926), Abdominal Operations, 2, 454. treatment after a suitable interval. OPIE, E. L. (I90O), Johns Hopkins Hosp. Bull., 12, I82. priate RICH, A. R. and DUFF, G. L. (1936), Johns Hopkin Hosp. Bull., The prognosis in these patients should always 56, 212. by copyright.

PULMONARY TUBERCULOSIS

(Postgraduate Medical Journal) http://pmj.bmj.com/ Price: 3s. 8d., post free INTRODUCTORY COLLAPSE THERAPY (MEDICAL) IN Maurice D.M., F.R.C.P. PULMONARY TUBERCULOSIS Davidson, F. H. Scadding, M.D., M.R.C.P. THE GENERAL MANAGEMENT OF IE SURGICAL COLLAPSE THERAPY IN PHTHISICAL PATIENT FROM THE PULMONARY TUBERCULOSIS PHYSICIAN'S STANDPOINT J. R. Belcher. on September 23, 2021 by guest. Protected L. E. Houghton, M.D. RESECTION FOR PULMONARY THE PRESENT POSITION OF CHEMO- TUBERCULOSIS THERAPY IN TUBERCULOSIS W. P. Cleland, M.R.C.P., F.R.C.S. John C. Roberts, M.D., M.R.C.P. MODERN METHODS OF DIAGNOSIS IN PULMONARY TUBERCULOSIS: THE PROBLEM OF TUBERCULOSIS IN CLINICAL, BACTERIOLOGICAL AND CHILDHOOD RADIOLOGICAL A. Margaret Macpherson, M.D., F.R.C.P. J. R. Bignall, M.D., M.R.C.P. Published by THE FELLOWSHIP OF POSTGRADUATE MEDICINE 60, Portland Place, London, W.1