THE AETIOLOGY,PATHOLOGY, •DIAGNOSIS AND TREATMENT # OP ACUTE PANCREATITIS BY R.A.RUSSELL TAYLOR B.Sc., M.B.Ch.B., F.R.C.S.,(Eng) M.R.C.O.G ProQuest Number: 13870162 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 13870162 Published by ProQuest LLC(2019). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 THE AETIOLOGY, PATHOLOGY, DIAGNOSIS AND TREATMENT OF ACUTE PANCREATITIS.. A REVIEW OF 110 CASES. In the preparation of this thesis, only eases which were proved at operation, at post-mortem, or clinically with a raised urinary diastase or serum amylase, have been included. In order to appreciate thoroughly the difficulties which face the surgeon in the diagnosis and treatment of acute pancreatitis,it is essential to.give a resume of the aetiology and pathology of this still obscure condition. A E T I O L O G Y . I am indebted to Mc¥horter (1932) for the following table giving the classification of the aetiology of acute pancreatitis and to which I have made a few additions 2- A. Non-infectious origin.. 1. Obstruction. Due to 1, Gall stones 2. Pancreatic calculi 3- Round worms h- Tumours of the head of the pancreas 5. Aneurysms in the neighbouring vessels 6* Foreign bodies, e.g. a barley corn 7. Spasm of sphincter of Oddi 8. Proliferative metaplasia of the pancreatic duct epithelium -2- 2. Chemical Activation of ferments resulting from 1. Bile infected fey bacteria. 2. Cell debris and degenerated duct contents 3. Duodenal contents Enterokinase in the mucosa of the gall bladder 5* Autolysis 3* Trauma 1. Penetrating or non-penetrating abdominal wounds 2. During operations on stomach, duodenum, or lower end of common bile duct. h* Degenerative changes in the pancreas 1. Ischaemia of pancreas 2. Vascular degeneration 3. Haemorrhage i+. Toxic changes following systemic disease 5« Secondary to malignant or benign tumours -B. Infectious origin. 1. Extension alqng the lymphatics to glandular group in region of head of pancreas 2. Blood stream - usually resulting from intestinal infection 3* Extension along the pancreatic ducts from the duodenum or bile tracts. I}.. By direct extension from an infected focus. 5. Following activation by bacteria in the normal gland. 6. By bacterial permeability from adjacent lateral viscera. 7. By direct contiguity through the bile duct when it is embraced by the head of the pancreas. C. Combination of two or more of the above factors. First of all it must be pointed out that the relative frequency of different types of ductal arrangement, varies greatly according to the observers. Mann and Giordano (1923) stated that a common channel could be formed by the bile duct and the duct of Wirsung by obstruction at the ampulla of Vater in only 3*5$ of subjects. Gameron and Noble (1924) prepared casts of the ducts and found that the bile and pancreatic ducts communicated in 75$ of cases, whilst Howard and Jones (1947) observed that in over 50% of cases there is the anatomical possibility for the formation of this common channel. Popper et al (194-8) state that there is a common channel in 89$ of cases of pancreatic oedema, acute pancreatitis and pancreatic necrosis, but very few observation similar to the above have been done on definite cases of acute pancreatitis and extensive investigations on this most important point would be invaluable. Howard and Jones (1947) found that where there was an obstruction at the ampulla of Vater, fluid injected into the common bile duct refluxed into the duct of Wirsung in 54$ of specimens. Incases where the duct of Santorini was present, the incidence of reflux rose to 82$. ft is, therefore, at present justifiable to suggest that, other things being equal, that there might be a greater -k- ineidence of acute pancreatitis in patients with a patent duct of Santorini. To pursue this further, it is also reasonable to assume that when there is an obstruction at the ampulla of Vater, the pressure in the pancreatic ducts is less than that in the biliary passages when there is a patent duct of Santorini, thus allowing a reflux of bile along the duct of Wirsung. That this is not the whole story is evident from the fact that cases of acute pancreatitis have also been described in which the ducts have opened separately into the duodenum, and rare cases in which the necrosis has been restricted to the region drained by the duct of Santorini. In 50% of cases, it is said that the obstruction is caused by a gall-stone, but in less than 5% of cases is this stone found, as it may have passed into the intestine after producing oedema or necrosis of the pancreas. Other causes of obstruction may be pancreatic calculi, round worms, ** tumours of the head of the pancreas, aneurysms in the neighbouring vessels and in a case described by Forty (1939) a barley corn. Obstruction which would allow reflux of bile along the pancreatic duct may also be produced by spasm of the sphincter of Oddi; the spasm is usually secondary to acute gastro-duodenitis which might be secondary to acute corrosive poisoning or occurs reflexly in the same way as pylorospasm, in cases of acute cholecystitis. In a large number of cases, there is a marked proliferative metaplasia of the pancreatic duct epithelium, which causes a certain degree of obstruction and stagnation of bile and pancreatic juice with a subsequent rise of -5- pressure and activation of the trypsinogen in the intraductal system. Acute haemorrhagic pancreatitis has also been produced by injecting a large number of irfitating fluids (hot bland substances) into the pancreatic duct, but it was pointed out by Rich and Duff (1936) that the typical lesion is not produced unless the amount of fluid injected is sufficient to rupture the pancreatic acini and they conclude that the escape of trypsin into the interstitial tissues is . the essential causative factor. Pure bile appears to be incapable of activating trypsinogen to trypsin, but it has been proved that •enterokinase in the mucosa of the gall bladder and bile infected by bacteria and cell debris may do so. If infected bile is forced along Wirsung*s duct, the bile salts will activate the pancreatic zymogens, and there is digestion of the tissues which produces oedema, necrosis and haemorrhage. Popper et al (1948) attempted to transform pancreatic oedema into pancreatic necrosis by the following methods, but all with negative results 1. Ligation of cisterna chyli ino rder to block the lymphatic drainage from the pancreas 2. Temporary clamping of the portal vein 3* Shock produced by "trypsin 4* Gross trauma 6- They also showed that temporary occlusion of the gastro­ duodenal artery applied for JO-ii-O minutes in a day, did not cause any marked microscopic changes in the pancreas, but the same experiment performed on an animal with pancreatic oedema led to the development of pancreatitis, the extent of ^hich was determined by the previous degree of oedema. In cases of low grade oedema, only fat necrosis developed, but in cases with extensive oedema, all the pathological changes of acute pancreatitis were present. Wightman (19US) pointed out that the amount of damage produced,depended upon the volume of juice which has diffused into the connective tissue of the gland, the concentration of the enzymes in the juice, usually greatest in amount 2-3 hours after a meal, and the number of large blood vessels with which it ;came in contact. The pancreas may also be infected from distant foci by the blood stream as is well illustrated in cases suffering from infective endocarditis, cholecystitis, ulcerative colitis, appendicitis, and pyaemia. Pancreatic abscesses may also result from retrograde thrombosis and suppurative pyelophlebitis. Acute pancreatitis may also be observed as a complication of influenza, typhoid fever, small pox and mumps, but in the latter cases, suppuration or necrosis never occur; very rarely it has been attributed to tuberculosis and syphilis. The frequent association of acute pancreatitis with infection of the biliary tract suggests that the lymphatic route ✓ is a possible connection between the inflamed gall-bladder -7- and the pancreas, but the experiments of Kaufmann (1927) on rabbits practically discounted this, but further investigations, however, on this point are definitely advisable. Paxton and Payne (19^+8) found that 18$ of their cases were admitted to hospital in an intoxicated condition, and that in 20$ of cases, the pain came on immediately after a heavy meal. Cole (1938), however, found that the interval between a meal and the onset of pain was usually 2 - 3 hours. Cases of acute pancreatitis have followed penetrating abdominal injuries. According to Naffziger and McCorkle (19U3) it may also occur during the course of operation on the stomach, duodenum or lower end of the common bile duct, where the pancreas has been injured. Shallow and Wagner (19U7) U% declare that there cases account for 2$- of all recorded cases and that there is a definite latent period preceding the appearance of the symptoms. Ackerman (19^+2) reported a case of acute pancreatitis which followed transfusion with incompatible blood, which at autopsy showed thrombosis of the pancreatic veins. Pagel and Woolf (19J48) recorded a case of aseptic necrosis of the pancreas due to arterial thrombosis occurring in malignant hypertension and concluded th t neither the clinical nor the anatomical picture revealed any relation ship to acute haemorihagic pane ■ atiti onn/or pancreatic fat s. necrosis* -8- P A T H O L O G Y , Acute pancreatitis occurs most commonly about i+,0-60 years of age and with about equal frequency in the two sexes. There also seems to be a definite association with obesity, cholecystitis and cholelithiasis. Pratt (19U0) maintains that acute pancreatitis is not an infection but an intoxication by the pancreatic ferments. Nevertheless, the intensity of the primary destructive changes determines the extent of the pathological changes because this condition of auto-digestion may be self perpetuating and progressive even although the original stimulus has been removed. The progress of the disease may be continuous or intermittent and it may become arrested at any stage. Appearances at Post Mortem. The body is sometimes very obese, and in approximately 50$ of‘cases the patient is overweight. There may be local discolouration of the abdominal wall around the umbilicus (Cullen1s sign) and in the loins (Grey Turner’s sign). This disoolouration is only seen in severe cases where the patient has lived for 2 - 3 days after the acute onset and must not be confused with post-mortem staining. On opening the abdomen, it must be remembered that acute necrosis may be present and yet macroscopically the pancreas may appear normal. The mildest type of acute pancreatitis is that known clinically as "transient pancreatitis"