The Clinical Picture of Pancreatic Insufficiency CHARLES L. BROWN, M.D.. Philadelphia

THERE ARE TWO KNOWN FUNCTIONS of the , * Minor degrees of pancreatic insufficiency that of internal secretion of , having to do may go unrecognized. There is a paucity of with the metabolism of carbohydrate, and that of symptoms and physical findings in mild and external secretion of , important in the proc- moderate degrees of insufficiency and in such ess of . The insufficiency of insulin results circumstances laboratory methods are neces- in the classic disease of mellitus. The insuf- sary to determine the presence of insufficiency. ficiency of the external secretion may be more ob- The clinical picture when insufficiency is well scure in its clinical manifestations. Pancreatic in- established may be characterized by loss in sufficiency, with or without disturbance in carbo- weighf; vague ; voluminous, light- hydrate metabolism, may be related to any of the colored, glistening stools in which fat globulets diseases of the pancreas which cause destruction or may be seen; changes in the concentration of impairment of function of the acinous glandular tis- pancreatic enzymes in the blood indicative of sue, such as chronic , tumor, hemor- lowered pancreatic function; diminished rhage, or stones. amounts of pancreatic enzymes in the duodenal Pancreatic insufficiency, theoretically, may arise juice, and the related poor digestion of fat and to some degree in other conditions in which the protein in the food. Lowered tolerance of car- nervous and/or humoral mechanisms of pancreatic bohydrate, as found in diabetes mellitus, may secretion are disturbed, but probably so-called func- or may not be present. The location and char- tional pancreatic insufficiency is of little or no clin- acter of the disease in the pancreas causing ical significance, since it would be expected to be so the insufficiency may or may not be apparent. mild, transient and masked by other symptoms as to be difficult of recognition. The external secretion of the pancreas contains dences of indigestion are immediate if complete three important enzymes: , which acts on obstruction of the pancreatic duct occurs. Partial starch; lipase, which splits fats; and trypsinogen, obstruction of the pancreatic duct may interfere which, after activation to trypsin, acts on proteins. with the egress of the only enough Insufficient amounts of these enzymes reaching the to make indigestion slower or intermittent in ap- intestinal tract produce the clinical features of the pearance. inadequate digestion of these three elementary food Minor degrees of pancreatic insufficiency may re- materials. Minor degrees of insfficiency go unrecog- main obscure or go unrecognized in chronic alco- nized. The digestion of fat and protein is not greatly holism, Laennec's of the liver, and gall- impaired until there is a pronounced decrease, prob- bladder disease. ably up to 75 per cent, in the lipase and trypsinogen Diseases which may have an associated pancreatic below hormal; and an even greater diminution of insufficiency are , carcinoma of the amylase is necessary before carbohydrate diges- pancreas, carcinoma of the ampulla of Vater, stone tion is measurably impaired. The appearance of in the ampulla or major ducts, and benign ulcer of gross evidence of the indigestion of these food ele- the involving the ampulla. ments, of which fat indigestion is the most easily Diseases in which pancreatic insufficiency most recognized, varies with the nature of the disease often occurs are of the pancreas and causing the insufficiency. In the chronic relapsing pancreatitis. In chronic relapsing disease process, except for the acute episodes, is pancreatitis, the pancreatic insufficiency is usually a slowly progressive, and the changes resulting from late manifestation. the indigestion may not appear clinically for weeks, months or years after the onset of the disease. Evi- SYMPTOMS OF PANCREATIC INSUFFICIENCY

From the Department of Medicine, Hahnemann Medical College The intent and purpose of this paper is primarily and Hospital, Philadelphia. concerned with the insufficiency of the external From the Symposium on Diseases of the Pancreas, presented before the Sections on G;eneral Medicine, General Surgery and Radiology at secretion of the pancreas; therefore, pancreatic dia- the 81st Annual Session of the California Medical Association, Los Angeles, April 27-30, 1952. betes mellitus, a form of pancreatic insufficiency of 172 CALIFORNIA MEDICINE the internal secretion, insulin, will not be included, vitamin deficiencies occur, and in particular the except as it may be related secondarily to severe and symptoms and physical findings of the deficiencies extensive destructive pancreatic disease. of vitamins A, B, D and K may be present, which The symptoms of pancreatic insufficiency per se will account for dryness of the skin, hyperkeratosis, are those of indigestion and malnutrition owing to glossitis, cheilosis, edema and neuritis, osteoporosis, the lack of proper digestive enzymes and inadequate and bleeding in the mucous membranes and skin. utilization of food materials. As was pointed out If the disease of the pancreas has been severe before, these inadequacies in slowly progressive dis- and extensive enough to involve enough islet cells, ease may be so minor, or so long in reaching clin- diabetes mellitus may be a part of the picture of ical proportions, as to remain unrecognized until pancreatic insufficiency. the disease causing the insufficiency is well advanced. Pancreatic insufficiency, in itself, probably does For these reasons the milder degrees of pancreatic not cause pain, and extensive and long standing pan- insufficiency may be without symptoms, and then creatic disease may not have associated pain. The accompanied by vague and indefinite symptoms of most severe and characteristic pain of pancreatic indigestion long before the gross evidences of the disease is associated with obstruction of the pan- nature of the insufficiency appear. creatic duct, or edema or hemorrhage into pancre- Acute pancreatic insufficiency accompanies com- atic tissue. However, the diseases of the pancreas plete, or nearly complete, obstruction of the pan- which lead to pancreatic insufficiency are frequently creatic duct, such as may occur with impaction by enough the cause of pain that the discussion of symp- stone, or compression by tumor or edematous in- toms would not be complete without some mention flammatory condition. The symptom of pain or of the location and character of pancreatic pain. painful discomfort owing to the obstruction so Indeed, the pain of pancreatic disease may lead to greatly overshadows the clinical evidences of the a diagnosis long before there is any clinical evi- insufficiency of enzymes that the clinical features of dence of pancreatic insufficiency. In the diagnosis insufficiency are unimportant except in the follow-up of chronic relapsing pancreatitis, one of the more observations, treatment and prognosis. common diseases with which pancreatic insufficiency The symptoms in chronic pancreatic insufficiency may be associated, the most important symptom is may be classified as general, digestive, nutritional, the recurrent episodes of upper abdominal pain." 2 and metabolic. This pain may be mild and last only a few hours, The general symptoms appear only in the more or it may be severe and prolonged. Usually it is profound and prolonged instances, and are manifest located in the epigastrium or more generally in the by weakness, fatigue, and gradual debilitation, prob- upper . At times it may be more on the ably related to the nutritional deficiency. right side of the upper abdomen and extend through The digestive symptoms vary in degree and char- or around to the corresponding level in the back, acter, but include sense of abdominal fullness, espe- which may simulate the pain of . At cially in the upper abdomen, flatulence, anorexia, other times it may be on the left side in the upper and minor abdominal cramping or discom- abdomen and extend to the corresponding level in fort. Vomiting may occur. The tendency is toward the back, and this location is considered more char- . or loose stools appear some acteristic. At still other times it may be described time in the course of the symptoms, usually when as band-like in the upper abdomen and back. It may and creatorrhea are well advanced. shift in these different locations and, indeed, it may When the insufficiency is severe the stools are volum- extend into or radiate into the anterior chest and inous, fatty or greasy, rancid, and malodorous, char- of shoulder regions. It tends to be gradual in onset and acteristic of the indigestion fat. disappearance. The character of the pain may be The nutritional and metabolic symptoms are re- steady or cramping, cutting, aching, boring, or lated to the severity and duration of the insufficiency, burning. The recumbent position may aggravate the and they vary from being unrecognizable to the pain, so that the patient may prefer to sit in a profound symptoms of weight loss, liver functional up impairment, hypoproteinemia, hypocalcemia, vita- bent forward position. min deficiency, and the vague painful discomforts The great variation in location and reference of which may be associated with osteoporosis. The in- pain probably is related to the extensiveness and ability to utilize fat and protein in particular ac- location or distribution of the pathologic lesion in counts for the weight loss, weakness, and wasting. the pancreas. Bliss, Burch, Martin, and Zollinger2 In the more severe instances there may be associated studied the localization of referred pancreatic pain fatty change in the liver with impaired hepatic func- induced by electric stimulation through electrodes tions. Severe hypoproteinemia will be accompanied placed in different parts of the human pancreas at by the clinical features of this condition. Multiple the time of surgical operation for biliary disease.

VOL. 77. NO. 3 * SEPTEMBER 1952 173 They found that pain stimulus in the head of the LABORATORY STUDIES pancreas localized in the epigastrium to the right of In general, laboratory tests of three types are em- midline and was distributed from the sixth to the ployed in the study of pancreatic insufficiency; eleventh thoracic dermatome on the right; pain namely, (1) gross, microscopic and chemical exam- arising in the body of the pancreas localized in the ination of stools; (2) examination of duodenal juice mid-epigastrium and was distributed from the sixth obtained through duodenal intubation under fluoro- to the eleventh thoracic dermatomes bilaterally; and scopic control; and (3) determination of response pain from the tail of the pancreas localized in the of lipase and amylase in the blood serum to pro- left epigastrium and was distributed from the sixth vocative stimulation. thoracic to the first lumbar dermatomes on the left. The high incidence of respiratory tract symptoms 1. The stool in pancreatic insufficiency in children with chronic pancreatic insufficiency Grossly the stool is bulky and light colored, and owing to fibrocystic disease of the pancreas should droplets of fat may be seen adherent to the fecal ma- be mentioned. These symptoms are associated with terial, or may be seen floating if the feces is put in bronchitis, bronchiectasis, or suppurative pulmo- water. Microscopically, there is an increased amount nary disease. It has been thought that this vulnera- of unhydrolysed fat, as demonstrated with Sudan 3 bility to respiratory infection is owing to nutri- stain; and many undigested meat fibers with the trans- tional deficiency; perhaps the keratomalacia of the verse striations clearly visible in the muscle fibers. bronchial mucosa associated with vitamin A defi- Chemically, there is pronounced increase in neutral ciency is a factor in partial bronchial obstruction and fat and nitrogen. With the patient on a low fat concurrent infection. Andersen' reported upon 22 diet, daily excretion of more than three grams of patients who, after early diagnosis, received dietary nitrogen suggests pancreatic insufficiency. therapy. A special formula supplemented by vita- Determination of the fat-nitrogen content in the mins and pancreatin was used and bronchial infec- stool does not identify the causes of the steatorrhea tion did not develop. or azotorrhea, but it is a measuring rod for the pres- ence of either. Further studies will be necessary to PHYSICAL EXAMINATION evaluate the causes. Chemical studies of partition of Usually in milder and moderate degrees of pan- fat may aid in distinction of idiopathic steatorrhea creatic insufficiency no abnormalities are noted upon from pancreatic deficiency but the quantitation of physical examination. When the insufficiency is pancreatic enzymes in the duodenum is more re- severe and of long standing, the physical abnormali- liable. ties are related to the secondary factors or complica- 2. Examination of duodenal juice obtained by duo- tions of nutritional and vitamin deficiencies and denal intubation under fluoroscopic control metabolic disorders. Abdominal distention, with Even though this method is subject to all of the flatulence, is usual. The disease of the pancreas inaccuracies of any procedure of capturing the fluid causing the insufficiency may be attended by abnor- contents in a hollow viscus by putting the end of a malities observable upon physical examination, such tube there under standardized circumstances, it pro- as general abdominal tenderness, especially in the vides the most reliable studies for directly defining upper abdomen, during and shortly after an acute or determining the degree of pancreatic insufficiency. episode of relapsing pancreatitis, or a palpable mass The studies on the duodenal juice obtained include of tumor or of the pancreas. It might be well quantity, determination of bicarbonate content, and to emphasize the importance of special effort to pal- quantitation of pancreatic enzymes. Decrease in the pate the pancreas. Grott5 described a method which enzymes is evidence of pancreatic insufficiency, and may be helpful. With the patient in lateral position the disturbance in the normal range pattern of these on his right side, the examiner stands in front of several factors may aid in differential diagnosis as to the patient and, with the left hand under the lower cause. Frequently in chronic pancreatitis there is portion of the thorax, uses his right hand to press decreased concentration of enzymes, although early inward and downward until it reaches the left edge in the' disease the volume may be normal. With pro- of the vertebral column. Then the procedure is re- gression of the disease, volume, bicarbonate content, peated with the patient in the lateral position on his and enzymes decrease. left side and the examiner using his left hand for palpatory maneuver. This permits the stomach and 3. Response of lipase and amylase in the blood duodenum to be pushed forward and the examining serum to provocative stimulation of the pancreas hand can get more nearly over the space between The agents used for stimulation are secretin, Ure- the stomach and the vertebral column. choline,® neostigmine, or combinations of any of 174 CALIFORNIA MEDICINE these with morphine. The experience with these tests Urecholine, or neostigmine, or any of them in com- in the department of of Hahne- bination with morphine. mann Medical College points to the following de- 235 North Fifteenth Street. ductions: (a) In general, if the pancreas is normal there is REFERENCES 1. Andersen, D. H.: Therapy and prognosis of fibrocystic no response to secretin, Urecholine, or neostigmine disease of the pancreas, Pediatrics, 3:406, 1949. alone, but a prompt increase in serum content of 2. Bliss, W. R., Burch, B., Martin, M. M., and Zollinger, lipase and amylase after combination with mor- R. M.: Localization of referred pancreatic pain induced by phine. electric stimulation, Gastroenterology, 16:317-323, Oct. 1950. 3. Comfort, M. W., Gambill, E. E., and Baggenstoss, A. H.: (b) In general, in the presence of obstructed pan- Chronic relapsing pancreatitis: a study of twenty-nine cases without associated disease of the biliary or gastrointestinal creas, without extensive acinous atrophy, there is an tract, Gastroenterology, 6:239-285, April; 376-408, May increase of 50 per cent or more (above a base line) 1946. in amylase or lipase content after the use of secretin, 4. Gambill, E. C., Comfort, M. W., and Baggenstoss, A. H.: Chronic relapsing pancreatitis: an analysis of 27 cases asso- Urecholine, or neostigmine. ciated with disease of the , Gastroenterology, (c) In general, if there is extensive acinous at- 11:1-33, July 1948. rophy of the pancreas no increase in serum content 5. Grott, J. W.: The palpatory examination of the pan- creas; description of a new method, American Journal of of amylase or lipase occurs after the use of secretin, Digestive Diseases, 16:332, 1949.

Telephone Technique How is the telephone answered in your office? Brusquely and loftily, or pleasantly and with implication that the patient is important? Thought given to telephone answering will be immediately helpful in your own relationship with patients, and ultimately in shaping the public attitude toward medicine. For example: 1. Initial response to ringing telephone: WRONG: "Doctor's office." "Just a minute, please." "Hello." RIGHT: "Doctor Jones's office, Miss Briarly speaking." "Garfield 00000" (if there are several physicians using the same number). "Doctors Jones and Black; may I help you?" 2. On making appointments: WRONG: "I can give you Thursday at two." "Doctor can see you Monday morning." "Wednesday afternoon is the doctor's day off." RIGHT: "Could you make it on Thursday at two?" "Monday morning would be a good time if that is convenient." "Doctor Jones will not be able to see you on Wednesday afternoon; could you come in Thursday?"

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