Diseases of the Pancreas

BY LOUIS STARR, M.D.

Until the middle of the seventeenth century the prevalent views upon the functions and diseases of the pancreas were vague in the extreme. By some the organ was regarded simply as a cushion provided for the protection of the neighboring blood-vessels and nerves; by others it was looked upon as the seat of lesion in many very diverse diseases, as ague, hypochondriasis, melancholia, and so on.

In 1642, Wirsung's discovery of an excretory duct demonstrated the fact that the pancreas was a special organ, and initiated the successful investigation of the physiology and pathology of the gland. For many years after this, however, little progress was made, and it is only comparatively recent investigations that have furnished definite and reliable information upon the subject. Even now our knowledge of the clinical and pathological features of diseases of the pancreas is far behind that of many of the other viscera of the body, the chief reasons for this being the uncertainty in regard to the physiology of the gland and the rarity with which its lesions are primary and uncomplicated.

ANATOMY AND PHYSIOLOGY.—The pancreas is a long, somewhat flattened, narrow, acinous gland, pinkish-white in color, and of looser texture than the salivary glands, which it otherwise closely resembles in structure. It is hammer-shaped, measures from six to eight inches in length, one and a half inches in breadth, and about three-fourths of an inch in thickness, and varies in weight from three to five ounces. The gland is situated in the upper part of the abdominal cavity; the expanded portion, or head, lies in the concavity of the duodenum; thence it extends transversely across the epigastric and both hypochondriac regions on a level with the first lumbar vertebra and in contact with the posterior abdominal wall. As it passes toward the left it gradually decreases in size, and the narrowest part, or tail, rests against the spleen. Behind the organ are the crura of the diaphragm, the aorta, the inferior cava, the superior mesenteric vessels, and the solar plexus; in front of it, the stomach and the left lobe of the liver. Its anterior surface alone is invested with peritoneum, being covered by the posterior layer of the lesser omentum. The ascending portion of the head is intimately connected with the duodenum by dense connective tissue, and at times the descending portion, by extending backward and outward, forms an almost complete ring around the gut; the body is loosely attached by connective tissue to the posterior abdominal wall, and the left extremity and tail are joined to the left kidney and suprarenal capsule and to the spleen by loose areolar tissue. The gland is supplied with arterial blood by branches springing from the pancreatico-duodenal and splenic vessels; its veins join the splenic and superior mesenteric veins; its lymphatics communicate with the lumbar glands; and its nerves are branches from the solar plexus. The principal excretory duct, the canal of Wirsung, has at its widest part the calibre of a goose-quill. It begins by the union of five small branches at the tail, and extends transversely through the substance of the gland from left to right, nearer the lower than the upper border, and the anterior than the posterior surface; it is joined throughout its course by numerous small branches from the acini, which enter it at acute angles. In the head the duct curves slightly downward, and as a rule opens with the ductus choledochus into the ampulla of Vater in the second portion of the duodenum; sometimes, however, it has a separate opening into the intestine. A second, smaller, duct runs from the ascending portion of the head, and usually joins the main duct, but may also open independently.

The acini of the gland are from .045 mm. to .090 mm. in diameter, and are composed of a very thin membrane lined with pavement cells. The thin walls of the excretory ducts are formed of connective tissue and elastic fibres, and are lined by a single layer of small cylindrical epithelial cells. The terminal extremities of the ducts form a complete network around the glandular cells, resembling the intralobular biliary canaliculi. The acini are imbedded in a mass of adipose tissue which contains the vessels and nerves.

The topographical relation of the head of the pancreas to the ductus choledochus is of clinical importance. As a rule (fifteen times in twenty-two, Wyss), the bile-duct descends near the head, toward the duodenum; frequently it runs through this part of the organ, being either partially or entirely surrounded by the gland substance. Now, when the bile-duct merely passes over the pancreas, any enlargement, unless excessive, would simply push it aside, but when it passes through the head, a comparatively slight amount of disease is sufficient to close it entirely and cause jaundice.

It is only since the observations of Bernard in 1848 that the prominence of the pancreatic juice as a digestive fluid has been recognized. It fulfils several important purposes: in the first place, it emulsifies the fatty articles of food; secondly, it converts starch and cane-sugar into glucose; and, finally, it supplements the action of the gastric juice upon nitrogenous materials and completes their digestion. Each of these changes is probably brought about through the agency of a special ferment (Danilewsky). The pancreatic juice is not secreted continuously. According to the observations of Bernstein, there are two separate secretory flows following each ingestion of food—one occurring shortly after the food enters the stomach; the other a few hours later, corresponding in time to the passage of the food from the stomach into the intestine, the latter being followed by a period of rest until the next meal. Both the condition of nausea and the act of vomiting arrest the secretion. When the vagus is divided and the central extremity of the cut nerve is irritated, the secretion is also arrested, and remains checked for a long time. The arrest in each instance is attributed to reflex action of the spinal cord and sympathetic nerve. At the same time, irritation of the mucous membrane of the stomach caused by the presence of food increases the flow of pancreatic juice, and so too does simple section of the nerves which accompany the arteries. It would seem, therefore, that the gland is under the influence of two sets of nerves from the vagus—one inhibiting, the other exciting, its secretion.

GENERAL ETIOLOGY.—Pancreatic disease occurs more frequently in men than in women. No period of life is exempt from it, but it is most commonly met with in the aged. The predisposing causes are constitutional syphilis, pregnancy, and hereditary tendency. Among the apparent exciting causes may be mentioned the habitual over-use of alcoholic drinks, gluttony, the excessive use of tobacco, suppression of the menstrual flux, the abuse of purgatives, excessive and prolonged mercurial medication, and mechanical injuries, either prolonged pressure or blows upon the epigastrium. As a secondary affection, disease of the pancreas is associated with chronic diseases of the heart, lungs, liver, alimentary canal, and abdominal glands, and the organ may be the seat of metastatic abscesses and tumors.

GENERAL SYMPTOMATOLOGY.—The objective symptoms are—rapid and extreme emaciation of the entire body; sialorrhoea; obstinate diarrhoea with viscid stools; fatty stools; lipuria; and the presence of masses of undigested striped muscular fibres in the stools.

The well-established fat-absorbing and peptonizing properties of the pancreatic juice furnish a ready explanation of the wasting of the body which occurs when this secretion is arrested, diminished in quantity, or altered in quality by disease. Emaciation is not a constant symptom of pancreatic disease. A number of cases are mentioned by Abercrombie, Claessen, and Schiff in which, notwithstanding disease of the gland and complete closure of the duct, revealed by post-mortem examination, the patients during life were not only well nourished, but even moderately corpulent. In such instances it is probable that the digestive functions of the absent pancreatic juice are more or less adequately performed by the bile and succus entericus. When present, emaciation is an early symptom; it is at the same time progressive, and is usually very intense in degree, being most marked in those cases where there is associated hepatic disease or obstruction to the passage of bile into the intestine, where the disease of the pancreas interferes mechanically with the processes of nutrition by pressing upon the pyloric extremity of the stomach or upon the duodenum, and when the organ is the seat of carcinomatous growths. In the last-named condition, in addition to the perversion or arrest of the secretion, the loss of flesh is attributable to the general causes of malnutrition attendant upon carcinoma wherever situated.

Sialorrhoea, or an excessive secretion from the salivary glands, is noticeable as a symptom of disease of the pancreas only when there is an associated lesion of the stomach, either of a catarrhal or cancerous nature. Under these circumstances a quantity—six or eight fluidounces—of a colorless, slightly opalescent, and adhesive and alkaline fluid may be expelled from the mouth at once as an early morning pyrosis; or by frequent and repeated acts of expectoration, following a sudden filling of the mouth with fluid, a large bulk of thin saliva may be expelled during the day. This hypersecretion must not be looked upon as any indication of an especial sympathy existing between the salivary glands and the pancreas, neither can it be regarded as a pancreatic flux with a regurgitation of the fluid from the duodenum into the stomach and thence through the oesophagus into the mouth, since during the nausea that must always attend the passage of the intestinal contents into the stomach the pancreatic secretion is arrested, and since the liquid contains salivary, and not pancreatic, elements.

The diarrhoea pancreatica is the least constant of all the objective symptoms; in fact, constipation is present in many pancreatic affections, notably carcinoma. The fecal evacuations in this condition are frequent, thin, viscid, and contain an abundance of leucin. Under the microscope the leucin appears either in the form of concentrically sheathed globules, or as small crystalline rods and scales collected together in the form of wheels or aggregated in clusters. This form of diarrhoea may be attributed to a hypersecretion from the pancreas.

That the presence of fat in the stools is an important diagnostic symptom of pancreatic disease is proved both by clinical and experimental observations. The characters of these stools vary considerably. The fat may appear mixed with the feces in small lumps, ranging in size from a pea to a hazelnut, yellowish-white in color, soluble in æther, and easily melted and burned. Again, after the evacuation has become cool fat may be seen covering the fecal masses, collected into a thick cake around the edges of the containing vessel, or, when the feces are liquid, floating as free oil on the surface. Finally, the fat may be in a crystalline form, the crystals being needle-shaped and aggregated into sheaves and tufts. The quantity of fat also varies. It may be present only in small quantities, or may even be entirely absent from the evacuations in those cases in which the secretion from the pancreas is simply diminished, and the amount is greatest in those instances where there is a simultaneous arrest of the pancreatic and hepatic secretions. It must be remembered, too, that even in health the stools may contain fat; this occurs when an excess of oleaginous food is consumed and after the administration of castor oil or cod-liver oil. These conditions must be eliminated, therefore, in estimating the value of fatty stools as a diagnostic symptom; if, then, at the same time, coincident disease of the liver can be excluded, the symptom becomes almost pathognomonic. The appearance of fat in the stools may be due not only to an arrest of the pancreatic secretion, but also to pressure upon the large lymphatic trunks, interfering with the circulation of the chyle and checking the absorption of fat from the intestine.

Usually, the amount of fat expelled is in direct proportion to the quantity consumed, but occasionally the former greatly exceeds the latter. In such cases there must be some other source for the evacuated fat than the food; and it is probable that fat from the adipose tissue passes into the blood, and thence through the mesenteric vessels into the intestine. This theory would likewise account in part for the rapid and extreme wasting, and for another less frequently observed symptom—namely, lipuria. A case is recorded by Clark of medullary cancer of the pancreas with nutmeg liver, and another by Bowditch of cancer of the pancreas and liver in which lipuria was noted. The fat was observed, after the urine had cooled, floating about on the surface in masses or globules; differing, therefore, from chyluria, for in this condition the fat is present in the form of an emulsion, and gives the urine either a uniform milk-like appearance, or, after it has been allowed to stand, rests upon the surface in a creamy layer.

When the pancreatic secretion is arrested, most of the animal food which has escaped gastric digestion will pass unchanged through the intestine and give rise to another characteristic condition of the evacuations—namely, the presence in the feces of undigested striped muscular fibres. The amount of these fibres, and indeed their appearance at all in any given case, will depend directly upon the nature of the food consumed.

SUBJECTIVE SYMPTOMS.—The subjective symptoms of disease of the pancreas are abnormal sensations in the epigastrium, and pain.

The abnormal sensations in the epigastrium are weight and pressure, attended at times by præcordial oppression and discomfort. The feeling of weight is usually deep-seated, may be intermittent or constant, and is generally increased or developed by pressure. It is often influenced by position, the assumption of the erect posture or turning from side to side giving rise to a stretching or dragging sensation, as if a heavy body were falling downward or moving about in the upper abdomen.

The pain may be due either to an inflammation of the peritoneum covering the gland or to pressure upon the solar plexus, and consequently varies in character. When it depends upon localized peritonitis, it is constant, circumscribed, and deeply seated in the epigastrium at a point midway between the tip of the ensiform cartilage and the umbilicus; it is rather acute, and is greatly augmented by pressure. The second variety occurs in paroxysms, and is neuralgic in character, the sharp, excessively severe lancinating pains extending from the epigastrium through to the back, upward into the thorax, and downward into the abdomen. These paroxysms—in reality attacks of coeliac neuralgia—are attended by great anxiety, restlessness, and oppression and a tendency to syncope. That calculi in the duct of Wirsung, tightly grasped at the position of arrest, may give rise to paroxysms of pain analogous to biliary colic, cannot be doubted, though there are no positive facts in support of this view.

PRESSURE SYMPTOMS.—When the pancreas becomes enlarged it encroaches upon the neighboring blood-vessels and viscera, interferes with their functions, and thus produces prominent symptoms.

The ductus choledochus from its close relation to the head of the gland is especially liable to become obstructed, with the consequent production of chronic jaundice and the general effects of the absence of bile from the intestinal canal. Pressure upon the portal vein gives rise to enlargement of the spleen; on the inferior cava, to oedema of the feet and legs; and on the aorta, occasionally, to aneurismal dilatation of the vessel above the point of obstruction and to subsequent alteration in the size of the heart. By encroaching on the stomach an enlarged pancreas may cause either displacement of the viscus or stenosis at its pyloric extremity, attended with occasional vomiting of large quantities of grumous, fermenting liquid, pain, constipation, general failure of health, and the distinctive physical signs of dilatation of the stomach. The duodenum may also be pressed upon and more or less occluded, and pain and vomiting occur several hours after food is taken. Occasionally hydronephrosis is produced, the accumulation being usually in the right kidney and due to obstruction of the corresponding ureter.

A sufficient number of cases have been collected to show that there is an intimate connection between disease of the pancreas and diabetes mellitus. One or other condition may take the precedence, melituria occurring during the progress of pancreatic disease, demonstrating the onset of diabetes, and the appearance of fatty stools in diabetes a secondary involvement of the pancreas. Various theories have been advanced to account for this association, but the true explanation seems to be based upon the experiments of Munk and Klebs. By experimenting upon dogs these observers found that extirpation of the solar plexus produced either permanent or temporary diabetes, whereas section of the hepatic and splanchnic nerves, removal of the pancreas, or ligature of the duct of Wirsung was without effect. From the intimate anatomical relation of the pancreas to the solar plexus it is easy to understand how disease of the gland may give rise to alterations in the nerve-structure, either by direct pressure or by the extension of inflammation along the nerve-fibres connecting the gland with the ganglia; and these alterations in time produce diabetes. In the instances in which diabetes is the primary affection the condition of the pancreas, as proved by post-mortem section, is usually one of simple or fatty atrophy; and it may be assumed that a lesion of the solar plexus is the cause of both diseases, the changes in the pancreas being produced in a similar way to the atrophy of the submaxillary gland after section of the vaso-motor nerves in Bernard's experiments.

The same nerve-lesion may give rise to bronzing of the skin, and two cases are recorded in which disease of the pancreas (cheesy infiltration, cancer) was attended by this symptom.

PHYSICAL SIGNS.—To make a successful exploration of the pancreas the stomach and colon should be as far as possible empty, and the patient placed in a position, with the head and shoulders slightly elevated and the thighs drawn up toward the belly, to relax the abdominal muscles; or if necessary this relaxation must be brought about by the administration of æther. The knee-elbow position is often preferable to the dorsal position in practising palpation.

The condition of the gland giving rise to physical signs is one of enlargement, affecting chiefly and primarily its head, and due generally to the presence of some morbid growth.

Inspection reveals either a diffuse bulging of the upper third of the abdomen to the right of the median line, or a well-defined tumor situated beneath the right costal border, about the line of junction of the right hypochondriac and epigastric regions. Often the pancreatic tumor does not come in direct contact with the abdominal wall, but presses against and thrusts forward the left lobe of the liver, producing simply a prominence in the epigastrium. In the first condition palpation elicits an ill-defined sense of resistance; in the second, the fingers readily outline a tumor, which is slightly movable, rounded in shape, firm or fluctuating, with a smooth or nodulated surface, usually tender to the touch, and often giving a false impulse transmitted from the aorta lying beneath; and in the third, the smooth surface and the sharp edge of the left lobe of the liver are easily distinguishable.

Percussion over a pancreatic tumor is commonly dully-tympanitic, absolute flatness occurring only when it is very large and comes directly in contact with the abdominal wall, pushing aside the stomach and intestines.

On auscultation a blowing murmur may, in some instances, be heard over the tumor. These murmurs are due to pressure upon the aorta, and must be distinguished from the sound produced in aneurism of this vessel.

The various complications of pancreatic disease, such as dilatation of the stomach, ascites, and secondary lesions of the liver, greatly modify the physical signs, and sometimes entirely prevent an exploration of the gland.