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nying the epithelial character of the cells which com-



HISTOLOGY OF THE PANCREAS. 75

pose them, have emphasized a supposed resemblance to
lymphoid tissue. By certain methods of preparation,
notably after hardening in alcohol, the cell protoplasm
is inconspicuous, and the nucleus deeply stained may
resemble that of a lymphocyte ; the arrangement of
cells in groups within the meshes of a capillary net-work
gives superficially the appearance of a lymphoid follicle.

Renaut has described the pancreas as a lympho-
glandular organ composed, he has conceived, of glan-
dular structures and lymphoid tissue in intimate relation.
He has described the cell-groups as "points foUiculaires"
in which cells of a glandular type are situated in the
meshes of a reticular tissue. Mouret has supported
Renaut's somewhat ill-defined conception of a lympho-
glandular organ, but has regarded the cell-groups as
small masses of lymphoid tissue. Kiihne and Lea
and Dieckhoff think it probable that they are small
lymph follicles. Schlesinger regards them as a variety
of lymph follicle of which the cells differ from those
of ordinary lymphoid tissue. Podwyssotski calls them
pseudo-follicles, and states that though they resemble
lymph follicles their cells have nothing in common with
lymphoid cells ; while Renaut in his recent treatise on
histology, abandoning his former view, describes the
common origin of the interacinar cell-groups and the
secreting acini.

It has been suggested by several observers, Laguesse
and others, that the islands of Langerhans represent a



76 DISEASE OF THE PANCREAS.

stage in the embryologlcal development of the glandular
acini, those found in the adult organ being persistent
rudimentary structures. Subsequent observations upon
the histogenesis of the pancreas have caused Laguesse
to abandon this view.

When throughout the pancreas are found structures
composed of cells differing from those of the acini,
having a different arrangement and bearing a peculiar
relation to the blood-vessels, it seems probable that,
formed in embryologlcal life, they possess an anatomical
identity as definite as that of the glomeruli of the kid-
neys or of the Malpighian bodies of the spleen, and like
them subserve some special function. Schaffer directs
attention to their similarity to the small ductless struc-
tures, the carotid and coccygeal glands and the para-
thyroid bodies, which are also composed of anasto-
mosing columns of epithelial cells.

The epithelial nature of the cells composing the
islands of Langerhans has been clearly demonstrated
by embryologlcal investigation. Laguesse has studied
the development of these bodies in the embryo sheep.
He finds that at an early period of growth the pancreas
is composed of tortuous anastomosing tubules formed
by a single layer of epithelial cells. Here and there
occur cells which stain more deeply than those about
them and, like the border cells of the stomach, are situ-
ated near the outer surface of the tubule. These cells
proliferate to form solid outgrowths upon the tubule and



HISTOLOGY OF THE PANCREAS. ^'^

constitute what he calls primary islands of Langerhans.
At a later stage the secreting acini are formed as buds,
from the wall of the original tubules, and within them can
be recognized two kinds of cells, the ordinary glandular
cell containing zymogen granules and the centro-acinar
cells which form a second more or less continuous row
superimposed upon the secreting cells. At a still later
stage islands of Langerhans continue to be formed, but
their development differs from that of those which are
first formed, for, accepting the observations of Lewas-
chew to be mentioned later, Laguesse thinks that groups
of acini undergo alterations by which they are trans-
formed into interacinar islands, designated by him
secondary islands of Langerhans. This mode of forma-
tion has not been confirmed, and, as will be shown later,
does not occur.

Renaut has described the histogenesis of the pan-
creatic lobule. His description of the early stages of
development agrees with that given by Laguesse.
The primitive dorsal and ventral outgrowths from the
wall of the duodenum form numerous branches which
ramify in the dorsal mesentery of the intestine. At
first these branches are solid, but soon they acquire a
lumen about which the cells are arranged in a single row,
and, anastomosing between themselves, they resemble
the tubular columns which form the liver of certain
lower vertebrates. At intervals along- their walls are
formed short outgrowths terminating in a rosette-like



78 DISEASE OF THE PANCREAS.

group of blind pouches. At the base or within such a
group of primitive acini at least one island of Langer-
hans is formed by differentiation and multiplication of
the peculiar cells already described by Laguesse. The -
rosette-like group of acini and at least one island of
Langerhans represent the primary gland lobule in its
undev.eloped form, and by subsequent growth give rise
to the primary lobule of the adult gland.

The cells which compose the interacinar islands in
the adult human pancreas resemble in type the epithe-
lial cells of the acini. They have a large, round, occa-
sionally oval vesicular nucleus and well-defined cell-
body. The basal zone of the secreting cell, as is well
known, stains deeply with nuclear dyes, for example,
hsematoxylin or methylene blue, while the central
part, which contains zymogen granules, remains un-
stained. The cells of the island, on the contrary, are
by nuclear dyes entirely unstained, while with eosin their
protoplasm takes a homogeneous bright pink color.
The nuclei differ but little from those of neighboring
acini ; they vary considerably in size, and not infre-
quently one finds very large, round vesicular nuclei
the diameter of which is two or more times that of the
adjacent cells. Occasionally the cells, forming columns
between which lie anastomosing capillaries, are very
closely packed together, and nuclei are situated almost
side by side ; more frequently the cells of the island are
less numerous and nuclei are less closely crowded.



HISTOLOGY OF THE PANCREAS. 79

Dog-iel and later Stangl have shown that fat is
normally present in the protoplasm of the cells. Nu-
merous very fine droplets of almost uniform size are
abundant in the islands of Langerhans, while fat drop-
lets within the secreting acini, often much larger, vary
greatly in size and are more sparsely scattered.

The outline of the island is usually round or oval,
and is not infrequently accentuated by a delicate circle
of fibrous tissue. In other instances the outline is less
sharp and the body accommodates its shape to that
of the neighboring acini. Occasionally one sees, ap-
parently within the island, cells arranged, as in the
acini, about a central lumen, and indeed in many in-
stances it is difficult to convince one's self that they do
not form part of it. An impression is produced that
the columns of the island are in continuity with cells
having an acinar arrangement. Since the islands and
the secreting acini have a common origin, it is not
inconceivable that they may occasionally remain con-
tinuous in the adult organ. When the foetal pancreas
is affected by congenital syphilis, the islands of Langer-
hans, I have found, retain their continuity with the
secreting structures (see chapter vii.).

In the human pancreas islands of Langerhans were
found to be more numerous in the splenic end or tail
than elsewhere. To obtain a numerical statement of
their relative abundance, their number was determined
n a sectional area of 0.5 square centimetre. Sections



8o



DISEASE OF THE PANCREAS.



about ten micromillimetres thick were made (a) from the
enlarged duodenal part of the pancreas, — that is, from the
head, — (d) from the mid-part of the body, and (c) from
the splenic end or tail. The following table gives the
number in 0.5 square centimetre of sections taken from
the head, body, and tail of ten normal organs :

TABLE.



Number.


Head.


Body.


Tail.


I


1 1


13

25


30

42


2 ...


30


3


4


4


19


4 . . , .


4


10


13


5


27


18


59


6


25


27


26


7


18


18


29


8


6


10


29


9 -


44


32


61


10


14


23


32




Mean


18.3


18.0


34-0



The table shows that islands of Langerhans are
more abundant in the tail or splenic end than in the
head or in the body, where they are present in ap-
proximately equal number. They are almost twice as
numerous in sections from the tail as in those from
other parts ; but since the number in only one plane is
recorded, in order to obtain their actual relative abun-
dance it is necessary to square these figures They are
then found to be slightly less than three and a half
times as numerous in the tail as elsewhere.

The islands of Langerhans are more numerous, as
pointed out by Kasahara, in the pancreatic tissue of



HISTOLOGY OF THE PANCREAS. 8 1

the foetus and of very young children than in the
adult. Should we assume that they are formed during
embr}^ological development and persist thereafter, this
fact is readily explicable. The organ being much
smaller in the foetus and in a young child, the same
number of islands, though themselves smaller, are
more closely together, and therefore appear to be
more numerous in sections.

Physiology of the Islands of Langerhans. — An attempt
to investigate experimentally the nature of the islands
of Langerhans has been made by Lewaschew, working
in Heidenhain's laboratory. He studied the pancreas
of dogs and cats killed after having been subjected to
conditions which cause the gland to secrete actively.
After prolonged overfeeding, or after the administra-
tion of pilocarpin, which stimulates the pancreas as it
does the salivary glands, he claims to have found struc-
tures representing transitions between the glandular
acini and the interacinar cell-groups. He has observed
acini containing one or more cells of which the proto-
plasm is non-granular and stains lightly. A whole
acinus or a number of acini may be composed of these
cells. In such areas some of the cells may assume a
polygonal shape and are no longer grouped about a
central lumen. Other cell-groups consist entirely of
polygonal cells without acinar arrangement, and these
represent, he thinks, the fully formed islands of Lan-
gerhans.



J

82 DISEASE OF THE PANCREAS.

In order to obtain a large increase in the number
of altered acini one even maximal stimulation of the
gland is not sufficient ; but by the repeated administra-
tion of pilocarpin this result is accomplished, and the
longer and more intense the action of the drug the
greater their number. To cause their increase by
overfeeding, a very large quantity of food is necessary.
Lewaschew believes that the cells composing the inter-
acinar groups may reassume their character of secreting
cells and again form acini. He mentions that he has
found an unusual number of islands under conditions
other than those of increased functional activity. They
were very numerous in a dog which several days before
its death had suffered with fever.

The observations of Lewaschew have not been con-
firmed. Statkewitsch has, however, described similar
alterations in the pancreas of dogs, cats, and rabbits
subjected to conditions having no resemblance to those
which Lewaschew produced. In animals which have
been starved, the secretino- cells, he claims, lose their
granular inner zone and by a series of transitions
similar to those described by Lewaschew assume the
character and arrangement of the interacinar cell-
groups. He thinks that his researches, as well as
those of Lewaschew, show that these structures are
merely the result of an intense alteration of the gland
cells. Jarotzky has made a careful study of the secreting
pancreatic cells in mice under various conditions of



HISTOLOGY OF THE PANCREAS. 83

inanition ; from some of his animals food was withheld,
others were given only sugar, others only fat, but in
none did he find changes similar to those described by
Statkewitsch ; and he reaches the conclusion that the
islands of Langerhans are independent structures em-
bedded in the glandular parenchyma.

In the normal human pancreas one occasionally finds
groups of acini composed of cells differing from the
typical glandular type and suggesting a transition from
the secreting cell to that of the island of Langerhans.
The cell-protoplasm does not take the nuclear dye as
does the basal part of the ordinary glandular cell,
and when stained with eosin has a bright pink color
and homogeneous refractive appearance. The nucleus,
which shows no evidence of degenerative change, is
situated near the centre of the cell. Occasionally one
or more cells of the character described form part of
an acinus which otherwise resembles those about it.
Usually, however, a group of acini are changed, and
such an area often corresponds in size to an island of
Langrerhans.

The presence of such groups of altered acini the
cells of which resemble those of the island of Langer-
hans confirms at first sight the view of Lewaschew, —
namely, that groups of acini may assume the character
of the interacinar structures. It is probable that these
foci, in part at least, represent what Laguesse and
Pischinger have described as stages of transition. The



84 DISEASE OF THE PANCREAS.

arrangement of more or less columnar cells about a
central lumen is, however, still preserved, and one does
not find similar areas in which this arrangement is lost.
The lumen, indeed, is usually very conspicuous and is
often considerably dilated, filled with products of secre-
tion which stains deeply with eosin. It seems probable
that these groups of acini are altered as the result of
peculiar functional activity, it may be, of hyperstimula-
tion of the gland. There is at least no evidence that
they represent transitional stages between glandular
acini and islands of Langerhans.

Such altered acini are observed in a small proportion
of normal glands. They were found in three of twenty-
seven glands examined carefully for their presence.
They were, moreover, present in three of seven relatively
normal organs from diabetic patients. The occurrence of
voracious appetite and increased food ingestion in indi-
viduals so affected may explain the occurrence of these
areas which represent possibly foci of peculiar secretory
activity. They were particularly abundant in one in-
stance of chronic interstitial pancreatitis not associated
with diabetes.

I have attempted to confirm the observations of Lew-
aschew by injecting subcutaneously pilocarpin muriate
into doofs. Since the number of islands varies in dif-
ferent parts of the gland, it was considered desirable
to study sections from corresponding parts of the
organ. Specimens were prepared {a) from the splenic



HISTOLOGY OF THE PANCREAS.



85



extremity, {b) from the part which is in contact with the
duodenum, and [c] from the descending arm which lies
in the mesentery of the duodenum. In order to deter-
mine with accuracy the relative abundance of the islands,
their number was counted in a measured sectional area
and compared with that found in the pancreas of an
animal to which pilocarpin had not been given.

Following is a summary of the experiments per-
formed :

Dog No. i. — The animal was given daily for nine successive days
0.02 to 0.03 gramme of pilocarpin muriate. Profuse salivation was
produced, often accompanied by vomiting and diarrhoea.

Dog No. 2. — During twenty -eight hours pilocarpin muriate 0.005
to 0.0 1 gramme was injected subcutaneously six times. The drug
produced repeatedly profuse flow of saliva.

Dog No. 3. — During twenty-four hours pilocarpin muriate o.oi
gramme was injected subcutaneously seven times. Profuse salivation
followed each injection.

In the table the figures represent the number of
islands in 0.5 square centimetre of sectional area. The
letters refer to the parts of the gland indicated above.



Injected Animal.

Dog No. I . . .

Dog No. 2 . . .
Dog No. 3 . . .

Average ....



61

55
54



56.6



21
20

72



37-6



6.6



Control Animal.

Dog No. I. . .
Dog No. II. . .
Dog No. III. .

Average ....



59
39
67



55



61



67.6



14

3

12



9.6



S6 DISEASE OF THE PANCREAS.

The figures show that no increase of the number of
islands was obtained in the three experiments. Transi-
tional stages between glandular acini and interacinar
islets were not observed. The number of islands in
that part of the descending arm of the pancreas which
lies in the mesentery of the duodenum (c) is constantly
much less than elsewhere ; the number in different
glands and in different parts of the same gland varies
considerably. In the experiments of Lewaschew these
sources of error have apparently not been given suffi-
cient weight.

The diversity of the opinions concerning the struc-
tures under consideration has justified, I believe, the
preceding detailed discussion of their nature. Certain
facts may be considered to be established. The islands
of L-angerhans are composed of cells of epithelial type
having the same origin as those which form the acini.
Ramifications of the pancreatic duct do not penetrate
the interacinar islands, while on the other hand these
bodies have an intimate relation to the vascular system.
They occupy a definite position within the pancreatic
lobule (of the cat) and are more numerous in certain
parts of the gland than in others. It is not possible to
transform secreting acini into islands of Langerhans.

The function of these structures has been the subject
of some speculation. Harris and Gow, and more re-
cently Jarotzky, have suggested that they are concerned
in the elaboration of the pancreatic secretion furnishing



HISTOLOGY OF THE PANCREAS. 87

possibly one or other ferment which it contains. Gian-
nelli and Giacomini, who found that in certain reptiles
the cells of the interacinar islands are arrang^ed about a
central lumen, hold a similar view. In higher animals,
however, numerous observations have shown that the
ducts do not penetrate the interacinar islands, and the
staining method of Golgi employed by Dogiel has failed
to demonstrate the presence of ducts, though their finest
ramifications become apparent in the adjacent acini.

The intimate relation of columns, of epithelial cells to
a rich capillary net-work has suggested that the islands
of Langerhans furnish some substance to the blood,
the hypothetical internal secretion of the pancreas.
Abundant experimental research inaugurated by von
Mering and Minkowski having shown that the pancreas
exerts an important influence on carbohydrate metabo-
Hsm, several writers, Laguesse, Schafer, Diamare, and
others, have suggested that the islands of Langerhans
perform this function. Ssobolew claims to have ob-
tained experimental evidence that assimilation of sugar
causes changes in the cells of these bodies comparable,
to those which occur, as Heidenhain has shown, in the
secreting cells as the result of increased functional
activity. The cells of the interacinar islands are, he
states, most granular after hunger which has lasted two
or three days, but after feeding with carbohydrates in
considerable quantity, or after intravenous injection of
sugar, the granules within the cells diminish in num-



88 DISEASE OF THE PANCREAS.

ber. Schmidt, however, was unable to produce similar
phenomena in mice and in guinea pigs after intraperi-
toneal and intravenous injection of solutions of sugar.

The study of pathological changes associated with the
disease of carbohydrate metabolism, diabetes mellitus,
has afforded convincing evidence that the islands of
Langerhans control the assimilation of sugar. It will
be the purpose of a subsequent chapter to define the
relationship of diabetes mellitus to diseases of the pan-
creas and to alterations of the islands of Langerhans.



CHAPTER IV.

VARIETIES OF ACUTE PANCREATITIS.

Acute inflammation of the pancreas has attracted
much attention, yet the nature and the cause of the
lesions which accompany it have been involved in ob-
scurity. While diffuse suppurative inflammation or
more localized abscess formation resembles similar
processes frequently observed in other organs, so-
called hemorrhagic and gangrenous pancreatitis finds
little analogy in the liver, spleen, kidneys, or indeed in
the salivary glands, which resemble in many respects
the pancreas. The difficulty of deciding what shall be
regarded an inflammatory process is here encountered ;
distinctions between hemorrhagic pancreatitis and hem-
orrhage into the organ, though usually emphasized in
writings upon diseases of the gland, are not clearly
drawn.

A well-defined classification of acute lesions of the
gland was introduced by Fitz, and was based upon an
analysis of cases studied by himself, as well as of those
recorded in the literature. Inflammatory changes asso-
ciated with hemorrhage into the organ, so-called hem-
orrhagic pancreatitis, had already been observed by
Rokitansky and by Klebs.

Both Friedreich and Fitz recognized as an indepen-



90 DISEASE OF THE PANCREAS.

dent condition, pancreatic hemorrhage, a lesion un-
accompanied by inflammatory changes. The existence
of acute inflammation, according to Fitz, is estabHshed
from an anatomical stand-point by the occurrence of
degenerative changes in the parenchymatous cells and
by exudation into the interstitial tissue ; but even when
anatomical evidence is lacking, clinical symptoms may
demonstrate the presence of an inflammatory process ;
the uncertain evidence of fever and other symptoms
of inflammation may suggest hemorrhagic pancreatitis
rather than simple hemorrhage. Fitz found that acute
inflammatory alterations of the pancreas fell into three
groups which, to emphasize their conspicuous feature,
he designated hemorrhagic, suppurative, and gangre-
nous pancreatitis.

Hemorrhagic pancreatitis, described by Fitz, occurs
most frequently in those who have had previous attacks
of "gastric or gastro-duodenal dyspepsia." It begins
with intense pain in the upper abdomen, followed by
vomiting and not infrequently by slight swelling of the
epigastrium, associated with tenderness and accompa-
nied by obstinate constipation. The temperature is
normal or subnormal, and symptoms of collapse precede
death, which usually occurs between the second and
fourth days. The pancreas is found to be enlarged,
and its interstitial tissue, as well as the tissues in its
neighborhood, is infiltrated with blood. Microscopic
examination shows the presence of cellular and fibrin-



VARIETIES OF ACUTE PANCREATITIS.



91



ous exudates together with necrosis of the paren-
chyma. In the fat of the omentum and of the sub-
peritoneal tissue are the disseminated foci of necrosis
to which Balser has directed attention.

Suppurative pancreatitis resembles suppurative in-
flammation of other organs ; the gland may contain ab-
scess cavities of varying size, the organ being enlarged
and the peri-pancreatic tissue indurated. Suppurative
inflammation rarely pursues an acute course, but per-
sists for weeks or months, and abscess cavities may
discharge into the stomach or duodenum, or, rupturing
into the lesser peritoneal cavity, may here produce an
abscess cavity of great size. Pylephlebitis and abscess
of the liver may accompany this condition.

Gangrenous pancreatitis, according to Fitz, though
it may follow other conditions, is usually the result of
hemorrhagic pancreatitis, and in at least half of the
recorded cases evidence of previous hemorrhage has
been present in the altered gland. The clinical symptoms
of the two conditions resemble one another closely, but
where the pancreas is found to be gangrenous the
illness has been of longer duration, proving fatal at the
end of several weeks. The organ is enlarged, often
soft and friable, and of a color which varies from mottled
red and gray to dark brown or black ; by extension
of the gangrenous process to the tissues about the organ
almost complete sequestration may result. Since the
gangrenous pancreas lies in the posterior wall of



92



DISEASE OF THE PANCREAS.



the lesser peritoneal cavity, peritonitis ensues, and
this cavity is converted into an abscess containing
pus and necrotic material. In some cases the com-
pletely sequestrated pancreas, attached by only a
few shreds of tissue, is surrounded by purulent


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Online LibraryEugene L. (Eugene Lindsay) OpieDisease of the pancreas, its cause and nature → online text (page 5 of 23)