CHAPTER IV
LESIONS IN ORGANS OUTSIDE OF THE RESPIRATORY TRACT
SKIN
Various skin lesions occurred during the course of influenza and the pneumonias which followed. In the absence of knowledge as to the etiology of influenza, it is impossible to state that these eruptions were due to the cause of influenza or to any of the organisms which were found in the respiratory tract as secondary invaders. It should be borne in mind that in a majority of the camps measles was endemic or epidemic at the time of the influenzal outbreak of the fall of 1918, and a rash occurring in patients whose clinical signs were those of epidemic influenza may have been measles. As is true in all epidemics, a certain proportion of the cases with other diseases were recorded as cases of the epidemic condition, and it appears impossible to state with any degree of positiveness that any eruption occurred in influenza uncomplicated by infections of other varieties. Exanthems resembling measles or scarlet fever were fairly frequent and in the absence of an epidemic of influenza the cases showing them might have been so diagnosed.
Miliaria was very frequent possibly as the result of profuse perspiration. Occasionally petechial hemorrhages were seen in the skin, sometimes larger areas of hemorrhagic extravasation, while an occasional case showed a more or less typical reaction of purpura hemorrhagica. At Camp Taylor hemorrhages into the papillae accompanied by more or less inflammatory cell exudation were seen. Occasionally the eruption was vesicular and sometimes the vesicles were filled with pus.
Jaundice was present in some cases, though not in the very early stages of the disease. This condition varied considerably, being present more frequently in some camps than others, yet it is impossible to state that any particular organism caused the condition more frequently than another, though it appeared to be more frequent in cases infected with the hemolytic streptococcus.
Subcutaneous emphysema was noted in most of the camps but its incidence can not be arrived at from a study of autopsy material. Cultures of the emphysematous tissues were uniformly sterile. The pathogenesis of this condition is discussed under the pathology of the respiratory tract.
MUSCLES
Necrosis of muscles was met with fairly frequently and undoubtedly was present more often than it was reported. It was reported most frequently in the rectus abdominis muscle but was recorded in other muscles, particularly the accessory muscles of respiration. In appearance the muscles were smooth, moist, light reddish-brown in color with a peculiar translucency. Rupture of individual fibers was sometimes followed by hemorrhage and occasionally considerable
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portions of the muscle were separated, the tear being filled with clotted blood. Leucocytic infiltration was usually minimal in amount but occasionally frank pus was formed and bacteria, pneumococci or streptococci, were found in a few cases. The etiology of this condition, which is not peculiar to this disease, is not clear, but the character of the lesion suggests a block in the arterial blood supply. As the condition appears most frequently in the muscles which are used in respiration the increased respiratory effort is probably partly responsible. (Pl. XIV; figs. 162, 163, 164, 165.)
PERITONEUM
Peritonitis occasionally occurred either from extension of the infection through the diaphragm or apparently independently of such extension, and when the latter occurred there was often a coexisting inflammation of the meninges and occasionally of the joints. The organisms found were usually pneumococci or streptococci, rarely both. Extensions from the pleura occurred relatively late during the course of the disease, but in cases of so-called polyserositis the spread to the serous membranes usually occurred relatively early.
HEART AND BLOOD VESSELS
Dilation of the heart, particularly of the right ventricle, was a common finding at necropsy. Various degrees of degeneration of the myocardium were reported, from a mild swelling and a slight obscuration of the cell markings to segmentation and fragmentation of the muscle fibers. In cases which were accompanied by a septicemic or pyemic condition occasionally small abscesses, the result of bacterial embolism, were found. Edema between the muscle fibers occasionally was reported.
FIG. 162.- Zenker's degeneration of rectus abdominis muscle in a case of influenza and pneumonia. Accession number 6945, Army Medical Museum. Negative number 30512
In the endocardium in a few instances small petechial hemorrhages were seen, but as a whole endocardial change was rarely reported during the pandemic period. In the post epidemic period subacute bacterial endocarditis from which the influenza bacillus was isolated was occasionally reported. Streptococcus endocarditis was also rarely reported.
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Aorta.-Yellowish streaks longitudinally arranged along the intima of the aorta were seen in cases where death followed influenza, but can not be said to be peculiar to the condition, as they have been reported following other acute infectious diseases and are commonly found during the age periods when the acute infectious diseases, particularly the exanthemata, occur. Their color varies from a pale opaque cream color to a fairly bright yellow. Only exceptionally were further changes found and these were not attributed to the disease from which the patient died. Elasticity of the aorta as a whole did not appear to be decreased. Microscopically the condition appeared to be an edema of the tissues below the internal elastic membrane, with swelling of the cells and an accumulation of large cells with vacuolated cytoplasm. Frequently these cells contained no recognizable nuclei. This degenerative condition was not distinguishable from the early stages of ordinary atheroma.
Hemoglobin tinting of the intima of the aorta was observed occasionally, probably due to blood destruction as the result of secondary invading organisms, most frequently the hemolytic streptococcus.
Small blood vessels in the vicinity of lesions in the lung showed various types of degenerative change, the most prominent being a proliferation of the capillary endothelium. Occasionally the walls of small vessels were hyaline, apparently necrotic, and some observers have reported seeing the actual point of rupture of these structures. That this rupture of small vessels occurred is evidenced by the hemorrhagic extravasation in the lungs, but whether it was due to the virus of influenza or secondary infecting organisms can not be determined. The occurrence of the hyaline or conglutination thrombi, the latter consisting of red corpuscles which had lost their hemoglobin, is reported by most observers. Their significance is not entirely clear. Where outlines of red blood corpuscles are seen it seems probable that the condition is one of thrombosis or vascular block of some kind. The hyaline thrombi appeared to be little more than coagulated plasma and were more frequent in poorly fixed tissues. These may be sections across a vessel in the vicinity of a clot which has contracted, leaving serum only in that part of the vessel seen in the specimen. They were found in vessels of considerable size though most frequently in the capillaries of the alveolar walls.
BLOOD
Reports of blood examinations indicate that there is primarily a decrease in the white blood corpuscles, particularly a decrease in the polymorphonuclear neutrophiles. This leucopenia persists throughout the course of the disease in uncomplicated influenza but the picture changes when secondary infection takes place, the blood picture then conforming to the usual reaction accompanying the secondary invading organism. Bunting,1 in a small series reported in 1921,
found that in clinically uncomplicated influenza there was an early neutrophile increase followed by a sharp drop, and that thereafter there was a leucopenia, a deficiency in the cells of marrow origin, and of blood platelets. An early polymorphonuclear leucocytosis was not observed or recorded from the Army camps and stations during the pandemic period. A decrease in platelets often was seen.
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Little was done on the physical characteristics of the blood, but it was the general experience at necropsy, particularly on cases dying early, that clotting was delayed.
Underhill and Ringer 2 reported a concentration of the blood in influenza and compared it with the changes found in the blood following poisoning with phosgene gas.
Symmers 3 found that blood pressure was usually low and the pulse rate was frequently slow even in patients who had not received digitalis. He considered that the capillary dilatation and injection and the low blood pressure were possibly related to the changes in the suprarenal medulla.
SPLEEN
There is no agreement as to the changes in the spleen. In general, it may be said to have been somewhat enlarged, but not excessively so. Here, again, it is impossible to determine whether the changes were due to the primary infection by the influenza virus or to the secondary infections. In general, the picture was that of the spleen of acute infectious disease, and when not involved in other conditions such as previous splenitis, it was soft, the pulp more or less diffluent, occasionally mushy, while follicular markings were rarely prominent. Microscopically, there was an excessive blood content, endothelial hyperplasia of the vessels and the cells of the reticulum. Occasionally, there appeared to be an excess of phagocytic cells throughout the reticulum of the organ. In some cases focal necrosis was seen, sometimes of the toxic type, at other times apparently due to embolic lesions from a septicemia or pyemic condition. The lesions in the spleen could not be said to be in any way characteristic.
SUPRARENALS
Necrotic areas, frank hemorrhage and occasionally abscesses were reported in and about these organs and rarely streptococci were isolated from the lesions. They presented grossly with either hemorrhages within the substance of the organ or both in the substance of the cortex and out in the surrounding tissues. When not involved in the hemorrhagic process they usually showed considerable congestion, the cells of the cortex were usually swollen, sometimes hydropic, and some observers reported decrease in the lipoid granules. Focal necroses were found occasionally, rarely considerable pus was present. (Figs. 166, 167.)
KIDNEYS
Usually the kidneys were involved in a parenchymatous degeneration of greater or lesser extent. Rarely glomerular nephritis was present, but it can not be considered at all characteristic of the disease. It was found more rarely than is usual in the acute exanthemata. The degree of degeneration varied markedly but some degree was practically constant.
LIVER
Degenerative changes in the liver cells was constantly present and varied markedly in degree. The differentiation between the changes due to influenza and those of secondary infecting organisms and the resultant toxemia, septicemia
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or pyemia was not always possible, but in the cases dying quickly and showing little pneumonic consolidation the changes in the liver were rarely more than a mild parenchymatous degeneration. The liver was usually somewhat enlarged and congested while the parenchyma on section was dull and opaque, frequently with a yellow mottling near the capsule where microscopically some fatty degenerative changes were seen. Granular or albuminous degeneration was always seen and occasionally some fatty change was present. An occasional liver showed fatty infiltration, but that can scarcely be attributed to the disease itself. Focal necroses in the intermediate zones were found and not infrequently in these cases bacteria were cultivated from the blood stream. Necrosis of the cells about the hepatic veins occasionally occurred, usually accompanied by passive congestion of considerable degree. Occasionally the sinuses contained numerous polymorphonuclear leucocytes, indicating a general bacterial invasion of the liver, yet not all of such cases showed jaundice. The Kupfer cells throughout the liver usually appeared swollen and in some cases were apparently increased in number.
PANCREAS
There was no characteristic change in this organ. When general visceral congestion was present its vessels were likewise congested. Usually there were mild degenerative changes in the cells of the islands of Langerhans and also of the acini. No marked degenerative changes were reported.
GASTROINTESTINAL TRACT
In many cases irregular areas of hyperemia, occasionally small hemorrhages, and rarely superficial erosions were seen in the upper digestive tract. They were apparently not particularly frequent. Frank hemorrhage from the stomach was seen occasionally, and hemorrhage with partial necrosis of the colon was reported. The hyperemia and occasional small hemorrhages into the mucosa of the tract appeared with sufficient frequence to warrant their being considered. The other more extensive lesions can scarcely be attributed to influenza on the data presented. The mucosa in early autopsies was commonly more or less swollen particularly in the upper portion of the tract. The lymphoid follicles and Peyer's patches frequently were swollen or hyperplastic, and occasionally there was a definite hyperemia and in rare instances hemorrhage about these structures. Less change was seen in the lymphoid structures of the colon than in those of the lower ileum.
BLADDER
Hyperemia, small hemorrhages and necrosis of part of the bladder wall were reported, but their relation to the clinical disease, influenza, was not established.
TESTICLES
Cessation of spermatogenesis was reported by several investigators and occasionally focal necrosis of the parenchyma was seen.
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MENINGES
Meningitis due to streptococci and pneumococci was reported frequently and was accompanied usually by infections of serous membranes. Congestion of the cerebral vessels was the rule and occasionally small hemorrhages were found. Some reports contained reference to lymphocytic infiltration in the meninges as occurring with relative frequency. This latter observation is noteworthy, since the conditions described are not unlike those seen in the meninges in lethargic encephalitis, a few cases of which were reported from Army camps and stations during the later stages of the epidemic and in the post-epidemic period.
PITUITARY
In relatively few cases in which observations were reported on this organ, it showed hyperemic changes, and at Camp Taylor it was considered that there was an increase in the colloid.
EYES
The subjective symptoms of pain in and behind the eyes was a rather characteristic complaint. The conjunctiva was commonly more or less reddened and occasionally conjunctivitis was diagnosed. The eyes were occasionally involved in pyemic processes.
Pericarditis and pleuritis are covered elsewherea and will not be considered at this place.
As previously stated, it is impossible from published reports to distinguish between the lesions due to influenza and to the organisms which were practically constantly present as secondary invaders. In the majority of reports the results of bacteriological investigations are not so recorded as to enable one to determine the frequency of the various visceral lesions in patients infected with the secondary invaders. Neither is it possible to coordinate the lesions in the viscera outside of the lungs with the positive blood cultures during life or at the necropsy table. In the absence of such data the occurence of these conditions can be recorded as having occurred in patients who exhibited the clinical condition, influenza, and their etiology must remain, at least for the present, unknown.
REFERENCES
(1) Bunting, C. H.: The Leucocytic Picture of Influenza. American Journal of Medical Sciences, Philadelphia, 1921, clxii, 1-9.
(2) Underhill, F. P., and Ringer, M.: Blood-concentration Changes in Influenza; with Suggestions for Treatment. Journal of the American Medical Association, Chicago, 1920, lxxx, 1531.
(3) Symmers, D.: The Significance of the Vascular Changes in the So-called Pandemic Influenza. New York Medical Journal, 1919, cx, 789.
a Consult Volume XI, Surgery, Pt. 2, Sec. 1, pp. 142, et seq.
