Ch. Mittermayer

The pulmonary air-blood barrier of human shock lungs (a clinical, ultrastructural and morphometric study).

Interstitial edema in the alveolar septa is the first morphologically recognisable change to be observed in cases of shock. It is brought about by the altered function of the membranes of the damaged epithelium and endothelium in the alveolar wall. At the same time there is an impairment of gaseous exchange, which is rendered more difficult by the exudative process in the interstitium. Pari passu with these events there is injury to the cells of both the alveolar epithelium and the alveolar capillary endothelium. Both these processes are still reversible. The point of irreversibility appears to be reached--so far as time is concerned--at the end of the first week, after which the injurious effects on the cell are established, since the thin alveolar wall necessary for the exchange of gases becomes overgrown with bulky alveocytes (Tpye II), and the fibroblasts in thealveolar interstitium push the capillaries away from the surface of the alveolus. In most of the advanced cases of shock this process of thickening of the alveolar wall exceeds the critical value, and respiratory exchange is so impaired that satisfactory functioning of the lungs is no longer possible.

Morphologic development of human shock lung.

In the initial phase of shock, edema spreads throughout the alveolar interstitium even before injury occurs in the alveolar epithelium and endothelium. The endothelium and the epithelium are damaged only subsequently, causing reduction in the average barrier thickness of the epithelium and the endothelium. A point of irreversibility is reached by the end of the first week. While early cell regeneration may be observed within the alveolar endothelium and epithelium, proliferation of fibroblasts and fibrosis of the alveolar wall occur in addition to edema which spreads within the interstitium. This widening of the gas exchange barrier may be considered as the anatomic substrate of respiratory insufficiency induced by shock. This enlargement continues up to the moment when thickening of the alveoli impedes satisfactory functioning of the lung, and, as consequence, threatens the life of the patient.

Intravitale und pathologisch-anatomische Beobachtungen beim Verbrennungsschock des Kaninchens

Abstract This paper describes results of intravital microscopic observations of the mesenteric blood and lymph vessels of the rabbit. 20% of the surface of the skin of these rabbits were burned. Immediately after producing the shock, general unspecific symptoms were seen: decrease of circulatory flow, aggregates of erythrocytes. Specific alterations consisted in leukocyte sticking, platelet aggregation, hemolysis and stasis. Vascular spasm and hemorrhage were conspicuously absent. These microcirculatory features were compared with those of different forms of shock. There was a striking similarity with the characteristics of the burn shock with the endotoxin shock. On the other hand hemorrhagic and traumatic shock exhibited similar phenomena, thus forming a second distinct group of shock as seen from a microcirculatory point. Differentiation between the groups is only possible from the specific features of microcirculation failure. These results confirm the view point, that different forms of shock evoke different pathological reactions in the terminal vascular bed.

Pathologie der Schocklunge

Der Begriff der Schocklunge ist bisher weder klinisch noch pathologisch-anatomisch scharf definiert. Dies mag seine Ursache in unterschiedlichen oder gegensatzlichen Auffassungen uber Pathogenese, Vorkommen und sogar Erscheinungsform des Krankheitsbildes haben.

Suppression of isoprenaline-induced increase in plasma renin concentration by vasoconstrictors in rats with nonfunctioning Macula densa.

SummaryThe mechanism of the increase in plasma renin concentration caused by the β-sympathomimetic agent isoprenaline has been further investigated.Rats were pretreated by occluding the left renal artery for 2 hrs, thus rendering the macula densa cells of this kidney nonfunctioning. After contralateral nephrectomy infusion of isoprenaline (1.5 μg/kg min) still caused a strong increase in plasma renin concentration. This increase was significantly suppressed by simultaneous infusion of angiotensin II (1.0 μg/kg min), the α-sympathomimetic amine phenylephrine (60 μg/kg min) or octapressin (10 mU/kg min). The results exclude any mediator-role of the macula densa receptors in the isoprenaline-induced release of renin.The possibility of a stimulation of renin release via the baroreceptors or a direct “secretomotoric” action of isoprenaline is discussed.

Human endothelial cell proliferation inhibiting activity in the sera of patients suffering from ‘shock’ or ‘sepsis’

Abstract. The response of DNA‐synthesis of human endothelial cells to sera derived from twenty‐five patients suffering from ‘sepsis’ or ‘shock’ was measured by autoradiographic methods. In eight cases a constant decrease in proliferative response was found compared to that of sera from healthy donors. These proliferation values were shown to lie below the ‘60%‐of‐control‐line’. The difference between the means of control and of corresponding ‘low‐response’ values was significant (P<0.05). In three cases a diminished response was caused only by some of several serum samples taken at different times. These results correlated well with the clinical state and outcome of patients but not with any of the over sixty clinical, therapeutic, laboratory and post‐mortem parameters of investigation. Evidence is presented for a proliferation inhibiting activity in sera of patients in clinically poor states, and some physico‐chemical properties of this ‘factor’ are described. Lethal injury to the cells or an impairment of cellular migration could not be observed within the observation periods used in this study.

Increased growth-stimulating activity of thoracic lymph after hemorrhagic shock

Summary During the late phase of shock, which must be regarded as an acute generalized circulatory failure, pronounced cell proliferation and increasing fibrosis is seen in the pulmonary interstitial space. Cell proliferation and fibrosis result in irreversible pulmonary changes and frequently cause death. Fibroblasts of different origin are stimulated in vitro by the thoracic lymph of pigs to produce increased proliferation after shock (Mittermayer et al., 1978). The question arises as to whether or not this stimulated growth is organ-specific and whether this phenomenon can also be demonstrated in vivo. The present study investigates the effect of thoracic lymph of the pig after a hemorrhagic shock which stimulates cell proliferation in vivo. Hemorrhagic shock was induced in domestic pigs by removal of 40-50% of the blood volume for 3 hours. Thoracic lymph which had been obtained before the beginning of the experiments, at the end of the shock phase, and 2-3 hours following retransfusion, was quick-frozen and lyophilized. The mitotic rate and DNA synthesis (3HTdR-index) were used as parameters of cell proliferation in various cell populations of the rat following intraperitoneal injection of lymph powder dissolved in saline solution. Application of thoracic pig lymph harvested before the shock-inducing event does not influence the mitotic rate as compared either to bovine serum albumin or to physiological saline solution. Pig lymph obtained during the shock-inducing event produces a significantly increased mitotic rate in the squamous epithelium of the stomach, which is even more increased by pig lymph after the shock-inducing event. This effect is most significant in the squamous epithelium of the stomach and in the alveolar cells of the lung. The mitotic rate of the glandular epithelium in the ileum is only slightly increased. DNS synthesis (3HTdR-incorporation) is significantly increased in the squamous epithelium of the stomach and the mouth as well as in the alveolar and endothelial cells of the lung. The DNA synthesis in the cells of the ileum mucosa is increased only insignificantly. As for the mitotic rate, DNA synthesis following application of pig lymph obtained during the shock-phase shows a significant increase only in the squamous epithelium of the stomach. Thoracic pig lymph from normal animals does not influence DNA synthesis. The effect of pig lymph following the shock-inducing event reveals the highest increase of cell proliferation in different cell populations, and is therefore not organ-specific. Aggregates of thrombocytes are most likely at least one possible source for the release of these growth factors.

A simple and rapid method for postmortem radiographic investigation of lung fine structure

Radiologic pathologic correlation of lung specimens requires a gas content identical to intravital conditions. Methods of air drying and formalin steam fixation are well known but time consuming. A new, rapid method is presented: the lungs are inflated with compressed air, frozen in liquid nitrogen, and cut into slices. Radiographs taken with soft tissue technique demonstrate structural details down to 200-300 mu. The excellent state of preservation also permits excellent quality of microscopic slides.

Proliferative response of human endothelial cultures to various types and treatments of human sera, to culture treatments and to various oxygen concentrations

Endothelial cells from the human umbilical vein were exposed to different human sera, differently treated serum, to various oxygen concentrations, and various culture treatments. Endothelial proliferation was determined by measuring the uptake of [3H]-thymidine by means of autoradiography and presented as thymidine labeling index (TI) values. TI values differed according to different serum concentrations, serum types, serum preparations (WBS-PDS) and serum pretreatments. Low oxygen concentrations in the incubator atmosphere induced an early DNA synthesis response without an increase in cell number. The addition of the protease inhibitors aprotinin and soybean trypsin inhibitor to the culture medium resulted in a dose dependent TI decrease, whereas PMSF showed no influence.

Besonderheiten bei 30 Malariaerkrankungen an der Medizinischen Klinik Freiburg

Nach eindrucksvollen Erfolgen in der weltweiten Bekampfung der Malaria bis etwa 1965 — der Mittelmeerraum und Nordamerika wurden malariafrei — ist es im letzten Jahrzehnt weltweit zu einer erneuten Zunahme der Malariaerkrankungen gekommen, z. B. allein in Indien zu einem Anstieg auf 10 × 106 Erkrankungen (von 0,1 × 106), d. h. um einen Faktor 100! [1,2]. Diese Zunahme wird erkl×rt durch ein Nachlassen in den seuchenhygienischen Masnahmen, durch das Auftreten resistenter Mutanten (DDT-Resistenz der Anophelen, besonders in Indien, Resochin-Resistenz der Plasmodien, besonders in Sudamerika [2, 3]), und bei uns in den gemasigten, nicht endemischen Zonen vor allem durch die Zunahme des Flugtourismus.