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Ikramov Adkham Ilkhamovich, Ph.D, Tashkent Institute of Postgraduate Medical Education PhD, professor of the Department of Medical radiology E-mail: [email protected] Magrupov Bakhodir Asadullaevich, Republican Scientific Center of Emergency Care PhD, professor, Head of the Department Pathological Anatomy Nizamova Madina Mirgabtizyanovna, Tashkent Institute of Postgraduate Medical Education assistant of the Department of Medical radiology E-mail: [email protected] Ubaydullaeva Vladlena Ulugbekovna, Republican Scientific Center of Emergency Care Ph.D, doctor of the Department of Pathological Anatomy Sattarov Hasan Ilkhamovich, Republican Scientific Center of Emergency Care Head of the Department of Medical Intensive Care
Differential diagnosis of cardiogenic and membranogenic pulmonary edema in medical radiology
Abstract: The article describes a typical computed tomography and X-ray semiotics of acute respiratory distress syndrome (ARDS) and cardiogenic pulmonary edema, which were compared with clinical and morphological data. The authors identified the distinctive features in the X-ray pattern of these critical conditions, which is crucial in the selection strategies of differentiated treatment.
Keywords: cardiogenic pulmonary edema, noncardiogenic pulmonary edema.
Background. Pathogenesis of pulmonary edema is well studied. Four types of pulmonary edema can be identified depending on the underlying cause: hemodynamic (cardiogenic), membranogenic (non-cardiogenic), centrogenic and mixed [1].
As a rule hemodynamic (cardiogenic) pulmonary edema is the result of left ventricular failure in essential hypertension (EH), cardiac failure, myocardial infarction, due to hemodynamic changes in pulmonary circulation (congestion in a pulmonary circulation and increase ofpulmonary capillary pressure) [2; 3]. The pathogenesis is based on accumulation of fluid in the interstitial lung septa (interlobular connective tissue layer) and pleura. Next stage of the pathological process progression is transition of interstitial edema to alveolar edema, when fluid accumulation occurs inside alveoli.
Membranogenic (noncardiogenic) edema implies profound disturbances of pulmonary capillary permeability with the release of high-protein level fluid, including fibrin, into alveolar lumen. The classic example of this type of edema is acute respiratory distress syndrome (ARDS). The development of acute respiratory distress syndrome may be due to "direct" damaging factors — aspiration of aggressive substances, trauma, inhalation of irritating gases and "indirect" factors, which include inflammatory mediators, which have damaging effect on the endothelium ofmicrovasculature [4; 5]. Lung tissue reactions in ARDS are always universal and non-specific [6].
Differential diagnosis between cardiogenic and noncardiogenic pulmonary edema is complex — both conditions have similar clinical and radiological manifestations [7-9].
Aim of the study was to identify specific radiological and computer tomography (CT) features that allow making differential diagnosis of hemodynamic and membranogenic pulmonary edema in acute patients with different pathologies on admission to a multi-disciplinary hospital.
Material and Methods: We conducted an extensive analysis of clinical, radiological and morphological findings in 61 patients with acute lung edema syndrome. The patients were from therapeutic and surgical departments. In the aspect of male: female ratio 43 patients were males, and 18 were females. The average age of patients was 47,3 ± 18,4 years. Of these, 30 patients were included in the first study group, 31 patients were included in the second study group.
Depending on the type of pulmonary edema patients were divided into two groups. The first group included 30 patients (25 men and 5 women) who received treatment for interstitial pneumonia, patients with severe pancreatic necrosis and severe blood loss with the development of membranogenic pulmonary edema. The second group included 31 patients (18 men and 13 women) with various manifestations of coronary heart disease (CHD): acute and recurrent myocardial infarction, mitral valve defect, essential hypertension with development of classic manifestations of cardiogenic pulmonary edema.
Chest radiographies were performed on portable analogous X-ray machine
(Siemens, Polymobil Plus), with subsequent digitizing of the image on CR 30-X 2nd; multi slice computed tomography was performed on Brillance-40 (Philips) machine. Spirometry testing was performed on Chest Graph HI-701 spiroanalyzer (Japan).
Radiological studies were compared with clinical manifestations of the disease and with received morphological data in different periods of time. Morphological examination of autopsy material was performed at the Department of Pathology of Republican Research Centre of Emergency Medicine (RRCEM) where preparation for microscopic examinations was performed. The lung tissue was taken from patients who had lethal outcome caused by edema. The resulting material was fixed in 10% neutral formalin solution
(pH 7.2-7.4), tissue processing was performed on "Carousel" type automatic machine "automatic system for tissue processing" (MICROM STP-120, Germany), and embedded in paraffin. From the obtained blocks serial slices of 4-5 micron were prepared and stained with hematoxylin and eosin. Ready histological preparations were placed under a digital video camera «ProgRes CT3», mounted on «Axioskop 40» microscope (Karl Zeiss, Germany) and connected to image processing and analyzing workstation; after that pictures of the preparations were taken.
Study results: The first study group included 30 patients, of them 25 men and 5 women. Average age of patients was 39,4±16,6 years.
Lethal outcome was registered in 21 patients (70%).
In the clinical picture of the study group signs of respiratory insufficiency dominated on admission among all symptoms and manifested as increased heart rate, shortness of breath, cyanosis, a compensatory increase in blood pressure
Radiological picture did not differ during the first-third days of the respiratory failure onset in 50% of patients, the second half of the patients in the interstitial lung edema phase had diffuse increased lung pattern, mainly mesh-like reticular type, lung hilum were little structured, sinuses were free, heart borders were not enlarged (Fig. 1a).
a) diffuse, symmetric increase of lung pattern, cellular, honeycomb type; interstitial phase of pulmonary edema
b) symmetrical focal lung lesions, predominantly in basal areas; alveolar phase of pulmonary edema.
d) deformation of pulmonary pattern
c) diffuse symmetrical focal lung lesions, predominantly in lateral and basal zones; alveolar phase of pulmonary edema
Fig. 1. Chest X Ray image in membranogenic pulmonary edema
At the same time while performing computed tomography, "opaque glass" type bilateral patchy uneven focal consolidation of lung tissue, more pronounced in the peripheral zone and posterior segments were found on the first day. In densitometric analysis of lung tissue "opaque glass" areas has increased density: up to -590±35 H. U. on the right side, up to 650±25 H. U. on the left side. Pleural effusion was not identified, heart chambers were not enlarged in almost all patients (Fig. 2 a).
Following days, beginning from the fourth day, all patients continued to have progressive shortness of breath and hypoxemia (Pa02 < 55 mm Hg, SO2 < 80-82%), which poorly correlated with artificial respiration and high positive pressure in the end of exhalation and high proportion of 02 in a gas mixture. Auscultation showed worsening of the situation and involvement of extended area of the alveolar lung damage into the pathological process. Failure of compensatory mechanisms led to the development of multiple organ failure. X- Ray examination performed in this time frame showed diffuse focal-confluent opacities, more in peripheral zones; with symmetrical damage of both lungs. Alveolar phase developed after interstitial stage of pul-
monary edema. In dynamics focal opacities formed large infiltrates due to confluence, mostly in basal segments, and "air bronchography" outlines were identified in their background. At the same time structure of hilum was not differentiated clearly, sinuses were identifiable in most patients. (Fig. 1 b, c) CT image in majority of cases was characterized by diffuse symmetric consolidation of the pulmonary tissue due to antero-posterior gradient in dependent zones; alveolar consolidation and "opaque glass" were largely found in the posterior and basal segments of the lung, "air bronchography" outlines were detected in the background. (Fig. 2b).
During densitometric analysis of lung tissue density in the alveolar type consolidated areas of basal segments was: right side -173 ± 35H.U, left side -291 ± 25 H. U. Pleural effusion was present in 30% of patients, predominantly on the left, thickness up to 23mm and density up to + 8 H. U. (Fig. 2b, c)
The progressing of the pathological process led to the need to perform patient respiratory support on days 7-10; oxygen saturation decrease to the critical numbers was the reason of transferring patients to artificial lung ventilation. Patient condition considered
as extremely severe, and diffuse cyanosis of the skin and extremities, depression of consciousness were observed, all of these indicated alteration of normal lung ventilation and development of hypoxia, hypoxemia which indirectly led to the damage of target organs (alteration of hemodynamics, decreased arterial pressure, heart arrhythmia, signs of multi organ failure).
Hypoxemia (Pa02 < 50 mm pT. ct., SO2 < 75%) was not correct-
able even at high levels of PEEP, in many cases pulse oximetry was not possible due to poor peripheral blood flow.
Chest X-Ray performed in this time period showed fine-and medium cellular lung pattern in all lung fields and zones, mostly in basal segments (Fig. 1 d). CT image was characterized by irregular reticular changes, predominantly in sub pleural areas, posterior and basal lung segments (fig. 2d).
a) «Ground glass» type bilateral lung tissue consolidation, interstitial phase of pulmonary edema
b) alveolar consolidation, alveolar phase of pulmonary edema
c) diffuse alveolar and «Ground glass» types consolidation of pulmonary tissue, in dependent zones, in basal and posterior lung segments. Alveolar phase of pulmonary edema
Fig. 2. Chest CT image in membranogenic pulmonary edema
d) reticular changes, predominantly in lateral zones
Morphological signs of acute lung alterations were non-specific and independent of etiological factor. Alteration of pulmonary capillary endothelium, basal membranes, as well as increased capillary permeability, accumulation of extravascular fluid and exudation of proteins developed a chain of pathological processes that were in the basis of developing non-cardiogenic pulmonary edema. Acute stage (Exudative phase) developed during the first four days after the onset of action of damaging factor. Lungs filled the entire chest cavity, their weight exceeded normal one by 2-3 times and comprised 1075±62,6 grams, compared to normal weight of445±15grams.
Signs of tracheobronchitis, congestion of the mucous membrane of the trachea and bronchi were observed in almost all cases. Hemorrhages on the lung surface and small atelectasis in the lung parenchyma were found. On cut surface of the lung small hemorrhages were present. In the proliferation phase "lobular" parenchyma were formed, lung weight increased.
In the resolution phase development of sclerosis was observed: consolidation of parenchyma, small and medium caliber vessels.
Interstitial edema was observed microscopically, it manifested through widening of alveolar walls and bulging of tissue into alveolar lumen (Fig. 3a), later alveolar edema has developed (exudative phase). Fibrin, focal alveolar and interstitial hemorrhages were
detected on internal alveolar surface. Margination of neutrophils (leucocyte stasis in microcirculation vessels), erythrocyte stasis were found on microvessels of alveolar septa. Formation of hyaline membranes in alveoli took place in proliferation phase (days 3-10), the number of alveoli with hyaline membranes (Fig 3b) increased together with the increasing length of the disease and directly correlated with clinical picture of developing respiratory failure.
Resolution phase began on the 2-3 weeks of the disease. This stage was characterized by further resolution of exudates (Fig 3c) and proliferation of pneumocytes. On thinned alveolar septa collagen fibers were found, and profound interstitial fibrosis was subsequently formed in these areas. (Fig. 3d). The more rapid collagen accumulated, the faster was development of interstitial and alveolar fibrosis. These morphological changes created conditions for the development of clinical changes, such as low lung compliance, pulmonary hypertension, decreased functional lung capacity, uneven ventilation and perfusion match and hypoxemia. Pathological changes affected both parenchyma and vascular system. Morphological criteria for vascular system changes were the following: in exudative stage — megakariocytosis of microcirculation vessels, in the proliferative stage — microdot formation, in fibrotic stage — pulmonary arterial sclerosis with obliteration of vessels.
a) widening of alveolar walls Hematoxylin-eosin staining
b) Formation of hyaline membrane Hematoxylin-eosin staining
c) formation of fibrin meshwork in the alveolar lumen Hematoxy- d) Fibrosis of pulmonary tissue parenchyma Hematoxylin-eosin lin-eosin staining. staining.
Fig. 3. Microscopic picture of lung in membranogenic edema
a) venous type increase of pulmonary pattern with peribronchov- b) symmetrical focal opacities, mostly in perihilar zone, alveolar asal infiltration; interstitial phase ofpulmonary edema phase of pulmonary edema
c) «Bat» symptom
d) pulmonary edema in patient with mitral cardiac malformation; alveolar phase
Fig. 4. Chest X-Ray in hemodynamic pulmonary edema
Second study goup included patients with cardiogenic pulmonary edema, of them 18 men and 13 women. Average age of patients 55,3±16,7 years. Lethal outcome was registered in 15 patients (48,4%). Clinical manifestations of hemodynamic pulmonary edema in patients admitted to emergency department were profound: cyanosis of the lips and nails, cold sweat, agitation.
Patients had tachypnea (respiratory rate of40-60 per minute), tachycardia, stentorious breathing and sibilant rales on auscultation. At the alveolar pulmonary edema phase the following clinical manifestations developed: respiratory failure, shortness of breath, face puffiness, swelling of the neck veins.
Bubbling breathing and moist rales, effusion of foam at the mouth were main criteria for the diagnosis of hemodynamic pul-
monary edema. In pulmonary edema CVP increased to 12 cm. w. g. and higher. Changes in blood gases were characterized by particular dynamics: initially a moderate hypocapnia developed; with the progression of pulmonary edema PaO2 and PaCO2 decreased; at a later stage increase of PaCO2 and decrease of PaO2 were found.
X-Ray findings in patients with myocardial infarction did not manifest in first hours of development of pathological process. Patients with chronic heart failure (CHF) and history of myocardial infarction with focal replacement of muscle by scar tissue had marked venous congestion as well as peribronchial and perivasal infiltration, which indicate organic changes in heart and restructuring of hemodynamics due to long duration of disease and contractile failure of left ventricle (Fig. 4a).
a) Increase of venous pattern, with perivasal infiltration and "ground glass" areas; interstitial phase of pulmonary edema
b) «alveolar consolidation" in perihilum, central zone, presence of effusion in left pleural cavity; alveolar phase of pulmonary edema
Fig. 5. Chest CT in hemodynamic pulmonary edema
In the stage of alveolar pulmonary edema X-Ray findings included focal opacities forming large infiltrate-like formations due to confluence, and symptom of "air bronchography" resembling the picture of "butterfly wings" or "bat". At the same time structure of hilum was not differentiated clearly, and sinus opacification, mostly on the right side due to the presence of effusion was
found and confirmed on CT examination. Heart cavities were dilated, left heart predominated (Fig. 4b, c, d). In dynamics X-ray picture followed the clinical course of events: relief of edema led to changes of chest X-ray manifestation, namely disappearance of focal opacities, whereas progression of the process usually caused lethal outcome.
a) Edematous fluid in alveolar lumen. Hematoxylin-eosin staining
Fig. 6. Microscopic picture of lung
CT examination performed to patients with hemodynamic edema and chronic heart failure (CHF) in the interstitial pulmonary edema stage was characterized by prominent peribronchial and perivasal infiltration, "ground glass" type symmetrical and irregular foci, density up to 594 ± 24 H. U. (Fig. 5a). CT — manifestations of alveolar edema were characterized by alveolar consolidation, located symmetrically in peri-hilum and central zones, with the presence of air bronchography (5b). Lung tissue consolidation density reached -45H. U. Pleural effusion was observed mostly of the right, thick-
b) Edematous fluid with erythrocytes/red blood cells in alveolar lumen. Hematoxylin-eosin staining in hemodynamic pulmonary edema
ness up to 3,6sm, density from +2 H. U. to + 7H. U. Dilatation of the left heart predominated.
The death of the patients in the second group occurred in the alveolar edema phase. Autopsy findings were the following: increased size and weight of lungs, however these figures were significantly lower than weights in membranogenic pulmonary edema and made 575 ± 4,0 gr (p <0.05). Lung was of light gray color on incision and cut surface had dripping foamy liquid.
Extravasation of fluid into alveolar lumen. Formation of fibrin in alveolar lumen Formation of fibrosis in alveolar tissue
Fig. 7. X-Ray and CT dynamics of ARDS development according to stages in comparison with morphological data
b) hyaline membranes in ARDS
c) cardiogenic pulmonary edema
c) cardiogenic pulmonary edema
d) Fluid accumulation in the alveolar lumen in cardiogenic pulmonary edema Fig. 8. X-Ray picture of ARDS and cardiogenic pulmonary edema in comparison with morphological data
Microscopic lung examination revealed fluid accumula- process, whereas ferric iron beads and hemosiderophages indi-tion in alveolar lumen (Fig. 6a), in some cases erythrocyte ef- cated chronic heart failure (Fig. 6b) due to primary heart pa-fusion into alveolar lumen was observed, which reflected acute thology.
Comparison ofdinical, morphological and radiographic data enables to see a complete "picture" ofpathological process, whereas development and prediction of outcome can be assessed based on dynamical X-Ray and CT examinations, which accurately reflects morphological stages of pathological process and following clinical manifestations. (Fig. 7, 8).
Conclusions:
1. X-ray picture in the initial phase of interstitial pulmonary edema was identical in patients of both groups. With the progression of the pathological process of X-ray and CT picture in ARDS was characterized by diffuse consolidation of lung tissue more in dependent zones, posterior and basal segments, while in patients with cardiogenic edema changes were found mostly in central zone, with the presence of pleural effusion and dilation of heart (borders). Reticular changes were observed in the resolution phase ofARDS edema, whereas cardiogenic pulmonary edema was characterized by increase of venous type pulmonary pattern with peribronchovasal infiltration.
2. Dependence of obtained X-ray/radiographic and CT data from the dynamics of clinical manifestations and a particular disease which led to the development of the pathological process were identified. Patients of the first group were generally admitted with acute,
first time occuring pathology (sepsis, pancreatitis, interstitial pneumonia, massive bleeding), dynamics of clinical symptoms depended on the disease severity and the rate of development of processes in the body. Patients of the second group, as a rule, had a history of chronic diseases (coronary heart disease, hypertension, valvular heart disease), with a long history, hemodynamic changes, heart muscle restructuring, congestion in the pulmonary circulation.
3. Morphological process in membranogenic and cardiogenic pulmonary edemas had different mechanisms. ARDS was characterized by damage of interalveolar septum capillaries. Morphologically three stages were identified: the first stage- exudative (6-24 hours after causative agent's affect) stage was characterized by congestion in capillaries, exudation of high protein level hemorrhagic fluid into alveoli, and formation of hyaline membranes, the second stage- proliferative stage was characterized by regeneration of alveolar epithelium and organization offibrous exudates, the third stage — fibrous stage was characterized by scarring of pulmonary tissue. All above-mentioned signs were not present in cardiogenic pulmonary edema and fluid leakage into alveoli was related to damage of contractile function of cardiac muscle.
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Irsalieva Fatima Khusnutdinovn, National Specialized Scientific Center of Allergology, Tashkent Kamalov Zaynitdin Sayfutdinovich, Institute of Immunology Academy of Sciences of the Republic of Uzbekistan E-mail: [email protected]
Immune status parameters and prognosis of the efficiency of allergen-specific immunotherapy in patients with persistent allergic rhinitis
Absrtact: The dynamics of the immunologic status parameters in 62 patients with persistent allergic rhinitis (PAR), who received the complete course of allergen specific immunotherapy (ASIT) was studied. Monitoring of the level of immunologic parameters was carried out before immunocorrecting therapy and upon completing ASIT course. ASIT efficiency in patients with PAR is characterized by high initial level of immunological parameters CD3+; CD4+; CD8+ and IgG and change in concentration of IL-4, IL-6, IL-8 in blood at the early stages of treatment.
Keywords: lymphocytes, immunocompetent cells, allergen specific immunotherapy, persistent allergic rhinitis, cytokines, interleykins.
Principal method of allergic diseases treatment, based upon gen-specific immunotherapy (ASIT) [8; 9]. This is the most bio-1st type allergic reaction, including grass pollen allergy, is aller- logically justified method of allergy treatment, aimed at switch
