Diagnosis of pneumonia

Diagnosis of pneumonia is based on the identification of 5 of the simplest and most informative clinical, laboratory and instrumental signs, called the "gold standard" of diagnosis:

1. Acute onset of the disease, accompanied by an increase in body temperature above 38 C.
2. Sudden onset or noticeable increase in cough with the release of sputum, predominantly purulent and/or hemorrhagic in nature.
3. The appearance of previously absent local dullness (shortening) of percussion sound and the auscultatory phenomena described above, characteristic of lobar (croupous) or focal pneumonia (weakening of breathing, bronchial breathing, crepitation, moist fine-bubble sonorous wheezing, pleural friction noise).
4. Leukocytosis or (less commonly) leukopenia in combination with a neutrophilic shift.
5. Radiological signs of pneumonia - focal inflammatory infiltrates in the lungs that were not previously detected.

Differential diagnosis of pneumonia

However, modern approaches to the etiotropic treatment of patients with pneumonia require a number of additional laboratory and instrumental tests for the purpose of possible identification of the pathogen, differential diagnosis of lung damage, assessment of the functional state of the respiratory system and timely diagnosis of complications of the disease. For this purpose, in addition to chest X-ray, general and biochemical blood tests, the following additional studies are provided:

• sputum examination (microscopy of a stained preparation and culture to identify the pathogen);
• assessment of external respiratory function;
• study of blood gases and arterial blood oxygen saturation (in cases
• severe pneumonia requiring treatment in intensive care;
• repeated blood tests “for sterility” (if bacteremia and sepsis are suspected);
• X-ray computed tomography (if traditional X-ray examination is not informative enough);
• pleural puncture (if there is effusion) and some others.

The choice of each of these methods is individual and should be based on an analysis of the characteristics of the clinical picture of the disease and the effectiveness of the diagnostics, differential diagnostics and treatment.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ]

X-ray diagnostics of pneumonia

X-ray examination methods are of crucial importance in diagnosing pneumonia. Currently, such methods as fluoroscopy and chest X-ray, tomography, and computed tomography are widely used in the clinic. A practicing physician should have a good understanding of the capabilities of these methods in order to correctly select the most informative of them in each specific case of the disease and, if possible, reduce the radiation load on the patient.

X-ray

It should be borne in mind that one of the most accessible and widespread methods of X-ray examination - chest X-ray - has a number of significant disadvantages, namely:

1. is characterized by a certain subjectivity in the interpretation of the X-ray image,
2. does not allow for objective comparison of radiological data obtained during repeated studies and
3. is accompanied by a large radiation load on the patient and medical staff.

Therefore, the scope of application of the fluoroscopy method in clinical practice should apparently be limited to the study of the chest organs during their movement (for example, the study of the mobility of the diaphragm, the nature of the heart's movements during its contraction, etc.) and the clarification of the topography of pathological changes in the lungs using various patient positions.

X-ray

The main method of X-ray examination of the respiratory organs is radiography in two projections - direct and lateral, allowing to obtain objective and documented information about the condition of the chest organs. In this case, it is necessary, if possible, to identify not only the nature of the pathological process, but also to accurately determine its localization, corresponding to the projection of a particular lobe of the lung and pulmonary segments.

Radiological diagnosis of pneumonia is based on the results of a study of the lung fields, including an assessment of:

• features of the pulmonary pattern;
• conditions of the roots of the lungs;
• the presence of widespread or limited darkening of the lung fields (compaction of lung tissue);
• the presence of limited or diffuse enlightenment of the lung tissue (increased airiness).

Of great importance is also the assessment of the condition of the skeleton of the chest and determination of the position of the diaphragm.

The roots of the lungs, located in the middle zone of the pulmonary fields between the anterior ends of the 2nd and 4th ribs, are formed by the shadows of the branches of the pulmonary artery and pulmonary veins, as well as large bronchi. Depending on their location relative to the plane of the screen, they are presented on the X-ray image as branching stripes or clear round or oval formations. The shadows of the vessels that form the root of the lung continue beyond it in the pulmonary fields, forming a pulmonary pattern. Normally, it is clearly visible in the central root zone, and on the periphery it is represented only by a few, very small vascular branches.

Below is a brief description of the radiographic picture characteristic of two clinical and morphological variants of pneumonia (lobar and focal), as well as some features of radiographic changes in pneumonia of various etiologies.

Tomography

Tomography is an additional method of "layer-by-layer" X-ray examination of organs, which is used in patients with pneumonia for a more detailed study of the pulmonary pattern, the nature of the pathological process in the pulmonary parenchyma and interstitium, the state of the tracheobronchial tree, the roots of the lungs, the mediastinum, etc.

The principle of the method is that as a result of the synchronous movement of the X-ray tube and the film cassette in the opposite direction, a sufficiently clear image of only those parts of the organ (its "layers") that are located at the level of the center, or the axis of rotation of the tube and cassette, is obtained on the film. All other parts ("elephant") located outside this plane are "smeared", as it were, their image becomes blurry.

To obtain a multilayer image, special cassettes are used, in which several films are placed at the required distance from each other. More often, so-called longitudinal tomography is used, when the layers to be isolated are in the longitudinal direction. The "swing angle" of the tube (and cassette) is usually 30-45°. This method is used to study the pulmonary vessels. To evaluate the aorta, pulmonary artery, inferior and superior vena cava, it is better to use transverse tomography.

In all cases, the choice of the depth of the tomographic examination, the exposure value, the swing angle and other technical parameters of the examination is carried out only after analyzing the previously taken X-ray image.

In diseases of the respiratory organs, the tomography method is used to clarify the nature and individual details of the pathological process in the lungs, as well as to assess morphological changes in the trachea, bronchi, lymph nodes, vessels, etc. This method is especially important in examining patients who are suspected of having a tumor process in the lungs, bronchi and pleura.

Screening program for suspected pneumonia

According to the consensus of the Russian Congress of Pulmonologists (1995), the following volume of research is recommended for pneumonia.

1. Research required for all patients
   • clinical examination of patients;
   • clinical blood test;
   • X-ray of the lungs in two projections;
   • bacterioscopy of sputum stained by Gram;
   • sputum culture with quantitative assessment of flora and determination of its sensitivity to antibiotics;
   • general urine analysis.
2. Research conducted according to indications
   • study of the function of external respiration in case of ventilation disorders;
   • study of blood gases and acid-base balance in severe patients with respiratory failure;
   • pleural puncture with subsequent examination of pleural fluid in patients with the presence of fluid in the pleural cavity;
   • tomography of the lungs if there is a suspicion of destruction of lung tissue or lung neoplasm;
   • serological tests (detection of antibodies to the pathogen) - for atypical pneumonia;
   • biochemical blood test for severe pneumonia in individuals over 60 years of age;
   • fibrobronchoscopy - if a tumor is suspected, if there is hemoptysis, or if pneumonia is protracted;
   • study of the immunological status - in the case of protracted pneumonia and in individuals with signs of immunodeficiency;
   • lung scintigraphy - if pulmonary embolism is suspected.

X-ray signs of lobar pneumonia

Stage of the tide

The earliest radiographic change that occurs in the first day of lobar pneumonia (the flush stage) is an increase in the pulmonary pattern in the affected lobe, caused by an increase in the blood supply to the pulmonary vessels, as well as by inflammatory edema of the pulmonary tissue. Thus, in the flush stage, an increase in both the vascular and interstitial components of the pulmonary pattern is observed.

There is also a slight widening of the root of the lung on the affected side, its structure becomes less distinct. At the same time, the transparency of the lung field remains practically unchanged or is slightly reduced.

If the focus of developing lobar pneumonia is located in the lower lobe, a decrease in the mobility of the corresponding dome of the diaphragm is observed.

Hepatization stage

The stage of hepatization is characterized by the appearance on the 2nd-3rd day from the onset of the disease of an intense homogeneous darkening corresponding to the projection of the affected lobe of the lung. The intensity of the shadow is more pronounced on the periphery. The size of the affected lobe is slightly increased or unchanged; a decrease in the volume of the lobe is observed relatively rarely. There is an expansion of the root of the lung on the side of the lesion, the root becomes non-structural. The pleura is compacted. The lumen of the large bronchi in lobar pneumonia remains free.

Resolution stage

The resolution stage is characterized by a gradual decrease in the intensity of the shadow and its fragmentation. In uncomplicated pneumonia, complete resorption of the infiltrate occurs in 2.5-3 weeks. In other cases, an increase in the pulmonary pattern with areas of its deformation remains at the site of the affected lobe, which is a radiological sign of pneumofibrosis. At the same time, a slight thickening of the pleura remains.

X-ray signs of focal pneumonia

Focal bronchopneumonia is characterized by infiltration of the alveolar and interstitial tissue and involvement of the lung root on the affected side in the inflammatory process. At the initial stages of the disease, localized enhancement of the pulmonary pattern and slight expansion of the lung root are observed. After some time, relatively small (from 0.3 to 1.5 cm in diameter) and various in shape foci of infiltration (darkening) begin to appear in the pulmonary field. They are characterized by multiplicity, varying size, low intensity of shadow, blurred outlines and, as a rule, are accompanied by an enhancement of the pulmonary pattern. The roots of the lungs become expanded, poorly structured, with unclear contours.

Slightly enlarged peribronchial lymph nodes are often found. Limited mobility of the dome of the diaphragm is also observed.

In uncomplicated cases, under the influence of anti-inflammatory treatment, positive dynamics of the X-ray picture is usually observed and after 1.5-2 weeks, pulmonary infiltrates are absorbed. Sometimes bronchopneumonia can be complicated by reactive pleurisy or destruction of lung tissue.

X-ray signs of staph pneumonia

The X-ray picture of staphylococcal pneumonia is characterized by the presence of multiple inflammatory infiltrates, most often located in both lungs. Inflammatory infiltrates often merge. There is a tendency for them to disintegrate with the formation of limited enlightenment with a horizontal fluid level against the background of shadows. In the "bullous form" of pneumonia, cavities can disappear without a trace in some places and appear in others. Effusion in the pleural cavity is often observed.

After the resolution of staphylococcal pneumonia, the increased pulmonary pattern persists for a long time, and in some cases areas of pleural sclerosis are formed, cysts remain in place of cavities, and the compaction of the pleural sheets (adhesions) persists.

X-ray signs of pneumonia caused by Klebsiella

A characteristic feature of Friedlander's pneumonia caused by Klebsiella is the extensiveness of the pulmonary tissue damage, which is radiologically evident from the first days of the disease. Multiple large or smaller inflammatory infiltrates quickly merge with each other, capturing large areas of the lung, often corresponding to the projection of an entire lobe of the lung ("pseudo-lobar" pneumonia). Quite quickly, multiple decay cavities appear in the infiltrate, which also tend to merge and form a large cavity with a horizontal fluid level. The disease is often complicated by the development of exudative pleurisy.

The course of Friedlander's pneumonia is long (up to 2-3 months). After recovery, as a rule, areas of pronounced pleural sclerosis and carnification of the lung remain. Bronchiectasis often forms, and the pleural cavity is partially obliterated.

X-ray signs of pneumonia caused by intracellular pathogens

In Legionella pneumonia, radiographic changes are varied. Most often, multiple infiltrates are detected in both lungs, which later merge into extensive lobar darkening. Tissue decay and abscess formation are quite rare. Resorption of infiltrates and normalization of the radiographic picture in uncomplicated cases of the disease occurs after 8-10 weeks.

In mycoplasma pneumonia, radiographs may show only localized enhancement and deformation of the pulmonary pattern, reflecting infiltration of the interstitial tissue. In some patients, low-intensity focal shadows appear in this foyer, which tend to merge. Normalization of the radiographic picture occurs after 2-4 weeks.

In chlamydial pneumonia, focal enhancement and deformation of the pulmonary pattern, expansion of the lung root and pleural reaction in the form of its compaction are also initially determined. Subsequently, against this background, numerous inflammatory foci of low intensity with unclear contours may appear. After their disappearance during treatment, the enhancement of the pulmonary pattern persists for a long time, sometimes discoid atelectases are visible. Normalization of the radiographic picture occurs after 3-5 weeks.

Computed tomography for pneumonia

Computer tomography (CT) is a highly informative method of X-ray examination of a patient, which is becoming increasingly widespread in clinical practice. The method is characterized by high resolution, allowing visualization of foci up to 1-2 mm in size, the ability to obtain quantitative information on tissue density and the convenience of presenting the X-ray picture in the form of thin (up to 1 mm) successive transverse or longitudinal "sections" of the organs being examined.

Each tissue layer is illuminated in a pulsed mode using an X-ray tube with a slit collimator, which rotates around the longitudinal axis of the patient's body. The number of such illuminations at different angles reaches 360 or 720. Each time the X-rays pass through a tissue layer, the radiation is weakened, depending on the density of individual structures of the layer being examined. The degree of X-ray weakening is measured by a large number of special highly sensitive detectors, after which all the information received is processed by a high-speed computer. As a result, an image of an organ section is obtained, in which the brightness of each coordinate point corresponds to the density of the tissue. Image analysis is performed both automatically using a computer and special programs, and visually.

Depending on the specific objectives of the study and the nature of the pathological process in the lungs, the operator can choose the thickness of the axial slices and the direction of tomography, as well as one of three study modes.

1. Continuous CT, when an image of all sections of an organ without exception is obtained sequentially. This method of tomography makes it possible to obtain maximum information about morphological changes, but is characterized by a high radiation load and the cost of the study.
2. Discrete CT with a given relatively large interval between slices, which significantly reduces the radiation load, but leads to the loss of some information.
3. Targeted CT involves a thorough layer-by-layer examination of one or more areas of the organ of interest to the physician, usually in the area of a previously identified pathological formation.

Continuous CT of the lungs allows obtaining maximum information about pathological changes in the organ and is indicated primarily for volumetric processes in the lungs, when the presence of lung cancer or metastatic lesions of the organs is not excluded. In these cases, CT makes it possible to study in detail the structure and size of the tumor itself and to clarify the presence of metastatic lesions of the pleura, mediastinal lymph nodes, lung roots and retroperitoneal space (in CT of the abdominal organs and retroperitoneal space).

Discrete CT is more indicated for diffuse pathological processes in the lungs (pyeumoconiosis, alveolitis, chronic bronchitis, etc.), when surgical treatment is assumed.

Targeted CT is used mainly in patients with an established diagnosis and an established nature of the pathological process, for example, to clarify the contour of a volumetric formation, the presence of necrosis in it, the state of the surrounding lung tissue, etc.

Computer tomography has significant advantages over conventional X-ray examination, as it allows detecting finer details of the pathological process. Therefore, the indications for using the CT method in clinical practice are, in principle, quite broad. The only significant factor limiting the use of the method is its high cost and its low availability for some medical institutions. Taking this into account, one can agree with the opinion of a number of researchers that "the most general indications for CT of the lungs arise in cases where the information content of a conventional X-ray examination is insufficient to establish a definitive diagnosis and the CT results are capable of influencing the treatment tactics."

In patients with pneumonia, the need for CT is about 10%. With CT, infiltrative changes in the lungs are detected at earlier stages of the disease.

[ 7 ], [ 8 ], [ 9 ], [ 10 ], [ 11 ], [ 12 ], [ 13 ]

General clinical blood test for pneumonia

A general clinical blood test is included in the mandatory examination plan for all inpatients and outpatients with pneumonia. The greatest diagnostic value is the count of leukocytes, determination of the leukocyte formula and ESR.

White blood cell count

Normally, the total number of leukocytes is (4.0-8.8) x 10 ⁹ /l.

Leukocytosis is typical for most patients with bacterial pneumonia. It indicates accelerated maturation of leukocytes in the hematopoietic organs under the influence of numerous natural stimulators of leukopoiesis: physical and chemical factors of inflammation, including mediators of inflammation, tissue decay products, hypoxemia, formed immune complexes, some toxic substances, increased function of the pituitary-adrenal system, which controls the maturation process of leukocytes, and others. Most of these factors are natural signals for the activation of the protective functions of leukocytes.

Leukocytosis in patients with pneumonia in most cases reflects satisfactory reactivity of the bone marrow hematopoiesis system in response to external and internal stimulators of leukopoiesis. At the same time, leukocytosis is a fairly sensitive marker of the severity of the inflammatory process in the lungs

At the same time, it should be remembered that in pneumonias caused by chlamydia, moderate leukopenia is observed in most cases (a decrease in the number of leukocytes to less than 4.0 x 10°/l). In mycoplasma pneumonias, the total number of leukocytes usually remains normal (about 8.0 x 10 ⁹ /l), although leukocytosis or leukopenia is determined in 10-15% of cases. Finally, viral infections are usually accompanied by an increase in ESR and a normal or decreased number of leukocytes (leukopenia).

In all other cases of bacterial pneumonia caused by pneumococci, streptococci, staphylococci, Haemophilus influenzae, Legionella, Klebsiella, Pseudomonas aeruginosa, etc., the appearance of leukopenia, as a rule, indicates a significant suppression of leukopoiesis in the hematopoietic organs and is a very unfavorable prognostic sign. This is more often observed in old people, exhausted and weakened patients, which is associated with a decrease in immunity and general resistance of the body. In addition, it should be remembered that leukopenia can be associated with the use of certain drugs (antibiotics, cytostatics, non-steroidal anti-inflammatory drugs, etc.) and autoimmune processes that complicate, in particular, the course of pneumonia.

Leukocytosis is typical for most patients with bacterial pneumonia. The exceptions are pneumonia caused by chlamydia and mycoplasma, as well as most viral infections, in which moderate leukopenia or normal leukocyte counts may be observed.

The appearance of leukopenia in patients with bacterial pneumonia may indicate significant suppression of leukopoiesis and is a very unfavorable prognostic sign, indicating a decrease in immunity and general resistance of the body. In addition, leukopenia may develop against the background of treatment with antibiotics, cytostatics and nonsteroidal anti-inflammatory drugs.

Leukocyte formula

The white blood cell count is the percentage ratio of different types of white blood cells in the peripheral blood. The white blood cell count is calculated using immersion microscopy of stained smears stained by Romanovsky-Giemsa or other methods.

Differentiation of different types of leukocytes and calculation of the leukocyte formula requires a good knowledge of the morphological features of different leukocytes and the general scheme of hematopoiesis. The myeloid series of hematopoiesis is represented by cells of the granulocytic, megakaryocytic, monocytic and erythrocytic hematopoietic lineages.

Granulocytes are blood cells whose most characteristic morphological feature is the distinct granularity of the cytoplasm (neutrophilic, eosinophilic or basophilic). These cells have a common ancestor and a single evolution up to the promyelocyte stage, after which there is a gradual differentiation of granulocytes into neutrophils, eosinophils and basophils, which differ significantly from each other in their structure and function.

Neutrophils have abundant, fine, dust-like granularity of a pinkish-violet color. Mature eosinophils are distinguished by large granularity, occupying the entire cytoplasm, having a scarlet color ("whale caviar"). Granularity of basophils is large, heterogeneous, dark violet or black.

Young immature granulocyte cells (myeloblast, promyelocyte, neutrophilic, eosinophilic and basophilic myelocytes and megamyelocytes) are larger in size, have a large round or slightly concave nucleus with a more delicate and fine pattern and light color. Their nuclei often contain nucleoli.

Mature granulocytes (band and segmented) are smaller in size, their nuclei are darker in color, and look like curved rods or separate segments connected by a "thread" of nuclear substance. The nuclei do not contain nucleoli.

The cells of the monocytic lineage are characterized by a pale blue or grayish color of the cytoplasm, devoid of the pronounced granularity that is characteristic of granulocytes. In the cytoplasm, one can find only individual small azurophilic granules, as well as vacuoles. In immature cells of the monocytic series (monoblast, promonocyte), the nucleus is large, occupying most of the cell. The nucleus of a mature monocyte is smaller in size and has the appearance of a butterfly or mushroom, although it can often take on quite bizarre shapes.

The cells of the lymphoid hematopoietic germ (lymphoblast, prolymphocyte and lymphocyte) are characterized by a very large, round, sometimes bean-shaped nucleus of a dense structure, occupying almost the entire cell. The cytoplasm of blue or light blue color is located in a narrow strip around the nucleus. It is devoid of specific granularity, due to which lymphocytes together with monocytes are called agranulocytes. Normally, as is known, only mature leukocyte cells are found in the peripheral blood:

• segmented neutrophils, eosinophils and basophils;
• band neutrophils (sometimes eosinophils);
• monocytes;
• lymphocytes.

Degenerative forms of leukocytes

In addition to the cells described above, so-called pre-generative forms of leukocytes are found in pneumonia, infections and purulent-inflammatory diseases. The following forms are most frequently detected

1. Neutrophils with toxic granularity and vacuolization of the cytoplasm. Toxic granularity of neutrophils occurs as a result of coagulation of cytoplasmic protein under the influence of an infectious or toxic agent. In these cases, in addition to the fine, delicate granularity characteristic of neutrophils, large, coarse, basophilically stained granules and vacuoles appear in the cytoplasm. Toxic granularity and vacuolization of the cytoplasm of neutrophils and monocytes are often encountered in severe pneumonia, such as severe pneumococcal lobar pneumonia and other purulent-inflammatory diseases accompanied by severe intoxication.
2. Hypersegmented neutrophils, the nucleus of which consists of 6 or more segments, are found in B12-folate deficiency anemia, leukemia, as well as in some infections and purulent-inflammatory diseases, reflecting the so-called nuclear shift of neutrophils to the right.
3. Degenerative changes in lymphocytes in the form of a pyknotic nucleus, sometimes having a bilobed structure, and weak development or absence of cytoplasm
4. Atypical mononuclear cells are cells that combine some morphological features of lymphocytes and monocytes: they are larger than normal lymphocytes, but do not reach the size of monocytes, although they contain a monocyte nucleus. In terms of morphology, lymphomonocytes resemble blast cells and are often found in infectious mononucleosis.

[ 14 ], [ 15 ], [ 16 ], [ 17 ], [ 18 ]

Interpretation of results

Leukocyte formula in healthy people

	Granulocytes				Agranulocytes
	Neutrophils		Eosinophils	Basophils	Lymphocytes	Monocytes
	Rod-nuclear	Segmented-nuclear
% of the total number of leukocytes	1-6%	47-72%	0.5-5%	0-1%	19-37%	3-11%
Absolute quantity (nx 10 9 /l)	0.04-0.3	2.0-5.5	0.02-0.3	0-0.65	1.2-3.0	0.09-0.6

In various pathological conditions, including pneumonia, the following may occur:

• change in the leukocyte formula (increase or decrease in any type of leukocytes);
• the appearance of various degenerative changes in the nucleus and cytoplasm of mature leukocyte cells (neutrophils, lymphocytes and monocytes);
• the appearance of young immature leukocytes in the peripheral blood.

To correctly interpret changes in the leukocyte formula, it is necessary to evaluate not only the percentage ratios of different types of leukocytes, but also their absolute content in 1 liter of blood. This is due to the fact that a change in the percentage of individual types of leukocytes does not always correspond to their true increase or decrease. For example, with leukopenia caused by a decrease in the number of neutrophils, a relative increase in the percentage of lymphocytes and monocytes may be detected in the blood, while their absolute number will actually be normal.

If, along with the percentage increase or decrease of individual types of leukocytes, a corresponding change in their absolute content in 1 liter of blood is observed, we speak of their absolute change. An increase or decrease in the percentage of cells with their normal absolute content in the blood corresponds to the concept of a relative change.

Let us consider the diagnostic significance of some changes in the leukocyte formula that are most frequently encountered in clinical practice, including in patients with pneumonia.

Neutrophilia - an increase in the number of neutrophils over 6.0 x 10 ⁹ /l - is a reflection of the body's unique defense in response to numerous exogenous and endogenous factors. The most common (but not the only) causes of neutrophilia, in most cases combined with leukocytosis, are:

1. Acute infections (bacterial, parasitic, fungal, rickettsial, etc.).
2. Acute inflammatory and purulent processes (pneumonia, sepsis, abscess, exudative pleurisy, pleural empyema and many others).
3. Diseases accompanied by necrosis, decay and damage to tissues.
4. Intoxication.

When assessing the diagnostic and prognostic significance of the neutrophil shift, it is important to determine the percentage ratio of immature and mature forms of neutrophils. For this purpose, the nuclear index of neutrophil shift is calculated - the ratio of the content of myelocytes, metamyelocytes and band neutrophils to segmented neutrophils.

Nuclear shift index = myelocytes + metamyelocytes + band/segmented

Normally, the nuclear shift index is 0.05-0.1.

• A left shift in the blood formula is an increase in the number of band neutrophils in the peripheral blood and (less frequently) the appearance of a small number of immature granulocytes (metamyelocytes, myelocytes, and even single myeloblasts), which indicates significant irritation of the bone marrow and acceleration of leukopoiesis. The nuclear index of neutrophil shift in this case exceeds 0.1.
• A shift in the blood formula to the right is an increase in the number of mature segmented neutrophils in the peripheral blood, the appearance of hypersegmented neutrophils and a decrease or disappearance of band neutrophils. The nuclear shift index is less than 0.05.

In most patients with pneumonia, acute infections, purulent-inflammatory and other diseases accompanied by neutrophilia, the shift in the blood formula to the left is limited only to an increase in the number of band neutrophils (hyporegenerative nuclear shift), which, in combination with moderate leukocytosis, as a rule, indicates a relatively mild infection or a limited purulent-inflammatory process and good resistance of the body.

In severe cases of the disease and preserved resistance of the body, a shift in the blood formula to metamyelocytes, myelocytes and (less often) to myeloblasts (hyperregenerative nuclear shift to the left) is observed, which in combination with high leukocytosis and neutrophilia is designated as a leukemoid reaction of the myeloid type, since it resembles the blood picture in myeloleukemia. These changes are usually accompanied by hypo- and aneosinophilia, relative lymphopenia and monocytopenia.

Neutrophilia with degenerative nuclear shift to the left, which is manifested by an increase in immature forms of neutrophils and the appearance in the peripheral blood of degeneratively altered segmented neutrophils (toxic granularity, pycnosis of nuclei, vacuolization of the cytoplasm) is also observed in severe pneumonia, purulent-inflammatory diseases and endogenous intoxications and indicates suppression of the functional activity of the bone marrow.

Neutrophilia with a pronounced shift in the blood formula to the left in combination with slight leukocytosis or leukopenia, as a rule, indicates a severe course of the pathological process and poor resistance of the body. Often, such a blood picture is observed in elderly and senile people and in weakened and exhausted patients.

Neutrophilia with a nuclear shift to the right (an increase in segmented and hyperpigmented neutrophils, a decrease or disappearance of band neutrophils), as a rule, indicates a good, adequate protective reaction of bone marrow hematopoiesis to infection or inflammation and a favorable course of the disease.

The severe course of many pneumonias, as well as infectious, generalized purulent-inflammatory, degenerative and other diseases with preserved body resistance is often accompanied by pronounced neutrophilia, leukocytosis and a hyperregenerative shift in the blood formula to the left.

The appearance of degenerative forms of neutrophils in the peripheral blood (toxic granularity, pycnosis of nuclei and other changes), as well as pronounced neutrophilia and a nuclear shift to the left in combination with slight leukocytosis or leukopenia in most cases indicate suppression of the functional activity of the bone marrow, a decrease in the body's resistance and are very unfavorable signs.

Neutropenia - a decrease in the number of neutrophils below 1.5 x 10 ⁹ /l - indicates functional or organic suppression of bone marrow hematopoiesis or intensive destruction of neutrophils under the influence of antibodies to leukocytes, circulating immune complexes or toxic factors (autoimmune diseases, tumors, aleukemic forms of leukemia, the effect of certain medications, hypersplenism, etc.). It should also be borne in mind the possibility of temporary redistribution of neutrophils within the vascular bed, which can be observed, for example, in shock. Neutropenia is usually combined with a decrease in the total number of leukocytes - leukopenia.

The most common causes of neutropenia are:

1. Infections: viral (flu, measles, rubella, chickenpox, infectious hepatitis, AIDS), some bacterial (typhoid fever, paratyphoid fever, brucellosis), rickettsial (typhus), protozoal (malaria, toxoplasmosis).
2. Other acute and chronic infections and inflammatory diseases that occur in severe forms and/or acquire the character of generalized infections
3. The effect of some medications (cytostatics, sulfonamides, analgesics, anticonvulsants, antithyroid drugs, etc.).

Neutropenia, especially when combined with a neutrophilic shift to the left and developing against the background of purulent-inflammatory processes, for which neutrophilia is typical, indicates a significant decrease in the body's resistance and an unfavorable prognosis for the disease. Such a reaction of bone marrow hematopoiesis in patients with pneumonia is most typical for exhausted, weakened patients and elderly and senile individuals.

Eosinophilia - an increase in the number of eosinophils in the peripheral blood of more than 0.4 x 10 ^e / l - is most often a consequence of pathological processes based on the formation of antigen-antibody complexes or diseases accompanied by autoimmune processes or bone marrow proliferation of the eosinophilic hematopoietic germ:

1. Allergic diseases (bronchial asthma, urticaria, hay fever, angioedema, serum sickness, drug sickness).
2. Parasitic infestations (trichinosis, echinococcosis, opisthorchiasis, ascariasis, diphyllobothriasis, giardiasis, malaria, etc.).
3. Connective tissue diseases (periarteritis nodosa, rheumatoid arthritis, scleroderma, systemic lupus erythematosus).
4. Non-specific ulcerative colitis.
5. Skin diseases (dermatitis, eczema, pemphigus, lichen, etc.).
6. Blood diseases (lymphogranulomatosis, erythremia, chronic myelogenous leukemia).
7. Eosinophilic infiltrate of the lung.
8. Löffler's fibroplastic mural endocarditis.

Moderate eosinophilia often develops during the recovery period of patients with pneumonia and other acute infectious and inflammatory diseases ("scarlet dawn of recovery"). In these cases, eosinophilia is usually combined with a decrease in previously observed neutrophilia and leukocytosis.

Eosinopenia - a decrease or disappearance of eosinophils in the peripheral blood - is often detected in infectious and purulent-inflammatory diseases and, along with leukocytosis, neutrophilia and a left shift in the nuclear blood formula, is an important laboratory sign of an active inflammatory process and a normal (adequate) response of bone marrow hematopoiesis to inflammation.

Eosinopenia, detected in patients with pneumonia and purulent-inflammatory diseases, in combination with neutropenia, leukopenia and a shift in the blood formula to the left, usually reflects a decrease in the body's resistance and is a very unfavorable prognostic sign.

Basophilia - an increase in the number of basophils in the blood - is quite rare in clinical practice, including pneumonia. Among the diseases most often accompanied by basophilia, the following can be distinguished:

1. Myeloproliferative diseases (chronic myelogenous leukemia, myelofibrosis with myeloid metaplasia, true polycythemia - Vaquez disease);
2. Hypothyroidism (myxedema);
3. Lymphograiulomatosis;
4. Chronic hemolytic anemia.

The absence of basophils in the peripheral blood (basopenia) has no diagnostic value. It is sometimes detected in hyperthyroidism, acute infections, after taking corticosteroids.

Lymphocytosis is an increase in the number of lymphocytes in the peripheral blood. In clinical practice, relative lymphocytosis is more common, i.e. an increase in the percentage of lymphocytes with a normal (or even slightly reduced) absolute number. Relative lymphocytosis is detected in all diseases accompanied by absolute neutropenia and leukopenia, including viral infections (flu), purulent-inflammatory diseases occurring against the background of decreased body resistance and neutropenia, as well as typhoid fever, brucellosis, leishmaniasis, agranulocytosis, etc.

An absolute increase in the number of lymphocytes in the blood of more than 3.5 x 10 ⁹ /l (absolute lymphocytosis) is characteristic of a number of diseases:

1. Acute infections (including so-called childhood infections: whooping cough, measles, rubella, chickenpox, scarlet fever, infectious mononucleosis, mumps, acute infectious lymphocytosis, acute viral hepatitis, cytomegalovirus infection, etc.).
2. Tuberculosis.
3. Hyperthyroidism.
4. Acute and chronic lymphocytic leukemia.
5. Lymphosarcoma.

Contrary to popular belief, lymphocytosis in purulent-inflammatory diseases and pneumonia cannot be considered as a reliable laboratory sign of a compensatory reaction of the immune system and the onset of recovery. Lymphocytopenia is a decrease in the number of lymphocytes in the peripheral blood. Relative lymphocytopenia is observed in such diseases and at such a stage of development of the pathological process, which is characterized by an absolute increase in the number of neutrophils (neutrophilia): various infections, purulent-inflammatory diseases, pneumonia. Therefore, in most cases, such relative lymphocytopenia does not have independent diagnostic and prognostic value.

Absolute lymphocytopenia with a decrease in the number of lymphocytes below 1.2 x 10 ⁹ /l may indicate a deficiency of the T-system of immunity (immunodeficiency) and requires a more thorough immunological study of the blood, including an assessment of the indicators of humoral cellular immunity and the phagocytic activity of leukocytes.

Monocytosis can also be relative and absolute.

Relative monocytosis is often found in diseases that occur with absolute neutropenia and leukopenia, and its independent diagnostic value in these cases is small.

Absolute monocytosis, detected in some infections and purulent-inflammatory processes, should be assessed, first of all, keeping in mind that the main functions of the monocyte-macrophage series are:

1. Protection against certain classes of microorganisms.
2. Interaction with antigens and lymphocytes at individual stages of the immune response.
3. Elimination of damaged or aged cells.

Absolute monocytosis occurs in the following diseases:

1. Some infections (infectious mononucleosis, subacute septic endocarditis, viral, fungal, rickettsial and protozoal infections).
2. Long-term purulent-inflammatory diseases.
3. Granulomatous diseases (active tuberculosis, brucellosis, sarcoidosis, ulcerative colitis, etc.).
4. Blood diseases: acute myeloid leukemia, chronic myelogenous leukemia, myeloma, lymphogranulomatosis, other lymphomas, aplastic anemia.

In the first three cases (infections, purulent-inflammatory diseases), absolute monocytosis may indicate the development of pronounced immune processes in the body.

Monocytonia - a decrease or even complete absence of monocytes in the peripheral blood - often develops in severe cases of pneumonia, infectious and purulent-inflammatory diseases.

Leukemoid reactions are pathological reactions of the hematopoietic system, accompanied by the appearance of young immature leukocytes in the peripheral blood, which indicates significant irritation of the bone marrow and acceleration of leukopoiesis. In these cases, the blood picture outwardly resembles the changes detected in leukemia. Leukemoid reactions are often combined with pronounced leukocytosis, although in rarer cases they can develop against the background of a normal number of leukocytes or even leukopenia.

A distinction is made between leukemoid reactions of 1) the myeloid type, 2) the lymphatic (or monocyte-lymphatic) type, 3) the eosinophilic type.

Leukemoid reaction of the myeloid type is accompanied by a shift in the blood formula to metamyelocytes, myelocytes and myeloblasts and is observed in severe infectious, purulent-inflammatory, septic, degenerative and other diseases and intoxications, which are characterized by a hyperregenerative nuclear shift of neutrophils to the left. A particularly severe and prognostically unfavorable sign in these diseases is the combination of a leukemoid reaction with a normal or reduced number of leukocytes and neutrophils (leukopenia and neutropenia).

Erythrocyte sedimentation rate (ESR)

The determination of ESR is based on the property of erythrocytes to settle at the bottom of the vessel under the influence of gravity. For this purpose, the micromethod of T.P. Panchenkov is usually used. ESR is determined 1 hour after the start of the study by the size of the plasma column above the settled erythrocytes. Normally, ESR in men is 2-10, and in women - 4-15 mm per hour.

The mechanism of agglomeration of erythrocytes and their sedimentation is extremely complex and depends on many factors, primarily on the qualitative and quantitative composition of blood plasma and on the physicochemical properties of the erythrocytes themselves.

As is known, the most common cause of increased ESR is an increase in the content of large-dispersed proteins in plasma (fibrinogen, a-, beta- and gamma-globulins, paraproteins), as well as a decrease in the content of albumins. Large-dispersed proteins have a lower negative charge. By adsorbing on negatively charged erythrocytes, they reduce their surface charge and promote the convergence of erythrocytes and their faster agglomeration.

An increase in ESR is one of the characteristic laboratory signs of pneumonia, the immediate cause of which is the accumulation in the blood of coarsely dispersed fractions of globulins (usually a-, beta- and gamma-fractions), fibrinogen and other proteins of the acute phase of inflammation. In this case, a certain correlation is observed between the severity of inflammation of the lung tissue and the degree of increase in ESR.

At the same time, it should be remembered that an increase in ESR is, although quite sensitive, a non-specific hematological indicator, an increase in which can be associated not only with inflammation, but also with any pathological process leading to severe dysproteinemia (connective tissue diseases, hemoblastoses, tumors, anemia, tissue necrosis, liver and kidney diseases, etc.).

On the other hand, in patients with pneumonia, ESR may not be increased if there is a simultaneous thickening of the blood (increased viscosity) or a decrease in pH (acidosis), which are known to cause a decrease in the agglomeration of red blood cells.

In addition, in the early stages of some viral infections, there is also no increase in ESR, which may to some extent distort the results of the study in patients with viral-bacterial pneumonia.

[ 19 ], [ 20 ], [ 21 ], [ 22 ]

Biochemical blood test for pneumonia

Evaluation of the results of biochemical blood tests in patients with pneumonia, especially in dynamics - in the process of disease development, has great diagnostic and prognostic value. Changes in various biochemical parameters, being in most cases non-specific, allow us to judge the nature and degree of metabolic disorders both in the whole organism and in individual organs. Comparison of this information with the clinical picture of the disease and the results of other laboratory and instrumental research methods makes it possible to evaluate the functional state of the liver, kidneys, pancreas, endocrine organs, the hemostasis system, and often - to form an idea of the nature of the pathological process, the activity of inflammation and to promptly recognize a number of pneumonia complications.

[ 23 ], [ 24 ], [ 25 ], [ 26 ], [ 27 ], [ 28 ], [ 29 ], [ 30 ]

Protein and protein fractions

Determination of protein and protein fractions in patients with pneumonia is of particular importance, primarily for assessing the activity of the inflammatory process. The concentration of proteins in the plasma of a healthy person ranges from 65 to 85 g/l. The bulk of the total plasma protein (about 90%) is albumin, globulin, and fibrinogen.

Albumins are the most homogeneous fraction of simple proteins, almost exclusively synthesized in the liver. About 40% of albumins are in plasma, and 60% in the intercellular fluid. The main functions of albumins are to maintain colloid-osmotic (oncotic) pressure, as well as participation in the transport of many endogenous and exogenous substances (free fatty acids, bilirubin, steroid hormones, magnesium ions, calcium, antibiotics, and others).

Serum globulins are represented by four fractions (a1, a2, beta and gamma), each of which is not homogeneous and contains several proteins that differ in their functions.

The composition of a1-globulins normally includes two proteins that have the greatest clinical significance:

• a1-antitrypsin, which is an inhibitor of a number of proteases (trypsin, chymotrypsin, kallikrein, plasmin);
• a1-glycoprotein involved in the transport of progesterone and testosterone, binding small amounts of these hormones.
• a2-globulins are represented by the following proteins:
• a2-macroglobulin is an inhibitor of a number of proteolytic enzymes (trypsin, chymotrypsin, thrombin, plasmin, kallikrein), synthesized outside the liver;
• haptoglobin is a protein that binds and transports free hemoglobin A into the cells of the reticuloendothelial system;
• ceruloplasmin - has oxidase activity and oxidizes divalent iron into trivalent iron, which ensures its transport by transferrin;
• apoproteins A, B and C, which are part of lipoproteins.

The globulin fraction also contains several proteins:

• transferrin is a protein involved in the transport of trivalent iron;
• hemopexin is a carrier of free heme and porphyrin, binds heme-containing chromoproteins (hemoglobin, myoglobin, catalase) and delivers them to the cells of the liver RES;
• lipoproteins;
• part of immunoglobulins;
• some protein components of complement.

Gamma globulins are immunoglobulins that function as antibodies produced in the body in response to the introduction of various substances with antigenic activity; modern methods make it possible to distinguish several classes of immunoglobulins (IgG, IgA, IgM, IgD and IgE).

Fibrinogen is a critical component of the blood coagulation system (factor I). It forms the basis of a blood clot, a three-dimensional network in which blood cells are trapped.

The content of total serum protein in a healthy person fluctuates between 65 and 85 g/l, and albumin - from 35 to 50 g/l. It should be emphasized that in different clinical laboratories using different automatic analyzers and methods for determining protein fractions, the standards may differ slightly from those given in the table.

Normal values of protein fractions of blood serum (in %)

Protein fractions	Electrophoresis on cellulose acetate films		Electrophoresis on paper
	Coloring
	Crimson C	Bromophenol blue
Albumen	52 (46.9-61.4)	58 (53.9-62.1)	50-70
A1-globulins	3.3 (2.2-4.2)	3.9 (2.7-5.1)	3-6
A2-globulins	9.4 (7.9-10.9)	8.8 (7.4-10.2)	9-15
Beta globulins	14.3(10.2-18.3)	13.0(11.7-15.3)	8-18
Y-globulins	21.4(17.6-25.4)	18.5(15.6-21.4)	15-25

The albumin-globulin ratio (A/G) is normally 1.2-1.8.

Changes in the content of globulin fractions, which are very characteristic of any acute or chronic inflammation, are usually also found in patients with pneumonia,

Most often, an increase in the content of a1 and a2 globulin fractions is observed. This is due to the fact that a-globulins include the so-called acute phase proteins (a1 antitrypsin, a1 glycoprotein, a2 macroglobulin, haptoglobulin, ceruloplasmin, seromucoid, C-reactive protein), which naturally increase with any inflammatory process in the body. In addition, an increase in the content of a-globulins is observed with significant damage and decay of tissues (dystrophic, necrotic processes), accompanied by cell destruction and the release of tissue proteases, kallikrein, thrombin, plasmin, etc., which naturally leads to an increase in the content of their natural inhibitors (a1 antitrypsin, a1 glycoprotein, a2 macroglobulin, etc.). Tissue damage also leads to the release of pathological C-reactive protein, which is a product of cell breakdown and is part of the a1-fraction of globulins.

An increase in the beta-globulin fraction is usually observed in acute and chronic diseases accompanied by an increase in the content of immunoglobulins in the blood (usually simultaneously with an increase in the content of γ-globulins), including infections, chronic inflammatory processes in the bronchi, liver cirrhosis, connective tissue diseases, malignant neoplasms, autoimmune and allergic diseases.

An increase in the y-globulin fraction is found in diseases accompanied by intensification of immune processes, since the y-globulin fraction consists mainly of immunoglobulins: in chronic infections, chronic liver diseases (chronic hepatitis and liver cirrhosis), autoimmune diseases (including connective tissue diseases - RA, SLE, etc.), chronic allergic diseases (bronchial asthma, recurrent urticaria, drug disease, atopic dermatitis and eczema, etc.). An increase in the y-globulin fraction is also possible in pneumonia, especially protracted ones.

Acute phase proteins

In addition to the described changes in protein fractions, patients with pneumonia are characterized by an increase in the content of so-called acute phase proteins of inflammation: fibrinogen, ceruloplasmin, haptoglobulin, a2-macroglobulin, C-reactive protein, etc., which also belong to non-specific markers of the inflammatory process.

Glycoproteins

Among the carbohydrate-containing compounds that are important in diagnostics are glycoproteins - proteins containing relatively short carbohydrate chains consisting of 10-20 monosaccharides. Their concentration in the blood also increases significantly during inflammatory processes and tissue damage (necrosis).

The carbohydrate components of glycoproteins, the quantitative determination of which forms the basis of most diagnostic tests, include:

1. hexoses (galactose, mannose, less often glucose);
2. pentoses (xylose and arabinose);
3. deoxysugars (fucose and rhamnose);
4. amino sugars (acetyl glucosamine, acetyl galactosamine);
5. sialic acids are derivatives of neuraminic acid (acetylneuraminic and glycolylneuraminic acids).

In clinical practice, the most widely used methods are for determining sialic acids and the total amount of protein-bound hexoses.

Of great diagnostic importance is also the determination of hexoses associated with the so-called seromucoids. Seromucoids are a special group of carbohydrate-containing proteins that differ from ordinary glycoproteins in their ability to dissolve well in perchloric acid. This latter property of seromucoids allows them to be identified from other glycoproteins containing hexoses.

Normally, the total content of hexoses associated with proteins in plasma or serum is 5.8-6.6 mmol/l. Of these, seromucoids account for 1.2-1.6 mmol/l. The concentration of sialic acids in the blood of a healthy person does not exceed 2.0-2.33 mmol/l. The content of total protein-associated hexoses, seromucoid, and sialic acids increases significantly with any inflammatory processes and tissue damage (pneumonia, myocardial infarction, tumors, etc.).

Lactate dehydrogenase (LDH)

Lactate dehydrogenase (LDH) (EC 1.1.1.27) is one of the most important cellular enzymes involved in the process of glycolysis and catalyzes the reversible reaction of the reduction of pyruvic acid (pyruvate) to lactic acid (lactate).

As is known, pyruvate is the end product of glycolysis. Under aerobic conditions, pyruvate undergoes oxidative decarboxylation, converts into acetyl-CoA and is then oxidized in the tricarboxylic acid cycle (Krebs cycle), releasing a significant amount of energy. Under anaerobic conditions, pyruvate is reduced to lactate (lactic acid). This latter reaction is catalyzed by lactate dehydrogenase. The reaction is reversible: in the presence of O2, lactate is again oxidized to pyruvate.

Electrophoresis or chromatography can detect 5 LDH isoenzymes, differing in their physicochemical properties. The two most important isoenzymes are LDH1 and LDH5. Most organs contain a full set of LDH isoenzymes, including fractions LDH2, 3, 4.

Normally, the activity of LDH in the blood serum does not exceed 0.8-4.0 mmol / h x l). Any damage to tissue cells containing a large amount of LDH, including damage observed during pneumonia, leads to an increase in the activity of LDH and its isoenzymes in the blood serum.

Non-specific biochemical criteria of the inflammatory process in patients with pneumonia are:

• an increase in the content of alpha and beta globulins in the blood serum, and with more significant activation of the immune system and/or chronicity of the process - an increase in the content of gamma globulins;
• increased levels of acute phase proteins in the blood: fibrinogen, ceruloplasmin, haptoglobulin, C-reactive protein, etc.;
• an increase in the content of total protein-associated hexoses, seromucoid and sialic acids;
• increased activity of lactate dehydrogenase (LDH) and its isoenzymes - LDH3.

Antibiotic susceptibility testing

Determination of sensitivity to antibiotics is based on the assessment of the growth of microorganisms cultivated on solid or liquid nutrient media in the presence of antibiotics. The simplest method is to sow a suspension of microorganisms of the isolated culture on the surface of a solid nutrient medium (agar) in Petri dishes. Discs with antibiotics in standard concentrations are placed on the surface of the dishes and incubated at 37.5°C for 18 hours. The results are assessed by measuring the diameter of the zone of inhibition of microbial growth with a ruler.

More accurate data can be obtained using quantitative methods with determination of the minimum inhibitory concentration (MIC) of antibiotics. For this purpose, a series of twofold dilutions of antibiotics in a liquid nutrient medium (broth) is prepared and 0.2 ml of a suspension of the culture of the studied microorganisms at a concentration of 10 ⁵ -10 ⁶ m.t./ml is added. All samples, including the control, which does not contain antibiotics, are incubated at 37.5°C for 24 hours. The minimum concentration of the antibiotic in the last test tube, in which complete inhibition of culture growth was observed, corresponds to the MIC of the drug and reflects the degree of sensitivity of microorganisms to the antibiotic.

According to the degree of sensitivity to antibiotics, microorganisms are divided into three groups:

1. Sensitive - microorganisms whose growth is suppressed at the MIC corresponding to the concentration of the drug in the blood serum when using the usual therapeutic doses of the drug.
2. Moderately resistant - those strains of microorganisms whose MIC is achieved when prescribing maximum therapeutic doses of antibiotics.
3. Resistant microorganisms whose growth is not suppressed by the maximum permissible doses of drugs.

Such determination of the degree of sensitivity to antibiotics is possible when using quantitative methods of dilution in liquid nutrient media. Nevertheless, there is a certain correlation between the MIC values and the size of the zones of inhibition of microbial growth when using paper disks with antibiotics, which gives grounds for using this simple and convenient method for an approximate quantitative description of the degree of sensitivity.

It should be remembered, however, that the results of in vitro antibiotic sensitivity testing do not always correspond to the actual clinical situation, especially in the case of mixed infections, decreased immunological reactivity of the body, difficulties that arise when trying to isolate a culture of the main pathogen, etc.

[ 31 ], [ 32 ], [ 33 ], [ 34 ], [ 35 ], [ 36 ]

Formulation of diagnosis

When formulating a diagnosis of pneumonia, it is necessary to reflect:

• etiological variant;
• localization and prevalence of the inflammatory process (segment, lobe, unilateral or bilateral lesion);
• severity of pneumonia;
• presence of complications;
• phase of the disease (peak, resolution, recovery, protracted course);
• concomitant diseases.

Examples of diagnosis formulation

1. Pneumococcal lobar pneumonia in the lower lobe of the right lung, severe course, acute phase. Acute subcompensated respiratory failure.
2. Streptococcal pneumonia in segments 6, 8, 10 of the right lung, moderate severity, acute phase. Initial stage of acute respiratory failure. Exudative pleurisy.

[ 37 ], [ 38 ], [ 39 ], [ 40 ]