Ph.D. KHANOV A.G.
The doctrine of inflammation has an ancient history, since the time of Hippocrates (400 years BC), but it began to develop rapidly in the middle of the XIX century, after the invention of the microscope. At present, the doctor has an opportunity to move from the symptoms or external manifestations of the disease to the essence of the ongoing processes. The laboratory tests and the results of additional methods of examination are related to external manifestations of the disease. But even the most advanced diagnostic methods do not bring us much closer to understanding the pathogenesis or driving forces of the disease. The real clinical practice is reduced to staging the “correct diagnosis”, corresponding to the classifier. The processes that generate a wide range of certain class diseases move to the background. At the end of the last century certain attempts were made to change the situation to single out an independent discipline – clinical pathology, universal for various clinical disciplines, from therapeutic to surgical, where attention is not paid to specific diseases, but to their internal mechanisms.
In order to take into account the disease-generating processes the biological principles of taxonomy and disease classification were proposed. But we must really understand that to become viable any classification must be tied to the realities (including the economic realities of our life).
The biological classification is very interesting from the methodological point of view, but within the real System of medical care it is unlikely to be realized.
But individual clinicians are able not only to formulate the clinical diagnosis, but also the pathogenetic diagnosis of the process with the process characteristic, its activity, phase, the tendency to destruction or various types of regeneration.
In fact, the work of a rheumatologist consists of treating inflammation in various forms and manifestations. Rheumatic diseases are inflammation of the connective tissue in general. When an inflammation emerges, the liver synthesizes proteins which are combined under the name of “acute phase proteins.”
Theoretical materials on the nature of inflammation are of great practical importance. The rheumatological patient is comorbid and in real life he has various medical situations: colds, bronchitis, pneumonia, kidney and other infections. And for choosing the tactics of treatment the doctor must determine, whether it is the activity of rheumatic disease or intercurrent infection.
The current state of affairs requires a radical improvement of the laboratory diagnosis of inflammation. The existing methods of laboratory diagnostics do not always reflect the situation in the focus of inflammation adequately.
Traditionally, to evaluate the activity of inflammation the number of leukocytes and the leukocyte formula (neutrophilia with a shift to the left) are counted. But the results of counting leukocytes can mislead the doctor. In the focus of inflammation there may be destruction processes, and the number of leukocytes in the blood does not increase, or even decreases. In this case, leukopenia can be either true or false. This is especially evident due to septic conditions because of intoxication or leukocytes adhesion to the walls of post-capillary venules.
The level of ESR does not fully reflect the state of inflammation either, as it depends on the number and properties of red blood cells. But the test continues to be widely used even in modern clinics because of its simplicity. The definition of ESR can not be compared with any other laboratory method by its simplicity. It should be pointed out that ESR can not serve to assess the effectiveness of treatment of the inflammatory process due to the fact that the rate of ESR, once raised, can remain high for a long time (trace reaction).
The way out is shown in the complex definition of proteins of the acute phase of inflammation, which must be correlated with clinical and other laboratory indicators. The acute phase response includes fever, leukocytosis, hyperproduction of glucocorticoids and catecholamines (adaptive hormones). At the same time, some of the proteins of the acute phase do not increase in the blood with inflammation, but on the contrary, decrease due to leaving for the extracellular space. They are also called negative BOP-albumin (negative nitrogen balance), α- and β-lipoproteins (lipolysis), trasferrin.
Besides, in cases of severe inflammation with intoxication and liver damage, the synthesis of proteins in the liver is reduced. This leads to the fact that the level of BFR gets low and does not correspond to the degree of inflammation. In order to bypass the diagnostic “trap”, it is necessary to determine not only the BF in blood, but also the cytokines that trigger the formation of BF in the liver.
In the laboratory there are diagnosticums for various BOPs (C1-2-3-4-5, kallikrein, kininogen, plasminogen, CRP, ceruloplasmin, acid glycoprotein, antitrepsin, macroglobulin, haptoglobin, serum amyloid protein). BOPs are formed in the liver under the influence of cytokines of inflammatory cells. Adaptive hormones (HA and CA) are involved in the induction of BOP synthesis. In most cases, hormones prepare, and cytokines trigger the synthesis. But macroglobulins are formed only under the influence of hormones. The sensitivity of the BOP results is different. The most sensitive BOP is serum amyloid protenin, then CRP, chymotrypsin, ceruloplasmin, acid glycoprotein (orosomucoid). The results of antitrypsin determination for the diagnosis of inflammation are not informative in connection with the often occurring congenital insufficiency of this protein. The determination of haptoglobin or fibrinogen are little informative, because they are consumed during clotting, hemolysis or are withdrawn from recirculation through RES. False positive results of sensitive BOP are also possible. Thus, SAP-A is included as a protein component in high-density lipoproteins. Therefore, its titres will depend on the lipid composition of blood.
CRP is the most popular of all BOPs, especially when defining the process in progress. For a single determination α1-antichymotrypsin is convenient, because of its narrow limit of the norm and the ability to be determined by different methods.
The nomenclature of clinical laboratory studies on acute phase proteins in blood serum, approved by the order of the Ministry of Health of the Russian Federation (2000), includes:
4.1.10. Proteins of acute phase in serum:
184.108.40.206. – C-reactive protein (CRP)
220.127.116.11. – serum amyloid A protein
18.104.22.168. – acid alpha-1-glycoprotein (orosomucoid)
22.214.171.124. – alpha-1-antitrypsin-ceruloplasmin
126.96.36.199. – Haptoglobin
188.8.131.52. – fibrinogen in the blood plasma
184.108.40.206. – complement proteins
220.127.116.11. – prealbumin
We offer a summary table for the practical application in the laboratory diagnostics of proteins in the acute phase of inflammation. The full text of the article is available at: http://visualrheumatology.ru/lab-pat-diag-vosp-rz.html.
Today there is a large number of independent laboratories, and the market receives all new sets of diagnosticums that do not require expensive equipment for their learning. But in this situation there are a number of medical and social problems. A thinking clinician wants to control the inflammatory process as widely as possible and in dynamics. But it is rather difficult to explain the patient the need to pay $ 20, for one analysis that does not directly affect the course of treatment. Another problem lies in the mentality of the Russian patient. Nobody thinks that you will have to get sick “hard” and rely on the medicines from “cheap” pharmacy. The “ostrich position” of the patient is the result of the sanitary press and television Health promotion, when they show individual “Victories over the diseases” and do not want to “upset” people with pictures of suffering and social consequences of “serious” diseases.