The procedure, which is called “study of synovial fluid,” is necessary for diagnosing a variety of dystrophic and inflammatory diseases of the joints.
Synovial fluid is an exudate produced by the articular membrane, consisting of connective tissue and lining the bone and cartilage surfaces. It performs the following functions in the joint:
- locomotor;
- metabolic;
- barrier;
- trophic.
The joint fluid quickly reacts to all inflammatory processes that occur in the joint, synovium and cartilage tissue. This substance is one of the most important articular components, which determines the morphofunctional state of the joint.
In a normal, healthy joint, the volume of fluid is moderate. But with the development of certain joint ailments, a so-called joint effusion is formed, which is subject to investigation. More often than others, a sample of synovial fluid from large joints (elbows, knees) is analyzed.
Synovial fluid can be obtained using a puncture. The most important condition when taking a puncture is the sterility of the joint.
Features of diagnosing synovial fluid
A standard analysis of a synovial fluid sample includes:
- Macroscopic analysis of punctured fluid (color, volume, turbidity, viscosity, mucin clot).
- Counting the number of cells.
- Microscopy of the native drug.
- Cytological analysis of the stained preparation.
In a healthy person, synovial fluid is light yellow (straw) in color. However, in both arthritis and ankylosing spondylitis (ankylosing spondylitis) the color of the test fluid remains yellow. During inflammatory processes, the color of the joint fluid may become different, depending on the characteristic changes in the synovial membrane.
In the presence of psoriatic or rheumatoid arthritis, the color of the examined exudate may vary from yellow to green. In traumatic or bacterial diseases, the color of the synovial fluid ranges from burgundy to brown.
The synovial fluid of a healthy joint is clear, but in the presence of psoriatic, rheumatoid or septic arthritis, it becomes cloudy.
The nature of viscosity depends on:
- pH level;
- salt concentration;
- the presence of previously administered drugs;
- degree of polymerization of hyaluronic acid.
An increased level of viscosity is observed when:
- systemic lupus erythematosus;
- various traumatic changes.
A decrease in viscosity indicators is observed when:
- Reiter's syndrome;
- rheumatism;
- arthrosis;
- ankylosing spondylitis;
- various arthritis (psoriatic, gouty, rheumatoid).
One of the most important features of synovial fluid is the ability to produce a mucin clot when mixed with acetic acid.
In this case, the presence of a loose clot indicates inflammatory processes occurring in the joints.
The main analysis that determines the pathology of the joint
The main study diagnosing a particular pathology is a microscopic analysis of a sample of synovial fluid.
First of all, doctors pay attention to counting the number of cells in the drug. The norm is up to 200 cells/μl. A significant increase in the number of cells is called cytosis. Cytosis makes it possible to diagnose dystrophic and inflammatory diseases and clearly assess the development of inflammatory processes.
During the acute stage of any type of arthritis, the patient experiences pronounced cytosis (the number of cells ranges from 30,000 to 50,000).
- With microcrystalline arthritis, the patient exhibits slight cytosis.
- In Reiter's syndrome, pseudogout or psoriatic arthritis, the cytosis is moderate (20,000 to 30,000 cells).
- If the cell count exceeds 50,000, the patient is diagnosed with bacterial arthritis.
Careful analysis can reveal the presence of a large number of different crystals in a patient, but only two types are important for diagnosis. In pseudogout, the patient has calcium dihydrogen pyrophosphate crystals, and the presence of sodium urate crystals indicates gout. These deposits can be detected using polarizing microscopy.
Healthy synovial fluid contains blood elements (lymphocytes, monocytes, neutrophils) and various tissue cells (histiocytes, synoviocytes).
During inflammatory processes, a special form of neutrophils, ragocytes, can be found in joint exudate. Such cells have a cellular structure formed due to the inclusion of immune complexes in the cytoplasm. The presence of ragocytes mainly indicates rheumatoid arthritis.
The detection of mononuclear cells in the synovial fluid is characteristic of tuberculous processes, allergic synovitis and arthritis that have developed against the background of neoplasms.
It is worth noting that inflammatory joint diseases are characterized by an increase in acute phase parameters and lactate dehydrogenase levels.
Microscopic examination of the smear can detect gram-positive cocci, chlamydia or gonococci. Fungal bacteria are often detected in patients. To accurately determine the nature of the infectious process and establish sensitivity to antibiotics, doctors culture the synovial fluid for pathogenic microflora.
Puncture of joint exudate can only be performed as prescribed by a rheumatologist. In conclusion, the video in this article will raise the very interesting issue of synovial fluid replacement.
Thanks to the achievements of modern laboratory diagnostics, it has become possible to identify many diseases even before the development of their characteristic symptoms. Each disease leads to the entry into the blood of some pathological substances that have a certain activity. When they accumulate in large quantities, the immune system is activated - its cells produce antibodies that allow them to quickly destroy the unfamiliar substance.
Similar mechanisms occur in rheumatoid arthritis, a chronic autoimmune disease that leads to joint damage. For quite a long time, the diagnosis of this disease was based only on confirmation of clinical symptoms using a blood test for rheumatoid factor (RF). But this indicator is not very specific, which makes it difficult to detect pathology in the early stages.
Studying the disease from a biochemical point of view made it possible to unravel one of the mechanisms - the formation of antibodies to cyclic citrullinated peptide (ACCP). An increase in their number in a blood test occurs only in rheumatoid arthritis, which makes the study highly specific. Their increased rates are observed even before external manifestations occur, which allows for timely initiation of treatment measures.
Concept
To understand the technology and the meaning of the study, it is necessary to dwell on the pathological processes leading to an increase in ACCP. They are based on the normal reaction of the immune system to abnormal mechanisms occurring in the joint cavity:
- Citrulline is an amino acid in structure - normally they form all protein structures in the human body. But such a structure is not suitable for inclusion in the composition of the main tissues - if it is detected by antibodies, then its instant disposal occurs.
- Destroyed fragments become building material for new normal amino acids. Such removal does not lead to an inflammatory process, since it occurs in the conditions of biological fluids.
- In rheumatoid arthritis, there is a disruption in the functioning of one of the enzymes that provides “maintenance” to the joint capsule. As a result, the amino acid citrulline, which is free in the synovial fluid, begins to attach to some membrane proteins, changing their structure.
- Antibodies that detect structures that are completely new to them (cyclic citrullinated peptides) recognize them as foreign. Since it is not possible to freely remove proteins from the membrane, an inflammatory process gradually develops inside the joint capsule.
- Since the pathological mechanisms are not interrupted, the amount of ACCP in the blood gradually increases. In this way, the body tries to remove the continuously produced defective protein.
A small amount of such antibodies is observed in the analysis in a healthy person, but it never goes beyond the permissible limits.
Standards
The examination is carried out as part of a biochemical analysis, so a small amount of blood is taken from a vein for diagnosis. Therefore, this requires standard preparation - come on an empty stomach, and also avoid smoking at least two hours before the test. Results are measured in units of activity per milliliter (U/ml):
- In some laboratories, values from 0.5 to 4.9 U/ml are considered normal. In this case, an increase in the number of ACCP above 5 is considered an indicator of pathology, even if the patient does not have any symptoms of joint damage.
- Certain laboratory analyzers have a normal limit of up to 17 U/ml. Therefore, after receiving the results of a blood test, it is necessary to clarify their meaning with a doctor. Sometimes normal indicators are indicated immediately on the form to eliminate diagnostic errors when assessing them.
- Typically, a test for ACCP has a range from 0.5 to 4500 U/ml, which creates a margin for its full determination during high activity of rheumatoid arthritis.
Despite the accuracy, the analysis is extremely rarely carried out without some reason - its importance is great in controversial cases when differential diagnosis between several diseases is required.
Rheumatoid arthritis
Determination of ACCP in the blood is carried out when other biochemical signs have not yet manifested themselves due to the low activity of the disease. If the scant data from an external examination nevertheless leads the doctor to a diagnosis, then the analysis will give him a positive result in the following cases:
- At an early stage of the disease (from 6 months to 1 year), when clinical and laboratory manifestations are too “general” in nature. At this time, some autoimmune diseases affecting the joints are characterized by a very similar course.
- In seronegative arthritis, when the main indicator of activity - rheumatoid factor - is practically not detected in the blood in significant quantities. Moreover, it is very important for determining the diagnosis, so the detection of antibodies to the citrullinated peptide in sufficient quantities allows us to confirm concerns.
- For the prognosis of the disease, it has been proven that the combination of high ACCP values in combination with other pronounced signs predicts a severe course of the disease.
Nowadays, most laboratories in large hospitals widely use the test in everyday practice, although until recently it could only be performed for a fee.
Determination of severity
Unlike other biochemical signs of activity, ACCP in rheumatoid arthritis has its own characteristics that predict long-term prognosis. Therefore, the following statements can be made regarding this analysis:
- If already in the early stages, when rheumatoid factor and ESR are within normal limits, and ACCP is significantly increased, then a rapid deterioration in the external manifestations of the disease should be expected.
- Equally high values of antibodies to citrullinated peptide and RF during an exacerbation cause severe joint damage. Without urgent treatment, persistent complications can be expected to develop, the signs of which will persist even after the disease activity has decreased.
- At the same time, the detection of ACCP is not a criterion for exacerbation, since its fluctuations do not depend on the number of affected joints. Their number can increase significantly before the development of symptoms, and never drops to normal after they are eliminated during therapy.
The level of ACCP is a kind of harbinger of joint destruction - the more antibodies are formed, the more intense the inflammation in the joint membranes will occur.
For treatment
The detection of an increased level of antibodies to citrullinated peptide allows one to immediately place a person at risk for developing rheumatoid arthritis. This does not mean immediately prescribing complex treatment regimens, but requires preventive measures - eliminating risk factors. The patient is also periodically monitored by performing the following activities:
- The external manifestations of the disease, as well as laboratory criteria for its activity, are regularly assessed.
- When the amount of ACCP increases in combination with even minimal signs of joint damage, standard therapy is immediately required.
- In this case, the indicators of rheumatoid factor and ESR do not matter, since their increase is observed only with obvious symptoms of exacerbation.
- But with a simultaneous sharp increase in all biochemical parameters, severe symptoms of arthritis are often observed. This serves as a signal for prescribing high doses of medications or adjusting the treatment to be more effective.
With a long course of the disease, ACCP loses its importance, since its indicators change slightly when changing periods of exacerbation and remission.
Differential diagnosis
Finally, one of the important purposes of this test for rheumatoid arthritis is to confirm the diagnosis. At an early stage of development, autoimmune diseases affecting joints are very similar, which often complicates the correct choice of drugs. Therefore, the appearance of ACCP in the blood allows us to exclude the following diseases:
- The Scandinavian form of ankylosing spondylitis, which is characterized by symmetrical damage to the small joints of the hands and feet.
- Psoriatic arthritis, which, with high activity, can affect not only large joints, but also give symptoms reminiscent of the development of rheumatoid arthritis.
- Systemic lupus erythematosus, if it is accompanied only by isolated joint damage.
In some cases, diagnostic difficulties may arise even in fairly advanced cases of the disease. Typically, such situations develop with pathology that has been defined using a small number of criteria. And an incorrect diagnosis immediately leads to fundamentally incorrect treatment, so rheumatoid arthritis must be confirmed using an ACCP test.
-->
Treatment of excess synovial fluid in the knee joint
The knee joint is a complex biomechanical complex that allows a person to implement the most important functions: support, walking, running. For the normal functioning of the knee joint, which involves a large number of “rubbing parts,” nature has developed a special fluid that enters the joint space and serves as a lubricant and damper for the components of the knee joint. The absence of this lubricant, as well as its excess, is a pathology, causes pain syndromes of varying intensity and requires treatment.
- Causes of fluid accumulation in the knee joint
- Symptoms of synovial fluid accumulation
- Main stages of treatment
- ethnoscience
- Fluid in the knee joint: treatment with folk remedies
Synovitis of the knee joint is an excess of joint fluid that accumulates and can lead to inflammation of various types.
Causes of fluid accumulation in the knee joint
There are several main reasons for the development of knee synovitis, which are divided into three groups:
Thus, during the exacerbation of rheumatological diseases, exudate accumulates, which is produced by the shell of the joint capsule in a large volume due to a specific reaction to the disease.
The main reasons causing the pathogenesis of the knee joint and the accumulation of synovial fluid include:
- Rheumatoid arthritis of the knee;
- Gonarthrosis of the knee joint;
- Systemic lupus erythematosus;
- Gout;
- Polymyositis:
- Ankylosing spondylitis.
The accumulation of synovial fluid in the knee can occur due to the penetration of various microorganisms into the cavity of the synovial bursa. The routes of their entry are different: from the external environment (as a result of traumatic exposure), from nearby inflammatory sources (purulent tissue inflammation or osteomyelitis), blood or lymph flow (systemic septic infections).
Separately, it is worth mentioning unusual allergic reactions that can lead to increased accumulation of synovial fluid. However, this is an extremely rare cause of knee synovitis.
Symptoms of synovial fluid accumulation
Signs of developing synovitis of the knee joint are:
- Swelling of the knee. This is especially noticeable against the background of a healthy knee.
- Increased local temperature and redness of the skin.
- Painful sensation when trying to fully bend the knee.
- Painful sensations when moving the leg.
All these symptoms only signal pathological changes in the knee joint. This is not enough for an accurate diagnosis of the disease, identifying the etiology and degree of pathogenesis.
In any case, at the first signs of synovial fluid accumulation, an early consultation and further treatment of the knee by a specialized specialist is necessary. Often there is an understatement of the danger of the disease, which can lead to rupture of the joint capsule, cause deformation of the knee and blood poisoning (sepsis). This is typical for the infectious nature of synovitis.
To effectively treat a disease, it is necessary, first of all, to determine the cause of the disease, as well as the stage and phase of the pathology. Conducting a visual examination, palpation of the knee, a complete medical history and various instrumental examination methods allow us to obtain reliable data necessary for treatment.
The main instrumental methods for studying internal organs are used:
- X-ray of the knee joint;
- Ultrasound examination (ultrasound);
- Magnetic resonance and computed tomography (MRI/CT);
In case of pronounced synovitis, when the accumulation of a large amount of fluid in the joint capsule is obvious, a puncture is made and the collected fluid is sent for analysis to identify infection.
In cases of severe pathology and unclear medical history, arthroscopy of the knee joint is performed (introduction of an arthroscope into the damaged joint through a microincision).
Main stages of treatment
Like any disease, synovitis begins to be treated after an accurate diagnosis. At the first stage, a puncture of the knee joint is performed to remove excess fluid. Then the joint cavity is cleaned and then special antibiotics are administered to avoid possible infection.
It is important to reduce the dynamic and static load on the sore knee. For these purposes, fixing bandages are used to ensure immobility of the knee joint. It must be done after the puncture and worn for about 5 - 7 days.
To reduce the risk of relapse of the disease, drug treatment is carried out. For this purpose, parenteral or oral administration of targeted nonsteroidal anti-inflammatory drugs (NSAIDs) is used. In order to increase therapeutic effectiveness, the use of various ointments and gels that have warming, irritating or anti-inflammatory effects is prescribed. They cope well with various symptoms of the disease (edema and swelling).
In some cases, antibiotics are prescribed. The reason is re-infection or ineffectiveness of the chosen treatment methods. To do this, a study of the intra-articular fluid is carried out to determine the causative agent of the disease. Depending on the results of bacterial culture, antibiotics of both broad and narrow spectrum of action are prescribed. Intramuscular or intravenous injections are used.
ethnoscience
Over its centuries-old history, traditional medicine has accumulated a variety of means to eliminate the main symptoms of the disease, which successfully complement the main therapy of the disease.
Like the medications and ointments used, traditional medicine has anti-inflammatory, analgesic, antiseptic effects, increases the body's immunity and joint resistance.
Fluid in the knee joint: treatment with folk remedies
Existing agents are used internally or used externally:
All traditional medicine should be used only as additional therapeutic procedures that enhance or complement the therapeutic effect of the main course of treatment. It is important not only to stop the symptoms of the disease, but to completely eliminate the causes of the disease.
General clinical examination (analysis) of joint fluid includes determination of the physicochemical properties of the fluid and microscopic examination of cellular elements.
Macroscopic characteristics of synovial fluid (color, degree of turbidity and viscosity) are assessed in transmitted light. Viscosity is assessed by the length of the mucin filament: the length of the filament formed by a drop released from a syringe should normally be more than 3 cm. With inflammation, the viscosity decreases, and accordingly the length of the filament decreases.
The manipulation is performed with the patient sitting with the arm lowered along the body and lying on the knee. The needle is inserted from the front, its end is directed slightly downward and laterally, towards the coracoid process of the scapula; the needle moves posteriorly, towards the articular surface of the scapula. It is also possible to puncture the shoulder joint through a posterior approach.
The patient bends the arm at the elbow joint at an angle of 60°, the wrist is in a pronated position. The needle insertion point is located on the lateral surface of the joint, between the lateral epicondyle of the humerus and the radius.
The knee joint and its periarticular bursae can be punctured with the patient in the supine position, with the lower limb extended at the knee joint. A needle, usually 0.8 mm in diameter, is inserted from the lateral side just below the caudal edge of the patella. As an alternative, it is possible to insert the needle from the medial side, also under the caudal edge of the patella.
Macroscopic characteristics make it possible in many cases to distinguish between non-inflammatory, inflammatory and infectious effusions. In addition, there may be blood in the joint fluid. The appearance of the effusion suggests a certain disease. So-called non-inflammatory effusions actually correspond to pathological processes characterized by mild to moderate inflammation, such as osteoarthritis.
Laboratory studies of intra-articular fluid include counting cells and assessing their qualitative composition, microbiological examination (if an infectious process is suspected), as well as microscopic examination of the native drug to identify various cells and crystals. However, the choice of a particular test depends on the suspected diagnosis.
Reference indicators (normal) of synovial fluid
The study of synovial fluid plays an important role in clarifying the nature of the process in the affected joint.
Indications for joint puncture: monoarthritis of unknown etiology, discomfort in the affected joint (if the diagnosis has been established), the need to monitor the effectiveness of treatment for infectious arthritis, for the differential diagnosis of arthritis and arthrosis, since the choice of a program for further examination and treatment of the patient depends on this.
Why perform a synovial fluid analysis?
In primary care situations, synovial fluid (SF) analysis can help determine the specialist to whom the patient should be referred.
- If the GS is non-inflammatory, see an orthopedist.
- If it’s inflammatory, see a rheumatologist.
Diagnostic value of synovial fluid analysis
- Inflammatory or non-inflammatory pathology
- Crystalline inflammation or sepsis, or exacerbation
- Helps identify groups of diseases based on cell number and cell type
- Determination of the type of prosthetic failure
- Prognostic value
- Orthopedic intervention
- Stage of specific disease
- Therapy monitoring. In particular, refusal of monoclonal antibody therapy.
In Fig. 1 and 2 reflect the algorithm for diagnosing joint diseases based on data from the analysis of synovial fluid
Pathological changes in the tissues surrounding the diseased joint are reflected in the volume, cellular composition and presence of solid particles in the fluid. Inflammatory joint diseases, differing in etiology, have characteristic cellular patterns that can be recognized and used in the diagnosis of a specific disease or group of diseases (Fig. 1, 2). In order to identify these differences, it is necessary to correctly select and properly store SF in order to minimize autolytic changes and degradation of characteristic cells. EDTA is used as an anticoagulant. Storage at 4°C is well tolerated by SF and gives excellent diagnostic results. Almost adequate results can be obtained up to 48 hours from aspiration, but longer storage, even at 4°C, usually allows only crystals and particles to be identified. Most cells undergo lysis.
Cytological analysis of synovial fluid
Fat cells can be found in the analysis of the SF of most patients with joint disease, but most often they are observed in inflammatory arthritis in patients with seronegative spondyloarthropathies and in non-inflammatory joint lesions associated with trauma.
This type of CL is often detected when analyzing the SF of patients with intra-articular hemorrhage or arthrography, as well as in allergic reactions to injected drugs, such as artificial SF.
Analysis of synovial fluid, depending on the results (appearance, total number of leukocytes and the proportion of neutrophils, the presence or absence of blood and the results of bacteriological examination), identifies four main classes of synovial fluid (SF). The characteristics of GS vary widely and may change during treatment. Thus, when diagnosing arthritis, the GS class serves only as a general guide.
Visual analysis of synovial fluid
Certain characteristics of GS allow the clinician to suspect the cause. Transparency reflects the density of a particular substance in the fluid. Normal SF or SF of a patient with osteoarthritis is colorless and transparent. In contrast, in systemic lupus erythematosus and mild rheumatoid arthritis, the synovial fluid is translucent, and in infectious arthritis it is opaque. In general, the transparency of inflammatory synovial fluid depends on the number of leukocytes. The analysis of synovial fluid from a patient with arthritis is characterized by xanthochromia, which is associated with the penetration of erythrocytes into the fluid from the inflamed synovium and the breakdown of heme. Red or bloody SF occurs with bleeding associated with trauma, hemophilia, pigmented villonodular synovitis and other pathological processes. Other substances that can reduce fluid clarity include lipids, crystals (such as DPA, monosodium uric acid, or hydroxyapatite), and accumulated breakdown products in destructive forms of arthritis (such as severe rheumatoid arthritis or Charcot arthropathy).
Normally, joint fluid is viscous due to the presence of hyaluronic acid. In inflammatory arthropathy, enzymes destroy hyaluronic acid, which leads to a decrease in the viscosity of the joint fluid. When a drop of normal fluid is squeezed out of a syringe, its surface tension is such that the plume or thread of liquid stretches 10 cm before the drop breaks off. The more inflammation in the joint, the more inflammatory cells there are and the higher the concentration of activated enzymes that destroy hyaluronic acid. In this case, the thread of the inflammatory fluid stretches by no more than 5 cm. Very viscous joint fluid, forming a long thread, is observed in hypothyroidism. In addition, determine the content of hyaluronic acid in synovial fluid by adding a few drops of a 2% acetic acid solution to it. In normal SF, a stable insoluble protein-hyaluronic complex, called a mucin clot, is formed. Inflammatory SF forms a loose mucin clot, which easily fragments, reflecting a change in the structure of hyaluronic acid.
Cell counting
The number of leukocytes and their composition is one of the most valuable characteristics of the analysis of synovial fluid. Normal synovial fluid contains less than 200 cells/mm3. With non-inflammatory arthropathy, the number of leukocytes reaches 2000 cells/mm3. In non-infectious arthritis, the number of leukocytes varies widely: from 2000 to 100,000 cells/mm3. Although in autoimmune arthritis the white blood cell count usually ranges from 2000-30,000 cells, in rheumatoid arthritis this figure often reaches 50,000 cells/mm3 or higher. In patients with crystal-induced arthritis (eg, acute gout), white blood cell counts typically exceed 30,000 cells/mm3, and 50,000-75,000 cells/mm3 are not unusual. The closer the white blood cell count is to 100,000 cells/mm3, the higher the likelihood of septic arthritis. Although white blood cell counts may exceed 10,000 cells/mm3 in some patients in crystalline arthropathy, rheumatoid arthritis, and even seronegative arthropathy, when this result is obtained on synovial fluid analysis, empirical treatment for septic arthritis should be initiated until microbiological evidence is available that excludes infection.
A white blood cell count of less than 100,000 cells does not exclude possible infection. Patients with chronic inflammatory arthritis (such as SLE or psoriatic arthritis) have an increased risk of joint infection, firstly due to structural damage to the joint due to chronic inflammation; secondly, due to the immunosuppressive effect of the drugs that are used to treat these diseases. Moreover, many disease-modifying drugs for such diseases (in particular, methotrexate, cyclosporine, leflunomide, azathioprine, cyclophosphamide and other cytotoxic drugs) can suppress the leukocyte response to infection and illusorily reduce the number of leukocytes in the SF. Compared with bacterial infections, more indolent processes (such as tuberculosis or fungal infection) tend to have lower white blood cell counts in synovial fluid analysis; usually Blood in synovial fluid
The presence of blood in a joint is usually caused by acute injury. If hemarthrosis is detected during arthrocentesis, it is necessary to completely evacuate the bloody fluid to prevent the formation of synechiae, which reduce the range of motion in the injured joint. Hemarthrosis is sometimes found in Charcot arthropathy, which is associated with chronic trauma to the affected joint. In the absence of a history of trauma, bloody SF may result from traumatic aspiration. In such situations, the blood in the SF is unevenly distributed, and the clinician experiences difficulty performing the procedure. If the puncture was not traumatic, but blood was obtained in the analysis of the synovial fluid, several causes must be excluded. Repeated hemarthrosis often occurs in patients with disorders of coagulation hemostasis (such as hemophilia and von Willebrand disease), platelet pathology, and in patients taking anticoagulants. The gastric fluid of patients with pigmented villonodular synovitis is always hemorrhagic or xanthochromic. Pigmentation is associated with hemosiderin, which accumulates from repeated hemorrhages into the joint. Hemorrhagic GS is often found in patients with tuberculosis, as well as in patients with local or metastatic tumors. Patients with congenital, metastatic, or hemorrhagic diseases (such as Ehlers-Danlos syndrome, pseudoxanthoma elasticus, sickle cell disease, or scurvy) sometimes also develop hemarthrosis.
Crystals
Although crystals in synovial fluid can be identified several days after collection, it is recommended to use fresh samples prepared immediately after aspiration. To prevent clotting of the fluid, only sodium heparin and ethylene-diamine-tetraacetic acid are used before the study, since lithium heparin and calcium oxalate cause the formation of birefringent crystals that interfere with the analysis. In addition, the glass containing the SG preparation must be covered with a cover slip, since talc, dust and other foreign bodies may resemble crystals.
A full examination for the presence of crystals requires polarizing light microscopy with an additional red compensator, although sodium urate crystals can be seen under a regular light microscope. The lower polarizing plate (polarizer), placed between the light source and the sample under study, blocks all light waves except those. that oscillate in one direction. The second polarizing plate (analyzer) is located between the test specimen and the researcher’s eye, at an angle of 90° to the polarizer. The light does not reach the researcher's eye, and through the microscope he sees only a dark field. A birefringent, or anisotropic, preparation refracts light waves passing through a polarizer so that they pass through the analyzer and the observer sees white objects against a dark background. If a first-order compensator is placed between the polarizer and the analyzer, the background field becomes red and the birefringent crystals become yellow or blue, depending on their features and orientation relative to the axis of slow light waves passing through the red compensator.
Passing through the red compensator, the light is refracted and bifurcated: two light waves, fast and slow, are perpendicular to each other. A similar phenomenon occurs when light passes through a birefringent crystal. Anisotropic crystals of sodium urate have a needle-shaped shape. The oscillations of a fast wave are oriented along their long axis. If the long axis of the sodium urate crystal is parallel to the direction of the slow light wave passing through the red compensator, a pattern of interference of slow and fast vibrations occurs with color subtraction, resulting in a yellow color. A yellow crystal whose long axis is parallel to the slow light wave of the red capacitor is conventionally called negatively birefringent. If the slow vibration wave of a birefringent crystal is parallel to its long axis. and the long axis of the crystal is parallel to the slow ray of the red compensator, the summative effect of slow-plus-slow oscillations results in a blue color. A blue crystal whose long axis is parallel to the slow light wave of the red compensator is conventionally called positively birefringent. For example, WPC crystals are positively birefringent. With a strongly pronounced property of birefringence, anisotropic crystals are bright and clearly visible; with a weak property, the crystals are difficult to distinguish and their boundaries are erased.
When identifying crystals, their shape and birefringence features are taken into account. Needle-shaped crystals of sodium urate are characterized by strong negative anisotropy. In contrast, short diamond-shaped WPC crystals have positive anisotropy. Calcium oxalate crystals observed in primary oxalosis or chronic renal failure are distinguished by their rod-shaped or tetrahedral shape and positive birefringence. Cholesterol crystals have a flat or box-like shape and jagged corners, and are often stacked on top of each other. Birefringent spherules in the shape of a Maltese cross are usually represented by lipids. However, it is believed that some forms of urate or apatite may also take a similar form. Typically, hydroxyapatite crystals are difficult to detect in synovial fluid. partly due to their lack of double refraction. However, sometimes they form large enough clumps that they can be identified by staining with alizarin red. Finally, glucocorticoid crystals. drugs injected into the joint for treatment may have birefringent properties, which leads to erroneous interpretation of the microscopic picture by an inexperienced specialist.
Intracellular crystals in synovial fluid analysis indicate crystalline arthropathy. However, even if crystals are detected, it is necessary to exclude concomitant infection. Moreover, a patient may simultaneously have several diseases associated with crystal deposition. For example, up to 15% of patients with gout also have a disease caused by the deposition of duodenal crystals. It is important to identify all crystal variants, as treatment depends on this. A patient with chronic gout usually only needs hypouricemic therapy (and possibly prophylactic colchicine). However, treatment of the combination of gout and disease associated with duodenal crystal deposition requires long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) against the background of continuous hypouricemic therapy.
Attempts to aspirate an inflamed joint are not always successful. For example, it is difficult to puncture an inflamed first metatarsophalangeal joint. However, if negative pressure is maintained in the syringe while withdrawing the needle from the joint or periarticular tissues, the amount of interstitial fluid in the needle is usually sufficient for polarization microscopy and crystal detection. Simply remove the needle from the syringe, fill the syringe with air, reattach the needle and squeeze its contents onto a glass slide. This method is especially effective for finding sodium urate crystals in gout.
Bacteriological examination of synovial fluid
Monoarthritis should always be considered infectious until proven otherwise. To diagnose most bacterial infections, it is necessary and sufficient to stain a Gram smear, bacteriological examination and determine sensitivity. Typically, synovial fluid only needs to be placed in a sterile culture tube and sent to the laboratory for routine testing. Unfortunately, some common infections are difficult to culture, so a negative culture and Gram stain does not necessarily rule out infection. For example, the results of bacteriological analysis of synovial fluid in more than 20% of patients with gonococcal arthritis are negative, even when chocolate agar was used as the culture medium. In addition, tuberculosis is difficult to culture from synovial fluid, and special methods and media are required to culture anaerobic or fungal pathogens. Sometimes mycobacterial and fungal infections are detected only by biopsy of the synovium. Early initiation of antibacterial therapy is important, since bacterial infections can quickly lead to joint destruction. Treatment should begin based on the results of counting and analyzing leukocytes, Gram staining of the smear, and, if necessary, adjust it taking into account the results of bacteriological examination and sensitivity determination.
The article was prepared and edited by: surgeon3.5 Microscopic examination of synovial fluid
3.5.1. Requirements for a sample of synovial fluid for microscopic examination.
Before conducting a microscopic examination, the doctor must have information about the time of obtaining synovial fluid and the results of assessing the physicochemical properties.
Currently, for collecting biological fluids, vacuum tubes are produced containing an anticoagulant (K 2 EDTA), which is also a preservative for cellular elements and does not affect their morphology.
Note 1─ Synovial fluid stabilized with K2EDTA cannot be used to detect ragocytes.
Three types of microscopic examination are carried out:
counting of cells in native synovial fluid in the Goryaev chamber (cytosis), study of the native drug and the drug stained with azure-eosin with calculation of the synoviocytogram.
3.5.2 Counting the number of cellular elements in 1 μl of synovial fluid in the Goryaev chamber (determination of cytosis).
Progress of the research:
The study is carried out in native or K2EDTA-stabilized synovial fluid.
Pour 0.4 ml of isotonic or hypotonic NaCI solution into a test tube.
Using a sampler or micropipette, add 20 μl of SF (1:20 dilution).
Gently stir the contents of the test tube without foam.
Calculate using the formula: , where
A – the number of cellular elements in 40 large squares of Goryaev’s chamber;
250 - 1/250 – the volume of one large square of the chamber;
20 - degree of dilution of the fluid.
The final version of the formula: 
If microscopy of a native SF preparation reveals that cells cover all fields of view or the SF has a high viscosity, a dilution of 1:200 is required (4 ml of isotonic or hypotonic NaCl solution and 20 μl of the studied SF).
To dilute SF, an isotonic 0.9% (150 mmol/l) NaCI solution is used. If it is necessary to lyse red blood cells in the SF, a hypotonic 0.3% (50 mmol/l) NaCI solution is used.
Isotonic and hypotonic NaCl solutions can be tinted with a 3% solution of methylene blue or methyl violet.
When diluted 200 times, the final calculation is carried out using the formula: X = A 1250
In normal SF, the number of cells varies and is 0.1 – 0.5 x10 9 /l.
Note ─ With articular pathology, cytosis increases, indicating an increase in the inflammatory process. In degenerative diseases and post-traumatic arthritis, cytosis in the SF is 2 - 2.5x10 9 /l. In inflammatory diseases of the joints (RA, ReA, ankylosing spondylitis, psoriatic arthritis, gout, pseudogout), cytosis varies from 3 to 75x10 9 /l, in septic arthritis it exceeds 80x10 9 /l.
3.5.3 Preparation of native and stained preparations for microscopic examination.
The laboratory must have approved the procedure for preparing synovial fluid and preparing native and azure-eosin-stained preparations for microscopic examination and the procedure for conducting these microscopic examinations. Each employee must perform all stages of analysis in the same way and evaluate cellular elements and crystals detected by microscopy using the same criteria for identification.
Preparations for microscopic examination (native and stained) can be prepared either directly from the fluid without centrifugation, or from a sediment obtained by centrifuging a sample of the fluid (for example, to determine crystals).
If the fluid is cloudy with low viscosity, it can be immediately applied to a glass slide.
To prepare a native preparation, a drop of SG is applied to a glass slide and covered with a coverslip.
A smear for subsequent staining is prepared in the same way as a blood smear: a drop of fluid is applied to the edge of a glass slide, the polished edge of another glass (or a plastic spatula) at an angle of 45 ◦ is used to align the drop on the glass and then with a quick movement with slight pressure to prevent cell destruction, spread over the glass , not reaching the edge of the glass by 1 - 1.5 cm.
To obtain a higher concentration of cells in a microscopic specimen, you can use the preparation of a smear based on a thick drop. A large (thick) drop of coolant is applied to the glass, which is distributed over it with ground glass slowly and without pressure.
An increase in cell concentration can also be achieved by centrifuging the fluid and obtaining a concentrated sediment.
It is recommended to centrifuge transparent or translucent fluid, regardless of the viscosity value.
Synovial fluid is placed in a centrifuge tube.
Centrifuge for 10 minutes at 1000 rpm. at 5-7 ◦ C. Using a Pasteur pipette, the supernatant synovial fluid (supernatant) is sucked off and only the sediment is left. Using the same pipette, carefully mix the sediment without foam.
1 drop of sediment (approximately 40 µl) is transferred with the same Pasteur pipette (with a balloon and a thinly drawn end) onto a glass slide and covered with a coverslip (native preparation). The coverslip should cover the drop of sediment completely without bubbles.
A smear is then prepared from this sediment for staining with azure-eosin. The cells in the sediment are concentrated, which certainly facilitates microscopy and calculation of the percentage of individual cells. However, this method has significant drawbacks: under the most gentle centrifugation conditions, the structure of some synovial cells may suffer, and their rupture may also occur.
If the volume of synovial fluid is small, for example, the fluid is only in the puncture needle, the contents of the needle are blown out with the piston of the syringe onto a glass slide and a smear is made from this drop or first covered with a cover glass and the native preparation is first examined on immersion. Then the cover slip is removed, the material is carefully distributed over the slide, dried, fixed and stained with azure-eosin.
If the drop of SG is viscous and thick, dilution is done on the same glass slide,
adding 2-4 drops of saline solution to a drop of SG, after which
carefully mix a drop of SF with drops of saline using the corner of a plastic spatula or glass slide, apply a drop of diluted SF to another slide, distributing it across the width of the polished surface of the spatula or ground glass, make a smear with a slight movement so that it occupies 2/3 of the slide.
Regardless of whether the smear is prepared from whole fluid or sediment, the smear should be uniform and end with a brush.
The usual methods of fixing and staining smears are used, similar to those used in hematological studies: the prepared smears are dried in air without heating, then fixed using the May-Grunwald method, stained using the Romanovsky-Giemsa method or a modification of this method; The Pappenheim method is considered the most sensitive and specific for determining the cellular composition of the fluid. (see GOST R Cytological studies of bone marrow punctate).
Standardization of preparation of preparations from synovial fluid allows obtaining comparable results of microscopic examination in different laboratories.
3.5.4. Microscopic examination of a native preparation of synovial fluid.
The study of the preparation begins with a low magnification (approx. x 7, 10 or x 20, vol. x 10) for a general overview and a more detailed study of the preparation at high magnification (approx. x10 and vol. x 40. For reliable detection of ragocytes in the native preparation, it is recommended to use phase contrast microscopy, or examine the preparation with immersion.To identify crystals, it is recommended to use a polarizing microscope.
In a native preparation, with a magnification of x70, x100 or x200, you can only get an approximate idea of leukocytes and detect red blood cells and tissue cellular elements. With a magnification of x400, the listed cellular elements are visible more clearly. When performing microscopy at these magnifications, it is convenient to raise the condenser all the way and close the diaphragm as much as possible. This mode of operation provides greater clarity of native cellular elements.
Red blood cells containing hemoglobin, at a magnification of x400, are shaped like doubly concave lenses of a yellowish-pinkish color. These are unchanged red blood cells; they retain their shape and hemoglobin due to the pH of the synovial fluid, which ranges from 7.0 to 8.5. Red blood cells enter the synovial fluid during joint injuries or during puncture.
Leukocytes in joint inflammation are represented in the synovial fluid by neutrophils. Neutrophils are colorless or grayish, fine-grained cells with a regular round shape. Sometimes (in allergic conditions) eosinophils can be found in the synovial fluid, which differ from neutrophils by their characteristic uniform, spherical, yellowish granularity, but leukocytes should not be differentiated in native preparations.
Ragocytes.
Ragocytes are macrophages containing in their cytoplasm granules that sharply refract light, the size of which is larger than the size of the intracellular granules in the cytoplasm of these cells. These granules can be colorless, greenish or black, depending on the refraction of light passing through them. The size of the granules varies from 0.20 to 0.33 microns. Due to these granules, the size of ragocytes is slightly larger than neutrophils, monocytes, and macrophages that do not contain this granule. These granules contain immune complexes, which include rheumatoid factor, as well as immunoglobulins and antinucleolar factor.
Detection and counting of ragocytes are carried out in native specimen using phase contrast microscopy or immersion.
A drop of immersion oil is applied to the cover glass that covers the native preparation and an immersion objective is installed, obtaining a magnification of x900 or x1000. Count 100 cellular elements (leukocytes, ragocytes and tissue cells) and note what percentage of them are ragocytes
Note 1 ─ In rheumatoid arthritis, the number of ragocytes can reach 50% of the cellular composition.
Crystals
Normally, SF does not contain crystals; they are found in various joint diseases.
To identify most crystals in SF, the method of polarization microscopy is used at a magnification of 300–500.
Crystals are counted in a native whole fluid specimen.
Crystals of monosodium urate (C 5 H 3 NaN 4 O 3) are needle- or strip-shaped, 2–30 μm long, have strong birefringence, are clearly visible in the native preparation and are easily distinguished from other crystals. In a polarizing microscope, needle-shaped crystals are clearly visible as “white sparks” against a black background.
These crystals are often found intracellularly in neutrophils and macrophages.
Note 2: Monosodium urate crystals are typical for gout.
Calcium pyrophosphate
Calcium pyrophosphate - calcium pyrophosphate dihydrate or calcium pyrophosphate dihydrogen (CaPPD) Ca 2 P 2 O 7 2H 2 O. These crystals have the shape of short or long strip-shaped rectangles or rhombuses with blunt ends measuring 2 - 10 μm and have weak birefringence, soluble in 10% EDTA solution.
Note 3 ─ these crystals in the synovial fluid are found in chondrocalcinosis and pyrophosphate arthropathy.
Hydroxyapatite
Hydroxyapatite - Ca 5 (PO 4) 3 OH. - the crystals are very small, practically indistinguishable under normal magnification, either in light or in polarizing microscopes. In a polarizing microscope, only druses of these crystals with a size of 5–20 µm can be detected. In a phase contrast microscope, hydroxyapatite crystals are detected inside polymorphonuclear leukocytes (neutrophils) and extracellularly, as light disks with a diameter of 2-3 microns.
These crystals can be identified by their bright red color when Alizarin Red is used.
Alizarin red staining method for SG.
Reagents: 2% aqueous solution of alizarin red with pH 4.2 (pH adjusted with ammonium hydroxide).
Filter the suspension and store in the refrigerator in a dark glass bottle. Immediately before testing, filter the required amount of paint through a millipore filter.
Mix 20 µl of paint with an equal volume of fluid or sediment obtained after centrifugation. It is better to prepare a native preparation and microscopy it in a polarizing microscope: the crystals are ovoid in shape, 2-3 microns in diameter, rich red in color with a pink halo.
Note 4 ─ These crystals are found in hydroxyapatite arthropathy.
Crystals of calcium oxalate, cholesterol, lipids, Charcot-Leyden, etc. can also be found in the synovial fluid.
Note 5 ─ Calcium oxalate crystals (C 2 CaO 4 H 2 O) usually have a cubic shape but can form colorless, shiny, highly refractive crystals of various sizes in the form of octahedra or rectangles, reminiscent of postage envelopes. Sometimes there are calcium oxalate crystals of a rounded shape and with an interception, resembling an hourglass, gymnastic weights or bows (C 2 CaO 4 2H 2 O). These crystals can be phagocytosed by polymorphonuclear leukocytes (neutrophils).
Note 6 ─ Liquid crystals of lipids are presented on a dark field in the form of black Maltese crosses, dividing each drop of lipid into four white shiny segments. Drops of neutral fat do not have the effect of bidirectional refraction of light.
Cholesterol, sodium oxalate crystals, and lipid liquid crystals are not specific to any particular joint disease and may occur in a variety of arthropathies, reflecting metabolic disturbances.
Note 7 ─ Amyloid lumps can be found in the SF. These are colorless formations of a round shape, a layered structure, reminiscent of a cut tree, with a characteristic shine. They are identified in native preparations at x400 magnification, as well as with immersion at x1000 magnification. Amyloid can be detected in native SF stained with Congo red. The resulting preparation can be viewed both in a light and in a polarizing microscope.
Amyloid lumps are found in diseases accompanied by amyloid arthropathy.
Hematoidin crystals.
Hematoidin crystals are formed during the breakdown of hemoglobin in hematomas without access to oxygen. These are slightly elongated diamonds and/or golden-yellow needles. Hematoidin crystals are clearly visible both in native and in azure-eosin-stained preparations. Since these crystals are usually quite small in SF, it is recommended to microscopy native preparations under immersion. At the site of inflammation, these crystals can be phagocytosed by macrophages or located on the surface of cellular elements.
Note 8 ─ In case of injury and intra-articular bleeding, conditions are created in the joint cavity under which hematoidin crystals can form.
Charcot-Leyden crystals.
Charcot-Leyden crystals are shaped like a compass needle or a sharply elongated rhombus. Typically, Charcot-Leyden crystals are located against the background of detritus or in combination with a large number of eosinophils and are formed during the breakdown of eosinophils from eosinophilic granularity; these crystals can be found in the SF of patients suffering from allergic synovitis.
Medicine crystals
Steroids. Intra-articular injections of steroid drugs lead to their crystallization inside the joints, where they can persist for up to 10 weeks. The detection of these crystals during microscopic examination of native preparations and subsequent incorrect differentiation can lead to erroneous conclusions.
Non-cellular and non-crystalline elements in the fluid.
Fragments of cartilage and damaged ligaments may be found in the SF. Fragments of cartilage in the native preparation can be recognized by their characteristic silky sheen. Fragments of cartilage are also found containing clusters of chondrocytes and fragments of the meniscus, which are represented by wavy collagen fibers and also chondrocytes; fragments of ligaments are represented by long thin fibrils and parallel threads of collagen
Note 9 ─ They occur most often in the SG after a knee joint injury.
Note 10 ─ Despite the high sensitivity of the polarization microscopy method, serious errors are possible when using it, which usually arise due to the insufficiently high resolution of a particular microscope, the presence of foreign crystal-like impurities and damage to the object or cover glass The microscopist must be aware of the possibility of interference and have a good understanding of crystal recognition principles.
3.5.5. Microscopic examination of synovial fluid preparations stained with azure-eosin (with synoviocytogram calculation).
Preparation of fluid smears and methods of staining them (section 5.5.2).
Cellular composition of synovial fluid (synoviocytogram).
Determination of the cellular composition of the GS is the most important stage of its study, which makes it possible to clarify the diagnosis, determine the degree of inflammatory activity of the process and the prognosis. Determination of the quantitative distribution of cells (synoviocytogram) is the most important indicator for the differential diagnosis of joint diseases. Calculation of the percentage of cells is carried out in the same way as the calculation of the leukocyte formula of the blood. (count 100 cells in a smear and calculate the percentage of each type of cell).
Normally, cells of tissue origin (synoviocytes and histiocytes) predominate in the SF – up to 65%. Lymphocytes make up about 30%, and monocytes and neutrophils - 1-2%.
Blood cells in the SF.
Neutrophils (polymorphonuclear leukocytes).
Neutrophils are 1.5-2 times larger than a red blood cell in diameter (14-16 microns). The ratio of nucleus and cytoplasm is shifted towards the nucleus. The cytoplasm is lilac in color, filled with small, dust-like granules that have the color of the cell nucleus. The nuclei consist of 3-4 segments, with a clear division into oxy- and basichromatin. With dystrophy, the number of segments in neutrophils sharply increases to 5-7 (hypersegmentation). During apoptosis in a neutrophil, nuclear fragments merge into one or two hyperchromatic homogeneous, structureless masses of a regular round shape.
In normal SF, the number of neutrophils does not exceed 1-2%.
Note 1 ─ In rheumatoid arthritis, the neutrophil content reaches 90%, and the number of lymphocytes decreases to 10%. A similar picture is observed in ankylosing spondylitis. In inflammatory diseases and intra-articular bleeding, neutrophils make up 60-80% of the SF formula, and in septic arthropathy - more than 95%.
Lymphocytes.
These are cells up to 12 microns in diameter. The ratio of cytoplasm and nucleus is shifted towards the nucleus (9: 1). The nucleus has a roughly clumpy structure; basophilic cytoplasm surrounds the nucleus with a narrow rim; sometimes a clearing zone is visible around the nucleus.
In normal SF, the number of lymphocytes ranges from 8 to 30%.
Note 2 ─ In inflammatory diseases, neutrophils predominate, and in degenerative diseases, lymphocytes predominate. In degenerative joint diseases and traumatic arthritis, the content of lymphocytes in the SF reaches 85%. Lymphocytes predominate in the formula also in toxic-allergic synovitis and the synovial form of tuberculosis. In arthritis of viral etiology, for example caused by the HTLV-1 virus, atypical lymphocytes appear, the number of which reaches 20%.
Monocytes.
Note 3 ─ Monocytes are found in various articular arthropathy, including viral arthritis and monocytic arthritis, as well as in cases of damage to implant prostheses.
In addition to these cells, other blood cells can be found in small quantities in the SF (in pathology): eosinophils, basophils, plasma cells.
Note 4 Eosinophils are extremely rare in the SF and are identical to peripheral blood eosinophils.
Note 5: Basophils are found in small quantities in inflammatory arthritis, seronegative arthropathy, and non-inflammatory arthropathy associated with trauma.
Note 6 ─ Plasma cells are found in the SF in inflammatory arthropathy. The detection of plasma cells is characteristic, in particular, of rheumatoid arthritis, i.e. for a long-term, sluggish inflammatory process.
Tissue cells in the SF.
Synoviocytes.
These cells belong to the single-layer flattened epithelium that covers the synovial membranes of the joints. Their morphology is identical to mesothelial cells. Sinoviocytes are epithelial cells with a diameter of 18-25 microns, with a different nuclear/cytoplasmic ratio. They contain centrally or eccentrically located nuclei of round or oval shape, small-clumpy or looped structure, surrounded by a wide rim of basophilic cytoplasm, sometimes with a “frill” along the periphery. The cytoplasm in the perinuclear zone of some synoviocytes contains fine granularity. Synoviocytes are rejected from the surface of the synovial membrane of the joint and are found in the SF during arthropathy. Synovial cells may contain 2 or more nuclei (multinuclear).
There are three types of synoviocytes:
type A – macrophage synoviocytes capable of phagocytosis;
type B – synovial fibroblasts capable of synthesis and secretion of hyaluronic acid;
type AB – transitional forms of cells that combine these two properties.
Histiocytes.
Tissue macrophages are cells 18-20-25 µm in size with a round or monocytoid compact nucleus surrounded by fine-grained or granular-free cytoplasm.
Note 7 ─ Histiocytes are always present in the SF during inflammatory processes.
Note 8 ─ In the SF, multinucleated cells can be found, which are synoviocytes or plasma cells and have the same significance as the mononuclear variants of these cells.
Note 9 ─ The detection of LE cells containing inclusions of homogenized nuclear material in the cytoplasm in the SF, in contrast to peripheral blood, is not a direct indication of SLE. However, the combination of LE cells with a large number of lymphocytes in the SF allows us to suspect that the patient has SLE.
Note 10 ─ Cells in mitosis.
Mitotic figures have no diagnostic value. Synoviocytes in a state of division confirm the process of proliferation of cells lining the joint capsule.
Undifferentiated cells.
Undifferentiated cells are noted in almost all synoviograms.
In thin, well-made smears of fluid, fixed with fixatives or dye-fixatives and stained with azure-eosin, all cellular elements are amenable to differentiation. Only in thick smears prepared by the inexperienced hand of a laboratory assistant from viscous, hypercellular and previously undiluted fluid are cells that cannot be differentiated found. These can be any cellular elements - both tissue and blood. It is almost impossible to detect crystals and microorganisms in such preparations.
Loading...