Breast fibrosis: causes and consequences of pathology, principles of treatment. Fibrosis - what is it? Pulmonary fibrosis

In many diseases, changes in the spleen are detected, but the interpretation of these changes is quite difficult. Most common anomaly, which occurs in approximately 10% of all autopsies - accessory spleens.

Every tenth carrier of accessory spleens has two or more. These are spherical bluish-red nodules with a smooth capsule ranging in size from 0.5 to 3 cm, less often smaller or larger. Their appearance on a section does not differ from the appearance of the main spleen. If there are pathological changes in the “main” spleen, they are repeated in additional ones. They are often located near the gate, but can be in the most unexpected places. In approximately 25% of cases, accessory spleens are located in the tail of the pancreas, in its parenchyma or along the course of the splenic vessels, very rarely in the pulp of the spleen (“adenomas” of the spleen) in the form of limited nodules with a diameter of up to 2-3 cm. Sometimes accessory spleens are attached to the wall stomach and intestines, to the parietal peritoneum along the spine at the left testicular artery. The latter localization refers to the intermittent form of splenic-gonadal fusion. This form occurs only in men and is usually combined with other developmental anomalies. The extended form of splenic-gonadal fusion occurs equally often in both sexes (or rather, equally rarely!) and consists of the presence of a cord of fibrous and splenic tissue connecting the spleen and the left gonads or the area of ​​​​the former mesonephros. Both types are often combined with the patient’s existing indirect inguinal hernia.

Splenosis should be distinguished from congenital accessory spleens - implantation of spleen particles in the peritoneum, in the omentum and occasionally on other organs, up to the organs of the chest cavity, in the subcutaneous tissue. This sometimes occurs as a result of injury and can take several months or even years to manifest itself. Cases of the development of splenosis after surgical removal of the spleen for various reasons have been described. Implants and nodules with splenosis differ from accessory spleens in their smaller sizes, sometimes tiny, several millimeters, often irregular in shape, fused with the base on which they were implanted.

Very rarely, heterotopic typical pancreatic tissue in the form of nodes is found in the spleen parenchyma.

Cases of true congenital lobulation, asplenia and polysplenia, i.e. the presence of several identical spleens, rather than small additional ones, are found only in the practice of pediatric pathologists and, as a rule, in combination with other severe developmental anomalies.

The spleen is located deep in the hypochondrium. The clinician detects it by palpation if the spleen reaches a large size (more than 400 g) or if it has a long stalk and is displaced downward. This “wandering spleen” is more common in multiparous women and is accompanied by stagnation of blood in it and hemosiderosis, which gives the pulp a brownish tint and increases the mass of the spleen.

Typically, the weight of the spleen of an adult ranges from 80 to 180 g. In old age, it is usually small. The spleen is also noticeably reduced in chronic diseases accompanied by cachexia. Particularly pronounced atrophy, sometimes to the complete disappearance of the spleen, occurs in sickle cell anemia. At the same time, hemorrhages and fibrosis are frequent in the pulp, sometimes with the deposition of calcium salts and hemosiderin. The “older” the disease, the more retracted scars form after heart attacks, making the spleen “lobulated”, the more it shrinks.

A small, very flabby, flattened spleen, with a wrinkled capsule, light gray-red or gray-pink on section, with granular pulp and emphasized trabeculae, but without significant scraping, is characteristic of cases of acute massive blood loss, including splenic ruptures. This is an "empty spleen".

Passive hyperemia of the spleen is characteristic of a corpse and is observed in almost 90% of autopsies. Acute postmortem hyperemia is not accompanied by a significant increase in its mass. In chronic passive hyperemia, the mass of the spleen is always increased, the pulp is compacted, cyanotic, and its trabeculae are emphasized. The increased density is due not only to blood supply, but to a greater extent to the developing fibrosis of the pulp, which is noticeable when the spleen is dissected in the form of grayish and whitish delicate stripes and specks. Sometimes there are deposits of calcium and iron salts. Such iron-calcium deposits with fibrosis, if they are sufficiently large, can be in the form of irregularly shaped small yellowish-brown nodules - “Gandhi-Gamna nodules”, or “tobacco nodules”.

The weight of the spleen in chronic stagnation associated with circulatory failure is usually not very large, rarely exceeding 500 g, and in stagnation caused by impaired portal circulation it can reach several kilograms. Cause portal hypertension may be intrahepatic, most often with cirrhosis, and extrahepatic - occlusion portal vein and its branches. So-called idiopathic portal hypertension without apparent reason. Close to this is splenomegaly, accompanied by normo- or hypochromic anemia, leukopenia and thrombocytopenia with the subsequent development of liver cirrhosis. This is not a universally recognized Bunty syndrome.

With severe splenomegaly, as a rule, adhesions with neighboring organs and thickening of the spleen capsule are formed.

Enlargement of the spleen can be associated not only with chronic passive stagnation of blood in it, but also with various infectious diseases, tumors, blood diseases, etc. Therefore, the assessment of splenomegaly is only possible with the involvement and analysis of all autopsy and clinical data.

In almost all infectious diseases, there is some degree of “swelling” of the spleen. Moderately enlarged, up to 300-500 g, rarely more, soft spleen, with loose, abundant scraping, sometimes even liquid pulp, which, when the organ is cut, falls out of the capsule, the color of the pulp is from gray-red to bright red, trabeculae and follicles are poorly distinguishable , - a picture characteristic of acute infectious swelling of the spleen. Such an acute “tumor of the spleen” is especially constant in sepsis, which is why another common name is “septic spleen.” The absence of this sign at autopsy makes the diagnosis of sepsis doubtful.

In addition to sepsis, such swelling can be expressed in typhoid fever, infectious mononucleosis, acute malaria and a number of other systemic infections with constant bacteremia. In contrast, localized infectious processes, including localized bacterial peritonitis, pneumonia and others, usually occur without noticeable enlargement of the spleen.

In case of sepsis and typhoid fever, small foci of liquefaction necrosis may be visible in the pulp, usually without suppuration. Only when infected emboli enter the spleen, for example when septic endocarditis, foci of necrosis suppurate and abscesses may form.

The spleen with acute and subacute swelling is very fragile, and even a small injury, sometimes not noticed by the patient, leads to its rupture. Thus, in infectious mononucleosis, among rare fatal outcomes, the main cause of death is splenic rupture.

In chronic malaria, the spleen is usually sharply enlarged (weighing up to several kilograms), dense, and on the surface there are whitish, pearlescent-looking islands of a thickened capsule. The pulp on sections is homogeneous, slate-gray due to the deposition of malarial pigment (hemozoin). This spleen is called the malarial spleen.

In all chronic leukemia, the spleen is enlarged. In chronic myeloid leukemia, its weight can reach several kilograms, in lymphocytic leukemia it is somewhat less, usually up to 1 kg. The spleen is unchanged or slightly enlarged and full of blood in acute and acute leukemia. Its pulp usually has a homogeneous appearance, gray-red, soft consistency, elastic. In 15% of cases, heart attacks occur.

In some forms of malignant lymphomas, an enlarged spleen has its own characteristics. With lymphogranulomatosis, the cut pulp is variegated - on a gray-red background there are multiple scattered whitish or slightly yellowish nodules of irregular shape, partly in contact with each other. Such a spleen is called porphyry (a type of marble), and those who are unfamiliar with this type of stone and are inclined to “gastronomic” terminology in pathology call this picture “pudding with interior lard.” A nodular form of lymphogranulomatosis is also possible, while in the enlarged spleen there are separate rather large whitish nodes.

With macrofollicular lymphoma, numerous grayish enlarged follicles, distributed fairly evenly, are clearly visible against a uniform gray-red background.

In malignant histiocytosis, the spleen is sharply enlarged, with a “rubbery” dark red pulp, on a section with fuzzy multiple protrusions of the same color. This is characterized by hepatomegaly, jaundice, and cachexia.

Moderate splenomegaly is sometimes observed with metastases malignant tumors into the spleen, which, according to various authors, occur with a frequency of 0.3 to 9%. With careful searches, as some authors claim, they are found in 50% of those who die from cancer. However, in practice, metastases to the spleen are recorded in protocols very rarely. More often than others, metastases to the spleen give lung cancer, breast, carcinoma gastrointestinal tract, sarcomas, melanomas.

There are always metastases in other internal organs.

At polycythemia vera(Bucke's disease) the spleen is moderately enlarged, the pulp is full-blooded and slightly compacted, trabeculae are clearly visible, and infarctions are common. Moderate splenomegaly with pulp hemosiderosis is common in pernicious anemia, hemolytic anemia (with hemoglobin C, hemoglobin C in combination with hemoglobin S), thrombocytopenic purpura, and Waldenström's macroglobulinemia. Only congenital spherocytic anemia occurs without hemosiderosis. Pulp hemosiderosis is expressed in hemoglobinopathies associated with the presence of only hemoglobin S or hemoglobin A, but there is usually no splenomegaly. In thalassemia major (Mediterranean anemia), the spleen reaches enormous sizes. Its capsule is thickened, the pulp is dense, dark red, often with “tobacco nodules.”

Moderate splenomegaly (sometimes with hemosiderosis) is observed occasionally in patients who have undergone heart surgery, as well as in autoimmune diseases.

A sharp degree of splenomegaly is observed in Gaucher disease, which is very rare in adults (the “juvenile or adult type” of lipidosis). This disease is somewhat more common among Jews and their descendants. The mass of the spleen can be increased to 10 kg, its surface is smooth, the tissue is dense, and when cut, it is light gray-red, somewhat “greasy.” Against this background, multiple large gray nodes with a diameter of up to several centimeters are visible. Heart attacks are common. In this case, the liver may be enlarged, yellowish-brown pigmentation of the skin and mucous membranes, and cortical defects in the bones are noted. Patients are usually short in stature.

Moderate splenomegaly (spleen weight rarely exceeds 500 g) is observed in another storage disease - amyloidosis, mainly secondary. The spleen is dense with a smooth capsule, its edges are rounded. The parenchyma is fragile. When cut, its tissue can have a double appearance. If amyloid is deposited along the central arterioles, then translucent grayish formations up to 2-3 mm in cross section clearly appear on a uniformly gray-red background, contrasting with the surrounding pulp. Another type of amyloidosis is diffuse protein deposition. The cut surface is homogeneous light gray-red with a greasy sheen. According to “gastronomic” terminology, the first type is called “sago spleen” or (according to Virchow) “red wine soup with sago”, and the second type is called “grease” or “ham spleen”.

Secondary amyloidosis usually complicates chronic suppurative processes, tuberculosis, and is also observed in combination with multiple myeloma.

A slightly enlarged spleen may occur with long-term diabetes mellitus, with prolonged obstructive jaundice due to the accumulation of lipids and lipoproteins in the parenchyma of the spleen.

With all types of splenomegaly, splenic ruptures, heart attacks, and adhesions with surrounding organs often occur. Ruptures of a pathologically altered spleen can occur with the most minor trauma: a person simply leaned with his left side on the edge of a table, a doctor simply “carefully” palpated the area of ​​the spleen, a person simply strained strongly during defecation or had a severe vomiting etc. The rupture can be direct, i.e. with rupture of the capsule and parenchyma and immediate bleeding into the abdominal cavity, but there can be a rupture of the parenchyma without rupture of the capsule with the formation of a subcapsular hematoma. As the hematoma enlarges, after a few hours or even days, when a person could forget about the injury, the capsule ruptures and bleeding into the abdominal cavity occurs. This is a delayed two-stage rupture of the spleen. To rupture an intact spleen, the injury must be significant, often combined with injury to other organs.

With ruptures delayed for several days, small (up to several millimeters in diameter) bubbles filled with clear liquid can be seen along the edge of the spleen, resembling herpetic rashes, in connection with which the picture itself is called “herpes of the spleen.” In addition to ruptures, there are cases of the spleen being torn off from vessels during trauma, including surgery, and sometimes rupture of the splenic artery or vein occurs during pregnancy.

With a minor injury, there may be small, deep internal ruptures with the formation of hemorrhages in the pulp. This can happen not only with trauma, but also with hemorrhagic diathesis, portal hypertension, and acute infections.

Splenic infarctions due to the terminal type of blood supply to the parenchyma are common. Initially, this is, as a rule, a hemorrhagic wedge-shaped area of ​​parenchyma, which quickly becomes ischemic in the form of a dull light yellow wedge, the base facing the capsule and surrounded by a hemorrhagic rim. Sometimes a heart attack has an irregular shape. In “aging” infarcts, a grayish zone of fibrosis and thickening of the capsule above the infarction may be noticeable along their periphery. A healed infarction leaves behind a deep retracted scar, sometimes dividing the spleen into false lobes. Lobulation is not typical for the spleen; sometimes there are only small depressions along its edge with the formation of tongues.

Heart attacks can be the result of both local vascular thrombosis and embolism, most often from the cavities of the left heart. If these are septic emboli, then a splenic abscess may develop.

Local arterial thrombosis often occurs in enlarged spleens with leukemia, splenitis, arteritis, including nodular arteritis. Thrombosis of the splenic veins occurs when blood clots spread from the portal vein, when there is pressure on the vein of a nearby tumor, or when tumor invasion veins, as well as when the leg of the “vagus spleen” is twisted.

Small yellowish or whitish areas of necrosis of irregular shape occur with acute infectious swelling of the spleen, and also occur in a non-enlarged spleen, without sepsis, vascular lesions. This is a “spotted spleen”, found in toxicosis and uremia.

Splenic cysts are a common finding. Inclusion (mesothelial) cysts are most often found. These are single or multiple, thin and smooth-walled cavities filled with transparent liquid. Their sizes are usually small, up to 1-3 cm in diameter, rarely larger. They are often located under the capsule and are often combined with similar cysts of the liver and kidneys.

Occasionally found hydatid cysts with hydatid disease. Cysts can be single or multiple. Their diameter ranges from a few centimeters to gigantic ones. Giant cysts are accompanied by atrophy of the spleen tissue, up to its almost complete disappearance, leaving only the echinococcal sac. The spleen capsule is usually thickened above the cyst, and fusion of the affected spleen with surrounding organs is very common. With multiple small cysts, the spleen may appear lumpy. The wall of the cyst is usually well defined, in its lumen clear liquid and daughter bubbles. Often the cyst suppurates, ruptures with emptying of pus into the abdominal cavity or into neighboring organs to which the spleen is fused - into the stomach, liver, through the diaphragm into pleural cavity, into the lung. In “old” cysts, after the death of the parasite, the wall and contents of the cavity undergo calcification.

• What is Fibrosis
• What Causes Fibrosis?
• Symptoms of Fibrosis
• Diagnosis of Fibrosis
• Fibrosis Treatment
• Which doctors should you contact if you have Fibrosis?

What is Fibrosis

Fibrosis represents the development (new formation) of connective tissue in the portal field, in the periportal zone (around hepatocytes and proliferating ductules), in the center of the lobule (around the hepatic vein) and intermedullary (around hepatocytes).

What Causes Fibrosis?

Fibroblasts play an important role in the development of fibrosis, while the collapse of the reticulistroma in foci of hepatocyte necrosis, previously considered the main mechanism for the development of fibrosis, is of secondary importance. Silent fibrogenesis in the liver is observed with damage to hepatocytes, inflammation, proliferation of ductules (especially with chronic hepatitis and cirrhosis). Fibrosis-inducing factors can be peptides, macromolecular substances or fragments of cytoplasmic organelles (lysosomes), released when hepatocytes are damaged. In the process of fibrogenesis, a certain role belongs to the sinusoidal surface of the damaged hepatocyte with the reduction of microvilli, the basement membrane, and iron-containing macrophages. With continued damage in the space of Disse, a basement membrane forms between the proliferating sinusoidal cells and hepatocytes. Subsequently, a vicious circle arises: damage to hepatocytes stimulates fibrogenesis, and fibrogenesis aggravates damage to hepatocytes due to malnutrition. As is known, the basement membrane surrounds proliferating small bile ducts. Its fibrous part consists of compressed connective tissue argyrophilic fibers, and the homogeneous, SIK-positive part is formed by epithelial components - ductular cells.

Pathogenesis (what happens?) during Fibrosis

The degree of fibrosis is determined by the ratio of collagen synthesis and breakdown. The reversibility of the process (disappearance of connective tissue) depends on the state of macrophages resorbing collagen, and chemical nature main substance.

In foci of fibrosis, active and passive connective tissue septa are distinguished. Active septa are rich in cellular elements and are formed in foci of active fibrogenesis as a result of the formation of connective tissue by fibroblasts. Passive septa result from the collapse of the reticulin stroma in areas of parenchymal necrosis and contain few cells.

Connective tissue fibers with big amount cellular elements undergo reverse development better than fibers containing few cells. Connective tissue septa growing into the lobule from the portal fields or from zones of collapse divide the parenchyma into separate sections - pseudo-lobules, which leads to a restructuring of the microarchitecture of the liver, and subsequently to the formation of cirrhosis of the liver. Active Education sept has great importance, especially in the cirrhotic stage. Along the septa there are blood vessels that are anastomoses between the branches of the portal vein and hepatic artery and branches of the hepatic veins, which leads to intrahepatic shunt blood flow and, as a result, there is a decrease in the amount of blood washing the liver parenchyma. Poor circulation leads to insufficient oxygen supply and nutrients into hepatocytes and loss of liver function, increased pressure in the portal vein system. In alcoholic liver damage, excessive formation of connective tissue occurs in the center of the lobule, around the hepatic vein, which also contributes to disruption of hemodynamic processes during passive blood stagnation, prolonged cholestasis, and some intoxications accompanied by the death of parenchyma in the center of the hepatic lobule. In areas of parenchymal necrosis, connective tissue collapses. In these cases, the formation of excess connective tissue determines active fibrogenesis, prevailing over collapse.

• Fibrosis classification

Based on its localization in the liver lobules. There are focal, perihepatocellular, zonal (centrilobular, portal, periportal), multilobular, bridge-like, as well as periductular, perivenular fibrosis.

Focal fibrosis characterized by the presence of introlobular small scars at the site of the granuloma, which may indicate previous liver damage.

For perihepatocellular fibrosis The formation of a basement membrane at the sinusoidal surface of hepatocytes is characteristic. If the process involves all the liver lobules or most of them, fibrosis is designated as diffuse. Perihepatocellular fibrosis can occur with alcoholic lesions, hypervitaminosis A, syphilis and a number of other conditions,

Zonal central fibrosis may lead to the formation connective tissue septa spreading from central veins towards the portal tracts. At the same time, when zonal portal fibrosis a cylindrical expansion of the portal fields is observed.

Sclerosis of the portal tracts with the spread of the process beyond them due to necrosis of adjacent hepatocytes is a characteristic feature zonal periportal fibrosis.

Multilobular fibrosis occurs as a result of massive necrosis of the liver parenchyma, covering the territory of several lobules. Against their background, the intact part of the liver tissue can retain its normal structure.

For bridging fibrosis The formation of connective tissue septa between the vessels of the liver is characteristic. In addition to complete septa, there are incomplete septa that blindly end in the liver lobule. Complete septa can be porto-portal, porto-central, or centro-central.

The central veins contain anastomoses through which blood flows bypassing the parenchyma. The consequence of the formation of full-fledged septa is a violation of the architectonics of the lobules, up to the formation of false lobules.

At periductular And periductal fibrosis collagen is deposited under the thickened basement membrane of the corresponding bile ducts, however, the fibers never penetrate between the epithelial cells of these formations. Periductal fibrosis reaches its greatest severity in sclerosing cholangitis.

Perivenular fibrosis more common with alcoholic liver damage, as well as in drug addicts. From the subsinusoidal spaces, fibrosis can spread to the central vein, and this leads to thickening of its walls.

A specific form of liver disease is congenital fibrosis. In this case, pronounced portal fibrosis, hypoplasia of the intrahepatic branches of the portal vein and hepatic artery, and a sharp dilation of the bile ducts are observed. There are clear boundaries between the sclerotic portal tracts and the parenchyma, and there is no inflammatory infiltration. Adjacent portal tracts can be connected by septa. A characteristic feature of congenital fibrosis is the absence of false lobules.

In the liver, the processes of fibrogenesis are primarily controlled by a complex of interacting cells of the sinusoids and parenchyma. Fibrous scar not only causes liver deformation, but is also the main cause of liver dysfunction, clinical manifestations, a number of complications. Excessive development of connective tissue in the liver can be observed in the portal tracts, in the periportal zone (around hepatocytes and proliferating ductules), in the center of the lobule (around the central vein), intramedianly, around hepatocytes. With fibrosis, a special variant of interaction between sinusoid cells and hepatocytes is formed. The formation of fibrosis (fibrogenesis) is a universal process caused by excessive deposition of extracellular matrix (ECM) proteins in tissues. In addition to collagen, the extracellular matrix includes glycoproteins, glycosaminoglycans (GAGs) and proteoglycans. There are 5 types of collagen in a normal liver: I, III, IV, V, VI. In fibrosis, one type of collagen predominates, which contributes to their disproportion.

Proteoglycans are complex macromolecules consisting of a core protein covalently linked to a series of polyanionic sulfated carbon polymers, or GAGs. Depending on the carbon chain of GAGs, heparan sulfate, dermatan sulfate, and chondroitin-4,6-sulfate are distinguished. ECM fibers are firmly associated with structural glycoproteins (lamin, fibronectin, nido-gene/entactin, undulin, tenascin), which envelop collagen fibers and thus separate the liver stroma from the parenchyma. Liver damage is accompanied by an increase in the production of all types of collagen. The main sources of ECM protein formation are hepatic stellate cells (HSCs) and Ito cells. When activated, their transformation into myofibroblasts, loss of vitamin A, the appearance of oc-actin fibers, an increase in the rough endoplasmic reticulum, the content of messenger RNA of collagen types I, C. IV, and the number of receptors for cytokines stimulating proliferation and fibrogenesis are observed. With fibrosis, one or another type of collagen begins to predominate. Fibrous tissue contains a lot of helical collagen types I and III, while type IV collagen predominates in the basement membranes.

Myofibroblasts take part in collagen synthesis and the formation of fibrosis. Activation of the sinusoid PGC begins with their paracrine stimulation, which promotes gene expression by Kupffer cells, endothelial cells, hepatocytes, and platelets. This enables Ito cells to respond to the effects of cytokines and other mediators, such as transforming growth factor -pi (TGF-(3i), platelet-derived epidermal growth factor, tumor necrosis factor-(TCR-os), thrombin. This stimulates proliferation processes , contractility, release of leukocyte chemoattractants, cytokines, excess production of ECM components, type I collagen.

Formation of fibrosis is largely due to the activity of tissue metalloproteinases (MPs), which destroy ECM proteins. Tissue MPs are synthesized by Kupffer and Ito cells. Their activity is regulated by tissue inhibitors, in particular TIMP, as well as plasmin and ag-macroglobulin. TIMPs are produced by various cells, including Ito cells (Fig. 5).

3 types of MP are described:

• interstitial collagenases (destroy collagen types I and III);
• gelatinases (destroy collagen types IV and V, fibronectin, elastin, denatured collagens);
• stromelysins (destroy fibronectin, laminin, collagen types III, IV, V, peptides, procollagen).

Depression of macrophages takes the system of Ito cells out of control, which gain the opportunity to realize their fibrogenic functions. At this stage of the disease, macrophages actively produce antifibrogenic cytokines (IFN-a/R), as well as metalloproteinases (collagenases, prostaglandins Ei/Er).

At acute lesions In the liver, there is a certain balance between the synthesis and destruction of ECM components. At the same time, during the chronic process, there is a predominance of ECM synthesis over its destruction, which leads to excessive activation of the fibrosis process. Thus, enhanced hepatic fibrogenesis is characterized by an increase in collagen production, a decrease in the secretion and activity of tissue MPs, and an increase in the concentration of tissue inhibitors of metalloproteinases, most often TIMP-1.

Triggers of hepatic fibrogenesis more often are alcohol, hepatotropic viruses hepatitis B, C, D, coinfection of the virus, autoimmune process, medicinal lesions liver, excessive accumulation of copper and iron in the liver tissue, metabolic disorders of carbohydrates and lipids, biliary obstruction at all levels, etc.

Changes in collagen synthesis by activated PGCs begin with increased expression of their genes. Messenger RNA serves as a carrier of information from the gene to the protein-synthesizing system of cells and acts as a matrix for protein synthesis. The main mechanism of collagen mRNA stability is determined by the interaction of the a-CP2 protein complex with the nucleotide sequence. Proteins of this complex are able to interact with collagen mRNA only in activated PGCs. Collagen is synthesized as an intracellular precursor molecule. The early precursor of collagen is preprocollagen, which contains a signal sequence at the N-terminus, which is cleaved off in the endoplasmic reticulum and turns into procollagen. After a series of specific transformations, collagen molecules in the ECM form fibrils. When exposed to damaging agents, fibrosis forms over several months or years. The timing of fibrosis formation can be altered by additional risk factors (alcohol, chronic infection, male gender, etc.). With biliary obstruction, fibrosis can develop within a period of 2.5 to 18 months.

The formation of fibrosis in the liver also depends on the nature and severity of the inflammatory process. Cirrhosis of the liver with manifestations arterial hypertension is considered as an irreversible condition, but at the precirrhotic stage there is a possibility of further development of the process. We have observed cases reverse development fibrosis in a patient with biliary cirrhosis of the liver with normalization of bile flow through the extrahepatic bile ducts. The longer fibrosis exists, the fewer opportunities there are for its correction. Currently great attention is devoted to methods that allow not only to ascertain fibrosis, but also to determine the activity of fibrogenesis in the liver, its tendency to stabilization, involution or progress. The degree of fibrosis in the liver is assessed using morphological methods. Conventional histological methods using standard dyes make it possible to give a qualitative assessment of the content of collagen and glycoproteins. Spectrophotometric analysis quantifies collagen based on the concentration of collagen-specific dyes. In addition, semi-quantitative systems for assessing the degree of fibrosis are widely used. For this purpose, inflammatory markers are determined in the blood - endothelial adhesive proteins from the E-selectin class (ICAM-1, VCAM-1), IL-8, which determine inflammatory infiltration in the liver. The destruction of the ECM and the activity of fibrogenesis can be judged by the content of hyaluronate, laminin, and other structural glycoproteins in the blood.

Symptoms of Fibrosis

On early stages fibrosis, the liver works relatively well, so only a small number of people notice that something is wrong. They can feel constant fatigue, note that after the slightest blow, bruises appear on the skin. Few people associate this with liver disease. However, as liver destruction continues, scar tissue grows and closes with existing scars, liver functions are impaired. Eventually the liver becomes so scarred that it impedes the flow of blood through it and significantly reduces its function.

The disease progresses slowly. It is believed that clinical symptoms occur 6-8 years after the onset of liver fibrosis. Clinical symptoms usually develop in the following sequence:

• significant enlargement of the spleen (splenomegaly);
• manifestations of portal hypertension (varicose veins of the esophagus and bleeding from them);
• the occurrence of hypersplenism (anemia, leukopenia, thrombocytopenia). In this case, there are no symptoms of liver cirrhosis and liver function tests are not changed or changed slightly. Despite the absence morphological changes There is a significantly increased portal and splenic pressure. There may be periodic appearance of small ascites, which then spontaneously disappears.

Diagnosis of Fibrosis

The early stage of fibrosis is difficult to detect, as it often occurs without any symptoms. To diagnose the disease, blood and urine tests are taken, and an ultrasound examination of the liver is performed. Currently the most the best method A liver biopsy is considered to determine the stage of the disease. A small sample of liver tissue is removed with a special needle, mixed with a special dye, and examined under a microscope. In order to monitor the development of the disease and respond to changes in a timely manner, it is recommended to repeat the biopsy every 3-5 years.

Fibrosis Treatment

Clinicians have very few effective options for treating liver fibrosis. Currently, correction of hepatic fibrogenesis can be carried out in several directions:

• treatment of the underlying disease in order to eliminate causative factor fibrosis;
• "inhibition of activation" of the PSC;
• reducing the activity of the inflammatory process in the liver;
• activation of fibrolysis mechanisms to destroy excess ECM proteins.

Elimination of the etiological factor of the pathological process in the liver serves as an important component of therapy aimed at reducing fibrosis processes. To the specified therapeutic measures include etiotropic therapy of viral lesions (interferons, interferon inducers, chemotherapy drugs), avoidance of alcohol, narcotic and hepatotropic drugs, elimination of excess iron and copper, decompression for bile duct obstruction, etc.

Under "inhibition" of activation of the slam-shut valve imply blocking the processes of transformation of stellate cells into active myofibroblasts, the triggers of which can be oxidative stress, endotoxemia, lipid metabolism disorders, etc. In order to inhibit the activation of stellate cells, antioxidants (a-tocopherol, vitamin C) can be used, under the influence of which glutathione accumulates in the liver part of glutathione peroxidase, which destroys reactive oxygen species. In addition, phosphatidylcholine, cholestyramine, antibacterial drugs, etc. can be used

In order to inhibit the activation of PZK, drugs with anti-inflammatory activity can be used - glucocorticoids, interferons (a, P), D-penicillamine, etc.

Activation of fibrolysis mechanisms can be carried out by enhancing the degradation of ECM proteins. Substances that have a similar effect include alkaloids such as cytochalasin B or colchicine, prostaglandins of group E. The toxicity of these alkaloids prevents them wide application V clinical practice. It must be remembered that exogenous PGEs are quickly destroyed in the body without having time to affect the connective tissue of the liver. Research is currently being conducted on its use as medicinal substances cytokines and antagonists of their receptors. In liver fibrosis, Ito cells have hypersensitivity to growth cytokines (TGF-bb). However, their sensitivity decreases under the influence of factors that stimulate hepatocyte regeneration, which confirms the promise of using growth factors in preventing the development of fibrosis.

SPLENIC INFARCTION

Splenic infarction is a disease based on thromboembolism of the branches of the splenic artery. The source of embologenic thrombosis is the left chambers of the heart. If splenic infarction develops against the background infective endocarditis, the next stage after embolism may be suppuration with the formation of a splenic abscess. The symptoms of splenic infarction are determined by the size of the infarction focus. Pain syndrome As a rule, it develops only when extensive heart attack with the development of perisplenitis.

Diagnostic imaging methods reveal a characteristic picture: the infarction fields are usually wedge-shaped, but can be round and/or linear in configuration (Fig. 62-8).

Rice. 62-8. Computer tomogram for splenic infarction: a - native scan; b - after intravenous enhancement (1 - infarction zone).

The fields of a fresh infarction are usually hypodense, but may temporarily acquire a spotty structure with hyperdense inclusions due to minor hemorrhages. Over time, the densitometric characteristics in the affected area normalize as the volume of the affected tissue decreases. This process can be identified by the appearance of small tuberosity of the capsule located above the infarct area. Infected fields may undergo liquorification with the development of a false cyst or become calcified. Splenic infarction, unlike many others pathological processes this localization is clearly visualized by gamma scintigraphy with erythrocytes labeled with 99Tc and damaged by heating.

SPLENIC RUPTURE, NON-TRAUMATIC

Patients with splenomegaly are at risk of spontaneous splenic rupture with minimal trauma and are advised to avoid physical activity. Rapid enlargement of the spleen in patients infectious mononucleosis, leukemia or lymphoma leads to excessive stretching of the capsule, which increases the risk of spontaneous rupture. Clinical picture corresponds to that for abdominal trauma with damage to the spleen. Imaging diagnostic methods make it possible to localize the source of bleeding into the abdominal cavity.

A situation similar in pathogenesis is a two-stage rupture of the damaged spleen. The only difference is that with spontaneous rupture, anamnestic indications of abdominal trauma cannot be identified, and capsule rupture occurs against the background of pathological changes in the pulp. In the second option, there is a history of abdominal trauma, and the source of bleeding is a rupture of the capsule due to the growth of a subcapsular hematoma, or a rupture of the paralienal hematoma occurs with bleeding into the free abdominal cavity.

As a rule, splenectomy is prescribed. Alternative treatment options: debridement laparoscopy with local hemostasis and dynamic observation, as well as non-operative management, described below.

TORSION (TURNSION) OF THE SPLEEN

Weakness ligamentous apparatus the spleen can lead to a change in its location in the abdominal cavity. The condition, described as a wandering spleen (lien mobilis), is characterized by a displacement of the organ downward to the pelvic cavity due to the elongation of the peritoneal duplications and the vessels enclosed in them.

In such a situation, volvulus (twisting) of the spleen is manifested by periodic intense pain radiating to the left upper quadrant of the abdomen. The condition under discussion has been described in women, elderly men, and can occur in combination with defects in the development of abdominal organs. With volvulus of the spleen (Fig. 62-9), a state of segmental venous hypertension develops, since arterial inflow is maintained during occlusion of the splenic vein in the pedicle of the vagus spleen, and venous collaterals are formed.

Rice. 62-9. Turning of the wandering spleen 180° around the vascular pedicle (photo of the moment of surgery).

Treatment is surgical. If ischemic damage the tissues of the organ are pronounced due to repeated episodes of volvulus, splenectomy is indicated. In case of pelvic dystopia, it can be performed from a projection approach in the hypogastric region. From the point of view of organ preservation, laparoscopic or open splenopexy is preferable.

SPLENIC FIBROSIS, PERISPLENITIS, SPLENITIS

If splenic fibrosis is predominantly a pathomorphological diagnosis (for example, perivascular proliferation of connective tissue in Banti's disease), then inflammatory changes in the capsule and pulp (perisplenitis and splenitis) can be observed during surgical interventions.

Under perisplenitis understand the presence of adhesions around the spleen, as well as (in an acute inflammatory process) the presence of abscesses involving the organ capsule. The most common examples are pancreatic suppuration with the formation of abscesses in the hilum of the spleen or in the left subdiaphragmatic space (Fig. 62-10), as well as abscess formation of a perilenal hematoma, usually localized along the diaphragmatic surface of the spleen.

Rice. 62-10. Abscess in the area of ​​the splenic hilum with pancreatogenic perisplenitis (computer tomograms): a - native scan; b - after intravenous enhancement (1 - spleen; 2 - infiltration of fiber in the area of ​​the splenic hilum; 3 - abscess in the splenic hilum; 4 - abscess capsule).

Inflammatory changes in the pulp are observed with splenic abscesses. In addition, splenitis is sometimes called stagnant changes in the pulp against the background of destructive pancreatitis with thrombosis of the splenic vein.

HEMATOLOGICAL DISEASES

Splenectomy serves the most effective way treatment cytopenic disorders . Congenital hemolytic anemia (microspherocytic anemia - Minkowski-Choffard disease, to a lesser extent thalassemia, sickle cell anemia) require removal of the spleen as the locus of destruction of erythrocytes due to inherited defects cell membrane. The actual indication for surgery is hypersplenism with a predominant lesion of the red germ. For autoimmune hemolytic anemia destruction of sensitized cells occurs not only in the spleen, so the effect of splenectomy may not be pronounced. Known alternative methods correction of hypersplenism, such as splenic resection or endovascular embolization of the splenic vessels, however, information about their effectiveness is contradictory.

Idiopathic thrombocytopenic purpura is an indication for splenectomy if conservative treatment is ineffective. Relapses of thrombocytopenia in the postoperative period are associated with the restoration of the function of residual spleen tissue, therefore important stage operations - search and removal of accessory spleens, as well as prevention of splenosis. Thrombotic thrombocytopenic purpura, as a multisystem disease, is much less often accompanied by the effect of splenectomy.

Malignant hematological processes affecting the spleen: leukemia, Hodgkin's disease (Hodgkin's lymphoma) and non-Hodgkin's lymphoma, as well as myelo- and lymphoproliferative disorders (myeloid metaplasia, various options chronic leukemia) V Lately- rare indications for removal of the spleen and always require coordinated actions of a hematologist, who determines the tactics of long-term treatment of the patient, and a surgeon, who evaluates the risk-benefit ratio of the operation.

For planned surgery for hematological pathology, laparoscopic splenectomy is the method of choice. A contraindication to laparoscopic intervention is severe splenomegaly (the length of the spleen is more than 20 cm).

Along with diseases of the spleen and secondary changes organs that can be classified as hematological pathology, in this chapter we will talk about “incidental” operations, when splenectomy is a stage of oncological intervention on the abdominal organs (most often on the stomach, pancreas, left flexure of the colon), as well as iatrogenic damage to the spleen. The concept of organ preservation is implemented in relation to all of the listed conditions.

K.A. Apartsin, E.G. Grigoriev

Principles ultrasound examination spleen

Results of a study of the spleen in healthy people

The spleen is located under the diaphragm, in the left half of the abdominal cavity. The longitudinal axis of the spleen is located mainly parallel to the X rib.

The spleen consists of supporting connective tissue and parenchyma. The fibrous capsule covering it also belongs to the connective tissue. Trabeculae extend from the capsule into the spleen, forming a large network.

Ultrasound examination of the spleen is preferably performed on an empty stomach, but it can also be performed without food intake. In patients with severe flatulence, adsorbents should be used for 3 days. medicines and a slag-free diet. The feasibility of these measures is obvious, since the stomach and splenic angle of the colon are located in close proximity to the spleen.

The spleen is visualized with the patient lying on the right side with a deep breath held. The sensor will be placed parallel to the intercostal space so as to avoid interference from the acoustic shadow coming from the ribs. The spleen is carefully examined from the diaphragmatic surface to the level of the portal vessels.

Rice. 1 The sensor is placed in the intercostal space above the left lateral abdomen and tilted towards the cephalic end and medially, so as to visualize the spleen (S) in its longitudinal section. The upper pole of the spleen is determined on the left side of the image, the lower pole - on its right side. The gauge is rotated, shifted and tilted until the maximum diameter is obtained. The length of the spleen and its thickness at the level of the hilum are determined.

Usually sagittal scanning through the anterior abdominal wall does not give good results due to the overlap of the stomach and intestinal loops on the projection of the spleen. But in the case of splenomegaly, this access is quite informative. In this case, the transducer is placed along the midline of the abdomen immediately below the costal arch and moved with smooth movements to the left by 0.5-1.0 cm, making a series of parallel sections to the outer edge of the spleen. The transducer is then moved to horizontal position, into the transverse scanning plane, and transfer it at the same intervals from the costal edge to the lower contour of the spleen. With an unchanged spleen, a sufficiently clear image of it can be obtained only with an oblique scan performed in the area of ​​the left hypochondrium, parallel to the edge of the costal arch. For better visualization, a number of techniques are used: taking a deep breath, inflating the abdomen, tilting the transducer relative to the patient’s body.

Rice. 2. To obtain an image in the left oblique subcostal plane from a position in the transverse plane of the mid-abdomen, the transducer is moved to a position under the left costal arch. The liver (L) is visualized on the left side of the image. The spleen (S) is identified posteriorly and laterally on the right side of the image, showing its true width and reduced longitudinal diameter

If the inhalation is too deep, the lung expands down into the diaphragmatic angle and closes the subdiaphragmatic part of the spleen. In this case, it is worth trying the “curtain technique” by asking the patient to take a deep breath exhale slowly until the image of the spleen appears. Like a curtain, the lung above the spleen moves back, moving back and up. During this uneven displacement, it is necessary to wait until the acoustic shadow from the lungs no longer interferes with the visualization of the spleen. At this point, the patient should be asked to hold his breath. Sometimes the spleen is visible better when lying on your back than on your right side. If the organ is small or it is difficult to visualize it, you can ask the patient to raise his left arm while lying on his back or lying on his right side and conduct the study with a full inspiration, in this case the intercostal spaces widen, which makes visualization of the spleen easier.

Echographically, the spleen appears as a crescent-shaped organ, which is limited by a highly echogenic linear echo signal originating from its capsule. The size of the spleen may be reduced due to the presence of an additional spleen, which may be located in the left hypochondrium or elsewhere. Accessory spleens are a very interesting phenomenon and have long been known in medicine. During the embryonic formation of the spleen, cracks, folds and grooves are sometimes so deep that they can lead to ligation of part of the organ. A small, cherry-sized accessory spleen located at the hilum of the organ is not a particular deviation from the norm, but it is quite difficult to detect. Sonographically, it is visualized as a round or oval structure, similar in structure and echogenicity to the main spleen. This is usually an accidental finding, although in some cases hematological diseases it hypertrophies, reaching significant sizes - 5 cm or more, and can be a source of abdominal pain.

Rice. 3. Accessory lobule of the spleen (^). The small rounded accessory lobule of the spleen has the same exogenicity as the splenic parenchyma.

The outer convex surface is adjacent to the costal part of the diaphragm, and the inner, concave surface faces the abdominal organs. The anterior end, often pointed, is adjacent to the stomach, and the posterior, more rounded, faces the left kidney and adrenal gland. About in the middle inner surface The spleen contains a gate with blood vessels and nerves. The splenic vein is normally visualized as an anechoic cord, its diameter is quite variable, does not have a clear age difference, but should not exceed 5 m

• Normally, the spleen always has a hypoechoic echo structure.
• The spleen has a crescent or wedge shape in a longitudinal section

Rice. 4. Detection of the spleen (Mi) on the lateral section;

and oval - on the transverse (left subcostal plane, the spleen is visible only on a magnified image).

Rice. 5. The cut is made slightly anteriorly. The spleen (Mi) and the upper pole of the kidney (N) are visible;

• The visceral surface of the spleen is adjacent to the left kidney, adrenal gland and tail of the pancreas.
• The spleen has smooth edges, but may have grooves (jagged edges) in the hilum area.
• Normal sizes: length<110 м, толщина <50 мм, ширина <70 мм.

Diffuse splenomegaly

Many diseases are accompanied by diffuse enlargement of the spleen. Differential diagnosis should be made not only with portal hypertension against the background of liver cirrhosis, but also with viral infections, for example, mononucleosis.

Rice. 6. Splenomegaly in congenital liver fibrosis The spleen (S) is noticeably enlarged for a thin patient, measuring 16 cm in length and 6 cm in thickness.

Liver pathology in cirrhosis and active hepatitis in 75% of cases is accompanied by changes in the spleen, resulting in the development of splenomegaly. Already in the initial stage of portal hypertension, an increase in the diameter of the splenic veins is noted. Over time, fibrosis of the spleen parenchyma occurs with an inhomogeneous increase in echostructure.

Rice. 7. Splenomegaly. Advanced		Rice. 8. Echogram of fibrous changes in
intrasplenic vessels.		spleen. Splenomegaly in cirrhosis

In addition, all diseases accompanied by accelerated destruction of red blood cells, for example, hemolytic anemia and polycythemia vera, can lead to splenomegaly. Since the pathological process in hemolytic anemia and hereditary microspherocytosis is associated with the state of erythropoiesis and the reticulohistiocytic system, i.e. red pulp, then the spleen has unchanged echogenicity of the parenchyma. Its dimensions can vary widely.

Splenomegaly is a typical manifestation of systemic blood diseases, such as acute or chronic leukemia, but can also be found in rheumatological, immunological and storage diseases. Chronic myeloid leukemia refers to myeloproliferative diseases, which are based on leukemic transformation of hematopoietic stem cells, common to granulocytes, megakaryocytes and erythrocytes. Splenomegaly in this disease, according to some authors, is observed in 94% of patients, the echostructure of the organ changes, and with the progression of the tumor process, connective tissue growths and foci of fibrosis are recorded in the parenchyma of both the liver and spleen.

Rice. 9. Chronic myeloid leukemia - splenomegaly.

Splenomegaly does not always indicate a pathological condition, since many diseases leave behind a slight or moderate enlargement of the spleen, for example, mononucleosis. An enlarged spleen begins with rounding of its normal crescent shape and can progress to what is called a “giant spleen.” A significantly enlarged spleen can reach the left lobe of the liver (the so-called “kissing phenomenon”). Sometimes the accessory spleen can reach significant sizes.

The spleen reacts quite quickly to various infections that can cause acute inflammation. The echographic picture of acute splenitis, especially in septic conditions, is accompanied by an increase in the size of the spleen and rounding of its ends; the echostructure remains uniformly fine-grained, its echogenicity usually remains unchanged or increases slightly. In some cases, it is possible to identify foci of acute necrosis in the form of small anechoic formations. In the chronic course of the infectious process, acute splenitis becomes chronic. In chronic splenitis, the size of the spleen remains enlarged due to the proliferation of fibrous tissue and the echogenicity of the parenchyma increases.

If splenomegaly is detected on abdominal sonography, systemic hematologic disease should be considered and all areas where lymph nodes are present should be examined for possible lymphadenopathy.

Rice. 10. Severe splenomegaly with a homogeneous echo structure of the splenic parenchyma (S) in non-Hodgkin's lymphoma. The arrow points to the accessory spleen. (NB: In this image and in the other images later in this chapter, the sensor was flipped 180°.)

In addition, portal hypertension should be excluded by measuring the internal lumen of the splenic, portal and superior mesenteric veins and searching for venous collaterals. The size of the spleen must be carefully measured. Only having the basic dimensions of the spleen can one establish any growth dynamics using control studies. When conducting an initial study, one should already take into account issues that will arise during control studies, for example, determining the dynamics of growth during the treatment process. Neither the size nor the echogenicity of the spleen allows us to draw conclusions about the nature of the underlying disease

In general, with splenomegaly the spleen has

· length >12 cm and width 5 cm;

· diffuse changes usually with a homogeneous echo structure;

· enlargement of the poles of the spleen;

· accentuation of splenic vessels.

Article I

Article II.

Article III.

Article IV.

Article V

Article VI.

Section 6.01

Section 6.02

Focal lesions of the spleen

Focal lesions of the spleen

A possible reason for the decrease in echogenicity of certain areas of the splenic parenchyma may be focal lymphomatous infiltration. In non-Hodgkin's lymphoma, these lymphomatous infiltrates may be diffusely located in the spleen, creating a heterogeneous picture.

Rice. 11. High-grade non-Hodgkin's lymphoma of the spleen (S).

Fig. 12. Small asymptomatic anechoic splenic cyst (CS).

Rice. 13. Echinococcal cyst of the spleen.

Identification of a splenic hematoma can be difficult because fresh bleeding is isoechoic to the surrounding splenic parenchyma. Typically, the echogenicity of blood leaking from the vessels decreases within a few days, and subacute or old hematomas are clearly visualized as hypoechoic space-occupying formations.

Rice. 14. Large post-traumatic hemorrhage in the spleen (N), occupying almost the entire organ. AO - aorta.

Splenic rupture is characterized by the following echographic signs: discontinuity of the contour resulting from rupture of the organ capsule, identification of a double contour with an echo-negative structure (the outer one corresponds to the capsule, the inner one corresponds to the parenchyma with blood), splenomegaly. signs of hematoma and an increase in the size of the spleen over time.

Parenchymal ruptures without capsular damage may initially cause unrecognized subcapsular hematomas. The risk of such hematomas is late spontaneous rupture of the capsule, which leads to massive bleeding into the abdominal cavity. More than 50% of these, so-called. “Late” splenic ruptures are observed within 1 week after injury, so it is recommended to do several control studies at least during this period of time.

Rice. 15. Spontaneous formation of a subcapsular hematoma (H) in a patient with chickenpox sepsis. S - spleen.

Patients with acute abdominal and chest trauma should be assessed for the presence of free fluid in confined spaces and below the diaphragm. and also near the spleen and liver. It is necessary to carefully examine the spleen to identify a double contour along the capsule (subcapsular hematoma?) and heterogeneous areas in the parenchyma, so as not to miss a possible splenic rupture.

Finally, echogenic foci may be found in the spleen. They may represent the rare splenic hemangiomas or the more common calcified granulomas seen in tuberculosis or histoplasmosis.

Rice. 16. Splenic hemangioma.

Foci of necrosis may become calcified during the process of reverse development. Single and multiple calcifications are visualized as small hyperechoic formations, sometimes with an acoustic shadow. Calcifications may be found in individuals. have had typhoid fever. sepsis, malaria. Splenic calcifications may also be found in liver cirrhosis. There may be many echogenic foci in the spleen. This picture is called “starry sky”.

Fig. 17. Multiple calcifications within the spleen in an asymptomatic patient. S - acoustic shadows.

Abscesses and metastases of the spleen are rare and have a varied sonomorphology, which partly depends on the duration of their existence and etiology. There are no simple and reliable differential diagnostic criteria, so it is recommended to consult reference books. Spleen abscesses develop as a complication of splenic infarctions; they can be a consequence of a general purulent infection or generalized infectious diseases that cannot be treated. A clinically important group is represented by abscesses that occur during bacteremia against the background of endocarditis or salmonellosis, and during infection of subcapsular hematomas. The development of a splenic abscess can also be caused by a rupture of a subdiaphragmatic abscess into it. The variety of abscess shapes is associated with a certain stage of its development. A developing abscess is characterized by insufficiently clear intermittent boundaries. When an abscess is formed, the walls of the formation become clearer, uneven, and heterogeneous in thickness and acoustic density. The internal structure of the formation is even more complex, depending on the type, size, phase of development of the abscess and the presence of reactive inflammation in the form of connective tissue or granulation tissue around.

Rice. 18. Splenic abscess: hypoechoic formation of the spleen with unclear boundaries.

The structure of abscesses varies from anechoic contents with a distal enhancing effect to echopositive contents, similar to the characteristics of a solid tissue formation. In the area of ​​the abscess, internal septa and small gas bubbles are often identified. But the main thing is the ability to differentiate layers of pus of different echogenicity, changing their relative positions when the patient’s body position changes. The presence of dense necrotic masses in the decay cavity complicates the differential diagnosis of an abscess with hematomas and metastases of the spleen.

In some cases, puncture and drainage are used to diagnose and treat splenic abscesses.

Rice. 19. a-c Therapeutic fine-needle aspiration and drainage, a Well-defined round formation inside the spleen with a heterogeneous internal echo structure, b Diagnostic fine-needle aspiration of the abscess contents. The location of the needle is indicated by an echo signal from its tip, with the contents of the abscess (140 ml) being evacuated for therapeutic purposes. S - spleen, A - abscess.

Splenic infarction can occur with splenomegaly with impaired blood supply. The size of the infarction depends on the size of the blocked vessel and can occupy up to one third of the spleen. Infarction in the acute stage looks like a wedge-shaped area with unclear contours and reduced echogenicity, located on the periphery of the spleen. Sometimes, in the projection of the infarction area, multiple thin linear echo signals originating from the gas are detected.

Rice. 20. Small hypoechoic wedge-shaped area of ​​splenic infarction (Inf) secondary to myeloproliferative disease.

At a later stage and in the process of organization and scarring of the infarction zone, a clearer delimitation of it and an increase in echogenicity are noted. In some cases, hyperechoic signals—deposits of calcium salts—are visualized in the infarction zone, and therefore it is detected as a formation of mosaic acoustic density. As a result of a heart attack, the contour of the spleen seems to be retracted at the site of scar formation and sclerosis, and this zone is characterized by increased echogenicity. Sometimes a cyst forms at the site of the infarction, and a decrease and deformation of the size and shape of the spleen may be observed, accompanied by an increase in the echogenicity of the parenchyma. As a result of multiple splenic infarctions, for example, in sickle cell anemia, so-called autosplenectomy can be observed. According to radionuclide research methods, there is no functional activity of the spleen. Echographically, in the projection area of ​​the spleen, a small formation with multiple hyperechoic foci, similar to old infarctions, can be detected

Rice. 21. A single echogenic splenic metastasis (arrows) with a peripheral halo and central liquefaction in a patient with colon carcinoma.

Metastatic lesions of the spleen are rare and may be accompanied by enlargement. Possible primary lesions are melanoma and colon carcinoma. In the vast majority of cases, metastases in the spleen are visualized as hyperechoic formations, although hypoechoic ones are also found.

Spleen(lien, splen) - unpaired parenchymal organ of the abdominal cavity; performs immune, filtration and hematopoietic functions, takes part in the metabolism, in particular iron, proteins, etc. The spleen is not one of the vital organs, but in connection with the listed functions it plays a significant role in the body.

Anatomy and histology. S. is located in the abdominal cavity in the left hypochondrium at the level of the IX-XI ribs. S.'s weight in adults is 150-200 G, length - 80-150 mm, width - 60-90 mm, thickness - 40-60 mm. The outer, diaphragmatic, surface of the S. is convex and smooth, the inner is flat, has a groove through which arteries and nerves enter the S., veins and lymphatic vessels exit (the hilum of the spleen). S. is covered with a serous membrane, under which there is a naya membrane (capsule), which is denser in the hilum area. Radially directed trabeculae extend from the membrane, connecting with each other, most of which contain intratrabecular vessels, nerve fibers and muscle cells. The connective tissue skeleton of the S. is a musculoskeletal system that provides significant changes in the volume of the S. and the performance of a depository function.

The blood supply to the pancreas is carried out by the largest branch of the celiac trunk - the splenic artery (a. leinalis), passing most often along the upper edge of the pancreas to the gate of the spleen ( rice. ), where it is divided into 2-3 branches. In accordance with the number of intraorgan branches of the first order, segments (zones) are distinguished in S. The branches of the intraorgan arteries pass inside the trabeculae, then inside the lymphatic follicles (central arteries). They emerge from the lymphatic follicles in the form of brush arterioles, equipped with so-called sleeves enveloping them around their circumference, consisting of reticular cells and fibers. Some of the arterial capillaries flow into the sinuses (closed circulation), the other part directly into the pulp (open circulation).

In the spleen, white (from 6 to 20% of the mass) and red (from 70 to 80%) pulp are distinguished. The white pulp consists of lymphoid tissue located around the arteries: periarterial, the majority of cells are T-lymphocytes, in the marginal zone of lymphatic follicles - B-lymphocytes. As they mature, light reactive centers (reproduction centers) containing reticular cells, lymphoblasts and macrophages are formed in the lymphatic follicles. With age, a significant part of the lymphatic follicles gradually atrophy.

The red pulp consists of a reticular skeleton, arterioles, capillaries, sinus-type venules and free cells (erythrocytes, platelets, lymphocytes, plasma cells), as well as nerve plexuses. When the sinuses are compressed, the connection between the sinuses and the pulp through the cracks in their wall is interrupted, the plasma is partially filtered out, and the blood cells remain in the sinuses. Sinuses (their diameter ranges from 12 to 40 µm depending on blood supply) represent the first link of the venous system of the spleen.

Normal and pathological physiology. S. participates in cellular and humoral immunity , control over circulating blood cells, as well as in hematopoiesis and etc.

The most important function of S. is immune. It consists in the capture and processing of harmful substances by macrophages, cleansing the blood of various foreign agents (bacteria, viruses). In the spleen, endotoxins, insoluble components of cellular detritus during ah, injuries and other tissue damage, are destroyed. S. actively participates in the immune response - its cells recognize antigens foreign to a given organism and synthesize specific antibodies .

The filtration (sequestration) function is carried out in the form of control over circulating blood cells. First of all, this applies to red blood cells, both aging and defective. In the spleen, granular inclusions (Jolly bodies, Heinz bodies, iron granules) are removed from red blood cells without destroying the cells themselves. Splenectomy and S. lead to an increase in the content of these cells in the blood. The increase in the number of siderocytes (cells containing iron granules) after splenectomy is especially clearly visible, and these changes are persistent, which indicates the specificity of this function of the spleen.

Splenic macrophages recycle iron from destroyed red blood cells, converting it into transferrin, i.e. the spleen takes part in iron metabolism.

There is an opinion that leukocytes under physiological conditions die in the spleen, lungs and liver; platelets in a healthy person are also destroyed mainly in the spleen and liver. Probably, S. takes some other part in thrombocytopoiesis, because after splenectomy for S.'s damage, thrombocytosis occurs.

The spleen not only destroys, but also accumulates the formed elements of blood - red blood cells, leukocytes, platelets. In particular, it contains from 30 to 50% or more of circulating platelets, which, if necessary, can be released into the peripheral circulation. In pathological conditions, their deposition is sometimes so great that it can lead to thrombocytopenia .

If there is a disturbance in the outflow of blood, for example portal hypertension , S. increases and can accommodate a large amount of blood. By contracting, S. is able to release the blood deposited in it into the vascular bed. At the same time, its volume decreases, and the number of red blood cells in the blood increases. However, normally S. contains no more than 20-40 ml blood.

The spleen is involved in protein metabolism and synthesizes albumin and globin (the protein component of hemoglobin). S.'s participation in the formation of immunoglobulins, which is provided by numerous cells producing immunoglobulins, probably of all classes, is important.

The spleen takes an active part in hematopoiesis, especially in fetus . In an adult, it produces lymphocytes and monocytes. S. is the main organ of extramedullary hematopoiesis when normal hematopoietic processes in the bone marrow are disrupted, for example, in osteomyelofibrosis, chronic blood loss, osteoblastic form a, e, miliary tuberculosis, etc. There is indirect evidence confirming S.'s participation in the regulation of bone marrow hematopoiesis.

S. plays a major role in the processes hemolysis . A large number of altered red blood cells can be retained and destroyed in it, especially with some congenital (in particular, microspherocytic) and acquired hemolytic (including autoimmune nature) anemia . A large number of red blood cells are retained in the S. during congestive plethora, polycythemia . It has also been established that the mechanical and osmotic resistance of leukocytes decreases as they pass through S.

S. dysfunction is observed in some pathological conditions (severe anemia, some infectious diseases, etc.), as well as in hypersplenism - a chronic increase in S. and a decrease in the blood cells of two or, less often, one or three hematopoietic sprouts. This suggests increased destruction of the corresponding blood cells in the spleen. Hypersplenism is primarily a pathology of the red pulp of S. and is caused by hyperplasia of macrophage elements. After S.'s removal in case of hypersplenism, the blood composition usually normalizes or improves significantly.

With hereditary and acquired disorders of lipid metabolism, large amounts of lipids accumulate in the spleen, which leads to splenomegaly .

Decreased S. function (hyposplenism) is observed with S. atrophy in old age, during starvation, and hypovitaminosis. It is accompanied by the appearance of Jolly bodies and target-like erythrocytes in erythrocytes, siderocytosis.

Pathological anatomy. The variety of its structural changes in many pathological processes is associated with the functional and morphological characteristics of S., in particular with its belonging to the organs of immunogenesis.

Increase in size and weight (more than 250-300 G) of the spleen is usually associated with pathological changes, which, however, can also be observed in a non-enlarged organ. The color and consistency of S. depend on its blood supply; they change with pulp hyperplasia, deposition of amyloid, various pigments, e, S. damage in acute and chronic infections, x, ah, malignant x, histiocytosis.

The most common manifestation of S.'s dystrophy is hyalinosis of small arteries and arterioles, usually observed normally after the age of 30; less commonly, hyaline is deposited in the form of clumps in the lymphatic follicles and marginal pulp. Mucoid and fibrinoid swelling of S.'s connective tissue, primarily the walls of venous sinuses and small vessels (up to their fibrinoid necrosis), loss of protein precipitates in the centers of lymphatic follicles is noted in autoimmune diseases. As a result, the walls of the sinuses become coarser, and periarterial, so-called bulbous, develops, most pronounced in systemic lupus erythematosus .

S. amyloidosis is usually observed with general amyloidosis and ranks second in frequency after a kidney. Sometimes, in diseases that cause secondary (tuberculosis, chronic purulent processes), only the spleen may appear. Lymphatic follicles, when amyloid is deposited in them, on a section have the appearance of glassy bodies, similar to sago grains. In such cases they talk about the “sago” spleen. At the same time, S.'s weight increased slightly. Diffuse loss of amyloid in the walls of the sinuses, blood vessels and along the reticular fibers is accompanied by an increase in the mass of the spleen (up to 500 G); S.'s tissue is dense, when cut, it is greasy, yellowish-red in color (“greasy”, “ham” spleen). Combined deposition of amyloid in lymphatic follicles and red pulp is also possible.

In a number of diseases, xanthoma cells are found to be scattered diffusely or lying in the form of clusters. They are formed during lipid metabolism disorders due to the accumulation of lipids in macrophages. Thus, with sugar e, e, familial xanthomatosis, cholesterol is deposited in excess amounts in the macrophages of the S. (and other organs); cells similar to xanthoma are sometimes found in idiopathic thrombocytopenic purpura; massive accumulation of certain types of lipids is observed in S. with thesaurismosis, which leads to the formation of cells characteristic of one or another form of the disease - Gaucher and Pick cells, to the development of significant secondary changes in S. and an increase in its size (see. Lipidoses ).

Hemosiderosis S. - excessive deposition of hemosiderin - is a manifestation of the general hemosiderosis and is observed at hemochromatosis , diseases and pathological conditions accompanied by increased hemolysis, in case of impaired iron utilization, especially in hemolytic, aplastic and refractory diseases, malaria , return e , e, chronic nutritional disorders (diseases of the stomach and intestines). In hemosiderosis, S. has a rusty-brown color, sometimes slightly enlarged. Histological examination reveals numerous siderophages in the red pulp; deposits of hemosiderin are found in the endothelium of the sinuses, vascular walls, trabeculae, and mucosa. Local hemosiderosis S. is often found in areas of hemorrhage. In their centers and extensive foci of necrosis, hemotoidin crystals can be detected. During malaria, hemomelanin deposits occur in S., which may disappear upon recovery. It is also possible that carbon pigment is deposited in S., penetrating hematogenously from the lungs.

Foci are often found in S. necrosis . Small lesions usually arise due to toxic effects during infections, large lesions are caused by circulatory disorders.

Circulatory disorders in S. are often detected. With general venous congestion due to heart failure, the veins are increased (its weight is 300-400 G), dark red. Portal leads to the development of significant changes of the same type in S. and its pronounced increase (cirrhotic, ic). The mass of S. can be increased to 1000 G and more, its tissue is fleshy, its shell is thickened, often contains extensive no-hyaline areas (“glazed” spleen), and fusion of the spleen with surrounding tissues is possible. The surface of S. in the section is mottled due to focal hemorrhages and the presence of multiple dense nodules of orange-brown color. A decrease in S.'s blood supply is observed with massive acute or prolonged repeated blood loss , aplastic anemia.

Inflammatory changes in S. (splenitis) are constantly detected in infectious diseases. Their nature and intensity depend on the characteristics of the pathogen and the immunological state of the body.

Productive inflammation in S. with the formation of granulomas of various structures and the development of splenomegaly can be observed in tuberculosis, e., brucellosis, tularemia, visceral diseases, and leprosy. Hyperplasia of S.'s lymphoid tissue reflects its participation in the body's immune reactions during antigenic irritation of various origins.

Research methods. Used in clinical practice percussion And palpation WITH., laparoscopy , X-ray, radionuclide and ultrasound examinations (see. Ultrasound diagnostics ), splenomanometry, puncture examination of S., adrenaline test.

Percussion of S. is carried out in a vertical or horizontal (on the right side) position of the patient. Dullness above the upper edge of the S. along the anterior axillary line is differentiated with a pulmonary sound, dullness along the edge of the costal arch or above it by 10-20 mm- with a tympanic sound over the stomach. The upper border of dullness over the S. runs almost horizontally, the lower - behind and above, down and forward. With a high standing, the upper outer surface of the S. can be at the level of the VIII rib, with a low standing - the XII rib.

Determination of the size of S. according to Kurlov is carried out with the patient lying down with an incomplete turn on the right side, if possible without displacing the pelvis. The tenth intercostal space is percussed, starting from the spine, and the length of the S is determined along the boundaries of the bluntness. If the S protrudes from the hypochondrium, then the size of its protruding part is taken into account. S.'s width is determined by percussion from above from the anterior axillary line towards the posterior axillary line. The results of the study are written down in the form of a fraction, in which the length is indicated in the numerator, and the width of C is indicated in the denominator. As C increases, the length of its protruding part is indicated before the fraction, for example cm.

Palpation of S. is carried out with the patient in a horizontal position on his back and in the right lateral position. With a deep breath, the enlarged S. lowers and “rolls” over the fingers of the examiner. With a significant increase in the S., its lower edge descends into the abdominal cavity, and it is possible to palpate the characteristic notch on it, the anterior surface of the S., and determine its consistency and soreness. Normally, the spleen is not palpable.

Laparoscopy in the absence of adhesions makes it possible to examine S., which is normally bluish-red in color: scars, retractions and other pathological changes can be seen on its surface.

X-ray examination of S. is carried out in the vertical and horizontal position of the patient. During fluoroscopy, the area of ​​the left half of the diaphragm is examined, noting its mobility, the abdominal organs located next to the S., and the left lung. To improve research conditions, gas is administered into the colon and stomach. Survey photographs are taken in frontal and lateral projections. Special methods of X-ray examination are computer X-ray tomography , celiacography and lienography, diagnostic pneumoperitoneum and pneumorenae, supplemented by tomography. In the differential and topical diagnosis of isolated lesions of S., arteriography plays an important role (see. Angiography ), computed tomography, diagnostic pneumoperitoneum.

Obtaining a radionuclide image of S. is based on the property of cells of the macrophage system to absorb damaged erythrocytes or colloids from the blood. For the study, red blood cells labeled with 51 Cr, 99 m Tc or 197 Hg are used (see. Radiopharmaceuticals ). On the scanogram (see. Scanning ) or scintigram (see. Scintigraphy ) the area of ​​S. with uniform accumulation of radionuclide is normally 35-80 cm 2; in case of S.'s diseases, the accumulation of radionuclide is uneven, the S.'s area increases.

S.'s puncture is indicated in cases where the reason for its increase has not been established. Contraindications to puncture are hemorrhagic diathesis , expressed. Before puncture, the size and position of the S. are determined using percussion and palpation, and X-ray and radionuclide studies are performed.

Pathology

S.'s pathology includes malformations, injuries, diseases, and tumors.

Developmental defects. These include the absence of S. (asplenia), and an unusual position in the abdominal cavity (dystopia or ectopia), wandering S., changes in its shape, additional S. Asplenia is rare, usually combined with malformations of the cardiovascular system, and is not clinically detected and is diagnosed based on radionuclide studies. In dystopia or ectopia, S. is located in the retroperitoneal space, in the hernial sac with an umbilical or diaphragmatic hernia, in the right half of the abdominal cavity. Vagus S. may arise due to the weakness of its ligamentous apparatus, for example when splanchnoptosis . S. may have an irregular shape with deep notches along the edge or elongated, in which its lower pole sometimes descends into the pelvis. The most common anomaly of S.'s development is additional S. in quantities from one to several hundred, located in various parts of the abdominal cavity.

Vagus S. can twist on the vascular pedicle. In this case, a picture of an acute abdomen is noted, laparotomy is necessary (see. Stomach ) and splenectomy. Additional S. is detected using radionuclide testing. In some diseases, for example, in autoimmune hemolytic anemia, if there are additional spleens, they are removed along with the main organ. Other malformations of S. do not have clinical symptoms; there is no need for treatment.

Damage are open and closed. Open injuries occur with gunshot, stab, or incised wounds of the abdomen, as well as with surgical interventions on the abdominal organs (stomach, colon, pancreas).

The causes of closed S. injuries are most often a blow to the left hypochondrium, a fall on the stomach, abdomen and lower chest, ribs on the left. With a sharp blow or compression, the membrane bends like a horseshoe, its poles move closer together, as a result of which the shell ruptures along the convex surface. When the ribs are eaten, their fragments can penetrate into the parenchyma of the ribs, tearing the membrane. If a fall from a height or a sharp shock occurs, tears in the S. membrane may occur in the places of attachment of ligaments, vascular pedicles, and adhesions. S.'s ruptures are often complicated by bleeding into the abdominal cavity. The victim is pale, complains of dizziness, a feeling of fullness in the left hypochondrium and aching pain radiating to the left shoulder and left shoulder blade, intensifying with a deep breath and coughing. Possible nausea and vomiting, fainting. A typical symptom is “vanka-stand up” - the patient strives to take a sitting position, in which abdominal pain decreases. On palpation, tension in the muscles of the anterior abdominal wall, in the left half of the abdomen, and the left hypochondrium is observed. Positive symptoms of peritoneal irritation are noted. Percussion may reveal dullness in the left half of the abdomen. A rectal examination may reveal pain and sagging of the anterior wall of the rectum, and a vaginal examination may reveal pain in the posterior vaginal fornix.

Secondary ruptures can occur several hours and even days after injury, causing the clinical picture intra-abdominal bleeding .

If there are difficulties in diagnosing closed lesions of S., data from X-ray examinations and computed tomography may be useful. The most informative are laparoscopy and diagnostic laparotomy. If S.'s damage is suspected, the patient can be observed for no more than two hours. In this case, it is necessary to focus on the general condition, hemoglobin and hematocrit indicators, and data from additional studies. In case of open S. injuries, primary surgical treatment of the wound is performed, followed by laparotomy. For closed injuries, surgical intervention begins with laparotomy.

In case of S.'s damage, both open and closed, splenectomy is often performed. In case of single ruptures, small tears and cracks of the vein, with preserved blood circulation in it, organ-preserving operations are performed. The prognosis depends on the severity of the injury and the timeliness of surgery.

Diseases. S. is involved in the pathological process in many infectious diseases - abdominal and rash (see. Abdominal , Epidemic rash ), sepsis , anthrax , infectious mononucleosis , acute viral e (see. Viral hepatitis ), infectious lymphocytosis (see. Acute infectious lymphocytosis ), cytomegaly (see. Cytomegalovirus infection ), malaria, visceral leishmaniasis (see. Leishmaniasis ), tularemia , listerizi , brucellosis , syphilis . S. is usually also affected by histiocytosis (Letterer-Siwe disease, Hand-Christian-Schüller disease - see. Histiocytoses X ).

Violation of the outflow of blood through the splenic vein leads to a progressive increase in C. With prolonged blockage of the outflow, bleeding from the dilated veins of the stomach, rectum, and esophagus is possible. Acute obliteration of the portal vein trunk is accompanied by symptoms resembling intestinal obstruction. The diagnosis is made based on the clinical picture and splenoportography data. Surgical treatment: splenorenal anastomosis, and in case of severe splenomegaly and cytopenia, splenectomy.

The clinical picture of S.'s infarction depends on its size. Diagnosis of small heart attacks of S. is difficult due to the paucity of clinical symptoms. With more extensive lesions as a result of a tense membrane, the development of perisplenitis, pain appears in the left hypochondrium, often radiating to the back and intensifying with inspiration. On the left, a pronounced phrenicus symptom is determined. In the area of ​​perisplenitis, a peritoneal friction rub may be heard. Treatment is aimed at eliminating the causes of the heart attack. The organization of S.'s infarction usually ends with the formation of a scar, and occasionally it forms. When S.'s infarction suppurates, splenectomy is indicated.

Spleen abscess. Small, asymptomatic S. are often found in generalized infectious diseases that cannot be treated. The most clinically important group is represented by large isolated S.'s, which can be observed with bacteremia against the background of a or a, during infection of S.'s infarctions, subcapsular hematomas, etc. The cause of the development of S.'s a may be a breakthrough of the subdiaphragmatic a.

When scanning the liver and liver, spores with a diameter of 20-30 can be detected. mm. S.'s abscess is also detected using ultrasound. The finding of non-vascularized organ tissue during arteriography against the background of the corresponding clinical picture also testifies in favor of a S. S.'s abscess can be complicated by hemorrhage into the cavity, a breakthrough into the abdominal cavity or pleural cavity, kidney, leukocytosis), lymphocytopenia. in some cases, neutropenia, thrombocytopenia, anemia. Sometimes aplastic syndrome develops, in which it is necessary to exclude tuberculosis of the bone marrow. An X-ray examination of the abdominal cavity may reveal petrified lesions in the area of ​​the spleen.

The diagnosis of S. tuberculosis is difficult if there are no signs of fresh or previously existing tuberculosis of other organs. It is based on the results of a cytological examination of S.'s punctate, but a reliable criterion is only the detection of Mycobacterium tuberculosis in a smear or their inoculation from the punctate. It is necessary to take into account that with concomitant S., its repeated punctures may turn out to be uninformative. If S. tuberculosis is suspected, even in the absence of reliable evidence, specific tuberculostatic therapy ex juvantibus is carried out.

E, x, chronic e. The cause of its development may be the disintegration of the tumor, the rapid increase in S. and overstretching of its membrane during splenomegaly. The clinical picture is characterized by sudden severe pain in the left hypochondrium, signs of peritoneal irritation, and rapidly increasing anemia. Treatment is surgical; as a rule, splenectomy is performed, but recently, especially in children, partial resection and suturing of the S. rupture (splenorrhaphy) have become more common. The prognosis depends on the underlying disease.

Tumors S. are rare and can be benign or malignant.

Among benign tumors, hemangiomas, lymphangiomas, lipomas, and hamartomas are identified; among malignant ones - lymphosarcoma, reticulosarcoma, angiosarcoma, hemangioendothelioma, fibrosarcoma are also possible. S.'s defeat at x is rarely isolated; More often, lymphadenopathy, hepatomegaly, and changes in the blood and bone marrow are detected simultaneously with splenomegaly. It is clinically impossible to diagnose the nature of an isolated S. tumor.

Symptoms of all tumors boil down to enlargement of the organ, a feeling of heaviness in the left hypochondrium, sometimes the appearance of dull, less often acute (heart attack) pain. On palpation, S. is densely elastic, sometimes lumpy. With x and angiosarcomas, increased sweating, weight loss, hypersplenism (anemia, leukemia) are possible. With angiosarcoma (in one third of cases), a rupture of the spleen is noted. The diagnosis can be established by cytological examination of punctate C. Preference should be given to splenectomy, which is both a diagnostic and therapeutic measure. In cases of benign tumors, treatment ends here; in x, depending on the histological structure of the tumor, splenectomy is supplemented with appropriate chemotherapy; For non-lymphoid malignant tumors, chemotherapy is prescribed in the presence of metastases. The prognosis for benign tumors is favorable; in other cases, it depends on the histological structure of the tumor; in malignant non-lymphoid tumors, the prognosis is unfavorable.

Bibliography: Almazov V.A. and others. Leukopenia, p. 157, L., 1981; Barta I. Spleen, trans. from Hungarian, Budapest, 1976; Borodin I.F. and Orlyanskaya V.F. Some issues in the diagnosis and treatment of closed injuries of the spleen, Klin. hir., No. 4, p. 29, 1980; Glanz R.M. and Rozhinsky M.M. Saving surgery for spleen injuries, M., 1973, bibliogr.; Carr Ya. et al. Lymphoreticular diseases, trans. from English, M., 1980; Lindenbraten L.D. and Naumov L.B. Methods of X-ray examination of human organs and systems, Tashkent, 1976; Guide to Hematology, ed. A.I. Vorobyova, vol. 1, M., 1985; Physiology of the circulatory system, Physiology of erythropoiesis, ed. V.N. Chernigovsky, p. 256, L., 1979; Folkov B. and Neil E. Blood circulation, trans. from English, M., 1976; Surgical treatment of diseases of the blood system, ed. OK. Gavrilova and D.M. Grozdova, M., 1981.