STUDY - Technical - New Dacian's Medicine
Lymphadenopathy
and Splenomegaly (3)
Translation Draft
The presence of an enlarged spleen can be more precisely determined, if necessary, by radioisotope scanning, computer tomography (CT), nuclear magnetic resonance (NMR) or ultrasonography.
The last technique is the selection procedure for routine evaluation of spleen dimensions (normal = a cefalochaudal diameter of not more than 13 cm), as it has a high sensitivity and specificity and is safe, non-invasive, fast and mobile and cheap.
Nuclear medical scanning is sensitive, accurate and reliable, but it is expensive, requires more data processing time and uses real estate equipment. It has the advantage of discovering the splenic tissue accessor. CT and MRI provide an accurate assessment of the size of the spleen, such as tumor formations, infarctions, non-homogeneous infiltrates and cysts, are best evaluated by CT, MRI or ultrasound. None of these techniques is very effective in discovering nodular infiltrations (e.g. in Hodgkin's disease).
In the case of differential diagnosis it is carried out by considering the elements about several diseases associated with splenomegaly grouped by the pathogenic mechanism: A. Enlargement due to splenic hyperfunction (with 1. hyperplasia of the reticuloendothelial system - for the elimination of erythrocytes altered with a. spherocytosis, b. early syclemia, c. ovalocytosis, d. thalasemia major, e. hemoglobinopathy, f. nocturnal paroxysmal hemoglobinuria, g. nutritional anemias; 2. immune hyperplasia with a. response to infections - viral, bacterial, fungal or parasitic as is the case with infectious mononucleosis, AIDS, viral hepatitis, cytomegali virus, subacute bacterial endocarditis, bacterial septicaemia, congenital syphilis, splenic abscesses, tuberculosis, histoplasmosis, malaria, leishmaniosis and tripanosomiasis and b. altered immunoregulation as in rheumatoid arthritis - Felty syndrome, systemic lupus erythematosus, vascular collagenosis, bo serum, immune hemolytic anaemia, immune thrombocytopenia, immune neutropenia, angioimunoblastic lymphadenopathy, sarcoidosis, thyrotoxicosis - benign lymphoid hypertrophy; and c. extramedular hematopoiesis with myelofibrosis, medullary lesions caused by toxins, radiation or stronium and medullary infiltration through tumors, leukaemia, Gaucher disease), B. enlargement due to portal or splenic abnormal blood flow (as is the case in cirrhosis, obstruction of the liver vein, obstruction of the intra or extrahepatic portal vein, cavernous transformation of the portal vein, obstruction of the splenic vein, aneurysm of the splenic artery , hepatic schistosomiasis, congestive heart failure, hepatic echinococosis and portal hypertension - any cause, including the above: Banti disease), C infiltration of the spleen (with 1. intra or extracellular deposits as in the case of a. amyloidosis, b. Gaucher disease, c. Niemann-Pick disease, d. Tangier disease, e. Hurler syndrome and other mucopolysaculisesis and f. hyperlipidemia 2. Benign or malignant cell infiltration as is the case in a. acute, chronic, lymphoid, myeloid or monocyte leukaemia, in b. lymphoma, c. Hodgkin's disease, in d. myeloproliferative syndromes such as in polycytemia vera, in e. angiosarcomas, f. metastatic tumors of which melanoma is most common, g. eosinophilic granuloma, h. histiocytosis Xtosis, i. hamartomas, j. hemangiomas , fibroids, lymphangiomas and k. splenic cysts) and D. of unknown etiology (as is the case with idiopathic splenomegaly, beryliosis or iron deficiency anemia).
So, they are grouped according to the basic mechanism assumed to be responsible for organ enlargement: 1. hyperplasia or hypertrophy related to a particular function of the spleen, such as reticuloendothelial hyperplasia (hypertrophy by hyperfunction), in sum diseases are hereditary spherotosis or talasemia, which requires the elimination of a large number of altered erythrocytes; immune hyperplasia in response to systemic infection (infectious mononucleosis, subacute bacterial endocarditis) or immunological diseases (immune thrombocytopenia, SLE, Felty syndrome), 2. passive congestion due to decreased blood flow to the spleen due to portal hypertension (in cirrhosis, Budd-Chiari syndrome, congestive heart failure) and 3. infiltrating diseases of the spleen (lymphoma, neoplastic metastases, amyloidosis, Gaucher disease, myeloproliferative disorders with extramedular hematopoiesis).
Differential diagnosis is much limited when the spleen is "massively enlarged", which means that it palpates more than 8 cm below the left costal rim or its dry weight is 1,000 g. Diseases associated with massive splenomegaly are chronic myeloid leukaemia, lymphoma, hairy cell leukemia, myeloid myelofibrosis, rubra vera polycytemia, Gaucher disease, chronic lymphatic leukaemia, sarcoidosis, autoimmune hemolytic anaemia or diffuse splenic hemangiomatosis. The vast majority of these patients have non-Hodgkin lymphoma, chronic lymphatic leukaemia, hairy cell leukemia, chronic myeloid leukemia, myelofibrosis with myeloid metaplasia or polycytemia vera.
From the point of view of laboratory investigations, the major laboratory abnormalities that accompany splenomegaly are caused by basic systemic disease. The number of erythrocytes may be normal, low (major talasemia, SLE, cirrhosis with portal hypertension) or increased (policitemia vera). The number of granulocytes can normally, decreased (Felty syndrome, congestive splenomegaly, leukaemia), or increased (infectious or inflammatory diseases, myeloproliferative disorders).
Similarly, the number of platelets may be normal, low, when there is an increased seizure or destruction of platelets in an increased volume spleen (congestive splenomegaly, Gaucher disease, immune thrombocytopenia), or increased in myeloproliferative disorders such as polycytemia vera. Hemoleucogram may reveal cytopenia of one or more types of blood cells, which suggests hypersplenism. This condition is characterized by splenomegaly, cytopenia, normal or hyperplastic bone marrow and responds favorably to splenectomy. The last feature is not very certain, because the disappearance of cytopenia, especially granulocytopenia, is not permanent after splenectomy.
Cytopenia occurs as a result of increased destruction of cellular elements, secondary to decreased blood flow through enlarged and congested cords (congestive splenomegaly) or immune-mediated mechanisms. In hypersplenism, different cell types usually have a normal morphology when examining peripheral blood smear, although erythrocytes may be spherical, due to the loss of some surface areas during prolonged transit through the enlarged spleen.
The increase in the production of erythrocytes in the marrow should be reflected by the increase in the reticulocyte index, although its value may be lower than expected due to the seizure of reticulocytes in the spleen. As mentioned above, the dimensions of the spleen can be confirmed, if necessary, by ultrasound, CT or MRI. The need for additional laboratory examinations is dictated by the differential diagnosis of basic diseases, manifested mainly by splenomegaly.
Splenectomy is rarely performed for diagnostic purposes, especially in the absence of other clinical manifestations or diagnostic tests suggesting the underlying disease. Much more frequently, splenectomy is performed to staging the spread of the condition in patients with Hodgkin's disease, for relieving symptoms in patients with massive splenomegaly, for relieving the disease in patients with hairy or prolymphocytic leukemia, for controlling bleeding in patients with traumatic rupture of the spleen or for correcting cytopenia in patients with hyperslenism or immune-mediated destruction of one or more blood cell types.
Splenectomy is routinely required for the staging of the disease in patients with Hodgkin's disease, radiotherapy being indicated only in those in stage I or II. Non-invasive staging in Hodgkin's disease does not provide sufficient safety in therapeutic decision-making, as one-third of normal-sized spleens may be involved in Hodgkin's disease and one-third of enlarged spleens will not have the tumor. Although it has been clearly established that splenectomy in chronic myeloid leukaemia does not influence the natural course of the disease, the elimination of the massive spleen gives patients more comfort and considerably simplifies the therapeutic approach, reducing the need for transfusions.
Splenectomy is an effective treatment for two chronic B-cell leukaemias, hairy cell leukaemia and prolymphocytic leukaemia and for the rare splenic marginal lymphoma. Splenectomy in these diseases is associated with a significant reduction of tumor in the bone marrow and other localizations of the disease. Similar regressions of systemic diseases were recorded after local irradiation of the spleen in some types of lymphoproliferative diseases, in particular chronic lymphocytic leukaemia.
This evolution has been called the abscopic effect. The fact that systemic tumors respond to local spleen irradiation suggests that there is a hormone or growth factor produced by the spleen that affects tumor cell proliferation, but this explanation is not yet consistent. The most common indication of splenectomy is traumatic or iatrogenic splenic rupture. In some patients with ruptured spleen, peritoneal seeding with spleen fragments may cause splenosis (the presence of multiple spleen debris not connected to portal circulation).
This ectopic splenic tissue can cause pain or gastrointestinal occlusion, as in endometriosis. A large number of haematological, immunological and congestive causes can lead to the destruction of one or more types of blood cells. In most cases, splenectomy can correct cytopenia, especially anemia and thrombocytopenia. Probably the only contraindication for splenectomy is the presence of medullary insufficiency, in this case the spleen being the only source of hematopoietic tissue.
The absence of the spleen has minimal long-term effects on the haematological profile. In the period immediately following splenectomy, leukocytosis (up to 25,000/ microlitercub) and thrombocytosis (up to 1 x 10 in strength 6 per cubic mm) may occur, but in 2-3 weeks the haemoleukogram and survival of each cell line are usually normal. Chronic manifestations of splenectomy are marked variations in the size and shape of erythrocytes (anisocytosis, poikilocytosis) and the presence of Howell-Jolly (nuclear debris), Heiny bodies (distorted hemoglobin), basophilic points and occasionally a nucleated erythrocyte in peripheral blood.
When such erythrocytic abnormalities occur in a patient whose spleen has not been removed, tumor infiltration of the spleen, which interferes with its normal selection and elimination function, may be suspected. The most serious consequence of splenectomy is increased susceptibility to bacterial infections, especially with capsular bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and some gram-negative intestinal bacteria. Patients under 20 years of age are particularly susceptible to septicaemia with S. pneumoniae, and the total statistical risk of sepsis in splenectomized patients is 7% in 10 years. Nearly 25% of these patients will develop an infection at some point. The most common is in the first 3 years after splenectomy.
About 15% of infections are polymicrobial, and the most common localizations are lungs, skin and blood. There appears to be no increased risk for viral infections in splenectomized patients. Susceptibility to bacterial infections is related to the inability to remove opsonized bacteria from the bloodstream and a defect in the production of antibodies against T-independent lymphocyte antigens, such as the polysaccharide components of the bacterial capsule. The pneumococcal vaccine may be prophylactic if administered before splenectomy, but there is no data to support its effectiveness after intervention.
In fact, since patients cannot synthesize antibodies against pneumococcal polysaccharides after splenectomy, administration of the vaccine may even decrease the titre of specific antipneumococcal antibodies and, theoretically, make the patient even more susceptible to infection. The H. influenzae vaccine should also be given to patients who are scheduled to have splenectomy. No other vaccine is routinely recommended under these conditions.
After splenectomy, vaccinations against T-dependent lymphocyte antigens are not contraindicated, but those against T-independent lymphocyte antigens are ineffective. In addition, compared to increased susceptibility to bacterial infections, splenectomized patients are also more susceptible to a parasitic disease called babesiosis.
Splenectomized patients should avoid regions where the Babesia parasite is endemic.
Surgical removal of the spleen is an obvious cause of hyposplenism. Patients with sickle cell emia often suffer from autosplenectomy as a result of the destruction of the spleen through numerous heart attacks associated with childhood seizures. Thus, the presence of a palpable spline in a patient with sickle cell disease after the age of 5 years suggests the coexistence of haemoglobinopathy, e.g. thalassemia or hemoglobin C. In addition, patients whose spleen is therapeutically irradiated for a neoplastic or autoimmune disease also have hyposplenism.
The term hyposplenism is preferred to that of asplenism when referring to the physiological consequences of splenectomy, since asplenia is a rare, specific and fatal congenital abnormality associated with a deficiency in the normal development of the left part of the celomic cavity (which includes splenic buds). Children with asplenia do not have spleen, but this is the least of their problems. The right side of the embryo is duplicated to the left, so the liver appears in place of the spleen, there are two right lungs, and the heart consists of two right atria and two right ventricles.
I think that's enough for this subject... Next time...
The presence of an enlarged spleen can be more precisely determined, if necessary, by radioisotope scanning, computer tomography (CT), nuclear magnetic resonance (NMR) or ultrasonography.
The last technique is the selection procedure for routine evaluation of spleen dimensions (normal = a cefalochaudal diameter of not more than 13 cm), as it has a high sensitivity and specificity and is safe, non-invasive, fast and mobile and cheap.
Nuclear medical scanning is sensitive, accurate and reliable, but it is expensive, requires more data processing time and uses real estate equipment. It has the advantage of discovering the splenic tissue accessor. CT and MRI provide an accurate assessment of the size of the spleen, such as tumor formations, infarctions, non-homogeneous infiltrates and cysts, are best evaluated by CT, MRI or ultrasound. None of these techniques is very effective in discovering nodular infiltrations (e.g. in Hodgkin's disease).
In the case of differential diagnosis it is carried out by considering the elements about several diseases associated with splenomegaly grouped by the pathogenic mechanism: A. Enlargement due to splenic hyperfunction (with 1. hyperplasia of the reticuloendothelial system - for the elimination of erythrocytes altered with a. spherocytosis, b. early syclemia, c. ovalocytosis, d. thalasemia major, e. hemoglobinopathy, f. nocturnal paroxysmal hemoglobinuria, g. nutritional anemias; 2. immune hyperplasia with a. response to infections - viral, bacterial, fungal or parasitic as is the case with infectious mononucleosis, AIDS, viral hepatitis, cytomegali virus, subacute bacterial endocarditis, bacterial septicaemia, congenital syphilis, splenic abscesses, tuberculosis, histoplasmosis, malaria, leishmaniosis and tripanosomiasis and b. altered immunoregulation as in rheumatoid arthritis - Felty syndrome, systemic lupus erythematosus, vascular collagenosis, bo serum, immune hemolytic anaemia, immune thrombocytopenia, immune neutropenia, angioimunoblastic lymphadenopathy, sarcoidosis, thyrotoxicosis - benign lymphoid hypertrophy; and c. extramedular hematopoiesis with myelofibrosis, medullary lesions caused by toxins, radiation or stronium and medullary infiltration through tumors, leukaemia, Gaucher disease), B. enlargement due to portal or splenic abnormal blood flow (as is the case in cirrhosis, obstruction of the liver vein, obstruction of the intra or extrahepatic portal vein, cavernous transformation of the portal vein, obstruction of the splenic vein, aneurysm of the splenic artery , hepatic schistosomiasis, congestive heart failure, hepatic echinococosis and portal hypertension - any cause, including the above: Banti disease), C infiltration of the spleen (with 1. intra or extracellular deposits as in the case of a. amyloidosis, b. Gaucher disease, c. Niemann-Pick disease, d. Tangier disease, e. Hurler syndrome and other mucopolysaculisesis and f. hyperlipidemia 2. Benign or malignant cell infiltration as is the case in a. acute, chronic, lymphoid, myeloid or monocyte leukaemia, in b. lymphoma, c. Hodgkin's disease, in d. myeloproliferative syndromes such as in polycytemia vera, in e. angiosarcomas, f. metastatic tumors of which melanoma is most common, g. eosinophilic granuloma, h. histiocytosis Xtosis, i. hamartomas, j. hemangiomas , fibroids, lymphangiomas and k. splenic cysts) and D. of unknown etiology (as is the case with idiopathic splenomegaly, beryliosis or iron deficiency anemia).
So, they are grouped according to the basic mechanism assumed to be responsible for organ enlargement: 1. hyperplasia or hypertrophy related to a particular function of the spleen, such as reticuloendothelial hyperplasia (hypertrophy by hyperfunction), in sum diseases are hereditary spherotosis or talasemia, which requires the elimination of a large number of altered erythrocytes; immune hyperplasia in response to systemic infection (infectious mononucleosis, subacute bacterial endocarditis) or immunological diseases (immune thrombocytopenia, SLE, Felty syndrome), 2. passive congestion due to decreased blood flow to the spleen due to portal hypertension (in cirrhosis, Budd-Chiari syndrome, congestive heart failure) and 3. infiltrating diseases of the spleen (lymphoma, neoplastic metastases, amyloidosis, Gaucher disease, myeloproliferative disorders with extramedular hematopoiesis).
Differential diagnosis is much limited when the spleen is "massively enlarged", which means that it palpates more than 8 cm below the left costal rim or its dry weight is 1,000 g. Diseases associated with massive splenomegaly are chronic myeloid leukaemia, lymphoma, hairy cell leukemia, myeloid myelofibrosis, rubra vera polycytemia, Gaucher disease, chronic lymphatic leukaemia, sarcoidosis, autoimmune hemolytic anaemia or diffuse splenic hemangiomatosis. The vast majority of these patients have non-Hodgkin lymphoma, chronic lymphatic leukaemia, hairy cell leukemia, chronic myeloid leukemia, myelofibrosis with myeloid metaplasia or polycytemia vera.
From the point of view of laboratory investigations, the major laboratory abnormalities that accompany splenomegaly are caused by basic systemic disease. The number of erythrocytes may be normal, low (major talasemia, SLE, cirrhosis with portal hypertension) or increased (policitemia vera). The number of granulocytes can normally, decreased (Felty syndrome, congestive splenomegaly, leukaemia), or increased (infectious or inflammatory diseases, myeloproliferative disorders).
Similarly, the number of platelets may be normal, low, when there is an increased seizure or destruction of platelets in an increased volume spleen (congestive splenomegaly, Gaucher disease, immune thrombocytopenia), or increased in myeloproliferative disorders such as polycytemia vera. Hemoleucogram may reveal cytopenia of one or more types of blood cells, which suggests hypersplenism. This condition is characterized by splenomegaly, cytopenia, normal or hyperplastic bone marrow and responds favorably to splenectomy. The last feature is not very certain, because the disappearance of cytopenia, especially granulocytopenia, is not permanent after splenectomy.
Cytopenia occurs as a result of increased destruction of cellular elements, secondary to decreased blood flow through enlarged and congested cords (congestive splenomegaly) or immune-mediated mechanisms. In hypersplenism, different cell types usually have a normal morphology when examining peripheral blood smear, although erythrocytes may be spherical, due to the loss of some surface areas during prolonged transit through the enlarged spleen.
The increase in the production of erythrocytes in the marrow should be reflected by the increase in the reticulocyte index, although its value may be lower than expected due to the seizure of reticulocytes in the spleen. As mentioned above, the dimensions of the spleen can be confirmed, if necessary, by ultrasound, CT or MRI. The need for additional laboratory examinations is dictated by the differential diagnosis of basic diseases, manifested mainly by splenomegaly.
Splenectomy is rarely performed for diagnostic purposes, especially in the absence of other clinical manifestations or diagnostic tests suggesting the underlying disease. Much more frequently, splenectomy is performed to staging the spread of the condition in patients with Hodgkin's disease, for relieving symptoms in patients with massive splenomegaly, for relieving the disease in patients with hairy or prolymphocytic leukemia, for controlling bleeding in patients with traumatic rupture of the spleen or for correcting cytopenia in patients with hyperslenism or immune-mediated destruction of one or more blood cell types.
Splenectomy is routinely required for the staging of the disease in patients with Hodgkin's disease, radiotherapy being indicated only in those in stage I or II. Non-invasive staging in Hodgkin's disease does not provide sufficient safety in therapeutic decision-making, as one-third of normal-sized spleens may be involved in Hodgkin's disease and one-third of enlarged spleens will not have the tumor. Although it has been clearly established that splenectomy in chronic myeloid leukaemia does not influence the natural course of the disease, the elimination of the massive spleen gives patients more comfort and considerably simplifies the therapeutic approach, reducing the need for transfusions.
Splenectomy is an effective treatment for two chronic B-cell leukaemias, hairy cell leukaemia and prolymphocytic leukaemia and for the rare splenic marginal lymphoma. Splenectomy in these diseases is associated with a significant reduction of tumor in the bone marrow and other localizations of the disease. Similar regressions of systemic diseases were recorded after local irradiation of the spleen in some types of lymphoproliferative diseases, in particular chronic lymphocytic leukaemia.
This evolution has been called the abscopic effect. The fact that systemic tumors respond to local spleen irradiation suggests that there is a hormone or growth factor produced by the spleen that affects tumor cell proliferation, but this explanation is not yet consistent. The most common indication of splenectomy is traumatic or iatrogenic splenic rupture. In some patients with ruptured spleen, peritoneal seeding with spleen fragments may cause splenosis (the presence of multiple spleen debris not connected to portal circulation).
This ectopic splenic tissue can cause pain or gastrointestinal occlusion, as in endometriosis. A large number of haematological, immunological and congestive causes can lead to the destruction of one or more types of blood cells. In most cases, splenectomy can correct cytopenia, especially anemia and thrombocytopenia. Probably the only contraindication for splenectomy is the presence of medullary insufficiency, in this case the spleen being the only source of hematopoietic tissue.
The absence of the spleen has minimal long-term effects on the haematological profile. In the period immediately following splenectomy, leukocytosis (up to 25,000/ microlitercub) and thrombocytosis (up to 1 x 10 in strength 6 per cubic mm) may occur, but in 2-3 weeks the haemoleukogram and survival of each cell line are usually normal. Chronic manifestations of splenectomy are marked variations in the size and shape of erythrocytes (anisocytosis, poikilocytosis) and the presence of Howell-Jolly (nuclear debris), Heiny bodies (distorted hemoglobin), basophilic points and occasionally a nucleated erythrocyte in peripheral blood.
When such erythrocytic abnormalities occur in a patient whose spleen has not been removed, tumor infiltration of the spleen, which interferes with its normal selection and elimination function, may be suspected. The most serious consequence of splenectomy is increased susceptibility to bacterial infections, especially with capsular bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and some gram-negative intestinal bacteria. Patients under 20 years of age are particularly susceptible to septicaemia with S. pneumoniae, and the total statistical risk of sepsis in splenectomized patients is 7% in 10 years. Nearly 25% of these patients will develop an infection at some point. The most common is in the first 3 years after splenectomy.
About 15% of infections are polymicrobial, and the most common localizations are lungs, skin and blood. There appears to be no increased risk for viral infections in splenectomized patients. Susceptibility to bacterial infections is related to the inability to remove opsonized bacteria from the bloodstream and a defect in the production of antibodies against T-independent lymphocyte antigens, such as the polysaccharide components of the bacterial capsule. The pneumococcal vaccine may be prophylactic if administered before splenectomy, but there is no data to support its effectiveness after intervention.
In fact, since patients cannot synthesize antibodies against pneumococcal polysaccharides after splenectomy, administration of the vaccine may even decrease the titre of specific antipneumococcal antibodies and, theoretically, make the patient even more susceptible to infection. The H. influenzae vaccine should also be given to patients who are scheduled to have splenectomy. No other vaccine is routinely recommended under these conditions.
After splenectomy, vaccinations against T-dependent lymphocyte antigens are not contraindicated, but those against T-independent lymphocyte antigens are ineffective. In addition, compared to increased susceptibility to bacterial infections, splenectomized patients are also more susceptible to a parasitic disease called babesiosis.
Splenectomized patients should avoid regions where the Babesia parasite is endemic.
Surgical removal of the spleen is an obvious cause of hyposplenism. Patients with sickle cell emia often suffer from autosplenectomy as a result of the destruction of the spleen through numerous heart attacks associated with childhood seizures. Thus, the presence of a palpable spline in a patient with sickle cell disease after the age of 5 years suggests the coexistence of haemoglobinopathy, e.g. thalassemia or hemoglobin C. In addition, patients whose spleen is therapeutically irradiated for a neoplastic or autoimmune disease also have hyposplenism.
The term hyposplenism is preferred to that of asplenism when referring to the physiological consequences of splenectomy, since asplenia is a rare, specific and fatal congenital abnormality associated with a deficiency in the normal development of the left part of the celomic cavity (which includes splenic buds). Children with asplenia do not have spleen, but this is the least of their problems. The right side of the embryo is duplicated to the left, so the liver appears in place of the spleen, there are two right lungs, and the heart consists of two right atria and two right ventricles.
I think that's enough for this subject... Next time...
Understanding, love and
gratitude!
Dorin, Merticaru