Mod 2.4 Splenomegaly
APPROACH TO A PATIENT WITH SPLENOMEGALY
(Harrison’s Principles of Internal Medicine [21E] Chapter 66 Enlargement of Lymph Nodes and Spleen)
CLINICAL ASSESSMENT Clinical Assessment of Splenomegaly
● Common Symptoms:
○ Pain and heavy sensation in the left upper quadrant (LUQ).
○ Massive splenomegaly may cause early satiety.
○ Pain can result from:
■ Acute swelling with capsule stretching.
■ Infarction or inflammation of the capsule.
● Historical Context:
○ Soma Weiss (1942) noted that splenic infarction can cause severe LUQ and pleuritic chest pain.
● Rupture of the Spleen:
○ Can occur from trauma or infiltrative disease.
○ May lead to intraperitoneal bleeding, shock, and death.
○ Rupture may be painless.
● Palpation:
○ A palpable spleen indicates enlargement.
○ Normal spleen size:
■ Weighs <250 g.
■ Maximum diameter: 13 cm (ultrasonography) or length 12 cm/width 7 cm (radionuclide scan).
○ Asymptomatic individuals may have palpable spleens (3% in a study of college students).
● Physical Examination Techniques:
○ Inspection: Fullness in LUQ that descends on inspiration may indicate massive splenomegaly.
○ Auscultation: May reveal venous hum or friction rub.
○ Palpation Techniques:
■ Bimanual palpation (most reliable).
■ Ballotment.
■ Middleton maneuver (palpation from above).
○ Measurement of spleen tip is crucial for tracking size over time.
● Percussion Techniques:
○ Nixon’s Method: Patient on right side; dullness >8 cm indicates splenic enlargement.
○ Castell’s Method: Dullness on full inspiration suggests splenomegaly.
○ Traube’s Space: Dull percussion note suggests splenomegaly.
● Reproducibility and Reliability:
○ Sensitivity of palpation: 56–71%.
○ Sensitivity of percussion: 59–82%.
○ More reliable in non-obese patients and those who haven't just eaten.
● Imaging Techniques:
○ Ultrasonography: Current procedure of choice; high sensitivity and specificity.
○ Radionuclide Scans: Accurate but costly; can show accessory splenic tissue.
○ CT and MRI: Accurate size determination; better for assessing structural changes but expensive
, and immobile.
● Diagnostic Caveats:
○ Not all LUQ masses are enlarged spleens; other tumors (gastric, colon, pancreatic, renal) can mimic
splenomegaly.
○ Detection of patchy infiltration (e.g., Hodgkin’s disease) is unreliable with imaging techniques.
DIFFERENTIAL DIAGNOSIS Differential Diagnosis of Splenomegaly
● Grouped by Mechanisms of Enlargement:
○ Hyperplasia or Hypertrophy:
■ Related to specific splenic functions:
■ Reticuloendothelial Hyperplasia (Work Hypertrophy):
■ Seen in hereditary spherocytosis or thalassemia syndromes requiring removal
of defective red blood cells.
■ Immune Hyperplasia:
■ Response to systemic infections (e.g., infectious mononucleosis, subacute
bacterial endocarditis).
■ Associated with immunologic diseases (e.g., immune thrombocytopenia,
systemic lupus erythematosus (SLE), Felty’s syndrome).
○ Passive Congestion:
■ Results from decreased blood flow:
■ Conditions producing portal hypertension (e.g., cirrhosis, Budd-Chiari syndrome,
congestive heart failure).
○ Infiltrative Diseases:
■ Involves pathological infiltration of the spleen:
■ Lymphomas (e.g., non-Hodgkin’s lymphoma).
■ Metastatic cancer.
■ Amyloidosis.
■ Gaucher’s disease.
■ Myeloproliferative disorders (e.g., with extramedullary hematopoiesis).
● Massive Splenomegaly:
○ Defined as a palpable spleen >8 cm below the left costal margin or drained weight ≥1000 g.
○ Common causes in such cases:
■ Non-Hodgkin’s lymphoma.
■ Chronic lymphocytic leukemia.
■ Hairy cell leukemia.
■ Chronic myeloid leukemia.
■ Myelofibrosis with myeloid metaplasia.
■ Polycythemia vera.
LABORATORY ASSESSMENT Laboratory Assessment of Splenomegaly
● Laboratory Abnormalities:
○ Dependent on the underlying systemic illness.
● Erythrocyte Counts:
, ○ Normal: Can be observed.
○ Decreased: Seen in conditions like thalassemia major, SLE, and cirrhosis with portal hypertension.
○ Increased: Found in polycythemia vera.
● Granulocyte Counts:
○ Normal: Possible.
○ Decreased: Associated with Felty’s syndrome, congestive splenomegaly, and leukemias.
○ Increased: Noted in infections, inflammatory diseases, and myeloproliferative disorders.
● Platelet Counts:
○ Normal: Can occur.
○ Decreased: Due to enhanced sequestration or destruction in conditions like congestive
splenomegaly, Gaucher’s disease, and immune thrombocytopenia.
○ Increased: Common in myeloproliferative disorders, such as polycythemia vera.
● Complete Blood Count (CBC):
○ May reveal cytopenia of one or more blood cell types, suggesting hypersplenism.
○ Hypersplenism Characteristics:
■ Splenomegaly.
■ Cytopenia(s).
■ Normal or hyperplastic bone marrow.
■ Response to splenectomy (not always sustained, especially for granulocytopenia).
● Mechanism of Cytopenias:
○ Increased destruction due to reduced blood flow through congested spleen (congestive
splenomegaly).
○ Immune-mediated mechanisms.
● Peripheral Blood Smear:
○ Generally normal morphology for cell types.
○ Red cells may appear spherocytic due to surface area loss during prolonged spleen transit.
● Reticulocyte Production Index:
○ Increased production expected due to increased marrow production of red cells.
○ May be less than expected due to reticulocyte sequestration in the spleen.
● Additional Laboratory Studies:
○ Needed based on the differential diagnosis of the underlying condition causing splenomegaly.
HEMATOPOIETIC PRECURSORS AND NEOPLASMS
Source: Robbins and Cotran’s Pathological Basis of Disease 9th Edition, Chapter 13 Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus
Components of the Hematopoietic System Components of the Hematopoietic System
● Traditional Division:
○ Myeloid Tissues:
■ Include bone marrow and its derived cells.
■ Cell types: red blood cells, platelets, granulocytes, and monocytes.
○ Lymphoid Tissues:
■ Comprise the thymus, lymph nodes, and spleen.
● Artificial Subdivision:
, ○ The separation of myeloid and lymphoid tissues is not strictly physiological or pathological:
■ Bone marrow has few lymphocytes but is the source of all lymphoid progenitors.
■ Bone marrow houses long-lived plasma cells and memory lymphocytes.
■ Myeloid leukemias originate in the bone marrow but can secondarily affect the spleen and
lymph nodes.
● Interconnection of Disorders:
○ Some red cell disorders (e.g., immunohemolytic anemia) result from autoantibody formation,
indicating a primary lymphocyte disorder.
○ There is no clear boundary between diseases of myeloid and lymphoid tissues.
● Organization of Disease Discussion:
○ Diseases of hematopoietic tissues are somewhat arbitrarily divided into two chapters:
■ This chapter focuses on white cell diseases and disorders of the spleen and thymus.
■ Chapter 14 covers red cell diseases and hemostasis disorders.
● Importance of Understanding Hematopoietic Cell Origins:
○ Many white cell and red cell disorders involve disturbances in normal development and maturation of
hematopoietic cells.
DEVELOPMENT AND MAINTENANCE OF Development and Maintenance of Hematopoietic Tissues
HEMATOPOIETIC TISSUES ● Early Development:
○ Blood cell progenitors appear in the yolk sac during the third week of embryonic development.
○ Yolk sac cells give rise to long-lived tissue macrophages (e.g., microglial cells, Kupffer cells).
○ Contribution to blood formation from the yolk sac is transient, mainly producing embryonic red blood
cells.
● Hematopoietic Stem Cells (HSCs):
○ Arise several weeks later in the mesoderm of the intraembryonic aorta/gonad/mesonephros region.
○ By the third month, HSCs migrate to the liver, the primary site of blood cell formation until shortly
before birth.
○ Some HSCs reside in the fetal placenta, clinically relevant for umbilical cord blood harvesting.
● Shift to Bone Marrow:
○ By the fourth month, HSCs shift to bone marrow, which becomes hematopoietically active by birth.
○ Hepatic hematopoiesis decreases significantly after birth.
● Hematopoietic Activity Changes:
○ Throughout childhood, hematopoietic marrow is found throughout the skeleton.
○ Post-puberty, active marrow is restricted to the axial skeleton; normal adults have about half the
marrow space active.
● Common Origin of Blood Cells:
○ All formed blood elements (red cells, granulocytes, monocytes, platelets, lymphocytes) originate
from HSCs.
○ HSCs are pluripotent, giving rise to various progenitor cells with restricted differentiation potential.
● Progenitor Cells and Differentiation:
○ Early progenitors lead to specific lineage commitment, forming colony-forming units (CFUs).
○ Derived cells include morphologically recognizable precursors (e.g., myeloblasts, proerythroblasts,
megakaryoblasts).
APPROACH TO A PATIENT WITH SPLENOMEGALY
(Harrison’s Principles of Internal Medicine [21E] Chapter 66 Enlargement of Lymph Nodes and Spleen)
CLINICAL ASSESSMENT Clinical Assessment of Splenomegaly
● Common Symptoms:
○ Pain and heavy sensation in the left upper quadrant (LUQ).
○ Massive splenomegaly may cause early satiety.
○ Pain can result from:
■ Acute swelling with capsule stretching.
■ Infarction or inflammation of the capsule.
● Historical Context:
○ Soma Weiss (1942) noted that splenic infarction can cause severe LUQ and pleuritic chest pain.
● Rupture of the Spleen:
○ Can occur from trauma or infiltrative disease.
○ May lead to intraperitoneal bleeding, shock, and death.
○ Rupture may be painless.
● Palpation:
○ A palpable spleen indicates enlargement.
○ Normal spleen size:
■ Weighs <250 g.
■ Maximum diameter: 13 cm (ultrasonography) or length 12 cm/width 7 cm (radionuclide scan).
○ Asymptomatic individuals may have palpable spleens (3% in a study of college students).
● Physical Examination Techniques:
○ Inspection: Fullness in LUQ that descends on inspiration may indicate massive splenomegaly.
○ Auscultation: May reveal venous hum or friction rub.
○ Palpation Techniques:
■ Bimanual palpation (most reliable).
■ Ballotment.
■ Middleton maneuver (palpation from above).
○ Measurement of spleen tip is crucial for tracking size over time.
● Percussion Techniques:
○ Nixon’s Method: Patient on right side; dullness >8 cm indicates splenic enlargement.
○ Castell’s Method: Dullness on full inspiration suggests splenomegaly.
○ Traube’s Space: Dull percussion note suggests splenomegaly.
● Reproducibility and Reliability:
○ Sensitivity of palpation: 56–71%.
○ Sensitivity of percussion: 59–82%.
○ More reliable in non-obese patients and those who haven't just eaten.
● Imaging Techniques:
○ Ultrasonography: Current procedure of choice; high sensitivity and specificity.
○ Radionuclide Scans: Accurate but costly; can show accessory splenic tissue.
○ CT and MRI: Accurate size determination; better for assessing structural changes but expensive
, and immobile.
● Diagnostic Caveats:
○ Not all LUQ masses are enlarged spleens; other tumors (gastric, colon, pancreatic, renal) can mimic
splenomegaly.
○ Detection of patchy infiltration (e.g., Hodgkin’s disease) is unreliable with imaging techniques.
DIFFERENTIAL DIAGNOSIS Differential Diagnosis of Splenomegaly
● Grouped by Mechanisms of Enlargement:
○ Hyperplasia or Hypertrophy:
■ Related to specific splenic functions:
■ Reticuloendothelial Hyperplasia (Work Hypertrophy):
■ Seen in hereditary spherocytosis or thalassemia syndromes requiring removal
of defective red blood cells.
■ Immune Hyperplasia:
■ Response to systemic infections (e.g., infectious mononucleosis, subacute
bacterial endocarditis).
■ Associated with immunologic diseases (e.g., immune thrombocytopenia,
systemic lupus erythematosus (SLE), Felty’s syndrome).
○ Passive Congestion:
■ Results from decreased blood flow:
■ Conditions producing portal hypertension (e.g., cirrhosis, Budd-Chiari syndrome,
congestive heart failure).
○ Infiltrative Diseases:
■ Involves pathological infiltration of the spleen:
■ Lymphomas (e.g., non-Hodgkin’s lymphoma).
■ Metastatic cancer.
■ Amyloidosis.
■ Gaucher’s disease.
■ Myeloproliferative disorders (e.g., with extramedullary hematopoiesis).
● Massive Splenomegaly:
○ Defined as a palpable spleen >8 cm below the left costal margin or drained weight ≥1000 g.
○ Common causes in such cases:
■ Non-Hodgkin’s lymphoma.
■ Chronic lymphocytic leukemia.
■ Hairy cell leukemia.
■ Chronic myeloid leukemia.
■ Myelofibrosis with myeloid metaplasia.
■ Polycythemia vera.
LABORATORY ASSESSMENT Laboratory Assessment of Splenomegaly
● Laboratory Abnormalities:
○ Dependent on the underlying systemic illness.
● Erythrocyte Counts:
, ○ Normal: Can be observed.
○ Decreased: Seen in conditions like thalassemia major, SLE, and cirrhosis with portal hypertension.
○ Increased: Found in polycythemia vera.
● Granulocyte Counts:
○ Normal: Possible.
○ Decreased: Associated with Felty’s syndrome, congestive splenomegaly, and leukemias.
○ Increased: Noted in infections, inflammatory diseases, and myeloproliferative disorders.
● Platelet Counts:
○ Normal: Can occur.
○ Decreased: Due to enhanced sequestration or destruction in conditions like congestive
splenomegaly, Gaucher’s disease, and immune thrombocytopenia.
○ Increased: Common in myeloproliferative disorders, such as polycythemia vera.
● Complete Blood Count (CBC):
○ May reveal cytopenia of one or more blood cell types, suggesting hypersplenism.
○ Hypersplenism Characteristics:
■ Splenomegaly.
■ Cytopenia(s).
■ Normal or hyperplastic bone marrow.
■ Response to splenectomy (not always sustained, especially for granulocytopenia).
● Mechanism of Cytopenias:
○ Increased destruction due to reduced blood flow through congested spleen (congestive
splenomegaly).
○ Immune-mediated mechanisms.
● Peripheral Blood Smear:
○ Generally normal morphology for cell types.
○ Red cells may appear spherocytic due to surface area loss during prolonged spleen transit.
● Reticulocyte Production Index:
○ Increased production expected due to increased marrow production of red cells.
○ May be less than expected due to reticulocyte sequestration in the spleen.
● Additional Laboratory Studies:
○ Needed based on the differential diagnosis of the underlying condition causing splenomegaly.
HEMATOPOIETIC PRECURSORS AND NEOPLASMS
Source: Robbins and Cotran’s Pathological Basis of Disease 9th Edition, Chapter 13 Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus
Components of the Hematopoietic System Components of the Hematopoietic System
● Traditional Division:
○ Myeloid Tissues:
■ Include bone marrow and its derived cells.
■ Cell types: red blood cells, platelets, granulocytes, and monocytes.
○ Lymphoid Tissues:
■ Comprise the thymus, lymph nodes, and spleen.
● Artificial Subdivision:
, ○ The separation of myeloid and lymphoid tissues is not strictly physiological or pathological:
■ Bone marrow has few lymphocytes but is the source of all lymphoid progenitors.
■ Bone marrow houses long-lived plasma cells and memory lymphocytes.
■ Myeloid leukemias originate in the bone marrow but can secondarily affect the spleen and
lymph nodes.
● Interconnection of Disorders:
○ Some red cell disorders (e.g., immunohemolytic anemia) result from autoantibody formation,
indicating a primary lymphocyte disorder.
○ There is no clear boundary between diseases of myeloid and lymphoid tissues.
● Organization of Disease Discussion:
○ Diseases of hematopoietic tissues are somewhat arbitrarily divided into two chapters:
■ This chapter focuses on white cell diseases and disorders of the spleen and thymus.
■ Chapter 14 covers red cell diseases and hemostasis disorders.
● Importance of Understanding Hematopoietic Cell Origins:
○ Many white cell and red cell disorders involve disturbances in normal development and maturation of
hematopoietic cells.
DEVELOPMENT AND MAINTENANCE OF Development and Maintenance of Hematopoietic Tissues
HEMATOPOIETIC TISSUES ● Early Development:
○ Blood cell progenitors appear in the yolk sac during the third week of embryonic development.
○ Yolk sac cells give rise to long-lived tissue macrophages (e.g., microglial cells, Kupffer cells).
○ Contribution to blood formation from the yolk sac is transient, mainly producing embryonic red blood
cells.
● Hematopoietic Stem Cells (HSCs):
○ Arise several weeks later in the mesoderm of the intraembryonic aorta/gonad/mesonephros region.
○ By the third month, HSCs migrate to the liver, the primary site of blood cell formation until shortly
before birth.
○ Some HSCs reside in the fetal placenta, clinically relevant for umbilical cord blood harvesting.
● Shift to Bone Marrow:
○ By the fourth month, HSCs shift to bone marrow, which becomes hematopoietically active by birth.
○ Hepatic hematopoiesis decreases significantly after birth.
● Hematopoietic Activity Changes:
○ Throughout childhood, hematopoietic marrow is found throughout the skeleton.
○ Post-puberty, active marrow is restricted to the axial skeleton; normal adults have about half the
marrow space active.
● Common Origin of Blood Cells:
○ All formed blood elements (red cells, granulocytes, monocytes, platelets, lymphocytes) originate
from HSCs.
○ HSCs are pluripotent, giving rise to various progenitor cells with restricted differentiation potential.
● Progenitor Cells and Differentiation:
○ Early progenitors lead to specific lineage commitment, forming colony-forming units (CFUs).
○ Derived cells include morphologically recognizable precursors (e.g., myeloblasts, proerythroblasts,
megakaryoblasts).
