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PA19.4 | Splenomegaly — Causes & Differentiation — SDL Guide (Part 2)

Category 1 — Congestive Splenomegaly

⚑ AI image — pending faculty review (auto-QA score 7/10; best of 3 attempts)

Diagram showing congestive splenomegaly from portal or splenic venous hypertension, including obstruction sites and red pulp sinusoidal congestion. — **Panel A:** Anterior abdominal overview showing liver, spleen, portal vein, splenic vein, hepatic veins, inferior vena cava, right heart, enlarged congested spleen, and pressure-backflow arrows.. **Panel B:** Cause-map of venous obstruction sites: hepatic cirrhosis, non-cirrhotic portal fibrosis, Budd-Chiari syndrome, portal vein thrombosis, splenic vein thrombosis, right heart failure, and constrictive pericarditis.. **Panel C:** Histology comparison showing normal red pulp sinusoids versus dilated congested sinusoids, red pulp congestion, fibrosis, and Gamna-Gandy bodies..

Any condition that raises pressure in the portal or splenic venous system causes passive engorgement of the red pulp sinusoids.

Causes:
• Hepatic cirrhosis (commonest cause in India) — intrahepatic block → portal hypertension → splenomegaly. Associated with hypersplenism (see block 9).
• Non-cirrhotic portal fibrosis (NCPF) — idiopathic hepatoportal sclerosis; common in India; massive splenomegaly with relatively preserved liver function.
• Budd-Chiari syndrome — hepatic vein thrombosis → post-hepatic block.
• Portal vein thrombosis — extra-hepatic block; often presents in children.
• Splenic vein thrombosis — causes isolated 'sinistral' (left-sided) portal hypertension.
• Right heart failure / constrictive pericarditis — raised systemic venous pressure backs up through the inferior vena cava into the portal circulation.

Pathology: sinusoidal dilatation, red pulp congestion, fibrocongestive splenomegaly on chronicity (Gamna-Gandy bodies = haemosiderin/calcium deposits visible on MRI).

Category 2 — Infective Splenomegaly

A multi-panel medical diagram explains infective splenomegaly mechanisms and major causes including malaria, kala-azar, EBV, endocarditis, tuberculosis, and typhoid. — **Panel A:** Enlarged spleen cutaway showing capsule, red pulp, white pulp follicles, splenic sinusoids, macrophage-rich red pulp expansion, and follicular white pulp hyperplasia.. **Panel B:** Two-route mechanism flow: blood-borne organisms to macrophage hyperplasia in red pulp; antigenic stimulation to immune follicular hyperplasia in white pulp.. **Panel C:** Malaria: Plasmodium-infected RBCs, red pulp macrophages, phagocytosis of parasitised RBCs, haemozoin pigment, chronic tropical splenomegaly syndrome, acute P. vivax rupture risk.. **Panel D:** Kala-azar/visceral leishmaniasis: Leishmania donovani amastigotes inside macrophages, massive red pulp macrophage expansion, massive splenomegaly, hypersplenism, pancytopenia, endemic belt of Bihar-Jharkhand-West Bengal.. **Panel E:** Other infective causes: EBV white pulp hyperplasia with atypical lymphocytes and rupture warning; infective endocarditis septic emboli and abscesses; tuberculosis granulomas; typhoid nodules and soft rupture-prone spleen..

Infections enlarge the spleen through two routes: (a) macrophage hyperplasia in response to phagocytosed organisms (red pulp expansion) and (b) immune/follicular hyperplasia in the white pulp.

Key pathogens:

Malaria — Plasmodium parasites parasitise RBCs; macrophages in red pulp phagocytose parasitised cells and deposit malarial pigment (haemozoin). Chronic malaria → tropical splenomegaly syndrome (massive, reactive). Rupture risk in acute P. vivax.
Kala-azar (visceral leishmaniasis, VL) — Leishmania donovani amastigotes multiply within red pulp macrophages → enormous macrophage expansion → massive splenomegaly (often the largest spleens in medicine; a hallmark of VL). Pancytopenia due to hypersplenism.
Infective endocarditis — septic emboli seed the spleen; small multiple abscesses or reactive splenomegaly.
EBV (infectious mononucleosis) — white pulp hyperplasia; atypical lymphocytes; risk of spontaneous splenic rupture (avoid contact sports for 4 weeks).
Tuberculosis — miliary spread → discrete granulomas in white and red pulp; rarely causes massive splenomegaly.
Typhoid — macrophage hyperplasia; typhoid nodules (collections of macrophages); spleen soft and prone to rupture.

Geography is a diagnostic clue: kala-azar (Bihar, Jharkhand, West Bengal — hyper-endemic belt); malaria (pan-India, seasonal).

SELF-CHECK

A 28-year-old man from Muzaffarpur (Bihar) has had fever, weight loss, and progressive abdominal distension for 8 months. Spleen reaches the right iliac fossa. Haemoglobin 6.8 g/dL, TLC 2.1 × 10⁹/L, platelets 55 × 10⁹/L. Bone marrow biopsy shows hypercellularity. The MOST likely diagnosis is:

A. Visceral leishmaniasis (kala-azar)

B. Chronic myeloid leukaemia

C. Thalassaemia major

D. Non-cirrhotic portal fibrosis

Reveal Answer

Answer: A. Visceral leishmaniasis (kala-azar)

Geography (Bihar hyper-endemic for Leishmania donovani), massive splenomegaly, pancytopenia, and hypercellular marrow (hypersplenism picture) are classic for kala-azar. CML would show leukocytosis and BCR-ABL. Thalassaemia major presents in childhood. NCPF rarely causes pancytopenia of this severity.

Category 3 — Haematological Splenomegaly

A four-panel medical diagram explains haematological splenomegaly through malignant infiltration, extramedullary haematopoiesis, and haemolytic work hypertrophy with clinical examples. — **Panel A:** Overview of enlarged spleen compared with normal spleen; two mechanisms: malignant infiltration and haemolytic work hypertrophy. **Panel B:** Bone marrow source, abnormal myeloid or lymphoid cells, splenic red pulp and white pulp infiltration, extramedullary haematopoiesis, CML, myelofibrosis, lymphoma/leukaemia. **Panel C:** Red pulp cords, slit pores, trapped spherocytes, macrophage destruction of RBCs, extramedullary haematopoietic islands, thalassaemia major and hereditary spherocytosis mechanisms. **Panel D:** Clinical pattern summary for thalassaemia major, hereditary spherocytosis, autoimmune haemolytic anaemia, and immune thrombocytopenic purpura.

Two distinct mechanisms operate here — infiltration by malignant cells, and work hypertrophy from haemolysis.

Myeloproliferative/Lymphoid infiltration:
• CML — neoplastic myeloid progenitors home to the spleen and proliferate; splenic extramedullary haematopoiesis compounds this. Spleen may reach 3–5 kg — the classic cause of massive splenomegaly in haematological malignancy. Cross-ref Cluster H7.
• Myelofibrosis (Primary myelofibrosis) — progressive marrow fibrosis drives haematopoiesis entirely to the spleen and liver (myeloid metaplasia); massive splenomegaly + leukoerythroblastic blood film.
• Lymphomas and leukaemias — NHL (especially splenic marginal zone lymphoma), CLL, hairy cell leukaemia, ALL — all infiltrate white and/or red pulp. Cross-ref Cluster H8.

Haemolytic work hypertrophy:
• Thalassaemia major — massive ineffective erythropoiesis in the marrow + extramedullary haematopoiesis in spleen → progressive splenomegaly. Splenectomy deferred as long as possible (removes residual haematopoietic reserve).
• Hereditary spherocytosis (HS) — spherocytes fail to traverse slit pores → trapped and destroyed in red pulp; spleen hyperplastic. Splenectomy is curative.
• Autoimmune haemolytic anaemia (AIHA) — IgG-coated RBCs destroyed in spleen (Fc-receptor-mediated); moderate splenomegaly.
• ITP — anti-platelet IgG; platelet destruction in spleen; spleen may be normal or mildly enlarged (important: splenomegaly in ITP is mild at most — a massively enlarged spleen in thrombocytopenia should suggest another diagnosis).

Cross-ref H5 (thalassaemia, HS, AIHA) and H7 (CML, myelofibrosis).