Hepatosplenomegaly

Function of the Spleen

Maintenance of quality control over erythrocytes in
the red pulp by removal of senescent and defective
red blood cells. The spleen accomplishes this
function through a unique organization of its
parenchyma and vasculature
Synthesis of antibodies in the white pulp.
The removal of antibody-coated bacteria and
antibody-coated blood cells from the circulation.

 three adaptive functions: (1) clearance of

bacteria and particulates from the blood, (2)
the generation of immune responses to
certain pathogens, and (3) the generation of
cellular components of the blood under
circumstances in which the marrow is unable
to meet the needs (i.e., extramedullary
hematopoiesis). The latter adaptation is a
recapitulation of the blood-forming function
the spleen plays during gestation

 1. Nixon's method: The patient is placed on

the right side so that the spleen lies above
the colon and stomach. Percussion begins at
the lower level of pulmonary resonance in
the posterior axillary line and proceeds
diagonally along a perpendicular line toward
the lower midanterior costal margin. The
upper border of dullness is normally 68 cm
above the costal margin. Dullness >8 cm in
an adult is presumed to indicate splenic
enlargement.

 2. Castell's method: With the patient supine,

percussion in the lowest intercostal space in
the anterior axillary line (8th or 9th)
produces a resonant note if the spleen is
normal in size. This is true during expiration
or full inspiration. A dull percussion note on
full inspiration suggests splenomegaly

 3. Percussion of Traube's semilunar space: The

borders of Traube's space are the sixth rib
superiorly, the left midaxillary line laterally, and
the left costal margin inferiorly. The patient is
supine with the left arm slightly abducted. During
normal breathing, this space is percussed from
medial to lateral margins, yielding a normal
resonant sound. A dull percussion note suggests
splenomegaly.

 The acinus occupies adjacent sectors of neighboring

hexagonal fields. Zones 1, 2, and 3, respectively, represent
areas supplied
with blood of first, second, and third quality with regard to
substrate,
oxygen, and nutrients. These zones center around the
terminal afferent
vascular branches, terminal bile ductules, lymph vessels,
and nerves and
extend into the triangular portal field from which these
branches crop out.
Zones 1, 2, and3 designate corresponding areas in a portion
of an
adjacent acinar unit. In zones 1 and 1, portal inlet venules
empty into
sinusoids. Note that zone 3 approaches the preterminal
portal tract, nearly
reaching the inner circle (A). PS, portal space; THV, terminal
hepatic venules

Causes of splenomegaly

Enlargement of the spleen may occur as a result of various

pathological factors:
1 reactive increase of white pulp in inflammation and infection;
2 congestive expansion of the red pulp compartment;
3 increased blood pool;
4 increased macrophage function;
5 proliferative cellular infiltration;
6 extramedullary haemopoiesis;
7 storage disease;
8 cysts;
9 solid tumours

Diseases Associated with Splenomegaly Grouped by

Pathogenic Mechanism

Enlargement Due to Increased Demand for Splenic Function

Reticuloendothelial system hyperplasia (for removal of defective
erythrocytes)
Spherocytosis
Early sickle cell anemia
Ovalocytosis
Thalassemia major
Hemoglobinopathies
Paroxysmal nocturnal hemoglobinuria
Pernicious anemia

Immune hyperplasia
Response to infection (viral, bacterial, fungal, parasitic)
Infectious mononucleosis
AIDS
Viral hepatitis
Cytomegalovirus
Subacute bacterial endocarditis
Bacterial septicemia
Congenital syphilis
Splenic abscess
Tuberculosis
Histoplasmosis
Malaria
Leishmaniasis
Trypanosomiasis
Ehrlichiosis

Disordered immunoregulation
Rheumatoid arthritis (Felty's syndrome)
Systemic lupus erythematosus
Collagen vascular diseases
Serum sickness
Immune hemolytic anemias
Immune thrombocytopenias
Immune neutropenias
Drug reactions
Angioimmunoblastic lymphadenopathy
Sarcoidosis
Thyrotoxicosis (benign lymphoid hypertrophy)
Interleukin 2 therapy

Extramedullary hematopoiesis

Myelofibrosis

Marrow damage by toxins, radiation, strontium

Marrow infiltration by tumors, leukemias, Gaucher's disease

Enlargement Due to Abnormal Splenic or Portal Blood Flow

Cirrhosis
Hepatic vein obstruction
Portal vein obstruction, intrahepatic or extrahepatic
Cavernous transformation of the portal vein
Splenic vein obstructionSplenic artery aneurysm
Hepatic schistosomiasis
Congestive heart failure
Hepatic echinococcosis
Portal hypertension (any cause including the above): "Banti's disease"

Infiltration of the Spleen

Intracellular or extracellular depositions

Amyloidosis
Gaucher's disease
Niemann-Pick disease
Tangier disease
Hurler's syndrome and other mucopolysaccharidoses
Hyperlipidemias

Benign and malignant cellular infiltrations

Leukemias (acute, chronic, lymphoid, myeloid, monocytic)
Lymphomas
Hodgkin's disease
Myeloproliferative syndromes (e.g., polycythemia vera, essential
thrombocytosis)
Angiosarcomas
Metastatic tumors (melanoma is most common)
Eosinophilic granuloma
Histiocytosis X
Hamartomas
Hemangiomas, fibromas, lymphangiomas
Splenic cysts

Unknown Etiology

Idiopathic splenomegaly

Berylliosis

Iron-deficiency anemia

Diseases Associated with Massive Splenomegaly *

and moderate hepatomegaly.

Chronic myeloid leukemia

Lymphomas
Hairy cell leukemia
Myelofibrosis with myeloid
metaplasia
Polycythemia vera
Gaucher's disease
Chronic lymphocytic leukemia
Sarcoidosis
Autoimmune hemolytic anemia
Diffuse splenic hemangiomatosis

 68. Chronic myeloproliferative disorders

Introduction
These disorders are characterized by cellular proliferation of one or more of the granulocytic,
megakaryocytic
or erythroid lineages. They are each a clonal haemopoietic stem cell disorder. There is relatively normal
maturation accompanying the proliferation.
This results in increased counts of granulocytic cells, platelets and, rarely, erythrocytes in chronic
myeloid
leukemia (CML).
In polycythaemia vera (PV) an increase occurs in the red cell count, in particular, the platelets and, to a
lesser
extent, the WBC count.
In essential thrombocythaemia (ET) the major manifestation is an increase in the platelet count.
A fourth member of the CMPD, idiopathic myelofibrosis (IMF), shows an increase in marrow reticulin and
later
fibrosis is a major feature. An increase in megakaryocytes, especially in the early phase, and myeloid
cells is
seen.
An increase in reticulin can be seen in the other disorders particularly in the late stage of PV where BM
fibrosis occurs.
In CML the Ph chromosome and/or BCR/ABL fusion gene allows a specific diagnosis.
Recently other disrupted protein kinases have been found in other members of the group. JAK2 has
been
found in PV, IMF and ET but has also been noted in other disorders including chronic myelomonocytic
leukemia (CMML) and the myelodysplastic syndrome (MDS).
There is overlap in the clinical, laboratory and morphological results in the CMPD members.
Organomegaly, in
particular splenomegaly, is found in all. Chronic myelomonocytic leukemia originally classified under the
myelodysplastic syndromes by the FAB group, has been included under the
myelodysplastic/myeloproliferative diseases by the WHO (2001).

CML

Chronic myelogenous leukemia: acquired defect of clonal origin.

Philadelphia chromosome, t(9;22), is the hallmark of the disease.
Increased WBC count; granulocytes in all stages of maturation.
Bone marrow shows hyperplasia; myelofibrosis in 10%-40% of
patients.
The leukocyte alkaline phosphatase score is low or zero in chronic
myelogenous leukemia, paroxysmal nocturnal hemoglobinuria,
infectious mononucleosis, and aplastic anemia.
Increased vitamin B12; increased acid phosphatase.
Typical clinical scenario: A patient without symptoms presents
with a high WBC count, myeloid bulge, basophilia, and
splenomegaly. Cytogenetic studies show t(9;22).

Chronic myelogenous leukemia. Blood film. Leukemic

promyelocytes, a basophilic myelocyte, and
segmented neutrophils with increased nuclear material

Peripheral blood (PB) film

of a patient with CGL showing two
promyelocytes, a myelocyte, an
eosinophil, a basophil and numerous
neutrophils and band forms.

Peripheral blood film of a patient with accelerated phase CML

showing two blasts, basophils, an eosinophil, aneosinophil
myelocyte, platelet anisocytosis and hypogranular platelets

Peripheral blood film of a patient with chronic myeloid leukaemia

in chronic phase showing myelocytes, eosinophil myelocytes ,
one basophil, several neutrophil band forms and some
neutrophils.

Chronic myelogenous leukemia. Blood film. Leukemic

promyelocytes, myelocytes, metamyelocyte, band, and
segmented neutrophils. Myeloblast in lower portion of field.
Basophilic myelocyte and segmented cell.

Myelodysplastic Syndromes

Patients with myelodysplastic disorders

present with various
degrees of cytopenia of peripheral blood
components.

MDS

 MDS needs to be distinguished from the

myeloproliferative
disorders (MPD), among which are
included polycythaemia vera (also known as
polycythaemia
rubra vera), essential thrombocythaemia,
idiopathic myelofibrosis and various chronic
myeloid
leukaemias

 In MPD, haemopoiesis is generally

effective and excessive with erythrocytosis,
thrombocytosis,
neutrophilia and basophilia being common
whereas in MDS haemopoiesis is generally
ineffective
with increased cell death in the marrow leading
to various cytopenias.

 Chronic
myelomonocytic leukaemia, which was classified
by
the FAB group as one of the myelodysplastic
syndromes,
shares many features with other members
of the myelodysplastic group but it resembles
other
chronic myeloid leukaemias in that production of
monocytes and, usually, neutrophils is effective
and
hepatomegaly and splenomegaly are common.

Myelofibrosis
The median survival approaches 5 years.
Agnogenic myeloid metaplasia: its
hallmark is splenomegaly.
Leukoerythroblastic peripheral blood smear
in 96% of patients.
Teardrop cells.
Basic event: fibroblastic proliferation of
bone marrow

Agnogenic myeloid metaplasia. The peripheral

blood smear
is leukoerythroblastic with dacryocytes

Chronic myelomonocytic
leukaemia

In the WHO classification, CMML

is defined as a myelodysplastic/myeloproliferative
disorder with a monocyte count of greater than 1
10 9/l, no Ph chromosome or BCR-ABL fusion gene
and fewer than 20% blasts plus promonocytes in
the
blood and marrow

Polycythemia Rubra Vera

Polycythemia rubra vera: very low erythropoietin.

The leukocyte alkaline phosphatase score may be increased in
polycythemia rubra vera.
Typical clinical scenario for polycythemia rubra vera: A
hemoglobin
concentration >18 g/dL in a white male or >2 g/dL that
is documented and persistent, microcytosis, absence of iron
stores,
and splenomegaly. Other features include postbathing pruritus,
unusual thrombosis, and erythromelalgia. The erythropoietin
level is low.

 polycythemia verarelated
features are present (thrombocytosis,
leukocytosis, microcytosis, iron
deficiency, splenomegaly, pruritus,
erythromelalgia, and unusual
thrombosis). The erythropoietin level, which
is usually low in polycythemia
rubra vera, may be normal,

Polycythemia vera. (A) Blood film. Note thickness of red cell layer in an area normally less
so. No area in which red cells were normally dispersed was found reflecting a very high
packed red cell volume. (B) Blood film. Note thickness of red cell layer in an area normally
less so. Neutrophilia also evident. (C) Blood film. Note thickness of red cell layer in an area
normally less so. Giant megathrombocyte. The hallmark of polycythemia vera are evident
on the blood film: elevated packed red cell volume, neutrophilia, and normal to elevated
platelet count with platelet dysmorphia

Essential
Thrombocythemia
Essential thrombocythemia is a clonal
hematologic disorder in
which patients present with asymptomatic
thrombocytosis, thrombotic
disorders, or hemorrhage

 The diagnosis of essential thrombocythemia

includes a platelet
count greater than 600 10 9/L, megakaryocytic
hyperplasia and
stainable iron in the bone marrow, splenomegaly,
absence of the
Philadelphia chromosome or rearrangement of the
major breakpoint
cluster region (Mbcr) of the bcr gene (100% of
patients), normal
RBC mass (100%), and no collagen fibrosis
no reactive thrombocytosis

 Clinical findings that suggest reactive

thrombocytosis
include a recent normal manual platelet
count, a clinical
condition associated with reactive
thrombocytosis, and no clinical
features of a myeloproliferative disorder.

 The secondary causes include

acute or chronic inflammatory disease, acute or
chronic bleeding,
iron deficiency, chronic bone marrow stimulation
(e.g., hemolysis),
rebound after thrombocytopenia, disseminated
malignancy,
splenectomy or congenital asplenia or functional
hyposplenism,
postoperative state, intense exercise, parturition,
trauma, and epinephrine.
An increased C-reactive protein level in patients
with
thrombocytosis suggests a reactive process.

Chronic lymphocytic leukemia. Blood films. (A) Blood film. Marked increase in
small lymphocytes. Smudge cells (lymphocyte nuclear remnant) characteristic
of the tendency of lymphocytes to be disrupted by the shear forces during the
preparation of the blood film. (B) Marrow film. Marrow replaced by diffuse
infiltrate of small leukemic lymphocytes.

Chronic lymphocytic leukemia. Blood films. (A) Lower power. Marked

increase in small lymphocytes. Frequent smudge cells (lymphocyte
nuclear remnant) characteristic of the tendency of lymphocytes to be
disrupted by the shear forces during the preparation of the blood film. (B)
Higher power. Range of lymphocyte size from very small to larger size.
The former have condensed nuclear chromatin and the latter have more
open chromatin pattern, often with overt nucleoli. Note characteristic
smudge cells.

Hairy cell leukemia. (A) and (B) Blood films. Nuclei have circular
shape. Nucleoli evident. The cytoplasm is more prominent than in
chronic lymphocytic leukemia of the classical type and the nucleus is
usually centrally placed giving a "fried egg" appearance. The
cytoplasmic surface is irregular with prominent villous projections.

Inherited Hemolytic Anemias

SPHEROCYTOSS

Tropical Splenomegaly (Hyperreactive

Malarial Splenomegaly)

Chronic or repeated malarial infections produce

hypergammaglobulinemia; normochromic, normocytic
anemia; and, in certain situations, splenomegaly.
Some residents of malaria-endemic areas in tropical Africa
and Asia exhibit an abnormal immunologic response to
repeated infections characterized by massive
splenomegaly, hepatomegaly, marked elevations in serum
titers of IgM and malarial antibody, hepatic sinusoidal
lymphocytosis, peripheral B cell lymphocytosis

 This immunologic process stimulates

reticuloendothelial hyperplasia and clearance
activity and eventually produces splenomegaly.
Patients with hyperreactive malarial splenomegaly
(HMS) present with an abdominal mass or a
dragging sensation in the abdomen and occasional
sharp abdominal pains suggesting perisplenitis.
Anemia and some degree of pancytopenia are
usually evident, and in some cases malarial
parasites cannot be found in peripheral-blood
smears

Visceral Leishmaniasis

A macrophage with numerous intracellular amastigotes(24m) in a

Giemsa-stained splenic smear from a patient with visceral leishmaniasis. Each
amastigote contains a nucleus and a characteristic kinetoplast consisting of
multiple copies of mitochondrial DNA. A few extracellular parasites are also
visible.

CHAGAS' DISEASE

Gaucher's Disease

 All patients with Gaucher's disease have

nonuniform infiltration of bone marrow by
lipid-laden macrophages termed Gaucher's
cells. This can lead to marrow packing with
subsequent infarction, ischemia, necrosis,
and cortical bone destruction. Bone marrow
involvement spreads from proximal to distal
in the limbs and can involve the axial
skeleton extensively, causing vertebral
collapse. In addition to bone marrow
involvement, bone remodeling is defective,
with loss of total bone calcium leading to
osteopenia, osteonecrosis, avascular
infarction, and vertebral compression
fractures and spinal cord involvement.
Aseptic necrosis of the femoral head is
common, as is fracture of the femoral neck.