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Pathogenesis: A reduction in the number of granulocytes in
the blood (neutropenia) can be seen in a wide variety of
conditions, including the effects of drugs, neoplasms and
autoimmune conditions.
2. Congenital Neutropenia: Periodic or cyclic neutropenia is an
autosomal dominant disorder with variable expression that
begins in infancy and persists for decades. It is characterised
by periodic neutropenia that develops approximately every
21 days and lasts approximately 2 to 3 days. It is thought to
result from impaired feedback regulation of granulocyte
production and release.
3. Acquired Neutropenia: Many cases of neutropenia are drug
related. Chemotherapeutic drugs used in the treatment of
cancer cause predictable dose-dependant suppression of
bone marrow function.
4. Clinical Course: > Infection; < 250/uL.
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Cause: Epstein Barr Virus
Mode of Transmission: Oral contact with EBVcontaminated saliva.
Pathogenesis: The virus initially penetrates the
nasopharyngeal, and salivary epithelial cells. It then spreads
to the underlying oropharyngeal lymphoid tissue , and more
specifically to B lymphocytes.
Incubation period: 4 to 8 weeks
Clinical Course: > Fever; Enlarged Lymph Nodes; Severe
Pharyngitis; > Leucocytes (of particular note lymphocytes)
Common Manifestations: Hepatitis and splenomegaly
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Leukaemia's are malignant neoplasms arising from the
transformation of a single blood cell line derived from
haematopoietic stem cells.
2. The leukaemia's are classified as acute and chronic
lymphocytic or myelogenous leukaemia’s according to cell
lineage.
3. Because leukemic cells are immature and poorly
differentiated, they proliferate rapidly and have a long life
span, they do not function normally, they interfere with the
maturation of normal blood cells, and they circulate in the
bloodstream, cross the blood brain barrier, and infiltrate
many body organs.
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Acute Lymphocytic Leukaemia (ALL):
Most common cancer in children and adults.
ALL encompasses a group of neoplasms composed of
precursor B or T lymphocytes referred to as
lymphoblast's. Most cases of ALL are of pre-B cell
origin.
Approximately 90 percent of persons with ALL have
numeric and structural changes in in the chromosomes
of their leukaemic cells.
Symptoms include fatigue resulting from anaemia, low
grade fever, night sweats and weight loss, bleeding due
to decreased platelet count and bone pain.
Increases in uric acid crystallization and infection.
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1. Acute Myeloid Leukaemia:
- Diverse group of neoplasms affecting myeloid
precursor cells in the bone marrow.
- Associated with acquired genetic alterations
that inhibit terminal myeloid differentiation.
- Normal marrow elements are replaced by an
accumulation of relatively undifferentiated
blast cells with a resultant suppression of the
remaining progenitor cells that leads to
anaemia, neutropenia and thrombocytopenia.
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Chronic Lymphocytic Leukaemia:
Accounts for approximately one third of all leukaemia’s.
Mainly a disorder of older persons.
Manifests as a result of differences in immunoglobulin
variable (V)- gene mutations, expression of cell surface CD
markers and the presence of zeta-associated protein (ZAP70).
Clinical Signs and Symptoms: progressive infiltration of the
bone marrow and lymphoid tissues by neoplastic
lymphocytes; lymphadenopathy, hepatosplenomegaly,
fever; abdominal pain, weight loss, progressive anaemia and
thrombocytopenia, rapid rise in lymphocyte count.
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The lymphomas represent malignancies that arise in the
peripheral lymphoid tissues.
2. Non-Hodgkin lymphomas represent a group of
heterogeneous lymphocytic cancers that are multi-centric
in origin and spread to various tissues throughout the body,
including the bone marrow.
3. Hodgkin lymphoma is a group of cancers characterised by
Reed-Sternberg cells that begins as a malignancy in a single
lymph node and then spreads to contiguous lymph nodes.
4. Both types of lymphomas are characterised by
manifestations related to uncontrolled lymph node and
lymphoid tissue growth, bone marrow involvement, and
constitutional symptoms (fever, fatigue, weight loss),
related to rapid growth of abnormal lymphoid cells and
tissues.
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1. Represent a diverse group of either B cell or t cell
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neoplasms.
Impairment of the immune system and infectious
agents may play a role (EBV infection; HTLV-1;
HIV; Acquired or Congenital immunodeficiencies;
Helicobacter pylori).
Origin: Lymph nodes (either B cells/T cells).
B Cell Lymphoma: Burkitt Lymphoma
T Cell Lymphoma: Anaplastic Large Cell
Lymphoma
Clinical Manifestations: Indolent or aggressive.
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1.
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3.
a)
b)
Specialised form of lymphoma that features the
presence of an abnormal cell called a Reed-Sternberg
cell.
Bimodal
Differs from NHL:
HL arises in a single node or chain of nodes and
spreads first to anatomically contiguous lymphoid
tissues; whereas, NHL frequently originates at extranodal sites and spreads in an unpredictable fashion.
HL has distinctive morphological features i.e. Reed
Sternberg Cells.
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Porth, C.M. 2011. Essentials of Pathophysiology, 3rd edn.
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Nodular lymphocyte-predominant Hodgkin
Lymphoma
2. Classical Hodgkin Lymphoma
3. Clinical manifestations: most persons with Hodgkin
lymphoma present with painless enlargement of a
single node or group of nodes. The initial lymph node
involvement typically is above the level of the
diaphragm . There may be complaints of chest
discomfort with cough or dyspnoea.
4. Additional Symptoms that suggest Hodgkin
Lymphoma include fevers, chills, night sweats and
weight loss.
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Is a B cell malignancy of terminally differentiated
plasma cells.
2. The cause of multiple myeloma is unknown. Risk
factors are thought to include chronic immune
stimulation, autoimmune disorders, exposure to
ionising radiation and occupational exposure to
pesticides and herbicides.
3. Characterised by proliferation of malignant plasma
cells in the bone marrow and osteolytic bone lesions
throughout the skeletal system.
4. Main sites involved in multiple myeloma are the bones
and bone marrow.
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Porth, C.M. 2011. Essentials of Pathophysiology, 3rd edn.
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2.
3.
4.
5.
The white blood cells include the ______________,
monocytes/macrophages and lymphocytes.
There are two types of acute Leukaemia: acute
____________ and acute ________________.
Neutrophils are very important as a first line of defence
against viral/bacterial infection. Explain what a neutrophil
does and the condition that results from a deficiency of
neutrophils.
Definitive marker for Hodgkin Lymphoma
_____________________.
What are the two major differences between Hodgkin
Lymphoma and NHL.
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1. Caused by defects associated with platelets,
coagulation factors and vessel integrity.
2. Disorders of platelet plug formation include a
decrease in platelet numbers due to inadequate
platelet production (bone marrow
dysfunction), excess platelet destruction
(thrombocytopenia), abnormal platelet
function (thrombocytopathia) or defects in von
Willebrand factor.
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Refers to a decrease in the number of circulating platelets to
a level less than 100,000/uL.
2. The greater the decrease in the platelet count, the greater
the bleeding.
3. Major causes: decreased platelet production (loss of bone
marrow function), decreased platelet survival (caused by a
variety of immune and non-immune mechanisms), splenic
sequestration (excessive pooling of platelets in the spleen)
and dilution (massive blood or plasma transfusions).
4. Immune Thrombocytopenia Purpura (ITP) . ITP includes a
history of bruising, bleeding from the gums, epistaxis,
melena and abnormal menstrual bleeding in those with
moderately reduced platelet counts.
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Porth, C.M. 2011. Essentials of Pathophysiology, 3rd edn.
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1. Blood coagulation defects can result from
deficiencies or impaired function of one
or more of the clotting factors.
2. Haemophilia A: is an X-linked recessive
disorder that primarily affects males.
3. Haemophilia A: can arise as a result of a
new mutation in the factor VIII gene.
4. Characteristically, bleeding occurs in soft
tissues, the GIT, hip, knee, elbow and
ankle joints.
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1. Describe the manifestations of thrombocytopenia.
2. _______________ from mucous membranes of the
nose, mouth, gastrointestinal tract, and uterine
cavity is characteristic of platelet bleeding
disorders.
3. A reduction in platelet number is referred to as
_______________.
4. Haemophilia A is an ________________ recessive
disorder that primarily affects males.
5. A common clinical manifestation of essential
_______________ is thrombosis and haemorrhage.
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Porth, C.M. 2011. Essentials of Pathophysiology, 3rd edn.
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1. The function of red blood cells, facilitated by
the iron-containing haemoglobin molecule, is
to transport oxygen from lungs to the tissues.
2. The production of red blood cells, which is
regulated by erythropoietin, occurs in the bone
marrow and requires iron, vitamin B12 and
folate.
3. The red blood cell, which has a life span of
approximately 120 days, is broken down in the
spleen.
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Porth, C.M. 2011. Essentials of Pathophysiology, 3rd edn.
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Deficiency of red cells or haemoglobin, results from
excessive loss (blood loss anaemia), increased destruction
(haemolytic anaemia), or impaired production of red blood
cells (iron deficiency, megaloblastic, and aplastic anaemia.
2. Blood loss anaemia is characterised by loss of ironcontaining red blood cells from the body; haemolytic
anaemia involves destruction of red blood cells in the body
with iron being retained in the body.
3. Manifestations of anaemia are caused by the decreased
presence of haemoglobin in the blood, tissue hypoxia due to
deficient oxygen transport and recruitment of compensatory
mechanisms designed to increase oxygen delivery to the
tissues.
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