HEAMATOLOGY

HEAMATOLOGY
Dr. musa k.hussien
Assistant Professor ,dep. of internal medicine
Al-kindy collage for medicine
5-10-2015
Blood diseases cover a wide spectrum of
illnesses, ranging from the anaemias,
leukaemias and congenital coagulation
.disorders
Haematological change may occur as a
consequence of disease affecting any
system and measurement of
haematological parameters is an
important part of routine clinical
..assessment
 FUNCTIONAL ANATOMY AND
HAEMATOPOIESIS

Blood flows throughout the body in the vascular

system, and consists of plasma and three
:cellular components
red cells, which transport oxygen from the -
lungs to the tissues
white cells, which protect against infection -
platelets, which interact with blood vessels and -
clotting factors to maintain vascular integrity
 SITES OF HAEMATOPOIESIS
Haematopoiesis: is the process of formation of blood cells
In the embryo this occurs initially in the yolk sac,
followed by the liver and spleen; by 5 months in
utero, haematopoiesis is established in the bone
marrow
At birth, haematopoietic (red) marrow is
found in the medullary cavity of all bones, but
with age this is progressively replaced by fat
(yellow marrow) so that by adulthood,
haematopoiesis is restricted to the vertebrae,
pelvis, sternum, ribs, clavicles, skull, upper
.humeri and proximal femora
red marrow can expand in response to
.increased demands for blood cells
 FORMATION OF BLOOD CELLS
Stem cells:All blood cells are derived from a pluripotent
stem cell which has the ability to self-renew (make more
stem cells) and to differentiate to form any of the blood
.elements
These comprise only 0.01% of the total marrow cells
As primitive progenitor cells cannot be distinguished
morphologically, they are named according to the types of
cell (or colony) they form during cell culture experiments
CFU-GM :a stem cell that produces granulocytic and monocytic lines -

CFU-E produces erythroid cells-

CFU-Meg produces megakaryocytes and ultimately platelets -

The proliferation and differentiation of stem cells and their
progeny are under the control of a range of growth factors
produced by several cells, including stromal cells and
lymphocytes. These growth factors bind to specific
receptors on the cell surface and promote not only
proliferation and differentiation but also survival and
.function of mature cells
Some growth factors such as GM-CSF, IL-3, SCF act on a
wide number of cell types at both early and late time
.points
Others, such as erythropoietin (Epo), (G-CSF) and thrombopoietin
(Tpo), are lineage-specific
.Many are synthesized & available for clinical use

.
:Red cells
Red cell precursors formed from the erythroid progenitor
.cells are called erythroblasts or normoblasts
These nucleated cells divide, the nucleus condenses and
is extruded from the cell
The first non-nucleated red cell is a reticulocyte which still
contains ribosomal material in the cytoplasm. then lose
their ribosomal material and mature over 3 days, during
.which time they are released into the circulation
.Reticulocytosis: reflect increased erythropoiesis
Red cell production is controlled by erythropoietin, a
. polypeptide hormone produced by renal tubular cells
Erythropoietin stimulates committed erythroid stem cells
.to proliferate and decreases maturation time
:White cells
Granulocytes (neutrophils, eosinophils, basophils) and
.monocytes are formed from the CFU-GM progenitor cell
The first recognisable granulocyte in the marrow is the
myeloblast As the cells divide and mature, the nucleus segments and
the cytoplasm acquires specific neutrophilic, eosinophilic or basophilic
.granules This takes about 14 days

Neutrophill: the most common WBC in the blood of adults, 10-14

micrometer in diameter multilobulated nucleus containing 2-5 segments
& granules in cytoplasm
Function: recognize, ingest, destroy foreign particles & microorganisms
Every day some 1011 neutrophils enter the circulation,
.
where cells may be freely circulating or attached to
endothelium in the marginating pool.
These two pools are equal in size; factors such as
exercise or catecholamines increase the number of
cells flowing in the blood. Neutrophils spend 6-10
hours in the circulation before being removed,
principally by the spleen. Alternatively, they pass into
the tissues and either are consumed in the
inflammatory process or undergo apoptotic cell death
and phagocytosis by macrophages.
:Causes of neutrophillia
infection: bacterial, fungal .1
trauma: surgery, burns .2
infarction: Myocardial infarctio, Pulmonary Embolisim, .3
sickle cell crices
inflammation: Gout, Ulcerative colitis, crohn’s disease .4
malignancy: solid tumors, Hodgkin's disease .5
myeloproliferative disease: polycythemia, CML -6
physical: exercise, pregnancy .7
:Causes of nutropenia
infection: viral, bacterial, salmonella, protozoal, malaria .1
drugs: analgesics, anti-inflammatory, anti thyroid, anti .2
arrhythmics, antihypertensive (captopril, nifidipien), anti
malarial (chlrolquine, pyrimethamine), anti biotics
(cephalosporin, pencillins), anti depressant (psychotic)
autoimmune: connective tissue disease .3
alcohol .4
congenital: Kostmann’s syndrome .5
Bone marrow infiltration: leukemia, myleodysplasia .6
:Eosinophils
Represents 1-6%ofthe circulating white cells. They are a
similar size to neutrophils but have a bi-lobed nucleus and
.Prominent orange granules on Romanowsky staining
They are Phagocytic, and their granules contain a
peroxidase capable of generating oxygen species and
proteins involved in the intracellular killing of protozoa
..and helminthes. they also involved in allergic reactions
:Causes of eosinophillia
allergy: Hay fever, asthma, eczema .1
infection: parasitic .2
Drug hypersensitivity: gold, sulphonamides .3
Skin disease.4
Connective tissue disease: poly arthritis nodosa .5
malegnancy: solid tumors, lymphomas .6
:Basophils
1%of circulating white cells, bind IgE antibody on their
surface, and exposure to specific antigen results in
degranulation with release of histamine, leukotrienes and
heparin These cells are involved in hypersensitivity
reactions .they contain dense black granules which
.obscure the nucleus
:Causes of basophilia
Myloproliferative disease: polycythemia, CML .1
Inflammation : acute hypersensitivity, ulcerative colitis, .2
crohn’s disease
Iron deficiency .3
:Monocytes
largest of the white cells, with a diameter of 12-20 μm
migrate into the tissue where they become macrophages
which phagocytose debris, apoptotic cells &
microorganisms. They produce a variety of cytokines when
Activated such as(IL-1),GM-CSF, tumor necrosis factor
alpha
:Causes of monocytosis
infection: bacterial (TB) .1
inflammation: connective tissue disease, ulcerative .2
colitis, crohn’s disease
malignancy: solid tumors .3
Lymphocytes
In children aged up to 7 years, lymphocytes are the most
abundant white cell, two main types T-cells (80%),which
.can be recognised by their expression of the CD antigens
T cells mediate cellular immunity. B-cell mediate humeral
immunity and can be recognised by their expression of
immunoglobulin light chain
Normal count 1.5-4*10^9/L
:Causes of lymphocytosis
infection: viral, bacterial, bordetella pertussis .1
Lymphoproliferative disease: CLL, lymphoma .2
post-splenectomy .3
:Causes of lymphopenia
inflammation: connective tissue disease .1
Renal faliure .2
Sarcoidosis .3
drugs: steroids, cytotoxics .4
congenital: sever combined immunodeficiency .5
Lymphoma .6
Platelets
Platelets are derived from megakaryocytes. Megakaryocytic
stem cells (CFU-Meg) divide to form a megakaryoblast
mature megakaryocytes are large cells with several nuclei
and cytoplasm containing platelet granules
The formation and maturation of megakaryocytes are under
the influence of Tpo
.Platelets are discoid with a diameter of 2-4 micrometer
INVESTIGATION OF DISEASES OF THE
BLOOD
:THE FULL BLOOD COUNT.1
the measurement of the number of circulating (RBC), (WBC) and
platelets, the concentration of (Hb) and the characteristics of the red
cells
blood is processed through blood analysers to measure the different
:haematological parameters. These include
numbers of circulating cells .1
the proportion of red cells present in blood (the haematocrit, Hct) .2
red cell indices which give information about the size of red cells .3
(mean cell volume, MCV) and the amount of haemoglobin present in the
red cells (mean cell haemoglobin, MCH)
detect the different types of white blood cell and give automated white .4
cell differential counts
:Blood film examination .2
Mandatory to detect RBC morphology, Hetrogenecity in RBC size
(anisocytosis) shape (poikilocytosis) specific RBC morphologic
abnormalities, WBC, platelet abnormalities may be seen
:Common RBC appearances & their causes
A. Microcytosis (reduced average cell size MCV< 76fl)
Iron deficiency anemia -
Thalassaemia
Sideroblastic anemia -
:B. macrocytosis(MCV>100fl)
vit. B12/folate deficiency-
liver disease-
hypothyroidism-
C-target cells(central area of •
haemoglobinisation)
liver disease- •
Thalassemia- •
post-splenctomy- •
Hemoglobn C disease- •
D-spherocytes(dense cells,no area of central
pallor)
autoimmune hemolysis-
post-splenctomy-
hereditary spherocytosis-
E-Red cell fragments( intravascular haemolysis) •
DIC- •
Hemolytic uremic syndrome •
TTP- •
F-neucleated red cells( normoblasts)
marrow infiltration-
sever haemolysis-
myelofibrosis-
acute hemorrhage-
G-Howell-Jolly bodies(small round nuclear remnants)
hypersplenism-
Hemorrhage
post-splenctomy-
dyshaemopoiesis-
H-Polychromasia(young red cells-
reticulocytes present)

hemolysis, acute haemorrhage-

-increased red cells turn over
I-Basophilic stippling(abnormal ribosomes
appear asBlue dots)
.dyshaematopoiesis
.lead poisoning
:Bone marrow examination .3
Bone marrow aspirate is used to assess the composition &
morphology of heamatopoitic cells or abnormal infiltrates
Atrephine biopsy is superior for assessing marrow cellularty, marrow
fibrosis & infilteration by abnormal cells
PRESENTING PROBLEMS IN BLOOD DISEASE
Anaemia
Anaemia refers to a state in which the level of
haemoglobin in the blood is below the normal range
appropriate for age and sex.
factors, including pregnancy and altitude, also affect
haemoglobin levels and must be taken into account when
considering whether an individual is anaemic.
The clinical assessment and investigation of
anaemia must not only assess its severity but
also define the underlying cause .
The clinical features of anaemia reflect
diminished oxygen supply to the
tissues .
A rapid onset of anaemia (e.g. due to
blood loss) causes more profound
symptoms than a gradually developing
anaemia.
Individuals with cardiorespiratory
disease are more susceptible to
symptoms of anaemia.
:Causes
:Decrease or ineffective marrow production .1
Lack of iron, vit B12, folate-
renal failure- -
anaemia of chronic disease--
Hypoplasia -
Invasion by malignant cells -
:Periphral causes .2
blood loss-
heamolysis-
hypersplenism-
•Irondeficiency anaemia is the most common
type of anaemia world-wide. A thorough
gastrointestinal history is important, looking in
particular for symptoms of blood loss.
page 997
Clinical assessment
Menorrhagia is a common cause of pageanaemia
998 in
pre-menopausal females, so women should
always be asked about their periods.
•A dietary history should assess the intake of
iron and folate which may become deficient in
comparison to needs (e.g. in pregnancy or
during periods of rapid growth.
•Past medical history may reveal a disease
which is known to be associated with anaemia,
such as rheumatoid arthritis (the anaemia of
chronic disease), or previous surgery (e.g.
resection of the stomach or small bowel which
may lead to malabsorption of iron and/or
vitamin B12).
Family history and ethnic background may
raise suspicion of haemolytic anaemias such
as the haemoglobinopathies and hereditary
spherocytosis. Pernicious anaemia may also
.be familial
A drug history may reveal the ingestion of
drugs which cause blood loss (e.g. aspirin
and anti-inflammatory drugs), haemolysis or
aplasia
 ,,On examination
a patient may be found to have a right iliac fossa mass due*
.to an underlying caecal carcinoma
.Haemolytic anaemias can cause jaundice*
Vitamin B12 deficiency may be associated with neurological*
signs including peripheral neuropathy, dementia and signs of
. subacute combined degeneration of the cord
Sickle-cell anaemia may result in leg ulcers, stroke or*•
.features of pulmonary hypertension
Anaemia may be multifactorial and the lack of specific
.symptoms and signs does not rule out silent pathology