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.

1. HEAMATOLOGY
INTRODUCTION
TO
HEAMATOLOGY

2. 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..

3. 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

4. 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

5. 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.

6. 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

7. 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.
.

8. 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.

10. 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

11. .
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.

13. Causes of neutrophillia:
1. infection: bacterial, fungal
2. trauma: surgery, burns
3. infarction: Myocardial infarctio, Pulmonary Embolisim,
sickle cell crices
4. inflammation: Gout, Ulcerative colitis, crohn’s disease
5. malignancy: solid tumors, Hodgkin's disease
6- myeloproliferative disease: polycythemia, CML
7. physical: exercise, pregnancy

14. Causes of nutropenia:
1. infection: viral, bacterial, salmonella, protozoal, malaria
2. drugs: analgesics, anti-inflammatory, anti thyroid, anti
arrhythmics, antihypertensive (captopril, nifidipien), anti
malarial (chlrolquine, pyrimethamine), anti biotics
(cephalosporin, pencillins), anti depressant (psychotic)
3. autoimmune: connective tissue disease
4. alcohol
5. congenital: Kostmann’s syndrome
6. Bone marrow infiltration: leukemia, myleodysplasia

15. Eosinophils:
Represents 1-6%of the 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..

17. Causes of eosinophillia:
1. allergy: Hay fever, asthma, eczema
2. infection: parasitic
3. Drug hypersensitivity: gold, sulphonamides
4.Skin disease
5. Connective tissue disease: poly arthritis nodosa
6. malegnancy: solid tumors, lymphomas

18. 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:
1. Myloproliferative disease: polycythemia, CML
2. Inflammation : acute hypersensitivity, ulcerative colitis,
crohn’s disease
3. Iron deficiency

20. 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:
1. infection: bacterial (TB)
2. inflammation: connective tissue disease, ulcerative
colitis, crohn’s disease
3. malignancy: solid tumors

22. 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:
1. infection: viral, bacterial, bordetella pertussis
2. Lymphoproliferative disease: CLL, lymphoma
3. post-splenectomy

24. Causes of lymphopenia:
1. inflammation: connective tissue disease
2. Renal faliure
3. Sarcoidosis
4. drugs: steroids, cytotoxics
5. congenital: sever combined immunodeficiency
6. Lymphoma

25. 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.

29. INVESTIGATION OF DISEASES OF THE
BLOOD
1.THE FULL BLOOD COUNT:
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:
1. numbers of circulating cells
2. the proportion of red cells present in blood (the haematocrit, Hct)
3. red cell indices which give information about the size of red cells
(mean cell volume, MCV) and the amount of haemoglobin present in the
red cells (mean cell haemoglobin, MCH)
4. detect the different types of white blood cell and give automated white
cell differential counts

30. 2. Blood film examination:
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

31. B. macrocytosis(MCV>100fl):
-vit. B12/folate deficiency
-liver disease
-hypothyroidism

33. C-target cells(central area of
haemoglobinisation)
-liver disease
-Thalassemia
-post-splenctomy
-Hemoglobn C disease

34. D-spherocytes(dense cells,no area of central
pallor)
-autoimmune hemolysis
-post-splenctomy
-hereditary spherocytosis

35. E-Red cell fragments( intravascular haemolysis)
-DIC
Hemolytic uremic syndrome
-TTP

36. F-neucleated red cells( normoblasts)
-marrow infiltration
-sever haemolysis
-myelofibrosis
-acute hemorrhage

37. G-Howell-Jolly bodies(small round nuclear remnants)
-hypersplenism
Hemorrhage
-post-splenctomy
-dyshaemopoiesis

38. H-Polychromasia(young red cells-
reticulocytes present)
-hemolysis, acute haemorrhage
-increased red cells turn over

39. I-Basophilic stippling(abnormal ribosomes
appear asBlue dots)
.dyshaematopoiesis
.lead poisoning

40. 3. Bone marrow examination:
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

41. 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 .

42. 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.

43. Causes:
1. Decrease or ineffective marrow production:
-Lack of iron, vit B12, folate
--renal failure
--anaemia of chronic disease
- Hypoplasia
- Invasion by malignant cells
2. Periphral causes:
-blood loss
-heamolysis
-hypersplenism

44. Clinical assessment
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•Iron deficiency anaemia is the most common
type of anaemia world-wide. A thorough
gastrointestinal history is important, looking in
particular for symptoms of blood loss.
Menorrhagia is a common cause of anaemia in
pre-menopausal females, so women should
always be asked about their periods.

45. •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).

46. 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

47. 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.