Introduction to Introduction to
HematologyHematology
What is What is hematologyhematology??
Hematology is the study of blood.Hematology is the study of blood.
Blood: is the fluid where the cells Blood: is the fluid where the cells
are free and suspended.are free and suspended.
It can cross the tissues.It can cross the tissues.
has red color.has red color.
Has volume of 5-6 liters, this is 7-Has volume of 5-6 liters, this is 7-
8% of the total body weight.8% of the total body weight.
Has PH of 7.3-7.4 (alkaline).Has PH of 7.3-7.4 (alkaline).
Specific gravity is 1.055-1.056Specific gravity is 1.055-1.056
It is composed of plasma (~53-58% It is composed of plasma (~53-58%
of the blood volume), before of the blood volume), before
clotting occurs, and serum after clotting occurs, and serum after
clotting occurs.clotting occurs.
Plasma consists of 91-92% water, Plasma consists of 91-92% water,
and 8-9%solids.and 8-9%solids.
Solids are:Solids are:
Albumin. Albumin.
Glucose.Glucose.
Fibrinogen.Fibrinogen.
Sodium.Sodium.
Calcium.Calcium.
Potassium. Potassium.
Cholesterol.Cholesterol.
Magnesium.Magnesium.
Carbon dioxide.Carbon dioxide.
Phosphorus.Phosphorus.
Neutral fats. Neutral fats.
NPN group.NPN group.
Oxygen.Oxygen.
Many other Many other
products.products.
Also there are such substances, like Also there are such substances, like
antibodies, hormones, complement and antibodies, hormones, complement and
enzymes.enzymes.
Cellular parts of the blood (45-47%):Cellular parts of the blood (45-47%):
Consists of:Consists of:
– The erythrocytes (RBCs) (~45%)The erythrocytes (RBCs) (~45%)
Contain hemoglobin Contain hemoglobin
Function in the transport of OFunction in the transport of O
22 and and
COCO
22
•
The LeukocytesThe Leukocytes
(WBCs) and platelets (WBCs) and platelets
(thrombocytes) (~1%)(thrombocytes) (~1%)
Leukocytes are involved in the Leukocytes are involved in the
body’s defense against the invasion body’s defense against the invasion
of foreign antigens.of foreign antigens.
PlateletsPlatelets
are involved in hemostasis which are involved in hemostasis which
forms a barrier to limit blood loss forms a barrier to limit blood loss
at an injured site.at an injured site.
The cells are forming about 45-47% The cells are forming about 45-47%
of the total blood volume in male and of the total blood volume in male and
42% in female. This percentage is 42% in female. This percentage is
determined by centrifugation and is determined by centrifugation and is
known as heamatocrit (PCV), which known as heamatocrit (PCV), which
is the percentage of the packed red is the percentage of the packed red
blood cells.blood cells.
Functions of the bloodFunctions of the blood::
1.1.Nutritive: The blood transports Nutritive: The blood transports
nutrients from the gut to all parts of nutrients from the gut to all parts of
the body for use or storage.the body for use or storage.
2.2.Respiratory: the blood carries the Respiratory: the blood carries the
oxygen to the tissue and remove oxygen to the tissue and remove
carbon dioxide and other waste carbon dioxide and other waste
products from the tissues to be products from the tissues to be
excreted by the lung, kidney, liver, excreted by the lung, kidney, liver,
and skinand skin
3- 3- The blood regulates the temperature of the The blood regulates the temperature of the
body, because it is constantly in motion.body, because it is constantly in motion.
4- Transportive: The blood transports the 4- Transportive: The blood transports the
hormones from the endocrine glands to the hormones from the endocrine glands to the
tissues.tissues.
5- Excretory: To excrete the waste products 5- Excretory: To excrete the waste products
of metabolism, for example urea, and uric of metabolism, for example urea, and uric
acid.acid.
6- Protection: versus invading
microorganisms
Blood Cell Production
(Hematopoiesis or
hemopoiesis)
Hematopoiesis is a term describing the formation
and development of blood cells.
In humans, occurs in bone marrow exclusively
All cellular elements derived from pluripotent
stem cell (PPSC)
PPSC retains ability to both replicate itself and
differentiate
Types of differentiation determined by the
influence of various cytokines
Only mature cells are released into the
peripheral blood.
Why do we need the
Hematopoiesis?
–Cells of the blood are constantly being
lost or destroyed. Thus, to maintain
homeostasis, the system must have the
capacity for self renewal.
Sites of productionSites of production::
–Fetus: Fetus: 0-2 months (yolk sac).0-2 months (yolk sac).
2-7 months ( liver and 2-7 months ( liver and spleen).spleen).
5-9 months (bone marrow).5-9 months (bone marrow).
– infants: bone marrowinfants: bone marrow
–Adults: bone marrow, ribs, sternum, skull, Adults: bone marrow, ribs, sternum, skull,
sacrum and pelvis.sacrum and pelvis.
–Hematopoiesis in the bone marrow is called Hematopoiesis in the bone marrow is called
medullary hematopoiesismedullary hematopoiesis
–Hematopoiesis in areas other then the bone Hematopoiesis in areas other then the bone
marrow is called marrow is called extramedullary extramedullary
hematopoiesishematopoiesis
–Extramedullary hematopoiesis may occur in
fetal hematopoietic tissue (liver and spleen),
and in adult when the bone marrow cannot
meet the physiologic needs of the tissues.
This can lead to hepatomegaly and/or
splenomegaly (increase in size of the liver or
spleen because of increased functions in the
organs).
Hematopoietic tissues ARE:Hematopoietic tissues ARE:
Includes tissues involved in the Includes tissues involved in the
proliferation, maturation, and proliferation, maturation, and
destruction of blood cellsdestruction of blood cells
Derivation of blood cells
- The committed lymphoid stem cells
will be involved in lymphopoiesis to
produce lymphocytes
- The committed myeloid stem cell
can differentiate into any of the other
hematopoietic cells including
erythrocytes, neutrophils, eosinophils,
basophils, monocytes, macrophages,
and platelets.
1.Erythrocyte:
•Normal erythrocyte is a round highly flexible biconcave
discs like cell; it is non-nucleated, containing haemoglobin.
• It measures about 7.2-7.8 microns, 80-100 femtoliters in
volume
•Flexibility essential for passage through capillaries
•Life span: the average is 80-120 days.
•Function: RBC carry oxygen from the lung to the body
cells and carry carbon dioxide from the body cells to the
lung.
Terminology:
Erythrocytosis: increased in the blood cells count,
which may lead to
Reticulocyte: is a very young erythrocyte which
contains remainant of RNA. The precipitated RNA is
seen when stained with a supravital stain such as
new methylene blue or brilliant crystal blue dyes.
Reticulocytosis: increased blood reticulocyte count.
Thrombocytopenia : decrease platelets number in the
blood
Thrombocytosis: increase platelets number in the
blood
1.Splenectomy (removal of the spleen), Hypersplenism
(splenomegaly) – in a number of conditions the spleen may
become enlarged.
2.Leukopenia decreased WBCs count.
3.Leukocytosis: increased WBCs count.
4.Pancytopenia: when all three cell types are decreased, which
may lead to anaemia.
5.Polycythemia which is an increasing in the Hg concentration
above 17.5 g/dl in adult males and 15.5 g/dl in adult females,
with elevated haematocrit and RBCs count.
Blood Cell Production Blood Cell Production
(Hemopoiesis)(Hemopoiesis)
Red bone marrow produces RBCs, WBCs and
platelets
Stem cells called hemocytoblasts multiply
continually and are pluripotent (capable of
differentiating into multiple cell lines)
committed cells are destined to continue
down one specific cell line
Stimulated by different Cytokines:
erythropoietin, thrombopoietin and colony
stimulating factors (CSFs).
B. Erythropoietin and Its B. Erythropoietin and Its
ReceptorReceptor : :
Cytokine – 90% is produced in the
kidney and the rest is produced in a
variety of extrarenal sites.
Necessary for erythroid proliferation
and differentiation
Absence results in apoptosis
(programmed cell death) of erythroid
committed cells
Anemia of renal failure leads to lack of
EPO
The signal that causes erythropoietin-secreting
cells to synthesize and release the cytokine is
hypoxia.
Whenever the oxygen level within the cytoplasm
of erythropoietin-producing cells falls below a
critical level, erythropoietin is synthesized in the
kidney and secreted into the bloodstream.
Once synthesized and released from the cell,
erythropoietin travels in the bloodstream to the
bone marrow, where it binds to receptors on
erythroid cells, thereby initiating their
proliferation and differentiation.
Erythrocyte Homeostasis:
Classic negative feedback control
Hypoxemia in kidneys leads to increased
EPO production
Stimulation of bone marrow
RBC count in 3-4 days
↑
Stimuli for erythropoiesis
Low levels of O2
Increase in exercise
Hemorrhaging
RBC Precursors
1.Pronormoblast or Proerythroblast.
2.Basophilic (early) normoblast
3.Polychromatophilic (intermediate) Normoblast
4.Orthrochromatophilic ( late) Normoblast
5.Reticulocyte
6.Mature Red Blood Cell
Erythrocyte Production
Erythropoiesis produces 2.5 million
RBCs/second from stem cells
(hemocytoblasts) in bone marrow
Pronormoblast has receptors for
erythropoietin (EPO) from kidneys; EPO
stimulates development of erythroblast
Erythroblasts multiply & synthesize
hemoglobin (late normoblast and
reticulocyte).
Late Normoblasts discarddiscard their nucleus to form a
reticulocyte (named for fine network of
endoplasmic reticulum)
Reticulocyte Enters bloodstream as 0.5 to 1.5% of
circulating RBCs
Development takes 3-5 days
This mechanism will involve reduction in cell size,
increase in cell number, synthesis of hemoglobin &
loss of nucleus
Blood loss speeds up the process increasing
reticulocyte count
RETICULOCYTE:
Young red blood cell; still have small amounts of
RNA present in their cytoplasm
Tend to stain somewhat bluer than mature RBC’s
on Wright stain (polychromatophilic)
Slightly larger than mature RBC
Undergo removal of RNA on passing through
spleen, in 1st day of life
Can be detected using supravital stain
Nutritional Needs for Erythropoiesis
Iron :
is key nutritional requirement for erythropoiesis
Lost daily through urine, feces, and bleeding
Dietary iron in 2 forms: ferric (Fe+3) and ferrous
(Fe+2)
Stomach acid converts Fe+3 to absorbable Fe+2
Gastroferritin from stomach binds Fe+2 &
transports it to intestine
Absorbed into blood & binds to Absorbed into blood & binds to
transferrintransferrin to travel bone marrow uses to travel bone marrow uses
to make to make hemoglobinhemoglobin, , musclemuscle used to used to
make myoglobin and all cells use to make myoglobin and all cells use to
make make cytochromescytochromes in mitochondria in mitochondria
Liver binds surplus to apoferritin to Liver binds surplus to apoferritin to
create ferritin for storagecreate ferritin for storage
2-B12 & folic acid2-B12 & folic acid (for rapid cell division).(for rapid cell division).
3-Vitamin C & copper 3-Vitamin C & copper (for cofactors for (for cofactors for
enzymes synthesizing RBCs)enzymes synthesizing RBCs)
22 - -Leukocyte Production (Leukopoiesis)Leukocyte Production (Leukopoiesis)
Committed cell types -- B and T progenitor Committed cell types -- B and T progenitor
lymphocytes and granulocyte-macrophage lymphocytes and granulocyte-macrophage
colony-forming unitscolony-forming units
Possess receptors for colony-stimulating Possess receptors for colony-stimulating
factors released by factors released by mature WBCs in in
response to infectionsresponse to infections
Red bone marrowRed bone marrow stores and releases stores and releases
granulocytes and monocytesgranulocytes and monocytes
Some lymphocytes leave bone marrow Some lymphocytes leave bone marrow
unfinished go to unfinished go to thymusthymus to complete their to complete their
development (T cells)development (T cells)
Circulating WBCs do not stay in Circulating WBCs do not stay in
bloodstreambloodstream
Granulocytes leave in 8 hours & live 5 Granulocytes leave in 8 hours & live 5
days longerdays longer
Monocytes leave in 20 hours, Monocytes leave in 20 hours,
transform into macrophages and live transform into macrophages and live
for several yearsfor several years
WBCs providing long-term immunityWBCs providing long-term immunity
(lymphocytes) last decades(lymphocytes) last decades
Granulocyte FunctionsGranulocyte Functions
Neutrophils Neutrophils
(↑ in bacterial infections)(↑ in bacterial infections)
Phagocytosis of bacteriaPhagocytosis of bacteria
Releases antimicrobial chemicalsReleases antimicrobial chemicals
Eosinophils Eosinophils
↑ ↑ in parasitic infections or allergiesin parasitic infections or allergies
Phagocytosis of antigen-antibody complexes, allergens & Phagocytosis of antigen-antibody complexes, allergens &
inflammatory chemicalsinflammatory chemicals
Release enzymes destroy parasites such as wormsRelease enzymes destroy parasites such as worms
Basophils Basophils
(↑ in chicken pox, sinusitis, diabetes)(↑ in chicken pox, sinusitis, diabetes)
Secrete histamine (vasodilator)Secrete histamine (vasodilator)
Secrete heparin (anticoagulantSecrete heparin (anticoagulant
Agranulocyte FunctionsAgranulocyte Functions
Lymphocytes (↑ in diverse infections & immune Lymphocytes (↑ in diverse infections & immune
responses)responses)
Destroy cancer & foreign cells & virally infected Destroy cancer & foreign cells & virally infected
cellscells
““Present” antigens to activate other immune cellsPresent” antigens to activate other immune cells
Coordinate actions of other immune cellsCoordinate actions of other immune cells
Secrete antibodies & provide immune memorySecrete antibodies & provide immune memory
Monocytes (↑ in viral infections & inflammation)Monocytes (↑ in viral infections & inflammation)
Differentiate into macrophagesDifferentiate into macrophages
Phagocytize pathogens and debrisPhagocytize pathogens and debris
““Present” antigens to activate other immune cells Present” antigens to activate other immune cells
(APC)(APC)
Platelet Production (Thrombopoiesis)Platelet Production (Thrombopoiesis)
Hemocytoblasts that develop receptors for Hemocytoblasts that develop receptors for
thrombopoietinthrombopoietin from from liver or kidney liver or kidney
become megakaryoblastsbecome megakaryoblasts
Megakaryoblasts repeatedly replicates its Megakaryoblasts repeatedly replicates its
DNA without dividing forms gigantic cell DNA without dividing forms gigantic cell
that remains in bone marrow called that remains in bone marrow called
megakaryocyte (100 μm in diameter)megakaryocyte (100 μm in diameter)
Infoldings of megakaryocyte cytoplasm Infoldings of megakaryocyte cytoplasm
splits off cell fragments that enter the splits off cell fragments that enter the
bloodstream as platelets (live for 10 days)bloodstream as platelets (live for 10 days)
Some stored in spleen and released as Some stored in spleen and released as
neededneeded
PlateletsPlatelets
Small fragments of megakaryocyte Small fragments of megakaryocyte
cytoplasmcytoplasm
2-4 μm diameter & containing 2-4 μm diameter & containing
“granules”“granules”
Pseudopods provide amoeboid Pseudopods provide amoeboid
movement & phagocytosismovement & phagocytosis
FunctionsFunctions::
Secrete clotting factors, growth factors Secrete clotting factors, growth factors
for endothelial repair, and for endothelial repair, and
vasoconstrictors in broken vesselsvasoconstrictors in broken vessels
Form temporary platelet plugsForm temporary platelet plugs
Dissolve old blood clotsDissolve old blood clots
Phagocytize bacteriaPhagocytize bacteria
Attract WBCs to sites of inflammationAttract WBCs to sites of inflammation