Download Hematology Introduction

Introduction to
Hematology
What is hematology?
 Hematology is the study of blood.
 Blood: is the fluid where the cells
are free and suspended.
 It can cross the tissues.
 has red color.
 Has volume of 5-6 liters, this is 78% of the total body weight.
Has
PH of 7.3-7.4 (alkaline).
Specific gravity is 1.055-1.056
 It is composed of plasma (~53-58%
of the blood volume), before
clotting occurs, and serum after
clotting occurs.
Plasma consists of 91-92% water,
and 8-9%solids.
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Solids are:
Albumin.
Glucose.
Fibrinogen.
Sodium.
Calcium.
Potassium.
Cholesterol.
Magnesium.
Carbon dioxide.
Phosphorus.
Neutral fats.
 NPN group.
 Oxygen.
 Many other products.
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 Also
there are such substances, like
antibodies, hormones, complement and
enzymes.
 Cellular parts of the blood (45-47%):
 Consists of:
– The erythrocytes (RBCs) (~45%)
Contain hemoglobin
Function in the transport of O2 and
CO2
•
The Leukocytes
 (WBCs)
and platelets
(thrombocytes) (~1%)
Leukocytes are involved in the
body’s defense against the invasion
of foreign antigens.
Platelets
 are
involved in hemostasis which
forms a barrier to limit blood loss
at an injured site.
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The cells are forming about 45-47%
of the total blood volume in male and
42% in female. This percentage is
determined by centrifugation and is
known as heamatocrit (PCV), which
is the percentage of the packed red
blood cells.
Functions of the blood:
Nutritive: The blood transports
nutrients from the gut to all parts of
the body for use or storage.
2. Respiratory: the blood carries the
oxygen to the tissue and remove
carbon dioxide and other waste
products from the tissues to be
excreted by the lung, kidney, liver,
and skin
1.
3- The blood regulates the temperature of the
body, because it is constantly in motion.
4- Transportive: The blood transports the
hormones from the endocrine glands to the
tissues.
5- Excretory: To excrete the waste products of
metabolism, for example urea, and uric
acid.
6- Protection: versus invading
microorganisms
Blood Cell Production
(Hematopoiesis or hemopoiesis)
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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 production:
– Fetus: 0-2 months (yolk sac).
2-7 months ( liver and spleen).
5-9 months (bone marrow).
– infants: bone marrow
– Adults: bone marrow, ribs, sternum, skull,
sacrum and pelvis.
– Hematopoiesis in the bone marrow is called
medullary hematopoiesis
– Hematopoiesis in areas other then the bone
marrow is called extramedullary
hematopoiesis
– 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).
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Hematopoietic tissues ARE:
Includes tissues involved in the proliferation,
maturation, and destruction 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.
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1.
Erythrocyte:
•
Normal erythrocyte is a round highly flexible biconcave
discs like cell; it is non-nucleated, containing haemoglobin.
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It measures about 7.2-7.8 microns, 80-100 femtoliters in
volume
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Flexibility essential for passage through capillaries
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Life span: the average is 80-120 days.
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Function: RBC carry oxygen from the lung to the body
cells and carry carbon dioxide from the body cells to the
lung.
Terminology:
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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
(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).
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B. Erythropoietin and Its Receptor:
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
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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).
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Late Normoblasts discard 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:
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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
transferrin to travel bone marrow
uses to make hemoglobin, muscle
used to make myoglobin and all cells
use to make cytochromes in
mitochondria
 Liver binds surplus to apoferritin to
create ferritin for storage
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2-B12 & folic acid (for rapid cell division).
3-Vitamin C & copper (for cofactors for
enzymes synthesizing RBCs)
2- Leukocyte Production (Leukopoiesis)
Committed cell types -- B and T progenitor
lymphocytes and granulocyte-macrophage
colony-forming units
 Possess receptors for colony-stimulating
factors released by mature WBCs in
response to infections
 Red bone marrow stores and releases
granulocytes and monocytes
 Some lymphocytes leave bone marrow
unfinished go to thymus to complete their
development (T cells)
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Circulating WBCs do not stay in
bloodstream
 Granulocytes leave in 8 hours & live 5
days longer
 Monocytes leave in 20 hours,
transform into macrophages and live
for several years
 WBCs providing long-term immunity
 (lymphocytes) last decades
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Leukocyte Descriptions (WBCs)
 Granulocytes
– eosinophils - 2-4%
– basophils - <1%
– neutrophils - 60-70%
 Agranulocytes
– Lymphocytes (B and T cells) - 2533%
– Monocytes - 3-8%
Granulocyte Functions
Neutrophils
 (↑ in bacterial infections)
 Phagocytosis of bacteria
 Releases antimicrobial chemicals
Eosinophils
 ↑ in parasitic infections or allergies
 Phagocytosis of antigen-antibody complexes, allergens &
inflammatory chemicals
Release enzymes destroy parasites such as worms
Basophils
(↑ in chicken pox, sinusitis, diabetes)
 Secrete histamine (vasodilator)
 Secrete heparin (anticoagulant
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Agranulocyte Functions
Lymphocytes (↑ in diverse infections & immune
responses)
 Destroy cancer & foreign cells & virally infected
cells
 “Present” antigens to activate other immune cells
 Coordinate actions of other immune cells
 Secrete antibodies & provide immune memory
Monocytes (↑ in viral infections & inflammation)
 Differentiate into macrophages
 Phagocytize pathogens and debris
 “Present” antigens to activate other immune cells
(APC)
Platelet Production (Thrombopoiesis)
Hemocytoblasts that develop receptors for
thrombopoietin from liver or kidney
become megakaryoblasts
 Megakaryoblasts repeatedly replicates its
DNA without dividing forms gigantic cell
that remains in bone marrow called
megakaryocyte (100 μm in diameter)
 Infoldings of megakaryocyte cytoplasm
splits off cell fragments that enter the
bloodstream as platelets (live for 10 days)
 Some stored in spleen and released as
needed
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Platelets
Small fragments of megakaryocyte
cytoplasm
 2-4 μm diameter & containing
“granules”
 Pseudopods provide amoeboid
movement & phagocytosis
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Functions:
Secrete clotting factors, growth factors
for endothelial repair, and
vasoconstrictors in broken vessels
 Form temporary platelet plugs
 Dissolve old blood clots
 Phagocytize bacteria
 Attract WBCs to sites of inflammation
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