Erythrocytes the red blood cells Leukocytes the white blood cells Thrombocytes the blood platelets All these are suspended in a fluid plasma Blood circulates in the vascular system and transports oxygen and absorbed ID: 912347
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Slide1
Blood
Blood is a tissue composed of
Erythrocytes
: the red blood cells
Leukocytes
: the white blood cells
Thrombocytes
: the blood platelets
All these are suspended in a fluid plasma.
Blood circulates in the vascular system and transports oxygen and absorbed
nutrients and also waste products such a carbon dioxide and the
nitrogenous wastes.
The volume of blood is between 5-6
litres
and represents 7-8% of body
weight.
Erythrocytes make up
45%
of the blood volume; referred to as
haemotocrit
.
The leukocytes and platelets make up about
1%
of blood volume.
The erythrocytes and platelets are restricted to and function within the
vascular system.
The leukocytes use the circulatory system as a means of transport and carry
out most of their functions in the connective tissue.
All cells of the blood are not true cells hence they are sometimes referred to
as the
formed elements
.
Slide2Blood plasma
Plasma is a homogeneous and slightly alkaline fluid, representing about
55% of blood volume.
Plasma consists of:
Water
– 93% by weight; is the medium for carrying all the other
constituents.
Electrolytes
– less than 1% by weight.
Na, Ca, K, Mg, CL, HCO₃, HPO₄, SO₄
Act as buffers, have a role in membrane excitability and
clotting. Keep water in the extracellular compartment.
Proteins
– 7.3g/100
Albumin
: 4.5g/100;
Globulins
: 2.5g/100 (
α
,
β
and
γ
)
Act as buffers, bind and transfer other plasma constituents (enzymes, hormones, metals, vitamins, etc.,)
immunoglobulins
.
Fibrinogen
: 0.3g/100; for blood clotting
Compliment
: group of 12 or more plasma proteins that
take part in immune reactions.
Slide3Nutrients
Glucose
: 100mg/100
Total amino acids
: 40 mg/100
Total lipids
: 500mg/100
Cholesterol
: 150-250 mg/100
Individual vitamins
: 0.0001-2.5 mg/100
Trace elements
: 0.0001-0.3 mg/100
Gases
Carbon dioxide
: 2 ml/100 ml
Oxygen:
0.2 ml/100 ml
Nitrogen
: 0.9 ml/100 ml
Waste products
Urea
: 34mg/100
Creatinine
: 1mg/100
Uric acid
: 5mg/100
Bilirubin
: 0.2-1.2 mg/100
Hormones
: 0.000001-0.05mg/100
Serum
: Plasma minus fibrinogen + other clotting factors
Slide4Erythrocytes
Lack a nucleus, Golgi complex,
centriole
, mitochondria and ER.
Shape s biconcave disc like, measuring 7.7 µm x 1.9 µm.
This shape gives greatest surface area to volume ratio.
It is 20-30% more than if it was spherical.
Shape can change and they can squeeze through the smallest capillaries.
They contain
haemoglobin
that can bind to oxygen.
200-300 million molecules of
haemoglobin
may be present per cell.
This represents 1/3 of the total weight of RBC.
Haemoglobin
is a protein with a mol. Wt of 68,000.
It consists of four polypeptide chains: two
α
and two
β
chains with an iron
containing
haem
group bound to each.
Average
haemoglobin
content is 14g/dl in females and 16g/dl in males.
Average RBC count is 5.4 million/ml in males and 4.8 million/ml in females.
The surface area of and RBC is 140² µm; in one ml it works out to be 640 mm²;
and 6litres it is 3800 m². This is nearly 2000 times the surface area of the
body.
Slide5Erythrocytes, platelets and
neutrophils
Platelets
Erythrocytes
Neutrophil
Slide6Erythrocytes (SEM)
Slide7Erythrocytes in capillaries (TEM)
Slide8Crenated
erythrocytes enmeshed in fibrin fibres
Slide9Reticulocytes
form about 0.8% of the RBC population.
They are also known as
polychromatophilic
erythrocytes
because they show a bluish-greenish tinge when stained with Wrights stain.When stained with brilliant
cresyl blue they show a delicate basophilic network in the acidophilic cytoplasm: hence reticulocytes
.RBCs in which granules of iron –containing protein (Papenheimer
bodies) are present are known as siderocytes
. The protein granules are usually removed in the spleen.
RBCGlobin
Haematin
Iron
Bilirubin
In the form of
ferritin
and
Liver
haemosiderin: taken up by macrophages and then to liver Bile Transferrin transfers circulating Gall bladder iron to bone marrow
Slide10In humans the
haemoglobin
has four different types of polypeptide chains
In adults:
96% is
Haemoglobin A (HbA) - with 2
α and 2β chains
2% is a second type (HbA2) - with 2α and 2δ
chains ˂ 2% is fetal Haemoglobin (
HbF) - with 2α
and 2γ chainsPersistance
of high levels of fetal haemoglobin results in Thalassemia
, also
known as Cooley’s anemia or Mediterranean anemia.
Anemias
: Reduction in quantity of
haemoglobin
resulting in excessive
tiredness, breathlessness, pallor and poor resistance to infection.
Secondary (Chlorotic): No of RBC normal but haemoglobin reduced. Pernicious (macrocytic): RBC No. reduced, size enlarged. Due to (Megaloblastic) lack of Vit
. B₁₂. Iron difficiency: No of RBC reduced, size is also small.
Haemolytic : Haemolysis
is faster than production. Sickle cell anemia: Abnormal haemoglobin.
β chain contains valine
instead of glutamine at position 6 (also known as Haemoglobin S).
Slide11RBC abnormalities
Polycythemia
: Increase in circulating RBC (
erthrocythaemia
. erythrocytosis
). Erythaemia: RBC count high accompanies by headache and lassitude.
Erythrocytopenia: Reduced RBC count.
Poikilocytosis: When the shape of RBC is distorted.
Anisocytosis: Variability in the size of the RBCs.
Slide12The leukocytes (White Blood Cells)
Leukocytes are true cells, show
ameboid
locomotion and lack
haemoglobin.They arise, function and die outside the circulatory system.The average number is 8000/ml (6000 – 10,000/ml).
The WBC:RBC ratio is 1:600.Their numbers may higher at birth ranging from 15,000 – 18,000/ml.
Leukocytes can be broadly categorized into two groups i
) Agranulocytes: comprising of lymphocytes and monocytes
. ii) Granulocytes: comprising of neutrophils,
eosinophils and
basophils.Lymphocytes
Average size 7-8 µm (7-12µm); average count is 20-25% (20-35%)
can go up to 45%.
Nucleus large, spherical, may have a dent, chromatin is dense.
Cytoplasm is basophilic and homogeneous.
Ribosomes
abundant, mitochondria few, Golgi complex small,
ER sparse. Move by sending out broad pseudopodia with nucleus in front.
Slide13Broadly two types of lymphocytes are known.
B lymphocytes (B cells) are precursors of plasma cells that produce
the circulating antibodies (
immunoglobins
) against antigens.
B cells react to antigens, migrate to the lymph organs and multiply, producing a clone of sensitized B. cells. These then return to the connective tissue and differentiate into
plasma cells and secrete antobodies into the body fluids (
humoral antibody response; humoral
immunity). T lymphocytes (T cells) react to grafts, fungal and viral infection
by producing i)
cytotoxic T cells (killer cells) which cause lysis
ii) active chemical agents – lymphokines T cells also form memory cells, suppressor cells, amplifier cells and
helper T cells.
Slide14Lymphocyte
Slide15Monocytes
These are large cells, 12-15 µm (9-12 µm)m may reach 20 µm.
They represent a small fraction of the WBC, usually 3-8%.
The nucleus is ovoid, kidney or horse-shoe shaped and
eccentri
-
cally placed with fine chromatin. The cytoplasm appears vacuolated or reticulated.
Movement is by ameboid motion by producing numerous small pseudopodia.
Promonocytes give rise to macrophages for
phagocytosis.Neutrophils
These cells account for the largest population of WBCs. Average numbers range fro 60-70% but may vary from 50-75%.
Their average size is 9-12 µm. Their count is 3,000-6,000/ml which is equivalent to 20-30 billion cells in circulation at any time.
The nucleus is polymorphic with three to five lobes.
Slide16Monocyte
Slide173% of female
neutrophils
have a Barr body or heterochromatin.
Cytoplasmic
granules are neutrophilic and of two types. Primary granules (
azurophilic) develop in the promyelocyte stage
and contain peroxidase, acid phosphatase
and β glucoronidase
Secondary granules (specific) develop in the myelocyte
stage and contain alkaline phosphatase,
hydrolases, antobacterial
lysozymes
,
lactoferin
,
collagenase
and a poorly
characterised
protein, phagocytin. Neutrophils also secrete leukotrienes which i) promote adhesion of neutrophils to endothelium.
ii) attract other neutrophils, monocytes and
eosinphils. iii) dilate capillaries and cause edema.
Slide18Neutrophil
Slide19Eosinophils
Average number 2-4% (1-3%), average size 10-14 µm, larger than
the
neutrophils
.
For one eosinophil
in blood there are 300 in the tissues. Nucleus large with two or three lobes. Cytoplasmic
granules large, coarse, refractile, membrane bound
Granules have a dense bar or crystalloid surrounded by matrix. Common in the connective tissue of the intestinal mucosa. Increase during allergy, e.g. hay fever, asthma, skin diseases and
parasitic infections. Produce histaminase which moderates the response to allergic
stimuli. Also produce peroxidase
, acid phosphatase, β
glucoronidae
, etc.
Eosinophil
Slide21Basophils
These are the least common of the WBCs, represented by just 0.5-1% cells.
Small in size, 8-10 µm.
Nucleus large, irregularly
lobulated
. Cytoplasm with coarse granules of uneven size.
Produce heparin and histamine. Increase in small pox, chicken pox and sinus inflammations. Total number in body approx. 200 million.
Basophil
Slide22Platelets
Platelets are
bicovex
discs in the living state, measuring 2-4 µm
in diam.
They arise from fragments of megakaryocytes.
Average number is 1,50,000 – 3,00,000/ml Mammalian platelets are anucleate
and occur only in mammals. In lower vertebrates they are nucleated and called thrombocytes.
Their structure consists of a central granulomere (chromomere
) and a peripheral hyalomere.
The hyalomere contains more actin
and myosin than any other cell except the muscles. The granulomere contains
ribosomes
and scattered particles of glycogen.
They also have a system of slender
anastomosing
tubules, thought to be residues of the ER.
A conspicuous feature of the
granulomere
is the presence of membrane bound granules about 0.2 µm in diam.
These are the
alpha granules
that contain i)
platelet factor IV which counters the anticoagulant heparin. ii)
von Willebrand factor that facilitates adhesion of platelets to the vessel wall.
iii) platelet derived growth factor that stimulated fibroblasts to
proliferate and contributes to the repair of the damaged vessel. iv) thrombospondin that is involved in platelet aggregation in
blood clotting. In species other than man there is a second category of granules.
These are called beta granules. They contain
serotonin, ATP and ADP
all potent promoters of
platelet aggregation.
Slide24Platelets in a capillary
Slide25Platelets (TEM)
Slide26Bone marrow and
haemopoiesis
Bone marrow
Bone marrow occupies the cavities of the of the long bones,
spongiosa
of the ribs, sternum, vertebrae and the flat bones of the cranium and girdles.
It represents about 4-6% of the body weight and its volume is equal to that of the liver.Marrow is made of up precursors of blood cells, macrophages, adipose cells,
reticular cells and reticular fibres.Proportions of the different cell types vary with different regions of the skeleton and also with age.At birth the marrow is deep red but gradually changes (after about 4-5 years)
to yellow as the number of adipose cells increase.In adults, red marrow is found in the proximal end of the humerus
and femur, vertebrae, ribs, sternum and the ilium of the pelvis.
In the marrow cavity, the
marrow or myeloid tissue
, has no independent
blood supply.
It receives blood that has passed through the osseous tissue.
Fine branches from the periosteal and endosteal arteries enter the marrow spaces.
Here they communicate with the capillary beds of the marrow through sinuses.Each day about
200 billion RBCs and 10 billion neutrophils are produced
in the marrow, and represents the numbers destroyed.The haemopoietic cells of the bone marrow consist of:
Granular leukocytes: about 60% (40% developing; 20% mature)
Lymphocytes, monocytes and megakaryocytes
: about 10-20% Erythrocytes: about 20-30%
Slide28Bone marrow
Slide29Bone marrow
Slide30Haemopoiesis
The
haemopoietic
stem cells in the marrow are the
P
luripotential Haemopoietic
Stem Cells (PHSC).
They proliferate and can differentiate into all blood cell types.In the marrow they represent just about 0.2% of the marrow cells.They differentiate into progenitor cells or
Colony Forming U
nits (CFU). These have a more limited potential for differentiation.CFUs may be multipotential, bipotential
or monopotential. CFU – GEMMe
is multipotential CFU – GM
is
bipotential
CFU –
G
, CFU –
M
, CFU –
Eo, CFU – Me are monopotential
Slide31General
haemopoiesis
pattern
Slide32Erythropoiesis
Proerythroblasts
:
Produced as a result of CFU proliferation
About 16 um in size with a rim of basophilic cytoplasm around nucleus. One large nucleolus or two nucleoli present. Divide and produce smaller basophilic erythroblasts
Basophilic erythroblasts
:
Cytoplasm basophilic. Nucleus with heterochromatin. Synthesis of haemoglobin commences. Divide and give rise to polychromatic erythroblasts
Polychromatic erythroblasts:
Smaller in size; chromatin is condensed. Cytoplasm blue, grey or olive green in colour. Nucleolus is absent. Last of the developing cells capable of division.
Orthochromatic erythroblasts (normoblasts
): Cytoplasm pink, chromatin core condensed. Nucleus quite small and eccentric. Finally the nucleus is extruded and an erythrocyte is produced.Young erythrocytes are
polychromatophilic
and known as
reticulocytes
Slide33Slide34Slide35Late erythroblast
Slide36Normoblasts
Slide37Granulopoiesis
Myeloblasts
:
they represent the
granulocte
precursors.
Abour 16 um in size, with a large nucleus and dispersed chromatin. Nucleolii
multiple.Divide and increase in size. When granule synthesis starts they transform into promyelocytes
.Promyelocytes:
Nucleus is indented, cytoplasm is basophilic and azurophilic
granules present.These two stages are common to
neutrophils, oesinophils and
basiphils
Neutrophilic
myelocyte
:
Small in size. Nucleus shape is variable and chromatin is condensed. A second type of granule – specific granules– arise at this stage.
Cell division ceases at this stage.Metamyelocyte: Nucleus deeply indented. Specific granules represent 80% of granule population. Finally the nuclear morphology changes by constricting at several places.The time required for the formation of a
neutrophil is about ten days
Slide38Oesinophilic
myelocytes
:
Nucleus with a coarse pattern of chromatin with peripheral clumps. Cytoplasm basophilic and specific granule
oesinophilic and larger than those of neutrophilic
myelocyte.
Metamyelocyte: Nucleus indented and finally becomes bi- or
trilobed . Specific granules begin to develop crystalloids.
Basophilic myelocytes:
Nucleus with little condensed chromatin and paler staining. Cytoplasm basophilic.Monopoiesis
Monoblasts
:
They are the precursor cells. Divide and give rise to
promonocytes
.
Promonocytes
:
Some differentiate rapidly into monocytes. Others form slow renewing precursor cells in the marrow.From stem cells to monocytes it takes about 55 h.
Slide39Eosinophilic
myelocyte
Slide40Thrombopoiesis
Megakaryoblasts
:
Arise from CFUs. Cells large with round nucleus. Chromatin is loose and nucleoli indistinct. Cytoplasm basophilic without granules. Increase in size following nuclear division only and become
polyploid
with 4n (1.6%), 8n (10%), 16 n (71.2%), 32 n (17.1 %), 62 n (0.1%)
Promegakaryocytes:
30-50 um in size Azurophilic granules appear and form the reserve
megakaryocyte.Reserve
megakaryocyte: Not yet active in platelet formation. Nucleus large and multilobular
. Azurophilic granules uniformly distributed in central cytoplasm but absent in periphery. Size from 50-70 µm
in diam.Platelet forming
megakaryocyte
:
Azurophilic
granules in groups separated by granule free cytoplasm. Nucleus multi-lobed. Chromatin coarse, nucleoli multiple but indistinct. Cytoplasm homogenous. Membrane limited tubules intersect and partition the cytoplasm. May produce 4000-8000 platelets.
Slide41Megakaryocyte
in bone marrow
Slide42Platelet forming
megakaryocyte
Slide43Humoral
regulation of
haemopoiesis
Erythropoiesis
stimulating factor – erythropoietin
Secreted from the kidneys- in the JG apparatus.
Erythropoietin secretion is inversely related to oxygen tension.For normal numbers to be maintained:
1) continuing stimulation of marrow 2) marrow capable of responding 3) adequate supply of iron
For leukocyte production:
Colony Stimulating Factors (CSF)CSF may be multipotential
, bipotential or unipotential
CFU – GEMMe (Multi CSF also known as interleukin 3)
CFU – GM (Bi
potentail
GM - CSF)
CFU - G (
Unipotential
G-CSF)
CFU – M (M- CSF)
Slide44Life span of leukocytes and platelets
Neutrophils
: 6-12 h in blood, then to tissues, live for a few days.
Eosinophils
: 6-12 h in blood, then to tissues, live for 8-12 days.
Lymphocytes: 8 h in blood, then to tissues, live for a few months to a few years.Monocytes: 1-2 days in blood, then tissues, survive for many months.
Platelets: In blood stream, survive for 9-10 days.Granulopoiesis
cell populationsStem cells: Less than 0.1% of nucleated cells of marrow.Myeloblasts: 2% of nucleated marrow cells.
Promyelocytes: about 5% of nucleated marrow cellsMyelocytes: about 12% (
neutrophils, oesinophils and
basophils)Metamyelocytes: 22%