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Blood Blood is a tissue composed of Blood Blood is a tissue composed of

Blood Blood is a tissue composed of - PowerPoint Presentation

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Blood Blood is a tissue composed of - PPT Presentation

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

marrow cells nucleus blood cells marrow blood nucleus granules 100 size cytoplasm platelets haemoglobin rbc µm neutrophils cfu erythrocytes

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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

.

Slide2

Blood 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.

Slide3

Nutrients

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

Slide4

Erythrocytes

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.

Slide5

Erythrocytes, platelets and

neutrophils

Platelets

Erythrocytes

Neutrophil

Slide6

Erythrocytes (SEM)

Slide7

Erythrocytes in capillaries (TEM)

Slide8

Crenated

erythrocytes enmeshed in fibrin fibres

Slide9

Reticulocytes

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

Slide10

In 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).

Slide11

RBC 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.

Slide12

The 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.

Slide13

Broadly 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.

Slide14

Lymphocyte

Slide15

Monocytes

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.

Slide16

Monocyte

Slide17

3% 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.

Slide18

Neutrophil

Slide19

Eosinophils

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.

Slide20

Eosinophil

Slide21

Basophils

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

Slide22

Platelets

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.

Slide23

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.

Slide24

Platelets in a capillary

Slide25

Platelets (TEM)

Slide26

Bone 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.

Slide27

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%

Slide28

Bone marrow

Slide29

Bone marrow

Slide30

Haemopoiesis

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

Slide31

General

haemopoiesis

pattern

Slide32

Erythropoiesis

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

Slide33

Slide34

Slide35

Late erythroblast

Slide36

Normoblasts

Slide37

Granulopoiesis

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

Slide38

Oesinophilic

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.

Slide39

Eosinophilic

myelocyte

Slide40

Thrombopoiesis

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.

Slide41

Megakaryocyte

in bone marrow

Slide42

Platelet forming

megakaryocyte

Slide43

Humoral

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)

Slide44

Life 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%