BLOOD

BLOOD Chapter 4

BLOOD
Blood Is a special type of connective tissue. (Mesenchymal in origin).

BLOOD ELEMENTS 45% PLASMA 55%

• Red blood corpuscles [erythrocytes] • Water 90%
• White blood cells [Leucocytes] • 9% organic compounds e.g.
• Platelets [Thrombocytes] Proteins & Hormones ...
• 1% inorganic salts: Ca, Mg …

ERYTHROCYTES OR RED BLOOD CORPUSCLES (RBCS):

 Origin: Red bone marrow.
 Shape:
« Non-nucleated.
« Biconcave disc-shaped cells in side view.
« Rounded in top view.
« Thick periphery 2.2 µm - thin center of 0.8 µm.
« In slow circulation: RBC's adhere to each other like
pile of coins (rouleaux appearance) due to high
surface tension. Which is non-permanent.
9 These long chains of RBCs sediment more easily.
9 This is the mechanism for increased "Erythrocyte
Sedimentation Rate"(ESR),which increases
nonspecifically with inflammation.
Abnormal Shapes: due to changes in the cell membrane or Hb.
« Spherocytes (spherical)
« Ovalocytes (oval in shape)
« Sickle cell (crescent-shaped)
« Poikilocytes (pear-shaped) RBCs.
They are more fragile & more prone to hemolysis causing anemia.

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 Size: The normal diameter of an RBC ranges from 6 -9 µm with a mean of 7.5 µm.
Abnormal sizes:
« Microcysts RBCs (less than 6 pm)
« macrocytic (more than 9 pm)
« Anisocytosis (different sizes).
 Color:
« Unstained blood film. RBCs appear colored due to Hb.
« blood film stained with Leishman’s stain, the erythrocytes appear acidophilic
(Hb is a basic protein), with pale center (Normochromic RBCs)
 Structure and composition:
« Mature RBC lack nucleus and organelles. giving more space for hemoglobin.
« RBC cytoplasm contains about:
9 66% water
9 33% hemoglobin (Hb) which appears electron-dense & homogenous.
9 1% Enzymes as: carbonic anhydrase and Hb reductase.
« RBCs are surrounded by flexible lipoprotein cell membrane.
9 Inner surface cell membrane is associated with cytoskeleton protein to
maintain the biconcave shape of RBC.
9 Outer surface is covered by carbohydrate-rich glycocalyx (call coat) which is
responsible for blood grouping (A, B, AB, O) & Rh factor.
 Number: Erythrocytic count is the number of erythrocytes per mm³ of blood
« In male: 5 – 5.5 million/mm³ due to the stimulatory effects of male hormones
on the bone marrow.
« In female 4.5 - 5 million/mm³ due to menstruation and estrogen.
« RBC count is highest in the newborns and decreases gradually.
Abnormality in number of erythrocytes:
1. Anemia (oligocythemia): it is the decrease of RBCs count below normal and a
significant decrease the amount of Hb in the blood below normal level
Types of anemia: Deficiency & Pernicious & Aplastic & Hemorrhagic & Hemolytic
; Pernicious anemia: (Vitamin B12 deficiency anemia) due to failed production
of intrinsic factor by the stomach.
; Aplastic anemia: destruction of the bone marrow e.g. by irradiation or
chemotherapy leading to pancytopenia (decreased count of all blood cells)
; Sickle cell anemia: an abnormal rigid type of Hb. called (HbS) that
accumulates at one side of the cell giving a crescent shape (Sickle RBCs).

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2. Polycythemia: it is the increase in the number of RBCs above 6 millions/ mm3

Cause : due to hypoxia that stimulates the bone marrow. It may be:
; Physiological e.g. high altitudes, muscular exercise, newborns.
; Pathological e.g. chronic lung and heart diseases.
 life span of erythrocytes: about 120 days
 fate:
« Old RBCs are phagocytosed by macrophages in the liver, bone marrow & spleen.
« It is excreted as bile pigments while Iron is reused to form new RBCs
 Osmotic Pressure (O.P): RBCs are osmotically fragile. They maintain their shape
only in isotonic solution, (0.9% NaCl [saline] = O.P of plasma)
« Crenation; in a hypertonic solution, they shrink and show notches.
« Hemolysis; in a hypotonic solution, they swell, burst and leak hemoglobin.
Leaving cell ghost.
 Functions or erythrocytes:
1. Transfer gases (oxygen and carbon dioxide) between the alveolar air & tissue
2. acid-base buffer playing a role in controlling the hydrogen ion concentration
in the blood.
 Structure function adaptation of erythrocytes:

Factor Mode of adaptation

• Plasticity (Flexible) to be squeezed inside narrow vessels.
Plasma lemma • Lipoproteins are highly selective for gas exchange & prevents
escape of Hb outside the cell..
• Biconcave to increase surface area for gases exchange & to give
Shape more space for Hb
• Rounded edge for easy flow & passage in BVs.
• No nuclei or organelles to give more space for Hb
Content • Contain enzymes (Hb. Reductase & carbonic anhydrase) to carry
O2 & CO2

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LEUCOCYTES OR WHITE BLOOD CELLS (WBCS)

They are true cells having nuclei and organelles.
 Leucocytic count
« Total leucocytic count : total number of WBCs/mm3 = 4000-11000 cell/mm³
« Differential leucocytic count: the percentage% of each type to the total count
 Abnormalities in total count:
« Leukocytosis: ↑↑ total No .of WBCs > 11,000/mm3 due to.
; Physiological: pregnancy, labor, cold bath & exercise.
; Pathological: infections
« Leukopenia; ↑↑ No of WBCs < 4,000/mm3 due to:
; X-ray - irradiation
; some antibiotics e.g. chloramphenicol
; Typhoid fever
; Influenza virus
; Leukemia = cancer with very high leucocytic count & abnormal and
immature WBCs

WBCS

GRANULAR NON-GRANULAR
• Neutrophils • lymphocytes
• Eosinophils • monocytes.
• basophils

• Bacterial infection → neutrophils

neutrophils ‫ا كترهم فى العدد‬
basophils ‫اقلهم فى العدد‬
monocytes ‫أ كبرهم فى الحجم‬
small lymphocytes ‫أصغرهم فى الحجم‬
• Parasitic infection → eosinophils
• • Viral infection & chronic diseases
• → lymphocytes
• • Allergy → basophil - eosinophils
• • Acute inflammation → neutrophil
• Chronic inflammation →
monocyte - lymphocyte

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1 Granular Leucocytes:
1- Neutrophils = Polymorphnuclear leucocytes = PMNLs = microphages
 %: 60-70%
 Shape : Rounded cells,
 Diameter:10-12 µm.
 Life span: few days
 By LM:
; Nucleus:
« Single - Multilobed (3:5 lobes) - segmented - dark - connected by
chromatin strands.
« Barr body seen in 3-6% of female cells.
; Cytoplasm: they show:
1. Specific granules: numerous – pale granules.
2. Non specific (azurophilic granules): few - purple with azure dye.
 By EM:
; Nucleus: Peripheral heterochromatin with small central euochromatin
; Cytoplasm:
« Pseudopodia - Few organelles.
« Two types of granules:

Specific granules(2ry) granules: Non specific Azurophilic granules(1ry):

; Small - many - pale ; Large - few - dark.
; Contain ; lysosomes containing:
1. Phagocytin 1. Myeloperoxidase
2. Lysozyme 2. Defensins against bacteria, fungi
3. Collagenase & viruses
4. Lactoferrin.

 Functions: First line of defense against bacteria.

1. Phagocytose bacteria: (microphages) the attack bacteria:
; First: by specific granules:
« Lactoferrin: binds to iron [Bacteriostatic]
« Phagocytin: kill bacteria [bactericidal]
« Lysozyme: destroys bacterial proteins.
« Collagenase: destroys collagen for movement of neutrophils

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; Second: by non specific (azurophil granules):

« Myeloperoxidase kill bacteria
« other enzymes cause their lysis.
2. Dead neutrophils form pus cells.
3. Pus increases body temperature (pyrogen).
4. Attract monocytes to site of infection.
5. Stimulate bone marrow to form more neutrophils.
6. Secrete trephone substance: help healing of wounds.
 Pathological increase: (neutrophilia) e.g.: acute pyogenic infections (tonsillitis
- appendicitis – abscess).
 Pathological decrease: (neutropenia) e.g.: Influenza virus - TB - typhoid fever.

Eosinophils
% 1-4%
Diameter 10-14 µm
Life span Few days
Nucleus:
« Peripheral heterochromatin
« More central euochromatin
than neutrophil.
Cytoplasm: few organelles & two
types of granules.
1. Specific granules:
« oval
« electron dense core
EM (internum)& less dense
periphery (externum)
« contain:
9 histaminase,
9 sulphatase
9 neurotoxin
2. Non specific (Azurophilic
granules): smaller - less.
lysosomes containing
hydrolytic enzymes.
Basophils
0-1%
10-12 µm
Few days
Nucleus:
« Minimal peripheral
heterochromatin
« More central euochromatin.
Cytoplasm: few organelles &
two types of granules:
1. Specific granules:
« large, rounded.
« electron dense contain
9 heparin.
9 Histamine
9 eosinophil chemotactic
factors.
9 leukotrienes.
2. Few Non specific (Azurophilic
granules): (lysosomes):
contain hydrolytic enzymes.
MCQ? Cell membrane shows
receptors for IgE.

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Nucleus:
Nucleus: « irregular, segmented, pale
« S shaped.
« bilobed or
« horse-show Cytoplasm:
LM « large basophilic granules
Cytoplasm:
masking the nucleus.
« large, refractile & acidophilic
« Metachromatically stained
granules.
with toluidine blue → purple
(due to presence of heparin)
1. Termination of allergic 1. Secrete Heparin prevents
reaction clotting & promotes allergy
a. Histaminase & sulphatase 2. Secrete Histamine
destroy histamine & heparin. vasodilatation causing sudden
b. Phagocytose the Ag-Ab ↓↓ in blood Pressure →
Complexes anaphylaxis
Function
2. Defense against parasites. 3. Attract eosinophils to site
a. Cytotoxic effect of basic of allergy by Eosinophil
proteins forming pores in chemotactic factor
their bodies. 4. Leukotrienes: Bronchospasm
b. Neurotoxins causing nervous causing BA.
dysfunction of parasites 5. Limited phagocytic power
1. Allergic diseases.
Increase 1. allergy 2. Parasitic diseases.
in umber 2. parasitic infection. 3. Viral infection (chicken pox).
4. Liver cirrhosis.
Decrease
Cortisone therapy
in number
 Comparison between Basophils and Mast Cell

Basophils Mast cells

Life span Few days Longer (weeks to months)
Size 10-12 um 20-30 um
the Nucleus Segmented Round
Phagocytosis Slight No
Granules Metachromatically stained due to (Histamine &heparin)
Surface receptors: Antibody Ig E

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2 Non-Granular Leucocytes:
1. Lymphocytes (2nd common of WBCs & 2nd line of defense)

 Number: 20-30% of total leucocytic count.

 Types of lymphocytes according to Size:
1. Small lymphocytes: 2. Large lymphocytes:
Inactive Active or NK cells
% 15-20% 5-10%
diameter 6-8 µm 10-15 µm
Nucleus: Dark & filling the cell
Nucleus: larger slightly indented,
By LM: Cytoplasm: Little, pale pale with clear nucleolus
basophilic rim around the
Cytoplasm: abundant basophilic
nucleus.
Nucleus:. Euchromatic with
Nucleus: heterochromatic
prominent nucleolus
Cytoplasm:
Cytoplasm.: more organelles:
9 few mit.,
By EM: 9 mit.,
9 small GA,
9 ribosomes,
9 many free ribosomes,
9 rER,
9 two centrioles
9 G.A.
9 small azurophil granules
9 lysosomes
 Abnormalities in number:
« Lymphocytosis: increase> 30%
; physiological in children.
; Chronic infections e.g. T.B & whooping cough.
; Leukemia.
« Lymphocytopenia (pancytopenia): decrease<20%
 Motility & distribution:
« Actively motile,
« continuously circulating between the blood & lymphatic organs where they
settle
« They are the only cells which can return to blood.
« Found in blood, lymph & lymphatic tissue.

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 Types of lymphocytes according to function:

B lymphocytes T lymphocytes Natural killer cells
% 20-30% 60-80% 5-10%
develop from precursors of T
Maturation bone marrow Thymus & B cells but do not mature
in thymus
Few days to
Life span Years Years
months
Surface T cell receptors.
Ig receptors CD16.
receptors (CD4 - CD8)
« Innate Immune response.
Humoral Cell mediated
Function « Similar to T cytotoxic.
immunity immunity
« Antiviral (interferon).

T lymphocytes (types & functions)

1-Cytotoxic CD8 T-cells (cell-mediated Immunity):

« Secrete perforins that form pores in the cell membrane of the cells directly
killing them.
« Attack : virally infected cells – neoplastic cells – transplanted cells.
2-Helper CD4T-cells:
« Activate B-lymphocytes.
3-Regulatory (Suppressor) T-cells:
« Suppress the immune response to self-antigen.
« Suppress excessive immune response.
4-Memory T-cells:
« Rapid response of T-cells on re-exposure to same Ag (2 nd immune response)
B lymphocytes
« activated by T- helper cells to Plasmablasts then plasma cells to produce
antibodies. (Humoral immunity)
« B memory cells responsible for the rapid (2 nd immune response).

HIV
Human Immunodeficiency virus that causes AIDs destroys the T- helper cells
suppressing immunity & the patient becomes susceptible to infections

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2. Monocytes

 Number: 3-8%
 Diameter: 20 µm (the largest).
 Life span: 3 days s in blood& 3months in CT.
 By L.M:
« Nucleus:
; Large,
; eccentric
; kidney-shaped
; pale with 1 or 2 nucleoli
« Cytoplasm
; non-granular
; non- clear
; Pale basophilic.
; frosted glass appearance due to lysosomes (azurophil granules).
 By L.M:
« Nucleus: Euchromatic with clear nucleolus
« Cytoplasm :
; Have pseudopodia,
; well-developed G.A. in the concavity of the Nucleus.
; Many lysosomes (1ry & 2ry).
; rER- ribosomes – mitochondria.
 Functions: Highly phagocytic cells:
1. Phagocytose bacteria & debris.
2. Antigen presenting cells.
3. The precursors of all phagocytic cells: e.g.
« dust cells of lungs
« Kupffer cells of liver
« osteoclasts of bone
« microglia of CNS.
 Monocytosis: Increase > 8% due to
1. chronic infections; T.B., syphilis & glandular fever
2. monocytic leukemia.
 Monocytopenia: pancytopenia

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BLOOD PLATELETS (THROMBOCYTES)

 Number: 200,000 - 400,000 /mm³
 Shape: small oval cell fragments.
 Origin: megakaryocytes.
 Size: are 2-4 µm in diameter.
 They lack nuclei.
 Cytoplasm:
« By L.M: 2 zones:
; Hyalomere: peripheral pale basophilic (clear) zone.
; Granulomere: Central dark granular zone
« By E.M: platelets show:
; thick cell coat that help platelets aggregation.
; hyalomere contains:
1- Cytoskeleton;
« Microtubules to maintain cell shape.
« Actin microfilaments help platelets to change their shape & aid clot
retraction.
2-Membranous Channels
« open canalicular system: to release serotonin (VC of injured vessel)
« dense tubular system: store for Ca++
; Granulomere contains:
« Few mitochondria, ribosomes, glycogen (energy)
« 3 types of granules:
1. Alpha (specific granules): contain clotting factors & growth factors
& Ca++.
2. Delta granules(Dense bodies) contain serotonin, ATP & ADP
3. Lambda granules are lysosomes for clot removal after healing of
the vessel.
 Purpura = thrombocytopenia:
« Decrease in number of platelets < 50.00/mm due to
; decreased production (Bone marrow depression) or
; increased breakdown (autoimmune disease)
« Characterized by:
; Prolonged bleeding time
; Excessive bleeding after minor trauma

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Bone Marrow (Myeloid tissue)

 Types:

Red Bone Marrow (active) Yellow Bone Marrow (inactive)

« Present in most bones of children « In shafts of long bones of adults
« flat, short & irregular bones of adults « A store for fat
« can change into active on need

 Structure of red bone marrow:

« 1- Stroma:
; Fixed cells:
« Reticular cells together with reticular fibers form a network in the
background,
« fat cells (the largest cells),
« undifferentiated mesenchymal cell (UMCs),
« fibroblasts,
« pericytes
« osteogenic cells.
; Blood Sinusoids: Wide irregular blood capillaries
« lined by endothelial cells with non-continuous basement membrane.
« Through their pores, blood cells leave to blood.
« 2- Free cells:
; These are the developing stages of all blood cells.
; The ratio of the immature WBCs to immature RBCs is 5:1 as the life span
of most WBCs is much shorter than that of RBCs.

; Donation and transplantation of BM: In leukemia, haemopoietic stem

cells taken from a donor are infused into the same or another person.
; Bone marrow Aspirate or biopsy to diagnose disorders e.g. aplastic
anemia or leukemia

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