- Small, non-nucleated fragments of cytoplasm

- Small. Round or oval, biconvex cytoplasmic disc

Lecture by: ​PLEASE EDIT
Date: 2 October 2018 - Size varies from 1.5 - 3.5 ​μ​m diameter
- In blood smear: ​central purple stained granular​ (granules are
Additional Reference: numerous organelles) and ​poorly seen, pale-staining periphery
Young, B., Woodford, P., & O’Dowd, G. (2014). ​Wheaters functional
histology: A text and colour atlas ​(6th ed.)​. Philadelphia, PA: - Platelet numbers in circulating blood: 150 - 500 x10​9​ /L
Churchill Livingstone/Elsevier. - Life span: 5-10 days
- Have most organelles of other cells EXCEPT NUCLEI
OUTLINE
I. BLOOD CELL Conspicuous granules / organelles seen on EM can be
a. Types classified into:
b. Methods used to study ● Alpha granules - variable in size and shape.
II. WHITE CELL SERIES - Contain many proteins related to
a. Granulocytes adhesion, blood clotting​and growth
b. Lymphocytes and monocytes factors for ​repair
III. HEMOPOIESIS ● Dense granules - electron-dense. Contain
serotonin, ADP, ATP, Ca​++​, Mg​++
● Lysosomes - membrane-bound vesicles
BLOOD CELL found elsewhere, contain usual enzymes
(chapter 1)

TYPES
Have ​marginal band of microtubules​in peripheral
cytoplasm, associated with abundant contractile proteins actin
METHODS USED TO STUDY and myosin that forms a ​contractile system

Dense tubular system - located deep to

WHITE CELL SERIES
marginal band of microtubules, scattered throughout
cytoplasm
GRANULOCYTES
- Narrow membranous tubules with homogenous
electron-dense contents
LYMPHOCYTES AND MONOCYTES - Contain ​Ca​++​ and enzymes for ​synthesis of
lipid-mediators of platelet activation​(specifically:
CYCLOOXYGENASE and THROMBOXANE)
HEMOPOIESIS
Surface-connected canalicular system
(SCCS) - interconnected membrane channels continuous with
external environment via ​external pits​;
PLATELETS (​THROMBOCYTES​)
Granules fuse with this system to release contents to exterior

- Platelets have 50 different types of surface receptors

- Respond to vessel injury to prevent bleeding
- Active in blood clotting and tissue repair
- Exposure to damaged tissue: adhere to exposed collagen
and other basement membrane proteins via surface membrane
receptors
- Activation: ​contraction of microtubule system​and
degranulation​with release of granule contents (serotonin and
ADP)
- Released from Megakaryocytes

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- Activated platelets: produce lipid-mediator ​thromboxane
which ​signals​ the ​recruit​ adherence of additional platelets ​to
form a​ ​platelet plug
- Degranulation leads to transfer of membrane proteins ​from
storage in granule membranes​via membrane fusion ​onto
platelet surface
Important receptors:
- Glycoprotein (GP) Ib-IX-V complex,
- Platelet integrin ​α-​II-b-​β​3 (GPIIb-IIIa)
- Surface for assembly of coagulation factor enzyme
complexes are made with the Release of coagulation factors
and Ca​++​, plus exposure of negatively charged platelet lipids
- Facilitates coagulation cascade with production of ​fibrin
fibrils which ​bind the platelets together​ to strengthen the
platelet plug.
- This fibrin ​entraps red blood cells​ and results in blood clot
- ​Activated platelet:​stellate shape with long pseudopodia
- Subsequent contraction of cytofilaments = ​clot retraction ​or
pulling the plug or clot tighter
-Platelets release array of​ growth factors​to stimulate ​repair​;
platelet derived growth factor (PDGF) and
transforming growth factor beta (TGF-​β)​ among
others
- Many of platelet functional products are inherited from
parents megakaryocyte, some obtained from plasma via
membrane receptors, subsequent endocytosis, storage in
granules (eg. 5-HT or serotonin)
Reduced platelet numbers - ​thrombocytopenia​(< 20 x10​9 ​/L -
associated with spontaneous small vessel bleeding or
petechiae,​ usually in skin and bowel wall)
life-threatening situation
Genetic disorders: ​Von Willebrand disease​- defect in
von willebrand factor
(FVII-VWF) - complex adhesion molecule in
endothelium and megakaryocytes
Drugs affecting platelet function: ​aspirin (acetylsalicylic acid)
blocks enzyme clyclooxygenase, inhibiting thromboxane
production and impairs platelet function
MONOPOIESIS
- Formation of Monocytes
- Three morphological stages:
● Monoblast - mature with development of
cytoplasmic granules and start of a frosted
glass character to the cytoplasm
HISTOLOGY > MODULE 6
● Promonocytes - proliferate and mature into
monocytes. Will undertake ​2 serial
divisions​to ​produce 4 monocytes​in a
process that takes ​60 hours
● Monocytes - largest of the white cells (up to
20 ​μ​m diameter), 2% - 10% leucocytes in
peripheral blood
a) monoblast b) promonocyte c) monocyte
- Circulate for 3-4 days before migrating to tissues
- Motile cells, highly phagocytic
- Mature in tissues as ​resident Macrophages​of varying kinds
with extended lifespans
Monocytes - large eccentrically located nucleus, stains less
intensely, with more open chromatin
- Nuclear shape is variable, often with deep indentation
in nucleus near to the center of cell (​horseshoe
shape​)
- Two or more nucleoli may be visible
- Cytoplasm abundant and stains​ pale greyish-blue​ with
romanowsky methods
- Numerous ​small purple stained lysosomal granules
and cytoplasmic vacuoles​ - confer frosted glass
appearance
- EM: cytoplasm seen to contain variable number of ribosomes,
polyribosomes, and little RER
- Golgi is well developed and located with ​centrosome in
vicinity of nuclear indentation
- Small elongated ​mitochondria are prolific
- Small pseudopodia, reflecting phagocytic ability and
amoeboid movement
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- Cytoplasmic granules of monocytes are electron-dense and
homogenous
- Half resemble primary (azurophilic) granules of neutrophils
and these contain ​myeloperoxidase, acid phosphatase,
elastase, and cathepsin-G​.
- Other half are ​secretory granules​containing plasma
proteins, membrane adhesion proteins, and tumor necrosis
factor alpha​ ​(TNF-​α​)
- Monocytes are capable of ​continuous lysosomal activity
and regeneration
- Utilise ​anaerobic ​metabolic pathways (depending on o2
availability in tissue)
Monocyte function:
1. Circulate​in blood
2. Respond to chemotaxic signals​from damaged
tissue, microorganism ​inflammation​by migration into
tissues
3. Differentiation into macrophages
4. Capacity for ​phagocytosis​and content of hydrolytic
enzymes - can engulf and destroy tissue debris and
foreign material
5. Survive and prolif in tissue as ​macrophage​if they are
stimulated by growth factor - Macrophage Colony
Stimulating Factor ​(M-CSF​), granulocyte-macrophage
colony stimulating factor (​GM-CSF​) or ​IL-3​but do not
re-enter circulation
- Have receptors for chemokines and cytokines
including interferon gamma (​IFN-​γ​) - cytokine
produced by T lymphocytes.
- Can process antigen and present antigen to T cells to
promote ​adaptive immune response​.
- Can ​secrete chemokines cytokines and growth
factors​involved in inflammation, immunity, tissue
healing and repair
LYMPHOCYTES
- Central role in immunologic defense mechanism
- Produced from hemopoietic stem cells in bone
marrow
● Lymphoblast - earlier form, larger than lymphocyte
- With fine, open nuclear chromatin, few pale
inconspicuous nucleoli, scant cytoplasm
- Some mature in bone marrow as ​B cells
(bone marrow)​, others into​ T cells
(thymus)​, others into natural ​KIller T Cells (bone
marrow)
HISTOLOGY > MODULE 6
a) Inactive lymphocyte (Lc) and lymphoblast
b) large granular lymphocyte
- Lymphocytes circulate between lymphoid tissues and other
tissues of body via blood and lymphatic vessels
- Transit into tissues as part of immune surveillance
- Variable lifespan - weeks to indefinite lifespan
- Unlike granulocytes, are not end cells - can proliferate.
Proliferation occurs in tissues
- Lymphopoiesis constant and relatively inconspicuous in bone
marrow
- 20-40% of circulating leucocytes, 1.0 - 4.5 x 10​9​ /L
- ​Inactive form:​Smallest of white cells, only slightly larger
than red blood cell
Round or oval stained nucleus with clumped
chromatin
Relatively small amount of pale basophilic
non-granular cytoplasm
- Large granular lymphocytes (LGL) - Proportion of normal
lymphoid cells are larger than bigger nuclei, ​more cytoplasm,
small number of cytoplasmic granules
- Represent natural killer T or cytotoxic T lymphocytes
- State of nucleus and amount of cytoplasm depends upon
activity of cell
- ​Activated form/proliferating:​increase in size with larger
nuclei, open chromatin, visible large nucleoli, more cytoplasm
- Circulate in blood during inflammatory
Process
- Active B cells settle in tissues, mature into
long-lived antibody-secreting ​plasma cells
Disorders of lymphocytes​:
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 - Infectious mononucleosis​- viral infection due to
Epstein-Barr virus
- Manifests as lymphadenopathy (enlarged nodes) and
often prominently increased blood lymphocyte counts
(lymphocytosis)
- Marked activation / reactive changes seen in blood
lymphocytes
- Increased uniform-appearing small lymphocytes
found in ​chronic lymphocytic leukaemia (CLL)​-
common in elderly

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