THE ROLE OF THE

BLOOD VESSELS IN
HEMOSTASIS
Mary Grace R. Agustin
Structure of Blood Vessels
Vascular system consists of:

Capilllaries
Arteries and Veins
CAPILLARIES
 Small structures
consisting of a
supportive
basement
membrane to
which a single
layer of
endothelium is
tightly
anchored
ARTERIES AND VEINS
Consists of 3
layers:
1. Tunica Intima
2. Tunica
Media
3. Tunica
Adventitia
Tunica intima
– Inner endothelial lining
– Separates blood cells from sub-
endothelium
Composed of:
a. Basement membrane
b. Elastic connective tissue
- Endothelial cells deposit von Willebrand
factor in the sub-endothelial matrix when
vWF binds to collagen
Tunica media
– Middle layer of the vessel lining
- Thickest coat
Composed of:
a. Smooth muscle cells (constrict or dilate)
b. Connective tissue
c. Collagen fibers
d. Occasional fibroblasts
Tunica adventitia

outer part of the vessel wall

Composed of:
a. Fibroblast
b. Connective tissues
c. Collagen Fibers
CHARACTERISTICS ARTERIES VEINS CAPILLARIES

Direction of Blood Carries blood from Carries blood from Carries blood
Flow heart -> organs organs -> heart arterioles ->
venules

Valves (Prevent Absent Present Absent

backflow) (Except in
pulmonary artery)

Size/Structure of Thick (3 layers) Thin (3 layers) Very thin (single

Wall layer)
CHARACTERISTICS ARTERIES VEINS CAPILLARIES

Layer of Elastic & Thick Thin Absent

Muscle Tissue

Lumen Narrow Wide Very narrow

Oxygen Content Oxygenated Deoxygenated Oxygenated ->

arteriole
Deoxygenated ->
venule
Color Red Bluish-red Bluish-red

Location Deep in muscle Nearer to body Inside all tissues

surface
Endothelium

Contains connective tissue such as

collagen and elastin
Regulates the permeability of the inner
vessel wall and provides the principal
stimuli to thrombosis following injury to a
blood vessel
Substances Released from Endothelial
Cells:
von Willebrand factor (vWF)- For platelet
adhesion
Tissue plasminogen activator (tPA)- Converts
plasminogen to plasmin
Thrombomodulin- Binds & inactivates
thrombin
Prostacyclin (PGI2)- inhibits platelet activation
Substances Released from Endothelial
Cells:
Nitric oxide- Inhibits platelet aggregation and
adhesion
Heparan sulfate- Enhances activity of anti-
thrombin III
CD39/CD73- Conversion of ATP/ADP to AMP
13-HODE (13-Hydroxyoctadecadienoic acid)-
inhibits platelet adhesion
Events Following Damaged Vessel
1. Vasoconstriction occurs as a neurogenic
response during blood vessel injury.

2. Collagen exposure initiates the contact

phase of coagulation known as the
intrinsic coagulation pathway.
Events Following Damaged Vessel

3. Tissue thromboplastin is released which

promotes coagulation through a series of
reactions known as the extrinsic
coagulatioln pathway

4. Vessel injury initiates fibrinolysis through

endothelial cell release of tissue
plasminogen activators (tPAs)
• In physiologic response to vessel
Injury, 4 steps in hemostasis are initiated
sequentially:
1. Vasoconstriction
2. Platelet activation
3. Coagulation
4. Fibrinolysis
 HEMATOPOIESIS
❑ Blood cell formation and development.
❑ Cellular formation, proliferation, differentiation,
maturation of blood cell.

HEMATOPOIETIC TISSUES:
฀ Organs and tissue areas in which blood cell production or
regulation occurs.
฀ Fetal hematopoiesis, spleen, lymphatic tissues, and bone
marrow.

PHASES:
a) Mesoblastic
b) Hepatic
c) Myeloid
 HEMATOPOIESIS
a) MESOBLASTIC PHASE
PoZeGa
GoZE
GAE

NOTE!
 HEMATOPOIESIS
b) HEPATIC PHASE
▪ Primary sites: FETAL LIVER
▪ Blood cell formed: Hb F: 2a 2g
- ERYTHROCYTES: still produced
- GRANULOCYTE AND
MEGAKARYOCYTE: 3RD month of NOTE!
gestation
- LYMPHOCYTE: 4 monthTH

- MONOCYTE: 5TH month

▪ Mid-fetal life: SPLEEN AND LN- limited role as
secondary lymphoid organs
- remain active in producing lymphocytes
throughout life.
▪ FETAL HEMOGLOBIN: 4TH month of gestation.
 HEMATOPOIESIS
c) MYELOID PHASE
▪ Primary sites: BONE MARROW Chief site
- Hematopoiesis begins to decrease hanggang
by the last trimester mamatay
(birth-death)
▪ ADULT HEMOGLOBIN
Hb A1: 2a 2b NOTE!
Hb A2: 2a 2d
 HEMATOPOIESIS
PRODUCTION OF SPECIFIC CELLS

❖GRANULOPOIESIS:2 ❖ LYMPHOPOIESIS:
ND month gestation 4TH month

❖MEGAKARYOPOIESIS2N ❖ MONOPOIESIS:
D month of gestation 4TH month
 HEMATOPOIESIS
HEMATOPOIETIC STEM CELL AND CYTOKINES
 HEMATOPOIESIS
HORMONES AND CYTOKINES OF MEGAKARYOCYTOPOIESIS

❖THROMBOPOIETIN (TPO)
• a 353-amino acid protein located on chromosome 3q27
• Primary signal for megakaryocyte production
• Has multilineage effects in hematopoiesis, not only stimulating
megakaryocytopoiesis but also acting in synergy with other cytokines and
hormones to enhance proliferation and survival of committed erythroid
progenitors and primitive HSC.

❖ OTHER CYTOKINES AND HORMONES:

a) Include stem cell factor also called kit ligand or mast cell growth factor;
b) GM-CSF
c) G-CSF
d) Acetylcholinesterase-derived megakaryocyte growth stimulating peptide.
 HEMATOPOIESIS
MEGAKARYOCYTE GROWTH INHIBITORS:
a) pPF4
b) B- thromboglobulin
c) Neutrophil-activating peptide 2
d) IL-8 and other factors
e) Reduction in the transcription factors FOG1,
GATA-1 and NF-E2 diminish megakaryopoiesis
at the progenitor, endomitosis and terminal
maturation phase.
 MEGAKARYOPOIESIS
❑Platelets are produced DIRECTLY
from MEGAKARYOCYTE
CYTOPLASM.
❑ MK matures=cluster of granules
aggregate to form platelets.

฀Platelets undergo endomitosis

(DNA replication without cell
division) and that nucleus is
polyploidy which means that it
contain an increased number of
chromosomes over the normal
diploid number (2N to 64N)
฀ PLOIDY: the number of
chromosome which occurs in the
nucleus of a cell.
 MEGAKARYOPOIESIS
PRECURSOR CELLS OF PLATELETS ❖PROMEGAKARYOCYTE (MKII)

• maturation of megakaryoblast which is a little

❖MEGAKARYOBLAST (MKI) bit larger than MKI.

• considered as the earliest and most immature • 20-80 um in diameter.

cell that is normally found in bone marrow but
cannot be found in circulation. • CYTOPLASMIC GRANULES: few in blue
cytoplasm.
• 15-20 um in diameter
• CYTOPLASMIC TAGS (PROTRUSION):
• CYTOPLASMIC GRANULES: absent in blue
present
cytoplasm.

• CYTOPLASMIC TAGS ( PROTRUSION): present • NUCLEAR FEATURES: double nucleus, fine

chromatin, visible nucleoli.
• NUCLEAR FEATURES: single nucleus visible
nucleoli. • no visible platelets

• no visible platelets
 MEGAKARYOPOIESIS
❖ MEGAKARYOCYTE ❖ METAMEGAKARYOCYTE
• Maturation of promegakaryocyte that accounts • stage of cytoplasmic division.
• 1-4 metamegakaryocyte=1000-4000 platelets a
for less than 0.5 % of all BM cells.

• 80-100 um in diameter. day

• CYTOPLASMIC GRANULES: numerous, • 9-12 days lifespan of cytoplasmic

small reddish granules in abundant megakaryocytes.

• 800-100 um in diameter.
pinkish-purple cytoplasm.

• CYTOPLASMIC TAGS (PROTRUSION):

• CYTOPLASMIC GRANULES: aggregated
usually absent

• NUCLEAR FEATURES: two or more • CYTOPLASMIC TAGS (PROTRUSION):

nuclei- endomitosis; coarse chromatin absent

• no visible platelets except in • NUCLEAR FEATURES: four or more nuclei

myeloproliferative disorder, myelophistic
process. • Has a visible platelets
 MEGAKARYOPOIESIS
MEGAKARYOCYTE
MEMRANE RECEPTORS
AND MARKERS

฀Immunostaining r fixed tissue or

flow cytometry with immunologic
probes or FISH method is usually
employed by the laboratorians in
specialty in tertiary laboratory.

฀They use particular marker

which is MPL.
TAKE NOTE!
 MEGAKARYOPOIESIS
TERMINAL MEGAKARYOCYTE
DIFFERENTIATION

❑During thrombopoiesis,
hematopoietic progenitor
cells differentiate to form
platelet precursors called
megakaryocytes, which
terminally differentiate to
release platelets from long
cytoplasmic processes
termed proplatelets.
PLEASE FAMILIARIZE!
THROMBOCYTOPOIESIS
(Platelet Shedding) WHAT ARE THE PRECURSOR
CELLS OF THROMBOCYTES?

▪ Megakaryoblast
▪ Promegakaryoblast
▪ Megakaryocyte
▪ Metamegakaryocyte
▪ Shed platelets

❖INITIATION OF PLATELET FORMATION: ฀Number of nucleus increases

฀Granularity of cell is absent at first but
1. DMS
eventually can be seen as part of the
2. Longitudinal bundles of tubules formed
structure of the cell
3. Proplatelet process extends
฀NC ratio decreases
4. Transverse constriction
฀Cytoplasmic protrusion or tags are
5. Proplatelet process pierces through the
present at the early stage of cell but
sinusoidal lining of endothelial cells
fades upon maturity.
6. Extends into the venous blood
฀Size increases as it matures.
7. Releases Platelet
KEYPOINTS:
1. Cell size increases with
maturation.
REFERENCES:
YouTube videos and some
2. The final mature notes from the past discussion
functional form is a of Professor Donna Therese
M. Taguinod, RMT, MPH
CYTOPLASMIC
FRAGMENT OR
PLATELET.
PLATELET: Functional forms
in the peripheral blood are
actually fragments of the
cytoplasm as part of the
shedding process.