LEC1 - PLATELET PRODUCTION, STRUCTURE AND FUNCTIONS Flashcards
do platelets have nucleus?
nope, they are anucleated
platelets circulate at a concentration of ___
150-400 10^9/L
- Platelet count in women is slightly __________ than in men.
higher
Platelet count older than 65 years ________________.
lower
platelet triggers what type of hemostasis
primary hemostasis
Platelets arise from a unique bone marrow cell called ___
megakaryocytes
platelet life span
8 - 9 days
what is the largest cell in the bone marrow
megakaryocytes
megakaryocyte posses multiple chromosomes copies called as
polypoid
Megakaryocytes is about ___________
um in diameter
30 - 50 mm
megakaryocyte
It is the only cell line where cells become
bigger as they mature.
true or false
true the fire
Instead of mitosis, megakaryocytes undergo what type of cell division
endomitosis
what’s the difference of endomitosis to mitosis
A form of mitosis wherein there is no cytoplasmic division but there is NUCLEAR DIVISION
3 STAGE OF PLATELET PRODUCTION
- proliferative stage
- terminal differentiation stage
- thrombopoiesis stage
3 stages of megakaryocyte progenitors
BFU - burst forming unit
CFU - colony forming unit
LD - CFU - light density colony forming unit
the 3 stages of megakaryocyte progenitors are always thought and looks like as
lymphocytes
among the 3 stages of megakaryocyte progenitor, which are the ones undergoing mitosis and endomitosis
BFU and CFU undergo mitosis
LD - CFU undergo endomitosis
stages under proliferative stage of platelet production
BFU - burst forming unit
CFU - colony forming unit
LD - CFU - light density colony forming unit
stage of meg progenitors that clones hundreds of colony
Burst forming unit
stage of megakaryocyte that forms daughter colony
colony forming unit - cfu
the most matured stage of megakaryocyte progenitors
light density colony forming unit
the replication of
chromosomes in the
absence of cell
or nuclear division,
Endomitosis
stages of terminal
megakaryocyte differentiation
megakaryoblast
promegakaryocyte
megakaryocyte
precursor % of megakaryoblast
20%
megakaryoblast is also known as
MK I
Diameter of MK I
14-18 um
Nucleolus shape of MK 1
round
serotonin in d granules serve as a vasoconstrictor of what?
endothelial cells and plasma membrane
how many nucleoli are found in MK I
2-6
describe the chromatin of MK 1
homogenous
n:c ratio of MK 1
3:1
describe the color of cytoplasm of MK1
dark blue - basophilic - due to presence of RNA
% of precursor of MK II
25%
diameter of MK II
15-40 um
hallmark of MK II
has cleavage or indentation
do MK I has blebs?
yes ofcors
Cytoplasm of MK II
Basophilic and granular
% Precursor of MK III
56%
Diameter of MK III
30-50 um
Nucleolus of MK III
multilobed
Nucleoli of MK III
Not visible
Nucleolus of MK II
indented
Nucleoli of MK II
variable
Chromatin of MK II
condensed
N:C ratio of MK II
1:2
Nucleoli of MK III
not visible
Chromatin of MK III
Deeply condensed
N:C ratio of MK III
1:4
Cytoplasm of MK III
Azurophilic and
granular
Least differentiated megakaryocyte precursor
MK 1
do MK 1 still looks like LYMPHOCYTES?
No longer looks like LYMPHOCYTES
what stage of meg precursor Begins to develop most of its cytoplasmic ultrastructure
MK 1
what are the example of cytoplasmic ultrastructure
a granules
d granules
DMS - demarcation system
stage of megakaryocyte precursor where Nuclear lobularity ( INDENTATION) takes place
MK II
among the megakaryocyte precursor, this one is the most abundant and can be easily recognized. It is as well the one that sheds platelets
megakaryocytes
divides the
cytoplasm into
small platelet
territories
DMS
a process of platelet releasing is called as
thrombocytopoiesis
- During thrombocytopoiesis, a single
megakaryocyte may shed
_________ platelet
2000 - 4000 platelets
a hormone or a growth fatctor that will stimulate the production of platelets
TPO - thrombopoietin
a stage of platelet production wherein a Shedding of platelet or shedding of
megakaryocyte takes place
thrombopoiesis stage
a ultrastructure of platelet which is a future site of fragmentation
DMS - demarcation system
a series of membrane lined channel. It will
invade from the plasma membrane and it will
grow inward to subdivide the entire cytoplasm. It
is identical to megakaryocyte plasma membrane
DMS - demarcation system
a cytoplasmic ultrastructure of platelet that is present in all stages of Meg precursor (MK I, II , III) and is main purpose is for adhesion
a-granules/ alpha granules
a condition or disease associated to lack of alpha granules is called as
Gray platelet syndrome
platelet’s size
2-4 um
color and appearance of platelet
pale blue cells with azurophilic granules
normal MPV of platelet
MPV : 8-10 fl
Shape of platelet
Disk-shaped or circular to
irregular lavender and granular under
wright stained wedge preparation
Reference value of platelet
150-400 x 10^9 /L
how many percent of platelet constitute the body’s circulation?
70%
70% 0f platelet are found in circulation. while the other 30% are found in ___
30% or 1/3 are sequestered by the spleen
what’s the purpose of the 30% platelets found in the spleen
it will use if there’s a trauma
if the platelets are involved in primary hemostasis, what are involved in secondary hemostasis
coagulation factors
if the MPV was too high it only means that
the platelets are bigger and it result to
conditions like GIANT PLATELET one of the
characteristic of what syndrome?
Bernard-Soulier Syndrome
Low MPV is a characteristic of what syndrome?
GLANZMANN syndrome
Reticulated Platelets is also called as
stress platelets
Reticulated Platelets appear in compensation for )))))
thrombocytopenia
reticulated platelets are ___ than normal platelet
(Larger, smaller)
Larger
Diameter and mpv of reticulated platelets
Diameter > 6 um
; MPV = 12-14 fl
shape of reticulated platelets in EDTA
rounded
shape of reticulated platelets in citrated blood
cylindrical
Thrombopoietin (TPO
_____ Dalton
70, 000
how many percent is TPO homology to EPO
23%
TPO are most likely produced in what organ
Liver
a cytokines that Acts in synergy with TPO to induce early differentiation of stem
cells
Interleukin-3 (IL-3)
- Interleukin-6 and Interleukin-11 (IL-6 and IL-11)
Enhance the later phenomena of
endomitosis, ________, ________and Platelet release.
Enhance the later phenomena of
endomitosis, differentiation of megakaryocytes, late maturation and Platelet release.
TPO helps and controls what stages
Differentiation to Progenitor
Differentiation to Megakaryocytes
Late Maturation
IL 11 helps and controls what stages
Differentiation to Megakaryocytes
Late Maturation
Thrombopoiesis
IL 3 helps and controls what stages
Differentiation to Progenitor
Differentiation to Megakaryocytes
IL 6 helps and controls what stages
Late Maturation
Thrombopoiesis
KL/SCF/MCGF helps and controls what stages
KL: Kit Ligand;
SCF: Stem Cell Factor;
MCGF: Mast cell Growth Factor
Differentiation to Progenitor
Colony Stimulating Factor-GEMM helps and controls what stages
Differentiation to Progenitor
Major Structural Feature of Platelet
- Peripheral Zone
- Sol-Gel Zone
- Organelle Zone
- Membranous System
Peripheral Zone is composed of which component of a platelet
glycocalyx and plasma membrane
a structural feature of a platelet that is composed of the
membranes and is
responsible for
platelet adhesion
and aggregation
Peripheral Zone
Peripheral Zone - originates from
the ____ of the
megakaryocytes
plasma
membrane
a Exterior coat primarily composed
of glycoproteins found in peripheral zone
glycocalyx
Maintains a negative surface
charge that repels other platelets
Glycocalyx
plasma membrane is composed of proteins and lipids.- mostly ____
phospholipids
Also absorbs albumin, fibrinogen, and other
plasma proteins, in many instances
transporting them to storage organelles within
using a process called endocytosis
glycocalyx
a platelet membrane outer surface of the
platelet
glycocalyx
glycoproteins or coagulationfactors that composed glycocalyx
FV-labile factor
FVIII- anti-hemophilic factor
Fibrinogen – for aggregation
Serves as the physical and chemical barrier
between the intracellular and extracellular
constituents of the plts.
PLASMA MEMBRANE
is the predominant lipid, it
gives us the basic structure of the platelet
aside from the microtubules and
microfilaments
phospholipid
are distributed throughout the
phospholipid
Cholesterol
Cholesterol also helps in ____
fluidity
2 Glycoprotein of Plasma Membrane
Glycoprotein Ib (GP Ib)
Glycoprotein IIb- IIIa
a glycoprotein of a plasma membrane that serves as the binding site for vWF,
necessary for platelet adhesion
Glycoprotein Ib (GP Ib)
calcium-dependent membrane protein
complex for fibrinogen receptor
necessary for platelet aggregation
Glycoprotein IIb-IIIa (GP IIb-IIIa)
lies directly beneath the platelet membrane
SOL-GEL ZONE
found in solgel zone and is composed of protein tubulin which maintains
the platelet disc shape
MICROTUBULES
located beneath the membrane and give the
platelet its structural support.
MICROTUBULES
contain actin and myosin which upon
stimulation of the platelet will interact to form
actomyosin (thrombosthenin) for clot retraction
MICROFILAMENTS
the part where the secretory products of platelet
come from
ORGANELLE ZONE (Centromere)
all the contents of the platelets are placed here
ORGANELLE ZONE (Centromere)
there are how many alpha granules found in each platelet
5-8 alpha granules
list down all the alpha granules
- Platelet factor 4
- Β-thromboglobulin
- Platelet-derived growth factor
- Fibrinogen
- Factor V
- VWF
- Thrombospondin
- Fibronectin
cytoplasmic granules that are primarily for adhesion
alpha granules
a coagulation factor that is included in a granule which also uses calcium and has an anti-heparin function
Platelet factor 4
aside from the
adhesion, will promote smooth muscle growth
for vessel repair.
β-thromboglobulin
promotes
smooth muscle growth
Platelet-derived growth factor
promote platelet to
platelet interaction and for adhesion
thrombospondin
How many dense granules are present per platelet
There are two to seven dense granules per
platelet
Dense Granules / delta are also called as
dense bodies
which granules appear later in megakaryocyte differentiation?
is it a granules or d granules?
d granules
what is the color of d granules when treated with OSMIUM in transmission electron microscopy
BLACK (OPAQUE)
dense granules migrate to the __ and release their contents directly into the plasma upon platelet activation.
plasma membrane
contents of Dense granules
ATP, ADP, calcium and magnesium, serotonin,
a content of dense granules that is involve in the platelet aggregation
ADP
content of dense granules that is an energy source of the platelet to achieve
the 8-12 days
ATP
a component/content of d granules that is important for the activation
of coagulation casting
calcium
a content of d granules that is for constriction
serotonin
what’s the purpose of mitochondria to platelet
like a usual cell, it synthesized ATP for platelet metabolism
Lysosomal Granules of platelets
acid phosphatase
hydrolytic enzymes
Site of the arachidonic acid metabolism and
provides small amounts of calcium to the resting
plat
Dense Tubular System
sequesters calcium for platelet activation process
Dense Tubular System
site of platelet cyclooxygenase and
of prostaglandin synthesis
DTS
the DTS sequesters Ca21 and bears a series of enzymes
that support platelet activation.
these enzymes includes
These enzymes include
phospholipase A2,
cyclooxygenase,
and thromboxane synthetase,
which support the
eicosanoid synthesis pathway
that produces thromboxane A2,
and phospholipase C, which supports production of inositol triphosphate (IP3) and diacylglycerol (DAG).
The ___ is the “control center” for platelet
activation.
DTS
Open to the outside of the platelet
Open Canalicular System
Open Canalicular System is Also known as ___
surface connecting system
an invagination of the plasma membrane
OCS
acts as a canal for the release of the granule
constituents and cytoplasm to the exterior of the platelet
Open Canalicular System
once the platelet activates and release its secretion, all the contents will be passed through OCS, upon the process, what will happen to the platelet as well as to it’s appearance?
the platelet will be destroyed as well and will form a protrusion looking like pseudopods
it will activate fibrinogen to fibrin
thrombin
a process where it involves adhesion, secretion and aggregation with the end view of
hemostatic plug
primary hemostasis - platelet involved
is a process by releasing platelet
factor 3 that plays a big role in forming fibrin
clot.
Blood coaguation
coagulation factors
Accelerates the conversion of PT to
thrombin
PF1
coagulation factors
Accelerates the clotting of purified
fibrinogen by thrombin
PF2
coagulation factor
Phospholipid needed in the intrinsic
coagulation pathway (we have 3
pathways: Intrinsic, Common, Extrinsic)
PF3
coagulation factor
Antiheparin -part of alpha granules, and we also
seen inside the platelets that neutralizes
the heparin
PF4
coagulation factor
Necessary for normal fibrin formation
PF5
coagulation factors
Antifibrinolysis
PF6
a coagulation factor that is Necessary in the formation of intrinsic
thromboplastin (also known as FIII or
tissue factor)
PF7
hemophilia was first recognized.
2nd century A.D
We have 3 types of
hemophilia
(PROBLEM WITH THE COAGULATION
FACTORS OR ABSENSCE)
Hemophilia A, B, C
Hemophilia A is about
problem with FVIII
Hemophilia B is about
problem with FIX(Christmas factor)
Hemophilia C is about
Hemophilia C- problem with FXI
described 2 male
siblings who died because of excessive
bleeding after circumcision
Moises Maimonides
Moises Maimonides described 2 male
siblings who died because of excessive
bleeding after circumcision on what year?
12th century A.D
clinical description of families with
hemophilia was first published on what year
1803
The disorder was given the name
HEMOPHILIA which means “love of
hemorrhage” by ___
Schonlein
The disorder was given the name
HEMOPHILIA which means “love of
hemorrhage” by Schonlein on what year?
1803
the disorder was first described in a
thesis published by Hoff on what year
1828
platelets were described on what year
1842
on what year does the theory of blood coagulation is accepted ?
1905
On 1905, Theory on Blood Coagulation by ___ was accepted.
Paul Morawitz
Lee & White WBCT (clotting time) was
performed on what year
1913
Prothrombin time was introduced by
____(because platelets has
reference value of 10-15 secs)
Quick
platelets has
reference value of 10-15 secs on what year
1930
an indirect count of platelet uses/ conductng ___
smear
an direct count of platelet uses/ conductng ___
uses RBC pipette and
hemocytometer
year when the “Cascade & Waterfall Theory” of
coagulation was introduced.
1964
