Megakaryocytopoiesis Flashcards
1
Q
- _______ are anucleate cells that circulate at a
concentration of _______. - Platelet count in ______ than men.
o When they reach the ___, both sexes will have
a ______. - Platelet count - older than 65 years decreases.
- Platelet triggers the _______.
o ______ – this involves your platelet and your blood vessels.
o ______ – this involves the coagulation factors. - Platelets arise from a unique bone marrow cell.
o Known as _______.
o When the megakaryocyte is mature, they can now
shed off platelets.
o 1 Mature Megakaryocyte can shed off _____ - Life Span of Platelets: ______
A
- Megakaryocytopoiesis
- Platelets
- 150 to 400x10^9 /L.
- women slightly higher
- age of 25
- slightly lower platelet count- decreases
- primary hemostasis
- Primary Hemostasis
- Secondary Hemostasis
- megakaryocyte
- 2000-4000 of platelets
- 8-9 days
2
Q
- Megakaryocytes are the _____ in the bone marrow, and possess multiple chromosomes copies, also known as _____.
- Megakaryocytes is about _____ in diameter.
o The series of maturation for platelet has a very
unique series. It increases in size then sheds to
platelets later on. - Megakaryocyte accounts for ____ of all bone marrow cells.
A
- largest cells
- Polypoid
- 30-50 um
- 0.5%
3
Q
Proliferative Stage (MG Progenitors)
A
- Burst forming unit
- Colony forming unit
- Light Density-CFU
4
Q
- ___ is a continuous cell production.
- For multipotential hematopoietic stem celll. It is - divided into 2 progentor cells.
A
Hematopoiesis
Common Lymphoid Progenitors
Common Myeloid Progenitors
5
Q
Common Lymphoid Progenitors
A
- Production of lymphocytes
6
Q
Common Myeloid Progenitors
A
- RBC Production
- Granulopoiesis
- Platelet
7
Q
______ – undifferentiated/ immature hematopoietic cell that is committed to a cell lines.
A
- Progenitors
8
Q
• The BFU & CFU are ______ (paired chromosome) and _____ (cell division).
• Their proliferative properties are reflected in their ability to form _____ (BFU-Megs) or _____ (CFU-Megs) of colonies in culture.
A
- diploid
- has mitosis
- hundreds
- dozens
9
Q
- The last stage will be the _____, there is _____.
Has no capacity to divide but it ________, instead of mitosis, it is now called as
_________.
A
- LD-CFU
- no mitosis
-retains its DNA replication - ENDOMITOSIS
10
Q
Terminal Megakaryocyte Differentiation Stage
A
• MK-I (Megakaryoblast)
• MK-II (Promegakaryocyte)
• MK-III (Megakaryocyte)
11
Q
- It is called __ because each characteristic of these three in terms of - percent precursor, nucleoli, etc
- There is _________
A
Terminal Megakaryocyte Differentiation Stage
- differentiation
- MEGAKARYOBLAST + TPO
12
Q
shedding of megakaryocyte of the platelets.
* In other words, 1 megakaryocte can release _______.
A
Thrombopoiesis Stage
- 2000-4000 platelets
13
Q
MK l (Megakaryoblast)
A
- 20
- 14-18 um
- Rounded
- 2-6
- Homogenous
- 3:1
- Absent
- Basophilic
- Present
- Present
- Present
14
Q
MK ll (Promegakaryocyte)
A
- 25
- 15-40 um
- Indented
- Variable
- Condensed
- 1:2
- Absent
- Basophilic and granular
- Present
- Present
- Present
15
Q
MK lll ( Megakaryocyte)
A
- 55
- 30-50 um
- Multilobed
- Not visible
- Deeply Condensed
- 1:4
- Absent
- Azurophilic and granular
- Present
- Present
- Present
16
Q
Homogenous meaning well mixed. The cytoplasm is basophilic meaning there is __
* MK-I, MK-II, MK-III possesses _____, _____ and __
A
MK-l
- bluish cytoplasm
- bluish
- a-granules, d-granules and DMS
17
Q
Has cleavage
A
MK-ll
18
Q
- ______ – immature hematopoietic cell that is morphologically identifiable compared to progenitors that are not identifiable
- ______ – pinkish and orange
A
- MK-lll
- Precursor
- AZURO
19
Q
______ in size, appearing as ______ with ______
o They are small but very active
o The purpose of being small is for them to be able to go to the site of injury much faster.
* anucleated
* MPV: ____
Increased platelets =_______
* Shape: __ under Wright-stained wedge preparation
* - 1/3 or 30% are sequestered by the _____ (for ,)
* - 70% in the _
* Reference value
o Normal value: ______
>Decreases - after 65 years old
o Men: _____
o Women: ______ (represents 2/3 of available platelets)
* Life span: _____
* Are responsible for ______
A
- Platelets (Thrombocytes)
- 2-4 um
- pale blue cells
- azurophilic granules
- 8-10 Fl
- Thrombocytosis
disk-shaped or circular to irregular, lavender and granular - spleen
- trauma, inflammation
- circulation
- 150 to 400x10^9 /L
- 220 to 350 3x10^9 /L
- 140 to 379 3x10^9 /L
- 8-9 DAYS
- hemostasis
20
Q
- “Stress Platelets”
- Appear in compensation for _
- Larger than normal platelet
- Diameter: _____
- MPV = ______
>An increase in the MPV is also an increase in the diameter of platelets. - Carry_ and _ (homologous to reticulocytes)
- _____ – round
- ______ – cylindrical (mistaken as megakaryocytes)
A
- RETICULATED PLATELETS
- thrombocytopenia
- > 6 um
- 12-14 fl
- free ribosomes and fragments of rough ER
- EDTA
- CITRATED
21
Q
- Most important hormone
- Dalton; 23% homology to _
- mRNA for TPO has been found in ____, ____, and ________.
- Induces _ to differentiate into megakaryocyte progenitor.
- glycoprotein hormone produced mainly by the _____ and the _____ that regulates the production of platelets by the bone marrow.
- It stimulates the production and differentiation of megakaryocytes.
A
- THROMBOPOIETIN (TPO)
70,000 - EPO
- kidney, liver, and smooth muscle cells
- stem cells
- glycoprotein hormone
- liver and the kidney
22
Q
• Acts in synergy with TPO to induce early differentiation of stem cells.
A
- Interleukin-3 (IL-3)
23
Q
• Enhance the later phenomena of endomitosis and platelet release.
• Maturation of platelets
A
- Interleukin-6 (IL-6) and Interleukin-11 (IL-6 and IL-11)
24
Q
OTHER HORMONES AND CYTOKINES
A
• Stem Cell Factor, GM-CSF, Granulocyte-CSF.
• EPO
25
TPO
- +
- +
- +
- 0
26
IL-3
- +
- +
- 0
- -
27
IL-11
- 0
- +
- +
- +
28
IL-6
- 0
- 0
- +
- +
29
KL/SCF/MCGF
- +
- 0
- 0
- 0
30
CFU-GEMM
- +
- 0
- 0
- 0
31
MAJOR STRUCTURAL FEATURES OF PLATELET
1. PERIPHERAL ZONE
2. SOL-GEL ZONE
3. ORGANELLE ZONE (CENTROMERE)
4. Membranous system
32
2 DIVISIONS OF PERIPHERAL ZONE
Glycocalyx
Plasma Membrane
33
serves as the binding site for ___, necessary for _______.
➢ _will help for the
adhesion, because without this the bleeding will be tenacious
Glycoprotein Ib (GP Ib)
- vWF
- platelet adhesion
- Von willebrand factor
34
calcium-dependent membrane protein complex for fibrinogen receptor necessary for platelet
aggregation.
Glycoprotein IIb-IIIa (GP IIb-IIIa)
35
is the predominant lipid, it gives us the
basic structure of the platelet aside from the
microtubules and microfilaments
> _ are distributed throughout the
phospholipid.
Phospholipid
- Cholesterol
36
Membranous System
- open canalicular system
- dense tubular system
37
* The star for the coagulation is the _____.
- Platelets
38
* Composed of the membranes and is responsible for _ and _
* Originates from the plasma membrane of megakaryocyte
-It originates in the resting plasma
membrane, which is mainly composed of_
o ______ is also part of it which gives basic
structure and maintain fluidity of platelets.
PERIPHERAL ZONE
- platelet adhesion and aggregation
- lipase (phospholipase)
- Cholesterol
39
o Stimulate platelet aggregation
a) ______
b) ______
c) ______
d) ______
e) ______
- Epinephrine
- Collagen
- Ristocetin
- Thrombin
- Arachidonic Acid
40
* primarily composed of glycoproteins including
factors _,_,_
o ___ – labile factor
o _____ – Anti-hemophilic factor
o _____ – for aggregation
* A platelet membrane outer surface of the platelet.
* Also absorbs _,_ and _, in many instances transporting them to storage organelles within using a process called _______ .
- Glycocalyx
V, VIII and fibrinogen, albumin.
- factors V, VIII and fibrinogen, albumin
- albumin, fibrinogen, and other plasma proteins
- endocytosis
41
* serves as the physical and chemical barrier between the intracellular and extracellular constituents of the platelets. composed of a bilayer of asymmetrically distributed ______ imbedded with integral for surface receptors.
- Plasma Membrane
- phospholipids
42
• _______ is the predominant lipid, it gives us the basic structure of the platelet aside from the microtubules and microfilaments
• _______ are distributed throughout the
phospholipid.
- Phospholipid
- Cholesterol
43
* Lies directly beneath the platelet membrane and is composed of:
SOL-GEL ZONE
- Microtubules
- Microfilaments
44
* Composed of _which maintains the platelet Disc shape
* Located beneath the membrane and give the platelet its structural support.
Microtubules
- protein tubulin
45
* Contain ____ and _____ which upon stimulation of the platelet will interact to form ______ (thrombosthenin) for _______.
* Between the membrane and the microtubules.
Microfilaments
- actin and myosin
- actomyosin
- clot retraction
46
• The part where the secretory products of platelet come from.
• All the contents of the platelets are placed here.
ORGANELLE ZONE (CENTROMERE)
47
* There are _______ in each platelet.
- stain _______ in osmium-dye transmission electron microscopy preparations
- are filled with proteins, some
endocytosed, some synthesized within the
megakaryocyte and stored in platelets.
* Several are membrane bound.
* As the platelet becomes activated, its
membranes fuse with the SCCS.
* Their contents flow to the nearby microenvironment, where they participate in platelet adhesion and aggregation and support plasma coagulation.
* Contain _,_,_,_,_,_,_among other substances.
- α Granules
- 50 to 80 a-granules
- medium gray
- platelet fibrinogen, factor V, von Willebrand
factor, platelet factor 4, β thromboglobulin, fibronectin, and albumin,
48
✓ ______________ – neutralizes heparin
✓ _________ – aside from the adhesion, will promote smooth muscle growth for vessel repair.
✓ __________ – promotes smooth muscle growth, cell growth division, healing of the wound, repair and growth of the blood vessel.
✓ ______
✓ ______
✓ ____
✓ _______ – promote platelet to platelet interaction and for adhesion
✓ _______
a-Granules
- Platelet factor 4 (Anti-heparin function)
- β-thromboglobulin
- Platelet-derived growth factor
- Fibrinogen
- Factor V
- vWF
- Thrombospondin
- Fibronectin
49
* There are ________ per platelet.
* Also called __ these granules appear later than a-granules in megakaryocyte differentiation and _________ when treated with osmium in transmission electron microscopy
* Small molecules are probably endocytosed and are stored in this
* migrate to the plasma membrane and release their contents directly into the plasma upon platelet activation.
* Composed of _,_,_,_, and several other components.
- Dense Granules/delta
- dense bodies
- 2-7 dense granules
- stain black (opaque)
- ATP, ADP, calcium, serotonin
50
_____ – involves in aggregation and activation of
platelets
____ – energy source of the platelet to achieve the 8-9 days
_____ is important for the activation of coagulation casting, without calcium activation will not happen and without activation bleeding will not stop.
_______ – for vasoconstriction which binds
endothelial cells and platelet membranes
- dense-Granules
- ADP
- ATP
- Calcium and Magnesium
- Serotonin
51
• For ATP synthesis used for platelet metabolism
- Mitochondria
52
similar to those in neutrophils, ____________ that - stain positive for ______, ______, _______, and _______.
- Lysosomal Granules
- 300-nm-diameter granules
- arylsulfatase
- b-glucuronidase
- acid phosphatase
- catalase
53
Lysosomal Granules
- Acid phosphatase
- Hydrolytic enxymes
54
- Site of the arachidonic acid metabolism and provides small amount of ca to the resting platelet.
* Derived from ________ and sequesters calcium for platelet activation process
* It is also the site of_________ and of _________
* Parallel and closely aligned to the SCCS is the dense tubular system (DTS), a condensed remnant of the rough endoplasmic reticulum.
* Having abandoned its usual protein production function upon platelet release, the _ and bears a series of enzymes that support platelet activation.
* These enzymes include p_,_,_ which support the eicosanoid synthesis pathway that produces thromboxane A2, and phospholipase C, which supports production of _,_
- Dense Tubular System
- smooth endoplasmic reticulum
- site of platelet cyclooxygenase and prostaglandin synthesis
- DTS sequesters Ca21
- hospholipase A2, cyclooxygenase, and thromboxane synthetase,
- inositol triphosphate (IP3) and diacylglycerol
(DAG).
55
* Important in the storage of ionized calcium
* Responsible for the formation of prostenoid
thromboxane waII and prostaglandin.
* Seen during platelet aggregation.
dts
56
* Open to the outside of the platelet
* - Surface connecting system
* An invagination of the plasma membrane
* Acts as a canal for the release of the granule constituents and cytoplasm to the exterior of the platelet.
* If the platelet activates or release mechanism or secretion, all the platelet contents will be passed throughit. And these platelets will destroy once
there is an activation. It will have a protrusion because of the platelets that release and it will have pseudopods.
- Open Canalicular System
57
* The _______ is less developed in the SCCS and lacks some of the glycoprotein receptors present on the platelet surface. However,the _ is the route for endocytosis and for secretion of a-granule contents upon platelet activation.
- glycocalyx
- SCCS
58
- PLATELET FUNCTION
Participates in a sequence of events that lead to the formation of a _______ and ultimately to the formation of a stable fibrin clot at the site of vessel interruption.
- platelet plug
> Primary hemostasis
> Blood Coagulation
> Clot retraction
> - Helps in localization of bacteria
59
________ by adhesion, secretion and
aggregation with the end view of hemostatic plug.
Primary hemostasis
60
________ by releasing platelet factor 3 that plays a big role in forming fibrin clot
i. _______ – Platelet factor VIII
ii. ______ – Platelet factor IX
iii. ______ – Platelet factor XI
- Blood Coagulation
- Hemophilia A
- Hemophilia B
- Hemophilia C
61
- Clot retraction by its _
actomysin
62
63
Accelerates the conversion of PT to thrombin
PF1
64
Accelerates the clotting of purified fibrinogen by thrombin
PF2
65
Phospholipid needed in the intrinsic coagulation pathway
PF3
66
Antiheparin – part of alpha granules, and
we also seen inside the platelets that neutralized the heparin
PF4
67
Necessary for normal fibrin formation
PF5
68
Antifibrinolysis
PF6
69
Necessary in the formation of intrinsic thromboplastin (also known as FII or tissue factor)
PF7
70
Hemophilia was first recognized.
- 2nd century A.D
71
__________ described 2 male siblings who died because of excessive bleeding after circumcision.
- 12th century A.D
- Moises Maimonides
72
Clinical description of families with hemophilia was first published. The disorder was given the name HEMOPHILIA which means “love of hemorrhage” by _______.
- 1803
- Schonlein
73
The disorder was first described in a thesis published by ______.
- 1828
- Hoff
74
Platelets were described
1842
75
Theory on Blood Coagulation by _______ was accepted.
- 1905
- Paul Morawitz
76
Lee & White WBCT was performed.
1913
77
Prothrombin time was introduced by __________
- 1930
- Quick (because platelets hasreference value of 10-15 secs)
78
Other tests for evaluating hemostatic mechanisms, like plt. Count & BT were introduced.
Platelet Count
1. ______ – uses RBC pipette and hemocytometer
2. ______ – smear
- 1940
- Direct Count
- Indirect
79
“Cascade & Waterfall Theory” of coagulation was introduced.
1964
80
• 2nd century A.D - ________
• WBCT (__________)
• BT (______)
- lack of factor VIII
- Whole Blood Clotting Time
- Bleeding Time
81
a partially characterized form of mitosis unique to megakaryocytes in which DNA replication and cytoplasmic maturation are normal but cells lose their capacity to divide.
endomitosis
82
is a growth factor that will help to stimulate of the production of the platelets.
Needed for MK I, II, III
TPO
83
o ____ – least differentiated megakaryocyte, it has blebs or pseudopods that is used for locomotion
MKI
84
o ____ – the hallmark is the present of indentation
MKII
85
o _____ – most abundant, easily to recognize, largest bone cells and they are capable now of shredding of platelets
MKIII
86
* ___________ – 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 __
DMS (Demarcation System)
- megakaryocyte plasma membrane
87
* ______ – are all present in and the major function are for adhesion.
o It has contents and without this a-granules, it will result to _____________ (No agranules)
a-granules
- GRAY PLATELET SYNDROME
88
o stimulates the production of RBC and resides in the _ but can also be found in the ___ and ____.
EPO
- peritubular tube of the kidney
- liver and lungs
89
* The _ probably digest vessel wall matrix components during in vivo aggregation and may also digest autophagic debris.
* They will digest the materials that brought into the platelet by endocytosis and they will be the one who destroy or lyse
lysosomes
90
is the “controlcenter” for platelet activation
DTS
