q3: platelets intro

The generation of platelets from MKs in the bone marrow.

thrombopoiesis

The process by which mature megakaryocytes (MKs) develop from hematopoietic stem cells (HSCs).

megakaryopoiesis

Production and development of megakaryocytes, the precursors to platelets, in the bone marrow.

megakaryopoiesis

Earlier influences on megakaryopoiesis include GM-CSF, IL-3, IL-6, IL-11, KIT ligand, and TPO.

megakaryopoiesis

Process where platelets are released into the bone marrow through shedding from megakaryocyte proplatelet processes.

thrombopoiesis

A form of mitosis that lacks telophase and cytokinesis.

endomytosis

There is nuclear division without cytoplasmic division

endomytosis

Results in giant multinucleated or polyploidy cells

endomytosis

A specific hormone responsible for Megakaryopoiesis and Thrombopoiesis.

TPO

It is mainly produced by the liver.

TPO

The maturation/differentiation of the cells of the megakaryocytic system has been divided into__

3

Platelet maturation step by step (11)

HSC

CMP

CFU-GEMM

BFU-MEG

CFU MEG

LD-CFU-MEG

MK-1

MK-2

MK-3

PROPLATELET PROCESS

PLATELET SHEDDING

Resemble lymphocytes and cannot be distinguished by wright-stained light microscopy

Progenitors

diploid and able to perform mitosis

Burst forming unit-Meg (BFU-Meg)

Colony forming unit - Meg (CFU-Meg)

cannot divide but it retains DNA replication and cytoplasmic maturation for endomitosis

Light density CFU-Meg (LD-CFU-Meg)

Nucleus: round

a. MK-I

b. MK-II

c. MK-III

a. MK-I

Nucleus: Indented

a. MK-I

b. MK-II

c. MK-III

b. MK-II

Nucleus: Multilobed

a. MK-I

b. MK-II

c. MK-III

c. MK-III

Chromatin: Homogenous

a. MK-I

b. MK-II

c. MK-III

a. MK-I

Chromatin: Moderately condensed

a. MK-I

b. MK-II

c. MK-III

b. MK-II

Chromatin: Deeply and variably condensed

a. MK-I

b. MK-II

c. MK-III

c. MK-III

Endomitosis: Present

a. MK-I

b. MK-II

c. MK-III

a. MK-I

Endomitosis: Ends

a. MK-I

b. MK-II

c. MK-III

b. MK-II

Endomitosis: Absent

a. MK-I

b. MK-II

c. MK-III

c. MK-III

The least mature specific progenitor

BFU-MEG

The most mature specific progenitor

LD-CFU-MEG

The least mature precursor

MK-I (MEGAKARYOBLAST)

The most mature precursor

MK-III (MEGAKARYOCYTE)

Endomitosis starts at

LD-CFU-Meg

Endomitosis ends at

MK-II or Promegakaryocyte

Projections that resemble strings of beads, through or between the endothelial cells and into the venous sinuses, releasing platelets from the tips of the processes into the circulation.

Proplatelet process

sheds platelets, cells consisting of granular cytoplasm with a membrane but no nuclear material, into the venous sinus of the bone marrow.

Proplatelet process

Proplatelet process occurs in

MK-III

Size of the platelets

2 to 4 or 1-4 um in diameter

Wright stained platelets appears

light violet-purple granular appearance and look like "specks of dust"

Cytoplasm of platelets

light blue, with evenly dispersed, fine red-purple granules

Platelets are fragments and produced directly from the

MEGAKARYOCYTE CYTOPLASM

Life span of platelets

8 to 11 days or 9 to 12 days (average of 9 ±1.0 day)

2/3 or around 65% of the platelets = found in the

circulation

1/3 or around 35% of the platelets = found in the

splene

Effect of splenectomy or asplenia in platelet count =

increased platelet count

Effect of hypersplenism or splenomegaly in plt count =

decreased platelet count

Effect of hypothermia or low body temperature in plt count =

decreased platelet count

Normal range of platelets

150-400 or 150-450 x109/L

Average count of platelets

250 x109/L

Effective thrombopoiesis (plt turnover)

350 × 109/L ± 4.3 × 109/L/day

are biconvex, although the platelets in blood collected using the anticoagulant ethylenediaminetetraacetic acid (EDTA, lavender closure tubes) tend to "round up."

Circulating, resting platelets

Known as stress platelets

Reticulated Platelets

Appear in compensation for thrombocytopenia

Reticulated Platelets

They immature and are larger than ordinary mature platelets

Reticulated Platelets

They carry free ribosomes and fragments of rough E.R

Reticulated Platelets

They are prothrombic, and may be associated with increased risk of cardiovascular disease

Reticulated Platelets

Composed of the membranes and is responsible for platelet adhesion and aggregation

PERIPHERAL ZONE

Composition of peripheral zone (3)

Glycocalyx (outermost part), Plasma or cell membrane, and the Sub-membrane

Outer surface, fuzzy coating, primarily composed of glycoproteins including clotting factors V, VIII and I

Glycocalyx

The glycoprotein receptors of the __ mediate the membrane contact reactions of platelet adherence, change of cellular shape, internal contraction, and aggregation.

glycocalyx

Bilayer of asymmetrically distributed phospholipids

Membrane

Where messages from external membrane are translated into chemical signals causing activation and physical change in platelet

Sub-membrane

Forms the cytoskeleton of the platelet

SOL GEL ZONE

provides the structure for maintaining the circulating discoid shape of the cell, and maintains the position of the organelles

SOL GEL ZONE

Control platelet shape, extension of pseudopods, and secretion of granules

SOL GEL ZONE

Composition of Sol Gel Zone (3)

Microfilaments (actin and myosin), intermediate filaments (desmin and vimentin), & Microtubules (tubulin)

Microtubule is composed of

Tubulin

Major responsible for platelet disc shape and it maintains platelet disc shape

Microtubule

On cross section, microtubules are cylindrical, with a diameter of

25 nm

Microtubule: Disassemble at refrigerator temperature or when platelets are treated with

colchicine

When microtubules disassemble in the cold, platelets become round, but on warming to __, they recover their original disc shape

37° C

Microfilament is composed of

Actin and myosin (thrombostenin)

is a contractile protein responsible for platelet contraction

Actomyosin

is present throughout the platelet cytoplasm, constituting 20% to 30% of platelet protein

Actin

is globular and amorphous

Resting platelet actin

becomes filamentous and contractile

Activated platelet actin

Intermediate filament is composed of

Desmin and Vimentin

They are ropelike polymers 8 to 12 nm in diameter

Intermediate filament

Intermediate filaments connect with actin and the tubules, maintaining the platelet shape

Intermediate filament

Organelle zone is composed of (4)

Mitochondria, Alpha granules, Dense (delta granules), and Lysosomes (lambda granules)

Site for energy production or ATP Synthesis

Mitochondria

Major source of energy for platelets

glucose / dextrose

300 to 500 nm in diameter

Alpha granules

largest and most predominant granules

Alpha granules

There are 50 to 80 alpha granules in each platelet

Alpha granules

They stain medium gray in osmium-dye transmission electron microscopy

Alpha granules

fuse with the Surface connecting canalicular system or open canalicular system

Alpha granules

Examples are platelet factor 4, platelet

derived growth factor, thrombospondin, vwf, fibrinogen, fibronectin, factor V, etc.

Alpha granules

250 to 350 nm in diameter

Dense granules

There are two to seven dense granules per platelet

Dense granules

Stain black (opaque) when treated with osmium in transmission electron microscopy

Dense granules

Dense granules migrate to the plasma

membrane and release their contents directly into the plasma on platelet activation

Dense granules

Calcium, ADP, Pyrophosphate, ATP, Serotonin, & Magnesium

Dense granules

300 nm in diameter

Lysosomal type

Stain positive for arylsulfatase, b-glucuronidase, acid phosphatase, and catalase

Lysosomal type

Digest autophagic debris and vessel wall matrix components during in vivo platelet aggregation

Lysosomal type

Digest autophagic debris and vessel wall matrix components during in vivo platelet aggregation

Lysosomal type

Examples are Acid hydrolases, ACP, and Hydrolytic enzymes

Lysosomal type

They do have "clearing" responsibilities to remove infectious agents and cellular debris

Lysosomal type

Composition of membranous system (2)

SCCS (Surface connected canalicular system) and DTS (Dense tubular system)

Derived from rough ER

DTS

Sequesters or hold calcium for platelet activation process & prostaglandin synthesis

DTS

sequesters calcium and bears a number of enzymes that support platelet activation including phospholipase A2, cyclooxygenase, and thromboxane synthetase, which support the production of thromboxane A2, and phospholipase C, which supports production of the signaling molecules inositol triphosphate (IP3) and diacylglycerol (DAG).

DTS

Control center for platelet activation

DTS