Karius Hemostasis

Question 1

Hemostasis

Answer 1

the steps taken by the body to limit blood loss, but hemostasis is NOT confined only to the blood clot

Question 2

Hemostasis four steps

Answer 2

1. vascular spasm
2. formation of platelet plug
3. formation of a blood clot
4. repair of damage

Question 3

TPO

Answer 3

thrombopoietin (TPO)
protein hormone with an amine terminal similar to erythropoietin (EPO) but unique carboxyl terminal
TPO stimulates megakaryocytes to produce platelets

made by liver and kidney

in liver, the parachymal sinusoidal cells
in the kidney, the proximal convoluted tubules
stimulus for its release is uncertain

Question 4

EPO

Answer 4

erythropoietin TPO
produced in liver, stimulates red blood cell production in the bone marrow in response to hypoxia

produced by liver and kidney

Question 5

Platelet production control

Answer 5

they bind thrombopoietin to their mpl receo

Question 6

mpl receptors

Answer 6

found in platelets, megakaryocytes, and other hematopoietic cells

utuilized Jak/Stat and phosphorylation, subsequent transcription and translation of various genes

Question 7

a high number of platelets indicates

Answer 7

lots of TPO bound to the mpl receptors. they internalize signal and destroy it.

not much free to act on megakaryocytes

not much free TPO in the body or to act on megakaryocytes

Question 8

low number of platelets indicates

Answer 8

small amount of TPO bound to platelets; TPO is not being destroyed

there’s LOTS of TPO free in the blood

Question 9

TPO increases

Answer 9

increases differentiation of stem cells and maturation rate/

effects on all cell lines

Question 10

megakaryoblast –> ______ —> ____

Answer 10

megakaryocyte, platelet (thrombocytes)

Question 11

TPO acts on

Answer 11

all cell lines in the body

Question 12

polycythemia vera

Answer 12

mutation in TPO receptor

, platelets unable to internalize and destrou TPO so its actions become continuous

Question 13

platelet internal mechanisms (7 things)

Answer 13

actin and myosin for cell contraction and emptying vesicles
mitochondria for ATP and ADP

remnant of the ER (for calcium storage)
COX1 (prostaglandin production
Cox1 produces thromboxane A2

Fibrin Stabilizing Factor (clot stability)
Platelet derived growth factor (repair)
Serotonin

Question 14

Platelet membrane becomes ____ when activated. It also contains important ________ and receptors for ______

Answer 14

sticky, phosholipids, collagen

Question 15

If platelet levels drop, what happens to TPO

Answer 15

their quantity increases, so they can act

Question 16

If platelet levels increase, what happen to TPO

Answer 16

their quantity decrease, and their destruction marks them off from acting

Question 17

What cell lines does TPO act on?

Answer 17

all cell line

Question 18

Erythropoiesis vs Thrombopoiesis

What is their respective sources?

Answer 18

Ery - kidneys and liver

Thrombo - liver

Question 19

what triggers EPO and TPO release?

Answer 19

EPO: low oxygen
TPO: constitutive (constant)

Question 20

Control of EPO and TPO hormones, respectively

Answer 20

EPO: Hypoxia Inducible Factor (HIF) accumulation in renal cells

TPO: internalization/destruction of TPO

Question 21

Receptors for EPO and HPO release

Answer 21

EPoR and MPL

Question 22

Cells that express receptors for EPO vs HPO

Answer 22

EPoR expressed by pluripotent stem cell, RBC precursors

MP: pluripotent stem cells, platelets, all hematopoietic cell lines

Question 23

Erythropoietin’s effect

Answer 23

causes daughter cells in Erythroid cell line to undergo mitosis

Question 24

Thrombopoietin’s effect

Answer 24

increases division and maturation of all blood cell lineages

Question 25

Hemostasis: step 1

Answer 25

MYOGENIC spasm induces vascular occlusion. | occurs spontaneously in response to injury, no neurons or reflexes involved

Question 26

Platelet factors include

Answer 26

serotonin and thromboxane A2 contribute to spasm

Question 27

"contributing factors" to the vascular spasm (step 1 of hemostasis)

Answer 27

neural reflex from nociceptors (mechanical response) not sufficient or necessary for spasm to occur, minor contribution

Question 28

Hemostasis Step 2: overview of steps

Answer 28

formation of the platelet plug followed by binding of platelets to exposed collagen (two step process)

Question 29

Hemostatic plug formation step 2: platelet activity

Answer 29

a. binds to exposed collagen at site of injury using VWF 1. uses Von Willebrand Factor 2. plasma protein 3. bind between collagen and platelet receptor b. platelet integrin receptor binding to collagen

Question 30

during the second phase of a hemostatic plug formation, what do platelets do upon activation?

Answer 30

1. swell and extend podocytes 2. contraction 3. granules leave platelet 4. platelets stick to vessel wall and each other

Question 31

What do thromboxane A2 and ADP do

Answer 31

they are released during self aggregation of platelets

Question 32

Hemostasis Step 3: role and steps

Answer 32

blood coagulation 1. formation of prothrombin activator 2. thrombin activation 3. conversion of fibrinogen to fibrin leading to CLOT RETRACTION

Question 33

Hemostasis step 3: Clot Retraction

Answer 33

This step gets rid of excess fluid in the clot to solidify it. Platelets are required (to bind fibrin together, as well as their actin/myosin platelet contractions) also requires calcium

Question 34

Hemostasis step 4 Repair of damage

Answer 34

Repair of damage Platelet secretion of Platelet derived fibroblast growth factor stimulates fibroblasts to grow into area fibroblasts grow into smooth muscle etc to close the hole

Question 35

Getting rid of the clot

Answer 35

achieved by plasminogen floating freely in blood tPA: tissue plasminogen activator, released by damaged tissues. tPAi: inhibits tPA, in the blood

Question 36

Thrombomodulin is located on the

Answer 36

endothelial cell, and bind thrombin

Question 37

Thrombomodulin activates thrombin on the endothelial cell: what does it activate

Answer 37

Protein C, which inactivates tPAi, allowing tPA to activate Plasminogen from zymogen form: Plasminogen ---> Plasmin plasmin lysis fibrin

Question 38

Prevention of Clotting: the role of smooth surfaces

Answer 38

prevents platelets from rupturing

Question 39

Prevention of clotting: the role of membrane proteins

Answer 39

endothelial cell glycocalyx repels platelets | thrombomodulin activates thrombin

Question 40

Chemicals which limit clotting (4)

Answer 40

1. Fibrin: binds thrombin and prevents it working 2. Prostacyclin (PG12) made by injured cells, limits platelet aggregation 3. Antithrombin III: binds and prevents thrombin from working 4. Heparin: made from mast cells, increases efficacy of antithrombin

Question 41

Protein C

Answer 41

Inhibits tPAi AND inactivates the VIIIa--Va complex responsible for activating prothrombin

Question 42

what is the outcome of TPO being internalized by platelets?

Answer 42

they are destroyed, so they cant stimulate other hematopoietic cell lines

Question 43

mpl biochemical pathway

Answer 43

JAK/STAT JAK2 activated ---> STATs 1, 3, 5 activated (Stat 1/3 dimerize, stat 5 homodimerizes

Question 44

TPO actions on megakaryocytes, platelets, and other hormone interactions

Answer 44

causes SIZE and NUMBER of megakaryocytes to increase causes platelet specific markers to develop stimulates endomitosis and polyploidy of megakaryocytes works with erythropoietin to stimulate RBC production works with IL-3, or Steel Factor to upregulate RBC and WBC factors to differentiate

Question 45

Platelets: actin and myosin?

Answer 45

just like in skeletal muscle, they have cross bridges that undergo cycling causing contraction of the cell they help SQUEEZE extra fluid out of clot help empty vesicles

Question 46

Cyclooxygenase (COX 1)

Answer 46

enzyme that catalyzes production of thromboxane A2. prostaglandins

Question 47

Fibrin Stabilizing Factor

Answer 47

XIII, causes covalent bonds to form between fibrin monomers

Question 48

platelet derived growth factor

Answer 48

aids in repair of damaged tissue

Question 49

what does Thromboxane do exactly?

Answer 49

binds to GPCR on smooth muscle and triggering calcium release causes an increase in IP3 causes release of calcium from intracellular stores of the smooth muscle cell

Question 50

how is the platelet held in place during clot formation?

Answer 50

two points of contact: von willebrand factor between collagen and platelet, and integrins on the platelets interacting with the collagen