module 1: role of vessels & platelets

status: unfinished

hemostasis

the process by which the body stops bleeding, prevents spontaneous bleeding, and maintains blood in fluid state (bleeding vs. clotting)

triad of hemostasis

vasculature (blood vessels), platelets, & coagulation proteins. all 3 must function normally or one will bleed or clot

tunica adventitia (tunica externa)

fibrous connective tissue. strength & support. provides strength to resist damage

tunica media

smooth muscle, elastic fibers. contraction/dilation

tunica intima (tunica interna)

endothelium

what are the 3 primary roles in hemostasis?

vascular integrity, reduce blood loss upon vascular injury, activate platelets (2nd arm) & clotting proteins (3rd)

role of vascular integrity

prevent blood loss from intact vessels. tunica externa provides strength to resist damage. clotting initiated upon vascular damage. platelets nurture endothelium: natural endothelial death & sloughing of dead endothelial cells, platelets replace lost endothelial cells, release PDGF to produce new endothelial cells

role of blood loss upon vascular injury

vasoconstriction. diversion of blood flow around damaged vessel

role of activating platelets (2nd arm) & clotting proteins (3rd)

initiation of platelet plug formation. activation of the coagulation factors (cascade)

peripheral zone (external surface)

one of the 3 layers of platelet ultrastructure. consists of glycocalyx, plasma membrane, and open canalicular system (OCS).

glycocalyx

outer membrane (glycolipids & glucoproteins). holds surface antigens (ABO) & receptors

plasma membrane

provides containment for the cytoplasm

open canalicular system (OCS)

tubular invaginations of the plasma membrane

sol-gel zone (sub-membranous)

one of the 3 layers of platelet ultrastructure. consists of circumferential microtubules & microfilaments

circumferential microtubules

organized bundles of contractile proteins (actin/myosin). maintains discoid shape & changes shape upon aggregation. circumferentially located

microfilaments

unorganized contractile proteins. connects ends of plasma membrane

organelle zone (cytoplasmic)

one of the 3 layers of platelet ultrastructure. consists of mitochondria, dense tubular system (DTS), granules, peroxisomes, & lysosomes

dense tubular system (DTS)

stores calcium. site for protein synthesis (like ER). prostglandin synthesis

alpha granules

20-200/platelets. coagulation factors, coagulation inhibitors, heparin inhibitors, platelet effectors, vessel repair, fibroblast effectors, albumin

coagulation factors

V, XIII, fibrinogen, XII

coagulation inhibitors

PAI-1 (inhibits TPA), protein S (inhibits clotting)

heparin inhibitors

platelet factor 4 (PF4)

platelet effectors

von willebrand factor (platelet adhesion)

vessel repair

thrombospondin (anti-angiogenic), beta-thromboglobulin, PDGF & FGF

fibroblast effectors

beta-thromboglobulin (fibroblast chemokine), platelet derived growth factor (fibroblast growth factor)

albumin

abundant blood protein (carrier)

dense granules

2-10/platelets. platelet activation: ADP, calcium, serotonin, epinephrine. energy source: ATP.

factor i (fibrinogen)

3 globular domains connected by polypeptides. 3 individual polypeptide chains: alpha, beta, gamma. 4 fibrinopeptides: 2 alpha, 2 beta, amino termini of both pairs of chains. synthesized in liver. 200-400 mg/dL. substrate

maintenance of vascular integrity

platelets nurture endothelium. replace endothelial cells that die. stimulate fibroblast (FGF). endothelial cell division (PDGF)

platelet plug formation (2nd arm)

1. adhesion

2. aggregation

3. secretion (release reaction)

adhesion

platelets binding to damaged subendothelium. synthesis of TXA₂ on DTS. activation of microtubules & microfilaments: plts change shape.

vWF functions in all vessels (arteries). plts bind collagen via GPIa/IIa & GPVI. plts bind a few hours, release, repeat. plts secrete FGF & PDGF to stimulate fibroblasts & endothelial cell growth

aggregation

platelets binding to adherent platelets

secretion (release reaction)

release of intracellular mediators that amplify aggregation

stabilization of platelet plug

plt plug unstable alone: would wash away from blood flow, dislodged from abrasion. requires coagulation proteins to stabilize