The Circulatory System: Blood Outline Part 3

Hemostasis

cessation of bleeding

hemorrhage

excessive bleeding

Platelets are fragments of

megakaryocytes

normal platelet count=

130,000 to 400,000 platelets per microliter

Platelet functions

• secrete vasoconstrictors- help reduce blood loss

• form platelet plugs to seal small breaks

• secrete procoagulants (clotting factors) to promote clotting

• initiate formation of clot dissolving enzyme

• secrete growth factors—stimulate mitosis to repair blood vessels

Thrombopoiesis

(platelet production)

stem cells become megakaryoblasts

Megakaryoblasts

replicate DNA without dividing

form gigantic 100 um cells (megakaryocytes)

Megakaryocytes

in bone marrow adjacent to blood sinusoids

• tendrils of cytoplasm (proplatelets) protrude into blood sinusoids: blood flow splits off fragments called platelets

Vascular Spasm (step 1 of hemostasis)

prompt constriction of broken vessel

• most immediate protection against blood loss

• platelets release serotonin (vasoconstrictor)

• pain and smooth muscle injury prompt quick constriction

• buys time for other 2 clotting pathways

Platelet Plug formation (step 2 of hemostasis)

normally prostacyclin (platelet repellent) coats endothelium

but…

broken vessel exposes collagen

platelets grow pseudopods (tendrils of platelet)—stick to damaged vessel; pseudopods contract and draw walls of vessel together forming platelet plug

platelets degranulate, release:

serotonin- vasoconstricts

Thromboxane A2- promotes platelet aggregation, degranulation, and vasoconstriction

Positive feedback cycle active until break in small vessel seals

Coagulation (clotting, step 3 of hemostasis)

most effective defense against bleeding

• conversion of fibrinogen (ogen=precursor to something else) to fibrin threads to form framework of clot

• Procoagulants (clotting factors)— usually made by liver; present in plasma

  • activate one factor, it activates next.. reaction cascade

extrinsic pathway

• factors released by damaged tissues begin cascade

intrinsic pathway

• factors in blood begin cascade (platelet degranulation)

coagulation extrinsic pathway

initiated by tissue thromboplastin (factor III) from damaged tissues

combines with VII to activate X

calcium required

Intrinsic pathway

initiated by Factor XII from platelets

cascade to factor XI to IX to VIII to X

calcium required

Rapid clotting

each activated cofactor activates more molecules in next step of sequence

Prothrombin activator

converts prothrombin to thrombin

Thrombin!

converts fibrinogen to fibrin

Positive feedback when thrombin speeds up formation of

prothrombin activator (which converts prothrombin to thrombin that converts fibrinogen to fibrin)

Platelet-derived growth factor (PDGF)

stimulates fibroblasts and smooth muscle cell mitosis—repair damaged vessel

Fibrinolysis

dissolution of clot

• factor XII speeds up formation of kallikrein enzyme

• kallikrein converts plasminogen into plasmin = fibrin-dissolving enzyme

Platelet repulsion (prevents inappropriate clotting)

platelets do not adhere to prostacyclin-coated endothelium

2 natural anticoagulants

Heparin (from basophils) interferes with formation of prothrombin activator (makes thrombin which then makes fibrin)

Anti-thrombin (from liver) deactivates thrombin

clotting disorders

deficiency of any clotting factor can shut down coagulation cascade (can’t clot)

Hemophilia

family of hereditary diseases characterized by deficiencies of factor

Hemophilia A and B vs C

sex-linked recessive vs autosomal

Thrombosis

abnormal clotting in unbroken vessel (overclotting)

thrombus=clot

Embolus

thrombus (clot) that travels in blood

Pulmonary embolism

clot from legs may travel to lungs

Infarction

tissue death

may occur if clot blocks blood supply to heart (MI) or brain (stroke)

coumarin, warfarin=

vitamin K (required for formation of clotting factors) antagonists (prevents clots)

aspirin suppresses

thromboxane A2 (makes platelets sticky) (prevents clots)

3 things for dissolving clots

Streptokinase: enzyme that dissolve clots in coronary vessels

Tissue Plasminogen Activator (TPA): faster and more specific (given to people who have had a stroke)