Lecture 13: Blood + Hemostasis

Question 1

Plasma

Answer 1

Organic and inorganic substances dissolved in water (90% water). Most solutes by weight are plasma proteins

Question 2

3 groups of plasma proteins

Answer 2

1. Albumins
2. Globulins
3. Fibrinogen

Question 3

Serum

Answer 3

Plasma w/ fibrinogen and other clotting proteins removed

Question 4

RBC shape

Answer 4

High surface area:volume of isc shape enables fast diffusion and flexibility

Question 5

RBC removal

Answer 5

Spleen and liver destroy old/damaged RBCs, producing bilirubin

Question 6

Active red marrow

Answer 6

Children: most bones
Adults: only chest, skull base, vertebrae, pelvis, limb ends

Question 7

Hemostasis

Answer 7

Stoppage of bleeding. Most effective in small vessel injuries

Question 8

Hematoma

Answer 8

Accumulation of blood in tissues from bleeding

Question 9

Hemostasis processes

Answer 9

2 interdependent processes
1. Formation of platelet plug
2. Blood coagulation (clotting)
Both involve platelets

Question 10

Constriction of injured vessels

Answer 10

Immediate intrinsic response of injured/severed vessels is constriction due to local substance changes from endothelium/blood cells. Slows blood flow and presses opposed endothelia together to induce “stickiness”

Question 11

Formation of platelet plug

Answer 11

1. CT exposure
2. Platelet-collagen binding + secretory vesicle release
3. Platelet activation and aggregation
4. Fibrinogen binding
5. Clot retraction

Question 12

CT exposure

Answer 12

Platelets must adhere to surface; vessel injury disrupts endothelium and exposes CT collagen

Question 13

Platelet-collagen binding

Answer 13

Plasma von Willebrand factor (vWF) intermediates platelet-collagen adhesion

Question 14

von Willebrand factor

Answer 14

vWF secreted by endothelial cells/platelets, binds+changes conformation of exposed collagen fibers as to bridge btwn damaged vessel wall and platelets

Question 15

Platelet secretory vesicle release

Answer 15

Binding to collagen triggers vesicle release to induce further platelet activation (ADP, serotonin, etc.) and platelet aggregation (pos. feedback loop where new platelets adhere to old ones)

Question 16

Platelet activation

Answer 16

Local factors induce changes in local platelet shape, metabolism, and surface protein to facilitate forming platelet plug. Platelet activity also induces local vasoconstriction.

Question 17

Fibrinogen binding to platelets

Answer 17

Platelet activation exposes fibrinogen binding sites; fibrinogen fills gaps in between platelets to seal plug

Question 18

Clot retraction

Answer 18

Platelets have high actin+myosin content; aggregation induces interaction to compress and strengthen clot.

Question 19

Platelet plug regulation

Answer 19

Undamaged endothelial cells secrete prostacyclin and NO; strong inhibs. of platelet aggregation, adhesion, activation, and vasodilator

Question 20

Prostacyclin

Answer 20

Aka prostaglandin I2 (PGI2). Acts to limit platelet plug formation to damaged area and prevent unnecessary plug formation

Question 21

Blood coagulation (clot formation)

Answer 21

Transformation of blood to solid gel clot (thrombus); chemical cleavage cascade. Dominant hemostatic defense.

Question 22

Thrombus

Answer 22

Primarily made of fibrin polymers, occurs locally around platelet plug. Traps RBCs/other cells

Question 23

Key point of clot formation

Answer 23

Activation of prothrombin -> thrombin; thrombin catalyzes fibrinogen -> fibrin and XIII -> XIIIa (X-linking of fibrin in clot).
Clotting also requires Ca++ (never deficient)

Question 24

Thrombin-platelet activation

Answer 24

Thrombin activated platelets bind several clotting factors and display platelet factor (PF); cofactor for clotting cascade

Question 25

2 pathways for clotting cascade, linked by collagen

Answer 25

1. Intrinsic: everything req. is in blood
2. Extrinsic: req. additional cellular element (Tissue Factor)

Question 26

Clotting pathway activation

Answer 26

Activated sequentially (not parallel!). Extrinsic typically initiates but requires intrinsic thrombin pos. feedback for adequate sustained coag.

Question 27

Role of liver in clotting

Answer 27

Liver produces many plasma clotting factors; also produces bile salts for Vit. K absorption. Vit. K req. for prothrombin/factor synthesis.

Question 28

Anti-clotting systems

Answer 28

Defects -> hypercoagulability
1. Tissue Factor Pathway Inhibitor
2. Thrombomodulin
3. Antithrombin III

Question 29

Tissue Factor Pathway Inhibitor

Answer 29

TFPI acts during initiation phase of clotting; secreted mainly by endothelial cells and limits extrinsic thrombin generation.

Question 30

Thrombomodulin

Answer 30

Endothelial cell receptor that binds thrombin and eliminates all clot producing effects. Bound thrombin binds/activates protein C -> inactivates VIIIa, Va. Thus intact endothelium makes thrombin inactivate clotting

Question 31

Antithrombin III

Answer 31

Inactivates thrombin/other factors, present on endothelial cell surface. Enhanced when bound to heparin (anticoagulant). Prevents clot spreading; rapid inactivat. of factors carried away by blood flow.

Question 32

Fibrinolytic (thrombolytic) system

Answer 32

Dissolves cells after forming (not limiting formation). Principal effector of clot removal via plasmin

Question 33

Plasmin

Answer 33

Plasminogen -> plasmin -> fibrin digestion; many plasminogen activators

Question 34

tissue Plasminogen Activator

Answer 34

tPA secreted by endothelial cells; plasminogen + tPA bind fibrin during clotting and is incorporated throughout the clot. tPA very weak w/o fibrin

Question 35

Anticlotting drugs

Answer 35

-Aspirin (inhib. cyclooxygenase to reduce platelet aggregation; low dose doesn’t affect endothelial COX)
-Oral anticoagulants interfere w/ clotting factors
-Thrombolytic therapy dissolves formed clots

Question 36

Cyclooxygenase (COX)

Answer 36

Generates prostaglandins, thromboxanes

Question 37

Spectrin

Answer 37

Long, rod shaped protein that scaffolds under RBC membrane to maintain shape/integrity.

Question 38

Spherocytosis

Answer 38

Spectrin deficiency leading to fragile, sphere-shaped RBCs

Question 39

Oxidation of hemoglobin to methemoglobin

Answer 39

Oxidation of Fe++ -> Fe3+ (nonfunctional); methemoglobin reductase in RBC counters. Req. NADH (glycolysis byproduct)

Question 40

Oxidation of hemoglobin cysteines

Answer 40

Cys oxid. -> irreversible crosslinking; inactivates Hb. Prevented w/ GSH + glutathione peroxidase, NADPH cofactor (maintain by G6P DH)

Question 41

Extravascular hemolysis

Answer 41

RBC senescence -> engulfment by splenic macrophages

Question 42

Intravascular hemolysis

Answer 42

Hb release into blood as dimers/methemoglobin -> haptoglobin/hemopexin -> bile. Excess Hb overwhelms haptoglobin, remaining to urine

Question 43

Erythroblastosis Fetalis

Answer 43

Hemolytic newborn disease based on Rh compatibility. Rh+ sperm + Rh- egg -> Rh+ fetus; first birth triggers Rh Ab generation in mother; future Rh+ babies trigger immune response, hemolysis -> neurotoxic bilirubin. Req. giving mothers anti-D Abs near birth for rapid removal of D Ag

Question 44

Basic blood groups

Answer 44

ABO antigens (A/B Abs), Rh +/- (D antigen)

Question 45

Activated Thromboplastin Time

Answer 45

aPTT test; time required for recalcified plasma to clot after adding activated partial thromboplastin; measures intrinsic clotting path

Question 46

Prothrombin Time

Answer 46

Assesses extrinsic clotting path.; time req. for recalcified plasma to clot after adding tissue thromboplastin. No clinical assay for tissue factor deficiency exists.