Physiology: Chapter 37

Guyton and Hall Textbook of Medical Physiology

→ Hemostasis - prevention of blood loss Contact with collagen fibers in subendothelium activates
platelets:
→ Achieved by several mechanisms:
1. Platelet swelling, irregular shape (pseudopods)
1. Vascular Constriction
2. Release of granules with active factors
2. Formation of Platelet Plug
3. Adherence to collagen and von Willebrand factor
3. Formation of Blood Clot = result of blood coagulation from injured tissue and each other forming clumps

4. Growth of fibrous tissue into blood clot 4. Release ADP and thromboxane A2

5. Activation of other platelets

6. platelet plug (loose without fibrin)

→ Begins ~ 15-20 s to 1 min after vascular damage

→ Initiated by:

1. Release of active factors from injured vessel wall

2. Activated platelets

3. Blood proteins adhering to damaged vessel wall

→ Immediately after cut or rapture in blood vessel → If vessel opening is not too large, in 3-6 min the
bleeding is stopped

→ In 20 min - clot retraction

1. LOCAL MYOGENIC SPASM

2. LOCAL AUTACOID FACTORS (thromboxane A2)

3. NERVOUS REFLEXES (pain)

→ Fibrous organization
→ spasm can last for many minutes or even hours o migration of fibroblasts

o forming connective tissue within 1-2 weeks

→ small cut = platelet plug rather than blood clot o Usually when clots are formed in the holes of
the vessel wall

→ Dissolving the clot

→ Platelets (thrombocytes) o Tissue clots

→ Fragments of megakaryocytes;
o diameter 1-4 um 150-300 x 10° /1 of blood

→ Contain many active factors:

o Actin, myosin, thrombosthenin

o ER, GA, Mitochondria

o Enzymes for prostaglandin production

o Fibrin-stabilizing factor

o Growth factors for vascular repair

o Glycoproteins on cell surface

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 Physiology: Chapter 37
Guyton and Hall Textbook of Medical Physiology

→ Balance of procoagulants and anticoagulants

1. Activation of prothrombin activator complex

(initiated by vessel or blood injury)

2. Conversion of prothrombin to thrombin.

3. Conversion of fibrinogen to fibrin fibers

→ mesh of blood cells & plasma forming a clot

→ Rate-limiting factor is step 1

→ Calcium = important

→ Prothrombin Activator converts:

o Prothrombin to Thrombin
o Fibrin to Fibrinogen

→ Mesh of fibrin fibers with trapped blood cells,

platelets and plasma

→ 60 min after clot formation all the fluid is expressed

out (serum)

→ Platelets are essential for retraction and pulling

together the edges of broken vessel

Clotting initiation;

1. Trauma to vascular wall and adjacent tissues

2. Trauma to blood itself

3. Contact of blood with collagen and damaged

endothelium

→ Two cascade pathways for prothrombin activator

formation: intrinsic and extrinsic

→ Disseminated Intravascular Coagulopathy

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 Physiology: Chapter 37
Guyton and Hall Textbook of Medical Physiology

→ Damage of blood vessel activates both pathways

→ They converge at the level of factor X

→ Extrinsic pathway - explosive (15 s)

→ Intrinsic pathway - slower (1-6 min)

→ Very important

1. Smoothness of endothelial surface

→ Prevents activation of intrinsic pathway

2. Glycocylix (mucopolisaccharide)
→ Repels platelets and clotting factors

→ Initiates when injured vascular wall or extravascular 3. Thrombomodulin

tissues come in contact with blood → Bound to endothelial membrane
→ Binds thrombin
→ Injured tissues release tissue factor (tissue → activates protein C (inhibitor of Factors V & VIII)
thromboplastin) = Activates Factor VII
o lipoprotein (proteolytic) & phospholipid

→ Factor VII activates Factor X 1. Fibrin fibers

→ Absorb 85-90 % of thrombin clot formation
→ Prevents excessive clot growth

2. Antithrombin Ill
→ binds thrombin
→ Interacts with heparin

→ Normally very low concentration in blood

→ Polysaccharide produced by basophil mast cells

o Lung
o liver capillaries).

→ Increases potency of antithrombin Ill 1000-fold

→ Besides thrombin, also removes Factors XI1, XI, X IX

→ Great clinical importance in blood clotting

→ Plasmin
→ Starts with trauma to the blood or contact of blood
with collagen o Strong proteolytic enzyme

→ More steps in cascade and thus slower than extrinsic o Cleaves fibrin and other clotting factors
pathway.
o Precursor is plasminogen (inactive),
→ All coagulation factors are in the blood
→ Plasmin is activated by tissue plasminogen activator
→ Factor IX activates Factor X (released from injured tissues 1-2 days after clot
formation)
→ Factor VIll - antihemophilic factor

→ Ca2+ necessary for all. but first 2 steps

→ removal of calcium (citrate, oxalate)

o prevention of clotting

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 Physiology: Chapter 37
Guyton and Hall Textbook of Medical Physiology

1. Femoral venous thrombosis & massive pulmonary

embolism

→ Liver produces most of clotting factors. → Occlusion of both pulmonary arteries

o liver disease = prone to bleeding o immediate death
→ Otherwise, therapy with IPA or streptokinase.
→ Vitamin K
2. Disseminated intravascular coagulation
o important co-factor for synthesis of prothrombin,
Factors VII, IX, and X, and protein C → Initiated by massive issue damage (tissue factor) or
sepsis (endotoxin)
o Produced by intestinal bacteria

o Absorbed in blood with fats

Treatment and prevention of thromboembolic conditions.
→ Liver insufficiency or lack of vitamin K (intestinal
disease, bile obstruction, neonates) 1. Heparin
→ immediate action, applied by injection
→ Short duration of anticoagulant effect (hours),

→ X-chromosome-related disease, affects males 2. Coumarins (warfarin)

→ Inhibit vitamin A epoxide complex 1
→ 85% cases - deficiency of Factor VIll o Inhibit reactivation of vitamin K in liver
o hemophilia A / classic hemophilia → Decrease effectiveness of prothrombin, and
factors VIL, IX, and X
→ 15% cases- Factor IX → Action after hours, but last longer (days)
o Christmas Disease
o Soft tissues injury

→ Various degrees of disease severity → Bleeding time

o After incision to fingertip or earlobe - 1-6 min
→ Prolonged bleeding from larger vessels after injury
→ Clotting time
→ Therapy: recombinant factor VIll injection after injury o Blood collection in glass tube
o invert tube every 30s
o wait until it clots (usually 6 min)
o Not reliable - not used clinically
→ Bleeding from small venules and capillaries
o thrombocytopenic purpura - blotchy skin → Prothrombin time

→ No symptoms unless platelet count o Relates to concentration of prothrombin in

o < 50 x109 /L (10 x 109 /L - lethal) patient's blood

→ Various causes: o Oxalated blood given large amounts of Ca2+ and

tissue factor - time to form a clot depends on the
o idiopathic – autoimmune amount of prothrombin

o iatrogenic -caused by bone-marrow o Usually, 12 sec

suppressing drugs (chemotherapy)
o Unreliable without normalization (INR) due to
variability of effectiveness of tissue factor

→ Thrombus - abnormal clot in blood vessel

→ Embolus - freely flowing thrombus.

Causes:

1. Roughened endothelial surface

→ arteriosclerosis, infection, trauma

2. Slow blood flow (blood stasis)

→ Prolonged sitting or prolonged immobility

3. Hypercoagulability
→ Cancer-related, genetic

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