1. Hemodynamic Disorders
Hemodynamic Disorders
 Edema
 Edema
 Hyperemia and Congestion
 Hyperemia and Congestion
 Hemorrhage
 Hemorrhage
 Hemostasis and Thrombosis
 Hemostasis and Thrombosis
 Embolism
 Embolism
 Infarction
 Infarction
 Shock
 Shock
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Dr. Krishna Tadepalli, MD, www.mletips.com

2. Feature
Hemostasis
Thrombosis
What is it?
Blood clot
Blood clot
Where is it?
Site of vascular
injury
In an uninjured
vessel
Why is it?
Trauma
(common)
Atherosclerosis
What happens
later?
Stops blood loss Produce
(deserved effect) complications
(Emboli)
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3. Hemostasis
Hemostasis
 Events following vascular injury
 Events following vascular injury
 1. transient vasoconstriction ( by neurogenic
 1. transient vasoconstriction ( by neurogenic
mechanisms, Endothelin – vasoconstrictor of
mechanisms, Endothelin – vasoconstrictor of
Endothelial cells), reduce blood loss
Endothelial cells), reduce blood loss
 2. Primary Hemostasis  formation of Primary
 2. Primary Hemostasis  formation of Primary
haemostatic plug (( by platelet adhesion, activation
haemostatic plug by platelet adhesion, activation
& Aggregation),
& Aggregation),
 3. Secondary Hemostasis  Platelets + Fibrin
 3. Secondary Hemostasis  Platelets + Fibrin
(( from coagulation pathways- either intrinsic or
from coagulation pathways- either intrinsic or
extrinsic), forms secondary haemostatic plug
extrinsic), forms secondary haemostatic plug
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4. Hemostasis
Hemostasis
 Role of Endothelium
 Role of Endothelium
 1. Produce Pro-thrombotic (( Plasminogen
 1. Produce Pro-thrombotic Plasminogen
activator inhibitors – PAI, Tissue factor, vWF)
activator inhibitors – PAI, Tissue factor, vWF)
and Anti-thrombotic factors (( Vasodilators –
and Anti-thrombotic factors Vasodilators –
PGI2, NO; tPA, Heparin like molecules &
PGI2, NO; tPA, Heparin like molecules &
Thombomodulin)
Thombomodulin)
 2. Balance of these factors determine the end result
 2. Balance of these factors determine the end result
(( clot or dissolution of clot)
clot or dissolution of clot)
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5. PAI
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6. Coagulation pathway
Coagulation pathway
 Role of Platelets
 Role of Platelets
 Granules  α granules( contain clotting factors &
 Granules  α granules( contain clotting factors &
Growth factors), Dense or δ granules (( ADP, Ca++++,
Growth factors), Dense or δ granules ADP, Ca ,
Neuropeptides, Epinephrine)
Neuropeptides, Epinephrine)
 Response to injury  bind to sub-endothelial
 Response to injury  bind to sub-endothelial
ECM (( vWF + Gp -Ib) Adhesion
ECM vWF + Gp -Ib) Adhesion
 Expose Phospholipid complexes (helps in intrinsic
 Expose Phospholipid complexes (helps in intrinsic
clotting pathway) & release ADP& Ca++++
clotting pathway) & release ADP& Ca
 Aggregate with other platelets (( with fibrin by Gp
 Aggregate with other platelets with fibrin by Gp
IIb-IIIa on platelet surfaces
IIb-IIIa on platelet surfaces
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7. Hemostasis
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8. Aspirin in patients at risk for coronary thrombosis8
It irreversibly acetylates and inactivates cyclooxygenase-1  due to
its ability to block TxA2 synthesis EQ
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9. 9
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10. Coagulation pathway
Coagulation pathway
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11. Coagulation pathway
Coagulation pathway
 Most important step in this pathway
 Most important step in this pathway
(either intrinsic or extrinsic)  formation of
(either intrinsic or extrinsic)  formation of
Thrombin
Thrombin
 Thrombin produces it effects  through
 Thrombin produces it effects  through
PARS( Protease activated receptors – 7 GPCR
PARS( Protease activated receptors – 7 GPCR
family)
family)
 Major effects of Thrombin
 Major effects of Thrombin
 Fibrin formation from Fibrinogen
 Fibrin formation from Fibrinogen
 On Platelets TxA2
 On Platelets TxA2
 On Endothelial cells NO, tPA, PGI2
 On Endothelial cells NO, tPA, PGI2
 act also on Lymphocytes, Neutrophils, Monocytes
 act also on Lymphocytes, Neutrophils, Monocytes
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12. Coagulation pathway
Coagulation pathway
 Thrombin
 Thrombin
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13. Anti -- Coagulants
Anti Coagulants
Natural ones
Natural ones
 1. Antithrombins( AT-III)  inactivate Thrombin;
 1. Antithrombins( AT-III)  inactivate Thrombin;
Factors IX to XII; bind to heparin like molecule on
Factors IX to XII; bind to heparin like molecule on
endothelium
endothelium
 2. Proteins – C & S  produced by liver; need Vit. K for
 2. Proteins – C & S  produced by liver; need Vit. K for
activation; inactivate Factors V, VIII
activation; inactivate Factors V, VIII
 Tissue Factor Pathway Inhibitors (TFPI)  inhibit
 Tissue Factor Pathway Inhibitors (TFPI)  inhibit
factors VII, X
factors VII, X
Clinical significance
Clinical significance
Heparin act through AT-III; Monitor PTT (Intrinsic pathway), Antidote is
Heparin act through AT-III; Monitor PTT (Intrinsic pathway), Antidote is
Protamine, can produce HIT (heparin induced thrombocytopenia); can be
Protamine, can produce HIT (heparin induced thrombocytopenia); can be
given in pregnancy (as it can’t cross placenta); need frequent injections
given in pregnancy (as it can’t cross placenta); need frequent injections
Warfarin  act through inhibition of Vit K mediated carboxylation of
Warfarin  act through inhibition of Vit K mediated carboxylation of
clotting factors (II,VII, IX, X); Extrinsic pathway Monitor PT; Antidote is
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clotting factors (II,VII, IX, X); Extrinsic pathway Monitor PT; Antidote is
Vit.K contraindicated in pregnancy (teratogenic)
Vit.K1 1;;contraindicated in pregnancy (teratogenic)
Dr. Krishna Tadepalli, MD, www.mletips.com

14. Fibrinolytic pathway
Fibrinolytic pathway
 Most important step in this pathway
 Most important step in this pathway
 formation of Plasmin from Plasminogen
 formation of Plasmin from Plasminogen
 Tissue Plasminogen activator (tPA) is important in this
 Tissue Plasminogen activator (tPA) is important in this
conversion
conversion
 Plasmin  breaks down excess Fibrin  Fibrin split
 Plasmin  breaks down excess Fibrin  Fibrin split
products or Fibrin degradation products (FSP or FDP)
products or Fibrin degradation products (FSP or FDP)
 Most important component of FDP  D-dimer
 Most important component of FDP  D-dimer
Clinical significance
Clinical significance
D-dimer positivity (≥200 ng) patient had clot and it is lysed by
D-dimer positivity (≥200 ng) patient had clot and it is lysed by
Plasmin
Plasmin
Conditions where D-dimer is positive  DIC, DVT, PE
Conditions where D-dimer is positive  DIC, DVT, PE
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15. Fibrinolytic pathway
Fibrinolytic pathway
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