WEEK 1- Introduction & The Vascular system Flashcards
a complex physiologic process that keeps circulating blood in a fluid state and then, when an injury occurs, produces a clot to stop the bleeding, confines the clot to the site of injury, and finally dissolves the clot as the wound heals
Hemostasis
uncontrolled bleeding
Hemorrhage
pathologic clotting
Thrombosis
Out of balance
Hemostasis
Overview of hemostasis
Vasoconstriction
Platelet adhesion and aggregation
Coagulation enzyme and activation
Cellular elements of hemostasis
Cells of vascular intima
Extravascular tissue factor (TF bearing cells)
Platelets
Plasma components of hemostasis
Coagulation proteins
Fibrinolytic proteins
Refers to the role of blood vessels and platelets in the initial response to a vascular injury or to the commonplace desquamation of dying or damaged endothelial cells
PRIMARY HEMOSTASIS
describes the activation of a series of coagulation proteins in the plasma, mostly serine proteases, to form a fibrin clot
Secondary Hemostasis
the final event of hemostasis
Fibrinolysis
the gradual digestion and removal of fibrin
clot as healing occurs
Fibrinolysis
Activated by desquamation and small injuries to blood vessels
Primary hemostasis
Activated by large injuries to blood vessels and surrounding tissues
Secondary hemostasis
Involves vascular intima and platelets
Primary hemostasis
Rapid, short-lived response
Primary hemostasis
Procoagulant substances exposed or released by damaged or activated endothelial cells
Primary hemostasis
Activated by large injuries to blood vessels and surrounding tissues
Secondary hemostasis
Delayed, long-term response
Secondary hemostasis
The activator, tissue factor, is exposed on cell membranes
Secondary hemostasis
Are complex and heterogeneous and distributed throughout the body
Endothelial cells
Display unique structural and functional characteristics and play essential roles in immune response, vascular permeability, proliferation, and hemostasis
Endothelial cells
Form a smooth, unbroken surface that eases the fluid passage of blood
Endothelial cells
Innermost vascular lining
Endothelial cells (endothelium)
Supporting the endothelial cells
Internal elastic lamina composed of elastin and collagen
Subendothelial connective tissue
Collagen and fibroblasts in veins
Collagen, fibroblasts, and smooth muscle cells in arteries
Anticoagulant Properties of Vascular Intima
Prostacyclin
Nitric oxide
Tissue factor pathway inhibitor
Thrombomodulin
Heparan sulfate
Procoagulant Properties of Vascular Intima
Vasoconstriction
Collagen
Von Willebrand Factor (vWF)
ADAMTS-13
P-selectin
Intercellular adhesion molecules (ICAMs)
Platelet endothelial cell adhesion molecules (PECAMs)
Smooth muscle cells and fibroblasts
Tissue Factor
Fibrinolytic Properties of Vascular Intima
Tissue Plasminogen Activator (TPA)
Plasminogen Activator Inhibitor-1 (PAI-1)
Thrombin Activatable Fibrinolysis Inhibitor (TAFI)
Platelet Morphology size
2-4 um
Platelet Morphology shape
disk-shaped, biconvex/spiky
Plate morphology Cytoplasm
light blue to purple, presence of chromomere and hyalomere
Platelet morphology Chromomere
granular and located centrally
Platelet morphology hyalomere
agranular and located in the periphery
serves as the body’s first line of defense against blood loss
Platelets
Platelets roll and cling to non platelet surfaces
Adhesion
Plateleys adhere to each other
Aggregation
Platelets discharge the contents of their granules
Secretion
Reversible
Adhesion
Irreversible
Aggregation
Secretion
Seals endothelial gaps, some secretion of growth factors , in arterioles VWF is necessary for adhesion
Adhesion
Platelet plugs form, platelet contents are secreted, requires fibrinogen
Aggregation
Occurs during aggregation, platelet contents are secreted, essential to coagulation
Secretion
Platelet dense granules
Adenosine diphosphaye (activates neighboring platelets)
Adenosine triphosphate
Calcium
Serotonin ( vasoconstrictor)
Plasma transports at least 16 procoagulant, also called
Coagulation fctors
Coagulation factors are synthesized in
Liver
How many enzymes that circulate as zymogens
8
In ________, the International Committee for the Standardization of the Nomenclature of the Blood Clotting Factors officially named the plasma procoagulants using _______________ in the order of their __________________.
1958
Roman numerals
Initial discovery / description
Factor 1
Fibrinogen
Factor II
Prothrombin
Factor III
Tissue factor
Factor IV
Ionic calcium
Factor VIII
Antihemophilic factor
Factor IX
Christmas factor
Factor X
Stuart-prower factor
Factor XII
Hageman factor
Prekallikrein
Fletcher factor
HMWK
Fritzegerald factor
Factor XIII
Fibrin-stabilizing factor
Platelet factor 3
Phospholipids, phosphatidyl serine, PF 3
Serine proteases
FACTOR IX, X,XI,VII, II, XII, pre-K
Thrombin substrate, polymerizes to form fibrin
Factor I - Fibrinogen
Cofactors
Factor III
Factor V
Factor VIII
HMWK
Mineral
Factor IV- ionic calcium
Factor VIII carrier and platelet adhesion
Von willebrand factor
Transglutaminase, transamidase
Factor XIII
Zymogens
• Prekallikrein
. FXII
. FXI
. FIX
F X
*FVII
* Prothrombin
* FXIII
Procoagulants in cofactor
HMWK
TISSUE FACTOR
FVIII
FV
Coagulation control proteins
Protein Z
Protein S
Thrombomodulin
These are named prothrombin group because of their structural resemblance to prothrombin
Vitamin-K Dependent Prothrombin Group
_____________ quinone found in green leafy vegetables and is produced by the intestinal organisms ____________ and ______________.
Vitamin K
Bacteroides fragilis and Escherichia coli
Vitamin K-Dependent Coagulation Factors Procoagulants
Prothrombin
VII
IX
X
Vitamin K-Dependent Coagulation Factors Regulatory Proteins
Protein C
Protein S
Protein Z
The pathways were characterized as cascades in
that as one enzyme becomes activated, it in turn
activated the next enzyme in sequence
Coagulation Pathways
Coagulation Pathways
● Intrinsic pathway
● Extrinsic pathway
● Common pathway
Intrinsic Pathway
VIII, IX, XI, XII
I, II, V, X
Extrinsic Pathway
VII I, II, V, X
Common pathway
I, II, V, X
The coagulation pathways are ____________
INTERDEPENDENT
Normal physiologic coagulation requires the presence of two cell types for formation of coagulation complexes:
- Cells that express tissue factor (usually extravascular)
- Platelets (intravascular)
Two Phases of Coagulation
Initiation
Propagation
Occurs on tissue-factor bearing cells
Initiation
Occurring on platelets
Propagation
Ensures that coagulation is localized and is not a systemic response (prevents excessive clotting or thrombosis)
Coagulation Regulatory Mechanisms
Principal regulators
- Tissue Factor Pathway Inhibitor (TFPI)
- Activated Protein C (APC)
- Antithombin (AT)
The final stage of hemostatic activation
Fibrinolysis
Is the systematic, accelerating hydrolysis of fibrin by plasmin
Fibrinolysis
binds to the lysine moieties on the fibrin molecule
Plasminogen
active form of plasminogen
Plasmin
Plasminogen Activation
Tissue Plasminogen Activator (TPA)
Urokinase Plasminogen Activator (UPA)
Control of Fibrinolysis
Plasminogen Activator Inhibitor-1 (PAI-1)
Alpha 2- Antiplasmin
Thrombin Activatable Fibrinolysis
Active form is the plasma serine protease plasmin, digests fibrin/fibrinogen
Plasminogen
Serine protease secreted by activated endothelium,
activates plasminogen
Tissue plasminogen activator (TA)
Serine protease secreted by kidney cells, activates
plasminogen
Urokinase plasminogen activator (UPA)
Serpin secreted by endothelium, inhibits tissue plasmino-
gen activator
Plasminogen activator inhibitor-1 (PAI-1)
Serpin, inhibits free plasmin
A2-Antiplasmin
Suppresses fibrinolysis by removing fibrin C-terminal lysine binding sites blocking TPA and plasminogen binding
Thrombin activatable fibrinolysis inhibitor (TAFI)
soft tissue hemorrhage – a generalized bleeding that is seen in acquired or congenital defects in secondary hemostasis
Anatomic hemorrhage
Pattern of inheritance in which the transmission of a dominant allele on an autosome causes a trait to be expressed in heterozygotes
Autosomal dominant
Pattern of inheritance resulting from the transmission of a recessive allele that is not expressed in heterozygotes
Autosomal recessive
Hemorrhagic spot, 1 cm or larger in diameter, typically forming an irregular blue or purplish patch. Also known as bruise
Ecchymoses
Nosebleed that requires intervention
Epistaxis
Bleeding from multiple sites, spontaneous and recurring bleeds, or hemorrhage that requires physical intervention of transfusion.
Generalized hemorrhage
Chronic joint bleeds that cause inflammation and immobilization
Hemarthroses
Vomiting of bright red blood
Hematemesis
Localized collection of extravasated blood, usually clotted, in an organ space or tissue
Hematoma
Intact RBCs in the urine
Hematuria
Free hemoglobin in the urine
Hemoglobinuria
Expectoration of blood secondary to hemorrhage in the larynx, trachea, bronchi and lungs
Hemoptysis
Acute severe blood loss requiring intervention and transfusions
Hemorrhage
Passage of fresh, red blood in your stool
Hematochezia
Bleeding from a single location
Localized hemorrhage
Stool containing dark red or black blood
Melena
Abnormally heavy or prolonged menstrual periods
Menorrhagia
Or systemic bleeding – a generalized bleeding that may indicate a disorder of primary hemostasis
Mucocutaneous hemorrhage
Pinpoint purple or red spots on the skin or mucous membranes, approximately 1mm in diameter
Petechiae
Purple skin discoloration, typically rounded with a diameter of greater than 3mm
Purpura
Formation, development, or presence of a clot in a blood vessel
Thrombosis