19+20 Flashcards
Yolk-sac phase, hepatic phase, and bone marrow phase
yolk = hematopoiesis begins week 3; formation of blood islands
hepatic = major blood forming organ in second trimester
bone marrow = begins during second trimester
main contributor after birth
hematopoiesis after birth? most to least
- vertebral and pelvis
- sternum
- ribs
- lymph nodes
- femur
- tibia
What do the pluripotent stem cells give rise too?
Myeloid stem cell and lymphoid stem cell
myeloid stem cell?
give rise too:
- proerythrocyte (RBC)
- megakaryocyte (thrombocytes)
- eosinophilic myeloblast (eosinophils)
- basophilic myeloblast (basophils)
- myeloblast (neutrophil)
- monoblast (monocytes)
lymphoid stem cell?
T lymphoblast and B lymphoblast
T-cell and B-cell
endosteal niche
found in spongy bone
used for storage of stem cells, self-renewal, and inhibition of differentiation
Vascular niche
found in bone marrow
Function:
support and promote differentiation
secrete growth factors
Yellow vs red bone marrow
Red: active hematopoiesis
yellow: fat, capillaries, reticular cells, inactive hematopoiesis
Erythropoietin / thrombopoietin / cytokines
Erythropoietin = produced by the kidney’s to increase RBC precursors
thrombopoietin = hormone from the liver to stimulate platelet formation
cytokines = stimulate proliferation
What stimulates leukocyte production?
colony-stimulating factor and interleukin
Erythropoiesis
stimulated by hypoxia
- proerythroblast
- basophilic erythoblast
- polychromatophilic erythoblast
- orthochromatophilic erythoblast
- reticulocyte
- RBC
Granulopoiesis
- myeloblasts
- promyeloblast (azurophilic granules)
- myeloblast (specific granules)
- metamyelocyte
- band (horseshoe nucleus)
- mature form
MONOCYTOPOIESIS
- monoblasts
- promonocytes
- monocytes
- once in tissue = macrophages
THROMBOPOIESIS
- megakaryoblast
- megakaryocyte
- platelets are formed from the fragments of the megakaryocyte cytoplasm
LYMPHOPOIESIS
- lymphoblasts
- prolymphocytes
from bone marrow to thymus = T-cells
remain in bone marrow = B-cells
NK cells
The role of vitamin K and gamma carboxylation
Required for hepatic synthesis of prothrombin (factor II)
factors VII, IX, X, and protein C+S
Vit K is a coenzyme for what enzyme
gamma- Glutamyl carboxylase
What is the benefit of gamma- carboxylation
allows for the binding of Ca that allows for efficient clotting
What two things are sensitive to Vitamin K
- INR
2. Factor VII
what does calcium chelators do?
they bind to all the Ca in the blood, this no clotting occurs
What do high levels of D-dimers indicate
the possibility of deep vein thrombosis
high risk for pulmonary embolism
The roles and prostacyclin and NO?
these chemicals are released by the endothelium to prevent aggregation
prostacyclin is an antagonist of thromboxane A2
Antithrombin III
Binds to and inhibits factor Xa, thrombin (IIa) and other activated clotting factors
role of protein C and S
Proteins C and S act together to inactivate cofactors Va and VIIIa of coagulation cascade
protein S is a cofactor of protein C
protein C is activated by the binding of thrombomodulin to thrombin
The role of plasmin
Plasmin causes fibrinolysis releasing fibrin degradation products (D -dimers).
Aspirin
inhibits thromboxane A2 formation in platelets
irreversible inhibitor of COX
prevents clots
heparin
activates antithrombin III and inactivates thrombin
prevents clots
warfarin
Blocks VKOR in the liver and prevents the activation of Vit. K
oral anticoagulant
streptokinase
Converts plasminogen to plasmin enabling dissolution of clots
Tissue plasminogen activator
used to dissolve a thrombus
Hemophilia A and B
X-linked recessive disorder
bleeding time = normal platelet count = normal INR = normal APTT = increased (defect in intrinsic pathway)
How to differentiate between hemophilia A and B
A = factor VIII deficiency
B = factor IX deficiency
Von Willebrand disease
bleeding time = prolonged platelet count = normal APTT = prolonged INR = normal vWF = low
defect in platelet plug formation
instability of factor VIII
Thrombocytopenia
increased bleeding time and low platelet count
increased bleeding time, but normal/ low platelet count?
platelet receptor defects
GpIb defect: Bernard-Soulier syndrome
GpIIb/IIIa defect: Glanzmann Thrombasthenia
