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RBCs (erythrocytes)
Transport of O2 and CO2
-lacks nucleus
Platelets (thrombocytes)
Hemostasis through blood clotting
WBCs (leukocytes)
Defense
Hematopoiesis
-blood cell formation
-occurs in bone marrow
-in neonates, most of skeleton is active bone marrow
-in adults, mainly in vertebrae, ribs, skull, pelvis, and proximal femur
-derived from stem cells
Common myeloid progenitor and common lymphoid progenitors
Hematopoietic stem cells differentiate into what?
Thrombopoietin (TPO)
Common myeloid progenitors differentiate into megakaryoblasts with the help of which hormone?
-regulates rate of platelet formation
-secreted by liver and kidneys
Erythropoietin (EPO)
Common myeloid progenitors differentiate into proerythroblasts with the help of which hormone?
-primary regulatory hormone
-released from kidneys when O2 tension is reduced
Megakaryoblasts, proerythroblasts, myeloblasts, and monoblasts (all eventually mature into -cytes)
Common myeloid progenitors differentiate into what 4 types of blasts?
Megakaryocyte
Megakaryoblast turns into?
Erythrocytes
Proerythroblast turns into?
Granulocytes: Eosinophil, basophil, and neutrophil
Myeloblasts differentiate into?
Monocyte (agranulocyte)
Monoblast turns into?
Lymphocyte (agranulocyte)
Lymphoblast turns into?
Erythropoiesis
Red blood cell formation
-replaces 0.8-1.0% of circulating RBCs daily
-regulated to provide adequate O2 to tissues
-requires Iron, Folic acid, and Vit B12
-produces Hb
-cell organelles disappear
Thrombopoiesis
Platelet production
-platelets have NO nucleus
-platelets are disk shaped
Leukopoiesis
WBC production
-T lymphocytes- thymus
-B lymphocytes- bone and lymph
Reticulocyte
Immature RBC
-if elevated, this means your body has increased its demand of RBCs
-useful index for RBC production
Number of platelets in circulation
Plasma concentration of TPO (thrombopoietin) is determined by what?
LOW platelet count (thrombocytopenia)
High TPO (thrombopoietin) is a result of what?
Monocytes
-agranulocyte
-leaves bone marrow as soon as its formed
-spends 2-3 days in circulation before becoming macrophages
Pliable; microcirculation
RBCs are ____ and allow passage through _______
LARGE osmotic pressures
RBCs can withstand ________, when they pass through renal medullary circulation
Hb, Glycolytic enzymes, and Carbonic Anhydrase
When RBCs leave the bone marrow, they contain what key cytoplasmic proteins?
Carbonic anhydrase
Essential for CO2 carriage in the blood
-carried by RBCs when they leave the bone marrow
Glycolyitic enzymes
No mitochondria, MUST GET ATP VIA GLYCOLYSIS
-carried by RBCs when they leave the bone marrow
Hemoglobin
Large O2 carrying capacity of blood
-carried by RBCs when they leave the bone marrow
100-120 days
Normal lifespan of a RBC?
Macrophages
Aging RBCs are removed by ______, mainly in the spleen
Bilirubin
End product of Hb breakdown is ______, which is conjugated in the liver and excreted in the bile
Anemia
Red cell mass decreased
Polycythemia
Red cell mass increased
Hb concentration
Hb per volume of blood
HCT/ packed cell volume
Ratio of red cells to volume of whole blood
RBC count
Number of RBC per liter of blood
Mean cell volume (MCV)
Average size of RBC
Femtoliters
Measures MCV, average volume of single red cells expressed
HCT/ RBC count
How to calculate MCV
Microlytic
<80 fL --> small
-MCV
Macrolytic
>100 fL --> large
-MCV
Mean cell hemoglobin (MCH)
Average amount of Hb in red cell
Hb/ RBC count
Mean cell hemoglobin concentration (MCHC)
Average concentration of Hb in RBC
MCH/MCV
Blood smear
Performed to look at size and shape of cells
-e.g. a reticulocyte count is determined in patients with anemia to assess rate of red cell production
So our body recognizes them as self
Why are our RBCs tagged with antigens?
Antigens (agglutinogen)
Found on the surface of cells to help immune system recognize self cells
Antibodies (agglutinins)
Secreted by lymphocytes in response to foreign cells (in plasma)
Type A
Has the A antigen
Type B
Has the B antigen
Type AB
Has BOTH A and B antigens
Type O
-can be given as universal donor because there are no antigens on O
Has NEITHER A nor B antigens
Anti- B antibodies
Type A blood has what kind of antibodies?
Anti- A antibodies
Type B blood has what kind of antibodies?
NO antibodies (universal recipient)
-the immune system would attack if there were any antibodies
Type AB blood has what kind of antibodies?
Anti A and anti B antibodies (universal donor)
Type O blood has what kind of antibodies?
Antibodies would bind to erythrocytes and cause agglutination and hemolysis
What would happen if a person received the wrong blood type?
Rh factor
Antigen D
Rh-positive
Has antigen D
Rh- negative
Does not have the D antigen
-Rh- mother that carries an Rh+ fetus will develop Anti-Rh antibodies
-first pregnancy is viable
-issue arises when second pregnancy involves another Rh+ fetus
-that fetus will be attacked by Anti-Rh antibodies produced by the mother in pregnancy number one
Describe Rh factor issues in pregnancy
RhoGAM
Inactivates the Anti-Rh antibodies (Anti-D ABs) made against Rh+ fetuses
Hemostasis
Regulated interactions between blood vessel walls, circulating platelets, and clotting proteins in plasma
Fibrinolysis
Once a stable clot is formed, it is removed via _______
Vasoconstriction
What is the first occurrence after a cut that allows for less volume in the area as well as less blood loss?
Serotonin and thromboxane A2
Platelet activation and clot formation at the site of injury results in the release of what two vasoconstrictors?
Thrombin
-clotting protein
-highly potent endothelin-1
Platelet plug formation
Primary hemostasis
-occurs at site of damage
-FAST
-BIGGEST AFFECT ON ARTERIES
Clot formation
Secondary hemostasis
-fibrin mesh forms with platelets and other trapped cells
-SLOW
-BIGGEST AFFECT ON VEINS
POSITIVE feedback loop
Platelet function is a ______
Platelet Adhesion
-phase 1
-encompasses Integrin family, vWF, Thromboxane A2, and Thrombin
Integrin family
Binds to extracellular matrix proteins (collagen) in Phase 1 Platelet Adhesion
von Willebrand factor (VWF)
Released by endothelial cells and activated by platelets
-promotes platelet adhesion by promoting cross links between platelets and collagen
-acts in Phase I Platelet Adhesion
-augments platelet adhesion and aggregation in Phase 2 Platelet Activation
Platelet Activation
-phase 2
-release of many factors that promote hemostasis (ADP, Serotonin and Thromboxane A2, vWF, Ca2+, Fibrinogen, Factor V, and Platelet-derived growth factor (PDGF))
ADP
What amplifies platelet activation response in Phase 2- Platelet Activation?
Ca2+, Fibrinogen, and Factor V
What facilitate coagulation in Phase 2 Platelet Activation?
Platelet- derived growth factor (PDGF)
What promotes wound healing through fibroblasts in Phase 2 Platelet Activation?
Platelet Aggregation
-phase 3
-completes formation of the platelet plug
Prostacyclin and nitric oxide
Platelet plug is prevented from extending beyond site of injury by ______ which are secreted by intact endothelial cells and INHIBIT PLATELET ACTIVATION
-occurs in Phase 3 Platelet Aggregation
Fibrinogen; Fibrin
Blood clot is formed when ______ is proteolytically cleaved to form ______
Platelet Activation (phase 2)
Clots can occur without ______, but there is usually parallel activation of primary and secondary hemostasis
Intrinsic and extrinsic pathways
How can clotting be initiated?
Cascade
Intrinsic and extrinsic pathways are both a _____ that turns inactive proteins (clotting factors) into active form
LOW
Clotting factors are normally ____ in circulation to prevent the clotting cascades from becoming active
Intrinsic pathway
-clotting cascade
-triggered when blood contacts a negatively charged surface (exposed subendothelial collagen, aggregation of platelets, etc.)
-thought to be most important pathway for maintaining thrombin generation
Extrinsic pathway
-clotting cascade
-activated when blood contacts cells outside the vascular endothelium
-thought to be the most important pathway for initiating thrombin activation
Tissue factor
Nonvascular cells express _____ which initiates the extrinsic pathway
Common pathway
Final coagulation pathway activated either by the intrinsic or the extrinsic pathway, and ending in the formation of a blood clot
Factor X
The common pathway begins with the activation of ________
-Prothrombin ---> Thrombin
Bleeding time
-sensitive test of platelet function
-small incision made on forearm, and record time it takes to stop bleeding
-ASA increases ______
Prothrombin time (PT)
-evaluates extrinsic coagulation pathway
-sample of blood plasma is incubated with tissue factor with excess Ca2+
Warfarin (anti-coagulant)
What increases prothrombin time?
Partial thromboplastin time (PTT)
-evaluates intrinsic pathway
-adds activator surface (silica) plus phospholipid and Ca2+ to sample
Heparin (anti-coagulant)
What increases PTT?
Capillary endothelium
What is the main source of anticoagulant factors?
Tissue factor pathway inhibitor (TFPI)
What blocks activated Favtor VII in the extrinsic pathway?
-acts as an anticoagulant
Antithrombin III
What binds to activated factor X and thrombin
-acts as an anticoagulant
-is augmented by Heparin
Protein C and S
-anticoagulants
-act together to inactivate activated Factor V and VIII
Plasminogen
Serum protein absorbed into clot
Plasmin
Breaks down fibrin and fibrinogen
-breakdown products are scavenged by macrophages
-NOT ACTIVE IN CIRCULATION
Tissue plasminogen activator and Urokinase-type plasminogen activator
Plasminogen activation is regulated by what two factors released by endothelial cells?
a2-antiplasmin
Free Plasmin is bound to what to prevent clot breakdown?
Heart
What pressurizes blood and provides the driving force?