plasma and cellular elements of blood hematopoiesis rbc physiology coagulation ch 16: blood
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Plasma and Cellular Elements of Blood Hematopoiesis RBC Physiology Coagulation
Ch 16: BloodCh 16: Blood
Fig 16-1
Blood = connective tissue
Extracellular matrix: Specialized cells:
Blood Components Overview
Fig 16-1/3
20-40%
50-70%
2-8%
Plasma
CellularElements
Blood
1- 4%
Total WBC: 4,000 - 11,000
Red Blood Cells
O2
Fig 16-5
Hem(at)opoiesis =Hem(at)opoiesis = Blood Cell Blood Cell FormationFormation
Few uncommitted stem cells in red bone marrow throughout life time (Fig 16-2)
Controlled by cytokines. Examples:Erythropoietin CSFs and ILs: e.g. M-CSF, IL-3 (=
multi CSF)Thrombopoietin
Leukemia vs. leukocytosis vs. leukopenia
Compare to Fig 16-2
Controlled by ____________,specifically CSFs and ILs
EPO Regulates RBC EPO Regulates RBC ProductionProduction
“Hormone” synthesized by kidneys in response to hypoxemia
EPO gene cloned in 1985 Recombinant EPO now available (Epogen, Procrit)
Use in therapy, abuse in sport
Erythropoiesis
RBC bag of Hb for carrying O2
lifespan ~ 120 days
source of ATP for RBC?
enter circulation
Reticulocytes
Tissue O2
Tissue
O2
EPO release Mitotic
rate
Maturation speed
Hemoglobin (Hb)Hemoglobin (Hb)
Requires iron (Fe) + Vit. B12 (cobalamin) p.698/Ch21
Quaternary protein structure ?
Reversible binding between Fe & O2
CO: a toxic gas (not in book)
Bilirubin to bile. Hyperbilirubinemia
HbA vs. HbF
Hb Structure
How many O2 can 1Hb carry?
Porphyrin ring with Fe in center
RBC DisordersRBC DisordersPolycythemia vera (PCV ~ 60-
70%)
Anemias (O2 carrying capacity too low) Hemorrhagic anemia Fe deficiency anemia Hemolytic anemia, due to genetic diseases (e.g.
Hereditary spherocytosis) or infections
Pernicious anemia
Renal anemia
Sickle Cell AnemiaSickle Cell Anemia1st genetic illness traced to a specific mutation:
DNA: CAC CTCaa: glutamic acid valine (aa #6 of 146)
HbA HbS crystallizes under low oxygen conditions
Platelets = Platelets = ThrombocytesThrombocytes
Megakaryocytes (MKs) are polyploid. Mechanism?
MK produces ~ 4,000 platelets which live an average of 10 days.
Platelets contain gra-nules filled with clotting proteins & cytokines
Activated when blood vessel wall damaged
HemostasisHemostasis= Opposite of hemorrhage stops bleeding
Too little hemostasis too much bleeding
Too much hemostasis thrombi / emboli
Three major steps:
1. Vasoconstriction2. Platelet plug (temporary blockage of hole)
3. Coagulation (clot formation seals hole until tissues repaired)
Steps of Steps of HemostasisHemostasis
Vessel damage exposes collagen fibers
Platelets adhere to collagen & release factors
local vasoconstriction & platelet aggregation
decreased blood flow platelet plug formation
+ feedback loop
Fig 16-11
Platelet Plug Formation
Platelet activating factor (PAF)
Steps of Hemostasis cont.Steps of Hemostasis cont.
Two coagulation pathways converge onto common pathway
• Intrinsic Pathway. Collagen exposure. All necessary factors present in blood. Slower.
• Extrinsic Pathway. Uses TF released by injured cells and a shortcut.
Usually both pathways are triggered by same tissue damaging events.
Fig 16-12
The Coagulation Cascade
Fig 16-12
“Cascade” is complicated network!
Numbering of coagulation factors according to time of discovery
Common Coagulation Common Coagulation PathwayPathway
reinforces platelet plug
fibrinogen fibrin
Prothrombin thrombin
clot
Intrinsic pathway Extrinsic pathway
Active factor X
Structure of Blood ClotStructure of Blood Clot
SEM x 4625
Plasmin, trapped in clot, will dissolve clot by fibrinolysis
Clot formation limited to area of injury: Intact endothelial cells release anticoagulants (heparin, antithrombin III, protein C).
Clot Busters & Anticoagulants
Dissolve inappropriate clots
Enhance fibrinolysis
Examples: Urokinase, Streptokinase & t-PA
Prevent coagulation by blocking one or more steps in fibrin forming cascade
Inhibit platelet adhesion plug prevention
Examples:
Hemophilia
Hemophilia A (Factor VIII Deficiency)
Blood Doping