What does blood do? Transport: Regulation: Protection: Ch 13: Blood What does blood do? Transport: Regulation: Protection:

SLOs Describe the composition of plasma and list the major functions of plasma proteins. Map hematopoiesis, starting from a pluripotent hematopoietic stem cell. Distinguishing characteristics of each type of leukocyte. Define hematocrit, describe how a person’s hematocrit is determined, and identify the clinical relevance of this value. Describe the molecular structure of hemoglobin and explain its function. Distinguish between the different types of anemias. Diagram the key steps of hemostasis, the coagulation cascade, and fibrinolysis.

Blood = connective tissue Extracellular matrix: Specialized cells: Average adult blood volume?

Fig 13.1

Function of plasma proteins?

Cellular Components of Blood - Overview 20-40% Total WBC: 4,000 - 11,000 2-8% Cellular Elements 50-70% 1- 4%

Blood Cells and Platelets Fig 13-3

Red Blood Cells Other name?

Hem(at)opoiesis = Blood Cell Formation Few uncommitted stem cells in red bone marrow throughout life time Controlled by ____________,specifically CSFs and ILs

Stages of Erythropoiesis 2.5 million RBCs/sec Whole process takes  3 days Most iron recycled from old RBCs, rest from diet Transferrin =? Fig 13-4

Erythropoiesis Reticulocytes lifespan ~ 120 days EPO release Mitotic rate  Tissue O2  Maturation speed  RBC  bag of Hb for carrying O2 lifespan ~ 120 days No aerobic respiration – source of ATP?  Tissue O2  Reticulocytes enter circulation

RBC Production Regulated by _______________ “Hormone” synthesized by kidneys in response to hypoxemia due to anemia blood flow to kidneys declining O2 content of air in lungs declining, due to disease or high altitude respiratory surfaces of the lungs damaged EPO gene cloned in 1985  Recombinant EPO now available

EPO Use in therapy (?) abuse in sport (?)

Hemoglobin (Hb) Quaternary protein structure ? Requires iron (Fe) See Ch 16, page 559! Hemoglobin (Hb) Quaternary protein structure ? Requires iron (Fe) HbA vs. HbF vs. HbS Reversible binding between Fe2+ & O2 Oxyhemoglobin vs. deoxyhemoglobin Carboxyhemoglobin – CO: A toxic gas (Fitness Application p. 560)

RBC Disorders Anemias (O2 carrying capacity too _____) Polycythemia vera (PCV ~ 60-70%) Anemias (O2 carrying capacity too _____) Hemorrhagic anemia  Fe deficiency anemia Hemolytic anemia, due to genetic diseases (e.g. Hereditary spherocytosis) or infections Pernicious anemia see p. 714 Renal anemia Aplastic anemia

Sickle Cell Anemia 1st genetic illness traced to a specific mutation: DNA: CAC CTC aa: glutamic acid valine (aa #6 of 146) HbA HbS  crystallizes under low oxygen conditions

Platelets = Thrombocytes Cytokine stimulating platelet production? Precursor cell in BM:____________________; polyploid Mechanism? ~ 4,000 platelets per cell live ~ 5 - 9 days Platelets contain gra- nules filled with clotting proteins & cytokines (e.g.: serotonin) Activated when blood vessel wall damaged Fig 16-7

Hemostasis Vasoconstriction Platelet plug (temporary blockage of hole) = stops bleeding. Opposite of hemorrhage. Too little hemostasis  Too much hemostasis  Three major steps of hemostasis: Vasoconstriction Platelet plug (temporary blockage of hole) Coagulation (clot formation seals hole until tissues repaired)

Steps of Hemostasis Vessel damage exposes collagen fibers Platelets adhere to collagen & release factors local vasoconstriction & platelet aggregation decreased blood flow platelet plug formation + feedback loop

Simultaneously: The Coagulation Cascade Fig 13-9 “Cascade” is complicated network! Numbering of coagulation factors according to time of discovery

Common Coagulation Pathway Intrinsic pathway Extrinsic pathway Active factor X Prothrombin thrombin fibrinogen fibrin reinforces platelet plug clot

Structure of Blood Clot 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). SEM x 4625

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 A

Hemophilia A (Factor VIII Deficiency) the end