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