Cardiovascular I: Blood

Blood Connective Tissue

Consists of: Cells + Plasma (matrix)

Fluid end up on top, plasma bottom (in hematocrit)

Hematocrit Packed cell volume

Normal value: Approximately 45%

Blood Cells Red blood cells

White blood cells Platelets

Blood Plasma Composition

Mostly water

Proteins Albumins (movement-osmosis)-fluid dynamics Globulins (transport proteins) Clotting proteins Regulatory proteins (protein hormones) Other Solutes Nutrients Electrolytes Respiratory gases Wastes (urea, bilirubin, lactate) Regulatory substances (steroid hormones in blood)

Homeostasis means keeping many of the constituents of blood (in plasma) within narrow limits Erythrocytes (RBC) Small, biconcave disk

Role of Cytoskeletal proteins (e.g., spectrin-gives/confers biconcave disc structure) STRUCTURE-FUNCTION Relationship

Surface area specialization (biconcave disk maximizes surface area for maximization of gas exchange by diffusion of O2 and CO2)

Anuclear; lack organelles

Short lived (120 days) No mitosis possible Use ATP by glycolysis

Primarily hemoglobin (made during development stage)

Hemoglobin (quarternary structure) globin = 4 protein subunits

heme = iron portion which binds oxygen (reversible)

Able to bind to 4 O2 molecules

Three forms of Hb Oxyhemoglobin (when bound to oxygen) Deoxyhemoglobin (oxygen off) Carbaminohemoglobin (CO2 bound) Fetal Hb (HbF) Higher affinity (oxygen sticks more tightly to HbF-allows for transport from mother to fetus) for O2

Anemias (not getting enough oxygen in blood) due to Abnormal Hemoglobin Thalassemia B

Abnormal amounts of Hb (due to lack of adequate production of Beta chain) Most common in Mediterranean region, and parts of Africa, India, Asia
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Sickle Cell Anemia Single wrong AA results in abnormal HbS

Abnormally shaped cells cannot move through bloodstream easily; thus hard to deliver O2 to tissues RBCs are fragile hemolytic (blood; to break) anemia (and thus more O2 deprivation) Cyanide and CO Poisoning Both cyanide and carbon monoxide bind the iron in heme (stronger than oxygen- have higher affinity for Hb than O2), and thus prevent Hb from carrying oxygen Hemopoeisis (Fig. 21.11 M)

Blood forming One stem cell (hemocytoblast) forms all blood cells Right chemical signal

Erythropoeisis Stem cell = Hemocytoblast stem cell for all types of blood cells Factors needed:

Iron Vitamin (how absorb) B12 Folic Acid

Hormone EPO gives signal (erythropoietin from kidneys) causes hemocytoblast to commit to erythrocyte developmental path Lifespan = 120 days Control of Erythropoeisis: Fig. 12.69 V

Red cells

In red bone marrow

Hemocytoblast (thru EPO) Proerythroblast (committed to pathway) Erythroblast (synthesize Hb) phases of erythroblasts Normoblast (losing organelles) Reticulocyte (nucleus ejected; enters circulation, matures) Erythrocyte

Homeostais (negative feedback)

Catabolism of RBCs Spleen, liver breakdown, recycle heme (still need iron [new iron]) More on Anemias: Decreased O2 Tissues Due to low RBC count

(Illustration b) Due to low hemoglobin (thalasemia) E.g., Iron-deficiency anemia Due to abnormal Hb E.g., Sickle Cell

Polycythemia: Increased RBC Count (increased hematocrit) Abnormal- ex: bone marrow cancer

Functional- physiological response to high altitude Blood doping = bad idea (giving yourself RBC)

Leukocytes (WBC)
General role: body defense Small proportion in blood Platelets Comes from hemocytoblast (stem cell)

Leukopoeisis

Regulated by Colony Stimulating Factors (rather than EPO)lead to become WBC Platelets Circulating fragments of megakaryocytes (found in bone marrow) = platelets Essential for clotting process

Regulated by Thrombopoietin (development of cells) thrombo = clot

II. Hemostasis = stopping of blood flow

Hemostasis: Vascular Spasm (1) Vascular Phase

Damaged blood vessel constricts because smooth muscle in vessel wall contracts Mechanism isnt clear Hemostasis: Platelet Plug (Platelet Phase) (2) Stimulus = Damaged Endothelium (collagen exposure in connective tissue)

Epithelium lining blood vessel (endothelium) Outer lining = connective tissue (with collagen) Common to all blood vessels but capillaries

Platelets swell, form processes, become sticky

Degranulation: release of chemicals from platelets into blood Platelet AGGREGATION = gathering together
Positive feedback (Fig. 12.72 V)

Chemicals favoring plug formation: von Willebrand Factor

Serotonin

ADP TxA2 (Thromboxane A2 an eicosanoid-from lipids)

Enhances vasospasm Positive feedback affect on itself (its own formation)

Clotting Factors

Chemicals limiting plug formation: inhibit clotting PGI2 (Prostacyclin or Prostagladins)

NO (Nitric Oxide)

Released by intact (normal) endothelial cells to inhibit formation

Overview: Clotting Pathway (Fig. 12.74V)***

Cause of clotting: same collagen that starts platelet plug starts this processstimulus Prothrombin activated to thrombin Causes fibrinogen to become fibrin Polymerise by factor 13 Factor 13A takes loose fibrin and makes fibrin Cascade of enzymes part of process (dont need to know specific) Goal= produce stabilized fibrin = polymer

Hemostasis: Coagulation Phase Clot (thrombus) = fibrin polymer Clotting occurs locally around platelet plug Platelet Factor (PF) from activated platelets is an essential cofactor Many other factors/cofactors (table 12.13V) Two pathways, normally activated sequentially, converge on the Common Pathway Intrinsic Pathway (1) intrinsic to blood Factor XII activated by CONTACT to collagen Extrinsic Pathway extrinsic to blood
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Requires Tissue Factor (from subendothelial cells in vessel wall-cells in connective tissue) Common Pathway Two pathways converge at activation of factor X

Hemostasis: Coagulation EXTRINSIC pathway typically activated first

Then triggers Thrombins positive feedback effects on INTRINSIC pathway Thus intrinsic pathway can be activated independent of contact activation and factor XII Procoagulants Clotting Factors (Table 12.13V)

Livers Roles in Blood Clotting (Fig. 12.77V)

Formation of Stabilized Fibrin Actions of Thrombin table 12.14 V Factor 13from lose to stable fibrin Factors Opposing Clot Formation Tissue Factor Pathway Inhibitor (TFPI) Limits amount of thrombin from extrinsic pathway

Makes plasma proteins that are clotting

Thrombomodulin Receptor that binds thrombin and activates Protein C, which INACTIVATES two clotting factors

Fibrinolytic System (to break system) Tissue Plasminogen Activator (TPA)

Clot Retraction & Repair Retraction = contractile process (make smaller)-squeezing out fluid Fibrinolysis: break it TPA (Tissue Plasminogen Activator) Plasminogen (inactive enzyme) Plasmin
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Endothelial cells have many anti-clotting functions (Table 12.15V) - Understand need balance between clotting factors; only do so when we really need to ***(NO, PGI2) Disorders of Hemostasis Thromboembolytic Conditions

Clot forms Breaks loose = embolus clot circulating May lodge in lungs (pulmonary embolism- broken, loose clot)

Patent foramen ovale (hole between hearts; patent means that closes) Where might embolism occur? (later!)