Chapter 18 - The Circulatory System: Blood

18.1 General Aspects of Blood

The circulatory system consists of the heart, blood vessels, & blood

The term cardiovascular system refers only to the heat & vessels

The Purposes of Blood Circulation

• Fundamental purpose of the circulatory system is to transport substanes from place to place

• Functions include:

  • Transport

    • Blood carries oxygen from the lungs to all of the body’s tissues, while it picks up carbon dioxide from those tissues & carries it to the lungs to be removed from the body

    • Picks up nutrients from the digestive tract and delivers them to all of the body’s tissues

    • Carries metabolic wastes to the kidney fro removal

    • Carries hormones from endocrine cells to their target organs

    • Transports a variety of stem cells from the bone marrow and other origins to the tissues where they lodge and mature

  • Protection

    • Blood plays several roles in inflammation, a mechanism for limiting the spread of infection

    • WBCs destroy microorganisms & cancer cells and remove debris from the tissues

    • Antibodies and other blood proteins neutralize toxins and help to destroy pathogens

    • RBCs bind foreign antigens and transport them to liver and spleen for disposal

    • Platelets secrete factor that initiate blood clotting and other processes for minimizing blood loss, and contribute to tissue growth and blood vessel maintenance

  • Regulation

    • By absorbing or giving off fluid under different conditions, blood capillaries stabilize fluid distribution in the body

    • By buffering acids and bases, blood proteins stabilize pH of the extracellular fluids

    • cutaneous blood flow is extremely important in dissipating metabolic heat from the body. Shifts in blood flow regulate body temperature by routing blood to the skin for heat loss or retaining in deeper in the body to conserve heat

      • usually from protiens

Components and General Properties of Blood

• 4-6 liters in human adult

• liquid connective tissue

• composed of an extracellular matrix

• Plasma: a clear light yellow fluid constituting a little over half of the blood volume

• Suspended in the plasma are the formed elements-cells and cell fragments including RBCs, WBCs, & platelets

  • they are called formed elements as they are contained by a plasma membranes

• The formed elements are classified as follows:

  • Erythrocytes (RBCs)

  • Leukocytes (WBCs)

    • Granulocytes

      • Neutrophils (5 lobed nucleus)

      • Eosinophils

      • Basophils

    • Agranulocytes

      • Lymphocytes

      • Monocytes

    • Platelets (not cells) - fragments of cells found in bone marrow

• Blood fractionation: the separation of blood into its basic components, is based on centrifugation and coagulation

  • serum = coagulated serum

  • RBCs or erythocytes are the densest elements & settle to the bottom

    

• General Properties of Blood

  • pH: 7.35-7.45

  • Hematocrit (packed cell volume):

    • Females: 36% to 48%

    • Males: 41% to 53%

  • Hemoglobin:

    • Female: 11-16 g/dL

    • Male: 14-18 g/dL

  • RBC count:

    • Female: 4.2-5.4 million/μL

    • Male: 4.6-6.2 million//μL

  • Platelet count: 130,000-360,000/μL

  • Total WBC count: 5,000-10,000/μL

  • 0.9% saline in blood plasma,

Blood Plasma

• complex mixture water, proteins, nutrients, electrolytes, nitrogenous wastes, hormones, and gases

• Albumin is the smallest and most abundant plasma protein

  • it serves to transport various solutes and buffer the pH of blood plasma

  • contributes two physical properties

    • viscosity & osmotic pressure

• Globulins are divided into three subclasses from smallest to largest

  • Alpha - Beta - Gamma globulins

  • Play various roles in solute transport, clotting, and immunity

  • Fibrinogen: sticky protein that forms the framework of a blood clot

• Composition of Blood Plasma

  • Nutrients

    • Glucose (dextrose): 70-110mg/dL

  • Electrolytes

    • Sodium: 135-145 mEq/L

    • Calcium: 9.2-10.4 mEq/L

    • Potassium: 3.5-5.0 mEq/L

    • Chloride: 100-106 mEq/L

    • Bicarbonate: 23.1-26.7 mEq/L

  • Nitrogenous Wastes

    • Urea: 10-20 mg/dL

    • Creatinine: 0.6-1.5 mg/dL

• Nitrogenous wastes

  • toxic end products

  • most abundant is urea

Blood Viscosity & Osmolarity

• viscosity is the resistance of a fluid to flow, resulting from the cohesion of its particles

• simply, it is the thickness or stickiness of a fluid

• whole blood is 4.5 to 5.5 more vicious than water, plasma alone is 2 times more viscous than water

• viscosity governs the flow of blood through the blood vessels

• osmolarity refers to the total concentration of solute particles. The rate of transfer of fluid between

• The movement of fluid in the capillaries and tissues depends mainly on their relative osmolarity between the two

• The osmolarity of the blood is mainly a product of the sodium and protein concentration and the number of RBCs called the Colloid Omnotic Pressure

How Blood Is Produced

• Everyday, an adult typically produces 400 million platelets, 200 billion RBCs, and 10 billion WBCs

• In animals that produce eggs, embryonic hematopoiesis occurs in the yoke sac

• there, Blood islands produce primitive stem cells that migrate to the bone marrow, liver, spleen, & thymus

• from infancy, the red bone marrow produced all 7 kinds formed elements while lymphocytes are produced in lymphoid tissue, especially the thymus, tonsils, lymph nodes, spleen, and mucous membranes

• All formed elements trace their origins to these hematopoietic stem cells (HSC)

• HSCs maintain a small but persistent population in the bone marrow

• some become colony forming units (CFUS) which are destined to produce one or the other of the formed units

18.2 Erythrocytes

• Erythrocytes or RBCs

• Have two principal functions:

  • pick up oxygen from the lungs and deliver it to tissues elsewhere

  • pick up carbon dioxide from the tissues and unload it in the lungs

Erythrocyte Form and Function

• RBCs are discoidal cells with a biconcave shape, a thick rim and a thing shrunken center

  • speculate that it maximizes surface area to volume thereby promoting quick diffusion

• Diameter of 7.5 micrometer

• RBCs lose their nucleus and organelles during maturation

• Rely on anaerobic fermentation to produce ATP, hence do not consume O2 they transport

• Their cytoplasm consists mainly of a solution of 33% hemoglobin, a red pigment about 280 molecules per cell

• The cytoplasm contain carbonic anhydrase which catalyzes the reaction CO2 + H2O >< H2CO3

• The glycolipids in the plasma membrane determine the blood type

• On its inner surface two cytoskeletal proteins, spectrin and actin, give the membrane resilience & durability

  • allows RBC to stretch, bend, & fold through small capillaries an then spring back into shape

Hemoglobin

• Hemoglobin consists of four protein chains called globins

• Two of them, alpha, the other two beta

• Fetal hemoglobin (HbF) has two gamma chains in place of beta chains

  • HbF binds oxygen more tightly than HbA (adult hemoglobin) does; this enables the fetus to extract oxygen from the mother’s bloodstream

Quantities of Erythrocytes and Hemoglobin

• Hemocrit: packed cell volume, the percentage of whole blood volume

  • Values tend me be lower in women than in men because

    • androgens stimulate RBC production, and men have higher androgen levels than women

    • most women of reproductive age have periodic menstrual losses

    • the hemocrit is inversely proportional to percentage body gat, which is greater in women than in men on average

The Erythrocyte Life History

• Erythropoiesis begins with a HSC becomes an erythrocyte colony-forming unit (CFU) with receptors for erythropoietin (EPO) , a hormone secreted by the kidneys

• EPO stimulates the CFU to transform into an erythroblast which multiply, build up a large cell population and being to synthesize hemoglobin

• The erythroblast’s nucleus shrivels and is exuded through the plasma membrane…the resulting cell is now called a reticulocyte

• Reticulocytes enter the circulation, and the polyribosomes (which give the recticulocyte its name) disintegrate, the cell now becoming a mature RBC

• reticulocytes normally constitute 0.5 to 1.5% of circulating RBCs. Blood loss would lead to an increase in the reticulocyte count

• Reticulocytes do not have nucleus

• Erythrocyte Homeostasis

  • RBC count is maintained in a classic negative feedback amnner

  • If the RBC count drops, it can result in hypoxemia

  • People who live in places with high elevations will tend to have higher RBC counts than those who live in places of lower elevation.

    • This is because of the lower O2 level

• Iron Metabolism

  • iron is a critical part of the hemoglobin molecule

  • Men and women lose iron at different levels

    • Men: 0.9 mg

    • Female (of reproductive age): 1.7mg

• Erythrocyte Death & Disposal

  • RBCs die in the spleen

  • Hemolysis, the rupture of RBCs, releases hemoglobin and leaves empty plasma membranes

  • The membranes are digested by macrophages in the liver and spleen

  • Macrophages will begin the disposal process by separating the heme from the globin

  • They will hydrolyze the globin into free amino acids which can be metabolized as fuel or recycled for protein synthesis

  • Heme must have its iron removed by the macrophage which then converts the rest to biliverdin which is further converted into bilirubin

    • bilirubin makes people look jaundice

Erythrocyte Disorders

• Primary Polycythemia

  • RBC excess d/t cancer of the erythropoietic line of the red bone marrow

• Secondary polycythemia

  • characterized by RBC counts as high as 6 to 8 million RBCs/uL

  • most often caused bby smoking, air pollution, emphysema, high alt., excesive aerobic exercise, or other factors that create a state of hypoxia

• Anemia

• Three categories

  • inadequate erythropoiesis

    • iron-deficiency anemia

  • Hemorrhagic anemia

    • hemophilia

  • hemolytic anemia

    • SC, penicillin allergy, malaria

• SC

  • Hereditary disease, recessive gene

  • a single amino acid change in the beta chains of hemoglobin

  • HbS does not bind to O2 as well as HbA

  • SC are sticky and tend to agglutinate, especially in low O2 situations

  • The clumping blocks vessels leading to joint pain, stroke, heart failure

  • SC disease verses SC trait

  • survival advantage

  • for those with sickle cell trait in the areas of the world with malaria-protects them from the disease, likely the reason the gene persists

18.3 Blood Types

Overview

• Ancient Greek physicians attempted to transfuse blood from one person to another by squeezing it from a pig’s bladder through a porcupine quill into the recipient’s vein

• Karl Landsteiner discovered blood types A, B, and O in 1900

• Blood types related to surface antigens

• all cells have surface antigens

• an antigen is a complex molecule made up of proteins, glycoproteins, and glycolipids, unique to everyone

• They are present to identify self, against foreign antigens

• If foreign antigen is detected, an immune reaction occurs leading to the development of an antibody against the foreign antigen

• The antigen-antibody complex then leads to an immune reaction to rid the body of the foreign substance

• In the case of RBCs, the reaction an agglutination reaction

  • in which each antibody molecule binds to two or more foreign cells and stick them together - repetition of this process produced large clumps of cells that can cause complications of the transfusion reaction

• Being transfused with mismatched blood will lead to this reaction, and if severe enough, can lead to death

The ABO Group

• Formed by A, B, and O

• Determined by the hereditary presence or absence of antigens A and B on the RBCs

• A person’s ABO blood type can be determined by placing one drop of blood in a pool of anti-A serum and another drop in a pool of anti-B serum.

  • AB exhibits conspicuous agglutination in both antisera

  • type A or B agglutinates only in the corresponding antiserium

  • Type O does not agglutinate in either

• Type O is the most common while AB is the rarest

• universal donor Type O

• universal recipient Type AB

• In transfusions, it is imperative that the donor’s RBCs not agglutinate as they enter the recipients bloodstream

  

The Rh Group

• Named for the rhesus monkey

• genotype DD or Dd are considered Rh-positive (Rh+) and those that lack the antigen (dd) are Rh-negative (Rh-)

  • Also O+ for Rh+ or for AB-, Rh-

Other Blood Groups

• Duffy, Kell, Kidd, Lewis, and MNS

• These rarely cause transfusion reaction but useful for legal purposes as paternity and criminal cases

Maternal-Fetal Mismatches

• Hemolytic disease of the newborn (HDN) or erythroblastosis fetalis

• Occurs when a woman has a baby with a mismatched blood type-most famously when she is Rh- and carries Rh+

• First pregnancy normal

• Second pregnancy she produced antibodies and if she becomes pregnant again with an Rh+ fetus, those antibodies can pass through the placenta and agglutinate the fetal erythrocytes, thus the baby is born with hemolytic anemia

18.4 Leukocytes

Overview

• Least abundant of the formed elements

• WBC count of 5000 to 10000 WBCs per microliter

• However, a large percentage of WBC exist outside the circulatory system, in various tissues. They enter and leave the blood

• They are different from RBCs in that they retain their nucleus and organelles

• All WBCs have granules in their cytoplasm, and their staining differentiates the varius types of WBCs

• Two types of WBCs have no granules, called agranlocytes, lymphocytes, and monocytes

Types of Leukocytes

• Granulocytes

  • neutrophils, eosinophils, & basophils'

• Neutrophils

  • 60 to 70% of leukocytes

  • has 4 to 5 lobed nucleus

  • absolute count around 4100

  • increase in bacterial infections

  • phagocytize bacteria

  • release antimicrobial chemicals

  

• Basophils

  • <0.5% of WBCs

  • Large U shaped or S shaped nucleus

  • coarse large blue to violet granules in cytoplasm

  • increase in chickenpox, sinusitis, diabetes, myxedema, and polycythemia

  • secretes histamine which dilates blood vessels, and heparin and anticoagulant and promotes movement of other WBCs and prevents clumping

• Eosinophil

  • 2% to 4% of WBC count

  • nucleus usually has two large lobes connected by thin strand

  • increases in parasitic infections, allergies, collagen diseases, and diseases of spleen and CNS

  • release enzymes that weaken or destroy parasites such as worms

• Lymphocytes

  • 25-33% WBC count

  • small in diameter, a little larger than RBCs

  • nucleus is large and fills most of the cell

  • increases in diverse infections, destroys cancer cells, foreign cells, and infected cells

  • coordinates actions of other immune cells

  • secretes antibodies

  • serve in immune memory

• Monocytes

  • 3%-8% of WBCs nucleus avoid or horseshoe shape

  • abundant cytoplasm with sparse nonspecific granules

  • increase in viral infections and inflammation

  • differentiate into macrophages, phagocytize pathogens, dead neutrophils and other dead cells

  • Present antigens to activate other cells of the immune system

Leukocyte Life History

• Leukopoiesis production of WBC begins with hematopoietic stem cells

  • Myleoblasts → granulocytes

  • Monoblasts → monocytes

  • Lymphoblasts → produce all lymphocyte types

Leukocyte Disorders

• WBC below 5,000 is called Leukopenia

  • seen in lead, arsenic, and mercury poisoning

• WBC count above 10,000 is called leukocytosis

  • usually indicated allergy, infection, or other diseases

• Leukemia

  • cancer of hematopoietic tissues that usually produces an extraordinarily high number of circulating leukocytes and their precursors

  • Classified as Myeloid or Lymphoid and Acute or Chronic

    • Myeloid Leukemia is marked by uncontrolled granulocyte production

    • Lymphoid Leukemia involved uncontrolled lymphocyte or monocyte production

    • Acute Leukemia appears suddenly, progresses rapidly, and causes death w/in few months

    • Chronic Leukemia develops more slowly and may undergo undetected for months to years

18.5 Platelets and the Control of Bleeding

Platelet Form and Function

• are not cells but fragments of marrow cells called megakaryocytes

• normal platelet count is 130,000 to 400,000 platelets

• the count can vary under different circumstances

• platelets contain lysosomes, mitochondria, granules filled with platelet secretions, microfilaments, and granules; and a system of channels called the Open Canalicular system which opens onto the platelet surface

• Functions of Platelets:

  • secrete vasoconstrictors, chemicals that stimulate spasmodic constriction of broken vessels and help to reduce blood loss

  • stick together to form temporary platelet plugs that seal small breaks in injured blood vessels

  • secrete procoagulants, or clotting factors, which promote the formation of blood clots more durable than platelet plugs

  • initiate the formation of clot-dissolving enzyme that dissolves blood clots that have outlasted their usefulness

  • secrete chemicals that attract neutrophils and monocytes to sites of inflammation

  • they internalize and destroy bacteria

  • secrete growth factors that stimulate mitosis in fibroblasts and smooth muscle and thereby help to maintain and repair blood vessels

• Platelet Production

  The production of platelets is called thrombopoiesis
  It is stimulated by a hormone from the liver and kidneys called thrombopoletin
  Under its influence hscs become megakaryoblasts
  It duplicates itself to become a megakaryocyte
  They are gigantic cells, up to 150 micrometers in diameter
  Most live in the bone marrow adjacent to blood-filled spaces called sinusoids
  It sprouts long tendrils called proplatelets that protrude through the endothelium, which breaks off pieces that become platelets
  More platelets leave the lung that proplatelet enter
  Circulation lifespan is 5 to 6 days
  25 to 40% of platelets are stored in the liver

• Hemostasis

  • Three hemostatic mechanisms

    • vascular spams, platelet plug formation, and blood clotting

  • Vascular spasm

    • protection against blood loss

    • prompt constriction of broken vessel

    • triggered by injury which stimulate pain receptors

  • Platelet Plug Formation

    • When a vessel is broken, collagen fibers of its wall are exposed to the blood - contact with collagen or other rough surfaces, platelets grow long spiny pseudopods that adhere to the vessel and to other platelets creating a large mass of cells

      • This mass is called the platelet plug

  • Coagulation

    • Objective is to convert the plasma protein fibrinogen into Fibrin, a sticky protein that adheres to the walls of a vessel

    • Extrinsic Mechanism

      • initiated by clotting factors released by the damaged blood vessel and perivascular tissues

      • comes form external forces to the blood itself

    • intrinsic mechanism

      • only uses clotting factors found in the blood itself

    • Reaction Cascade

      • a series of reactions, each of which depends on the product of the preceding one.

• Factor VIII deficiency leads to hemophilia

• Thrombosis - abnormal clotting of the blood in an unbroken vessel, slowest, do not move

• Embolus - clot that travels through the bloodstream

• DIC (Disseminated intravascular coagulation) - widespread clotting within broken vessels, limited to one organ or occurring throughout the body. Marked by widespread hemorrhaging, congestion of the vessel with clotted blood, and tissue necrosis in blood deprived organs