Chapter 19

The Cardiovascular System: The Blood

 

Lecture Outline

INTRODUCTION

•      Blood inside blood vessels, interstitial fluid around body cells, and lymph inside lymph vessels constitute one’s internal environment.

•      To obtain nutrients and remove wastes, cells must be serviced by blood and interstitial fluid.

•      Blood, a connective tissue, is composed of plasma and formed elements.

•      Interstitial fluid bathes body cells (Figure 19.1).

•      The branch of science concerned with the study of blood, blood-forming tissues, and the disorders associated with them is called hematology.

Chapter 19  The Cardiovascular System: The Blood

Fluids of the Body

•      Cells of the body are serviced by 2 fluids

–  blood

•   composed of plasma and a variety of cells

•   transports nutrients and wastes

–  interstitial fluid

•   bathes the cells of the body

•      Nutrients and oxygen diffuse from the blood into the interstitial fluid & then into the cells

•      Wastes move in the reverse direction

•      Hematology is study of blood and blood disorders

 

Functions of Blood

•      Transportation

–   O2, CO2, metabolic wastes, nutrients, heat & hormones

•      Regulation

–  helps regulate pH through buffers

–  helps regulate body temperature

•   coolant properties of water

•   vasodilatation of surface vessels dump heat

–  helps regulate water content of cells by interactions with dissolved ions and proteins

•      Protection from disease & loss of blood

Physical Characteristics of Blood

•      Thicker (more viscous) than water and flows more slowly than water

•      Temperature of 100.4 degrees F

•      pH 7.4 (7.35-7.45)

•      8 % of total body weight

•      Blood volume

–  5 to 6 liters in average male

–  4 to 5 liters in average female

–  hormonal negative feedback systems maintain constant blood volume and osmotic pressure

Techniques of Blood Sampling

•      Venipuncture

–  sample taken from vein with hypodermic needle & syringe

–  median cubital vein (see page 717)

–  why not stick an artery?

•   less pressure

•   closer to the surface

•      Finger or heel stick

–  common technique for diabetics to monitor daily blood sugar

–  method used for infants

COMPONENTS OF BLOOD

•      Blood consists of 55% plasma and 45% formed elements (Figure 19.1).

•      Blood plasma consists of 91.5% water and 8.5% solutes.

•      Principal solutes include proteins (albumins, globulins, fibrinogen), nutrients, enzymes, hormones, respiratory gases, electrolytes, and waste products.

•      Table 19.1 summarizes the chemical composition of plasma.

Components of Blood

•      Hematocrit

–  55% plasma

–   45% cells

•   99% RBCs

•   < 1% WBCs and platelets

 

Blood Plasma

•      0ver 90% water

•      7% plasma proteins

•    created in liver

•    confined to bloodstream

–   albumin

•    maintain blood osmotic pressure

–   globulins (immunoglobulins)

•    antibodies bind to foreign
substances called antigens

•    form antigen-antibody complexes

–   fibrinogen

•    for clotting

•      2% other substances

–   electrolytes, nutrients, hormones, gases, waste products

Formed Elements of Blood

•      Red blood cells ( erythrocytes )

•      White blood cells ( leukocytes )

–  granular leukocytes

•   neutrophils, eosinophils, basophils

–  agranular leukocytes

•   lymphocytes = T cells, B cells, and natural killer cells

•   monocytes

•      Platelets (special cell fragments)

FORMATION OF BLOOD CELLS

•      Blood cells are formed from pluripotent hematopoietic stem cells (Figure 19.3).

•      Bone marrow may be obtained through aspiration or biopsy.  The sample is then sent to pathology for examination.

•      Originating from the pluripotent stem cells are the myeloid stem cells and lymphoid stem cells.

Hematocrit

•      Percentage of blood occupied by cells

–   female normal range

•    38 - 46% (average of 42%)

–   male normal range

•    40 - 54% (average of 46%)

•    testosterone

•      Anemia

–   not enough RBCs or not enough hemoglobin

•      Polycythemia

–   too many RBCs (over 65%)

–   dehydration, tissue hypoxia, blood doping in athletes

Blood Doping

•      Injecting previously stored RBC’s before an athletic event

–   more cells available to deliver oxygen to tissues

•      Dangerous

–   increases blood viscosity

–   forces heart to work harder

•      Banned by Olympic committee

Formation of Blood Cells

•      Most blood cells types need to be continually replaced

–   die within hours, days or weeks

–   process of blood cells formation is hematopoiesis or hemopoiesis

•      In the embryo

–    occurs in yolk sac, liver, spleen, thymus, lymph nodes & red bone marrow

•      In adult

–    occurs only in red marrow of flat bones like sternum, ribs, skull & pelvis and ends of long bones

Hematopoiesis

Stages of Blood Cell Formation

•      Pluripotent stem cells

–   .1% of red marrow cells

–   replenish themselves as they differentiate into either myeloid or lymphoid stem cells

•      Myeloid stem cell line of development continues:

–   progenitor cells(colony-forming units) no longer can divide and are specialized to form specific cell types

•    example: CFU-E develops eventually into only red blood cells

–   next generation is blast cells

•    have recognizable histological characteristics

•    develop within several divisions into mature cell types

•      Lymphoid stem cell line of development

–   pre-B cells & prothymocytes finish their develop into B & T lymphocytes in the lymphatic tissue after leaving the red marrow

Hemopoietic Growth Factors

•      Regulate differentiation & proliferation

•      Erythropoietin (EPO)

–  produced by the kidneys increase RBC precursors

•      Thrombopoietin (TPO)

–  hormone from liver stimulates platelet formation

•      Cytokines are local hormones of bone marrow

–  produced by some marrow cells to stimulate proliferation in other marrow cells

–  colony-stimulating factor (CSF) & interleukin stimulate WBC production

 

Medical Uses of Growth Factors

•      Available through recombinant DNA technology

–  recombinant erythropoietin (EPO) very effective in treating decreased RBC production of end-stage kidney disease

–  other products given to stimulate WBC formation in cancer patients receiving chemotherapy which kills bone marrow

•   granulocyte-macrophage colony-stimulating factor

•   granulocyte colony stimulating factor

–  thrombopoietin helps prevent platelet depletion during chemotherapy

Blood Cells

•      Myeloid stem cells give rise to RBCs, platelets, and all WBCs except for lymphocytes.

•      Lymphoid stem cells give rise to lymphocytes.

•      Myeloid stem cells differentiate into progenitor cells or precursor cells (blast cells) which will develop into the actual formed elements of blood.

•      Lymphoid stem cells differentiate into pre-B and prothymocytes which develop into B-lymphocytes and T-lymphocytes, respectively.

•      This process of hemopoiesis (or hematopoiesis) is stimulated by several hematopoietic growth factors. These hematopoietic growth factors stimulate differentiation and proliferation of the various blood cells.

Red Blood Cells or Erythrocytes (Figure 19.4a)

•      Contain oxygen-carrying protein hemoglobin that gives blood its red color

–  1/3 of cell’s weight is hemoglobin

•      Biconcave disk 8 microns in diameter

–  increased surface area/volume ratio

–  flexible shape for narrow passages

–  no nucleus or other organelles

•   no cell division or mitochondrial ATP formation

•      Normal RBC count

–  male 5.4 million/drop ---- female 4.8 million/drop

–  new RBCs enter circulation at 2 million/second

Hormones

•      Erythropoietin increases the number of RBC precursors.

•      Thrombopoietin increases the number of platelet precursors.

•      Cytokins (colony-stimulating factors and interleukins) increase the number of WBC precursors.

•      Growth factors, available through recombinant DNA technology, hold great potential for use in patients who cannot normally form the blood cells.

Hemoglobin

•      Globin protein consisting of 4 polypeptide chains

•      One heme pigment attached to each polypeptide chain

–   each heme contains an iron ion (Fe+2) that can combine reversibly with one oxygen molecule

 Transport of O2, CO2 and Nitric Oxide

•      Each hemoglobin molecule can carry 4 oxygen molecules from lungs to tissue cells

•      Hemoglobin transports 23% of total CO2 waste  from tissue cells to lungs for release

–  combines with amino acids in globin portion of Hb

•      Hemoglobin transports nitric oxide & super nitric oxide helping to regulate BP

–  iron ions pick up nitric oxide (NO) & super nitric oxide (SNO)& transport it to & from the lungs

–  NO causing vasoconstriction is released in the lungs

–  SNO causing vasodilation is picked up in the lungs

RBCs

•      Production of abnormal hemoglobin can result in serious blood disorders such as thalassemia and sickle cell anemia. (Figure 19.15)

•      The blood test, hemoglobin A1c, can be used to monitor blood glucose levels in diabetics

RBC Life Cycle

•      RBCs live only 120 days

–   wear out from bending to fit through capillaries

–   no repair possible due to lack of organelles

•      Worn out cells removed by fixed macrophages in  spleen & liver

•      Breakdown products are recycled

Recycling of Hemoglobin Components

•      In macrophages of liver or spleen

–   globin portion broken down into amino acids & recycled

–   heme portion split into iron (Fe+3) and biliverdin (green pigment)

Fate of Components of Heme

•      Iron(Fe+3)

–  transported in blood attached to transferrin protein

–  stored in liver, muscle or spleen

•   attached to ferritin or hemosiderin protein

–  in bone marrow being used for hemoglobin synthesis

•      Biliverdin (green) converted to bilirubin (yellow)

–  bilirubin secreted by liver into bile

•   converted to urobilinogen  then stercobilin (brown pigment in feces) by bacteria of large intestine

•   if reabsorbed from intestines into blood is converted to a yellow pigment, urobilin and excreted in urine

Erythropoiesis: Production of RBCs

•      Erythrocyte formation, called erythropoiesis, occurs in adult red bone marrow of certain bones (Figure 19.3).

•      The main stimulus for erythropoiesis is hypoxia (Figure 19.6).

 

•      Proerythroblast starts to produce hemoglobin

•      Many steps later, nucleus is ejected  & a reticulocyte is formed

–  orange in color with traces of visible rough ER

•      Reticulocytes escape from bone marrow into the blood

•      In 1-2 days, they eject the remaining organelles to become a mature RBC

Feedback Control of RBC Production

•      Tissue hypoxia (cells not getting enough O2)

–  high altitude since air has less O2

–  anemia

•   RBC production falls below RBC destruction

–  circulatory problems

•      Kidney response to hypoxia

–  release erythropoietin

–  speeds up development of proerythroblasts into reticulocytes

 

Normal Reticulocyte Count

•      Should be .5 to 1.5% of the circulating RBC’s

•      Low count in an anemic person might indicate bone marrow problem

–  leukemia, nutritional deficiency or failure of red bone marrow to respond to erythropoietin stimulation

•      High count might indicate recent blood loss or successful iron therapy

WHITE BLOOD CELLS

•      Leukocytes (white blood cells or WBCs) are nucleated cells and do not contain hemoglobin. Two principal types are granular (neutrophils, eosinophils, basophils) and agranular (lymphocytes and monocytes) (Figure 19.7).

–  Granular leukocytes include eosinophils, basophils, and neutrophils based on the straining of the granules.

–  Agranular leukocytes do not have cytoplasmic granules and include the lymphocytes and monocytes, which differentiate into macrophages (fixed and wandering).

•      Leukocytes have surface proteins, as do erythrocytes. They are called major histocompatibility antigens (MHC), are unique for each person (except for identical siblings), and can be used to identify a tissue.

WBC Physiology

•      Less numerous than RBCs

–  5000 to 10,000 cells per drop of blood

–  1 WBC for every 700 RBC  

•      Leukocytosis is a high white blood cell count

–  microbes, strenuous exercise, anesthesia or surgery

•      Leukopenia is low white blood cell count

–  radiation, shock or chemotherapy

•      Only 2% of total WBC population is in circulating blood at any given time

–  rest is in lymphatic fluid, skin, lungs, lymph nodes & spleen

 

Function of WBCs

•      Different WBCs combat inflammation and infection in different ways.

–  Neutrophils and wandering or fixed macrophages (which develop from monocytes) do so through phagocytosis.

–  Eosinophils combat the effects of histamine in allergic reactions, phagocytize antigen-antibody complexes, and combat parasitic worms.

–  Basophils develop into mast cells that liberate heparin, histamine, and serotonin in allergic reactions that intensify the inflammatory response.

–  B lymphocytes, in response to the presence of foreign substances called antigens, differentiate into tissue plasma cells that produce antibodies.

–  T lymphocytes destroy foreign invaders directly.

Function of WBCs

•      WBCs leave the blood stream by emigration (Figure 19.8).

•      Some WBCs, particularly neutrophils and macrophages, are active in phagocytosis.

•      The chemical attraction of WBCs to a disease or injury site is termed chemotaxis.

WBC examination

•      A differential white blood cell count is a diagnostic test in which specific white blood cells are enumerated. Because each type of WBC plays a different role, determining the percentage of each type in the blood assists in diagnosing the condition.

•      Table 19.2 shows the significance of elevated or depressed counts of the various WBCs.

•      Bone marrow transplants may be used to treat several types of anemia, leukemia, and numerous other blood disorders. (Clinical Application)

WBC Anatomy and Types

•      All WBCs (leukocytes) have a nucleus and no hemoglobin

•      Granular or agranular classification based on presence of  cytoplasmic granules made visible by staining

–  granulocytes are neutrophils, eosinophils or basophils

–  agranulocytes are monocyes or lymphocytes

Neutrophils (Granulocyte)

•      Polymorphonuclear Leukocytes or Polys

•      Nuclei = 2 to 5 lobes connected by thin strands

–  older cells have more lobes

–  young cells called band cells because of horseshoe shaped nucleus (band)

•      Fine, pale lilac practically invisible granules

•      Diameter is 10-12 microns

•      60 to 70% of circulating WBCs

Eosinophils (Granulocyte)

•      Nucleus with 2 or 3 lobes connected by a thin strand

•      Large, uniform-sized granules stain orange-red with acidic dyes

–  do not obscure the nucleus

•      Diameter is 10 to 12 microns

•      2 to 4% of circulating WBCs

Basophils (Granulocyte)

•      Large, dark purple, variable-sized granules stain with basic dyes

–  obscure the nucleus

•      Irregular, s-shaped, bilobed nuclei

•      Diameter is 8 to 10 microns

•      Less than 1% of circulating WBCs

Lymphocyte (Agranulocyte)

•      Dark, oval to round nucleus

•      Cytoplasm sky blue in color

–  amount varies from  rim of blue to normal amount

•      Small cells 6 - 9 microns in diameter

•      Large cells 10 - 14 microns in diameter

–  increase in number during viral infections

•      20 to 25% of circulating WBCs

Monocyte (Agranulocyte)

•      Nucleus is kidney or horse-shoe shaped

•      Largest WBC in circulating blood

–   does not remain in blood long before migrating to the tissues

–   differentiate into macrophages

•    fixed group found in specific tissues

–   alveolar macrophages in lungs

–   kupffer cells in liver

•    wandering group gathers at sites of infection

•      Diameter is 12 - 20 microns

•      Cytoplasm is a foamy blue-gray

•      3 to 8% o circulating WBCs

Emigration & Phagocytosis in WBCs

•      WBCs roll along endothelium, stick to it & squeeze between cells.

–   adhesion molecules (selectins) help WBCs stick to endothelium

•    displayed near site of injury

–   molecules (integrins) found on neutrophils assist in movement through wall

•      Neutrophils & macrophages phagocytize bacteria & debris

–   chemotaxis of both

•     kinins from injury site & toxins

Neutrophil Function

•      Fastest response of all WBC to bacteria

•      Direct actions against bacteria

–  release lysozymes which destroy/digest bacteria

–  release defensin proteins that act like antibiotics & poke holes in bacterial cell walls destroying them

–  release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria

Monocyte Function

•      Take longer to get to site of infection, but arrive in larger numbers

•      Become wandering macrophages, once they leave the capillaries

•      Destroy microbes and clean up dead tissue following an infection

Basophil Function

•      Involved in inflammatory and allergy reactions

•      Leave capillaries & enter connective tissue as mast cells

•      Release heparin, histamine & serotonin

–   heighten the inflammatory response and account for hypersensitivity (allergic) reaction

Eosinophil Function

•      Leave capillaries to enter tissue fluid

•      Release histaminase

–  slows down inflammation caused by basophils

•      Attack  parasitic worms

•      Phagocytize antibody-antigen complexes

Lymphocyte Functions

•      B cells

–  destroy bacteria and their toxins

–  turn into plasma cells that produces antibodies

•      T cells

–  attack viruses, fungi, transplanted organs, cancer cells & some bacteria

•      Natural killer cells

–  attack many different microbes & some tumor cells

–  destroy foreign invaders by direct attack

 

Complete Blood Count

•      Screens for anemia and infection

•      Total RBC, WBC & platelet counts;  differential WBC; hematocrit and hemoglobin measurements

•      Normal hemoglobin range

–  infants have 14 to 20 g/100mL of blood

–  adult females have 12 to 16 g/100mL of blood

–  adult males have 13.5 to 18g/100mL of blood

Differential WBC Count 

•      Detection of changes in numbers of circulating WBCs (percentages of each type)

–  indicates infection, poisoning, leukemia, chemotherapy, parasites or allergy reaction

•      Normal WBC counts

–  neutrophils 60-70% (up if bacterial infection)

–  lymphocyte 20-25% (up if viral infection)

–  monocytes   3 -- 8 % (up if fungal/viral infection)

–  eosinophil   2 -- 4 % (up if parasite or allergy reaction)

–  basophil   <1% (up if allergy reaction or hypothyroid)

Bone Marrow Transplant

•      Intravenous transfer of healthy bone marrow

•      Procedure

–  destroy sick bone marrow with radiation & chemotherapy

–  donor matches surface antigens on WBC

–  put sample of donor marrow into patient's vein for reseeding of bone marrow

–  success depends on histocompatibility of donor & recipient       

•      Treatment for leukemia, sickle-cell, breast, ovarian or testicular cancer, lymphoma or aplastic anemia

PLATELETS

•      Thrombopoietin stimulates myeloid stem cells to produce platelets.

•      Myeloid stem cells develop into megakaryocyte-colony-forming cells that develop into megakaryoblasts (Figure 19.2).

•      Megakaryoblasts transform into megakaryocytes which fragment.

•      Each fragment, enclosed by a piece of cell membrane, is a platelet (thrombocyte).

•      Normal blood contains 250,000 to 400,000 platelets/mm³. Platelets have a life span of only 5 to 9 days; aged and dead platelets are removed by fixed macrophages in the spleen and liver.

PLATELETS

•      Platelets help stop blood loss from damaged vessels by forming a platelet plug. Their granules also contain chemicals that promote blood clotting.

•      A complete blood count (CBC) is a test that screens for anemia and various infections.  It usually includes counts of RBCs, WBCs, and platelets per μL of whole blood; hematocrit and differential white blood cell count.  The amount of hemoglobin in grams per ml is also determined.

•      Table 19.3 summarizes the formed elements in blood.

Platelet (Thrombocyte) Anatomy

•      Disc-shaped, 2 - 4 micron cell fragment with no nucleus

•      Normal platelet count is 150,000-400,000/drop of blood

•      Other blood cell counts

–   5 million red &  5-10,000 white blood cells

Platelets--Life History

•      Platelets form in bone marrow by following steps:

–   myeloid stem cells to megakaryocyte-colony forming cells to megakaryoblast to megakaryocytes whose cell fragments form platelets

•      Short life span (5 to 9 days in bloodstream)

–   formed in bone marrow

–   few days in circulating blood

–   aged ones removed by fixed macrophages in liver and spleen

STEM CELL TRANSPLANT FROM BONE MARROW AND CORD-BLOOD

•      Bone marrow transplant replaces diseased marrow with healthy marrow.

•      Patient’s diseased marrow is destroyed.

•      Healthy marrow is supplied by a donor or the patient.

•      There are several problems with this method.

Cord-blood transplant

•      Stem cells are taken from the umbilical cord and frozen

•      This method offers several advantages over marrow transplant.

HEMOSTASIS

•      A clot is a gel consisting of a network of insoluble protein fibers (fibrin) in which formed elements of blood are trapped (Figure 19.10).

•      The chemicals involved in clotting are known as coagulation (clotting) factors; most are in blood plasma, some are released by platelets, and one is released from damaged tissue cells (Table 19.4).

•      Blood clotting involves a cascade of reactions that may be divided into three stages: formation of prothrombinase (prothrombin activator), conversion of prothrombin into thrombin, and conversion of soluble fibrinogen into insoluble fibrin (Figure 19.11).

HEMOSTASIS

•      The clotting cascade can be initiated by either the extrinsic pathway or the intrinsic pathway.

•      Normal coagulation requires vitamin K and also involves clot retraction (tightening of the clot) and fibrinolysis (dissolution of the clot).

•      The fibrinolytic system dissolves small, inappropriate clots and clots at a site of damage once the damage is repaired.

•      Plasmin (fibrinolysin) can dissolve a clot by digesting fibrin threads and inactivating substances such as fibrinogen, prothrombin, and factors V, VIII, and XII.

Hemostasis

•      Stoppage of bleeding in a quick & localized fashion when blood vessels are damaged

•      Prevents hemorrhage (loss of a large amount of blood)

•      Methods utilized

–  vascular spasm

–  platelet plug formation

–  blood clotting (coagulation = formation of fibrin threads)

Vascular Spasm

•      Damage to blood vessel produces stimulates pain receptors

•      Reflex contraction of smooth muscle of small blood vessels

•      Can reduce blood loss for several hours until other mechanisms can take over

•      Only for small blood vessel or arteriole

Platelet Plug Formation

•      Platelets store a lot of chemicals in granules needed for platelet plug formation

–  alpha granules

•   clotting factors

•   platelet-derived growth factor

–   cause proliferation of vascular endothelial cells, smooth muscle & fibroblasts to repair damaged vessels

–  dense granules

•   ADP, ATP, Ca+2, serotonin, fibrin-stabilizing factor, & enzymes that produce thromboxane A2

•      Steps in the process

–  (1) platelet adhesion  (2) platelet release reaction (3) platelet aggregation

 

 

Platelet Adhesion

•      Platelets stick to exposed collagen underlying damaged endothelial cells in vessel wall

Platelet Release Reaction

•      Platelets activated by adhesion

•      Extend projections to make contact with each other

•      Release thromboxane A2 & ADP activating other platelets

•      Serotonin & thromboxane A2 are vasoconstrictors decreasing blood flow through the injured vessel

Platelet Aggregation

•      Activated platelets stick together and activate new platelets to form a mass called a platelet plug

•      Plug reinforced by fibrin threads formed during clotting process

Blood Clotting

•      Blood drawn from the body thickens into a gel

–   gel separates into liquid (serum) and a clot of insoluble fibers (fibrin) in which the cells are trapped

•      If clotting occurs in an unbroken vessel is called a thrombosis

•      Substances required for clotting are Ca+2, enzymes synthesized by liver cells and substances released by platelets or damaged tissues

•      Clotting is a cascade of reactions in which each clotting factor activates the next in a fixed sequence resulting in the formation of fibrin threads

–   prothrombinase & Ca+2 convert prothrombin into thrombin

–   thrombin converts fibrinogen into fibrin threads