Basic A & P II Chapter Outline

Dr. L. Bacha (Martini & Nath 2010)

An Introduction to the Cardiovascular System - the cardiovascular system includes blood, the heart, and blood vessels

Functions and Characteristics of Blood - blood is a type of CT with cells and platelets suspended in a fluid extracellular matrix (plasma)  Functions of Blood List (and read about!) the five general functions of blood:

 Composition of Blood (see Fig. 17-1) 1. plasma - the fluid matrix 2. formed elements - list the three types of formed elements:

- formed elements are produced through a process called what?

 Physical Characteristics of Blood  the temperature of blood is about 38° C (100.4 °F) - how does it compare to normal body temperature?  blood is denser and more viscous (more sticky) than water  the pH of blood is slightly alkaline, about 7.4  blood makes up about 7 % of the total body weight  what is the normal volume of blood in an adult male? in an adult female?

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Plasma The Composition of Plasma (see Fig. 17-1)  makes up what percent of the volume of whole blood?  straw colored liquid portion of blood  92 % water  8 % solutes  plasma proteins– most are synthesized by hepatocytes of the liver:  albumins - most abundant of the plasma proteins - are major contributors to what? - also transport substances in the blood, such as what?

 globulins - transport lipids & fat-soluble vitamins; form antibodies  fibrinogen – a clotting factor for blood clotting  hormones  other solutes = electrolytes, organic nutrients, gases, wastes, etc.

Red Blood Cells  also called RBCs or erythrocytes  RBCs account for what percent of the formed elements?  name the red pigment that red blood cells contain and indicate what it binds and transports:

 ABUNDANCE OF RBCS • what does a red blood cell count report?  in an adult male, what is the normal number of RBCs in a microliter of blood?  in an adult female, what is the normal number of RBCs in a microliter of blood? • define hematocrit :

- what is the normal average hematocrit in adult males? - what is the normal average hematocrit in adult females?

- poiesis is Greek for “production of”

- the hematocrit value is due almost entirely of RBCs (99.9%), and is commonly reported as the volume of packed red cells (VPRC) or the packed cell volume (PCV)  STRUCTURE OF RBCS • biconcave discs, each with a thinner central region and a thicker outer margin (Fig. 17-2) • what is the average diameter of a RBC?

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• have a strong and flexible plasma membrane - allows the cells to fold so that they can squeeze through capillaries of smaller diameter • the plasma membrane has glycolipids that are antigens that account for different blood types • RBCs are anucleate and they lack other organelles • the cytosol contains hemoglobin molecules • name (and read about) the three important effects that the unusual shape has on RBC function:

• what is the normal life span of a red blood cell?

 HEMOGLOBIN • RBCs contain hemoglobin (Hb; Hgb), which binds reversibly to O2 and CO2 to transport O2 and CO2 • several features of RBCs related to their ability to transport gases include: 1. biconcave shape - increases surface area for diffusion of O2 (and CO2) 2. lack of a nucleus and other organelles - allows more room for hemoglobin in the cytoplasm 3. produce ATP anaerobically, so they do not use the O2 that they carry • what is the normal hemoglobin content in males? • what is the normal hemoglobin content in females? Structure of Hemoglobin - (see Fig. 17-3) components of one molecule of Hb: (a) globin - a globular protein of 4 chains of polypeptides (2 alpha & 2 beta) - the “globin” is the part to which CO2 binds (b) heme unit - ringlike nonprotein red pigment - one heme is in the center of each polypeptide chain - in the center of each heme unit is an iron ion (Fe+2) - the iron ion in each heme can bind reversibly with one O2:  oxyhemoglobin forms when the iron of the heme is bound to oxygen - blood containing RBCs filled with oxyhemoglobin is what color?  deoxyhemoglobin forms when the iron of the heme is not bound to oxygen - blood containing RBCs filled with deoxyhemoglobin is what color? Hemoglobin Function  each red blood cell contains how many hemoglobin molecules?

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 RBC FORMATION AND TURNOVER • RBCs live about how many days? • old or damaged RBCs are eliminated by phagocytic cells; new RBCs form at an equal rate to maintain normal numbers of RBCs - about what percent of circulating RBCs are replaced each day? - about how many new RBCs enter the bloodstream each second? Hemoglobin Conservation and Recycling  Destruction of RBCs: • old or damaged RBCs are recognized and phagocytized by macrophages in the liver, spleen and bone marrow • after phagocytosis, hemoglobin is split into: a. globin – is broken down into amino acids that are reused for protein synthesis b. heme unit - is broken down into: iron – recycled to make more Hb noniron portion – is converted to bilirubin  bilirubin enters the blood and is transported to the liver  within the liver, bilirubin is secreted by hepatocytes into bile, which passes into the small and large intestine  bacteria convert bilirubin in to other substances  some are resorbed and excreted in urine; the rest is excreted from the large intestine in the feces. erythropoiesis  RBC Production: “poiesis” is Greek for “production of”; ◦ erythropoiesis is the production of RBCs and it takes place in red bone marrow “erythro” means red ◦ begins with a precursor cell and involves cell division and differentiation of a series of cells  near the end of erythropoiesis a precursor cell loses its nucleus and becomes a reticulocyte  the reticulocyte enters the bloodstream  after 1 to 2 days in circulation the reticulocyte becomes a mature RBC (see Fig. 17-5)

◦ Regulation of Erythropoiesis: - normal erythropoiesis requires adequate supplies of amino acids, iron, and vitamins (B12, B6, and folic acid) - erythropoietin = a hormone produced by cells of the kidneys (and liver) released in response to: hypoxia target: red bone marrow effect: stimulates erythropoiesis  normally a continuous, moderate amount of erythropoietin is produced to keep the rate of production of RBCs in balance with the rate of destruction of RBCs  an increase or decrease in erythropoietin will change the rate of erythropoiesis e.g., if low levels O2 in the blood (hypoxia) are detected by cells in the kidney  the kidneys produce more erythropoietin  stimulates increased erythropoiesis in the red bone marrow  increased number of RBCs are produced

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◦ reticulocyte count - used to measure the rate of erythropoiesis - normal reticulocyte count: ~ 0.5 – 1.5% of RBCs in the blood are reticulocytes - a low reticulocyte count in a person who is anemic might indicate a shortage of erythropoietin or an inability of the red bone marrow to respond to erythropoietin, perhaps because of a nutritional deficiency or leukemia - a high reticulocyte count might indicate a good red bone marrow response to previous blood loss or to iron therapy in someone who had been iron deficient

Anemia is a low oxygen-carrying capacity of the blood 1) anemias due to low numbers of RBCs ◦ hemorrhagic anemia = anemia due to excessive loss of RBCs through bleeding ◦ hemolytic anemia = anemia due to rupture of RBCs ◦ aplastic anemia= anemia due to destruction of red bone marrow, such as caused by toxins, gamma radiation, and certain medications that inhibit enzymes needed for hemopoiesis ◦ pernicious anemia - anemia due to insufficient hemopoiesis resulting from an inability of the stomach to produce intrinsic factor, which is needed for absorption of vitamin B12 in the small intestine 2) anemias due to low hemoglobin content or abnormal hemoglobin in the RBCs ◦ iron deficiency anemia = anemia due to inadequate absorption of iron, excessive loss of iron, increased iron requirement, or insufficient intake of iron ◦ thalassemia = anemia due to deficient synthesis of hemoglobin

WHITE BLOOD CELLS

(go to page 566!)

 also called leukocytes or WBCs  do WBCs have a nucleus and other organelles?  do WBCs contain hemoglobin?  list the two groups of WBCs based on their appearance after staining:

 a normal total WBC count is 5,000 to 10,000 WBCs/microliter of blood  are most WBCs circulating in the bloodstream, or only a small fraction of them? - where are most WBCs in the body at any moment?

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WBC Circulation and Movement List the 4 numbered characteristics of WBCs: 1. - define emigration (diapedesis):

2.

3. - this characteristic of being attracted to specific chemicals is called what?

4.

Types of WBCs  which types of WBCs contribute to the body’s nonspecific defenses?

 which type of WBCs are responsible for specific defenses?

1. Granular leukocytes (Granulocytes) - generally have abundant granules in the cytoplasm after staining - are produced in red bone marrow

a. Neutrophils ∙ comprise 50-70% of all leukocytes in humans ∙ 10 to 12 µm diameter ∙ polymorphic nucleus (2 - 5 lobes); looks like sausage links! (neutrophils are also called polymorphonuclear leukocytes, or polymorphs)

∙ their cytoplasm is packed with pale granules containing what?

∙ the granules appear as fine lavender/pink speckles in the cytoplasm ∙ are neutrophils highly mobile? ∙ they respond first, before other WBCs, during inflammation ∙ summarize the functions of neutrophils (from Table 17-2 on page 570):

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b. Eosinophils ∙ comprise 2 to 4% of all leukocytes ∙ 10 to 12 µm diameter ∙ nucleus is polymorphic, often bilobed ∙ round, red/red-orange cytoplasmic granules that stain with acid dyes such as eosin ∙ summarize the functions of eosinophils (from Table 17-2 on page 570):

c. Basophils ∙ comprise less than 1% of all leukocytes ∙ 8 to 10 µm diameter ∙ irregularly shaped nucleus, often obscured by cytoplasmic granules ∙ basophilic granules of various sizes that stain darkly with basic dyes (deep purple/black) ∙ their granules contain what two substances? - what does histamine do? - what does heparin prevent?

∙ summarize the functions of basophils (from Table 17-2 on page 570):

2. Agranular leukocytes (agranulocytes) - lack abundant cytoplasmic granules - produced in red bone marrow and lymphatic tissue

a. Monocytes ∙ comprise 2 to 8% of all leukocytes ∙12 to 20 µm diameter ∙ nucleus is variable in shape (oval, kidney or horse-shoe) and usually eccentric ∙ cytoplasm is pale, gray-blue and frequently vacuolated ∙ migrate into surrounding CT and differentiate into macrophages, which phagocytize bacteria and debris in larger numbers than neutrophils

b. Lymphocytes ∙ comprise 20 to 30% of all leukocytes ∙ 6 to 14 µm diameter ∙ most are small cells with a darkly stained, round or slightly indented nucleus surrounded by a thin rim of robin's egg blue cytoplasm, which is often not visible

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∙ list the three types of lymphocytes classified functionally and state what each type is responsible for:

∙ summarize the functions of lymphocytes (from Table 17-2 on page 570):

WBC Counts  what do the values reported in a differential white blood cell count indicate?  normal total WBC count = 5,000 to 10,000 WBCs per microliter of blood ∙ define leukopenia: ∙ define leukocytosis:

WBC Production  observe Fig. 17-10 and note the series of cell stages involved in giving rise to the different types of WBCs

Platelets  are cytoplasmic fragments of large cells in the bone marrow called megakaryocytes  about 4 µm in diameter; disc shaped; pale staining with fine granules  what is the average concentration of platelets in a microliter of circulating blood? - define thrombocytopenia: - define thrombocytosis:  list (and read about!) the three functions of platelets:

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Platelets are also called thrombocytes. Why is “thrombocyte” not an appropriate name?

HEMOSTASIS  define hemostasis:  there are three phases of hemostasis: 1. Vascular Spasm  damage to a blood vessel triggers a local contraction of the smooth muscle cells of the vessel wall; what is this local contraction called? - vascular spasm decreases what? - what is the effect of such a constriction?  vascular spasm is initiated by damage to the smooth muscle, substances released from activated platelets, and reflexes initiated by pain receptors

2. Platelet Plug Formation  platelets contact and stick to parts of a damaged blood vessel, such as collagen fibers deep to the damaged endothelium  as more and more platelets arrive, they stick to one another; forming a platelet plug  as platelets arrive in the area of a damaged vessel, they become activated: - they develop cytoplasmic processes that extend toward other platelets and they also release a wide variety of compounds - list the 5 substances that activated platelets release and indicate the function of each:

 several factors limit the size of the platelet plug, including prostacyclin: - what does prostacyclin inhibit? - what type of cell is prostacyclin released by?

3. Blood Clotting (Coagulation)  coagulation involves a complex sequence of steps that leads to the conversion of circulating fibrinogen into what?  a blood clot consists of a network of fibrin threads and trapped formed elements (Fig. 17-12b)  clotting involves 13 clotting factors (I to XIII) (see Fig. 17-12a and Table 17-3)

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∙ these clotting factors include calcium ions and 11 different proteins (mostly synthesized by hepatocytes, platelets or released by damaged tissues)

 we will summarize the 3 STAGES OF BLOOD CLOTTING in class! 1.

the “common pathway”

There are two pathways that lead to the formation of prothrombinase: The Extrinsic Pathway - a tissue protein that leaks into the blood from damaged cells outside of blood vessels initiates the formation of prothrombinase The Intrinsic Pathway - the formation of prothrombinase is initiated by activators within the blood (damaged endothelial cells exposed to underlying collagen or damaged platelets)

2.

3.

anticoagulants = substances that inhibit blood clotting  examples of anticoagulants in plasma:  antithrombin-III ∙ blocks the action of several clotting factors, including prothrombin (factor II)  heparin ∙ what cells produce heparin? ∙ what does heparin accelerate?

 examples of other anticoagulants:  warfarin - given to patients to prevent unwanted clots from forming; it interferes with the action of vitamin K used by the liver to synthesize 4 clotting factors

 EDTA and citric acid – remove calcium to prevent blood from clotting in a test tube Calcium Ions, Vitamin K, and Blood Clotting - which pathways require calcium ions? - adequate amounts of vitamin K must be present for what?

Aspirin inhibits vasoconstriction and platelet aggregation by blocking synthesis of thromboxane A2 and decreases the chance of thrombus formation

Clot Retraction - once a clot forms, platelets contract and pull on the fibrin threads of the clot, which condenses the clot into a denser, more consolidated mass Repair of the Damaged Vessel - fibroblasts form new connective tissue and new endothelial cells repair the vessel

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Fibrinolysis  fibrinolysis is the dissolution of the blood clot  plasminogen (an inactive enzyme incorporated into the blood clot) is activated to plasmin (fibrinolysin)  plasmin digests what?

 list the two substances that activate plasminogen to plasmin:

Intravascular clotting  blood sometimes clots in unbroken vessels  unwanted clotting can be initiated by: 1. roughening of the endothelium (such as with arteriosclerosis; infection), which induces adhesions of platelets 2. slowly flowing blood – allows clotting factors to accumulate  a clot that forms in an unbroken vessel is called a thrombus  a blood clot that becomes dislodged (or a bubble of air, fat from broken bones, or a piece of debris) and is transported by the blood stream is called an embolus  thrombolytic agents are substances administered to dissolve unwanted blood clots that have formed e.g., tissue plasminogen activator (t-PA) and streptokinase

BLOOD TYPES

(go back to page 562!)

The surfaces of erythrocytes contain a genetically determined assortment of surface antigens that the person’s immune system recognizes as “self”, not foreign. Your blood type is a classification determined by what?  how many different kinds of surface antigens do RBCs have?  what are the three surface antigens that are of particular importance? There are two major blood groups: ABO and Rh  ABO Blood Group:  the ABO blood group is based on the presence of two antigens: antigen A and antigen B  blood plasma has antibodies that will attack antigens on foreign RBCs - do you think that people normally have antibodies that react with antigens on their own RBCs?

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- there are two types of antibodies in the ABO blood group: anti-A and anti-B antibodies  examine Fig. 17-6; what are the four possible blood types in the ABO blood group?  we will fill in the chart below in class to characterize the RBCs and plasma of each type in the ABO blood group: BLOOD TYPE

RBCs

Plasma

possible donors of RBCs (to a recipient of each type listed above)

- in an incompatible blood transfusion, antibodies in the recipient’s plasma bind to antigens on the donated RBCs; the RBCs become crosslinked, causing agglutination and hemolysis:  Rh Blood Group  named “Rh” because the antigen was first discovered in the blood of the Rhesus monkey  the term “Rh positive” indicates what?  the term “Rh negative” indicates what?

The End!

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