Chapter 19: The Cardiovascular System: The Blood

Question 1

describe the functions of blood.

Answer 1

Blood – liquid connective tissue composed of ECF called blood plasma and formed elements: cells and particles.

interstitial fluid – extracellular fluid that bathes body cells. Nutrients and wastes diffuse from blood/body cells through interstitial fluid, and into the other.

functions of blood – 3 main functions

1. Transportation – of oxygen, CO2, nutrients, hormones, heat, wastes
2. Regulation – of pH, body temp, water content of cells
3. Protection – against blood loss through clotting, disease through phagocytic WBCs, and proteins as antibodies, interferons, and complement.

Question 2

know the characteristics and components of blood.

Answer 2

physical characteristics of blood

1. denser and thicker than water
2. feels slightly sticky
3. temp = 38 degrees Celsius / 100.4 F
4. slightly alkaline pH at 7.35-7.45
5. color when oxygenated = bright red
6. non-saturated with O2 = dark red
7. 8% total body mass, accounts for 20% of ECF in the body
8. Blood volume average 5-6 L in males, 4-5 L in females

Not true Hemocytoblasts are a common component of circulating blood.

Question 3

List the major components of plasma and explain their importance.

Answer 3

components of blood – two components: blood plasma, formed elements

• buffy coat – layer in centrifuged blood between blood plasma and RBCs. Consists of WBCs and platelets. Less than 1% of the formed elements.

Plasma – roughly 55% of total volume.

• The ECF found in blood vessels; blood minus formed elements
• By weight, about 91.5% water and 8.5% solutes
• 7% by weight of the 8.5% are proteins

1) plasma proteins – proteins found only in blood plasma. Synthesized by hepatocytes. 3 proteins:

1. albumins – 54% of plasma proteins

lOMoARcPSD|7277012

• smallest and most numerous of plasma proteins
• responsible for colloid osmotic pressure.
• Major contributor to blood viscosity
• Transport hormones (steroid), fatty acids, and calcium
• Help regulate blood pH

2. globulins – 38% of plasma proteins

gamma globulin – important type of globulin

• large proteins.
• Alpha and beta globulins transport iron, lipids, and fat-soluble vitamins
• certain blood cells develop into plasma cells that produce gamma globulins called antibodies or immunoglobulins

3. fibrinogen – 7% of plasma proteins

• large protein
• plays essential role in blood clotting

2) antibodies or immunoglobulins – protein produced by plasma cells in response to a specific antigen

• the antibody combines with that antigen to neutralize, inhibit, or destroy it.

3) Other solutes – include electrolytes, nutrients, gases, regulatory substances (enzymes, hormones, vitamins) and waste products.

formed elements – about 45% total volume. 3 principal components: RBCs, WBCs, platelets

1. red blood cells (RBCs) – AKA erythrocytes
   * transport O2 and CO2 from lungs to tissues and back again
2. white blood cells (WBCs) – AKA leukocytes

• protect body from invading pathogens and other foreign substances
• Several types of EBCs: neutrophils, basophils, eosinophils, monocytes, lymphocytes
• 3 types of lymphocytes: B lymphocytes, T lymphocytes, natural killer cells
  1. platelets – fragments of cells that do not have a nucleus
• promote clotting when blood vessels are damaged by releasing chemicals
• functional equivalent to thrombocytes – nucleated cells in lower vertebrates that prevent blood loss by clotting.

Hematocrit – percentage of total blood volume occupied by RBCs

• Females – 38-46% (average 42%)
• Males – 40-54% (average 47%)
• Higher in males because testosterone stimulates synthesis of erythropoietin (EPO) which stimulates production of RBCs
• May also be lower in women of reproductive age due to menstruation.
• Significant drop in hematocrit indicates anemia

Polycythemia – abnormally high hematocrit (above 55%)

• Raises viscosity of blood, increases resistance to flow, makes more difficult for heart to pump, increases risk of stroke.
• Htn, thrombosis, and hemorrhage can occur
• Causes: abnormal increases in RBC production, tissue hypoxia, dehydration, blood doping (use of EPO by athletes)

Question 4

explain the origin of blood cells.

Answer 4

formation of blood cells

hemopoiesis or hematopoiesis – the process by which formed elements of the blood develop

• blood cell production
• before birth, occurs first in embryo’s yolk sac and then in the liver, spleen, thymus, and lymph nodes of a fetus
• occurs in red bone marrow from month 6 of fetus and continues after birth

red bone marrow – highly vascularized connective tissue located in the microscopic spaces between trabecula of spongy bone tissue

• present mainly in bones of the axial skeleton, pectoral and pelvic girdles, and proximal epiphyses of the humerus and femur.
• In newborns, all bone marrow is red. As we age, the rate of blood cell formation decreases, red bone marrow in the medullary cavity of long bones is replaced by yellow bone marrow.
• Under certain conditions, such as severe bleeding, yellow bone marrow can revert to red bone marrow which occurs as blood-forming stem cells from red bone marrow migrate to yellow bone marrow which is then repopulated by pluripotent stem cells.

pluripotent stem cells – about 0.05-0.1% of red bone marrow cells

• AKA Hemocytoblasts, AKA hematocytoblasts
• Derived from mesenchyme (tissue from which almost all connective tissues develop)
• Immature stem cell in red bone marrow that gives rise to precursors of all the different mature blood cells.
• Have capacity to develop into many different kinds of cells Divide further into two types of stem cells: myeloid stem cells, and lymphoid stem cells
• Resemble lymphocytes, cannot be distinguished by microscopic appearance alone.

progenitor cells – formed by some myeloid stem cells during hemopoiesis.

1. No longer capable of reproducing themselves
2. Are committed to giving rise to more specific elements of blood.
3. Some progenitor cells are known as the colony-forming units (CFUs)
   
   • Following the CFU designation is an abbrev that indicates the nature elements in blood that they will produce:

• CFU-E become erythrocytes
• CFU-Meg become megakaryocytes
• CFU-GM become granulocytes and monocytes

1. Still resemble lymphocytes and cannot be distinguished microscopically.

precursor cells or blasts – the next generation of blood cells.

• Over several cell divisions they develop into the actual formed elements of blood.

hemopoietic growth factors- hormones that regulate the differentiation and proliferation of particular progenitor cells.

• erythropoietin or EPO – increases the number of red blood cell precursors (proerythroblasts). Produced primarily by peritubular interstitial cells in the kidneys between the kidney tubules.
• thrombopoietin or TPO – hormone produced by the liver that stimulates formation of platelets from megakaryocytes.

cytokines – small glycoproteins that are typically produced by cells such as red bone marrow cells, leukocytes, macrophages, fibroblasts, and endothelial cells

1. regulate development of different blood cell types
2. generally act as a local hormone (auto or paracrine)
3. stimulate proliferation of progenitor cells in red bone marrow
4. regulate the activities of cells involved in nonspecific defenses and immune responses
5. two important families of cytokines that stimulate WBC formation: colony stimulating factors and interleukins

• colony stimulating factors (CSFs) – stimulates development of WBCs
• interleukins – stimulate WBC formation

Question 5

describe the structure, functions, life cycle, and production of red blood cells.

Answer 5

red blood cells or erythrocytes - major function GAS TRANSPORT

• replaced at a rate of at least 2 million per second.
• Healthy adult male: 5.4 million RBCs per microliter of blood
• Healthy adult female: 4.8 million RBCs per microliter.

hemoglobin – oxygen-carrying protein 280 million in each RBC

• consists of the protein globin and the iron-containing red pigment heme
• transports most of the O2 and some CO2 in the blood.
• Gives whole blood its red colour

RBC anatomy

1. Biconcave discs with a diameter of 7-8 micrometers (1uL = 1/000 of a mm)
   * Greater surface area for diffusion of gas molecules than a sphere or cube.
2. Lack a nucleus and other organelles
3. Can neither reproduce nor carry on extensive metabolic activities
4. Certain glycolipids in the cell membrane are antigens that account for the ABO and Rh groups
5. The cytosol contains hemoglobin molecules
6. About 280 million hemoglobin molecules per RBC

• important molecules synthesized before loss of the nucleus during RBC production (is a reticulocyte before loss of nucleus)
• constitute about 33% of the RBC’s weight.

1. Plasma membrane is both strong and flexible, allowing them to deform without rupturing as they squeeze through narrow capillaries.

RBC physiology

a. Generate ATP anaerobically and do not use up any O2 they transport
b. Hemoglobin molecules:

• Globin – protein composed of four polypeptide chains (2 alpha and 2 beta chains)
• Heme – ringlike nonprotein bound to each of the four chains with an iron ion (Fe2+) at the center of each heme ring that can combine reversibly with one oxygen molecule allowing each hemoglobin to bind 4 oxygen (O2) molecules. Each oxygen molecule from the lungs is bound to an iron ion. As blood flows through capillaries, the iron-oxygen reaction reverses, hemoglobin releases oxygen, which diffuses first into interstitial fluid and then cells.
• Hemoglobin transports about 23% of the total CO2 (the remainder dissolved in plasma or carried as bicarbonate ions) Blood picks up CO2 in the capillaries which binds with amino acids in the globin part of the hemoglobin and is released as blood flows into the lungs.
• Hemoglobin also plays a role in regulation of blood flow and blood pressure with nitric oxide
• nitric oxide (NO) – produced by endothelial cells that line blood vessels
• binds to hemoglobin
• under some circumstances, hemoglobin releases NO, causing vasodilation, improving blood flow, enhancing O2 delivery to cells near the site of NO release
  
  • It allows about 70% of the CO2 to be transported in blood plasma from tissue cells to the lungs in the form of HCO3-

c. Carbonic anhydrase (CA) – enzyme contained in RBCs that catalyzes the conversion of carbon dioxide and water to carbonic acid which in turn dissociates into H+ and HCO3-. The entire reaction is reversible.

This reaction is significant for two reasons:

• Serves as an important buffer in ECF

RBC life cycle

a. RBCs last about 120 days

• Their plasma membrane becomes more fragile due to wear and tear and inability to replace damaged parts.
• Ruptured RBCs are digested by fixed phagocytic macrophages in the spleen and liver and the breakdown parts are recycled and reused.

b. Life cycle:

1. Macrophages in spleen, liver, and red bone marrow phagocytize ruptured and worn out RBCs
2. The globin and heme portions of hemoglobin are split apart
3. Globin is broken down into amino acids, which can be reused to synthesize proteins
4. Iron is removed from the heme portion in the form of Fe3+, which associates with the plasma protein transferrin Transferrin – a transporter for Fe3+ in the blood stream
5. In muscle fibers, liver cells, and macrophages of the spleen and liver, Fe3+ detaches from transferrin and attaches to ferritin 1. Ferritin – an iron storage protein located in muscle fibers, liver cells, and macrophages of the spleen and liver stores iron in the liver.
6. On release from a storage site or absorption from the GI tract, Fe3+ reattaches to transferrin
7. The Fe3+-transferrin complex is then carried to red bone marrow, where RBC precursor cells take it up through receptor mediated endocytosis for use in hemoglobin synthesis 1. Iron is needed for the heme portion of hemoglobin molecules and amino acids are needed for the globin portion. Vitamin B12 is also needed for synthesis of hemoglobin.
8. Erythropoiesis in red bone marrow results in the production of RBCs, which enter circulation
9. When iron is removed from heme, the non-iron portion of heme is converted to biliverdin, a green pigment, and then into bilirubin. 1. Bilirubin – a yellow-orange pigment that is one of the end products of hemoglobin breakdown in the hepatocytes and is excreted as a waste material in bile.
10. Bilirubin enters the blood and is transported to the liver.
11. Within the liver, bilirubin is released by liver cells into bile, which passes into the intestines
12. In the large intestine, bacteria convert bilirubin into urobilinogen
13. Some urobilinogen is absorbed back into the blood, converted to a yellow pigment called urobilin, and excreted in urine
14. Most urobilinogen is eliminated in the feces in the form of a brown pigment called stercobilin which gives feces its brown colour.

c. Free iron damages molecules in cells or in the blood. Transferrin and Ferritin act as protective protein escorts resulting in virtually no free iron in the body.

1. Iron overload – iron present in the body builds up.
2. No way to excrete excess iron
3. Leads to diseases of liver, heart, pancreatic islets, gonads and allows iron-dependent microbes to flourish that otherwise would not.

Erythropoiesis – production of RBCs

1. Starts in red bone marrow with a precursor cell called a proerythroblast
2. Proerythroblast forms from CFU-E cells (progenitor cells that rise from myeloid stem cells from pluripotent stem cells)
3. Erythropoietin promotes the division of proerythroblasts
   
   • Divides many times, producing cells that start synthesizing hemoglobin

Reticulocyte – a cell near the end of the development sequence that ejects its nucleus

• Loss of nucleus causes center of cell to indent, producing distinctive biconcave shape.
• Reticulocytes retain some mitochondria, ribosomes, and EF
• They pass from red bone marrow to blood by squeezing between the endothelial cells of blood capillaries.
• Reticulocytes develop into mature RBCs within 1-2 days after release from red bone marrow.
• Make up 0.5-1.5% of all RBCs in a normal blood sample

Hypoxia – cellular oxygen deficiency

• Lack of adequate oxygen at the tissue level.
• May be caused by high altitude, anemia (causes: low iron, lack of certain amino acids, lack of Vitamin B12), circulatory problems reducing blood flow to tissues
• Hypoxia stimulates the kidneys to increase release of erythropoietin which speeds up development of proerythroblasts into reticulocytes in the red bone marrow.
• More RBCs = more O2 to body tissues

Negative feedback – normally erythropoiesis and RBC destruction occur at same rate.

a. If O2 carrying capacity of blood falls because erythropoiesis is not keeping up with RBC destruction, a negative feedback system increases RBC production.
b. Premature newborns usually exhibit anemia due in part to inadequate production of erythropoietin.

• For first weeks after birth, the liver, not kidneys, produces most EPO.
  
  • Liver is less sensitive than kidneys to hypoxia, so newborns have a smaller EPO response to anemia than adults.
  • Fetal hemoglobin carries up to 30% more oxygen, so the loss of fetal hemoglobin due to insufficient erythropoietin production makes the anemia worse.

Question 6

describe the structure, functions, and production of white blood cells.

Answer 6

white blood cells or leukocytes – nucleated blood cells responsible for protecting the body

through phagocytosis or immune responses.

Contain all organelles.

Classified as granular or agranular depending on staining results Chemical filled cytoplasmic granules (vesicles) that stain various colours and are visible through a light microscope.

• granular leukocytes – 3 kinds: neutrophils, eosinophils, basophils. Develop from myeloid stem cells.
  
  1. Eosinophil – large uniform-sized granules that stain red-orange in acidic dye.
• Two lobed nucleus connected by a thin or thick strand of nuclear material.
• Granules do not cover the nucleus.

1. basophil – round variable sized granules that stain dark blue/purple in basic dye, cover the nucleus which is difficult to see. 1. 2 lobed nucleus
2. neutrophil – small evenly spaced granules that stain pale lilac and do not attract blue or red dye strongly

• lobed nucleus – 2-5 lobes
• more lobes as cell ages
• older neutrophils with several differently shaped lobes are called polymorphonuclear leukocytes, polymorphs, or polys.

agranular leukocytes – 2 kinds: lymphocytes (lymphoid stem cells) and monocytes (myeloid stem cells)

• actually do contain granules but they are small and do not stain so not visible under a light microscope.

Lymphocyte – type of WBC that helps carry out cell-mediated and antibodymediated immune responses.

• Found in blood and lymphatic tissues
• Nucleus stains dark, is round or slightly indented.
• Cytoplasm stains sky blue, forms a rim around the nucleus
• Classified by cell diameter as large (10-14micrometers) or small (6-9 micrometers) 1. Functional difference unclear but clinically, increase innumber of large lymphocytes = diagnostic significance in
• acute viral infections and some immunodeficiency diseases.
  
  • Larger the cell, more cytoplasm visible.

Monocyte – largest type of WBC.

• Nucleus is usually kidney shaped or horseshoe shaped
• Cytoplasm is blue-gray and has a foamy appearance due to very fine azureophilic granules which are lysosomes
• Monocytes travel in blood and migrate into tissues where they enlarge and differentiate into macrophages.

Macrophage – phagocytic cell derived from a monocyte. May be fixed or wandering

fixed macrophage – reside in a particular tissue 1. ex. Alveolar macrophages in lungs or macrophages in the spleen

wandering macrophage – roam tissues and gather at sites of infection or inflammation

major histocompatibility (MHC) antigens – surface proteins on all WBC and nucleated blood cells of the body

• unique to each person (except identical twins)
• used to type tissues and help prevent rejection of transplanted tissues
• AKA human leukocyte antigens (HLA)

WBC physiology

a. Most WBCs live only a few days. Lymphocytes can live for several months or years.
* During infection, phagocytic WBCs may live only a few hours
b. WBCs are far less numerous than RBCs: about 5000-10000 cells per microliter of blood
* RBCs outnumber WBCs 700:1
c. Leukocytosis – increases in number of WBCs above 10000/microliter
* Normal protective response to stresses such as invading microbes, strenuous exercise, anesthesia, and surgery.
d. Leukopenia – abnormally low number of WBCs, below 5000/microliter.

• Never beneficial
• Causes: radiation, shock, certain chemotherapeutic agents.
  
  1. Granular leukocytes and monocytes never return to the blood stream once they migrate out to fight injury or infection.

Circulation of WBCs:

1. Lymphocytes continually recirculate, from blood to interstitial spaces to lymphatic fluid, and back to blood.
   * 2% of lymphocytes is circulating in blood at any given time. The rest is in lymphatic fluid and organs such as skin, spleen, lymph nodes, and lungs.

emigration (diapedesis) – process by which WBCs leave the blood stream.

1. WBCs roll along the endothelium, stick to it, then squeeze between endothelial cells.
2. Signals that stimulate emigration through a particular blood vessel vary for different types of WBCs.
3. Adhesion molecules help WBCs stick to the endothelium

• Selectins – adhesion molecules displayed on endothelial cells in response to nearby injury and inflammation These selectins stick to carbohydrates on the surface of neutrophils, causing them to slow down and roll along the endothelial surface.
• Integrins – other adhesion molecules on the surface of the neutrophil 1. Tether neutrophils to the endothelium and assist their movement through the blood vessel wall and into the interstitial fluid of the injured tissue.

Phagocytosis – the process by which phagocytes ingest and destroy microbes, cell debris, and other foreign matter.

• Neutrophils and macrophages perform phagocytosis
• Ingest bacteria and dispose of dead matter
• Eosinophils phagocytize antigen-antibody complexes
• Neutrophils respond fastest to tissue destruction by bacteria

Chemotaxis – phenomenon in which chemicals released by microbes and inflamed tissues that attract phagocytes

• Substances include toxins produced by microbes, kinins (specialized products of damaged tissues), some of the colony-stimulating factors (CSFs)
• CSFs also enhance the phagocytic activity of neutrophils and macrophages
  
  • Destroys certain bacteria, strong oxidants: superoxide anion O2-, hydrogen peroxide H2O2, hypochlorite anion (OCl-)

Lysozyme – bactericidal enzyme found in tears, saliva, perspiration

Defensins – proteins in neutrophils that exhibit a broad range of antibiotic activity against bacteria and fungi.

• Defensins for peptide spears that poke holes in the microbe membranes, killing the invader.

Eosinophils leave capillaries and enter tissue fluid

• Believed to release enzymes, such as histaminase, that combat effects of histamine and other substances involved in inflammation during allergic reactions
• Also phagocytize antigen-antibody complexes and are effective against certain parasitic worms
• High eosinophil count often indicates an allergic condition or a parasitic infection.

Basophils – leave capillaries and enter tissues at sites of inflammation

• Release granules that contain heparin, histamine, and serotonin.
• The substances intensify the inflammatory response and are involved in hypersensitivity allergic reactions.
• Similar in function to mast cells (connective tissue cells that originate from pluripotent stem cells in red bone marrow.
  
  • Mast cells are widely dispersed in the body, particularly in connective tissues of the skin and mucous membranes of the respiratory and GI tracts.

Lymphocytes – major soldiers in lymphatic system battles

• Continually move among lymphoid tissues, lymph, and the blood, spending only a few hours at a time in the blood.
• 3 main types of lymphocytes: B cells, T cells, and natural killer cells
• B Cells – effective in destroying bacteria and inactivating their toxins Plasma cells that produce antibodies
• T cells – attack viruses, fungi, transplanted cells, cancer cells, some bacteria Are responsible for transfusion reactions, allergies, and transplant rejections
• Natural killer cells – attack a wide variety of infectious microbes and certain spontaneously arising tumor cells

Monocytes – take longer to reach infection site than neutrophils but arrive in larger numbers and destroy more microbes.

• On arrival, enlarge, differentiate into wandering macrophages, clean up cellular debris and microbes by phagocytosis after an infection.

differential white blood cell count – a count of each of the five types of WBCs

• to detect infection or inflammation
• determine effects of possible poisoning by chemicals or drugs
• monitor blood disorders (ex. leukemia) and effects of chemotherapy
• detect allergic reactions and parasitic infections
• each WBC type plays a different role, determine the percentage of each type in the blood assists in diagnosing a condition.

TABLE 19.2 Significance of High and Low White Blood Cell Counts

Neutrophils HIGH COUNT MAY INDICATEBacterial or fungal infection, burns, stress, inflammation. LOW COUNT MAY INDICATE Radiation exposure, drug toxicity, vitamin B12 deficiency, systemic lupus erythematosus (SLE).

Lymphocytes HIGH COUNT MAY INDICATE Viral infections, some leukemias, infectious mononucleosis. LOW COUNT MAY INDICATE Prolonged illness, HIV infection, immunosuppression, treatment with cortisol.

Monocytes HIGH COUNT MAY INDICATEViral or fungal infections, tuberculosis, some leukemias, other chronic diseases. LOW COUNT MAY INDICATE Bone marrow suppression, treatment with cortisol.

Eosinophils HIGH COUNT MAY INDICATEAllergic reactions, parasitic infections, autoimmune diseases. LOW COUNT MAY INDICATE Drug toxicity, stress, acute allergic reactions.

Basophils HIGH COUNT MAY INDICATEAllergic reactions, leukemias, cancers, hypothyroidism. LOW COUNT MAY INDICATE Pregnancy, ovulation, stress, hypothyroidism

Question 7

describe the structure, function, and origin of platelets.

Answer 7

platelets or thrombocytes

platelets – irregularly disk-shaped fragments of a megakaryocyte

• megakaryocyte splinters into 2000-3000 platelets
• Each platelet has many vesicles but no nucleus
• 2-4 micrometers in diameter.
• Short life span: 5-9 days
• 150,000-400,000 platelets per microliter of blood
• The granules release chemicals that promote blood clotting 1. Help stop blood loss from damaged blood vessels by forming a platelet plug

Megakaryoblast – precursor cell that transforms into megakaryocyte

• Myeloid stem cells develop into megakaryoblasts under influence of the hormone thrombopoietin

fixed macrophages – remove aged and dead platelets in the spleen and liver

complete blood count – valuable test that screens for anemia and various infections

• usually included: counts of RBCs, WHCs, platelets per microliter of whole blood; hematocrit, differential WBC count, hemoglobin in grams per milliliter of blood
• Normal hemoglobin: infants: 14-20g/100mL; adult females: 12-16 g/100mL, adult males 13.5-18g/100mL

TABLE 19.3 Summary of Formed Elements in Blood

RED BLOOD CELLS (RBCS) OR ERYTHROCYTES NUMBER 4.8 million/μL in females; 5.4 million/μL in males. CHARACTERISTICS 7–8 μm diameter, biconcave discs, without nuclei; live for about 120 days. FUNCTIONS Hemoglobin within RBCs transports most oxygen and part of carbon dioxide in blood.

WHITE BLOOD CELLS (WBCS) OR LEUKOCYTES NUMBER 5000– 10,000/μL. CHARACTERISTICS Most live for a few hours to a few days. FUNCTIONS Combat pathogens and other foreign substances that enter body.

Granular leukocytes Neutrophils S NUMBER 60–70% of all WBCs. CHARACTERISTICS 10–12 μm diameter; nucleus has 2–5 lobes connected by thin strands of chromatin; cytoplasm has very fine, pale lilac granules. FUNCTIONS Phagocytosis. Destruction of bacteria with lysozyme, defensins, and strong oxidants, such as superoxide anion, hydrogen peroxide, and hypochlorite anion.

Eosinophils NUMBER 2–4% of all WBCs. CHARACTERISTICS 10–12 μm diameter; nucleus usually has 2 lobes connected by thick strand of chromatin; large, red-orange granules fill cytoplasm. FUNCTIONS Combat effects of histamine in allergicreactions, phagocytize antigen– antibody complexes, and destroy certain parasitic worms.

Basophils NUMBER 0.5–1% of all WBCs. CHARACTERISTICS 8–10 μm diameter; nucleus has 2 lobes; large cytoplasmic granules appear deep blue-purple. FUNCTIONS Liberate heparin, histamine, and serotonin in allergic reactions that intensify overall inflammatory response.

Agranular leukocytes Lymphocytes (T cells, B cells, and natural killer cells) NUMBER 20–25% of all WBCs. CHARACTERISTICS Small lymphocytes are 6– 9 μm in diameter; large lymphocytes are 10–14 μm in diameter; nucleus is round or slightly indented; cytoplasm forms rim around nucleus that looks sky blue; the larger the cell, the more cytoplasm is visible. FUNCTIONS Mediate immune responses, including antigen–antibody reactions. B cells develop into plasma cells, which secrete antibodies. T cells attack invading viruses, cancer cells, and transplanted tissue cells. Natural killer cells attack wide variety of infectious microbes and certain spontaneously arising tumor cells.

Monocytes 3–8% of all 12–20 μm diameter; nucleus Phagocytosis (after

NUMBER WBCs. CHARACTERISTICS is kidney- or horseshoeshaped; cytoplasm is bluegray and appears foamy. FUNCTIONS transforming into fixed or wandering macrophages).

PLATELETS NUMBER 150,000– 400,000/μL. CHARACTERISTICS 2–4 μm diameter cell fragments that live for 5–9 days; contain many vesicles but no nucleus. FUNCTIONS Form platelet plug in hemostasis; release chemicals that promote vascular spasm and blood clotting.

Question 8

describe the three mechanisms that contribute to hemostasis.

Answer 8

Hemostasis – sequence of responses that stops bleeding.

• When blood vessels are damaged or ruptured, the hemostatic response must be quick, localized to the region of damage, and carefully controlled to be effective.
• Hemorrhage – the loss of a large amount of blood from the vessels
• Hemostatic mechanisms can prevent hemorrhage from smaller blood vessels, but extensive hemorrhage from larger vessels usually requires medical intervention.

Three mechanisms reduce blood loss: vascular spasm, platelet plug formation, blood clotting

1.vascular spasm – contraction of the smooth muscle in the wall of a damaged blood vessel to prevent blood loss.

• Reduces blood loss for several minutes to several hours, during which time the other hemostatic mechanisms occur.
• The spasm is probably caused by damage to the smooth muscle, substances released from activated platelets, and by reflexes initiated by pain receptors.

2. platelet plug formation

platelets – small size but store tons of chemicals

• clotting factors, ADP, ATP, Ca2+, serotonin, and enzymes
• the enzymes produce thromboxane A2 (a prostaglandin), fibrinstabilizing factor (helps strengthen a blood clot), lysosomes, mitochondria, glycogen, and membrane systems for storing calcium and releasing granule contents
• platelet-derived growth factor (PDGF) – also present in platelets 1. a hormone that causes proliferation of vascular endothelial cells, vascular smooth muscle fibers, and fibroblasts to help repair damaged blood vessel walls

The process of platelet plug formation:

1. platelet adhesion – platelets contact and stick to parts of a damaged blood vessel, such as collagen fibers of the connective tissue underlying the damaged endothelial cells
2. platelet release reaction – phase during which due to adhesion, the platelets become activated.

• Characteristics change dramatically
• Extend many projections that enable them to contact and interact with one another
• Begin to liberate contents of their vesicles
• Liberated ADP and thromboxane A2 activate nearby platelets
• Serotonin and thromboxane A2 fcn as vasoconstrictors, causing and sustaining contraction of vascular smooth muscle, decreasing blood flow through the injured vessel

1. platelet aggregation – gathering of platelets caused by the release of ADP making other platelets in the area sticky, and the stickiness of the newly recruited and activated platelets causes them to adhere to the originally activated platelets

platelet plug – the accumulation and attachment of large numbers of platelets forming a mass.

• Very effective in preventing blood loss in a small vessel.

3. blood clotting (or coagulation)

• serum – straw colored liquid of blood plasma minus the clotting proteins
• blood clot – a gel that consists of the formed elements of blood trapped in a network of insoluble protein fibers.
• Clotting – AKA coagulation – a series of chemical reactions that culminates in formation of fibrin threads.

Question 9

explain the various factors that promote and inhibit blood clotting.

Answer 9

Clot – a gel that consists of the formed elements of blood trapped in a network of insoluble protein fibers

Factor XIII stengthens and stabilizes blood clot

Thrombosis – the formation of a clot in an unbroken blood vessel, usually a vein.

• Caused by blood clotting too easily

Hemorrhage can occur if blood takes too long to clot.

clotting (coagulation) factors – several substances involved in clotting

• include calcium ions, several inactive enzymes that are synthesized by hepatocytes and released into the bloodstream, and various molecules associated with platelets or released by damaged tissues
• most clotting factors are identified by Roman numerals that indicate the order of discovery, not the order of participation in the clotting process.

stages of clotting (coagulation) – 3 stages: 1)pathway (extrinsic or intrinsic) that leads to formation

of prothrombinase, (2) conversion of prothrombin into thrombin, and (3) conversion of soluble

fibrinogen into insoluble fibrin.

1extrinsic pathway – fewer steps than the intrinsic pathway

1. occurs rapidly, within a matter of seconds if trauma is severe
2. tissue factor (TF) or thromboplastin – tissue protein that leaks into the blood from cells outside blood vessels and initiates the formation of prothrombinase. a. A complex mixture of lipoproteins and phospholipids released from the surfaces of damaged cells.
3. In the presence of Ca2+, TF begins a sequence of reactions that ultimately activates clotting factor X.
4. Once factor X is activated, it combines with factor V in the presence of Ca2+ to form the active enzyme prothrombinase, completing the extrinsic pathway.

1intrinsic pathway – more complex than extrinsic pathway.

1. Occurs more slowly, usually requiring several minutes
2. Activators are either in direct contact with blood or contained within the blood; outside tissue damage is not needed
3. Contact with collagen fibers (or the glass sides of a collection tube) activated clotting factor XII
4. Factor XII begins a sequence of reactions that eventually activate clotting factor X.
5. Platelet phospholipids and Ca2+ can also participate in the activation of factor X
6. Once factor X is activated, it combines with factor V to form the enzyme prothrombinase, completing the intrinsic pathway.

2common pathway – begins once prothrombinase is formed.

I. The second stage of blood clotting - Prothrombinase and Ca2+ catalyze the conversion of prothrombin to thrombin.

3.Third stage of clotting – thrombin in presence of Ca2+ converts soluble fibrinogen to insoluble loose fibrin threads.

• Thrombin also activates factor XIII (fibrin stabilizing factor) which strengthens and stabilizes the fibrin threads into a sturdy clot
• Plasma contains some factor XIII which is also released by platelets trapped in the clot.
• Thrombin has 2 positive feedback loops:
• Involves factor V, prothrombin accelerates the formation of prothrombinase which in turn accelerates the production of more thrombin, and so on
• Thrombin activates platelets, which reinforces their aggregation and release of platelet phospholipids

clot retraction – the consolidation or tightening of the fibrin clot

1. once formed, the clot plugs the ruptured area of the blood vessel and thus stops blood loss
2. the fibrin threads attached to the damaged surfaces of the blood vessel gradually contract as platelets pull on them
3. as the clot retracts, it pulls the edges of the damaged vessel closer together, decreasing the risk of further damage.
4. During retraction, some serum can escape between the fibrin threads, but the formed elements in blood cannot.
5. Normal retraction depends on an adequate number of platelets in the clot, which release factor XIII and other factors, thereby stabilizing and strengthening the clot.
6. Permanent repair of the blood vessel can then take place. a. In time, fibroblasts form connective tissue in the ruptured area, and new endothelial cells repair the vessel lining.

role of vitamin K in clotting – normal clotting depends on adequate levels of vitamin K in the body.

1. Not involved in clotting itself, but required for the synthesis of 4 clotting factors
2. Vitamin K is a fat-soluble vitamin that can be absorbed through the lining of the intestine if absorption of lipids is normal. a. Normally produced by bacteria in the large intestine
3. Those suffering from lipid absorption disorders often experience uncontrolled bleeding due to vitamin K deficiency.

hemostatic control mechanisms

1. fibrinolytic system – dissolves small, inappropriate clots. Also dissolves clots at a damage site once repaired.
2. Fibrinolysis – dissolution of clot
3. Plasminogen – an inactive enzyme incorporated into a clot when formed.
4. plasmin or fibrinolysin – activated form of plasminogen

• activated by substances in body tissues and blood 1. substances include thrombin, activated factor XII, and tissue plasminogen activator (t-PA)
• once activated, plasmin can dissolve the clot by digesting the fibrin threads and inactivating substances such as fibrinogen, prothrombin, and factors V and XII.

1. Anticoagulants – a substance that can delay, suppress, or prevent the clotting of blood

• Antithrombin – present in the blood; blocks the action of several factors, including XII, X, and II. b. Heparin – produced by mast cells and basophils 1. Combines with antithrombin and increases its effectiveness in blocking thrombin
• activated protein C – inactivates the two major clotting factors not blocked by antithrombin and enhances activity of plasminogen activators 1. babies that lack the ability to produce APC due to a genetic mutation usually die of blood clots in infancy.

intravascular clotting – despite anticoagulating and fibrinolytic mechanisms, sometimes blood clots form within the cardiovascular system.

• May be initiated by roughened endothelial surfaces of a blood vessel resulting from atherosclerosis, trauma, or infection, or when blood flows too slowly (stasis), allowing clotting factors to accumulate locally in high enough concentrations to initiate coagulation.
• Thrombosis – clotting in an unbroken blood vessel (usually a vein)
• Thrombus – the clot itself inside an unbroken blood vessel. A stationary clot. May dissolve spontaneously.

Embolus – a blood clot, bubble of air, fat from broken bones, or a piece of debris or foreign material transported by the blood

• If an embolus breaks away from an arterial wall, it may lodge in a smaller diameter artery downstream and block blood flow to a vital organ

pulmonary embolism – the presence of a blood clot or a foreign substance in a pulmonary arterial blood vessel that obstructs circulation to lung tissue.

Question 10

distinguish between the ABO and Rh blood groups.

Answer 10

blood groups and blood types

cytokines – small glycoproteins that are responsible for regulating the development of different blood types

antigens – a substance that has immunogenicity (the ability to provoke an immune response) and reactivity (the ability to react with the antibodies or cells that result from the immune response

agglutinogens – antigens on the surface of erythrocytes composed of glycoproteins and glycolipids

• genetically determined
• occur in characteristic combinations.

ABO blood group – based on two glycolipid antigens called A and B.

• Type A – people whose RBCs display ONLY antigen A. a. People have anti-B antibodies
• Type B – RBCs display ONLY antigen B. People have anti-A antibodies
• Type AB – RBCs have BOTH A and B antigens. People have NEITHER anti-A or anti-B antibodies
• Type O – RBCs have NEITHER A nor B antigens. People have BOTH anti-A and anti-B antibodies

Agglutinins – antibodies contained in blood plasma that react with A or B antigens if the two are mixed.

• anti A antibody – react with antigen A
• anti B antibody – react with antigen B
• start to appear in the blood within a few months after birth, but the reason for their presence is unclear.
• The antibodies are large IgM-type antibodies that do not cross the placenta 1. ABO incompatibility between a mother and fetus rarely causes problem

Transfusions – the transfer of whole blood or blood components (RBCs only or blood plasma only) into the bloodstream or red bone marrow.

• Most often to alleviate anemia, to increase blood volume or to improve immunity
• Blood is the most easily shared of human tissues
• Can result in transfusion reactions

Agglutination – clumping of blood cells, typically due to an antigen-antibody reaction

• In an incompatible blood transfusion, antibodies in the recipient’s plasma bind to the antigens on the donated RBCs, causing agglutination. (not the same as clotting)
• When these antigen-antibody complexes form, they activate plasma proteins of the complement family. 1. Complement molecules make the donated RBC plasma membranes leaky, causing hemolysis

Hemolysis – the escape of hemoglobin from the interior of a RBC into the surrounding medium.

• Results from disruption of the cell membrane by toxins, drugs, freezing or thawing, hypotonic solutions, or agglutination
• Rupture of the RBCs and release of hemoglobin into the blood plasma.
• Liberated hemoglobin may cause kidney damage by clogging filtration membranes.

universal recipients – type AB blood

• does not have anti-A or anti-B antibodies in their blood plasma
• no antibodies to attack antigens on donor RBCs

universal donors – type O blood

• does not have A antigens or B antigens on their RBC surfaces, no antigens for recipient anti-A or anti-B antibodies in plasma to react with
• the donated O blood would have anti-A and anti-B antigens which would react with the recipients type A, B, or AB blood, however the donated blood is so dilute in the recipient that it does not cause significant agglutination and hemolysis of the recipient’s RBCs.

Rh blood group – named for the Rh factor

Rh factor – the Rh antigen so named because it was first found in the blood of the Rhesus monkey

• If RBCs have Rh antigens, person is Rh+
• If RBCs do not have Rh antigens, person is Rhc. Normally, the blood plasma does not contain anti-Rh antibodies.
• If an Rh- person receives an Rh+ blood transfusion, the immune system starts to make anti-Rh antibodies that will remain in the blood. 1. If a second Rh+ transfusion is given, the previously formed anti-Rh antibodies will cause agglutination and hemolysis of the RBCs in the donated blood, and a severe reaction may occur.

hemolytic disease of the newborn (HDN) – a hemolytic anemia of a newborn child that

results from the destruction of the infant’s erythrocytes (RBCs) by antibodies produced by the mother.

• Usually the antibodies are due to an Rh blood type incompatibility.
• AKA erythroblastosis fetalis
• Caused by an Rh- mother receiving a small fetal Rh+ blood leakage into her blood stream (usually during delivery).
• Her body then starts making anti-Rh antibodies
• First baby is not usually affected as the leakage occurs during delivery
• The second baby, if Rh+ again, will experience HDN because the anti- Rh antibodies will cross the placenta during the subsequent pregnancy.

Treatment: an Rh- mother should receive RhoGAM (anti-Rh gamma globulin) before delivery, and soon after every delivery, miscarriage, or abortion.

• These antibodies bind to and inactivate the fetal Rh antigens before the mother’s immune system can respond to the foreign antigens by producing anti-Rh antibodies.

Question 11

explain why it is so important to match donor and recipient blood types before administering a transfusion.

Answer 11

typing and cross matching blood for transfusion – donor blood of same ABO and Rh type is selected

cross matching – possible donor RBCs are mixed with the recipient’s serum.

Screening – alternately, recipient’s serum can be screened against a test panel of RBCs having antigens known to cause blood transfusion reactions to detect any antibodies that may be present

Agglutination – If agglutination does not occur, the recipient does not have antibodies that will attack the donor RBCs

disorders

anemia – condition of the blood in which the oxygen carrying capacity of the blood is reduced

• number of functional RBCs or their hemoglobin content is below normal
• Symptoms: fatigue, intolerant of cold (both related to lack of oxygen needed for ATP and heat production), paleness (due to low content of red-colored hemoglobin circulating in skin blood vessels)

Most important causes and types of anemia:

• Iron-deficiency anemia – inadequate absorption or iron, excessive loss of iron, increased iron requirement, insufficient intake of iron

Most common type of anemia

• Women at higher risk due to menstruation and pregnancy
• GI losses related to malignancy or ulceration also contribute

Megaloblastic anemia – inadequate intake of vitamin B12 or folic acid

1. Red bone marrow produces large, abnormal red blood cells (megaloblasts)
2. May also be caused by drugs that alter gastric secretion or treat cancer

Pernicious anemia – 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.

Hemorrhagic anemia – excessive loss of RBCs through bleeding

• From large wounds, stomach ulcers, or heavy menstruation

Hemolytic anemia – RBC plasma membranes rupture and release hemoglobin into the plasma

• May damage filtering units (glomeruli) in the kidneys
• Results from inherited defects such as abnormal RBC enzymes, parasites, toxins, or antibodies from incompatible transfused blood.

Thalassemia – a group of hereditary hemolytic anemias

• Characterized by deficient synthesis of hemoglobin
• RBCs are small (microlytic), pale (hypochromic), and short lived
• Occurs primarily in populations from countries bordering the Mediterranean Sea

Aplastic anemia – destruction of red bone marrow

• Caused by toxins, gamma radiation, certain medications that inhibit enzymes needed for hemopoiesis.

sickle cell disease – disease of RBCs which contain Hb-S, an abnormal kind of hemoglobin

• when Hb-S gives up oxygen to the interstitial fluid, it forms long, stiff, rodlike structures that bend the erythrocyte into a sickle shape
• The sickled cells rupture easily
• Erythropoiesis is stimulated by the loss of cells but cannot keep up with the pace of hemolysis.
• An inherited disease.
• People with two sickle cell genes have severe anemia, those with only one defective gene have the sickle cell trait
• Found primarily in the populations and their descendants near the malaria belt of the world: Mediterranean Europe, sub-saharan Africa, tropical Asia
• Sickle cell gene alters permeability of plasma membranes of sickled cells, causing potassium ions to leak out. 1. The lower concentration of potassium ions leads to increased resistance to malaria as the parasite requires potassium to survive

Signs and symptoms: anemia, causing SOB, fatigue, paleness, delayed growth and development of children. Jaundice caused by rapid breakdown and loss of blood cells. Fever, rapid heart rate, swelling and inflammation of the hands and/or feet, leg ulcers, eye damage, excessive thirst, frequent urination, painful and prolonged erection in males

• Blockages in blood vessels due to sickled cells sticking together and forming clumps, depriving body organs of
• oxygen and causing pain, serious infections, organ damage, especially in lungs, brain, spleen, kidneys
• The painful episodes last from hours to days, vary from several times a year to every few years, range in severity from mild to requiring hospitalization.
• Sickle cell crisis – worsening of the anemia, pain in the abdomen and long bones of the limbs, fever, SOB. 1. Caused by any activity that reduces the amount of oxygen in the blood, such as vigorous exercise.

Treatment: analgesics for pain, fluids for hydration, oxygen for O2 deficiency, antibiotics to counter infections, blood transfusions.

Hemophilia – inherited deficiency of clotting in which bleeding may occur spontaneously or after only minor trauma.

• Oldest known hereditary bleeding disorder
• Usually affects males
• Sometimes called the royal disease
• Different types of hemophilia are due to deficiencies of different blood clotting factors, exhibit varying degrees of severity, ranging from mild to severe bleeding tendencies.
• Characterized by spontaneous or traumatic SQ and IM hemorrhaging, nosebleeds, hematuria, hemorrhages in joints that produce pain and tissue damage

Treatment: transfusions of fresh blood plasma or concentrates of the deficient clotting factor to relieve the tendency to bleed. Also desmopressin (DDAVP) which can boost levels of clotting factors.

Leukemia – a group of red bone marrow cancers in which abnormal WBCs multiply uncontrollably.

• Characterized by either uncontrolled production and accumulation of immature leukocytes in which many cells fail to reach maturity (acute) or an accumulation of mature leukocytes in the blood because they do not die at the end of their normal life span (chronic)
• The accumulation of the cancerous WBCs in red bone marrow interferes with production of RBCs, WBCs, and platelets.
• As a result, the oxygen-carrying capacity of the blood is reduced, an individual is more susceptible to infection, and blood clotting is abnormal.
• In most leukemias, the cancerous blood cells spread to lymph nodes, liver, and spleen, causing them to enlarge.
• All leukemias cause anemia. Also, weight loss, fever, night sweats, excessive bleeding, and recurrent infections may occur.
• Two classifications based on symptom development:
• In acute, symptoms develop rapidly.
• In chronic, symptoms take years to develop.

Two classifications based on type of WBC that becomes malignant:

• Lymphoblastic leukemia – cells derived from lymphoid stem cells (lymphoblasts) and/or lymphocytes
• Myelogenous leukemia – cells derived from myeloid stem cells (myeloblasts)

4 types of leukemia based on onset of symptoms and cells involved:

• Acute lymphoblastic leukemia (ALL) – most common leukemia in children, also occurs in adults
• Acute myelogenous leukemia (AML) – affects both children and adults
• Chronic lymphoblastic anemia (CLA) – most common leukemia in adults, usually over 55
• Chronic myelogenous leukemia (CML) – occurs mostly in adults.

Cause for most types of leukemia is unknown.

• Risk factors: exposure to radiation or chemo for other cancers, genetics (some genetic disorders such as down syndrome), environmental factors (smoking and benzene), microbes such as the human T cell leukemia-lymphoma virus-1 (HTLV-1), Epstein-Barr virus

Treatment: chemo, radiation, stem cell transplantation, interferon, antibodies, blood transfusion

medical terminology

I. cyanosis – slightly bluish/dark purple skin discoloration.

• Most easily seen in nail beds and mucous membranes
• Due to an increased quantity of methemoglobin: hemoglobin not combined with oxygen in the systemic blood

II. Jaundice – abnormal yellowish discoloration of the sclerae of the eyes, skin, and mucous membranes due to excess bilirubin in the blood

3 main categories of jaundice:

• Prehepatic jaundice – due to excess production of bilirubin
• Hepatic jaundice – abnormal bilirubin processing by the liver caused by congenital liver disease, cirrhosis of the liver, or hepatitis
• Extrahepatic jaundice – due to blockage of bile drainage by gallstones or cancer of the bowel or pancreas

III. Septicemia – toxins or dis-causing bacteria in the blood. AKA blood poisoning.

IV. Thrombocytopenia – very low platelet count that results in a tendency to bleed from capillaries.