Ch 18. Cardiovascular System: Blood

List the 3 components of centrifuged blood sample.

(Bottom to top) Erythrocytes (RBC) make up about 44% of sample Buffy coat composed of leukocytes & platelets forms <1% Plasma makes up about 55% of sample

Describe the steps in Extrinsic Pathway of coagulation

1. Tissue Factor, thromboplastin (Factor III) is released from damaged tissues & combines with Factor VII & Ca2+ to form a complex 2. Complex converts inactive Factor X to active Factor X

Discuss the different types and functions of the various leukocytes found within blood. What is leukopenia, leukocytosis and leukemia?

2 main divisions of leukocytes: Granulocytes & Agranulocytes Granulocytes consist of 3 types of leukocytes that all have visible specific granules within cytosol--these are the neutrophils, eosinophils, & basophils. Neutrophils: most numerous, have neutral/pale colored granules, multilobed nucleus & function to phagocytize infection pathogens, especially bacteria Eosinophils: have reddish/pink-orange granules within cytosol, nucleus is bilobed & two lobes are connected via thin strand, these function to phagocytize numerous antigen-antibody complexes & allergens & also release chemical mediators to destroy parasitic worms Basophils: have abundant deep blue-violet granules in cytosol, have a bilobed nucleus & release histamine & heparin during the inflammatory response Agranulocytes do not have visible specific granules within cytosol--these include monocytes & lymphocytes Monocytes: can be up to 3x larger than erythrocytes, nucleus is kidney shaped or c-shaped, these exit the blood vessel & become macrophages which phagocytize bacteria, viruses, cell fragments, dead cells, & debris Lymphocytes: have dark-staining nucleus that is typically rounded & indented, it takes up majority of space in cell, these cells include T-lymphocytes which manage & direct the immune response, B-lymphocytes which produce antibodies, & NK cells which attack infected/abnormal cells Leukopenia: reduced number of leukocytes that may increase a persons risk of developing infection & decrease effectiveness in fighting one Leukocytosis: slightly elevated leukocyte count can result from recent infection Leukemia is a malignancy in the leukocyte forming cells, Acute Leukemia is fast progressing form that results in death fairly soon after symptoms start & chronic Leukemia is slow progressing form that results in death about a year later

What is hemophilia? Explain the cause of this disease.

A group of bleeding disorders caused by specific gene mutations Hemophilia A: results in a deficiency or complete lack of normal Factor VIII protein in clotting cascade Hemophilia B: deficiency of Factor IX Hemophilia C: RARE, deficiency of Factor XI

What are acute & chronic Leukemia?

Acute Leukemia: progresses rapidly & death typically occurs within a few months after onset of symptoms, symptoms include severe anemia, hemorrhages, & recurrent infection--typically in children & young adults Chronic Leukemia: progresses more slowly, survival exceeds 1 year after onset of symptoms, symptoms include anemia & tendency to bleed--usually middle-aged & older adults

Explain the process by which erythrocyte components are recycled.

Aged & damaged erythrocytes are removed from circulation and phagocytized by macrophages within the liver & spleen; in the liver & spleen hemoglobin is removed from the erythrocyte, heme with iron still attached is removed from the globin protein which is then broke down into free amino acids that are used to make new proteins, the iron is removed from the heme & the heme group released from hemoglobin is converted within the macrophage into biliverdin which is then converted into bilirubin; next the bilirubin is released into the blood & transported by Albumin to the liver; in the liver the bilirubin is eliminated into the small intestine as a component of bile (secretion from gallbladder that facilitates digestion); in the small intestine bilirubin is converted to urobilinogen; from the small intestine urobilinogen can go to either the large intestine or kidneys; urobilinogen continues through the small intestine into the large intestine where its eventually converted into stercobilin which is expelled in feces; urobilinogen can be absorbed back into the blood from small intestine & then gets converted into urobilin which is excreted by the kidneys

Identify the types of plasma proteins & explain general functions

Albumin: smallest, most abundant, makes up about 58% of all plasma proteins, exerts greatest colloid osmotic pressure to maintain blood volume & BP, these transport substances within blood Globulins: form about 37% of plasma proteins, three types-smaller alpha-globulins & larger beta-globulins primarily bind & transport certain lipids & hormones, gamma-globulins (antibodies) play a part in immune system Fibrinogen: makes up about 4% of plasma proteins, clotting protein responsible for blood clot formation, converts into long, insoluble strands of fibrin to help form a blood clot Regulatory proteins: minor class making up <1% plasma proteins, includes both enzymes to accelerate chemical reactions in blood & hormones being transported throughout the body to target cells

Compare the production of granulocytes, monocytes, & lymphocytes in Leukopoiesis

All 3 types of Granulocytes are derived from a myeloid stem cell, this stem cell is stimulated by multi-CSF & GM-CSF to form a progenitor cell; the granulocyte line develops when the progenitor cell forms a myeloblast under the influence of G-CSF, this myeloblast eventually differentiates into 1 of 3 granulocytes Monocytes are also derived from myeloid stem cells, the myeloid stem cell differentiates into a progenitor cell & under the influence of M-CSF it forms a monoblast; eventually the monoblast forms a promonocyte which differentiates into the monocyte Lymphocytes are derived from a lymphoid stem cell through the lymphoid line, the lymphoid stem cell differentiates into B-lymphoblasts & T-lymphoblasts; these mature into B-lymphocytes & T-lymphocytes; some lymphoid stem cells differentiate directly into NK (Natural Killer) cells

What is hypercoagulation & what causes it?

An increase tendency for blood to clot; leads to thrombus (clot in blood vessel); when thrombus dislodges & travels its an embolus; embolus within blood vessel can travel to brain & cause strokes, or heart & cause MI Some medications can cause increased risk for hypercoagulation (BC & hormone replacements); smoking increases risk of clots; prolonged bedrest, surgery, pregnancy, & sitting on airplane for long period can all lead to clots; genetic causes of hypercoagulation can be due to mutations of several genes (most common is Leiden Mutation-mutation of gene for synthesis of Factor V)

Explain the causes of anemia & polycythemia

Anemia is any condition where the percentage of erythrocytes is lower than normal or the oxygen-carrying capacities of blood is reduced; can be caused by a number of variables Aplastic anemia-significantly decreased formation of erythrocytes & hemoglobin; Congenital hemolytic anemia-destruction of erythrocytes is more rapid than normal, usually due to genetic defect; Erythroblastic anemia-hereditary disease in which person inherits a gene mutation that affects hemoglobin production & results in abnormal erythrocyte development; Hemorrhagic anemia-results from some form of heavy bleeding; Pernicious anemia- chronic, progressive anemia of adults caused by failure of body to absorb Vitamin B12; Sickle Cell Anemia-autosomal recessive disorder occurs when a person inherits 2 copies of the sickle-cell gene & erythrocytes become sickle-shaped at lower blood oxygen levels making them unable to flow efficiently Polycythemia: an abnormally high number of RBC in the blood, as a primary disease or secondary condition

Discuss the survival response that occurs when blood loss exceeds 10%.

As blood volume decreases, BP drops If greater than 10% is lost the sympathetic division of ANS is activated, bringing about increased vasoconstriction, increased HR, increased force of heart contraction all in attempt to maintain BP, blood flow is also redistributed to the heart & brain to keep them functioning; body can maintain BP like this until 40% of blood is lost, this results in insufficient blood volume within blood vessels & BP decreases to levels unable to support life

What is blood doping & what are the dangers associated with this?

Blood doping is an illegal procedure used by athletes to enhance performance by trying to boost the bodies ability to deliver oxygen to the muscles by increasing the number of erythrocytes in the blood Athletes will either donate erythrocytes to themselves by first removing a unit of blood & storing it, which causes kidneys to detect decrease in blood oxygen & secrete EPO to increase production of erythrocytes, & then a few days before competing transfer stored unit back into body OR inject themselves with pharmaceutical EPO to increase erythrocyte levels Potentially deadly because by increasing the number of erythrocytes per measured unit of blood the blood also has an increase in viscosity of blood which makes the heart work harder to pump the more viscous blood which could lead to cardiovascular damage

Name 6 characteristics that describe blood & explain significance of each in health & homeostasis.

Color: color depends on whether its oxygen-rich or oxygen-poor, oxygen-rich blood is bright red & oxygen-poor blood is darker red Volume: average volume of blood in an adult is about 5 L (4-6 L), sustaining normal blood volume is essential in maintaining BP Viscosity: blood is about 4-5x more viscous than water (thicker), viscosity depends on the amount of dissolved substances in blood relative to amount of fluid, its increased if amount of substances (mainly RBC) increase the amount of fluid, decrease, or both Plasma Concentration: relative concentration of solutes in plasma, normally a 0.9% concentration & determine whether fluids move into or out of plasma by osmosis as blood goes through capillaries, this is used to determine IV solution concentration which are usually isotonic to plasma Temperature: temperature of blood is almost 1C (2 F) higher than measured body temperature (37 C; 98.6 F), the blood helps to warm areas of the body as it travels Blood pH: blood plasma is slightly alkaline with a pH between 7.35-7.45, plasma proteins have a 3D shape that depends upon H+ concentration (pH), if pH is altered from normal, plasma proteins become denatured & unable to carry out function

What is thrombocytopenia? What causes it?

Deficiency in platelet count May be caused by increased breakdown of platelets or decreased production of new platelets; may occur with some bone marrow infections or cancers

Name the 3 types of formed elements which are found in blood, give the function of each & compare the relative abundance for different types

Erythrocytes are red blood cells that transport O2 & CO2, they average about 4.8 million in females & 5.4 million in males Leukocytes are white blood cells that initiate immune response, defend against potentially harmful substances, there are 5 different types & they average about 4500-11000 cells per mm3 of blood Platelets participate in hemostasis and average about 150,000-400,000 cells per mm3 of blood

Describe the structure of erythrocytes and the process by which erythrocyte components are recycled.

Erythrocytes are small, flexible cells with a biconcave disc structure; they have no nucleus or organelles; composed of a plasma membrane enclosing about 280 million hemoglobin molecules; Erythrocytes transport O2 & CO2 between tissues & lungs; production of erythrocytes is regulated by the hormone EPO As erythrocytes age & become damaged they are removed from blood vessels and phagocytized by macrophages within the liver & spleen; 3 molecular components result from destruction of erythrocytes: globin protein, iron ion, & heme group; Hemoglobin is first removed from an erythrocyte with iron still attached, heme molecule is removed from the globin protein and then the iron ion is removed from the heme; the heme group is converted within macrophages into biliverdin which is then converted into bilirubin while still in the macrophage; bilirubin is then released into blood & transported by albumin to the liver; bilirubin is then eliminated from the liver into small intestine as a component of bile; in the small intestine bilirubin is converted into urobilinogen which will either continue through the small intestine into the large intestine where it is converted into stercobilin and excreted in feces or it gets reabsorbed into the blood where it travels to the kidneys and is converted into urobilin for excretion in urine.

What antibodies and antigens occur in the blood of different blood types? When discussing blood typing, explain universal donor and universal recipient. Discuss the Rh factor and its relationship to the hemolytic disease of the newborn.

Erythrocytes have surface antigens that determine which ABO blood type is present. Blood cells can either have Surface Antigen A or Surface Antigen B. Erythrocytes with only Surface Antigen A are classified as Type A blood. Erythrocytes with only Surface Antigen B are classified at Type B blood. Erythrocytes with both Surface Antigen A & B are classified as Type AB blood. Erythrocytes with neither Surface Antigen A or B are classified as Type O blood. Along with surface antigens, erythrocytes have antibodies within the plasma. Type A blood contain Anti-B antibodies within the plasma. Type B blood contains Anti-A antibodies within the plasma. Type AB blood contains neither Anti-A or Anti-B antibodies in the plasma. Type O blood contains both Anti-A & Anti-B antibodies in the plasma. Universal donors have blood types O-, this means that people with type O- blood can donate to individuals with any other blood type without causing agglutination. Universal recipients have blood type AB +, this means that people with type AB+ blood can receive blood transfusions from individuals with any other blood type without causing agglutination. Rh factor is another type of surface antigen present in some blood types. It's determined by the presence or absence of Surface Antigen D. When individuals blood has Surface Antigen D on the erythrocytes they are Rh positive. When individuals blood does not have Surface Antigen D on the erythrocytes they are Rh negative.

List the events by which erythrocyte production is stimulated

Erythropoiesis (production of erythrocytes) is controlled by Erythropoietin (EPO) which is primarily formed in the kidneys; the initial stimulus for EPO release is decrease in blood oxygen level, chemoreceptors in the kidney detect this decrease as the blood is transported through blood vessels within the organ; as a result certain cells in the kidney release EPO into blood where it is transported to the red bone marrow; EPO stimulates myeloid cells in red bone marrow to increase the rate of erythrocyte production which leads to additional erythrocyte release into circulating blood & more oxygen being transported form the lungs to cells of the body, increasing blood oxygen levels

What are the steps in the Common Pathway of coagulation?

Factor X (activated by either pathway) is the 1st step 1. Active Factor X combines with Factors II & V, Ca2+, & PF3 to form a Prothrombin Activator 2. Prothrombin Activator activates Prothrombin to Thrombin 3. Thrombin converts soluble Fibrinogen into insoluble Fibrin 4. In the presence of Ca2+, Factor XIII is activated which stabilizes the Fibrin monomers into Fibrin polymers that serve as framework for the clot

Distinguish between granulocytes & agranulocytes. Compare & contrast the various types.

Granulocytes are types of leukocytes which have special granules within their cytosol that are clearly visible when viewed under light microscopy Agranulocytes are types of leukocytes that have such small specific granules in their cytosol that they aren't clearly visible under light microscopy; 3 Types of Granulocytes: Neutrophils-(most numerous) have neutral/pale colored granules, exhibit multilobed nucleus, responsible for phagocytizing pathogens (especially bacteria); Eosinophils-have reddish/pink-orange granules, nucleus is bilobed with 2 lobes being connected by thin strand, responsible for phagocytizing antigen-antibody complexes & allergens as well as releasing chemical mediators to destroy parasites; Basophils-have abundant blue-violet granules, have a bilobed nucleus, & responsible for releasing histamine & heparin during inflammatory reactions. 2 types of Agranulocytes: Lymphocytes-has a dark-staining nucleus that is typically rounded & indented, smaller lymphocytes exhibit only a thin rim of blue-gray cytosol Monocytes-up to 3x larger than erythrocytes, has a kidney shaped or c-shaped nucleus that's usually pale in color & responsible for transforming into macrophages & phagocytizing pathogens, cellular fragments, dead cells, & debris

Define hematocrit, explain how the medical definition differs from clinical usage

Hematocrit is the percentage of the volume of all formed elements in the blood This is the medical definition, the clinical definition equates hematocrit to the percentage of only erythrocytes

Explain the cause of hemolytic disease of the newborn & what kind of steps are taken by doctors to prevent it.

Hemolytic disease can occur in a newborn when the pregnant woman has Rh- blood while the fetus has Rh+ blood; this may occur if the mother has been previously exposed to Rh+ blood; as a result to the prior exposure the mother will have Anti-D Antibodies that could cross the placenta & destroy the fetal erythrocytes which could result in severe illness or death--this illness is Hemolytic Disease of the Newborn; Doctors try to prevent this from occurring by giving pregnant Rh- women special immunoglobulins between weeks 28-32 of pregnancy & at birth which should prevent the mother from developing Anti-D Antibodies

What is hemostasis? Briefly describe the three phases of hemostasis. Discuss the survival response that occurs when blood loss exceeds 10%.

Hemostasis is the stopping of bleeding with a clot; has three phases-vascular spasm, platelet plug formation, & coagulation Vascular Spasm: 1st phase that begins immediately after blood vessel injury, damage to smooth muscle within vessel wall causes smooth muscle contractions which results in vasoconstriction & limits the amount of blood that can be lost from damaged vessel, continues into next phase as various chemicals are released that further stimulate vascular spasm Platelet Plug Formation: once blood vessel is damaged, collagen fibers within connective tissue internal to endothelial cells become exposed, platelets begin to stick to exposed collagen fibers, platelets then start to stick to vessel wall & morphology changes & develop long processes to help further adhere to blood vessel wall, as more platelets aggregate to the site of injury a platelet plug develops to close off injury Coagulation Phase: blood clotting occurs in this phase, a meshwork of fibrin protein traps other elements of the blood to form a clot, clotting process requires calcium, clotting factors, platelets, & vitamin K, formation of the clot involves a cascade of changes As blood volume decreases, BP drops If greater than 10% is lost the sympathetic division of ANS is activated, bringing about increased vasoconstriction, increased HR, increased force of heart contraction all in attempt to maintain BP, blood flow is also redistributed to the heart & brain to keep them functioning; body can maintain BP like this until 40% of blood is lost, this results in insufficient blood volume within blood vessels & BP decreases to levels unable to support life

What are the two mechanisms of initiation of coagulation?

Intrinsic pathway (if damage to the inside of a vessel) Extrinsic pathway (if damage to the outside of a vessel) Both pathways converge at the Common Pathway

Describe the steps in the Intrinsic Pathway of coagulation

Its initiated by platelets 1. Platelets adhering to a damaged vessel wall release Factor XII 2. Factor XII converts inactive Factor XI to active Factor XI 3. Factor XI converts inactive Factor IX to active Factor IX 4. Factor IX binds with Ca2+ & Platelet Factor 3 (PF3) to form a complex that converts inactive Factor VIII to active Factor VIII 5. Factor VIII concerts inactive Factor X to active Factor X

Explain what is meant by a differential count & how its clinically useful.

Measures the amount of each type of leukocyte in the blood & determines whether any of the circulating leukocytes are immature; these are useful in helping to diagnose diseases & the change in relative number of leukocytes (whether increase/decrease) helps facilitate the process

Define Colloid Osmotic Pressure

Osmotic pressure exerted by the plasma proteins to prevent loss of fluid from the blood as it moves through capillaries; osmotic force is responsible for drawing fluids into the blood & preventing excess fluid loss from blood capillaries into interstitial fluid, helping to maintain blood volume & consequently BP

What is leukopenia?

Reduced number of leukocytes; could increase the risk of developing an infection or decrease ability to fight infection effectively

What is leukocytosis?

Slightly elevated leukocyte count

What is hemostasis?

Stoppage of bleeding

Blood plasma is mainly comprised of water. Identify the 3 types of blood plasma proteins, and explain the general function of each. In addition, what other solutes are found in blood plasma?

The different types of plasma proteins consist of Albumin, Globulins, & Fibrinogen. Albumin is the smallest & most abundant plasma protein. These proteins transport substances within the blood like ions, hormones, & some lipids. Globulins are the second largest group and consist of three different types of proteins. Small alpha-globulins & large beta-globulins primarily bind & transport certain lipids & hormones as well as metals & ions. Gamma-globulins (antibodies) play a role in the immune response. Blood plasma also contains other solutes such as dissolved ions, organic & inorganic molecules. These substances include electrolytes, nutrients, respiratory gases, some hormones, & waste products.

Compare & contrast the different blood types & their importance when transfusing blood.

The plasma membrane of erythrocytes has numerous surface antigens that project from the surface & have significant implications for blood transfusion & pregnancy Type A blood: contains erythrocytes with Surface Antigen A only & have Anti-B Antibodies within the plasma Type B blood: contains erythrocytes with Surface Antigen B only & have Anti-A Antibodies within the plasma Type AB blood: contains erythrocytes with both Surface Antigen A & B & have neither Anti-A or Anti-B Antibodies in plasma Type O blood: contains erythrocytes with neither Surface Antigen A or B & has both Anti-A & Anti-B Antibodies within the plasma + blood types have the Rh Surface Antigen on erythrocytes - blood types do not have Rh Surface Antigen on erythrocytes -Blood types are important when transfusing blood because if an individual is given blood of an incompatible type then antibodies in the plasma bind to surface antigens of the transfused blood & clumps of erythrocytes bind together in process called agglutination

Describe Erythropoiesis

The process of erythrocyte production Rate of production is controlled by hormone Erythropoietin (EPO) which increases rate of production when secreted Process begins with a myeloid stem cell which under the influence of Multi-CSFs forms a progenitor cell; progenitor cell forms the proerythroblast; proerythroblast becomes an erythroblast; the erythroblast becomes a normoblast which no longer contains a nucleus; normoblast eventually forms a reticulocyte which has lost all organelles except some ribosomes; reticulocyte eventually becomes the mature erythrocyte

Define Hemopoiesis

The production of formed elements in the blood; begins in embryonic period of development, primary site being in the liver until about 5th month of development when it moves to the red bone marrow Starts with hematopoietic stem cells (hemocytoblasts) that produce 2 different lines for blood cell development--myeloid line (forms erythrocytes, leukocytes, & megakaryocytes) & lymphoid line (forms only lymphocytes) Process is influenced by colony-stimulating factors (CSFs)

Summarize the process by which platelets are formed in thrombopoiesis

The production of platelets is called thrombopoiesis; from the myeloid stem cell, a committed cell called megakaryoblast is produced, under the influence of thrombopoietin megakaryoblast matures to form a megakaryocyte; each megakaryocyte forms 1000s platelets by forming long extensions from themselves called proplatelets, these proplatelets extend through the blood vessel wall while still attached to megakaryocyte, the force of blood flow "slices" the proplatelets into fragments (platelets)

Describe the general functions of blood

Transportation: transport formed elements & dissolved molecules/ions throughout body, transports O2 from & CO2 to lungs for gas exchange, "delivery system." Regulation: participates in regulation of blood pH, body temperature, & fluid balance Protection: leukocytes, plasma proteins, & various molecules within blood help protect body against potentially harmful substances

Briefly describe the 3 phases of hemostasis

Vascular Spasm: 1st phase that begins immediately after blood vessel injury, damage to smooth muscle within vessel wall causes smooth muscle contractions which results in vasoconstriction & limits the amount of blood that can be lost from damaged vessel, continues into next phase as various chemicals are released that further stimulate vascular spasm Platelet Plug Formation: once blood vessel is damaged, collagen fibers within connective tissue internal to endothelial cells become exposed, platelets begin to stick to exposed collagen fibers, platelets then start to stick to vessel wall & morphology changes & develop long processes to help further adhere to blood vessel wall, as more platelets aggregate to the site of injury a platelet plug develops to close off injury Coagulation Phase: blood clotting occurs in this phase, a meshwork of fibrin protein traps other elements of the blood to form a clot, clotting process requires calcium, clotting factors, platelets, & vitamin K, formation of the clot involves a cascade of changes

Identify body sites used for blood collection, list the basic physical characteristics of blood samples drawn from them, & briefly explain the importance of these different types of blood samples

Venipuncture: uses median cubital vein at elbow; utilize superficial veins that are easy to locate & have thinner walls to cause less damage, collection method most common with blood work/tests Peripheral capillaries: utilize the fingers, ear lobe, toes, heel; drop of blood used to prepare a blood smear, used only when small quantity is needed, puncture heals & stops bleeding almost immediately Arterial puncture: utilize the radial or brachial artery to check the efficiency of gas exchange in the lungs or when need to compare oxygen levels prior to reaching the capillaries (before gas exchange)

Describe the structure of erythrocytes

Very small, flexible cells with no nucleus or organelles, has a biconcave disc structure; composed of plasma membrane which encloses about 280 million hemoglobin

Explain the main function of leukocytes.

help defend the body against pathogens