Anatomy Ch.17: Blood

stages of erythryopoiesis

- begins when a hematopoietic stem cell descendant called a myeloid stem cells transforms into a proerythroblast -proeryhtroblasts give rise to basophilic erythroblasts that produce huge numbers of ribosomes -during these first two stages, the cells divide many times -hemoglobin is synthesized and iron accumulates as the basophilic erythroblast transforms into a polychromatic erythroblast and then an orthochromatic erythroblast -the " color" of the cell cytoplasm changes as the blue-staining ribosomes become masked by the pink color of hemoglobin -when an orthochromatic erythroblast has accumulated almost all of its hemoglobin, it ejects most of its organelles -additionally, its nucleus degenerates and is pinched off, allowing the cell to collapse inward and eventually assume the biconcave shape -the result is the reticulocyte (young erythrocyte), so named because it still contains a scant reticulum (network) of clumped ribosomes -the entire process takes about 15 days -the reticulocytes enter the bloodstream to begin their task of oxygen transport -usually they become fully mature erythrocytes within two days of release as their ribosomes are degraded by intracellular enzymes

fibrinolysis

-a clot is not a permanent solution to blood vessel injury, and a process called _______ removes unneeded clots when healing has occurred -this cleanup detail is crucial because small clots form continually in vessels throughout the body -without this, blood vessels would gradually become completely blocked -the critical natural "clot buster" is a fibrin-digesting enzyme called plasmin, which is produced when the plasma protein plasminogen is activated -like a built-in self-destruction mechanism, plasminogen is incorporated into a forming clot, where it remains inactive until appropriate signals reach it -the presence of a clot in and around the blood vessel causes the endothelial cells to secrete tissue plasminogen activator (tPA) -activated factor XII and thrombin released during clotting also activate plasminogen -as a result, most plasmin activity is confined to the clot, and circulating enzymes quickly destroy any plasmin that strays into the plasma -______ begins within two days and continues slowly over several days until the clot finally dissolves

thrombus

-a clot that develops and persists in an unbroken blood vessel is called a _____ -if it is large enough, it may block circulation to the cells beyond the blockage and lead to death of those tissues -for example, if the blockage occurs in the coronary circulation of the heart, the consequences may be death of heart muscle and a fatal heart attack

anemia

-a condition in which the blood's oxygen-carrying capacity is too low to support normal metabolism -it is a sign of some disorder rather than a disease in itself -its hallmark is blood oxygen levels that are inadequate to support normal metabolism -individuals are fatigued, often pale, short of breath, and chilled -causes can be divided into three groups: blood loss, not enough red blood cells produced, or too many of them destroyed -lack of vitamin B12 in the diet also leads to _______ -this is usually a problem only in strict vegetarians because meats, poultry, and fish provide ample B12

erythropoietin (EPO)

-a glycoprotein hormone, stimulates the formation of erythrocytes -normally, a small amount of EPO circulates in the blood at all times and sustains red blood cell production at a basal rate -the kidneys play the major role in EPO production, although the liver also produces some -when certain kidney cells become hypoxic (oxygen deficient), oxygen-sensitive enzymes are unable to carry out their normal functions of degrading an intracellular signaling molecule called hypoxia-inducible factor (HIF) -as HIF accumulates, it accelerates the synthesis and release of erythropoietin the drop in normal blood oxygen levels that triggers EPO formation can result from: -reduced number of red blood cells due to hemorrhage (bleeding) or excessive RBC destruction -insufficient hemoglobin per RBC (as in iron deficiency) -reduced availability of oxygen, as might occur at high altitudes or pneumonia -conversely, too many erythrocytes or excessive oxygen in the bloodstream depresses erythropoietin production -it is not the number of erythrocytes in blood that controls the rate of erythropoiesis -instead, control is based on their ability to transport enough oxygen to meet tissue demands -bloodborne erythropoietin stimulates red marrow cells that are already committed to becoming erythrocytes, causing them to mature more rapidly -two to three days after erythropoietin levels rise in the blood, the rate of reticulocyte release and the reticulocyte count rise markedly -hypoxia does not activate the bone marrow directly -it stimulates the kidneys, which in turn provide the hormonal stimulus that activates the bone marrow -the male sex hormone testosterone also enhances the kidneys' production of EPO -testosterone may be at least partially responsible for the higher RBC counts and hemoglobin levels seen in males

thrombopoietin

-a hormone that regulates platelet formation -their immediate ancestral cells , the megakaryocytes, are descendants of the hematopoietic stem cell and the myeloid stem cell, but their formation is quite unusual -in this line, repeated mitoses of the megakaryoblast (stage I megakaryocyte) occur, but cytokinesis does not -the final result is the mature (stage IV) megakaryocyte, a bizarre cell with a huge, multilobed nucleus and a large cytoplasmic mass -after it forms, the megakaryocyte presses against a sinusoid (the specialized type of capillary in the red marrow) and sends cytoplasmic extensions through the sinusoid wall into the bloodstream -these extensions rupture, releasing platelets like leaves blowing off a tree, seeding the blood with platelets -the plasma membranes associated with each fragment quickly seal around the cytoplasm to form the grainy, roughly disc-shaped platelets each with a diameter of 2-4 um -each microliter of blood contains 150,000 to 400,000 tiny platelets

not enough red blood cells produced

-a number of problems can decrease erythrocyte production. these problems range from lack of essential raw materials (such as iron) to complete failure of the red bone marrow

carbaminoahemoglobin

-about 20% of the carbon dioxide transported in the blood combines with hemoglobin, but it binds to globin's amino acids rather than to the heme group -this formation of ________ occurs more readily when hemoglobin is in the reduced state (dissociated from oxygen) -carbon dioxide loading occurs in the tissues, and the direction of transport is from tissues to lungs, where carbon dioxide is eliminated from the body

eosinophils

-account for 2-4% of all leukoctyes and are approx. the size of neutrophils -their nucleus usually has two lobes connected by a broad band of nuclear material and so resembles earmuffs -large, coarse granules that stain from brick red to crimson with acid (eosin) dyes pack the cytoplasm -these granules are lysosome-like and filled with a unique variety of digestive enzymes -however, unlike typical lysosomes, they lack enzymes that specifically digest bacteria -the most important role is to lead the counter-attack against parasitic worms, such as flatworms and roundworms that are too large to phagocytized -these worms are ingested in food or invade the body via the skin and then typically burrow into the intestinal or respiratory mucosae -reside in the loose connective tissues at the same body sites and when they encounter a parasitic worm "prey", they gather around and release the enzymes from their cytoplasmic granules onto the parasite's surface, digesting it away -have complex roles in many other diseases including allergies and asthma -while they contribute to the tissue damage that occurs in many immune processes, we are also beginning to recognize them as important modulators of the immune response

lymphocytes

-account for 25% or more of the WBC population -are the second most numerous leukocytes in the blood -when stained, a typical lymphocyte has a large, dark-purple nucleus that occupies most of the cell volume -the nucleus is usually spherical but may be slightly indented, and it is surrounded by a thin rim of pale-blue cytoplasm -are often classified by size (diameter) as small, medium, or large -large numbers of lymphocytes exist in the body, but relatively few are found in the bloodstream -are so called because most are closely associated with lymphoid tissues, where they play a crucial role in immunity -T lymphocytes (T cells) function in the immune response by acting directly against virus-infected cells and tumor cells -B lymphocytes give rise to plasma cells, which produce antibodies (immunoglobins) that are released to the blood

monocytes

-account for 3-8% of WBCs -they are the largest leukocytes -they have abundant pale-blue cytoplasm and a darkly staining purple nucleus, which is often U or kidney shaped -when circulating monocytes leave the bloodstream and enter the tissues, they differentiate into highly mobile macrophages with prodigious appetites -macrophages are actively phagocytic, and they are crucial in the body's defense against viruses, certain intracellular bacterial parasites, and chronic infections such as tuberculosis

albumin

-accounts for some 60% of plasma protein -it acts as a carrier to shuttle certain molecules through the circulation -is the major blood protein contributing to the plasma osmotic pressure (the pressure that helps to keep water in the bloodstream)

hematopoietic stem cell

-all various formed elements arise from __________ ________ _____, sometimes called a hemocytoblast -these precursor cells reside in the red bone marrow -however, the maturation pathways of the various formed elements differ, and once a cell is committed to a specific blood cell pathway, it cannot change -this commitment is signaled by the appearance of membrane surface receptors that respond to specific hormones or growth factors, which in turn "push" the cell toward further specialization

functions of erythrocytes

-are completely dedicated to their job of transporting respiratory gases -hemoglobin binds easily and reversibly to oxygen, and most oxygen carried in blood is bond to hemoglobin -normal values for hemoglobin are 13-18 grams per 100 mL of blood in adult males, and 12-16 g/mL in adult females

warfarin and direct oral anticoagulants

-are mainstays of outpatient treatment to reduce the risk of stroke in those prone to atrial fibrillation, a condition in which blood pools in the heart -_________ interferes with the action of vitamin K in the production of some clotting factors -because treatment with _________ is difficult to manage, the introduction of direct oral anticoagulants using other mechanisms has been welcomed

platelet

-are not cells, but fragments of extraordinarily large cells called megakaryoctyes -are about 1/4 the diameter of a lymphocyte -in blood smears, each platelet exhibits a blue-staining outer region and an inner area containing granules that stain purple -the granules contain an impressive array of chemicals that act in the clotting process, including serotonin, Ca, a variety of enzymes, ADP, and platelet-derived growth factor (PDGF) -are essential for the clotting process that occurs in plasma when blood vessels are ruptured or their lining is injured -by sticking to the damaged site, platelets form a temporary plug that helps seal the break -because they are anucleate, platelets age quickly and degenerate in about 10 days if they are not involved in clotting -in the meantime, they circulate freely, kept mobile but inactive by molecules secreted by endothelial cells lining the blood vessels

plasma proteins

-are outnumbered by the lighter electrolytes -are the most abundant plasma solutes by weight, accounting for about 8% of plasma weight -except for hormones and gamma globulins (antibodies), most plasma proteins are produced by the liver -plasma proteins serve a variety of functions, but they are not normally taken up by cells to be used as fuels or metabolic nutrients as are most other organic solutes such as glucose, fatty acids, and amino acids

basophils

-are the rarest WBCs, accounting for only 0.5-1% of the leukocyte population -their cytoplasm contains large, coarse, histamine-containing granules that have an affinity for the basic dyes and stain purplish-black -histamine is an inflammatory chemical that acts as a vasodilator and attracts other white blood cells to the inflamed site; drugs called antihistamines counter this effect -the deep purple nucleus is generally U or S shaped with one or two constrictions

hematopoietic hormones (EPO and several CSFs)

-are used clinically -these hormones stimulate the bone marrow of cancer patients who are receiving chemotherapy (which suppresses the marrow) and of those who have received stem cell transplants -they are also used to beef up the protective responses of AIDS patients

bleeding disorders

-arise from abnormalities that prevent normal clot formation -the most common causes are platelet deficiency (thromocytopenia) and deficits of some clotting factors, which can result from impaired liver function or genetic conditions such as hemophilia

factors preventing undesirable clotting

-as long as the endothelium is smooth and intact, platelets are prevented from clinging and piling up -also, antithrombic substances-- nitric oxide and prostacyclin--secreted by the endothelial cells normally prevent platelet adhesion.

anticoagulant drugs

-aspirin -heparin -warfarin and direct oral anticoagulants

hematopoiesis

-blood cell formation -occurs in the red bone marrow, which is composed largely of a soft network of reticular connective tissue bordering on wide blood capillaries called blood sinusoids -within this network are immature blood cells, macrophages, fat cells, and reticular cells (which secrete the connective tissue fibers) -in adults, red marrow is found chiefly in the bones of the axial skeleton and girdles, and in the proximal epiphyses of the humerus and femur -the production of each type of blood cell varies in response to changing body needs and regulatory factors -as blood cells mature, they migrate through the porous walls of the sinusoids to enter the bloodstream -on average, the marrow turns out an ounce of new blood containing 100 billion new cells every day

physical characteristics and volume

-blood is a sticky, opaque fluid with a characteristic metallic taste -is salty -depending on the amount of oxygen it is carrying, the color of blood varies from scarlet (oxygen rich) to dark red (oxygen poor) -is slightly alkaline, with a pH between 7.35 to 7.45 -is more dense than water and about 5x more viscous, largely because of its formed elements -blood accounts for approx 8% of body weight -its average volume in heavy adult males is 5-6 L

thalassemia and sickle-cell anemia

-can be serious, incurable, and sometimes fatal diseases -in both diseases, the globin part of hemoglobin is abnormal and the erythrocytes produced are fragile and rupture prematurely

arteries

-carry blood away from the heart -branch repeatedly until they become tiny capillaries

coagulation phase 1: two pathways to prothrombin activator

-coagulation may be initiated by either the intrinsic or the extrinsic pathway -in the body, the same tissue-damaging events usually trigger both pathways -crucial components in both pathways are negatively charged membranes -in particular, activated platelets display negatively charged phosphatidylserine, once known as PF3 (platelet factor 3) -many intermediates of both pathways can be activated only when on such phospholipid surfaces -the intermediate steps of each pathway cascade toward a common intermediate, factor X -once factor X has been activated, it complexes with calcium ions and factor V on a phospholipid surface to form prothrombin activator -this is usually the slowest step of the blood clotting process, but once prothrombin activator is present, the clot forms in 10 to 15 seconds -the intrinsic and extrinsic pathways usually work together and are interconnected in many ways, but there are significant differences between them the intrinsic pathway is: -called intrinsic because the factors needed for clotting are present within the blood -triggered by negatively charged surfaces such as activated platelets, collagen, or glass (the negative charges on glass explain why this is the pathway that initiates clotting outside the body in test tubes) -slower because it has many intermediate steps the extrinsic pathway is: -called extrinsic because the tissue factor it requires is outside of blood -triggered by exposing blood to a factor found on cells in tissues surrounding the blood vessel. this factor is called tissue factor (TF) or factor III -faster because it bypasses several steps of the intrinsic pathway. in severe tissue trauma, it can form a clot in 15 seconds -phase I ends with the formation of a complex substance called prothrombin activator

thromboembolic disease

-conditions that roughen the vessel endothelium, such as atherosclerosis or inflammation, cause _______ ______ by allowing platelets to gain a foothold -slowly flowing blood or blood stasis is another risk factor, particularly in bedridden patients and those taking a long flight without moving around -in this case, clotting factors are not washed away as usual and accumulate, allowing clots to form

granulocytes

-contain obvious membrane-bound cytoplasmic granules -include neutrophils, eosinophils, and basophils -are all roughly spherical in shape -are larger and much shorter-lived than erythrocytes -characteristically have lobed nuclei (rounded nuclear masses connected by thinner strands of nuclear material) and their membrane-bound cytoplasmic granules stain quite specifically with Wright's stain

transport functions of blood

-delivering oxygen from the lungs and nutrients from the digestive tract to all body cells -transporting metabolic waste products from cells to elimination sites (to the lungs to eliminate carbon dioxide, and to the kidneys to dispose of nitrogenous wastes in urine) -transporting hormones from the endocrine organs to their target organs

hemolytic anemia

-erythrocytes rupture, or lyse, prematurely -hemoglobin abnormalities, transfusion of mismatched blood, and certain bacterial and parasitic infections are possible causes

formed elements of the blood

-erythrocytes, leukocytes, and platelets -two of the three are not even true cells: erythrocytes have no nuclei or organelles, and platelets are cell fragments. only leukocytes are complete cells -most types of formed elements survive in the bloodstream for only a few days -most blood cells do not divide. instead, stem cells divide continuously in red bone marrow to replace them

mast cells

-granulated cells similar to basophils -are found in connective tissues -although mast cell nuclei tend to be more oval than lobed, the cells are similar microscopically, and both cell types bind to a particular antibody that causes the cells to release histamine -however, mast cells and basophils arise from different cell lines

disseminated intravascular coagulation (DIC)

-has characteristics of both types of disorders, involves both widespread clotting and severe bleeding -clotting occurs in intact blood vessels and the residual blood becomes unable to clot -blockage of blood flow accompanied by severe bleeding follows -DIC most commonly happens as a complication of pregnancy or a result of septicemia or incompatible blood transfusions

blood loss

-hemorrhagic anemia is caused by ______ _____ -in acute hemorrhagic anemia, blood loss is rapid (as might follow a severe stab wound) -is treated by replacing the lost blood -slight but persistent blood loss (due to hemorrhoids or an undiagnosed bleeding ulcer) causes chronic hemorrhagic anemia -once the primary problem is resolved, normal erythropoietic mechanisms replace the lost blood cells

embolus

-if a thrombus breaks away from the vessel wall and floats freely in the bloodstream, it becomes an ______ -is usually no problem until it encounters a blood vessel too narrow for it to pass through -then it becomes an embolism, obstructing the vessel -for example, emboli that become trapped in the lungs dangerously impair the body's ability to obtain oxygen -a cerebral embolism may cause a stroke

step 2: platelet plug formation

-in the second step, platelets play a key role in hemostasis by aggregating (sticking together) , forming a plug that temporarily seals the break in the vessel wall -they also help orchestrate subsequent events that form a blood clot -as a rule, platelets do not stick to each other or to the smooth endothelium that lines blood vessels -intact endothelial cells release nitric oxide and a prostaglandin called prostacyclin -both chemicals prevent platelet aggregation in undamaged tissue and restrict aggregation to the site of injury -however, when the endothelium is damaged and the collagen fibers of the underlying connective tissue are exposed, platelets adhere tenaciously to the collagen fibers -a large plasma protein called von willebrand factor stabilizes bound platelets by forming a bridge between collagen and platelets -platelets become activated: they swell, form spiked processes, and become stickier -as more platelets aggregate, they release more chemicals, aggregating more platelets, and so on in a positive feedback cycle -within one minute, a platelet plug is built up, further reducing blood loss -platelets alone are sufficient for sealing the thousands of minute rips and holes that occur unnoticed as part of the daily wear and tear in your smallest blood vessels -larger breaks, however, need additional reinforcement because platelet plugs are loosely knit in addition, they release chemical messengers including the following: -adenosine diphosphate (ADP)- a potent aggregating agent that causes more platelets to stick to the area and release their contents -serotonin and thromboxane A2 ; a short-lived prostaglandin derivative-- messengers that enhance vascular spasm and platelet aggregation

step 1: vascular spasm

-in this first step, the damaged blood vessels respond to injury by constricting -factors that trigger this _____ ______ include direct injury to vascular smooth muscle, chemicals released by damaged endothelial cells and activated platelets, and reflexes initiated by local pain receptors -the spasm mechanism becomes more and more efficient as the amount of tissue damage increases, and is most effective in the smaller blood vessels -the spasm response is valuable because a strongly constricted artery can significantly reduce blood loss for 20-30 minutes, allowing time for the next two steps to occur

agranulocytes

-include lymphocytes and monocytes -although similar to each other structurally, lymphocytes and monocytes are functionally distinct and unrelated cell types -their nuclei are typically spherical or kidney shaped

role of anticoagulants

-inhibit clotting -whether or not blood clots depends on a delicate balance between clotting factors and anticoagulants -normally, anticoagulants dominate and prevent clotting, but when a vessel is ruptured, clotting factor activity in that area increases dramatically and a clot begins to form -clot formation is normally complete within 3 to 6 minutes after blood vessel damage

polycythemia

-is an abnormal excess of erythrocytes that increases blood viscosity, causing it to flow sluggishly -polycythemia vera, a bone marrow cancer, is characterized by dizziness and an exceptionally high RBC count -the hematocrit may be as high as 80% and blood volume may double, causing the vascular system to become engorged with blood and severely impairing circulation -severe polycthemia is treated by removing some blood ( a procedure called a therapeutic phlebotomy)

aspirin

-is an antiprostaglandin drug that inhibits thromboxane A2 formation (blocking platelet aggregation and platelet plug formation -clinical studies of men taking low-dose ______ over several years demonstrated a 50% reduction in incidence of heart attack

pernicious anemia

-is an autoimmune disease that most often affects the elderly -the immune system of these individuals destroys cells of their own stomach mucosa -these cells normally produce a substance called intrinsic factor that must be present for vitamin B12 to be absorbed by intestinal cells -without B12, the developing erythrocytes grow but cannot divide, and large, pale cells called macrocytes result -treatment involves regular intramuscular injections of vitamin B12 or application of a B12-containing gel to the nasal lining once a week

renal anemia

-is caused by the lack of EPO, the hormone that controls RBC production -frequently accompanies renal disease because damaged or diseased kidneys cannot produce enough EPO -it can be treated by administering EPO

thrombocytopenia

-is characterized by a low number of circulating platelets -in severe cases, it causes spontaneous bleeding from small blood vessels all over the body -even normal movement leads to widespread hemorrhage, evidenced by many small purplish spots, called petechiae on the skin -can arise from any condition that suppresses or destroys the red bone marrow, such as bone marrow malignancy, exposure to ionizing radiation, or certain drugs -transfusions of concentrated platelets provide temporary relief from bleeding

iron-deficiency anemia

-is generally a secondary result of hemorrhagic anemia -also results from inadequate intake of iron-containing foods or impaired iron absorption -the erythrocytes produced under these conditions, called microcytes, are small and pale because they cannot synthesize their normal complement of hemoglobin -the treatment is to increase iron intake in diet or through iron supplements

buffy coat

-is present at the erythrocyte-plasma junction -contains leukocytes

chronic leukemia

-is slowly advancing because it involves proliferation of later cell stages -occurs more often in elderly people

blood

-is the only fluid tissue in the body -appears to be a thick, homogenous liquid, but microscopes reveal it has both cellular and liquid components -is a specialized connective tissue in which living blood cells, called the formed elements, are suspended in a nonliving fluid matrix called plasma -lacks the collagen and elastic fibers typical of other connective tissues, but dissolved fibrous proteins become visible as fibrin strands during blood clotting -if we spin a sample of blood in a centrifuge, centrifugal force packs down the heavier formed elements and the less dense plasma remains at the top -most of the reddish mass at the bottom of the tube is erythrocytes -a thin, whitish layer called the buffy coat is present at the erythyrocyte-plasma junction

three structural characteristics contribute to erythrocyte gas transport functions

-its small size and shape provide a huge surface area relative to volume (about 30% more surface area than comparable spherical cells). the disc shape is ideally suited for gas exchange because no point within the cytoplasm is far from the surface -discounting water content, an erythrocyte is over 97% hemoglobin, the molecule that binds to and transports respiratory gases -because erythrocytes lack mitochondria and generate ATP by anaerobic mechanisms, they do not consume any of the oxygen they carry, making them very efficient oxygen transporters

leukemias

-literally means "white blood" -refers to a group of cancerous conditions involving overproduction of abnormal WBCs -as a rule, the renegade leukocyte are members of a single clone that remain unspecialized and proliferate out of control, impairing normal red bone marrow function -are named according to the rate at which they progress and the type of cell primarily involved -the more serious acute forms primarily affect children -without therapy, all leukemias are fatal, and only the time course differs -in all leukemias, cancerous leukocytes fill the red bone marrow and immature WBCs flood into the bloodstream -the others blood cell lines are crowded out, so severe anemia and bleeding problems result -other symptoms include fever, weight loss, and bone pain -although tremendous numbers of leukocytes are produced, they are nonfunctional and cannot defend the body in the usual way -the most common causes of death are internal hemorrhage and overwhelming infections -irradiation and antileukemic drugs can destroy the rapidly dividing cells and induce remissions (symptom-free periods) lasting from months to years -stem cell transplants are used in selected patients when compatible donors are available

regulatory functions of blood

-maintaining appropriate body temperature by absorbing and distributing heat throughout the body and to the skin surface to encourage heat loss -maintaining normal pH in body tissues. many blood proteins and other bloodborne solutes act as buffers to prevent excessive or abrupt changes in blood pH that could jeopardize normal cell activities. blood also acts as the reservoir for the body's alkaline reserve of bicarbonate ions -maintaining adequate fluid volume in the circulatory system. as we will see, blood proteins prevent excessive fluid loss from the bloodstream into the tissue spaces. as a result, the fluid volume in the blood vessels remains ample to support sufficient blood circulation to all parts of the body

plasma

-makes up most of the remaining 55% of whole blood -is straw-colored -is mostly water (about 90%), contains over 100 different dissolved solutes, including nutrients, gases, hormones, wastes, and products of cell activity, proteins, and inorganic ions -electrolytes vastly outnumber the other solutes composition is kept relatively constant by various homeostatic mechanisms ex: when blood protein levels drop undesirably, the liver makes more proteins. when the blood becomes too acidic (acidosis), both the lungs and kidneys are called into action to restore the plasma's normal pH

aplastic anemia

-may result from destruction or inhibition of the red marrow by certain drugs and chemicals, ionizing radiation, or viruses -in most cases, though, the cause is unknown -because marrow destruction impairs formation of all formed elements, anemia is just one of its signs -defects in blood clotting and immunity are also present -blood transfusions provide a stopgap treatment until stem cells harvested from a donor's blood, bone marrow, or umbilical cord blood can be transplanted

different lineages of the two types of agranulocytes

-monocytes are derived from myeloid stem cells, and share a common precursor with neutrophils that is not shared with the other granulocytes -cells following the monocyte line pass through the monoblast and promonocyte stages before leaving the bone marrow and becoming monocytes -T and B lymphocytes are derived from T and B lymphocyte precursors, which arise from the lymphoid stem cell -the T lymphocyte precursors leave the bone marrow and travel to the thymus, where their further differentiation occurs -B lymphocyte precursors remain and mature in the bone marrow -monocytes may live for several months, whereas the life span of lymphocytes varies from a few hours to decades

hemostasis

-normally, blood flows smoothly past the intact blood vessel lining (endothelium) -but if a blood vessel wall breaks, a whole series of reactions is set in motion to accomplish ____, which stops the bleeding -without this plug-the-hold defensive reaction, we would quickly bleed out our entire blood volume from even the smallest cuts -the _______ response is fast, localized, and carefully controlled -involves many clotting factors normally present in plasma as well as several substances that are released by platelets and injured tissue cells -following this process, the clot retracts -it then dissolves as it is replaced by fibrous tissue that permanently prevents blood loss three steps occur in rapid sequence: 1) vascular spasm 2) platelet plug formation 3) coagulation (blood clotting)

materials required for erythropoiesis

-nutrients: amino acids, lipids, and carbs are essential for the synthesis of all cells -two B-complex vitamins: vitamin B12 and folic acid are necessary for normal DNA synthesis. even slight deficits jeopardize rapidly dividing cell populations, such as developing erythrocytes -iron: iron is essential for hemoglobin synthesis -iron is available from the diet, and intestinal cells precisely control its absorption into the bloodstream in response to changing body stores of iron -approximately 65% of the body's iron supply is in hemoglobin -most of the remainder is stored in the liver, spleen, and bone marrow -free iron ions are toxic, so iron is stored inside cells as protein-free complexes such as ferritin and hemosiderin -in blood, iron is transported loosely bound to a transport protein called transferrin, and developing erythrocytes take up iron as needed to form hemoglobin -small amounts of iron are lost every day in feces, urine, and perspiration. the average daily loss is 1.7 mg in women and 0.9 mg in men. the menstrual flow accounts for the additional losses

factors limiting normal clot growth

-once the clotting cascade has begun, it continues until a clot forms -normally two homeostatic mechanisms prevent clots from becoming unnecessarily large: 1) swift removal of clotting factors 2) inhibition of activated clotting factors -for clotting to occur, the concentration of activated clotting factors must reach certain critical levels -clots do not usually form in rapidly moving blood because the activated clotting factors are washed away and diluted (this is why vasoconstriction is so important to assist clot formation and also why you apply pressure to a wound to slow bleeding) -for the same reasons, a clot stops growing when it contacts blood flowing normally -other mechanisms block the final step in which fibrinogen is polymerized into fibrin -they work by restricting thrombin to the clot or by inactivating it if it escapes into the general circulation -as a clot forms, almost all of the thrombin produced is bound onto the fibrin threads -this is an important safeguard because thrombin exerts positive feedback effects on the coagulation process prior to the common pathway -not only does it speed up the production of prothrombin activator by acting indirectly through factor V, but it also accelerates the earliest steps of the intrinsic pathway by activating platelets -by binding thrombin, fibrin effectively acts as an anticoagulant, preventing the clot from enlarging and thrombin from acting elsewhere -antithrombin III, a protein present in plasma, quickly inactivates any thrombin not bound to fibrin -antithrombin III and protein C, another protein produced in the liver, also inhibit the activity of other intrinsic pathway clotting factors -heparin, the natural anticoagulant contained in basophil and mast cell granules, is also found on the surface of endothelial cells -it inhibits thrombin by enhancing the activity of antithrombin III -like most other clotting inhibitors, heparin also inhibits the intrinsic pathway

respiratory burst

-one way that neutrophils kill bacteria -the cells metabolize oxygen to produce potent germ-killer oxidizing substances such as bleach and hydrogen peroxide -in addition, defensin-containing granules merge with the microbe-containing phagosome -as a result, defensins form peptide spears that pierce holes in the membrane of the ingested "foe" and the bacterium lyses

deoxyhemoglobin

-oxygen detaches from iron, hemoglobin resumes its former shape, and the resulting _______ or reduced hemoglobin, becomes dark red -the released oxygen diffuses from the blood into the tissue fluid and then into tissue cells

blood doping

-practiced by some athletes competing in aerobic events, is artificially induced polycthemia -some of the athlete's RBCs are drawn off and stored -the body quickly replaces these erythrocytes because removing blood triggers the erythropoietin mechanism -then, when the stored blood is reinfused a few days before the athletic event, a temporary polychthemia occurs -since RBCs carry oxygen, the additional infusion should translate into increased oxygen-carrying capacity due to a higher hemocrit, and greater endurance and speed should result -other than the risk of stroke and heart failure due to high hematocrit and high blood viscosity, blood doping seems to work -however, the practice is considered unethical and has been banned from competitive sports

protective functions of the blood

-preventing blood loss. when a blood vessel is damaged, platelets and plasma proteins initiate clot formation, halting blood loss -preventing infection. drifting along in blood are antibodies, complement proteins, and leukocytes (white blood cells), all of which help defend the body against foreign invaders such as bacteria and viruses

fate and destruction of erythrocytes

-red blood cells have a useful life span of 100 to 120 days -their anucleate condition carries with it some important limitations -red blood cells are unable to synthesize new proteins, grow, or divide -erythrocytes become "old" as they lose their flexibility, become increasingly rigid and fragile, and their hemoglobin begins to degenerate -they become trapped and fragment in smaller circulatory channels, particularly those of the spleen -macrophages engulf and destroy dying erythrocytes -the heme of their hemoglobin is split off from globin -its core of iron is salvaged, bound to protein (as ferritin or hemosiderin) and stored for reuse -the balance of the heme group is degraded to bilirubin, a yellow pigment that is released to the blood and binds to albumin for transport -liver cells pick up bilirubin and in turn secrete it (in bile) into the intestine, where it is metabolized to urobilinogen -most of this degraded pigment leaves the body in feces, as a brown pigment called stercobilin -the protein (globin) part of hemoglobin is metabolized or broken down to amino acids, which are released to the circulation

erythrocytes

-red blood cells that transport oxygen -normally constitute about 45% of the total volume of a blood sample, a percentage known as the hematocrit -are the major factor contributing to blood viscosity -women typically have a lower red blood cell count than men -when the number of red blood cells increases beyond the normal range, blood becomes more viscous and flows more slowly -as the number of red blood cells drops below the lower end of the range, the blood thins and flows more rapidly

hemophilia

-refers to several hereditary bleeding disorders that have similar signs and symptoms -hemophilia A,B, and C -hemophilia A and B occur primarily in males (they are X-linked genetic conditions) -symptoms begin in early life -even minor tissue trauma causes prolonged and potentially life-threatening bleeding into tissues -commonly, the person's joints become seriously disabled and painful because of repeated bleeding into the joint cavities after exercise or trauma -are managed clinically by transfusions of fresh plasma or injections of the appropriate purified clotting factor -these therapies provide relief for several days but are expensive and inconvenient -in addition, dependence on transfusions or injections has caused other problems -in the past, many patients became infected by the hepatitis virus, and, beginning in the early 1980s, by HIV, a blood-transmitted virus that depresses the immune system and causes AIDS -new infections are now avoided due to the availability of genetically engineered clotting factors, hepatitis vaccines, and new testing methods for HIV

platelet-derived growth factor (PDGF)

-released by platelets stimulates smooth muscle cells and fibroblasts to divide and rebuild the vessel wall -as fibroblasts form a connective tissue patch in the injured area, endothelial cells, stimulated by vascular endothelial growth factor (VEGF) multiply and restore the endothelial lining

thromboembolic disorders

-result from conditions that cause undesirable clot formation

secondary polycthemias

-result when less oxygen is available or EPO production increases -the ___________ _______ that appears in individuals living at high altitudes is a normal physiological response to the reduced atmospheric pressure and lower oxygen content of the air in such areas -RBC counts of 6-8 million are common in such people

hemophilia B

-results from a deficiency of factor IX -occurs primarily in males cuz it's an X-linked genetic condition

hemophilia A

-results from a deficiency of factor VIII (anti-hemophilic factor) -accounts for 77% of cases -occurs primarily in males cuz it's an X-linked genetic condition

structural characteristics of erythrocytes

-small cells, about 7.5 um in diameter -are shaped like biconcave discs-- flattened discs with depressed centers -under the microscope, they appear lighter in color at their thin centers than at their edges -are bound by a plasma membrane, but lack a nucleus and have essentially no organelles -are little more than "bags" of hemoglobin -other proteins are present, such as antioxidant enzymes that rid the body of harmful oxygen radicals, but most function as structural proteins, allowing the RBC to deform yet spring back into shape -a network of proteins, especially one called spectrin, attached to the cytoplasmic face of RBC plasma membranes maintains the biconcave shape of an erythrocyte -the spectrin net is deformable, allowing erythrocytes to change shape as necessary-- to twist, turn, and become cup shaped as they are carried passively through capillaries with diameters smaller than themselves-- and then to resume their biconcave shape -it picks up oxygen in the capillaries of the lungs and releases it to tissue cells across other capillaries throughout the body -it also transports some 20% of the carbon dioxide released by tissue cells back to the lungs

abuse of EPO

-some athletes-- particularly professional bike racers and marathon runners seeking increased stamina and performance-- abuse recombinant EPO -by injecting EPO, healthy athletes increase their normal hematocrit from 45% to as much as 65% -then, with the dehydration that occurs in a long race, the blood concentrates even further, becoming a thick, sticky "sludge" that can cause clotting, stroke, or heart failure

infectious mononucleosis

-sometimes called the "kissing disease" -is a highly contagious viral disease most often seen in young adults -caused by the Epstein-Barr virus, the disease has a hallmark of excessive numbers of lymphocytes -many of these lymphocytes are so large and atypical that they were originally misidentified as monocytes, and the disease was mistakenly named mononucleosis -the affected individual complains of being tired and achy, and has a chronic sore throat and lowgrade fever -there is no cure, but with rest, the condition typically runs its course to recovery in four to six weeks

hemoglobin

-the RBC protein that functions in gas transport -is made up of the red heme pigment bound to the protein globin -globin consists of four polypeptide chains, each binding a red ringlike heme group -each heme group bears an iron ion set like a jewel in its center -a hemoglobin molecule can transport four molecules of oxygen because each iron atom can combine reversibly with one molecule o oxygen - a single RBC contains about 250 million hemoglobin molecules -the fact that it is contained in erythrocytes, rather than existing free in plasma, prevents it from leaking out of the bloodstream (through porous capillary walls) and clogging up the kidneys -large amounts of free hemoglobin in the blood would also make blood more viscous and would draw water from the tissues into the bloodstream by osmosis -as oxygen-deficient blood moves through the lungs, oxygen diffuses from the air sacs of the lungs into the blood and then into the erythrocytes, where it binds to the iron in hemoglobin -the iron is partially oxidized by the oxygen. as a result, the protein, now called oxyhemoglobin, assumes a new three-dimensional shape and becomes ruby red

coagulation phase 3: common pathway to the fibrin mesh

-the end point of phase 3 is a fibrin mesh that traps blood cells and effectively seals the hole until the blood vessel can be permanently repaired -thrombin catalyzes the transformation of the soluble clotting factor fibrinogen into fibrin -the fibrin molecules then polymerize (join together) to form long, hairlike insoluble fibrin strands (unlike other clotting factors, activating fibrinogen does not convert it into an enzyme, but instead allows it to polymerize) -the fibrin strands glue the platelets together and make a web that forms the structural basis of the clot -fibrin makes the liquid plasma become gel-like and traps formed elements that try to pass through it -in the presence of calcium ions, thrombin also activates factor XIII (fibrin stabilizing factor), a cross-linking enzyme that binds the fibrin strands tightly together, forming a fibrin mesh -cross-linking further strengthens and stabilizes the clot, effectively sealing the hole until the blood vessel can be permanently repaired

sickle-cell anemia

-the havoc caused by the abnormal hemoglobin, hemoglobin S, results from a change in just one of the 146 amino acids in a beta chain of the globin molecule -this alteration causes the beta chains to link together under low-oxygen conditions, forming stiff rods so that hemoglobin S becomes spiky and sharp -this, in turn, causes the RBCs to become crescent shaped when they unload oxygen molecules or when the oxygen content of the blood is lower than normal, as during vigorous exercise and other activities that increase metabolic rate -the stiff, deformed erythrocytes rupture easily and tend to jam up in small blood vessels -these events interfere with oxygen delivery, leaving the victims gasping for air and in extreme pain -bone and chest pain are particularly severe, and infection and stroke often follow -blood transfusion is still the standard treatment, but preliminary results using inhaled nitric oxide to dilate blood vessels are promising -occurs chiefly in black people who live in the malaria belt of africa and among their descendants -it strikes nearly one of every 500 african american newborns -globally, about 250 million people are infected with malaria and about a million die each year -while individuals with two copies of the sickle-cell gene have sickle-cell anemia, individuals with only one copy of the gene have a better chance of surviving malaria -their cells only sickle under abnormal circumstances, most importantly when the are infected with malaria -sickling reduces the malaria parasites' ability to survive and enhance macrophages' ability to destroy infected RBCs and the parasites they contain -several treatment approaches for sickle-cell anemia focus on preventing RBCs from sickling -fetal hemoglobin (HbF) does not "sickle" even in those destined to have sickle-cell anemia -hydroxyurea, a drug used to treat chronic leukemia, switches the fetal hemoglobin gene back on -this drug dramatically reduces the excruciating pain and overall severity and complications of sickle-cell anemia -in children who are severely affected, bone marrow stem cell transplants offer a complete cure, but carry high risks

transfusion can replace lost blood

-the human cardiovascular system minimizes the effects of blood loss by 1) reducing the volume of the affected blood vessels 2) stepping up production of RBCs -however, the body can only compensate for only so much blood loss -losing 15-30% causes pallor and weakness -losing more than 30% of blood volume results in severe shock, which can be fatal

neutrophils

-the most numerous WBCs -account for 50-70% of the WBC population -are about twice as large as erythrocytes -the neutrophil cytoplasm contains very fine granules ( of two varieties) that are difficult to see -get their name ("neutral-loving" because their granules take up both basic (blue) and acidic (red) dyes -together, the two granules give the cytoplasm a lilac color -some of these granules contain hydrolytic enzymes and are regarded as lysosomes -others, especially the smaller granules, contain a potent "brew" of antimicrobial proteins called defensins -typically have three to six lobes, and are often called polymorphonuclear leukocytes -are our body's bacteria slayers, and their numbers increase explosively during acute bacterial infections such as meningitis and appendicitis -are chemically attracted to sites of inflammation and are active phagocytes -are especially partial to ingesting bacteria and some fungi, which they can enclose in a vesicle called a phagosome

regulation and requirements for erythropoiesis

-the number of circulating erythrocytes is remarkably constant and reflects a balance between red blood cell production and destruction -this balance is important because having too few erythrocytes leads to tissue hypoxia (oxygen deprivation), whereas having too many makes the blood undesirably viscous -to ensure the number of erythrocytes remains within the homeostatic range, new cells are produced at a rate of more than 2 million per second in health people -this process is controlled hormonally and depends on adequate supplies of iron, amino acids, and certain B vitamins

leukopoiesis

-the production of WBCs -is stimulated by chemical messengers -these messengers, which can act either as paracrines or hormones, glycoproteins that fall into two families of hematopoietic factors, interleukins, and colony-stimulating factors -the interleukins are numbered, bust most CSFs are named for the leukocyte population they stimulate -hematopoietic factors, released by supporting cells of the red bone marrow and mature WBCs, not only prompt the white blood cell precursors to divide and mature, but also enhance the protective potency of mature leukocytes -pathways start with the hematopoietic stem cell that gives rise to all of the formed elements in the blood -an early branching of the pathway divides the lymphoid stem cells, which produce lymphocytes, from the myeloid stem cells, which give rise to all other formed elements -in each granulocyte line, the committed cells, called myeloblasts accumulate lysosomes, becoming promyelocytes -the distinctive granules of each granulocyte type appear next in the myelocyte stage and then cell division stops -next, the nuclei becomes U shaped, producing the band cell stage -just before granulocytes leave the marrow and enter the circulation, their nuclei constrict, beginning the process of nuclear segmentation -the bone marrow stores mature granulocytes and usually contains about ten times more granulocytes than are found in the blood -the normal ratio of granulocytes to erythrocytes produced is about 3:1, which reflects granulocytes' much shorter life spans ex: granulocyte-CSF stimulates production of granulocytes

step 3: coagulation

-the third step reinforces the platelet plug with fibrin threads that act as a "molecular glue" for the aggregated platelets -the resulting blood clot (fibrin mesh) is quite effective in sealing larger breaks in a blood vessel -blood is transformed from a liquid to a gel when dissolved blood proteins assemble into fibrin threads -this multistep process involves a series of substances called clotting factors or procoagulants -most clotting factors are plasma proteins synthesized by the liver -they are number I to XIII according to the order of their discovery; as a result, the numerical order does not reflect their reaction sequence -all (except tissue factor) normally circulate in blood in inactive form until mobilized -although vitamin K is not directly involved in coagulation, this fat-soluble vitamin is required for synthesizing four of the clotting factors -the coagulation sequence shows how clotting factors work together to form a clot -in most cases, activation turns clotting factors into enzymes by clipping off a piece of the protein, causing it to change shape -once one clotting factor is activated, it activates the next in sequence, and so on, in a cascade (two important exceptions to this are fibrinogen and Ca) -also important to recognize that coagulation occurs in three phases

thalassemia

-typically occurs in people of mediterranean ancestry -one of the globin chains is absent or faulty, and the erythrocytes are thin, delicate, and deficient in hemoglobin -there are many subtypes of ______ that range in severity from mild to so severe that monthly blood transfusions are required

restoring blood volume

-when a patient's blood volume is so low that death from shock is imminent, there may not be time to type blood, or appropriate whole blood may be unavailable -such emergencies demand that blood volume be replaced immediately to restore adequate circulation -fundamentally, blood consists of proteins and cells suspended in a salt solution -replacing lost blood volume essentially consists of replacing that isotonic salt solution -normal saline or a multiple electrolyte solution that mimics the electrolyte composition of plasma are the preferred choices -volume replacement restores adequate circulation but cannot replace the oxygen-carrying capacity of the lost RBCs -to date, only transfusion of RBCs can do that, but research on ways to replace that capability by using artificial blood substitutes is ongoing

impaired liver function

-when the liver is unable to synthesize its usual supply of clotting factors, abnormal and often severe bleeding occurs -the causes can range from an easily resolved vitamin K deficiency (common in newborns) to nearly total impairment of liver function (as in hepatitis or cirrhosis) -liver cells require vitamin K to produce clotting factors -although intestinal bacteria make some vitamin K, we obtain most of it from vegetables in our diet and dietary deficiencies are rarely a problem -however, vitamin K deficiency can occur if fat absorption is impaired, because vitamin K is a fat-soluble vitamin that is absorbed into the blood along with fats -in liver disease, the nonfunctional liver cells fail to produce not only the clotting factors, but also bile that is required to absorb fat and vitamin K

leukocytosis

-whenever white blood cells are mobilized for action, the body speeds up their production and their numbers may double within a few hours -a WBC count of over 11,000 cells/ul -this condition is a normal response to an infection in the body

leukocytes

-white blood cells -are the only formed elements that are complete cells, with nuclei and the usual organelles -accounting for less than 1% of total blood volume, leukocytes are far less numerous than RBCS -are crucial to our defense against disease -form a mobile army that helps protect the body from damage by bacteria, viruses, parasites, toxins, and tumor cells -are able to slip out of the capillary blood vessels-- a process called diapedesis -the circulatory system is simply their means of transport to areas of the body (mostly loose connective tissues or lymphoid tissues) where they mount inflammatory or immune responses -the signals that prompt WBCs to leave the bloodstream at specific locations are cell adhesion molecules displayed by endothelial cells forming the capillary walls at sites of inflammation -once out of the bloodstream ,leukocytes move through the tissue spaces by amoeboid motion (they form flowing cytoplasmic extensions that move them along) -by following the chemical trail of molecules released by damaged cells or other leukocytes, a phenomenon called positive chemotaxis, they pinpoint areas of tissue damage and infection and gather there in large numbers to destroy foreign substances and dead cells -are grouped into two major categories on the basis of structural and chemical characteristics: granulocytes and agranulocytes

leukoycytes

-white blood cells that act in various ways to protect the body -_________ and platelets contribute less than 1% of blood volume

clot retraction

-within 30 to 60 minutes, platelet-induced process called ________ ________ further stabilizes the clot -platelets contain contractile proteins (actin and myosin), and they contract in much the same manner as smooth muscle cells -as the platelets contract, they pull on the surrounding fibrin strands, squeezing serum (plasma minus the clotting proteins) from the mass, compacting the clot and drawing the ruptured edges of the blood vessel more closely together -even as clot retraction is occurring, the vessel is healing

leukocytes in order from most abundant to least abundant

Never- neutrophils Let-lymphocytes Monkeys-monocytes Eat - eosinophils Bananas - basophils

hemophilia C

a less severe form of hemophilia seen in both sexes, due to a lack of factor XI -the relative mildness of this hemophilia reflects the fact that the clotting factor (factor IX) that the missing factor XI activates can also be activated by factor VII

heparin

administered in injectable form, is the anticoagulant most used in the hospital (for heart patients undergoing various procedures and to prevent or treat venous thrombosis)

veins

carry blood back to the heart from the capillaries

platelets

cell fragments that stop bleeding

lymphocytic leukia

involves lymphocytes

myeloid leukemia

involves myeloblast descendants

leukopenia

is an abnormally low white blood cell count, commonly induced by drugs, particularly glucocorticoids and anticancer agents

acute leukemia

is quickly advancing because it derives from stem cells

coagulation phase 2: common pathway to thrombin

prothrombin activator catalyzes the conversion of a plasma protein called prothrombin into the active enzyme thrombin

reticulocyte counts

provide a rough index of the rate of RBC formation-- reticulocyte counts below or above this range indicate abnormal rates of erythrocyte formation

capillaries

service all of the tissues in the body -oxygen and nutrients leave the blood, crossing capillary walls into the body's tissues -carbon dioxide and wastes move from the tissues to the capillaries -oxygen-deficient blood flows from the capillaries into larger veins