BIO139FALL2021/CHAP18/SALADIN

COAGULATION

-(clotting) of blood is last but most effective defense against bleeding. -It is important for blood to clot quickly when vessel has broken, but equally important for it not to clot in absence of vessel damage. -Because of this delicate balance, coagulation is one of the most complex processes in body, involving over 30 chemical reactions The goal of clotting is to convert plasma protein fibrinogen into fibrin, a sticky protein that adheres to walls of vessel. -As blood cells and platelets arrive, they stick to fibrin -The mass of fibrin, blood cells, and platelets seals break in blood vessel. -complexity of clotting lies in how FIBRIN is formed.

*THALASSEMIA

-A group of hereditary anemias -most common in Greeks, Italians, and others of Mediterranean descent; -shows a deficiency or absence of alpha or beta hemoglobin and RBC counts that may be less than 2 million/µL.

*THROMBOCYTOPENIA

-A platelet count below 100,000/mL. -Causes include bone marrow destruction by radiation, drugs, poisons, or leukemia. -Signs include small hemorrhagic spots in the skin or hematomas in response to minor trauma.

OTHER BLOOD GROUPS

-ABO and Rh are not the only known blood groups. -There are 33 groups in all, with more than 300 RBC antigens in addition to A, B, and D. -Other groups include: Duffy, Kell, Kidd, Lewis, and MNS groups. -These rarely cause transfusion reactions, but are useful for such legal purposes as paternity and criminal cases and for research in anthropology and population genetics. -DNA sequencing is more economical, and has replaced blood typing in many applications.

STARVATION AND PLASMA PROTEIN DEFICIENCY

-Several conditions can lead to hypoproteinemia -HYPOPROTEINEMIA: deficiency of plasma protein: extreme starvation or dietary protein deficiency, liver diseases that interfere with protein synthesis, and protein loss through urine or body surface in cases of kidney disease and severe burns -As protein content of blood plasma drops, so does its osmolarity. -Bloodstream loses more fluid to tissues than it reabsorbs by osmosis. -Thus tissues become edematous and pool of fluid may accumulate in abdominal cavity—a condition called ascites -Children who suffer severe dietary protein deficiencies often exhibit a condition called kwashiorkor The arms and legs are emaciated for lack of muscle, skin is shiny and tight with edema, and abdomen is swollen by ascites. -Kwashiorkor is a Ghanian word for a "deposed" or "displaced" child who is no longer breast-fed. -Symptoms appear when child is weaned and placed on diet consisting mainly of rice or other cereals. -Children with kwashiorkor often die of diarrhea and dehydration.

MAJOR PROTEINS OF BLOOD PLASMA

Albumin (60%)* -Responsible for colloid osmotic pressure; -major contributor to blood viscosity; -transports lipids, hormones, calcium, and other solutes; -buffers blood pH Globulins (36%)* -Transport and defense functions as itemized below Alpha (α) Globulins *Haptoglobulin -Transports hemoglobin released by dead erythrocytes *Ceruloplasmin -Transports copper *Prothrombin -Promotes blood clotting *Others -Transport lipids, fat-soluble vitamins, and hormones Beta (β) Globulins *Transferrin -Transports iron *Complement proteins -Aid in destruction of toxins and Microorganisms *Others -Transport lipids Gamma (γ) Globulins Antibodies; combat pathogens Fibrinogen (4%)* -Becomes fibrin, the major component of blood clots

GENERAL PROPERTIES OF BLOOD FOR HEALTHY ADULT:

Mean fraction of body weight: -8% Volume in adult body: -Female: 4-5 L; -Male: 5-6 L Volume/body weight: -80-85 mL/kg Mean temperature -38°C (100.4°F) pH: -7.35-7.45 Viscosity (relative to water): -Whole blood: 4.5-5.5; -plasma: 2.0 Osmolarity: -280-296 mOsm/L Mean salinity (mainly NaCl): -0.9% Hematocrit (packed cell volume): -Female: 37% to 48% -Male: 45% to 52% Hemoglobin -Female: 12-16 g/dL -Male: 13-18 g/dL Mean RBC count -Female: 4.2-5.4 million/µL -Male: 4.6-6.2 million/µL Platelet count -130,000-360,000/µL Total WBC count -5,000-10,000/µL

The extrinsic pathway of coagulation is activated by _________ from damaged perivascular tissues.

THROMBOPLASTIN

CIRCULATORY FUNCTIONS

TRANSPORT -carries oxygen from lungs to all body tissues -collects carbon dioxide from tissues & carries to lungs for removal -carries metabolic wastes to kidneys for removal -carries hormones from endocrine glands to target cells -transports variety of stem cells from bone marrow & other origins to tissues where they lodge & mature PROTECTION -plays roles in inflammation/mechanism for limiting spread of infection -white blood cells destroy microrganisms & cancer cells, and remove debris from tissues -antibodies & other blood proteins neutralize toxins & help to destroy pathogens -platelets secret factors that initiate blood clotting & other processes for minimizing blood loss, & contribute to tissue growth & blood vessel maintenance REGULATION -blood capillaries stabilize fluid distribution by absorbing or giving off

HEMOSTASIS

There are three hemostatic mechanisms: -VASCULAR SPASM -PLATELET PLUG FORMATION -BLOOD CLOTTING -Platelets play important role in all three.

Which of these is a granulocyte? a monocyte a lymphocyte a macrophage an eosinophil an erythrocyte

EOSINOPHIL

The first clotting factor that the intrinsic and extrinsic pathways have in common is thromboplastin. Hageman factor. factor X. prothrombin activator. factor VIII.

FACTOR X

Excess iron is stored in the liver as a complex called gastroferritin. transferrin. ferritin. hepatoferritin. erythropoietin.

FERRITIN

COMPOSITION OF BLOOD PLASMA

WATER -92% by weight PROTEINS -Total 6-9 g/dL Albumin -60% of total protein, 3.2-5.5 g/dL Globulins 36% of total protein, 2.3-3.5 g/dL Fibrinogen 4% of total protein, 0.2-0.3 g/dL NUTRIENTS Glucose (dextrose) 70-110 mg/dL Amino acids 33-51 mg/dL Lactate 6-16 mg/dL Total lipid 450-850 mg/dL Cholesterol 120-220 mg/dL Fatty acids 190-420 mg/dL High-density lipoprotein (HDL) 30-80 mg/dL Low-density lipoprotein (LDL) 62-185 mg/dL Triglycerides (neutral fats) 40-150 mg/dL Phospholipids 6-12 mg/dL Iron 50-150 µg/dL Trace elements -Traces Vitamins Traces ELECTROLYTES Sodium (Na+) 135-145 mEq/L Calcium (Ca2+) 9.2-10.4 mEq/L Potassium (K+) 3.5-5.0 mEq/L Magnesium (Mg2+) 1.3-2.1 mEq/L Chloride (Cl-) 100-106 mEq/L Bicarbonate (HCO3-) 23.1-26.7 mEq/L Phosphate (HPO42-) 1.4-2.7 mEq/L Sulfate (SO42-) 0.6-1.2 mEq/L NITROGENOUS WASTES Urea 10-20 mg/dL Uric acid 1.5-8.0 mg/dL Creatinine 0.6-1.5 mg/dL Creatine 0.2-0.8 mg/dL Ammonia 0.02-0.09 mg/dL Bilirubin 0-1.0 mg/dL OTHER COMPONENTS Dissolved CO2 2.62 mL/dL Dissolved O2 0.29 mL/dL Dissolved N2 0.98 mL/dL Enzymes of diagnostic value — Hormones —

Which of the following is not a component of hemostasis? platelet plug formation agglutination clot retraction vascular spasm degranulation

agglutination

The RBC antigens that determine transfusion compatibility are called __________.

agglutinogens

With all these extra white cells, why isn't the body's infection fighting capability increased in leukemia?

although numerous, WBCs are immature and incapable of performing defensive roles

Which of the following contributes most to the viscosity of blood? albumin sodium globulins erythrocytes fibrin

erythrocytes

The kidney hormone _________ stimulates RBC production

erythropoietin

Antibodies belong to a class of plasma proteins called albumins. gamma globulins. alpha globulins. procoagulants. agglutinins.

gamma globulins.

EOSINOPHIL

harder to find in a blood film because they are only 2% to 4% of the WBC total, typically averaging about 170 cells/µL. Although relatively scanty in the blood, eosinophils are abundant in the mucous membranes of the respiratory, digestive, and lower urinary tracts. The eosinophil nucleus usually has two large lobes connected by a thin strand, and the cytoplasm has an abundance of coarse rosy to orange-colored specific granules. Eosinophils secrete chemicals that weaken or destroy relatively large parasites such as hookworms and tapeworms, too big for any one WBC to phagocytize. They also phagocytize and dispose of inflammatory chemicals, antigen-antibody complexes, and allergens (foreign antigens that trigger allergies). Allergies, parasitic infections, collagen diseases, and diseases of the spleen and central nervous system can cause an elevated eosinophil count called eosinophilia. The eosinophil count also fluctuates greatly from day to night, seasonally, and with the phase of the menstrual cycle. Differential count (% of WBCs) 2% to 4% Mean absolute count 165 cells/µL Diameter 10-14 µm Appearance Nucleus usually has two large lobes connected by thin strand Large orange-pink specific granules in cytoplasm Variations in Number Fluctuate greatly from day to night, seasonally, and with phase of menstrual cycle Increases in parasitic infections, allergies, collagen diseases, and diseases of spleen and central nervous system Functions Phagocytize antigen-antibody complexes, allergens, and inflammatory chemicals Release enzymes that weaken or destroy parasites such as worms

The percentage of blood volume composed of RBCs is called the ________.

hematocrit (packed cell volume)

Production of all the formed elements of blood is called ________.

hematopoiesis

The hereditary lack of factor VIII causes a disease called ________.

hemophilia

The overall cessation of bleeding, involving several mechanisms, is called __________.

hemostasis

GRANULOCYTES

neutrophils, eosinophils, basophils

An excessively high RBC count is called ________.

polycythemia

PROCOAGULANTS

promote clotting

LEUKOCYTE STRUCTURE

single nucleus and have primary granules -may or may not have secondary (specific) granules -performs function outside of blood vessel

HEMATOLOGY

study of blood and blood forming tissues

Intrinsic factor enables the small intestine to absorb _________.

vitamin B12

FIBRINOGEN

-soluble precursor of FIBRIN (sticky protein that forms framework of a blood clot). -other plasma proteins are enzymes involved in clotting process. -liver produces 4 g of plasma protein per hour, contributing all major proteins except gamma globulins -gamma globulins come from PLASMA CELLS -(connective tissue cells that descend from white blood cells called B lymphocytes.)

HEMOLYTIC DISEASE OF NEWBORN (HDN)

(a) When Rh- woman is pregnant with an Rh+ fetus, she is exposed to D (Rh) antigens, especially during childbirth. (b) Following that pregnancy, her immune system produces anti-D antibodies. (c) If she later becomes pregnant with another Rh+ fetus, her anti-D antibodies can cross placenta and agglutinate blood of that fetus, causing that child to be born with HDN. -If an Rh- woman has had one or more previous Rh+ pregnancies, her subsequent Rh+ children have about a 17% probability of being born with HDN. -Such infants are often severely anemic. -As fetal hematopoietic tissues respond to need for more RBCs, erythroblasts (immature RBCs) enter circulation prematurely—hence name erythroblastosis fetalis. -Hemolyzed RBCs release hemoglobin, which is converted to bilirubin. -High bilirubin levels cause kernicterus, a syndrome of toxic brain damage that can be lethal or leave child with motor, sensory, and mental deficiencies. -HDN can be treated with phototherapy—exposing infant to ultraviolet radiation, which degrades bilirubin as blood passes through capillaries of skin. -In more severe cases, an exchange transfusion is given to completely replace infant's Rh+ blood with Rh-. -In time, infant's hematopoietic tissues will replace donor's RBCs with Rh+ cells, and by then mother's antibody will have disappeared from infant's blood. -Rh-based HDN is easier to prevent than to treat. -If Rh- woman gives birth to (or miscarries) an Rh+ child, she can be given Rh immune globulin (sold under such trade names as RhoGAM and Gamulin Rh). -The immune globulin binds fetal RBC antigens so they cannot stimulate her immune system to produce anti-D. -It is common to give immune globulin at 28 to 32 weeks' gestation and at birth in any pregnancy in which mother is Rh-. -Although Rh mismatch produces most severe HDN, it isn't most common cause. -Two out of three cases are due to ABO mismatches. -In about 15% of U.S. pregnancies, mother is type O and fetus is type A, B, or AB. -About 3% of these pregnancies also result in HDN, but usually with mild effects. -Mismatches in Kell blood group are third most common cause of HDN, followed by Kidd and Duffy mismatches.

7 Formed Elements of Blood.

* ERYTHROCYTES (red blood cells, RBCs) * PLATELETS LEUKOCYTES (Five types, white blood cells, WBCs) GRANULOCYTES: *Neutrophils, * Eosinophils, * Basophils -AGRANULOYTES: * Lymphocytes * Monocytes -there are 7 kinds of formed elements: erythrocytes, platelets, and five kinds of leukocytes. -The five leukocyte types are divided into two categories, granulocytes and agranulocytes

List the three major classes of plasma proteins. Which one is absent from blood serum?

*Albumin: -smallest & most abundant; -transport various solutes and buffer the pH of plasma. *Globulins: -various roles in solute transport, clotting, & immunity. *Fibrinogen: -clotting protein -ABSENT from serum.

SOME DISORDERS OF BLOOD

*DISSEMINATED INTRAVASCULAR COAGULATION (DIC) *INFECTIOUS MONONUCLEOSIS *SEPTICEMIA *THALASSEMIA *THROMBOCYTOPENIA

CLINICAL MANAGEMENT OF BLOOD CLOTTING

-For many cardiovascular patients, goal of treatment is to prevent clotting or to dissolve clots that have already formed. -Several strategies employ inorganic salts and products of bacteria, plants, and animals with anticoagulant and clot-dissolving effects.

In what way does this exemplify a quaternary protein structure? What is the prosthetic group of hemoglobin?

-Hemoglobin consists of noncovalent association of 4 protein chains -The prosthetic group is the HEME MOIETY of each of the 4 chains

ABO GROUP

-ABO bloodtype is determined by presence or absence of antigens (agglutinogens) on RBCs -Blood types A, B, AB, and O form the ABO blood group -ABO blood type is determined by hereditary presence or absence of antigens A and B on the RBCs. -The antigens are glycolipids—membrane phospholipids with short carbohydrate chains bonded to them. -Antibodies of the ABO group begin to appear in plasma 2 to 8 months after birth. -They reach their maximum concentrations between 8 and 10 years of age and then slowly decline for the rest of one's life. -They are produced mainly in response to bacteria that inhabit intestines, but cross-react with RBC antigens and are best known for their significance in transfusions. -Antibodies of the ABO group react against any A or B antigen except one's own. -The antibody that reacts against antigen A is called alpha agglutinin, or anti-A; it is present in plasma of people with type O or type B blood—(anyone who does not possess antigen A). -The antibody that reacts against antigen B is beta agglutinin, or anti-B, and is present in type O and type A individuals—(those who do not possess antigen B). -Each antibody molecule has 10 binding sites where it can attach to either an A or B antigen. -An antibody can attach to several RBCs at once and agglutinate them -Type O blood is most common -AB is rarest in United States. -Percentages differ from one region of world to another and among ethnic groups. -People tend to marry within their locality and ethnic group, thus perpetuating statistical variations particular to that group -In giving transfusions, it is imperative that donor's RBCs not agglutinate as they enter recipient's bloodstream. -For example, if type B blood were transfused into a type A recipient, the recipient's anti-B would immediately agglutinate donor's RBCs -A mismatch causes a transfusion reaction—the agglutinated RBCs block small blood vessels, hemolyze, and release their hemoglobin over next few hours to days. -Free hemoglobin can block kidney tubules and cause death from acute renal failure within a week or so. -For this reason: -person with type A (anti-B) blood must never be given transfusion of type B or AB blood. -person with type B (anti-A) must never receive type A or AB blood. -Type O (anti-A and anti-B) individuals cannot safely receive type A, B, or AB blood. -Type AB is called universal recipient because it lacks both anti-A and anti-B antibodies; -will not agglutinate donor RBCs of any ABO type. -However, the donor's plasma can agglutinate recipient's RBCs if it contains anti-A, anti-B, or both. -type O is called universal donor. -plasma of type O donor, however, can agglutinate RBCs of a type A, B, or AB recipient. -There are procedures for reducing risk of transfusion reaction in certain mismatches such as giving packed RBCs with minimum of plasma. -Contrary to some people's belief, blood type is not changed by transfusion. -It is fixed at conception and remains same for life.

Components and General Properties of Blood

-Adults have 4 to 6 liters of blood. -A liquid connective tissue composed of cells and extracellular matrix. -Its matrix is blood PLASMA, a clear, light yellow fluid constituting little over half of blood volume. -Suspended in plasma are FORMED ELEMENTS —cells and cell fragments including red blood cells, white blood cells, and platelets -term formed element alludes to the fact that these are membrane-enclosed bodies with definite structure visible with microscope. -they can't all be called cells because platelets are merely fragments torn from certain bone marrow cells.

ERYTHROCYTE DISORDERS

-Any imbalance between rates of erythropoiesis and RBC destruction may produce excess or deficiency of red cells. -RBC excess is called polycythemia -deficiency of either RBCs or hemoglobin is called anemia

FIVE MAIN TYPES OF BLOOD VESSELS ARE:

-Arteries, -Arterioles -Capillaries, -Venules, -Veins

ERYTHROCYTE DEATH AND DISPOSAL

-As RBCs age and membrane proteins (especially spectrin) deteriorate, the membrane grows increasingly fragile. -Without a nucleus or ribosomes, RBCs cannot synthesize new spectrin. -Many RBCs die in spleen, which has been called "erythrocyte graveyard." -spleen has channels as narrow as 3 µm that severely test ability of old, fragile RBCs to squeeze through organ. -Old cells become trapped, broken up, and destroyed. -enlarged and tender spleen sometimes indicates diseases in which RBCs are rapidly breaking down. -HEMOLYSIS (rupture of RBCs), releases hemoglobin and leaves empty plasma membranes. -The membrane fragments are easily digested by macrophages in liver and spleen, but hemoglobin disposal is more complicated. -It must be disposed of efficiently, however, or it can block kidney tubules and cause renal failure. -Macrophages begin disposal process by separating heme from globin. -They hydrolyze globin into free amino acids, which can be used for energy-releasing catabolism or recycled for protein synthesis. -Disposing of heme is another matter. -First, macrophage removes iron and releases it into blood, where it combines with transferrin and used or stored in same way as dietary iron. T -macrophages converts rest of heme into a greenish pigment called biliverdin, then further converts most of this to yellow-green pigment called bilirubin. -Bilirubin is released by macrophages and binds to albumin in blood plasma. -Liver removes it from albumin and secretes it into bile, to which it imparts a dark green color as bile becomes concentrated in gallbladder. -Biliverdin and bilirubin are collectively known as bile pigments. -Gallbladder discharges bile into small intestine, where bacteria convert bilirubin to urobilinogen, responsible for brown color of feces. -Another hemoglobin breakdown pigment, urochrome, produces yellow color of urine. -High level of bilirubin in blood causes jaundice, a yellowish cast in skin and whites of eyes. -Jaundice may be sign of rapid hemolysis or liver disease or bile duct obstruction that interferes with bilirubin disposal.

*SEPTICEMIA

-Bacteremia (bacteria in the bloodstream) accompanying infection elsewhere in the body. -Often causes fever, chills, and nausea, and may cause DIC or septic shock.

MATERNAL-FETAL MISMATCHES

-Hemolytic disease of the newborn (HDN), or erythroblastosis fetalis, occurs when woman has a baby with mismatched blood type -most famously, but not all cases, when she is Rh- and carries an Rh+ fetus. -First pregnancy likely to be uneventful because placenta normally prevents maternal and fetal blood from mixing. -However, if there is placental leakage during pregnancy, or at time of birth, or if miscarriage occurs, mother is exposed to Rh+ fetal blood. -She will produce anti-D antibodies -If she becomes pregnant again with Rh+ fetus, her anti-D antibodies may pass through placenta and agglutinate fetal erythrocytes. -Agglutinated RBCs hemolyze, and baby is born with hemolytic anemia, HDN.

BLOOD TYPES

-Blood types and transfusion compatibility are matter of interactions between plasma and erythrocytes. -Ancient Greek physicians attempted to transfuse blood from one person to another by squeezing it from a pig's bladder through a porcupine quill into recipient's vein. -Although some patients benefited from the procedure, it was fatal to others. -The reason some people have compatible blood and some don't remained obscure until 1900, when Karl Landsteiner discovered blood types A, B, and O—a discovery that won him a Nobel Prize in 1930; type AB was discovered later. -World War II stimulated great improvements in transfusions, blood banking, and blood substitutes -Blood types are based on large molecules called ANTIGENS and ANTIBODIES -ANTIGENS are complex molecules such as proteins, glycoproteins, and glycolipids that are genetically unique to each individual (except identical twins). -They occur on surfaces of all cells and enable body to distinguish its own cells from foreign matter. -When body detects an antigen of foreign origin, it activates an immune response. -This response consists partly of plasma cells, and Secreting proteins called antibodies. -Antibodies bind to antigens and mark them, or cells bearing them, for destruction. -One method of antibody action is agglutination, in which each antibody molecule binds to two or more foreign cells and sticks them together. -Repetition of this process produces large clumps of cells that can cause complications of transfusion reaction . T -The RBC surface antigens that trigger agglutination are called agglutinogens and the plasma antibodies that bind to them are called agglutinins

BONE MARROW AND CORD BLOOD TRANSPLANTS

-Bone marrow transplant is one treatment option for leukemia, sickle-cell disease, and other disorders. -The principle is to eradicate patient's original bone marrow with radiation or chemotherapy, including immune T cells that would attack transplanted marrow, and then replace with donor stem cells in hopes that they rebuild a population of normal marrow and blood cells. -Marrow is drawn from donor's sternum or hip bone and injected into recipient's circulation. -Donor stem cells colonize patient's marrow cavities and build healthy marrow. -Bone Marrow Transplant Drawbacks: -difficult to find compatible donors; -surviving T cells in patient may attack donor marrow; -donor T cells may attack patient's tissues (the graft-versus-host response). -To inhibit graft rejection, patient must take immunosuppressant drugs for life. -These leave person vulnerable to infection and have other adverse side effects. -Infections sometimes contracted from donated marrow itself. -Marrow transplant is high-risk procedure; -up to 1/3 of patients die from complications of treatment -Alternative is to use blood from placentas, which are normally discarded at every childbirth. -Placental blood contains more stem cells than adult bone marrow, and less likely to carry infectious microbes. -With the parents' consent, it can be harvested from umbilical cord with syringe and stored indefinitely at cord blood banks. -Immature immune cells in cord blood have less tendency to attack recipient's tissues; -cord blood transplants have lower rejection rates and don't require as close a match between donor and recipient, meaning that more donors are available to a patient in need. -Pioneered in 1980s, cord blood transplants have successfully treated leukemia and wide range of other blood diseases. -Use of cord blood may soon be overshadowed, however, by stem cell harvesting from peripheral blood (drawn from the blood vessels). -Peripheral blood is more accessible than bone marrow, and with improvements in technique, it yields faster replacement of hematopoietic stem cells in recipient.

CLOTTING DISORDERS

-Clotting deficiencies can result from causes as diverse as malnutrition, leukemia, and gallstones LIVER DISEASE AND BLOOD CLOTTING -Proper blood clotting depends on normal liver function for two reasons. (1) liver synthesizes majority of clotting factors. -diseases such as hepatitis, cirrhosis, and cancer that degrade liver function result in deficiency of clotting factors. (2) synthesis of clotting factors II, VII, IX, and X require vitamin K. -absorption of vitamin K from diet requires bile, a liver secretion. -Gallstones can lead to clotting deficiency by obstructing bile duct and interfering with bile secretion and vitamin K absorption. -Efficient blood clotting especially important in childbirth, since both mother and infant bleed from trauma of birth. -pregnant women may take vitamin K supplements to ensure fast clotting, and newborn infants may be given vitamin K injections. -deficiency of any clotting factor can shut down coagulation cascade. -Shutdown of COAGULATION CASCADE happens in hemophilia -a family of hereditary diseases characterized by deficiencies of one factor or another. -Because of sex-linked recessive mechanism of heredity, hemophilia occurs predominantly in males. -They inherit it only from mothers -Lack of factor VIII causes classical hemophilia (hemophilia A), which accounts for 83% of cases and afflicts 1 in 5,000 males worldwide. -Lack of factor IX causes hemophilia B, which accounts for 15% of cases and occurs in about 1 out of 30,000 males. -Factors VIII and IX are known as antihemophilic factors A and B. -rarer form called hemophilia C (factor XI deficiency) is autosomal and not sex-linked, and occurs equally in both sexes. -Before purified factor VIII became available in 1960s, more than half with hemophilia died before age 5 and only 10% lived to age 21. -Physical exertion causes bleeding into muscles and joints. -Excruciating pain and eventual joint immobility results from intramuscular and joint hematomas (masses of clotted blood in tissues). -Hemophilia varies in severity -Half the normal level of clotting factor is enough to prevent symptoms, and symptoms are mild even in individuals with as little as 30% of the normal amount. -Such cases go undetected even into adulthood. -Bleeding can be relieved for few days by transfusion of plasma or purified clotting factors. -Failure of blood to clot takes far fewer lives than unwanted clotting. *THROMBOSIS -abnormal clotting of blood in unbroken blood vessel -becomes increasingly problematic in old age. -25% of people over age 50 experience venous blockage by thrombosis, -especially people who don't exercise regularly or are confined to bed or wheelchair. -blood clots especially easily in veins, where blood flow is slowest. *THROMBUS (clot) -may grow large enough to obstruct small vessel, or piece of it may break loose and travel in bloodstream as an EMBOLUS *EMBOLUS can lodge in small artery and block blood flow from that point on. -If blocked vessel supplies vital tissue of heart, brain, lung, or kidney, INFARCTION (tissue death) may result. -650,000 Americans die annually of thromboembolism (traveling blood clots) in cerebral, coronary, and pulmonary arteries. -Most strokes and heart attacks due to thrombosis, and pulmonary failure often results from thromboembolism. -Thrombosis more likely to occur in veins than in arteries because blood flows more slowly in veins and doesn't dilute thrombin and fibrin as rapidly. -Most venous blood flows directly to heart and then to lungs. -Therefore, blood clots arising in limbs commonly lodge in lungs and cause pulmonary embolism. -When blood cannot circulate freely through lungs, it cannot receive oxygen and person may die of hypoxia.

BLOOD

-Connective tissue made of plasma, erythrocytes, leukocytes, and platelets.

PLATELET FUNCTIONS

-Despite their small size, platelets have greater variety of functions than any of the true blood cells: -They secrete vasoconstrictors, chemicals that stimulate spasmodic constriction of broken vessels and help reduce blood loss. -They stick together to form temporary platelet plugs that seal small breaks in injured blood vessels. -They secrete procoagulants, or clotting factors, which promote blood clotting. -They initiate formation of a clot-dissolving enzyme that dissolves blood clots that have outlasted their usefulness. -They secrete chemicals that attract neutrophils and monocytes to sites of inflammation. -They internalize and destroy bacteria. -They secrete growth factors that stimulate mitosis in fibroblasts and smooth muscle and help maintain and repair blood vessels.

EFFECTS OF MISMATCHED TRANSFUSION

-Donor RBCs become agglutinated in recipient's blood plasma. -agglutinated RBCs lodge in smaller blood vessels downstream from this point and cut off blood flow to vital tissues. -There are procedures for reducing risk of transfusion reaction in certain mismatches, such as giving packed RBCs with a minimum of plasma. -Contrary to some people's belief, blood type is not changed by transfusion. It is fixed at conception and remains the same for life.

BLOOD TYPING

-Each row shows appearance of a drop of blood mixed with anti-A and anti-B antisera. -Blood cells become clumped if they possess the antigens for the antiserum (top row left, second row right, third row both) but otherwise remain uniformly mixed. -Thus, type A agglutinates only in anti-A; -type B agglutinates only in anti-B; -type AB agglutinates in both; -type O agglutinates in neither of them. -The antisera in vials at top are artificially colored to make them more easily distinguishable.

CELL-TO-CELL COMMUNICATION

-In chemical signaling, a cell may target itself (autocrine signaling), a cell connected by gap junctions, a nearby cell (paracrine signaling), or a distant cell (endocrine signaling). -Paracrine signaling acts on nearby cells, -Endocrine signaling uses circulatory system to transport ligands, -Autocrine signaling acts on the signaling cell. -Signaling via gap junctions involves signaling molecules moving directly between adjacent cells. GAP JUNCTIONS: -JOINS: Single-unit smooth muscle, cardiac muscle, epithelial, and other cells together -SPEED: Quickly & easily transmits signals AUTOCRINE SIGNALING: -RELEASED BY: Signaling cells that also bind to Ligand that is released -The signaling cell and target cell can be same or similar cell. -occurs during early development of organism to ensure that cells develop into correct tissues and take on proper function. -regulates pain sensation and inflammatory responses. -If cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process -SPEED: Fast PARACRINE SIGNALING: -CHARACTERISTICS: -Signals that act locally between cells that are close together -signals move by diffusion through extracellular matrix. -In order to keep response localized, paracrine ligand molecules are quickly degraded by enzymes or removed by neighboring cells. -Removing signals reestablish concentration gradient for the signal, allowing them to quickly diffuse through intracellular space if released again. -One example of paracrine signaling is the transfer of signals across synapses between nerve cells -SPEED: Quick responses that last only a short amount of time. NEUROTRANSMITTERS: -RELEASED BY: Presynaptic cells in the presynaptic terminal at active zones, the regions of the membrane where small molecule neurotransmitters are released. -At active zones, some synaptic vesicles are docked and ready for immediate release upon arrival of action potential. -SPEED: Immediate/ neurotransmitters are transported across very small distances between nerve cells, which are called chemical synapses. The small distance between nerve cells allows signals to travel quickly; this enables immediate response HORMONE/ENDOCRINE SIGNALING: -CHARACTERISTICS: -originate from endocrine cells. -produce slower response but have longer-lasting effect. -ligands released in endocrine signaling are called hormones, that are produced in one part of body but affect other body regions some distance away. -Hormones travel large distances between endocrine cells and their target cells via bloodstream, which is a slow way to move throughout body. -Because of their form of transport, hormones get diluted and present in low concentrations when they act on their target cells. -This is different from paracrine signaling, in which local concentrations of ligands can be very high.

*INFECTIOUS MONONUCLEOSIS

-Infection of B lymphocytes with Epstein-Barr virus, -most commonly in adolescents and young adults. -Usually transmitted by exchange of saliva, as in kissing. -Causes fever, fatigue, sore throat, inflamed lymph nodes, and leukocytosis. -Usually self-limiting and resolves within a few weeks.

IRON METABOLISM

-Iron is critical part of hemoglobin molecule -one key nutritional requirements for erythropoiesis. -Men lose 0.9 mg of iron per day through urine, feces, and bleeding -women of reproductive age lose 1.7 mg/day through these routes and menstruation. -we absorb only fraction of iron in food, -must consume 5 to 20 mg/day to replace losses. -pregnant woman needs 20 to 48 mg/day, especially last 3 months, to meet needs of mother and fetus. -Dietary iron exists in two forms: -ferric (Fe3+) -ferrous (Fe2+) ions. -Stomach acid converts most Fe3+ to Fe2+, -Fe2+ only form small intestine can absorb -protein gastroferritin, produced by stomach, binds Fe2+ and transports it to small intestine. -absorbed into blood while in small intestine, -binds to plasma protein called transferrin, and travels to bone marrow, liver, and other tissues. -Bone marrow uses iron for hemoglobin synthesis; -muscle uses it to make oxygen-binding protein myoglobin; -nearly all cells use iron to make electron-transport molecules called cytochromes in their mitochondria. -liver binds surplus iron to protein called apoferritin, forming iron-storage complex called ferritin. -It releases Fe2+ into circulation when needed. -other nutritional requirements for erythropoiesis are: -vitamin B12 and folic acid, required for rapid cell division and DNA synthesis that occurs in erythropoiesis, -vitamin C and copper, which are cofactors for enzymes that synthesize hemoglobin.

MODERN USE OF LEECHING How does the modern theory behind leeching differ from the theory of leeching that was popular a few centuries ago?

-Leeches secrete local anesthetic that makes bites painless; -as early as 1567 bce, physicians used them for bloodletting. -This method was less painful and repugnant to patients than phlebotomy—cutting a vein— -In seventeenth-century France, LEECHING was quite the rage; -tremendous numbers of leeches were used in ill-informed attempts to treat headaches, insomnia, whooping cough, obesity, tumors, menstrual cramps, mental illness, and almost anything else doctors or their patients imagined to be caused by "bad blood." -The first known anticoagulant was discovered in saliva of the medicinal leech -Hirudo medicinalis, in 1884. -Named hirudin, it is a polypeptide that prevents clotting by inhibiting thrombin. -It causes blood to flow freely while leech feeds and for as long as an hour thereafter. -While doctrine of bad blood is now long discredited, leeches have lately reentered medical usage for other reasons -A major problem in reattaching a severed body part such as a finger or ear is that tiny veins draining these organs are too small to reattach surgically. -Since arterial blood flows into reattached organ and can't flow out as easily, it pools and clots there. -Pooling inhibits regrowth of veins and flow of fresh blood through organ, and often leads to necrosis. -Some vascular surgeons now place leeches on reattached parts. -Their anticoagulant keeps blood flowing freely and allows new veins to grow. -After 5 to 7 days, venous drainage is restored and leeching can be stopped.

FATE OF BLOOD CLOTS

-Once clot has formed, a process of local tissue repair begins. -Platelets and endothelial cells secrete mitotic stimulant named platelet-derived growth factor (PDGF). -PDGF stimulates fibroblasts and smooth muscle cells to multiply and repair damaged blood vessel. -Fibroblasts invade clot and produce fibrous connective tissue, which helps strengthen and seal vessel while repairs occur -once tissue repair is completed, clot must be disposed of. -Fibrinolysis (dissolution of clot), is achieved by small cascade of reactions with positive feedback component -In addition to promoting clotting, factor XII catalyzes formation of plasma enzyme called kallikrein -Kallikrein converts inactive protein plasminogen into plasmin, a fibrin-dissolving enzyme that breaks up clot. -Thrombin activates plasmin, and plasmin indirectly promotes formation of more kallikrein, thus completing a positive feedback loop.

ERYTHROCYTES (Red Blood Cells, RBCs)

-have two principal functions: (1) to pick up oxygen from lungs and deliver it to tissues elsewhere (2) to pick up carbon dioxide from tissues and unload it in lungs. -RBCs are most abundant formed elements and most obvious things under microscopic examination. -most critical to survival; severe deficiency of leukocytes or platelets can be fatal within few days -severe deficiency of RBCs can be fatal within minutes. -It is the lack of life-giving oxygen, carried by erythrocytes, that leads rapidly to death in cases of major trauma or hemorrhage.

COMPLETION OF COAGULATION

-Once factor X is activated, remaining events are identical in intrinsic and extrinsic mechanisms -Factor X combines with factors III and V in presence of Ca2+ and PF3 to produce prothrombin activator. -This enzyme acts on a globulin prothrombin (factor II) and converts it to enzyme thrombin. -Thrombin converts fibrinogen into shorter strands of fibrin monomer. -These monomers covalently bond to each other end to end and form longer fibers of fibrin polymer. -Factor XIII cross-links these strands to create dense aggregation that forms structural framework of blood clot -Once clot begins to form, it launches self-accelerating positive feedback process that seals off damaged vessel more quickly. -Thrombin works with factor V to accelerate production of prothrombin activator, which produces more thrombin. -cascade of enzymatic reactions acts as amplifying mechanism to ensure rapid clotting of blood -Each activated enzyme in pathway produces larger number of enzyme molecules at following step. -One activated molecule of factor XII at start of intrinsic pathway very quickly produces thousands if not millions of fibrin molecules. -the extrinsic mechanism requires fewer steps to activate factor X than intrinsic mechanism; -EXTRINSIC MECHANISM is "shortcut" to coagulation. -It takes 3 to 6 minutes for clot to form by intrinsic pathway but only 15 seconds by extrinsic pathway. -For this reason, when small wound bleeds, you can stop bleeding sooner by massaging site. -massaging releases thromboplastin from perivascular tissues and activates/speeds up extrinsic pathway. -After clot has formed, spinous pseudopods of platelets adhere to strands of fibrin and contract. -This pulls on fibrin threads and draws edges of broken vessel together, like a drawstring closing a purse. -Through this process of clot retraction, clot becomes more compact within about 30 minutes. -Normally, bleeding of fingerstick should stop within 2-3 minutes, and sample of blood in clean test tube should clot within 15 minutes. -Bleeding time is most precisely measured by the IVY METHOD —inflating blood pressure cuff on arm to 40 mm Hg, making a 1 mm deep incision in forearm, and measuring time for bleeding to stop -Normally it should stop in 1 to 9 minutes. -Other techniques are available that can separately assess effectiveness of intrinsic and extrinsic Mechanisms

What are the two principal components of the blood?

-PLASMA -FORMED ELEMENTS

SECONDARY POLYCYTHEMIA

-Polycythemia from all other causes -characterized by RBC counts as high as 6 to 8 million RBCs/µL. -can result from dehydration because water is lost from bloodstream while erythrocytes remain and become abnormally concentrated. -More often, caused by smoking, air pollution, emphysema, high altitude, excessive aerobic exercise, or other factors that create state of hypoxemia and stimulate erythropoietin secretion. -principal dangers of polycythemia are increased blood volume, pressure, and viscosity. -Blood volume can double in primary polycythemia and cause circulatory system to become tremendously engorged. -Blood viscosity may rise to three times normal. -Circulation is poor, capillaries are congested with viscous blood, and heart is dangerously strained. -Chronic (long-term) polycythemia can lead to embolism, stroke, or heart failure. -deadly consequences of emphysema and some other lung diseases are due in part to polycythemia

PREVENTION OF INAPPROPRIATE CLOTTING

-Precise controls required to prevent coagulation when it isn't needed. These include: *PLATELET REPULSION -platelets don't adhere to smooth prostacyclin-coated endothelium of healthy blood vessels. *DILUTION -Small amounts of thrombin form spontaneously in plasma -at normal rates of blood flow, thrombin is diluted so quickly that clot has little chance to form. -If flow decreases, thrombin accumulates to cause clotting. -This can happen in circulatory shock. -When output from heart is diminished and circulation slows down, widespread clotting throughout circulatory system may occur. *ANTICOAGULANTS -Thrombin formation is suppressed by anticoagulants in plasma. -Antithrombin, secreted by liver, deactivates thrombin before acts on fibrinogen. -Heparin, secreted by basophils and mast cells, interferes with formation of prothrombin activator, blocking action of thrombin on fibrinogen, and promoting action of antithrombin. -Heparin injection given to patients with abnormal clotting tendencies.

QUANTITIES OF ERYTHROCYTES AND HEMOGLOBIN

-RBC count and hemoglobin concentration are important clinical data because they determine amount of oxygen blood can carry. -3 of most common measurements are: -hematocrit -hemoglobin concentration -RBC count *Hematocrit (packed cell volume, PCV) is percentage of whole blood volume composed of RBCs -MALES 42%-52%; -FEMALES 37%-48%. *Hemoglobin concentration of whole blood is - (13-18 g/dL) in men - (12 to 16 g/dL) in women. *RBC count -4.6 to 6.2 million RBCs/µL in men -4.2 to 5.4 million/µL in women. -often expressed as cells per cubic millimeter (mm3); 1 µL = 1 mm3. -Notice lower values in women than in men. -There are three physiological reasons for this: (1) Androgens stimulate RBC production, and men have higher androgen levels than women; (2) women of reproductive age have periodic menstrual losses; (3) hematocrit is inversely proportional to percentage body fat, which averages higher in women than in men. -In men, blood also clots faster and skin has fewer blood vessels than in women. -Such differences are not limited to humans. -From evolutionary standpoint, their adaptive value may lie that male animals fight more than females and suffer more injuries. -These traits may serve to minimize or compensate for blood loss.

ERYTHROCYTE HOMEOSTASIS

-RBC count is maintained in negative feedback manner -If count should drop it may result in state of hypoxemia (oxygen deficiency in blood). -kidneys detect low oxygen and increase EPO output. -Three-four days later, RBC count begins to rise and reverses hypoxemia that started process.

The Rh GROUP

-Rh blood group is named for rhesus monkey, in which Rh antigens were discovered in 1940. -This group includes numerous RBC antigens, of which principal types are antigens C, D, and E. -Antigen D is most reactive of these, so a -person is Rh-positive (Rh+) if he/she has the D antigen (genotype DD or Dd) -person is Rh-negative (Rh-) when lacking (genotype dd). -Rh blood type is tested by using an anti-D reagent. -Rh type combined with ABO type in a single expression such as O+ for type O, Rh-positive; or AB- for type AB, Rh-negative. -Rh frequencies vary among ethnic groups just as ABO frequencies do. -85% of white Americans are Rh+ -15% are Rh- -99% of Asians are Rh+. -ABO blood type has no influence on Rh type, or vice versa. -If frequency of type O whites in United States is 45%, and 85% of these are also Rh+, then frequency of O+ individuals is product of these separate frequencies: or 38%. -In contrast to ABO group, anti-D antibodies are not normally present in blood. -Anti-D antibodies form only in Rh- individuals who are exposed to Rh+ blood. -If Rh- person receives an Rh+ transfusion, recipient produces anti-D. -Since anti-D doesn't appear instantaneously, this presents little danger in first mismatched transfusion. -But if that person should later receive another Rh+ transfusion, his or her anti-D could agglutinate donor's RBCs.

OSMOSIS

-important that blood maintain optimal osmolarity. -BLOOD OSMOLARITY produced mainly of sodium ions, protein, and erythrocytes. -contribution of PROTEIN to blood osmotic pressure—called COLLOID OSMOTIC PRESSURE (COP)—is especially important

SICKLE CELL DISEASE

-Sickle-cell disease and thalassemia are hereditary hemoglobin defects that occur mostly among people of African and Mediterranean descent. -Sickle-cell disease afflicts 1.3% of people of African-American heritage. -caused by recessive allele that modifies hemoglobin. -Sickle-cell hemoglobin (HbS) differs from normal HbA only in sixth amino acid of beta chain, where HbA has glutamic acid and HbS has valine. -People who are homozygous for HbS exhibit sickle-cell disease. -People who are heterozygous for it—about 7.7% of African-Americans—have sickle-cell trait but rarely have severe symptoms. -if two carriers reproduce, each of their children has a 25% chance of being homozygous and having the disease. -HbS doesn't bind oxygen very well. -At low oxygen concentrations, it becomes deoxygenated, polymerizes, and forms gel that makes erythrocytes become elongated and pointed at ends -Sickled erythrocytes are sticky; agglutinate (clump) and block small blood vessels, causing intense pain in oxygen-starved tissues. -Blockage of circulation can also lead to kidney or heart failure, stroke, severe joint pain, or paralysis. -Hemolysis of fragile cells causes anemia, which results in hypoxemia that triggers further sickling in deadly positive feedback loop. -Chronic hypoxemia also causes fatigue, weakness, poor mental development, and deterioration of heart and other organs. -In futile effort to counteract hypoxemia, hematopoietic tissues become so active that bones of cranium and elsewhere become enlarged and misshapen. -spleen reverts to hematopoietic role, while also disposing of dead RBCs, and becomes enlarged and fibrous. -Sickle-cell disease is prime example of pleiotropy—the occurrence of multiple phenotypic effects arising from change in a single gene. -Without treatment, child with sickle-cell disease has little chance of living to age 2. -Advances in treatment have steadily raised life expectancy to beyond age 50. -In Africa, where it originated, vast numbers of people die of malaria. -Malaria is caused by parasite that invades RBCs and feeds on hemoglobin. -Sickle-cell hemoglobin is detrimental to parasites, and people heterozygous for sickle-cell disease are resistant to malaria. -The lives saved by this gene far outnumber deaths of homozygous individuals, so the gene persists in the population. -The sickle-cell gene is less common in United States and other essentially nonmalarious regions than it is in Africa.

Why are erythrocytes caved in at the center?

-The sunken center represents former location of nucleus

PATHWAYS OF COAGULATION

-There are two reaction pathways to coagulation: -EXTRINSIC MECHANISM -INTRINSIC MECHANISM -EXTRINSIC MECHANISM is initiated by clotting factors released by damaged blood vessel and perivascular tissues. -word extrinsic means factors come from sources external to blood. -INTRINSIC MECHANISM uses only clotting factors found in blood itself. Example: when platelets adhere to a fatty plaque of atherosclerosis or to a test tube. -In most cases of bleeding, both extrinsic and intrinsic mechanisms work simultaneously and interact with each other to achieve hemostasis. -Clotting factors are called PROCOAGULANTS, in contrast to anticoagulants -Most procoagulants are proteins produced by liver. -PROCOAGULANTS always present in plasma in inactive form, but when one factor is activated, it functions as enzyme that activates next one in pathway. That factor activates next, and so on, in a sequence called REACTION CASCADE —a series of reactions, each one depending on product of preceding one. -Many clotting factors are identified by roman numerals, which indicate order in which they were discovered, not order of reactions. -Factors IV and VI were abandoned when it was found that factor IV was calcium and factor VI was activated factor V. -PLATELET FACTORS (PF1 through PF4) are Procoagulants produced by platelets.

HOW BLOOD IS PRODUCED (HEMOPOIESIS/HEMATOPOIESIS)

-We lose blood continually from bleeding, from aging & death of blood cells, and from consumption and excretion of plasma components -we must continually replace blood -Every day, adult typically produces: 400 billion platelets, 200 billion RBCs, and 10 billion WBCs. -Production of blood, especially its formed elements, is called HEMATOPOIESIS -tissues that produce blood cells are called HEMATOPOIETIC TISSUES -First hematopoietic tissues of embryo form in YOLK SAC. -Cell clusters called BLOOD ISLANDS form in YOLK SAC third week of human development. -BLOOD ISLANDS produce primitive stem cells that migrate into embryo proper and colonize BONE MARROW, LIVER, SPLEEN, & THYMUS -Stem cells migrate to BONE MARROW, LIVER, SPLEEN, & THYMUS where they multiply and give rise to blood cells throughout fetal development. -Liver stops producing blood cells around time of birth. -Spleen stops producing RBCs soon after, but continues producing lymphocytes for life. -From infancy all 7 FORMED ELEMENTS are produced in RED BONE MARROW -LYMPHOCYTES are produced in lymphatic tissues/organs—especially thymus, tonsils, lymph nodes, spleen, and mucous membranes. -Blood formation in bone marrow and lymphatic organs is called, MYELOID and LYMPHOID HEMATOPOIESIS -All formed elements trace origins to common type of hematopoietic stem cell (HSC) in bone marrow. -In stem-cell terminology HSCs would be classified as multipotent stem cells, that develop into multiple mature cell types. -Hematologists often call them pluripotent stem cells (PPSCs). -HSCs multiply to maintain small but persistent population in bone marrow, but some become variety of specialized cells called colony-forming units (CFUs). -Each CFU produces one or another class of formed elements. -BLOOD PLASMA requires continual replacement. -composed mainly of water, which obtained by absorption from digestive tract. -electrolytes and organic nutrients absorbed from digestive tact -gamma globulins come from connective tissue plasma cells -other proteins come from liver.

DISSOLVING CLOTS THAT HAVE ALREADY FORMED

-When clot has already formed, it can be treated with clot-dissolving drugs such as streptokinase, an enzyme made by certain bacteria (streptococci). -Intravenous streptokinase is used to dissolve blood clots in coronary vessels, -It is nonspecific and digests almost any protein. -Tissue plasminogen activator (TPA) works faster, more specific, and now made by transgenic bacteria. -TPA converts plasminogen into clot-dissolving enzyme plasmin. -Some anticoagulants of animal origin also work by dissolving fibrin. -A giant Amazon leech, Haementeria, produces one such anticoagulant named hementin. -HEMENTIN has been successfully produced by genetically engineered bacteria and used in cardiac patients to dissolve blood clots that do not yield to streptokinase or other drugs.

*DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

-Widespread clotting within unbroken vessels, limited to one organ or occurring throughout the body. -Usually triggered by septicemia but also occurs when blood circulation slows markedly (as in cardiac arrest). -Marked by widespread hemorrhaging, congestion of the vessels with clotted blood, and tissue necrosis in blood-deprived organs.

POLYCYTHEMIA

-increased number of erythrocytes and hemoglobin in blood

BLOOD VISCOSITY AND OSMOLARITY

-arise from formed elements and plasma composition. -VISCOSITY is resistance of fluid to flow, resulting from cohesion of its particles. (it is the thickness or stickiness of a fluid) -Whole blood is 4.5 to 5.5 times as viscous as water (mainly because of the RBCs); -plasma alone is 2.0 times as viscous as water (mainly because of its protein) -Viscosity is important in circulatory function because it partially governs flow of blood through vessels. -An RBC or protein deficiency reduces viscosity and causes blood to flow too easily, whereas an -excess RBCs or proteins causes blood to flow too sluggishly. -Either of these conditions puts strain on heart that may lead to serious cardiovascular problems if not corrected. -OSMOLARITY of blood, is total molarity of dissolved particles that cannot pass through blood vessel wall. -In order to nourish surrounding cells and remove wastes, substances must pass between bloodstream and tissue fluid through capillary walls. -This transfer of fluids depends on a balance between filtration of fluid from A capillary and its reabsorption by osmosis -Rate of reabsorption is governed by relative osmolarity of blood versus tissue fluid. -If blood osmolarity is too high, bloodstream absorbs too much water. -This raises blood volume, resulting in high blood pressure and potentially dangerous strain on heart and arteries. -If osmolarity drops too low, too much water remains in tissues. -They become edematous (swollen) and blood pressure may drop to dangerously low levels because of water lost from bloodstream.

PREVENTING CLOTS FROM FORMING

-calcium is essential requirement for blood clotting -blood samples can be kept from clotting by adding few crystals of sodium oxalate, sodium citrate, or EDTA29—salts that bind calcium ions and prevent them from participating in coagulation reactions. -Blood-collection equipment such as hematocrit tubes may be coated with heparin, a natural anticoagulant -Since vitamin K is required for synthesis of clotting factors, anything that antagonizes vitamin K usage makes blood clot less readily. -One vitamin K antagonist is coumarin, a sweet-smelling extract of tonka beans, sweet clover, and other plants, used in perfume. -Taken orally by patients at risk for thrombosis, coumarin takes up to 2 days to act, but has longer-lasting effects than heparin. -A similar vitamin K antagonist is pharmaceutical preparation warfarin (Coumadin), which was originally developed as a pesticide—it makes rats bleed to death.

INTRINSIC CLOTTING MECHANISM

-can begin without tissue damage. -Activation of HAGEMAN FACTOR (FACTOR XII) initiates intrinsic clotting. -occurs when blood is exposed to foreign surface such as collagen in connective tissue instead of smooth endothelial lining of intact blood vessels or when blood is stored in glass container. -Activated FACTOR XII activates FACTOR XI, which activates FACTOR IX. -FACTOR IX joins with FACTOR VIII and platelet phospholipids to activate FACTOR X. -These reactions require calcium ions -lead to production of PROTHROMBIN ACTIVATOR. -Subsequent steps of blood clot formation are same as extrinsic mechanism. -When FACTOR X is activated, remaining events are same in intrinsic and extrinsic mechanisms, represented by COMMON PATHWAY

ANEMIA

-causes of anemia fall into three categories: (1) inadequate erythropoiesis or hemoglobin synthesis, (2) hemorrhagic anemia from bleeding, and (3) hemolytic anemia from RBC destruction. often results from kidney failure, because RBC production depends on erythropoietin, which is produced mainly by kidneys. -Erythropoiesis declines with age, because kidneys atrophy and produce less EPO as we get older. -elderly get less exercise and eat less well, both factors reduce erythropoiesis. -Nutritional anemia results from dietary deficiency of any requirements for erythropoiesis -most common form is iron-deficiency anemia, characterized by small pale erythrocytes. -Iron-deficiency anemia caused by blood loss without getting enough dietary iron to compensate for it. -deficiency of vitamin B12 also causes anemia, but B12 is so abundant in meat that deficiency is rare except in strict vegetarians. -More often, B12 deficiency occurs when glands of stomach fail to produce substance called intrinsic factor that small intestine needs to absorb B12 -Elderly people develop pernicious anemia, an autoimmune disease in which antibodies destroy stomach tissue. -Pernicious anemia can be hereditary. -Without proper postsurgical management, gastric-bypass and gastrectomy patients can develop similar anemia because of removal of stomach tissue or surgical rearrangement of stomach, disconnecting it from small intestine where intrinsic factor is needed. -Such anemias are treatable with vitamin B12 injections or oral B12 and intrinsic factor. -Hypoplastic anemia is caused by decline in erythropoiesis, whereas complete failure or destruction of myeloid tissue produces aplastic anemia, -Aplastic anemia is complete cessation of erythropoiesis. -Aplastic anemia leads to grotesque tissue necrosis and blackening of skin. -Barring successful treatment, most victims die within a year. -About half of all cases of hypoplastic anemia are of unknown or hereditary cause, especially in adolescents and young adults. -Anemia has three potential consequences: -tissues suffer hypoxia (oxygen deprivation). -The individual is lethargic and becomes short of breath upon physical exertion. -The skin is pallid because of deficiency of hemoglobin. -Severe anemic hypoxia can cause life-threatening necrosis of brain, heart, and kidney tissues. -Blood osmolarity is reduced. -More fluid transfers from bloodstream to intercellular spaces, resulting in edema. -Blood viscosity is reduced. -Because blood puts up less resistance to flow, heart beats faster than normal and cardiac failure may ensue. -Blood pressure drops because of reduced volume and viscosity.

HEMOGLOBIN (Hgb)

-consists of four protein chains called GLOBINS Two of these: -alpha (α) chains, are 141 amino acids long, and other two, -beta (β) chains, are 146 amino acids long. -Each chain is conjugated with nonprotein moiety called HEME GROUP, which binds oxygen to iron atom (Fe) at its center. -Each heme carries one molecule of O2; -Hemoglobin molecule can transport up to 4 O2. -5% of CO2 in bloodstream is transported by hemoglobin but bound to globin rather than to heme. - Hemoglobin exists in several forms with slight differences in globin chains. -ADULT HEMOGLOBIN (HbA). -2.5% of adult's hemoglobin is form called HbA2 -HbA2 has two delta (δ) chains in place of beta chains. -most common adult form of hemoglobin -fetus produces form called fetal hemoglobin (HbF), which has two gamma (γ) chains in place of beta chains. -delta and gamma chains are same length as beta chains but differ in amino acid sequence. -HbF binds oxygen more tightly than HbA does; this enables fetus to extract oxygen from mother's bloodstream.

LEUKOCYTES (WBCs)

-least abundant formed elements, totaling only 5,000 to 10,000 WBCs/µL. -cannot live long without them, because they afford protection against infection and other diseases. -easily recognized in stained blood films because they have conspicuous nuclei that stain from light violet to dark purple with most common blood stains. -much more abundant in body than their low number in blood films, because they spend only a few hours in blood, then migrate to connective tissues and spend rest of lives there. -differ from erythrocytes in that they retain organelles throughout life; when viewed with transmission electron microscope, they show complex internal structure Among their organelles are instruments of protein synthesis—nucleus, rough endoplasmic reticulum, ribosomes, and Golgi complex -leukocytes must synthesize proteins in order to carry out functions. -Some proteins are packaged into lysosomes and other organelles, which appear as conspicuous cytoplasmic granules that distinguish one WBC type from another.

ERYTHROCYTE LIFE HISTORY

-lives for 120 days from time it is produced in red bone marrow until it dies -birth and death of RBCs amount to nearly 100 billion cells per day (1 million per second), or a packed cell volume of 20 mL/day.

ERYTHROCYTE STRUCTURE

-cytoplasm of an RBC consists mainly of 33% solution of hemoglobin (about 280 million molecules per cell). -HEMOGLOBIN is red pigment that gives RBCs color and name. -known especially for role in oxygen transport -aids in transport of carbon dioxide -aids buffering of blood pH. -cytoplasm contains enzyme, carbonic anhydrase (CAH), that catalyzes reaction -plasma membrane of mature RBC has glycolipids on outer surface that determines blood type. -2 cytoskeletal proteins, spectrin and actin on INNER surface that give membrane resilience and durability. -especially important when RBCs pass through small blood capillaries and sinusoids. -Many passages are narrower than diameter of RBC, forcing RBCs to stretch, bend, and fold as they squeeze through. -When they enter larger vessels, RBCs spring back to discoidal shape like an air-filled inner tube. -Some believe that biconcave shape maximizes ratio of cell surface area to volume and promotes quick diffusion of oxygen to all the hemoglobin in cell. -only place RBCs load oxygen is in capillaries, and while squeezing through tiny capillaries, they are not biconcave but compressed into ovoid or teardrop shapes. -They spring back to biconcave shape when reentering larger blood vessels, but no oxygen pickup occurs here. -Another hypothesis is: biconcave shape minimizes RBC spin (like a spinning ice-skater with her arms extended) and turbulence, enabling dense slurry of RBCs to flow through larger blood vessels with a smooth laminar flow. -It has been argued that it is easiest, most stable shape for cell and its cytoskeleton to relax into when nucleus is removed, and it may have no physiological function at all.

INITIATION OF COAGULATION

-damaged blood vessel and perivascular tissues release lipoprotein mixture called tissue thromboplastin (factor III). -Factor III combines with factor VII to form complex that, in presence of Ca2+, activates factor X. -extrinsic and intrinsic pathways differ only in how they arrive at active factor X. -Therefore, before examining their common pathway from factor X to end, consider how intrinsic pathway reaches this step. -Everything needed to initiate INTRINSIC MECHANISM is present in plasma or platelets. -When platelets degranulate, they release factor XII/Hageman factor, (named for patient in whom it was discovered). -Through a cascade of reactions, this leads to activated factors XI, IX, and VIII, in that order—each serving as enzyme that catalyzes the next step—and finally to factor X. -This pathway requires Ca2+ and PF3.

HYPOXEMIA

-deficient amount of oxygen in blood -Hypoxemia has many causes other than blood loss. -low level of oxygen in atmosphere. If you were to move from Miami to Denver, for example, lower O2 level at high elevation of Denver would produce temporary hypoxemia and stimulate EPO secretion and erythropoiesis. -blood of average adult has about 5 million RBCs/µL -people who live at high elevation have counts of 7 to 8 million RBCs/µL. -Another cause of hypoxemia is abrupt increase in body's oxygen consumption. -If formerly lethargic person takes up tennis or aerobics, the muscles consume oxygen more rapidly and create state of hypoxemia that stimulates erythropoiesis. -Endurance-trained athletes commonly have RBC counts as high as 6.5 million RBCs/µL. -"Doping" with erythropoietin to build RBC count and endurance has cost many athletes careers and honors. -Not all hypoxemia corrected by increasing erythropoiesis. -In emphysema less lung tissue is available to oxygenate blood. -Raising RBC count cannot correct this, but kidneys and bone marrow have no way of knowing it. -The RBC count continues to rise in futile attempt to restore homeostasis, resulting in dangerous excess called polycythemia

ERYTHROCYTE FORM & FUNCTION

-discoidal cell with biconcave shape—thick rim and thin sunken center. -7.5 µm in diameter and 2.0 µm thick at rim -most cells, including white blood cells, have abundance of organelles, RBCs lose nucleus and other organelles during maturation and devoid of internal structure. -When viewed with transmission electron microscope, interior of RBC appears gray. -Lack mitochondria, and rely exclusively on anaerobic fermentation to produce ATP. -lack of aerobic respiration prevents them from consuming oxygen that they transport to other tissues. -RBCs made to deliver oxygen, not consume it. -only human cell that carry on anaerobic fermentation indefinitely.

GLOBULINS

-divided into three subclasses; -from smallest to largest in molecular weight, they are: -alpha (α), -beta (β), -gamma (γ) globulins. -play various roles in solute transport, clotting, and immunity.

PRIMARY POLYCYTHEMIA

-due to cancer of erythropoietic line of red bone marrow. -can result in RBC count as high as 11 million RBCs/µL and hematocrit as high as 80%.

ERYTHROPOIESIS

-formation of red blood cells -Reticulocytes leave bone marrow and enter circulating blood. -In day or two, last of polyribosomes disintegrate and disappear, and cell is mature erythrocyte. -Normally 0.5% to 1.5% of circulating RBCs are reticulocytes, but percentage rises under certain circumstances. -Blood loss stimulates accelerated erythropoiesis and leads to increasing number of reticulocytes in circulation —because bone marrow hurries to replenish lost RBCs it rushes many developing RBCs into circulation early.

BLOOD PLASMA

-has no anatomy that we can study visually, -matrix of blood -complex mixture of water, proteins, nutrients, electrolytes, nitrogenous wastes, hormones, and gases -Protein is most abundant plasma solute by weight, totaling 6 to 9 g/dL. -Plasma proteins play variety of roles including clotting, defense against pathogens, and transport of other solutes such as iron, copper, lipids, and hydrophobic hormones. -There are three major categories of plasma proteins: albumin, globulins, and fibrinogen -Many other plasma proteins are indispensable to survival, but account for less than 1% of total. -In addition to protein, plasma contains such nitrogen-containing compounds as free amino acids and nitrogenous wastes. -Nitrogenous wastes are toxic end products of catabolism. -The most abundant is urea, a product of amino acid catabolism. -These wastes are normally excreted by kidneys at rate that balances their production. -plasma also transports nutrients absorbed by digestive tract, including glucose, amino acids, fats, cholesterol, phospholipids, vitamins, and minerals. -transports dissolved oxygen, carbon dioxide, and nitrogen . -dissolved nitrogen normally has no physiological role in body . -Electrolytes are another important component of blood plasma. -Sodium ions constitute 90% of plasma cations. -Sodium is more important than any other solute to osmolarity of blood. -As such, it has a major influence on blood volume and pressure; -people with high blood pressure are often advised to limit their sodium intake. -Electrolyte Concentrations are carefully regulated by body and have rather stable concentrations in plasma.

NEUTROPHIL

-most abundant WBCs —4,150 cells/µL and constituting 60% to 70% of circulating leukocytes. -nucleus is clearly visible -typically consists of three to five lobes connected by slender nuclear strands. -strands are sometimes so delicate that they are scarcely visible, and may seem as if it had multiple nuclei. -Young neutrophils have undivided band-shaped nucleus and are called band cells. -Neutrophils are also called polymorphonuclear leukocytes (PMNs) because of their varied nuclear shapes. -The cytoplasm contains fine reddish to violet specific granules, which contain lysozyme and other antimicrobial agents. -The individual granules are barely visible with the light microscope, but their combined effect gives the cytoplasm a pale lilac color. -Neutrophils are aggressively antibacterial cells. -Their numbers rise—a condition called neutrophilia—in response to bacterial infections. -They destroy bacteria Differential count (% of WBCs) 60% to 70% Mean absolute count 4,150 cells/µL Diameter 9-12 µm Appearance Nucleus usually with 3-5 lobes in S- or C-shaped array Fine reddish to violet specific granules in cytoplasm Variations in Number Increase in bacterial infections Functions Phagocytize bacteria Release antimicrobial chemicals

PLATELETS

-not cells, but small fragments of marrow cells called megakaryocytes. -second most abundant formed elements, after erythrocytes; -normal platelet count from 130,000 to 400,000 platelets/µL (averaging about 250,000). -platelet count can vary greatly under different physiological conditions and in blood samples taken from various places in body. -platelets are so small (2 to 4 µm in diameter) that they contribute even less than WBCs to blood volume. -Platelets have complex internal structure that includes lysosomes, mitochondria, microtubules, and microfilaments; granules filled with platelet secretions; and system of channels called open canalicular system, which opens onto platelet surface -no nucleus. -When activated, they form pseudopods and capable of ameboid movement.

CARDIOVASCULAR SYSTEM

-only refers to Heart & Vessels/ NOT blood

HEMOPOIESIS (HEMATOPOIESIS)

-process of blood cell formation -occurs primarily in red bone marrow -starts with undifferentiated cells called HEMOCYTOBLASTS -Hemocytoblasts give rise to many different cell types that make up cellular elements of blood -Number of hormones and growth factors known as COLONY STIMULATING FACTORS (CSFs), influence hemocytoblasts to differentiate along either MYELOID or LYMPHOID Cell line -As hematopoietic stem cells divide, new cells, myeloid and lymphoid stem cells, respond to different secreted growth factors, called hematopoietic growth factors, that turn on and off genes -MYELOID CELL LINE forms ERYTHROCYTES (RBCs) and MEGAKARYOCYTES which give rise to PLATELETS -MYELOID STEM CELLS form LEUKOCYTES (WBCS), except for Lymphocytes -LYMPHOID CELL LINE produce LYMPHOCYTES -Hemopoiesis along MYELOID Cell Line follows one of 3 pathways: -ERYTHROPOIESIS -THROMBOPOIESIS -LEUKOPOIESIS -ERYTHROPIESIS produces RBCs-begins with stimulation of MYELOID STEM CELLS by CSFs This produces a PROGENITOR CELL that gives rise to a PROERYTHROBLAST-(1st committed cell along pathway) -Hormone ERYTHROPOIETIN initiates ERYTHROBLAST stage that stimulate PROERYTHROBLASTS to form ERYTHROBLASTS -ERYTHROBLASTS synthesize HEMOGLOBIN and decrease in size which gives rise to NORMOBLAST -NORMOBLAST ejects nucleus which forms a RETICULOCYTE -After RETICULOCYTE enters blood organelles degenerate and then considered MATURE ERYTHROCYTE -Exposure to growth factors sculpts formed elements of blood, including cellular components of immune system.

ERYTHROCYTE PRODUCTION

-process takes 3 to 5 days -involves four major developments: -reduction in cell size, -increase in cell number, -synthesis of hemoglobin -loss of nucleus and other organelles. -Erythropoiesis begins when hematopoietic stem cell (HSC) becomes an erythrocyte colony-forming unit (ECFU) which has receptors for erythropoietin (EPO), a hormone secreted by kidneys. -EPO stimulates ECFU to transform into an erythroblast (normoblast). -Erythroblasts multiply, build up large cell population, and synthesize hemoglobin. -When completed, nucleus shrivels and discharged from cell. -cell is now called a reticulocyte, named for temporary network (reticulum) of ribosome clusters transcribing cell's remaining mRNA

PLATELET PRODUCTION

-production of platelets is division of hematopoiesis called thrombopoiesis (Platelets occasionally called thrombocytes) -Thrombopoiesis is stimulated by hormone from liver and kidneys called thrombopoietin . -Some hematopoietic stem cells develop receptors for thrombopoietin and, become megakaryoblasts—cells committed to platelet-producing line. -megakaryoblast duplicates its DNA repeatedly without undergoing nuclear or cytoplasmic division. The result is a megakaryocyte. -MEGAKARYOCYTE is a gigantic cell up to 150 µm in diameter, visible to naked eye, with a huge multilobed nucleus and multiple sets of chromosomes -Most megakaryocytes live in red bone marrow adjacent to blood-filled spaces called sinusoids, lined with thin simple squamous epithelium called endothelium -Recent research has discovered that megakaryocytes migrate freely between lungs and bone marrow and produce most platelets while in lungs. -A megakaryocyte sprouts long tendrils called proplatelets that protrude through endothelium into blood of sinusoid. -The blood flow shears off proplatelets, which break up into platelets as they travel in bloodstream. -Much of this breakup is thought to occur when they pass through small vessels of lungs, because blood counts show more proplatelets entering lungs than leaving and more platelets exiting. -25%-40% of platelets are stored in spleen and released as needed. -The remainder circulate freely in blood and live for 5-6 days. -Anything that interferes with platelet production can produce dangerous platelet deficiency called thrombocytopenia

HEMOLYSIS

-rupture or destruction of red blood cells.

BLOOD FRACTIONATION

-separation of blood into its basic components: formed elements, plasma, and serum -based on centrifugation and coagulation -First, a sample of blood in a tube is spun in a centrifuge for a few minutes. -RBCs, the densest elements, settle to bottom of tube and constitute 37% to 52% of total volume—a value called hematocrit or packed cell volume. -WBCs and platelets settle into a narrow cream- or buff-colored zone called the buffy coat just above RBCs; they total 1% or less of the blood volume. -At top of tube is plasma, which is 47% to 63% of blood volume. -If plasma is separated, allowed to coagulate (clot), and centrifuged again, clotting proteins (mainly fibrin) settle to bottom of tube and overlying fluid is called blood serum. -Serum is clinically valuable as vehicle for vaccines, antivenins, and other therapies; for certain blood tests, such as for hepatitis and prostate cancer; and for many clinical and research laboratory uses.

ALBUMIN

-smallest and most abundant plasma protein. -serves to transport various solutes and buffer pH of blood plasma. -makes major contribution to two physical properties of blood: its viscosity and osmolarity -changes in albumin concentration can significantly affect blood volume, pressure, and flow.

TYPES OF LEUKOCYTES

-there are five kinds of leukocytes. -distinguished from each other by size and abundance, size and shape of nuclei, presence or absence of certain cytoplasmic granules, coarseness and staining properties of granules, most importantly by functions. -Individual WBC types rise or fall in number in various disease conditions and physiological states. -All WBCs have lysosomes called nonspecific granules in cytoplasm, also called azurophilic granules because they absorb blue or violet dyes of blood stains. -Three of the five types—neutrophils, eosinophils, and basophils—are granulocytes because they have various kinds of specific granules that stain conspicuously and distinguish each cell type from others. -Basophils granules stain with methylene blue, a basic dye in common blood-staining mixture called Wright's stain. -Eosinophils stain with eosin, an acidic dye in Wright's stain. -The granules of neutrophils don't stain intensely with either basic or acidic stains. -Specific granules contain enzymes and other chemicals employed in defense against pathogens. -The two remaining WBC types—monocytes and lymphocytes—are agranulocytes because they lack specific granules. -Nonspecific granules are inconspicuous to light microscope, and have clear-looking cytoplasm

LEUKOCYTE DISORDERS

-total WBC count 5,000 to 10,000 WBCs/µL. -count below this range, called leukopenia is seen in lead, arsenic, and mercury poisoning; radiation sickness; and such infectious diseases as measles, mumps, chickenpox, polio, influenza, typhoid fever, and AIDS. -can also be produced by glucocorticoids, anticancer drugs, and immunosuppressant drugs given to organ-transplant patients. -Since WBCs are protective cells, leukopenia presents an elevated risk of infection and cancer. -count above 10,000 WBCs/µL, called leukocytosis, indicates infection, allergy, or other diseases but can occur in response to dehydration or emotional disturbances -DIFFERENTIAL WBC count is more useful than a TOTAL WBC because it identifies what percentage of the total WBC count consists of each type of leukocyte

EXTRINSIC CLOTTING MECHANISM

-triggered when blood contacts damaged blood vessel walls or tissues outside blood vessels. -damaged tissues release tissue THROMBOPLASTIN (FACTOR III), that is associated with disrupted cell membranes. -Tissue thromboplastin activates FACTOR VII, which combines with and activates FACTOR X. -FACTOR X combines with and activates FACTOR V. -These reactions require CALCIUM IONS (FACTOR IV), lead platelets to produce and release an enzyme called PROTHROMBIN ACTIVATOR -PROTHROMBIN (FACTOR II) is an alpha globulin that liver continually produces and is normal constituent of plasma. -In presence of calcium ions, PROTHROMBIN ACTIVATOR converts prothrombin into THROMBIN (FACTOR IIa). -THROMBIN catalyzes reaction that fragments FIBRINOGEN (FACTOR I). -FIBRINOGEN FRAGMENTS join, forming long threads of fibrin. -FIBRINOGEN is soluble plasma protein -FIBRIN is insoluble. -THROMBIN activates FACTOR XIII, which strengthens and stabilizes fibrin threads -Once fibrin threads form, they stick to exposed surfaces of damaged blood vessels, creating meshwork that entraps blood cells and platelets -Resulting mass is a blood clot, which blocks vascular break and prevent further blood loss. -Amount of prothrombin activator in blood is directly proportional to degree of tissue damage. -Once blood clot begins to form, it promotes additional clotting, because thrombin acts directly on prothrombin activator, causing prothrombin to form more thrombin. -This type of self-initiating action is an example of positive feedback, in which original action stimulates more of same type of action. -Such mechanism produces unstable conditions and can operate for only a short time in a living system, because life requires maintenance of a stable internal environment -Normal clotting is temporary response to injury that helps preserve internal environment by minimizing blood loss. -Normally, blood flow throughout body prevents formation of massive clot in cardiovascular system by rapidly carrying excess thrombin away and keeping concentration too low to promote further clotting. -ANTITHROMBIN, in blood and on surfaces of endothelial cells that line blood vessels, limits thrombin formation. -blood coagulation usually occurs only in blood that is standing still or moving slowly, and clotting ceases where clot contacts circulating blood. -In DISSEMINATED INTRAVASCULAR COAGULATION (DIC), clotting is abnormally activated in several regions of cardiovascular system. -This condition is associated with bacterial infection or bacterial toxins in blood or with disorder causing widespread tissue damage. -Many small clots form and obstruct blood flow into various tissues and organs, particularly kidneys. -As plasma clotting factors and platelets are depleted, severe bleeding may occur.

It is impossible for a type O+ baby to have a type ________ mother. AB- O- O+ A+ B+

AB-

CIRCULATORY SYSTEM

CONSISTS OF: -Heart -Blood vessels -Blood PURPOSE: -transport substances from place to place in blood

CHARLES DREW

BLOOD-BANKING PIONEER: -scientist remembered for his seminal contributions in hematology and civil rights, and for sadly ironic end to his life. -After receiving his M.D. from McGill University of Montreal in 1933, Drew became first black person to pursue advanced degree of Doctor of Science in Medicine, for which he studied transfusion and blood banking at Columbia University. -He became director of a new blood bank at Columbia Presbyterian Hospital in 1939 and organized numerous blood banks during World War II. 1904-50: -Drew saved countless lives by convincing physicians to use plasma rather than whole blood for battlefield and other emergency transfusions. -Whole blood could be stored for only a week and given only to recipients with compatible blood types. -Plasma could be stored longer and was less likely to cause transfusion reactions. -When the U.S. War Department issued a directive forbidding the storage of "Caucasian and Negro blood" in the same military blood banks, Drew denounced the order and resigned his position. -He became a professor of surgery at Howard University in Washington, D.C., and later chief of staff at Freedmen's Hospital. -He was a mentor for numerous young black physicians and campaigned to get them accepted into the medical community. -The American Medical Association, however, refused to admit black members until the 1960s, excluding even Drew himself. -Late one night in 1950, Drew and three colleagues set out to volunteer their medical services to an annual free clinic in Tuskegee, Alabama. -Drew fell asleep at the wheel and was critically injured in the resulting accident. -Contrary to a myth that Drew was refused emergency treatment because of his race, doctors at the nearest hospital administered blood and attempted to revive him. -Yet, for all the lives he saved through his pioneering work in transfusion, Drew himself bled to death at the age of 45.

After birth, what one cell type is the starting point for all hematopoiesis?

Hematopoietic stem cells in RED BONE MARROW is starting point for all hemopoiesis

LEUKOCYTE LIFE HISTORY

Leukopoiesis: production of white blood cells, begins with hematopoietic stem cells (HSCs) -Some HSCs differentiate into distinct types of colony-forming units (CFUs) and then go on to produce other cell lines -each of them irreversibly committed to a certain outcome -CFUs have receptors for colony-stimulating factors (CSFs). -Mature lymphocytes and macrophages secrete several types of CSFs in response to infections and other immune challenges. -Each CSF stimulates different WBC type to develop in response to specific needs. -bacterial infection may trigger production of neutrophils -allergy stimulates eosinophil production -each process working through its own CSF. -Red bone marrow stores granulocytes and monocytes until they are needed and contains 10 to 20 times more of these cells than circulating blood does. -Lymphocytes begin developing in bone marrow but don't stay there. -Some types mature in bone marrow and others migrate to thymus to complete development. -Mature lymphocytes from both locations then colonize spleen, lymph nodes, and other lymphatic organs and tissues. -Circulating leukocytes don't stay in blood very long. -Granulocytes circulate for 4 to 8 hours and then migrate into tissues, where they live another 4 or 5 days. -Monocytes travel in blood for 10 to 20 hours, then migrate into tissues and transform into variety of macrophages, which live a few years. -Lymphocytes, responsible for long-term immunity, survive from few weeks to decades; -they leave bloodstream for tissues and then enter lymphatic system, which empties them back into bloodstream. -Leukocytes continually recycled from blood to tissue fluid to lymph and back to blood. -When leukocytes die, they are phagocytized and digested by macrophages. -Dead neutrophils are responsible for creamy color of pus, and are disposed of by rupture of blister onto skin surface.

COMPLETE BLOOD COUNT

One of the most common laboratory tests in both routine medical examinations and the diagnosis of disease is a complete blood count (CBC). The CBC yields a highly informative profile of data on multiple blood values: the number of RBCs, WBCs, and platelets per microliter of blood; the relative numbers (percentages) of each WBC type, called a differential WBC count; hematocrit; hemoglobin concentration; and various RBC indices such as RBC size (mean corpuscular volume, MCV) and hemoglobin concentration per RBC (mean corpuscular hemoglobin, MCH). RBC and WBC counts used to require the microscopic examination of films of diluted blood on a calibrated slide, and a differential WBC count required examination of stained blood films. Today, most laboratories use electronic cell counters. These devices draw a blood sample through a very narrow tube with sensors that identify cell types and measure cell sizes and hemoglobin content. These counters give faster and more accurate results based on much larger numbers of cells than the old visual methods. However, cell counters still misidentify some cells, and a medical technologist must review the results for suspicious abnormalities and identify cells that the instrument cannot. The wealth of information gained from a CBC is too vast to give more than a few examples here. Various forms of anemia are indicated by low RBC counts or abnormalities of RBC size, shape, and hemoglobin content. A platelet deficiency can indicate an adverse drug reaction. A high neutrophil count suggests bacterial infection, and a high eosinophil count suggests an allergy or parasitic infection. Elevated numbers of specific WBC types or WBC stem cells can indicate various forms of leukemia. If a CBC does not provide enough information or if it suggests other disorders, additional tests may be done, such as coagulation time and bone marrow biopsy

How does a blood clot differ from a platelet plug?

PLATELET PLUG lacks FIBRIN MESH that a Blood clot has

PLATELET PLUG FORMATION

Platelets don't adhere to the endothelium that lines healthy blood vessels and the heart. The endothelium is normally very smooth and coated with prostacyclin, a platelet repellent. When a vessel is broken, however, collagen fibers of its wall are exposed to the blood. Upon contact with collagen or other rough surfaces, platelets grow long spiny pseudopods that adhere to the vessel and to other platelets; the pseudopods then contract and draw the walls of the vessel together. The mass of platelets thus formed, called a platelet plug, may reduce or stop minor bleeding. The platelet plug is looser and more delicate than the blood clot to follow; for this reason, a bleeding injury should be blotted with absorbent paper rather than wiped. As platelets aggregate, they undergo degranulation—the exocytosis of their cytoplasmic granules and release of factors that promote hemostasis. Among these are serotonin, a vasoconstrictor; adenosine diphosphate (ADP), which attracts more platelets to the area and stimulates their degranulation; and thromboxane A2, an eicosanoid that promotes platelet aggregation, degranulation, and vasoconstriction. Thus, a positive feedback cycle is activated that can quickly seal a small break in a blood vessel.

________ results from a mutation that changes one amino acid in the hemoglobin molecule.

SICKLE-CELL DISEASE

LEUKEMIA

cancer of the hematopoietic tissues that usually produces an extraordinarily high number of circulating leukocytes and their precursors (fig. 18.19). Leukemia is classified as myeloid or lymphoid, acute or chronic. Myeloid leukemia is marked by uncontrolled granulocyte production, whereas lymphoid leukemia involves uncontrolled lymphocyte or monocyte production. Acute leukemia appears suddenly, progresses rapidly, and causes death within a few months if it is not treated. Chronic leukemia develops more slowly and may go undetected for many months; if untreated, the typical survival time is about 3 years. Both myeloid and lymphoid leukemia occur in acute and chronic forms. The greatest success in treatment and cure has been with acute lymphoblastic leukemia, the most common type of childhood cancer. Treatment employs chemotherapy and marrow transplants along with the control of side effects such as anemia, hemorrhaging, and infection -As leukemic cells proliferate, they replace normal bone marrow and a person suffers from a deficiency of normal granulocytes, erythrocytes, and platelets. Although enormous numbers of leukocytes are produced and spill over into the bloodstream, they don't provide the usual protective functions of WBCs. They are like an army of children, present in vast numbers but too immature to perform a useful defensive role. The deficiency of competent WBCs leaves the patient vulnerable to opportunistic infection—the establishment of pathogenic organisms that usually cannot get a foothold in people with healthy immune systems. The RBC deficiency renders the patient anemic and fatigued, and the platelet deficiency results in hemorrhaging and impaired blood clotting. The immediate cause of death is usually hemorrhage or infection. Cancerous hematopoietic tissue often metastasizes from the bone marrow or lymph nodes to other organs of the body, where the cells displace or compete with normal cells. Metastasis to the bone tissue itself is common and leads to bone and joint pain.

Serum is blood plasma minus its sodium ions. calcium ions. clotting proteins. globulins. albumin.

clotting proteins.

MONOCYTE

largest WBCs seen on a blood slide, often two or three times the diameter of an RBC. They average about 460 cells/µL and about 3% to 8% of the WBC count. The nucleus is large and clearly visible, often a relatively light violet, and typically ovoid, kidney-shaped, or horseshoe-shaped. The cytoplasm is abundant and contains sparse, fine granules. In prepared blood films, monocytes often assume sharply angular to spiky shapes (see fig. 18.1). The monocyte count rises in inflammation and viral infections. Monocytes go to work only after leaving the bloodstream and transforming into large tissue cells called macrophages (MAC-ro-fay-jez). Macrophages are highly phagocytic cells that consume dead or dying host and foreign cells, pathogenic chemicals and microorganisms, and other foreign matter equivalent to as much as 25% of their own volume per hour. They also chop up or process foreign antigens and display fragments of them on the cell surface to alert the immune system to the presence of a pathogen. Thus, they and a few other cells are called antigen-presenting cells (APCs Differential count (% of WBCs) 3% to 8% Mean absolute count 456 cells/µL Diameter 12-15 µm Appearance Nucleus ovoid, kidney-shaped, or horseshoe-shaped; violet Abundant cytoplasm with sparse, fine nonspecific granules Sometimes very large with stellate or polygonal shapes Variations in Number Increase in viral infections and inflammation Functions Differentiate into macrophages (large phagocytic cells of the tissues) Phagocytize pathogens, dead neutrophils, and debris of dead cells Present antigens to activate other cells of immune system

AGRANULOCYTES

lymphocytes, monocytes.

VASCULAR SPASM

most immediate protection against blood loss is vascular spasm, a prompt constriction of the broken vessel. Several things trigger this reaction. An injury stimulates pain receptors, some of which directly innervate nearby blood vessels and cause them to constrict. This effect lasts only a few minutes, but other mechanisms take over by the time it subsides. Injury to the smooth muscle of the blood vessel itself causes a longer-lasting vasoconstriction, and platelets release serotonin, a chemical vasoconstrictor. Thus, the vascular spasm is maintained long enough for the other two hemostatic mechanisms to come into play.

Which of the following conditions is most likely to cause hemolytic anemia? folic acid deficiency iron deficiency mushroom poisoning alcoholism hypoxemia

mushroom poisoning

BASOPHIL

rarest of all formed elements. They average about 40 cells/µL and usually constitute less than 0.5% of the WBC count. They can be recognized mainly by an abundance of very coarse, dark violet specific granules. The nucleus is largely hidden from view by these granules, but is large, pale, and typically S- or U-shaped. Basophils secrete two chemicals that aid in the body's defense processes: (1) histamine, a vasodilator that widens the blood vessels, speeds the flow of blood to an injured tissue, and makes the blood vessels more permeable so that blood components such as neutrophils and clotting proteins can get into the connective tissues more quickly; and (2) heparin, an anticoagulant that inhibits blood clotting and thus promotes the mobility of other WBCs in the area. They also release chemical signals that attract eosinophils and neutrophils to a site of infection. Differential count (% of WBCs) < 0.5% Mean absolute count 44 cells/µL Diameter 8-10 µm Appearance Nucleus large and U- to S-shaped, but typically pale and obscured from view Coarse, abundant, dark violet specific granules in cytoplasm Variations in Number Relatively stable Increase in chickenpox, sinusitis, diabetes mellitus, myxedema, and polycythemia Functions Secrete histamine (a vasodilator), which increases blood flow to a tissue Secrete heparin (an anticoagulant), which promotes mobility of other WBCs by preventing clotting

LYMPHOCYTE

second to neutrophils in abundance and are thus quickly spotted when you examine a blood film. They average about 2,200 cells/µL and are 25% to 33% of the WBC count. They include the smallest WBCs; at 5 to 17 µm in diameter, they range from smaller than RBCs to two and a half times as large. They are sometimes classified into three size classes (table 18.6), but there are gradations between them. Medium and large lymphocytes are usually seen in fibrous connective tissues and only occasionally in the circulating blood (see fig. 18.1). The lymphocytes seen in blood films are mostly in the small size class. These are sometimes difficult to distinguish from basophils, but most basophils are conspicuously grainy, whereas the lymphocyte nucleus is uniform or merely mottled. Basophils also lack the rim of clear cytoplasm seen in most lymphocytes. Large lymphocytes are sometimes difficult to distinguish from monocytes. The lymphocyte nucleus is round, ovoid, or slightly dimpled on one side, and usually stains dark violet. In small lymphocytes, it fills nearly the entire cell and leaves only a narrow rim of light blue cytoplasm, often barely detectable, around the cell perimeter. The cytoplasm is more abundant in medium and large lymphocytes. There are several subclasses of lymphocytes with different immune functions (see section 21.1b), but they cannot be distinguished by microscopic examination of blood films. Collectively, they destroy cells that have been infected with viruses or turned malignant, and foreign cells (including parasites) that have been introduced into the body; they secrete chemicals that communicate with other WBCs and coordinate their actions; they present antigens to activate immune responses; they give rise to the cells that secrete antibodies; and they provide long-term immunity to pathogens. Differential count (% of WBCs) 25% to 33% Mean absolute count 2,185 cells/µL Diameter Small class 5-8 µm Medium class 10-12 µm Large class 14-17 µm Appearance Nucleus round, ovoid, or slightly dimpled on one side, of uniform or mottled dark violet color In small lymphocytes, nucleus fills nearly all of the cell and leaves only a scanty rim of clear, light blue cytoplasm. In larger lymphocytes, cytoplasm is more abundant; large lymphocytes may be hard to differentiate from monocytes. Variations in Number Increase in diverse infections and immune responses Functions Several functional classes usually indistinguishable by light microscopy Destroy cancer cells, cells infected with viruses, and foreign cells Present antigens to activate other cells of immune system Coordinate actions of other immune cells Secrete antibodies Serve in immune memory