Blood – Physical Characteristics

• Adult ♂ contains 5-6L • Adult ♀ contains 4-5L • T is about 100.4 F
– Is this higher or lower than normal body T?

• 5 times as viscous as water
– Is it more or less resistant to flow than water? – What accounts for its viscosity?

• pH ranges from 7.35 – 7.45 (slightly alkaline) • Color ranges from scarlet (oxygenated blood) to a deep red (deoxygenated blood).

Whole Blood

Plasma

Formed Elements (37-54%)

(46-63%)

1. Water (92%) 2. Plasma Proteins (7%) 3. Other Solutes (1%)

1. Red Blood Cells (99.9%) 2. Platelets 3. White Blood Cells
(0.1%)

Functions of Blood
• Transportation of dissolved gases, nutrients, hormones, and metabolic wastes • Regulation of the pH and electrolyte composition of interstitial fluids throughout the body • Restriction of fluid losses • Defense against toxins and pathogens • Stabilization of body temperature

These red blood cells function in oxygen transport

Blood and Transportation
• Red blood cells are packed with the protein hemoglobin (Hb) which carries O2 • CO2 is carried by Hb, and dissolved in plasma in multiple ways • Nutrients absorbed at the GI tract, or released by the liver or adipocytes, are distributed by blood • Hormones (blood-borne chemical messengers) are transported from the endocrine glands where they’re produced to their target organs via the bloodstream • Metabolic wastes produced by tissue cells are absorbed by the blood and carried to the kidneys for excretion

g.) • Blood volume is regulated in response to the body’s water levels. • The blood acts as both a conduit and reservoir for important electrolytes (Na+. . If body T is too low.. lactic acid from skeletal muscles).Blood & Regulation • Blood absorbs heat from active skeletal muscles and distributes it to other tissues. that heat will be lost across the skin surface. that heat will be directed to the brain and to other T sensitive organs. • The blood absorbs and neutralizes the acids generated by active tissues (e. Ca2+. The above represents a relative distribution of blood in response to warm and cold ambient temperatures. If body T is already high. etc.

Notice the RBCs. . proteins that attack invading organisms and foreign compounds. Above. we have a SEM image of a blood clot. • Blood contains enzymes that respond to a break in a blood vessel wall by forming a clot to restrict further fluid loss.Blood & Protection • Blood transports white blood cells. specialized cells that migrate into peripheral tissues to fight infections and remove debris. • Blood delivers antibodies.

2-5.3 million RBCs – In ♀.5 million RBCs • Contains the red pigment hemoglobin which binds and transports O2 and CO2 • Each RBC is a biconcave disc Diameter → 8µm Thickness → 2.Red Blood Cells (Erythrocytes) • Most abundant blood cells (99.5µm . 1µL of blood contains 4.5-6. 1µL of blood contains 4.9% of formed elements) – In ♂.

Erythrocytes • Why a biconcave disc? – Provides a large surface area for O2 entry/exit – Enables them to bend and flex when entering small capillaries • RBCs lack a nucleus and most organelles. we have an RBC bending to fit thru a small capillary . – Instead they are simply membranous bags of hemoglobin – What is a functional advantage of the fact that the RBC lacks mitochondria? Here.

how many molecules of O2 can each Hb protein bind? . O2 can bind to Hb at the lungs and then be released at the tissues Note the 2  chains and 2 β chains. an iron-containing pigment – The iron ion in heme is able to reversibly bind an oxygen molecule. • Based on the above.Hemoglobin • Large protein consisting of 4 polypeptides – 2  chains and 2 β chains • Each chain contains a single molecule of heme. – Meaning. Notice how each has an associated heme molecule with an iron atom.

RBC Formation (Erythropoiesis) • In the adult. all blood cell formation (including erythropoiesis) occurs in the red bone marrow • All blood cells develop from stem cells called hemocytoblasts Red Blood Cells Monocytes Platelets Granulocytes Myeloid Stem Cell Hemocytoblast Lymphoid Stem Cell Lymphocytes .

Control of Erythrocyte Production Figure 10.5 .

the RBC cell membrane ruptures. • If the RBC hemolyzes. we have a macrophage phagocytizing multiple RBCs . – Why are they unable to synthesize replacements for damaged parts? • After ≈120d. its contained Hb will be excreted by the kidneys Above.Lifecycle of an RBC • RBCs are subjected to incredible mechanical stress. or the damage is detected by phagocytic cells and the RBC is engulfed.

• Liver modifies and then secretes bilirubin into the small intestine as a component of bile. plasma [bilirubin] rises and diffuses into peripheral tissues where it can impart a yellow color to the skin and sclera of the eye (jaundice) • Inside the large intestine. • Some urobilinogens are absorbed back into the circulation and excreted by the kidneys as urine. . • Bilirubin is released into the circulation where it binds to albumin and is transported to the liver. which has an orange-yellow color. The brownish color of feces is due to the presence of urobilinogens and stercobilinogens. Heme • Stripped of its iron and converted to bilirubin. Globular proteins • Disassembled into component amino acids and metabolized by the cell or released into the circulation for use by other cells 2.• Once an RBC has been engulfed & broken down by a phagocytic cell. 1. or if the liver is unable to absorb/excrete bilirubin. bacteria convert the bilirubin into urobilinogens and stercobilinogens. each component of Hb has a different fate. – If the bile ducts are blocked. Urobilinogen gives urine its yellow color.

Complete Blood Count (CBC) • Determination of the number of red and white blood cells per mL of blood • One of the most routinely performed clinical tests and a very valuable screening and diagnostic technique • Can be performed manually or via an electric counter • Different disorders can have a dramatic effect on the total number or relative proportion of blood cells. .

g. testosterone) stimulate RBC synthesis while estrogens do not • Determined by centrifuging a blood sample so that all formed elements come out of suspension • Low Hct values may indicate anemia whereas high values may indicate polycythemia ..Hematocrit • Percentage of whole blood occupied by packed red blood cells • Average in a ♂ is 46 (range of 40-54) • Average in a ♀ is 42 (range of 37-47) – Greater in ♂ b/c androgens (e.

• May be primary (polycythemia vera) and due to cancer of the bone marrow • May be secondary when less oxygen is available or erythropoietin (kidney hormone that stimulates RBC synthesis) production increases.e.. • How does polycythemia affect blood viscosity and thus affect blood flow? • Polycythemia can be treated by blood dilution – removing blood and replacing it with isotonic saline. • Endurance athletes often attempt to induce polycythemia as a means of increasing their athletic performance.Polycythemia • An elevated hematocrit with a normal blood volume • I. Why? . an increase in the number of erythrocytes in the blood.

and chilly? • Types: – – – – Hemorrhagic Aplastic Pernicious Thalassemia – Hemolytic – Iron-deficiency – Sickle Cell .Anemia • Condition where the blood has an abnormally low oxygen-carrying capacity • Symptom rather than a disease in/of itself • Why are anemic individuals often short of breath. fatigued.

. Left-hand slide is during aplastic anemia. or radiation. Why? . right-hand slide is almost back to normal – RBCs rupture (lyse) prematurely – Can be due to hemoglobin abnormalities. RBC loss) – Can be acute (stab wound perhaps) or chronic (due to hemorrhoids or an undiagnosed bleeding ulcer) • Hemolytic Compare the 2 slides of red bone marrow.e. Blue dots indicates developing blood cells. • Aplastic – Results from destruction of red bone marrow from bacterial toxins. drugs. parasitic or bacterial infection. Not only impacts RBCs but WBCs and platelets as well. mismatched blood transfusions.Anemia • Hemorrhagic – Results from blood loss (i. or autoimmune.

– Lack of intrinsic factor is often a cause of pernicious anemia • Thalassemias – Often seen in people of Mediterranean origin.Anemia • Iron-Deficiency – What role does iron play in oxygen transport? – Iron-deficiency anemia can be secondary to hemorrhagic anemia or can occur due to inadequate iron intake or absorption • Pernicious – Due to a lack of Vitamin B12 intake or absorption. – Stomach mucosa produces a substance called intrinsic factor which is necessary for Vitamin B12 absorption. – One of the globin genes is absent or faulty. .

• This causes the RBCs to become sickle-shaped and these malformed RBCs can then block and clog small blood vessels.Sickle-cell Anemia • A single mutation in the gene for the β chain of the globin molecule results in abnormal hemoglobin (HbS) • Due to the structural change. the β chains link together and become stiff rods under low-O2 conditions. .

This condition is erythroblastosis fetalis (a. hemolytic disease of the newborn) • The baby becomes anemic and hypoxic.. • The 1st child is fine – he/she has already been born.Erythroblastosis Fetalis • A type of hemolytic anemia • Suppose we have an Rh. the placenta ruptures and the baby’s blood mixes with the mother’s blood.k.mom whose 1st child is Rh+.a. her anti-Rh antibodies will cross the placenta and begin to attack the fetal RBCs. This sensitizes the mom to the Rh antigen and she begins to produce antibodies against the Rh antigen. . • However if the mom has a 2nd Rh+ child. At birth. brain damage and death may result if blood transfusions are not performed.

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Blood Types Recipient[1] Donor[1] O− O− Y O+ A− A+ B− B+ AB− AB+ O+ A− Y Y Y Y A+ B− Y Y Y Y Y Y B+ Y Y Y Y AB− Y Y Y Y AB+ Y Y Y Y Y Y Y Y .

Blood typing • http://nobelprize.org/educational_games/m edicine/landsteiner/ .

and they remove toxins. Compare that to RBCs • Most of the WBCs in the body at a given moment are in the connective tissue proper or in organs of the lymphatic system • Circulating WBCs are just a fraction of the total # . cyte=cell) • All contain nuclei and organelles unlike… • Help defend the body against invasion by pathogens.White Blood Cells • Leukocytes (leuko=white. wastes. and abnormal/damaged cells • A typical µL of blood contains 6000-9000 WBCs.

Agranulocytes – Do not contain visible granules. Granulocytes – Contain visible granules.1 Types of WBCs • Can be classified based on the appearance of granules when viewed under the light microscope. Includes: • • • Basophils Eosinophils Neutrophils 2 2. 1. Includes: • • Lymphocytes Monocytes .

This is known as positive chemotaxis and allows WBCs to converge on pathogens and damaged tissues . • Characteristics of circulating WBCs: – Capable of amoeboid movement • What role might this play in WBC function? – They can migrate out of the bloodstream by squeezing thru endothelial cells (this process is called diapedesis) – They are attracted to specific chemical stimuli.WBC Circulation and Movement • Use the bloodstream mainly to travel from organ to organ or to quickly go to areas of invasion/injury.

They are a. • Survive in the bloodstream for only about 10hrs .a polymorphonuclear leukocytes.Granulocytes Neutrophils • 50-70% of circulating WBCs • Cytoplasm is packed with pale (“neutral colored”) granules that contain bactericidal compounds • Mature neutrophils have a segmented nucleus. • Specialize in attacking and digesting bacteria that have been “marked” for destruction. • About 12µm in diameter. • Highly mobile and generally the first WBCs to arrive at an injury site.k.

multicellular parasites such as flukes or parasitic worms. • They will phagocytize antibody-coated bacteria. protozoa. • Important defenders against large. but their main method of attack is the exocytosis of toxic compounds onto the surface of their target. They  in # dramatically during a parasitic infection. • Also sensitive to allergens and  in # during allergic reactions as well.Granulocytes Eosinophils • 2-4% of circulating WBCs • Similar in size to neutrophils but have reddish-orange staining granules (Eos is the Greek goddess of dawn) and a bilobed nucleus. • Move into tissues after several hours and survive from minutes to days. . and cellular debris.

Granulocytes Basophils • >1% of circulating leukocytes • Smaller than neutrophils and eosinophils. • Contain granules that appear deep purple or blue • Basophils migrate to injury sites and discharge the contents of their granules – histamine (a vasodilator and increaser of capillary permeability) and heparin (an anticoagulant). This enhances the local inflammation initiated by mast cells and attracts other WBCs . only about 8-10µm in diameter.

. staying in circulation for only about 24hrs before entering peripheral tissues to become a tissue macrophage. an aggressive phagocyte.Agranulocytes Monocytes • 2-8% of circulating WBCs • Almost twice as big as an RBC • Nucleus is large and tends to be oval or kidney-shaped • Individual monocytes use the bloodstream as a highway.

• Circulating blood contains 3 classes: – T cells: defend against foreign cells and tissues and coordinate the immune response – B cells: produce and distribute antibodies that attack foreign materials . In blood smears. • Circulating lymphocytes are only a minute fraction of the total # in the body. • Continuously migrate from the bloodstream thru peripheral tissues and back into the bloodstream. Most are in other connective tissues and in lymphatic organs. you typically only see a thin halo of cytoplasm around a relatively large nucleus.Agranulocytes Lymphocytes • 20-30% of circulating leukocytes • Slightly larger than RBCs.

.WBCs in order of abundance: Never (neutrophils Let (lymphocytes) Monkeys (monocytes) Eat (eosinophils) Bananas (basophils) How do I remember the relative percentages? 60 + 30 + 6 + 3 +1 (i.e. 30% lymphocytes. 3% eosinophils & 1% basophils) . 6% monocytes. 60% neutrophils.

Platelets • Flattened disk-like cell fragments that are about 1µm by 4µm.000 platelets/µL of blood. • Act as a participant in the vascular clotting system. Platelets are sometimes referred to as thrombocytes (thrombus=clot) • Continuously being replaced. • On average there are 350. • Produced in the bone marrow. . Each platelet circulates for 9-12 days before being removed by splenic phagocytes. Large cells called megakaryocytes release fragments (platelets) into the circulation.

Platelet Functions • Transport of chemicals important to the clotting process. platelets help initiate the clotting process • Formation of a temporary patch (platelet plug) in the walls of damaged blood vessels. By releasing enzymes and other factors. • What do you suppose thrombocytopenia is? What process would it impact? .

Hemopoiesis = Leukopoiesis + Erythropoiesis + Thrombopoiesis Lymphoid Stem Cell Hemocytoblast Lymphocyte Myeloid Stem Cell Megakaryocyte Platelet Where does all of this take place? Erythrocyte .

Hemostasis (Blood Clotting) • Prevents blood loss thru the walls of damaged blood vessels • Also establishes a framework for further tissue repairs • 3 main phases: – Platelet Phase – Vascular Phase – Coagulation Phase .

.Platelet Phase • Occurs within 15sec of the injury • Platelets begin to attach to sticky endothelial cells.” they become “activated. the basement membrane. and to exposed collagen fibers.” Activated platelets release: • The aggregation of platelets eventually results in a platelet plug. a temporary mass of platelets that stops blood loss and forms a framework for the clot. • As platelets “stick.

Blood Vessel Damage Vascular Phase • Lasts about 30 mins • Endothelial cells at the injury site undergo changes: – Contract and expose their basement membrane to the bloodstream – Release chemical factors and local hormones – serotonin initiates spasms – Endothelial cell membranes become sticky Smooth muscle in BV wall contracts – Vascular Spasm BV diameter  Blood loss slows .

. forming a blood clot that effectively seals the damaged vessel wall. RBCs and additional platelets are trapped in this tangle.Coagulation Phase • Begins 30sec or more after vessel damage occurs (unlike the first 2 phases which begin almost immediately) • Involves a sequence of steps leading to the conversion of fibrinogen (a circulating plasma protein) to the insoluble protein fibrin. • A network of fibrin grows and covers the surface of the platelet plug.

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making it easier for fibroblasts. reducing residual bleeding and stabilizing the injury site – Reduces the size of the injured area. RBCs & platelets stick to the fibrin strands. . smooth muscle cells. • The platelets then contract and the clot undergoes clot retraction which: – Pulls the torn edges of the vessel closer together.Clot Retraction • Once the fibrin meshwork has appeared. and endothelial cells to complete repairs.

Manipulating Hemostasis • Important anticoagulant drugs include: – Heparin  Inactivates thrombin – Coumadin  Blocks the action of Vitamin K – Streptokinase  Converts plasminogen to plasmin – Aspirin  Inhibits platelet aggregation .

– What problems could an embolus cause? . it is called an embolus. – What problems could a growing thrombus pose? Above: Normal artery Below: Same artery with a large thrombus (arrow) • If the clot (thrombus) breaks off and begins to drift in the bloodstream.Thrombi & Emboli • A thrombus is formed when platelets begin to stick to the wall of an intact blood vessel – Platelets are often attracted to plaques – where endothelial and smooth muscle cells contain lots of lipids.

Due to deficiency of Factor IX – Also X-linked What symptoms do you suppose are characteristic of hemophiliacs? .Hemophilia • Refers to several different hereditary bleeding disorders with similar signs/symptoms • Hemophilia A – Results from lack of Factor VIII. Most common type (83%) – X-linked • Hemophilia B – Less common.