Blood Phys iology I. Introduction: A.

Cells within the human body are susceptible to changes in temperature, pH, and to toxic chemicals. 1. Since most c ells in the body are fixed within tissues they mus t have nutrients and oxygen brought to them and waste removed. 2. Blood se rves this transp ortation function. B. The bloo d is c lass ified a s a fluid matrix conne ctive tissue consisting of ce lls and ce ll fragments surrounded by a liquid matrix which circulates through the heart and blood vessels. 1. The cells and cell fragme nts a re the formed elements and the matrix of the bloo d is fluid. 2. Therefore blood can be divided like other connective tissues into a cellular component and a matrix component. C. Formed elements make up about 45% and plasma 55% of the total blood volume. D. Blood volume: 4-5 L in females, 5-6 L in males Functions of the Blood A. Distribution and transport (estimate 60 ,000 miles o f vessels in bod y) 1. Respiration a. RBC transport Oxygen, CO 2, 2. Nutritive a. Carries absorbed nutrients, electrolytes and water from intestines: 3. Excretory a. Meta bolic Wa ste -urea, exc ess w ater, ions a re carried to the kidney. 4. Negative - also transports bacteria, viruses, toxins etc. B. Regulation and maintenance 1. Hormonal regulation a. From glands to ta rget organs b. Transport of various enzymes 2. Thermoregulation a. Diversion of blood from deeper to superficial cutaneous vessels to cool body or vice versa to retain heat. 3. pH / acid-base balance a. Blood acts as a buffering system for the body. b. pH 7.35-7.45
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II.

4. Fluid volume C. Protection 1. Clotting a. Protects against blood loss when tissues / vessels are damaged 2. Immunity a. Leukocytes protect against disease causing agents. (1) toxins, b acteria III. Major Components of the Circulatory System A. Two d ivisions: Cardiovas cular system a nd lymphatic syste m. B. Cardiovascular: Heart, bloo d vesse ls 1. Hea rt: a. 4 chambersb. at rest pumps 5 liters / min. c. Completely recirculates the blood every minute. 2. Vesse ls a. Form a tubular network. b. Arteries carry blood away from heart to arterioles c. Blood enters capillaries (1) thinnest and most numerous of vessels.. (2) exchange of nutrients, fluids and waste occurs in capillaries. d. Blood flows into venules which enter into larger veins. C. Lymphatic: lymphatic vess els and lymphoid tiss ues in spleen, thymus, tonsils, and lymph nodes. 1. The fluid portion of the blood (plasma) passes through the capillary walls under hydrostatic pressure (interstitial fluid). a. Some inte rstitial fluid returns to the bloo d and so me enters the lymphatic system b. Lymphatic vess els carry interstitial fluid now ca lled lymph back to the venous blood. c. Lymph nodes along the way filter and cleanse the blood before it is returned. IV. Components of the blood. A. Fluid components 1. Plasma - straw colored liquid composed of water and dissolved solutes. a. 90% w ater - solvent a nd suspe nding medium for blood c omponents b. Over 10 0 different solutes - p roteins, ions, nutrients , gases and wa ste products. (1) 7% Pro teins
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B.

(a) Albumins (58% ) - buffer / maintains osmotic p ressure / visc osity (b) Globulins (38%) - " & $ -transport lipids and hormones. (-Act as antibodies (c) Fibrinogen (4%) - B lood clotting (2) 2% Other solutes (a) Ions - Na+, K+, Ca++, etc. (b) Nutrients - Glucose, amino acids, cholesterol, triaclglyerol (c) Waste products - Urea, uric acid, creatinine, ammonia salts. (d) Gases - Oxygen, CO 2, Nitrigen (e) Regulatory substances- enzymes, hormones. Formed Elements (Cells) 1. Erythrocytes (RBC) a. Hematocrit = % of blood composed of RBC 2. Leukocytes (W BC) - 5 types a. Granulocytes neutrophils, eosinophils, bas ophils b. Agranulocytes lymphocytes a nd monocytes 3. Thrombocytes (platelets)

V.

Erythroc ytes - red bloo d ce lls (RBCs) A. Characteristics 1. Numbers : Female - 4.3 to 5.2 million / mm3 and M ale 5.1 to 5.8 million / mm3. 2. Shape biconcave disks - increases surface area 3. 7 um in diameter and 2.2 um thick. 4. Contains he moglobin and iron. 5. No nucleus, very few organelles. B. Functions 1. Carry oxygen to tissues and carbon dioxide away from tissues. 2. Function d epe ndent on hemo globin
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b.

Hemoglobin (1) Structure: (a) Composed of 4 protein chains, 2 alpha chains and 2 beta chains. (b) Each chain contains an iron containing heme group. (c) iron in these heme gro ups is critical for oxygen to bind to the hemo globin (d) Each hemoglobin is capable of binding 4 oxygens. i) Considerations: Each blood cell contains 280 million hemoglobin molecules . Each R BC there fore has the c apability to bind over 1 billion oxygen molecules. (2) The majority of CO 2 (70%) is c arried in the blood as bicarb onate ions HCO 3(a) CO 2 + H 2O W H 2CO 3 W HCO 3- + H+ (b) catalyzed by carbonic anhydrase in the RBC (3) Carbon monoxide binds to He moglo bin fro ming a stable carboxyhe moglobin - result O 2 cant bind to hemoglobin and d eath occurs. RBC Production: (1) RBCs are produced within the bone marrow. Through a process called erythropoesis. (2) Most blood cells derive from a common ancester cell known as a hemocytoblast. (3) Und er appropriate conditions the hemocytob last differentia tes into a cell known as a proerythroblast (early erythrocyte forming cell) etc. (4) History (a) Stem cell > (b) proerythrob last > (c) early (baso philic) erythroblast > (d) intermediate (polychromatic)erythroblast > (hemoglobin production begins) (e) late erythroblast (loss of nucleus) > (f) reticulocyte > (g) erythrocyte (5) Changes that occur d uring RBC d evelopment: (a) decrea se in size, loo se nucleus a nd many of its organe lles including mitoc hond ria (6) Regulation of production
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(a) production requires: i) folate and B12 for cell division and ii) iron for hemoglobin to be produced. (b) Erythrocyte production is stimulated by low blood oxygen i) Cause s: decrea sed or d efective erythroc ytes, dise ases o f the lungs, high altitude, cardiovascular delivery problems, increased de mands for oxygen (endurance exercise). (c) Decreased blood oxygen causes increased erythropoietin release from the kidneys. i) erythropoietin stimulates bone marrow to produce more erythrocytes and increas e the rate o f maturation. c. Fate and destruction of RBCs: (1) As RBC circulate they eventually become ragged and worn out as they squeeze through capillaries. (a) (RBC cannot produce new proteins - no nucleus) (b) Typical life span 100 - 120 days. (2) As RBC s squee ze through the narrow c apillaries of the spleen (or liver) the worn out cells become trapped and broken down by fixed macrophages. (3) Breakdown products are recycled as follows: (a) Macrophages engulf and destro y worn out R BCs in sp leen and liver. (b) Hemoglobin is split into heme and globin (c) Globin is broken d own into amino a cids which c an be use d to synthesize other proteins. (d) Heme (iron + porphyrin) liberates its iron core which is recycled. i) Iron a) Fe 3+ is pic ked up and transported in blood b y a plasma protein called transferrin b) Fe is carried to marrow for synthesis of Hb in new RBC or c) Is stored in muscle or liver where iron detaches from transferrin and binds to an iron storage protein called ferritin. d) Upon re leas e from sto rage , iron can rea ttac hes to transferrin e) Iron is then transported to bone marrow where RBC precurs ors take it up through re cep tor media ted endocytosis for use in producing new hemoglobin molecules.
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f) Erythropoiesis in red bone marrow results in the production of RBC which enter the circulation. (4) Porphyrin (a) Non iron portion of heme (prophyrin) is converted to biliverdin (green pigment) (b) biliverdin is converted to bilirub in (orange pigment) (c) bilirubin enters the blood stream and is transported to the liver. (d) Within the liver, bilirub in is secreted by the liver cells into bile which pas ses into the small inte stine (e) In the large inte stine bacteria convert bilirubin into urobilinogen (f) Some of the U robilinogen is abso rbed ba ck into the bloo d and converted to urobilin (yellow pigment) and is excreted in the urine (g) Mos t urobiligen is elimina ted in fece s in the form of stercob ilin which gives feces its characteristic color. d. Jaundice - ye llowish staining of skin and s clera caus es by buildup o f bilirubin. Disorders of Erythrocytes 1. Anemias (deficiency of hemoglobin in blood) a. Result of either a decrease in hemoglobin / RBC or in the number of RBCs. b. Symptoms: pale, lethargic, shortness of breath, tired. c. Aplas tic anem ia: inability of red bone marrow to produce RBCs (1) caused by: (a) damage to Red bone marrow by chemicals, drugs, radiation (b) Iron defic iency - RBCs are smaller than normal. (c) Folate deficiency - ne cessa ry for DNA replication - poo r pregnant women and alcoholics d. Pernic ious anem ia - Vitman B12 deficiency - Vitamin B12 is necessary for production of folate. e. Hem orhagic a nemia - results from loss o f blood. Ie. U lcers, mens tration. f. Hem olytic anem ia - erythrocytes rupture or are destroyed at an increased rate. (1) caused by: (a) genetic membrane problems, (b) snake venom, (c) immune diseases, (d) heart valve problems. g. Thalasemia - defective hemoglobin production (1) insufficient globin production - genetic disorder
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(2) Sickle cell anemia - a bnormal shap ed hemoglob in (a) cells are rigid, fragile and sickle shaped (b) death by age 30. (c) protective a gains t mala ria i) caused by a proto zoan (plas modium) ii) carried by a nopheles mo squito iii) protozoan develops in the RBCs releases toxins that cause RBCs to rupture. VI. Leukocytes: A. Broad c lass ification of white blo od c ells B. 4,000 -11,00 0 / mm 3 (5-9,000 considered normal range) C. Characteristics 1. Diapedesis - can cross capilary bounderies to fight infection 2. Ameboid mo tion -cytoplasmic fluid moveme nt 3. Positive chemotaxis - ability to follow chemical trail through the body D. Characterized as granulocytes or agranulocytes 1. Granulocytes - twice the size of RBC, cytoplasmic granules present, survive 12h to 3 days. a. Neutrophils (1) Appea rance -se e lab hando ut (a) 2-5 lobes , cytoplas mic granules that sta in slightly pink (b) 10-12um (c) 54 to 62 % of white ce lls (2) Characteristics (a) most common WBC (b) chemically attracted to sites fo infection (c) good at fighting bacte rial and fungal infections (d) contain peroxidases and other hydrolytic enzymes (e) contain defens ins which act to digest foreign subs tances a nd punc ture holes in bacteria (f) Numbers increase rapid ly with meningitis and app endicitis b. Eos inophils (1) Appearance (a) bilobed nucleus (b) cytoplasmic granules that stain red or bright red (c) 11-14 um
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(d) 1-3% of white blo od c ells (2) Characteristics (a) most effective in working against parasitic worms such as tape worms, flukes, pinwo rms, and ho okwo rms (b) release chemical that reduce inflammation (c) secrete enzymes that break down clots. c. Bas ophils (1) Appearance (a) two indistinct lobes (b) cyto plas mic granule s stain blue-p urple (c) 10-12 um (d) less than 1% of white c ells (2) Characteristics (a) contain and re lease histamine (b) act as a chemoattractant to attract other WBC (c) release he parin - prevents clots Agranulocytes a. Lymphocytes (1) Appearance (a) only slightly larger than RBC (b) round nuc leus nearly fills c ell. (c) 6-14um (d) 25-33% of white b lood cells (2) Characteristics (a) Genera lly found in lymphoid tissue (b) provides specific immune response i) T-lymphocytes act directly against virus infected cells and tumor cells ii) B-Lymphocyte s produc e plasma c ells which give rise to antibodies. b. Monocytes (1) Appearance (a) Nucleus round, kidney of horseshoe shaped (b) contains more cytoplasm tha n lymphocyte (c) 12-20um (d) 3-9% of white ce lls (2) Characteristics
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(a) Once activated transform into macrophages which attack and digest everything in their way (dead cells, bacteria, etc.) VII. Platelets A. Responsible for blood clot formation and are not cells at all but are fragments of cells. 1. Characteristics a. Cytoplasmic fragment surrounded by a plasma membrane containing granules b. 2-4um c. 130,0 00 to 40 0,000 / mm3 d. Enables c lotting e. Releases seratonin which causes vasoconstriction B. Hemostasis (prevention of bloo d loss) by c lotting 1. Can be divided into three stages (vascular sp asm, plate let plug formation, coaggulation). a. Vascular spasm (1) Once a blood ves sel has be en injured the first and mo st immediate respons e is for the blood vessel to s tart to spa sm. (a) smooth muscle contraction (2) Vascular spas m is caused b y nervous system reflexes a nd by che micals (thromboxane s, endo thelin) b. Platele t plug form ation (1) Sea ls up small breaks in blood vess els (2) Process: (a) platelet adhesion i) Von willib rand s fa ctor from endothe lial wall ii) binds pla telets to colla gen in vessel w all. (b) platelet activation i) release ADP and thromboxanes ii) casca de of chemica l release by o ther platelets (c) Activated platelets also bind fibrinogen i) causes platelet aggrega tion. ii) Forms a plug. (d) Platelets also release p latelet factor III and coagulation factor V. i) important in clot formation (discussed later). (3) Aspirin inhibits plug formation by block ing prostiglandin and thromboxane production. c. Coagula tion (1) blood clot formation
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(a) fibrin protein fibers trap blood cells, platelets and fluid. (b) Formation depends o f a number of factors (c) Coagulation fac tors are no rmally inactive (d) Injury causes activation of clotting factors (e) Activation depends on surface proteins on activated platlets. (2) Process: (three main stages) Fig. 19.10 (a) formation of prothrombinase by two p athways (b) convers ion of prothrom bin to thromb in (by prothrombinase) (c) convers ion of fibrinog en to fibrin by thromb in (d) 2 pathways for the formation of prothrombinase i) Extrinsic pathway - begins with factors released outside of plasma in dama ged tissue a) Thro mboplas tin (tissue factors ) released by damage d tissue b) Thromboplastin complexes with Factor VII to activate Factor X c) Factor X complexes with Factor V platelet phos pholipids and Ca+ to activate prothrombinase. ii) Intrinsic pathway - begins with factors inside (intrinsic to ) the blood. a) damage to blood vessels exposes collagen in C. T. b) factor XII is activated by collagen c) activated factor XII a ctivates factor XI d) Factor XI ac tivates factor IX e) IX joins w ith factor VIII, p latelet phosp holipids and C a+ to activate factor X f) Factor X complexes with Factor V platelet phos pholipids and Ca+ to activate prothrombinase. Control of clot formation a. Anticoagulants prevent blood from clotting outside of the injury area. (1) Anticoagulants can counteract low levels of clotting factors. (2) Antic oagulants include: antithrombin and he parin Clot retraction a. Fibrin meshwork adheres to the walls of the vessel b. Clot condenses (1) Platelets co ntain actin and myos in (2) bind to fibrin and pull it tight causing retraction
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c. d.

(3) Serum (=plasma - clotting factors) is extruded Consolidation pulls the edges of the vessel together to stop blood flow, reduce infection a nd enhance healing. Hea ling - fibroblasts multiply and produce new C.T., epithelial cells proliferate to fill in torn area

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Clot and dissolution (Fibrinolysis) a. Clot is dissolved b y plasm in which hydrolyze s fibrin. b. Plasmin is formed from inactive plasminogen (1) plasminogen is activated by tissue plasminogen activator (t-PA) or urokinase. (2) t-PA and urokinase can be injected as clot busters in case of blockage of major vess els due to inap propriate c lotting. (3) streptokinase (produce d by bac terial enzyme) ca n also be injec ted at the clot site as a clot dissolving drug. 5. Clinical notes a. Vitamin K (1) is a necessary cofactor for factor VII, IX and X to be activated. (2) Vitamin K is prod uced by b acteria in our gut and absorb ed by the intestine. (a) absorption requires the presence of bile. (3) Low amo unts of Vitamin K ca n lead to hemo rrhage (Ie. Infants who dont have bacteria.) b. Thrombus - formation of clot within major vessels. c. Embolus - clot floating in the circulation (1) can result in dea th - block of hea rt, brain, lung (2) counteracted by heparin, warfarin ( vitamin K dependent factor suppres sor; rat po ison) Blood Grouping (types) 1. Covered in lab

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