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Power. Point® Lecture Slides prepared by Vince Austin, Bluegrass Technical and Community College CHAPTER

Power. Point® Lecture Slides prepared by Vince Austin, Bluegrass Technical and Community College CHAPTER Elaine N. Marieb Katja Hoehn Human Anatomy & Physiology SEVENTH EDITION Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings 17 Blood

Body Water Content § § Infants: 73% or more water (low body fat, low

Body Water Content § § Infants: 73% or more water (low body fat, low bone mass) Adult males: ~60% water Adult females: ~50% water (higher fat content, less skeletal muscle mass) Water content declines to ~45% in old age Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Fluid Compartments § Total body water = 40 L 1. Intracellular fluid (ICF) compartment:

Fluid Compartments § Total body water = 40 L 1. Intracellular fluid (ICF) compartment: 2/3 or 25 L in cells 2. Extracellular fluid (ECF) compartment: 1/3 or 15 L § Plasma: 3 L § Interstitial fluid (IF): 12 L in spaces between cells § Other ECF: lymph, CSF, humors of the eye, synovial fluid, serous fluid, and gastrointestinal secretions Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Total body water Volume = 40 L 60% body weight Extracellular fluid (ECF) Volume

Total body water Volume = 40 L 60% body weight Extracellular fluid (ECF) Volume = 15 L 20% body weight Intracellular fluid (ICF) Volume = 25 L 40% body weight Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Interstitial fluid (IF) Volume = 12 L 80% of ECF Figure 26. 1

OBTAIN THE BLOOD § 1. Venipuncture § 2. Arterial Stick § 3. Capillary Stick

OBTAIN THE BLOOD § 1. Venipuncture § 2. Arterial Stick § 3. Capillary Stick Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Composition of Blood § § Blood is the body’s only fluid tissue It is

Composition of Blood § § Blood is the body’s only fluid tissue It is composed of (1) liquid plasma and (2) formed elements Formed elements include: § Erythrocytes, or red blood cells (RBCs) § Leukocytes, or white blood cells (WBCs) § Platelets Hematocrit – the percentage of RBCs out of the total blood volume Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Components of Whole Blood Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin

Components of Whole Blood Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17. 1

Blood Tube Colors § § § Red Top-This is the red top used for

Blood Tube Colors § § § Red Top-This is the red top used for serum chemistries; your electrolytes, your basic and complete metabolic panel, your hepatic and your renal panels, are all done using this red top tube. Lavender Top This has an EDTA anticoagulant in it. It is used for your blood counts — your whole blood counts (CBC), your Sed rates are all taken using the lavender top tube. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Blood Tube Colors § § Blue Top -The blue top tube has a different

Blood Tube Colors § § Blue Top -The blue top tube has a different anticoagulant in it. It’s the citrate-based anticoagulant, and this one is used for plasma coagulation tests; your PT, PTT, APTT, the different prothrombin times, and the activated partial thromboplastin time; also fibrinogens and factor essays are all done using the blue top. Gray Top -Gray top has a fluoride that inhibits cellular glycolysis, and this is used for making accurate glucose measurements to diagnose diabetes patients. This is the gray top. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Blood Tube Colors Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Blood Tube Colors Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Physical Characteristics and Volume § Blood is a sticky, opaque fluid with a metallic

Physical Characteristics and Volume § Blood is a sticky, opaque fluid with a metallic taste § Color varies from scarlet to dark red § The p. H of blood is 7. 35– 7. 45 § Temperature is varies – upper end of body temp 100. 4 § Blood accounts for approximately 8% of body weight § Average volume: 5– 6 L for males, and 4– 5 L for females § Hematocrit (Hct. ) 30% – 60% § Viscosity 4. 5 – 5. 5 centipoise per second Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

§ Temperature classification § Core (rectal, esophageal, etc. ) § Hypothermia <35. 0 °C

§ Temperature classification § Core (rectal, esophageal, etc. ) § Hypothermia <35. 0 °C (95. 0 °F) § Normal 36. 5– 37. 5 °C (97. 7– 99. 5 °F) § Fever >37. 5– 38. 3 °C (99. 5– 100. 9 °F) § Hyperthermia >37. 5– 38. 3 °C (99. 5– 100. 9 °F) § Hyperpyrexia >40. 0– 41. 5 °C (104. 0– 106. 7 °F) § The commonly accepted average core body temperature (taken internally) is 37. 0 °C (98. 6 °F). The typical oral (under the tongue) measurement is slightly cooler, at 36. 8° ± 0. 4 °C (98. 2° ± 0. 7 °F), and temperatures taken in other places (such as under the arm or in the ear) produce different typical numbers. [ Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Functions of Blood § Blood performs a number of functions dealing with: § Transport

Functions of Blood § Blood performs a number of functions dealing with: § Transport § Regulation of blood levels of particular substances § Protection Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Transportation § Blood transports: § § § Oxygen from the lungs and nutrients from

Transportation § Blood transports: § § § Oxygen from the lungs and nutrients from the digestive tract Metabolic wastes from cells to the lungs and kidneys for elimination Hormones from endocrine glands to target organs Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Regulation § Blood maintains: § Appropriate body temperature by absorbing and distributing heat §

Regulation § Blood maintains: § Appropriate body temperature by absorbing and distributing heat § Normal p. H in body tissues using buffer systems § Adequate fluid volume in the circulatory system Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Protection § § Blood prevents blood loss by: § Activating plasma proteins and platelets

Protection § § Blood prevents blood loss by: § Activating plasma proteins and platelets § Initiating clot formation when a vessel is broken Blood prevents infection by: § Synthesizing and utilizing antibodies § Activating complement proteins § Activating WBCs to defend the body against foreign invaders Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Formed Elements § Erythrocytes, leukocytes, and platelets make up the formed elements § §

Formed Elements § Erythrocytes, leukocytes, and platelets make up the formed elements § § Only WBCs are complete cells RBCs have no nuclei or organelles, and platelets are just cell fragments Most formed elements survive in the bloodstream for only a few days Most blood cells do not divide but are renewed by cells in bone marrow Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

§ § Red Blood Cells (Erythrocytes) 4. 8 – 5. 2 million per microliter

§ § Red Blood Cells (Erythrocytes) 4. 8 – 5. 2 million per microliter White Blood Cells (Leukocytes) 5, 000 – 10, 000 per microliter § Granulocytes § Neutrophils, Eosinophils, Basophils § Agranulocytes § Lymphocytes, Monocytes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Percentages of Leukocytes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Percentages of Leukocytes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17. 9

The Formed Elements of Blood Figure 19. 1 Copyright © 2006 Pearson Education, Inc.

The Formed Elements of Blood Figure 19. 1 Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings 19 -21

Components of Whole Blood Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin

Components of Whole Blood Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17. 2

Blood Plasma § Blood plasma contains over 100 solutes, including: § § § Proteins

Blood Plasma § Blood plasma contains over 100 solutes, including: § § § Proteins – albumin, globulins, clotting proteins, and others Lactic acid, urea, creatinine Organic nutrients – glucose, carbohydrates, amino acids Electrolytes – sodium, potassium, calcium, chloride, bicarbonate Respiratory gases – oxygen and carbon dioxide Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Blood Plasma § 91% – 92 % Water § 7% Plasma Proteins 55% Albumins

Blood Plasma § 91% – 92 % Water § 7% Plasma Proteins 55% Albumins 38% Globulins 7% Fibrinogen 1. 5% Other Solutes 0. 9 % Electrolytes – 0. 3% Nutrients – 0. 1% Gases 0. 1% Hormones, Enzymes 0. 1% Wastes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hematopoiesis § Formation of Blood Copyright © 2006 Pearson Education, Inc. , publishing as

Hematopoiesis § Formation of Blood Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hematopoiesis § § Formation of Blood 1. Conception (Sperm fertilizes egg) – giving first

Hematopoiesis § § Formation of Blood 1. Conception (Sperm fertilizes egg) – giving first complete cell (1 n + 1 n) = 2 n 2. Rapid mitosis of first cell to provide many cells – culminating in a morula (mulberry) 3. Cells begin to migrate and differentiate – giving the first germ (germination) layers – (ectoderm, mesoderm, endoderm) § 4. From mesoderm comes the blood Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 2

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 2

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 3

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 3

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 4

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 4

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 5

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 5

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 7

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 7 a–c

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 7

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 28. 7 d

Week 1– 3 5– 7 days after fertilization, the blastocyst attaches to the wall

Week 1– 3 5– 7 days after fertilization, the blastocyst attaches to the wall of the uterus (endometrium). When it comes into contact with the endometrium it performs implantation. Implantation connections between the mother and the embryo will begin to form, including the umbilical cord. The embryo's growth centers around an axis, which will become the spine and spinal cord. The brain, spinal cord, heart, and gastrointestinal tract begin to form. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Week 4– 5 Chemicals produced by the embryo stop the woman's menstrual cycle. Neurogenesis

Week 4– 5 Chemicals produced by the embryo stop the woman's menstrual cycle. Neurogenesis is underway, showing brain activity at about the 6 th week. The heart will begin to beat around the same time. Limb buds appear where arms and legs will grow later. Organogenesis begins. The head represents about one half of the embryo's axial length, and more than half of the embryo's mass. The brain develops into five areas. Tissue formation occurs that develops into the vertebra and some other bones. The heart starts to beat and blood starts to flow. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Week 6– 8 Myogenesis and neurogenesis have progressed to where the embryo is capable

Week 6– 8 Myogenesis and neurogenesis have progressed to where the embryo is capable of motion, and the eyes begin to form. Organogenesis and growth continue. Hair has started to form along with all essential organs. Facial features are beginning to develop. At the end of the 8 th week, the embryonic stage is over, and the fetal stage begins. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

2 Weeks – primitive red blood cells (nucleated) seen in yolk sac 6 Weeks

2 Weeks – primitive red blood cells (nucleated) seen in yolk sac 6 Weeks – primitive red blood cells start development in primordial liver 6 ½ Weeks – see definitive red blood (non-nucleated) cells developed in liver 8 weeks – begin to see red blood cell development in the spleen along with development of granulocytes, and thrombocytes 4 th month – see blood cell development to start in bone marrow – also start to see development of lymphocytes 5 th month – see development of monocytes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Embryonic Development of Blood Vessels • Angiogenesis begins at 13– 15 days of gestation

Embryonic Development of Blood Vessels • Angiogenesis begins at 13– 15 days of gestation • Mesenchymal cells differentiate into blood islands • Hemoblasts become blood cells • Angioblasts become endothelial cells Figure 21. 34 Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings 21 -38

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Types of Developmental Cells § § Pluripotential Hematopoietic Stem Cells (Hemocytoblast) – usually amitotic

Types of Developmental Cells § § Pluripotential Hematopoietic Stem Cells (Hemocytoblast) – usually amitotic but may undergo bursts of cell division giving rise to more PHSC Multipotential Stem Cells – less potentiality – can do mitosis and further differentiation – CFU-S and CFU – Ly (Colony Forming Unit) in other classification – Myeloid Stem Cell and Lymphoid Stem Cell Progenitor Cell- unipotential- creates a single cell line like eosinophils mitotic ability and differentiation are controlled by hematopoietic factors – only limited ability for selfrenewal Precursor Cell – arise from progenitor cell – no selfrenewal Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Growth Factors for Hematopoiesis § § Chemicals or other factors that stimulate the various

Growth Factors for Hematopoiesis § § Chemicals or other factors that stimulate the various type of blood forming cells to proliferate and/or differentiate Three types- (1) Cytokines – small protein, peptide or glycoproteins secreted locally (paracrine) – like the interleukins and colony stimulating factors (2) Hormones – like erythropoietin and Thrombopoietin and (3) Direct cell contact – like the Steel Factor (Stem Cell Factor) which is produced by stromal cells and inserted into the various stem cells to stimulate them. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Erythrocytes (RBCs) § § § Biconcave discs, anucleate, essentially few organelles Filled with hemoglobin

Erythrocytes (RBCs) § § § Biconcave discs, anucleate, essentially few organelles Filled with hemoglobin (Hb), a protein that functions in gas transport Contain the plasma membrane protein spectrin and other proteins that: § Give erythrocytes their flexibility § Allow them to change shape as necessary Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Erythrocytes (RBCs) Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure

Erythrocytes (RBCs) Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17. 3

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 3. 3

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 3. 3

Erythrocytes (RBCs) § § Erythrocytes are an example of the complementarity of structure and

Erythrocytes (RBCs) § § Erythrocytes are an example of the complementarity of structure and function Structural characteristics contribute to its gas transport function § § § Biconcave shape has a huge surface area relative to volume Erythrocytes are more than 97% hemoglobin ATP is generated anaerobically, so the erythrocytes do not consume the oxygen they transport Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Erythrocyte Function § § § RBCs are dedicated to respiratory gas transport Hb reversibly

Erythrocyte Function § § § RBCs are dedicated to respiratory gas transport Hb reversibly binds with oxygen and most oxygen in the blood is bound to Hb Hb is composed of the protein globin, made up of two alpha and two beta chains, each bound to a heme group Each heme group bears an atom of iron, which can bind to one oxygen molecule Each Hb molecule can transport four molecules of oxygen Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Structure of Hemoglobin Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Structure of Hemoglobin Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17. 4

Hemoglobin (Hb) § Oxyhemoglobin – Hb bound to oxygen § § § Oxygen loading

Hemoglobin (Hb) § Oxyhemoglobin – Hb bound to oxygen § § § Oxygen loading takes place in the lungs Deoxyhemoglobin – Hb after oxygen diffuses into tissues (reduced Hb) Carbaminohemoglobin – Hb bound to carbon dioxide § PLAY Carbon dioxide loading takes place in the tissues Inter. Active Physiology ®: Respiratory System: Gas Transport, pages 3– 13 Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Production of Erythrocytes § § § Hematopoiesis – blood cell formation Hematopoiesis occurs in

Production of Erythrocytes § § § Hematopoiesis – blood cell formation Hematopoiesis occurs in the red bone marrow of the: § Axial skeleton and girdles § Epiphyses of the humerus and femur Hemocytoblasts give rise to all formed elements Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Production of Erythrocytes: Erythropoiesis § A hemocytoblast is transformed into a proerythroblast § Proerythroblasts

Production of Erythrocytes: Erythropoiesis § A hemocytoblast is transformed into a proerythroblast § Proerythroblasts develop into early erythroblasts § The developmental pathway consists of three phases § 1 – ribosome synthesis in early erythroblasts § 2 – Hb accumulation in late erythroblasts and normoblasts § § 3 – ejection of the nucleus from normoblasts and formation of reticulocytes Reticulocytes then become mature erythrocytes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Production of Erythrocytes: Erythropoiesis § § A hemocytoblast is transformed into a proerythroblast Proerythroblasts

Production of Erythrocytes: Erythropoiesis § § A hemocytoblast is transformed into a proerythroblast Proerythroblasts develop into early erythroblasts Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

§ Erythropoiesis Synopsis RBC produced at 2 million per second § Proerythroblast – all

§ Erythropoiesis Synopsis RBC produced at 2 million per second § Proerythroblast – all cell components present § Early Erythroblast – loss of nucleolus § Intermediate Erythroblast – start of Hgb. Synthesis § Late Erythroblast – Maximum rate of synthesis of Hgb. § § Reticulocyte – nucleus has been extruded – still has ribosomes and mitochondria Mature RBC – no ribosomes and no mitochondria Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Production of Erythrocytes: Erythropoiesis Normoblast – the red blood cell precursor still has a

Production of Erythrocytes: Erythropoiesis Normoblast – the red blood cell precursor still has a nucleus Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17. 5

Regulation and Requirements for Erythropoiesis § Circulating erythrocytes – the number remains constant and

Regulation and Requirements for Erythropoiesis § Circulating erythrocytes – the number remains constant and reflects a balance between RBC production and destruction § § § Too few RBCs leads to tissue hypoxia Too many RBCs causes undesirable blood viscosity Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hormonal Control of Erythropoiesis § § Erythropoietin (EPO) release by the kidneys is triggered

Hormonal Control of Erythropoiesis § § Erythropoietin (EPO) release by the kidneys is triggered by: § Hypoxia due to decreased RBCs § Decreased oxygen availability § Increased tissue demand for oxygen Enhanced erythropoiesis increases the: § RBC count in circulating blood § Oxygen carrying ability of the blood Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Dietary Requirements of Erythropoiesis § § Erythropoiesis requires: § Proteins, lipids, and carbohydrates §

Dietary Requirements of Erythropoiesis § § Erythropoiesis requires: § Proteins, lipids, and carbohydrates § Iron, vitamin B 12, and folic acid The body stores iron in Hb (65%), the liver, spleen, and bone marrow Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin Circulating iron is loosely bound to the transport protein transferrin Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Fate and Destruction of Erythrocytes § § The life span of an erythrocyte is

Fate and Destruction of Erythrocytes § § The life span of an erythrocyte is 100– 120 days Old RBCs become rigid and fragile, and their Hb begins to degenerate Dying RBCs are engulfed by macrophages Heme and globin are separated and the iron is salvaged for reuse Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Fate and Destruction of Erythrocytes § Heme is degraded to a yellow pigment called

Fate and Destruction of Erythrocytes § Heme is degraded to a yellow pigment called bilirubin § The liver secretes bilirubin into the intestines as bile § The intestines metabolize it into urobilinogen § This degraded pigment leaves the body in feces, in a pigment called stercobilin Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Fate and Destruction of Erythrocytes § § Globin is metabolized into amino acids and

Fate and Destruction of Erythrocytes § § Globin is metabolized into amino acids and is released into the circulation Hb released into the blood is captured by haptoglobin and phgocytized Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Synopsis of RBC destruction § When the RBC has loss its ability to bend

Synopsis of RBC destruction § When the RBC has loss its ability to bend its cell membrane – then it must be removed so it does not cause blood clots § § § Macrophages in the spleen (main organ) and other organs like the liver – engulf the RBC Enzymes in macrophage tear the RBC apart separating the cell from its hemoglobin The components of the rest of the cell are enzymatically degraded into carbohydrate, protein and lipid. These then are used by the macrophage or transported to other cells for use or eliminated. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Synopsis of Fate of Hgb. destruction § § § Enzymes in the macrophage split

Synopsis of Fate of Hgb. destruction § § § Enzymes in the macrophage split hemoglobin into heme and globin. The globin, a protein, is broken down into its basic amino acids by proteolytic enzymes in the macrophage. The amino acids are either used by the macrophage or transported to other cells in the body or eliminated by being converted to urea in the liver. The heme is enzymatically split into the iron portion and the tetrapyrrole rings. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

§ § Fate of Iron See Iron Power. Point Some iron is maintained in

§ § Fate of Iron See Iron Power. Point Some iron is maintained in the macrophage and some iron is transported out of the macrophage and attached to the protein carrier known as apotransferrin – so as not to allow the iron to be a free radical in the bloodstream. Once iron is attached to apotransferrin – the molecule’s name is changed to transferrin. The transferrin iron circulates until it is picked up by cell surface receptors for transferrin- particularly cells in the bone marrow, liver and spleen. However all cells have some receptors for iron – in that all cells need some iron. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

§ § Fate of the Tetrapyrrole rings In the macrophage the tetrapyrrole rings are

§ § Fate of the Tetrapyrrole rings In the macrophage the tetrapyrrole rings are enzymatically converted to biliverdin (green bile pigment) – they then are further converted to bilirubin (yellow bile pigment) Bilirubin is transported out of the macrophage into the circulation – but since bilirubin is not soluble in the water of the blood it must hook to a carrier – which is plasma albumin. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Fate of Tetrapyrrole rings (2) § § Upon the albumin – bilirubin circulating through

Fate of Tetrapyrrole rings (2) § § Upon the albumin – bilirubin circulating through the liver – the bilirubin is removed from the albumin and goes into the liver (hepatic cell) – where it is “conjugated” with glucuronic acid (80%) or sulfate (10%) or other substances. The conjugation process makes the bilirubin very water soluble and allows it to be placed into a substance known as bile – which is made in liver and stored in the gallbladder. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Bile Composition Bile is formed in the liver and stored in the gallbladder its

Bile Composition Bile is formed in the liver and stored in the gallbladder its function is to solubilize (emulsify) fats in the small intestines. § Water – when stored in gallbladder considerable water is removed from the bile so as to make it more concentrated thus easier to store. § Unesterified Cholesterol § Bile pigments (Bilirubin) § Bile salts (glycocholic acid & taurocholic acid) § Bile acids – primary – cholic acid and chenodeoxycholic acid § Bile acids – secondary – deoxycholic acid and lithocholic acid § Phospholipids (mainly lecithin) Dipalmitoyl phosphatidyl choline § Electrolytes § Bicarbonate Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Fate of Tetrapyrrole Rings (3) § § § Bile gets secreted into the small

Fate of Tetrapyrrole Rings (3) § § § Bile gets secreted into the small intestines for the purpose of emulsifying fat from the diet. The conjugated bilirubin component of bile in the intestine is enzymatically converted by bacterial (normal flora) enzymes in the large intestines into urobilinogen. Some urobilinogen is reabsorbed with the bile in the large intestine (enterohepatic recirculation) and some that is not reabsorbed is further degraded through oxidation by bacterial action into Stercobilin. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Fate of Tetrapyrrole Rings (4) § Some of the urobilinogen reabsorbed with the bile

Fate of Tetrapyrrole Rings (4) § Some of the urobilinogen reabsorbed with the bile is eliminated by the kidneys. After the urobilinogen is urinated out – air oxidizes it to urobilin. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Right and left hepatic ducts of liver Cystic duct Common hepatic duct Bile duct

Right and left hepatic ducts of liver Cystic duct Common hepatic duct Bile duct and sphincter Accessory pancreatic duct Mucosa with folds Gallbladder Major duodenal papilla Hepatopancreatic ampulla and sphincter Tail of pancreas Pancreas Jejunum Duodenum Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Main pancreatic duct and sphincter Head of pancreas Figure 23. 21

Sternum Nipple Liver Bare area Falciform ligament Left lobe of liver Right lobe of

Sternum Nipple Liver Bare area Falciform ligament Left lobe of liver Right lobe of liver Gallbladder (a) Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Round ligament (ligamentum teres) Figure 23. 24 a

(a) Lobule (b) Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

(a) Lobule (b) Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Central vein Connective tissue septum Figure 23. 25 a, b

Interlobular veins (to hepatic vein) Central vein Sinusoids Bile canaliculi Plates of hepatocytes Bile

Interlobular veins (to hepatic vein) Central vein Sinusoids Bile canaliculi Plates of hepatocytes Bile duct (receives bile from bile canaliculi) Fenestrated lining (endothelial cells) of sinusoids Portal vein Hepatic macrophages in sinusoid walls Bile duct Portal venule Portal arteriole Portal triad (c) Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 23. 25 c

Jaundice Causes § Pre-hepatic – example massive internal hemorrhage § Hepatic – example hepatitis

Jaundice Causes § Pre-hepatic – example massive internal hemorrhage § Hepatic – example hepatitis or cirrhosis § Post-Hepatic – obstruction of bile duct Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Blood Transfusions § § Whole blood transfusions are used: § When blood loss is

Blood Transfusions § § Whole blood transfusions are used: § When blood loss is substantial § In treating thrombocytopenia Packed red cells (cells with plasma removed) are used to treat anemia Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Discussion of Blood Typing § Surface markers on cells – MHC versus RBC markers

Discussion of Blood Typing § Surface markers on cells – MHC versus RBC markers § ABO – Glycoproteins § Rh - Proteins Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 3. 3

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 3. 3

Human Blood Groups § § RBC membranes have glycoprotein antigens on their external surfaces

Human Blood Groups § § RBC membranes have glycoprotein antigens on their external surfaces These antigens are: § § Unique to the individual Recognized as foreign if transfused into another individual Promoters of agglutination and are referred to as agglutinogens Presence or absence of these antigens is used to classify blood groups Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Blood Groups § § § Humans have 30 varieties of naturally occurring RBC antigens

Blood Groups § § § Humans have 30 varieties of naturally occurring RBC antigens The antigens of the ABO and Rh blood groups cause vigorous transfusion reactions when they are improperly transfused Other blood groups (M, N, Dufy, Kell, and Lewis) are mainly used for legalities Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

ABO Blood Groups § § § The ABO blood groups consists of: § Two

ABO Blood Groups § § § The ABO blood groups consists of: § Two antigens (A and B) on the surface of the RBCs § Two antibodies in the plasma (anti-A and anti-B) ABO blood groups may have various types of antigens and preformed antibodies Agglutinogens and their corresponding antibodies cannot be mixed without serious hemolytic reactions Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Blood Types § § Several genetically determined blood groups with multiple types ABO and

Blood Types § § Several genetically determined blood groups with multiple types ABO and Rh most common Red blood cell contains glycolipid antigens on membrane Plasma contains antibodies that react against foreign antigens Figure 19. 6 Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings 19 -83

ABO Blood Groups Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

ABO Blood Groups Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Table 17. 4

Blood Typing § § When serum containing anti-A or anti-B agglutinins is added to

Blood Typing § § When serum containing anti-A or anti-B agglutinins is added to blood, agglutination will occur between the agglutinin and the corresponding agglutinogens Positive reactions indicate agglutination Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Blood Typing Blood type being tested RBC agglutinogens Serum Reaction Anti-A Anti-B AB A

Blood Typing Blood type being tested RBC agglutinogens Serum Reaction Anti-A Anti-B AB A and B + + B B – + A A + – O None – – Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Rh Blood Groups § § § There are eight different Rh agglutinogens, three of

Rh Blood Groups § § § There are eight different Rh agglutinogens, three of which (C, D, and E) are common Presence of the Rh agglutinogens on RBCs is indicated as Rh+ Anti-Rh antibodies are not spontaneously formed in Rh– individuals However, if an Rh– individual receives Rh+ blood, anti-Rh antibodies form A second exposure to Rh+ blood will result in a typical transfusion reaction Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemolytic Disease of the Newborn § § Hemolytic disease of the newborn – Rh+

Hemolytic Disease of the Newborn § § Hemolytic disease of the newborn – Rh+ antibodies of a sensitized Rh– mother cross the placenta and attack and destroy the RBCs of an Rh+ baby Rh– mother becomes sensitized when exposure to Rh+ blood causes her body to synthesize Rh+ antibodies Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemolytic Disease of the Newborn § § The drug Rho. GAM can prevent the

Hemolytic Disease of the Newborn § § The drug Rho. GAM can prevent the Rh– mother from becoming sensitized Treatment of hemolytic disease of the newborn involves pre-birth transfusions and exchange transfusions after birth Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Transfusion Reactions § § Transfusion reactions occur when mismatched blood is infused Donor’s cells

Transfusion Reactions § § Transfusion reactions occur when mismatched blood is infused Donor’s cells are attacked by the recipient’s plasma agglutinins causing: § Diminished oxygen-carrying capacity § Clumped cells that impede blood flow § Ruptured RBCs that release free hemoglobin into the bloodstream Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Transfusion Reactions § Circulating hemoglobin precipitates in the kidneys and causes renal failure Copyright

Transfusion Reactions § Circulating hemoglobin precipitates in the kidneys and causes renal failure Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Plasma Volume Expanders § § When shock is imminent from low blood volume, volume

Plasma Volume Expanders § § When shock is imminent from low blood volume, volume must be replaced Plasma or plasma expanders can be administered Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Plasma Volume Expanders § Plasma expanders § § Have osmotic properties that directly increase

Plasma Volume Expanders § Plasma expanders § § Have osmotic properties that directly increase fluid volume Are used when plasma is not available Examples: purified human serum albumin, plasminate, and dextran Isotonic saline can also be used to replace lost blood volume Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Erythrocyte Disorders § Anemia – blood has abnormally low oxygencarrying capacity § § §

Erythrocyte Disorders § Anemia – blood has abnormally low oxygencarrying capacity § § § It is a symptom rather than a disease itself Blood oxygen levels cannot support normal metabolism Signs/symptoms include fatigue, paleness, shortness of breath, and chills Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Anemia: Insufficient Erythrocytes § § § Hemorrhagic anemia – result of acute or chronic

Anemia: Insufficient Erythrocytes § § § Hemorrhagic anemia – result of acute or chronic loss of blood Hemolytic anemia – prematurely ruptured RBCs Aplastic anemia – destruction or inhibition of red bone marrow Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Anemia: Decreased Hemoglobin Content § Iron-deficiency anemia results from: § § § A secondary

Anemia: Decreased Hemoglobin Content § Iron-deficiency anemia results from: § § § A secondary result of hemorrhagic anemia § Inadequate intake of iron-containing foods § Impaired iron absorption Pernicious anemia results from: § Deficiency of vitamin B 12 § Lack of intrinsic factor needed for absorption of B 12 Treatment is intramuscular injection of B 12; application of Nascobal Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Anemia: Abnormal Hemoglobin § Thalassemias – absent or faulty globin chain in Hb §

Anemia: Abnormal Hemoglobin § Thalassemias – absent or faulty globin chain in Hb § § RBCs are thin, delicate, and deficient in Hb Sickle-cell anemia – results from a defective gene coding for an abnormal Hb called hemoglobin S (Hb. S) § § Hb. S has a single amino acid substitution in the beta chain This defect causes RBCs to become sickle-shaped in low oxygen situations Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Polycythemia § § Polycythemia – excess RBCs that increase blood viscosity Three main polycythemias

Polycythemia § § Polycythemia – excess RBCs that increase blood viscosity Three main polycythemias are: § Polycythemia vera § Secondary polycythemia § Blood doping Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Leukocytes (WBCs) § § Leukocytes, the only blood components that are complete cells: §

Leukocytes (WBCs) § § Leukocytes, the only blood components that are complete cells: § Are less numerous than RBCs § Make up 1% of the total blood volume § Can leave capillaries via diapedesis § Move through tissue spaces Leukocytosis – WBC count over 11, 000 / mm 3 § Normal response to bacterial or viral invasion Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Granulocytes § Granulocytes – neutrophils, eosinophils, and basophils § Contain cytoplasmic granules that stain

Granulocytes § Granulocytes – neutrophils, eosinophils, and basophils § Contain cytoplasmic granules that stain specifically (acidic, basic, or both) with Wright’s stain § Are larger and usually shorter-lived than RBCs § Have lobed nuclei § Are all phagocytic cells Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Granulocyte Development Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Granulocyte Development Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Neutrophils § Neutrophils have two types of granules that: § Take up both acidic

Neutrophils § Neutrophils have two types of granules that: § Take up both acidic and basic dyes § Give the cytoplasm a lilac color § § Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like proteins) Neutrophils are our body’s bacteria slayers Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Eosinophils § Eosinophils account for 1– 4% of WBCs § § Have red-staining, bilobed

Eosinophils § Eosinophils account for 1– 4% of WBCs § § Have red-staining, bilobed nuclei connected via a broad band of nuclear material Have red to crimson (acidophilic) large, coarse, lysosome-like granules Lead the body’s counterattack against parasitic worms Lessen the severity of allergies by phagocytizing immune complexes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Basophils § Account for 0. 5% of WBCs and: § § § Have U-

Basophils § Account for 0. 5% of WBCs and: § § § Have U- or S-shaped nuclei with two or three conspicuous constrictions Are functionally similar to mast cells Have large, purplish-black (basophilic) granules that contain histamine § Histamine – inflammatory chemical that acts as a vasodilator and attracts other WBCs (antihistamines counter this effect) Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Agranulocytes § Agranulocytes – lymphocytes and monocytes: § § § Lack visible cytoplasmic granules

Agranulocytes § Agranulocytes – lymphocytes and monocytes: § § § Lack visible cytoplasmic granules Are similar structurally, but are functionally distinct and unrelated cell types Have spherical (lymphocytes) or kidney-shaped (monocytes) nuclei Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Lymphocytes § Account for 25% or more of WBCs and: § § § Have

Lymphocytes § Account for 25% or more of WBCs and: § § § Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm Are found mostly enmeshed in lymphoid tissue (some circulate in the blood) There are two types of lymphocytes: T cells and B cells § § T cells function in the immune response B cells give rise to plasma cells, which produce antibodies Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Monocytes § Monocytes account for 4– 8% of leukocytes § They are the largest

Monocytes § Monocytes account for 4– 8% of leukocytes § They are the largest leukocytes § They have abundant pale-blue cytoplasms § § They have purple-staining, U- or kidney-shaped nuclei They leave the circulation, enter tissue, and differentiate into macrophages Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Macrophages § Macrophages: § § § Are highly mobile and actively phagocytic Activate lymphocytes

Macrophages § Macrophages: § § § Are highly mobile and actively phagocytic Activate lymphocytes to mount an immune response by producing cytokines Some act as antigen presenting cells Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Mononuclear phagocyte system § § § The mononuclear phagocyte system is a part of

Mononuclear phagocyte system § § § The mononuclear phagocyte system is a part of the immune system that consists of the phagocytic cells located primarily in reticular connective tissue. The cells are primarily monocytes and macrophages, and they accumulate in lymph nodes, bone marrow, the spleen and some other areas. The Kupffer cells of the liver and tissue histiocytes are also part of the MPS. Its functions include: Formation of new red blood cells (RBCs) and white blood cells (WBCs). Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Mononuclear phagocyte system (Functions) § Formation of new red blood cells (RBCs) and white

Mononuclear phagocyte system (Functions) § Formation of new red blood cells (RBCs) and white blood cells (WBCs). § Destruction of old RBCs and WBCs. § Assist in formation of plasma proteins. § Formation of bile pigments. § "Reticuloendothelial system" is an older term for the mononuclear phagocyte system, but it is used less commonly now, as it is understood that most endothelial cells are not macrophages Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Leukocytes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17.

Leukocytes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17. 10

Summary of Formed Elements Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin

Summary of Formed Elements Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Table 17. 2. 1

Summary of Formed Elements Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin

Summary of Formed Elements Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Table 17. 2. 2

Production of Leukocytes § Leukopoiesis is stimulated by interleukins and colony-stimulating factors (CSFs) §

Production of Leukocytes § Leukopoiesis is stimulated by interleukins and colony-stimulating factors (CSFs) § § § Interleukins are numbered (e. g. , IL-1, IL-2), whereas CSFs are named for the WBCs they stimulate (e. g. , granulocyte-CSF stimulates granulocytes) Macrophages and T cells are the most important sources of cytokines Many hematopoietic hormones are used clinically to stimulate bone marrow Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Formation of Leukocytes § § All leukocytes originate from hemocytoblasts Hemocytoblasts differentiate into myeloid

Formation of Leukocytes § § All leukocytes originate from hemocytoblasts Hemocytoblasts differentiate into myeloid stem cells and lymphoid stem cells § Myeloid stem cells become myeloblasts or monoblasts § Lymphoid stem cells become lymphoblasts § Myeloblasts develop into eosinophils, neutrophils, and basophils § Monoblasts develop into monocytes § Lymphoblasts develop into lymphocytes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Stem cells Hemocytoblast Myeloid stem cell Committed Myeloblast cells Myeloblast Lymphoid stem cell Myeloblast

Stem cells Hemocytoblast Myeloid stem cell Committed Myeloblast cells Myeloblast Lymphoid stem cell Myeloblast Develop. Promyelocyte mental pathway Eosinophilic myelocyte Basophilic myelocyte Neutrophilic myelocyte Eosinophilic band cells Basophilic band cells Neutrophilic band cells Eosinophils Basophils Neutrophils (a) (b) (c) Lymphoblast Promonocyte Prolymphocyte Monocytes Lymphocytes (e) (d) Agranular leukocytes Granular leukocytes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Some become Macrophages (tissues) Some become Plasma cells Figure 17. 11

Leukocytes Disorders: Leukemias § § Leukemia refers to cancerous conditions involving WBCs Leukemias are

Leukocytes Disorders: Leukemias § § Leukemia refers to cancerous conditions involving WBCs Leukemias are named according to the abnormal WBCs involved § Myelocytic leukemia – involves myeloblasts § Lymphocytic leukemia – involves lymphocytes Acute leukemia involves blast-type cells and primarily affects children Chronic leukemia is more prevalent in older people Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Leukemia § § § Immature WBCs are found in the bloodstream in all leukemias

Leukemia § § § Immature WBCs are found in the bloodstream in all leukemias Bone marrow becomes totally occupied with cancerous leukocytes The WBCs produced, though numerous, are not functional Death is caused by internal hemorrhage and overwhelming infections Treatments include irradiation, antileukemic drugs, and bone marrow transplants Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Platelets § See Platelet Power. Point Copyright © 2006 Pearson Education, Inc. , publishing

Platelets § See Platelet Power. Point Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemostasis § § A series of reactions for stoppage of bleeding During hemostasis, three

Hemostasis § § A series of reactions for stoppage of bleeding During hemostasis, three phases occur in rapid sequence 1. Vascular spasms – immediate vasoconstriction in response to injury 2. Platelet plug formation 3. Coagulation (blood clotting) Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Vascular Spasm § The first step is immediate constriction of damaged vessels caused by

Vascular Spasm § The first step is immediate constriction of damaged vessels caused by (1) disturbance of myogenic tone and (2) vasoconstrictive paracrine secretions released by the endothelium – like endothelin and thromboxane. Vasoconstriction temporarily decreases blood flow and pressure within the vessel. When you put pressure on a bleeding wound, you also decrease flow within the damaged vessel. Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Platelet Plug Formation § Platelets do not stick to each other or to blood

Platelet Plug Formation § Platelets do not stick to each other or to blood vessels § Upon damage to blood vessel endothelium platelets: § § Are stimulated by thromboxane A 2 § Stick to exposed collagen fibers and form a platelet plug § § With the help of von Willebrand factor (VWF) adhere to collagen Release serotonin and ADP, which attract still more platelets The platelet plug is limited to the immediate area of injury by prostacyclin Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Coagulation § § § A set of reactions in which blood is transformed from

Coagulation § § § A set of reactions in which blood is transformed from a liquid to a gel Coagulation follows intrinsic (new name contact activation pathway) and extrinsic pathways (new name tissue factor pathway) The final three steps of this series of reactions are: § Prothrombin activator is formed § Prothrombin is converted into thrombin § Thrombin catalyzes the joining of fibrinogen into a fibrin mesh Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Classes of Clotting Factors § Thrombin sensitive – Factors I, V, VIII and XIII

Classes of Clotting Factors § Thrombin sensitive – Factors I, V, VIII and XIII § Vitamin K Dependent – II, VII, IX, X Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Coagulation Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17.

Coagulation Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17. 13 a

Detailed Events of Coagulation Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin

Detailed Events of Coagulation Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 17. 13 b

Coagulation Phase 1: Two Pathways to Prothrombin Activator § May be initiated by either

Coagulation Phase 1: Two Pathways to Prothrombin Activator § May be initiated by either the intrinsic or extrinsic pathway § § Triggered by tissue-damaging events § Involves a series of procoagulants § Each pathway cascades toward factor X Once factor X has been activated, it complexes with calcium ions, PF 3, and factor V to form prothrombin activator Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Coagulation Phase 2: Pathway to Thrombin § Prothrombin activator catalyzes the transformation of prothrombin

Coagulation Phase 2: Pathway to Thrombin § Prothrombin activator catalyzes the transformation of prothrombin to the active enzyme thrombin Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Coagulation Phase 3: Common Pathways to the Fibrin Mesh § Thrombin catalyzes the polymerization

Coagulation Phase 3: Common Pathways to the Fibrin Mesh § Thrombin catalyzes the polymerization of fibrinogen into fibrin § § § Insoluble fibrin strands form the structural basis of a clot Fibrin causes plasma to become a gel-like trap Fibrin in the presence of calcium ions activates factor XIII that: § Cross-links fibrin § Strengthens and stabilizes the clot Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Factor XIII action Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Factor XIII action Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Clot Retraction and Repair § § Clot retraction – stabilization of the clot by

Clot Retraction and Repair § § Clot retraction – stabilization of the clot by squeezing serum from the fibrin strands Repair § § § Platelet-derived growth factor (PDGF) stimulates rebuilding of blood vessel wall Fibroblasts form a connective tissue patch Stimulated by vascular endothelial growth factor (VEGF), endothelial cells multiply and restore the endothelial lining Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Factors Limiting Clot Growth or Formation § Two homeostatic mechanisms prevent clots from becoming

Factors Limiting Clot Growth or Formation § Two homeostatic mechanisms prevent clots from becoming large § Swift removal of clotting factors § Inhibition of activated clotting factors § § § Protein C – glycoprotein produced in the liver and is the major inhibitor of coagulation. It degrades factors V and VIII. It needs Protein S to work. Protein S – Produced in liver and acts as a cofactor for Protein C. Thrombomodulin – binds to thrombin and activates Protein C Antithrombin III – produced in liver and is major inhibitor of Thrombin - Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings §

Heparin § § Produced by mast cells, basophils and endothelial cells. Complexes with Antithrombin

Heparin § § Produced by mast cells, basophils and endothelial cells. Complexes with Antithrombin III to inhibit Thrombin – but also inhibits XII, X, IX Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Plasminogen Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Plasminogen Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Inhibition of Clotting Factors § § Thrombin not absorbed to fibrin is inactivated by

Inhibition of Clotting Factors § § Thrombin not absorbed to fibrin is inactivated by antithrombin III Heparin, another anticoagulant, also inhibits thrombin activity Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Inhibition of Clotting Factors § Fibrin acts as an anticoagulant by binding thrombin and

Inhibition of Clotting Factors § Fibrin acts as an anticoagulant by binding thrombin and preventing its: § § § Positive feedback effects of coagulation Ability to speed up the production of prothrombin activator via factor V Acceleration of the intrinsic pathway by activating platelets Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Factors Preventing Undesirable Clotting § § Unnecessary clotting is prevented by endothelial lining the

Factors Preventing Undesirable Clotting § § Unnecessary clotting is prevented by endothelial lining the blood vessels Platelet adhesion is prevented by: § The smooth endothelial lining of blood vessels § Heparin and PGI 2 secreted by endothelial cells § Vitamin E quinone, a potent anticoagulant Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemostasis Disorders: Thromboembolytic Conditions § Thrombus – a clot that develops and persists in

Hemostasis Disorders: Thromboembolytic Conditions § Thrombus – a clot that develops and persists in an unbroken blood vessel § § Thrombi can block circulation, resulting in tissue death Coronary thrombosis – thrombus in blood vessel of the heart Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemostasis Disorders: Thromboembolytic Conditions § Embolus – a thrombus freely floating in the blood

Hemostasis Disorders: Thromboembolytic Conditions § Embolus – a thrombus freely floating in the blood stream § § Pulmonary emboli can impair the ability of the body to obtain oxygen Cerebral emboli can cause strokes Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Prevention of Undesirable Clots § Substances used to prevent undesirable clots: § § §

Prevention of Undesirable Clots § Substances used to prevent undesirable clots: § § § Aspirin – an antiprostaglandin that inhibits thromboxane A 2 Heparin – an anticoagulant used clinically for pre- and postoperative cardiac care Warfarin – used for those prone to atrial fibrillation Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemostasis Disorders § § Disseminated Intravascular Coagulation (DIC): widespread clotting in intact blood vessels

Hemostasis Disorders § § Disseminated Intravascular Coagulation (DIC): widespread clotting in intact blood vessels Residual blood cannot clot Blockage of blood flow and severe bleeding follows Most common as: § § A complication of pregnancy A result of septicemia or incompatible blood transfusions Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemostasis Disorders: Bleeding Disorders § Thrombocytopenia – condition where the number of circulating platelets

Hemostasis Disorders: Bleeding Disorders § Thrombocytopenia – condition where the number of circulating platelets is deficient § § Patients show petechiae due to spontaneous, widespread hemorrhage Caused by suppression or destruction of bone marrow (e. g. , malignancy, radiation) Platelet counts less than 50, 000/mm 3 is diagnostic for this condition Treated with whole blood transfusions Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemostasis Disorders: Bleeding Disorders § § Inability to synthesize procoagulants by the liver results

Hemostasis Disorders: Bleeding Disorders § § Inability to synthesize procoagulants by the liver results in severe bleeding disorders Causes can range from vitamin K deficiency to hepatitis and cirrhosis Inability to absorb fat can lead to vitamin K deficiencies as it is a fat-soluble substance and is absorbed along with fat Liver disease can also prevent the liver from producing bile, which is required for fat and vitamin K absorption Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemostasis Disorders: Bleeding Disorders § Hemophilias – hereditary bleeding disorders caused by lack of

Hemostasis Disorders: Bleeding Disorders § Hemophilias – hereditary bleeding disorders caused by lack of clotting factors § § § Hemophilia A – most common type (83% of all cases) due to a deficiency of factor VIII Hemophilia B – due to a deficiency of factor IX Hemophilia C – mild type, due to a deficiency of factor XI Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Hemostasis Disorders: Bleeding Disorders § § Symptoms include prolonged bleeding and painful and disabled

Hemostasis Disorders: Bleeding Disorders § § Symptoms include prolonged bleeding and painful and disabled joints Treatment is with blood transfusions and the injection of missing factors § PT (Prothrombin Time) § PTT (Partial Thromboplastin Time) § INR (International Normalized Ratio) Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Diagnostic Blood Tests § § Laboratory examination of blood can assess an individual’s state

Diagnostic Blood Tests § § Laboratory examination of blood can assess an individual’s state of health Microscopic examination: § § § Variations in size and shape of RBCs – predictions of anemias Type and number of WBCs – diagnostic of various diseases Chemical analysis can provide a comprehensive picture of one’s general health status in relation to normal values Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Developmental Aspects § § Before birth, blood cell formation takes place in the fetal

Developmental Aspects § § Before birth, blood cell formation takes place in the fetal yolk sac, liver, and spleen By the seventh month, red bone marrow is the primary hematopoietic area Blood cells develop from mesenchymal cells called blood islands The fetus forms Hb. F, which has a higher affinity for oxygen than adult hemoglobin Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings

Developmental Aspects § § § Age-related blood problems result from disorders of the heart,

Developmental Aspects § § § Age-related blood problems result from disorders of the heart, blood vessels, and the immune system Increased leukemias are thought to be due to the waning deficiency of the immune system Abnormal thrombus and embolus formation reflects the progress of atherosclerosis Copyright © 2006 Pearson Education, Inc. , publishing as Benjamin Cummings