Blood Physiology (HES 029) Lecture Notes PDF

PHYSIOLOGY BLOOD PART 1 HES 029: Human Anatomy and Physiology with Pathophysiology Prepared by: Tiongson, Jonathan Jr A, RMT Learning Objectives: At the end of each session, the students with 75% accuracy will be able to: Explain the general functions of blood Describe the characterist...

PHYSIOLOGY BLOOD PART 1 HES 029: Human Anatomy and Physiology with Pathophysiology Prepared by: Tiongson, Jonathan Jr A, RMT Learning Objectives: At the end of each session, the students with 75% accuracy will be able to: Explain the general functions of blood Describe the characteristics of normal red blood cell and how it is produced. Explain the importance of erythropoietin in RBC production as well as the function of cyanocobalamin and folic acid Describe the metabolism of iron and describe the condition related to the deficiency of iron in the body Define Hematopoiesis Describe general morphologic changes that occur during blood cell maturation List and describe the erythroid precursors in order of maturity, including the morphologic characteristics, cellular activities, normal location, and length of time in the stage for each Anatomy Lesson 1: Human Structure Organization HES 029: Human Anatomy and Physiology with Pathophysiology Learning Objectives: At the end of each session, the students with 75% accuracy will be able to: Explain how hypoxia stimulates RBC production Discuss the various mechanisms by which EPO contributes to erythropoiesis. Describe the components and structure of hemoglobin Describe the mechanism by which hemoglobin transports oxygen to the tissues and transports carbon dioxide to the lungs Name and discuss the important functions of neutrophil, eosinophil, and basophil and its different stages development and describe the morphology of each stage. Discuss the functions of monocytes, macrophages, T cells, B cells, and natural killer cells in the immune response Discuss the megakaryocyte differentiation, the proplatelet process, and thrombocytopoiesis. Anatomy Lesson 1: Human Structure Organization HES 029: Human Anatomy and Physiology with Pathophysiology FUNCTIONS AND COMPOSITION OF BLOOD ❑Transports of gases, nutrients and waste products ❑Transports of processed and regulatory molecules ❑Regulation of pH and osmosis ❑Maintenance of body temperature ❑Protection against foreign substance ❑Clot formation GENERAL CHARACTERISTICS OF BLOOD 1. In vivo, blood is in fluid form; In vitro, it coagulates 5-10 minutes 2. Thick and viscous; 3.5-4.5 times thicker than water 3. Approximately 20 grams solid per 100 ml blood 4. Blood pH: 7.35-7.45 ( average: 7.40) 5. Color Arterial Blood- BRIGHT RED Venous Blood- DARK Red PLASMA SERUM Fluid portion of anticoagulated blood Fluid portion of non-anticoagulated blood Slightly hazy appearance Clear appearance COMPOSITION OF BLOOD Peripheral Blood Smear ▪ Blood film well stained with Wright’s stain have a pink to purple color when viewed with the naked eye ▪ Fixative:______ ▪ Stain: _______ ▪ Buffer : ______  TESTS NORMAL VALUES MALE FEMALE Red Blood Cell count 4.20 – 6.00 x1012/L 3.80 – 5.20 X1012/L Hemoglobin count 13.5-18 g/dl 12-15 g/dl Hematocrit 40-to 54% 35-49% White Blood Cell 4.0 – 11.0 X10 12/L count Platelet count 150-400 x1012/L DIFFERENTIAL COUNT REFERENCE INTERVALS Neutrophils : 50-70% Lymphocytes : 18-42% Monocytes : 2-11% Eosinophils : 1-4 Basophils : 0-1% Formed Elements of the Blood CHECK FOR UNDERSTANDING Ideal characteristics of a well-prepared blood smear: I. 2/3 the length of the film slide II. Bullet-shaped III. Appears smooth with irregularities, holes and streaks IV. Feathery edge a. I, II, III, IV b. I, II, III c. I, II, IV d. I and IV CHECK FOR UNDERSTANDING What is the effect of trapped plasma in microhematocrit result? A. Falsely increased in manual method B. Falsely increased in automated method C. Falsely decreased in manual method D. Falsely decreased in automated method CHECK FOR UNDERSTANDING Which of the following is a cause of absolute erythrocytosis (increased hemoglobin and red cell count)? A. Dehydration B. Infection C. Polycythemia vera D. Hemolysis CHECK FOR UNDERSTANDING What is the first type of cell produced by the developing embryo? A.Granulocyte B.Lymphocyte C.Thrombocyte D.Erythrocyte HEMATOPOIESIS Is a continuous, regulated process of blood cell production that includes cell renewal, proliferation, differentiation and maturation. Hematopoietic Stem Cells Retain the ability to differentiate into any cell lines Referred to as colony-forming units Capable of self renewal and directed differentiation into all required cell lineages PROGENITOR CELLS - Differentiate into only one cell line PRECURSOR CELLS - blasts forms -include myeloblast, megakaryoblast, erythroblast HEMATOPOIESIS MEDULLARY EXTRAMEDULLARY HEMATOPOIESIS HEMATOPOIESIS Type Primary Site/s Occurrence Hepatomegaly Splenomegaly BONE MARROW RED/ACTIVE MARROW Developing blood cells and their progenitors YELLOW/INACTIVE MARROW Composed primarily of adipocytes Retrogression: the process of replacing the active marrow by adipocytes during the development CHECK FOR UNDERSTANDING The hemapoietically active marrow: a. Yellow b. Red c. Both are active d. No correct response CHECK FOR UNDERSTANDING What percentage of tissue located in the bone marrow cavities of adults is fat? A. 10% B. 25% C. 50% D. 75% CHECK FOR UNDERSTANDING Which of these organ/tissue is the extramedullary site of blood production? A. Pelvis B. Liver C. Bone marrow D. Thymus CHECK FOR UNDERSTANDING All of the following processes are allowed to take place in an ideal environment for hematopoietic stem cells, EXCEPT: A. Differentiation B. Self-renewal C. Necrosis D. Proliferation CHECK FOR UNDERSTANDING Which of the following is NOT characteristic of pluripotent hematopoietic stem cells? A. Possess self-renewal ability B. Produce progenitor cells committed to a single cell lineage C. Express the stem cell marker CD13 D. Are morphologically unrecognizable CHECK FOR UNDERSTANDING Short draw in an evacuated tubes causes the hematocrit reading to be _______. A. erratic B. Increased C. Inconsistent D. Decreased CHECK FOR UNDERSTANDING Which are locations of the adult hematopoiesis tissue? I. Lymph nodes II. Spleen III. Liver IV. Thymus A. I , III, and IV B. II, III and IV C. I, II, and III D. I, II, III and IV RED BLOOD CELLS ▪ Biconcave discs ▪ One-third hemoglobin or: Oxyhemoglobin Deoxyhemoglobin ▪ Able to readily squeeze through capillaries ▪ Lack nuclei and cytoplasmic organelles (mitochondria) ▪ Human Erythrocytes are 7.5 um in diameter, 2.6 um thick at the rim and 0.8 um thick in the center ▪ The normal concentration of erythrocytes in blood is approximately 3.9- 5.5 million/uL in women and 4.1-6 million/uL in men RED BLOOD CELLS ▪ The process of RBC development from stem cells takes about 7 days and is called erythropoiesis. ▪ They pass through several stages of development before entering the blood ERYTHROPOIESIS Red Blood Cell Maturation Series (The Precursors) ❑ PRONORMOBLAST Earliest morphologically recognizable precursor ❑ BASOPHILIC NORMOBLAST Intense basophilic cytoplasm The chromatin may be partially clumped, and the pattern may suggest a wheel with broad spokes  Red Blood Cell Maturation Series (The Precursors) ❑ POLYCHROMATOPHILIC NORMOBLAST Blue-gray to pink-gray cytoplasm Last stage of capable of mitosis First stafe of hemoglobin synthesis ❑ ORTHOCHROMATIC NORMOBLAST Small pyknotic nucleus Enucleation Last nucleated stage First stage that is incapable of mitosis  Red Blood Cell Maturation Series (The Precursors) ❑ RETICULOCYTE Pink to slightly pinkish gray cytoplasm Contains fine basophilic reticulum of RNA which is only visible with supravital stain Last stage capable for the production of hemoglobin ❑ MATURE ERYTHROCYTE 6-8 um diameter Salmon pink in color Non-nucleated, round, biconcave disc with a central pallor that occupies the middle 1/3 of the cell No mitochondria ERYTHROCYTE MEMBRANE PHYSIOLOGY Three components of RBC Membrane: ❑ PROTEIN (52%) ❑ LIPID (40%) ❑ CARBOHYDRATES (8%) ERYTHROCYTE MEMBRANE PHYSIOLOGY PROTEIN (50%) ❑ INTEGRAL PROTEINS They serve as transport and adhesion sites and signaling receptors They support the blood group antigens ❑ PERIPHERAL PROTEINS Provides the shape and flexibility of the RBC LIPID (40%) Main physiologic functions: External Surface ✓ Maintain cell and deformability Phospholipids ✓ Maintain osmotic balance between plasma Phosphatidylcholine and the cell cytoplasm ✓ Act as supporting skeletal system for Glycolipid surface antigens and receptors Sphingomyelin ✓ Aid in the transportation of essential cellular Internal Surface ions and gases Phosphatidyl ethanolamine Phosphatidyl inositol Phosphatidyl serine ERYTHROPOIETIN ▪ The immature cells are released into the blood stream as reticulocytes and then mature into erythrocytes over 1-2 days within circulation. ▪ Erythropoietin (EPO) is a hormone glycoprotein produced in the kidney and liver and stimulates the production of globin and enhances the release reticulocytes in the circulation and enhances reticulocytes maturation to mature RBC. Major Stimulus: Hypoxia Other Stimulus: Testosterone Estrogen, Pituitary and Thyroid Hormone Dietary Factors Affecting Red Blood Cell Production CHECK FOR UNDERSTANDING Which are the primary target cells of EPO? A. Leukemic myeloblasts B. Fibroblasts C. Bone marrow erythroid progenitors D. Neutrophils precursors CHECK FOR UNDERSTANDING Which is the general description of cytoplasmic color in younger cells? A. Lighter blue B. Pinkish C. Grayish D. Dark blue CHECK FOR UNDERSTANDING Which is the precursor of the orthochromic normoblast? A. Polychromatic erythrocyte B. Pronormoblast C. Basophilic normoblast D. Polychromatic normoblast CHECK FOR UNDERSTANDING What is the last RBC maturation stage that undergoes mitosis? A. 5th stage B. 2nd stage C. 3rd stage D. 4th stage HEMOGLOBIN ▪ The main component of a red blood cell is the pigmented protein hemoglobin which accounts for about a third of the cell’s volume ▪ It is responsible for transport of O2 from lungs to tissues and CO2 from tissues to lungs. ▪ Hemoglobin is composed of four subunits. Each subunit with heme and globin ▪ 4 Heme- consists of protoporphyrin IX and ferrous iron ▪ 4 Globin- consists of 2 identical pairs of unlike polypeptide chains HEMOGLOBIN AGE GROUP REFERENCE VALUE Children 12 to 15 g/dl Adult Male 14 to 18 g/dl Adult Female 12 to 15 g/dl TYPES OF HEMOGLOBIN ❑ FETAL HEMOGLOBIN (HB F) - present in the fetus during the last seven months of development in the uterus and replaced by adult hemoglobin within 6 months after birth ❑ ADULT HEMOGLOBIN (HB A) -predominate hemoglobin in an adult - subdivided into glycosylated fractions A1c which reflects glucose level in the blood DESTRUCTION OF HEMOGLOBIN Macrophages break down hemoglobin into heme and globin The globin chains of hemoglobin are broken down to individual amino acids and are metabolized or used to build new proteins Iron is released from the heme of hemoglobin. The heme is converted into bilirubin. Iron is transported in the blood to the red bone marrow and used in the production of new hemoglobin Bilirubin is transported in the blood to the liver. Bilirubin is excreted as part of the bile into the small intestine. Some bilirubin derivatives contribute to the color of feces Other bilirubin derivatives are reabsorbed from the intestine into the blood and excreted from the kidneys in the urine, contributing to the color of urine  ANEMIA Anemia is defined as a DECREASE in RBC, Hb, and hematocrit resulting in decreased oxygen delivery to the tissues. The anemias can be classified morphologically using RBC indices. They can be classified based on etiology/cause. IRON DEFICIENCY ANEMIA/NUTRITIONAL ANEMIA Most common form of anemia Prevalent in INFANTS and CHILDREN, PREGNANCY, excessive menstrual flow, elderlty with poor diets, malabsorption syndromes, chronic blood loss. ETIOLOGY ✓ Inadequate intake of iron ✓ Increase demand (Pregnancy, Infancy and childhood) ✓ Impaired iron absorption (Celiac disease and decrease stomach acidity) ✓ Chronic blood loss Clinical signs and symptoms Fatigue, weakness, and shortness of breath, esp. with exertion, sore tongue, inflamed cracks at the corners of the mouth, Koilonychia may be seen if the deficiency is long standing. Patients also may be experience cravings for nonfood items, called pica. CHECK FOR UNDERSTANDING The storage form of iron in insoluble form: A. Ferritin B. Hemosiderin C. Transferrin D. Ferrous CHECK FOR UNDERSTANDING Which of the following is considered a normal hemoglobin? A. Carboxyhemoglobin B. Methemoglobin C. Sulfhemoglobin D. Deoxyhemoglobin CHECK FOR UNDERSTANDING What are the initial laboratory tests that are performed for the diagnosis of anemia? A. Complete blood count, Iron studies and Reticulocyte count B. Complete blood count, Reticulocyte, Peripheral blood film examination C. Reticulocyte count, Serum Iron. Vitamin B12,and Folate assays D. Bone marrow study, Iron studies, and Peripheral blood film examination WHITE BLOOD CELLS ▪ Leucocytes are the largest blood cells. ▪ They account for only about 1% of the blood volume ▪ They are true cells, each leucocyte having a nucleus, mitochondria, and other organelles ▪ Leucocytes can actively move while erythrocytes do not have mobility of their own ▪ Most leucocytes have a relatively short life span ▪ Leukocytes can squeeze between the cells of a capillary wall and enter the tissue space outside the blood vessel FIVE TYPES OF LEUKOCYTES FUNCTIONS: ✓ To protect the body against invading microorganisms and other pathogens ✓ To remove dead cells and debris from the tissued by phagocytosis GRANULOCYTES ▪ Neutrophil ▪ Eosinophil ▪ Basophil AGRANULOCYTES ▪ Lymphocyte ▪ Monocyte GRANULOPOIESIS General Cell Maturation Characteristics for Leukocytes IMMATURE CELLS MATURE CELLS Cell is LARGE Cell becomes SMALLER Nucleoli is present Nucleoli absent Chromatin fine and delicate Chromatin coarsed and clumped Nucleus ROUND Nucleus ROUND, LOBULATED or SEGMENTED Cytoplasm Dark blue (rich in RNA) Cytoplasm light blue (Less RNA) GRANULOCYTES NEUTROPHIL ▪ Constitute 60-70% of circulating leukocytes ▪ They are 12-15 µm in diameter with nucleus consisting of 2-5 lobes ▪ The cytoplasm of the neutrophil contains 2 main types of granules (specific granules and azurophilic granules) ▪ Have short half life 6-7 hours in blood and 1-4 days in the tissues ▪ Have phagocytic activity against bacteria and other small particles ▪ During phagocytosis, superoxide (O2-) and hydrogen peroxide (H2O2-) are formed that kill microorganisms ▪ Myeloperoxidase with (O2-) form a powerful killing system. GRANULOCYTES EOSINOPHIL ▪ constitute 2-4% of leukocytes in normal blood ▪ These cells have bilobed nucleus ▪ Life span in circulation is about 10 hours and 10 days in tissues ▪ The cytoplasm of eosinophil contains large granules that are stained by eosin ▪ This granules contain a protein called the major basic protein. This protein has ability to kill parasitic worm ▪ An increase in the number of eosinophils in the blood is associated with allergic reaction and parasitic infection GRANULOCYTES BASOPHIL ▪ make up less than 1% of blood leukocytes ▪ There are about 12-15 µm in diameter ▪ The nucleus is divided into irregular lobes or S shaped ▪ The cytoplasm contains very large granules that are stained with basic dye ▪ The granules contain mainly histamine and heparin ▪ These cells play an important role in the allergy and hypersensitivity CHECK FOR UNDERSTANDING The washing of prepared blood smear must be done properly. When the smeared blood is washed out with water, a ghost cell will be produced, which is primarily the ________. A. Neutrophil B. Eosinophil C. Basophil D. Monocyte CHECK FOR UNDERSTANDING The indention of nucleus in WBC maturation series is first evidently seen with ____. A. Promyelocyte B. Myelocyte C. Metamyelocyte D. Band cell CHECK FOR UNDERSTANDING Youngest cell to appear in peripheral blood smear, with its characteristic sausage-shaped nucleus. A. Promyelocyte B. Band cell C. Metamyelocyte D. Band cell CHECK FOR UNDERSTANDING What is the name of the process by which phagocytic cells are attracted to a substance such as a bacterial peptide? A. Diapedesis B. Degranulation C. Chemotaxis D. Phagotaxis CHECK FOR UNDERSTANDING This is the most predominant cell in the bone marrow A. Promyelocyte B. Myelocyte C. Metamyelocyte D. Band cell CHECK FOR UNDERSTANDING Which cells contains granules with Charcot-Leyden crystals protein? A. Neutrophil B. Eosinophil C. Monocyte D. Basophil CHECK FOR UNDERSTANDING Which cells contains granules with Charcot-Leyden crystals protein? A. Neutrophil B. Eosinophil C. Monocyte D. Basophil The precursor of neutrophil is ______ A. Myelocyte B. Band cell C. Promyelocyte D. Metamyelocyte AGRANULOCYTES AGRANULOCYTES MONOCYTES ▪ They account 4-11% ▪ The nucleus is horseshoe- or kidney-shaped ▪ The cytoplasm of monocyte is basophilic and contains very fine azurophilic granules (lysosomes) ▪ Blood monocytes migrate into the tissues and develop into macrophages ▪ Macrophages engulf large particles and pathogens ▪ The life span in the circulation is few days but 60-120 days in the tissues ▪ The main function monocyte is phagocytosis but also has ability to secret certain substances like interleukins ▪ Macrophages have important functions in inflammation and immunity AGRANULOCYTES MACROPHAGES ▪ These are tissue monocytes ▪ Cells that usually have an oval nucleus with a netlike (reticulated) chromatin pattern. Their cytoplasm is pale, frequently vacuolated, and often filled with debris of phagocytized cells or organisms NOMENCLATURE OF DIFFERENT MACROPHAGES ON ITS SPECIFIED TISSUE LOCATION TISSUE/ORGAN Liver Kidney Brain Bone Lungs Connective tissue Skin Spleen Placenta AGRANULOCYTES AGRANULOCYTES LYMPHOCYTES ▪ Lymphocytes are spherical cells ▪ There are small lymphocytes with diameter of 6-8 µm and large lymphocytes with diameter up to 18 µm. ▪ The nucleus of lymphocyte are large and rounded ▪ The cytoplasm of the small lymphocytes is scanty and in blood smear it appears as a thin rim rounded the nucleus ▪ And it is slightly basophilic ▪ Lymphocytes vary in life span; some live only a few days and other survive for many years. ▪ Lymphocytes are classified according to their function to; B lymphocyte, T lymphocyte, and Natural Killer cell. ▪ All types of lymphocytes are related to immune reactions in defending against invading microorganisms, foreign macromolecules, and cancer cells. T LYMPHOCYTES ▪ Represents 60-80% of circulating lymphocytes in the peripheral blood ▪ Matures at the thymus ▪ End products of activation are CYTOKINES B LYMPHOCYTES ▪ Represents 20-35% of lymphocytes population ▪ Matures at bone marrow ▪ Precursors cells in antibody production ▪ B cells are the precursor of plasma cells NATURAL KILLER CELLS ▪ Represents 10-15% of total lymphocytes population ▪ They are under the NATURAL IMMUNITY, thus they are non specific compared to B and T cells ▪ They are essential mediators of virus immunity ▪ They can destroy virally infected cells or tumor cells PLATELETS MEGAKARYOPOIESIS Maturation time : 5 days Endomitosis: Nuclear division without cytoplasmic division a form of mitosis that lacks telophase and cytokinesis CHECK FOR UNDERSTANDING Regarded as NOT an end cell: A. Neutrophil B. Monocyte C. Lymphocyte D. Platelets CHECK FOR UNDERSTANDING Which are antibody producing lymphocytes? A. T cell B. Monocyte C. B cell D. Natural Killer cell PLATELETS ▪ Blood platelets are non-nucleated disc like cell fragments 2-4 µm in diameter ▪ Platelets are considered as NOT TRUE CELLS ▪ They originate from fragments of megakaryocyte cytoplasm that reside in the red bone marrow. ▪ Platelets promote blood clotting and help repair gaps in the walls of blood vessels, preventing loss of blood ▪ Normal platelets counts range from 200,000- 400000 per microliter of blood ▪ Thrombopoietin released by kidneys has ability to stimulate platelets synthesis PLATELET CLUMPING CHECK FOR UNDERSTANDING Megakaryocytic cells are able to undergo multiple mitotic division without cytoplasmic division, which generate giant multinucleated cells. A. Mitosis B. Endomitosis C. Meiosis D. Exomitosis CHECK FOR UNDERSTANDING Which of the following blood anticoagulants is utilized for platelet studies? A. EDTA B. Thrombin C. Citrate D. Heparin CHECK FOR UNDERSTANDING Using an automated hematology analyzer, presence of large platelet clumps may increase ______ count. A. RBC B. Band cell C. Nucleated RBC D. WBC SUMMARY OF POINTS PARAMETERS INCREASED DECREASED RBC Count Polycythemia vera Anemia Secondary due to dehydration After age 50 y.o and effect of altitude Hemoglobin count Strenous muscular activity Anemia Smoker, altitude After age 50 y.o dehydration Hematocrit Polycythemia vera Anemia After age 50 y.o WBC Count Bacterial Infection Viral diseases (measles) Leukemia Typhoid fever Appendicitis Infectious hepatitis Pregnancy Strenuous exercise, emotional stress, anxiety Platelet count Polycythemia vera Thrombocytopenia purpura CML Aplastic anemia Splenectomy Acute leukemia REFERENCE Keohane, E. M., Walenga, J. M., & Otto, C. N. (2020). Rodaks Hematology: Clinical principles and applications (6th ed.) Elsevier. Vanputte, C.L., Regan, J. L., & Russo, A. F. (2022). Seeley’s essentials of anatomy & physiology (11th ed.). McGraw-Hill Education. Keller, E. M. (2017). Essentials of Human Anatomy and Physiology. Redwood: Pearson. Hall, J.E. (2016). Guyton and Hall textbook of medical physiology (14th ed.) Elsevier.