Hematologic part 1 2024 for PRESENTATION IN CLASS REV 10 (5).pdf

Advanced Anatomy & Physiology Structure and Function of the Hematologic System Chapter 27 (McCance-Heuther) 1 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Learning Objectives q Identify and describe the constituents of whole blood: formed elements (white blood cells [WBCs...

Advanced Anatomy & Physiology Structure and Function of the Hematologic System Chapter 27 (McCance-Heuther) 1 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Learning Objectives q Identify and describe the constituents of whole blood: formed elements (white blood cells [WBCs], red blood cells [RBCs], platelets), plasma proteins, and solutes (electrolytes, gases, nutrients, waste products). q Describe the constituents and functions of the three major classes of plasma proteins. q Identify the structural characteristics, normal values, and function of RBCs q Characterize the cellular changes that take place in RBC maturation. q Discuss Development of RBCs, WBCs and Platelets. q Describe the structure of the hemoglobin molecule. q Identify the vitamins & hormones essential to the generation/maturation of RBCs. q Describe the sequence of recycling for senescent erythrocytes. q Characterize the structure and function of the granulocytes (Neutrophils, Eosinophils, and Basophils). q Characterize the structure and function of the agranulocytes (monocytes, lymphocytes, and natural killer (NK) cells). q Describe the development and function of platelets (thrombocytes). Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. 2 Learning Objectives q Describe the locations and process of hematopoiesis. q Compare and contrast the development of granulocytes, monocytes, macrophages, and lymphocytes. q Describe the maturation sequence for platelets (thrombocytes). q Explain blood typing. q Describe the stages of the hemostatic mechanism. q Characterize the coagulation cascade. q Compare the activation of the intrinsic and extrinsic pathways. q Describe the various mechanisms of anticoagulation. q Identify and describe the system responsible for lysis of blood clots; discuss the roles of tissue plasminogen activator (PA), plasminogen, plasmin, and urokinase type PA. q Describe the association of fibrin degradation products (FDPs) and D-dimers to the fibrinolytic system. 3 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Centrifuged Blood 4 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Components of the Hematologic System 5 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Components of the Hematologic System Plasma proteins § 7% of plasma total weight § Majority are synthesized in the liver Albumin (57%): 30-50 g/L o Function as carriers; control plasma osmotic pressure Globulins (38%): 20-40 g/L α, β, γ Clotting factors (5%): 2-4 g/L 6 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Globulins α (Liver) ˜ α1 Ø ˜ A1AT ˜ ˜ ˜ γ (B cells) β (Liver) α2 ˜ Ø Angiotensiongen Ø Haptoglobin Ø Ceruloplasmin Transferrin Lipoproteins Plasminogen β2-macroglobulin Ø ˜ Part of Class I MHC molecule immunoglobulins (Ig) = antibodies, IgG (most abundant antibody) (binds Hgb) (binds Cu++) 7 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Components of the Hematologic System Other solutes § 2% of the plasma total weight Electrolytes (ions): Nutrients: Electrolyte Sodium Potassium Calcium Magnesium Chloride HCO3- (venous) Phosphate SO4- Range 135-145 mEq/L 3.5-5.0 mEq/L 8.4-10.6 mg/dL 1.3-2.1 mg/dL 96-106 mEq/L 23-29 mEq/L 3.0-4.5 mg/L 1 mEq/L SI units 135-145 mmol/L 3.5 - 5.0 mmol/L 2.10 - 2.65 mmol/L 0.65 - 1.05 mmol/L 96 - 106 mmol/L 23 - 29 mmol/L 1.0 - 1.5 mmol/L 0.25 - 0.75 mmol/L 8 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Components of the Hematologic System Other solutes Gases: Regulatory substances: o Hormones Waste products: o Urea (BUN) o Uric acid o Creatinine o Bilirubin 9 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Properties of Blood ˜ ˜ Viscosity - resistance to flow Ø whole blood 5 times as viscous as water Osmolarity - dissolved particles Na+ ions, proteins and RBCs Ø high osmolarity draws water from tissues into blood = BP Ø low osmolarity water remains in tissues, possibly = edema 10 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Formed Elements 11 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Formed Elements (45% by volume) Most abundant, carry O2 and CO2 “PMN” leukocytes, most abundant wbc Involved in allergic rxns & attack parasites account for 20 – 30% of circulating leukocytes Phagocytosis; antigen processing and presenting Formed from Megakaryocytes, form platelet plug in hemostasis Contain histamine & heparin 12 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Formed Elements (45% by volume) Basophil Eosinophil Neutrophil Lymphocyte Monocyte 13 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. 14 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Erythrocytes (RBCs) § Gas transport and exchange - major function increased surface area:volume ratio o due to loss of organelles during maturation o increases diffusion rate of substances 95% of cytoplasmic protein content is hemoglobin (Hb) o O2 delivery to tissue and CO2 transport to lungs § Carbonic anhydrase (CAH) produces carbonic acid from CO2 and water important role in gas transport and pH balance 15 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Erythrocytes (RBCs) § Are the most abundant cells of the blood (4.2-6.2 x 106/µL) § ~48% blood volume in men; ~42% in women. § Are responsible for tissue oxygenation. § Contain hemoglobin. § Have biconcavity and reversible deformity. Biconcavity: provides a high surface to volume ratio for optimal gas diffusion. Reversible deformity: Enables the erythrocyte to assume a more compact shape, squeeze through the microcirculation, and return to normal. § No nucleus or mitochondria; cannot divide; constantly replenished § erythropoiesis § Blood Type determined by surface glycoproteins. § 120-day life cycle. 16 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Erythrocytes (RBCs) Hemoglobin - oxygen-carrying protein (~300 million hemoglobin molecules/RBC) § § § § § 4 Heme groups conjugate with 4 protein chains (two α and two β) each Porphyrin Ring of heme contains an Iron (Fe2+) Each Hgb molecule can carry 4 O2 = Oxyhemoglobin Can also transport some CO2 = Carboxyhemoglobin (carbaminohemoglobin) Porphyrin Ring 17 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Tense State of Hgb 18 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Relaxed State of Hgb As more O2 binds, Hgb changes shape and O2 binds more easily = responsible for Sigmoidal curve of oxyhemoglobin dissociation. Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. 19 Hemopoiesis § Average Adult Production Per Day: § 10 billion WBCs § 200 billion RBCs § 400 billion platelets § Myeloid hemopoiesis in Red Bone Marrow § produces RBCs, WBCs and platelets Lymphoid hemopoiesis - early stages occur in Red Bone Marrow, then shift to peripheral lymphoid tissues (ex. thymus, tonsils, lymph nodes, spleen and peyers patches) § Differentiation & Proliferation of WBCs Granulocytes circulate only in blood vessels and migrate one-way into target tissues. § Lymphocytes travel in both blood and lymphatic vessels and continually circulate between blood, tissues, and lymphatics. Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. 20 § Lymphocytes in Lymphatics protect against interstitial infx § WBCs in Spleen protect against blood borne infx 21 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Hormones of Hemopoiesis § Erythropoietin (EPO) – produced by kidneys – stim.s marrow to produce erythrocytes § Thrombopoietin – produced by liver – stim.s marrow to produce platelets § (“Leukopoietin”) Leukocyte promoting factors – produced by neutrophils, T lymphocytes, Monocytes/Macrophages – stim. marrow & lymphoid tissue (production, differentiation & proliferation of leukocytes) 22 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. 23 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Erythropoiesis § Erythropoietin (EPO) § Numbers of circulating RBCs in healthy individuals remain constant. § Interstitial cells (myofibroblasts) of the peritubular capillaries@ PCT produce erythropoietin (in kidney) § Hypoxia stimulates the production and release of erythropoietin. § Erythropoietin causes an increase in RBC production and release from the bone marrow. Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. 24 Peritubular capillary myofibroblasts @ the PCT 25 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Hematopoiesis Blood cell production in adult bone marrow or in the (liver and/or spleen in the fetus). Two stages: Mitosis (proliferation) and Maturation (differentiation) § Continues throughout life to replace blood cells that grow old and die, are killed by disease, or are lost through bleeding. Bone marrow Primary site of hematopoietic stem cells Also called myeloid tissue Red versus yellow bone marrow Adult active bone marrow o Pelvic bones, vertebrae, cranium & mandible, sternum & ribs, humerus, and femur 26 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. 27 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. 28 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Erythropoiesis – RBC Development Erythrocyte differentiation In each step, hemoglobin increases and nucleus size decreases Development takes 3 – 5 days Reticulocyte count: Index of erythropoietic activity Indicates whether new RBCs are being produced Normal range < 1.5% 2.5 Million RBCs produce every second 29 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Hematopoiesis Totipotent: cells that can become any cell of the body. Pluripotent: cells continue to have unlimited differentiation potential and can grow into different kinds of tissue. Multipotent: cells are more limited but have abilities to differentiate into many different types of cells. Colony-stimulating factors (CSFs) or hematopoietic growth factors: Stimulate progenitor cells to mature; can be used to increase neutrophils. 30 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Leukopoiesis (same as previous slide but without RBCs) 31 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. RBCs - Iron Cycle 32 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Heme metabolism 33 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Hgb Recycling Animation 34 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. RBC Life-Cycle (Bilirubin + Albumin in blood = Unconjugated) (Bilirubin + Glucoronic acid = Conjugated) 35 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Nutritional Requirements for Erythropoiesis § Amino acids for protein synthesis § Structural support and synthesis of hemoglobin Vitamins B12 o Synthesis of deoxyribonucleic acid (DNA), maturation of erythrocytes, facilitator of folate metabolism § B6 , B5 (pantothenic acid) and E o Heme synthesis B9 (Folic acid) (also called folate) o Synthesis of DNA and ribonucleic acid (RNA); maturation of erythrocytes Vitamin C: Iron metabolism B2 (Riboflavin): Oxidative reactions B3 (Niacin): Needed for respiration in mature erythrocytes Minerals Iron: Hemoglobin synthesis and oxygen transport Copper: Required for mobilization of iron from tissues to plasma 36 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Anemia and Polycythemia Anemia: Low oxygen-carrying capacity of blood § Low RBC count/volume § § § § § § hematocrit - percentage of total blood volume occupied by RBCs o Normal female range = 38 - 46% (average 42%) o Normal male range = 40 - 54% (average 46%) o Low hematocrit indicates anemia (< 38%) Iron deficient anemia Pernicious anemia - Low vitamin B12 / intrinsic factor Sickle Cell anemia - genetic defect Aplastic anemia - Kidney failure, bone marrow failure, chemotherapy, etc Hemolytic anemia – RBC destruction Hemorrhagic anemia - bleeding Polycythemia: high hematocrit (>65% ) o Will cause: increased viscosity/resistance, high BP, risk of stroke o Signs: Erythroid hyperplasia (high reticulocytes), tissue hypoxia, high EPO 37 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Sickle-cell Anemia Autosomal Recessive inherited disorder § Point mutation of the hemoglobin gene § GAG (Glu) to GTG (Val) on chromosome 11 § Stiff & sticky RBCs tend to clump and get stuck (blocks blood flow) § Pain, infections, stroke, and organ damage § Heterozygote = carrier/”sickle-cell trait” § Heterozygote advantage lead to increase incidence in certain populations Malaria parasite unable to reproduce in sickle-cells – makes these patients resistant to malaria 38 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. 39 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. RBC Morphology § Target cell - precipitated Hgb (Causes: Sickle-cell, Thalassemias, low Fe) § Spherocyte - a form of autoimmune hemolytic anemia § Ovalocyte - hereditary elliptocytosis (destabilization of cytoskeletal scaffold) § Stomatocyte - bowl shaped, loses biconcavity due to membrane defect § Acanthocyte - thorny cells - alteration in membrane lipids (abetalipoproteinemia) § Helmet cell/Schistocytes - fragmented rbcs from mechanical destructuion § Tear drop "dacrocyte" - from Hgb defect in Beta Thalasemia § Burr cell - many causes - from mix with anticoag (EDTA - ethylene diamine tetra acetic acid) also seen in uremia, PKd (pyruvate kinase deficiency), low Mg, low Phos § § Pappenheimer bodies/found in sideroblasts - excessive iron granules Cabot’s ring – remnants of mitotic spindles seen in megaloblastic anemia § Basophilic stippling - ribosomes from myelodysplastic syndrome, heavy metal poisoning § Howell-Jolly - nuclear remnants in circulating RBCs - seen in damaged or absent spleen § Rouleaux - high fibrinogen reacts with sialic acid on RBC surface, causes them to stick together surface-to-surface 40 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. ABO Blood Types 41 41 Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc. Blood Groups and Blood Types 42 Surface of RBCs contain assortment of antigens (membrane glycoproteins) Blood group – based on presence or absence of various surface antigens § ABO Blood Group (based on A and B antigens) o Type A has only antigen A o Type B has only antigen B o Type AB has antigens A and B o Type O has neither antigen § Most common blood types are O+ (~38%) and A+ (34%) § Least common is AB- (