Blood & Myeloid Tissue Lecture Notes PDF

ANATOMY-LEC: LE 2 | TRANS 4 Blood & Myeloid Tissue IMELDA D. RIVERA, MD | Lecture Date (SEPT/24/2024) OUTLINE I. Blood VI. Hematopoietic Stem A. Plasma Cells II. Blood C...

ANATOMY-LEC: LE 2 | TRANS 4 Blood & Myeloid Tissue IMELDA D. RIVERA, MD | Lecture Date (SEPT/24/2024) OUTLINE I. Blood VI. Hematopoietic Stem A. Plasma Cells II. Blood Cells VII. Major Changes in A. Erythrocytes Developing B. Leukocytes Hematopoietic Cells C. Platelets VIII. Stages of Blood D. Plasma Development III. Peripheral Blood IX. Erythrocyte Maturation Smear X. Granulopoiesis IV. Complete Blood XI. Lymphopoiesis [Junqueira] Figure 1. Composition of whole blood Count XII. Monopoiesis V. Hematopoietic Tissue XIII. Compartments of Centrifuged Anticoagulated Tube would show 3 layers: E. Phases of Blood Neutrophil in the body Top layer: Plasma Cell Development XIV. Thrombocytopoiesis Thin, middle layer: Buffy coat (WBC and Platelets) F. Bone Marrow XV. How do Cells enter the Bottom layer: Red blood cells (also called hematocrit) G. Platelets Circulation A. PLASMA H. Important/Nice To XVI. Review Questions Plasma has a pH of 7.4 I. Important/Nice To XVII. Formative Quiz Know Information XVIII. References Table 1. Composition of Blood Plasma SUMMARY OF ABBREVIATIONS Plasma Component Functions (Percentage of Plasma) RBC Red Blood Cell Water The solvent in which formed WBC White Blood Cell (~92% of plasma) elements are suspended PDGF Platelet-derived Growth Factor and proteins and solutes MCV Mean Red Cell Volume / Mean Corpuscular are dissolved Volume Plasma Proteins All proteins serve to buffer MCH Mean Red Cell Hemoglobin (~7% of Plasma) against pH changes MCHC Mean Cell Hemoglobin Concentration Albumin Exerts osmotic force to RDW Red Cell Distribution Width (~58% of plasma proteins) retain fluid within the BM Bone Marrow (most abundant) microvasculature Must know ❗️ 📣 Lecturer 📖 Book 📋 Previous Trans Contributes viscosity to blood’s LEARNING OBJECTIVES ✔ At the end of the module, a student should be able to Binds and transports some correlate the morphologic differences of the blood fatty acids, electrolytes, components with their function. hormones and drugs ✔ At the end of the session, the student should be able Globulins α-Globulins transport lipids (~37% of plasma proteins) and some metal ions to differentiate the hematopoietic cells presented in a bone marrow smear. β-Globulins transport iron ions and lipids in I. BLOOD bloodstream ❗️ Specialized CT Total blood volume in an average adult: 6 – 7L (7 to 8% of the total body weight) γ-Globulins are antibodies with various immune Composed of: functions → Formed elements Fibrinogen Participates in blood ▪ Cells (~4% of plasma proteins) coagulation (clotting); ▪ Platelets precursor of fibrin → Extracellular matrix (Fluid) Regulatory proteins Consists of enzymes, ▪ Plasma (>1% of plasma proteins) proenzymes, hormones, ▪ Serum and the complement system − The same with plasma EXCEPT the clotting Other Solutes (~1% of Blood Plasma) factors had been removed Electrolytes Help establish and maintain − Contains growth factors and other proteins (eg, sodium, potassium, membrane potentials, released from the platelets during clot formation calcium, chloride, iron, maintain pH balance, and regulate osmosis (control of LE 2 TRANS 4 TG-A1: JM Sicat, JC Sigua, JR Silva, LA Simeon Cua, CD TE: ZF Siazon AVPAA: A. Roluna Page 1 of 18 Sison, CM Sibug  bicarbonate, and the percentages of water Protein (50%) hydrogen) and salt in the blood) → Integral Membrane protein Nutrients Energy source; precursor ▪ Band 3 protein (eg, amino acids, glucose, cholesterol, vitamins, fatty for synthesizing molecules other − 📣 ▪ Glycophorin A Responsible for the antigen on the RBC as this is for blood typing (ABH system) acids) Respiratory gases Oxygen is needed for → Peripheral Membrane protein (eg, oxygen: >2% aerobic cellular respiration; ▪ Spectrin (alpha, beta) dissolved in plasma, 98% carbon dioxide is a waste ▪ Ankyrin protein complex (Ankyrin, band 4.2) bound to hemoglobin product produced by cells ▪ Band 4.1 protein complex (Band 4.1, actin, within erythrocytes; and carbon dioxide: ~7% during this process ▪ 📣 tropomyosin, tropomodulin, adducin, dematin) These proteins are responsible for the RBC to change its shape and become pliable when passing dissolved in plasma, ~27% bound to hemoglobin through very small spaces or areas. within erythrocytes, ~66% converted to HCO3–) Wastes Waste products serve no (breakdown products of function in the blood metabolism) (eg, lactic plasma; they are merely acid, creatinine, urea, being transported to the bilirubin, ammonia) liver and kidneys where they can be removed from [Junqueira] the blood Figure 2. Normal human erythrocyte PBS: found on page 5 DEFECTS II. THREE TYPES OF BLOOD CELLS Any defect in the expression of genes that encode A. ERYTHROCYTES / RED BLOOD CELL / RBC cytoskeleton proteins can result in abnormally shaped and Lacks nuclei and organelles to accommodate oxygen fragile RBC. carrying protein called Hemoglobin. In hereditary spherocytosis and hereditary elliptocytosis, → (-) Mitochondria; they rely on anaerobic glycolysis for RBC are unable to adapt causing premature energy destruction/hemolysis. Its color is salmon pink with a central pallor, which HEREDITARY SPHEROCYTOSIS occupies 1/3 of the entire cell. Autosomal dominant mutation in ankyrin complex → Central pallor is more than 1/3 of the cell = hypochromic proteins. → Less than 1/3 or no central pallor = became spherical in shape, which indicates certain abnormal conditions, namely spherocytosis. Only blood cell that are NOT required to leave the vasculature to perform their function, unlike the leukocytes. Flexible, biconcave discs: ~7.5 um in diameter → Rim: 2.6 um Figure 3. RBC with Hereditary spherocytosis. [Junqueira] → Center: 0.7 um (thinner than the rim) → Their shape allows them to bend, flex, or squeeze into HEREDITARY ELLIPTOCYTOSIS small blood vessels like capillaries Mutations affecting spectrin. → They tend to pile up on one another, forming Rouleaux ▪ 📣 formation to increase surface tension. It is abnormal when you find it in an area where the cells are distributed in mono-layer (i.e. thinly spread RBCs). Normally seen in thick areas. Histologic ruler: Due to their consistent size in fixed tissue, they can be used to estimate the size of other cells and structures. Average lifespan: 120 days Figure 4. RBC with Hereditary elliptocytosis. [Junqueira] ~1% of RBC is removed from circulation each day due to B. LEUKOCYTES / WHITE BLOOD CELL / WBC senescence. However, the BM continuously makes up for the loss Leaves the vasculature and relocate to tissues to perform their function related to immunity CELL MEMBRANE Classification of WBCs: (+/-) of granules is the basis It is important to maintain integrity of cell membrane to → Granulocyte prevent hemolysis or premature destruction of RBC. ▪ Neutrophil Presence of A, B or O antigens that determines the 4 ▪ Eosinophil primary blood types (Types A/B/AB/O) ▪ Basophil → Made up of glycoproteins and glycolipids attached in the RBC’s integral membrane proteins called glycophorins ▪ 📣 → Agranulocyte Do NOT have specific granules but they contain primary or non-specific granules Lipid (40%) Carbohydrate (10%) ▪ Lymphocyte ▪ Monocyte ANATOMY Blood & Myeloid Tissue Page 2 of 18  EOSINOPHIL Azurophilic/Primary/Non-specific granules → Lysosomal acid hydrolases Specific granules/Secondary (numerous, large, elongated) → MBP (Major basic protein) → ECP (Eosinophil cationic protein) → EPO (Eosinophil Peroxidase) ▪ MBP/ECP/EPO - contains strong cytotoxic effect on protozoans and helminthic parasites → EDN (Eosinophil derived neurotoxin) – causes nervous system dysfunction in parasitic organisms → Histaminase – neutralize histamine Figure 5. Classification of Leukocytes → Arylsulfatase – neutralize leukotrienes secreted by ***See Table 2 in appendix: Differences of WBC basophils and mast cells → Collagenase GRANULOCYTES Possess 2 major types of abundant cytoplasmic granules: 📣 → Cathepsins → Refractile intensely pink or orange granules → Azurophilic → Specific Granules Have polymorphic nuclei with almost separated 2 or more distinct lobes NEUTROPHILS AKA Segmenter or polymorphonuclear leukocyte or polymorph → Size: 12-15 um in diameter (larger than RBCs) → Mature Neutrophil: 2-4 (3-5) lobes of nuclear material joined by thinner strands (arrangement is NOT static, their lobes and connecting strands change their shape and position and even the number) 📣 l [Junqueira] Figure 7. Eosinophi Azurophilic/Primary/Non-specific granules (larger but About the same size as neutrophils, but have bilobed less numerous) nuclei and more abundant coarse granules → Myeloperoxidase (MPO) ▪ Generates hypochlorite and other agents toxic to BASOPHIL bacteria Azurophilic/Primary/Non-specific granules → Lysozyme → Lysosomal acid hydrolases ▪ Degrades components of bacterial cell walls Specific granules/Secondary (numerous, large) → Defensins → Heparin - anticoagulant ▪ Small cysteine-rich proteins that bind and disrupt the → Histamine – vasoactive agents that causes dilation of cell membrane of many types of bacteria and other small blood vessels microorganisms → Heparan sulfate – vasoactive agents that causes Specific granules/Secondary (more obviously seen) dilation of small blood vessels → Enzymes (type IV collagenase, gelatinase, → Leukotrienes – trigger prolong constriction of smooth phospholipase) muscles in the pulmonary nerves → Complement activators 📣 → IL-4 & IL-13 – promotes trigger of IgE antibodies 📣 → Antimicrobial peptides (lysozyme, lactoferrins) → Metachromatic and large granules obscuring the → Fine, pinkish to lilac granules lobed nucleus Barr Body → Drum-stick like appendage protruding from one of the lobes of the nuclei → Condensed, single, inactive X chromosome found in the blood specimens of females 📣 [Junqueira] Figure 8. Basophil Approximately the same size as neutrophils and 📣 eosinophils Basophils are the least numerous of the WBCs and account for