Histology of Blood and Bone Marrow PDF - Dr. Merjem Purelku

HISTOLOGY OF BLOOD AND BONE MARROW Ass. Prof. MERJEM PURELKU, MD, PhD BAU School of Medicine, Histology and Embryology Department December 2024  LEARNING OUTCOMES Histology of blood and bone marrow (T-2) 1. Tell the histological features...

HISTOLOGY OF BLOOD AND BONE MARROW Ass. Prof. MERJEM PURELKU, MD, PhD BAU School of Medicine, Histology and Embryology Department December 2024  LEARNING OUTCOMES Histology of blood and bone marrow (T-2) 1. Tell the histological features of blood tissue 2. Explain bone marrow structures BLOOD ❑Blood: A connective tissue composed of blood cells and plasma. ❖When collected in a tube containing anticoagulant and centrifuged: The formed elements (cells) and plasma separate from each other.  BLOOD ❑Hematocrit and Plasma ❖The HEMATOCRIT is the sediment formed by erythrocytes (red blood cells RBCs) and represents about 45% of total blood volume. ❖PLASMA is a yellow, transparent, viscous fluid that constitutes about 55% of total blood volume.  BLOOD ❑Buffy Coat and Normal Blood Volume Just above the erythrocyte layer, there is a white-gray buffy coat containing leukocytes (white blood cells - WBCs) and thrombocytes (platelets - PLTs). ❖The normal blood volume in an adult ranges from 5 to 6 liters. BLOOD CELLS (%45) PLASMA (%55) Plasma Composition ✓ Water (90-92%), ✓ Proteins; ▪ albumin (volume regulation), ▪ globulins (immune function), and ▪ fibrinogen (coagulation), ✓ Lipids; ✓ Glucose; ✓ Amino Acids; ✓ Electrolytes ▪ (Includes Na+, K+, Cl-, and HCO3-, regulating pH and osmotic balance), ✓ Waste Products (Creatinine, Urea). PLASMA COMPOSITION MAIN PLASMA PROTEINS: Albumin: most abundant and smallest plasma protein, produced by the liver. It helps maintain colloid osmotic pressure. α and β Globulins: transport and immune functions. δ Globulins (Immunoglobulins/Antibodies): immune defense. Fibrinogen: The largest plasma protein, produced by the liver. It plays a crucial role in blood coagulation when activated by thrombin. Complement Proteins: inflammation and immune response.  PLASMA COMPOSITION ❑ β Globulins (Ig) - help transport metal ions and large molecular lipids. ❑Transferin: A protein that carries iron through the blood. ❑Lipid carriers: carry fat molecules and can be seen under electron microscope. They include: ✓ Chylomicrons and High-Density Lipoproteins (HDL): types of fats that transport cholesterol and other lipids. ✓ Low-Density Lipoproteins (LDL): usually round in shape, but they can become disk-shaped if there is a bile duct blockage. ✓ Very Low-Density Lipoproteins (VLDL). Plasma and Serum: Plasma is the liquid part of blood. ✓It is made up of water, salts, and organic substances like amino acids, lipids, vitamins, proteins, and hormones. When a test tube, lacks anticoagulants.. the cells in the blood (red blood cells, white blood cells, and platelets) and plasma proteins (especially fibrinogen) will clot together. ❑The liquid part of the blood that remains after the clot (coagulum) forms, is called SERUM.  PLASMA COMPOSITION Blood and Anticoagulants: Blood is being mixed with anticoagulants like : ✓Sodium Citrate, Sodium Oxalate, and Heparin in a test tube, to prevent clotting. ✓After mixing, the blood is centrifuged (spun at high speed). ❖The liquid part that stays on top is plasma. ❖Plasma is different from serum because it contains COAGULATION FACTORS (such as fibrinogen) which help in blood clotting.  SERUM ❖Serum contains growth factors and other proteins released by platelets during clot formation, including thrombin. Fibrinogen (a coagulation factor) is absent in serum, as it is consumed during the clotting process. ❑SERUM IS ESSENTIALLY PLASMA, WithOUT COAGULATION FACTORS! Functions of Blood 1) TRANSPORT: Blood transports substances between cells and the external environment. I. Transporting Nutrients to cells and tissues. II. Transporting Metabolites and Enzymes. III. Waste Removal of waste products to the kidneys. IV. Oxygen and Carbon Dioxide Transport to the tissues and lungs. V. Hormone Transport from their gland of origin to the target organs. VI. Transfer of Heat to surfaces where it can be released. 2) HOMEOSTASİS: A process by which the body maintains a stable internal environment. pH Regulation and Body Temperature: ✓ Blood helps maintain the body's pH within a narrow range (7.35 to 7.45) by carrying buffer compounds. This prevents the body from becoming too acidic or too alkaline, ensuring normal cell function. ✓ The optimal body temperature is around 36-37°C. 3) PROTECTION Defense Against Foreign Invaders: ✓ WBCs (leukocytes) help protect the body by phagocytosing bacteria and viruses. Blood also produces antibodies to neutralize harmful agents. 4) STOPPING BLEEDING (HEMOSTASIS) Platelets (thrombocytes) and enzymes work together to form blood clots when blood vessels are injured, preventing excessive blood loss.  CELLULAR ELEMENTS OF BLOOD Preparation of Blood Smears and Staining Techniques In order to examine blood cells under a microscope, a blood smear needs to be prepared. Staining with Giemsa and Wright's stains makes the cells more visible and helps identify different types of blood cells. ▪ In this case Eosin stains acidic parts (like RBCs) and methylen blue stains basic parts (like the nucleus of WBCs). Spreading a small drop of blood on a glass slide, which is then stained with special dyes to highlight the different cell types.  Erythrocytes (4) Granulocytes Basophils (1) Eosinophils (7) Neutrophils (8) Agranulocytes Monocytes (3,5) Lymphocytes (6, 9) Platelets (Thrombocytes) (2)  BLOOD’S CELLULAR ELEMENTS Erythrocytes (Red Blood Cells - RBCs) ✓ Biconcave shape. ✓ Lack a nucleus (anucleate) and organelles - more space for hemoglobin. Hemoglobin - key molecule in RBCs - allows them to carry O2 from the lungs to tissues. ❖ The plasma membrane of RBCs contains HEMOGLOBIN and glycolytic enzymes. Function: RBCs are the only blood cells that perform their function (gas exchange) without leaving the circulatory system. BLOOD SMEAR  RED BLOOD CELLS (ERITHROCYTES); The biconcave shape of RBCs allows for greater surface area and efficient oxygen transport. This shape brings hemoglobin closer to the surface, enhancing its ability to carry oxygen. This design helps RBCs maximize their ability to deliver oxygen to tissues. ❖ Highest in number - 4-5 million. They circulate in the blood for about 120 days, after which - removed and recycled by the spleen and liver.  CLINICAL CORRELATIONS ANEMIA.. Defined as having a lower-than-normal red blood cell concentration. Clinical Symptoms: Common causes include: Fatigue ; Iron deficiency Shortness of breath; Excessive menstrual bleeding Weakness ; Stomach ulcers, and more. Paleness of the skin; Heart palpitations... Tissues don't receive enough oxygen !  CLINICAL CORRELATIONS POLYCYTHEMIA (ERITHROCYTOSIS).... refers to an elevated concentration of red blood cells above the normal range. Causes and Observations: Seen in individuals living at high altitudes where oxygen pressure is low (physiological adaptation). Clinical Impact: Increased Hct (hematocrit) (% of red blood cells) Increased blood viscosity, which may affect blood flow. ❖SEVERE POLYCYTHEMIA can impair circulation, especially in capillaries, leading to slower blood flow and potential complications.  ERYTHROCYTE MEMBRANE PROTEINS ❖ The shape of erythrocytes is maintained by membrane proteins. They provide the membrane with elasticity and strength, ensuring its flexibility and durability. Any disruption in the expression of genes encoding cytoskeletal proteins can result in abnormally shaped and fragile erythrocytes. This can lead to conditions where red blood cells are prone to breaking, causing HEMOLYSIS !  ERYTHROCYTE MEMBRANE COMPOSITION ❖ Integral Membrane Proteins: The ER membrane contains: ✓ ion channels, 50% proteins ✓ band 3, 4.2, 4.1 proteins & 40% lipids ✓ glycophorin C 10% carbohydrates ▪ serve as anion transporters. These proteins have glycosylated extracellular regions, contain antigenic sites, responsible for the ABO blood group system. ❖ Peripheral Membrane Proteins: ✓ Spectrin and ankyrin are key proteins; help anchor and stabilize the membrane structure, maintaining the shape and flexibility of the erythrocyte.  CLINICAL CORRELATIONS HEREDITARY (SPHEROCYTOSIS).. Cause: Abnormal formation of the cell skeleton due to a mutation in the gene that synthesizes band 4.1 protein. Effect: Leads to abnormal spectrin synthesis, disrupting the normal structure and function of erythrocytes. Consequences: ✓ Inefficient oxygen transport due to the altered shape of the erythrocytes. ✓ Spherocytes (abnormally shaped red blood cells) are destroyed prematurely in the spleen, leading to splenomegaly (enlarged spleen) and anemia.  CLINICAL CORRELATIONS HEREDITARY (ELLIPTOCYTOSIS).. Cause: Abnormal formation of the cell skeleton - shape distortion. Effect: Erythrocytes change from the normal biconcave disc to an elliptical shape. ❑Inheritance: Autosomal dominant. Defects: ✓ Defect in band 4.1 protein. ✓ Binding defects in spectrin and ankyrin. ✓ Abnormal glycophorin protein. Consequences: Splenomegaly (enlarged spleen) and anemia due to premature destruction of elliptic-shaped red blood cells in the spleen.  CLINICAL CORRELATIONS SICKLE CELL ANEMIA Cause: A point mutation in the gene responsible for synthesizing the beta chain of hemoglobin. Glutamic acid is replaced by valine at a specific position in the hemoglobin molecule. Result: Hereditary change in hemoglobin, known as HbS (Hemoglobin S). Effects: ✓ The flexibility of red blood cells (erythrocytes) decreases, and their fragility increases. ✓ Sickle-shaped red blood cells form and polymerize within capillaries, creating rigid clusters. ✓ Blockages in capillaries, leading to reduced blood flow. ✓ Damage to capillary walls - complications of the disease. CLINICAL CORRELATIONS THALASEMIA Cause: Defect in the synthesis of hemoglobin's beta or alpha chains. Abnormal hemoglobin molecule - inherited genetic changes. The red blood cells change shape from biconcave discs to elliptical forms. Classification: Alpha Thalassemia: Caused by defects in the alpha chains of hemoglobin. Beta Thalassemia: Caused by defects in the beta chains of hemoglobin. ❑ The disease is named according to which globin chain is affected. LEUKOCYTES (WBC) Leukocytes leave the bloodstream & migrate to tissues.. immune-related functions - defending against infections & foreign invaders. Classification: based on the presence and type of granules in the cytoplasm.. I. Granulocytes: contain granules in their cytoplasm, classified into: ❖ Primary (Azurophilic) Granules: Contain enzymes and antimicrobial agents. ❖ Secondary (Specific or Specific Granules): Contain specific enzymes or molecules for different immune responses. Neutrophils, eosinophils, and basophils. II. Agranulocytes: have only primary granules and lack secondary granules. Lymphocytes and monocytes. LEUKOCYTES (WBC)  GRANULOCYTES Granulocyte cells all end with ‘PHIL’ ….(Neutrophil, Eosinophil, Basophil). Key characteristic are the GRANULES which are involved in immune responses: 1.Azurophilic (Primary) Granules: contain enzymes like lysosyme and myeloperoxidase - help break down pathogens. 2.Specific (Secondary) Granules: contain more specialized enzymes and proteins, and their content can be neutral, acidic, or basic. ❖Granulocytes have a lobed nucleus - helps them move through tissues and respond quickly to infection. ❖Lifespan: about 5 days. Types of Granulocytes: 1.Neutrophils: Nucleus: Lobed (multilobed nucleus). Granules: Contains both primary (azurophilic) and secondary (specific) granules. Function: First responders to bacterial infections and key in phagocytosis. 2.Eosinophils: Nucleus: Bilobed nucleus (two-lobed nucleus). Granules: Contains large, refractile granules that are red/pink in color upon staining. Function: Involved in responses to parasitic infections and allergic reactions, also play a role in inflammation. 3.Basophils: Nucleus: Bilobed nucleus, but often obscured by large granules. Granules: Contains large, basophilic (basic) granules that stain dark purple/blue. Function: Play a role in delayed hypersensitivity immune responses, and are involved in allergic reactions by releasing histamine.  GRANULOCYTES NEUTROPHIL EOSINOPHIL NEUTROPHIL  GRANULOCYTES NEUTROPHILS (Polymorphonuclear Leukocytes) Most common white blood cell (WBC): ✓make up about 50-60% of all WBCs. ✓Size: About 12-15 μm micrometers in diameter. ✓Nucleus: Has 2-5 lobes, making it look like a multi-lobed shape. In females: One of the X chromosomes can be inactivated and appears as a drumstick-shaped structure attached to one of the lobes of the nucleus.  GRANULOCYTES NEUTROPHILS (Polymorphonuclear Leukocytes) Azurophilic Primary Granules: These granules are similar to lysosomes, which are cell structures that help break down waste. They play a key role in killing microorganisms (like bacteria) and protecting the body from infections. ✓ Myeloperoxidase ✓ Lysosyme Antibacterial proteins ✓ Defensins  GRANULOCYTES NEUTROPHILS (Polymorphonuclear Leukocytes) Specific (Secondary) Granules ✓Smaller and less dense than primary granules. ❖Light pink when stained. They are responsible for secretion of: Collagenase and other enzymes that help break down tissue components. Producing enzymes in the phagosomes to kill and digest bacteria. Neutrophils Are Motile Cells! ❖ Active phagocytes that move towards infection sites. Use various surface receptors to recognize and attack bacteria and other infection-causing agents. ❑ They play a crucial role in the inflammatory response by helping to fight infections and clear pathogens.  GRANULOCYTES EOSINOPHILS (Polymorphonuclear Leukocytes) ❖Less common than neutrophils, make up - 1-3% of white blood cells. ✓Have a bi-lobed (two-lobed) nucleus. ✓Their cytoplasm contains large acidophilic (pink or red) granules, which can be seen under a microscope.  GRANULOCYTES EOSINOPHILS (Polymorphonuclear Leukocytes) Specific Granules in Eosinophils: Major Basic Protein (MBP) Eosinophilic Cationic Protein (ECP) Eosinophilic Peroxidase (EPO) Eosinophilic Derived Neurotoxin (EDN) These granules are responsible for eosinophil staining, which is why eosinophils appear pinkish-red under a microscope. EOSINOPHILS Important in allergic reactions: They help control inflammation by releasing chemicals like cytokines and chemokines. ✓ Increase in number during worm infections (helminths) and allergic reactions. ✓ Help remove antigen-antibody complexes from tissues, which helps reduce inflammation. (Also more likely seen in smokers rather than nonsmokers). Basophils in Allergy-related Inflammation: They play a crucial role by releasing important cytokines, chemokines, and lipid mediators. These substances help regulate the inflammatory response.  GRANULOCYTES BASOPHILS (Polymorphonuclear Leukocytes) Rarity: They make up less than 1% of the WBCs in the blood, so they are hard to find in normal blood smears. Size: About 12-15 μm in diameter. Nucleus: The nucleus has 2 lobes.  GRANULOCYTES BASOPHILS Specific granules cover the nucleus, often making its shape indistinct. ❖Granules are strongly basophilic (stain blue/purple because they absorb the stain) ✓Heparin (prevents clotting); ✓Histamine (vasodilator- helps expand blood vessels); ✓Eosinophilic chemotactic factor (attracts eosinophils). Assist mast cells (Basophils help mast cells in allergic reactions). Have IgE receptors on their surface which are involved in allergies. BASOPHILS BASOPHILS  AGRANULOCYTES Mononuclear cells with either a round or indented nucleus (single nucleus leukocytes). No specific granules ! LYMPHOCYTES: Round nucleus, basophilic cytoplasm ❖ B lymphocytes: produced in bone marrow and differentiate into plasma cells ❖ T lymphocytes: produced in bone marrow, mature in the thymus. MONOCYTES: Nucleus is kidney-shaped or oval  AGRANULOCYTES No SPECIFIC granules, only azurophilic granules that contain enzymes and proteins important for immune response. Nucleus: Indentation-shaped, not lobed; ✓Capable of DIAPEDESIS (moving out of blood vessels into tissues).  AGRANULOCYTES LYMPHOCYTE MONOCYTE  AGRANULOCYTES LYMPHOCYTES Smallest white blood cells (6-15μm in diameter) ✓ High in number. ❑ T-Lymphocytes: Help fight infections by directly attacking infected cells (cell-mediated immunity) ❑ B-Lymphocytes: Produce antibodies to fight infections (humoral immunity) Responsible for antibody production ❑Natural Killer (NK) cells: Specialized in killing virus-infected cells and tumor cells. LYMPHOCYTES  AGRANULOCYTES MONOCYTES Precursor Cells: for macrophages, osteoclasts, microglia, and other mononuclear phagocytic system cells in connective tissue. Function: ❖ They act as ANTİGEN-PRESENTİNG CELLS! Nucleus: The nucleus is C-shaped and indented. Cytoplasm: The cytoplasm is basophilic and contains azurophilic granules, giving the cytoplasm a bluish-gray appearance. MONOCYTES  PLATELETS (THROMBOCYTES) Origin: Derived from large cells in the bone marrow, called MEGAKARYOCYTES. Size: 2-4 μm in diameter Function: Serve as filler material during blood coagulation.  PLATELETS (THROMBOCYTES) Clustered Appearance Two main regions: Hyalomere: Light-staining peripheral area Granulomere: Dark-staining central region with granules Granules: Delta Granules: Contain ADP, ATP, and serotonin Alpha Granules: Contain PDGF & platelet factor 4 protein. Type Nucleus Specific Number Lifespan Main Function granules (%) Granulocytes Neutrophils 3-5 lobes Pale/light pink 57-67 1-4 days Bacterial phagocytosis and killing Eosinophils 2 lobes Red/ dark pink 1-3 1-2 weeks Elimination of helminths and other parasites and regulation of local inflammation Basophils 2 (bilobed) or 5 Dark blue 0-0.75 Several Regulation of inflammation and lobed /purple months histamine release during allergy Agranulocytes Lymphocytes spherical (none) 25-33 Hours or Influential and regulatory cells in shape years the adaptation of immunity. Monocytes indented. (No) 3-7 Hours or Precursors of macrophages and or C-shaped. years other mononuclear phagocytic cells. Neutrophils Monocyte Lymphocyte Platelets Eosinophil Basophil  Table: Histological Characteristics of Blood Cells BLOOD CELL TYPE SUBTYPE HISTOLOGICAL CHARACTERISTICS FUNCTION Red Blood Cells (RBCs) - - Size: 7-8 micrometers - Oxygen transport via hemoglobin Erythrocytes - Appearance: Anucleate, pale pink cytoplasm - Carbon dioxide removal from tissues White Blood Cell Type (WBCs) - Neutrophils - Nucleus: 2-5 lobes -Phagocytosis of bacteria Leukocytes - Cytoplasm: Light blue, fine, neutral-staining - First responders to bacterial infections granules Granulocytes Eosinophils - Nucleus: Bilobed - Combat parasitic infections - Cytoplasm: Large, red-orange granules - Involved in allergic reactions Basophils - Nucleus: Irregular, U-shaped or lobed - Release histamine during allergic - Cytoplasm: Large, dark purple granules responses - Inflammation mediator White Blood Cell Type - Leukocytes Lymphocytes - Nucleus: Large, round, dark-staining - B cells: Antibody production - Cytoplasm: Thin, light blue rim around nucleus - T cells: Cell-mediated immunity Agranulocytes - NK cells: Viral defense Monocytes - Nucleus: Kidney-shaped or horse-shoe shaped - Differentiate into macrophages - Cytoplasm: Pale with fine granules - Phagocytosis of debris and pathogens Thrombocytes ( Platelets ) - - Shape: Small, disc-shaped Hemostasis: Blood clotting - Size: 2-4 micrometers - Form platelet plugs at injury sites - Appearance: No nucleus, granular cytoplasm BONE MARROW Haematopoietic Stem Cells & Their Development Mesodermal Origin Haematopoietic stem cells (HSCs) arise from mesodermal cells. ✓ Stimulated by: Fibroblast Growth Factor 2 (FGF2). ✓ FGF2 binds to Fibroblast Growth Factor Receptors (FGFR). This binding triggers the conversion of mesodermal cells into hemangioblasts. Hemangioblasts: Dual Role Hemangioblasts serve as precursors for both blood vessels and blood cells. These cells are found in the yolk sac wall of the developing embryo. Key Processes Angiogenesis: Formation of new blood vessels from existing ones. Haematopoiesis: Formation of blood cells (e.g., red blood cells, white blood cells, etc.) Bone Marrow Structure and Function Bone marrow fills the cavity left by the trabecular bone network. Unlike bone, bone marrow is jelly-like in consistency, not rigid. Accounts for about 4-5% of total body weight. Principal Functions of Bone Marrow Blood Cell Production: Essential for the continuous generation of red and white blood cells. Fat Storage: Stores fat in the form of adipocytes (fat cells), particularly in yellow marrow. Two Types of Bone Marrow Red Marrow: Highly vascular and actively involved in HAEMATOPOIESIS (blood cell production). Found mainly in flat bones (e.g., pelvis, sternum, ribs) and the proximal ends of long bones (e.g., femur, humerus). Yellow Marrow: Fat-rich and contains fewer haematopoietic centres (areas where blood cells are produced). Primarily composed of adipocytes (fat cells). Found in the medullary cavity of long bones (e.g., femur, tibia) in adults. RED BONE MARROW Red bone marrow (histological slide)  YELLOW BONE MARROW Structure and Function of Yellow Marrow: Yellow marrow mainly consists of adipocytes and supportive connective tissue. Yellow marrow contains inactive blood cell precursors that can be reactivated when the body needs more red blood cells, such as after blood loss or during certain illnesses. Yellow bone marrow (histological slide)  Bone Marrow Hematopoietic Microenvironment - Key Components: ✓ Hematopoietic cells (blood-forming cells) ✓ Support cells (connective tissue cells) ✓ Extracellular matrix (ECM) proteins ✓ Soluble factors (cytokines, hormones) How They Work Together: Cells interact with each other and the ECM, influencing their behavior Soluble factors, like cytokines and hormones, affect cell function and movement Cell Movement & Localization: Cells move to specific areas in the bone marrow (niches) using adhesion molecules like integrins and other receptors These receptors also help cells respond to chemical signals (chemokines, hormones) Cell Communication: Cells interact with matrix components and chemical signals that control their activity and location. Understanding these interactions is key to studying bone marrow diseases and injuries  Table : Histological Characteristics of Bone Marrow Cells Cell Type Histological Characteristics Function Hematopoietic Stem Cells - Size: Small, round - Multipotent progenitors: Differentiate into all blood - Nucleus: High nuclear-to-cytoplasm ratio cell types - Appearance: Prominent nucleolus Progenitor Cells - Size: Larger than stem cells, less nucleocytoplasmic - Develop into specific blood cell lineages (erythroid, ratio myeloid, etc. - Appearance: Distinct nucleus and cytoplasm Erythroblasts - Shape: Round with large, dark nucleus - Precursor to erythrocytes: Start hemoglobin - Cytoplasm: Blue due to ribosomal RNA production and mature into red blood cells Myeloblasts - Shape: Large, round with large nucleus - Precursor to granulocytes (neutrophils, eosinophils, - Cytoplasm: Blue with no granules basophils Megakaryocytes - Size: Very large (up to 100 micrometers) - Platelet production via cytoplasmic fragmentation - Nucleus: Multilobed, often 8-16 nuclei Macrophages - Shape: Large, irregular shape - Phagocytosis of cellular debris, pathogens - Cytoplasm: Abundant and pale, large vacuoles - Immune response  CLINICAL SIGNIFICANCE Bone Marrow Cellularity Bone marrow can become either: Hypercellular: Increased haematopoietic cells (more RBCs, WBCs, platelets). Hypocellular: Reduced haematopoietic cells (low blood cell production). Cellularity refers to the quantity of haematopoietic cells in relation to the amount of adipocytes (fat cells) in the marrow.  CLINICAL SIGNIFICANCE: BONE MARROW ASPIRATION AND BIOPSY Bone marrow aspiration and biopsy are performed to assess bone marrow cellularity and diagnose conditions affecting haematopoiesis. Aspiration involves using a large bore needle to obtain a liquid sample of marrow, ideal for cytological analysis (examining individual cells). Biopsy involves obtaining a core tissue sample, allowing a larger sample for assessing marrow architecture and cellularity. Bone Marrow Aspiration Provides cytological information about individual cells, useful for identifying abnormalities such as leukemia, anemia, and other haematological disorders. Bone Marrow Biopsy Biopsy provides a larger sample for more comprehensive assessment: Cellularity of the marrow, detection of focal lesions such as cancer or infection and gives insight into the structural organization of the marrow.  INDICATIONS FOR BONE MARROW ASPIRATION AND BIOPSY I. Investigating Depletion of Blood Cell Lines Leukopenia (low white blood cells) Thrombocytopenia (low platelets) Anaemia (low red blood cells) Myelodysplasia (disordered blood cell production) Bone marrow biopsy can help identify the cause of cell line depletion. II. Investigating Abnormal Increase in Cell Lines For unexplained elevations in blood cell counts (e.g., leukocytosis, polycythemia, or thrombocytosis), a biopsy can help determine the cause. III. Investigating Morphological Discrepancies IV. Monitoring Disease Progression and Therapy Response V. Detecting Marrow Involvement in Metastatic Neoplasms VI. Investigating Fever of Unknown Origin (FUO) and Lymphadenopathy. BONE MARROW SUPPRESSION Bone marrow suppression is commonly caused by chemotherapeutic agents used to treat cancer and can lead to PANCYTOPENIA (fall in all cell lines). PANCYTOPENIA can cause anaemia, increased infection risk, and bleeding disorders due to decreased production of all blood cell types. Common drugs involved in marrow suppression include: ✓methotrexate, ✓azathioprine, ✓cyclophosphamide, and others  BONE MARROW FAILURE In more severe cases, the bone marrow can be immensely affected by disease processes where it is unable to produce one or all of the cell lines (i.e. a pancytopenia). This syndrome is referred to as BONE MARROW FAILURE! Bone marrow failure can result from : damage to haematopoietic stem cells, nutrient deficiencies, or dysfunctional differentiation of blood cells. ❖The condition can be: ✓congenital (e.g., Fanconi’s anaemia) or ✓acquired (e.g., aplastic anaemia or chemotherapy).