Hematopoiesis and Blood Cells Quiz

Histology of Blood and Bone Marrow

• Blood is a connective tissue composed of blood cells and plasma.
• When blood is collected in an anticoagulant tube and centrifuged, formed elements (cells) and plasma separate.
• Plasma makes up 55% of total blood volume, a pale yellow, transparent, viscous fluid
• The formed elements include erythrocytes (red blood cells), that comprise 45% of total blood volume; leukocytes and platelets (the "buffy coat") which comprise less than 1% of total blood volume.
• The hematocrit is the sediment formed by erythrocytes (red blood cells RBCs) and represents about 45% of total blood volume.
• Plasma is composed of water (90-92%), proteins (albumin, globulins, and fibrinogen), lipids, glucose, amino acids, electrolytes, and waste products.
• Plasma proteins include albumin, globulins (α and β, and γ/immunoglobulins), and fibrinogen.
• Albumin is the most abundant protein, maintaining colloid osmotic pressure.
• Globulins (α and β) have roles in transport and immunity.
• Immunoglobulins/Antibodies (γ globulins) are important for immune defense
• Fibrinogen crucial for blood clotting.
• The plasma also contains important components, such as lipids (chylomicrons, HDL, LDL and VLDL; transferrin important for iron transport in the blood).
• Blood volume in an adult is typically between 5 to 6 liters.
• Serum is essentially plasma, without coagulation factors (such as fibrinogen).
• Blood is commonly mixed with anticoagulants (like sodium citrate, sodium oxalate, and heparin) to prevent clotting.
• The liquid part of the blood that stays on top after centrifuging is plasma.
• Serum contains growth factors and other proteins released by platelets during clot formation, including thrombin.

Blood Cells

• The cellular components of blood include: erythrocytes (4), granulocytes (basophils(1), eosinophils(7), neutrophils(8)), agranulocytes (monocytes(3.5), lymphocytes(6,9)), and platelets (thrombocytes) (2)

Blood's Cellular Elements - Erythrocytes (Red Blood Cells - RBCs)

• Erythrocytes are biconcave shaped.
• They lack a nucleus.
• They contain hemoglobin, to carry oxygen from the lungs to tissues
• The function of erythrocytes is gas exchange, without exiting the circulatory system

Blood Smear

• A blood smear is prepared to examine blood cells under a microscope.
• Staining with Giemsa and Wright's stains helps identify different types of blood cells.

Red Blood Cells (Erythrocytes)

• The biconcave shape of RBCs maximizes surface area for efficient oxygen transport.
• RBCs have a high number, approximately 4-5 million.
• RBCs circulate for about 120 days before being removed and recycled by the spleen and liver.

Clinical Correlations - Anemia

• Defined as having lower-than-normal red blood cell concentration
• Causes include: iron deficiency, excessive menstrual bleeding, stomach ulcers
• Symptoms include: fatigue, shortness of breath, weakness, paleness of the skin, heart palpitations.

Clinical Correlations - Polycythemia (Erythrocytosis)

• Elevated red blood cell concentration
• Occurs in high altitudes due to physiological adaptation
• Increased hematocrit and blood viscosity, affecting blood flow, especially in capillaries

Erythrocyte Membrane Proteins

• Membrane proteins maintain erythrocyte shape, elasticity, and strength.
• Any disruption in cytoskeletal protein gene expression can cause abnormally shaped and fragile erythrocytes, leading to hemolysis

Erythrocyte Membrane Composition

• The Erythrocyte membrane contains proteins (including ion channels, protein bands like band 3,4.1, and 4.2, and glycophorin C) and lipids.
• Membrane proteins serve as anion transporters, and some have antigenic sites, relevant for the ABO blood group system.
• Peripheral membrane proteins like spectrin and ankyrin maintain erythrocyte shape and flexibility.

Clinical Correlations - Hereditary Spherocytosis

• A hereditary condition caused by abnormal cell skeleton formation due to a mutation on the gene that synthesizes band 4.1 protein.
• Abnormally shaped red blood cells (spherocytes) are destroyed prematurely in the spleen.
• This condition leads to splenomegaly (enlarged spleen) and anemia since the spherocytes are destroyed
• Inefficient oxygen transportation due to the altered shape

Clinical Correlations - Hereditary Elliptocytosis

• Hereditary condition causing an abnormal cell skeleton formation, thus, changing the shape of blood cells (from biconcave to elliptical)
• Defects in band 4.1 protein, as well as, in spectrin and ankyrin, and the glycophorin protein, can result in this condition
• Splenomegaly (enlarged spleen) and anemia since the elliptic cells are broken prematurely.

Clinical Correlations - Sickle Cell Anemia

• A hereditary condition resulting from a point mutation in the beta-chain hemoglobin gene.
• The mutated hemoglobin (HbS) results in sickle-shaped red blood cells which decreases flexibility and increases fragility.
• Sickle-shaped cells polymerize and form rigid clusters in capillaries.
• Reduced blood flow to tissues leads to complications.

Clinical Correlations - Thalassemia

• Genetic defect in hemoglobin synthesis (alpha or beta chains).
• Altered hemoglobin structure results in altered red blood cell shape (from biconcave to elliptical)

Leukocytes (WBCs)

• Leukocytes leave the bloodstream and migrate to tissues to defend against infections and foreign invaders.
• Classified based on cytoplasmic granules (granulocytes or agranulocytes).
  • Granulocytes contain specific granules in the cytoplasm (primary and secondary) and are further categorized into neutrophils, eosinophils, and basophils
  • Agranulocytes lack visible cytoplasmic granules and are lymphocytes and monocytes.

Granulocytes

• Granulocytes have a lobed nucleus and various specific granules in their cytoplasm (different types of granules (azurophilic, specific) contain enzymes and proteins.).
• Neutrophils are the most numerous WBCs, involved in phagocytosis.
• Eosinophils respond to parasitic infections and allergic reactions, and release chemicals to control inflammation.
• Basophils play a role in allergy-related inflammation, releasing chemicals like histamine to regulate inflammation.

Agranulocytes

• Agranulocytes have a non-lobed nucleus. The major agranulocytes are lymphocytes and monocytes.
• Lymphocytes are classified into B and T lymphocytes. B lymphocytes are responsible for antibody production (humoral immunity), while T lymphocytes are involved in cell-mediated immunity by directly attacking infected cells. Also included are Natural Killer cells (NK cells) which target virus-infected cells and tumors.
• Monocytes are phagocytic cells that differentiate into macrophages, critical in the immune system

Platelets (Thrombocytes)

• Platelets are derived from megakaryocytes in the bone marrow.
• Their function is in blood clotting and serving as filler material during blood coagulation.
• Different granules, like alpha and delta granules, contain specific proteins important in the process.

Bone Marrow: Structure and Function

• Bone marrow fills the cavities left by the trabecular bone network.
• Unlike bone, it is jelly-like and accounts for approximately 4-5% of total body weight
• It is responsible for blood cell production.
• It also stores fat in the form of adipocytes (particularly in yellow marrow)

Two Types of Bone Marrow

• Both types contain specialized cells
• Red marrow is involved in hematopoiesis (producing blood cells). found in flat bones and in the proximal ends of long bones
• Yellow marrow is primarily composed of adipocytes (fat cells) and found in the medullary cavity of long bones in adults.

Bone Marrow Hematopoietic Microenvironment

• Hematopoietic cells (blood-forming cells) interact with support cells, the extracellular matrix (ECM) proteins and soluble factors like cytokines and hormones.
• Cells interact with each other and the ECM, affecting their behavior.
• Soluble factors like cytokines and hormones influence cell function and movement.
• Cells move to specific areas in the bone marrow (niches).
• These interactions are important for bone marrow diseases and injuries

Bone Marrow Cells

• Hematopoietic stem cells are the initial cells, being multipotent, differentiating into all blood cell types
• Progenitor cells develop from hematopoietic stem cells into blood cell lineages (erythroid myeloid, etc.)
• Erythroblasts, Myeloblasts and Megakaryocytes are precursors to specialized cells
• Macrophages have the function of phagocytosis and participating in the immune response

Clinical Significance of Bone Marrow Cellularity

• Hypercellularity means an increase in haematopoietic cells in the bone marrow
• Hypocellularity means a decrease in haematopoietic cells in the bone marrow.

Clinical Significance: Bone Marrow Aspiration and Biopsy

• Bone marrow aspiration and biopsy are crucial diagnostic procedures for bone marrow problems and assessment
• Bone marrow cellular assessment is done thru Aspiration, to look at individual cells
• Further assessment is done thru Biopsy to study tissue samples for architectural details (and focal lesions).

Indications for Bone Marrow Aspiration and Biopsy

• Evaluating blood cell line depletion (leukopenia, thrombocytopenia, anaemia), to find the cause of cellular depletion.
• Investigating abnormal cellular increase (leukocytosis, polycythemia, thrombocytosis), to find the cause.
• Assessing Morphological discrepancies and Monitoring disease progression, and therapy effectiveness
• Detecting metastatic neoplasms
• Investigating Fever of Unknown Origin (FUO) and Lymphadenopathy

Bone Marrow Suppression

• Bone marrow suppression, often caused by chemotherapy, results in pancytopenia (reduced production of all blood cell types)
• Common drugs causing suppression include methotrexate, azathioprine, and cyclophosphamide

Bone Marrow Failure

• A severe condition where the bone marrow can't produce blood cells.
• Causes can include damage to hematopoietic stem cells, nutrient deficiencies, or dysfunctional differentiation of blood cells.
• Conditions include congenital (e.g., Fanconi's anaemia) or acquired (e.g., aplastic anaemia or chemotherapy).