Blood Cell Formation: Hematopoiesis

• Blood is mostly inside your blood
• Blood cells have very specific functions

Blood Cell Production

• Blood cells are created in the bone marrow, specifically in the red bone marrow found in the middle of long bones.
• Red bone marrow contains hematopoietic stem cells, which are blood-forming stem cells.

Word Bank:

• Heme or hemato means blood
• Poiesis means formation or creation

Stem Cells

• Stem cells are undifferentiated, meaning they have not yet determined their specific cell type or function.
• The zygote, the first cell formed from the fusion of an egg and sperm, is the most undifferentiated cell, capable of creating an entire human.
• Differentiation is not a single-step process but involves multiple smaller steps.
• A zygote can differentiate into a hematopoietic stem cell, which is then limited to becoming blood cells.

Potency

• Totipotent stem cells, like the zygote, have total potential and can differentiate into any cell type, creating an entire organism.
• Pluripotent stem cells can become many different things but not all things; a hematopoietic stem cell is pluripotent.

Myeloid vs Lymphoid

• Hematopoietic stem cells differentiate into either myeloid or lymphoid stem cells in the red bone marrow.
• In fetuses, this process occurs in the liver and spleen, switching to the red bone marrow after birth.

Lymphoid Stem Cells

• Lymphoid stem cells differentiate into T cells, B cells, and natural killer (NK) cells.
• B cells, once activated by an antigen, mature into plasma cells that produce antibodies, also known as immunoglobulins (Ig).
• Antibodies are created against viruses like the common cold, COVID-19, and chickenpox.

T Cells

• T cells include killer T cells (also called cytotoxic T cells), helper T cells, and regulatory T cells.
• Killer T cells kill virally infected host cells (the body's own cells infected with a virus).
• Cytotoxic means toxic to cells
• Helper T cells assist other immune cells, including killer T cells, B cells, and cells from the myeloid lineage.
• Regulatory T cells inhibit immune responses, signaling when an immune response is no longer needed, such as after recovery from a cold.

Natural Killer Cells

• Natural killer (NK) cells kill any cell in the body that appears abnormal, such as tumor cells, cancer cells, or virally infected cells.
• Killer T cells specifically target virally infected host cells, while NK cells target anything that doesn't look right non-specifically.
• Killer T cells require specific instructions (e.g., to target a specific virus with a particular protein), often communicated via interleukins.
• NK cells acts as part of the body's innate, nonspecific immunity, while Killer T cells are very specific and part of adaptive immunity

Myeloid Stem Cells

• Myeloid stem cells can differentiate into red blood cells (erythrocytes), platelets (thrombocytes), or white blood cells (granulocytes and agranulocytes).

Erythrocytes

• Erythrocytes, or red blood cells, are primarily bags of hemoglobin, with approximately 280 million hemoglobin molecules per cell.
• Erythro means red

Hemoglobin

• Each hemoglobin molecule binds four oxygen molecules, enabling red blood cells to transport oxygen throughout the body.
• Hematocrit (HCT) measures the percentage of blood volume occupied by red blood cells, indicating oxygen-carrying capacity.

Platelets

• Platelets, also known as thrombocytes or clotting cells, are not full cells but fragments of megakaryocytes.
• Thrombocytes produce clots (thrombi).

Whiteblood Cells

• White blood cells from the myeloid lineage include granulocytes and agranulocytes.
• Agranulocytes, lacking granules in their cytoplasm, include monocytes.

Monocytes

• Monocytes that leave blood circulation and enter tissues are called macrophages.
• Monocytes are in blood, macrophages are in tissue
• Macrophages perform phagocytosis, engulfing and digesting bacteria and other pathogens.
• Phagocytosis means a cell that eats
• Macrophages are antigen-presenting cells (APCs), presenting antigens to T cells and B cells to activate the specific immune response.

Immune Cells

• Immune cells involved in specific immunity include killer T cells, helper T cells, B cells, and macrophages.
• Interleukins are paracrine and autocrine regulatory molecules, with over three dozen identified, influencing various immune functions and diseases.

Granulocytes

• Granulocytes, characterized by granules in their cytoplasm, include neutrophils, eosinophils, and basophils.
• Phil means love
• Eosinophils granules love eosin, an acidic red dye, and are red in color.
• Basophils granules love basic dye and are dark blue or purple.
• Neutrophils granules do not take up either red or purple dye and are barely visible under the microscope.
• Neutrophils phagocytize pathogens, and are not antigen-presenting cells
• They are the most numerous white blood cells, comprising 65-75% of the total count.
• Neutrophils have segmented nuclei and are the first white blood cells to arrive at an infection site.
• Number in blood increase with a bacterial infection
• Eosinophils are associated with allergic reactions or parasitic infections.
• Basophils are implicated in allergic reactions.

Leukocytes

• Leukocytes is term for white blood cells
• Leukocytes encompass granulocytes, agranulocytes, and lymphocytes.

Medical Terms

• Leukocytosis: Too many white blood cells, often due to infection or inflammation.
• Leukopenia: Too few white blood cells, commonly caused by chemotherapy.
• Thrombocytosis: Too many platelets, increasing the risk of thrombosis (clotting).
• Thrombocytopenia: Too few platelets, increasing the risk of bleeding.
• Anemia: Low number of red blood cells.
• Polycythemia: Too many red blood cells, often due to dehydration, but can indicate cancer.

CBC

• Complete Blood Count (CBC) is a simple test providing data like red blood cell count, hematocrit, neutrophil count, and platelet count.

Reticulocytes

• Reticulocytes and band cells are specifically important in CBC results
• Reticulocytes are immature red blood cells, with elevated counts indicating rapid red blood cell production to compensate for blood loss or hemolysis.

Bands

• Bands are immature neutrophils
• Elevated band counts indicate increased neutrophil production due to bacterial infection.

Rhesus Factor

• An Rh-negative pregnant woman carrying an Rh-positive fetus can develop Rh antibodies.

Pregnancy

• During pregnancy, maternal and fetal blood do not mix unless there is trauma, such as during a difficult delivery.
• Traumatic delivery is a leading cause of mixing fetal and maternal blood.
• Development of gestational diabetes and delivery implications, babies can be too big and cause complications such as tearing.
• Resulting in mom making anti Rh antibodies, which can take a couple of weeks.

Second Pregancy

• In subsequent pregnancies, maternal anti-Rh antibodies can cross the placenta and attack the Rh-positive fetal blood cells.
• Results in in utero hemolysis of the baby's red blood cells

Hemolytic Disease

• Lead to hemolytic disease of the newborn, resulting in jaundice, anemia, or stillbirth.
• Pre- or prenatal tests are used to determine the RH factors of parents

Modern Treatments

• RhoGAM is administered to Rh-negative pregnant women to prevent the development of Rh antibodies.
• RhoGAM contains lab-made anti-Rh immunoglobulins that destroy fetal red blood cells in the mother's circulation before her immune system can respond.
• Mothers receive RhoGAM in the second and third trimesters, before delivery, or after delivery to ensure it is effective.

RhoGAM Indications

• Invasive procedures like amniocentesis, and in cases of elective or spontaneous abortions (miscarriages).
• Giving RhoGAM is essential, even in young girls or women before childbearing age, particularly after a blood transfusion or trauma, to prevent future complications.
• Approximately 85% of the world population is Rh-positive, while 15% is Rh-negative.
• Rh-negative individuals should never receive Rh-positive blood, as this can lead to the production of Rh antibodies.

Endothelial Health

• Blood vessels are lined by endothelial cells
• It's important to support endothelial health to prevent platelet aggregation
• Most healthy endothelial cells have the glycoprotein CD 39 on their surface that protrudes
• They also produce PGI2 (prostaglandin 12)
• Plus nitric oxide
• All these substances aim to stop clotting

CD39

• CD39 is an enzyme that converts adenosine diphosphate (ADP) into adenosine monophosphate (AMP), removing ADP is platelet glue.

Potent Vasodilators

• PGI2 (prostaglandin 12) dilates blood vessels, ensuring continuous blood flow and preventing stagnation.
• Stagnant blood increases risk of clotting

Platelet Adhesion

• Platelets readily adhere to rough surfaces like subendothelial collagen, but not to the smooth surface of healthy endothelial cells.

Activated Platelets

• Platelets at site of injury come across some endothelial collagen and become activated
• Release thromboxane A2, ADP, and serotonin.
• Platelet release reaction
• Causing more platelets to arrive and form a platelet plug, which blocks the injury hole.
• A strong plug is required to resist blood pressure within the vessel.

Fibrin

• Fibrin is like a thread that supports platelet contraction and strengthens the platelet plug to form a clot.
• Derived from blood

Blood Proteins

• Fibrinogen is a soluble protein in the blood
• Can be converted to insoluble fiber to solidify clot
• Requires activation from the liquid state

Thrombin

• Thrombin cleaves fibrinogen molecules to create the insoluble fibrin threads, which stabilizes the platelet plug.
• Must be in inactive state to flow freely
• Prothrombin is the inactive soluble form

Factor 10 Activation

• Prothrombin is activated by factors 10
• Cascade event through injury stimulates activators

Intrinsic and Extrinsic Pathways

• Two methods
• Starts with different pathways
• The intrinsic pathway is activated by rough surfaces and factor 12.
• The extrinsic pathway is activated by tissue fluid.

Clotting Requirements

• Overall clotting process is as follows:
• Requires smooth walls of the vessel, if smooth is lost clotting starts
• Blood must be in constant flow, lack of flow stimulates clotting
• Overall injury is amplified if there are rough surfaces to attach to
• Results in platelets and fiber 12 to activate coagulation