Hematopoiesis

Transport

• Nutrients (O2, sugars, fats, amino acids, vitamins, inorganic nutrients, hormones, etc.)

• Wastes (CO2, metabolites which may be complexed to carrier proteins, necrotic cell debris)

• Cells

  • Red blood cells (RBCs, erythrocytes)

  • White blood cells (WBCs, leukocytes)

  • Platelets (PLTs, thrombocytes)

4.5-5.5 L

Plasma: 55% of blood volume

• 91% water

• 7% proteins

  • Examples: albumin, fibrinogen, globulins = antibodies

• 2% nutrients, hormones, and electrolytes

Formed elements: 45% of blood volume

• Buffy coat = WBCs (7000-9000/mm³) + Platelets (250,000/mm³)

• RBCs (5,000,000/mm³)

Serum

• Proteins

  • Albumin + globulins

• Nutrients, hormones, and electrolytes

Clot

• WBCs, PLTs and RBCs

  • Enmeshed in fibrin clot containing consumed coagulation proteins

1. Oxygen from the pulmonary alveolus binds to hemoglobin

2. Hemoglobin in the blood carries oxygen from the lungs to rest of tissues

3. Red blood cells carry carbon dioxide back from the tissues to the lungs

In response to injury, platelets released from Megakaryocytes aggregate at the site, forming a temporary plug. Clotting factors then activate a cascade, converting fibrinogen into fibrin. Fibrin forms a mesh that traps blood cells, creating a stable clot. Eventually, the clot is dissolved by enzymes.

The primary function of WBCs is defense (immune system).

Innate

• Interact with complement, granulocytes, and macrophages

Adaptive

• Humoral immunity: Antigen specific antibodies, produced by plasma cells

• Cell-mediated immunity: cell-to-cell combat sensitized cytotoxic T lymphocytes target cells bearing foreign antigens

A method used in particle counting and sizing. It involves passing particles through an aperture and measuring the changes in electrical resistance to determine their size and concentration. Used in various industries, such as healthcare and environmental monitoring.

Describes the RBC size and shape. Includes:

• MCV (mean corpuscular volume)

• MCH (mean corpuscular hemoglobin)

• MCHC (mean corpuscular hemoglobin concentration)

• RDW (red cell distribution width)

mean corpuscular volume: cell size

mean corpuscular hemoglobin: how much hemoglobin per cell

mean corpuscular hemoglobin concentration: hemoglobin per concentration of blood

red cell distribution width: degree of difference in RBC size

Flow cytometry is a technique that measures and analyzes characteristics of individual cells as they pass through a laser beam.

Fluorescence activated cell sorter (FACS) is a type of flow cytometer that can sort cells based on their fluorescence properties.

Cell surface molecules used to identify and classify immune cells (surface protein signatures for immunophenotyping). They play a crucial role in immune response and cell communication. CD molecules are numbered and serve as markers for specific cell types or functions. Examples include CD4 (helper T cells) and CD8 (cytotoxic T cells).

• Essential for production of adequate numbers of RBCs, WBCs, and PLTs

• Driven by hematopoietic stem cell signals

bone marrow

CD34

Stem cells can reside in a state of reversible growth arrest, or quiescence, for prolonged periods of time.

1. telomerase allows >40 divisions

2. growth factors prevent apoptosis

1. self-renewal to maintain the population within the niche

2. leave and differentiate and proliferate (mitosis)

• EPO can increase RBC production

• G-CSF can increase WBC production and release stem cells from bone marrow into circulation for stem cell transplant

  • Separate using antibodies against CD34

1. Self-renewal: Hematopoietic stem cells have the unique ability to both self-renew and differentiate. They can undergo mitosis to produce two daughter cells, one of which remains a stem cell while the other becomes a more specialized, committed progenitor cell. This process ensures a constant source of HSCs.

2. Commitment to lineage: The first step in differentiation is the commitment of a hematopoietic stem cell to a specific blood cell lineage, such as red blood cells (erythropoiesis), white blood cells (leukopoiesis), or platelets (thrombopoiesis). This decision is influenced by various factors and signaling molecules in the bone marrow microenvironment.

3. Multipotent progenitor cells: Once committed, the HSC gives rise to multipotent progenitor cells (MPPs). These MPPs have more limited differentiation potential and are committed to a specific lineage but can still give rise to a variety of related cell types. For example, myeloid MPPs can generate various types of myeloid cells, including granulocytes, monocytes, and platelets.

4. Progenitor cells: Multipotent progenitor cells further differentiate into more specialized progenitor cells, which are often unipotent, meaning they are committed to a single cell type. For example, common myeloid progenitors (CMPs) differentiate into either megakaryocyte-erythroid progenitors (MEPs) for red blood cells and platelets or granulocyte-monocyte progenitors (GMPs) for white blood cells.

5. Maturation and terminal differentiation: These progenitor cells continue to differentiate and mature into their final forms. For instance, erythroid progenitors develop into reticulocytes, which eventually mature into red blood cells (erythrocytes). Each type of blood cell follows a specific maturation pathway, characterized by changes in cell shape, size, and the expression of specific proteins.

6. Release into circulation: Once fully matured, the differentiated blood cells are released into the bloodstream, where they can perform their intended functions. Red blood cells carry oxygen, white blood cells are involved in immune responses, and platelets play a crucial role in blood clotting.

• EPO is the primary growth factor for RBC synthesis and development

• Excessive amounts of EPO leads to polycythemia

• EPO activates the JAK/STAT pathway

• This leads to the gene expression of

  • BCL-2

  • Globin

Erythropoietin, often abbreviated as EPO, is a glycoprotein hormone that plays a central role in the regulation of red blood cell production, a process known as erythropoiesis. It is primarily produced and released by the kidneys, although some EPO is also synthesized in the liver, in response to low oxygen levels in the blood. Erythropoietin is a critical component of the body's homeostatic mechanism to ensure an adequate supply of oxygen to body tissues.

The primary function of erythropoietin is to stimulate the proliferation and differentiation of hematopoietic stem cells and committed erythroid progenitor cells within the bone marrow. This stimulation leads to an increase in the production of red blood cells (erythrocytes). EPO acts on these precursor cells to promote their maturation into mature red blood cells, which can transport oxygen from the lungs to various tissues throughout the body.

EPO production is tightly regulated by a negative feedback mechanism, where the kidneys sense oxygen levels in the blood. When oxygen levels are low (such as in situations of hypoxia), the kidneys increase the production and release of erythropoietin, which then stimulates red blood cell production. This response helps to maintain adequate oxygen delivery to tissues in conditions like high-altitude living, anemia, or in response to certain medical conditions. Erythropoietin has also been synthesized as a medication for individuals with anemia related to chronic kidney disease, cancer, or other conditions that affect red blood cell production.

Polycythemia is a medical condition characterized by an excessive increase in the number of red blood cells (erythrocytes) in the bloodstream. This condition can be due to various underlying causes, such as primary polycythemia (polycythemia vera), where there is an overproduction of red blood cells by the bone marrow, or secondary polycythemia, which results from factors like chronic hypoxia (low oxygen levels), kidney disease, or certain genetic mutations. Polycythemia can lead to an increased blood viscosity, which may result in symptoms like fatigue, headache, and an increased risk of blood clot formation.

The JAK/STAT pathway is a crucial cell signaling pathway involved in a wide range of biological processes, including immune responses, cell growth, and development. The name "JAK/STAT" stands for Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT). In this pathway, extracellular signals, such as cytokines and growth factors, bind to cell surface receptors, leading to the activation of JAK proteins. Activated JAKs, in turn, phosphorylate STAT proteins, enabling them to translocate into the cell nucleus and regulate gene expression. The JAK/STAT pathway plays a central role in regulating immune function and is frequently dysregulated in various diseases, including certain cancers and inflammatory disorders.

BCL-2 (B-cell lymphoma 2) is a family of proteins that play a key role in the regulation of apoptosis, which is a process of programmed cell death. Specifically, BCL-2 proteins are known for their anti-apoptotic functions, meaning they help to prevent cell death. They do so by inhibiting the activation of pro-apoptotic proteins, such as BAX and BAK, which promote cell death. Dysregulation of BCL-2 proteins can lead to abnormal cell survival and is implicated in the development of various cancers and other diseases. In cancer therapy, drugs targeting BCL-2 proteins have been developed to promote apoptosis in cancer cells.

Globins are a family of proteins that are essential components of hemoglobin, the molecule responsible for transporting oxygen in red blood cells. Hemoglobin is composed of four globin protein subunits, which can be either alpha or beta globins, depending on the specific type of hemoglobin. In adults, the most common form of hemoglobin is hemoglobin A (HbA), which consists of two alpha and two beta globin subunits. Globins are highly oxygen-binding proteins due to the presence of heme groups, and they play a crucial role in oxygen transport and exchange within the body. Hemoglobinopathies, such as sickle cell anemia and thalassemia, result from genetic mutations affecting the globin genes, leading to abnormal hemoglobin and potentially causing health problems.

• Totipotent stem cells: capable of differentiating into all cell types, including embryonic and extraembryonic tissues

• Pluripotent stem cells: potential to differentiate into almost any cell type in the body but cannot give rise to extraembryonic tissues

• Multipotent stem cells: can differentiate into a limited range of cell types within a particular tissue or organ

• Oligopotent stem cells: can differentiate into only a few cells and include the myeloblast stem cells that produce 3 types of white blood cells – eosinophils, neutrophils, and basophils

• Unipotent stem cells: can only differentiate into a single cell type

• Tissue-specific progenitor cells: play a role in tissue repair and regeneration