Blood Composition and Hematopoiesis

• The circulatory system transports, regulates, and protects the body.

General Characteristics of Blood

• Composition, temperature, color, pH level, and density are general characteristics of blood.

Blood Composition

• Blood consists of formed elements and plasma.
• Plasma makes up 55% of blood volume.
• The buffy coat, containing leukocytes and platelets, is less than 1% of blood.
• Erythrocytes, or red blood cells, constitute 45% of blood volume.

Plasma Composition

• Plasma's liquid portion is composed of water, proteins, gases, and nutrients.
• Waste products are also components of plasma.
• Plasma proteins are mainly produced by the liver.
• Albumin influences blood viscosity and osmolarity.
• Globulins include alpha, beta, and gamma types.
• Fibrinogen, making up about 4% of all plasma proteins, is a precursor to fibrin.

Hematopoiesis

• Hematopoiesis is the process of producing blood, especially its formed elements.
• All formed elements originate from hematopoietic stem cells (HSC) or pluripotent stem cells (PPSCs).
• Erythropoiesis is the production of red blood cells, stimulated by erythropoietin (EPO).
• Leukopoiesis is the production of white blood cells, involving myeloid and lymphoid stem cells, and colony-stimulating factors (CSFs).
• Thrombopoiesis is production of thrombocytes, also known as platelets.

Red Blood Cells

• Bags of hemoglobin carry oxygen (O2) and carbon dioxide (CO2).
• Normal range is 4.2-6.2 million RBCs/µL.
• Hematocrit represents % volume of RBC in blood.
• RBCs are shaped like biconcave discs and lack a nucleus.
• They are designed to maximize O2 carrying capacity and increase flexibility.

Hemoglobin Composition

• Each hemoglobin consists of four protein chains called globins (α-chains and β-chains) and four heme group molecules.
• Hemoglobin is made in red bone marrow.
• It lives in red blood cells.
• Destroyed or recycled in the liver or by phagocytic cells.
• Hemoglobin gains O2 from lungs and delivers O2 to tissues.
• Hemoglobin claims CO2 from tissues and delivers CO2 to lungs.

Erythropoietin (EPO)

• Erythropoietin (EPO) is a hormone that controls RBC production.
• It is produced in the kidney in response to decreased O2 for example during Hemorrhage or reduced availability of O2 when at a high altitude, pneumonia, or during exercise.
• Erythroblasts (Normoblasts) multiply and synthesize hemoglobin.
• Reticulocytes form a temporary network. They leave the bone marrow.
• Reticulocytes in the circulating blood mature to form Erythrocytes, which are mature RBCs.

Hemolysis

• Hemolysis occurs when an aged RBC reaches the end of its functional life.
• Hemolysis takes place in the spleen and all components are re-used.

Erythrocytes Disorders

• Deficiency (anemia) and excess (polycythemia) are erythrocytes disorders.
• Pernicious anemia is caused by a lack of vitamin B12.
• Iron deficiency anemia is characterized by impaired hemoglobin production due to lack of iron.
• Thalassemia involves impaired synthesis of globin proteins.
• Aplastic anemia is caused by reduced erythrocyte mitosis in red bone marrow.
• Sickle-cell anemia is hereditary hemoglobin defect where low oxygen causes cells to sickle, lodge in small vessels and reduce blood flow.
• Hemorrhagic anemia results from loss of blood.
• Hemolytic anemia can be due to anything that causes the destruction of erythrocytes.

Blood Typing

• Blood types are based on molecules called antigens and antibodies.
• Antigens are unique molecules on the surface of ALL cells, differentiating own cells (self) vs foreign materials (non-self).
• Antibodies are proteins secreted as a specific immune response to a foreign antigen and they mark them for destruction, form large clumps causing agglutination.
• Type A blood has A antigens and produces anti-B antibodies.
• Type B blood has B antigens and produces anti-A antibodies.
• Type AB blood has both A & B antigens and no antibodies.
• Type O blood has no antigens and produces both anti-A & anti-B antibodies.

Determining Blood Type

• Antibodies present in blood plasma are specific to antigens, but not on the own red blood cells.
• Antibodies are opposite of the antigens present.

Blood Transfusions

• Transfusions require compatibility between donor antigens and recipient antibodies.

Rhesus Factor

• Rhesus factor (Antigen D) originally found in the Rhesus monkey.
• Presence of D antigen on red blood cells (RBCs) define Rh-positive. Absence of D antigen is Rh-negative.
• Anti-D antibodies are not normally present in blood and form only in Rh-negative individuals who have been exposed to Rh+ blood.
• Hemolytic disease of the newborn (HDN), or erythroblastosis fetalis. happens when Rh- mother carries an Rh+ fetus which causes placental leakage during pregnancy triggering production of anti-D antibodies.

White Blood Cells

• Leukocytes, or white blood cells (WBCs) are the least numerous formed elements.
• They primary job is to fight off infections
• They are the only living formed element
• There are 5 different types

Types of WBCs

• Granulocytes - ...phils
• Agranulocytes - ...cytes
• Neutrophils phagocytize bacteria and release antimicrobial chemicals. 60-70% which contain 3-5 lobes and violet-staining specific granules in the cytoplasm.
• Eosinophils phagocytize antigen-antibody complexes and target allergens, inflammatory chemicals, parasitic worms. Making up 2-4% which contain bi-lobed nucleus with an abundance of red-orange specific granules in the cytoplasm.
• Basophils secrete histamine (a vasodilator) and heparin (an anticoagulant). Being <0.5% and Serotonin: attracts neutrophils and eosinophils for inflammatory response.
• Monocytes are Largest being horseshoe-shaped or kidney-shaped nucleus. Responsible for Macrophages and Phagocytosis while Present antigens activating immune system (APCs).
• Lymphocytes: B-Cells (bone marrow) produce antibodies. T-Cells (thymus). NK-Cells (natural killers) destroy: cancer cells, viral infected cells, foreign cells and Antigen presentation activate immunity. Plasma B cells- Secrete antibodies makes up 25-33%.

Leukopoiesis

• Leukopoiesis is the production of white blood cells.
• Leukopenia is when total white blood cell (WBC) count is below the normal range of 5,000-10,000 cells/m.
• Leukocytosis is when total count is above the normal range (between 10,000-11,000 cells/m).
• Leukemia is cancer of the hematopoietic tissues that produces a very high number of leukocytes (above 11,000 cells/m).

Platelets

• Megakaryocytes produce platelets.
• Thrombopoietin hormone, from the liver and kidneys, stimualte thrombopoiesis
• Platelets cause blood clotting, which is cessation of bleeding, or hemostasis.
• The normal range is 130,00 – 400,000 cell count.
• Platelets are fragmented cells that have Granules

Platelets role in Hemostasis

• Hemostasis – blood clotting involves three steps.
• Vascular spasm: reduces blood flow to damaged tissue.
• Platelet Plug Formation: traps large objects like a chain link fence.
• Coagulation: traps everything to achieve Clot formation.
• The Extrinsic pathway is triggered by a damaged blood vessel, clotting factors that are released by the damaged blood vessel or nearby tissues.
• The Intrinsic pathway is when no damage is present to blood vessel, reaction pathway that uses clotting factors that are within the blood itself.
• Platelet repulsion, Dilution and Anticoagulation all prevent inappropriate clotting.
• Both pathways will eventually arrive to activate Factor X.
• Common pathway - chemical chain found in both other pathways.
• Extrinsic or Intrinsic Pathway Factor X Prothrombin activator Thrombin Fibrinogen into Fibrin
• Clotting factors, are mostly made by liver using Calcium and Vitamin K.
• Fibrinolysis is the process in which clots are disposed of once tissue repair is completed.
• Kallikrein converts an inactive protein called plasminogen into plasmin, which dissolves fibrin (sticky protein), breaking up the clot.
• Platelet repulsion, Dilution and Anticoagulation all prevent inappropriate clotting.
• Thrombopoietin from the liver and kidney starts birth of platelets,
• Platelets achieve Hemostasis, Destroy bacteria and Attract WBCs
• Eventually the platelet will go through phagocytosis