Blood and Circulation

• The cardiovascular system is powered by the pumping action of the heart
• The cardiovascular system provides a mechanism for rapid transport of nutrients, waste products, respiratory gases, and cells.
• Blood is the only fluid tissue in the human body.
• Blood is classified as a connective tissue.
• Living cells in blood are called formed elements.
• The non-living matrix in blood is called plasma.
• Fibers in blood are Fibrin.

Blood and Circulation

• Blood leaves the heart via arteries that branch repeatedly until they become capillaries
• Oxygen (O₂) and nutrients diffuse across capillary walls and enter tissues
• Carbon dioxide (CO₂) and wastes move from tissues into the blood.
• Oxygen-deficient blood leaves the capillaries and flows in veins to the heart.
• This blood flows to the lungs where it releases CO₂ and picks up O₂
• The oxygen-rich blood returns to the heart.

Blood Composition

• Blood is the body's only fluid tissue
• Blood is composed of liquid plasma and formed elements.
• Formed elements include erythrocytes (red blood cells or RBCs).
• Further, the formed elements include leukocytes (white blood cells or WBCs).
• Also the formed elements include thrombocytes or platelets.
• Plasma composes 55% blood, and formed elements make up
• Red blood cells number around 5-6 million/ml.
• White blood cells number around 5000/ml.

Components of Whole Blood

• Plasma constitutes 55% of whole blood
• Leukocytes and platelets make up less than 1% of whole blood.
• Erythrocytes constitute 45% of whole blood.

Characteristics and Volume of Blood

• Blood is a sticky, opaque fluid with a metallic taste.
• Blood color varies from scarlet (oxygen-rich) to dark red (oxygen-poor).
• pH of blood is 7.35-7.45.
• Blood temperature is 38°C, which is slightly higher than "normal" body temperature.
• Blood accounts for approximately 8% of body weight
• The average volume of blood is 5-6 L for males.
• Average blood volume is 4-5 L for females.

Blood's Main Functions

• Blood performs functions dealing with substance distribution, regulation of the blood, and body protection.
• Blood transports oxygen from the lungs and nutrients from the digestive tract.
• Blood carries metabolic wastes from cells to the lungs and kidneys for elimination.
• Blood transports hormones from endocrine glands to target organs.
• Blood maintains appropriate body temperature by absorbing and distributing heat.
• Blood maintains normal pH in body tissues using buffer systems.
• Blood maintains adequate fluid volume in the circulatory system.
• Blood prevents blood loss by activating plasma proteins and platelets.
• Blood initiates clot formation when a vessel is broken.
• Blood prevents infection by synthesizing and utilizing antibodies.
• Blood activates complement proteins.
• Blood activates WBCs to defend the body against foreign invaders.

Blood Plasma Solutes

• Blood plasma contains over 100 solutes, including proteins, non-protein nitrogenous substances, organic nutrients, electrolytes, and respiratory gases.
• Plasma proteins include albumin, globulins, and clotting proteins.
• Non-protein nitrogenous substances include lactic acid, urea, and creatinine.
• Organic nutrients include glucose, carbohydrates, and amino acids.
• Electrolytes include sodium, potassium, calcium, chloride, and bicarbonate.
• Respiratory gases include oxygen and carbon dioxide.

Plasma Proteins

• More than 90% of plasma proteins are synthesized in the liver.
• Albumins make up 60% of plasma proteins.
• Albumins are responsible for viscosity and osmotic pressure of blood.
• Albumins act as carrier proteins and buffers.
• Globulins constitute ~35% of plasma proteins.
• Globulins include immunoglobulins, which attack foreign proteins and pathogens.
• Globulins include transport globulins, which bind ions, hormones, and other compounds.
• Fibrinogen is converted to fibrin during clotting.
• Serum is what remains after removing fibrinogen.

Formed Elements

• Erythrocytes, leukocytes, and platelets make up the formed elements.
• Only WBCs are complete cells: RBCs have no nuclei or organelles, and platelets are just cell fragments.
• Most formed elements survive in the bloodstream for only a few days.
• Most blood cells do not divide but are renewed by cells in bone marrow.

Erythrocytes (RBCs)

• Erythrocytes are biconcave discs, anucleate, with essentially no organelles
• Erythrocytes are filled with hemoglobin (Hb), a protein that functions in gas transport.
• Erythrocytes contain the plasma membrane protein spectrin and other proteins.
• Spectrin gives erythrocytes their flexibility.
• Spectrin allows erythrocytes to change shape as necessary.
• Erythrocytes are an example of the complementarity of structure and function.
• Its biconcave shape gives each red blood cell a huge surface area relative to its volume.
• Discounting water content, erythrocytes are more than 97% hemoglobin.
• ATP is generated anaerobically, so the erythrocytes do not consume the oxygen they transport.

Erythrocyte Function

• Erythrocytes are dedicated to respiratory gas transport.
• Hemoglobin reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobin.
• Hemoglobin is composed of the protein globin, made up of two alpha and two beta chains.
• Each chain is bound to a heme group.
• Each heme group bears an atom of iron, which can bind to one oxygen molecule.
• Each hemoglobin molecule can transport four molecules of oxygen.
• Each erythrocyte has 250 million hemoglobin molecules.
• Oxyhemoglobin is hemoglobin bound to oxygen.
• Oxygen loading takes place in the lungs.
• Deoxyhemoglobin is hemoglobin after oxygen diffuses into tissues (reduced Hb).
• Carbaminohemoglobin is hemoglobin bound to carbon dioxide.
• Carbon dioxide loading takes place in the tissues.

Production of Erythrocytes

• Hematopoiesis refers to blood cell formation.
• Hematopoiesis occurs in the red bone marrow of the axial skeleton and girdles.
• Hematopoiesis also occurs in the epiphyses of the humerus and femur.
• Hemocytoblasts give rise to all formed elements.
• Hemocytoblasts are hematopoietic stem cells.
• Hemocytoblasts give rise to all formed elements.
• Hormones and growth factors push the hemocytoblast along a specific pathway of blood cell development.
• New blood cells enter blood sinusoids.
• A hemocytoblast is transformed into a committed cell called the proerythroblast.
• Proerythroblasts develop into early erythroblasts
• The developmental pathway consists of three phases: ribosome synthesis, hemoglobin accumulation, ejection of the nucleus.
• Ribosome synthesis occurs in early erythroblasts (Phase 1)
• Hemoglobin accumulation occurs in late erythroblasts and normoblasts (Phase 2).
• Ejection of the nucleus occurs in normoblasts and formation of reticulocytes (Phase 3).
• Reticulocytes then become mature erythrocytes.
• Maturation stages of RBCs includes proerythroblast, erythroblasts, basophilic erythroblast, polychromatophilic erythroblast, reticulocyte, mature red blood cell

Regulation and Requirements for Erythropoiesis

• Circulating erythrocytes- number remains constant and reflects a balance between RBC production and destruction.
• Too few red blood cells leads to tissue hypoxia.
• Too many red blood cells causes undesirable blood viscosity.
• Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins.

Hormonal Control of Erythropoiesis

• Erythropoietin (EPO) released by the kidneys is triggered by hypoxia.
• Hypoxia is due to decreased RBCS, decreased oxygen availability, or increased tissue demand for oxygen.
• Enhanced erythropoiesis increases the RBC count in circulating blood.
• Enhanced erythropoiesis affects the oxygen carrying ability of the blood.
• Hypoxia can be caused by hemorrhage or increased RBC destruction, or insufficient hemoglobin, or reduced oxygen availability.
• The effects of EPO lead to a more rapid maturation of committed bone marrow cells and/or increased circulating reticulocyte count.
• Testosterone also enhances EPO production, resulting in higher RBC counts in males.
• Normal blood oxygen levels maintain balance
• Imbalance from stimulus of hypoxia from decreased RBC count, decreased oxygen availability, or increased tissue demands
• Kidney's release of erythropoetin causes kidneys to release erythropoietin
• Which stimualtes red bone marrow leading to more oxygen carrying ablity of blood

Dietary Requirements and the Fate of Erythrocytes

• Erythropoiesis requires proteins, lipids, carbohydrates, iron, vitamin B₁₂ and folic acid.
• The body stores iron in hemoglobin (65%), the liver, spleen, and bone marrow.
• Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin.
• Circulating iron is loosely bound to the transport protein transferrin.
• The life span of an erythrocyte is 100-120 days.
• Old erythrocytes become rigid and fragile, and their hemoglobin begins to degenerate.
• Dying erythrocytes are engulfed by macrophages.
• Heme and globin are separated and the iron is salvaged for reuse.
• Heme is degraded to a yellow pigment called bilirubin.
• The liver secretes bilirubin into the intestines as bile.
• The intestines metabolize bilirubin into urobilinogen.
• The degraded pigment leaves the body in feces, in a pigment called stercobilin.
• Globin is metabolized into amino acids and is released into the circulation.
• Hb is released into the blood, captured by haptoglobin, and phgocytized.

Erythrocyte Disorders

• Anemia is when blood has low O₂ carrying capacity, and is typically caused by insufficient RBC or iron deficiency or B12 deficiency.
• Anemia - is when blood has abnormally low oxygen-carrying capacity.
• Anemia is a symptom rather than a disease itself.
• Blood oxygen levels in anemia cannot support normal metabolism.
• Anemia has signs/symptoms including fatigue, paleness, shortness of breath, and chills.
• Hemorrhagic anemia results from acute or chronic loss of blood.
• Hemolytic anemia involves prematurely ruptured erythrocytes.
• Aplastic anemia involves destruction or inhibition of red bone marrow.
• Iron-deficiency anemia results from hemorrhagic anemia, inadequate intake of iron, or impaired iron absorption.
• Pernicious anemia results from a deficiency of vitamin B12 or a lack of intrinsic factor required for B12 absorption.
• Pernicious anemia treatment involves intramuscular injection of B12.
• Thalassemais cause an absent or faulty globin chain in hemoglobin.
• Erythrocytes affected by thalassemias are thin, delicate, and deficient in hemoglobin.
• Sickle-cell anemia results from a defective gene coding for an abnormal hemoglobin called hemoglobin S (HbS).
• HbS has a single amino acid substitution in the beta chain, causing RBCs to become sickle-shaped in low oxygen situations.
• HbS results from a single change of the 287 amino acids in the beta chain in the globin molecule, and is found in 1 out of 400 African Americans.
• Malaria attacks the RBC.
• Sickle cell shaped RBC cannot contract malaria.
• Polycythemia involves excess RBC that increase blood viscosity.
• Polycythemia involves 8-11 million cells/mm3, usually caused by cancer, and naturally occurs at high elevations.
• Blood doping involves removing blood for athletes days before an event and replacing it and is banned by the Olympics.

Key Questions

• Average adult blood volume is ~5 liters
• Blood plasma is the straw colored, non-living part of blood, 90% water
• Select materials carried by plasma include RBC, Hormones, and digested materials.