CoverModule 1.0. Homeostasis, Membranes, Electrophysiology and ANS1.1. Homeostasis1.1.1. Homeostasis Defined1.1.2. Homeostatic Control Systems1.1.3. Feedback Response Loop1.2. Cell Transport; Water & Solutes1.2.1. Fluid Compartments1.2.2. Osmosis1.2.3. Diffusion of Solutes1.2.4. Active Transport1.2.5. Bulk Transport1.3. Electrophysiology1.3.1. Ions and Cell Membranes1.3.2. Membrane Potentials1.3.3. Graded Potential1.3.4. Action Potentials1.3.5. Refractory Periods1.3.6. Propagation of an Action Potential1.4. The Synapse1.5. The Autonomic Nervous System1.5.1. Organization of the Nervous System1.5.2. Structural Organization of the ANS1.5.3. The SNS and the PNS1.5.4. The Enteric Nervous System1.5.5. Physiology of the ANS1.5.6. Neurotransmitters of the ANS1.5.7. Receptors of the ANS1.5.8. Actions of the Autonomic Nervous System1.5.9. Table of Actions for the SNS and PNS and Some Common DrugsModule 2.0. Skeletal Muscle and Special Senses2.1. Structural Organization of Skeletal Muscle2.2.1. Neuromuscular Junction, Excitation-Contraction Coupling2.2.2. Muscle Contractures and Cramps2.3. Whole Muscle Contraction, Fiber Type, Fatigue and Muscle Pharmacology2.3.1. Motor Units2.3.2. Factors that Influence the Force of Contraction2.3.2. Factors that Influence the Force of Muscle Contraction2.3.3. Energy Source for Muscle Contraction2.3.4. Skeletal Muscle Fiber Types2.3.5. Fatigue2.3.6. Muscle Pharmacology2.4. Smooth Muscle2.4.1. Smooth Muscle Contraction2.5. Control of Body Movement2.5.1. Voluntary Control of Muscle2.5.2. Reflexes2.6. Taste and Smell2.6.1. Taste2.6.2. The Sense of Smell2.7. Vision2.7.1. Structure of the Eye2.7.2. Focusing Light on the Retina2.7.3. Converting Light to Action Potentials2.7.4. The Retina2.7.5. Phototransduction2.7.6. Receptive Fields2.8. Hearing and Equilibrium2.8.1. The Nature of Sound2.8.2. The Hearing Apparatus2.8.3. Sound Vibrations to Action Potentials2.8.4. The Sense of Balance and EquilibriumModule 3.0. Cardiovascular System3.1. Structure of the Heart3.1.1. Chambers and Circulation3.2. Cardiac Cell Action Potentials3.2.1. Action Potentials in Cardiac Muscle Cells3.2.2. Action Potentials in Cardiac Autorhythmic cells3.2.3. Cellular Mechanisms of Inotropy and Chronotropy3.3. Electrophysiology of Heart Muscle3.3.1. Heart Conduction System3.3.2. Electrocardiogram (ECG)3.3.3. Abnormal ECG - Current of Injury3.4. The Cardiac Cycle3.4.1. Cardiac cycle3.4.2. Cardiac Measurements and Pressure Volume Loops3.5. Blood vessels and Blood Pressure3.5.1. Arteries and Veins3.5.2. Capillaries3.5.3. Blood Pressure Regulation and Shock3.5.4. Capillary Exchange3.5.5. Myogenic and Paracrine Regulation of Vasoconstriction and Vasodilation3.6. Blood3.6.1. Composition of Blood3.6.2. Hematopoeisis3.6.3. Breaking Down Red Blood Cells3.6.4. HemostasisModule 4.0. Urinary and Respiratory Systems4.1. Function and Structure of the Kidney4.1.1. Urinary System Function4.1.2. Functional Anatomy of the Urinary System4.1.3. The Nephron: Functional Unit of the Kidney4.1.4. The Renal Corpuscle: Bowman's Capsule4.2. Physiology of Urine Production4.2.1. Filtration4.2.2. Renal Clearance4.2.3. Tubular Reabsorption4.2.4. Urine Concentration and Dilution4.2.5. Hormonal Regulation of Urine Production4.3. Acid/Base Balance4.3.1. Buffers4.3.2. Acid/Base Disturbances4.4. The Respiratory System4.4.1. Respiratory System Structure and Function4.4.2. Respiratory Membrane4.4.3. Respiratory pressures and Inspriation/Expiration4.4.4. Alveoli and Surfactant4.4.5. Pneumothorax4.4.6. Pressure-Volume Loops and the Work of Breathing4.5. Gas Exchange and Transport4.5.1. Gas Laws4.5.2. Partial Pressure Gradients in the Lung4.5.3. Alveolar Gas Equation4.5.4. Oxygen and Carbon Dioxide Transport in the Blood4.5.5. Alveolar Ventilation4.5.6. Ventilation/Perfusion Ratio4.6. Chronic Bronchitis and Emphysema4.6.1. Respiratory Control by the Medulla Oblongata4.6.2. Chemicals that Regulate VentilationModule 5.0. Digestive, Endocrine and Reproductive Systems5.1. Functional Anatomy of the Digestive System5.1.1. Layers of the Digestive Tract5.1.2. Enteric Nervous System5.1.3. Organs of the Digestive System5.2. Digestion5.2.1. Carbohydrates5.2.2. Proteins5.2.3. Lipids5.2.4. Lipoproteins5.3. Regulation of Digestive Secretions5.4. Endocrine System5.4.1. Overview of the Endocrine System5.4.2. Hormone Receptors5.4.3. Hormones of the Body5.4.4. Other Hormones: Melatonin and Pheromones5.5. The Hypothalamus and Pituitary Gland5.5.1. Structure and Function of the Hypothalamus and Pituitary Gland5.5.2. The Posterior Pituitary5.5.3. The Anterior Pituitary5.5.4. Growth Hormone5.5.5. Prolactin5.5.6. Thyroid Hormones5.5.7. Adrenal Hormones5.6. Pancreas5.6.1. Insulin and Glucagon5.6.2. Diabetes Mellitus5.7. Reproductive System Anatomy5.7.1. Female Reproductive Anatomy5.7.2. Male Reproductive Anatomy5.7.3. Sexual Development at Puberty5.7.4. Male Reproductive Endocrine Axis5.7.5. Spermatogenesis5.7.6. Female Reproductive System: Oogenesis5.7.7. Ovulation and Fertilization5.7.8. The Ovarian Cycle5.7.9. The Uterine Cycle5.7.10. PregnancyAppendix A. GenderAppendix B. The Placebo EffectB.2.1. The Placebo EffectB.2.2. Examples of the Placebo EffectB.2.3. How do Placebos Work?B.2.4. Are Placebos Ethical?B.2.5. How do we validate actual effectiveness of placebosB.2.6. Tips for evaluating scientific evidenceB.2.7. What about Faith Healingstest chapter
3.6.2

Hematopoeisis

image129.png
The figure above shows hematopoiesis or the formation of blood cells. The various types of cellular components of blood are each created from a single stem cell called a hemocytoblast. Note that megakaryocytes produce thrombocytes (or platelets), erythrocytes make up the red blood cells and everything else is one of the types of “white blood cells” (also called leukocytes).
Author: A. Rad;  License: Creative Commons Attribution-Share Alike 3.0 Unported license. Link: https://commons.wikimedia.org/wiki/File%3AHematopoiesis_simple.svg

Each of the cells and platelets found in the blood arise through a process called hematopoiesis. Hematopoiesis begins with a single type of stem cell. These stem cells, known as hemocytoblasts, are located in red bone marrow in children and adults. In a developing fetus, hemocytoblasts are also found in the liver, spleen and lymph nodes as well as bone marrow. Ultimately, through the process of hematopoiesis, hemocytoblasts will differentiate into red blood cells, white blood cells, and cell fragments known as platelets. As we will learn later, platelets are important in blood clotting processes. White blood cells include macrophages, neutrophils and lymphocytes. Macrophages are large phagocytic cells that gobble up foreign material and damaged cell parts. Macrophages perform an important step in the breakdown of red blood cells. Neutrophils are very common with infections and Lymphocytes are an important part of our immune system and are the source of antibodies which you have probably heard about.

Platelets

Platelets or thrombocytes are not actually whole cells. Rather they are denucleated cell fragments of a large bone marrow cell known as a megakaryocyte. Though they are cell fragments, they still contain mitochondria and several other types of organelles. Platelets play an important role in blood clotting. 

Red Blood Cells

The most abundant blood cell is the red blood cell, or erythrocyte. Erythrocytes possess a disk-like shape and are considered to be biconcave, as they possess a central indentation on both sides of the cell. This shape is critical to the proper function of a red blood cell, as it provides greater surface area for the rapid exchange of oxygen and carbon dioxide. This biconcave shape also allows the red blood cells to bend which helps them flow through small vessels.

Red blood cells contain a specialized type of protein known as hemoglobin, which is responsible for binding to and transporting oxygen and carbon dioxide. It should be noted, however, that while hemoglobin is solely responsible for transporting oxygen, it is only minimally involved in carbon dioxide transport. Most carbon dioxide is located in the blood in the form of bicarbonate ions. The conversion of carbon dioxide to bicarbonate occurs through a process that is catalyzed by a protein enzyme known as carbonic anhydrase, which is also located within red blood cells. The role of red blood cells in oxygen and carbon dioxide transport will be discussed in more detail during the respiratory chapter.

Hemoglobin

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Hemoglobin Structure.
File 1904 Hemoglobin.jpg; Author: OpenStax College; Site: https://commons.wikimedia.org/wiki/File:1904_Hemoglobin.jpg;License: licensed under the Creative Commons Attribution 3.0 Unported license.

Hemoglobin is composed of 8 subunits: 4 polypeptide chains known as globins (2a and 2b) and 4 iron-containing heme-groups. Each heme group contains a single iron atom, which lends erythrocytes their distinctive red crimson color. Each heme group can transport one molecule of oxygen. When oxygen is bound to hemoglobin, the complex (can also be referred to as a pigment) is known as oxyhemoglobin, which possesses a bright red color. Hemoglobin without oxygen is known as deoxyhemoglobin, which possesses a dark red color.

Erythropoiesis

In a healthy adult's body, it is estimated that around twenty-five trillion red blood cells exist at any given moment. These blood cells will last for approximately 120 days before being broken down by macrophages. If not continually replaced, the overall oxygen containing capacity of the blood decreases. To maintain the twenty-five trillion cells, over two million new red blood cells enter the blood stream each second to replace those lost! If you are ever accused of being lazy, wait two seconds, look up and say: “who you calling lazy, I just made 4 million new red blood cells!” This process of producing new red blood cells is called erythropoiesis and occurs within the red bone marrow of the axillary skeleton.

Erythrocytes (or Red Blood Cells) are unique in that they contain no nucleus or any organelles. During erythropoiesis, hemocytoblast stem cells ultimately differentiate into mature erythrocytes. Small signaling molecules known as hematopoietic growth factors (HGF's) stimulate the production and differentiation of the various types of blood cells. The HGF responsible for the production of red blood cells is known as erythropoietin (EPO). Upon sensing low blood oxygen levels, special cells in the kidneys release EPO into the bloodstream where it travels to target cells within the red bone marrow. Erythropoietin stimulates hemocytoblasts to differentiate into cells known as proerythroblasts. Ultimately, several more intermediates will be produced via mitotic division before the cells reach the reticulocyte stage, which is the final stage before maturation is reached. By this point, hemoglobin is contained within the cells, the nuclei are absent, and only a few ribosomes remain in the cytoplasm. Upon staining a reticulocyte, these remaining ribosomes give the appearance of a sort of net-like or reticular network which explains the origin of the name reticulocyte.

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Reticulocyte/Erythrocyte Comparison
License: Creative Commons Attribution-Share Alike 3.0 Unported license. Link: https://en.wikipedia.org/wiki/Reticulocyte

Reticulocytes have a reticular (mesh - like) organization of ribosomes that can be seen with certain microscopic staining techniques. Reticulocytes are found in the blood for about a day after leaving the bone marrow and then they mature into a fully formed red blood cell and cannot be distinguished as a reticulocyte anymore.

The reticulocytes are released into the blood where they differentiate to become mature erythrocytes about 24 hours later. It is interesting to note that in certain conditions which require accelerated erythrocyte production, the number of reticulocytes in the blood increases. A measurement of the number of reticulocytes in the circulation can give an indication of how strong the recent EPO stimulus has been (*Note: measuring the number of reticulocytes is one way in which athletes who cheat by using synthetic EPO are caught).

Erythropoiesis requires dietary intake of iron, folic acid, and vitamin B12. Any sort of deficiency related to these required dietary elements can cause a condition known as anemia. Anemia results when the bloodstream is unable to properly distribute oxygen throughout the circulatory system to the cells of the human body.

If a vitamin deficiency results in the decreased production of red blood cells, then the oxygen carrying capacity of blood is certainly diminished. Anemi caused by Vitamin B12 deficiency is called pernicious anemia. Vitamin B12 absorption requires a molecule synthesized by the stomach called intrinsic factor. Individuals with certain types of stomach issues may also develop anemia (more specifically, pernicious anemia) because they do not release intrinsic factor and therefore cannot absorb Vitamin B12, even though they eat plenty of it.

Anemia may also be caused by severe hemorrhaging (called hemorrhagic anemia), conditions that result in defective hemoglobin production (sickle cell anemia is one example), or any condition that causes excessive destruction of red blood cells (also called hemolytic anemia).

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