Bio 13.1 Part 1 - Circulation System PDF

Chapter 13: Circulation 450 Lesson 13.1 **Circulatory System** Introduction The **circulatory system**, also known as the **cardiovascular system**, is composed of the **heart**, **blood vessels** (ie, vasculature), and **blood**. The circulatory system functions to transport materials througho...

Chapter 13: Circulation 450 Lesson 13.1 **Circulatory System** Introduction The **circulatory system**, also known as the **cardiovascular system**, is composed of the **heart**, **blood vessels** (ie, vasculature), and **blood**. The circulatory system functions to transport materials throughout the body. This transport includes delivery of necessary substances obtained from the environment to the body\'s cells and movement of waste products away from cells to be eliminated from the body. The circulatory system also transports heat, molecules and cells that function in body defense, and signaling molecules involved in cell communication. This lesson covers general cardiovascular system functions, composition and functional characteristics of blood, and structure and function of the heart. In addition, this lesson describes blood vessel structure and function, pattern and regulation of blood flow, and control mechanisms affecting circulation. 13.1.01 Cardiovascular Function The cardiovascular system distributes blood between the heart and the rest of the body. This distribution is achieved through the pumping action of the heart and regulation of blood vessel diameter, which together create pressure differences that determine the extent to which blood flows to specific parts of the body. Typically, blood flow distribution is well matched to the needs of tissues for delivery of oxygen, nutrients, water, electrolytes, and signaling molecules (ie, [hormones](javascript:void(0))) as well as for removal of metabolic wastes (eg, carbon dioxide, nitrogenous waste). The flow of blood also delivers defensive immune system cells and molecules to infected or injured tissues. In addition, the relative distribution of blood between the body\'s core and periphery (ie, [skin](javascript:void(0))) contributes to body temperature regulation. The main functions of the cardiovascular system are summarized in Figure 13.1. Chapter 13: Circulation 451 **Figure 13.1** Primary functions of the cardiovascular system. 13.1.02 Blood Components **Blood** is a fluid connective tissue composed of living cells (ie, formed elements) and a nonliving extracellular matrix. Formed elements originate in the [bone marrow](javascript:void(0)) and include **erythrocytes** (ie, red blood cells \[RBCs\]) and **leukocytes** (ie, white blood cells \[WBCs\]). Blood also contains **thrombocytes** (ie, platelets), which are cell fragments derived from large bone marrow cells called megakaryocytes. RBCs function to transport oxygen and carbon dioxide, WBCs provide [immune defense](javascript:void(0)) for the body (see Concept 20.1.01), and platelets play a crucial role in blood clotting. RBC membranes possess molecules (ie, antigens) that are the basis for human blood groups (ie, blood types). Furthermore, most individuals\' blood naturally contains [antibodies](javascript:void(0)) that cause destruction of RBCs transfused (ie, received) from a blood donor with different RBC antigens than the recipient. There are A diagram of a human body Description automatically generated Chapter 13: Circulation 452 many different groups of RBC antigens; however, antigens responsible for the Rh and ABO blood groups are of special importance because these antigens can cause potentially fatal transfusion reactions in recipients of mismatched blood. Antigens and antibodies are discussed in detail in Concepts 20.2.03 and 20.2.06. Rh blood groups (ie, Rh+, Rh−) are based on the presence or absence of an antigen called the Rh factor, which follows an [autosomal dominant](javascript:void(0)) inheritance pattern (see Lesson 7.2). ABO blood groups (summarized in Table 13.1) are determined based on the presence or absence of type A and type B RBC antigens, which are encoded by codominant alleles designated *IA* and *IB* (or simply *A* and *B*), respectively. In addition, a recessive allele of the *ABO* gene exists*,* designated *i* (or *O*). Individuals homozygous for this allele (ie, genotype *ii*) produce RBCs that lack type A and type B antigens, resulting in type O blood. **Table 13.1** Characteristics of ABO blood groups. Unlike the ABO system, in which anti-A and anti-B antibodies can be present in an individual\'s blood without prior exposure to type A and type B antigens, production of anti-Rh antibodies (ie, anti-D) requires that an Rh− individual be exposed to Rh+ RBCs. Such exposure can occur when an Rh− mother gives birth to an Rh+ baby. If this mother subsequently becomes pregnant with another Rh+ offspring, the previously formed anti-Rh antibodies can cross the placenta and cause destruction of fetal RBCs (see Figure 13.2), which can lead to a potentially fatal condition called hemolytic disease of the fetus and newborn (ie, erythroblastosis fetalis).  Chapter 13: Circulation 453 **Figure 13.2** Situation leading to hemolytic disease of the fetus and newborn. A collage of images of two people Description automatically generated Chapter 13: Circulation 454 The relative abundance of each type of formed element in the blood differs, with the number of RBCs in a sample of blood greatly exceeding the number of WBCs and platelets. RBCs typically account for approximately 45% of a blood sample\'s total volume, whereas the combined volume of WBCs and platelets accounts for less than 1% of the total volume. The fraction (ie, percent) of a blood sample\'s total volume that consists of RBCs is called the **hematocrit**, with normal values ranging from approximately 37% to 52% in adults. **Plasma**, the liquid matrix in which blood cells are suspended, accounts for roughly 55% of blood\'s volume. Plasma is approximately 90% water, and the remaining 10% is composed of a variety of dissolved substances. Figure 13.3 shows a breakdown of the general blood components. **Figure 13.3** Components of blood. Blood cells are produced by cell division of [hematopoietic stem cells](javascript:void(0)) in the bone marrow. Most mature blood cells in circulation do not divide and must be continually removed and replaced as they reach the end of their life span. The [spleen](javascript:void(0)) plays an important role in the removal of aged or damaged RBCs and platelets from circulation via [phagocytosis](javascript:void(0)) by the abundant macrophages present in the spleen. 13.1.03 Oxygen Transport Transportation of molecular oxygen (O2) from the lungs to all cells of the body is a primary function of the cardiovascular system. Of the total O2 carried by the blood, only about 2% is present as gas dissolved in the blood plasma. The remaining O2 in the blood is reversibly bound to the protein **hemoglobin** and transported within red blood cells (RBCs). As shown in Figure 13.4, a molecule of hemoglobin consists of four polypeptide chains (ie, subunits), each of which is attached to an iron-containing **heme group** that can reversibly bind one O2 molecule. This configuration enables each hemoglobin molecule to transport up to four O2 molecules. RBCs are specialized for O2 transport. Due to a small diameter and flattened, biconcave shape (see Figure 13.4), RBCs have a large surface area to volume ratio, which facilitates diffusion of O2 into and out of RBCs. In addition, mature mammalian RBCs lack [membrane-bound organelles](javascript:void(0)) (eg, nuclei, mitochondria), which is likely an adaptation (see Concept 8.2.03) allowing mature RBCs to hold more  Chapter 13: Circulation 455 hemoglobin molecules, therefore increasing the cells\' O2 carrying capacity. Furthermore, RBCs\' lack of mitochondria prevents aerobic cellular respiration, keeping RBCs from consuming the O2 they carry. **Figure 13.4** Structural features of red blood cells and hemoglobin. In addition to RBC structural specializations, hemoglobin molecules within RBCs have specialized features that enhance O2 transport. Hemoglobin is able to efficiently pick up O2 at the lungs (as discussed in Concept 14.2.02) because hemoglobin\'s affinity for O2 progressively *increases* as each O2 is loaded onto hemoglobin. Likewise, hemoglobin is able to efficiently drop off O2 at the tissues because hemoglobin\'s affinity for O2 progressively *decreases* as each O2 is unloaded. The changes in hemoglobin\'s affinity for O2 that occur during O2 loading and unloading are due to **positive cooperativity** among hemoglobin\'s four subunits. Binding of an O2 molecule to one subunit induces a conformational change in hemoglobin that makes binding of O2 by the remaining subunits progressively easier. Similarly, the release of an O2 molecule from one subunit of an oxygen-saturated hemoglobin molecule (ie, hemoglobin carrying four O2 molecules) facilitates the progressive unloading of O2 from the remaining subunits. The graph shown in Figure 13.5 is called an **oxygen-hemoglobin dissociation curve (OHDC)**. This type of graph shows the fraction of hemoglobin present in a blood sample saturated with O2 when the blood is exposed to different [partial pressures](javascript:void(0)) of O2 (ie, PO2). A diagram of a cell Description automatically generated Chapter 13: Circulation 456 **Figure 13.5** Oxygen-hemoglobin dissociation curve. Positive cooperativity in O2 binding among hemoglobin\'s subunits (ie, hemoglobin\'s variable O2 affinity) causes the OHDC to be **sigmoidal** (ie, S-shaped). Hemoglobin without any bound O2 has low affinity for O2; therefore, as PO2 increases from zero, the fraction of O2-saturated hemoglobin increases slowly at first. As hemoglobin\'s O2 affinity increases (due to positive cooperativity during O2 loading), small PO2 increases result in significant increases in the percentage of O2-saturated hemoglobin. As O2 saturation approaches 100% with increasing PO2, the curve flattens (see Figure 13.5). Various environmental factors also affect hemoglobin\'s O2 affinity and can result in changes to the OHDC known as **left or right shifts** (Figure 13.6). These factors include temperature, carbon dioxide partial pressure (PCO2), pH, and concentration of 2,3-bisphosphoglycerate (2,3-BPG), a molecule derived from an intermediate produced during [glycolysis](javascript:void(0)).  Chapter 13: Circulation 457 **Figure 13.6** Factors causing shifts to the oxygen-hemoglobin dissociation curve. As shown in Figure 13.6, hemoglobin\'s O2 affinity increases (resulting in a left-shifted OHDC) in response to decreased temperature, PCO2, or 2,3-BPG concentration, as well as increased pH. These conditions frequently characterize tissues at rest without an elevated demand for O2. Conversely, hemoglobin\'s O2 affinity decreases (thereby facilitating O2 unloading) in response to increased temperature, PCO2, or 2,3-BPG concentration, as well as decreased pH. Such changes, which cause the OHDC to shift to the right, typically occur in tissues experiencing elevated metabolic activity (eg, skeletal muscle during exercise). This means that hemoglobin tends to unload O2 with greatest efficiency to the tissues consuming O2 most rapidly via [aerobic metabolism](javascript:void(0)). A right shift in the OHDC caused by increased PCO2 and/or decreased pH is referred to as the **Bohr effect**. RBCs produced during fetal development contain a specialized type of hemoglobin called **fetal hemoglobin (hemoglobin F)**. This type of hemoglobin contains polypeptides with an amino acid sequence that differs from that of polypeptides present in adult hemoglobin (hemoglobin A). The resulting structural differences between hemoglobin F and hemoglobin A cause hemoglobin F to have greater O2 A graph of a diagram Description automatically generated with medium confidence Chapter 13: Circulation 458 affinity than hemoglobin A. This difference in O2 affinity allows O2 to readily pass from maternal blood to fetal blood at the placenta, which is adaptive because the fetus must extract O2 from maternal blood rather than from air (see Concept 10.4.02). 13.1.04 Carbon Dioxide Transport Cells generating ATP via [aerobic cellular respiration](javascript:void(0)) produce carbon dioxide (CO2) as a metabolic waste product. This CO2 is carried away from CO2-producing cells and to the lungs for disposal (see Concept 14.2.02) via the circulatory system. There are three primary ways that CO2 is transported in the blood, as illustrated in Figure 13.7: Approximately 7% of the CO2 in the blood is carried as gas dissolved in the blood plasma. The poor solubility of CO2 in water explains the minority of CO2 transported in this manner. The remaining CO2 in the blood is taken up by red blood cells (RBCs), in which approximately 23% of the blood\'s total CO2 reversibly binds to hemoglobin. Unlike O2, CO2 does not bind to hemoglobin\'s heme groups; rather, CO2 binds to the [N-terminal](javascript:void(0)) amino acids of hemoglobin\'s four polypeptide chains, forming **carbaminohemoglobin**. The remaining CO2 within RBCs (approximately 70% of the blood\'s total CO2) is acted upon by **carbonic anhydrase**, an enzyme that catalyzes a reversible reaction between CO2 and water. This reaction produces carbonic acid (H2CO3), which dissociates into hydrogen ions (H+) and **bicarbonate ions (HCO3−)**. Upon formation, HCO3− ions exit RBCs via transport proteins and travel in the plasma. These transport proteins also bring chloride ions (Cl−) into RBCs, preventing an imbalance of electric charge that would otherwise occur due to loss of HCO3−. This transfer is known as the **chloride shift**. **Figure 13.7** Transport of carbon dioxide in the blood. When CO2-rich blood reaches the lungs, CO2 is transferred from the pulmonary capillaries to the lung air spaces (ie, alveoli) for disposal from the body via [expiration](javascript:void(0)). The steps of this transfer are depicted in Figure 13.8:  Chapter 13: Circulation 459 1.Because the carbon dioxide partial pressure (PCO2) of pulmonary capillary plasma is higher than the PCO2 of alveolar air, CO2 gas diffuses from the blood into the alveoli, that is, from high to low partial pressure. 2.Loss of CO2 from the plasma decreases plasma PCO2, allowing CO2 diffusion out of RBCs. 3.Diffusion of CO2 out of RBCs causes carbaminohemoglobin within RBCs to release bound CO2, which then diffuses from the RBCs into the plasma. 4.As CO2 continues to exit RBCs, carbonic anhydrase in the RBCs converts H2CO3 into CO2 and H2O, reversing the reaction that occurred at the tissues. The resulting decrease in RBC H2CO3 concentration triggers the production of additional H2CO3 via the reaction between H+ and HCO3−, which causes RBC HCO3− concentration to decrease. 5.Decreased RBC HCO3− concentration causes HCO3− to be pulled into the RBCs from the plasma, which further promotes the carbonic anhydrase--catalyzed reaction converting HCO3− to CO2. This additional CO2 diffuses out of the RBCs and ultimately into the alveoli. **Figure 13.8** Steps involved in the transfer of carbon dioxide from the blood to the lungs. 13.1.05 Blood Clotting Injuries that cause breaks in blood vessel walls result in a loss of blood from the circulatory system. To prevent excessive blood loss from such injuries, the circulatory system responds to damaged blood vessels by forming blood clots that function as plugs to stop additional blood from escaping through broken vessel walls. A disease known as **hemophilia** occurs when this clotting process is impaired, which can lead to potentially life-threatening blood loss following minor injuries. Hemophilia is typically an inherited disorder that exhibits an [X-linked recessive](javascript:void(0)) pattern of transmission from parents to offspring (see Concept 7.3.02). The process by which blood clots are formed is called **hemostasis** and requires the activity of platelets (thrombocytes) in the blood. The steps that occur during hemostasis are summarized in Figure 13.9. A diagram of a human body Description automatically generated Chapter 13: Circulation 460 **Figure 13.9** Steps involved in the process of hemostasis. The first step in hemostasis is **vasoconstriction** (or vascular spasm), which causes narrowing of the broken blood vessel. Vasoconstriction occurs via contraction of [smooth muscle cells](javascript:void(0)) in the wall of the blood vessel and reduces blood flow through the damaged vessel, slowing blood loss. The inner lining of a blood vessel is called the **endothelium**, and damage to endothelial cells causes the release of [chemical signals](javascript:void(0)) (eg, endothelin) that help trigger vasoconstriction. The second step in hemostasis involves the formation of a **platelet plug**. Platelets typically do not adhere to undamaged endothelial cells; however, platelets stick tightly to the collagen fibers hidden beneath the endothelium in undamaged vessels but exposed in damaged vessels. As platelets begin sticking to exposed collagen, they become activated, causing further stickiness. The platelets release chemical signals and aggregate, forming a plug by adhering to one another. This signaling process, which enhances vasoconstriction and activates even more platelets, is an example of [positive feedback](javascript:void(0)).  The final step in hemostasis is **coagulation**, which produces the actual blood clot. Coagulation involves a complex series of steps in which multiple clotting factors in the blood plasma are sequentially activated (see Figure 13.10 for a simplified model; detailed knowledge of clotting factors is beyond the scope of the exam). **Figure 13.10** Simplified model of the coagulation cascade. Near the end of the coagulation cascade, a clotting factor called **prothrombin** is converted into an active enzyme called **thrombin**, which cleaves soluble **fibrinogen** molecules into insoluble **fibrin** molecules. These fibrin molecules polymerize into fibrin strands that become cross-linked to form a mesh that traps platelets and red blood cells, producing a clot that stops additional blood loss from the broken blood vessel. After the damaged blood vessel has healed, the blood clot undergoes **fibrinolysis**, in which the fibrin mesh is digested by an enzyme called **plasmin**, and the clot dissolves. Plasmin is produced via activation of an inactive precursor, a plasma protein known as **plasminogen**.