A&P II Exam 1

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Effect of Binding Proteins

(a) Free hormones (those that circulate freely in the blood) immediately activate target cells once they are delivered from the blood. Thus, the blood levels of these hormones tend to fluctuate to a greater degree than the levels of hormones that attach to binding proteins; water-soluble hormones bind their receptors, which are membrane bound. (b) Hormones that are transported in the blood attached to binding proteins circulate in the blood as bound or free hormones. As the concentration of free hormones decreases, bound hormones are released from the binding proteins. This provides a chronic, stable supply of hormone and, thus, more consistent control of target cells. This is especially important for hormones that regulate basal metabolism. Lipid-soluble hormones bind their receptors in either the cytoplasm or the nucleus.

General comparison of nuclear and membrane-bound receptors

(a) Lipid-soluble hormones diffuse through the plasma membrane of their target cell and bind to a cytoplasmic receptor or a nuclear receptor. In the nucleus, the combination of the hormone and the receptor initiates protein synthesis, described later in this chapter. (b) Water-soluble hormones bind to the external portion of membrane-bound receptors, which are integral membrane proteins on their target cell.

Comparison of the nervous and endocrine systems - Similarities

1.Both systems use structures in the brain. In chapter 13, the hypothalamus is discussed as a critical area of the brain responsible for many functions, including nervous system functions and hormone production. An example of nervous function is when the hypothalamus detects changes in body temperature; it sends action potentials to either the sweat glands or skeletal muscle, depending on whether the body is too hot or too cold. On the other hand, an example of endocrine function is when the hypothalamus sends hormones to the pituitary gland that regulate the secretion of hormones from the pituitary. In addition, hypothalamic neurons synthesize two hormones, antidiuretic hormone and oxytocin, which are secreted directly into the bloodstream. Thus, the hypothalamus plays a role in both the nervous and endocrine systems. 2.In many cases, the nervous system may use certain molecules as neurotransmitters, whereas the endocrine system may use these molecules as hormones. For example, when a neuron secretes epinephrine into a synaptic cleft, it is a neurotransmitter. In contrast, when cells of the adrenal gland secrete epinephrine into the bloodstream, it is a hormone. 3.The two systems work together to regulate critical body processes. For example, the introduction to this chapter pointed out that epinephrine, the hormone, is important in stressful situations. However, the initial, immediate release of epinephrine, the neurotransmitter, in times of crisis is from the nervous system. Thus, the two systems work almost simultaneously. 4.Some neurons secrete hormones. In this case, the neuron's chemical messenger enters the bloodstream, where it functions as a hormone. As a strict part of their definition, recall that hormones circulate in the bloodstream. To help distinguish these chemical messengers from neurotransmitters and other hormones, they are often called neuropeptides, or neurohormones. An example of a neuropeptide is the labor-inducing hormone oxytocin. 5.Both neurotransmitters and hormones can affect their targets through receptors linked to G proteins.

Patterns of hormone secretion

1.Chronic hormone secretion results in relatively constant blood levels of hormone over long periods of time. This type of secretion is exemplified by thyroid hormones, which circulate in the blood within a small range of concentrations. Recall that thyroid hormones are lipid-soluble and thus bind to binding proteins, which also helps maintain them at chronic levels. 2.Acute hormone secretion occurs when the hormone's concentration changes suddenly and irregularly, and its circulating levels differ with each stimulus. This secretion pattern is represented by the amino acid derivative epinephrine, which is released in large amounts in response to stress or physical exercise. In addition, because epinephrine is small and usually circulates as a free hormone, it has a short half-life, which contributes to the fact that blood levels of epinephrine drop significantly within a few minutes of its secretion. 3.Episodic hormone secretion occurs when hormones are secreted at fairly predictable intervals and concentrations. This pattern is often observed in steroid reproductive hormones, which fluctuate over a month in cyclic fashion during the human reproductive years. Additionally, because steroid hormones also often have binding proteins, they have longer half-lives than other hormones, which contributes to their relative stablity in the circulation.

Classes of receptors

1.Lipid-soluble hormones bind to nuclear receptors. Lipid-soluble hormones are relatively small and are nonpolar. Because of these properties, they easily diffuse through the plasma membrane and bind to nuclear receptors. Nuclear receptors are most often found in the cell nucleus, but they can also be located in the cytoplasm. These cytoplasmic receptors move to the nucleus when activated. When hormones bind to nuclear receptors, the hormone-receptor complex interacts with DNA in the nucleus or with cellular enzymes to regulate the transcription of particular genes in the target tissue. The lipid-soluble hormones include thyroid hormones and steroid hormones (testosterone, estrogen, progesterone, aldosterone, and cortisol). These hormones bind to nuclear receptors. 2.Water-soluble hormones bind to membrane-bound receptors. Water-soluble hormones are large molecules and cannot pass through the plasma membrane. Instead, they interact with membrane-bound receptors, which are proteins that extend across the plasma membrane, with their hormone-binding sites exposed on the plasma membrane's outer surface. When a hormone binds to a receptor on the outside of the plasma membrane, the hormone-receptor complex initiates a response inside the cell. Hormones that bind to membrane-bound receptors include proteins, peptides, and some amino acid derivatives, such as epinephrine and norepinephrine.

Comparison of the nervous and endocrine systems - Differences

1.Mode of transport. The endocrine system secretes hormones, which are transported in the bloodstream, whereas the nervous system secretes neurotransmitters, which are released directly onto their target cells. 2.Speed of response. In general, the nervous system responds faster than the endocrine system. However, it is not accurate to say the endocrine system responds slowly; rather, it responds more slowly than the nervous system. Neurotransmitters, such as acetylcholine, are delivered to their target cells in milliseconds, whereas some hormones are delivered to their target cells in seconds. 3.Duration of response. The nervous system typically activates its targets quickly and only for as long as action potentials are sent to the target. The target cells' response is terminated shortly after action potentials cease. In contrast, the endocrine system tends to have longer-lasting effects. Hormones remain in the bloodstream for minutes, days, or even weeks and activate their target tissues as long as they are present in the circulation. The target tissue products may remain active for a substantial length of time.

General characteristics of hormones

1.Stability. For hormones to activate their targets continuously, they must remain active in the circulation long enough to arrive at their target cells. This means that hormone concentrations remain stable in the bloodstream; however, some hormones are more stable than others. The life span of a given hormone varies with its chemical nature. Larger, more complex hormones are more stable, whereas smaller, simpler hormones are less stable. A hormone's life span can be expressed as its half-life, which is the amount of time it takes for 50% of the circulating hormone to be removed from the circulation and excreted. Some hormones have a short half-life, whereas others have a much longer half-life. For example, thyrotropin-releasing hormone (TRH) is a three-amino-acid hormone with a short half-life. Because of TRH's simple composition, it is quickly degraded in the circulation and can activate only the target cells it can reach within 2 minutes of being secreted. On the other hand, cortisol is a steroid hormone with a longer half-life, 90 minutes. Due to its lipid-soluble nature, it is not easily degraded and can activate target cells for more than an hour. 2.Communication. Hormones must be able to interact with their target tissue in a specific manner in order to activate a coordinated set of events. For example, the formation of reproductive organs in the fetus is activated by reproductive steroid hormones. Without proper functioning of the male reproductive steroid testosterone, a newborn will have the outward appearance of a female despite being genetically male. Hormones must be able to regulate specific cellular pathways once they arrive at their targets and bind to their receptors. 3.Distribution. Hormones are transported by the blood to many locations and therefore have the potential to activate any cell in the body, including those far away from where they were produced. However, the blood contains many hydrolytic enzymes, which break down substances, and is an aqueous solution. These factors can present a challenge when transporting hormones to their targets. Small, water-soluble hormones are quickly digested by hydrolytic enzymes in the blood, because, with their small size, they become inactive with very little alteration in their structure. In addition, they are easily filtered from the blood in the kidneys because they are so small. Still other hormones, such as lipid-soluble hormones, have low solubility in the blood plasma. Their chemical nature does not allow them to easily dissolve in the plasma. Thus, some hormones require a chaperone, which binds to and protects hormones so that they arrive safely at their target. Hormones requiring a transport chaperone bind to blood proteins called binding proteins. Once hormones attach to a binding protein, they are then called bound hormones. For small hormones, the binding protein protects them from degradation by hydrolytic enzymes and from being filtered from the blood in the kidney. For lipid-soluble hormones that are insoluble in plasma, being bound to a binding protein causes them to become more water-soluble. Hormones bind only to selective binding proteins. For example, thyroid hormones bind to a specific binding protein, transthyretin; testosterone binds to a different type of binding protein, called testosterone-binding globulin; and progesterone binds to yet another type of binding protein, called progesterone-binding globulin.

Life History of Red Blood Cells

25 trillion red blood cells contained in the normal adult circulation. Homeostasis is maintained by replacing the 2.5 million cells lost every second with an equal number of new red blood cells. Thus, approximately 1% of the total number of red blood cells is replaced each day. The process by which new red blood cells are produced is called erythropoiesis (ĕ-rith′rō-poy-ē′sis; see figure 19.2). The time required to produce a single red blood cell is about 4 days. Myeloid stem cells, Page 653derived from hemocytoblasts, give rise to proerythroblasts. After several mitotic divisions, proerythroblasts become early erythroblasts. These cells are also called basophilic erythroblasts because they stain with a basic dye. The dye binds to the large numbers of ribosomes necessary for the production of hemoglobin, giving the cytoplasm a purplish color. Early erythroblasts give rise to intermediate erythroblasts. These cells are also called polychromatic erythroblasts because they stain different colors with basic and acidic dyes. For example, when an acidic dye is used, intermediate erythroblasts stain a reddish color when it interacts with the hemoglobin accumulating in the cytoplasm. Intermediate erythroblasts continue to produce hemoglobin, and then most of their ribosomes and other organelles degenerate. The resulting late erythroblasts have a reddish color because about one-third of the cytoplasm is hemoglobin. The late erythroblasts lose their nuclei to become immature red blood cells, called reticulocytes (re-tik′ū-lō-sītz). Reticulocyte refers to a reticulum, or network, that can be observed in the cytoplasm when a special staining technique is used. The reticulum is artificially produced by the reaction of the dye with the few remaining ribosomes in the reticulocyte. Reticulocytes are released from the bone marrow into the circulating blood. A normal reticulocyte level is 0.5-2% of circulating red blood cells.

Complete Blood Count

A complete blood count (CBC) is an analysis of blood that provides much useful information. A CBC consists of a red blood count, hemoglobin and hematocrit measurements, a white blood count, and a differential white blood count.

Conducting System

A conducting system relays action potentials through the heart. This system consists of modified cardiac muscle cells that form two nodes (knots or lumps) and a conducting bundle (figure 20.13). The two nodes are contained within the walls of the right atrium and are named according to their position in the atrium. The sinoatrial (SA) node is medial to the opening of the superior vena cava, and the atrioventricular (AV) node is medial to the right atrioventricular valve. The AV node gives rise to a conducting bundle of the heart, the atrioventricular (AV) bundle (bundle of His). This bundle passes through a small opening in the fibrous skeleton to reach the interventricular septum, where it divides to form the right and left bundle branches, which extend beneath the endocardium on each side of the interventricular septum to the apex of both the right and the left ventricles.

Hemoglobin Measurement

A hemoglobin measurement determines the amount of hemoglobin in a given volume of blood, usually expressed as grams of hemoglobin per 100 mL of blood. The normal hemoglobin count for a male Page 667is 14-18 g/100 mL of blood, and for a female it is 12-16 g/100 mL of blood.

Platelet Plug Formation

A platelet plug is an accumulation of platelets that can seal small breaks in blood vessels. A platelet plug is not the same thing as a blood clot, but the formation of the platelet plug is an important step in blood clot formation. Platelet plug formation is very important in maintaining the integrity of the circulatory system. Small tears occur in the smaller vessels and capillaries many times each day, and platelet. 1.Platelet adhesion occurs when platelets bind to collagen that is exposed when a blood vessel is damaged. Most platelet adhesion is mediated through von Willebrand factor (vWF), a protein produced and secreted by blood vessel endothelial cells. Platelets have surface receptors on their membrane. These surface receptors bind to von Willebrand factor released from damaged blood vessels. Von Willebrand factor also binds to the exposed collagen of the damaged vessel, thereby forming a bridge between exposed collagen and platelets. In addition, other platelet surface receptors can bind directly to collagen. 2.After platelets adhere to collagen, they become activated. These activated platelets then initiate the platelet release reaction, in which adenosine diphosphate (ADP), thromboxanes, and other chemicals are released from the activated platelets by exocytosis. The ADP and thromboxane bind to their respective receptors on the surfaces of other platelets, Page 658activating them. These activated platelets release additional chemicals, thereby producing a cascade of chemical release by the platelets. Thus, more and more platelets become activated. This is an example of positive feedback. 3.As platelets become activated, they change shape and express fibrinogen receptors that can bind to fibrinogen, a plasma protein. In platelet aggregation, fibrinogen forms a bridge between the fibrinogen receptors of different platelets, resulting in a platelet plug.

Red Blood Count

A red blood count (RBC) is the number (expressed in millions) of red blood cells per microliter of blood.

Rh Blood Group

A second clinically important blood group is the Rh blood group. The Rh blood group is so named because it was first studied in rhesus monkeys. The antigen involved in this blood group is the D antigen. People are Rh-positive if they have the D antigen on the surface of their red blood cells, and people are Rh-negative if they do not have the D antigen. About 85% of Caucasians in the United States and 88% of African-Americans are Rh-positive. The ABO blood type and the Rh blood type are usually expressed together. For example, a person designated type A in the ABO blood group and Rh-positive is said to be A-positive. The rarest combination in the United States is AB-negative, which occurs in less than 1% of the population.

Atrioventricular Valves

An atrioventricular valve is in each atrioventricular canal and is composed of cusps, or flaps. Atrioventricular valves ensure blood flows from the atria into the ventricles, preventing blood from flowing back into the atria. The atrioventricular valve between the right atrium and the right ventricle is called the tricuspid (trī -kŭs′pid) valve because it consists of three cusps (figures 20.7 and 20.8a). The atrioventricular valve between the left atrium and the left ventricle is called the bicuspid (bī-kŭs′pid) valve because it has two cusps. Each ventricle contains cone-shaped, muscular pillars called papillary (pap′i-lār-ē; nipple) muscles. These muscles are attached to the cusps of the atrioventricular valves by thin, strong connective tissue strings called chordae tendineae (kōr′dē ten′di-nē-ē; heart strings) (figures 20.7 and 20.8a).

Antidiuretic Hormone (ADH)

Antidiuretic (an′tē-d-ī-ū-ret′ik) hormone (ADH) is a water-conservation hormone. ADH prevents (anti-) the output of large amounts of urine (diuresis). An alternate name for ADH is vasopressin (vā-sō-pres′in, vas-ō-pres′in) because it also constricts blood vessels and raises blood pressure when large amounts are released. ADH molecules are synthesized predominantly by neurosecretory neuron cell bodies in the supraoptic nuclei of the hypothalamus and are transported within the axons of the hypothalamohypophysial tract from the supraoptic nuclei to the posterior pituitary, where they are stored in axon terminals. Action potentials in these neurons stimulate the release of ADH into the blood, where it is carried to its primary target tissue, the kidney tubules. Kidney tubules are the sites of urine production in the kidneys. ADH promotes the reabsorption of water from kidney tubules, which reduces urine volume (see chapter 26).

Blood Pressure and Blood Volume

Because ADH regulates blood volume, its secretion is also controlled by blood pressure changes. Sensory receptors that detect changes in blood pressure send action potentials through sensory nerve fibers of the vagus nerve that eventually communicate these changes to the ADH neurosecretory neurons. A decrease in blood pressure, which normally accompanies a decrease in blood volume, causes an increased action potential frequency in Page 606the neurosecretory neurons and increased ADH secretion, which stimulates the kidneys to retain water. Because the water in urine is derived from blood as it passes through the kidneys, ADH slows any further reduction in blood volume.

Transport of lipid-soluble hormones

Because of their small size and low solubility in aqueous fluids, lipid-soluble hormones travel in the bloodstream bound to binding proteins, proteins that chaperone the hormone. As a result, the rate at which lipid-soluble hormones are degraded or eliminated from the circulation is greatly reduced and their life spans range from a few days to as long as weeks. Without the binding proteins, the lipid-soluble hormones would quickly diffuse out of capillaries and be degraded by enzymes of the liver and lungs or be filtered from the blood by the kidneys. Circulating hydrolytic enzymes can also metabolize free lipid-soluble hormones. The breakdown products are then excreted in the urine or the bile. Additionally, lipid-soluble hormones are removed from the circulation when specific enzymes in the liver attach water-soluble molecules to the hormones, a process called conjugation (kon-jŭ-gā′shŭn). These conjugation molecules are usually sulfate or glucuronic acid. Once the hormones are conjugated, the kidneys and liver excrete them into the urine and bile at a greater rate.

Transport of water-soluble hormones

Because water-soluble hormones can dissolve in the plasma of the blood, many circulate as free hormones, meaning that most of them dissolve directly into the plasma and are delivered to their target tissue without binding to a binding protein. Because many water-soluble hormones are quite large, they do not readily diffuse through the walls of all capillaries. Instead, they tend to diffuse from the blood into tissue spaces more slowly. Thus, capillaries of organs that are regulated by protein hormones tend to be very porous, or fenestrated. On the other hand, other water-soluble hormones are quite small and require attachment to a larger protein, a binding protein, to avoid being filtered out of the blood. All hormones are destroyed either in the circulation or at their target cells. The destruction and elimination of hormones limit the length of time they are active, and body processes change quickly when hormones are secreted and remain functional for only short periods. The water-soluble hormones have relatively short half-lives because they are rapidly broken down by hydrolytic enzymes, called proteases, within the bloodstream. The kidneys then remove the hormone breakdown products from the blood. Target cells also destroy water-soluble hormones when the hormones are internalized via endocytosis. Once the hormones are inside the target cell, lysosomal enzymes degrade them. Often, the target cell recycles the amino acids of peptide and protein hormones and uses them to synthesize new proteins. Thus, hormones with short half-lives normally have concentrations that change rapidly within the blood and tend to regulate activities that have a rapid onset and short duration. However, some water-soluble hormones are more stable in the circulation than others. In many instances, protein and peptide hormones are made more stable by having a carbohydrate attached to them and are then called glycoproteins. Other hormones are made more stable by having a modified terminal end. These modifications protect them from protease activity to a greater extent than water-soluble hormones lacking such modifications (table 17.2). In addition, some water-soluble hormones attach to binding proteins and therefore circulate in the plasma longer than free water-soluble hormones do.

Cardiac Muscle

Cardiac muscle cells are elongated, branching cells that have one, or occasionally two, centrally located nuclei. Cardiac muscle cells contain actin and myosin myofilaments organized to form sarcomeres, which join end-to-end to form myofibrils (see chapter 9). The actin and myosin myofilaments are responsible for muscle contraction, and their organization gives cardiac muscle a striated (banded) appearance. The striations are less regularly arranged and less numerous than in skeletal muscle (figure 20.12). Cardiac muscle cell contraction is very similar to that of skeletal muscle; however, the onset of contraction is longer and prolonged in cardiac muscle. These differences in contraction are partially due to differences in cell anatomy. Cardiac muscle has a smooth sarcoplasmic reticulum, which stores Ca2+, similar to skeletal muscle. But the sarcoplasmic reticulum is not as regularly arranged as in skeletal muscle fibers, and there are no dilated cisternae, as in skeletal muscle.

Decrease (Down-Regulation) in Receptor Number

Densensitization occurs when the number of receptors rapidly decreases after exposure to certain hormones, a phenomenon called down-regulation.

Control of Hormone Secretion - Neural

Following action potentials, neurons release a neurotransmitter into a synapse with hormone-producing cells. In these cases, the neurotransmitter stimulates the cells to secrete their hormone.

Hemostasis

Hemostasis (hē′mō-stā-sis, hē-mos′tă-sis), the cessation of bleeding, is very important to the maintenance of homeostasis. If not stopped, excessive bleeding from a cut or torn blood vessel can result in a positive-feedback cycle, consisting of ever-decreasing blood volume and blood pressure that disrupts homeostasis and results in death. Fortunately, when a blood vessel is damaged, a series of events helps prevent excessive blood loss. Hemostasis involves three processes: (1) vascular spasm, (2) platelet plug formation, and (3) coagulation.

Control of Hormone Secretion - Hormonal

Hormonal stimuli occurs when hormones stimulate the secretion of other hormones.

Control of Hormone Secretion - Humoral

Metabolites and other molecules in the bloodstream can directly stimulate the release of some hormones. These molecules are referred to as humoral stimuli because they circulate in the blood, and the word humoral refers to body fluids, including blood. The cells that secrete these hormones have receptors for certain substances in the blood

Control of Hormone Secretion - Negative Feedback

Most hormones are regulated by a negative-feedback mechanism, whereby the hormone's secretion is inhibited by the hormone itself once blood levels have reached a certain point and there is adequate hormone to activate the target cell. The hormone may inhibit the action of other, stimulatory hormones to prevent the secretion of the hormone in question. Thus, it is a self-limiting system.

Common Pathway

On the surface of platelets, activated factor X, factor V, platelet phospholipids, and Ca2+ combine to form prothrombinase, or prothrombin activator. Prothrombinase converts the soluble plasma protein prothrombin to the enzyme thrombin. A major function of thrombin is to convert the soluble plasma protein fibrinogen to the insoluble protein fibrin. Fibrin is the protein that forms the fibrous network of the blood clot (see figure 19.10). In addition, thrombin also stimulates factor XIII activation, which is necessary to stabilize the clot. Vitamin K is required for the formation of many of the factors involved in blood clot formation (table 19.3). Humans rely on two sources for vitamin K. About half comes from the diet, and half comes from bacteria within the large intestine. Antibiotics taken to fight bacterial infections sometimes kill these intestinal bacteria, thereby reducing vitamin K levels and causing bleeding. Vitamin K supplements may be necessary for patients on prolonged antibiotic therapy. Newborns lack these intestinal bacteria; thus, Page 660Page 661they routinely receive a vitamin K injection at birth. Infants can also obtain vitamin K from food, such as milk.

Parathyroid Hormone (PTH)

Parathyroid hormone (PTH), also called parathormone, is a polypeptide hormone that is important in regulating calcium levels in body fluids (see table 18.3). The major target tissues for PTH are bone, the kidneys, and the small intestine. PTH stimulates osteoclast activity in bone and can cause the number of osteoclasts to increase. The increased osteoclast activity results in bone reabsorption and the release of calcium and phosphate, causing an increase in blood calcium levels. PTH causes calcium reabsorption within the kidneys, so that less calcium leaves the body in urine. It also increases the enzymatic formation of active vitamin D in the kidneys.

Platelets

Platelets, or thrombocytes (table 19.2; see figure 19.7), are minute fragments of cells. They consist of a small amount of cytoplasm surrounded by a plasma membrane. Platelets are roughly disc-shaped and average about 3 μm in diameter. The life expectancy of platelets is about 5-9 days. Platelets are derived from megakaryocytes (meg-ă-kar′ē-ō-sitz), which are extremely large cells found in the red bone marrow. Small fragments of these cells break off and enter the blood as platelets. Platelets play an important role in preventing blood loss by (1) forming platelet plugs that seal holes in small vessels and (2) promoting the formation and contraction of clots that help seal off larger wounds in the vessels.

Rh Incompatibility

Rh incompatibility can pose a major problem in a pregnancy when the mother is Rh-negative and the fetus is Rh-positive. If fetal blood leaks through the placenta and mixes with the mother's blood, the mother becomes sensitized to the Rh antigen and produces anti-Rh antibodies. These antibodies can cross the placenta and enter the fetal blood. In the fetal blood, the Rh antibodies will act against the D antigens on the red blood cells and cause agglutination and hemolysis of fetal red blood cells.

Osmoreceptors

Specialized neurons, called osmoreceptors (os′mō-rē-sep′terz), synapse with the ADH neurosecretory neurons in the hypothalamus. Osmoreceptors are sensitive to changes in blood osmolality. When blood osmolality increases, the frequency of action potentials in the osmoreceptors increases, resulting in a greater frequency of action potentials in the axons of ADH neurosecretory neurons

Size, Shape, and Location of the Heart

The adult heart is shaped like a blunt cone and is approximately the size of a closed fist, with an average mass of 250 g in females and 300 g in males. It is larger in physically active adults than in other healthy adults. The heart generally decreases in size after approximately age 65, especially in people who are not physically active. The blunt, rounded point of the heart is the apex; the larger, flat part at the opposite end of the heart is the base. The heart is located in the mediastinum (me′dē-as-tī′nŭm; see figure 1.14), a midline partition of the thoracic cavity that also contains the trachea, the esophagus, the thymus, and associated structures. It is important for health professionals to know the location of the heart in the thoracic cavity. Positioning a stethoscope to hear the heart sounds and positioning electrodes to record an electrocardiogram from chest leads depend on this knowledge. Effective cardiopulmonary resuscitation (kar′dē-ō-pŭl′mo-nār-ē rē-sŭs′i-tā-shŭn; CPR) also depends on a reasonable knowledge of the position of the heart. The heart lies obliquely in the mediastinum, with its base directed posteriorly and slightly superiorly and its apex directed anteriorly and slightly inferiorly. The apex is also directed to the left, so that approximately two-thirds of the heart's mass lies to the left of the midline of the sternum (figure 20.2). The base of the heart is located deep to the sternum and extends to the second intercostal space. The apex is located deep to the fifth intercostal space, approximately 7-9 centimeters (cm) to the left of the sternum and medial to the midclavicular line, a perpendicular line that extends down from the middle of the clavicle.

Anterior Pituitary

The anterior pituitary develops as an outpocketing of the roof of the embryonic oral cavity called the pituitary diverticulum, or Rathke pouch. The pituitary diverticulum continues growing toward the posterior pituitary. As it nears the posterior pituitary, the pituitary diverticulum loses its connection with the oral cavity and becomes the anterior pituitary, which includes an area called the pars intermedia that is not functional in adult humans (figure 18.2). Because the anterior pituitary is derived from epithelial tissue of the embryonic oral cavity, not from neural tissue, the hormones secreted from the anterior pituitary are traditional hormones, not neurohormones.

Regulatory Systems - Amplitude Modulated System

The concentration of the hormone determines the strength of the signal and the magnitude of the response. For most hormones, a small concentration of a hormone is a weak signal and produces a small response, whereas a larger concentration is a stronger signal and results in a greater response.

Anatomy of the Heart-Heart Wall Layers

The heart wall is composed of three layers of tissue: (1) the epicardium, (2) myocardium, and (3) endocardium (figure 20.4). The epicardium (ep-i-kar′dē-ŭm), or visceral pericardium, is the superficial layer of the heart wall. It is a thin serous membrane that constitutes the smooth, outer surface of the heart. The serous pericardium is called the epicardium when considered a part of the heart and the visceral pericardium when considered a part of the pericardium. The myocardium (mī-ō-kar′dē-ŭm) is the thick, middle layer of the heart. It is composed of cardiac muscle cells and is responsible for the heart's ability to contract. The endocardium (en-dō-kar′dē-ŭm) is deep to the myocardium. It consists of simple squamous epithelium over a layer of connective tissue. The endocardium forms the smooth, inner surface of the heart chambers, which allows blood to move easily through the heart. The endocardium also covers the surfaces of the heart valves.

Hormones of the Pituitary Gland

The hormones secreted from the pituitary gland are separated into two categories: posterior pituitary hormones and anterior pituitary hormones (table 18.2). Recall that the posterior pituitary is composed of neural tissue. Thus, the hormones stored and secreted by the posterior pituitary gland are the neurohormones, antidiuretic hormone and oxytocin. The anterior pituitary is different from the posterior pituitary because its hormones are synthesized by cells in the anterior pituitary. These anterior pituitary hormones are regulated by releasing and inhibiting hormones. These hormones pass from the hypothalamus through the hypothalamohypophysial portal system to the anterior pituitary and influence anterior pituitary secretions. For some anterior pituitary hormones, the hypothalamus produces both releasing hormones and inhibiting hormones. For others, regulation is primarily by releasing hormones (see table 18.1).

Parathyroid Glands

The parathyroid (par-ă-thī′royd) glands are usually embedded in the posterior part of each lobe of the thyroid gland and are made up of two cell types: chief cells and oxyphils. The chief cells secrete parathyroid hormone, but the function of the oxyphils is unknown. Usually, four parathyroid glands are present, with their cells organized in densely packed masses, or cords, rather than in follicles (figure 18.11). In some cases, one or more of the parathyroid glands do not become embedded in the thyroid gland and remain in the nearby connective tissue.

Anatomy of the Heart-Pericardium

The pericardium (per-i-kar′dē-ŭm), or pericardial sac, is a double-layered, closed sac that surrounds the heart (figure 20.3). It consists of two layers: the outer fibrous pericardium and inner serous pericardium. The fibrous pericardium is a tough, fibrous connective tissue layer that prevents overdistension of the heart and anchors it within the mediastinum.

Structure of the pituitary gland

The pituitary gland is connected to the base of the brain, just inferior to the hypothalamus. A stalk of tissue called the infundibulum (in-fŭn-dib′u-lŭm) connects the pituitary gland to the hypothalamus. The pituitary gland rests in the sella turcica of the sphenoid bone and is roughly the size of a pea—1 cm in diameter, weighing 0.5-1.0 g. The pituitary gland is divided into two lobes: the posterior pituitary gland, or neurohypophysis (noor′ō-hī-pof′i-sis), and the anterior pituitary gland, or adenohypophysis (ad′ĕ-nō-hī-pof′i-sis; adeno, gland).

Relationship of the pituitary gland to the brain: The Hypothalamus

The pituitary is regulated, in part, by hormones produced and secreted by neurons in the hypothalamus. Some of these hypothalamic hormones are delivered to the anterior pituitary via a circulatory system called a portal system. Most blood vessels follow the prescribed pattern of artery to capillary network then to a vein. Portal system vessels directly connect a primary capillary network to a secondary capillary network. The hypothalamohypophysial (hī′pō-thal′ă-mō-hī′pō-fiz′ē-ăl) portal system is one of the major portal systems in the body. The others include the hepatic portal system and the renal nephron portal systems (see chapters 21 and 26). The hypothalamohypophysial portal system extends from the floor of the hypothalamus to the anterior pituitary (figure 18.3).

Posterior Pituitary

The posterior pituitary is called the neurohypophysis because it is continuous with the hypothalamus in the brain (neuro- refers to the nervous system). During embryonic development, the posterior pituitary forms from an outgrowth of the inferior part of the brain in the area of the hypothalamus (see chapter 29). The outgrowth of the brain forms the infundibulum, and the distal end of the infundibulum enlarges to form the posterior pituitary (figure 18.1b). Because the posterior pituitary is a part of the nervous system, its hormones are called neuropeptides, or neurohormones (noor-ō-hōr′mōnz).

Signal Amplification

The rate and magnitude at which a hormone's response is elicited are determined by its mechanism of action at the receptor. Nuclear receptors work by activating protein synthesis, which for some hormones can take several hours. However, hormones that stimulate the synthesis of second messengers can produce an almost instantaneous response, because the second messenger influences existing enzymes. In other words, the response proteins are already present. Additionally, each receptor produces thousands of second messengers, leading to a cascade effect and ultimately amplification of the hormonal signal. With amplification, a single hormone activates many second messengers, each of which activates enzymes that produce an enormous amount of final product (figure 17.19). The efficiency of this second-messenger amplification is virtually unparalleled in the body and can be thought of as an "army of molecules" launching an offensive. In a war, the general gives the signal to attack, and thousands of soldiers carry out the order. The general alone could not kill thousands of enemies. Likewise, one hormone could not single-handedly produce millions of final products within a few seconds. However, with amplification, one hormone has an army of molecules working simultaneously to produce the final products.

PTH and Blood Phosphate Levels

The regulation of PTH secretion and the role of PTH and calcitonin in regulating blood Ca2+ levels are outlined in figure 18.12. The primary stimulus for the secretion of PTH is a decrease in blood Ca2+ levels, whereas elevated blood Ca2+ levels inhibit PTH secretion. This regulation keeps blood Ca2+ levels fluctuating within a normal range of values. Both hypersecretion and hyposecretion of PTH cause serious symptoms (table 18.6). The regulation of blood Ca2+ levels is discussed more thoroughly in chapter 27.

Osmolality

The secretion rate for ADH changes in response to alterations in blood osmolality and blood volume (figure 18.5). The osmolality of a solution increases as the concentration of solutes in the solution increases

Regulatory Systems - Frequency Modulated System

The strength of the system depends on the frequency, not the size, of the action potentials. All action potentials are the same size in a given tissue. A low frequency of action potentials is a weak stimulus, and a higher frequency is a stronger.

Blood Grouping; Antigens; Antibodies; Agglutination

The surfaces of red blood cells have marker molecules called antigens (an′ti-jenz), which identify the cells. The plasma contains proteins called antibodies, which bind to antigens. Antibodies are very specific, meaning that each antibody can bind only to a certain antigen. When the antibodies in the plasma bind to the antigens on the surfaces of the red blood cells, they form molecular bridges that connect the red blood cells. As a result, agglutination (ă-gloo-ti-nā′shŭn), or clumping, of the cells occurs. The combination of the antibodies with the antigens can also initiate reactions that cause hemolysis. Because the antigen-antibody combinations can cause agglutination, the antigens are often called agglutinogens (ă-gloo-tin′ō-jenz), and the antibodies are called agglutinins (ă-gloo′ti-ninz).

Thyroid Hormones

The thyroid hormones include triiodothyronine (trī-ī′ō-dō-thī′rō-nēn), commonly called T3, and tetraiodothyronine (tet′ră-ī′ō-dō-thī′rō-nēn). A more common name for tetraiodothyronine is thyroxine (thī-rok′sēn; thī-rok′sin), or even more commonly T4. T4 is the precursor for T3, and both are major secretory products of the thyroid gland, consisting of 10% T3 and 80% T4, respectively (table 18.3). Although calcitonin (10%) is secreted by the parafollicular cells of the thyroid gland, T3 and T4 are considered the thyroid hormones because they are more clinically important and because they are secreted from the thyroid follicles

T3 and T4 Synthesis

Thyroid-stimulating hormone (TSH) from the anterior pituitary stimulates thyroid hormone synthesis and secretion. TSH causes an increase in the synthesis of T3 and T4, which are then stored inside the thyroid follicles as part of thyroglobulin. TSH also causes T3 and T4 to be released from thyroglobulin and enter the plasma of the blood. Because iodine is an integral component of the T3 and T4 molecules, humans must consume an adequate amount of iodine in the diet to support thyroid hormone synthesis. 1.Iodide ions (I-) are taken up by thyroid follicle cells via secondary active transport by a sodium-iodide symporter. The active transport of the I- is against a concentration gradient of approximately 30-fold in healthy individuals. 2.Thyroglobulins, which contain numerous tyrosine molecules, are synthesized within the cells of the follicles. 3.Nearly simultaneously, the I- are oxidized to form iodine (I), and either one or two iodine atoms are bound to some of the tyrosine molecules of thyroglobulin by the enzyme thyroid peroxidase. 4.This occurs close to the time the thyroglobulin molecules are secreted by exocytosis into the lumen of the follicle. As a result, the secreted thyroglobulin contains iodinated tyrosine amino acids with either one iodine atom (monoiodotyrosine) or two iodine atoms (diiodotyrosine). 5.Within the colloid in the lumen of the follicle, two diiodotyrosine molecules of thyroglobulin combine to form tetraiodothyronine (T4), or one monoiodotyrosine and one diiodotyrosine molecule combine to form triiodothyronine (T3). Large amounts of T3 and T4 are stored within the thyroid follicles as part of thyroglobulin. A reserve sufficient to supply thyroid hormones for approximately 2-4 months is stored in this form. 6.Thyroglobulin is taken into the thyroid follicle cells by endocytosis. 7.Lysosomes fuse with the endocytotic vesicles. Proteolytic enzymes break down thyroglobulin to release T3 and T4. The remaining amino acids of thyroglobulin are recycled to synthesize more thyroglobulin. 8.T3 and T4 either diffuse through the plasma membranes or are carried by specific transporters of the follicular cells into the interstitial spaces and finally into the capillaries of the thyroid gland.

Effects of Body Temperature

Under resting conditions, the temperature of cardiac muscle normally does not change dramatically, although alterations in temperature influence the heart rate. Small increases in cardiac muscle temperature cause the heart rate to speed up, and decreases in temperature cause the heart rate to slow. For example, during exercise or fever, increased heart rate and force of contraction accompany temperature elevations, but the heart rate drops under conditions of hypothermia. During heart surgery, body temperature is sometimes reduced dramatically on purpose to slow the heart rate and other metabolic functions.

Increase (Up-Regulation) in Receptor Number

Up-regulation results in an increase in the rate of receptor synthesis in the target cells, which increases the total number of receptor molecules in a cell. An example of up-regulation is a process that occurs to stimulate ovulation of the oocyte. During each menstrual cycle, there are an increased number of receptors for luteinizing hormone (LH) in ovary cells. Follicle-stimulating hormone (FSH) secreted by the pituitary gland increases the rate of LH receptor synthesis in ovary cells. This is important because a surge in LH will cause release of the oocyte. Thus, a tissue's exposure to one hormone

Vascular Spasm

Vascular spasm is the immediate but temporary constriction of a blood vessel. Vascular spasm occurs when smooth muscle within the wall of the vessel contracts

Cascade of Events in Intrinsic Pathway

When plasma factor XII comes into contact with collagen, factor XII is activated. Subsequently, activated factor XII stimulates factor XI, which in turn activates factor IX. Activated factor IX joins with factor VIII, platelet phospholipids, and Ca2+ to activate factor X, which, as stated in the extrinsic pathway description, initiates the common pathway.


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