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Therefore quality 400 mg hoodia, the explains the dilation of coronary arterioles and small arter- mechanical compression of systole has more effect on the ies when the metabolic rate of the heart is increased cheap 400 mg hoodia, or blood flow through the endocardial layers where compres- when pathological or experimental means are used to re- sive forces are higher and microvascular pressures are strict blood flow trusted 400 mg hoodia. This problem occurs particularly in heart diseases of dothelial cells—in response to blood flow-mediated dila- all types, and most kinds of tissue impairment affect the tion (see Chapter 16) and in response to ATP, adenosine subendocardial layers. Coronary Vascular Resistance Is Primarily Coronary arteries and arterioles are innervated by the Regulated by Responses to Heart Metabolism sympathetic nervous system and can be constricted by nor- Animal studies indicate that about 75% of total coronary epinephrine, whether released from nerves or carried in the vascular resistance occurs in vessels with inner diameters of arterial blood. This observation is supported by more important in equalizing blood flow through the lay- clinical measurements in humans that show little arterial ers of the heart than in reducing blood flow to the heart pressure dissipation in normal coronary arteries prior to muscle in general. The coronary arteries and larger arteri- their smaller branches entering the heart muscle tissue. The oles predominately have 1 receptors, which induce vascu- majority of the coronary resistance vessels—the small ar- lar constriction when activated by norepinephrine. Smaller teries and arterioles—are surrounded by cardiac muscle arterioles predominately have receptors, which cause va- cells and are exposed to chemicals released by cardiac cells sodilation in response to epinephrine released by the adre- into the interstitial space. For example, adenosine, nephrine increases the metabolic rate of the heart via 1 278 PART IV BLOOD AND CARDIOVASCULAR PHYSIOLOGY what would exist without sympathetic effects on resist- Systole Diastole ance vessels, for improved perfusion of the tissue at risk in the deeper layers of the heart. Prior to death, most of these people have impaired cardiac function as a result of coronary artery disease, lead- 100 ing to heart failure with decreased quality of life. Progres- sive occlusion of coronary arteries by atherosclerotic plaques and acute occlusion as a result of the formation of blood clots in damaged coronary arteries are life-threaten- ing because the metabolic needs of the cardiac muscle can no longer be met by the blood flow. Because the plaque or clot partially occludes the vessel lumen, vascular resistance is increased, and blood flow would decrease if smaller coro- nary vessels did not dilate to restore a relatively normal blood flow at rest. In doing so, the reserve for dilation of 0 these vessels is compromised. While this usually has no ef- fect at rest, when cardiac metabolism is increased, the de- 50 creased ability to increase blood flow can limit cardiac per- formance. In many cases, inadequate blood flow is first noticed as chest pain—known as angina pectoris—origi- nating from the heart, and a feeling of shortness of breath during exercise or work. The vascular occlusion can cause 0 conditions ranging from impaired contractile ability of the 0. Note that left coronary artery blood flow decreases dramati- be used to cause coronary vasodilation or decreased car- cally during the isovolumetric phase of systole, prior to opening diac work, or both. Left coronary artery blood flow remains lower normal, various approaches are used to lower the blood during systole than during diastole because of compression of the pressure, decreasing the heart’s workload and oxygen coronary blood vessels in the contracting myocardium. The left ventricle receives most of its arterial blood inflow during diastole. In addition to pharmacological treatment, mild to Right coronary artery blood flow tends to be sustained during moderate exercise, depending on the status of the coro- both systole and diastole because lower intraventricular pressures nary disease, is often advised. Aerobic exercise stimulates are developed by the contracting right ventricle, resulting in less the development of collateral vessels in the heart, im- compression of coronary blood vessels. Systemic and coronary energetics in the tem, and increases the efficiency of the body during work resting unanesthetized dog. Phasic right coronary artery blood flow in output needed for a given task, thereby decreasing the conscious dogs with normal and elevated right ventricular pres- heart’s metabolic energy requirement. This, in turn, leads to dilatory stimuli that po- have been shown to greatly slow and even slightly reverse tentially could overcome vasoconstriction. The goal is to lower blood lev- The overall concept evolving from both human and els of low-density lipoproteins (LDLs), which are known animal studies is that the sympathetic nervous system to accelerate the formation of cholesterol-containing ar- suppresses the decrease in coronary vascular resistance terial plaques. The LDL concentration should typically be during exercise despite the metabolic effects of epineph- lowered below 120 mg/dL, but some cardiologists favor rine mentioned. The partial constriction of large coro- lowering levels below 100 mg/dL. For most people, re- nary arterioles and most arteries by norepinephrine ap- ductions in LDL below 120 mg/dL are not attainable with pears to limit the retrograde flow of blood during diet and exercise. In those persons, drugs, known as ventricular systole and, in doing so, prevents part of the statins, which block the formation of cholesterol in the decreased flow in the deep layers of the heart wall. In ef- liver, appear to be highly effective in decreasing the risk fect, the body trades a small decrease in flow, relative to and severity of coronary artery disease. Simultaneous CHAPTER 17 Special Circulations 279 treatment with an aerobic exercise program and large CEREBRAL CIRCULATION amounts of niacin, to increase high-density lipoproteins The ultimate organ of life is the brain.

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If the cell is transferred to ample buy 400 mg hoodia with amex, the osmotic coefficient of NaCl is 1 generic hoodia 400 mg with amex. As we will see below order 400 mg hoodia free shipping, many At any given T, since R is constant, equation 4 shows cells have regulatory mechanisms that keep cell volume that the osmotic pressure of a solution is directly propor- within a certain range. This term is known as the osmolal- throcytes, do not have volume regulatory mechanisms and ity or osmotic concentration of a solution and is expressed large volume changes occur when the solute concentration in osm/kg H2O. Most physiological solutions, such as of the extracellular fluid is changed. The os- plasma membrane is the difference in water concentration molality of a solution containing a complex mixture of between the two sides of the membrane. For historical rea- solutes is usually measured by freezing point depression. The os- lower than that of pure water and depends on the total motic pressure of a solution is defined as the pressure nec- number of solute particles. Compared with pure water, essary to stop the net movement of water across a selec- which freezes at 0 C, a solution with an osmolality of 1 tively permeable membrane that separates the solution osm/kg H2O will freeze at 1. When a membrane separates two solu- osmolality can be measured has led to the wide use of this tions of different osmotic pressure, water will move from parameter for comparing the osmotic pressure of different the solution with low osmotic pressure (high water con- solutions. The osmotic pressures of physiological solutions 32 PART I CELLULAR PHYSIOLOGY are not trivial. Consider blood plasma, for example, which A usually has an osmolality of 0. Many Cells Can Regulate Their Volume Cell volume changes can occur in response to changes in the osmolality of extracellular fluid in both normal and pathophysiological situations. Accumulation of solutes also can produce volume changes by increasing the intracellular osmolality. Volume regulation is particularly important in the brain, for example, where cell swelling can have serious consequences because expansion is strictly limited by the rigid skull. A solution’s osmolality is de- termined by the total concentration of all the solutes pres- B ent. In contrast, the solution’s tonicity is determined by the concentrations of only those solutes that do not enter (“penetrate”) the cell. Tonicity determines cell volume, as illustrated in the following examples. Na behaves as a nonpenetrating solute because it is pumped out of cells by the Na /K -ATPase at the same rate that it enters. The NaCl solu- tion is also hypotonic because cells will accumulate water and swell when placed in this solution. The solution is isotonic, however, because it produces no per- manent change in cell volume. The reason is that cells shrink initially as a result of loss of water but urea is a pen- etrating solute that rapidly enters the cells. Urea entry in- creases the intracellular osmolality so water also enters FIGURE 2. Cell volume changes when a cell is urea concentration is the same inside and outside the placed in either a hypotonic or a hypertonic solution. A, In a hy- potonic solution, the reversal of the initial increase in cell volume cells. At this point, the total osmolality both inside and is known as a regulatory volume decrease. B, In a hypertonic solution, the reversal of the ini- tial decrease in cell volume is a regulatory volume increase. When cell volume increases because port systems for solute entry are activated, and water follows of extracellular hypotonicity, the response of many cells is solute into the cell. Different cells use dif- ferent regulatory volume decrease (RVD) mechanisms to move solutes out of the cell and decrease the number of creased volume triggers regulatory volume increase (RVI) particles in the cytosol, causing water to leave the cell. Because Na is sium, many RVD mechanisms involve an increased efflux of the main extracellular ion, many RVI mechanisms involve K , either by stimulating the opening of potassium chan- an influx of sodium into the cell. Other K -2Cl symport, and Na /H antiport are some of the cells activate the efflux of some amino acids, such as taurine mechanisms activated to increase the intracellular concen- or proline.

In living systems discount 400 mg hoodia mastercard, conditions Ordinary extracellular fluid is subdivided into interstitial are often displaced from equilibrium by the constant ex- fluid—lymph and plasma; these fluid compartments are sep- penditure of metabolic energy hoodia 400 mg online. If we were to increase the rate of in- flow (open the tap) order hoodia 400 mg visa, the fluid level would rise, and with time, a new steady state might be established at a higher level. Note that the term steady state can Autocrine Paracrine apply to a single or several compartments; the term equi- Receptor librium describes the relation between at least two adjacent compartments that can exchange matter or energy with each other. Coordinated Body Activity Requires Integration of Many Systems Nervous Target cell Body functions can be analyzed in terms of several sys- tems, such as the nervous, muscular, cardiovascular, res- piratory, renal, gastrointestinal, and endocrine systems. Neuron Synapse These divisions are rather arbitrary, however, and all systems interact and depend on each other. The nerv- ous system coordinates the movements of the limbs and Endocrine body, stimulates the muscles to contract, and senses Endocrine cell Target cell muscle tension and limb position. The cardiovascular system supplies blood to the muscles, providing for Blood- stream nourishment and the removal of metabolic wastes and heat. The gastrointestinal system Neuroendocrine Target cell supplies energy-yielding metabolites. The endocrine system helps adjust blood flow and the supply of various metabolic substrates to the working muscles. Coordi- Blood- nated body activity demands the integration of many stream systems. Recent research demonstrates that many diseases can be explained on the basis of abnormal function at the molecu- FIGURE 1. This reductionist approach has led to incredible communicate with each other directly via gap advances in our knowledge of both normal and abnormal junctions or chemical messengers. With autocrine and paracrine signaling, a chemical messenger diffuses a short distance through function. Diseases occur within the context of a whole or- the extracellular fluid and binds to a receptor on the same cell or ganism, however, and it is important to understand how all a nearby cell. Nervous signaling involves the rapid transmission of cells, tissues, organs, and organ systems respond to a dis- action potentials, often over long distances, and the release of a turbance (disease process) and interact. Endocrine signaling involves the whole is more than the sum of its parts,” certainly applies to release of a hormone into the bloodstream and the binding of the what happens in living organisms. Neuroendocrine signal- ogy has the unique challenge of trying to make sense of the ing involves the release of a hormone from a nerve cell and the complex interactions that occur in the body. Understand- transport of the hormone by the blood to a distant target cell. Gap Junctions Provide a Pathway for Direct Communication Between Adjacent Cells MODES OF COMMUNICATION AND SIGNALING Adjacent cells sometimes communicate directly with each The human body has several means of transmitting infor- other via gap junctions, specialized protein channels made mation between cells. Six connexins form a communication between adjacent cells through gap junc- half-channel called a connexon. Two connexons join end tions, autocrine and paracrine signaling, and the release of to end to form an intercellular channel between adjacent neurotransmitters and hormones produced by endocrine cells. Gap junctions allow the flow of ions (hence, electri- and nerve cells (Fig. The production of NO results from the activation of ni- tric oxide synthase (NOS), which deaminates arginine to Ions, citrulline (Fig. NO, produced by endothelial cells, nucleotides, regulates vascular tone by diffusing from the endothelial etc. The activation of cytoplasmic guanylyl cyclase re- sults in increased intracellular cyclic guanosine monophos- Connexin phate (cGMP) levels and the activation of cGMP-depend- ent protein kinase. This enzyme phosphorylates potential Channel target substrates, such as calcium pumps in the sarcoplas- mic reticulum or sarcolemma, leading to reduced cytoplas- mic levels of calcium. In turn, this deactivates the contrac- tile machinery in the vascular smooth muscle cell and produces relaxation or a decrease of tone (see Chapter 16). In contrast, during autocrine signaling, the cell releases a chemical into the interstitial fluid that affects its own ac- tivity by binding to a receptor on its own surface (see Fig. These molecules act as local hormones to influence a vari- ety of physiological processes, such as uterine smooth mus- Paired connexons cle contraction during pregnancy.

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