By A. Jensgar. University of Southern Maine.

Even in untrained individuals generic cardizem 90mg on-line, the ejection fraction (stroke volume as a percentage of end-diastolic volume) reaches 80% in less than in dynamic work (Fig buy 90 mg cardizem mastercard. This response results from the combination of a ocardial oxygen demands. These demands are met by a lin- small, dilated active muscle mass with powerful central ear increase in coronary blood flow during exercise that can sympathetic vasoconstrictor drive. This increase in flow emplify a medium muscle mass; shoveling snow is a good is driven by local, metabolically linked factors (nitric oxide, example of primarily arm and heavily isometric exercise. The elevated pressure places compromised traction, high at rest, increases further with exercise (up to cerebral arteries at risk and presents an ischemic or failing 80% of delivered oxygen). In healthy people, there is no heart with a greatly increased afterload. Acute and Chronic Responses of the Heart Over longer periods of time, the heart adapts to exercise and Blood Vessels to Exercise Differ overload much as it does to high-demand pathological In acute dynamic exercise, vagal withdrawal and increases states: by increasing left ventricular volume when exercise in sympathetic outflow elevate heart rate and contractility requires high blood flow, and by left ventricular hypertro- in proportion to exercise intensity (Table 30. Cardiac phy when exercise creates high systemic arterial pressure output is also aided in dynamic exercise by factors enhanc- (high afterload). These include the “muscle pump,” which adapted to prolonged, rhythmic exercise that involves rel- compresses veins as muscles rhythmically contract, and the atively low arterial pressure exhibit large left ventricular TABLE 30. To increase demands on the heart and coronary circulation, an ECG is performed while the patient walks on a treadmill or rides a stationary bicy- RR RR cle. TT TT Exercise increases the heart rate and the systemic arte- rial blood pressure. These changes increase cardiac work and the demand for coronary blood flow. In many patients, SS SS coronary blood flow is adequate at rest, but because of coronary arterial blockage, cannot rise sufficiently to meet 1 the increased demands of exercise. During a stress test, specific ECG changes can indicate that cardiac muscle is not receiving sufficient blood flow and oxygen delivery. As heart rate increases during exercise, the distance be- tween any portion of the ECG (for example, the R wave) on the ECG becomes shorter (Fig. In patients RR RR RR suffering from ischemic heart disease, however, other TT TT TT changes occur.

The people of ancient Mesopotamia regarded the liver as the seat of human emotions cheap 120mg cardizem amex. Many early investigations of the body represented an at- tempt to describe basic life forces cardizem 60mg on line. For example, people wondered which organ it was that constituted the soul. Certain diseases, injuries, deformities, and occasionally causes was extensively studied in sacrificial animals (fig. Even today, several European cul- tures associate the liver with various emotions. The Egyptian techniques of embalming could have con- The warm blood and arrangement of blood vessels are obvi- tributed greatly to the science of anatomy had they been recorded. In fact, em- Therefore, some concluded, blood must contain a vital, life-giving balmers were frequently persecuted and even stoned. The scholars of Mesopotamia were influenced by this idea, as was Aristotle, the Greek scientist who lived centuries later. Aristotle was a mystic art related more to religion than to science, and be- believed that the seat of the soul was the heart and that the brain cause it required a certain amount of mutilation of the dead body, functioned in cooling the blood that flowed from the heart. Consequently, embalming techniques ciation of the heart, in song and poetry, with the emotions of love and that could have provided embalmed cadavers as dissection speci- caring has its basis in Aristotelian thought. The ancient Egyptian culture neighbored Mesopotamia to the Several written works concerning anatomy have been dis- west. Here, the sophisticated science of embalming the dead in covered from ancient Egypt, but none of these influenced succeed- the form of mummies was perfected (fig. Menes, a king-physician during the first Egyptian tempts were made to perform anatomical or pathological studies dynasty of about 3400 B.

In In the axon 30mg cardizem fast delivery, anterograde transport occurs at both slow the axon terminal discount 120 mg cardizem amex, mitochondria provide both a source of and fast rates. The rate of slow axoplasmic transport is 1 to energy for processes associated with synaptic transmission 2 mm/day. Structural proteins, such as actin, neurofilaments, CHAPTER 3 The Action Potential, Synaptic Transmission, and Maintenance of Nerve Function 59 and microtubules, are transported at this speed. They are transported to transport is rate limiting for the regeneration of axons fol- the growth cone by slow axoplasmic transport. The rate of fast axoplasmic trans- The direction of axonal growth is dictated, in part, by port is about 400 mm/day. Fast transport mechanisms are cell adhesion molecules (CAMs), plasma membrane glyco- used for organelles, vesicles, and membrane glycoproteins proteins that promote cell adhesion. In dendrites, anterograde trans- (N-CAM) is expressed in postmitotic neurons and is partic- port occurs at a rate of approximately 0. Dendritic ularly prominent in growing axons and dendrites, which transport also moves ribosomes and RNA, suggesting that migrate along certain types of glial cells that provide a protein synthesis occurs within dendrites. The secretion of tropic factors In retrograde axoplasmic transport, material is moved from by target cells also influences the direction of axon growth. This provides a mechanism When the proper target site is reached and synaptic con- for the cell body to sample the environment around its synap- nections are formed, the processes of growth cone elonga- tic terminals. In some neurons, maintenance of synaptic con- tion and migration are terminated. This pruning of connections is a result of a selection process in which the most electrically active inputs predominate and Nerve Fibers Migrate and Extend survive and the less active contacts are lost. While the num- ber of connections between different neurons decreases dur- During Development and Regeneration ing this process, the total number of synapses increases dra- One of the major features that distinguishes differentiation matically as the remaining connections grow stronger. When axons are severed, the distal portion— cific pathway to form synaptic connections with appropriate that is, the portion cut off from the cell body—degenerates. Axonal growth is determined largely by interactions The proximal portion of the axon then develops a growth between the growing axon and the tissue environment.

Ka [HA] [H ] (4) [A ] The Acid Dissociation Constant Ka Shows the If we take the negative logarithms of both sides cheap cardizem 180 mg amex, Strength of an Acid At equilibrium 90mg cardizem sale, the rate of dissociation of an acid to form [A ] –log [H ] log K log (5) H A , and the rate of association of H and base A a [HA] to form HA, are equal. The equilibrium constant (Ka), which is also called the ionization constant or acid dissoci- Substituting pH for log [H ] and pKa for log Ka, we ation constant, is given by the expression get [H ] [A ] [A ] Ka (1) pH pKa log (6) [HA] [A] The higher the acid dissociation constant, the more an This equation is known as the Henderson-Hasselbalch acid is ionized and the greater is its strength. It shows that the pH of a solution is determined acid (HCl) is an example of a strong acid. It has a high Ka by the pKa of the acid and the ratio of the concentration of and is almost completely ionized in aqueous solutions. Other strong acids include sulfuric acid (H2SO4), phos- phoric acid (H3PO4), and nitric acid (HNO3). A most (99%) of the acid is nonionized and little (1%) is pres- pH buffer is defined as something that minimizes the change ent as acetate and H. The acidity (concentration of free in pH produced when an acid or base is added. A chemical pH buffer is carbonic acid (H2CO3), ammonium ion (NH4 ), and dihy- a mixture of a weak acid and its conjugate base (or a weak drogen phosphate (H2PO4 ). Following are examples of buffers: pKa Is a Logarithmic Expression of Ka Weak Acid Conjugate Base Acid dissociation constants vary widely and often are small H CO HCO H 2 3 3 numbers. It is convenient to convert Ka to a logarithmic (carbonic acid) (bicarbonate) (7) form, defining pKa as H PO HPO 2– H 2 4 4 pK log (1/K ) log K (2) (dihydrogen phosphate) (monohydrogen phosphate) (8) a 10 a 10 a In aqueous solution, each acid has a characteristic pKa, NH NH H 4 3 which varies slightly with temperature and the ionic (ammonium ion) (ammonia) (9) 428 PART VI RENAL PHYSIOLOGY AND BODY FLUIDS Generally, the equilibrium expression for a buffer pair 2– basic form of phosphate: H HPO4 H2PO4. Go- can be written in terms of the Henderson-Hasselbalch ing from left to right as strong base is added, OH com- equation: bines with H released from the acid form of the phos- 2– phate buffer: OH H2PO4 HPO4 H2O. In most cases, pH buffering is effec- 2– tive when the solution pH is within plus or minus one pH [HPO4 ] pH 6. Beyond that range, the pH shift that [HPO4 ] a a given amount of acid or base produces may be large, so The effectiveness of a buffer—how well it reduces pH the buffer becomes relatively ineffective.

Voltage-gated potassium channels nities for the polar peptide bonds to form hydrogen open with a delay relative to voltage-gated sodium bonds with one another in the hydrophobic interior of channels in response to depolarization 180mg cardizem visa. These segments are composed largely tantly purchase 90 mg cardizem with visa, there is a delay in their closing relative to the of amino acids with nonpolar hydrophobic side chains sodium channels. During the afterhyperpolarization that interact with the surrounding lipids. There are no phase of the action potential, the sodium channels are covalent bonds with cholesterol or phospholipids, and closed, but the potassium channels remain open. An outward calcium cur- membrane potential that develops when a single ion is rent, an outward sodium current, or an inward chloride distributed at equilibrium across a membrane. The current could conceivably hyperpolarize the cell, but Goldman equation gives the value of the membrane these currents are not the basis for this phase of the ac- potential when all permeable ions are accounted for. A specialization occurs in myelinated sure of a solution, and Fick’s law refers to the diffu- axons in which the voltage-gated sodium channels are sional movement of solute. The permeability coeffi- preferentially distributed to the axonal membrane be- cient accounts for several factors that determine the neath the nodes of Ranvier. Intracellular K is high compared action potential jumps from node to node. Active transport always moves solute ance and a decreased capacitance associated with the against its electrochemical gradient. All the other op- myelinated regions of the axon, both of which pro- tions are shared by both active transport and equili- mote the electrotonic spread of the positive charge brating carrier-mediated transport systems. Nongated ion channels available at the terminals, using enzymes that reside in are not involved in the generation of action potential. Myelin contributes substantially to by ribosomes, which are not found in axons or termi- the effective membrane resistance, Rm. The supply of peptide transmitters in the axon stant increases as Rm increases because it is more diffi- terminal must be continuously replenished via axoplas- cult for ions to flow across the membrane relative to mic transport from the cell body.