By T. Tragak. South Pacific University. 2018.
This process enables the translocation of noradrenaline from the extracellular space towards the neuronal cytosol buy indinavir 400mg with amex. Point-mutation and splicing studies indicate that different zones of the transporter determine its substrate affinity and selectivity generic indinavir 400mg amex, ionic dependence cheap 400mg indinavir amex, Vmax buy 400 mg indinavir visa, and the binding site for uptake inhibitors such as desipramine (Povlock and Amara 1997). Because the cloned transporter is a target for the reuptake inhibitor, desipramine, it is thought to reflect the native transporter in the brain and peripheral tissues. These are quite distinct uptake mechanisms because they have different substrate affinities and antagonist sensitivities. As yet, few studies have investigated the possibility that more than one uptake process exists in the brain but since two mRNAs for noradrenaline transporters have been isolated from brain tissue (Pacholczyk, Blakely and Amara 1991) there could be more than one transcription factor. At the very least, intracellular messengers could modify substrate affinity of the transporter, by causing its phosphorylation or glycosylation (Bonisch, Hammermann and Bruss 1998), and so markedly affect its function. Whether or not there are different gene products, splice variants, or posttranslational changes, it has been suggested that abnormal distributions of functionally distinctive noradrena- line transporters could underlie some psychiatric and neurological disorders. METABOLISM After reuptake into the cytosol, some noradrenaline may be taken up into the storage vesicles by the vesicular transporter and stored in the vesicles for subsequent release (see above). However, it is thought that the majority is broken down within the cytosol of the nerve terminal by monoamine oxidase (MAO; EC1. The metabolic pathway for noradrenaline follows a complex sequence of alternatives because the metabolic product of each of these enzymes can act as a substrate for the other (Fig 8. This could enable one of these enzymes to compensate for a deficiency in the other to some extent. MAO is bound to the outer membrane of mitochondria and is responsible for the oxidative deamination of noradrenaline. There are two isoforms of this enzyme, MAO-A 176 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION Figure 8. MAO is responsible for the oxidative deamination of noradrenaline derivatives while COMT O-methylates noradrenaline. Most intraneuronal metabolism involves MAO while COMT is mainly found extraneuronally. The reasons for this complex network of metabolites are not known and MAO-B, which hybridise to different cDNAs and are encoded by different genes on the X chromosome. MAO-A is the more important in vivo because it preferentially metabolises noradrenaline. However, in vitro, MAO-B will metabolise noradrenaline at high substrate concentrations. MAO probably also has an important role in development: a genetic deficiency of MAO-A causes some mental retardation and a tendency to bouts of aggression. MAO-B deficiency has no overt effects in the phenotype but a deficiency of both enzymes causes severe mental retardation and behavioural problems (Lenders et al. Of course, some of these abnormalities could be due to disruption of the metabolism of other monoamines, such as tyramine, which are also substrates for MAO. Certainly, such a complex system for metabolism of noradrenaline (which is shared with the other catecholamines) strongly suggests that its function extends beyond that of merely destroying transmitter sequestered from the synapse. However, as yet, little is known about the regulation of this pathway and any influence it might have on noradrenergic transmission. One crucial, additional role for MAO appears to be the NORADRENALINE 177 regulation of the intraneuronal stores of noradrenaline. Its predominantly intraneur- onal location would suggest that its primary function is to ensure that there is always a low concentration of cytoplasmic noradrenaline. What can happen when the concentration of cytosplasmic noradrenaline is increased is illustrated by amphetamine. This drug causes a rise in the cytoplasmic noradrenaline and results in increased binding of this transmitter to the cytoplasmic side of the transporter which then carries it out of the neuron. By maintaining low concentrations of cytoplasmic noradrenaline, MAO will also regulate the vesicular (releasable) pool of transmitter.
In some of its as- pects order indinavir 400mg on line, it also took on a somewhat theatrical quality order indinavir 400 mg with mastercard. Elaborate Leeuwenhoek amphitheaters were established in various parts of Europe for Antoni van Leeuwenhoek (la′ven-hook) (1632–1723) was a public demonstrations of human dissections (fig discount 400 mg indinavir fast delivery. Exorbi- Dutch optician and lens grinder who improved the microscope tantly priced tickets of admission were sold to the wealthy generic indinavir 400 mg amex, and to the extent that he achieved a magnification of 270 times. His the dissections were performed by elegantly robed anatomists many contributions included developing techniques for examin- who were also splendid orators. The subjects were usually exe- ing tissues and describing blood cells, skeletal muscle, and cuted prisoners, and the performances were scheduled during the lens of the eye. Although he was the first to accurately de- cold weather because of the perishable nature of the cadavers. History of Anatomy © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 16 Unit 1 Historical Perspective salivary glands and lymph nodes within the neck and facial re- gions. In 1664, Thomas Willis published a summary of what was then known about the nervous system. A number of anatomical structures throughout the body are named in honor of the early anatomists. Thus we have graafian follicles, Stensen’s and Wharton’s ducts, fallopian tubes, Bartholin’s glands, the circle of Willis, and many others. Because these terms have no descriptive basis, they are not particularly useful to a student of anatomy. Nineteenth Century The major scientific contribution of the nineteenth century was the formulation of the cell theory. It could be argued that this theory was the most important breakthrough in the history of bi- ology and medicine because all of the body’s functions were eventually interpreted as the effects of cellular function. The term cell was coined in 1665 by an English physician, Robert Hooke, as he examined the structure of cork under his mi- croscope in an attempt to explain its buoyancy. What Hooke actu- ally observed were the rigid walls that surrounded the empty cavities of the dead cells. The significance of cellular structure did not be- come apparent until approximately 150 years after Hooke’s work. Rather, he thought that a spermatozoan contained a teen years later, René H. Dutrochet described the differences be- miniature human being called a homunculus. The development of the microscope added an entirely new Two German scientists, Matthias Schleiden and Theodor dimension to anatomy and eventually led to explanations of Schwann, are credited with the biological principle referred to as basic body functions. Schleiden, a botanist, suggested in 1838 that each invaluable for understanding the etiologies of many diseases, and plant cell leads a double life—that is, in some respects it behaves thus for discovering cures for many of them. Although Leeuwen- as an independent organism, but at the same time it cooperates hoek improved the microscope, credit for its invention is usually with the other cells that form the whole plant. The first Schwann, a zoologist, concluded that all organisms are composed scientific investigation using a microscope was performed by of cells that are essentially alike. Nineteen years later, the addi- Francisco Stelluti in 1625 on the structure of a bee. In 1858, the German pathologist Rudolf Malpighi and Others Virchow wrote a book entitled Cell Pathology in which he pro- Marcello Malpighi (mal-pe′ge) (1628–94), an Italian anatomist, posed that cells can arise only from preexisting cells. He discovered nism of cellular replication, however, was not understood for the capillary blood vessels that Harvey had postulated and de- several more decades. In 1672, the Dutch teaching career, science was sufficiently undeveloped to allow anatomist Regnier de Graaf described the ovaries of the female him to handle numerous disciplines at once. By the time of his reproductive system, and in 1775 Lazzaro Spallanzani showed death, however, knowledge had grown so dramatically that sev- that both ovum and sperm cell were necessary for conception.
Ilium Anterior Iliac crest Ilium gluteal line Iliac tuberosity Iliac crest Posterior gluteal line Anterior superior Anterior Auricular iliac spine superior surface Posterior iliac spine superior iliac spine Inferior Posterior superior gluteal line Anterior iliac spine inferior Posterior Anterior iliac spine Posterior inferior inferior inferior iliac spine iliac spine Arcuate line iliac spine Greater Superior sciatic notch Greater ramus of Superior sciatic notch ramis of pubis Spine of ischium pubis Lesser sciatic notch Spine of ischium Pubic Pubis tubercle Obturator foramen Lesser sciatic notch Inferior ramus Symphysial Ischium Ischium of pubis surface Obturator foramen Pubis Ischial Inferior ramus Inferior ramus Ischial tuberosity tuberosity Inferior ramus of pubis of ischium of ischium Acetabulum FIGURE 7 buy indinavir 400mg amex. Skeletal System: The © The McGraw−Hill Anatomy buy 400 mg indinavir with amex, Sixth Edition Appendicular Skeleton Companies trusted 400 mg indinavir, 2001 Chapter 7 Skeletal System: The Appendicular Skeleton 183 TABLE 7 generic 400 mg indinavir amex. The obturator foramen is cov- ered by the obturator membrane, to which several muscles attach. The body contributes to the formation of the symphysis pubis—the joint between the two ossa coxae. At the lateral end of the anterior border of the body is the pubic tubercle, one of inferior iliac spine. The posterior termination of the iliac crest is the attachments for the inguinal ligament. The weight of the viscera may weaken the surface of the ilium is the roughened auricular surface, which walls of the lower abdominal area and cause hernias. The iliac fossa is the smooth, con- problems of childbirth are related to the structure of the mother’s cave surface on the anterior portion of the ilium. Finally, the hip joint tends to deteriorate with age, so that muscle originates from this fossa. The iliac tuberosity, for the at- many elderly people suffer from degenerative arthritis (osteoarthrosis). Three roughened ridges are present on the gluteal surface of the posterior aspect of the ilium. These ridges, which Sex-Related Differences in the Pelvis serve to attach the gluteal muscles, are the inferior, anterior, Structural differences between the pelvis of an adult male and and posterior gluteal lines (see fig. In a vaginal delivery, a Ischium baby must pass through its mother’s lesser pelvis. Diameters may be deter- the ischium is the projection immediately posterior and inferior mined by vaginal palpation or by sonographic images. The ischial tuberosity is the bony projection that supports the weight of the body in the Thigh sitting position. Skeletal System: The © The McGraw−Hill Anatomy, Sixth Edition Appendicular Skeleton Companies, 2001 184 Unit 4 Support and Movement Head of femur Greater trochanter Greater trochanter Fovea capitis femoris Intertrochanteric crest Intertrochanteric line Neck of femur Gluteal tuberosity Lesser trochanter Linea aspera Body of femur Lateral epicondyle Lateral epicondyle Medial epicondyle Intercondylar fossa Patellar surface Medial condyle Lateral condyle (a) (b) FIGURE 7. Femur The body of the femur has a slight medial curve to bring the knee joint in line with the body’s plane of gravity. The body of the femur has several distinguishing features femur articulates with the acetabulum of the os coxae. On the proximolateral side of the body is roughened shallow pit, the fovea capitis femoris, is present in the greater trochanter, and on the medial side is the lesser the lower center of the head of the femur. It Lateral also articulates both proximally and distally with the fibula. Two epicondyle of femur slightly concave surfaces on the proximal end of the tibia, the medial and lateral condyles (fig. The condyles are separated by a slight up- Patella ward projection called the intercondylar eminence, which pro- vides attachment for the cruciate ligaments of the knee joint (see Head of figs. The tibial tuberosity, for attachment of the tibia patellar ligament, is located on the proximoanterior part of the Tibia body of the tibia. The anterior crest, commonly called the “shin,” is a sharp ridge along the anterior surface of the body. A fibu- lar notch, for articulation with the fibula, is located on the disto- FIGURE 7. In that the tibia is the weight-bearing bone of the leg, it is much larger than the fibula. The patellar surface is located between the condyles on fibula articulates with the proximolateral end of the tibia. Above the condyles on the lateral and medial distal end has a prominent knob called the lateral malleolus. Both processes can be seen as prominent surface features and are easily palpated. Fractures to the fibula above the lateral malleolus are common in Patella skiers. Articular facets on the articular surface of the patella ar- The foot contains 26 bones, grouped into the tarsus, metatarsus, ticulate with the medial and lateral condyles of the femur.
Endocrine System © The McGraw−Hill Anatomy buy 400mg indinavir with visa, Sixth Edition Coordination Companies indinavir 400 mg overnight delivery, 2001 464 Unit 5 Integration and Coordination TABLE 14 purchase indinavir 400 mg overnight delivery. Neurons in the hypothalamus secrete hormones into explain how the hypothalamus controls the secretion of the region of the median eminence order indinavir 400mg with mastercard, where they enter a net- each hormone. Which hormone secreted by the anterior pituitary does not through the pituitary stalk transports the hypothalamic hor- affect some other endocrine gland? Which hormone secreted by the pituitary gland affects scribed in chapter 16. Endocrine System © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 Chapter 14 Endocrine System 465 FIGURE 14. Endocrine System © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 466 Unit 5 Integration and Coordination FIGURE 14. Hypothalamic hormones (shown as dots) enter this system in the first set of capil- laries of the median eminence and are transported through the portal veins of the pituitary stalk to a second set of capillaries of the anterior pituitary. Description of the Thyroid Gland THYROID AND PARATHYROID GLANDS The thyroid gland is located in the neck, just below the larynx (fig. The thyroid is the are critically important for proper growth and development. It thyroid also secretes calcitonin, which may antagonize the action receives an abundant blood supply (80–120 ml/min) through the of parathyroid hormone in the regulation of calcium and phos- paired superior thyroid branches of the external carotid arteries phate balance. The venous return is through the paired superior and middle of the thyroid gland and list the actions of the thyroid hormones. Objective 11 Describe the location and structure of the parathyroid glands and list the actions of parathyroid thyroid: Gk. Endocrine System © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 Chapter 14 Endocrine System 467 Thyroid follicle Follicular cells Colloid FIGURE 14. Each follicle consists of follicular cells sur- rounding the fluid known as colloid. These follicles are lined with a simple cuboidal epithelium com- posed of follicular cells. The follicular cells synthesize the two principal thyroid hormones (see table 14. Endocrine System © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 468 Unit 5 Integration and Coordination – Hypothalamus Pharynx TRH Thyroid gland Parathyroid glands Anterior pituitary Left common carotid artery Esophagus TSH Normal thyroid Trachea Thyroid If iodine If iodine adequate Negative inadequate feedback Low T and T T and T 3 4 3 4 FIGURE 14. Low negative feedback Iodine is the most common component of thyroxine and tri- iodothyronine, and a continual intake of iodine is essential for normal thyroid function. Seafood contains adequate amounts of io- Anterior dine, and commercial salt generally has iodine as an additive. Ab- pituitary sorbed iodine is transported through the blood to the thyroid gland, where an active transport mechanism called an iodine pump moves the iodides into the follicle cells. Here, they combine with amino acids in the synthesis of thyroid hormones. Excess TSH Most of the thyroxine in blood is attached to carrier pro- teins. Only the very small percentage of thyroxine that is free in Thyroid Enlarged thyroid blood plasma can enter the target cells. In the target cells, it is (goiter) Hypertrophy— converted to triiodothyronine and attached to nuclear receptor produces goiter proteins. Through the activation of genes, thyroid hormones stimulate protein synthesis, promote maturation of the nervous FIGURE 14. A lack of ade- system, and increase the rate of energy utilization by the body. This trophic effect shows up dramatically in people who develop an iodine-deficiency (endemic) goiter. In the absence of sufficient dietary iodine, the thyroid cannot produce ade- quate amounts of T4 and T3.
Make certain that the basic medical information that the plain- tiff attorney certainly will have has been provided to your attorney buy indinavir 400 mg with amex. From the plaintiff attorney’s perspective effective 400mg indinavir, when doctors work closely with their attorneys generic 400 mg indinavir with visa, are not in denial about a lawsuit indinavir 400mg line, and discharge their responsibilities to their patients, the chances of winning are diminished. ONCE YOUR DEPOSITION IS SCHEDULED, THE PLAINTIFF ATTORNEY IS LOOKING FOR SPECIFIC THINGS The order of the information the plaintiff attorney seeks is as impor- tant as their content. Thus, it is important for you to react to people in an accommodating manner. The effort you make in relating to those around you during the deposition and during the trial will be key to whether you are successful in the litigation. If you do not respect your attorney, ask your insurance carrier for another one. Do not show your contempt or lack of respect for the justice system through your lack of respect for your attorney. Plaintiff attorneys are allowed to ask you questions during a deposi- tion. If you are courteous and respectful when asked questions, the plaintiff attorney will conclude that you will behave that way in trial as well. To show respect and be the kind of caring doctor that jurors will love is not how a plaintiff attorney wants you to behave. Study the medical aspects of the case and then teach them to your attorney. You may think you will remember the facts of the case simply by having experienced them, but you will be surprised at the details you have forgotten. However, you still must understand that this is the least important thing the plaintiff attorney is looking for when he or she assesses your ability to fight a potential suit. The most important thing is you and the impression you will makeon a jury. If you are honest and straightforward with your patients when there is a complication and you are honest and straightforward to a jury, you have maximized your risk reduction. The attorney for the injured person must assess his or her ability to win in trial. That attorney is risking his or her time and money to pursue a case for which a fee will only be recovered if he or she wins. The assessment takes place before the attorney ever meets you and is based on what you have written in your medical records. The attorney looks to see if you are honest and forthcoming, which is not something he or she wants to see in a potential defendant. If you share your concerns with the patient when there is a complication, that openness will be a very effec- tive deterrent to a plaintiff lawyer. You may feel you are raising a red flag by documenting that something is wrong. However, you may be keeping your patient from going to an attorney for answers, and you will be showing what a wonderful doctor (and witness) you will be if there is a lawsuit. Your goal is to minimize the chances of your patient seeking legal aid to get answers. Your goal is also to be successful if all that occurred was a complication rather than a deviation from the standard of medi- cal care. Hopefully, this chapter helps you understand some simple ways of accomplishing these goals. Chapter 4 / Physician As a Witness 41 4 The Physician As a Witness Joel A. Mattison, MD, FACS SUMMARY This chapter is a personal reflection on the role of the physician as an expert witness in medical malpractice litigation. It looks at both the individual experience and professional obligations of the expert from both the medical and the legal perspectives.